Xiaoqing Gu

<h2>Summary</h2><h3>Background</h3> A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. <h3>Methods</h3> All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. <h3>Findings</h3> By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. <h3>Interpretation</h3> The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. <h3>Funding</h3> Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.

<h2>Summary</h2><h3>Background</h3> Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. <h3>Methods</h3> In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. <h3>Findings</h3> 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. <h3>Interpretation</h3> The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. <h3>Funding</h3> Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2.We conducted a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, and an oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao2) to the fraction of inspired oxygen (Fio2) of less than 300 mm Hg. Patients were randomly assigned in a 1:1 ratio to receive either lopinavir-ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care, or standard care alone. The primary end point was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever came first.A total of 199 patients with laboratory-confirmed SARS-CoV-2 infection underwent randomization; 99 were assigned to the lopinavir-ritonavir group, and 100 to the standard-care group. Treatment with lopinavir-ritonavir was not associated with a difference from standard care in the time to clinical improvement (hazard ratio for clinical improvement, 1.31; 95% confidence interval [CI], 0.95 to 1.80). Mortality at 28 days was similar in the lopinavir-ritonavir group and the standard-care group (19.2% vs. 25.0%; difference, -5.8 percentage points; 95% CI, -17.3 to 5.7). The percentages of patients with detectable viral RNA at various time points were similar. In a modified intention-to-treat analysis, lopinavir-ritonavir led to a median time to clinical improvement that was shorter by 1 day than that observed with standard care (hazard ratio, 1.39; 95% CI, 1.00 to 1.91). Gastrointestinal adverse events were more common in the lopinavir-ritonavir group, but serious adverse events were more common in the standard-care group. Lopinavir-ritonavir treatment was stopped early in 13 patients (13.8%) because of adverse events.In hospitalized adult patients with severe Covid-19, no benefit was observed with lopinavir-ritonavir treatment beyond standard care. Future trials in patients with severe illness may help to confirm or exclude the possibility of a treatment benefit. (Funded by Major Projects of National Science and Technology on New Drug Creation and Development and others; Chinese Clinical Trial Register number, ChiCTR2000029308.).

<h2>Summary</h2><h3>Background</h3> The long-term health consequences of COVID-19 remain largely unclear. The aim of this study was to describe the long-term health consequences of patients with COVID-19 who have been discharged from hospital and investigate the associated risk factors, in particular disease severity. <h3>Methods</h3> We did an ambidirectional cohort study of patients with confirmed COVID-19 who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7, 2020, and May 29, 2020. Patients who died before follow-up, patients for whom follow-up would be difficult because of psychotic disorders, dementia, or re-admission to hospital, those who were unable to move freely due to concomitant osteoarthropathy or immobile before or after discharge due to diseases such as stroke or pulmonary embolism, those who declined to participate, those who could not be contacted, and those living outside of Wuhan or in nursing or welfare homes were all excluded. All patients were interviewed with a series of questionnaires for evaluation of symptoms and health-related quality of life, underwent physical examinations and a 6-min walking test, and received blood tests. A stratified sampling procedure was used to sample patients according to their highest seven-category scale during their hospital stay as 3, 4, and 5–6, to receive pulmonary function test, high resolution CT of the chest, and ultrasonography. Enrolled patients who had participated in the Lopinavir Trial for Suppression of SARS-CoV-2 in China received severe acute respiratory syndrome coronavirus 2 antibody tests. Multivariable adjusted linear or logistic regression models were used to evaluate the association between disease severity and long-term health consequences. <h3>Findings</h3> In total, 1733 of 2469 discharged patients with COVID-19 were enrolled after 736 were excluded. Patients had a median age of 57·0 (IQR 47·0–65·0) years and 897 (52%) were men. The follow-up study was done from June 16, to Sept 3, 2020, and the median follow-up time after symptom onset was 186·0 (175·0–199·0) days. Fatigue or muscle weakness (63%, 1038 of 1655) and sleep difficulties (26%, 437 of 1655) were the most common symptoms. Anxiety or depression was reported among 23% (367 of 1617) of patients. The proportions of median 6-min walking distance less than the lower limit of the normal range were 24% for those at severity scale 3, 22% for severity scale 4, and 29% for severity scale 5–6. The corresponding proportions of patients with diffusion impairment were 22% for severity scale 3, 29% for scale 4, and 56% for scale 5–6, and median CT scores were 3·0 (IQR 2·0–5·0) for severity scale 3, 4·0 (3·0–5·0) for scale 4, and 5·0 (4·0–6·0) for scale 5–6. After multivariable adjustment, patients showed an odds ratio (OR) 1·61 (95% CI 0·80–3·25) for scale 4 versus scale 3 and 4·60 (1·85–11·48) for scale 5–6 versus scale 3 for diffusion impairment; OR 0·88 (0·66–1·17) for scale 4 versus scale 3 and OR 1·77 (1·05–2·97) for scale 5–6 versus scale 3 for anxiety or depression, and OR 0·74 (0·58–0·96) for scale 4 versus scale 3 and 2·69 (1·46–4·96) for scale 5–6 versus scale 3 for fatigue or muscle weakness. Of 94 patients with blood antibodies tested at follow-up, the seropositivity (96·2% <i>vs</i> 58·5%) and median titres (19·0 <i>vs</i> 10·0) of the neutralising antibodies were significantly lower compared with at the acute phase. 107 of 822 participants without acute kidney injury and with estimated glomerular filtration rate (eGFR) 90 mL/min per 1·73 m² or more at acute phase had eGFR less than 90 mL/min per 1·73 m² at follow-up. <h3>Interpretation</h3> At 6 months after acute infection, COVID-19 survivors were mainly troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations, and are the main target population for intervention of long-term recovery. <h3>Funding</h3> National Natural Science Foundation of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, and Peking Union Medical College Foundation.

No specific antiviral drug has been proven effective for treatment of patients with severe coronavirus disease 2019 (COVID-19). Remdesivir (GS-5734), a nucleoside analogue prodrug, has inhibitory effects on pathogenic animal and human coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro, and inhibits Middle East respiratory syndrome coronavirus, SARS-CoV-1, and SARS-CoV-2 replication in animal models.We did a randomised, double-blind, placebo-controlled, multicentre trial at ten hospitals in Hubei, China. Eligible patients were adults (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia. Patients were randomly assigned in a 2:1 ratio to intravenous remdesivir (200 mg on day 1 followed by 100 mg on days 2-10 in single daily infusions) or the same volume of placebo infusions for 10 days. Patients were permitted concomitant use of lopinavir-ritonavir, interferons, and corticosteroids. The primary endpoint was time to clinical improvement up to day 28, defined as the time (in days) from randomisation to the point of a decline of two levels on a six-point ordinal scale of clinical status (from 1=discharged to 6=death) or discharged alive from hospital, whichever came first. Primary analysis was done in the intention-to-treat (ITT) population and safety analysis was done in all patients who started their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04257656.Between Feb 6, 2020, and March 12, 2020, 237 patients were enrolled and randomly assigned to a treatment group (158 to remdesivir and 79 to placebo); one patient in the placebo group who withdrew after randomisation was not included in the ITT population. Remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1·23 [95% CI 0·87-1·75]). Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less (hazard ratio 1·52 [0·95-2·43]). Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients. Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early.In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits. However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies.Chinese Academy of Medical Sciences Emergency Project of COVID-19, National Key Research and Development Program of China, the Beijing Science and Technology Project.

The full range of long-term health consequences of COVID-19 in patients who are discharged from hospital is largely unclear. The aim of our study was to comprehensively compare consequences between 6 months and 12 months after symptom onset among hospital survivors with COVID-19.We undertook an ambidirectional cohort study of COVID-19 survivors who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7 and May 29, 2020. At 6-month and 12-month follow-up visit, survivors were interviewed with questionnaires on symptoms and health-related quality of life (HRQoL), and received a physical examination, a 6-min walking test, and laboratory tests. They were required to report their health-care use after discharge and work status at the 12-month visit. Survivors who had completed pulmonary function tests or had lung radiographic abnormality at 6 months were given the corresponding tests at 12 months. Non-COVID-19 participants (controls) matched for age, sex, and comorbidities were interviewed and completed questionnaires to assess prevalent symptoms and HRQoL. The primary outcomes were symptoms, modified British Medical Research Council (mMRC) score, HRQoL, and distance walked in 6 min (6MWD). Multivariable adjusted logistic regression models were used to evaluate the risk factors of 12-month outcomes.1276 COVID-19 survivors completed both visits. The median age of patients was 59·0 years (IQR 49·0-67·0) and 681 (53%) were men. The median follow-up time was 185·0 days (IQR 175·0-198·0) for the 6-month visit and 349·0 days (337·0-361·0) for the 12-month visit after symptom onset. The proportion of patients with at least one sequelae symptom decreased from 68% (831/1227) at 6 months to 49% (620/1272) at 12 months (p<0·0001). The proportion of patients with dyspnoea, characterised by mMRC score of 1 or more, slightly increased from 26% (313/1185) at 6-month visit to 30% (380/1271) at 12-month visit (p=0·014). Additionally, more patients had anxiety or depression at 12-month visit (26% [331/1271] at 12-month visit vs 23% [274/1187] at 6-month visit; p=0·015). No significant difference on 6MWD was observed between 6 months and 12 months. 88% (422/479) of patients who were employed before COVID-19 had returned to their original work at 12 months. Compared with men, women had an odds ratio of 1·43 (95% CI 1·04-1·96) for fatigue or muscle weakness, 2·00 (1·48-2·69) for anxiety or depression, and 2·97 (1·50-5·88) for diffusion impairment. Matched COVID-19 survivors at 12 months had more problems with mobility, pain or discomfort, and anxiety or depression, and had more prevalent symptoms than did controls.Most COVID-19 survivors had a good physical and functional recovery during 1-year follow-up, and had returned to their original work and life. The health status in our cohort of COVID-19 survivors at 12 months was still lower than that in the control population.Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, the National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, the China Evergrande Group, Jack Ma Foundation, Sino Biopharmaceutical, Ping An Insurance (Group), and New Sunshine Charity Foundation.

With the ongoing COVID-19 pandemic, growing evidence shows that a considerable proportion of people who have recovered from COVID-19 have long-term effects on multiple organs and systems. A few longitudinal studies have reported on the persistent health effects of COVID-19, but the follow-up was limited to 1 year after acute infection. The aim of our study was to characterise the longitudinal evolution of health outcomes in hospital survivors with different initial disease severity throughout 2 years after acute COVID-19 infection and to determine their recovery status.We did an ambidirectional, longitudinal cohort study of individuals who had survived hospitalisation with COVID-19 and who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7 and May 29, 2020. We measured health outcomes 6 months (June 16-Sept 3, 2020), 12 months (Dec 16, 2020-Feb 7, 2021), and 2 years (Nov 16, 2021-Jan 10, 2022) after symptom onset with a 6-min walking distance (6MWD) test, laboratory tests, and a series of questionnaires on symptoms, mental health, health-related quality of life (HRQoL), return to work, and health-care use after discharge. A subset of COVID-19 survivors received pulmonary function tests and chest imaging at each visit. Age-matched, sex-matched, and comorbidities-matched participants without COVID-19 infection (controls) were introduced to determine the recovery status of COVID-19 survivors at 2 years. The primary outcomes included symptoms, modified British Medical Research Council (mMRC) dyspnoea scale, HRQoL, 6MWD, and return to work, and were assessed in all COVID-19 survivors who attended all three follow-up visits. Symptoms, mMRC dyspnoea scale, and HRQoL were also assessed in controls.2469 patients with COVID-19 were discharged from Jin Yin-tan Hospital between Jan 7 and May 29, 2020. 1192 COVID-19 survivors completed assessments at the three follow-up visits and were included in the final analysis, 1119 (94%) of whom attended the face-to-face interview 2 years after infection. The median age at discharge was 57·0 years (48·0-65·0) and 551 (46%) were women. The median follow-up time after symptom onset was 185·0 days (IQR 175·0-197·0) for the visit at 6 months, 349·0 days (337·0-360·0) for the visit at 12 months, and 685·0 days (675·0-698·0) for the visit at 2 years. The proportion of COVID-19 survivors with at least one sequelae symptom decreased significantly from 777 (68%) of 1149 at 6 months to 650 (55%) of 1190 at 2 years (p<0·0001), with fatigue or muscle weakness always being the most frequent. The proportion of COVID-19 survivors with an mMRC score of at least 1 was 168 (14%) of 1191 at 2 years, significantly lower than the 288 (26%) of 1104 at 6 months (p<0·0001). HRQoL continued to improve in almost all domains, especially in terms of anxiety or depression: the proportion of individuals with symptoms of anxiety or depression decreased from 256 (23%) of 1105 at 6 months to 143 (12%) 1191 at 2 years (p<0·0001). The proportion of individuals with a 6MWD less than the lower limit of the normal range declined continuously in COVID-19 survivors overall and in the three subgroups of varying initial disease severity. 438 (89%) of 494 COVID-19 survivors had returned to their original work at 2 years. Survivors with long COVID symptoms at 2 years had lower HRQoL, worse exercise capacity, more mental health abnormality, and increased health-care use after discharge than survivors without long COVID symptoms. COVID-19 survivors still had more prevalent symptoms and more problems in pain or discomfort, as well as anxiety or depression, at 2 years than did controls. Additionally, a significantly higher proportion of survivors who had received higher-level respiratory support during hospitalisation had lung diffusion impairment (43 [65%] of 66 vs 24 [36%] of 66, p=0·0009), reduced residual volume (41 [62%] vs 13 [20%], p<0·0001), and total lung capacity (26 [39%] vs four [6%], p<0·0001) than did controls.Regardless of initial disease severity, COVID-19 survivors had longitudinal improvements in physical and mental health, with most returning to their original work within 2 years; however, the burden of symptomatic sequelae remained fairly high. COVID-19 survivors had a remarkably lower health status than the general population at 2 years. The study findings indicate that there is an urgent need to explore the pathogenesis of long COVID and develop effective interventions to reduce the risk of long COVID.

Abstract With the availability of low‐cost high‐quality head‐mounted displays (HMDs) since 2013, there is a growing body of literature investigating the impact of immersive virtual reality (IVR) technology on education. This meta‐analysis aims to synthesize the findings on the overall effects of IVR using HMDs compared to less immersive desktop virtual reality (DVR) and other traditional means of instruction. A systematic search was carried out on the literature published between 2013 and 2019. Thirty‐five randomized controlled trials (RCTs) or quasi‐experimental studies were identified. We conducted an analysis using the random effects model (REM) to calculate the pooled effect size. The studies were also coded to examine the moderating effects of their characteristics, such as learner stage, learning domain, learning application type, testing format, control group treatment and learning duration, on the outcome measure. The results showed that IVR using HMDs is more effective than non‐immersive learning approaches with a small effect size ( ES = 0.24). The key findings of the moderator analysis were that HMDs have a greater impact (a) on K‐12 learners; (b) in the fields of science education and specific abilities development; (c) when offering simulation or virtual world representations; and (d) when compared with lectures or real‐world practices. The meta‐analysis also suggested that HMDs can improve both knowledge and skill development, and maintain the learning effect over time. Practitioner Notes What is already known about this topic Head‐mounted displays (HMDs) have been widely applied in various disciplines across both K‐12 and post‐secondary education. HMDs have a positive impact on learning attitudes and perceptions. HMDs have produced mixed results on learning performance. What this paper adds Immersive virtual reality (IVR) using HMDs is more effective than non‐immersive learning approaches with a small effect size. The critical factors of learning implementation and research design moderate the impact of HMDs on learning performance. HMDs can improve both knowledge and skill development and maintain the learning effect over time. Implications for practice and/or policy HMD‐based immersive learning appears to be a better complement to non‐immersive learning approaches. Theory‐driven learning design should be incorporated to guide HMD‐based teaching and learning practice.

Student satisfaction is of great significance in online learning, but few studies have explored its determinants in emerging countries. This study investigated the determinants of university students' satisfaction with online learning platforms in China through applying the Technology Satisfaction Model during the COVID-19 pandemic, when an unprecedented amount of learning began to take place online due to the closure of educational institutions. A total of 928 students from five universities in four Chinese provinces or municipalities were surveyed through a purposive sampling technique and analyzed through structural equation modeling and the Rasch model. Findings show that Chinese university students' satisfaction with online learning platforms is directly and indirectly impacted by their computer self-efficacy and the perceived ease of use and usefulness of the platforms. Findings also show that regional differences moderate the associations among these components. The current study adds to theoretical, methodical and practical understanding of university students' satisfaction with using online learning platforms, which have been recognized as irreplaceable emergency educational tools.

Rapidly progressing hypoxemia and acute respiratory distress syndrome were commonly observed in patients with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) viral pneumonia [1]. Although several severity scores including Pneumonia Severity Index (PSI) [2], CURB-65 and CRB-65 (confusion, (urea >7 mmol·L−1), respiratory rate ≥30 breaths·min−1, blood pressure <90 mmHg (systolic) ≤60 mmHg (diastolic), age ≥65 years), [3], A-DROP [4] and SMART-COP [5] have been developed to identify community acquired pneumonia (CAP) patients at high risk and offer therapeutic advice, the underestimation of risk of death from viral pneumonia in these scores has been reported by previous studies [6, 7]. The National Early Warning Score 2 (NEWS2) was developed by National Health Service (NHS) England [8] and, along with quick sequential organ failure assessment score (qSOFA), was proposed as a candidate for prognostic prediction for severe coronavirus disease 2019 (COVID-19) in the situation of limited medical source [9]. The aim of this study was to compare the accuracy of current score rules in hospitalised patients with COVID-19 pneumonia for predicting the risk of death and evaluate feasibility in improving medical decisions by adopting appropriate scores in clinical practice. A-DROP is a reliable tool for risk stratification of death in COVID-19 hospitalised patients on admission <https://bit.ly/3iDZipD> We acknowledge all healthcare workers involved in the diagnosis and treatment of patients in Wuhan, China.

The memory immune response is crucial for preventing reinfection or reducing disease severity. However, the robustness and functionality of the humoral and T-cell response to SARS-CoV-2 remains unknown 12 months after initial infection. The aim of this study is to investigate the durability and functionality of the humoral and T-cell response to the original SARS-CoV-2 strain and variants in recovered patients 12 months after infection.In this longitudinal cohort study, we recruited participants who had recovered from COVID-19 and who were discharged from the Wuhan Research Center for Communicable Disease Diagnosis and Treatment at the Chinese Academy of Medical Sciences, Wuhan, China, between Jan 7 and May 29, 2020. Patients received a follow-up visit between Dec 16, 2020, and Jan 27, 2021. We evaluated the presence of IgM, IgA, and IgG antibodies against the SARS-CoV-2 nucleoprotein, Spike protein, and the receptor-binding domain 12 months after initial infection, using ELISA. Neutralising antibodies against the original SARS-CoV-2 strain, and the D614G, beta (B.1.351), and delta (B.1.617.2) variants were analysed using a microneutralisation assay in a subset of plasma samples. We analysed the magnitude and breadth of the SARS-CoV-2-specific memory T-cell responses using the interferon γ (IFNγ) enzyme-linked immune absorbent spot (ELISpot) assay and intracellular cytokine staining (ICS) assay. The antibody response and T-cell response (ie, IFN-γ, interleukin-2 [IL-2], and tumour necrosis factor α [TNFα]) were analysed by age and disease severity. Antibody titres were also analysed according to sequelae symptoms.We enrolled 1096 patients, including 289 (26·4%) patients with moderate initial disease, 734 (67·0%) with severe initial disease, and 73 (6·7%) with critical initial disease. Paired plasma samples were collected from 141 patients during the follow-up visits for the microneutralisation assay. PBMCs were collected from 92 of 141 individuals at the 12-month follow-up visit, of which 80 were analysed by ELISpot and 92 by ICS assay to detect the SARS-CoV-2-specific memory T-cell responses. N-IgG (899 [82·0%]), S-IgG (1043 [95·2%]), RBD-IgG (1032 [94·2%]), and neutralising (115 [81·6%] of 141) antibodies were detectable 12 months after initial infection in most individuals. Neutralising antibodies remained stable 6 and 12 months after initial infection in most individuals younger than 60 years. Multifunctional T-cell responses were detected for all SARS-CoV-2 viral proteins tested. There was no difference in the magnitude of T-cell responses or cytokine profiles in individuals with different symptom severity. Moreover, we evaluated both antibody and T-cell responses to the D614G, beta, and delta viral strains. The degree of reduced in-vitro neutralising antibody responses to the D614G and delta variants, but not to the beta variant, was associated with the neutralising antibody titres after SARS-CoV-2 infection. We also found poor neutralising antibody responses to the beta variant; 83 (72·2%) of 115 patients showed no response at all. Moreover, the neutralising antibody titre reduction of the recovered patient plasma against the delta variant was similar to that of the D614G variant and lower than that of the beta variant. By contrast, T-cell responses were cross-reactive to the beta variant in most individuals. Importantly, T-cell responses could be detected in all individuals who had lost the neutralising antibody response to SARS-CoV-2 12 months after the initial infection.SARS-CoV-2-specific neutralising antibody and T-cell responses were retained 12 months after initial infection. Neutralising antibodies to the D614G, beta, and delta viral strains were reduced compared with those for the original strain, and were diminished in general. Memory T-cell responses to the original strain were not disrupted by new variants. This study suggests that cross-reactive SARS-CoV-2-specific T-cell responses could be particularly important in the protection against severe disease caused by variants of concern whereas neutralising antibody responses seem to reduce over time.Chinese Academy of Medical Sciences, National Natural Science Foundation, and UK Medical Research Council.

Seasonal human coronaviruses (HCoVs) including HCoV-229E, -OC43, -NL63, and -HKU1 widely spread in global human populations. However, the relevance of humoral response against seasonal HCoVs to COVID-19 pathogenesis is elusive. In this study, we profiled the temporal changes of IgG antibody against spike proteins (S-IgG) of SARS-CoV-2 and seasonal HCoVs in 838 plasma samples collected from 344 COVID-19 patients. We tested the antigenic cross-reactivities of S protein between SARS-CoV-2 and seasonal HCoVs and evaluated the correlations between the levels of HCoV-OC43 S-IgG and the disease severity in COVID-19 patients. We found that SARS-CoV-2 S-IgG titres mounted until days 22–28, whereas HCoV-OC43 antibody titres increased until days 15–21 and then plateaued until day 46. However, IgG titres against HCoV-NL63, −229E, and -HKU1 showed no significant increase. A two-way cross-reactivity was identified between SARS-CoV-2 and HCoV-OC43. Neutralizing antibodies against SARS-CoV-2 were not detectable in healthy controls who were positive for HCoV-OC43 S-IgG. HCoV-OC43 S-IgG titres were significantly higher in patients with severe disease than those in mild patients at days 1–21 post symptom onset (PSO). Higher levels of HCoV-OC43 S-IgG were also observed in patients requiring mechanical ventilation. At days 1–10 PSO, HCoV-OC43 S-IgG titres correlated to disease severity in the age group over 60. Our data indicate that there is a correlation between cross-reactive antibody against HCoV-OC43 spike protein and disease severity in COVID-19 patients.

The long-term health consequences of COVID-19 remain largely unclear. The aim of this study was to describe the long-term health consequences of patients with COVID-19 who have been discharged from hospital and investigate the associated risk factors, in particular disease severity.We did an ambidirectional cohort study of patients with confirmed COVID-19 who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7 and May 29, 2020. Patients who died before follow-up; patients for whom follow-up would be difficult because of psychotic disorders, dementia, or readmission to hospital; those who were unable to move freely due to concomitant osteoarthropathy or immobile before or after discharge due to diseases such as stroke or pulmonary embolism; those who declined to participate; those who could not be contacted; and those living outside of Wuhan or in nursing or welfare homes were all excluded. All patients were interviewed with a series of questionnaires for evaluation of symptoms and health-related quality of life, underwent physical examinations and a 6-min walking test, and received blood tests. A stratified sampling procedure was used to sample patients according to their highest seven-category scale during their hospital stay as 3, 4, and 5-6, to receive pulmonary function test, high resolution CT of the chest, and ultrasonography. Enrolled patients who had participated in the Lopinavir Trial for Suppression of SARS-CoV-2 in China received SARS-CoV-2 antibody tests. Multivariable adjusted linear or logistic regression models were used to evaluate the association between disease severity and long-term health consequences.In total, 1733 of 2469 discharged patients with COVID-19 were enrolled after 736 were excluded. Patients had a median age of 57·0 years (IQR 47·0-65·0) and 897 (52%) were male and 836 (48%) were female. The follow-up study was done from June 16 to Sept 3, 2020, and the median follow-up time after symptom onset was 186·0 days (175·0-199·0). Fatigue or muscle weakness (52%, 855 of 1654) and sleep difficulties (26%, 437 of 1655) were the most common symptoms. Anxiety or depression was reported among 23% (367 of 1616) of patients. The proportions of 6-min walking distance less than the lower limit of the normal range were 17% for those at severity scale 3, 13% for severity scale 4, and 28% for severity scale 5-6. The corresponding proportions of patients with diffusion impairment were 22% for severity scale 3, 29% for scale 4, and 56% for scale 5-6, and median CT scores were 3·0 (IQR 2·0-5·0) for severity scale 3, 4·0 (3·0-5·0) for scale 4, and 5·0 (4·0-6·0) for scale 5-6. After multivariable adjustment, patients showed an odds ratio (OR) of 1·61 (95% CI 0·80-3·25) for scale 4 versus scale 3 and 4·60 (1·85-11·48) for scale 5-6 versus scale 3 for diffusion impairment; OR 0·88 (0·66-1·17) for scale 4 versus scale 3 and OR 1·76 (1·05-2·96) for scale 5-6 versus scale 3 for anxiety or depression, and OR 0·87 (0·68-1·11) for scale 4 versus scale 3 and 2·75 (1·61-4·69) for scale 5-6 versus scale 3 for fatigue or muscle weakness. Of 94 patients with blood antibodies tested at follow-up, the seropositivity (96·2% vs 58·5%) and median titres (19·0 vs 10·0) of the neutralising antibodies were significantly lower compared with at the acute phase. 107 of 822 participants without acute kidney injury and with an estimated glomerular filtration rate (eGFR) of 90 mL/min per 1·73 m2 or more at acute phase had eGFR less than 90 mL/min per 1·73 m2 at follow-up.At 6 months after acute infection, COVID-19 survivors were mainly troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations, and are the main target population for intervention of long-term recovery.National Natural Science Foundation of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, and Peking Union Medical College Foundation.

Abstract Background Immunotherapy has recently emerged as a treatment strategy which stimulates the human immune system to kill tumor cells. Tumor immunotherapy is based on immune editing, which enhances the antigenicity of tumor cells and increases the tumoricidal effect of immune cells. It also suppresses immunosuppressive molecules, activates or restores immune system function, enhances anti-tumor immune responses, and inhibits the growth f tumor cell. This offers the possibility of reducing mortality in triple-negative breast cancer (TNBC). Main body Immunotherapy approaches for TNBC have been diversified in recent years, with breakthroughs in the treatment of this entity. Research on immune checkpoint inhibitors (ICIs) has made it possible to identify different molecular subtypes and formulate individualized immunotherapy schedules. This review highlights the unique tumor microenvironment of TNBC and integrates and analyzes the advances in ICI therapy. It also discusses strategies for the combination of ICIs with chemotherapy, radiation therapy, targeted therapy, and emerging treatment methods such as nanotechnology, ribonucleic acid vaccines, and gene therapy. Currently, numerous ongoing or completed clinical trials are exploring the utilization of immunotherapy in conjunction with existing treatment modalities for TNBC. The objective of these investigations is to assess the effectiveness of various combined immunotherapy approaches and determine the most effective treatment regimens for patients with TNBC. Conclusion This review provides insights into the approaches used to overcome drug resistance in immunotherapy, and explores the directions of immunotherapy development in the treatment of TNBC.

The Edu-Metaverse, a vast ensemble of different technologies, has initiated a great and unprecedented change in the field of education. This change has been effected through the following Edu-Metaverse characteristics: embodied and multimodal interaction; immersive teaching scenarios, which can accelerate learning and skill acquisition; and the emergence of AI-enabled agents. In comparison to traditional classroom teaching models, smart education is a collaborative and visual model that adopts the latest AI technologies to reach a learning outcome. However, a problem that should be considered is how a smart education model, enabled by the Edu-Metaverse, can be developed to enhance better learning outcomes for students. Such a model should highlight smart pedagogy in the context of the Edu-Metaverse, together with a smart teaching environment, multimodal teaching resources, and AI-enabled assessment. In this study, we focused on the teaching of college English to 60 students from Zhejiang Open University. We investigated the effectiveness of a smart education model, which was empowered by the Edu-Metaverse, in enhancing better learning outcomes for the students, using a combination of qualitative and quantitative research. After the one-semester-long experiment, questionnaires were sent out to complement the interview findings. It was found that the students who engaged in the smart education model in the Edu-Metaverse yielded higher scores in oral English, vocabulary and grammar, reading comprehension, English-to-Chinese translation, and writing than those who engaged in traditional instruction. Therefore, this study suggests that a smart education model enabled by the Edu-Metaverse, which is characterized by a highly immersive experience, multimodal interaction, and a high degree of freedom for resource sharing and creation can help learners to realize deep learning, develop their capacity for high-order thinking, and help them to become intelligent individuals in an online learning space. In order to facilitate this smart learning, we make the following suggestions for educational institutions: (1) teachers should improve the design of teaching scenarios, (2) teachers should focus on learning assessment that is based on core literacy, and (3) teachers’ knowledge of the architecture of the Edu-Metaverse should be enhanced.

Simnotrelvir is an oral 3-chymotrypsin-like protease inhibitor that has been found to have in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and potential efficacy in a phase 1B trial.In this phase 2-3, double-blind, randomized, placebo-controlled trial, we assigned patients who had mild-to-moderate coronavirus disease 2019 (Covid-19) and onset of symptoms within the past 3 days in a 1:1 ratio to receive 750 mg of simnotrelvir plus 100 mg of ritonavir or placebo twice daily for 5 days. The primary efficacy end point was the time to sustained resolution of symptoms, defined as the absence of 11 Covid-19-related symptoms for 2 consecutive days. Safety and changes in viral load were also assessed.A total of 1208 patients were enrolled at 35 sites in China; 603 were assigned to receive simnotrelvir and 605 to receive placebo. Among patients in the modified intention-to-treat population who received the first dose of trial drug or placebo within 72 hours after symptom onset, the time to sustained resolution of Covid-19 symptoms was significantly shorter in the simnotrelvir group than in the placebo group (180.1 hours [95% confidence interval {CI}, 162.1 to 201.6] vs. 216.0 hours [95% CI, 203.4 to 228.1]; median difference, -35.8 hours [95% CI, -60.1 to -12.4]; P = 0.006 by Peto-Prentice test). On day 5, the decrease in viral load from baseline was greater in the simnotrelvir group than in the placebo group (mean difference [±SE], -1.51±0.14 log10 copies per milliliter; 95% CI, -1.79 to -1.24). The incidence of adverse events during treatment was higher in the simnotrelvir group than in the placebo group (29.0% vs. 21.6%). Most adverse events were mild or moderate.Early administration of simnotrelvir plus ritonavir shortened the time to the resolution of symptoms among adult patients with Covid-19, without evident safety concerns. (Funded by Jiangsu Simcere Pharmaceutical; ClinicalTrials.gov number, NCT05506176.).

Background There is a paucity of data on the natural trajectory of outcomes in survivors of COVID-19 beyond 2 years after symptom onset, and no evidence exists on the effect of re-infection in people with long COVID symptoms. We aimed to investigate the 3-year health outcomes of COVID-19 survivors and the effect of omicron re-infection. Methods In this single-centre, longitudinal cohort study, we recruited participants with confirmed COVID-19 who were discharged from the Jin Yin-tan hospital in Wuhan, China, between Jan 7 and May 29, 2020. Participants completed three follow-up visits at 6 months (June 16 to Sept 13, 2020), 1 year (Dec 16, 2020, to Feb 7, 2021), and 2 years (Nov 16, 2021, to Jan 10, 2022) since symptom onset (reported previously). At 1-year follow-up, community controls without a history of SARS-CoV-2 infection were recruited from two communities in Wuhan and at 2 years were matched (1:1) with survivors of COVID-19 who underwent pulmonary function tests. We did a 3-year follow-up from Feb 23, 2023, to April 20, 2023, after the omicron (B.1.1.529) wave in winter, 2022. All eligible survivors of COVID-19 and community controls matched at 2-year follow-up were invited to the outpatient clinic at the hospital to complete several face-to-face questionnaires, a 6-min walking test (6MWT), and laboratory tests. A subgroup of survivors of COVID-19 identified by stratified sampling on the basis of disease severity scale score during hospitalisation and community controls underwent pulmonary function tests. Survivors of COVID-19 who received high-resolution CT and showed abnormal lung images at 2-year follow-up were invited for another assessment. We identified participants with and without long COVID at 2 years. The primary outcomes were sequelae symptoms, omicron infection, lung function, and chest imaging at the 3-year follow-up. Findings Of 1359 COVID-19 survivors who completed 2-year and 3-year follow-up, 728 (54%) had at least one sequelae symptom at 3 years after symptom onset and before omicron infection, mainly mild to moderate severity. During the omicron wave, participants with long COVID at 2 years had a significantly higher proportion of re-infection (573 [76%] of 753 vs 409 [67%] of 606 without long COVID; p=0·0004), pneumonia (27 [5%] of 568 vs seven [2%] of 403; p=0·012). 3 months after omicron infection, 126 (62%) of 204 survivors with long COVID at 2 years had newly occurring or worse symptoms, which was significantly higher than the proportion in the non-long COVID group (85 [41%] of 205; p<0·0001) and community controls (81 [40%] of 205; p<0·0001), and not significantly different between COVID-19 survivors without long COVID and matched community controls (85 [41%] of 205 vs 81 [39%] of 206; p=0·66). Re-infection was a risk factor for dyspnoea (odds ratio 1·36 [95% CI 1·04 to 1·77]; p=0·023), anxiety or depression (OR 1·65 [1·24 to 2·20]; p=0·0007), EuroQol visual analogue scale score (β –4·51 [–6·08 to –2·95]; p<0·0001), but not for reduced daily activity (0·72 [0·38 to 1·37]; p=0·32) at 3 years. Lung function of survivors at 3 years was similar to that of matched community controls. We found irregular line, traction bronchiectasis, subpleural lines and ground glass opacity at 3 years, but the volume ratio of lung lesion to total lung was only 0·2–0·3%. Interpretation Most long COVID symptoms at 3 years were mild to moderate, with lung function recovering to levels of matched controls. Survivors with long COVID had a higher proportion of participants with re-infection and newly occurring or worse symptoms 3 months after omicron infection than those without long COVID. Re-infection had increased symptom occurrence but not increased reduced daily activity. Although the organ function of survivors of COVID-19 recovered over time, those with severe long COVID symptoms, abnormal organ function, or limited mobility require urgent attention in future clinical practice and research. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Natural Science Foundation of China.

<h2>Summary</h2><h3>Background</h3> SARS-CoV-2-specific adaptive immunity more than 1 year after initial infection has not been well characterised. The aim of this study was to investigate the durability and cross-reactivity of immunological memory acquired from natural infection against SARS-CoV-2 in individuals recovered from COVID-19 2 years after infection. <h3>Methods</h3> In this longitudinal cohort study, we recruited patients who had recovered from laboratory-confirmed COVID-19 and were discharged from Jinyintan Hospital (Wuhan, China) between Jan 7 and May 29, 2020. We carried out three successive follow-ups between June 16 and Sept 3, 2020 (6 months), Dec 16, 2020, and Feb 7, 2021 (1 year), and Nov 16, 2021, and Jan 10, 2022 (2 years), in which blood samples were taken. We included participants who did not have re-infection or receive a SARS-CoV-2 vaccination (infected–unvaccinated), and participants who received one to three doses of inactivated vaccine 1–2 years after infection (infected–vaccinated). We evaluated the presence of IgG antibodies, neutralising antibodies, and memory B-cell and memory T-cell responses against the prototype strain and delta and omicron variants. <h3>Findings</h3> In infected–unvaccinated participants, neutralising antibody titres continually declined from 6-month to 2-year follow-up visits, with a half-life of about 141·2 days. Neutralising antibody responses to omicron sublineages (BA.1, BA.1.1, BA.2, BA.4/5, BF.7, BQ.1, and XBB) were poor. Memory B-cell responses to the prototype strain were retained at 2 years and presented cross-reactivity to the delta and omicron BA.1 variants. The magnitude of interferon γ and T-cell responses to SARS-CoV-2 were not significantly different between 1 year and 2 years after infection. Multifunctional T-cell responses against SARS-CoV-2 spike protein and nucleoprotein were detected in most participants. Recognition of the BA.1 variant by memory T cells was not affected in most individuals. The antibody titres and the frequencies of memory B cells, but not memory T cells, increased in infected–vaccinated participants after they received the inactivated vaccine. <h3>Interpretation</h3> This study improves the understanding of the duration of SARS-CoV-2-specific immunity without boosting, which has implications for the design of vaccination regimens and programmes. Our data suggest that memory T-cell responses primed by initial viral infection remain highly cross-reactive after 2 years. With the increasing emergence of variants, effective vaccines should be introduced to boost neutralising antibody and overall T-cell responses to newly emerged SARS-CoV-2 variants. <h3>Funding</h3> Chinese Academy of Medical Sciences, National Natural Science Foundation of China, Fundamental Research Funds for the Central Universities for Peking Union Medical College, Beijing Natural Science Foundation, UK Medical Research Council.

Recent large high-quality trials have questioned the clinical effectiveness of medical expulsive therapy using tamsulosin for ureteral stones. To evaluate the efficacy and safety of tamsulosin for distal ureteral stones compared with placebo. We conducted a double-blind, placebo-controlled study of 3296 patients with distal ureteral stones, across 30 centers, to evaluate the efficacy and safety of tamsulosin. Participants were randomly assigned (1:1) into tamsulosin (0.4 mg) or placebo groups for 4 wk. The primary end point of analysis was the overall stone expulsion rate, defined as stone expulsion, confirmed by negative findings on computed tomography, over a 28-d surveillance period. Secondary end points included time to stone expulsion, use of analgesics, and incidence of adverse events. Among 3450 patients randomized between September 1, 2011, and August 31, 2013, 3296 (96%) were included in the primary analysis. Tamsulosin benefits from a higher stone expulsion rate than the placebo (86% vs 79%; p < 0.001) for distal ureteral stones. Subgroup analysis identified a specific benefit of tamsulosin for the treatment of large distal ureteral stones (>5 mm). Considering the secondary end points, tamsulosin-treated patients reported a shorter time to expulsion (p < 0.001), required lower use of analgesics compared with placebo (p < 0.001), and significantly relieved renal colic (p < 0.001). No differences in the incidence of adverse events were identified between the two groups. Our data suggest that tamsulosin use benefits distal ureteral stones in facilitating stone passage and relieving renal colic. Subgroup analyses find that tamsulosin provides a superior expulsion rate for stones >5 mm, but no effect for stones ≤5 mm. In this report, we looked at the efficacy and safety of tamsulosin for the treatment of distal ureteral stones. We find that tamsulosin significantly facilitates the passage of distal ureteral stones and relieves renal colic.

Background and Purpose— Previous results on the association between lipids and stroke were controversial. We investigated the association of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C ), high-density lipoprotein cholesterol (HDL-C), and triglyceride with stroke. Methods— Six cohort studies in China with 267 500 participants were included. Cox proportional hazards regression models and restricted cubic spline analyses were used to estimate hazard ratios and 95% CIs and explore linear and nonlinear relationships of lipids and stroke, respectively. Results— The median follow-up duration ranged from 6 to 19 years. During 2 295 881 person-years, 8072 people developed stroke. Multivariable adjusted hazard ratios (95% CIs) per 1 mmol/L increase in TC, LDL-C, triglyceride were 1.08 (1.05–1.11), 1.08 (1.04–1.11), 1.07 (1.05-1.09) for ischemic stroke, respectively. Compared with participants with TC 160-199.9 mg/dL, hazard ratios (95% CIs) were 1.43 (1.11–1.85) for hemorrhagic stroke in those with TC &lt;120 mg/dL. Compared with participants with HDL-C 50 to 59.9 mg/dL, hazard ratios (95% CIs) were 1.23 (1.12–1.35), 1.13 (1.04–1.22) for ischemic stroke, and 1.28 (1.10–1.49), 1.17 (1.03–1.33) for hemorrhagic stroke in those with HDL-C &lt;40 and 40 to 49.9 mg/dL, respectively. Restricted cubic spline analyses showed linear relationships of TC and LDL-C, and nonlinear relationships of HDL-C and triglyceride with ischemic stroke (all P &lt;0.001). Hemorrhagic stroke showed linear relationships with TC and HDL-C ( P =0.029 and &lt;0.001 respectively), but no relationship with LDL-C and triglyceride (all P &gt;0.05). Conclusions— TC, LDL-C, and triglyceride showed positive associations with ischemic stroke. The risk of hemorrhagic stroke was higher when TC was lower than 120 mg/dL. LDL-C and triglyceride showed no association with hemorrhagic stroke. The risks of ischemic and hemorrhagic stroke might be higher when HDL-C was lower than 50 mg/dL.

Objectives: To evaluate the prevalence of cardiac injury and its association with mortality in hospitalized patients infected with avian influenza A (H7N9) virus. Design: Retrospective cohort study. Setting: A total of 133 hospitals in 17 provinces, autonomous regions, and municipalities of mainland China that admitted influenza A (H7N9) virus–infected patients between January 22, 2015, and June 16, 2017. Patients: A total of 321 patients with influenza A (H7N9) virus infection were included in the final analysis. Interventions: None. Measurements and Main Results: Demographics and clinical characteristics were collected from medical records. Cardiac injury was defined according to cardiac biomarkers, electrocardiography, or echocardiography. Among the 321 patients, 203 (63.2%) showed evidence of cardiac injury. Compared with the uninjured group, the cardiac injury group had lower Pa o 2 /F io 2 (median, 102.0 vs 148.4 mm Hg; p &lt; 0.001), higher Acute Physiology and Chronic Health Evaluation II score (median, 17.0 vs 11.0; p &lt; 0.001), longer stay in the ICU (10.0 vs 9.0 d; p = 0.029), and higher proportion of in-hospital death (64.0% vs 20.3%; p &lt; 0.001). The proportion of virus clearance until discharge or death was lower in the cardiac injury group than in the uninjured group (58.6% vs 86.4%; p &lt; 0.001). Multivariable-adjusted Cox proportional hazards regression analysis showed that cardiac injury was associated with higher mortality (hazards ratio, 2.06; 95% CI, 1.31–3.24) during hospitalization. Conclusions: Cardiac injury is a frequent condition among hospitalized patients infected with influenza A (H7N9) virus, and it is associated with higher risk of mortality.

Blended learning (B-learning) is a common practice in higher education, and various principles, characteristics, models, and strategies have been widely studied to improve B-learning performance. However, crucial differences in student–group interactions have not been explored between online and face-to-face sessions, the two key components of B-learning. This study applied social network analysis and thematic analysis to investigate the nature and differences of group interactions in these learning components of a B-learning course. A total of 53 respondents participated in this study and Baidu Post Bar was used as a tool to facilitate group interactions. A total of 604 dialogues comprising 5090 posts were analyzed to identify the differences in group characteristics and interactions. A strong “group-controlling” pattern was found in the online learning component, whereas an “individual-controlling” pattern was found in the face-to-face mode. The depth of the interactions among students increased from the beginning to the middle of the class and reached a relatively stable state from the middle to the end of the class. The interaction in the classroom was more in-depth than that in the online learning mode. The dialogue clusters of students were stronger when the interactions focused on their real lives and were related to the subject of the course. Through the findings of this study, course designers and instructors of B-learning can gain better understanding of these interactions and further enhance student engagement and learning.

To explore characteristics of urinary stone composition in China, and determine the effects of gender, age, body mass index (BMI), stone location, and geographical region on stone composition.We prospectively used Fourier-transform infrared spectroscopy to analyse stones from consecutive patients presenting with new-onset urolithiasis at 46 hospitals in seven geographical areas of China, between 1 June 2010 and 31 May 2015. Chi-squared tests and logistic regression analyses were used to determine associations between stone composition and gender, age, BMI, stone location, and geographical region.The most common stone constituents were: calcium oxalate (CaOx; 65.9%), carbapatite (15.6%), urate (12.4%), struvite (2.7%), and brushite (1.7%). CaOx and urate stones occurred more frequently in males, whereas carbapatite and struvite were more common in females (P < 0.01). CaOx and carbapatite were more common in those aged 30-50 and 20-40 years than in other groups. Brushite and struvite were most common amongst those aged <20 and >70 years. The detection rate of urate increased with age, whilst cystine decreased with age. Obese patients were more likely to have urate stones than carbapatite or brushite stones (P < 0.01). CaOx, carbapatite, brushite, and cystine stones were more frequently found in the kidney than other types, whereas urate and struvite were more frequent in the bladder (P < 0.01). Stone composition varied by geographical region.The most common stone composition was CaOx, followed by carbapatite, urate, struvite, and brushite. Stone composition differed significantly in patients grouped by gender, age, BMI, stone location, and geographical region.

Kidney damage in COVID-19 patients has been of special concern. The association of acute kidney injury (AKI) with post-acute kidney function among COVID-19 survivors was not sufficiently elucidated.An ambidirectional cohort study was conducted with enrollment of COVID-19 survivors discharged from hospital between Jan 7, and May 29, 2020. Study participants were invited to follow-up visits at 6 and 12 months after symptom onset. The primary outcome was percentage of estimated glomerular filtration rate (eGFR) decreased from acute phase (between symptom onset and hospital discharge) to follow-up, and secondary outcome was reduced renal function at follow-up.In total, 1,734 study participants were included in this study. Median follow-up duration was 342.0 days (IQR, 223.0-358.0) after symptom onset. After multivariable adjustment, percentage of eGFR decreased from acute phase to follow-up was 8.30% (95% CI, 5.99-10.61) higher among AKI participants than those without AKI at acute phase. Participants with AKI had an odds ratio (OR) of 4.60 (95% CI, 2.10-10.08) for reduced renal function at follow-up. The percentage of eGFR decreased for participants with AKI stage 1, stage 2, and stage 3 was 6.02% (95% CI, 3.48-8.57), 15.99% (95% CI, 10.77-21.22), and 17.79% (95% CI, 9.14-26.43) higher compared with those without AKI, respectively.AKI at acute phase of COVID-19 was closely related to the longitudinal decline and post-acute status of kidney function at nearly one-year after symptom onset. Earlier and more intense follow-up strategies on kidney function management could be beneficial to COVID-19 survivors.Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS 2020-I2M-CoV19-005, 2018-I2M-1-003, and 2020-I2M-2-013); National Natural Science Foundation of China (82041011); National Key Research and Development Program of China (2018YFC1200102); Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis (2020ZX09201001).

Rationale: It remains unknown whether long-term ozone exposure can impair lung function. Objectives: To investigate the associations between long-term ozone exposure and adult lung function in China. Methods: Lung function results and diagnosis of small airway dysfunction (SAD) were collected from a cross-sectional study, the China Pulmonary Health Study (N = 50,991). We used multivariable linear and logistic regression models to examine the associations of long-term ozone exposure with lung function parameters and SAD, respectively, adjusting for demographic characteristics, individual risk factors, and longitudinal trends. We then performed a stratification analysis by chronic obstructive pulmonary disease (COPD). Measurements and Main Results: We observed that each 1 SD (4.9 ppb) increase in warm-season ozone concentrations was associated with a 14.2 ml/s (95% confidence interval [CI], 8.8-19.6 ml/s] decrease in forced expiratory flow at the 75th percentile of vital capacity and a 29.5 ml/s (95% CI, 19.6-39.5 ml/s) decrease in mean forced expiratory flow between the 25th and 75th percentile of vital capacity. The odds ratio of SAD was 1.09 (95% CI, 1.06-1.11) for a 1 SD increase in warm-season ozone concentrations. Meanwhile, we observed a significant association with decreased FEV1/FVC but not with FEV1 or FVC. The association estimates were greater in the COPD group than in the non-COPD group. Conclusions: We found independent associations of long-term ozone exposure with impaired small airway function and higher SAD risks, while the associations with airflow obstruction were weak. Patients with COPD appear to be more vulnerable.

As a debilitating condition that can impact a whole spectrum of people and involve multi-organ systems, long COVID has aroused the most attention than ever. However, mechanisms of long COVID are not clearly understood, and underlying biomarkers that can affect the long-term consequences of COVID-19 are paramount to be identified.Participants for the current study were from a cohort study of COVID-19 survivors discharged from hospital between Jan 7, and May 29, 2020. We profiled the proteomic of plasma samples from hospitalised COVID-19 survivors at 6-month, 1-year, and 2-year after symptom onset and age and sex matched healthy controls. Fold-change of >2 or <0.5, and false-discovery rate adjusted P value of 0.05 were used to filter differentially expressed proteins (DEPs). In-genuity pathway analysis was performed to explore the down-stream effects in the dataset of significantly up- or down-regulated proteins. Proteins were integrated with long-term consequences of COVID-19 survivors to explore potential biomarkers of long COVID.The proteomic of 709 plasma samples from 181 COVID-19 survivors and 181 matched healthy controls was profiled. In both COVID-19 and control group, 114 (63%) were male. The results indicated four major recovery modes of biological processes. Pathways related to cell-matrix interactions and cytoskeletal remodeling and hypertrophic cardiomyopathy and dilated cardiomyopathy pathways recovered relatively earlier which was before 1-year after infection. Majority of immune response pathways, complement and coagulation cascade, and cholesterol metabolism returned to similar status of matched healthy controls later but before 2-year after infection. Fc receptor signaling pathway still did not return to status similar to healthy controls at 2-year follow-up. Pathways related to neuron generation and differentiation showed persistent suppression across 2-year after infection. Among 98 DEPs from the above pathways, evidence was found for association of 11 proteins with lung function recovery, with the associations consistent at two consecutive or all three follow-ups. These proteins were mainly enriched in complement and coagulation (COMP, PLG, SERPINE1, SRGN, COL1A1, FLNA, and APOE) and hypertrophic/dilated cardiomyopathy (TPM2, TPM1, and AGT) pathways. Two DEPs (APOA4 and LRP1) involved in both neuron and cholesterol pathways showed associations with smell disorder.The study findings provided molecular insights into potential mechanism of long COVID, and put forward biomarkers for more precise intervention to reduce burden of long COVID.National Natural Science Foundation of China; Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences; Clinical Research Operating Fund of Central High Level Hospitals; the Talent Program of the Chinese Academy of Medical Science; Training Program of the Big Science Strategy Plan; Ministry of Science and Technology of the People's Republic of China; New Cornerstone Science Foundation; Peking Union Medical College Education Foundation; Research Funds from Health@InnoHK Program.

Room-temperature phosphorescence (RTP) polymers have important applications for biological imaging, oxygen sensing, data encryption, and photodynamic therapy. Despite the many advantages polymeric materials offer such as great control over gas permeability and processing flexibility, disorder is traditionally considered as an intrinsic negative impact on the efficiency for embedded RTP luminophores, as various allowed thermal motions could quench the emitting states. However, we propose that such disorder-enabled freedoms of microscopic motions can be beneficial for charge-transfer-mediated RTP, which is facilitated by molecular conformational changes among different electronic transition states. Using the "classic" pyrene-aniline exciplex as an example, we demonstrate the mutual enhancement of red/near-infrared and green RTP emissions from the pyrene and aniline moieties, respectively, upon doping the aniline polymer with trace pyrene derivatives. In comparison, a pyrene-doped crystal formed with the same aniline structure exhibits only charge-transfer fluorescence with no red or green RTP observed, suggesting that order suppresses the RTP channels. The proposed polymerization strategy may be used as a unified method to generate multi-emissive polymeric RTP materials from a vast pool of known and unknown exciplexes and charge-transfer complexes.

Abstract Background Autoimmune responses mediated by cluster of differentiation 4 + T cells may contribute to the development of chronic obstructive pulmonary disease ( COPD ). However, little is known about the frequency of peripheral blood T h17 cells and of regulatory T cells ( T regs) in C hinese patients with COPD . This study is aimed at determining the frequency of circulating T h17 and T regs in patients with moderate and severe COPD , heavy smokers and healthy controls ( HC ). Method The percentages of circulating T ‐helper type ( T h)17 cells and T regs were determined by flow cytometry in 32 patients with moderate COPD , 33 patients with severe COPD , 35 smokers, and 31 HC . The concentrations of serum T h17‐ and T reg‐related cytokines were measured by enzyme‐linked immunosorbent assay ( ELISA ). The levels of retinoic acid orphan receptor ( ROR )‐γt and F orkhead box p3 ( F oxp3) m RNA transcripts in peripheral blood mononuclear cells were determined by real‐time polymerase chain reaction. The potential correlation between the percentages of T h17 T regs, serum cytokines and lung function was evaluated. Results In comparison with that in the smokers and HC , significantly higher frequencies of T h17 cells and higher levels of ROR ‐γt m RNA transcripts and serum interleukin ( IL )‐17 A , IL ‐6, IL ‐21, IL ‐22 and IL ‐23, but lower frequency of T regs and lower levels of F oxp3 and serum IL ‐10 were detected in patients with moderate and severe COPD . The increased ratios of T h17 to T regs were negatively correlated with the values of forced vital capacity ( FVC ), forced expiratory volume in 1 s ( FEV 1) and FEV 1/ FVC . Conclusions An imbalance of circulating T h17 cells and T regs is associated with the deterioration of pulmonary function in patients with moderate and severe COPD .

The primary objective was to evaluate whether a molecular point-of-care test (POCT) for viral and atypical pathogens added to routine real-time PCR could reduce duration of intravenous antibiotics in hospitalized patients with lower respiratory tract infection (LRTI) compared with routine real-time PCR.In this single-centre, open-label, randomized controlled study, we enrolled hospitalized adults diagnosed with LRTI. Patients were randomized to an intervention group (POCT FilmArray Panel for 20 viruses, atypical pathogens and bacteria plus routine real-time PCR) or a control group (routine real-time PCR for ten pathogens). The primary outcome was duration of intravenous antibiotics during hospitalization. The secondary outcomes included length of stay, cost of hospitalization and de-escalation within 72 hours and between 72 hours and 7 days. Intention-to-treat analysis was used.Between October 2017 and July 2018, we enrolled 800 eligible patients (398 in the intervention group and 402 in the control group). Duration of intravenous antibiotics in the intervention group was shorter than in the control (7.0 days (interquartile range (IQR) 5.0-9.0) versus 8.0 days (IQR 6.0-11.0); p <0.001). Length of hospital stay in the intervention group was significantly shorter (8.0 days (IQR 7.0-11.0) versus 9.0 days (IQR 7.0-12.0; p <0.001) and the cost of hospitalization in the intervention group was significantly lower ($1804.7 (IQR 1298.4-2633.8) versus $2042.5 (IQR 1427.4-2926.2); p 0.002) than control group. More patients in the intervention group achieved de-escalation within 72 hours (7.9%, 29/367 versus 3.2%, 12/377; p 0.005) and between 72 hours and 7 days (29.7%, 109/367 versus 22.0%, 83/377; p 0.024).Use of molecular POCT testing for respiratory viruses and atypical pathogens might help to reduce intravenous antibiotic use in hospitalized LRTI patients.clinicaltrials.gov Identifier: NCT03391076.

According to the Third International Consensus Definition for Sepsis and Septic Shock, sepsis is a life-threatening organ dysfunction resulting from dysregulated host responses to infection. Epidemiological data about sepsis from the 2017 Global Burden of Diseases, Injuries and Risk Factor Study showed that the global burden of sepsis was greater than previously estimated. Bacteria have been shown to be the predominant pathogen of sepsis among patients with pathogens detected, while sepsis caused by viruses is underdiagnosed worldwide. The coronavirus disease that emerged in 2019 in China and now in many other countries has brought viral sepsis back into the vision of physicians and researchers worldwide. Although the current understanding of the pathophysiology of sepsis has improved, the differences between viral and bacterial sepsis at the level of pathophysiology are not well understood. Diagnosis methods that can broadly differentiate between bacterial and viral sepsis at the initial stage after the development of sepsis are limited. New treatments that can be applied at clinics for sepsis are scarce and this situation is not consistent with the growing understanding of pathophysiology. This review aims to give a brief summary of current knowledge of the epidemiology, pathophysiology, diagnosis and treatment of viral sepsis.

The possible effects of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) on COVID-19 disease severity have generated considerable debate. We performed a single-center, retrospective analysis of hospitalized adult COVID-19 patients in Wuhan, China, who had definite clinical outcome (dead or discharged) by February 15, 2020. Patients on anti-hypertensive treatment with or without ACEI/ARB were compared on their clinical characteristics and outcomes. The medical records from 702 patients were screened. Among the 101 patients with a history of hypertension and taking at least one anti-hypertensive medication, 40 patients were receiving ACEI/ARB as part of their regimen, and 61 patients were on antihypertensive medication other than ACEI/ARB. We observed no statistically significant differences in percentages of in-hospital mortality (28% vs. 34%, P = 0.46), ICU admission (20% vs. 28%, P = 0.37) or invasive mechanical ventilation (18% vs. 26%, P = 0.31) between patients with or without ACEI/ARB treatment. Further multivariable adjustment of age and gender did not provide evidence for a significant association between ACEI/ARB treatment and severe COVID-19 outcomes. Our findings confirm the lack of an association between chronic receipt of renin-angiotensin system antagonists and severe outcomes of COVID-19. Patients should continue previous anti-hypertensive therapy until further evidence is available.

The associations of long-term exposure to various constituents of fine particulate matter (≤2.5 μm in aerodynamic diameter, PM2.5) air pollution with lung function were not clearly elucidated in developing countries. The aim was to evaluate the associations of long-term exposure to main constituents of PM2.5 with lung function in China. This is a nationwide, cross-sectional analysis among 50,991 study participants from the China Pulmonary Health study. Multivariable linear regression models were used to obtain differences of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, peak expiratory flow (PEF), and forced expiratory flow at 25–75% of exhaled FVC (FEF25-75%) associated with an interquartile range (IQR) change of PM2.5 or its constituents. Residential annual PM2.5 levels varied from 26 μg/m3 to 92 μg/m3 (average: 53 μg/m3). An IQR increase of PM2.5 concentrations was associated with lower FEV1 (19.82 mL, 95% CI: 11.30–28.33), FVC (17.45 mL, 95% CI: 7.16–27.74), PEF (86.64 mL/s, 95% CI: 59.77–113.52), and FEF25-75% (31.93 mL/s, 95% CI: 16.64–47.22). Black carbon, organic matter, ammonium, sulfate, and nitrate were negatively associated with most lung function indicators, with organic matter and nitrate showing consistently larger magnitude of associations than PM2.5 mass. This large-scale study provides first-hand epidemiological evidence that long-term exposure to ambient PM2.5 and some constituents, especially organic matter and nitrate, were associated with lower large- and small- airway function.

Long noncoding RNAs (lncRNAs) have been reported to be important regulators in pathogenesis of human cancers, including nasopharyngeal carcinoma (NPC). Here, we mainly aimed to explore the mechanisms of LncRNA-SNHG5/ miR-1179/HMGB3 axis in NPC progression.RT-qPCR and Western blot analysis were employed to detect mRNA and protein expressions. CCK-8, Transwell and dual luciferase reporter assays were applied to investigate functions of LncRNA-SNHG5/miR-1179/HMGB3 axis.Upregulation of lncRNA-SNHG5 and downregulation of miR-1179 were identified in NPC, which were associated with adverse clinical outcomes. Functionally, upregulation of lncRNA-SNHG5 and downregulation of miR-1179 accelerated NPC cell proliferation, migration and invasion. Furthermore, lncRNA-SNHG5 acted as a molecular sponge of miR-1179 in NPC. Besides that, upregulation of HMGB3 was found in NPC, and knockdown of HMGB3 restrained NPC progression. Moreover, HMGB3, a target of miR-1179, regulated NPC progression by mediating LncRNA-SNHG5/miR-1179 axis.LncRNA SNHG5 serves as a tumor promoter in NPC by sponging miR-1179 and upregulating HMGB3.

Abstract Background The characteristics of neutralizing antibodies (NAbs) and antibody against major antigen proteins related to clinical outcomes in severe coronavirus disease 2019 (COVID-19) patients were still less known. Methods NAbs and antibodies targeting nucleocapsid (N), spike protein (S), and the receptor-binding domain (RBD) in longitudinal plasma samples from the LOTUS China trial were measured by microneutralization assay and enzyme-linked immunosorbent assay (ELISA). Viral load was determined by real-time reverse transcription polymerase chain reaction (RT-PCR). A total of 576 plasma and 576 throat swabs were collected from 191 COVID-19 patients. Antibody titers related to adverse outcome and clinical improvement were analyzed. Multivariable adjusted generalized linear mixed model for random effects were developed. Results After day 28 post symptoms onset, the rate of antibody positivity reached 100% for RBD-immunoglobulin M (IgM), 97.8% for S-IgM, 100% for N-immunoglobulin G (IgG), 100% for RBD-IgG, 91.1% for N-IgM, and 91.1% for NAbs. The NAbs titers increased over time in both survivors and nonsurvivors and correlated to IgG antibodies against N, S, and RBD, whereas its presence showed no statistical correlation with death. N-IgG (slope −2.11, 95% confidence interval [CI] −3.04 to −1.18, P &amp;lt; .0001), S-IgG (slope −2.44, 95% CI −3.35 to −1.54, P &amp;lt; .0001), and RBD-IgG (slope −1.43, 95% CI −1.98 to −.88, P &amp;lt; .0001) were negatively correlated with viral load. S-IgG titers were lower in nonsurvivors than survivors (P = .020) at week 4 after symptoms onset. Conclusions IgM and IgG against N, S, and RBD and NAbs developed in most severe COVID-19 patients and do not correlate clearly with clinical outcomes. The levels of IgG antibodies against N, S, and RBD were related to viral clearance.

<h2>Abstract</h2><h3>Objectives</h3> Use of corticosteroids is common in the treatment of coronavirus disease 2019, but clinical effectiveness is controversial. We aimed to investigate the association of corticosteroids therapy with clinical outcomes of hospitalized COVID-19 patients. <h3>Methods</h3> In this single-centre, retrospective cohort study, adult patients with confirmed coronavirus disease 2019 and dead or discharged between 29 December 2019 and 15 February 2020 were studied; 1:1 propensity score matchings were performed between patients with or without corticosteroid treatment. A multivariable COX proportional hazards model was used to estimate the association between corticosteroid treatment and in-hospital mortality by taking corticosteroids as a time-varying covariate. <h3>Results</h3> Among 646 patients, the in-hospital death rate was higher in 158 patients with corticosteroid administration (72/158, 45.6% vs. 56/488, 11.5%, p < 0.0001). After propensity score matching analysis, no significant differences were observed in in-hospital death between patients with and without corticosteroid treatment (47/124, 37.9% vs. 47/124, 37.9%, p 1.000). When patients received corticosteroids before they required nasal high-flow oxygen therapy or mechanical ventilation, the in-hospital death rate was lower than that in patients who were not administered corticosteroids (17/86, 19.8% vs. 26/86, 30.2%, log rank p 0.0102), whereas the time from admission to clinical improvement was longer (13 (IQR 10–17) days vs. 10 (IQR 8–13) days; p < 0.001). Using the Cox proportional hazards regression model accounting for time varying exposures in matched pairs, corticosteroid therapy was not associated with mortality difference (HR 0.98, 95% CI 0.93–1.03, p 0.4694). <h3>Discussion</h3> Corticosteroids use in COVID-19 patients may not be associated with in-hospital mortality.

Abstract There have been arguments on whether angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) treatment alters the risk of coronavirus disease 2019 (COVID-19) susceptibility and disease severity. We identified a total of 102 eligible studies for systematic review, in which 49 studies adjusting for confounders were included in the meta-analysis. We found no association between prior ACEI/ARB use and risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the general population (adjusted odds ratio [aOR], 1.00; 95% confidence interval [CI], .94–1.05). The risk of mortality (aOR, .87; 95% CI, .66–1.04) and severe outcomes (aOR, .95; 95% CI, .73–1.24) were also unchanged among COVID-19 patients taking ACEIs/ARBs. These findings remained consistent in subgroup analyses stratified by populations, drug exposures, and other secondary outcomes. This systematic review provides evidence-based support to current medical guidelines and position statements that ACEIs/ARBs should not be discontinued. Additionally, there has been no evidence for initiating ACEI/ARB regimen as prevention or treatment of COVID-19.

Background Cytokine storm observed in patients with severe Coronavirus Disease 2019 (COVID-19) contributes to poor clinical outcomes and increased mortality. Janus kinases (JAKs) are important mediators in the cytokine storm. Therefore, we conduct a living systematic review and meta-analysis of the literature investigating efficacy and safety of JAK inhibitors for patients with COVID-19. Methods Databases were searched up to December 1, 2021 for interventional and observational studies comparing JAK inhibitor treatment with concurrent control in patients with COVID-19. Efficacy and safety outcomes were evaluated by pooled risk ratio (RR). Results Of 3,170 records retrieved, 15 studies were eligible and 13 were evaluated in the meta-analysis ( n = 3,977). Based on data from three randomized controlled trials (RCTs), baricitinib treatment significantly decreased mortality by day 28 in hospitalized patients with COVID-19 (RR = 0.64, 95% CI 0.51–0.80) without increasing the incidence of adverse outcomes. In subgroup analysis, patients who required supplemental oxygen (RR = 0.62, 95% CI 0.41–0.95) or high-flow oxygen/non-invasive ventilation (RR = 0.59, 95% CI 0.42–0.85) at baseline benefited most. Pooled analysis of all eligible studies for JAK inhibitors (baricitinib, ruxolitinib, tofacitinib, and nezulcitinib) demonstrated a significant decrease in mortality (RR = 0.62, 95% CI 0.49–0.78) with no increase in the risk of adverse events. Conclusion Baricitinib probably decreases mortality in hospitalized adult patients with COVID-19, especially for patients who required supplemental oxygen or high-flow oxygen/non-invasive ventilation at baseline. The efficacy and safety of other JAK inhibitors, such as ruxolitinib, tofacitinib, and nezulcitinib, await more evidence. Systematic Review Registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021261414 , identifier: CRD42021261414.

Self-regulated learning (SRL) ability is the key determinant of the success of full-time online learning. Thus, exploring the influencing factors of SRL and their influencing mechanisms is necessary to improve this ability among K-12 students.The purpose of this study was to investigate the influence mechanism of teacher autonomy support on students' online SRL by examining the structural relationship among teacher autonomy support, parental autonomy support, students' self-efficacy, and students' online SRL.We use structural equation modelling and effect analysis to analyse the collected data from 961 Chinese K-12 students who engaged in full-time online learning in their homes during the coronavirus disease 2019 (COVID-19) outbreak.Parental autonomy support and students' self-efficacy play crucial independent mediating roles in the influence of teacher autonomy support on students' online SRL. Parental autonomy support and students' self-efficacy have a chain mediating effect on the influence of teacher autonomy support on students' online SRL.On the basis of the results, we suggest that in order to develop students' online SRL ability, it is important for teacher to improve parental autonomy support and students' self-efficacy. In addition, base on the chain mediating effect, to improve students' online SRL, teacher autonomy support needs focus on parental autonomy support, and then parental autonomy support needs focus on improving students' self-efficacy.

In the last decade, the use of e-Textbooks has received attention in research and practice. However, the expanded use of e-Textbooks was not easily achieved because of the missing standards in learning content and functionalities, and barriers in utilizing e-Textbooks, such as screen reading and intellectual property protection. This paper provides insights on the design, development, and learning with e-Textbooks by reviewing studies, project reports, and cases on its use. Results reveal the increased promotion and implementation of e-Textbook development in several countries. Criticisms on different e-Textbook types began during the early stages of open multimedia learning resources and digitized textbooks, and continued until the integration of information and communication technologies, authoring tools, and learning platforms. The study examined advantages of e-Textbooks and different factors that influenced e-Textbook applications. The study also reviewed the literature on learning through e-Textbooks in terms of acceptance and perception of users, and the comparison of the learning effectiveness of this format with printed textbooks. Moreover, learning in e-Textbooks is not fully realized, and requires increased in-depth studies. This paper suggests investigating the pedagogical design of e-Textbooks and further evaluation of e-Textbook functions to support learning.

Cancer chemoresistance is regulated by complex genetic and epigenetic networks. In this study, the features of gene expression, methylation, and microRNA (miRNA) expression were investigated with high-throughput sequencing in human breast cancer MCF-7 cells resistant to adriamycin (MCF-7/ADM) and paclitaxel (MCF-7/PTX). We found that: ① both of the chemoresistant cell lines had similar, massive changes in gene expression, methylation, and miRNA expression versus chemosensitive controls. ② Pairwise integration of the data highlighted sets of genes that were regulated by either methylation or miRNAs, and sets of miRNAs whose expression was controlled by DNA methylation in chemoresistant cells. ③ By combining the three sets of high-throughput data, we obtained a list of genes whose expression was regulated by both methylation and miRNAs in chemoresistant cells; ④ Expression of these genes was then validated in clinical breast cancer samples to generate a 17-gene signature that showed good predictive and prognostic power in triple-negative breast cancer patients receiving anthracycline-taxane-based neoadjuvant chemotherapy. In conclusion, our results have generated a new workflow for the integrated analysis of the effects of miRNAs and methylation on gene expression during the development of chemoresistance.

Asian education is known for its examination-driven orientation, with the downsides of distorting the processes of learning and teaching, diminishing students’ interest in learning, and failing to nurture twenty-first century competencies among students. As a group of Asian researchers, we have been developing Interest-Driven Creator (IDC) Theory, a design theory based on three anchored concepts, namely interest, creation, and habit. Each of these anchored concepts is represented by a loop composed of three components. In the interest loop, the three components are triggering, immersing, and extending. The components of the creation loop are imitating, combining, and staging. The habit loop consists of cuing environment, routine, and harmony. These three loops are interconnected in various ways, with their characteristics revealed by the design process. We hypothesize that technology-supported learning activities that are designed with reference to IDC Theory will enable students to develop interest in learning, be immersed in the creation process, and, by repeating this process in their daily routines, strengthen habits of creation. Furthermore, students will excel in learning performance, develop twenty-first century competencies, and become lifelong interest-driven creators. To sharpen our understanding and further the development of the theory, we need more discussion and collaborative efforts in the community. Hypotheses arising from this theory can be tested, revised, or refined by setting up and investigating IDC Theory-based experimental sites. By disseminating the framework, foundations, and practices to the various countries and regions of Asia, we hope that it will bring about compelling examples and hence a form of quality education for the twenty-first century, which is an alternative to the examination-driven education system. In this paper, we present an overall introduction to IDC Theory and its history, and discuss some of the steps for advancing it in the future.

<bold>TPE-Br</bold> with aggregation induced emission can inhibit the growth of HeLa cells both <italic>in vitro</italic> and <italic>in vivo</italic>.

Studies on the association of greenness with respiratory health are scarce in developing countries, and previous studies in China have focused on only one or two indicators of lung function.The study aims to evaluate the associations of residential greenness with full-spectrum lung function indicators and prevalence of chronic obstructive pulmonary disease (COPD).This nationwide cross-sectional survey included 50,991 participants from the China Pulmonary Health study. Lung function indicators included four categories: indicators of obstructive ventilatory dysfunction (FEV1, FVC and FEV1/FVC); an indicator of large-airway dysfunction (PEF); indicators of small-airway dysfunction (FEF25-75% and FEV3/FEV6); and other indicators. Residential greenness was assessed by the Normalized Difference Vegetation Index (NDVI). Multivariable linear regression models and logistic regression models were used to analyze associations of greenness with lung function and COPD prevalence.Within the 500 m buffer, an interquartile range (IQR) increase in NDVI was associated with higher FEV1 (24.76 mL), FVC (16.52 mL), FEV1/FVC (0.38), FEF50% (56.34 mL/s), FEF75% (33.43 mL/s), FEF25-75% (60.73 mL/s), FEV3 (18.59 mL), and FEV6 (21.85 mL). However, NDVI was associated with lower PEF. In addition, NDVI was significantly associated with 10% lower odds of COPD. The stratified analyses found that the associations were only significant in middle-young people, females, and nonsmokers. The associations were influenced by geographic regions.Residential greenness was associated with better lung function and lower odds of COPD in China. These findings provide a scientific basis for healthy community planning.

miRNAs can regulate the biological processes, including differentiation, proliferation and apoptosis. DICER and DROSHA are two members of RNase III family, playing pivotal roles in the pathway of miRNAs biogenesis. In this study, we hypothesized that genetic variations of the DICER and DROSHA genes were associated with the bladder cancer risk.We performed a case-control study of 685 bladder cancer cases and 730 controls to investigate the association between the seven functional SNPs of DICER and DROSHA genes and bladder cancer risk. We then evaluated the functionality of the important SNPs.We found that rs10719T>C polymorphism located in 3' untranslated region (UTR) of DROSHA gene was associated with the increased risk of bladder cancer. Stratified analysis suggested that rs10719TC/CC genotype can increase risk of bladder cancer among male patients (Adjusted OR = 1.34, 95% CI = 1.05-1.70, P = 0.018), and ever smokers (1.56, 1.14-2.14, 0.006), compared with TT genotype. Furthermore, DROSHA rs10719T>C polymorphism was predicted to regulate the binding activity of hsa-miR-27a/b. Luciferase reported gene assay confirmed that rs10719 T to G substitution disrupted the binding site for hsa-miR-27b, resulting the increased levels of DROSHA protein.Taken together, these findings suggested that DROSHA rs10719T>C polymorphism may be associated with bladder cancer risk in a Chinese population, and hsa-miR-27b can influence the expression of DROSHA protein by binding with 3'UTR.

Since Francis Peyton Rous’s landmark study of identifying avian oncogenic virus, seven viruses have been found to cause 10–15 % of human cancers worldwide [1]. Recent findings by Buehring’s group have suggested that another virus, bovine leukemia virus (BLV) – which is highly prevalent in cows worldwide [2] – might be linked to human breast cancer [3–5]. In a study of 218 women from four states in the USA, Buehring’s group showed that the BLV positivity in women with breast cancer (67/114) is significantly higher than that in women without breast cancer (30/104) [4].

The problem motivating this study is the fact that almost 19.70 million university students in China have been required to engage in e-learning under the government’s initiative of “Classes are Suspended, yet Learning is still Ongoing” during the COVID-19 epidemic, coupled with varied responses, uneven adoption of e-learning platforms and varying degrees of satisfaction toward them. Using the online database adoption and satisfaction (ODAS) model, this study examines the determinants which impact university students’ adoption of and satisfaction with e-learning platforms at this particular time in China. The ODAS model was also cross-validated using gender as a moderating variable. A purposive sampling procedure was used to survey a total of 1,136 students from six universities in five provinces or municipalities of China. The data for this survey were estimated using the Rasch model and structural equation modeling. Results exhibit that students’ adoption of and satisfaction with e-learning platforms were significantly measured by their computer self-efficacy, their intention to use e-learning platforms, and their perceived ease of use and perceived usefulness of these platforms, while the relationships among these components were moderated by gender differences. This empirically-based cross-validation of the ODAS provides recommendations for future studies, including practical implications for e-learning. This current study contributes to the body of knowledge in evaluating e-learning platforms during the COVID-19 epidemic.

Current therapies for HER2-positive breast cancer have limited efficacy in patients with triple-positive breast cancer (TPBC). We conduct a multi-center single-arm phase 2 trial to test the efficacy and safety of an oral neoadjuvant therapy with pyrotinib, letrozole and dalpiciclib (a CDK4/6 inhibitor) in patients with treatment-naïve, stage II-III TPBC with a Karnofsky score of ≥70 (NCT04486911). The primary endpoint is the proportion of patients with pathological complete response (pCR) in the breast and axilla. The secondary endpoints include residual cancer burden (RCB)-0 or RCB-I, objective response rate (ORR), breast pCR (bpCR), safety and changes in molecular targets (Ki67) from baseline to surgery. Following 5 cycles of 4-week treatment, the results meet the primary endpoint with a pCR rate of 30.4% (24 of 79; 95% confidence interval (CI), 21.3-41.3). RCB-0/I is 55.7% (95% CI, 44.7-66.1). ORR is 87.4%, (95% CI, 78.1-93.2) and bpCR is 35.4% (95% CI, 25.8-46.5). The mean Ki67 expression reduces from 40.4% at baseline to 17.9% (P < 0.001) at time of surgery. The most frequent grade 3 or 4 adverse events are neutropenia, leukopenia, and diarrhoea. There is no serious adverse event- or treatment-related death. This fully oral, chemotherapy-free, triplet combined therapy has the potential to be an alternative neoadjuvant regimen for patients with TPBC.

Abstract Computational thinking (CT) is vital for success in numerous domains. However, the nature, definition, and scope of CT are ill‐defined, and research on how best to develop CT is very limited. This study focused on how thinking styles and STEM attitudes have effects on computational thinking. Using a proportionate stratified random sampling procedure, 1195 students from two universities were surveyed. A structural equation modeling analysis showed that students' thinking styles and STEM attitudes directly predicted their computational thinking skills and that thinking styles mediated the relationship between STEM attitudes and computational thinking skills. Thinking styles and STEM attitudes are strong predictors of CT skills. Based on the results, we recommended that the conceptualization of CT be broadened to reflect its trans‐disciplinary nature within the context of STEM education. This study adds to the limited theoretical understanding of CT and CT‐predictors in higher education, which has been studied much less than in K‐12 education.

The emergence of educational video platforms has led to microlearning resources becoming increasingly mainstream. These platforms offer unique ecosystems and resource designs that better cater to the needs of learners. In this study, we examined the technology acceptance model (TAM) and task-technology fit (TTF) theory and conducted an empirical analysis of user satisfaction with new online learning spaces. We learned that perceived usefulness, perceived ease of use, and task-technology fit had significantly impacted user satisfaction, with these three factors collectively contributing to 78.2% of the variance in user satisfaction. Additionally, user satisfaction and task-technology fit significantly influenced the continuance intentions of users toward using these spaces, with both factors contributing to 66.7% of the variance in continuance intention. Overall, our findings revealed that the future development of new online learning spaces should consider the task requirements of learners and improve the platforms accordingly.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, and only 15% of lung cancer patients live more than 5 years. microRNAs (miRNAs) are endogenously expressed non-coding RNAs, and dysregulation of miRNAs is a common feature in human cancers including lung cancer. In this study, we describe the epigenetic regulation of miRNA-148a and its prognostic value in NSCLC. Due to hypermethylation of the miRNA‑148a encoding region, the expression levels of miRNA-148a were decreased in NSCLC tissues and cells. Decreased miRNA‑148a expression was associated with lymph node metastasis, advanced clinical stage and shortened disease-free survival and overall survival in NSCLC, and was an independent prognostic factor for overall survival in multivariate analysis. In vitro, overexpression of miRNA-148a significantly suppressed the migratory and invasive abilities of A549 and H1299 lung cancer cells. Enforced expression of miRNA-148a in lung cancer cell lines resulted in a significant reduction in the expression of DNMT1. This, in turn, led to a decrease in DNA methylation of the tumor-suppressor gene E-cadherin and induced an increase in the protein levels of E-cadherin. By understanding the function and molecular mechanism of miRNA-148a in NSCLC, miRNA-148a may have therapeutic potential to suppress lung cancer metastasis.

Breast cancer is a threat to the health of women, and metastasis of breast cancer cells plays an important role in the deterioration of breast cancer. MicroRNAs play a critical role in the tumorigenesis and development of breast cancer. MicroRNA-148a (miR-148a) is associated with the growth and metastasis of tumor cells. In the present study, we investigated the role of miR-148a in migration of breast cancer cells as well as the underlying mechanism. MiR-148a was found to inhibit the proliferation and migration of breast cancer cells. To further explore the mechanism through which miR-148a plays its antitumor role, matrix metalloproteinase-13 (MMP-13) was identified as a target of miR-148a by western blot and luciferase reporter assay. Moreover, silence of MMP-13 mimicked the effect of miR-148a, whereas overexpression of MMP-13 rescued the impaired migration caused by miR-148a. Our study demonstrates that miR-148a inhibits the migration of breast cancer cells by targeting MMP-13 and also lays theoretical foundation for further exploration for the function of miR-148a.

The predictive effect of non–high-density lipoprotein cholesterol (non-HDL-C) for cardiovascular disease (CVD) in Chinese general population has not been well demonstrated. The aim of our study was to examine the relation between non-HDL-C and CVD and compare the predictive effect of non-HDL-C and low-density lipoprotein cholesterol (LDL-C) for CVD in Chinese population. The baseline examination of 27,020 participants aged 35 to 74 years from the China Cardiovascular Health Study and the China Multicenter Collaborative Study of Cardiovascular Epidemiology was conducted in 1998 to 2001. Follow-up evaluation was conducted in 2007 to 2008 with a response rate of 79.8%. Cox proportional hazards regression models were used to obtain the multivariable-adjusted hazard ratios and 95% confidence intervals (CIs) for CVD. Compared with those with non-HDL-C level of <130 mg/dl, multivariable-adjusted hazard ratios of CVD were 1.30 (95% CI 1.04 to 1.62) and 1.93 (95% CI 1.50 to 2.47) in participants with non-HDL-C levels of 160 to 189.9 and ≥190 mg/dl, respectively. An increase of 30 mg/dl in non-HDL-C level would correspond to 15%, 24%, and 12% increase in risk of CVD, coronary heart disease, and stroke, respectively. Using likelihood ratio tests, non-HDL-C appeared to be a similar predictor for CVD incidence as LDL-C (chi-square for non-HDL-C, 18.02, p <0.001; chi-square for LDL-C, 18.90, p <0.001). In conclusion, higher non-HDL-C level is associated with the increased CVD incidence and has a similar effect as LDL-C on predicting CVD risk in Chinese. The predictive effect of non–high-density lipoprotein cholesterol (non-HDL-C) for cardiovascular disease (CVD) in Chinese general population has not been well demonstrated. The aim of our study was to examine the relation between non-HDL-C and CVD and compare the predictive effect of non-HDL-C and low-density lipoprotein cholesterol (LDL-C) for CVD in Chinese population. The baseline examination of 27,020 participants aged 35 to 74 years from the China Cardiovascular Health Study and the China Multicenter Collaborative Study of Cardiovascular Epidemiology was conducted in 1998 to 2001. Follow-up evaluation was conducted in 2007 to 2008 with a response rate of 79.8%. Cox proportional hazards regression models were used to obtain the multivariable-adjusted hazard ratios and 95% confidence intervals (CIs) for CVD. Compared with those with non-HDL-C level of <130 mg/dl, multivariable-adjusted hazard ratios of CVD were 1.30 (95% CI 1.04 to 1.62) and 1.93 (95% CI 1.50 to 2.47) in participants with non-HDL-C levels of 160 to 189.9 and ≥190 mg/dl, respectively. An increase of 30 mg/dl in non-HDL-C level would correspond to 15%, 24%, and 12% increase in risk of CVD, coronary heart disease, and stroke, respectively. Using likelihood ratio tests, non-HDL-C appeared to be a similar predictor for CVD incidence as LDL-C (chi-square for non-HDL-C, 18.02, p <0.001; chi-square for LDL-C, 18.90, p <0.001). In conclusion, higher non-HDL-C level is associated with the increased CVD incidence and has a similar effect as LDL-C on predicting CVD risk in Chinese.

This study aimed to investigate the potential influence of microRNA-451 (miR-451) in drug resistances of the Paclitaxel-resistant breast cancer cell line by transfecting miR-451 mimics and miR-451 inhibitors to MCE-7, MCF-7/EPI, and MCF-7/DOC.Real-time quantitative PCR (qRT-PCR) was performed for detecting whether transfected miR-451 mimics and miR-451 inhibitors could regulate the expression of miR-451 effectively. The apoptosis of the 3 cell lines was measured by applying Annexin V-APC/PI staining. Western blot was used for the detection of the protein expression of Bcl-2 and Caspase 3 after the transfection of miR-451 mimics /inhibitors. Bioinformatics analysis demonstrated that Bcl-2 protein is a potential target gene for miR-451.In comparison to the control group, after transfection with miR-451 mimics, there was a significant increase in miR-451 expression in MCF-7, MCF-7/EPI, and MCF-7/DOC. Cells in the three cell lines had increased apoptosis, Bcl-2 protein expression decreased significantly, and Caspase protein expression increased obviously. After the transfection with miR-451 inhibitors, miR-451 expression was significantly decreased and apoptosis in the 3 cell lines had no significant decrease compared with the control group.Increased miR-451 expression may negatively regulate Bcl-2 mRNA and protein expression, followed by affecting the protein expression of caspase 3, and accelerate the apoptosis in breast cancer, indicating that miR-451 might influence the drug resistances of the Paclitaxel-resistant breast cancer cell line.

We assessed the efficacy and safety of external physical vibration lithecbole for the treatment of residual stones after retrograde intrarenal surgery.A total of 173 patients (128 males and 45 females) were selected for study. All patients had residual fragments after retrograde intrarenal surgery for renal or upper ureteral stones. They were prospectively randomized into 2 groups. One group underwent external physical vibration lithecbole 1 week after retrograde intrarenal surgery and the other underwent only retrograde intrarenal surgery as the control group. Stone size and location, stone-free rate and complications were compared.Of 173 patients 87 (66 males and 21 females) were in the treatment group and 86 (62 males and 24 females) were in the control group. The stone-free rate in the treated and control groups 2 weeks after retrograde intrarenal surgery was 52.9% and 31.4%, at 3 weeks it was 71.3% and 51.2%, and at 5 weeks it was 89.7% and 59.3%, respectively (all p <0.05). The hematuria incidence 5 weeks after retrograde intrarenal surgery was 3.4% in the treated group compared to 20.9% in the control group (p <0.05). The incidence of positive urine leukocytes in the treated vs control groups was 4.6% vs 19.8% 3 weeks after retrograde intrarenal surgery and 3.4% vs 11.6% at 5 weeks (p <0.05).External physical vibration lithecbole as a supplement to retrograde intrarenal surgery was more effective than retrograde intrarenal surgery alone in terms of stone clearance speed, stone-free rate and patient compliance.

Matrix metalloproteinases (MMPs) are closely associated with tumor proliferation, invasion and metastasis.In this study, we determined the MMPs expression and their clinical significances in gastric cancer (GC).We first extensive studied MMPs expression in GC in The Cancer Genome Atlas (TCGA) RNA sequence database and found MMP16 was candidate biomarker in GC.Then we validated clinical significance of MMP16 mRNA expression in 167 GC by RT-PCR.Survival analysis showed that high expression of MMP16 indicated poor overall and disease free survival (P<0.001).The proliferation and invasion potential of GC cells were determined by CCK8, colony formation and Transwell assays.Silencing of MMP16 expression significantly decreased the invasion and proliferation capacity of GC cells (P<0.05).In conclusion, MMP16 was highly expressed and correlated with poor prognosis in GC patients by promoting proliferation and invasion of GC cells.MMP16 could be a novel molecular target and prognostic marker for GC.

Objective To evaluate the efficacy and safety of Serenoa repens among patients with benign prostatic hyperplasia (lower urinary tract symptoms/benign prostatic hyperplasia [LUTS/BPH]) in China. Methods We conducted a double blind, placebo-controlled study of 354 patients with LUTS/BPH from 19 institutions, to evaluate the efficacy and safety of Serenoa repens. Participants were randomly assigned (1:1) into the Serenoa repens extract (320 mg) or placebo groups for 24 weeks. Primary efficacy parameters were changes in International Prostate Symptom Score and peak urinary flow from baseline to each assessment. Secondary efficacy parameters included improvement of storage symptom and voiding symptom scores, prostate volume, urinary frequency, and total prostate-specific antigen level. Other parameters assessed were quality of life score, a four‐item male sexual function questionnaire score, and International Index of Erectile Function score across the consecutive double-blind visits. Results Statistically significant improvement in the peak urinary flow, International Prostate Symptom Score, scores of storage symptoms and voiding symptoms, quality of life score, four‐item male sexual function questionnaire score, and International Index of Erectile Function score were observed in the Serenoa repens extract group compared with those in the placebo group (P <.05). Two (1.18%) of 169 patients in the placebo group and 3 (1.89) of 159 patients in the Serenoa repens extract group experienced 1 or more adverse events. Conclusion The Serenoa repens extract was effective, safe, well-tolerated, and clinically and statistically superior to placebo in the target LUTS/BPH population.

Objective: To identify novel and confirm previously reported metabolites associated with SBP, DBP, and hypertension in a biracial sample of Bogalusa Heart Study (BHS) participants. Methods: We employed untargeted, ultra-high performance liquid chromatography tandem mass spectroscopy metabolomics profiling among 1249 BHS participants (427 African-Americans and 822 whites) with BP and covariable data collected during the 2013 to 2016 visit cycle. A total of 1202 metabolites were tested for associations with continuous and binary BP phenotypes using multiple linear and logistic regression models, respectively, in overall and race-stratified analyses. Results: A total of 24 novel metabolites robustly associated with BP, achieving Bonferroni-corrected P less than 4.16 × 10 −5 in the overall analysis and consistent effect sizes across race groups. The identified metabolites included three amino acid and nucleotide metabolites from histidine, pyrimidine, or tryptophan metabolism sub-pathways, seven cofactor and vitamin or xenobiotic metabolites from the ascorbate and aldarate metabolism, bacterial/fungal, chemical, and food component sub-pathways, 10 lipid metabolites from the eicosanoid, phosphatidylcholine, phosphatidylethanolamine, and sphingolipid metabolism sub-pathways, and four still unnamed metabolites. Six previously described metabolites were robustly confirmed by our study (Bonferroni-corrected P &lt; 4.95 × 10 −4 and consistent effect directions across studies). Furthermore, previously reported metabolites for SBP, DBP, and hypertension demonstrated 5.92-fold, 4.77-fold, and 4.54-fold enrichment for nominally significant signals in the BHS ( P = 3.08 × 10 −10 , 5.93 × 10 −8 , and 2.30 × 10 −8 , respectively). Conclusion: In aggregate, our study provides new information about potential molecular mechanisms underlying BP regulation. We also demonstrate reproducibility of findings across studies despite differences in study populations and metabolite profiling methods.

Abstract The problem motivating this research is the rapid introduction of educational technologies and the strong push to use new technologies in technical and vocational training in China coupled with varied responses and uneven adoption of new tools on the part of practitioners. This study investigated the factors that influence technical and vocational college teachers' adoption and appreciation of information and communication technology (ICT) in China using the technology adoption and gratification (TAG) model. At total of 535 teachers from public technical and vocational colleges were surveyed using a purposive sampling procedure. The survey data were analyzed through structural equation modeling. Findings suggest that the use of ICT had three primary determinants: teaching purpose, research purpose and academic purpose. Technical and vocational college teachers' technology adoption and gratification was directly and indirectly predicted by their computer self‐efficacy, intention to use, perceived ease of use and usefulness of ICT. Most importantly, the TAG model accounted for 77% of the variance in teachers' gratification using those predictive variables. This research successfully applied the TAG model and it further fosters recommendations for future investigations. This study contributes to theoretical, methodical and practical understandings of the use of ICT in technical and vocational education, which has been much less explored than in K‐12 education and university settings. Practitioner Notes What is already known about this topic Information and Communication Technology (ICT) helps explain teacher acceptance. Investigations have revealed that many gaps exist in identifying ICT facilities, access, skills and usage in technical and vocational education. Studies have suggested that ICT development requires significant training on the part of teachers and creates new demands for students. What this article adds This research exhibited that vocational and technical college teachers’ use of ICT had three primary determinants: teaching purpose, research purpose and academic purpose. Chinese technical and vocational college teachers’ adoption and gratification in new technologies were directly and indirectly predicted by their computer self‐efficacy, intention to use, perceived ease of use and usefulness of ICT. The findings of this study recommend that the quality of teaching, learning and research in vocational and technical education could be enhanced through the application of emerging ICT. Implications for practice and/or policy The larger goal is to use the results as a basis for future studies in the relatively unexplored area of ICT use and adoption in teaching and training in developing countries. By conducting cross‐cultural studies, researchers could be able to comprehend the overall scenarios of ICT in vocational and technical education as proposed. This study contributes to theoretical, methodical and practical understandings of the use of ICT in technical and vocational education, which has been much less explored than in K‐12 education and university settings. Teachers' skills to use ICT should be enhanced through ongoing training programs offered by the authorities of technical education.

Chronic rhinosinusitis (CRS) is featured with chronic symptoms of inflammation or infection in the nasal and sinus tissues. MicroRNAs (miRNAs/miRs), such as dysregulated expression of miR-125b and miR-26a, has been previously demonstrated to be related to CRS. The present study is intended to define the role of miR-335-5p in inflammation and the related mechanism in a mouse model of CRS. The differentially expressed genes associated with CRS were screened by microarray analysis. The targeting relationship between miR-335-5p and TPX2 was analyzed by target prediction program and dual luciferase reporter gene assay. The mouse model of CRS was established, and mice were introduced with miR-335-5p mimics, miR-335-5p inhibitors, or siRNA against TPX2 to explore the regulatory functions of miR-335-5p. The regulatory effect of miR-335-5p on inflammation with the involvement of the AKT signaling pathway was also analyzed with the expression of inflammatory cytokines and AKT signaling pathway-related factors measured. It was indicated that miR-335-5p regulated the TPX2 gene-mediated AKT signaling pathway. TPX2 was identified as a target gene of miR-335-5p, and miR-335-5p elevation inhibited the activation of the AKT signaling pathway. In mice with CRS, up-regulation of miR-335-5p or silence of TPX2 inhibited the inflammation, as evidenced by decreased levels of TNF-α, IL-6 and IL-8, and higher levels of GSK3β and IL-10. Collectively, miR-335-5p inhibits the activation of AKT signaling pathway by negatively mediating TPX2, which may confer anti-inflammatory protection in CRS.

Interest-driven creator (IDC) theory is a design theory that intends to inform the design of future education in Asia. It consists of three anchored concepts, namely, interest, creation, and habit. This paper presents the third anchored concept habit as well as the habit loop. IDC theory assumes that learners, when driven by interest, can be engaged in knowledge creation. Furthermore, by repeating such process in their daily learning routines, learners will form interest-driven creation habits. The habit loop, the process of building such a habit, consists of three component concepts—cuing environment, routine, and harmony. The cuing environment is a habit trigger that tells the students’ brain to get prepared and go into an automatic mode, letting a learning behavior unfold. Routine refers to the behavioral patterns the students repeat most often, literally etched into their neural pathways. Harmony refers to the affective outcome of the routine activity as well as the integration or stabilization of habits; that is, through the routine behavior and action, students may feel that their needs get fulfilled, feel satisfied, and experience inner peace. It is our hope that such habitual behavior of creating knowledge can be sustained so long that students ultimately become lifelong interest-driven creators. This paper focuses on the description of the three components of the habit loop and discusses how these components are related to the interest loop and the creation loop in supporting learners in developing their interest-driven creation capability.

As an intangible cultural heritage of Anhui Province, Fuyang embroidery has strong local characteristics and aesthetic value. However, due to the transformation of modern aesthetic needs, the impact of mechanized large-scale production and other factors, the market-oriented operation of Fuyang embroidery is difficult and declined. With the party and the country's emphasis on intangible cultural heritage and the emphasis on the inheritance and innovation of intangible cultural heritage, it provides new ideas for Fuyang embroidery. Therefore, this paper explores the business model of Fuyang embroidery based on the rural revitalization strategy, from the Internet+ professional platform exhibition, digital promotion, and cultural core connotation The four aspects of financial support are discussed in order to provide a development path for the commercial operation of Fuyang embroidery and realize the connection between tradition and modernity.

Quantum dot light-emitting diodes (QLEDs) are increasingly being recognized as next-generation display technology, owing to their wide color gamut, high saturation levels, and low energy consumption. However, the primary challenge in QLED display fabrication lies in precisely depositing these inorganic quantum dot (QD) nanoparticles over a large area multiple times. Nowadays, solution processes such as inkjet printing and screen printing have been employed to address these challenges; however, they still have some trade-offs between multicolor deposition, precise spatial arrangement, and equipment cost. Here, the precise assembly of multiple QD patterned arrays on one target substrate was achieved using an asymmetric wettability interface assembly (AWIA) template, resulting in a high-pixel resolution and full-color QLED device. The asymmetric wettability interface between the top and bottom of the silicon pillar on the template allows for precise splitting and pinning of a continuous liquid film, facilitating further assembly of QD pattern arrays. Additionally, the multicolor and multishape QD pattern array was created through QD surface modification (orthogonal solvent protection) and dislocation pinning processes (reducing dissolution time) during the repetition process. Consequently, high-resolution (each pixel ≈ 10 μm; PPI ≈ 1278) full-color (yellow, cyan, violet, and white) QLED devices were fabricated efficiently. This approach offers a perspective for assembling multiple micropatterned arrays for high-resolution electronic devices.

Cyclin D1 (CCND1) is a key protein in regulation of cell cycle at the G1-to-S transition phase and is essential for regulation of cell proliferation, differentiation, and transcriptional control. We hypothesized that the CCND1 G870A polymorphism is associated with risk of bladder cancer. The CCND1 G870A polymorphism was genotyped in a hospital-based case–control study of 402 bladder cancer cases and 402 control subjects using the polymerase chain reaction–restriction fragment length polymorphism method. Unconditional univariate and multivariate logistic regression analyses were used to evaluate the associations between the CCND1 G870A polymorphism and bladder cancer risk. A significantly increased risk of bladder cancer was associated with the combined variant CCND1 870GA/AA genotypes (adjusted odds ratio, 1.54; 95% confidence interval, 1.08–2.20) compared with the GG genotype, particularly among subgroups of age ≥65 years (1.74; 1.06–2.88), men (1.67; 1.15–2.44), and smokers (1.82; 1.12–2.93). Further, the G870A polymorphism was significantly associated with risk of developing superficial bladder cancer (grade 1). In addition, a meta-analysis of the G870A polymorphism and bladder cancer risk showed that the variant 870GA/AA genotypes were associated with an increased risk of bladder cancer in Asians, but not in Caucasians, which was consistent with the results of our study. The CCND1 G870A polymorphism may be a marker for the development of bladder cancer in Chinese populations. Larger studies are required to validate these findings in diverse populations.

Abstract BACKGROUND A resequencing study of renal epithelial sodium channel (ENaC) genes was conducted to identify rare variants associated with blood pressure (BP) salt-sensitivity. METHODS The Genetic Epidemiology Network of Salt-Sensitivity (GenSalt) study was conducted among 1,906 participants who underwent a 7-day low-sodium followed by a 7-day high-sodium feeding-study. The 300 most salt-sensitive and 300 most salt-resistant GenSalt participants were selected for the resequencing study. Three ENaC genes (SCNN1A, SCNN1B, and SCNN1G) were resequenced using capillary-based sequencing methods. Traditional burden tests were utilized to examine association between rare variants and BP salt-sensitivity. Associations of low-frequency and common variants were tested using single-marker analyses. RESULTS Carriers of SCNN1A rare variants had a 0.52 [95% confidence interval (CI): 0.32–0.85] decreased odds of BP salt-sensitivity compared with noncarriers. Neither SCNN1B nor SCNN1G associated with salt-sensitivity of BP in rare variant analyses (P = 0.65 and 0.48, respectively). In single-marker analyses, 3 independent common variants in SCNN1A, rs11614164, rs4764586, and rs3741914, associated with salt-sensitivity after Bonferroni correction (P = 4.4 × 10–4, 1.1 × 10–8, and 1.3 × 10–3). Each copy of the minor allele of rs4764586 was associated with a 1.36-fold (95% CI: 1.23–1.52) increased odds of salt-sensitivity, whereas each copy of the minor allele of rs11614164 and rs3741914 was associated with 0.68-fold (95% CI: 0.55–0.84) and 0.69-fold (95% CI: 0.54–0.86) decreased odds of salt-sensitivity, respectively. CONCLUSIONS This study demonstrated for the first time a relationship between rare variants in the ENaC pathway and BP salt-sensitivity. Future replication and functional studies are needed to confirm the findings in this study. CLINICAL TRIAL REGISTRY Trial Number NCT00721721

Bacterial infection of the lower respiratory tract is believed to play a major role in the pathogenesis of chronic obstructive pulmonary disease (COPD) and acute exacerbations of COPD (AECOPD). This study investigates the potential relationship between AECOPD and the load of six common bacterial pathogens in the lower respiratory tract using real-time quantitative PCR (RT-qPCR) in COPD patients.Protected specimen brush (PSB) and bronchoalveolar lavage fluid (BALF) samples from the lower respiratory tract of 66 COPD patients and 33 healthy subjects were collected by bronchoscopy. The load of Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Pseudomonos aeruginosa, Haemophilus influenzeae, and Moraxella catarrhalis were detected by RT-qPCR.High Klebsiella pneumoniae, Pseudomonos aeruginosa, Haemophilus influenzeae and Moraxella catarrhalis burden were detected by RT-qPCR in both PSB and BALF samples obtained from stable COPD and AECOPD patients compared with healthy subjects. The load of the above four pathogenic strains in PSB and BALF samples obtained from AECOPD patients were significantly higher compared with stable COPD patients. Finally, positive correlations between bacterial loads and inflammatory mediators such as neutrophil count and cytokine levels of IL-1β, IL-6 and IL-8, as well as negative correlations between bacterial loads and the forced expiratory volume in one second (FEV1) % predicted, forced vital capacity (FVC) % predicted, and FEV1/FVC ratio, were detected.These findings suggest that increased bacterial loads mediated inflammatory response in the lower respiratory tract and were associated with AECOPD. In addition, these results provide guidance for antibiotic therapy of AECOPD patients.

• Systematically designed Immersion & Infusion instructional approaches were compared. • Both approaches resulted in significant improvement on near-transfer of CT skills. • Infusion-based learning environments appear to be useful for far-transfer. • Far-transfer of CT skills remains to be a challenge in CT research. • Systematic and explicit approach to CT instruction is a promising approach.

Purpose: Lymph node metastasis is a multifactorial event. Several scholars have developed nomograph models to predict the sentinel lymph nodes (SLN) metastasis before operation. According to the clinical and pathological characteristics of breast cancer patients, we use the new method to establish a more comprehensive model and add some new factors which have never been analyzed in the world and explored the prospect of its clinical application. Materials and methods: The clinicopathological data of 633 patients with breast cancer who underwent SLN examination from January 2011 to December 2014 were retrospectively analyzed. Because of the imbalance in data, we used smote algorithm to oversample the data to increase the balanced amount of data. Our study for the first time included the shape of the tumor and breast gland content. The location of the tumor was analyzed by the vector combining quadrant method, at the same time we use the method of simply using quadrant or vector for comparing. We also compared the predictive ability of building models through logistic regression and Bagged-Tree algorithm. The Bagged-Tree algorithm was used to categorize samples. The SMOTE-Bagged Tree algorithm and 5-fold cross-validation was used to established the prediction model. The clinical application value of the model in early breast cancer patients was evaluated by confusion matrix and the area under receiver operating characteristic (ROC) curve (AUC). Results: Our predictive model included 12 variables as follows: age, body mass index (BMI), quadrant, clock direction, the distance of tumor from the nipple, morphology of tumor molybdenum target, glandular content, tumor size, ER, PR, HER2, and Ki-67.Finally, our model obtained the AUC value of 0.801 and the accuracy of 70.3%.We used logistic regression to established the model, in the modeling and validation groups, the area under the curve (AUC) were 0.660 and 0.580.We used the vector combining quadrant method to analyze the original location of the tumor, which is more precise than simply using vector or quadrant (AUC 0.801 vs. 0.791 vs. 0.701, Accuracy 70.3 vs. 70.3 vs. 63.6%). Conclusions: Our model is more reliable and stable to assist doctors predict the SLN metastasis in breast cancer patients before operation.

Chronic cough is a common complaint, but there are no population-based data on its burden in China. We determined the prevalence of chronic cough and its impact on health status in adults stratified by sex, age and the diagnosis of COPD or the presence of small airway dysfunction (SAD).A representative sample of 57 779 Chinese adults aged 20 years or older was recruited and pulmonary function test was measured. Chronic cough was defined as cough lasting for >3 months in each year. Quality of life was assessed by the 12-item Short Form Health Survey (SF-12), and self-reported history of hospital visits was recorded.Chronic cough was found in 3.6% (95% CI 3.1-4.1) of Chinese adults, 2.4% (95% CI 1.9-3.1) of those aged 20-49 years and 6.0% (95% CI 5.3-6.8) of those aged 50 years or older. Individuals with chronic cough had an impaired physical component summary (PCS) score of the SF-12 (p<0.0001) and more emergency visits (p=0.0042) and hospital admissions (p=0.0002). Furthermore, the impact of chronic cough on PCS score was more significant in those aged 50 years or older, or with COPD (p=0.0018 or 0.0002, respectively), with the impact on hospital admission being more significant in those with COPD or with SAD (p=0.0026 or 0.0065, respectively).Chronic cough is prevalent in China and is associated with a poorer health status, especially in individuals aged 50 years or older and those with the diagnosis of COPD or SAD.

Sanghuangporus vaninii (Ljub.) L.W. Zhou & Y.C. Dai (SV) is a major cultivar of Sanghuang, which is well known as an excellent anti-tumour drug and reaches the mainstream market in China. Water, 60% ethanol and 95% ethanol were used to extract the drug, and three kinds of polar extracts were obtained separately. Compared with water extracts and 95% ethanol extracts, the 60% ethanol extract had the highest flavonoid content, and its polysaccharide content was greater than that in the 95% ethanol extract and lower than that in the water extract. Its essential components were phenolics whose majority were phenolic acids, flavonoids and phenylpropanoids. This extract has better inhibition effects on the proliferation of SW480 human colon cancer cells, inducing cell apoptosis and blocking G2/M period cells. It can significantly inhibit gene expression and reduce the activation of the AKT/mTOR signalling pathway. The anti-cancer activity of the 60% ethanol extract is satisfactory and may be a result of the combined effects of polysaccharides and flavonoids. The data suggest that the 60% ethanol extract can be used as an adjuvant for chemotherapy and as a potential anti-cancer agent with broad development prospects.

Multiple myeloma (MM) is a hematological tumor with high mortality and recurrence rate. Carfilzomib is a new-generation proteasome inhibitor that is used as the first-line therapy for MM. However, the development of drug resistance is a pervasive obstacle to treating MM. Therefore, elucidating the drug resistance mechanisms is conducive to the formulation of novel therapeutic therapies. To elucidate the mechanisms of carfilzomib resistance, we retrieved the GSE78069 microarray dataset containing carfilzomib-resistant LP-1 MM cells and parental MM cells. Differential gene expression analyses revealed major alterations in the major histocompatibility complex (MHC) and cell adhesion molecules. The upregulation of the tumor necrosis factor (TNF) receptor superfamily member 1A (TNFRSF1A) gene was accompanied by the downregulation of MHC genes and cell adhesion molecules. Furthermore, to investigate the roles of these genes, we established a carfilzomib-resistant cell model and observed that carfilzomib resistance induced TNFRSF1A overexpression and TNFRSF1A silencing reversed carfilzomib resistance and reactivated the expression of cell adhesion molecules. Furthermore, TNFRSF1A silencing suppressed the tumorigenesis of MM cells in immunocompetent mice, indicating that TNFRSF1A may lead to carfilzomib resistance by dampening antitumor immunity. Furthermore, our results indicated that TNFRSF1A overexpression conferred carfilzomib resistance in MM cells and suppressed the expression of MHC genes and cell adhesion molecules. The suppression of MHC genes and cell adhesion molecules may impair the interaction between immune cells and cancer cells to impair antitumor immunity. Future studies are warranted to further investigate the signaling pathway underlying the regulatory role of TNFRSF1A in MM cells.

<h2>Abstract</h2><h3>Objectives</h3> Equitable distribution of quality healthcare services among different subpopulations in China and Nigeria is inconsistent. This necessitates an examination of potential avenues for improving healthcare provision in both countries. A comparative analysis of both health systems was carried out to provide insights into the progress each nation has made, the obstacles they face, and areas both countries can learn from each other. <h3>Methods</h3> We assessed 3 key dimensions of these systems using the Hsiao analytical framework. First, we scrutinized the policy levers of the health systems. Next, we evaluated intermediate outcomes, such as access to healthcare and the quality of care. Lastly, we assessed the extent to which the health systems achieve their ultimate goals, including improving citizen health status and enhancing overall patient satisfaction with the healthcare services. <h3>Results</h3> China surpasses Nigeria in terms of better birth outcomes, life expectancy, and management of communicable diseases. Both countries offer minimal protection against out-of-pocket spending on medical bills, which consequently exacerbates the poverty rate. <h3>Conclusions</h3> China surpasses Nigeria in every health metrics. However, Nigeria's healthcare system offers services to a larger proportion of its populace because of the involvement of the private sector in healthcare delivery. Both countries continue to experience significant challenges, such as limited access to healthcare services in rural areas and overall patient dissatisfaction with the quality of care provided.

Community-acquired pneumonia (CAP) is a leading cause of mortality worldwide, but disease burden of CAP is not clear so far. We aim to explore the spatial and temporal trends of mortality and years of life lost (YLL) due to CAP during 2013-2021 in mainland China, especially the mortality changes before and during COVID-19 pandemic due to COVID-19 related non-pharmaceutical interventions (NPIs).We used data from the National Mortality Surveillance System to estimate the age-standardized rates of death and YLL of CAP at national and provincial level in China during 2013-2021. Monthly and provincial NPIs data were obtained from Oxford COVID-19 Government Response Tracker. The Average annual percentage change (AAPC) and mortality reduction were estimated by log-linear regression and interrupted time series, respectively.In China, most CAP that caused deaths had no clear etiology, and bacterial pneumonia and viral pneumonia were the leading 2 causes among CAP deaths with determined etiology before and during COVID-19 pandemic. The age-standardized CAP mortality rate decreased from 11.18 per 100,000 in 2013 to 8.76 per 100,000 in 2019, and to 5.74 per 100,000 in 2021 (AAPC -4.51% vs -7.89%). Trends were similar in age-standardized rate of YLL. Both rates declined more for viral pneumonia, compared with bacterial pneumonia. After adjusting for NPIs at provincial level after 2020, the NPIs for COVID-19 was associated with significant reductions in CAP mortality (-0.34 per 100,000, -0.41 to -0.27; p < 0.0001), and provinces that economically developed and conducted strict regular NPIs against COVID-19 contributed the most reduction.We observed a decreasing trend of age-standardized CAP mortality from 2013 to 2019, and a dramatical reduction during COVID-19 pandemic, especially for viral pneumonia. Our study provided the evidence for the effectiveness of regular NPIs on the significant reductions in CAP mortality.This work has been supported by Beijing Municipal Science and Technology Project Z191100006619101, Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS 2021-I2M-1-048), CAMS Institute of Respiratory Medicine Grant for Young Scholars (2023-ZF-8) and the New Cornerstone Science Foundation.

Vitiligo is a common depigmenting skin disorder. This work is performed to systematically evaluate the efficacy and safety of fire needles combined with 308 nm excimer laser therapy in treating vitiligo.We searched the PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, Wanfang, and VIP databases. Randomized controlled trials (RCTs) on fire needles combined with 308 nm excimer laser therapy with 308 nm excimer laser therapy alone for vitiligo were included. The Cochrane Collaborative Network Tool was used to assess the risk of bias. Statistical analysis was completed using RevMan5.3 software and Stata 15.0 software. The GRADE system was used to evaluate the quality of evidence for outcomes.In this study, 10 RCTs and 1333 patients were included. The results showed that compared with 308 nm excimer laser therapy alone, fire needle combined with 308 nm excimer laser therapy is more effective in improving clinical effective rate (RR = 1.36, 95% CI [1.24, 1.50], p < 0.00001), serum CD4+ level (MD = 3.12, 95% CI [2.50, 3.74], p < 0.00001), CD4+/CD8+ ratio (MD = 0.24, 95% CI [0.09, 0.39], p = 0.001), and quality of life measured by the Dermatology Life Quality Index (DLQI) (MD = 3.76, 95% CI [3.33, 4.19], p < 0.00001), and reducing the Vitiligo Area Score Index (VASI) (MD = -5.47, 95% CI [-6.56, -4.37], p < 0.00001). The reported adverse events, including redness, swelling, pain, blisters, and itching, were controllable, and all these events were well tolerated.The current evidence indicates that fire needle combined with 308 nm excimer laser therapy is effective and safe for vitiligo. However, owing to the suboptimal quality of the included studies, more high-quality and large-scale RCTs are needed for comprehensive analysis and further validation.

Prognostic indicators for gastrointestinal stromal tumors (GISTs) are under investigation. The latest risk classification criteria may still have room for improvement. This study aims to investigate prognostic factors for primary GISTs from three aspects, including clinicopathological parameters, immunohistochemical (IHC) expression of PTEN, and Ki-67 labeling index (LI), and attempts to find valuable predictors for the malignancy potential of primary GISTs.Tumor samples and clinicopathological data from 84 patients with primary GISTs after R0 resection were obtained. Immunohistochemical analysis was performed based on tissue microarray (TMA) to estimate expression of PTEN and Ki-67 in tumor cells.The cut-off point of Ki-67 LI was determined as 1%, using a receiver operator characteristic test with a sensitivity of 71.7% and a specificity of 64.5%. Univariate analysis demonstrated the following factors as poor prognostic indicators for relapse-free survival (RFS) against a median follow-up of 40.25 months: gastrointestinal (GI) bleeding (P = 0.009), non-gastric tumor location (P = 0.001), large tumor size (P = 0.022), high mitotic index (P < 0.001), high cellularity (P = 0.012), tumor rupture (P = 0.013), absent or low expression of PTEN (P = 0.036), and Ki-67 LI >1% (P = 0.043). Gastrointestinal bleeding (hazard ratio, 3.85; 95% confidence interval, 1.63 to 9.10; P = 0.002) was a negative independent risk predictor in multivariate analysis, in addition to tumor size (P = 0.023), and mitotic index (P = 0.002). In addition, GI bleeding showed a good ability to predict recurrence potential, when included in our re-modified risk stratification criteria.This study suggests that GI bleeding is an independent predictor of poor prognosis for RFS in primary GISTs. Expression of PTEN and Ki-67 are correlated with high risk potential and may predict early recurrence in univariate analysis.

The practice of breast cancer diagnosis and treatment in China varies to that in western developed countries. With the unavailability of radioactive tracer technique for sentinel lymph nodes biopsy (SLNB), using blue dye alone has been the only option in China. Also, the diagnosis of breast malignant tumor in most Chinese centres heavily relies on intraoperative instant frozen histology which is normally followed by sentinel lymph nodes mapping, SLNB and the potential breast and axillary operations in one consecutive session. This practice appears to cause a high false negative rate (FNR) for SLNB. The present study aimed to investigate the impact of the current practice in China on the accuracy of SLNB, and whether partial axillary lymph node dissection (PALND), dissection of lymph nodes inferior to the intercostobrachial nerve (ICBN), was a good complementary procedure following SLNB using blue dye.289 patients with clinically node-negative breast cancer were identified and recruited. Tumorectomy, intraoperative instant frozen histological diagnosis, SLNB using methylene blue dye, and PALND or complete axillary node dissection (ALND) were performed in one consecutive operative session. The choice of SLNB only, SLNB followed by PALND or by ALND was based on the pre-determined protocol and preoperative choice by the patient. Clinical parameters were analyzed and survival analysis was performed.37% patients with clinically negative nodes were found nodes positive. 59 patients with positive SLN underwent ALND, including 47 patients with up to two positive nodes which were all located inferior to the ICBN. 9 patients had failed SLNB and underwent PALND. Among them, 3 (33.3%) patients were found to have one metastatic node. 149 patients showed negative SLNB but chose PALND. Among them, 30 (20.1%), 14 (9.4) and 1 (0.7%) patients were found to have one, two and three metastatic node(s), respectively. PALND detected 48 (30.4%) patients who had either failed SLNB or negative SLNB to have additional positive nodes. All the patients with up to two positive nodes had their nodes located inferior to the ICBN. The FNR of SLNB was 43%. The accuracy rate was 58%. The follow-up ranged 12-33 months. The incidence of lymphedema for SLNB, PALND, and ALND was 0%, 0%, and 25.4%, respectively (P < 0.005). The disease-free survivals for SLNB, PALND, and ALND groups were 95.8%, 96.8%, and 94.9%, respectively (p > 0.05).Under the circumstances of current practice in China, PALND is a good complementary procedure following SLNB in clinically node-negative breast cancer.

As information and communication technology (ICT) continues to develop, it is essential for teachers to acquire ability for teaching with ICT. In China, new higher education (HE) teachers often lack teaching experience because there are limited teaching opportunities during their postgraduate studies. This status quo may compromise the quality of teaching and learning in higher education institutions. In 2013, Shanghai Municipal Education Commission initiated a professional development program for new teachers from all local higher education institutions. This article examines their ICT professional development through the lens of Kirkpatrick’s evaluation model. Data were collected from online surveys both immediately after an ICT module and 6 months later. The results showed that participants intended to integrate ICT in teaching and had an above-average level of Technological Pedagogical and Content Knowledge (TPACK). Participants and their department heads also confirmed distinctive teaching performance of these new teachers and better learning behavior of their students. The study revealed that demographic variables of new HE teachers may also affect their perception of ICT and TPACK. This study suggests that ICT professional development can have positive impacts on new HE teachers’ perception of ICT, their TPACK competence, and ICT-related teaching practice and student learning.

Abstract BACKGROUND Metabolomics study may help identify novel mechanisms underlying arterial stiffening. METHODS We performed untargeted metabolomics profiling among 1,239 participants of the Bogalusa Heart Study. After quality control, 1,202 metabolites were evaluated for associations with augmentation index (AI) and pulse wave velocity (PWV), using multivariate linear regression adjusting for age, sex, race, education, smoking, drinking, body weight, body height, physical activity, and estimated glomerular filtration rate. Heart rate, blood pressure and antihypertensive medication usage, lipids, and fasting glucose were sequentially adjusted in the sensitivity analyses for significant metabolites. Weighted correlation network analysis was applied to build metabolite networks. RESULTS Six novel metabolites were negatively associated with AI, of which, 3-methyl-2-oxobutyrate had the lowest P value and the largest effect size (β = –6.67, P = 5.99 × 10–6). Heart rate contributed to a large proportion (25%–58%) of the association for each metabolite. Twenty-one novel metabolites were identified for PWV, of which, fructose (β = 0.61, P = 6.18 × 10–10) was most significant, and histidine had the largest effect size (β = –1.09, P = 2.51 × 10–7). Blood pressure played a major contribution (9%–54%) to the association for each metabolite. Furthermore, 16 metabolites were associated with arterial stiffness independent of traditional risk factors. Network analysis identified 2 modules associated with both AI and PWV (P &amp;lt; 8.00 × 10–4). One was composed of metabolites from the glycerolipids synthesis and recycling pathway, and the other was involved in valine, leucine, and isoleucine metabolism. One module related to sphingomyelin metabolism was associated with PWV only (P = 0.002). CONCLUSIONS This study has identified novel and important metabolites and metabolic networks associated with arterial stiffness.

Gardeniae Fructus (GF) and carbonized GF (GFC) have been shown to exert a gastrointestinal protective effect and are frequently used in clinical practice for the treatment of hemorrhage and brown stool. In this study, we employed a combination of pharmacological methods and metabolomics in a rat model of ethanol-induced acute stomach ulcer to investigate the gastroprotective effect of GF and GFC water extracts and the potential mechanism involved in this process. The levels of nitric oxide (NO) and interleukin 6 (IL-6) in the plasma of rats were determined. The results showed that both GF and GFC reduced the ethanol-induced gastric lesions and expression of NO and IL-6 in these rats. Of note, 16 and 11 feature metabolites were filtered and identified in the GF and GFC groups, respectively. Both GF and GFC act by restoring the biosynthesis of valine, leucine, and isoleucine, and the metabolism of glycerophospholipids. Moreover, histological evaluation revealed that heat processing of GF to create GFC enhanced the gastric mucosa protective effect. Furthermore, heat processing converted the main pathway from alanine, aspartate, and glutamate metabolism, associated with GF, to histidine metabolism, associated with GFC. GF and GFC ameliorated gastric mucosa lesions in rats via reductions in NO production and inflammatory cytokine secretion, and the induction of prostaglandin E2.

Objectives Long-term use of high-dose glucocorticoids can lead to severe immunosuppression and increased risk of treatment-resistant pneumonia and mortality. We investigated the aetiology and prognostic risk factors of mortality in hospitalised patients who developed pneumonia while receiving glucocorticoid therapy alone or glucocorticoid and other immunosuppressant therapies. Design Retrospective cohort study. Setting Six secondary and tertiary academic hospitals in China. Participants Patients receiving glucocorticoids who were hospitalised with pneumonia between 1 January 2013 and 31 December 2019. Main outcomes We analysed the prevalence of comorbidities, microbiology, antibiotic susceptibility patterns, 30-day and 90-day mortality and prognostic risk factors. Results Conclusions A total of 716 patients were included, with pneumonia pathogens identified in 69.8% of patients. Significant morbidities occurred, including respiratory failure (50.8%), intensive care unit transfer (40.8%) and mechanical ventilation (36%), with a 90-day mortality of 26.0%. Diagnosis of pneumonia occurred within 6 months of glucocorticoid initiation for 69.7% of patients with Cytomegalovirus (CMV) pneumonia and 79.0% of patients with Pneumocystis jirovecii pneumonia (PCP). Pathogens, including Pneumocystis , CMV and multidrug-resistant bacteria, were identified more frequently in patients with persistent lymphocytopenia and high-dose glucocorticoid treatment (≥30 mg/day of prednisolone or equivalent within 30 days before admission). The 90-day mortality was significantly lower for non-CMV viral pneumonias than for PCP (p&lt;0.05), with a similar mortality as CMV pneumonias (24.2% vs 38.1% vs 27.4%, respectively). Cox regression analysis indicated several independent negative predictors for mortality in this patient population, including septic shock, respiratory failure, persistent lymphocytopenia, interstitial lung disease and high-dose glucocorticoid use. Patients who developed pneumonia while receiving glucocorticoid therapy experienced high rates of opportunistic infections, with significant morbidity and mortality. These findings should be carefully considered when determining treatment strategies for this patient population.

Lipase member H (LIPH), a novel member of the triglyceride lipase family. The clinical implications of its expression in breast cancer are still unclear. Therefore, in this study, we investigated the associations between LIPH and the tumorigenic behaviours of 144 triple-negative breast cancer (TNBC) patients. The ratio and mammosphere-forming ability of CD44+/CD24- stem-like cells were tested. The role of LIPH in breast cancer cell migration and invasion was also evaluated. In addition, the effect of LIPH silencing on mitochondrial respiration was determined using the Seahorse assay. Finally, the effect of LIPH silencing on protein expression was determined via tandem mass tag-based spectrometry and Western blotting. We found that LIPH expression was associated with metastasis in lymph nodes and distant organs (P = 0.025), resulting in poor survival among breast cancer patients (P = 0.027). LIPH knockdown significantly decreased both the ratio of CD44+ /CD24- stem-like cells and their mammosphere-forming ability. LIPH silencing promoted apoptosis, arrested cell cycle in the G2/M phase, mitigated the oxidation-related oxygen consumption rate in the mitochondria, and reduced metabolism. LIPH inhibited adhesion between tumour cells and enhanced the epithelial-mesenchymal transition. Tandem mass spectrometric analysis presented 68 proteins were differentially expressed in LIPH-silenced cells and LIPH-mediated modulation of tumour cell adhesion depended on integrin-related CAPN2 and paxillin signalling. Overall, our findings provided strong evidence that LIPH up-regulation promoted metastasis and the stemness of TNBC cells. Therefore, targeting LIPH is a potentially viable strategy for preventing metastasis in TNBC.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a great threat to public health worldwide. Approximately 5% of patients are complicated with critical illness, with some of them experiencing multi-organ dysfunction and even death.1,2

It is not clear whether polymyxin B/tigecycline (PMB/TGC) combination is better than PMB or TGC alone in the treatment of hospital-acquired pneumonia (HAP) caused by carbapenem-resistant organisms (CROs).We conducted a multicenter, retrospective cohort study in patients with HAP caused by CROs. The primary outcome was 28-day mortality, and the secondary outcomes included clinical success and the incidence of acute kidney injury (AKI). Multivariate Cox regression analysis was performed to examine the relationship between antimicrobial treatments and 28-day mortality by adjusting other potential confounding factors.A total of 364 eligible patients were included in the final analysis, i.e., 99 in the PMB group, 173 in the TGC group, and 92 in the PMB/TGC combination group. The 28-day mortality rate was 28.3% (28/99) in the PMB group, 39.3% (68/173) in the TGC group, and 48.9% (45/92) in the PMB/TGC combination group (p = 0.014). The multivariate Cox regression model showed that there was a statistically significant lower risk of 28-day mortality among participants in the PMB group when compared with the PMB/TGC combination group [hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.31-0.81, p = 0.004] and that participants in the TGC group had a lower risk of 28-day mortality than in the PMB/TGC combination group but without statistical significance. The incidence of AKI in the PMB group (52.5%) and the PMB/TGC combination group (53.3%) was significantly higher than that in the TGC group (33.5%, p = 0.001).The appropriate PMB/TGC combination was not superior to appropriate PMB therapy in the treatment of HAP caused by carbapenem-resistant Enterobacteriaceae/carbapenem-resistant Acinetobacter baumannii (CRE/CRAB) in terms of 28-day mortality.

Can we identify diurnal oscillations in human semen parameters as well as peak times of semen quality?Human semen parameters show substantial diurnal oscillation, with most parameters reaching a peak between 1100 and 1500 h.A circadian clock appears to regulate different physiological functions in various organs, but it remains controversial whether diurnal rhythms occur in human semen parameters.The medical record of a provincial human sperm bank (HSB) with 33 430 semen samples collected between 0800 and 1700 h from 1 March 2010 to 8 July 2015 was used to analyze variation in semen parameters among time points. A laboratory study was conducted to collect semen samples (n = 36) from six volunteers at six time points with identical time intervals (2 days plus 4 h) between 6 June and 8 July in 2019, in order to investigate the diurnal oscillation of semen parameters in vivo, with a strictly controlled abstinence period. Therefore, the sperm bank study with a large sample size and the in vivo study with a strictly controlled abstinence period in a 24-h time window could be compared to describe the diurnal rhythms in human semen parameters.Samples were obtained from potential HSB donors and from participants in the laboratory study who were volunteers, recruited by flyers distributed in the community. Total sperm count, sperm concentration, semen volume, progressive motility and total motility were assessed using computer-aided sperm analysis. In addition, sperm chromatin integrity parameters (DNA fragmentation index and high DNA stainability) were assessed by the sperm chromatin structure assay, and sperm viability was measured with flow cytometry in the laboratory study.The 33 430 samples from the HSB showed a temporal variation in total sperm count, sperm concentration, semen volume, progressive motility and total motility (all P < 0.001) between 0800 and 1700 h. Consequently, the eligibility of semen samples for use in ART, based on bank standards, fluctuated with time point. Each hour earlier/later than 1100 h was associated with 1.14-fold risk of ineligibility. Similarly, the 36 samples taken during the 24-h time window showed diurnal oscillation. With the pre-collection abstinence period strictly controlled, most semen parameters reached the most favorable level between 1100 and 1500 h.Some of the possible confounding factors, such as energy intake, which might influence semen quality or diurnal rhythms, were not adjusted for in the analyses. In addition, the findings should be considered with caution because the study was conducted in a specific population, time and place, while the timing of oscillations could differ with changing conditions.The findings could help us to estimate semen quality more precisely and to obtain higher quality sperm for use in ART and in natural conception.This study was supported by the National Natural Science Foundation of China (81871208) and National Key R&D Program of China (2017YFC1002001). There are no conflicts of interest to declare.N/A.

This study aimed to verify the applicability of the community of inquiry (CoI) survey instrument in MOOC involving 1,186 college students from 11 different disciplines in China. Exploratory factor analysis was used to explore potential factor structure models, and confirmatory factor analysis was utilized to verify the four-factor structure obtained from exploratory factor analysis. The original three- and new six-factor structure models were also included in the study. Confirmatory factor analysis results indicating that all three models fit very well with the data. Then Chi-square difference test was used to select the optimal model. Results indicate that the six-factor structure model with teaching presence, social presence, cognitive presence, design and organization, affective expression, and resolution is the optimal one, with good convergent and discriminant validity. Especially, the chi-square difference results indicate that design and organization can be significantly distinguished from teaching presence, whereas affective expression can be significantly distinguished from social presence, and resolution can be significantly distinguished from cognitive presence. Based on these findings, the present study argues that the six-factor structure model can provide a better understanding for the fine design and implementation of MOOC.

The importance of optimising antimicrobial therapy is highlighted in the hospital intensive care unit (ICU) patients. But roles of ICU pharmacists are still in its infancy in China.This study's objective was to evaluate the values of clinical pharmacist interventions in the antimicrobial stewardship (AMS) on ICU patients with infections.The aim of this study was to evaluate the value of clinical pharmacist interventions in the antimicrobial stewardship (AMS) in critically ill patients with infections.From 2017 to 2019, a propensity score matching retrospective cohort research was conducted on critically ill patients with infectious illnesses. The trial was split into groups that received pharmacist assistance and those who did not. Baseline demographics, pharmacist actions, and clinical results were compared between the two groups. Factors influencing mortality were demonstrated using univariate analysis and bivariate logistic regression. The State Administration of Foreign Exchange in China monitored the exchange rate between the RMB and the US dollar and also gathered the charges of the agents as an economic indicator.Out of the 1523 patients who were evaluated, 102 critically ill patients with infectious diseases were included in each group after matching. The top five prescription regimens adjusted were settled by sickness progression, microbiological results, de-escalation, drug withdrawal, and therapeutic drug monitoring suggestions. The pharmacist exposure group's antibiotic use density (AUD) decreased significantly (p = 0.018) compared to the control group, going from 241.91 to 176.64 defined daily doses/100 bed days. Following pharmacist interventions, the AUD proportion for carbapenems dropped from 23.7 to 14.43%, while for tetracyclines, it dropped from 11.5 to 6.26%. In the group exposed to the pharmacist, the median cost of antibiotics decreased significantly from $836.3 to $362.15 per patient stay (p < 0.001), and the median cost of all medications dropped from $2868.18 to $1941.5 per patient stay (p = 0.06). RMB was converted into US dollars according to the current exchange rate. According to univariate analyses, pharmacist interventions did not differ between the groups that survived and died (p = 0.288).This study showed that antimicrobial stewardship had a significant financial return on investment without raising the mortality rate.

The COVID-19 pandemic has highlighted the profound impact of the SARS-CoV-2 virus as a significant threat to human health. There is an urgent need to develop a comprehensive understanding of the current outbreak by studying the dynamics of the virus within the human body. In this research, we present a mathematical model that explores the progression of SARS-CoV-2 infection, taking into account both the innate and adaptive immune responses. We calculated the basic reproduction number and analyzed the stability of the equilibria. Additionally, we demonstrated the existence of a periodic solution through numerical simulations. By conducting a global sensitivity analysis, we determined the significance of the model parameters and investigated the influence of key parameters on viral load. The results emphasized the crucial roles of cytokines and antibodies in shaping the dynamics of SARS-CoV-2. Furthermore, we evaluated the effectiveness of antiviral treatment in controlling the dynamics of SARS-CoV-2 infection. Our findings revealed a direct relationship between the basic reproduction number and the impact of antiviral treatment. To evaluate the effect of antiviral treatment on viral load, we conducted numerical simulations.

Abstract Background The mechanisms whereby CYFIP2 acts in tumor development and drives immune infiltration have been poorly explored. Thus, this study aimed to identifying the role of CYFIP2 in tumors and immune response. Methods In this study, we first explored expression patterns, diagnostic role and prognostic value of CYFIP2 in cancers, particularly in lung adenocarcinoma (LUAD). Then, we performed functional enrichment, genetic alterations, DNA methylation analysis, and immune cell infiltration analysis of CYFIP2 to uncover its potential mechanisms involved in immune microenvironment. Results We found that CYFIP2 significantly differentially expressed in different tumors including LUAD compared with normal tissues. Furthermore, CYFIP2 was found to be significantly correlated with clinical parameters in LUAD. According to the diagnostic and survival analysis, CYFIP2 may be employed as a potential diagnostic and prognostic biomarker. Moreover, genetic alterations revealed that mutation of CYFIP2 was the main types of alterations in different cancers. DNA methylation analysis indicated that CYFIP2 mRNA expression correlated with hypomethylation. Afterwards, functional enrichment analysis uncovered that CYFIP2 was involved in tumor-associated and immune-related pathways. Immune infiltration analysis indicated that CYFIP2 was significantly correlated with immune cells infiltration. In particular, CYFIP2 was strongly linked with immune microenvironment scores. Additionally, CYFIP2 exhibited a significant relationship with immune regulators and immune-related genes including chemokines, chemokines receptors, and MHC genes. Conclusion Our results suggested that CYFIP2 may serve as a prognostic cancer biomarker for determining prognosis and might be a promising therapeutic strategy for tumor immunotherapy.

Abstract Background Targeted drugs are not quite effective for prolonging the survival of patients with gastric cancer due to off-target effects as well as tumor immune escape mechanisms. Circular RNAs widely exist in tumor regions as biomarkers and can be developed as effective drug targets. Methods Western blot, QRT-PCR, fluorescence in situ hybridization, and flow cytometry were used to investigate the function of hsa_circ_0136666 in promoting the proliferation of gastric cancer cells. Tissue immunofluorescence, enzyme-linked immunosorbent assay (ELISA), as well as flow cytometric analysis, was conducted to explore the process of tumor immune evasion in tumor-bearing mice. The differences of circRNA expression in clinical samples were analyzed through tissue microarray FISH. The effect of siRNA on improving the efficacy of anti-PDL1 drugs and suppressing the immune microenvironment was evaluated by the coadministration model. Results We demonstrated that hsa_circ_0136666 was widely and highly expressed in gastric cancer tissues and cells. Functionally, hsa_circ_0136666 promoted gastric cancer tumor proliferation and tumor microenvironment formation, leading to tumorigenesis immune escape, and this effect was dependent on CD8 + T cells. Mechanistically, we confirmed that hsa_circ_0136666 competitively upregulated PRKDC expression by sponging miR-375-3p, regulating immune checkpoint proteins, prompting phosphorylation of PD-L1 to preventing its degradation, driving PD-L1 aggregation and suppressing immune function, thereby impairing cancer immune responses. In terms of application, we found that LNP-siRNA effectively improved anti-PDL1 drug efficacy and inhibited immune escape. Conclusion Our results reveal an oncogenic role played by hsa_circ_0136666 in gastric cancer, driving PD-L1 phosphorylation via the miR-375/PRKDC signaling axis, prompting immune escape. This work proposes a completely new pathogenic mechanism of gastric cancer, uncovers a novel role for hsa_circ_0136666 as an immune target, and provides a rationale for enhancing the efficacy of anti-PD-L1 therapy for gastric cancer.

Energy shortages and environmental pollution are significant challenges in modern industries. Photocatalysts with a broad absorption spectrum, extended stability, superior charge separation efficiency, and strong redox capabilities exhibit considerable potential for addressing these issues. In this study, we designed a unique heterojunction photocatalyst composed of two semiconductors with staggered band structures: ZnFe2O4 (ZFO) and ZnGa2O4 (ZGO). This heterojunction facilitates the spatial separation of photogenerated carriers through the type II carrier transfer mechanism, thereby significantly prolonging their lifetime. Additionally, carrier separation enhances the formation of an internal electric field (IEF) at the interface, leading to enhanced photocatalytic quantum efficiency. Absorption and band structure analysis revealed that the band gap of the ZFO/ZGO heterojunction is 1.26 eV. Compared to pure ZFO and ZGO matrices, this heterojunction exhibits a "red-shifted" absorption edge and an enlarged optical response range. Furthermore, the ZFO/ZGO heterojunction displays semi-metallic characteristics that are advantageous for application-based control and retrieval, while inheriting the magnetic properties of ZFO. This strategy provides a new perspective to design photocatalysts.

The current study employed a solvent-free method to prepare a series of crosslinked polyurethane/lauric acid-stearic acid composite form-stable phase change materials (FSPCMs). FTIR, SEM, and XRD results collectively indicate that lauric acid (LA) and stearic acid (SA) have been successfully adsorbed into the polyurethane (PU) mesh-like structure, maintaining their respective crystalline characteristics and exhibiting good compatibility. DSC and TGA data show the wide phase transition temperature range of FSPCMs from 39.6 °C to 70.0 °C, with decomposition commencing at 190.4 °C and the latent heat of FSPCM reaching 181.9 J/g. In conclusion, the broad phase transition temperature range and high latent heat of FSPCMs make them particularly suitable for thermal energy storage.

To investigate the clinical outcomes of percutaneous transforaminal endoscopic discectomy assisted with selective nerve root block for treating radicular pain with diagnostic uncertainty in the elderly.A total number of 36 elderly patients were included in the study. Clinical outcomes collected for analysis include operative time, hospital stay time, Visual Analog Scale, and Oswestry Disability Index before and after the surgery, the global outcome based on the Macnab outcome criteria.Seventeen males and nineteen females with a mean age of 73.72 ± 7.15 were included in this study. Radicular pain was the main complaint of all the patients with the least symptom duration of two months. Radiological findings showed that 80.6% of the patients with multilevel disc herniation, 16.7% received lumbar fusion surgery before, and 8.3% with degenerative scoliosis. Besides, 69.4% of the patients have at least one comorbidity. 85.4% of the patients showed a positive response to selective nerve root block, and 91.6% of the patients reported a favorable outcome at the last follow-up. The mean value of pre-operative leg pain was 7.56 ± 0.74 and dramatically decreased after surgery (2.47 ± 0.81, P < 0.001). Besides, the mean value of Oswestry Disability Index decreased from 43.03 ± 4.43 to 5.92 ± 5.24 (P < 0.001) one year after the surgery.Multilevel degeneration of the lumbar spine is common in elderly patients. Identifying the responsible segment and decompressing the nerve root through minimally invasive surgery can provide a satisfactory clinical outcome for those with radicular pain as their primary complaint. And selective nerve root block is a reliable diagnostic tool for those with an ambiguous diagnosis.

In the context of spectral hole-burning, normal dispersion with subluminal propagation is usually observed in the spectral hole-burning depth region. However, anomalous dispersion can occur in the continuous absorption peak region, which leads to superluminal light propagation. In this paper, we report an unusual behaviour of dispersion at discontinued absorption kink regions. We demonstrate both normal dispersion at the kink absorption region and anomalous dispersion at the spectral hole-burning depth region. The unusual dispersion leads to a positive group index in the absorption kink region and a negative group index in the spectral hole-burning depth region. The spectral hole-burning is due to variation of magnetization rather than the molecular distribution. The outcomes of our work offer promising applications in communication technologies and storage devices.

Forever Summer Hydrangea (Hydrangea macrophylla) is a common flowering plant in the Yangtze River Valley area of China, and it is widely cultivated globally (Chen et al. 2015). In July 2023, H. macrophylla leaves exhibiting visible diseased lesions were reported in a nursery in Wuhu, Anhui Province, China. The incidence reached 40% in a 0.2 ha area. The primary disease symptom was multiple irregular necrotic spots (0.5 to 1 mm in diameter) appearing on the leaves. These spots on the leaves were faded yellow around the perimeter and grayish brown in the center.). 15 leaf samples were sterilized with 75% alcohol and rinsed three times in sterile distilled water, then transferred to antibiotic-added potato dextrose agar (PDA) for incubation at 27°C. The colonies were fluffy, flocculent, or hairy, dark green, gray-green to gray-brown in color, and spreading or protruding punctate with a colorless halo on PDA. The conidiophores were brown to dark brown, smooth or rough surface, mostly unbranched, clearly differentiated, erect or curved. The conidia displayed a light brown to brown hue, lemon shape, fusiform, elongated ellipsoid or others with obvious spore markings and spore umbilicus. Genomic DNA was extracted from fungal colonies on infected leaves of three collections separately (Braun et al. 2003) and the internal transcribed spacer regions (ITS), actin (ACT) genes and partial translation elongation factor-l-alpha (EF) were amplified and sequenced using the primers ITS1/4 (Yin et al. 2012), ACT-512F/ACT-783R and EF 1-728F/986R (Carbone and Kohn 1999), respectively. DNA sequences of isolates were identical and deposited in GenBank (accession no. OR362754 for ITS, OR611929 for ACT and PP209106 for EF). The consensus sequences from ITS, EF and ACT showed 100%, 98.98% and 100% identical to Cladosporium strains (accession no. OQ186140.1, MT154169.1 and OL322092.1), respectively. To confirm the pathogenicity of the isolates, hydrangeas were planted in 15-cm pots containing commercial potting mix (one plant/pot). Three healthy plants were inoculated at the five to eight leaf stage by spraying 50 μL of the isolate conidial suspension (4 × 106 spores/mL) on healthy leaves. Three plants treated with sterile distilled water were used as controls. After inoculation, all plants were placed in a humidity chamber (>95% relative humidity, 26°C) for 48 h and then transferred to a greenhouse at 22/27°C. All inoculated leaves exhibited symptoms similar to those observed in the nursery 10 days after inoculation, while no symptoms were observed for control leaves. The fungus was re-isolated and confirmed to be C. tenuissimum. Based on the above morphological characterization and molecular identification, the causal agent for this leaf spot disease was identified as C. tenuissimum. Although C. tenuissimum has been reported to cause disease on H. paniculata in northern China (Li et al.2021), this is the first time that C. tenuissimum has been found on H. macrophylla in southern China. This new disease of H. macrophylla caused by C. tenuissimum is a threat to urban greening and is worth further investigation.

Corticosteroids have beneficial effects in improving outcomes in hospitalized patients with severe COVID-19 by suppressing excessive immune responses. However, the effect of corticosteroids on the humoral and T-cell responses of survivors of COVID-19 1 year after infection remains uncertain because it relates to the extent of immediate, antigen-specific defense provided by protective memory.What is the effect of corticosteroids on long-term humoral and T-cell immune responses?In this retrospective cohort study conducted at a single center, we analyzed data from a cohort who had survived COVID-19 to compare the 1-year seropositivity and titer changes in neutralizing antibodies (NAbs) and SARS-CoV-2-specific antibodies. Additionally, we evaluated the magnitude and rate of SARS-CoV-2-specific T-cell response in individuals who received corticosteroids during hospitalization and those who did not.Our findings indicated that corticosteroids do not statistically influence the kinetics or seropositive rate of NAbs against the Wuhan strain of SARS-CoV-2 from 6 months to 1 year. However, subgroup analysis revealed a numerical increase of absolute NAbs titers, from 20.0 to 28.2, in categories where long-term (> 15 days) and high-dose (> 560 mg) corticosteroids are administered. Similarly, corticosteroids showed no significant effect on nucleoprotein and receptor-binding domain IgG at 1 year, except for spike protein IgG (β, 0.08; 95% CI, 0.04-0.12), which demonstrated a delayed decline of titers. Regarding T-cell immunity, corticosteroids did not affect the rate or magnitude of T-cell responses significantly. However, functional assessment of memory T cells revealed higher interferon-γ responses in CD4 (β, 0.61; 95% CI, 0.10-1.12) and CD8 (β, 0.63; 95% CI, 0.11-1.15) memory T cells in the corticosteroids group at 1 year.Based on our findings, short-term and low-dose corticosteroid therapy during hospitalization does not have a significant effect on long-term humoral kinetics or the magnitude and rate of memory T-cell responses to SARS-CoV-2 antigens. However, the potential harmful effects of long-term and high-dose corticosteroid use on memory immune responses require further investigation.