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Ruilin Ding

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DOI: 10.2147/cmar.s252181
2020
Cited 31 times
<p>Anlotinib Suppresses Colorectal Cancer Proliferation and Angiogenesis via Inhibition of AKT/ERK Signaling Cascade</p>
Anlotinib is a highly potent multi-target tyrosine kinase inhibitor, with very good anti-tumor activity against a variety of solid tumors. However, its effect on colorectal cancer (CRC) is not yet clearly understood. The objective of this study was to investigate the anti-tumor effect and underlying mechanism of anlotinib in the pathogenesis of CRC.Effects of anlotinib on CT26 cells proliferation and microvessel formation in endothelial cells were determined by MTT assay and tube formation assay. Cell migration and invasion were analyzed by using the wound healing assay and transwell assay. Cell cycle and apoptosis were detected by flow cytometry. A CRC xenograft mouse model was used for conducting in-vivo studies to verify the effect of anlotinib. The expression of Ki-67 and CD31 in the tumor tissue was detected by immunohistochemistry and protein expression was measured by Western blot.In-vitro studies revealed that anlotinib inhibited the proliferation, migration, and invasion of CT26 cells and the tube formation of HUVECs in a dose-dependent manner. Anlotinib also significantly induced cell apoptosis and G2/M arrest. It effectively inhibited tumor growth and prolonged survival time in the CRC xenograft mouse model. Immunohistochemical analysis of the tumor tissue revealed that anlotinib downregulated CD31 and Ki-67 which are the biomarkers of microvessel density and proliferation. Furthermore, anlotinib was able to inhibit the activation of VEGFR-2/AKT and FGFR, PDGFRβ and their downstream signaling ERK.The findings of the present study suggested that anlotinib suppressed cell proliferation and angiogenesis via inhibition of AKT/ERK signaling pathway in colorectal cancer and could be a novel therapeutic strategy for treatment of CRC.
DOI: 10.1080/10717544.2016.1247927
2017
Cited 31 times
Preparation of endostatin-loaded chitosan nanoparticles and evaluation of the antitumor effect of such nanoparticles on the Lewis lung cancer model
The purpose of this study was to prepare ES-loaded chitosan nanoparticles (ES-NPs) and evaluate the antitumor effect of these particles on the Lewis lung cancer model. ES-NPs were prepared by a simple ionic cross-linking method. The characterization of the ES-NPs, including size distribution, zeta potential, loading efficiency and encapsulation efficiency (EE), was performed. An in vitro release test was also used to determine the release behavior of the ES-NPs. Cell viability and cell migration were assayed to detect the in vitro antiangiogenic effect of ES-NPs. In order to clarify the antitumor effect of ES-NPs in vivo, the Lewis lung cancer model was used. ES-NPs were successfully synthesized and shown to have a suitable size distribution and high EE. The nanoparticles were spherical and homogeneous in shape and exhibited an ideal releasing profile in vitro. Moreover, ES-NPs significantly inhibited the proliferation and migration of human umbilical vascular endothelial cells (HUVECs). The in vivo antiangiogenic activity was evaluated by ELISA and immunohistochemistry analyses, which revealed that ES-NPs had a stronger antiangiogenic effect for reinforced anticancer activity. Indeed, even the treatment cycle in which ES-NPs were injected every seven days, showed stronger antitumor effect than the free ES injected for 14 consecutive days. Our study confirmed that the CS nanoparticle is a feasible carrier for endostatin to be used in the treatment of lung cancer.
DOI: 10.1080/10717544.2017.1378938
2017
Cited 30 times
<i>In vivo</i> antitumor effect of endostatin-loaded chitosan nanoparticles combined with paclitaxel on Lewis lung carcinoma
The purpose of this study was to prepare endostatin-loaded chitosan nanoparticles (ES-NPs) and evaluate their antitumor effect when combined with paclitaxel (PTX) on Lewis lung carcinoma (LLC) mouse xenografts. ES-NPs were prepared by ionic cross-linking. Characterization of the ES-NPs included size distribution, drug-loading efficiency (DL), and encapsulation efficiency (EE). An in vitro release test was also used to determine the release behavior of the ES-NPs. A subcutaneous LC xenograft model of C57BL/6J mice was established. The mice were randomly divided into six groups: control (0.9% NaCl), ES, PTX, ES-NPs, ES + PTX, and ES-NPs + PTX. The tumor volume was dynamically measured for the duration of the experiment. Immunohistochemistry was performed to determine the Ki-67 and microvascular density (MVD) in each group. Serum vascular endothelial growth factor (VEGF) and ES levels were determined by enzyme-linked immunosorbent assay (ELISA). ES-NPs were successfully synthesized and had suitable size distribution and high EE. The NPs were homogenously spherical and exhibited an ideal release profile in vitro. In vivo, tumor growth was significantly inhibited in the ES-NPs + PTX group. The tumor inhibitory rate was significantly higher in the ES-NPs + PTX group than in the other groups (p < .05). The results of the immunohistochemical assay and ELISA confirmed that ES-NPs combined with PTX had a strong antiangiogenic effect. ES-NPs can overcome the shortcomings of free ES, such as short retention time in circulation, which enhances the antitumor effect of ES. The antitumor effect was more pronounced when treatment included PTX and ES-loaded NPs.
DOI: 10.1016/j.omto.2022.10.012
2022
Cited 10 times
PROTACs in gastrointestinal cancers
Proteolysis targeting chimera (PROTAC) presents a powerful strategy for targeted protein degradation (TPD). The heterobifunctional PROTAC molecule consists of an E3 ligase ligand covalently linked to a protein of interest (POI) via a linker. PROTAC can induce ubiquitinated proteasomal degradation of proteins by hijacking the ubiquitin-proteasome degradation system (UPS). This technique has the advantages of broad targeting profile, good cell permeability, tissue specificity, high selectivity, oral bioavailability, and controllability. To date, a growing number of PROTACs targeting gastrointestinal cancers have been successfully developed, and, in many cases, their POIs have been validated as clinical drug targets. To the best of our knowledge, 15 PROTACs against various targets are currently tested in clinical trials, and many more are likely to be added in the near future. Therefore, this paper details the mechanism, research progress, and application in clinical trials of PROTACs, and summarizes the research achievements related to PROTACs in gastrointestinal cancers. Finally, we discuss the advantages and potential challenges of PROTAC for cancer treatment.
DOI: 10.1371/journal.pone.0200845
2018
Cited 23 times
In vitro and in vivo apatinib inhibits vasculogenic mimicry in melanoma MUM-2B cells
The effect of apatinib on the formation of vasculogenic mimicry (VM) was studied in a malignant melanoma cell line. MUM-2B cells cultured in three-dimensional Matrigel were treated with varying concentrations (0, 0.01, 0.05, 0.1, 0.5 μmol/L) of apatinib to test its effect on VM in vitro, followed by MTT proliferation and transwell invasion assays to determine the effect of apatinib on cell proliferation and invasion of MUM-2B cells. In vivo, we used a melanoma cancer model to test the effect of short-term apatinib (100, 200, 300 mg/kg) treatment on VM. Western blotting, immunohistochemistry staining, and CD31-PAS dual staining were performed to assess the expression of VEGFR-2, ERK-1/2, PI3K, and MMP-2, and formation of VM. The results showed apatinib-treated groups formed a lesser number of VM in 3D matrigel, while the cell viability in MTT proliferation assay and the number of migration cells in transwell invasion assay were significantly lower in apatinib-treated groups. In addition, short-term apatinib treatment inhibited angiogenesis, VM formation, and tumor growth in models of melanoma cancer. Mice in apatinib-treated groups showed a markedly reduced expression of VEGFR-2, ERK-1/2, PI3K, and MMP-2. In summary, apatinib could inhibit the expression of VEGFR-2, and downregulate the ERK1/2/PI3K/MMP-2 signaling cascade, which may be one of the underlying mechanisms by which apatinib inhibits angiogenesis and the development of VM in models of melanoma cancer, and restrains the formation of VM by MUM-2B cells. Apatinib shows inhibitory effects on cell proliferation and invasion of MUM-2B cells, which is a close relationship with the VM.
DOI: 10.3892/ol.2016.5508
2016
Cited 19 times
Danshensu, a major water-soluble component of Salvia miltiorrhiza, enhances the radioresponse for Lewis Lung Carcinoma xenografts in mice
The molecule 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoic acid (danshensu), a herbal preparation used in traditional Chinese medicine, has been found to possess potential antitumor and anti-angiogenesis effects. The aim of the present study was to investigate the efficacy of the combination of radiation therapy (RT) with danshensu in the treatment of Lewis lung carcinoma (LLC) xenografts, whilst exploring and evaluating the mechanism involved. In total, 8-week old female C57BL/6J mice were randomly assigned into 3 groups to receive: RT, RT + cisplatin and RT + danshensu, respectively, when LLC reached 100-150 mm3. Each group was divided into 7 subgroups according to the different irradiation doses that were administered. Tumor growth curves were created and the sensitization enhancement ratios of the drugs were calculated. The experiment was then repeated, and the 4 groups of tumor-bearing mice were treated with natural saline, danshensu, RT + danshensu and RT, respectively. The mice were sacrificed on day 7, and tumor tissue and blood were collected to determine microvessel density, the expression of proangiogenic factors, and the levels of blood thromboxane B2 and 6-keto-prostaglandin-F1α. Tumor hypoxia was also detected using in vivo fluorescence imaging. With respect to LLC xenografts, treatment with danshensu + RT significantly enhanced the effects of tumor growth inhibition (P<0.05). Furthermore, tumor vasculature was remodeled and microcirculation was improved, which significantly reduced tumor hypoxia (P<0.05). The present study demonstrated that danshensu significantly enhanced the radioresponse of LLC xenografts in mice. The mechanism involved may be associated with the alleviation of tumor cell hypoxia following treatment with danshensu + RT, caused by the improvement of tumor microcirculation and the remodeling of tumor vasculature.
DOI: 10.3892/ijo.2021.5174
2021
Cited 9 times
Novel therapies for malignant pleural effusion: Anti‑angiogenic therapy and immunotherapy (Review)
Patients with a variety of malignancies can develop malignant pleural effusion (MPE). MPE can cause significant symptoms and result in a marked decrease in quality of life and a poor prognosis. MPE is primarily considered as an immune and vascular manifestation of pleural metastases. In the present review, the existing evidence supporting the applicability of anti‑angiogenic therapy and immunotherapy for the treatment of MPE was summarized. Patients with MPE have benefited from anti‑angiogenic agents, including bevacizumab and endostar; however, no relevant prospective phase III trial has, thus far, specifically analyzed the benefit of anti‑angiogenic therapy in MPE. Immunotherapy for MPE may be sufficient to turn a dire clinical situation into a therapeutic advantage. Similar to anti‑angiogenic therapy, more clinical data on the efficiency and safety of immunotherapy for controlling MPE are urgently required. The combined use of anti‑angiogenic therapy and immunotherapy may be a promising strategy for MPE, which requires to be further understood.
DOI: 10.1016/j.arcmed.2020.10.006
2021
Cited 8 times
Effect of Irisin on Pressure Overload–Induced Cardiac Remodeling
Irisin has been considered a prognostic factor in several cardiovascular diseases. Nevertheless, no data are available on the role of irisin in cardiac remodeling. This study aimed to determine the potential role of irisin in cardiac remodeling and explore potential mechanisms. A total of 40 rats that underwent transverse abdominal aortic constriction (TAC) surgery or sham operation were divided into four groups: sham + saline (NS), sham + irisin, TAC + NS, and TAC + irisin. After 6 weeks of treatment, echocardiography was performed to assess in vivo cardiac morphology. The left ventricular myocardium was prepared and observed by pathological examination. The effect of irisin on cardiomyocyte apoptosis and the expression of oxidative stress and cardiac hypertrophy markers were observed. Then, the effect of irisin on the Akt signaling system was also detected. The rats in the TAC group displayed obvious signs of cardiac dysfunction and cardiac hypertrophy, and irisin treatment could reverse these changes. Irisin could inhibit the expression of nicotinamide adenine dinucleotide phosphate oxidase 2 and xanthine oxidase in TAC rats and increase the expression of antioxidant enzymes. Furthermore, the expression of phosphorylated protein kinase B (p-Akt), phosphorylated mammalian target of rapamycin (p-mTOR), and phosphorylated glycogen synthase kinase 3β (p-GSK3β) was much higher in the cardiac remodeling groups (p <0.05 vs. sham rats). Irisin could relieve the inhibition effect and reduce the expression level of these three proteins. Irisin treatment could significantly improve cardiac remodeling by inhibiting oxidative stress via attenuating the Akt signaling activation.
DOI: 10.3389/fonc.2022.905520
2022
Cited 4 times
Therapeutic targeting of VEGF and/or TGF-β to enhance anti-PD-(L)1 therapy: The evidence from clinical trials
Normalizing the tumor microenvironment (TME) is a potential strategy to improve the effectiveness of immunotherapy. Vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-β pathways play an important role in the development and function of the TME, contributing to the immunosuppressive status of TME. To inhibit VEGF and/or TGF-β pathways can restore TME from immunosuppressive to immune-supportive status and enhance sensitivity to immunotherapy such as programmed death protein-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibitors. In this review, we described the existing preclinical and clinical evidence supporting the use of anti-VEGF and/or anti-TGF-β therapies to enhance cancer immunotherapy. Encouragingly, adopting anti-VEGF and/or anti-TGF-β therapies as a combination treatment with anti-PD-(L)1 therapy have been demonstrated as effective and tolerable in several solid tumors in clinical trials. Although several questions need to be solved, the clinical value of this combination strategy is worthy to be studied further.
DOI: 10.1007/s40261-023-01274-7
2023
A Phase I Study to Evaluate the Pharmacokinetic Drug‒Drug Interaction of HP501, Febuxostat, and Colchicine in Male Chinese Patients with Hyperuricemia
DOI: 10.1097/md.0000000000034313
2023
Prognostic models for predicting overall and cancer-specific survival of patients with initially diagnosed metastatic cervical squamous cell carcinoma: A study based on SEER database
Cervical squamous cell carcinoma (CSCC) is the most common histological type of cervical cancer (CC). And mCSCC is the end stage of CSCC. The aim of this study was to develop prognostic nomograms that provide better predictions for overall survival (OS) and cancer-specific survival (CSS) in mCSCC patients. Data from patients with initially diagnosed mCSCC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. The nomograms for OS and CSS were constructed based on Cox regression analysis. The validation of the newly established nomograms was evaluated by concordance index (C-index), calibration curves, and decision curve analyses (DCAs). A total of 2198 patients with mCSCC were included and randomly split into training (n = 1539) and validation (n = 659) cohorts in a 7:3 ratio. Multivariate analyses revealed that the prognostic variables significantly related to the OS and CSS were marital status, T stage, brain metastasis, lung metastasis, tumor size, number of positive lymph nodes, chemotherapy, and radiotherapy. The nomograms were constructed based on these factors. The C-index value of the nomograms for predicting OS and CSS was 0.714 and 0.683, respectively. The calibration curves of the nomograms showed good consistency between nomogram prediction and actual survival for both OS and CSS, and the DCAs showed great clinical usefulness of the nomograms. The mCSCC patients were classified into low- and high-risk groups based on the scores from the nomograms. In the validation cohort, mCSCC patients with low-risk had much higher OS and CSS than those with high-risk. We constructed nomograms for predicting the OS and CSS of patients with initially diagnosed mCSCC. Our models had satisfactory predictive performance and could be useful in survival prediction for mCSCC.
DOI: 10.3892/mmr.2021.12191
2021
Cited 6 times
Long non‑coding RNA HCG11 suppresses the malignant phenotype of non‑small cell lung cancer cells by targeting a miR‑875/SATB2 axis
Long non‑coding RNAs (lncRNAs) are involved in the development and progression of a variety of diseases. However, the role of the lncRNA HLA complex group 11 (HCG11) in non‑small cell lung cancer (NSCLC) remains unclear. The present study showed that the expression levels of HCG11 were reduced in tumor tissues compared with adjacent normal tissues, and similar results were obtained in experiments using lung cancer cell lines. Additionally, patients with high HCG11 expression had an increased survival rate compared with patients with low HCG11 expression. Further studies have shown that overexpression of HCG11 inhibited NSCLC cell proliferation <em>in vitro</em> and <em>in vivo</em>. Interestingly, it was observed that HCG11 expression was negatively associated with the expression levels of oncogenic microRNA‑875 (miR‑875) in patient specimens. Specifically, HCG11 served as a sponge of miR‑875. Notably, it was determined that special AT‑rich sequence‑binding protein 2 (SATB2) was a direct target gene of miR‑875, and overexpression of miR‑875 largely abrogated the effects of HCG11 in NSCLC cells. In conclusion, HCG11 was shown to suppress the malignant properties of NSCLC cells by targeting a miR‑875/SATB2 axis, and may therefore be a promising target for the treatment of NSCLC.
DOI: 10.3892/etm.2017.4421
2017
Cited 6 times
Lymph node tuberculosis mimicking malignancy on 18F-FDG PET/CT in two patients: A case report
18F-fluorodeoxyglucose positron emission/computed tomography (18F-FDG PET/CT) imaging, an established procedure for evaluation of malignancy, reports an increased 18F-FDG uptake in acute or chronic inflammatory condition. Lymph node tuberculosis (LNTB) is the most common form of extrapulmonary tuberculosis. However, the absence of clinical symptoms and bacteriological basis makes it difficult to diagnose. In the current case report, two patients with LNTB mimicking malignant lymphoma are presented by 18F‑FDG PET/CT. The objective of the present report is to emphasize that LNTB should be considered as a noteworthy differential diagnosis in patients with enlarged lymph nodes, particularly in tuberculosis‑endemic countries, and that lymph node biopsy serves a vital role in diagnosing LNTB.
DOI: 10.3389/fcimb.2022.1068324
2022
Cited 3 times
New insights of necroptosis and immune infiltration in sepsis-induced myocardial dysfunction from bioinformatics analysis through RNA-seq in mice
Sepsis is a life-threatening organ dysfunction caused by dysregulated host immune response to infection. Sepsis-induced myocardial dysfunction (SIMD) is a common complication in patients with severe sepsis and is associated with increased mortality. The molecular mechanisms underlying SIMD are complex and not well characterized. Excessive inflammation due to impaired regulation of immune response is one of the major causes of SIMD. Necroptosis is a novel type of cell death that is closely related to tissue injury and inflammation. However, the role of necroptosis in SIMD is not known. Therefore, in this study, we performed an in-depth bioinformatics analysis to investigate the relationship between necroptosis and SIMD using a mouse model generated by intraperitoneal injection of lipopolysaccharide (LPS) and the underlying mechanisms. Myocardial function was assessed by echocardiography. Histopathological changes in SIMD were analyzed by hematoxylin and eosin (H&E) staining. Gene expression profiles of the heart tissues from the SIMD and control mice were analyzed by bioinformatics analysis. Transcriptome sequencing demonstrated significant differences in the expression levels of 3654 genes in the heart tissues of SIMD mice including 1810 up-regulated and 1844 down-regulated genes. The necroptosis pathway genes were significantly enriched in the heart tissues from the SIMD group mice. We identified 35 necroptosis-related differentially expressed genes (NRDEGs) including MLKL and RIPK3. Cardiomyocyte necroptosis was confirmed by qRT-PCR and western blot analysis. The expression levels of most NRDEGs showed positive correlation with the infiltration levels of mast cells, macrophages, and neutrophils, and negative correlation with the infiltration levels of B cells and plasma cells in the heart tissues of the SIMD group mice. In conclusion, this study demonstrated that necroptosis was associated with changes in the infiltration levels of several immune cell types in the heart tissues of the SIMD model mice. This suggested that necroptosis influenced SIMD development by modulating the immune microenvironment. This suggested that NRDEGs are potential diagnostic biomarkers and therapeutic targets for patients with SIMD.
DOI: 10.3389/fpubh.2022.942800
2022
Degarelix vs. leuprorelin for the treatment of prostate cancer in China: A cost-utility analysis
To explore the cost-effectiveness of degarelix acetate for injection (degarelix) compared to leuprorelin in prostate cancer (Pca) castration treatment from Chinese healthcare system perspective.A Markov model, adapted from the one established in Finland was conducted for the cost-effectiveness analysis of degarelix and leuprorelin for Pca treatment. The main data were derived from global phase III clinical trials of degarelix (CS21), published study and expert surveys. Outcomes, utility and costs of prostate cancer patients were calculated on a 30-year time horizon. The CS21 study based population of intention-to-treat (ITT) population and three scenarios were modeled. Taking three times of the Gross domestic product (GDP) per capita (242,928 yuan, 2021) as the acceptable threshold for cost-effectiveness. One-way and probabilistic sensitivity analyses were performed on key parameters, including transition probabilities, costs, utility, and discount rate to test the robustness of the model.Base case analysis for ITT population revealed that total costs of degarelix and leuprorelin were 566,226 yuan and 489,693 yuan, while the total quality-adjusted life years (QALYs) were 5.19 and 4.51 during the 30-year time horizon, resulting an incremental cost effectiveness ratio (ICER) of 112,674 yuan/QALY which was 1.39 times the GDP per capita, lower than willingness-to-pay level of three times the GDP per capita. The results for scenario analyses revealed that compared to leuprorelin, degarelix for Pca treatment in China was cost-effective. One-way sensitivity analysis showed that the model was most sensitive to price of 80 mg degarelix, utility of 1st-line therapy, hazard ratio of PSA recurrence, price of 3.75 mg leuprorelin, response rate of docetaxel per cycle, and discount rate of cost. In probabilistic sensitivity analysis, compared to leuprorelin, the probability of degarelix to be cost-effective was 53 and 81% for willingness-to-pay threshold of one and three times the GDP per capita.Compared to leuprorelin, degarelix for prostate cancer treatment is cost-effective. Moreover, scenario, one-way, and probabilistic sensitivity analyses revealed that the model was robust.
DOI: 10.7150/jca.36076
2020
Cited 3 times
Comparison of different images in gross target volume delineating on VX2 nasopharyngeal transplantation tumor models
Background: To determine the optimum conditions for diagnosis of nasopharyngeal carcinoma, we established VX2 rabbit model to delineate gross target volume (GTV) in different imaging methods. Methods:The orthotopic nasopharyngeal carcinoma (NPC) was established in sixteen New Zealand rabbits.After 7-days inoculation, the rabbits were examined by CT scanning and then sacrificed for pathological examination.To achieve the best delineation, different GTVs of CT, MRI, 18 F-FDG PET/CT, and 18 F-FLT PET/CT images were correlated with pathological GTV (GTVp). Results:We found 45% and 60% of the maximum standardized uptake value (SUV max ) as the optimal SUV threshold for the target volume of NPC in 18 F-FDG PET/CT and 18 F-FLT PET/CT images, respectively (GTV FDG45% and GTV FLT60% ).Moreover, the GTV MRI and GTV CT were significantly higher than the GTVp (P ≤ 0.05), while the GTV FDG45% and especially GTV FLT60% were similar to the GTVp (R = 0.892 and R = 0.902, respectively; P ≤ 0.001).Conclusions: Notably, the results suggested that 18 F-FLT PET/CT could reflect the tumor boundaries more accurately than 18 F-FDG PET/CT, MRI and CT, which makes 18 F-FLT PET-CT more advantageous for the clinical delineation of the target volume in NPC.
DOI: 10.3892/ijo.2020.5091
2020
Cited 3 times
Development of immunotherapy for brain metastasis (Review)
Brain metastasis (BM) is associated with a poor prognosis, with the typical overall survival rate ranging from weeks to months in the absence of treatment. Although the concept of immune privilege in the central nervous system has eroded over time, the advent of immunotherapy has opened a new set of potential therapeutic options for patients with BM. Recently, immunotherapy has been demonstrated to confer survival advantages to patients with multiple malignancies commonly associated with BMs. Data from a number of clinical trials have demonstrated that immune checkpoint inhibitors are effective for patients with BM. In addition, cellular therapies, including the application of chimeric antigen receptors T‑cell therapy and dendritic cell vaccine, have also been utilized in the treatment of BM. In the present review, preclinical and clinical evidence supporting the applicability of immunotherapy for the treatment of BMs from melanoma, non‑small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) were examined, where the challenges and safety of this treatment modality were also discussed.
DOI: 10.1117/12.2651847
2023
Research on noise simulation analysis of time-modulated Fourier spectrometer
Many sources of spectrometer system noise are introduced, which will be superimposed on the interference data. In this paper, the statistical properties of noise are analyzed, and Gaussian models are established by extracting features from the actual collected interferometric data. For 30-degree and 35-degree target radiation sources, the same sets of interferometric data are collected, and the histogram of noise is established and the curve is fitted to match the corresponding Gaussian model. The ideal interference fringe is simulated for the studied spectrometer object, and the effect of Gaussian noise on the interference fringe is analyzed, and the experiments prove that the effect of the noise-added interference fringe is close to that of the measured interference fringe.
DOI: 10.1007/s40271-023-00659-2
2023
Preferences and Willingness to Pay for Medication in Patients with Renal Cell Carcinoma in China: A Discrete-Choice Experiment
DOI: 10.1038/s41598-023-49052-x
2023
A dose-escalation study of HP501, a highly selective URAT1 inhibitor, in male Chinese patients with hyperuricemia
Abstract HP501 is a highly selective renal urate transporter 1 (URAT1) inhibitor used for treating hyperuricemia. This study aimed to evaluate the tolerability, pharmacokinetics, and pharmacodynamics of HP501 in male Chinese patients. Patients with hyperuricemia were sequentially assigned to receive oral doses of HP501 (30, 50, 60, 90, and 120 mg) as a single dose on Day 1 and as once-daily doses from Days 4 to 13. Safety, pharmacokinetic, and pharmacodynamic data were collected. Multiple oral doses of HP501 were well-tolerated in all the cohorts. The most common adverse events (≥ 10% of patients) of any grade regardless of drug relationship were gout flare (14 patients, 25.93%), diarrhea (12 patients, 22.22%), elevated ALT (8 patients, 14.81%), hypertriglyceridemia (7 patients, 12.96%), dry mouth (7 patients, 12.96%) and oral ulcer (7 patients, 12.96%). All adverse events were mild or moderate. The C max and exposure (AUC) of HP501 was approximately dose-proportional between 30 and 120 mg. A dose-dependent serum uric acid (UA)-lowering effect was observed in the dose range of 30 to 60 mg and the serum UA lowering effect was similar between 90 and 120 mg on day 13, indicating that the maximal serum UA lowering effect of HP501 was achieved at 90 mg in the patients with hyperuricemia. In conclusion, the tolerability, pharmacokinetics, and pharmacodynamics supported 90 mg HP501 for subsequent clinical studies of this highly selective URAT1 inhibitor. Clinical Trial registration: No. CTR20212259 ( http://www.chinadrugtrials.org.cn/ ) was registered in September 2021, and No. CTR20222257 was registered in September 2022.
DOI: 10.1007/978-3-319-68505-2_30
2017
Low-Energy Security-Enhanced Routing Protocol Based on DBSCAN Partition
The heterogeneity of node distribution of large-scale wireless sensor networks and its vulnerability to attack bring great challenges to the design of routing protocols. Under the uneven condition, balance network node energy consumption, prolong the network life cycle and improve the network security have become the main goal of designing routing protocols. In this paper, we propose a low-energy security-enhanced routing protocol based on DBSCAN partition (LESERP-DP). The DBSCAN algorithm is used to optimize the clustering in the case of non-uniform nodes distribution, and the key distribution mechanism is designed to enhance the anti-attack ability of the protocol. The simulation results show that the routing protocol is excellent in energy consumption and to a certain extent, reduces the threat of node capture to sensor networks.
DOI: 10.1016/j.ijrobp.2017.06.1076
2017
Chinese Medicinal Formulas as Retention Enemas in Patients With Radiation Proctitis: A Multicenter Retrospective Survey
This study aimed to assess whether Chinese medicinal formulas as retention enemas could effectively treat radiation proctitis following radiotherapy in patients with pelvic malignant disease. This study was an open-label, retrospective, multicenter study of patients with radiation proctitis treated with Chinese medicinal formulas as retention enemas. The diagnosis adhered to the Diagnostic Criteria for Radiation Proctitis (GBZ 111-2002). The degree of radiation proctitis was classified into a graded system devised by Radiation Therapy Oncology Group (RTOG). Retrospective data were collected from patients’ medical records in 5 hospitals for the 2011-2016 period. Patient follow-up was conducted via outpatient service and telephone. The patients were divided into 3 treatments based on the ingredient present in the Chinese medicinal formulas, as follows: Treatment A (intestinal mucosa protector, symptomatic treatment), Treatment B (symptomatic treatment), and Treatment C (Chinese Medicinal Formulae, symptomatic treatment). Data were analyzed using SPSS ver. 20.0, and quantitative data were summarized using mean±standard deviation. Comparison of treatments was conducted using analysis of variance (one-way ANOVA). Qualitative data were analyzed using the chi-square test or Fisher’s exact probabilities test. P©,0.05 was considered statistically significant. A total of 1463 patients who received pelvic radiotherapy were reviewed in our study. The incidence rate of radiation proctitis was 10.1% (n=148), consisting of acute radiation proctitis (ARP) and chronic radiation proctitis (CRP) at 5.6% (n=83) and 5.1% (n=75), respectively. The retention enema was used in 105 cases of patients with radiation proctitis, including ARP (n=49) and CRP (n=56). The patients mostly experienced RTOG acute grade 1 (n=34) or 2 (n=15), or chronic grade 1 (n=35) to 2 (n=21) toxicities. Most patients suffered from diarrhea, bleeding, pain, and tenesmus. The symptoms were partially or completely improved in 85.7% of patients with ARP after therapy. The response rates of ARP administered with Treatments A, B, and C, were 70.6%, 90.5%, and 100%, respectively.Approximately 69.6% of patients with CRP exhibited partial to good response after retention enema. The response rates of CRP administered with Treatments A, B, and C, were 46.1%, 66.6%, and 84%, respectively. The response of grade-1 CRP to Treatment C (93.3%) was better than its response to Treatments A (50%) and B (70%). Kangfuxin (n=34) and Xilei powder (n=33) were the most common intestinal mucosa protective agent and Chinese Medicinal Formulae in the treatment of radiation proctitis in Groups A and C, respectively. Kangfuxin and Xilei powder in Chinese medicinal formulas used as retention enemas may significantly improve the clinical symptoms of patients with radiation proctitis. In particular, Xilei powder for grade-1 CRP exhibited an obvious effect.
DOI: 10.1201/9781003308577-50
2022
Axial compressive behavior of grout-filled double-skin tubular (GFDST) columns with stainless-steel outer tubes: Experimental investigation
In this paper, the axial compression performance of GFDST columns with stainless-steel outer tubes was investigated. A total of 24 column specimens were fabricated and tested. The test specimens' parameters include the thickness of the stainless-steel tube, the width of the carbon steel tube, and the grouting, if any, between the stainless-steel tube and the carbon steel tube. Failure mode, load-displacement curve, and ultimate strength were investigated. Results show that the local buckling of the stainless-steel tube occurs, while the carbon steel tube shows no obvious deformation when there is no grout interlayer. The local buckling of the carbon steel tube occurs when there is a grout interlayer. Before reaching the peak load, the N-Δ curves first shows linearity, then a transition to plasticity. The ultimate strength increases by 31.56%–78.02% with increase in the thickness of stainless-steel tube. When there is no grout between the stainless-steel tube and the carbon steel tube, increasing the width of the carbon steel tube can increase the ultimate strength by 97.03%. The ultimate strength of the specimens filled with grout can be improved by 66.73%.
DOI: 10.2139/ssrn.3346505
2019
Comparison of Different Images in Gross Target Volume Delineating on VX2 Nasopharyngeal Transplantation Tumor Models
Background: To determine optimum conditions for diagnosis of nasopharyngeal carcinoma, we established VX2 rabbit model to delineate gross target volume (GTV) in different imaging methods. Methods: The orthotopic nasopharyngeal carcinoma (NPC) was established in sixteen New Zealand rabbits. After 7-days inoculation, the rabbits were examined by CT scanning and then sacrificed for pathological examination. To achieve best delineation, different GTVs of CT, MRI, 18F-FDG PET/CT, and 18F-FLT PET/CT images were correlated with pathological GTV (GTVp). Findings: We found a 45% and 60% of the maximum standardized uptake value (SUVmax) as the optimal SUV threshold for the target volume of NPC in 18F-FDG PET/CT and 18F-FLT PET/CT images, respectively (GTVFDG45% and GTVFLT60%). Moreover, the GTVMRI and GTVCT were significantly higher than the GTVp (P ≤ 0.05), while the GTVFDG45% and especially GTVFLT60% were similar to the GTVp (R = 0.892 and R = 0.902, respectively; P ≤ 0.001). Interpretation: Notably, the results suggested that 18F-FLT PET/CT could reflect the tumor boundaries more accurately than 18F-FDG PET/CT, MRI and CT, which makes 18F-FLT PET-CT more advantageous for the clinical delineation of the target volume in NPC. Funding Statement: This research received financial support from the Scientific Research Project Fund of the Affiliated Hospital of Southwest Medical University (2013-60). Declaration of Interests: The authors have no financial interests related to the material in the manuscript. The authors declare that there are no conflicts of interest. Ethics Approval Statement: This study was approved by an independent ethics committee/institutional review board at Department of Oncology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China. All animal-related procedures and protocol were approved under the guidelines of the National Institutes of Health (NIH) Animal Care (1995, USA) and the local Ethics Committee guidelines by Institutional Animal Care and Treatment Committee of Southwest Medical University (Luzhou, China).