Chi Tang

A large body of evidence indicates that pulsed electromagnetic fields (PEMF), as a safe and noninvasive method, could promote in vivo and in vitro osteogenesis. Thus far, the effects and underlying mechanisms of PEMF on disuse osteopenia and/or osteoporosis remain poorly understood. Herein, the efficiency of PEMF on osteoporotic bone microarchitecture, bone strength, and bone metabolism, together with its associated signaling pathway mechanism, was systematically investigated in hindlimb-unloaded (HU) rats. Thirty young mature (3-month-old), male Sprague-Dawley rats were equally assigned to control, HU, and HU + PEMF groups. The HU + PEMF group was subjected to daily 2-hour PEMF exposure at 15 Hz, 2.4 mT. After 4 weeks, micro-computed tomography (µCT) results showed that PEMF ameliorated the deterioration of trabecular and cortical bone microarchitecture. Three-point bending test showed that PEMF mitigated HU-induced reduction in femoral mechanical properties, including maximum load, stiffness, and elastic modulus. Moreover, PEMF increased serum bone formation markers, including osteocalcin (OC) and N-terminal propeptide of type 1 procollagen (P1NP); nevertheless, PEMF exerted minor inhibitory effects on bone resorption markers, including C-terminal crosslinked telopeptides of type I collagen (CTX-I) and tartrate-resistant acid phosphatase 5b (TRAcP5b). Bone histomorphometric analysis demonstrated that PEMF increased mineral apposition rate, bone formation rate, and osteoblast numbers in cancellous bone, but PEMF caused no obvious changes on osteoclast numbers. Real-time PCR showed that PEMF promoted tibial gene expressions of Wnt1, LRP5, β-catenin, OPG, and OC, but did not alter RANKL, RANK, or Sost mRNA levels. Moreover, the inhibitory effects of PEMF on disuse-induced osteopenia were further confirmed in 8-month-old mature adult HU rats. Together, these results demonstrate that PEMF alleviated disuse-induced bone loss by promoting skeletal anabolic activities, and imply that PEMF might become a potential biophysical treatment modality for disuse osteoporosis.

Abstract In the mucosal immune system, resident dendritic cells are specialized for priming Th2-polarized immunity, whereas the Ag-presenting activity of macrophages has been linked with the development of Th1 phenotype. As an immune switch toward Th1 can protect against Th2-mediated allergic response, this study investigated the capacity of lung macrophages to stimulate Th1 responses during the secondary exposure to inhaled allergen, thereby suppressing Th2-mediated allergic airway inflammation in a murine model of allergic asthma. Following airway macrophage depletion in OVA-sensitized mice, lung T cells defaulted to a phenotype that produced less Th1 (IFN-γ) and more Th2 (IL-4 and IL-5) cytokines, leading to more severe airway hyperreactivity and inflammation after intranasal Ag challenge. After OVA pulsing and adoptive transfer, lung macrophages selectively promoted a Th1 response in Ag-sensitized recipients and did not induce pulmonary eosinophilia. By contrast, OVA pulsing and adoptive transfer of a lung cell preparation, consisting of dendritic cells, B cells, and macrophages, promoted a Th2 response with an associated inflammatory response that was suppressed when macrophages were present and pretreated with IFN-γ, but exacerbated when macrophages were depleted before IFN-γ treatment. In addition, Th1-promoting activity of lung macrophages was not related to the autocrine production of IL-12p40. These results suggest that the Th1-promoting APC activity may be an inherent property of the lung macrophage population, and may play an important role, upon stimulation by IFN-γ, in antagonizing an ongoing Th2 immunity and Th2-dependent allergic responses.

Curcumin (diferuloylmethane) inhibits tumour cell growth by inducing apoptosis in many tumour types, including melanoma, via complex and ill-defined pathways. Recent studies have shown that curcumin is both a nitric oxide scavenger and an inhibitor of inducible nitric oxide synthase (iNOS) expression, low levels of which correlate with antiapoptotic function and poor survival and which may be regulated by inhibition of nuclear factor-kappaB (NFkappaB) activation. To elucidate the mechanisms by which curcumin inhibits melanoma proliferation, we tested the in vitro effects of curcumin on specific cell cycle pathways and melanoma cell survival, including NFkappaB activation. Curcumin induced melanoma cell apoptosis and cell cycle arrest, which is associated with the downregulation of NFkappaB activation, iNOS and DNA-dependent protein kinase catalytic subunit expression, and upregulation of p53, p21(Cip1), p27(Kip1) and checkpoint kinase 2. Curcumin also downregulated constitutive iNOS activity in melanoma cells. Our results demonstrate that curcumin arrested cell growth at the G(2)/M phase and induced apoptosis in human melanoma cells by inhibiting NFkappaB activation and thus depletion of endogenous nitric oxide. Therefore, curcumin should be considered further as a potential therapy for patients with melanoma.

The influence of MSI on treatment outcome of colorectal cancers remains unclear and deserves further investigation. We recruited 244 patients with stage IV sporadic colorectal cancers for our study, based on appropriate eligibility criteria. Patients were nonrandomly allocated to 2 treatment groups of either with or without high-dose 5-FU plus leucovorin chemotherapy (HDFL, 5-FU 2,600 mg/m(2) leucovorin 300 mg/m(2) maximum 500 mg). Each treatment group was further divided into 2 subgroups according to high-frequency MSI (MSI-H) status. MSI-H was defined as the appearance of MSI in at least 2 of the 5 examined chromosomal loci (BAT-25, BAT-26, D5S346, D2S123, D17S250). We compared clinicopathologic parameters, p53 overexpression and overall survival between the groups. In addition, 4 subgroups were identified as follows: MSI-H(+)HDFL(+), n = 35; MSI-H(-)HDFL(+), n = 134; MSI-H(+)HDFL(-), n = 17; MSI-H(-)HDFL(-), n = 58. There was no significant difference of background clinicopathologic data between the HDFL(+) and HDFL(-) treatment groups (p > 0.05). Survival analyses indicated that the patients of subgroup MSI-H(+)HDFL(+) survived significantly longer than those of subgroup MSI-H(-)HDFL(+), with median survival times of 24 (95% CI 20.2-27.9) and 13 (95% CI 11.6-14.4) months, respectively (p = 0.0001, log-rank test). In contrast, in patients without chemotherapy, the prognosis was poor irrespective of MSI status, with median survival times of 7.0 (95% CI 4.6-9.4) and 7.0 (95% CI 6.1-7.9) months in the MSI-H(+)HDFL(-) and MSI-H(-)HDFL(-) subgroups, respectively (p = 0.8205, log-rank test). MSI-H cancers responded significantly better to HDFL (p = 0.001), with a mean response rate of 65.71% (95% CI 49.98-81.44%) in subgroup MSI-H(+)HDFL(+) compared to 35.07% (95% CI 26.99-43.15%) in subgroup MSI-H(-)HDFL(+). There appeared to be no preferential metastatic site where response to HDFL can be predicted based on the MSI status of the primary tumor. Toxicity to HDFL was similarly minimal between MSI-H(+) and MSI-H(-) patients (p > 0.05). Multivariate analysis of all patients further indicated that MSI-H and chemotherapy were independent favorable prognostic parameters (p < 0.05). Thus, the better prognosis of stage IV sporadic colorectal cancers with MSI-H may be associated with better chemosensitivity, rather than lower aggressiveness in biologic behavior.

Pulsed electromagnetic fields (PEMF) has been investigated as a noninvasive alternative method to prevent bone loss for postmenopausal osteoporosis (OP), and the bone tissue involved in these studies are usually long bones such as femur and tibia in OP patients or rat models. However, few studies have investigated the effects of PEMF on the vertebral bone in mice with OP. This study aimed to investigate whether PEMF preserve lumbar vertebral bone mass, microarchitecture and strength in ovariectomized (OVX) mouse model of OP and its associated mechanisms. Thirty 3-month-old female BALB/c mice were randomly divided into three groups (n=10): sham-operated control (Sham), ovariectomy (OVX), and ovariectomy with PEMF treatment (OVX+PEMF). The OVX+PEMF group was exposed to 15Hz, 1.6 mT PEMF for 8h/day, 7days/week. After 8weeks, the mice were sacrificed. The OVX+PEMF group showed lower body weight gain of mice induced by estrogen deficiency compared with OVX group. Biochemical analysis of serum demonstrated that serum bone formation markers including bone specific alkaline phosphatase (BALP), serum osteocalcin (OCN), osteoprotegerin (OPG) and N-terminal propeptide of type I procollagen (P1NP) were markedly higher in OVX+PEMF group compared with OVX group. Besides, serum bone resorption markers including tartrate-resistant acid phosphatase 5b (TRAP-5b) and C-terminal crosslinked telopeptides of type I collagen (CTX-I) were markedly lower in OVX+PEMF group compared with OVX group. Biomechanical test observed that OVX+PEMF group showed higher compressive maximum load and stiffness of the lumbar vertebrae compared with OVX group. Micro-computed tomography (μCT) and histological analysis of lumbar vertebrae revealed that PEMF partially prevented OVX-induced decrease of trabecular bone mass and deterioration of trabecular bone microarchitecture in lumbar vertebrae. Real-time PCR showed that the canonical Wnt signaling pathway of the lumbar vertebrae, including Wnt3a, LRP5 and β-catenin were markedly up-regulated in OVX+PEMF group compared with OVX group. Moreover, the mRNA expressions of RANKL and OPG were markedly up-regulated in OVX+PEMF group compared with OVX group, whereas no statistical difference in RANKL/OPG mRNA ratio was found between OVX+PEMF group and OVX group. Besides, our study also found that the RANK mRNA expression was down-regulated in OVX+PEMF group compared with OVX group. Taken together, we reported that long-term stimulation with PEMF treatment was able to alleviate lumbar vertebral OP in postmenopausal mice through a combination of increased bone formation and suppressed bone resorption related to regulating the skeletal gene expressions of Wnt3a/LRP5/β-catenin and OPG/RANKL/RANK signaling pathways.

The expression of inducible nitric-oxide synthase in melanoma tumor cells was recently shown to correlate strongly with poor patient survival after combination biochemotherapy (<i>p</i> < 0.001). Furthermore, evidence suggests that nitric oxide, a reaction product of nitricoxide synthase, exhibits antiapoptotic activity in melanoma cells. We therefore hypothesized that nitric oxide antagonizes chemotherapy-induced apoptosis. Whether nitric oxide is capable of regulating cell growth and apoptotic responses to cisplatin treatment in melanoma cell lines was evaluated. We demonstrate herein that depletion of endogenously produced nitric oxide can inhibit melanoma proliferation and promote apoptosis. Moreover, our data indicate that the depletion of nitric oxide leads to changes in cell cycle regulation and enhances cisplatin-induced apoptosis in melanoma cells. Strikingly, we observed that the depletion of nitric oxide inhibits cisplatin-induced wild type p53 accumulation and p21^{Waf1/Cip1/Sdi1} expression in melanoma cells. When cisplatin-induced p53 binding to the p21^{Waf1/Cip1/Sdi1} promoter was examined, it was found that nitric oxide depletion significantly reduced the presence of p53-DNA complexes after cisplatin treatment. Furthermore, dominant negative inhibition of p53 activity enhanced cisplatin-induced apoptosis. Together, these data strongly suggest that endogenously produced nitric oxide is required for cisplatin-induced p53 activation and p21^{Waf1/Cip1/Sdi1} expression, which can regulate melanoma sensitivity to cisplatin.

<para xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> A study on correlation between structure and resistivity variations was performed for live adult human skull. The resistivities of 388 skull samples, excised from 48 skull flaps of patients undergoing surgery, were measured at body temperature (36.5 <formula formulatype="inline"><tex>$^{\circ}$</tex></formula>C) using the well-known four-electrode method in the frequency range of 1–4 MHz. According to different structures of the skull samples, all the 388 samples were classified into six categories and measured their resistivities: standard trilayer skull (7943 <formula formulatype="inline"><tex>$\pm$</tex></formula> 1752 <formula formulatype="inline"><tex>$\Omega$</tex> </formula>·cm, 58 samples), quasi-trilayer skull (14471 <formula formulatype="inline"><tex>$\pm$</tex></formula> 3061 <formula formulatype="inline"><tex>$\Omega$</tex></formula>·cm, 110 samples), standard compact skull (26546 <formula formulatype="inline"><tex>$\pm$</tex></formula> 5374 <formula formulatype="inline"><tex>$\Omega$</tex> </formula>·cm, 62 samples), quasi-compact skull (19824 <formula formulatype="inline"><tex>$\pm$</tex></formula> 3232 <formula formulatype="inline"><tex>$\Omega$</tex></formula>·cm, 53 samples), dentate suture skull (5782 <formula formulatype="inline"><tex>$\pm$</tex></formula> 1778 <formula formulatype="inline"><tex>$\Omega$</tex> </formula>·cm, 41 samples), and squamous suture skull (12747 <formula formulatype="inline"><tex>$\pm$</tex> </formula> 4120 <formula formulatype="inline"><tex>$\Omega$</tex></formula>·cm, 64 samples). The results showed that the skull resistivities were not homogenous and were significantly influenced by local structural variations. The presence of sutures appeared to decrease the overall resistivity of particular regions largely and dentate suture decreased the resistivity more than squamous suture. The absence of diploe appeared to increase skull resistivity. The percentage on thickness of diploe would be the primary factor in determining the resistivity of the skull sample without suture. From resistivity spectra results, an inverse relationship between skull resistivity and signal frequency was found. </para>

Human melanoma tumors cells are known to express the enzyme, inducible nitric oxide synthase (iNOS), which is responsible for cytokine induced nitric oxide (NO) production during immune responses. This constitutive expression of iNOS in many patients’ tumor cells, as well as its strong association with poor patient survival, have led to the consideration of iNOS as a molecular marker of poor prognosis, as well as a possible target for therapy. The expression of iNOS in patient tumors was found to associate with nitrotyrosine, COX2, pSTAT3, and arginase. Using human melanoma patients’ samples as well as cell lines, we have further evidence supporting intracellular NO production by detection of nitrotyrosine and also by use of DAF-2DA staining. Experiments were performed to scavenge the endogenous NO (with c-PTIO) resulting in melanoma cell growth inhibition; this was restored with SIN-1 (NO and O2-donor) providing data to support a functional role of this gas. Our goal is to understand the aberrant biology leading to this curious phenomenon, and to regulate it in favor of patient treatments.

Growing evidence has demonstrated that pulsed electromagnetic field (PEMF), as an alternative noninvasive method, could promote remarkable in vivo and in vitro osteogenesis. However, the exact mechanism of PEMF on osteopenia/osteoporosis is still poorly understood, which further limits the extensive clinical application of PEMF. In the present study, the efficiency of PEMF on osteoporotic bone microarchitecture and bone quality together with its associated signaling pathway mechanisms was systematically investigated in ovariectomized (OVX) rats. Thirty rats were equally assigned to the Control, OVX and OVX+PEMF groups. The OVX+PEMF group was subjected to daily 8-hour PEMF exposure with 15 Hz, 2.4 mT (peak value). After 10 weeks, the OVX+PEMF group exhibited significantly improved bone mass and bone architecture, evidenced by increased BMD, Tb.N, Tb.Th and BV/TV, and suppressed Tb.Sp and SMI levels in the MicroCT analysis. Three-point bending test suggests that PEMF attenuated the biomechanical strength deterioration of the OVX rat femora, evidenced by increased maximum load and elastic modulus. RT-PCR analysis demonstrated that PEMF exposure significantly promoted the overall gene expressions of Wnt1, LRP5 and β-catenin in the canonical Wnt signaling, but did not exhibit obvious impact on either RANKL or RANK gene expressions. Together, our present findings highlight that PEMF attenuated OVX-induced deterioration of bone microarchitecture and strength in rats by promoting the activation of Wnt/LRP5/β-catenin signaling rather than by inhibiting RANKL-RANK signaling. This study enriches our basic knowledge to the osteogenetic activity of PEMF, and may lead to more efficient and scientific clinical application of PEMF in inhibiting osteopenia/osteoporosis.

A physiological system encompasses numerous components that function at various time scales. To characterize the scale-dependent feature, the multiscale entropy (MSE) analysis has been proposed to describe the complex processes on multiple time scales. However, MSE analysis uses the relative scale factors to reveal the time-related dynamics, which may cause in-comparability of results from diverse studies with inconsistent sampling rates. In this study, in addition to the conventional MSE with relative scale factors, we also expressed MSE with absolute time scales (MaSE). We compared the effects of sampling rates on MSE and MaSE of simulated and real EEG time series. The results show that the previously found phenomenon (down-sampling can increase sample entropy) is just the projection of the compressing effect of down-sampling on MSE. And we have also shown the compressing effect of down-sampling on MSE does not change MaSE’s profile, despite some minor right-sliding. In addition, by analyzing a public EEG dataset of emotional states, we have demonstrated improved classification rate after choosing appropriate sampling rate. We have finally proposed a working strategy to choose an appropriate sampling rate, and suggested using MaSE to avoid confusion caused by sampling rate inconsistency. This novel study may apply to a broad range of studies that would traditionally utilize sample entropy and MSE to analyze the complexity of an underlying dynamic process.

The diatomic radical nitric oxide has been the focus of numerous studies involved with every facet of cancer. It has been implicated in carcinogenesis, progression, invasion, metastasis, angiogenesis, escape from immune surveillance, and modulation of therapeutic response. In recent years, an increasing number of studies have suggested the possible involvement of nitric oxide in multiple cancer types, including melanoma. It is perhaps not surprising that conflicting viewpoints have arisen as to whether nitric oxide is beneficial or deleterious in cancer. However, it has become clear that nitric oxide possesses modulatory properties in a number of signal transduction pathways that depend on concentration and context. Our laboratory has shown that tumor expression of inducible nitric oxide synthase in melanoma patients results in poor survival. Furthermore, we demonstrated that the removal of endogenous nitric oxide in melanoma cell lines led to increased sensitivity to cisplatin-induced apoptosis in a p53-dependent manner. Others have shown anti-apoptotic properties of NO in melanoma cells. However, several studies also suggest that NO can inhibit metastasis and diminish resistance. Despite the apparently conflicting observations, it is evident that NO is involved in melanoma pathology. The purpose of this review is to summarize the current literature relating to the role of NO in cancer with particular emphasis on its relevance to therapeutic resistance in melanoma. Recent evidence suggests the involvement of an intricate and complex interplay between reactive nitrogen species and reactive oxygen species. The importance of nitric oxide and its balance with other oxidative agents in the regulation of cancer cell response to therapies will be discussed. This balance may serve as an important focal point in determining patient response to therapy. The ability to control this balance could significantly influence outcome.

Growing evidence has shown that pulsed electromagnetic fields (PEMF) can modulate bone metabolism in vivo and regulate the activities of osteoblasts and osteoclasts in vitro. Osteocytes, accounting for 95% of bone cells, act as the major mechanosensors in bone for transducing external mechanical signals and producing cytokines to regulate osteoblastic and osteoclastic activities. Targeting osteocytic signaling pathways is becoming an emerging therapeutic strategy for bone diseases. We herein systematically investigated the changes of osteocyte behaviors, functions, and its regulation on osteoclastogenesis in response to PEMF. The osteocyte-like MLO-Y4 cells were exposed to 15 Hz PEMF stimulation with different intensities (0, 5, and 30 Gauss [G]) for 2 hr. We found that the cell apoptosis and cytoskeleton organization of osteocytes were regulated by PEMF with an intensity-dependent manner. Moreover, PEMF exposure with 5 G significantly inhibited apoptosis-related gene expression and also suppressed the gene and protein expression of the receptor activator of nuclear factor κB ligand/osteoprotegerin (RANKL/OPG) ratio in MLO-Y4 cells. The formation, maturation, and osteoclastic bone-resorption capability of in vitro osteoclasts were significantly suppressed after treated with the conditioned medium from PEMF-exposed (5 G) osteocytes. Our results also revealed that the inhibition of osteoclastic formation, maturation, and bone-resorption capability induced by the conditioned medium from 5 G PEMF-exposed osteocytes was significantly attenuated after abrogating primary cilia in osteocytes using the polaris siRNA transfection. Together, our findings highlight that PEMF with 5 G can inhibit cellular apoptosis, modulate cytoskeletal distribution, and decrease RANKL/OPG expression in osteocytes, and also inhibit osteocyte-mediated osteoclastogenesis, which requires the existence of primary cilia in osteocytes. This study enriches our basic knowledge for further understanding the biological behaviors of osteocytes and is also helpful for providing a more comprehensive mechanistic understanding of the effect of electromagnetic stimulation on bone and relevant skeletal diseases (e.g., bone fracture and osteoporosis).

An accurate impedance model of a skull plays an important role in the simulation research on source localization of EEG and brain EIT (electrical impedance tomography), etc. On the basis of the large number of impedance and resistivity data obtained from our previous measurement on the live human skull, in this study we established the equivalent circuit models of six types of skull samples in the 30 Hz–3 MHz frequency range and analyzed the fitting performance of the models. The six types of skull samples are standard tri-layer, quasi-tri-layer, standard compact, quasi-compact, dentate suture and squamous suture. The results showed that the difference of the real part between the CPE (constant phase model) model and the measured data was less than 1% for all skull tissue types when the optimized characteristic parameters (ρ0, ρ∞, α and fc) were adopted in the model. It is the first time studying the impedance model of different types of skulls, and it may provide accurate modeling of the skull to improve the accuracy of the related research on bioelectricity of the head and the biological effects of the electromagnetic field.

Abstract Diabetic wound (DW) problems are becoming a formidable clinical challenge due to the sharp increase in the diabetic population and the high incidence of DW. Static magnetic field (SMF) therapy, an inexpensive and accessible noninvasive method, has been proven to be effective on various tissue repairs. However, the issue of the therapeutic effect of SMF on DW healing has never been investigated. The objective of this study was to systematically evaluate the effect of a 180 mT moderate‐intensity gradient SMF on DW healing in streptozotocin‐induced diabetic rats. Forty‐eight 3‐month‐old male Sprague–Dawley rats (32 diabetic and 16 non‐diabetic rats) were assigned to three equal groups: normal wound, DW, and DW + SMF groups. An open circular wound with 1.5 cm diameter was created in the dorsum. The wound was covered with a dressing and the magnet was fixed on top of the dressing. On days 5, 12, and 19, four rats of each group were euthanized and gross wound area, histology and tensile strength were evaluated. The wound area determination suggested that SMF significantly increased the healing rate and reduced the gross healing time. This result was further confirmed by histological observations. The wound tensile strength, reflecting the amount and quality of collagen deposition, increased to a larger extent in the DW + SMF group on days 12 and 19 compared with the DW group. The results indicated that 180 mT SMF presented a beneficial effect on DW healing, and implied the clinical potential of SMF therapy in accelerating DW repair and releasing the psychological and physical burdens of diabetic patients. Bioelectromagnetics 31:640–648, 2010. © 2010 Wiley‐Liss, Inc.

Abstract Background Bone marrow mesenchymal stem cells (BMSCs) have been used as important cell-based tools for clinical applications. Oxidative stress-induced apoptosis causes a low survival rate after transplantation, and the underlying mechanisms remain unknown. The endoplasmic reticulum (ER) and mitochondria are vital organelles regulated by adenosine monophosphate (AMP)-activated protein kinase (AMPK), especially during oxidative stress injury. Melatonin exerts an antioxidant effect by scavenging free radicals. Here, we aimed to explore whether cytoprotective melatonin relieves ER stress-mediated mitochondrial dysfunction through AMPK in BMSCs after oxidative stress injury. Methods Mouse BMSCs were isolated and exposed to H 2 O 2 in the absence or presence of melatonin. Thereafter, cell damage, oxidative stress levels, mitochondrial function, AMPK activity, ER stress-related proteins, and apoptotic markers were measured. Additionally, the involvement of AMPK and ER stress in the melatonin-mediated protection of BMSCs against H 2 O 2 -induced injury was investigated using pharmacologic agonists and inhibitors. Results Melatonin improved cell survival and restored mitochondrial function. Moreover, melatonin intimately regulated the phosphorylation of AMPK and molecules associated with ER stress pathways. AMPK activation and ER stress inhibition following melatonin administration improved the mitochondrial membrane potential (MMP), reduced mitochondria-initiated oxidative damage, and ultimately suppressed apoptotic signaling pathways in BMSCs. Cotreatment with N -acetyl- l -cysteine (NAC) significantly enhanced the antioxidant effect of melatonin. Importantly, pharmacological AMPK activation/ER stress inhibition promoted melatonin-induced cytoprotection, while pharmacological AMPK inactivation/ER stress induction conferred resistance to the effect of melatonin against H 2 O 2 insult. Conclusions Our data also reveal a new, potentially therapeutic mechanism by which melatonin protects BMSCs from oxidative stress-mediated mitochondrial apoptosis, possibly by regulating the AMPK-ER stress pathway.

Brain electrical impedance tomography (EIT) is an emerging method for monitoring brain injuries. To effectively evaluate brain EIT systems and reconstruction algorithms, we have developed a novel head phantom that features realistic anatomy and spatially varying skull resistivity. The head phantom was created with three layers, representing scalp, skull, and brain tissues. The fabrication process entailed 3-D printing of the anatomical geometry for mold creation followed by casting to ensure high geometrical precision and accuracy of the resistivity distribution. We evaluated the accuracy and stability of the phantom. Results showed that the head phantom achieved high geometric accuracy, accurate skull resistivity values, and good stability over time and in the frequency domain. Experimental impedance reconstructions performed using the head phantom and computer simulations were found to be consistent for the same perturbation object. In conclusion, this new phantom could provide a more accurate test platform for brain EIT research.

There is increasing evidence to suggest a key role for interleukin-5 (IL-5) in the regulation of airway eosinophilia in asthma. We compared the capacity for IL-5 production in atopic asthmatic, nonatopic asthmatic, atopic nonasthmatic and normal subjects, and evaluated the usefulness of peripheral blood cells for reflecting airway cell reactivity. Bronchoalveolar lavage (BAL) cells and peripheral blood mononuclear cells (PBMC) from 12 atopic and 10 nonatopic asthmatics (without inhaled steroid therapy), 9 atopic nonasthmatics, and 10 normal controls were cultured with or without house dust mite (HDM, 10 microg x mL-1) stimulation. CD4+ T-cell activation, IL-5 and interferon-gamma (IFN-gamma) production in the cultures were assessed. Both for BAL and PBMC samples, atopic and nonatopic asthmatic subjects showed comparable spontaneous production of IL-5, which was significantly higher than that either for atopic nonasthmatics or normal controls (p<0.05 or p<0.01). There was a significant correlation between the percentage of eosinophils in BAL and spontaneous production of IL-5 by BAL cells in both asthmatic groups (p<0.05 or p<0.01). Both these parameters were also associated with asthmatic airway narrowing as denoted by a negative relationship with baseline forced expiratory volume in one second (FEV1) as percentage predicted (p<0.05 and p<0.01, respectively). In contrast, IFN-gamma production by unstimulated BAL cells from normal controls was higher than that for BAL cell cultures of nonatopic asthmatic subjects (p<0.05). Following HDM stimulation, both atopic groups had comparable positive responses in terms of CD4+ T-cell activation, but there was relatively greater IL-5 production in asthmatic PBMC (p<0.05) and, in particular, BAL cell cultures (p<0.01). These findings suggest that elevated IL-5 production is a common feature of BAL cells and PBMC in atopic and nonatopic asthma. In addition, atopic asthmatics show greater IL-5 production in response to specific allergen compared with atopic nonasthmatics, an effect most marked in BAL cells compared to PBMC. Hence, peripheral blood mononuclear cells can reflect cytokine immunoreactivity of airway cells, but lack local cellular interactions, which limits their usage in asthma research.

We have previously demonstrated that allergen inhalation induces expansion of bone marrow eosinophil progenitors in sensitized mice and subjects with asthma and that the inhaled corticosteroid, budesonide, reduced baseline but not allergen-induced increase in bone marrow eosinophil/basophil progenitors (EoB-CFU) in subjects with asthma. Here, we evaluated the effects of intranasal budesonide on allergen-induced increases in interleukin (IL)-5 and eotaxin in the airway and peripheral blood, expansion of bone marrow Eo-CFU and eosinophilia in bone marrow, peripheral blood and airway, as well as airway hyperresponsiveness, in ovalbumin (OVA)-sensitized mice. Budesonide treatment attenuated allergen-induced eosinophilia in bone marrow, peripheral blood, and airways as well as allergen-induced increases in bone marrow eosinophil progenitors but not allergen-induced increases in IL-5 or eotaxin 12 h following the second of two daily exposures to allergen; at later time points treatment was associated with attenuation of IL-5, eosinophilia, Eo-CFU, and airway hyperresponsiveness. These results suggest that a component of the mechanism by which corticosteroid treatment attenuates allergen-induced airway inflammation is through suppression of bone marrow eosinophilopoiesis, and that this is likely not mediated simply through the blocking of IL-5 production at the airway.

Saponin 1 is a triterpeniod saponin extracted from Anemone taipaiensis, a traditional Chinese medicine against rheumatism and phlebitis. It has also been shown to exhibit significant anti-tumor activity against human leukemia (HL-60 cells) and human hepatocellular carcinoma (Hep-G2 cells). Herein we investigated the effect of saponin 1 in human glioblastoma multiforme (GBM) U251MG and U87MG cells. Saponin 1 induced significant growth inhibition in both glioblastoma cell lines, with a 50% inhibitory concentration at 24 h of 7.4 µg/ml in U251MG cells and 8.6 µg/ml in U87MG cells, respectively. Nuclear fluorescent staining and electron microscopy showed that saponin 1 caused characteristic apoptotic morphological changes in the GBM cell lines. Saponin 1-induced apoptosis was also verified by DNA ladder electrophoresis and flow cytometry. Additionally, immunocytochemistry and western blotting analyses revealed a time-dependent decrease in the expression and nuclear location of NF-κB following saponin 1 treatment. Western blotting data indicated a significant decreased expression of inhibitors of apoptosis (IAP) family members,(e.g., survivin and XIAP) by saponin 1. Moreover, saponin 1 caused a decrease in the Bcl-2/Bax ratio and initiated apoptosis by activating caspase-9 and caspase-3 in the GBM cell lines. These findings indicate that saponin 1 inhibits cell growth of GBM cells at least partially by inducing apoptosis and inhibiting survival signaling mediated by NF-κB. In addition, in vivo study also demonstrated an obvious inhibition of saponin 1 treatment on the tumor growth of U251MG and U87MG cells-produced xenograft tumors in nude mice. Given the minimal toxicities of saponin 1 in non-neoplastic astrocytes, our results suggest that saponin 1 exhibits significant in vitro and in vivo anti-tumor efficacy and merits further investigation as a potential therapeutic agent for GBM.

Recent studies have demonstrated that different antigen-presenting cell (APC)-related factors in the microenvironment of a T cell may determine its profile and quantity of cytokine expression and production. We have therefore examined the effects of alveolar macrophages and peripheral blood monocytes on interleukin (IL)-5 production by peripheral blood CD4+ T cells from atopic people with asthma (AA), atopic people without asthma (AN), and nonatopic normal subjects (N). In response to allergen stimulation, IL-5 production was significantly enhanced by the addition of monocytes to CD4+ cell cultures in AA and AN patients (p < 0.05 and 0.01, respectively), but not in N subjects. In mitogen-stimulated CD4+ cell plus monocyte cocultures, there was a small increase in IL-5 production in all three groups (p < 0.05 for AN). In contrast, the addition of alveolar macrophages to parallel cultures significantly amplified IL-5 production only in AA patients (p < 0.05 or 0.01). Furthermore, IL-5 production by CD4+ cells in alveolar macrophage cocultures, stimulated by allergen or mitogen, was higher than that in monocyte cocultures in AA patients (p < 0.05). Conversely, in AN and N subjects, the IL-5 values for alveolar macrophage cocultures were lower than those for peripheral blood monocytes. In blocking studies, antibodies against IL-1alpha, IL-1beta, IL-6, or tumor necrosis factor-alpha differentially suppressed macrophage-enhanced IL-5 production (p < 0.05 for IL-1beta and IL-6) and expression of the activation marker CD25 (p < 0.05 for IL-1alpha and IL-6) by allergen-stimulated CD4+ cells in AA patients. These observations suggest that alveolar macrophages influence the quantity of IL-5 production by T cells in the airways and, as a consequence, the development of asthma in atopic individuals.

The quantification of mental fatigue (MF) in aviation remains a long-lasting problem which has a bearing on flight safety. In this study, we have developed a complexity-based MF index based on multiscale entropy (MSE) analysis of instantaneous frequency variation (IFV) in auditory steady-state response (ASSR). Subjects were asked to undertake a flight simulation task, before and after which, electroencephalograms (EEGs) were recorded with no auditory stimulus, and with Don chirp sound to elicit ASSR. In the anti-interference tests, our proposed MF index showed higher performance in terms of anti-interference from electrooculogram (EOG) and environment. In the flight simulation task, fatigue evaluations based on ASSR have achieved a better fatigue detection effect comparing with the conventional methods: 95% in the fatigue detection rate and −13.885% in the MF index. In conclusion, the proposed MF index has high sensitivity and high anti-interference capacities, therefore has potential applications in a variety of fields that require robust monitoring of MF outside a shielded chamber.

Previous studies have suggested that quantitative differences in TH2-type cytokine responses in the airways are of particular importance in the pathogenesis of asthma. In this study we investigated whether alveolar macrophages (AMs) and peripheral blood monocytes (PMNs) are able to significantly influence the profiles of allergen-induced TH1 (IFN-gamma) and TH2 (IL-4 and IL-5) cytokine production by CD4+ T cells in atopic asthmatic subjects versus atopic nonasthmatic subjects and nonatopic normal subjects.Peripheral blood CD4+ T cells were cultured alone or cocultured with either PMNs or AMs with allergen stimulation in the 3 groups.Although allergen stimulation did not change TH1 or TH2 cytokine responses in cultures of CD4+ T cells alone, the addition of PMNs to the cultures induced a significant increase in production of IL-4, IL-5, and IFN-gamma (P < .01 or P < .001) in atopic asthmatic subjects and atopic nonasthmatic subjects. However, PMNs induced a significant increase for IFN-gamma (P < .05) only in normal subjects. AMs from atopic asthmatic subjects significantly enhanced production of all 3 cytokines (P < .01 or P < .001), whereas the AMs from atopic nonasthmatic subjects significantly increased only production of IL-4 (P < .01) and IFN-gamma (P < .05) but not IL-5. Furthermore, IL-4 (P = .066) and IL-5 (P < .01) production in allergen-stimulated AM-CD4+ cell cocultures was higher in atopic asthmatic subjects but significantly lower in atopic nonasthmatic subjects (P < .05) as compared with the PMN-cocultures. For IFN-gamma, no difference was found between the AM and PMN cocultures in either atopic group. Allergen-stimulated IL-5 production in coculture with both AMs and PMNs inversely correlated with both baseline FEV1 percent predicted and PD20 methacholine in atopic asthmatic subjects (P < .05, P < .01, or P < .001).These data suggest that AMs from atopic asthmatic subjects but not atopic nonasthmatic subjects, play a significant role in airway pathogenic immunity through enhancing TH2-type cytokine production.

Although numerous clinical studies have reported that pulsed electromagnetic fields (PEMF) have a neuroprotective role in patients with diabetic peripheral neuropathy (DPN), the application of PEMF for clinic is still controversial. The present study was designed to investigate whether PEMF has therapeutic potential in relieving peripheral neuropathic symptoms in streptozotocin (STZ)-induced diabetic rats. Adult male Sprague-Dawley rats were randomly divided into three weight-matched groups (eight in each group): the non-diabetic control group (Control), diabetes mellitus with 15 Hz PEMF exposure group (DM+PEMF) which were subjected to daily 8-h PEMF exposure for 7 weeks and diabetes mellitus with sham PEMF exposure group (DM). Signs and symptoms of DPN in STZ-treated rats were investigated by using behavioral assays. Meanwhile, ultrastructural examination and immunohistochemical study for vascular endothelial growth factor (VEGF) of sciatic nerve were also performed. During a 7-week experimental observation, we found that PEMF stimulation did not alter hyperglycemia and weight loss in STZ-treated rats with DPN. However, PEMF stimulation attenuated the development of the abnormalities observed in STZ-treated rats with DPN, which were demonstrated by increased hind paw withdrawal threshold to mechanical and thermal stimuli, slighter demyelination and axon enlargement and less VEGF immunostaining of sciatic nerve compared to those of the DM group. The current study demonstrates that treatment with PEMF might prevent the development of abnormalities observed in animal models for DPN. It is suggested that PEMF might have direct corrective effects on injured nerves and would be a potentially promising non-invasive therapeutic tool for the treatment of DPN.

Extremely low frequency pulsed magnetic fields (ELFPMF) have been shown to induce Faraday currents and measurable effects on biological systems. A kind of very high frequency electromagnetic field was reported that it improved the symptoms of diabetic nephropathy (DN) which is a major complication of diabetes. However, few studies have examined the effects of ELFPMF DN at the present. The present study was designed to investigate the effects of ELFPMF on DN in streptozotocin (STZ)-induced type 1 diabetic rats.Adult male SD rats were randomly divided into three weight-matched groups: Control (non-diabetic rats without DN), DN + ELFPMF (diabetic rats with DN exposed to ELFPMF, 8 h/days, 6 weeks) and DN (diabetic rats with DN exposed to sham ELFPMF). Renal morphology was examined by light and electron microscopy, vascular endothelial growth factor (VEGF)-A and connective tissue growth factor (CTGF) were measured by enzyme linked immune sorbent assay.After 6 weeks' ELFPMF exposure, alterations of hyperglycemia and weight loss in STZ-treated rats with DN were not found, while both positive and negative effects of ELFPMF on the development of DN in diabetic rats were observed. The positive one was that ELFPMF exposure attenuated the pathological alterations in renal structure observed in STZ-treated rats with DN, which were demonstrated by slighter glomerular and tubule-interstitial lesions examined by light microscopy and slighter damage to glomerular basement membrane and podocyte foot processes examined by electron microscopy. And then, the negative one was that ELFPMF stimulation statistically significantly decreased renal expression of VEGF-A and statistically significantly increased renal expression of CTGF in diabetic rats with DN, which might partially aggravate the symptoms of DN.Both positive and negative effects of ELFPMF on the development of DN in diabetic rats were observed. The positive effect induced by ELFPMF might play a dominant role in the procession of DN in diabetic rats, and it is suggested that the positive effect should be derived from the correction of pathogenic diabetes-induced mediators.

Electromagnetic fields (EMF) was considered as a non-invasive modality for treatment of osteoporosis while the effects were diverse with EMF parameters in time domain. In present study, we extended analysis of EMF characteristics from time domain to frequency domain, aiming to investigate effects of four kinds of EMF (LP (1-100 Hz), BP (100-3,000 Hz), HP (3,000-50,000 Hz) and AP (1-50,000 Hz)) on ovariectomized (OVX) osteoporosis (OP) in mice. Forty-eight 3-month-old female BALB/c mice were equally assigned to Sham, OVX, OVX + LP, OVX + BP, OVX + HP and OVX + AP groups (n = 8). After 8-week exposure (3 h/day), LP and BP significantly increased serum bone formation markers and osteogenesis-related gene expressions compared with OVX. Bedsides, LP and BP also slightly increased bone resorption activity compared with OVX, evidenced by increased RANKL/OPG ratio. HP sharply decreased serum bone formation and resporption markers and osteogenesis and osteoclastogenesis related gene expressions compared with OVX. AP had accumulative effects of LP, BP and HP, which significantly increased bone formation and decreased bone resporption activity compared with OVX. As a result, LP, BP and HP exposure did not later deterioration of bone mass, microarchitecture and mechanical strength in OVX mice with OP. However, AP stimulation attenuated OVX-induced bone loss.

Chronic high-altitude hypoxia (HAH) results in compensatory pathological adaptations, especially in the cardiorespiratory system. The oxygen enrichment technology can provide long-lasting oxygen supply and minimize oxygen toxicity, which has proven to be effective to increase oxygen saturation, decrease heart rate, and improve human exercise performance after ascending to high altitudes. Nevertheless, it remains unknown whether oxygen enrichment can resist chronic HAH-induced cardiorespiratory alterations. Thirty-six male rats were equally assigned to the normal control (NC), HAH, and HAH with oxygen enrichment (HAHO) groups. The HAH and HAHO rats were housed in a hypobaric hypoxia chamber equivalent to 5,000 m for 4 weeks. The HAHO rats were exposed to oxygen-enriched air for 8 h/day. We found that oxygen enrichment mitigated the augmented skin blood flow and improved the locomotor activity of HAH-exposed rats. Oxygen enrichment inhibited HAH-induced increase in the production of red blood cells (RBCs). The hemodynamic results showed that oxygen enrichment decreased right ventricular systolic pressure (RVSP) and mean pulmonary artery pressure (mPAP) in HAH-exposed rats. HAH-associated right ventricular hypertrophy and cardiomyocyte enlargement were ameliorated by oxygen enrichment. Oxygen enrichment inhibited HAH-induced excessive expression of cytokines associated with cardiac hypertrophy and myocardial fibrosis [angiotensin-converting enzyme (ACE)/angiotensin-converting enzyme 2 (ACE2), angiotensin II (Ang II), collagen type I alpha 1 (Col1α1), collagen type III alpha 1 (Col3α1), and hydroxyproline] in the right ventricle (RV). Oxygen enrichment inhibited medial thickening, stenosis and fibrosis of pulmonary arterioles, and cytokine expression related with fibrosis (Col1 α 1, Col3α1, and hydroxyproline) and pulmonary vasoconstriction [endothelin-1(ET-1)] in HAH-exposed rats. This study represents the first effort testing the efficacy of the oxygen enrichment technique on cardiopulmonary structure and function in chronic HAH animals, and we found oxygen enrichment has the capability of ameliorating chronic HAH-induced cardiopulmonary alterations.

Increasing evidence suggests that the pattern of T-cell cytokine production can be modulated by antigen presenting cell (APC)-derived factors during the cell interactions. Recently, it has been shown that alveolar macrophages (AMs) from atopic asthmatics (AA) but not atopic nonasthmatics (AN) enhance interleukin (IL)-5 production by CD4+ T-cells. The present study compared AM production of IL-1beta, IL-6, and IL-12, as well as their associated functional capacity to influence IL-5 production by allergen-specific CD4+ T-cells in 10 AA, 10 AN, and nine nonatopic control subjects (C). AMs from AA showed a relatively high production of IL-1beta and IL-6 (p<0.05) and a relatively low secretion of IL-12 compared to C, whereas AMs from AN and C behaved similarly. This study confirmed previous findings that co-culture with AMs augments IL-5 production from allergen-stimulated CD4+ T-cells only in AA and not in nonasthmatics even if they are atopic. On the other hand, stimulation with allergen alone did not enhance IL-5 production by CD4+ T-cells in either AA nor AN. AM-induced changes in CD4+ T-cell IL-5 production upon allergen stimulation significantly correlated with their ability to produce IL-1beta (r=0.59, p<0.01), IL-6 (r=0.56, p<0.01), and inversely with IL-12 (r=-64, p=0.002) in all atopic subjects, and even more closely with the ratio of IL-12/IL-1beta (r=-0.75, p<0.001) and IL-12/IL-6 production (r=-0.81, p<0.001) in these subjects. These findings suggest that the role of alveolar macrophages from atopic asthmatics in enhancing interleukin-5 production by allergen-specific CD4+ T-cells is due, at least partly, to their aberrant production of interleukin-1beta, interleukin-6, and particularly of interleukin-12.

To investigate the changes of calcitonin gene-related peptide (CGRP) in rat's blood plasma, spinal anterior motorneuron, and dorsal root ganglion (DRG) after fractures combined with central or peripheral nerve injuries and its influence on fracture healing, 72 healthy adult SD rats (male or female) were divided into 4 groups (18 rats in each group): group A, simple(left) tibial fracture; group B, left tibial fracture combined with left sciatic nerve injury; group C, left tibial fracture combined with T9-11 spinal cord transection injury; group D, left tibial fracture combined with right cerebral cortex injury. Group A was the control group. The concentration of serum CGRP was measured immediately, 1w, 2w, and 4w after injury using radio immunoassay. X-ray photograph was taken at 1w, 2w, and 4w after injury to assess fracture healing. The concentration of serum CGRP in spinal anterior motorneuron and dorsal root ganglion was measured 1w, 2w, and 4w after injury. Bony callus at 2w after injury using H.E.staining was observed. 1w and 2w after injury, the fracture line was still clear on the X-ray of all groups, but 4w after injury the fracture line disappeared with complete healing except the peripheral nerve injury group. By H.E. staining, we found lesser bony callus contents in the peripheral nerve injury group than the simple fracture group at 2w after injury; irregular bone trabecula and healing defect were found in the former group. While the spinal injury group and cerebral cortex injury group represented more bony callus than the simple fracture group, increased bone trabecula and regularity, medullary cavity occluded and finally solid bony connections were found. CGRP concentration in blood plasma and spinal anterior motorneuron represented no apparent differences among all groups during each observation period. For the dorsal root ganglion group, 1w after fracture, there was no apparent difference of CGRP concentration in the peripheral nerve injury group and cerebral cortex group compared with the control group (P > 0.05), but the spinal injury group showed more CGRP than the control group (P < 0.01). 2w after injury, the peripheral nerve injury group and cerebral cortex group also showed no difference compared with the control group, but the cerebral cortex group had more CGRP contents than the peripheral nerve injury group (P < 0.05), and the spinal injury group showed more CGRP than the control group (P < 0.01). 4w after injury, the peripheral nerve group, spinal injury group, and cerebral cortex injury group all showed higher concentration of CGRP than the control group. Among the 3 groups, the spinal injury group is the highest (P < 0.01). When fracture combined with peripheral nerve injury, the healing process can be slowed down. In contrast, fracture combined with spinal injury and cerebral cortex injury will accelerate the healing process. The CGRP in dorsal root ganglion in spinal injury group and cerebral cortex injury group increased, which may have positive effects on fracture healing.

Abundant evidence has substantiated the positive effects of pulsed electromagnetic fields (PEMF) and static magnetic fields (SMF) on inhibiting osteopenia and promoting fracture healing. However, the osteogenic potential of rotating magnetic fields (RMF), another common electromagnetic application modality, remains poorly characterized thus far, although numerous commercial RMF treatment devices have been available on the market. Herein the impacts of RMF on osteoporotic bone microarchitecture, bone strength and bone metabolism were systematically investigated in hindlimb-unloaded (HU) rats. Thirty two 3-month-old male Sprague-Dawley rats were randomly assigned to the Control (n = 10), HU (n = 10) and HU with RMF exposure (HU+RMF, n = 12) groups. Rats in the HU+RMF group were subjected to daily 2-hour exposure to moderate-intensity RMF (ranging from 0.60 T to 0.38 T) at 7 Hz for 4 weeks. HU caused significant decreases in body mass and soleus muscle mass of rats, which were not obviously altered by RMF. Three-point bending test showed that the mechanical properties of femurs in HU rats, including maximum load, stiffness, energy absorption and elastic modulus were not markedly affected by RMF. µCT analysis demonstrated that 4-week RMF did not significantly prevent HU-induced deterioration of femoral trabecular and cortical bone microarchitecture. Serum biochemical analysis showed that RMF did not significantly change HU-induced decrease in serum bone formation markers and increase in bone resorption markers. Bone histomorphometric analysis further confirmed that RMF showed no impacts on bone remodeling in HU rats, as evidenced by unchanged mineral apposition rate, bone formation rate, osteoblast numbers and osteoclast numbers in cancellous bone. Together, our findings reveal that RMF do not significantly affect bone microstructure, bone mechanical strength and bone remodeling in HU-induced disuse osteoporotic rats. Our study indicates potentially obvious waveform-dependent effects of electromagnetic fields-stimulated osteogenesis, suggesting that RMF, at least in the present form, might not be an optimal modality for inhibiting disuse osteopenia/osteoporosis.

Whether static magnetic field (SMF) can affect microcirculation and microvasculature in human is still ambiguous. In this study, laser Doppler flowmetry (LDF) combined with spectral analysis by wavelet transform was applied to investigate acute SMF-related effects on resting skin blood flow (SBF) at the nail walls. 18 healthy young male volunteers were randomly categorized into two groups: (1) intervention group (INT; n = 9) and (2) control group (CTL; n = 9). In each group, three 30-minute intervals (pre-exposure, exposure and post-exposure intervals) of continuous LDF recording were taken to evaluate the baseline, SMF effects and its deferred effects. During the exposure interval in the INT group, a neodymium–iron–boron magnet was laid under the middle finger prominence while a sham was used in the CTL group. The effective flux density range of SMF along the axis of the magnet was about 46 to 223 mT between the sites of SBF measurement and the magnet. No intervention existed during other 30-minute intervals in either group. Thereafter, analysis of variance with repeated-measures combined with Bonferroni's multiple comparison tests was adopted to analyze the SBF value and its spectral variants obtained by wavelet transform. The major finding of this study was that SMF exposure induced significant increases in the absolute amplitudes of frequency band III and V (aIII and aV), which indicated intrinsic myogenic and endothelial related activities (P < 0.05) respectively while the mean amplitude of SBF flux still maintain on the basal level (P > 0.05). Furthermore, after removal of the SMF, variations of rhythmic flow motion of SBF in SMF exposure interval vanished gradually, which suggest the limitations of the deferred-effect of SMF on SBF.

Previous studies have suggested that peripheral blood T cell cytokine release may reflect the situation in the bronchial mucosa in atopic asthmatics. We have therefore examined spontaneous, rye grass pollen-stimulated, and PHA-stimulated secretion of IL-2, IL-4, IL-5, and IFN-gamma in cultures of peripheral blood mononuclear cells (PBMC) from atopic asthmatic, atopic non-asthmatic and normal controls in and out of the rye grass pollen season. Compared to normal controls, both atopic groups showed higher IL-2 and IL-5 production (p < 0.01 and p < 0.05) and higher percentages of CD4 cells expressing CD25 and HLA-DR (p < 0.05) in response to rye grass pollen, elevated IL-4 production in response to PHA (p < 0.01), and a non-significant trend towards lower IFN-gamma production. However, the capacity of PBMC from atopic asthmatics to produce IL-5 was greater than that for atopic non-asthmatics (p < 0.05). Furthermore, seasonal changes in symptom score, FEV1 % predicted, and PD20 methacholine correlated with seasonal elevated production of IL-5 by PBMC in the asthmatic group (r = 0.862, -0.679, and -0.620; p < 0.01, 0.02, and 0.05, respectively). Our results suggest that elevated production of IL-2 and IL-4 and higher percentages of activated CD4 T cells are associated with atopy per se, but elevated production of IL-5 also relates to the clinical expression of atopic asthma.

We have previously shown that airway macrophages (AMs) from atopic nonasthmatic subjects, but not atopic asthmatic subjects, inhibit T-cell IL-5 production during an allergen-dependent interaction. However, the mechanisms responsible for the IL-5-modulating effect of the AMs are less clear.The aim of the present study was to define the roles of B7 and CD40 costimulatory signals delivered by AMs in regulating T-cell IL-5 responses in an allergen-stimulated coculture system.Peripheral blood CD4(+) T cells and AMs were cocultured under different conditions.Compared with those from well-matched atopic nonasthmatic subjects, AMs from atopic asthmatic subjects demonstrated a significantly lower expression of B7-1 and CD40, but not B7-2 and HLA-DR, after either fresh isolation or coculture with allergen-reactive CD4(+) T cells. Lower IL-12 production by the AMs from asthmatic subjects was also observed under the same conditions. Allergen-related T-cell IFN-gamma and IL-5 production was inhibited by the addition of either neutralizing B7-1 or B7-2 antibody to the cocultures in both atopic groups. In contrast, IL-5 production was significantly increased by the addition of blocking CD40 antibody, whereas IL-12 production by the AMs was inhibited. Anti-IL-12 mAb enhanced IL-5 production in the cocultures from atopic nonasthmatic subjects, whereas a dose-dependent suppressive effect of recombinant human IL-12 on IL-5 production was seen in atopic asthmatic subjects.In this coculture model system, lower IL-12 production by AMs and higher IL-5 production by CD4(+) T cells in atopic asthmatic subjects compared with that found in atopic nonasthmatic subjects are related to the lower expression of CD40 rather than B7-1 signals on the AMs from these patients.

The structural similarity of the head model affects the accuracy of forward solution to electrical impedance tomography (EIT). Generally, the four-concentric circle model (FCCM) is used as the head model, which ignores the inhomogeneous distribution of the conductivity of real skull. In order to decrease the errors caused by using FCCM, a more accurate head model named inhomogeneous skull model (ISM) has been proposed and a reconstruction algorithm incorporated with ISM has been developed for brain EIT. Simulation results have shown improvement in image quality and localization accuracy when using ISM. It is also suggested that the reconstructed image could be more sensitive to the location of bony sutures than to the variation of skull thickness. In conclusion, incorporating skull inhomogeneity into image reconstruction is an effective way to improve image quality and localization accuracy for brain EIT.

Abstract Background Acute mountain sickness (AMS) is common for people who live in low altitude areas ascending to the high altitude. Many instruments have been developed to treat mild cases of AMS. However, long-lasting and portable anti-hypoxia equipment for individual is not yet available. Methods Oxygen-increased respirator (OIR) has been designed to reduce the risk of acute mountain sickness in acute exposure to low air pressure. It can increase the density of oxygen by increasing total atmospheric pressure in a mask. Male subjects were screened, and eighty-eight were qualified to perform the experiments. The subjects were divided into 5 groups and were involved in some of the tests at 4 different altitudes (Group 1, 2: 3700 m; Group 3,4,5: 4000 m, 4700 m, 5380 m) with and without OIR. These tests include heart rate, saturation of peripheral oxygen (SpO 2 ), malondialdehyde (MDA), superoxide dismutase (SOD), blood lactate (BLA) and PWC (physical work capacity) -170. Results The results showed that higher SpO 2 , lower heart rate (except during exercise) and better recovery of heart rate were observed from all the subjects ’with OIR’ compared with ’without OIR’ (P&lt;0.05). Moreover, compared with ’without OIR’, subjects ’with OIR’ in Group 1 had lower concentrations of MDA and BLA, and a higher concentration of SOD (P&lt;0.05), while subjects ’with OIR’ in Group 2 showed better physical capacity (measured by the PWC-170) (P&lt;0.05). The additional experiment conducted in a hypobaric chamber (simulating 4,000 m) showed that the partial pressure of oxygen in blood and arterial oxygen saturation were higher ’with OIR’ than ’without OIR’ (P&lt;0.05). Conclusions We suggested that OIR may play a useful role in protecting people ascending to high altitude before acclimatization.

Infrasound is a kind of environmental noise. It can evoke biological resonance in organismic tissues including the central nervous system (CNS), causing displacement and distortion of cellular architectures. Several studies have revealed that certain intensity infrasound can impair normal functions of the brain, but the underlying mechanisms still remain largely unknown. Growing evidence has demonstrated that axonal degeneration is responsible for a variety of CNS dysfunctions. To explore whether neuronal axons are affected under infrasonic insults, we exposed cultured hippocampal neurons to infrasound with a frequency of 16 Hz and a pressure level of 130 dB for 1 h, and examined the morphological and molecular changes of neuronal axons by immunocytochemistry and Western blotting, respectively. Our results showed that infrasound exposure significantly resulted in axonal degeneration of cultured hippocampal neurons, which was relatively independent of neuronal cell death. This infrasound-induced axonal degeneration can be significantly blocked by Ca2+ chelator EGTA and Rho kinase inhibitor Fasudil, but not by proteasome inhibitor MG132. Moreover, calcium imaging and RhoA activation assays revealed a great enhancement of Ca2+ influx within axons and RhoA activation after infrasound exposure, respectively. Depletion of Ca2+ by EGTA markedly inhibited this Ca2+ influx and attenuated RhoA activation as well. Thus, our findings revealed that axonal degeneration may be one of the important mechanisms underlying infrasound-induced CNS impairment, and Ca2+ influx pathway is likely implicated in the process.

Cai, Jing, Junyong Ruan, Xi Shao, Yuanjun Ding, Kangning Xie, Chi Tang, Zedong Yan, Erping Luo, and Da Jing. Oxygen enrichment mitigates high-altitude hypoxia-induced hippocampal neurodegeneration and memory dysfunction associated with attenuated tau phosphorylation. High Alt Med Biol. 22:274–284, 2021. Background: Brain is predominantly vulnerable to high-altitude hypoxia (HAH), resulting in neurodegeneration and cognitive impairment. The technology of oxygen enrichment has proven effective to decrease the heart rate and improve the arterial oxygen saturation by reducing the equivalent altitude. However, the efficacy of oxygen enrichment on HAH-induced cognitive impairments remains controversial based on the results of neuropsychological tests, and its role in HAH-induced hippocampal morphological and molecular changes remains unknown. Therefore, this study aims to systematically investigate the effects of oxygen enrichment on the memory dysfunction and hippocampal neurodegeneration caused by HAH. Materials and Methods: Fifty-one male Sprague-Dawley rats were equally assigned to three groups: normal control, HAH, and HAH with oxygen enrichment (HAHO). Rats in the HAH and HAHO groups were exposed to hypoxia for 3 days in a hypobaric hypoxia chamber at a simulated altitude of 6,000 m. Rats in the HAHO group were supplemented with oxygen-enriched air, with 12 hours/day in the hypobaric hypoxia chamber. Results: Our results showed that oxygen enrichment improved the locomotor activity of HAH-exposed rats. The Morris water maze test revealed that oxygen enrichment significantly ameliorated HAH-induced spatial memory deficits. Oxygen enrichment also improved morphological alterations of pyramidal cells and the ultrastructure of neurons in the hippocampal CA1 region in rats exposed to acute HAH. Tau hyperphosphorylation at Ser396, Ser262, Thr231, and Thr181 was also significantly attenuated by oxygen enrichment in HAH-exposed rats. Conclusions: Together, our study reveals that oxygen enrichment can ameliorate HAH-induced cognitive impairments associated with improved hippocampal morphology and molecular expression, and highlights that oxygen enrichment may become a promising alternative treatment against neurodegeneration for humans ascending to the plateau.

MOFs (Metal-Organic Framework), as promising crystalline materials of adsorption and separation, has been the subject of many recent investigations. However, the H2O stability of MOFs and the variation of adsorption selectivity in humid environments largely hinder attempts as excellent adsorbents in numerous scenarios. This study employs hydro-thermal synthesis [Cd0.5(DPETA)0.5]n using 2,3′,5,5′-Diphenyl tetracarboxylic acid (DPETA) and Cd(NO3)2·4H2O as ligands and metal ions, respectively. And it is modified by adding auxiliary ligands 4-4′-bipyridyl (bpy) and 1,2-bis (4-pyridyl) ethylene(bpe) to obtain [Cd1.5bpy2(DPETA)]n and [Cd2bpe2(DPETA)]n.The phase purity of the MOFs is examined using PXRD and FT-IR spectrum. The adsorption capacities of three MOFs are tested separately for water, ethanol and methanol using vapor adsorption. Their adsorption conformations and hydrogen bond lengths are also calculated by the GCMC method. The adsorption selection ratios of methanol and ethanol are deduced in combination with the IAST method under three components of water, methanol and ethanol. The results shows a methanol/ethanol adsorption separation ratio of 45 for [Cd1.5bpy2(DPETA)]n at 297 K, which is consistent with the of GCMC demonstrated. These results suggest that the methanol/ethanol adsorption selectivity ratio can be improved by increasing the adsorption force on methanol through by adding of auxiliary pyridyl ethylene. It can be used for efficient methanol/ethanol separation in humid environments.

Mental fatigue (MF) jeopardizes performance and safety through a variety of cognitive impairments and according to the complexity loss theory, should represent "complexity loss" in electroencephalogram (EEG). However, the studies are few and inconsistent concerning the relationship between MF and loss of complexity, probably because of the susceptibility of brain waves to noise. In this study, MF was induced in thirteen male college students by a simulated flight task. Before and at the end of the task, spontaneous EEG and auditory steady-state response (ASSR) were recorded and instantaneous frequency variation (IFV) in alpha rhythm was extracted and analyzed by multiscale entropy (MSE) analysis. The results show that there were significant differences in IFV in alpha rhythm either from spontaneous EEG or from ASSR for all subjects. Therefore, the proposed method can be effective in revealing the complexity loss caused by MF in spontaneous EEG and ASSR, which may serve as a promising analyzing method to mark mild mental impairments.

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, and is related to disturbed lipid metabolism and redox homeostasis. However, a definitive drug treatment has not been approved for this disease. Studies have found that electromagnetic fields (EMF) can ameliorate hepatic steatosis and oxidative stress. Nevertheless, the mechanism remains unclear. Methods NAFLD models were established by feeding mice a high-fat diet. Simultaneously, EMF exposure is performed. The effects of the EMF on hepatic lipid deposition and oxidative stress were investigated. Additionally, the AMPK and Nrf2 pathways were analysed to confirm whether they were activated by the EMF. Results Exposure to EMF decreased the body weight, liver weight and serum triglyceride (TG) levels and restrained the excessive hepatic lipid accumulation caused by feeding the HFD. The EMF boosted CaMKKβ protein expression, activated AMPK phosphorylation and suppressed mature SREBP-1c protein expression. Meanwhile, the activity of GSH-Px was enhanced following an increase in nuclear Nrf2 protein expression by PEMF. However, no change was observed in the activities of SOD and CAT. Consequently, EMF reduced hepatic reactive oxygen species (ROS) and MDA levels, which means that EMF relieved liver damage caused by oxidative stress in HFD-fed mice. Conclusions EMF may activate the CaMKKβ/AMPK/SREBP-1c and Nrf2 pathways to control hepatic lipid deposition and oxidative stress. This investigation indicates that EMF may be a novel therapeutic method for NAFLD.

Abstract Background When ascending to the high altitude, people living in low altitude areas will suffer from acute mountain sickness. The aim of this study is to test the hypothesis that whether an oxygen concentration membrane can be made and used to construct a new portable oxygen enrichment device for individuals in acute exposure to the high altitude. Methods The membrane was fabricated using vinylsiloxane rubber, polyphenylene oxide hydrogen silicone polymers, chloroplatinic acid and isopropyl alcohol. The membrane was assembled in a frame and the performance was tested in terms of concentration of oxygen, flow rate of oxygen enriched air, pressure ratio across the membrane and ambient temperature. Furthermore, the oxygen concentration device was constructed using the membrane, a DC fan, vacuum pump and gas buffer. A nonrandomized preliminary field test was conducted, in which eight healthy male subjects were flown to Tibet (Lhasa, 3,700 m). First, subjects wore the oxygen enrichment device and performed an incremental exercise on cycle ergometer. The test included heart rate (HR), saturation of peripheral oxygen (SpO 2 ) and physical work capacity (PWC). Then, after a rest period of 4 hours, the experimental protocol was repeated without oxygen enrichment device. Results The testing showed that the membrane could increase the oxygen concentration by up to 30%. Simulation test indicated that although the performance of the oxygen enrichment device decreased with altitudes, the oxygen concentration could still maintain 28% with flow rate of enriched air 110 cm 3 /s at 5000 m. The field test showed that higher SpO 2 , lower HR, and better PWC (measured by the PWC-170) were observed from all the subjects using oxygen enrichment device compared with non-using ( P &lt; 0.01). Conclusions We concluded that the new portable oxygen enrichment device would be effective in improving exercise performance when ascending to the high altitude.

Acute leukemia presenting with central nervous system (CNS) signs and symptoms is uncommon and prone to be misdiagnosed. Here, we report nine patients with acute leukemia, including five patients with acute lymphoblastic leukemia (ALL) and four patients with acute myeloid leukemia (AML). These patients presented with symptoms suggestive of involvement of multiple cranial nerves, the spinal cord, and meningeal involvement. Moreover, we found that all these patients unexpectedly showed the presence of blasts in the cerebrospinal fluid (CSF) but not in the peripheral blood despite repeated examinations. Bone marrow examination confirmed the presence of acute leukemia in these patients. Seven patients died within 18 months of diagnosis and two patients developed stable disease. Our findings show a novel presenting feature of acute leukemia and highlight the importance of CSF cytology in the diagnosis of acute leukemia.

Quantifying the complexity of physiologic time series has long attracted interest from researchers. The multiscale entropy (MSE) algorithm is a prevailing method to quantify the complexity of signals in a variety of research fields. However, the MSE method assigns increased complexity to the mixed signal of a physiologic time series added with white noise, although the mixed signal should become less complex due to the broken correlation. In addition, the MSE method needs users to visually examine its scale dependence (shape) to better characterize the complexity of a physiologic process, which is sometimes not feasible. In this paper, we proposed a new method, namely the power-law exponent modulated multiscale entropy (pMSE), as a complexity measure for physiologic time series. We tested the pMSE method on simulated data and real-world physiologic interbeat interval time series and demonstrated that it could solve the above two difficulties of the MSE method. We expect that the proposed pMSE method or its future variants could serve as a useful complement to the MSE method for the complexity analysis of physiologic time series.

Generally, for healthy adults, the entropy of electroencephalogram (EEG) signals gradually decreases from wake to sleep stages N1, N2, to N3, and increases during REM. However, some researchers found that multiscale entropy curves of sleep and wakefulness intercept, a cross-over phenomenon whose origin remains unexplored. The objective of the present work is to trace the origin of the cross-over phenomenon and to propose a workaround strategy. We simulated EEG by generating 1/f broadband signal and chirp signals with continuously varying frequencies. We then retrieved the rhythmic component from simulated EEG and real-world EEG and conducted MSE analysis of the instantaneous frequency variation (IFV) of the rhythmic component. The simulation revealed that this interception was ubiquitous in the MSE analysis of simulated EEG with rhythmic components of different frequencies. The cross-over point moved toward larger scale factors with the increasing sampling rate. We found that the MSE curve of IFV from real-world EEG for the wakefulness group was higher than that for sleep, showing no interception. These results suggest that (1) for a rhythmic signal like EEG, MSE analysis of the raw signal is highly affected by the rhythmic component, presenting artificial cross-over curves in sleep EEG study, (2) frequency variation of rhythmic components are complex signal which differs between wakefulness and sleep, in accordance with the complexity loss theory.

Abstract Background Osteoporosis affects 200 million people worldwide and places an enormous economic burden on society. We aim to identify the feature genes that are related to osteoprotegerin in osteoporosis and to perform function analysis with DNA microarray from human bone marrow. Methods We downloaded the gene expression profile GSE35957 from Gene Expression Omnibus database including nine gene chips from bone marrow mesenchymal stem cells of five osteoporotic and four non-osteoporotic subjects. The differentially expressed genes between normal and disease samples were identified by LIMMA package in R language. The interactions among the osteoprotegerin gene ( OPG ) and differentially expressed genes were searched and visualized by Cytoscape. MCODE and Bingo were used to perform module analysis. Finally, GENECODIS was used to obtain enriched pathways of genes in an interaction network. Results A total of 656 genes were identified as differentially expressed genes between osteoporotic and non-osteoporotic samples. IL17RC, COL1A1, and ESR1 were identified to interact with OPG directly from the protein-protein interaction network. A module containing ERS1 was screened out, and this module was most significantly enriched in organ development. Pathway enrichment analysis suggested genes in the interaction network were related to focal adhesion. Conclusions The expression pattern of IL17RC , COL1A1 , and ESR1 can be useful in osteoporosis detection, which may help in identifying those populations at high risk for osteoporosis, and in directing treatment of osteoporosis.

ABSTRACT Microdamage accumulation contributes to impaired skeletal mechanical integrity. The bone can remove microdamage by initiating targeted bone remodeling. However, the spatiotemporal characteristics of microdamage initiation and propagation and their relationship with bone remodeling in response to fatigue loading, especially for more physiologically relevant daily bouts of compressive loading, remain poorly understood. The right forelimbs of 24 rats were cyclically loaded with a ramp waveform for 1,500 cycles/day, and contralateral ulnae were not loaded as the controls. The rats were divided into four equal groups and loaded for 1, 4, 7, and 10 days, respectively. We demonstrated that linear microcracking accumulation exhibited a non‐linear time‐varying process within 10 days of loading with peaked microcrack density at Day 7. Disrupted canaliculi surrounding linear microcracks showed high similarity with the temporal changes of linear microcracking accumulation. Observable intracortical resorption regions were found on Day 10. We found more linear microcracks accumulated in the tensile cortex, but longer cracks were observed in the compressive sides. Increased accumulation of diffuse microdamage was observed from Day 4, but no obvious peak was observed within the 10‐day loading period. Diffuse damage first initiated in the compressive cortices but extended to tension from Day 7. The diffuse damage exhibited no impacts on the surrounding osteocyte integrity. Together, our findings revealed a time‐dependent, bone remodeling‐mediated varying process of linear microcracking accumulation following daily bouts of fatigue loading (with observable peak at Day 7 under our loading regime). Our study also identified distinct spatial accumulation of linear and diffuse microdamage in rat ulnae with tensile and compressive strains. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2112–2121, 2019

To determine the ideal length of stay and glycemic control after resolution of acidosis in patients hospitalized for diabetic ketoacidosis, in order to reduce 30-day readmission. We hypothesized that both discharging patients within 24 hours of acidosis resolution and hyperglycemia at discharge are associated with higher probability of readmission.We examined data from 208 consecutive patients hospitalized for diabetic ketoacidosis. Logistic regression was performed adjusting for age, blood glucose (BG) level at presentation, prior hospitalization within 30 days, season of current hospitalization, and length of hospital stay.Higher BG at discharge is associated with lower probability of readmission (odds ratio, 0.990; 95% CI, 0.983-0.996; P=0.002). Higher average BG over the 24 hours prior to discharge is also associated with lower readmission rate (odds ratio, 0.991; 95% CI, 0.982-1.000; P=0.044). The direction of the association remains the same even after these predictive variables are converted to categorical variables. In addition, discharge within 24 hours of acidosis resolution is not inferior to discharge after 24 hours of normalized BG (odds ratio, 0.431; 95% CI, 0.083-2.252; P=0.318).Neither discharging patients within 24 hours of acidosis resolution nor hyperglycemia at discharge is associated with higher readmission rate. Randomized prospective studies are needed to confirm or refute our study.

Allergen-specific cytokine responses in the airways are thought to play a critical role in the pathogenesis of atopic asthma. This study examined whether there is a quantitative difference in bronchoalveolar lavage (BAL) cell allergen-induced IL-5 production between atopic subjects with and without asthma which may relate to a difference in airway response induced by allergen exposure. Twelve atopic asthmatics (AA), nine atopic non-asthmatics (AN) and 10 normal controls (N) underwent inhalation challenge with house dust mite allergen (HDM) extract. AA differed from AN in having late airway reactions (LAR) after HDM inhalation (P < 0.01), which correlated with an increased percentage of BAL eosinophils and increased BAL cell IL-5 production after in vivo or in vitro HDM challenge for the AA group (P < 0.01). IL-5 production by PBMC from both atopic groups was elevated with HDM stimulation in vitro, but AA again had a higher level under baseline conditions than AN (P < 0.02). Furthermore, there was a greater effect of BAL fluid from AA on ECP release by eosinophils compared to that for AN (P < 0.01). These findings suggest that increased IL-5 production in atopic asthmatic airways contributes to the increased physiological response to allergen inhalation, by modulating local eosinophil recruitment and activation.

A new single soft-fault diagnosis approach for analog circuit with parameter tolerance is proposed in this paper. The approach uses multi-objective linear programming (MLP) concept and fuzzy function together to diagnose the circuit under test. Node-voltage incremental equations, as constraints of MLP equation, are built based on the sensitivity analysis. Though evaluating the parameters deviations from the solution of the MLP equation and determining the deviation range using fuzzy function, it enable us to locate faulty components. Example illustrates the proposed approach and shows its effectiveness.

The most severe challenge for troops in a high-altitude environment is hypoxia. Pressure swing adsorption coupled with membrane separation is an ideal solution for oxygen production in high-altitude areas, but the molecular sieve membranes and organic membranes used in this technique are greatly affected by the ambient temperature, humidity, and pressure. Compared with traditional porous materials, metal-organic frameworks (MOFs) have outstanding features such as low densities, large specific surface areas, high crystallinities, and flexible structures. Cr-MIL-101 (MIL: Matérial Institut Lavoisier) and its derivatives are MOFs with high nitrogen adsorption capacities and can be used for oxygen production by air separation. However, since the plateau climate is complex, the applicability of Cr-MIL-101 for oxygen production in high-altitude environments awaits clarification. Therefore, this study constructed a molecular model of Cr-MIL-101, simulated the adsorption equilibrium of N2 and O2 molecules on this material using the grand canonical Monte Carlo (GCMC) method, and obtained their adsorption isotherms and densities. At 298 K and 100 kPa, the maximum adsorption capacities of Cr-MIL-101 for N2 and O2 were 0.94 per cell and 0.23 per cell, respectively. While at 238 K and 100 kPa, the maximum adsorption amounts of Cr-MIL-101 for N2 and O2 were 5.10 and 1.07 per cell, respectively. The thermodynamic parameters and adsorption equilibrium parameters during the adsorption process were analyzed. The conclusion of this study provides theoretical support for optimizing the N2/O2 separation performance of Cr-MIL-101 in high-altitude environments.

Acute high-altitude hypoxia can lead to intestinal damage and changes in gut microbiota. Sustained and reliable oxygen enrichment can resist hypoxic damage at high altitude to a certain extent. However, it remains unclear whether oxygen enrichment can protect against gut damage and changes in intestinal flora caused by acute altitude hypoxia. For this study, eighteen male Sprague–Dawley rats were divided into three groups, control (NN), hypobaric hypoxic (HH), and oxygen-enriched (HO). The NN group was raised under normobaric normoxia, whereas the HH group was placed in a hypobaric hypoxic chamber simulating 7,000 m for 3 days. The HO group was exposed to oxygen-enriched air in the same hypobaric hypoxic chamber as the HH group for 12 h daily. Our findings indicate that an acute HH environment caused a fracture of the crypt structure, loss of epithelial cells, and reduction in goblet cells. Additionally, the structure and diversity of bacteria decreased in richness and evenness. The species composition at Phylum and Genus level was characterized by a higher ratio of Firmicutes and Bacteroides and an increased abundance of Lactobacillus with the abundance of Prevotellaceae_NK3B31_group decreased in the HH group. Interestingly, after oxygen enrichment intervention, the intestinal injury was significantly restrained. This was confirmed by an increase in the crypt depth, intact epithelial cell morphology, increased relative density of goblet cells, and higher evenness and richness of the gut microbiota, Bacteroidetes and Prevotellaceae as the main microbiota in the HO group. Finally, functional analysis showed significant differences between the different groups with respect to different metabolic pathways, including Amino acid metabolism, energy metabolism, and metabolism. In conclusion, this study verifies, for the first time, the positive effects of oxygen enrichment on gut structure and microbiota in animals experiencing acute hypobaric hypoxia.

Accurate time delay is indispensable for many sorts of signal processing applications particular in the field of communication and detection. Traditionally, due to easy operation, interpolation-filter-delay-decimation (IFDD) algorithm was regarded as an intuitive and straightforward way to delay specific signals. However, the computational complexity of this approach will increase sharply with the increase of interpolation factor. In addition, the IFDD algorithm will also induce a fixed additional delay in the delayed signal, limiting its widespread application. To solve these issues, this study presented a cascaded IFDD algorithm without additional delay (C-IFDD-WAD) by decomposing the large interpolation factor into several small interpolation factors. The authors obtained the expression of C-IFDD-WAD algorithm and analysed the spectrum characteristics of C-IFDD-WAD algorithm in this study. Their theoretical analysis combined with the simulation results show that the computation cost of C-IFDD-WAD significantly decreased in the form of cascade based on their present new method. Moreover, the additional delay of traditional IFDD algorithm was also eliminated using the present method.

Many people who live in the low altitude areas are often suffered from hypoxia when they entered the high plateau.This problem may seriously influence the physical and mental state and work efficacy for the travelers and workers.Oxygen enrichment of a small space air at high altitude is considered as a simple way to provide lowlanders enriched oxygen for sleeping and resting, improving work efficiency, so we developed an oxygen concentration machine based on the technology of oxygen enrichment membrane.This paper tested 8 healthy male lowlanders (age 21.63±1.77yr) who have never exposed to plateau performed an incremental exercise on cycle ergometer at sea-level in order to be used as sea-level controls.Two days later, the same subjects were taken to Lhasa (3700 m) by air and exposed to the plateau, performed the same exercise as they did at sea-level.The next day, all subjects were asked to enter the experimental tent which was enriched with oxygen (higher than 24%) by the oxygen concentration machine and sleep for 10 hours at night, then exposed to plateau and performed the same exercise twice at different time (2 hours and 10 hours after oxygen enrichment).During the tests, subjects must cycled continuously at 60 rpm beginning with a 3 min exercise intensity of 0 W followed by incremental increases of 25 W every 3 min until 150 W, pulse oxygen saturation (SpO 2 ) and heart rate (HR) were recorded.After sleeping in an oxygen enrichment of tent air, 2 hours later, the subjects' load capacity had no difference compared with control group, but significant difference than before (higher SpO 2 and lower HR), which indicated that oxygen concentration machine is effective in increasing the oxygen concentration of the air for the tent and sleeping in the oxygen enrichment tent for l0 h might be effective in improving exercise performance during high-altitude hypoxia.At the same time, 10 hours later, when work-load exceeded 125 W, the same effects were also found.The results indicated the effects of oxygen enrichment of tent air could last a certain period of time.

General Concept Inclusion (GCI) absorption algorithms have shown to play an important role in classical Description Logic (DL) reasoners. They allow to transform GCIs into simpler forms to which we may apply specialised inference rules, returning important performance gains. In this work, we develop the first absorption algorithm for fuzzy DLs, implement it in the fuzzyDL reasoner and evaluate it extensively over both classical and fuzzy ontologies. The results show that our algorithm improves the performance of the reasoner significantly.

A novel method is presented to estimate sinusoidal frequency from highly contaminated single channel signals by constructing multi-channel surrogates using multiple signal classification (MUSIC) method in frequency domain beam-space (FB-MUSIC). According to the comparability of sampled data in time domain and observed data in uniform linear array, the FB-MUSIC method is proposed and the explicit expressions for the covariance elements of the estimation errors associated with FB-MUSIC are derived. These expressions are then used to analyse the statistical performance of FB-MUSIC and MUSIC. These expressions for the estimation error covariance are also used to compare the theoretical results and simulation results. Monte-Carlo simulations show that the root-mean-square error of frequency estimation in simulations keep consistent with the theoretical covariance for FB-MUSIC and MUSIC, and the signal-to-noise ratio resolution threshold of FB-MUSIC with reduced dimensionality is lower than that of MUSIC. This method may provide a higher resolution of sinusoidal frequency estimation and lower computation cost as compared with the conventional MUSIC method.

Metallic foreign body penetration remains a common clinical problem, which always leads to more suffering of patients and difficulties of doctors' management. Considering the drawbacks and limitations of traditional radiological detection, we present a fast method in this paper based on gradient measurement of cheap fluxgate sensors. A theoretical model for locating ferromagnetic and nonferromagnetic metal was elaborated and experimentally validated. A non-magnetic steel skeleton bound with metglas ribbons was chosen and digital signal processor was utilized to design magnetic exciting and signal processing algorithm, which provided a better fluxgate performance. A good symmetric configuration between the two sensors has been demonstrated through the calibration experiment, which lays the foundation for further animal and clinical experiment..

Canonical and systematic quality-oriented education of medical metrology for undergraduate students has not been started in colleges and universities. The standardized training and professional cultivation system are also deficient for most medical metrological employees at present. In this study, special funds were invested to develop the teaching laboratory based on the establishment standards of national medical metrology stations. Experienced experts were also invited for the argumentation of curriculum construction and optimization of medical metrology. As a result, two undergraduate courses of medical metrology for the students majoring in Biomedical Engineering (BME) were developed for the first time based on the talent cultivation mode “basic knowledge + practical ability”. An internationally-advanced teaching laboratory for medical metrology was established, and the series textbooks were compiled and published. It is of vital significance to strengthen the curriculum construction of medical metrology for undergraduate students of BME, which may provide beneficial reference for further medical metrological talent cultivation.

Abstract Pressure swing adsorption (PSA) coupling with molecular sieves, especially the Li low silica X (Li‐LSX) zeolite, adsorption technology is widely used in O 2 generator instrument under plateau environment. However, the studies of N 2 and O 2 adsorption and separation properties on zeolite under plateau environment are still obscure to date. In this work, the influence of N 2 and O 2 adsorptions on the LSX zeolites in harsh plateau environment (3000 ‐ 5000 m) was investigated by Grand Canonical Monte Carlo (GCMC) simulations. Three kinds of LSX zeolites including Li‐LSX, Ag‐LSX and LiCa‐LSX were taken into consideration. The simulation results indicate that the adsorption amount and affinity of both N 2 and O 2 elevate with the increasing altitude and following the order of Ag‐LSX &gt; Li‐LSX &gt; LiCa‐LSX. The N 2 adsorption was dominated over all three LSX zeolites, leaving O 2 much easier to permeate through the LSX zeolites. The isosteric adsorption heat and adsorption density results further proved that N 2 and O 2 have extremely different adsorption strategies. Moreover, the selectivity and separation coefficients based on ideal adsorption solution theory (IAST) were calculated from GCMC simulations, and the results indicate Ag‐LSX has the highest diffusion selectivity and the steadiest diffusion coefficient among the three LSX zeolites. These findings may contribute to the N 2 /O 2 separation molecular sieves for plateau applications by tailoring the LSX zeolite with different extra‐framework cations.

Abstract Background: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, and is related to disturbed lipid metabolism and redox homeostasis. However, a definitive drug treatment has not been approved for this disease. Studies have found that electromagnetic fields (EMFs) can ameliorate hepatic steatosis and oxidative stress. Nevertheless, the mechanism remains unclear.Methods: NAFLD models were established by feeding mice a high-fat diet. Simultaneously, EMF exposure is performed. The effects of the EMF on hepatic lipid deposition and oxidative stress were investigated. Additionally, the AMPK and Nrf2 pathways were analysed to confirm whether they were activated by the EMF.Results: Administration of the EMF decreased the body weight, liver weight and serum triglyceride (TG) levels and restrained the excessive hepatic lipid accumulation caused by feeding the HFD. This EMF function is achieved by boosting CaMKKβ protein expression, activating AMPK phosphorylation and suppressing mature SREBP-1c protein expression. Meanwhile, the activity of GSH-Px was enhanced following an increase in nuclear Nrf2 protein expression by EMF. However, no change was observed in the activities of SOD and CAT. Consequently, EMF reduced hepatic reactive oxygen species (ROS) and MDA levels, which means that EMF relieved liver damage by oxidative stress in HFD-fed mice.Conclusions: EMF can activate the CaMKKβ/AMPK/SREBP-1c and Nrf2 pathways to control hepatic lipid deposition and oxidative stress. This investigation indicates that EMF may be a novel therapeutic method for NAFLD.

Aiming at the problem of low efficiency and low accuracy of traditional interpolation algorithms, a new numerical control interpolation method-velocity interpolation, is presented in this paper.The realization steps of the quadratic curve in the numerical control system are described.Through the analysis of the error caused by the error caused by the stepper motor in the stepper motor control system, a correction method is proposed to improve the machining accuracy.The simulation program is developed by VC++ to simulate the process of the quadratic curve, which is the representative of a parabola, and the feasibility of the modified method is verified.

This study was conducted to determine the association between vasopressor requirement and outcome in medical intensive care patients in an environment where treatment is not withdrawn.This was an observational study of patients in the medical intensive care unit (ICU) over a period of 18 months to determine the correlation between vasopressor requirement and mortality. Outcome was determined for all medical ICU patients, for patients receiving “low dose” (< 40 μg/min) vasopressors (noradrenaline and/or adrenaline) or “high dose” (≥ 40 μg/min) vasopressors. Receiver operator characteristic curves were constructed for ICU and hospital mortality and high-dose vasopressor use. High-dose vasopressor use as an independent predictor for ICU and hospital mortality was also determined by multiple logistic regression analysis.Patients receiving high-dose noradrenaline at any time during their ICU admission had an 84.3% mortality in ICU and 90% in hospital. The receiver operator characteristic curves for high-dose vasopressors had an area under the curve of 0.799 for ICU mortality and 0.779 for hospital mortality. High-dose vasopressor was an independent predictor of ICU mortality, with an odds ratio of 5.1 (confidence interval, 2.02-12.9; P = .001), and of hospital mortality, with an odds ratio of 3.82 (confidence interval 1.28-11.37; P = .016).The requirement for high-dose vasopressor therapy at any time during ICU admission was associated with a very high mortality rate in the ICU and the hospital.

To investigate the roles of CD4+ T cells and Th2 cytokine interleukin (IL)-5 in asthma, we examined the activation of CD4+ T cells and IL-5 production in cultures of bronchoalveolar lavage (BAL) cells and PBMC with and without allergen stimulation, in vitro, in 12 atopic asthmatic, 10 non-atopic asthmatic and 9 atopic non-asthmatic patients, as well as 10 normal control subjects. The patients with atopic and non-atopic asthma had significantly increased percentages of CD4+ T cells expressing CD25 (10.1% +/- 1.8% and 10.6% +/- 2.9%) and HLA-DR (11.2% +/- 3.1% and 12.0% +/- 3.6%, respectively) as compared with normal control subjects (P < 0.01) in unstimulated BAL cell cultures. IL-5 levels in the supernatants of those BAL cells from atopic and non-atopic asthmatic patients significantly enhanced (43.8 +/- 14.2 pg/ml and 85.5 +/- 15.1 pg/ml) as compared with those for atopic non-asthmatic and normal control subjects (P < 0.01). Meanwhile, increased percentages of activated CD4+ T cells and IL-5 secretion were also observed in the cultures of unstimulated PBMC from both types of asthmatic patients. In the cultures of allergen-stimulated BAL cells and PBMC, atopic asthmatic patients demonstrated marked increase in the percentage of CD4+ CD25+ T cells (17.9% +/- 13.9% and 29.0% +/- 27.5%) and IL-5 production (30.5 +/- 13.3 pg/ml and 109.3 +/- 35.0 pg/ml, for BAL cell and PBMC cultures respectively) as compared with nona-topic asthmatic patients (P < 0.01). Although the percentages of activated CD4+ T cells and IL-5 secretion elevated significantly in allergen-stimulated culture of PBMC from atopic non-asthmatic subjects, the IL-5 release by the allergen-stimulated BAL cells from the same subjects were still significantly lower than both forms of asthmatic patients (P < 0.01). Our findings show that activation of CD4+ T cells and IL-5 production are strongly implicated in the pathogenesis of both atopic and non-atopic asthma.

When ascending to the high altitude, people living in low altitude areas will suffer from hypoxia and acute mountain sickness. To reduce the risk of acute mountain sickness, based on the technology of oxygen concentration membrane, we developed a new portable oxygen enrichment device for individual. Eight healthy male subjects were screened and flew to Tibet (Lhasa, 3,700 m) to perform the experiment. First, subjects wore the oxygen enrichment device and performed an incremental exercise on cycle ergometer. The test included heart rate (HR), saturation of peripheral oxygen (SpO2) and physical work capacity (PWC). Then, after a rest period of 4 hours, the experimental protocol was repeated without oxygen enrichment device. The results showed that higher SpO2, lower HR, and better PWC (measured by the PWC-170) were observed from all the subjects 'with oxygen enrichment device' compared with 'without oxygen enrichment device' (P<0.01). We suggested that the new portable oxygen enrichment device would be effective in improving exercise performance when ascending to the high altitude.

In the present study, on the basis of our previous study on the relationship between the resistivity and structure of the live human skull, a 2D simulation model of human skull with inhomogeneous resistivity distribution was successfully obtained from CT image. The results showed that the˰̻̼̼̓ͅ˰̵̹̹̹͉͂̓̓̈́͆̈́˰͇̱̓˰̷̶̹̹̹̳̱̼͉̓̾̾̈́˰̸̷̵̵̹̾̿̽̿̾̿̓ͅ˼˰̴̱̾˰̸̵̈́˰̵̱̼͆̓ͅ˰̶̿˰̻̼̼̓ͅ˰̵̹̹̹͉͂̓̓̈́͆̈́˰̶̿͂˰̸̹̈́̓˰̵̳̹̓̈́̿̾˰̷̵̴̱͂̾˰̶͂̿̽˰̅̇̈̂˰̈́̿˰́̅̀̃̄Ω˾̳̽˾˰ In this study, we explored the method of establishing the head simulation model with real resistivity distribution of human skull, which provided feasibility for future application and should be meaningful for the improvement of the accuracy of the studies on bioelectro-magnetic effects and EIT of the head.

Place field size is stable for a given neuron in a familiar environment, yet increases along the septotemporal axis of hippocampal CA1. It is suggested that place cell assemblies are velocity controlled oscillators (VCO), i.e., the place cell’s oscillation frequency is positively correlated with the running velocity. The VCO model has the potential assumption that the velocity is correctly perceived. However, the perception of velocity may not be faithful to the actual physical velocity in some pathological and behavioral conditions. In this study, we examine the scenario in which perceived velocity deviates from the actual value. Place field size and distribution density change with the precision of perceived velocity. Simulation studies verify that this model is in accordance with previous studies. Testable predictions are also proposed.

Utilizing the noise of PC soundcard as random resource to obtain random sequences,which was then processed by the secure hash algorithm SHA-256.Thus a method of random sequences producinging was made.The random sequences were tested according to American standard FIPS14022.It shows that the method is feasible and practical with the testing results.

Purpose: Spontaneous rupture of spleen (SRS) is a rare but fatal complication of Infectious Mononucleosis (IM) with a reported incidence of 0.1 - 0.5%. Management usually consists of splenectomy in hemodynamically unstable patients and non-operative surveillance in stable patients. We report the successful use of splenic artery embolization as an alternative treatment in an unstable patient. Case: A previously healthy 18-year-old male admitted to the hospital with the sudden onset of left sided abdominal pain and pre-syncope after 1 week of fever and sore throat. On examination, he had BP of 86/46 and HR of 112 with severe left upper quadrant tenderness. Blood work showed Hemoglobin (Hb) of 12.3 which dropped to 6.4 in 6 hours of presentation and he was transfused with 2 units of packed RBCs. Abdominal CT scan revealed a grade III splenic laceration with large amount of blood in peritoneal cavity (Figure 1). Splenic artery arteriography along with embolization of the main splenic artery was performed (Figure 2). After the procedure his Hb stabilized, abdominal pain improved and fever resolved. Subsequently Epstein-barr virus serology was positive with a titer >160 u/ml. Repeat CT scan in 4 days after the procedure showed multiple regions of splenic infarction but the majority of the spleen was preserved. His Hb stabilized and was discharged on day 6 of his hospitalization.Figure 1Figure 2Discussion: Splenic artery embolization has not been studied well in cases of SRS secondary to IM. The majority of the literature is on splenectomy in unstable patients or non-operative watchfulness in stable patients. This methodology preserves spleen and prevents the dreadful complication of overwhelming post splenectomy infection, risks of laparotomy and the consequent morbidity and mortality in apslenic patients.

This paper describes a new method of temperature measurement in microwave field. This method resolves a series of problems such as the microwave field suppression, the linearization of the temperature sensor and the sensor exchangeability.

In the present study, the influence of the variation of immersion fluid volume (or air-drying time) on skull resistivity was studied. The results showed that the skull resistivity increased significantly with the increasing of air-drying time. For air-drying time of 10 min, the skull resistivity increased approximately 2 times, and for 30 min and 60 min, the skull resistivity increased significantly about 7 times and 19 times. This study suggests that we should pay more attention to the humidity of experimental environment to keep the natural immersion fluid from volatilizing in the measurement on skull resistivity. Preserving the freshly excised skull samples in gauze soaked with physiological saline can effectively keep the immersion fluid and maintain the natural physiological status.

In the present study, the resistivities of the live monkey skulls were measured in the frequency range of 1Hz-3 MHz and in a carefully controlled experimental situation. The measurement results showed that the resistivities of monkey skulls were inhomogeneous and ranged from 6630 to 11243 Ω.cm (f = 1 kHz). Due to the absence of the suture and pure compact skull, the resistivity variation of monkey skull is not remarkable compared to that of human skull. The resistivity spectroscopy of monkey skull showed that there was an inverse relationship between skull resistivity and frequency in a wide frequency range, especially when the frequency was higher than 10 kHz. In order to parameterize the resistivity spectroscopy properties of monkey skull, four characteristic parameters (ρ0, ρ ∞ , αand f c ) of resistivity spectroscopy were extracted and calculated respectively, and the characteristic frequency of monkey skull was around 750 kHz.

The structural similarity of the head model affects the accuracy of solutions to electrical impedance tomography (EIT) forward problem. The conductivity of skull is one of the most sensitive head model parameters. Generally, the skull is considered as a homogeneous whole, while in fact it is inhomogeneous. In this paper EIT images are reconstructed with different head models to detect and localize the conductivity changes in brain. The simulation results show that localization accuracy of the conductivity changes in brain has been improved when skull inhomogeneities are taken into account. Incorporation of skull inhomogeneities into image reconstruction is an effective way to improve image quality of brain EIT.

To implement a fast location of metallic foreign body in human body and fast preoperative or postoperative detection of surgical instruments,a portable device based on gradient measurement of fluxgate sensors was designed.Two working modes based on remnant magnetic effect and eddy current effect were proposed for locating two different kinds of metal,thereby solving the problem that nonferromagnetics could not be sensed by fluxgate.Metglas ribbon and modified race-track core were chosen and digital signal processor was utilized to implement harmonic extraction and cross correlation algorithm,which could mean a better fluxgate performance.Database of the depth information was established to provide the ability of analyzing the depth in human body.The locating experiments of 15 foreign body patients has demonstrated the effectiveness of the proposed portable device in clinic applications.

Objective To investigate the changes of calcitonin gene-related peptide (CGRP) in rat' s blood plasma, spinal anterior motorneuron and dorsal root ganglion (DRG) after fractures combined with central or peripheral nerve injuries and possible influence on fracture healing. Methods A total of 72 healthy adult SD rats were divided into four groups, ie, left tibial fracture group (Group A), left tibial fracture combined with left sciatic nerve injury group (Group B), left tibial fracture combined with T9-11 spinal cord transection injury group (Group C) and left tibial fracture combined with right cerebral cortex injury group (Group D). The concentration of serum CGRP was measured by radioimmunoassay immediately, 1, 2 and 4 weeks after injury. The concentration of serum CGRP in spinal anterior motor-neuron and dorsal root ganglion was measured and X ray photograph taken at 1,2 and 4 weeks after inju-ry. Bony callus was collected at 2 weeks after injury for HE staining. Results The fracture line was still clear on X-ray of all groups 1 and 2 weeks after injury but disappeared with complete healing four weeks after injury in all groups except for Group B. Two weeks after injury, HE staining showed less bony callus contents in Group B than that of Group A but more bony callus contents in Groups C and D than that of Group A. CGRP concentration in blood plasma and spinal anterior motorneuron represented no apparentstatistical difference among all groups at each time point (P>0.05). Changes of CGRP con-centration in dorsal root ganglion were as follows: one week after injury, there was no apparent statistical difference in Groups B and D compared with Group A (P > 0.05), but Group A showed more CGRP than Group C (P 0.05), but CGRP in Group D was more than that in Group B (P < 0.05) and CGRP in Group C more than Group A (P <0.01); four weeks after injury, CGRP concentration was elevated in all groups especially Group C compared with Group A (P < 0.01). Conclusions When fracture is combined with peripheral nerve injury, the healing process can be slowed down. In contrast, fracture combined with spinal'injury and cerebral cortex injury will accelerate healing process, when CGRP may exert positive effect. Key words: Wounds and injuries;  Nervous system;  Fracture healing;  Calcitonin gene-re-lated peptide

Multiscale entropy (MSE) has attracted many applications in revealing the complexity of bio-signals since its introduction in early 2000.To better understand the MSE method, a lot of researchers have been working on its analytical solution.The existing analytical solutions are limited either to bulky double integrals, or to a proportional relation.This study intends to solve the double integrals and further approximate the analytical formula of MSE.Combining Costa's method with Briggs' integral and Taylor series expansion, we approximated the analytical formula of MSE for uncorrelated (white) noise.With the additional help of the eigenvalue of a fractal Brownian motion process, we approximated the analytical formula of MSE for correlated noise (1/f noise).The analytical formulae were verified on simulated power noise with known scaling exponent.The proposed analytical solution may shed some light on the understanding of MSE in analyzing biological time series.

To review the current situation and to solve the personnel training problems of the subject of medical metrology, the practice and exploration on undergraduate course construction of medical metrology was developed in Air Force Medical University so as to improve the personnel training capacity of medical metrology on biomedical engineering (BME) undergraduates. By means of the investigation and expert argumentation and the practice and exploration on course construction, a course system on medical metrology was established, which integrated the basic knowledge and practice skills. Furthermore, the combination of course teaching with authentication capability was firstly developed, which can greatly improve the competence of position of BME undergraduates. The study is hopeful to provide reference and support for the further personnel training on medical metrology in the colleges and universities. Key words: Medical metrology; Course construction; Biomedical engineering; Practice

Objective:In order to suit the need of military itinerant inspection,an acoustic output measurement system,which is the basement for the manufacture of a portable instrument,is developped.Method:A hydrophone is used as energy converting equipment to collect waves of acoustic pressure in the field of ultrasonic.Though some calculations,a series of acoustic output parameters are achieved.Results:The main acoustic output parameters can be measured in the range of permitted errors.Conclusions:This method is feasible and data can be well repeated.

Respiration is an important physiological process. The detection of th e respiratory signal is a main part of the modern wardship. This paper discusses the detection methods of the respiratory signal and compares their performances and application ranges.

Aiming at the weakness of experimental teaching in the course of metrology, and improving the skill of metrology for students majoring in biomedical engineering, Air Force Military Medical University has demonstrated and built a special medical metrology for teaching. This paper mainly introduces the exploration and the construction of metrology teaching laboratory, including the construction principle, structure design, equipment configuration, condition construction, laboratory management and experimental training, in order to provide reference and help for the future development of metrology teaching laboratory construction in colleges and universities. Key words: Medical metrology; Teaching; Laboratory construction; Biomedical engineering

Abstract Background: Conventional manual sleep stage classification is time-consuming and relies on the knowledge and experience of the specialists. The emergence of automatic sleep stage classification greatly improves the classification efficiency. The feature extraction in automatic sleep stage classification is particularly important, which usually uses the linear methods based on techniques in the time domain, frequency domain, or time-frequency domain. Electroencephalograms (EEGs) contain a wealth of physiological information, have been widely used for the classification of sleep stage. Due to the nonlinear, non-stationary, and multifractal characteristics of EEGs, some nonlinear methods have been used to extract features of sleep stages in recent years, such as complexity, multifractal theory, and chaos theory. The Wavelet Leader Multifractal Formalism (WLMF) of the multifractal theory is widely applied to different physiological signals. The current researches focus on discussing the mean H¨older exponent (h0) and the width of the multifractal singularity spectrum (WD(h)) estimated by the WLMF method. However, in the field of sleep staging, a number of researches focused on h0, but few studies on WD(h). Results: This paper aims to assess the multifractal characteristic for sleep EEG time series from the Sleep-EDF Expanded Database by the WLMF method. In the young group, the mean h0 increased from the Wake stage to the S3 stage (p&lt;0.01). So did the elderly group (p&lt;0.001). WD(h) of the Wake stage was less than that of the S3 stage for the young group, and this relationship was reversed for the elderly group(χ2=13.769, df=1, p&lt;0.001). Gender did not affect, with statistical significance, WD(h) of the Wake stage and the S3 stage (χ2=0.085, df=1, p=0.608), nor did the brain region (χ2=3.137, df=1, p=0.078). Conclusions: The result shows that WD(h) was influenced by aging. The gender and location of brain regions did not show significant influence on the multifractal characteristics of wakefulness and sleeping. This finding extends the application of the multifractal singularity spectrum on sleep staging, and raises a fundamental question on what might be the underlying mechanisms of the WD(h) reversion.

To understand the reasons and roles of CD4+ T cell activation and IL-5 production in atopic and asthmatic patients.Bronchoalveolar lavage(BAL) cells and peripheral blood mononuclear cells (PBMC) from 12 atopic and 10 nonatopic asthmatics, 9 atopic nonasthmatics, and 10 normal controls were cultured with or without house dust mite(HDM), CD4+ T cell activation, and IL-5 production were assessed.The percentage of CD4+, CD25+ in unstimulated PBMC cultures were not significantly different in the four groups, but it increased following HDM stimulation in both PBMC and BAL cultures in two atopic groups(P < 0.01). The percentage of CD4+, CD25+ in unstimulated BAL cell culture increased in two asthmatic groups (P < 0.05, P < 0.01). The levels of spontaneous IL-5 released from both BALF cells and PBMC in two asthmatic groups were higher than those in AN and N (P < 0.05, P < 0.01). A significant elevation in IL-5 release following HDM stimulation in PBMC and BALF cells was observed in the both asthmatic and atopic groups; but the value in AA was higher than that in NAA, and it was also higher in BALF cells than in PBMC.The allergen stimulation is important reasons for CD4+ T cell activation and IL-5 production in atopics. CD4+ T cell activation and IL-5 production are common feature in atopic and nonatopic asthma, it correlates with both asthmatic and atopic status.