Double neutron star (DNS) merger events are promising candidates of short gamma-ray burst (sGRB) progenitors as well as high-frequency gravitational wave (GW) emitters. On August 17, 2017, such a ...coinciding event was detected by both the LIGO-Virgo gravitational wave detector network as GW170817 and Gamma-Ray Monitor on board NASA's Fermi Space Telescope as GRB 170817A. Here, we show that the fluence and spectral peak energy of this sGRB fall into the lower portion of the distributions of known sGRBs. Its peak isotropic luminosity is abnormally low. The estimated event rate density above this luminosity is at least Formula: see text Gpc
yr
, which is close to but still below the DNS merger event rate density. This event likely originates from a structured jet viewed from a large viewing angle. There are similar faint soft GRBs in the Fermi archival data, a small fraction of which might belong to this new population of nearby, low-luminosity sGRBs.
Diosgenin, a well-known steroid sapogenin derived from plants, has been used as a starting material for production of steroidal hormones. The present review will summarize published literature ...concerning pharmacological potential of diosgenin, and the underlying mechanisms of actions. Diosgenin has shown a vast range of pharmacological activities in preclinical studies. It exhibits anticancer, cardiovascular protective, anti-diabetes, neuroprotective, immunomodulatory, estrogenic, and skin protective effects, mainly by inducing apoptosis, suppressing malignant transformation, decreasing oxidative stress, preventing inflammatory events, promoting cellular differentiation/proliferation, and regulating T-cell immune response, etc. It interferes with cell death pathways and their regulators to induce apoptosis. Diosgenin antagonizes tumor metastasis by modulating epithelial-mesenchymal transition and actin cytoskeleton to change cellular motility, suppressing degradation of matrix barrier, and inhibiting angiogenesis. Additionally, diosgenin improves antioxidant status and inhibits lipid peroxidation. Its anti-inflammatory activity is through inhibiting production of pro-inflammatory cytokines, enzymes and adhesion molecules. Furthermore, diosgenin drives cellular growth/differentiation through the estrogen receptor (ER) cascade and transcriptional factor PPARγ. In summary, these mechanistic studies provide a basis for further development of this compound for pharmacotherapy of various diseases.
Summary
Men with type 2 diabetes (T2D) and obesity are often characterised by low testosterone (T). We aimed to determine whether exenatide (EXE) combined metformin (MET) treatment has a better ...effect on serum total testosterone (TT) levels than glimepiride (GLI) combined MET treatment in men with T2D and obesity. In a multicentre, 12‐week observational study, 176 obese T2D men with failed glycaemic control were included in the study: ninety men (mean age, 43.00 ± 8.50 years) in EXE + MET group and 86 men (mean age, 44.00 ± 7.00 years) in GLI + MET group. Serum TT levels were more significantly increased in EXE + MET group than GLI + MET group (121.72 ± 56.73 ng/dl versus 34.67 ± 16.30 ng/dl). The increasement of TT levels in those patients who lost body weight ≥5% was significantly greater than those who lost weight <5% in the two groups. The changes in TT levels are closely related to the changes in waist circumference (r = −.443, p < .001). Sexual function assessment of EXE + MET group was more significantly improved than GLI + MET group (p < .001). No serious adverse events were observed. In conclusion, short‐term combined treatment with EXE and MET is superior to GLI combined MET treatment in the improvement of serum TT levels, which could lead to an improvement of sexual hypofunction in patients with obesity and T2D.
With the aim of gathering temporal trends on bacterial epidemiology and resistance from multiple laboratories in China, the CHINET surveillance system was organized in 2005. Antimicrobial ...susceptibility testing was carried out according to a unified protocol using the Kirby-Bauer method or automated systems. Results were analyzed according to Clinical and Laboratory Standards Institute (CLSI) 2014 definitions. Between 2005 and 2014, the number of bacterial isolates ranged between 22 774 and 84 572 annually. Rates of extended-spectrum β-lactamase production among Escherichia coli isolates were stable, between 51.7 and 55.8%. Resistance of E. coli and Klebsiella pneumoniae to amikacin, ciprofloxacin, piperacillin/tazobactam and cefoperazone/sulbactam decreased with time. Carbapenem resistance among K. pneumoniae isolates increased from 2.4 to 13.4%. Resistance of Pseudomonas aeruginosa strains against all of antimicrobial agents tested including imipenem and meropenem decreased with time. On the contrary, resistance of Acinetobacter baumannii strains to carbapenems increased from 31 to 66.7%. A marked decrease of methicillin resistance from 69% in 2005 to 44.6% in 2014 was observed for Staphylococcus aureus. Carbapenem resistance rates in K. pneumoniae and A. baumannii in China are high. Our results indicate the importance of bacterial surveillance studies.
Abstract The aim of this study was to identify the risk factors for free flap failure after head and neck reconstructive surgery. The data of 881 consecutive patients who underwent free flap surgery ...at the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, between January 2013 and November 2016, were reviewed retrospectively. All surgeries were performed by a single head and neck surgical team. Patient demographic and surgical data that may have an influence on free flap outcomes were recorded. The χ2 test and multivariate logistic regression analysis were used to identify relevant risk factors. In total, 881 free tissue transfer surgeries were included in this study. Free flap failure occurred in 26 of 881 flaps (2.9%). A history of irradiation (odds ratio 0.205, 95% confidence interval 0.07–0.56; P = 0.002) was a statistically significant risk factor for free flap failure. Age, diabetes mellitus, history of previous neck surgery to the anastomosis side, donor site, choice of recipient vein, use of a coupler device, and postoperative anticoagulation were not associated with free flap outcomes. Thus, it is concluded that when performing head and neck reconstructive surgery, special attention should be paid to patients who have previously undergone irradiation.
The Davis—Kahan theorem is used in the analysis of many statistical procedures to bound the distance between subspaces spanned by population eigenvectors and their sample versions. It relies on an ...eigenvalue separation condition between certain population and sample eigenvalues. We present a variant of this result that depends only on a population eigenvalue separation condition, making it more natural and convenient for direct application in statistical contexts, and provide an improvement in many cases to the usual bound in the statistical literature. We also give an extension to situations where the matrices under study may be asymmetric or even non-square, and where interest is in the distance between subspaces spanned by corresponding singular vectors.
Summary Background The novel influenza A H7N9 virus emerged recently in mainland China, whereas the influenza A H5N1 virus has infected people in China since 2003. Both infections are thought to be ...mainly zoonotic. We aimed to compare the epidemiological characteristics of the complete series of laboratory-confirmed cases of both viruses in mainland China so far. Methods An integrated database was constructed with information about demographic, epidemiological, and clinical variables of laboratory-confirmed cases of H7N9 (130 patients) and H5N1 (43 patients) that were reported to the Chinese Centre for Disease Control and Prevention until May 24, 2013. We described disease occurrence by age, sex, and geography, and estimated key epidemiological variables. We used survival analysis techniques to estimate the following distributions: infection to onset, onset to admission, onset to laboratory confirmation, admission to death, and admission to discharge. Findings The median age of the 130 individuals with confirmed infection with H7N9 was 62 years and of the 43 with H5N1 was 26 years. In urban areas, 74% of cases of both viruses were in men, whereas in rural areas the proportions of the viruses in men were 62% for H7N9 and 33% for H5N1. 75% of patients infected with H7N9 and 71% of those with H5N1 reported recent exposure to poultry. The mean incubation period of H7N9 was 3·1 days and of H5N1 was 3·3 days. On average, 21 contacts were traced for each case of H7N9 in urban areas and 18 in rural areas, compared with 90 and 63 for H5N1. The fatality risk on admission to hospital was 36% (95% CI 26–45) for H7N9 and 70% (56–83%) for H5N1. Interpretation The sex ratios in urban compared with rural cases are consistent with exposure to poultry driving the risk of infection—a higher risk in men was only recorded in urban areas but not in rural areas, and the increased risk for men was of a similar magnitude for H7N9 and H5N1. However, the difference in susceptibility to serious illness with the two different viruses remains unexplained, since most cases of H7N9 were in older adults whereas most cases of H5N1 were in younger people. A limitation of our study is that we compared laboratory-confirmed cases of H7N9 and H5N1 infection, and some infections might not have been ascertained. Funding Ministry of Science and Technology, China; Research Fund for the Control of Infectious Disease and University Grants Committee, Hong Kong Special Administrative Region, China; and the US National Institutes of Health.
Although significant advances have recently been made in the diagnosis and treatment of cervical carcinoma, the long-term survival rate for advanced cervical cancer remains low. Therefore, an urgent ...need exists to both uncover the molecular mechanisms and identify potential therapeutic targets for the treatment of cervical cancer. MicroRNAs (miRNAs) have important roles in cancer progression and could be used as either potential therapeutic agents or targets. miR-506 is a component of an X chromosome-linked miRNA cluster. The biological functions of miR-506 have not been well established. In this study, we found that miR-506 expression was downregulated in approximately 80% of the cervical cancer samples examined and inversely correlated with the expression of Ki-67, a marker of cell proliferation. Gain-of-function and loss-of-function studies in human cervical cancer, Caski and SiHa cells, demonstrated that miR-506 acts as a tumor suppressor by inhibiting cervical cancer growth in vitro and in vivo. Further studies showed that miR-506 induced cell cycle arrest at the G1/S transition, and enhanced apoptosis and chemosensitivity of cervical cancer cell. We subsequently identified Gli3, a hedgehog pathway transcription factor, as a direct target of miR-506 in cervical cancer. Furthermore, Gli3 silencing recapitulated the effects of miR-506, and reintroduction of Gli3 abrogated miR-506-induced cell growth arrest and apoptosis. Taken together, we conclude that miR-506 exerts its anti-proliferative function by directly targeting Gli3. This newly identified miR-506/Gli3 axis provides further insight into the pathogenesis of cervical cancer and indicates a potential novel therapeutic agent for the treatment of cervical cancer.
Buying is easier than shorting for many equity investors. Combining this arbitrage asymmetry with the arbitrage risk represented by idiosyncratic volatility (IVOL) explains the negative relation ...between IVOL and average return. The IVOL-return relation is negative among overpriced stocks but positive among underpriced stocks, with mispricing determined by combining 11 return anomalies. Consistent with arbitrage asymmetry, the negative relation among overpriced stocks is stronger, especially for stocks less easily shorted, so the overall IVOL-return relation is negative. Further supporting our explanation, high investor sentiment weakens the positive relation among underpriced stocks and, especially, strengthens the negative relation among overpriced stocks.
Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is associated with an increased risk of graft failure and severe graft-versus-host disease (GVHD). Recent studies have shown that ...mesenchymal stromal cells (MSCs) display potent immunosuppressive effects and can support normal hematopoiesis. In a multi-center trial, we co-transplanted culture-expanded donor-derived bone marrow MSCs (BM-MSCs) into 35 children with severe aplastic anemia (SAA) undergoing haplo-HSCT. All 35 patients (100%) achieved hematopoietic reconstitution and showed sustained full donor chimerism. The median time for myeloid engraftment was 14 days (range 10–22 days), while that for platelet engraftment was 18 days (range 9–36 days). The incidence of grade II–IV acute GVHD and chronic GVHD was 25.71 and 22.86%, respectively. The overall survival rate was 85.71% with a median of 22 months (range 3.5–37 months). The combined transplantation of haploidentical HSCs and BM-MSCs into children with SAA without an HLA-identical sibling donor is relatively safe and may represent an effective new therapy to improve survival rates and reduce the risk of graft failure.
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