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Structure-Based Discovery of the SARS-CoV-2 Main Protease Noncovalent Inhibitors from Traditional Chinese Medicine
Traditional Chinese medicine (TCM) has been extensively employed for the treatment of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is demand for discovering more SARS-CoV-2 Mpro inhibitors with diverse scaffolds to optimize anti-SARS-CoV-2 lead compounds. In this study, comprehensive in silico and in vitro assays were utilized to determine the potential inhibitors from TCM compounds against SARS-CoV-2 Mpro, which is an important therapeutic target for SARS-CoV-2. The ensemble docking analysis of 18263 TCM compounds against 15 SARS-CoV-2 Mpro conformations identified 19 TCM compounds as promising candidates. Further in vitro testing validated three compounds as inhibitors of SARS-CoV-2 Mpro and showed IC50 values of 4.64 ± 0.11, 7.56 ± 0.78, and 11.16 ± 0.26 μM, with EC50 values of 12.25 ± 1.68, 15.58 ± 0.77, and 29.32 ± 1.25 μM, respectively. Molecular dynamics (MD) simulations indicated that the three complexes remained stable over the last 100 ns of production run. An analysis of the binding mode revealed that the active compounds occupy different subsites (S1, S2, S3, and S4) of the active site of SARS-CoV-2 Mpro via specific poses through noncovalent interactions with key amino acids (e.g., HIS 41, ASN 142, GLY 143, MET 165, GLU 166, or GLN 189). Overall, this study provides evidence indicating that the three natural products obtained from TCM could be further used for anti-COVID-19 research, justifying the investigation of Chinese herbal medicinal ingredients as bioactive constituents for therapeutic targets.
期刊论文
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Association between the number of retrieved lymph nodes and demographic/tumour-related characteristics in colorectal cancer: a systematic review and meta-analysis
Objective Clinical practice guidelines recommend retrieving at least 12 lymph nodes for correct staging in colorectal cancer. However, it is difficult to retrieve adequate lymph nodes because of various factors. We aimed to evaluate the association between the number of retrieved lymph nodes and demographic/tumour-related characteristics in colorectal cancer.Design Systematic review and meta-analysis of primary studies.Data sources PubMed, Embase, Cochrane and Web of Science were searched from January 2016 to June 2023.Eligibility criteria for selecting studies Studies that evaluated the association between retrieved lymph nodes and demographic/tumour-related characteristics in colorectal cancer were included.Data extraction and synthesis OR with 95% conference intervals was extracted and pooled.Results A total of 54 studies containing 2 05 821 patients were included in this meta-analysis. The results showed that fewer nodes were retrieved from elderly patients (OR=0.70, 95% CI (0.54 to 0.90), p=0.005), and from tumours located in the left colon than in the right colon (OR=0.43, 95% CI (0.33 to 0.56), p<0.001). More lymph nodes were obtained from females than males (OR=1.15, 95% CI (1.04 to 1.28), p=0.006), from the advanced T stage (T3+T4) than T1+T2 stage (OR=1.57, 95% CI (1.25 to 1.97), p<0.001) and from the N2 stage than N0 stage (OR=1.32, 95% CI (1.15 to 1.51), p<0.001). Body mass index, ethnicity, N1 stage, M stage, tumour differentiation and lymph-vascular invasion were not significantly associated with the lymph node yield.Conclusions The study results suggest that clinicians have an increased opportunity to retrieve sufficient lymph nodes for accurate pathological staging to guide treatment decisions in patients with colorectal cancer who are young, female, with tumours located in the right colon, advanced T stage and N2 stage.
期刊论文
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Health research capacity of professional and technical personnel in a first-class tertiary hospital in northwest China: multilevel repeated measurement, 2013-2017, a pilot study
Objectives To explore the health research capacity (HRC) and factors associated with professional and technical personnel (PTP) in a first-class tertiary hospital in northwest China. Methods We collected the repeated measurement data from a first-class tertiary hospital in northwest China between 2013 and 2017. HRC of PTP was assessed by a comprehensive evaluation system and measured by research capacity score (RCS). The participants were divided into research group (RCS >0) and comparison group (RCS = 0); participants of the comparison group were selected by two-stage stratified random sampling. Multilevel model for repeated measures was used to investigate the potential factors associated with HRC. Results A total of 924 PTP were included (308 in the research group and 616 in the comparison group). This study found consistent growth in RCS and associated 95% CIs for the hospital during 2013 and 2017. The linear multilevel model showed PTP with a doctorate degree had higher RCS than those with a master's degree (beta, 1.74;P<0.001), bachelor's degree (beta, 2.02;P <0.001) and others without a degree (beta, 2.32;P<0.001). Furthermore, the PTP with intermediate (beta, 0.13;P = 0.015), vice-high (beta, 0.27;P= 0.001) and senior (beta, 0.63;P<0.001) professional titles had higher RCS than those with junior positions. Compared with PTP in the administration, those in paediatrics had higher RCS (beta, 0.28;P= 0.047) though similar to PTP in other departments. PTP with an administrative position had a higher RCS than those in non-administrative positions (beta, 0.26;P<0.001). The RCS increased with the research fund (beta, 0.15;P<0.001). However, no associations were found between RCS and sex, age, ethnic, graduate school or technical type. Conclusions HRC with associated variation of PTP for the hospital in northwest China increasingly improved and degree, professional title, administrative position, and research fund were related to HRC of PTP. Multi-central prospective studies are needed to clarify the potential relationship of related factors and HRC of PTP.
期刊论文
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Effects of antiepileptic drugs on bone mineral density and bone metabolism in children: a meta-analysis
OBJECTIVE: The aim of our meta-analysis was to assess the effects of antiepileptic drugs on bone mineral density and bone metabolism in epileptic children. METHODS: Searches of PubMed and Web of Science were undertaken to identify studies evaluating the association between antiepileptic drugs and bone mineral density and bone metabolism. RESULTS: A total of 22 studies with 1492 subjects were included in our research. We identified: (1) a reduction in bone mineral density at lumbar spine (standardized mean difference (SMD)=-0.30, 95% confidence interval (CI) [-0.61, -0.05]), trochanter (mean difference (MD)=-0.07, 95% CI [-0.10, -0.05]), femoral neck (MD=-0.05, 95% CI [-0.09, -0.02]), and total body bone mineral density (MD=-0.33, 95% CI [-0.51, -0.15]); (2) a reduction in 25-hydroxyvitamin D (MD=-3.37, 95% CI [-5.94, -0.80]) and an increase in serum alkaline phosphatase (SMD=0.71, 95% CI [0.38, 1.05]); (3) no significant changes in serum parathyroid hormone, calcium, or phosphorus. CONCLUSIONS: Our meta-analysis suggests that treatment with antiepileptic drugs may be associated with decreased bone mineral density in epileptic children
研究证据
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1191. A meta-analysis on the impact of disease-specific education programs on health outcomes for patients with chronic obstructive pulmonary disease
Disease-specific education programs have become an important factor in the treatment and care of chronic conditions, such as heart failure and diabetes mellitus. However, the effectiveness of these educational methods on chronic obstructive pulmonary disease (COPD) remains unclear. The objective of this meta-analysis was to evaluate whether disease-specific education programs were beneficial to health-related quality of life (HRQoL) variables and other long-term health outcomes in patients with COPD. Using electronic databases (PubMed, Cochrane Library, Science Direct, Chinese Biomedical Data System, China National Knowledge Infrastructure, and Wanfang Database) and individual searches (published and unpublished Chinese studies), we identified 12 randomized controlled trials (RCTs; English and/or Chinese) from 1991 to 2011. A meta-analysis on these studies revealed a positive relationship between disease-specific education programs and HRQoL scores (as measured by the St. George's Respiratory Questionnaire). Moreover, educational programs were associated with increased knowledge about COPD, improved disease management skills, inhaler adherence, and decreased COPD-related emergency department visits and hospital admissions, as well as long-term effects on improving COPD patients' health outcomes. Although significant effects were not detected across all HRQoL variables and health measures, our findings suggest that education programs have the potential to be a valuable intervention for COPD patients. Our results provide a foundation for future research in this area, which we recommend as including more rigorously designed, large, randomized studies.
研究证据
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Interferon Treatment of Hepatitis C Reinfection after Liver Transplantation: A Meta-Analysis
Background. Graft reinfection with hepatitis C (HCV) after liver transplantation is a significant problem in transplant hepatology. This meta-analysis was performed to compare the effectiveness and risk of adverse events of interferon-based therapy with no treatment after liver transplantation. Methods. We searched electronic databases up to July 31, 2013, to obtain relevant research reports that satisfied the inclusion criteria. Meta-analyses were done on randomized controlled trials (RCTs) and nonrandomized trials. Results. A meta-analysis was performed on 2 RCTs and 2 cohort studies comprising a total of 326 patients (171 of whom accepted interferon-based antiviral therapy). The treatment group was found to have higher virological response (VR) rates than controls at 12, 24, 48, and 72 weeks. Patients in the antiviral group had higher sustained virological response (SVR) rates and lower mean alanine aminotransferase levels relative to controls at 48 weeks, but more total serious adverse events (AEs) than controls. Conclusions. Interferon-based treatment has some efficacy in the treatment of HCV graft reinfection following liver transplantation
研究证据
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