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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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Intravenous immunoglobulin for treatment of hospitalized COVID-19 patients: an evidence mapping and meta-analysis
Background: The clinical efficacy and safety of intravenous immunoglobulin (IVIg) treatment for COVID-19 remain controversial. This study aimed to map the current status and gaps of available evidence, and conduct a meta-analysis to further investigate the benefit of IVIg in COVID-19 patients. Methods: Electronic databases were searched for systematic reviews/meta-analyses (SR/MAs), primary studies with control groups, reporting on the use of IVIg in patients with COVID-19. A random-effects meta-analysis with subgroup analyses regarding study design and patient disease severity was performed. Our outcomes of interest determined by the evidence mapping, were mortality, length of hospitalization (days), length of intensive care unit (ICU) stay (days), number of patients requiring mechanical ventilation, and adverse events. Results: We included 34 studies (12 SR/MAs, 8 prospective and 14 retrospective studies). A total of 5571 hospitalized patients were involved in 22 primary studies. Random-effects meta-analyses of very low to moderate evidence showed that there was little or no difference between IVIg and standard care or placebo in reducing mortality (relative risk [RR] 0.91; 95% CI 0.78-1.06; risk difference [RD] 3.3% fewer), length of hospital (mean difference [MD] 0.37; 95% CI - 2.56, 3.31) and ICU (MD 0.36; 95% CI - 0.81, 1.53) stays, mechanical ventilation use (RR 0.92; 95% CI 0.68-1.24; RD 2.8% fewer), and adverse events (RR 0.98; 95% CI 0.84-1.14; RD 0.5% fewer) of patients with COVID-19. Sensitivity analysis using a fixed-effects model indicated that IVIg may reduce mortality (RR 0.76; 95% CI 0.60-0.97), and increase length of hospital stay (MD 0.68; 95% CI 0.09-1.28). Conclusion: Very low to moderate certainty of evidence indicated IVIg may not improve the clinical outcomes of hospitalized patients with COVID-19. Given the discrepancy between the random- and fixed-effects model results, further large-scale and well-designed RCTs are warranted
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Influence of occupational exposure to antineoplastic agents on adverse pregnancy outcomes among nurses: A meta-analysis
AIM: This study aimed to explore the relationship between nurses' occupational exposure to antineoplastic agents and adverse pregnancy outcomes. DESIGN: Meta-analysis. METHODS: Data were retrieved from studies published before April 2022 in PubMed, the Cochrane Library, the Web of Science, Embase databases, the China National Knowledge Infrastructure (CNKI), China Biology Medicine disc (CBM), China Science and Technology Journal databases (VIP) and Wan Fang databases (WF). Stata MP (Version 17.0) was used to conduct this meta-analysis. RESULTS: The current evidence shows that occupational exposure to antineoplastic agents increases nurses' risk of spontaneous abortions, stillbirths, and congenital abnormalities. It is necessary to pay attention to occupational exposures caused by antineoplastic agents, especially for female nurses of reproductive age. Managers should take timely and effective countermeasures to ensure their occupational safety and reduce the risk of adverse pregnancy outcomes.
研究证据
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Use of traditional Chinese medicine for the treatment and prevention of COVID-19 and rehabilitation of COVID-19 patients: An evidence mapping study
Background: The potential effectiveness of traditional Chinese medicine (TCM) against "epidemic diseases " has highlighted the knowledge gaps associated with TCM in COVID-19 management. This study aimed to map the matrix for rigorously assessing, organizing, and presenting evidence relevant to TCM in COVID-19 management.Methods: In this study, we used the methodology of evidence mapping (EM). Nine electronic databases, the WHO International Clinical Trials Registry Platform (ICTRP) Search Portal, , gray literature, reference lists of articles, and relevant Chinese conference proceedings, were searched for articles published until 23 March 2022. The EndNote X9, Rayyan, EPPI, and R software were used for data entry and management.Results: In all, 126 studies, including 76 randomized controlled trials (RCTs) and 50 systematic reviews (SRs), met our inclusion criteria. Of these, only nine studies (7.14%) were designated as high quality: four RCTs were assessed as "low risk of bias " and five SRs as "high quality. " Based on the research objectives of these studies, the included studies were classified into treatment (53 RCTs and 50 SRs, 81.75%), rehabilitation (20 RCTs, 15.87%), and prevention (3 RCTs, 2.38%) groups. A total of 76 RCTs included 59 intervention categories and 57 efficacy outcomes. All relevant trials consistently demonstrated that TCM significantly improved 22 outcomes (i.e., consistent positive outcomes) without significantly affecting four (i.e., consistent negative outcomes). Further, 50 SRs included nine intervention categories and 27 efficacy outcomes, two of which reported consistent positive outcomes and two reported consistent negative outcomes. Moreover, 45 RCTs and 38 SRs investigated adverse events; 39 RCTs and 30 SRs showed no serious adverse events or significant differences between groups.Conclusion: This study provides evidence matrix mapping of TCM against COVID-19, demonstrating the potential efficacy and safety of TCM in the treatment and prevention of COVID-19 and rehabilitation of COVID-19 patients, and also addresses evidence gaps. Given the limited number and poor quality of available studies and potential concerns regarding the applicability of the current clinical evaluation standards to TCM, the effect of specific interventions on individual outcomes needs further evaluation.
期刊论文
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Guidelines on the treatment with integrated traditional Chinese medicine and western medicine for severe coronavirus disease 2019
Severe Coronavirus Disease 2019 (COVID-19) is characterized by numerous complications, complex disease, and high mortality, making its treatment a top priority in the treatment of COVID-19. Integrated traditional Chinese medicine (TCM) and western medicine played an important role in the prevention, treatment, and rehabilitation of COVID-19 during the epidemic. However, currently there are no evidence-based guidelines for the integrated treatment of severe COVID-19 with TCM and western medicine. Therefore, it is important to develop an evidence-based guideline on the treatment of severe COVID-19 with integrated TCM and western medicine, in order to provide clinical guidance and decision basis for healthcare professionals, public health personnel, and scientific researchers involved in the diagnosis, treatment, and care of COVID-19 patients. We developed and completed the guideline by referring to the standardization process of the "WHO handbook for guideline development", the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, and the Reporting Items for Practice Guidelines in Healthcare (RIGHT).
期刊论文
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The effects of clinical decision support systems on insulin use: A systematic review
BACKGROUND: A clinical decision support system (CDSS) is a computerized system using case-based reasoning to assist clinicians in assessing disease status, in selecting appropriate therapy or in making other clinical decisions. Previous randomized controlled trials (RCTs or trials) have shown that CDSSs have the potential to improve the insulin use, but the evidence was conflicting and uncertain. The purpose of our study was to determine whether a CDSS improves the use of insulin. METHOD: PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from their inception to October 2018. The quality assessment was based on the risk of bias criteria of the Cochrane Handbook. RESULTS: Twenty-four RCTs, involving 7653 participants, were included. Thirteen of those trials (54.2%) used a computerized algorithm or a computer-assisted insulin protocol for insulin dose and therapy adjustment, of which 30.8% (four of 13) found significant changes. Of 10 trials that measured mean blood glucose levels and the 11 trials reported HbA1c, the computerized insulin dose adjustment resulted in lower mean blood glucose levels in 70.0% (seven of 10) and 36.4% (four of 11) of RCTs, respectively. Additionally, a significant reduction of hyperglycaemia events was reported in three of six RCTs. The evidence in a majority of the 24 RCTs was of moderate quality. CONCLUSIONS: CDSSs have the potential to improve the insulin use and blood glucose control in a clinical setting. The methodologies in these studies were of mixed quality. Better designed and longer-term studies are required to ensure a larger and more reliable evidence base on the effects of CDSS intervention on insulin use.
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