基于文本挖掘和生物医学数据库的新型冠状病毒肺炎药物发现

目的 基于文本挖掘技术和生物医学数据库对新型冠状病毒肺炎（COVID-19）相关文献进行数据挖掘分析，探究COVID-19及其主要症状发热、咳嗽、呼吸障碍相关基因靶点，筛选潜在有效的化学药和中药。方法 使用GenCLiP 3网站获取COVID-19和其主要症状咳嗽、发热、呼吸障碍共4个关键词的共有靶点，在METASCAPE数据库中对其进行基因本体（GO）和通路富集分析，再利用String数据库和Cytoscape软件构建共有靶点的蛋白质相互作用网络，筛选获得核心基因，运用DGIdb数据库、SymMap数据库针对核心基因进行中西医治疗药物预测。结果 获得COVID-19及其主要症状共有基因靶点28个，其中有IL2、IL1B、CCL2等核心基因16个，使用DGIdb数据库筛选获得与16个关键靶点相互作用的化学药包括沙利度胺、来氟米特、环孢素等28种，中药包括虎杖、黄芪、芦荟等70味。结论 COVID-19及其主要症状的病理机制可能和CD4、KNG1、VEGFA等28个共有基因相关，可能通过介导TNF、IL-17等信号通路参与COVID-19病理过程。潜在有效药物可能通过作用相关靶点通路起到治疗COVID-19的作用。     

Atrial fibrillation after cardiac surgery: A systematic review and meta-analysis

ObjectiveNew-onset postoperative atrial fibrillation (POAF) after cardiac surgery is common, with rates up to 60%. POAF has been associated with early and late stroke, but its association with other cardiovascular outcomes is less known. The objective was to perform a meta-analysis of the studies reporting the association of POAF with perioperative and long-term outcomes in patients with cardiac surgery.MethodsWe performed a systematic review and a meta-analysis of studies that presented outcomes for cardiac surgery on the basis of the presence or absence of POAF. MEDLINE, EMBASE, and the Cochrane Library were assessed; 57 studies (246,340 patients) were selected. Perioperative mortality was the primary outcome. Inverse variance method and random model were performed. Leave-one-out analysis, subgroup analyses, and metaregression were conducted.ResultsPOAF was associated with perioperative mortality (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.58-2.33), perioperative stroke (OR, 2.17; 95% CI, 1.90-2.49), perioperative myocardial infarction (OR, 1.28; 95% CI, 1.06-1.54), perioperative acute renal failure (OR, 2.74; 95% CI, 2.42-3.11), hospital (standardized mean difference, 0.80; 95% CI, 0.53-1.07) and intensive care unit stay (standardized mean difference, 0.55; 95% CI, 0.24-0.86), long-term mortality (incidence rate ratio [IRR], 1.54; 95% CI, 1.40-1.69), long-term stroke (IRR, 1.33; 95% CI, 1.21-1.46), and longstanding persistent atrial fibrillation (IRR, 4.73; 95% CI, 3.36-6.66).ConclusionsThe results suggest that POAF after cardiac surgery is associated with an increased occurrence of most short- and long-term cardiovascular adverse events. However, the causality of this association remains to be established.     

Deciphering the molecular landscape of microcephaly in 87 Indian families by exome sequencing

Microcephaly is a frequent feature of neurodevelopmental disorders (NDDs). Our study presents the heterogeneous spectrum of genetic disorders in patients with microcephaly either in isolated form or in association with other neurological and extra-neural abnormalities. We present data of 91 patients from 87 unrelated families referred to our clinic during 2016–2020 and provide a comprehensive clinical and genetic landscape in the studied cohort. Molecular diagnosis using exome sequencing was made in 45 families giving a yield of 51.7%. In 9 additional families probable causative variants were detected. We identified disease causing variations in 49 genes that are involved in different functional pathways Among these, 36 had an autosomal recessive pattern, 8 had an autosomal dominant pattern (all inherited de novo), and 5 had an X-linked pattern. In 41 probands where sequence variations in autosomal recessive genes were identified 31 were homozygotes (including 16 from non-consanguineous families). The study added 28 novel pathogenic/likely pathogenic variations. The study also calls attention to phenotypic variability and expansion in spectrum as well as uncovers genes where microcephaly is not reported previously or is a rare finding. We here report phenotypes associated with the genes for ultra-rare NDDs with microcephaly namely ATRIP, MINPP1, PNPLA8, AIMP2, ANKLE2, NCAPD2 and TRIT1.     

What is the impact of zinc deficiency for pancreatectomies in patients with pancreatic ductal adenocarcinoma?

Backgroundand purpose: Zinc is an essential element for human health and plays an important role in metabolic, immunological and other biological processes. The present study was conducted to investigate the association between zinc deficiency (ZD) and the perioperative clinical course in patients with pancreatic ductal adenocarcinoma (PDAC).MethodsOf 216 patients with PDAC who underwent elective pancreatectomy between 2013 and 2017 at our institution, 206 patients with sufficient clinical data were retrospectively reviewed. The perioperative variables were compared and the risk factors associated with infectious complications were identified.ResultsZD was preoperatively present in 36 (17.5%) of 206 patients with PDAC. In the patients of the ZD group, a higher proportion of males, higher preoperative modified Glasgow prognostic scores, a higher neutrophil-to-lymphocyte ratio, and a higher occurrence of postoperative infectious complications after pancreatectomy were observed, compared to the non-ZD group. By a univariate analysis, three risk factors were significantly associated with infectious complications after pancreatectomy: ZD (vs non-ZD: p = 0.002), serum albumin <3.5 g/dl (vs ≥ 3.5 g/dl: p = 0.005), and the procedure of pancreaticoduodenectomy (vs others: p = 0.013). By multivariate logistic regression analysis, the occurrence of infectious complications was significantly associated with ZD (OR 3.430, 95%CI 1.570 to 7.490, p = 0.002) and the procedure of pancreaticoduodenectomy (OR 2.030, 95%CI 1.090 to 3.770, p = 0.025).ConclusionsThe current study newly demonstrated that ZD could serve as a preoperative predictor of infectious complications after pancreatectomies in the patients with PDAC.     

超声引导下关节腔内注射重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(益赛普)治疗血友病性关节病

目的 观察超声引导下关节腔内注射重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白（益赛普）治疗血友病性关节病（HA）的价值。方法 回顾性分析32例接受超声引导下穿刺关节腔注射益赛普的HA患者，对比观察治疗前及治疗后1个月血友病关节健康评分（HJHS）、视觉模拟评分（VAS），以及超声所示目标关节增生滑膜厚度、血流信号、Melchiorre及中国早期血友病性关节病超声检测（HEAD-US-C）评分，评估其治疗价值。结果 对32例均成功完成超声引导下穿刺关节腔及腔内注射益赛普，共对18例膝关节、7例肘关节及7例踝关节进行治疗。术后未出现感染、出血等并发症。治疗后1个月，目标关节HJHS、VAS、Melchiorre评分、HEAD-US-C评分及增生滑膜最大厚度、平均厚度、血流信号均低于治疗前（P均<0.01）。结论 超声引导下关节腔内注射益赛普治疗HA安全、有效。