Optimization of Compound Ranking for Structure‐Based Virtual Ligand Screening Using an Established FRED–Surflex Consensus Approach

The use of multiple target conformers has been applied successfully in virtual screening campaigns; however, a study on how to best combine scores for multiple targets in a hierarchic method that combines rigid and flexible docking is not available. In this study, we used a data set of 59 479 compounds to screen multiple conformers of four distinct protein targets to obtain an adapted and optimized combination of an established hierarchic method that employs the programs FRED and Surflex. Our study was extended and verified by application of our protocol to ten different data sets from the directory of useful decoys (DUD). We quantitated overall method performance in ensemble docking and compared several consensus scoring methods to improve the enrichment during virtual ligand screening. We conclude that one of the methods used, which employs a consensus weighted scoring of multiple target conformers, performs consistently better than methods that do not include such consensus scoring. For optimal overall performance in ensemble docking, it is advisable to first calculate a consensus of FRED results and use this consensus as a sub‐data set for Surflex screening. Furthermore, we identified an optimal method for each of the chosen targets and propose how to optimize the enrichment for any target.     

创面修复科护士职业标准的全国专家共识

创面修复科是一门新兴学科,目前尚没有护士职业标准。为更好地规范和加强创面修复科护士队伍的能力和体系建设,中国老年医学学会烧创伤分会、中国医师协会中国创面修复科标准化建设专家委员会、全国创面修复专科联盟组织国内专家,从术语和定义、通用条件、职业要求、技能要求、培训要求、考试考核及颁证等方面,撰写了创面修复科护士职业标准的全国专家共识,供全国同行参考。     

成人心脏外科术后脑损伤诊治的中国专家共识

背景：脑损伤作为成人心脏外科术后一种严重的并发症,发病率依然较高,是除心功能不全以外导致心脏外科手术患者预后不良的最主要因素之一。 目的：为减少心脏外科手术后脑卒中并发症,建立相关方面的诊治规范。 方法：为了降低成人心脏外科术后脑损伤的发生率,减少神经系统并发症,中国研究型医院学会神经再生与修复专业委员会心脏重症脑保护学组联合神经重症护理与康复学组,组织国内心脏内外科、神经内外科、重症监护、体外循环、麻醉以及急诊等医学专家,参考国内外相关指南,结合中国的实际情况,从成人心脏外科术后脑损伤的表现形式、危险因素、非药物性保护策略、术中神经监测以及药物性保护策略等方面,旨在促进患者脑神经功能康复角度进行撰写,经多次讨论最终成稿,制定该专家共识,以期指导临床工作。 结果与结论：为了降低成人心脏手术后脑损伤的发生率,减少神经系统并发症,需要采用个性化、以患者为中心的方法来管理那些可改变的脑损伤危险因素,采用包括术中栓塞的预防,血压、血糖、体温的管理,以及针对术后神经炎性反应药物治疗等方法,达到改善手术效果、提高患者生活质量的目的。然而,目前仍需要进一步的研究,尤其是高质量的以结果为导向的随机对照试验,以进一步提高脑损伤处理策略的证据支持。 ORCID: 0000-0002-0850-5922(韩宏光) 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

呼吸道传染病产生气溶胶高风险护理操作防护专家共识

目的 制订呼吸道传染病产生气溶胶高风险护理操作防护专家共识（以下简称《共识》）。方法 查阅国内外相关文献,结合临床护理专家工作经验,通过2轮德尔菲专家咨询和专家会议,对《共识》内容进行调整。结果 《共识》包含防护基本要求和护理操作防护要点2个方面。防护基本要求从环境控制、个人防护、行政管控3个维度展开;涉及氧气吸入疗法、机械通气的护理、吸痰、雾化吸入、咽拭子采集、心肺复苏等6个产生气溶胶高风险护理操作防护要点。结论 《共识》具有一定的科学性,可为呼吸道传染病产生气溶胶高风险护理操作的防护提供临床指导。     

Interaction of Shiga toxin 2 with complement regulators of the factor H protein family

Shiga toxin 2 (Stx2) is believed to be a major virulence factor of enterohemorrhagic Escherichia coli (EHEC) contributing to hemolytic uremic syndrome (HUS). The complement system has recently been found to be involved in the pathogenesis of EHEC-associated HUS. Stx2 was shown to activate complement via the alternative pathway, to bind factor H (FH) at short consensus repeats (SCRs) 6–8 and 18–20 and to delay and reduce FH cofactor activity on the cell surface.     

Up-regulation of hormone response of human papillomavirus type 16 expression and increased DNA-protein binding by consensus mutations of viral glucocorticoid response elements

Human papillomaviruses (HPVs) and steroid hormones are linked to the development of cervical cancer. Studies from our laboratory and others showed that the steroid glucocorticoid and progesterone hormones activated the expression of HPV type 16. This activation was attributed to the specific interaction of the glucocorticoid receptor (GR) with the three glucocorticoid response elements (GREs) in the HPV16 regulatory region. In the present study, we first examined the glucocorticoid response mediated through the GREs, using GRE consensus (GREc) mutations and expression assays from a heterologous basal promoter. Both single and triple HPV16 GREc constructs increased expression in the presence of the dexamethasone glucocorticoid in HeLa cervical carcinoma cells and primary baby rat kidney epithelial cells, in comparison with the triple wild-type GREs. Further, the hormone increased significantly the expression of the viral E6-E7 oncogene mRNA from intact HPV in primary human ectocervical cells in in situ hybridization assays. Three in vitro assays of DNA-protein interaction with oligonucleotides and HeLa cell extracts showed a higher binding of protein to two of the HPV16 GREcs than to the wild-type GREs. This applied especially to the GRE containing an overlapping NF1 half site, that also had a greater differential induction by dexamethasone of expression in vivo. The NF1 site was mutated in the GREc that also was bound by unique, lower-mobility complexes in electrophoretic mobility shift assays. UV-crosslinking assays confirmed the increased binding and showed binding by a 96-kDa protein, probably the GR. Our results show an important role of glucocorticoids in HPV16 expression. The direct action through the HPV16 GREs is suggested to be mediated by the hormone-activated GR in association with other factors. © 1996 Wiley-Liss, Inc.