基于网络药理学探讨搜风愈喘方拆方“祛宿痰方”调控儿童哮喘的作用机制＊

目的 基于“伏风暗瘀宿痰”小儿哮喘病机新说，采用网络药理学及实验验证的方法，探索搜风愈喘方拆方“祛宿痰方”治疗儿童哮喘的作用机制，验证中医“宿痰”病机与西医细胞外基质改变病理之间的交通性。方法 通过TCMSP数据库建立“祛宿痰方”的有效成分和靶点数据集，利用OMIM、GeneCards、DrugBank、TTD疾病数据库建立哮喘疾病靶点数据集，利用Cytoscape软件取交集并构建“祛宿痰方”与哮喘的蛋白质互作网络，筛选关键靶点蛋白。利用Metascape数据库进行基因本体（Gene ontology，GO）分析以及京都基因和基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）富集分析。复制卵蛋白（OVA）诱导的哮喘大鼠模型，对核心通路及关键靶点进行实验验证。结果 共得到“祛宿痰方”治疗哮喘的靶点98个，包括IL-13、TP53、TGF-β1、VEGF-A、MMP9等，KEGG得到与哮喘相关的通路287条（P＜0.05），包括NF-κB信号通路、PI3K-AKT信号通路、IL-17信号通路等。GO结果显示与哮喘相关生物进程包括炎症反应、细胞外基质调控、氧化应激、血管生成等。动物实验证实“祛宿痰方”可下调大鼠肺组织中p-NF-κB-P65磷酸化水平，抑制NF-κB信号通路的激活，降低IL-13、TGF-β1 mRNA表达量（P<0.05），减少哮喘大鼠肺组织中炎症细胞浸润、黏液产生，从而延缓哮喘的进程。结论 “祛宿痰方”可抑制NF-κB信号通路的激活，降低肺组织中IL-13、TGF-β1 mRNA表达量，可能通过抑制炎症反应、调控细胞外基质等途径作用于哮喘，中医“宿痰”病机与西医细胞外基质改变病理之间存在一定的的交通性。     

人工智能在中医药领域的应用进展及现状思考

人工智能（Artificial Intelligence，AI）的蓬勃兴起为现代社会带来了前所未有的机遇，中医药是中华民族传承千年的文化瑰宝。随着人工智能技术不断在中医药领域的科技创新中崭露头角，二者的融合不断加深，人工智能在中医药领域的发展前景、争议挑战也引发了诸多思考。本文将从人工智能在中医药领域的应用入手，对人工智能辅助中医诊断、智能决策与数据挖掘、健康管理及中草药现代化研究等方面，就近年来国内外研究进展进行总结与分析，以期为AI视域下实现中医药现代化、智能化赋能。     

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。     

基于真实世界数据探讨中医药治疗糖尿病肾病用药规律的研究＊

目的 基于临床信息系统分析总结真实世界的数据，采用数据挖掘的方法探讨中医药治疗糖尿病肾病的用药规律。方法 收集2018年1月-2020年12月上海中医药大学附属曙光医院宝山分院健康信息系统确诊的糖尿病肾病的门诊或住院患者的诊疗信息，建立Excel数据库，采用Excel 2010软件统计高频药物的四气、五味、归经及功效；使用SPSS Modeler 18.0软件中的Apriori算法分析关联规则，采用web节点建构药对关联网状图；运用SPSS 25统计软件进行因子分析。结果 本研究最终纳入477例接受中药饮片治疗的DKD患者，在1203条方剂信息中，涉及中药462种；使用频数排名前5位的中药分别是黄芪、黄精、石斛、山茱萸、麦冬；使用频数前5类的中药类别分别是补气药、补阴药、清热燥湿药、活血调经药、息风止痉药；在30味高频药物中，苦、甘、辛药味最为常见；药性寒、温数量接近；归脾经、肝经、肺经、肾经居多；关联规则提示，药物组合中置信度最高的组合为地龙-当归-僵蚕，因子分析共得到5个有效因子，累积贡献率为47.33%。结论 中医药治疗DKD在补益气血阴阳的同时，兼顾对瘀血、湿邪和痰饮的治疗，结合证型，可考虑使用黄芪、黄精、石斛、山茱萸、麦冬、金蝉花等药物的使用，清热燥湿药物如黄连、黄芩、黄柏可适当加入，为使邪有去处，大黄、车前子或可增添疗效。     

数据挖掘法探讨周珉教授治疗原发性肝癌用药规律及经验总结

[目的]数据挖掘法分析周珉教授治疗原发性肝癌的中医用药规律,探讨相关病机并进行经验总结。[方法]收集2016年2月—2018年5月周珉教授门诊期间治疗原发性肝癌的方剂,运用"中医传承辅助系统(V2.50)"进行数据挖掘,并结合周珉教授临床经验,进行原发性肝癌病机探讨及用药规律分析。[结果]共收集治疗原发性肝癌方剂176首,涉及中药235种,列出方剂中的高频药物及组合规律。[结论]总结原发性肝癌以"湿热痰毒、气阴两伤"为基础病机,"清热化湿、健脾养阴"治则贯穿原发性肝癌治疗始末,同时,根据疾病不同发展阶段及治疗措施,权衡"扶正"与"祛邪"的主次分配,斟酌应用"攻毒散结""行气化瘀"等治法,以达到改善患者生活质量、延缓疾病进展的目的。     

Reference set for performance testing of pediatric vaccine safety signal detection methods and systems

BackgroundSafety signal detection in spontaneous reporting system databases and electronic healthcare records is key to detection of previously unknown adverse events following immunization. Various statistical methods for signal detection in these different datasources have been developed, however none are geared to the pediatric population and none specifically to vaccines. A reference set comprising pediatric vaccine-adverse event pairs is required for reliable performance testing of statistical methods within and across data sources.MethodsThe study was conducted within the context of the Global Research in Paediatrics (GRiP) project, as part of the seventh framework programme (FP7) of the European Commission. Criteria for the selection of vaccines considered in the reference set were routine and global use in the pediatric population. Adverse events were primarily selected based on importance. Outcome based systematic literature searches were performed for all identified vaccine-adverse event pairs and complemented by expert committee reports, evidence based decision support systems (e.g. Micromedex), and summaries of product characteristics. Classification into positive (PC) and negative control (NC) pairs was performed by two independent reviewers according to a pre-defined algorithm and discussed for consensus in case of disagreement.ResultsWe selected 13 vaccines and 14 adverse events to be included in the reference set. From a total of 182 vaccine-adverse event pairs, we classified 18 as PC, 113 as NC and 51 as unclassifiable. Most classifications (91) were based on literature review, 45 were based on expert committee reports, and for 46 vaccine-adverse event pairs, an underlying pathomechanism was not plausible classifying the association as NC.ConclusionA reference set of vaccine-adverse event pairs was developed. We propose its use for comparing signal detection methods and systems in the pediatric population.     

Bibliometric analysis of orthopaedic related publications by Indian authors from the last decade

PurposeBibliometric studies have been established methods of analysing publications on a particular topic. These studies have been done on various orthopaedic topics and are increasing. The advantages of these studies have been highlighted in previous publications. Although some studies have been done on Indian publications from other specialties, those analysing Indian Orthopaedic Publications are lacking.MethodsWe performed a search in Scopus to look for all publications related to orthopaedics from India. Our search strategy in Scopus included ((TITLE-ABS-KEY(Orthopaedics OR Orthopaedics) AND AFFIL(India)) AND PUBYEAR > 2009 AND PUBYEAR < 2020) which resulted in 3270 articles on 02/11/2021. We analyzed the most publishing universities, city, state, specialty, authors, and anatomic location of these publications. We also mined the data to draw word clouds based on data obtained from the titles of articles, keywords and the affiliations of each of the articles published.ResultsTamil Nadu and New Delhi and their institutes appear to be the epicenter of publication activities in Orthopaedics in India. There has been a healthy trend of growth of articles in the orthopaedic specialty. Since there is a significant overlap of technology and engineering, it is not surprising to see engineering and technology institutes among the top 10 published institutes and even journals for the publications on orthopaedics.ConclusionThere has been a steady increase in the number of publications in the last decade. New Delhi and its Universities and Institutes appear to contribute the majority of citations and publications related to orthopaedics. Journal of Clinical Orthopaedics and Trauma was the most publishing journal for Indian authors on Orthopaedic related articles.     

Neural Correlates of Failed Inhibitory Control as an Early Marker of Disordered Eating in Adolescents

BackgroundBinge eating and other forms of disordered eating behavior (DEB) are associated with failed inhibitory control. This study investigated the neural correlates of failed inhibitory control as a potential biomarker for DEB.MethodsThe study used prospective longitudinal data from the European IMAGEN study adolescent cohort. Participants completed baseline assessments (questionnaires and a brain scan [functional magnetic resonance imaging]) at 14 years of age and a follow-up assessment (questionnaires) at 16 years of age. Self-reported binge eating and/or purging were used to indicate presence of DEB. Neural correlates of failed inhibition were assessed using the stop signal task. Participants were categorized as healthy control subjects (reported no DEB at both time points), maintainers (reported DEB at both time points), recoverers (reported DEB at baseline only), and developers (reported DEB at follow-up only). Forty-three individuals per group with complete scanning data were matched on gender, age, puberty, and intelligence (N = 172).ResultsAt baseline, despite similar task performance, incorrectly responding to stop signals (failed inhibitory control) was associated with greater recruitment of the medial prefrontal cortex and anterior cingulate cortex in the developers compared with healthy control subjects and recoverers.ConclusionsGreater recruitment of the medial prefrontal and anterior cingulate regions during failed inhibition accords with abnormal evaluation of errors contributing to DEB development. As this precedes symptom onset and is evident despite normal task performance, neural responses during failed inhibition may be a useful biomarker of vulnerability for DEB. This study highlights the potential value of prospective neuroimaging studies for identifying markers of illness before the emergence of behavior changes.     

中药复方配伍的研究方法及其进展

中药复方是由2味或2味以上中药遵循中医理论组合而成的方剂。多味中药在合适的剂量配比之下,协同发挥作用,实现中医的整体调节治疗。研究中药复方的配伍对推动中药现代化发展、新药开发以及临床应用有着重要意义。近年来,研究者们在传统的"七情和合"与"君臣佐使"的基础上,运用新技术和新方法对中药复方的成分、药效活性和药代动力学性质等进行了研究,从不同角度探讨了中药复方配伍的科学内涵。同时,多种数理方法和模型的建立、网络药理学和数据挖掘方法的发展与应用,也对中药复方配伍研究提供了很大帮助。研究方法的发展虽促进了中药复方配伍的科学研究,但还需进一步建立适合中药复方配伍复杂关系的研究方法,以阐明中药复方及其成分/组分配伍的内在规律,进而构建新的现代中药复方,这也是目前中药复方配伍研究的重点任务。