基于网络药理学方法研究大黄牡丹汤治疗阑尾炎的作用机制及物质基础

目的 运用网络药理学方法研究大黄牡丹汤治疗阑尾炎的作用机制及分子基础。方法 在TCMSP数据库中,检索大黄牡丹汤中五味中药的主要化学成分,通过TCMSP平台查找及预测中药化合物对应靶点,在genecards数据库中搜索阑尾炎疾病靶点,取二者靶点交集导入Swiss平台获得PPI网络,筛选核心作用靶点并构建大黄牡丹汤-潜在靶点-阑尾炎作用网络。对核心靶点进行基因本体（gene ontology,GO）分子功能及基因组百科全书（kyto encyclopedia of genes and genomes,KEGG）富集分析。采用DiscoverStiudio软件对活性成分与靶点进行分子对接。结果 筛选得大黄牡丹汤中主要活性成分有11个,该活性成分的有效靶点有166个,阑尾炎疾病709个,取交集得核心靶点66个;GO富集分析显示靶点基因主要涉及RNA聚合酶II启动子的转录正调控、一氧化氮生物合成过程的正调控、平滑肌细胞增殖正调控、蛋白磷酸化正调控等;KEGG富集结果显示大黄牡丹汤可能具有调控FoxO信号通路、鞘脂类信号通路、toll样受体信号通路等功效;结论 大黄牡丹汤可通过调控机体炎症反应、NF-kappa B信号通路、炎症介质对TRP通道,参与促炎症细胞因子的转录调节等治疗阑尾炎。     

基于网络药理学探讨扶正抗癌方治疗肝癌的作用机制

目的 基于网络药理学方法研究扶正抗癌方治疗肝癌的有效成分、作用靶点及可能作用机制.方法 利用中药系统药理学数据库和分析平台(TCMSP)筛选扶正抗癌方的生物活性成分,并预测其靶点,构建药效分子-靶点网络,进行蛋白相互作用分析,进一步寻找潜在靶点,最后通过KEGG通路、GO富集分析可能的分子机制.结果 从TCMSP中获得...     

天南星-生姜药对治疗疼痛机制的网络药理学研究

目的:运用网络药理学方法,分析天南星-生姜药对治疗疼痛的潜在靶点和作用机制.方法:通过中药系统药理学数据库和分析平台(TCMSP)检索出天南星和生姜的活性成分和靶点.以"pain"为关键词,通过DisGeNet数据库检索出和疼痛相关的靶基因,并得到共同的靶点.通过String数据库构建蛋白互作网络图(protein-p...     

桔梗治疗支气管扩张的网络药理学研究

目的:通过网络药理学研究,总结桔梗对于支气管扩张治疗的作用机制.方法:借助中药系统药理学分析平台(TCMSP)检索桔梗的有效化学成分及作用靶点,再借助GeneCard、OMIM等数据库检索支气管扩张的相关基因,同时根据UniProt数据库分析靶点所对应的基因,应用Cytoscape构建化合物靶点关系网络,应用STRING数据库构建靶点蛋白相互作用的关系网络.将得到的所有与治疗相关的靶点导人Bioconductor数据库中,对其进行GO生物学过程富集分析和KEGG代谢通路富集分析.结果:桔梗治疗支气管扩张的主要活性成分为毛地黄黄酮,刺槐黄素,相关靶点包括PRSS1、CHEK1、VEGFA、IL6、MDM2、PCNA、ICAM1,对支气管扩张具有治疗效果.结论:本研究初步展示了桔梗对于支气管扩张的多成分、多靶点、多通路作用机制,为桔梗用于治疗支气管扩张提供了现代理论依据.     

基于网络药理学探讨冬虫夏草治疗糖尿病肾病的作用机制

目的 通过网络药理学探讨冬虫夏草治疗糖尿病肾病方面的作用机制研究.方法 首先利用TCMSP平台检索冬虫夏草的化学成分和作用靶点,并通过GeneCards、OMIM、TTD和CTD等数据库筛选出治疗糖尿病肾病的靶标,借助Uniprot数据库对靶点进行基因注释,基于STRING 10.0构建PPI蛋白互作网络,通过R语言中...     

从分子学角度探讨柴胡-郁金对卒中后抑郁潜在作用机制

目的:基于网络药理学探讨柴胡-郁金药对治疗卒中后抑郁(PSD)的潜在分子学机制。方法:通过检索TCMSP(中药系统药理学技术平台)数据库结合文献挖掘筛选出柴胡-郁金药对的主要活性成分及靶点,采用GeneCard与OMIM数据库获得卒中后抑郁的作用靶点,得到药物与疾病相交的靶点,通过Cytoscape软件建立疾病-药物-成分-靶点网络图,将数据输入String数据库,利用Cytoscape构建靶点相互作用的PPI网络,通过Metascape进行GO和KEGG富集分析。结果:从数据库中筛选了“柴胡-郁金”与PSD的36个共有靶基因和8种共有化合物,PPI网络共涉及节点36个,核心蛋白为IL6、AKT1、VEGFA、CRP、CCL2、MMP9、SERPINE1,GO生物学过程、细胞组成和分子功能分别为39条、8个、11个,KEGG通路共12条。结论:通过网络药理学探讨了“柴胡-郁金”对PSD发挥效应的可能潜在机制,为PSD的进一步研究提供了可能。     

运用网络药理学方法探讨心痛方治疗冠心病的作用机制

目的:运用网络药理学的研究方法分析心痛方,探讨心痛方治疗冠心病的潜在靶点及作用机制,为后续研究提供理论指导.方法:在中药系统药理学数据库与分析平台(TCMSP)查询柴胡、桃仁、郁金、川芎、白芥子、石菖蒲、瓜蒌、蒲黄、甘草、九香虫10味药物的有效成分及靶点信息,采用Swiss Target Prediction服务器进行补充,在Uniprot平台上对靶点进行标准化命名.通过OMIM、GeneCards、DrugBank数据库检索冠心病靶点基因.对心痛方靶基因和冠心病靶基因进行映射后,获得药物与疾病的共同基因.运用Cytoscape3.7.2绘制药物-成分-疾病-靶点网络,筛选关键成分;在String平台构建PPI网络,获得核心靶基因;运用Metascape平台对核心基因进行GO分析和KEGG通路分析.结果:通过TCMSP数据库检索及其他方法补充,获得心痛方有效成分417个,发现心痛方治疗冠心病的91个可能的重要靶点,经GO富集分析得到657个细胞生物学过程、33个细胞组分、68个分子功能;经KEGG富集分析得到245个相关通路.结论:心痛方对冠心病的治疗作用是多成分、多靶点、多通路的.并可以推测心痛方是通过花生四烯酸、槲皮素、山奈酚等成分介导IL6、AKT1、TNF、VEGFA、CCL2等靶点调节细胞黏附、细胞迁移、氧化应激反应、炎症反应等基因功能和丝裂原活化蛋白激酶(MAPK)信号通路、液体剪切应力与动脉粥样硬化、肿瘤坏死因子(TNF)信号通路等通路发挥治疗冠心病的作用.     

基于网络药理学及分子对接研究黄连温胆汤治疗缺血性脑梗死作用机制

目的 通过网络药理学和分子对接方法预测黄连温胆汤治疗缺血性脑梗死的潜在机制。方法 利用中药系统药理学分析平台(TCMSP)等数据库资料,并查阅文献获取黄连温胆汤的成分与靶点,导入Cytoscape 3.7.2软件创建中药-活性成分-靶点-疾病网络。借助在线人类孟德尔遗传数据库(OMIM)、人类基因综合数据库(GeneCards)、治疗目标数据库(TTD)、DisGeNET和药物靶标数据库(DrugBank)等数据在线平台获取疾病相对应的靶点,基于STRING线上平台构建黄连温胆汤与缺血性脑梗死重合的蛋白质-蛋白质互作(PPI)网络图。运用DAVID数据库对共同靶点进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。最后,利用PyMOL及Auto Dock等软件进行分子对接。结果 获得黄连温胆汤活性成分167种,包括豆甾醇和β-谷甾醇等,相对应的作用靶标322个;缺血性脑梗死疾病靶点2 529个,如肿瘤坏死因子(TNF)及细胞肿瘤抗原p53(TP53)等;药物与疾病交集靶点167个;GO富集分析共得到407条基因功能信息,KEGG富集分析发现133条通路,包括TNF信号通...     

基于网络药理学的治伤风颗粒治疗感冒的作用机制探讨

目的应用网络药理学技术探讨治伤风颗粒治疗感冒的作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)和药物靶点信息数据库(DrugBank)检索治伤风颗粒的化学成分及作用靶点;基于GeneCards数据库检索“感冒”的靶点,取药物与疾病靶点交集,应用Cytoscape软件构建“活性成分-靶点-疾病”网络。应用STRING数据库建立蛋白质互作(PPI)网络,应用R软件进行基因本体(GO)富集分析和京都基因和基因组百科全书(KEGG)通路富集分析。结果通过筛选共得到治伤风颗粒有效成分146种,药物靶点280个,疾病靶点1 418个,提取出两者的共同靶点117个。将药物与靶点导入Cytoscape软件,分析得出槲皮素、山奈酚和木犀草素等为中药中度值较高的活性成分,无水咖啡因为西药中度值最高的活性成分。STRING数据库分析得出IL-6、AKT1、INS、VEGFA、MAPK8等属于感冒的关键靶点。GO分析显示生物过程(BP)、细胞组分(CC)和分子功能(MF)3个方面的富集条目。KEGG通路富集分析筛选得出TNF信号通路、IL-17信号通路等20条信号通路,并绘制了“通路-靶点”关系图。结论基于网络药理学分析筛选出了治伤风颗粒治疗感冒的活性成分、作用靶点和通路,初步得出了其作用机制,为该药的深入研究提供了一定的依据。     

太子参-牡丹皮药对治疗糖尿病心肌病网络药理学机制探讨

目的：探究太子参-牡丹皮药对治疗糖尿病心肌病的作用机制。方法：利用网络药理学方法,借助中药系统药理学分析平台（TCMSP）、Pubchem网站、Swiss Target Prediction数据库预测活性成分候选靶点。通过Disgenet和GeneCards数据库筛选出糖尿病心肌病的靶点基因,利用Venny图取中药与疾病的交集靶点,通过STRING数据库建立蛋白互作网络图,并通过Cytoscape 3.9.0软件对网络图进行优化,筛选出核心靶点。利用Metascape数据库对交集靶点进行GO分析和KEGG富集分析。结果：中药共筛选出19个活性成分,277个作用靶点,糖尿病心肌病筛选出疾病靶点2424个,通过韦恩图得出交集靶点109个。通过药物-活性成分-靶点网络图分析可得山奈酚、槲皮素、刺槐素、木犀草素对疾病的治疗可能发挥重要作用。通过PPI网络图可知核心靶点为TNF、AKT1、SRC、TP53、EGFR等。根据KEGG分析,预测该药对主要通过干预癌症、MAPK、PI3K-Akt等信号通路发挥对糖尿病心肌病的治疗作用。结论：太子参-牡丹皮药对可通过多种活性成分、多靶点、多途径对糖尿病心...     

Guns and Knives in New Mexico: Patterns of Penetrating Trauma, 1978–1993

Objective: To identify patterns of nonfatal and fatal penetrating trauma among children and adults in New Mexico using ED and medical examiner data.
Methods: The authors retrospectively sampled in 5-year intervals all victims of penetrating trauma who presented to either the state Level-1 trauma center or the state medical examiner from a 16-year period (1978–1993). Rates of nonfatal and fatal firearm and stabbing injury were compared for children and adults.
Results: Rates of nonfatal injury were similar (firearm, 34.3 per 100,000 person-years; stabbing, 35.1). However, rates of fatal injury were significantly different (firearm, 21.9; stabbing, 2.7; relative risk: 8.2; 95% confidence interval: 5.4, 12.5). From 1978 to 1993, nonfatal injury rates increased for children (p = 0.0043) and adults (p < 0.0001), while fatal penetrating injury remained constant. The increase in nonfatal injury in children resulted from increased firearm injury rates. In adults, both stabbing and firearm nonfatal injury rates increased.
Conclusions: Nonfatal injury data suggest that nonfatal violence has increased; fatal injury data suggest that violent death rates have remained constant. Injury patterns vary by age, mechanism of trauma, and data source. These results suggest that ED and medical examiner data differ and that both are needed to guide injury prevention programs.     

Systematic Reviews Published in the January 2011 Issue of The Cochrane Library

ABSTRACT

The Cochrane Library of Systematic Reviews is published quarterly as a DVD and monthly online. The January 2011 issue (first quarterly DVD for 2011) contains 4515 complete reviews, 1985 protocols for reviews in production, and 13,521 one-page summaries of systematic reviews published in the general medical literature. In addition, there are citations of 641,000 randomized controlled trials, and 14,018 cited papers in the Cochrane methodology register. The health technology assessment database contains over 9300 citations. One hundred and seven new reviews have been published in the last 3 months, of which five have potential relevance for practitioners in pain and palliative medicine.     

Prise en charge des entorses externes de cheville : étude clinique préliminaire sur l’efficacité du dispositif Myolux™

Ankle sprains are the most common injury of the musculoskeletal system and are associated with significant societal and economic impacts. It has been proven that classical therapeutic strategies may not be effective in preventing recurrent injuries: the recurrence rates reported in the literature can reach 73%. In order to provide an effective rehabilitation solution, a destabilizing orthosis was developed. This device is equipped with a mechanical articulator reproducing the subtalar mechanics and placed under the heel. In this paper, we present the main results of a preliminary clinical study conducted between 2004 and 2007. All subjects included in this study were treated with the abovementioned orthosis during 10 rehabilitation sessions of 30 minutes each. Data show a relatively low recurrence rate of 12% for the overall population. Moreover, it's of primary importance to note that this satisfactory ratio is largely reduced (3% of recurrence rate) for the 29 patients who performed one training session per month after the 10th initial rehabilitation sessions. Hence, the destabilizing orthosis appears to be an effective solution to prevent recurrent ankle sprains. However, joint protection requires long-term and regular training sessions. This result has motivated the development of a similar device allowing patients to perform training sessions at home. Finally, data obtained in this study are promising awaiting the final results of the comparative, multicentric and independent clinical trials currently managed by the Hospices Civils de Lyon.     

Interprofessional approaches to creating safe,high quality health care

Three supplementary perspectives are presented arguing that interprofessional collaboration is both necessary and desirable. Nonetheless, there are often too many serious intra-professional barriers and obstacles to interprofessional collaboration to make it successful. Some of these barriers, it is argued and illustrated, are found in the multiple ways in which professional identity is tacitly acquired and embodied in the practitioners' habitual, everyday practice. The paper then explores ways in which reflection, especially Second order reflection, can help to elucidate and overcome these obstacles, as well as increasing professional adaptability and competence.     

Clinical Trial Updates and Hotline Sessions presented at the European Society of Cardiology Congress 2007

This article provides information and commentaries on trials which were presented at the Hotline and Clinical Trial Update Sessions at the European Society of Cardiology Congress 2007 in Vienna. The key presentations were performed by leading experts in the field with relevant positions in the trials or registries. It is important to note that unpublished reports should be considered as preliminary data, as the analysis may change in the final publications. The comprehensive summaries have been generated from the oral presentation and the webcasts of the European Society of Cardiology and should provide the readers with the most comprehensive information of relevant publications.     

Balance and Boundaries in Grief Counseling: An Intervention Framework for Volunteer Training

Volunteers or paraprofessional counselors are commonly used to provide supportive care to the bereaved. These counselors generally are trained in basic listening skills, providing a generic, nonspecific approach to intervention that remains to be proven effective. The present paper outlines a framework that provides paraprofessionals with a broader model for intervention with the bereaved. Attention to boundaries as a helper and balance in the grief recovery are central to the model. Interventions are described that provide the paraprofessional counselor with more options for tailoring their counseling strategy to the individual. These include techniques that are presumed to be more specific to the enhancement of grief recovery.     

A new method for the simultaneous analysis of unmodified and modified urinary nucleosides and nucleobases by high performance liquid chromatography

Details are given of a new, rapid and simple pre-fractionation method and an isocratic high performance liquid chromatography system suitable for parallel analysis of nucleosides and nucleobases from urine and other biological fluids. The quantitative recovery and excellent reproducibility of the method is demonstrated by analysis of representative standard RNA catabolites. The advantage of this new method for application to biological samples is discussed.     

Adsorption of Charged Non-albumin Bound Drugs by Amorphous Silica

We investigated the in vitro drug adsorption of PQ 10150 sodium silicate gel (AIS, Santa Clara, CA) with particle size of 230 um and surface area of 400 nr/g. We observed 99% to 88% adsorption of gentamicin; a mean 91 % of disopyramide; a mean 89% of quinidine at low concentration, falling to 75% at higher concentration. Insulin was 88% adsorbed at low concentrations but less so (65%) at higher concentrations. We observed a mean 83 % adsorption of procainamide, a mean 84% of N-acetyl procainamide, 74% oflidocaine, 73% of amitriptyline; and 44% of desipramine. We found an average 14% reduction of total digoxin concentration when serum containing digoxin (2 to 33 ng/mL) was exposed to sodium silicate, while the reduction in free digoxin concentration was 16%. Five percent ethosuximide was also removed. The adsorption of theophylline, phenobarbital, acetaminophen, phenytoin, ethylene glycol, methotrexate, salicylate, thiocyanate and diazepam was minimal and not significant. We conclude that significant amounts of charged, non-albumin bound drugs can be removed by PQ 10150 sodium silicate gel.