Understanding thoracic surgeons' perceptions of administrative database analyses and guidelines in clinical decision-making

ObjectivesThis study explored cardiothoracic surgeons' perceptions of health services research and practice guidelines, particularly how both influence providers' clinical decision-making.MethodsA trained interviewer conducted open-ended, semistructured phone interviews with cardiothoracic surgeons across the United States. The interviews explored surgeons' experiences with lung cancer treatment and their perceptions of health services research and guidelines. Researchers coded the transcribed interviews using conventional content analysis. Interviews continued until thematic saturation was reached.ResultsThe 27 surgeons interviewed mostly were general thoracic surgeons (23/27) who attend tumor board weekly (21/27). Five themes relating to physician perceptions of health services research and guidelines emerged. Databases analyses' inherent selection bias and perceived deficit of pertinent clinical variables made providers skeptical of using these studies as primary decision drivers; however, providers thought that database analyses are useful to supplement other data and drive future research. Likewise, providers generally felt that although guidelines provide a useful framework, they often have difficulty applying guidelines to individual patients. An analysis of provider characteristics revealed that younger physicians in practice for fewer years appeared more likely to report using guidelines, and physicians who were aged 50 years or more and not purely academic surgeons appeared to find database analyses less impactful.ConclusionsHealth services research, including database analyses, comprise much of the surgical literature; however, this study suggests that perceptions of database analyses and guidelines are mixed and questions whether thoracic surgeons routinely use either to inform their decisions. Researchers must address how to present compelling data to influence clinical practice.     

Network pharmacology used to decode potential active ingredients in Ferula assafoetida and mechanisms for the application to Alzheimer’s disease

BackgroundAlzheimer’s disease (AD) is a neurodegenerative disease that primarily manifests as progressive memory loss and cognitive impairment. Traditional herbal medicines may be helpful in the discovery of new anti-AD drugs. Studies have shown that Ferula assafoetida has neuroprotective and memory-enhancing effects, which may be beneficial for the treatment of AD. However, the combination of active ingredients and their mechanisms remain unclear. Therefore, we aimed to identify potential active ingredients in F. assafoetida and their mechanisms of action against AD by using network pharmacology.MethodsIn our study, an integrated network pharmacological approach, that included adsorption, distribution, metabolism and excretion screening, target identification, network construction, topological analysis, gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and molecular docking, was used to predict the pharmacological material basis and potential mechanisms through which these ingredients may treat and prevent AD.ResultsThe results indicated that 12 key active ingredients, obtained by topological analysis (including farnesiferol a, conferol, farnesiferol b, ferulic acid, etc.), may be the primary pharmacological components that may ameliorate AD. The 2 key significant pathways identified are the cholinergic synapse signaling pathway (critical targets include ACHE, CHRM1, CHRM2, MAPK1, PIK3CA, PIK3CB, PIK3CD, and PIK3CG) and the AD signaling pathway (critical targets include APP, BACE1, GSK3B, MAPK1, NCSTN, NOS1, PSEN1). These critical targets are closely related to the regulation of three typical pathological features of AD [central nervous system (CNS) cholinergic hypofunction, amyloid-β (Aβ) plaques, and hyperphosphorylated tau proteins]. Finally, 14 critical targets in the 2 key significant pathways were validated by molecular docking analysis.ConclusionF. assafoetida may be effective for alleviating AD symptoms, through multi-component, multi-target, and multi-pathway synergistic effects, associated with the multiple pathogenesis hypotheses of AD. Our study may provide certain clues for the further development and utilization of this natural herbal medicine.     

A network pharmacology-based strategy for predicting anti-inflammatory targets of ephedra in treating asthma

Asthma, the most common chronic respiratory disease in the world, is involved in a sustained inflammatory response caused by a variety of immune cells. Ephedra with multi-target, multi-pathway functions is an effective treatment for asthma. However, the ingredients and anti-inflammatory targets of ephedra in treating asthma are unclear. Therefore, there is a need for further research. Ephedra-related and anti-inflammatory targets were found and then combined to get intersection, which represented potential anti-inflammatory targets of ephedra. Moreover, compound-anti-inflammatory target and asthma-target protein-protein interaction network were merged to get the protein-protein interaction network intersection and core genes in asthma-target protein-protein interaction network. For the anti-inflammatory targets of ephedra in treating asthma, Gene Ontology and pathway analysis were executed to confirm gene functions of ephedra in antagonizing inflammation of asthma. Finally, molecular docking, qRT-PCR, WB and ELISA were performed to assess the binding activities between the compounds and anti-inflammatory targets of ephedra in treating asthma. Critical compounds and anti-inflammatory targets of ephedra in treating asthma were identified, including quercetin, luteolin, kempferol, naringenin, beta-sitosterol, SELE, IL-2 and CXCL10. The biological processes of anti-inflammatory targets of ephedra in treating asthma were involved in immune response, inflammatory response, cell-cell signaling and response to lipopolysaccharide. Moreover, 22 pathways were obtained and we proved that critical compounds inhabited the expression of SELE, IL-2 and CXCL10 at mRNA and protein levels.     

基于网络药理学探讨“黄芪-当归-大枣”角药补气养血的分子机制＊

目的 运用网络药理学探讨“黄芪-当归-大枣”角药补气养血的分子机制。方法 利用中药系统药理学TCMSP数据库收集黄芪、当归和大枣的化学成分，并预测作用靶点。通过STRING数据库和Cytoscape软件构建蛋白互作PPI网络，获得关键靶点。借助DAVID数据库对筛选靶点进行GO功能和KEGG通路富集分析。进一步构建气血两虚小鼠模型，灌胃“黄芪-当归-大枣”水煎剂，检测各组PTGS₂ mRNA表达水平与肿瘤坏死因子-α(TNF-α)含量，完成验证实验。结果 筛选得到“黄芪-当归-大枣”角药化学成分47个，预测作用靶点43个，关键靶点10个，生物功能主要定位在内质网膜和线粒体，通过介导癌症信号通路，TNF、P53、Foxo、HIF-1信号通路，钙信号通路等发挥补气养血作用。动物实验显示“黄芪-当归-大枣”角药可调控气血两虚小鼠中PTGS₂ mRNA表达，降低TNF-α释放，进而抑制TNF信号通路的激活，进一步证实了预测的可靠性。结论 本研究深入诠释“黄芪-当归-大枣”角药补气养血作用多成分、多靶点和多通路的复杂机制，为其进一步临床应用和功能食品开发提供科学依据。     

基于网络药理学研究络石藤-伸筋草药对治疗骨关节炎的作用机制

目的：运用网络药理学方法研究络石藤-伸筋草药对治疗骨关节炎的生物活性成分和潜在的作用机制。方法：从中药系统药理学数据库和分析平台（TCMSP）和中国科学院化学专业数据库（CASC）中收集已知的络石藤-伸筋草药对中的生物活性化学成分；使用Swiss Target Prediction网络服务器预测化合物的蛋白靶点；从疾病数据库中挖掘已知的骨关节炎相关靶点数据；利用收集到的数据分别构建蛋白质-蛋白质相互作用（PPI）网络并提取其交集作为药物-疾病相互作用网络，通过网络拓扑学分析筛选出核心靶点；使用DAVID数据库对核心靶点进行GO注释分析和KEGG通路分析。结果：从TCMSP和CASC数据库中共收集到108个已知的络石藤-伸筋草药对中的化学成分，虚拟筛选后得到17个生物活性化合物，并预测出117个潜在的蛋白靶点；从疾病数据库中一共检索到191个骨关节炎相关靶点；对化合物和疾病的交集PPI网络进行网络拓扑学分析得到208个核心靶点，这些靶点主要富集到自噬、凋亡、炎性反应、雌激素相关的生物过程和信号通路。结论：络石藤-伸筋草药对可能通过多条生物途径发挥调节炎性反应、自噬、凋亡和类雌激素样作用发挥抗骨关节炎作用。     

Split liver transplantation is utilized infrequently and concentrated at few transplant centers in the United States

Split liver transplantation (SLT) is 1 strategy for maximizing the number of deceased donor liver transplants. Recent reports suggest that utilization of SLT in the United States remains low. We examined deceased donor offers that were ultimately split between 2010 and 2014. SLTs were categorized as “primary” and “secondary” transplants. We analyzed allocation patterns and used logistic regression to evaluate factors associated with secondary split discard. Four hundred eighteen livers were split: 54% from adult, 46% from pediatric donors. Of the 227 adult donor livers split, 61% met United Network for Organ Sharing “optimal” split criteria. A total of 770 recipients (418 primary and 352 secondary) were transplanted, indicating 16% discard. Ninety‐two percent of the 418 primary recipients were children, and 47% were accepted on the first offer. Eighty‐seven percent of the 352 secondary recipients were adults, and 7% were accepted on the first offer. Of the 352 pairs, 99% were transplanted in the same region, 36% at the same center. In logistic regression, shorter donor height was associated with secondary discard (odds ratio 0.97 per cm, 95% CI 0.94‐1.00, P = .02). SLT volume by center was not predictive of secondary discard. Current policy proposals that incentivize SLT in the United States could increase the number of transplants to children and adults.     

Alcohol,tobacco and coffee consumption and liver disease severity among individuals with Chronic Hepatitis B infection in North America

Introduction and objectivesThe prevalence of alcohol, tobacco, and coffee use and association with liver health among North Americans with Chronic Hepatitis B (CHB) infection has not been well described.Materials and methodsThe Hepatitis B Research Network includes an observational study of untreated CHB adults enrolled at 21 sites in the United States and Canada. Alcohol use was categorized as none, moderate, and at-risk based on the definition from the National Institute on Alcohol Abuse and Alcoholism; tobacco use as never, current and former; coffee use as none, 1–2 cups/day, and ≥3 cups/day. Linear regression and linear mixed models were used to associate lifestyle behaviors with ALT and FIB-4 values.Results1330 participants met eligibility: 53% males, 71% Asian and the median age was 42 years (IQR: 34–52). Median ALT was 33 U/L (IQR: 22–50), 37% had HBV DNA <10³ IU/mL, 71% were HBeAg negative, and 65% had a FIB-4 <1.45. At baseline, 8% of participants were at-risk alcohol drinkers, 11% were current smokers and 92% drank <3 cups of coffee/day. Current tobacco and ‘at-risk’ alcohol use, were significantly associated with elevated ALT levels in univariable analyses, however, these associations were not statistically significant when controlling for sociodemographic and HBV characteristics.ConclusionsIn this large diverse cohort of untreated CHB participants, at-risk alcohol use, current tobacco use and limited coffee consumption did not have an association with high ALT and FIB-4 values. In contrast, significant associations were found between the frequency of these lifestyle behaviors and sociodemographic factors.     

医学信息管理专业网络技术模拟仿真实验教学

针对网络技术实验,采用模拟仿真的实验环境,将抽象的教学内容变成直观教学,利用基于问题的教学法培养学生科学思维,以任务驱动法激发学习积极性,实现理论与实验交叉教学