Measuring urinary testosterone levels of the great apes--problems with enzymatic hydrolysis using Helix pomatia juice

Helix pomatia (Hp) juice is a common enzymatic preparation for deconjugation of urinary steroids. It has been used in many published studies on urinary testosterone (T) in chimpanzees and bonobos, although the ability of Hp juice to convert other urinary steroids into T has been reported for human urine. We developed a protocol for determination of reliable T levels in primate urine using liquid chromatography–mass spectrometry. T levels were determined in a set of human, bonobo and chimpanzee urine samples (A) by measurement of intact testosterone glucuronide (TG) and testosterone sulfate (TS), (B) after hydrolysis/solvolysis with β-glucuronidase from Hp and (C) from Escherichia coli. When samples were hydrolyzed with Hp juice, results were not correlated with the direct assay of TG and TS, and determined T concentrations were considerably higher. By contrast, hydrolysis with E. coli β-glucuronidase yielded a good agreement of T concentrations. We demonstrated the ability of Hp juice to convert androst-5-ene-3β, 17β-diol (A⁵diol) into T using commercial standards and within the urine of all three species. As A⁵diol usually is present at higher levels in urine than T, this artifact leads to erroneous results for T concentrations in primate urine.The proportion of T excreted as sulfate (TS) is often neglected as TS can only be cleaved by additional solvolysis. In all three species, we found substantial amounts of TS in the urine of some subjects and a high variance of TS proportion between and within subjects. Therefore the inclusion of solvolysis into the sample preparation seems necessary.     

Perceptions of post-transplant recidivism in liver transplantation for alcoholic liver disease

Although alcoholic liver disease (ALD) is regarded as a common indication for liver transplantation (LT), debatable issues exist on the requirement for preceding alcoholic abstinence, appropriate indication criteria, predictive factors for alcoholic recidivism, and outcomes following living-donor LT. In most institutions, an abstinence period of six months before LT has been adopted as a mandatory selection criterion. Data indicating that pre-transplant abstinence is an associated predictive factor for alcoholic recidivism supports the reasoning behind this. However, conclusive evidence about the benefit of adopting an abstinence period is yet to be established. On the other hand, a limited number of reports available on living-donor LT experiences for ALD patients suggest that organ donations from relatives have no suppressive effect on alcoholic recidivism. Prevention of alcoholic recidivism has proved to be the most important treatment after LT based on the resultant inferior long-term outcome of patients. Further evaluations are still needed to establish strategies before and after LT for ALD.     

Triage Nurse Application of the Ottawa Knee Rule

OBJECTIVE: To determine interobserver agreement between triage registered nurses (RNs) and emergency physicians (EPs) regarding indication for knee radiographs by applying the Ottawa knee rule (OKR) and individual components of the rule. METHODS: This was a prospective, observational study in a suburban, teaching emergency department. The study enrolled a convenience sample of patients aged >17 years with traumatic knee injuries less than one week old. Patients with prior knee surgery or distracting conditions were excluded. Before study initiation, the RNs and EPs were in-serviced in the OKR. Nurses and EPs independently examined each patient for OKR criteria, blinded to the other's assessment. Knee radiographs were ordered at the discretion of the EP and were interpreted by board-certified radiologists. All patients received follow-up with a structured telephone interview to identify any undetected fractures. Kappa was calculated for each component and the overall application of the OKR to assess interobserver agreement. RESULTS: Ninety-six patients were enrolled. The mean age was 39.6 +/- 18.7 years; 50% were male. Eight patients (8%) had knee fractures. Interobserver agreements between the RNs and EPs for individual components of the OKR were: age > or =55 years (kappa = 0.97); inability to weight bear (kappa = 0.51); inability to bend knee to 90 degrees (kappa = 0.52); fibular head tenderness (kappa = 0.45); and isolated patellar tenderness (kappa = 0.40). The EPs and RNs agreed with OKR criteria for x-ray 71% of the time (kappa = 0.41). CONCLUSIONS: The only criterion that resulted in almost perfect agreement between the RNs and EPs was patient age; agreement for the other four criteria and the overall decision to order x-rays was moderate.     

医院产权制度改革若干理论问题的思考

当前,医院产权制度改革实践中的一些领域仍然需要理论支持,从理论角度对产权明晰、医院治理、产权经营、效果评价方面做了分析,指出了当前存在的一些误区,并就某些问题提出了建议。     

基于生物信息学的中药调控糖酵解用药规律探究及实验验证

目的：探究调节糖酵解的中药活性成分及用药规律。方法：基于GeneCards数据库获得与糖酵解有关靶点,DAVID数据库分析靶点参与的生物学过程及信号通路。将靶点信息导入中药系统药理学数据库与分析平台（TCMSP）获取其对应的活性成分和中药,构建糖酵解“靶点-活性成分-中药”网络,并统计药物性味归经及功效,分析调节糖酵解的中药用药规律。最后采用细胞实验验证丹参、黄芪对胃癌前病变细胞（MC）中糖酵解相关蛋白表达的影响。结果：获得24个糖酵解相关靶点,与238种活性成分及337种中药相匹配。其中槲皮素、山柰酚、木犀草素等可能是干预糖酵解的主要有效成分,甘草、钩藤、丹参等可能是干预糖酵解的主要中药。用药规律分析显示,药性以寒、温为多;药味以苦、甘为主;归经以肝经、肺经居多;功效以清热药、补虚药等为主。实验结果表明,丹参、黄芪均可降低MC细胞糖酵解相关蛋白缺氧诱导因子-1α（HIF-1α）、葡萄糖转运蛋白1（GLUT1）、己糖激酶2（HK2）、丙酮酸激酶M2型（PKM2）、乳酸脱氢酶A（LDHA）的表达。结论：本研究通过生物信息学方法分析得到了调控糖酵解的活性成分及中药用药规律,以期为治疗与糖酵解相关疾病提供组方用药思路,并为相关中药新药研发及机制研究等提供一定参考。     

情志病的中医芳香精油疗法

情志病是因精神情志变化引起脏腑阴阳气血失调而导致的疾病。随着社会的快速发展,人们的心理压力逐渐增大,使得情志病成为威胁人类身心健康和影响人类正常生活的一种疾病。中医芳香疗法是一种历史悠久的自然疗法,其利用芳香药物经鼻腔、皮肤等吸收,来调节气机和调和脏腑阴阳,达到预防、减轻或治疗情志病的作用。     

基于数据挖掘和网络药理学探讨中医药治疗糖尿病牙周炎的组方规律及作用机制

目的 挖掘中医药治疗糖尿病牙周炎 （diabetic periodontitis,DP） 的组方规律,并探讨核心药物组合的作用机制。方法 以中国知网、万方数据库、维普中文期刊、中国生物医学文献服务系统收录的中医药治疗 DP文献为资料来源,建立 DP 处方信息数据库,运用 Excel 2021、SPSS Modeler 18.0 和 SPSS Statistics 26.0,对纳入中药进行频次、功效分类、性味归经统计,并进行关联规则分析和聚类分析,筛选出核心药物组合;通过中药系统药理学数据库与分析平台 （TCMSP） 、HERB 获取核心药物组合的活性成分,预测药物作用靶点;运用GeneCards 预测疾病相关靶点;运用 Venny 平台得到疾病与药物的交集靶点;运用 Cytoscape 建立“活性成分-靶点”网络,筛选出关键成分;以 STRING 平台数据为基础,利用 Cytoscape 软件构建蛋白质-蛋白质相互作用网络,筛选核心靶点;通过 DAVID 数据库对交集靶点进行基因本体论 （GO） 和京都基因与基因组百科全书（KEGG） 富集分析;采用 AutoDockVina 对关键成分与核心靶点进行分子对接。结果 共纳入中医药治疗 DP 文献 36 篇,提取方剂 50 首,涉及药物 100 味;最常见的药物有泽泻、熟地黄、黄芪等,使用最多的药物类别为补虚药,药性以寒、温为主,药味以甘、苦味为主,归经以肾、肝经居多,系统聚类分析可归为 6 大类;筛选出牡丹皮-山茱萸-熟地黄为核心药物组合,涉及 18 个活性成分、164 个作用靶点,与 DP 有 104 个交集靶点;槲皮素、豆甾醇、山奈酚、β-谷甾醇、四氢鸭脚木碱、谷甾醇等为核心成分,AKT1、IL-6、TNF、IL-1B、PTGS2、JUN、TP53、ESR1、MMP9 等为关键靶点;GO 分析得到生物过程 3 724 项、细胞组成 228 项、分子功能 404 项;KEGG 分析显示主要涉及 235 条信号通路;分子对接显示关键靶点与核心成分具有良好亲和力。结论 DP 的中医治法主要以补虚为主,兼以清热利湿、活血化瘀、益气养阴,核心药物组合牡丹皮-山茱萸-熟地黄可通过多成分、多靶点、多通路治疗 DP,为临床诊疗提供参考。     

围绝经期综合征中医证候及用药规律文献研究

目的总结围绝经期综合征证候分布以及中药使用规律。方法检索中国期刊全文数据库（CNKI）和PubMed数据库中医或中西医结合治疗围绝经期综合征的临床研究,文献发表时间范围为2008年3月1日至2019年3月31日。提取纳入研究文献中的证候、证候要素、使用药物信息建立数据库,分别统计证候类型、证候要素、药物及药物类别分布情况,并对常用药物在纳入方剂中的分布进行可视化分析。结果共纳入文献345篇。证候类型116个,频次前3位的证候类型有肾阴虚（209）、肝郁气滞（164）、肝肾阴虚（105）。病位证素5个,出现频次分布为肾（798）、肝（404）、心（148）、脾（118）、肺（3）;病性证素10个,出现频次前3位的为阴虚（317）、气虚（161）、气郁（115）。使用中药109种,涉及17个类别,中药出现频次前3位分别为熟地黄（169）、山茱萸（141）、白芍（134）,类别前3位分别为补虚药（1658）、清热药（458）、温里药（278）。结论围绝经期综合征病性虚实夹杂,以虚证为主,主要病变脏腑为肾、肝、心,治疗用药以补虚、清热、温里药为多。     

近20年中药治疗慢性阻塞性肺疾病稳定期组方用药规律文献研究

目的总结中医药治疗慢性阻塞性肺疾病（COPD）稳定期的用药配伍及组方规律。方法检索中国知网、万方数据库、维普期刊数据库1998年1月1日至2018年8月31日关于中医药复方治疗COPD稳定期的临床研究文献,提取纳入文献中方剂及药物信息,分别统计药物使用及性味归经分布情况,对高频药物进行二项、三项关联分析及聚类分析。结果共纳入文献109篇,筛选方剂109首,涉及药物161味,药物类别15种。用药频次≥10次的中药共计35味,其中使用频次前3位的分别为黄芪（76）,甘草（60）,白术（56）;药物类别出现频次前3位的分别为补益药（46）,化痰止咳平喘药（21）,清热药（19）。用药频次≥5的中药共计48味,其药性频次前3位分别为温（15）、平（11）、微温（9）,药味分别为甘（25）、辛（23）、苦（18）,归经分别为肺（26）、脾（24）、肝（17）。用药频次≥10次的35味药物中二项关联共12对,三项关联共9组,聚为7类时聚类效果较好。结论COPD稳定期的治疗药物以辛温、归肺脾经者为多,组方思路以补肺健脾益肾、化痰止咳平喘、化瘀通络为主。     

中风病气虚血瘀证用药规律文献研究

目的通过文献总结归纳中风病气虚血瘀证临床用药规律。方法检索1995年1月至2017年5月中国期刊数据库、中国期刊全文数据库、中国学术期刊数据库中治疗中风病气虚血瘀证临床研究文献,提取纳入文献中处方名称、组成药物信息,并对药物使用频次、剂量及药物类别进行统计。结果共纳入合格文献46篇,涉及处方41首,涉及相关药物78种,合计治疗患者2489例。治疗病例数前3位的处方为补阳还五汤（200）、加味抵当汤（134）、黄七汤（125）;使用频次前3位的药物为黄芪（42）、川芎（35）、当归（32）;使用频次前3位的药物类别为活血化瘀药（163）、补虚药（119）、平肝熄风药（45）。主要治疗药物黄芪其常用剂量为60g,30g及以上剂量使用情况占90.7%。结论活血化瘀药和补虚药是治疗中风病气虚血瘀证的基础用药,其主要治疗药物黄芪常以大剂量使用,同时随证加减平肝熄风、化痰、清热等药物可取得更好疗效。