补充与替代疗法治疗肠易激综合征的研究进展

肠易激综合征是临床常见的功能性胃肠病之一。由于多数患者的症状经过一线药物治疗后仍不能得到较好改善，许多患者为获得更好的治疗效果，转向选择补充与替代疗法进行治疗。然而，由于研究质量和数量的限制，大部分治疗肠易激综合征的补充与替代疗法并未被相关共识和指南所推荐。本文从补充与替代疗法的分类入手，从天然产品、身心治疗、传统医药3个方面就目前国内外常用的补充与替代疗法治疗肠易激综合征的研究进行概述，以期为临床工作者和患者更好地了解和应用提供帮助。     

基于CiteSpace可视化分析代谢组学在中医药领域的研究现状及趋势＊

目的 应用可视化方法分析代谢组学在中医药领域的现状及趋势。方法 检索中国知网数据库（CNKI）和Web of Science 核心合集数据库2021年3月15日之前收录的中医药领域代谢组学研究的相关文献，应用CiteSpace软件对纳入的文献进行关键词、作者、研究机构等内容进行可视化分析。结果 共纳入中文文献247篇，英文文献350篇。文献数量在波动中迅速上升。中、英文文献作者合作网络显示，张爱华是中医药领域代谢组学研究发文量最多的作者，并形成了核心研究团队。发文机构显示，中国医学科学院是该领域的重要研究机构，机构间合作紧密。中、英文文献关键词分析显示，研究内容主要集中在核磁共振、代谢标记物、冠心病、质谱技术、代谢通路等相关领域。结论 中医药领域代谢组学研究的热点主要为中医药治疗代谢性疾病的机制研究。研究趋势为卵泡代谢组学研究及中药有效成分的研究。     

Comparison between tension band and cerclage with X-Plate and lag screws in treatment of comminuted patellar fractures

BackgroundComminuted patellar fractures are not rare, and the ideal treatment method remains controversial. The present study was conducted to evaluate effects and compare complications of two different methods used to treat comminuted patellar fractures.MethodsFrom March 2010 to August 2016, 102 cases of 34-C2 or 34-C3 comminuted patellar fractures were treated at our hospital, wherein patients received two different treatments: titanium cable tension band with cerclage method (group A) and intrafragmentary screws with X-shaped plating technique (group B). At follow-ups, articular step-off, range of motion (ROM), Lysholm scores, time of union, and complications were recorded and analyzed. Radiographic and clinical data as well as rate of complications were statistically analyzed.ResultsIn total, 87 patients were included in the final analysis (n = 47 in group A and n = 40 in group B). No significant differences were noted in terms of cost of implant, age, gender, rate of 34-C3 fractures, rate of layered inferior pole fractures, postoperative articular step-off and union time. At 2-year follow-up, average Lysholm scores, ROM and rate of complications were (89.0 ± 4.5), (122°±12°) and (27.7%) in group A and (90.2 ± 3.9), (124°±11°) and (17.5%) in group B, respectively, with no significant differences (p > 0.05). The mean time of surgery in group B was shorter than that in group A with significant difference (p < 0.05).ConclusionsTreatment using the intrafragmentary screws and plate method for amenable comminuted patellar fractures achieved similar complication rate and favorable functional outcomes at the 2-year follow-up, which was comparable to the titanium cable tension band with cerclage method. Thus, the intrafragmentary screws and plate method is effective, safe and convenient for 34-C2/C3 comminuted patellar fractures, especially appropriate for patients with layered fragments.     

王琦教授新冠肺炎预防方预防新型冠状病毒肺炎机制的网络药理学探讨＊

目的 借助网络药理学的方法，探究两组王琦教授新冠肺炎预防方（简称预防方）预防新型冠状病毒肺炎（COVID-19）的分子靶点和机制。方法 通过TCMSP数据库检索并筛选其活性成分及其作用靶点，通过Uniprot数据库进行蛋白标准化处理。从Genecards数据库中以“Novel coronavirus pneumonia”为关键词搜索获取COVID-19的靶标，构建相交靶点韦恩图。通过cytoscape3.7.2构建PPI蛋白互作网络，寻找富集数目最多的靶点。通过R语言对预防方治疗COVID-19的靶点进行GO和KEGG富集分析，并绘制气泡图。结果 预防方与新冠肺炎相关靶点涉IL-6、TNF、CXCL8、VEGFA、MMP9；GO功能富集分析分别获得53、57条通路；27、29条KEGG相关信号通路。结论 王琦教授新冠肺炎预防方中的主要活性成分为槲皮素、山奈酚、木犀草素、β-谷甾醇、植物甾醇等，可能通过作用于IL-6、TNF、CXCL8、VEGFA、MMP9、CXCL8、IL10、CCL2、IL1B等靶点和介导TNF信号通路、T细胞受体信号通路、Toll样受体信号通路等发挥作用，从而促进免疫反应、炎症反应及细菌防御反应，预防COVID-19。     

Dectin-2受体介导宿主抵抗烟曲霉菌感染的研究

目的探讨C型凝集素受体Dectin-2在烟曲霉菌感染中的作用及机制。方法用紫外线灭活的烟曲霉菌膨胀态分生孢子刺激野生型(wild type, WT)和Dectin-2缺失(Clec4n-/-)小鼠骨髓来源的巨噬细胞(bone marrow derived macrophages, BMDMs)。刺激20min及40min后，利用Western印迹法检测BMDMs中脾酪氨酸激酶(spleen tyrosine kinase, Syk)和核转录因子κB抑制因子(inhibitor-κB, IκBα)的磷酸化水平。刺激16h后，利用酶联免疫吸附法(enzyme-linked immunosorbent assay, ELISA)检测BMDMs细胞上清液中IL-6、TNF-α和IL-12p40的水平。另一方面，利用压舌感染的方法在WT和Clec4n-/-小鼠中构建烟曲霉菌肺部感染模型。感染2d后，统计小鼠整个肺脏荷菌量，并检测肺脏匀浆液中IL-6和IL-12p40水平。结果体外试验提示，烟曲霉菌刺激后，Dectin-2缺失的BMDMs中Syk和IκBα的磷酸化水平及IL-6、TNF-α和IL-12p40水平显著下降(P＜0.05)。体内试验发现，烟曲霉菌感染后，Dectin-2缺失小鼠中肺脏荷菌量显著升高(P＜0.05)，肺脏匀浆液内IL-6、IL-12p40水平显著降低(P＜0.05)。结论C型凝集素受体Dectin-2激活烟曲霉菌诱导的NF-κB信号通路并介导促炎细胞因子的产生，可在小鼠肺烟曲霉菌病动物模型中发挥保护性作用。     

Confounded association between proton pump inhibitor use and risk of biliary tract cancer: Result from three cohorts

Recent epidemiological studies suggested that proton pump inhibitor (PPI) use was associated with an increased risk of biliary tract cancer (BTC), however, confounders were not adequately controlled. Our study aimed to evaluate PPI use and subsequent risk of BTC and its subtypes in three well-established cohorts. We conducted a pooled analysis of the subjects free of cancers in UK Biobank (n = 463 643), Nurses' Health Study (NHS, n = 80 235) and NHS II (n = 95 869). Propensity score weighted Cox models were used to estimate marginal HRs of PPIs use on BTC risk, accounting for potential confounders. We documented 284 BTC cases in UK Biobank (median follow-up: 7.6 years), and 91 cases in NHS and NHS II cohorts (median follow-up: 15.8 years). In UK biobank, PPI users had a 96% higher risk of BTC compared to nonusers in crude model (HR 1.96, 95% CI 1.44-2.66), but the effect was attenuated to null after adjusting for potential confounders (HR 0.95, 95% CI 0.60-1.49). PPI use was not associated with risk of BTC in the pooled analysis of three cohorts (HR 0.93, 95% CI 0.60-1.43). We also observed no associations between PPI use with risk of intrahepatic (HR 1.00, 95% CI 0.49-2.04), extrahepatic bile duct (HR 1.09, 95% CI 0.52-2.27) and gallbladder cancers (HR 0.66, 95% CI 0.26-1.66) in UK Biobank. In summary, regular use of PPIs was not associated with the risk of BTC and its subtypes.     

基于网络药理学和分子对接技术探讨黄芪干预腹膜纤维化的机制

目的 运用网络药理学方法及分子对接技术探讨黄芪干预腹膜纤维化的可能机制。方法 利用中药系统药理学数据库及分析平台(TCMSP)检索黄芪的主要化学成分及靶点,并补充文献报道相关药理作用的成分作为潜在活性成分。以"peritoneal fibrosis"为关键词分别在OMIM、Genecards获取目前已知的与腹膜纤维化相关的疾病靶点,后取两者的交集靶点;对交集基因通过STRING数据库与Cytoscape 3.7.2软件构建"药物-成分-靶点-疾病"网络及蛋白互作(PPI)网络并筛选核心网络。基于R软件使用Bioconductor生物信息软件对核心靶点进行GO及KEGG富集分析,最终采用AutoDock软件将主要有效成分与核心靶点进行分子对接,得出其结合能力。结果 筛选出20个黄芪活性成分及文献报道有相关药理作用4个, 457药物作用靶点,与674个腹膜纤维化病靶点取交集,得到86个共同靶点。GO功能富集分析提示黄芪拮抗腹膜纤维化主要参与了蛋白激酶B信号转导的调节、细胞对化学的应激反应、炎症反应的调节等通路; KEGG通路富集分析主要涉及调控肿瘤、磷脂酰肌醇-3-羟激酶-蛋白激酶B(PI3K-Akt)、晚期糖基化终末产物/晚期糖基化终末产物受体(AGE-RAGE)、人类巨细胞病毒感染、HIF-1信号通路等;分子对接结果显示关键靶点与活性成分具有较好的结合能力。结论 黄芪治疗腹膜纤维化的分子机制,可能与抑制炎症及氧化应激反应、调节多种信号通路等相关。     

嘌呤能受体X1与肺腺癌预后及免疫细胞浸润的相关性研究

目的：探索嘌呤能受体X1(purinergic receptor，P2RX1)与肺腺癌(LUAD)患者预后及免疫细胞浸润的相关性。方法：利用生物信息学技术分析非小细胞肺癌中P2RX1的表达及其甲基化与患者预后的关系，对P2RX1共表达基因进行富集分析并筛选核心基因。利用TIMER 2.0数据库、R软件等分析P2RX1与免疫细胞、免疫检查点、免疫基质评分等的相关性。结果：P2RX1在LUAD中表达下调，低表达P2RX1的患者预后较差(P<0.05)，且P2RX1与肿瘤纯度、分期等临床病理因素有关(P<0.05)。P2RX1的表达与肺鳞癌患者预后无明显相关。Cg06475633等P2RX1 CpG位点甲基化与患者预后相关。P2RX1共表达基因主要富集于免疫细胞活化、分化等通路和生物学进程，核心基因主要包括BTK、IKZF1等。P2RX1的表达与B细胞浸润、免疫/基质评分、PD-1、CTLA-4等多个免疫检查点显著相关(P<0.05)。结论：P2RX1有望成为LUAD诊断和免疫治疗的新靶点。     

《本草图经》“牛皮胶制作不甚精”实验求证

《本草图经》记载:"牛皮胶制作不甚精。"为求证原因,笔者以北魏《齐民要术》所载煮胶法为基础,分别用鲜牛皮与牛皮鞋制作牛皮胶。结果显示,鲜牛皮制作的牛皮胶出胶率高,胶呈琥珀色,色泽明亮,拍之即碎,断面有玻璃茬,无腥秽气味;而用牛皮鞋制作的牛皮胶出胶率低,胶呈黑褐色,色泽晦暗,不易干燥,拍之难碎,断面无玻璃茬,有轻度腥秽气味。由于北宋的皮革业发展水平远远高于北魏时期,后者鞋履等旧皮多为未经过鞣制的生皮,前者则为经过鞣制的熟皮。因此,《本草图经》记载的"牛皮胶制作不甚精"真实原因可能是煮制过程中使用了充分鞣制过的熟牛皮。