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。     

特发性肺纤维化急性加重期证候与血清生物标志物的相关性研究＊

目的 通过分析特发性肺纤维化急性加重期（AE-IPF）患者证候与血清生物标志物的关系，为中医辨证治疗提供参考。方法 采用观察性研究设计，收集2019年3月至2019年11月三个中心的AE-IPF患者76例，其中痰热壅肺证26例、痰浊阻肺证50例，并纳入健康志愿者10例作为对照。采用ELISA测定患者血清CCL18、HMGB1、KL-6、MMP-7、SP-A和SP-D水平，分析与中医证候的相关性。结果 AE-IPF患者血清CCL18、HMGB1、KL-6、MMP-7、SP-A和SP-D水平均显著高于健康对照组。血清CCL18、HMGB1、KL-6、MMP-7和SP-D水平在痰热壅肺证和痰浊阻肺证患者间无显著性差异（P＞0.05），而血清SP-A水平存在显著性差异（P＜0.05）。结论 血清SP-A与AE-IPF证候存在一定的相关性，血清SP-A的浓度升高，与痰热壅肺证关系越密切，反之，血清SP-A浓度降低，则与痰浊阻肺证关系越密切。AE-IPF痰热壅肺证患者的预后可能较痰浊阻肺证患者更差。     

Effect of root perforation repair with mineral aggregate-based cements on the retention of customized fiberglass posts

Odontology - The purpose of this study was to investigate whether the root perforation repair with mineral aggregate-based cements affects the retention of customized fiberglass posts to bovine...     

Knockdown of DEAD-box 51 inhibits tumor growth of esophageal squamous cell carcinoma via the PI3K/AKT pathway

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most prevalent malignancies that seriously threaten people’s health worldwide.DEAD-box helicase 51(DDX51)is a member of the DEAD-box(DDX)RNA helicase family,and drives or inhibits tumor progression in multiple cancer types.AIM To determine whether DDX51 affects the biological behavior of ESCC.METHODS The expression of DDX51 in ESCC tumor tissues and adjacent normal tissues was detected by Immunohistochemistry(IHC)analyses and quantitative PCR(qPCR).We knocked down DDX51 in ESCC cell lines by using a small interfering RNA(siRNA)transfection.The proliferation,apoptosis,and mobility of DDX51 siRNAtransfected cells were detected.The effect of DDX51 on the phosphoinositide 3-kinase(PI3K)/AKT pathway was investigated by western blot analysis.A mouse xenograft model was established to investigate the effects of DDX51 knockdown on ESCC tumor growth.RESULTS DDX51 exhibited high expression in ESCC tissues compared with normal tissues and represented a poor prognosis in patients with ESCC.Knockdown of DDX51 induced inhibition of ESCC cell proliferation and promoted apoptosis.Moreover,DDX51 siRNA-expressing cells also exhibited lower migration and invasion rates.Investigations into the underlying mechanisms suggested that DDX51 knock down induced inactivation of the PI3K/AKT pathway,including decreased phosphorylation levels of phosphate and tensin homolog,PI3K,AKT,and mammalian target of rapamycin.Rescue experiments demonstrated that the AKT activator insulin-like growth factor 1 could reverse the inhibitory effects of DDX51 on ESCC malignant development.Finally,we injected DDX51 siRNA-transfected TE-1 cells into an animal model,which resulted in slower tumor growth.CONCLUSION Our study suggests for the first time that DDX51 promotes cancer cell proliferation by regulating the PI3K/AKT pathway;thus,DDX51 might be a therapeutic target for ESCC.     

基层医疗卫生机构居家护理服务的安全支持和医务人员服务意愿调查研究

背景 人口老龄化趋势下，罹患多种慢性病的失能或半失能老年人对居家医疗护理服务需求迫切，但基层医务人员提供居家医疗护理服务存在较大的医疗风险和安全隐患，加强居家医疗护理服务的安全管理，有利于提高基层医务人员提供居家医疗护理服务的意愿。 目的 调查基层医疗卫生机构对居家护理服务的安全支持情况和医务人员的服务意愿，为进一步推动居家医疗护理服务发展提供参考依据。 方法 2021年8—10月，采用便利抽样法在四川省五大经济区抽取49所基层医疗卫生机构的1 131例医务人员。自行设计调查问卷，以"问卷星"电子问卷的形式收集资料。问卷内容包括医务人员的一般情况（8个条目）、提供居家医疗护理服务的经历（2个条目）、医疗机构对医务人员的安全支持（7个条目）、医务人员的居家医疗护理服务意愿（1个条目）。比较不同特征医务人员提供居家医疗护理服务的意愿，采用二元Logistic回归分析医务人员提供居家医疗护理服务意愿的影响因素。 结果 1 131例基层医务人员中，692例（61.18%）报告有过居家医疗护理服务的经历，193例（17.06%）报告在服务过程中发生过不良事件/安全事件，531例（46.95%）报告其所在医疗机构未评估过患者接受居家医疗护理服务的安全风险，199例（17.60%）表示所在机构评估了医务人员提供居家医疗护理服务的安全风险，299例（26.44%）在居家医疗护理服务过程中使用APP定位系统，273例（24.14%）由机构配备报警、延迟预警等设备，807例（71.35%）表示居家医疗护理服务过程中没有获得所在机构内其他医务人员的支持措施，303例（26.79%）表示机构曾组织居家医疗护理服务的专项研讨活动，352例（31.12%）表示接受过有关居家医疗护理服务专项培训，853例（75.42%）表示愿意提供居家医疗护理服务。二元Logistic回归分析结果显示，就职的基层医疗卫生机构类型，目前受聘的专业技术职称，医疗机构是否评估过患者接受居家医疗护理服务的安全风险，在居家医疗护理服务过程中是否配备报警、延迟预警等设备，是否参加过有关居家医疗护理服务的专项培训，对医务人员提供居家医疗护理服务意愿有影响（P<0.05）。 结论 现阶段居家医疗护理服务的安全支持不足，多种因素影响基层医务人员提供居家医疗护理服务的意愿。基层医疗卫生机构应加强对患者接受居家医疗护理服务安全风险的评估，为提供居家医疗护理服务的医务人员配备报警、延迟预警等设备，积极举办居家医疗护理服务相关的专项培训并鼓励医务人员参加，以降低医务人员提供居家医疗护理服务的风险，保障其人身安全。