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。     

我国老年人认知水平变化轨迹及其分化

目的 探究影响我国老年人认知水平的变化趋势，分离出年龄、队列效应。方法 基于CLHLS（2002—2018）多重队列追踪数据，以Stata16.0软件为工具，运用分层生长曲线模型进行统计分析。结果 本研究发现，个体行为生活方式、社会经济地位、性别、慢性病数量对认知水平均具有统计学意义；年龄、队列对认知水平的变化具有独立效应；随着年龄的增长，我国老年人认知水平下降，认知水平的城乡、性别差异明显；较年轻出生队列的老年人认知水平较好，认知水平的城乡差异随着队列的年轻化而变大，性别差异在较年轻队列有略微缩小的趋势。结论 影响认知水平因素复杂，认知障碍会增加医疗成本及照护负担，因此需准确把握老年认知水平的变化规律与作用路径，从而为卫生服务、养老保障、长期医疗照护的资源配置提供科学依据。     

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.     

“中国科技期刊卓越行动计划”领军期刊与对标期刊的指标特征分析与发展建议

【目的】 通过比较2019年获得“中国科技期刊卓越行动计划”领军期刊项目资助的期刊(以下简称“领军期刊”)与其对标期刊,探索我国科技期刊缩小与世界顶级期刊差距的对策,为我国一流科技期刊建设提供参考和借鉴。【方法】 利用Web of Science (WoS) 数据库和期刊官网,检索并总结领军期刊与其对标期刊的各项指标数据,分析领军期刊最近5年来的发展情况。【结果】 22种领军期刊的主要指标数据明显上升。2020年领军期刊共发表Article 和Review文章4025篇,比2019年的2630篇增长53.0%,2020年刊均载文量为183篇,比2019年的120篇增长53.0%;领军期刊总被引频次由2019年的99767 次大幅增长至2020年的153610次,增幅达54.0%;2020年领军期刊的平均被引半衰期为3.73年,而对标期刊的平均被引半衰期为9.35年。2020年,16种领军期刊跻身JCR学科排名前10%,10种领军期刊跻身JCR学科排名前5%。【结论】 领军期刊应构建良性的期刊发展生态、动态调整期刊的发展目标、紧扣国家战略和重大需求布局期刊发展方向、重视人才发展与储备、构建自主可控的国际传播平台与渠道,以完成引领行业发展的使命任务,实现可持续发展,从而带动我国期刊行业的整体发展与进步。