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.     

基于规律成簇的间隔短回文重复序列及其相关蛋白技术检测乙型肝炎病毒共价闭合环状DNA方法的建立

目的建立一种基于规律成簇的间隔短回文重复序列及其相关蛋白(CRISPR/Cas13a)的乙型肝炎病毒(HBV)共价闭合环状DNA(HBV cccDNA)检测方法。方法提取2017年6月至2020年10月于首都医科大学附属北京佑安医院就诊的4例乙型肝炎患者肝脏总DNA后,使用HindⅢ内切酶和质粒安全性ATP依赖DNA酶(PSAD)分别进行酶切;根据松弛环状DNA(rcDNA)和cccDNA的结构差异,设计特异性扩增HBV cccDNA的引物,对酶切后的产物进行滚环扩增(RCA)和PCR扩增;并筛选crRNA,建立基于CRISPR/Cas13a技术的HBV cccDNA检测新方法。结果利用α-1-抗胰蛋白酶(A1AT)和HBV表面抗原(HBsAg)引物对双重酶切后的产物进行扩增,验证产物中HBV基因组的存在;利用HBV cccDNA和HBV rcDNA引物对PSDA酶切后的产物扩增,验证了产物中只存在HBV cccDNA;利用RCA后的阳性样本作为模板梯度稀释,然后进行PCR扩增转录后使用CRISPR/Cas13a检测,计算出检测下限为10拷贝/μl。结论本研究建立了RCA-PCR-CRISPR-Cas13a的新型检测方法,可对HBV cccDNA进行高灵敏度和高特异性检测,为乙型肝炎患者抗病毒治疗评估、治疗终点的确定以及调整治疗方案提供了有效的监测手段。     

Primary localized gastric amyloidosis: A scoping review of the literature from clinical presentations to prognosis

Localized gastric amyloidosis (LGA) is a rare disease characterized by abnormal extracellular deposition of amyloid protein restricted to the stomach and it is confirmed by positive results of Congo red staining. Over decades, only a few cases have been reported and studies or research focusing on it are few. Although LGA has a low incidence, patients may suffer a lot from it and require proper diagnosis and management. However, the pathology of LGA remains unknown and no overall review of LGA from its presentations to its prognosis has been published. Patients with LGA are often asymptomatic or manifest atypical symptoms, making it difficult to differentiate from other gastrointestinal diseases. Here, we report the case of a 70-year-old woman with LGA and provide an overview of case reports of LGA available to us. Based on that, we conclude current concepts of clinical manifestations, diagnosis, treatment, and prognosis of LGA, aiming at providing a detailed diagnostic procedure for clinicians and promoting the guidelines of LGA. In addition, a few advanced technologies applied in amyloidosis are also discussed in this review, aiming at providing clinicians with a reference of diagnostic process. With this review, we hope to raise awareness of LGA among the public and clinicians.     

The efficacy and safety of Xiangsha Liujunzi decoction in the treatment of chronic non-atrophic gastritis: A protocol for a systematic review and meta-analysis

Background:Chronic non-atrophic gastritis is the most common type of chronic gastritis. Even if treated with current standard pharmacotherapy, the efficacy is not very satisfactory due to many factors. Traditional Chinese Medicine decoctions are increasingly used in the treatment of chronic gastritis, and many studies have shown that Xiangsha Liujunzi decoction is effective and safe in the treatment of chronic non-atrophic gastritis. However, it is controversy if Xiangsha Liujunzi decoction can provide an evidence-based clinical efficacy and safety in the treatment of chronic non-atrophic gastritis.Methods:We will go through 8 databases, and conduct a systematic review of Xiangsha Liujunzi decoction and health-related outcomes in chronic non-atrophic gastritis patients according to the Preferred Reporting Items for Systematic Reviews. The primary objective is to assess the impact of Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines on clinical outcomes relevant to chronic non-atrophic gastritis patients, such as clinical effective rate,Helicobacter pylori eradication rate, efficacy under endoscopy, 1-year recurrent rate, and number of reported adverse events. Cochrane Risk Assessment Tool will be used to assess the quality of eligible studies according to the Cochrane handbook.Results:The results of this systematic review will provide a synthesis of current evidence of Xiangsha Liujunzi decoction and we have a specific opportunity to determine the efficacy and safety of it.Conclusion:This study will explore whether or not Xiangsha Liujunzi decoction can be used as one of the complementary and alternative therapies in the treatment of chronic non-atrophic gastritis.Registration number:Identifier: DOI 10.17605/OSF.IO/TX27U (https://osf.io/tx27u/).     

染料木黄酮对前列腺癌细胞增殖、迁移和侵袭的影响及机制

本研究拟探讨染料木黄酮对前列腺癌细胞LNCaP和CWR22RV1的增殖、迁移和侵袭能力的影响。一、材料与方法1.材料:前列腺癌细胞株LNCaP和CWR22RV1(中国科学院上海生命科学研究院);Genistein(天津科瑞泰科技有限公司);RPMI 1640、胎牛血清(FBS)、胰蛋白酶(美国Gibco公司);E-钙黏蛋白(E-cadherin)、N-钙黏蛋白(N-cadherin)、波形蛋白(Vimentin,Abcam公司);聚氰基丙烯酸正丁酯(BCA)试剂盒、十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE)上样缓冲液(×5)及蛋白质印迹法(Western blot)试剂盒(上海市碧云天生物公司);2.实验方法:采用噻唑蓝(MTT)实验、划痕实验和Transwell实验检测Genistein对细胞增殖、迁移及侵袭能力的影响。采用Western blot检测E-cadherin、N-cadherin、Vimentin、CD44和Oct-4的表达水平。     

基于十二指肠异常探讨功能性消化不良的中医研究进展＊

功能性消化不良（functional dyspepsia， FD）是一种常见的功能性胃肠病（functional gastrointestinal disorder， FGID），属于中医“痞满”“胃脘痛”范畴，多因“气机升降失常”所致。目前，FD发病机制主要涉及脑肠互动异常、胃容受性受损、内脏敏感性增高、胃动力不足、幽门螺杆菌感染、十二指肠异常、心理精神因素等。随着罗马Ⅳ标准的颁布，十二指肠的作用在FD的发病中日益凸显。十二指肠高敏性、十二指肠黏膜屏障受损及十二指肠黏膜低度炎症等在FD病理生理过程中起着非常重要的作用，十二指肠可能是治疗FD的新靶点。本文综述FD发病中十二指肠的作用及中医药研究，为FD的基础研究及临床治疗提供理论依据。