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.     

Hepatotoxicity of cantharidin is associated with the altered bile acid metabolism

Cantharidin (CTD) is an effective antitumor agent. However, it exhibits significant hepatotoxicity, the mechanism of which remains unclear. In this study, biochemical and histopathological analyses complemented with ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS)-based targeted metabolomic analysis of bile acids (BAs) were employed to investigate CTD-induced hepatotoxicity in rats. Sixteen male and female Sprague–Dawley rats were randomly divided into two groups: control and CTD (1.0 mg/kg) groups. Serum and liver samples were collected after 28 days of intervention. Biochemical, histopathological, and BA metabolomic analyses were performed for all samples. Further, the key biomarkers of CTD-induced hepatotoxicity were identified via multivariate and metabolic pathway analyses. In addition, metabolite–gene–enzyme network and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to identify the signaling pathways related to CTD-induced hepatotoxicity. The results revealed significantly increased levels of biochemical indices (alanine aminotransferase, aspartate aminotransferase, and total bile acid). Histopathological analysis revealed that the hepatocytes were damaged. Further, 20 endogenous BAs were quantitated via UHPLC-MS/MS, and multivariate and metabolic pathway analyses of BAs revealed that hyocholic acid, cholic acid, and chenodeoxycholic acid were the key biomarkers of CTD-induced hepatotoxicity. Meanwhile, primary and secondary BA biosynthesis and taurine and hypotaurine metabolism were found to be associated with the mechanism by which CTD induced hepatotoxicity in rats. This study provides useful insights for research on the mechanism of CTD-induced hepatotoxicity.     

癫痫发作后状态及其临床意义

癫痫发作后状态(PIS)是指癫痫发作停止到恢复至发病前水平的异常状态,包括认知、运动、感觉、自主神经和精神行为等异常,症状多样,严重程度不一,持续数秒至数天不等,对患者的健康和生活质量产生很大影响。然而,目前国内外相关的研究较少,临床医生对此缺乏正确认识,容易误诊误治。本文将从PIS的定义、病理生理机制、临床表现、诊断和鉴别诊断、临床意义以及干预策略等进行综述,以提高临床医生的认识,并为今后临床研究提供参考。     

Effect of pneumatic leg compression on post-induction hypotension in elderly patients undergoing robot-assisted laparoscopic prostatectomy: a double-blind randomised controlled trial

Post-induction hypotension is common and associated with postoperative complications. We hypothesised that pneumatic leg compression reduces post-induction hypotension in elderly patients undergoing robot-assisted laparoscopic prostatectomy. In this double-blind randomised study, patients were allocated randomly to the pneumatic leg compression group (n = 50) or control (n = 50). In the intervention group, pneumatic leg compression was initiated before induction of anaesthesia. In the control group, pneumatic leg compression was initiated 20 min after anaesthesia induction. The primary outcome was the incidence of post-induction hypotension in these groups. Post-induction hypotension was defined as systolic blood pressure < 90 mmHg during the first 20 min after induction. Haemodynamic variables and area under the curve of post-induction systolic blood pressure over time were assessed. Complications associated with pneumatic leg compression were recorded, including: peripheral neuropathy; compartment syndrome; extensive bullae beneath the leg sleeves; and pulmonary thromboembolism. The incidence of post-induction hypotension decreased in the pneumatic leg compression group compared with that in the control group; 5 (10%) vs. 29 (58%), respectively, p < 0.001. In the pneumatic leg compression group, the lowest systolic, diastolic and mean blood pressures 20 min after induction of anaesthesia were significantly greater than the control group. Pneumatic leg compression resulted in an increased area under the curve of systolic blood pressure in the first 20 min after induction, p = 0.001. There were no pneumatic leg compression-related complications. Pneumatic leg compression reduced post-induction hypotension in elderly patients undergoing robot-assisted laparoscopic prostatectomy, suggesting that it is an effective and safe intervention to prevent post-induction hypotension among elderly patients undergoing general anaesthesia.     

Trends in radiation dose for low grade gliomas across the United States

Journal of Neuro-Oncology - Adjuvant radiation is often used in patients with low grade gliomas with high-risk characteristics with a recommended dose of 45–54&nbsp;Gy. We used the...     

不完全契约理论视阈下某跨区域医联体核心医院运行效率评价研究

目的对某跨区域医联体核心医院的运行效率进行评价，以不完全契约理论为分析视角探讨影响因素，为深化医联体建设提供借鉴和参考。方法收集2014年-2021年核心医院相关数据，采用DEA数据分析方法，计算运行效率变化情况。结果核心医院各项投入明显增加，医疗业务产出同步增长，医院运行效率经历了动态波动后持续向好。结论通过构建管理共同体，逐步优化契约，争取医保政策支持，合作共建初见成效。     

中医药治疗动脉粥样硬化临床研究进展

中医药防治动脉粥样硬化的研究具有良好的实践基础和应用前景,治疗方法可归于四类,即活血化瘀、化痰调脂、痰瘀同治、扶正祛邪,研究者辨证施治,多在临床上取得了满意的疗效。目前研究仍存在一些亟待解决的问题:首先,中医药防治动脉粥样硬化临床研究重复性差,缺乏大样本、多中心、高质量的临床研究及系统深入的实验研究;其次,对专家经验方及中药复方研究不够深入,临床药效物质基础不明确,缺乏对其作用机制的深入挖掘;再次,目前的研究不够系统和全面,主要集中在对动脉粥样硬化的形成和发展过程的研究,对斑块易损性研究相对较少。针对上述问题,今后应加强中医药治疗动脉粥样硬化的基础及临床研究,为治疗提供更加明确的理论依据和临床证据;同时,建立具有中医特色的研究模式,以中医宏观辨证理论为指导,利用现代医学技术,参考现代中药药理实验结果选药组方,扩大辨证选药思路,加强对中药方剂配伍规律的研究,以及对其有效成分的分离提取、鉴定和作用机制研究,并将传统组方理论与针对发病机制的对病治疗相结合,多角度、多层次探索中医药的作用机理。此外,应不断深入探索动脉粥样硬化的发病机制,并结合细胞工程、分子生物学及基因科学,积极研究中医药的药效学基础和机制。