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.     

核医学学科新增医疗服务项目定价方法研究

目的：基于以价值为基础的定价方法，计算核医学学科新增医疗服务项目镭[²²³ Ra]骨转移瘤治疗的医疗服务价格。为相关新增医疗服务项目的申报和定价打下循证基础，为合理补偿医务人员劳动价值、提升患者服务项目可及性提供依据。方法：采集2021年3—12月使用“镭核素[²²³ Ra]骨转移瘤治疗资源投入及费用数据采集表”相关数据，开展专家访谈进行系数赋值和基线对照项目确定，得到镭[²²³ Ra]骨转移瘤治疗服务各个环节的成本和新增服务的价值。结果：镭[²²³ Ra]骨转移瘤治疗服务按服务特点分为注射前评估、治疗计划、给药、给药后监测、废弃物处理与监测等环节，各环节3地平均人力耗时分别为104分钟、39分钟、25分钟、72分钟和56分钟，中位物耗成本为48.20元，3地总成本(平均人力成本+中位物耗成本)为763.68元。结合系数赋值结果和基线对比项目，得到新增项目的价值为810.19元。结论：运用基于技术难度和风险程度的价值定价理论，计算镭[²²³ Ra]骨转移瘤治疗新增医疗服务项目的服务价值，建议以价值作为服务定价依据。该定价公式和研究方法不仅可用于其他核医学学科新增服务项目的定价，还适用于现行医疗服务项目的价格动态调整，为未来学科价格工作提供方法学参考。     

基于动脉自旋标记技术的麻痹性痴呆患者脑血流量特点及其与认知障碍相关性

目的探讨麻痹性痴呆（GPI）患者脑血流量（CBF）特点及其与认知障碍的相关性。 方法纳入2018年1月至2019年12月于首都医科大学附属北京地坛医院就诊的GPI患者18例和健康体检者18例（健康对照组），采用蒙特利尔认知评估量表评定认知功能。采用磁共振动脉自旋标记技术扫描评估其各个脑区CBF，并进一步应用Spearman相关分析CBF异常区域与认知功能的相关性。 结果GPI患者蒙特利尔认知评估量表评分低于健康对照组[（16.00 ± 7.19）vs. （27.90 ± 1.21）：t =－7.853、P < 0.001）]。18例GPI患者中，头颅MRI正常5例，脑白质病变1例，脑萎缩9例，3例患者同时存在脑萎缩和脑白质病变。健康对照组头颅MRI均未见异常。GPI患者脑13、14、28、37、38、41、42、43、44、46、48、49、50、51、52、69、70、77、78、83、84、88、109、117、165、166、167、168、169、177、178、179、187、188、211、212、213、214、215、216、219、223、227、237和238区CBF显著高于健康对照组（P均< 0.001）。GPI患者认知障碍中的注意力障碍与脑69、70、77、78、166和168区CBF异常有一定的负相关性（r =－0.476、P = 0.046，r =－0.487、P = 0.034，r =－0.604、P = 0.008，r = －0.545、P = 0.019，r =－0.544、P = 0.02，r =－0.522、P = 0.026）。 结论GPI患者存在全脑血流量升高。GPI患者认知功能障碍中的注意力障碍可能与局部脑区血流量升高有一定相关性。局部CBF越高，注意力障碍越严重。这可能也是GPI发病机制之一。     

A Case of Refractory Childhood Glaucoma Secondary to Weill-Marchesani Syndrome: Management with Combined CO2 Laser-Assisted Sclerectomy Surgery and Trabeculectomy

A 2-year-old girl was diagnosed as Weill-Marchesani syndrome with typical systemic features of short stature, short and stubby hands and feet, language disorders and mental retardation. He developed bilateral angle closure glaucoma, ectopia lentis and suffered visual loss from the ocular features of Weill-Marchesani syndrome. The child was successfully treated by combined CO₂ laser-assisted sclerectomy surgery and trabeculectomy.     

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。     

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.