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.     

亚慢性硝酸钇暴露对雌性大鼠学习记忆能力的影响

目的：观察稀土化合物硝酸钇[Y（NO₃）₃]亚慢性（90 d）暴露对大鼠学习记忆能力的影响，并探究其可能的机制，为全面评估稀土元素钇的健康风险提供科学依据。方法：选用刚离乳（PND21）SD雌性大鼠，根据质量随机分为4组，分别为对照组（ddH₂O），Y（NO₃）₃低剂量组[10 mg/（kg·d）]、中剂量组[40 mg/（kg·d）]和高剂量组[160 mg/（kg·d）]，每组15只。连续灌胃受试物90 d后进行旷场实验、高架十字迷宫实验、转棒实验、Morris水迷宫实验。水迷宫检测后，每组取5只雌鼠心脏原位灌注，进行脑组织病理学检查。每组剩余10只雌鼠摘取脑组织，紫外分光光度计检测雌鼠大脑皮质和海马中谷氨酸（Glu）的含量；Western blot检测海马组织中N-甲基-D-天冬氨酸（NMDA）受体蛋白表达情况。结果：与对照组相比，硝酸钇90 d暴露后，转棒实验中160 mg/（kg·d）剂量组大鼠在棒时间、在棒圈数、掉落速度明显升高（P<0.05）。在Morris水迷宫定位航向实验第4天时，40、160 mg/（kg·d）剂量组大鼠逃避潜伏期明显降低（P<0.05）；Morris水迷宫空间探索实验中，40 mg/（kg·d）剂量组大鼠穿越平台次数、目标象限游泳时间明显增加（P<0.05）；160 mg/（kg·d）剂量组穿越平台次数、进入目标象限次数、目标象限游泳时间明显增加（P<0.05）；160 mg/（kg·d）剂量组大鼠东北、东南、西南象限的逃避潜伏期明显低于西北象限的逃避潜伏期（P<0.05）。160 mg/（kg·d）剂量组大鼠海马中Glu含量和NMDA受体NR1含量均明显低于对照组（P<0.05）。40和160 mg/（kg·d）剂量组大鼠海马中NMDA受体NR2A含量明显低于对照组（P<0.05）。结论：硝酸钇亚慢性（90 d）暴露可以引起雌性大鼠空间学习记忆能力增强；硝酸钇可能通过降低海马组织神经元细胞外Glu含量，抑制NMDA受体激活，增强雌性大鼠的空间学习记忆能力。     

Durability of humoral immune responses to rubella following MMR vaccination

BackgroundWhile administration of the measles-mumps-rubella (MMR-II®) vaccine has been effective at preventing rubella infection in the United States, the durability of humoral immunity to the rubella component of MMR vaccine has not been widely studied among older adolescents and adults.MethodsIn this longitudinal study, we sought to assess the durability of rubella virus (RV)-specific humoral immunity in a healthy population (n = 98) of adolescents and young adults at two timepoints: ~7 and ~17 years after two doses of MMR-II® vaccination. Levels of circulating antibodies specific to RV were measured by ELISA and an immune-colorimetric neutralization assay. RV-specific memory B cell responses were also measured by ELISpot.ResultsRubella-specific IgG antibody titers, neutralizing antibody titers, and memory B cell responses declined with increasing time since vaccination; however, these decreases were relatively moderate. Memory B cell responses exhibited a greater decline in men compared to women.ConclusionsCollectively, rubella-specific humoral immunity declines following vaccination, although subjects’ antibody titers remain well above the currently recognized threshold for protective immunity. Clinical correlates of protection based on neutralizing antibody titer and memory B cell ELISpot response should be defined.     

Curcumin attenuates spatial memory impairment by anti-oxidative,anti-apoptosis,and anti-inflammatory mechanism against methamphetamine neurotoxicity in male Wistar rats: Histological and biochemical changes

ObjectiveMethamphetamine is used extensively around the world as a psychostimulant. The complications related to methamphetamine include methamphetamine-induced neurotoxicity, mainly involving intraneuronal processes, such as oxidative stress and excitotoxicity. Curcumin is effective against neuronal injury due to its antioxidant, anti-inflammatory effects. In this study, we examined the protective effects of curcumin against methamphetamine neurotoxicity.MethodsSixty male Wistar rats were divided into the following groups: control (n = 12), DMSO (n = 12), methamphetamine (n = 12), and methamphetamine + curcumin (100 and 200 mg/kg, respectively, intraperitoneal [IP]; n = 12). Neurotoxicity was induced by 40 mg/kg of methamphetamine administrated through 4 injections (4 × 10 mg/kg, q2h, IP). Curcumin (100 and 200 mg/kg) was administered at 7 days after the last methamphetamine injection. By using a Morris water maze task, the hippocampus-dependent memory and spatial learning were evaluated 1 day after the last curcumin injection. Then, the animal brains were isolated for biochemical measurements, as well as glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor protein-1(Iba-1) and caspase-3 immunohistochemical staining.ResultsThe current study demonstrated that administration of curcumin significantly attenuates spatial memory impairment (P < 0.01) following methamphetamine neurotoxicity. Curcumin caused a significant increase in the levels of superoxide dismutase and glutathione peroxidase (P < 0.05). However, it decreased tumor necrosis factor (TNF-α) (P < 0.05) and malondialdehyde (P < 0.01) levels as compared to the methamphetamine group. Also, curcumin significantly reduced Iba-1 (P < 0. 01), GFAP and caspase-3 positive cells in the hippocampus (P < 0.001).ConclusionCurcumin exerted neuroprotective effects on methamphetamine neurotoxicity because of its antioxidant and anti-inflammatory effect.     

德宏傣族景颇族自治州接受抗病毒治疗的HIV/AIDS糖尿病累积发病率的研究

  目的  探究德宏傣族景颇族自治州(简称德宏州)接受抗病毒治疗(antiretroviral therapy, ART)的HIV感染者和AIDS病人(简称HIV/AIDS) 糖尿病3年累积发病率及其危险因素。  方法  采用队列设计,于2017年7月―2018年6月招募接受ART的HIV/AIDS为研究对象,于2021年1月―2021年7月进行队列随访,采集静脉血检测糖化血红蛋白(hemoglobin A1c, HbA1c)。糖尿病判定标准为符合其中任意一项:HbA1c≥6.5%或最近1次FPG≥7.0 mmol/L。采用logistic回归分析模型分析糖尿病发病的影响因素。  结果  本次分析纳入3 647例基线未患糖尿病的HIV/AIDS,平均年龄为42(36, 49)岁,男性占比51.4%,抗HCV IgG阳性率为21.5%,HIV感染确证平均时间为12.1(9.3, 14.6)年,ART平均时间为9.3(7.6, 12.2)年。糖尿病3年累积发病率为6.0%,其中HbA1c≥6.5%发病率为2.5%,FPG≥ 7.0 mmol/L发病率为5.3%。多因素logistic回归分析模型分析显示,年龄≥50岁、男性、HCV合并感染、基线TG升高、基线HIV病毒载量≥50 copies/mL和基线ART药物含依非韦伦(efavirenz, EFV)与糖尿病发病均呈正相关(均有P＜0.05)。  结论  德宏州HIV/AIDS糖尿病累积发病率较高,应对该人群针对性采取综合防治措施,降低糖尿病累积发病风险。     

中国成年人生活方式和心血管代谢因素与甲基化年龄加速的相关性分析

目的比较分析5种甲基化年龄加速指标与生活方式和心血管代谢因素间的相关性。方法基于中国慢性病前瞻性研究中有基线外周血全基因组甲基化检测数据的研究对象980人, 计算Horvath时钟、Hannum时钟、DNAm PhenoAge、GrimAge和Li时钟5种甲基化年龄。根据甲基化年龄对实足年龄回归的残差值计算甲基化年龄加速。研究的生活方式因素包括吸烟、饮酒、饮食习惯、体力活动、经BMI和腰围联合定义的体型。心血管代谢因素包括血压、血糖和TC。利用一般线性模型分析生活方式和心血管代谢因素与各甲基化年龄加速指标的相关性[β值(95%CI)]。结果 GrimAge加速指标与吸烟、饮酒、体力活动水平及BMI存在关联。与不吸烟、不饮酒或BMI为18.5～23.9 kg/m2 者相比, 吸烟者(每天吸烟1～14、15～24、≥25支者对应的β值依次为0.71(95%CI:0.57～0.86)、0.88(95%CI:0.73～1.03)、0.99(95%CI:0.81～1.18)、重度饮酒者[每日纯乙醇量≥60 g:0.33(95%CI:0.11～0.55)]、BMI<18.5 kg/m2者[0...     

学龄儿童肥胖与肠道菌群多样性及菌属丰度的关联研究

目的分析学龄肥胖儿童和正常体重儿童肠道菌群多样性差异, 识别肥胖儿童肠道特征菌属, 为后续相关机制研究和学龄儿童肥胖的防治提供依据。方法基于2016年在上海市嘉定区某小学建立的研究队列人群, 将2016-2018年3年均处肥胖状态的儿童共63名纳入肥胖组, 其中男生43名, 女生20名。在3年均为正常体重的儿童中, 根据年龄、性别和所在班级, 将其与肥胖组儿童进行1∶1匹配, 共选择63名纳入对照组。采用问卷收集儿童基本信息、饮食状况、母乳喂养等情况, 收集两组儿童的粪便样本并进行16S rDNA测序。对质量优化后的测序序列按照97%相似性进行可操作分类单元聚类及物种注释。分析肥胖组和对照组儿童肠道菌群多样性及菌属丰度差异。计算肠道菌群的Ace、Chao1、Shannon、Simpson 4种α多样性指数, 并利用主坐标分析, 在非加权Unifrac距离和加权Unifrac距离的基础上表示β多样性。使用相似性分析(ANOSIM)比较两组β多样性的差异。利用STAMP软件挑选出两组儿童共有菌属中的差异细菌, 并利用广义线性模型(GLM)分析肥胖与α多样性以及显著差异菌属的关联。结果肥胖组...     

浙江省海岛农村社区成年人代谢综合征发病率及其危险因素

目的估计浙江省海岛农村社区成年人代谢综合征发病情况, 探索该地区代谢综合征发病的相关影响因素。方法 2018年6-12月在浙江省玉环市对2012年开展的代谢综合征基线调查人群中无代谢综合征调查对象进行随访调查, 获取相关调查表信息以及实验室数据, 描述代谢综合征发病情况, 使用logistic回归探索发病危险因素及调整风险比(aRR)和95%CI。结果 3 162名随访对象中新发代谢综合征522例, 6年累积发病率为16.5%, 男女性累积发病率分别为12.3%、20.6%, 女性高于男性(P<0.001)。无业、吸烟、饮酒调查对象中代谢综合征发病率较高。女性(aRR=1.96, 95%CI:1.50～2.58)和高血压家族史(aRR=1.31, 95%CI:1.04～1.63)为代谢综合征发病独立危险因素。结论海岛农村社区成年人代谢综合征发病率相对较高, 其中女性以及有高血压家族史者发病风险更高。