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.     

Quantile regression and empirical likelihood for the analysis of longitudinal data with monotone missing responses due to dropout,with applications to quality of life measurements from clinical trials

The analysis of quality of life (QoL) data can be challenging due to the skewness of responses and the presence of missing data. In this paper, we propose a new weighted quantile regression method for estimating the conditional quantiles of QoL data with responses missing at random. The proposed method makes use of the correlation information within the same subject from an auxiliary mean regression model to enhance the estimation efficiency and takes into account of missing data mechanism. The asymptotic properties of the proposed estimator have been studied and simulations are also conducted to evaluate the performance of the proposed estimator. The proposed method has also been applied to the analysis of the QoL data from a clinical trial on early breast cancer, which motivated this study.     

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.     

德尔菲法构建儿童伤害预防家庭监护能力评估指标体系

  目的  探索构建儿童伤害预防家庭监护评估能力指标并确定指标权重,为针对家长进行儿童伤害干预提供依据。  方法  邀请中国24位伤害预防、儿童保健等领域专家参与德尔菲专家咨询,根据咨询结果筛选并确定最终指标体系,采用层次分析法确定一、二级指标权重。  结果  最终构建的评估指标体系由0,1~2,3~5,6~11和12~17岁5个分量表构成,每个分量表都包括4个一级指标和11个二级指标。层次分析法得到一级指标权重:“环境”为0.28,“产品”为0.16,“行为与技能”为0.31,“心理”为0.25。“环境”“产品”和“行为与技能”对应二级指标中权重最高的均是“水域”;“心理”对应的5个二级指标权重排前3位的是“家庭氛围”“教养方式”和“情绪管理”,权重都在0.2以上。  结论  经专家咨询构建的儿童伤害预防家庭监护能力评估指标体系内容完整,且家长的监护行为与技能是伤害预防监护的评估重点。     

儿童伤害预防家庭监护能力评估研究分析

  目的  对现有研究中关于儿童伤害预防家庭监护能力评估的内容进行分析,为开发适用于中国儿童的伤害家庭监护能力评估指标体系提供参考依据。  方法  从中国生物医学文献数据库(CBM)、万方、中国知网、维普、PubMed、Medline、Springer和Web of Science中英文数据库检索儿童伤害预防家庭监护能力评估的相关研究,从评估方法、评估内容和所用评估工具的信效度对相关文献进行梳理。  结果  共纳入文献47篇,纳入研究中的评估方法包括定性研究和定量调查,以通过量表或问卷开展的定量调查为主。评估内容包括家长的儿童伤害预防知信行(44篇)和家庭环境安全性(3篇),评估对象主要集中在学龄前儿童家长。定量调查中,8篇研究验证了所用评估工具的信效度,信度检验指标包括重测信度和Cronbach α系数,效度指标包括内容效度、结构效度和效标效度。  结论  现有研究中缺乏适用于中国儿童及家长的儿童伤害预防家庭监护能力评估工具,今后开发相应评估工具时应考虑不同儿童年龄段特点、不同伤害类型以及信效度问题。     

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。