Effects of Wenyang Zhenshuai Granules on the Expression of Key Mitochondrial Autophagy Proteins in the Doxorubicin-Induced Model of H9c2 Cardiomyocyte Injury

Bulletin of Experimental Biology and Medicine - This study aimed to explore the effects of Wenyang Zhenshuai granules (WZG) on the morphology of cardiomyocytes, cell viability, and the expression...     

某高校大学生艾滋病主动检测意愿与影响因素

目的 了解青年学生艾滋病主动检测意愿的现状,提出促进青年学生主动检测意愿的建议,为进一步提高青年学生艾滋病检测意愿的策略和措施提供科学依据。方法 采用自编促进大学生HIV主动检测意愿调查问卷,用整群抽样方法抽取成都某高校778名在校大学进行问卷调查。结果 在被调查的778名大学生中,91.6%的学生有艾滋主动检测意愿,在不同年级(χ2=11.416,P=0.010)、认为自己感染艾滋病风险情况(χ2=18.615,P＜0.001)等因素上差异均有统计学意义。多因素 logistic 回归分析显示年级为大二或大三、认为自己艾滋病感染风险为非常低或比较低或一般(P均＜0.05)的青年学生更愿意进行艾滋病主动检测。结论 该高校大学生艾滋病主动检测意愿较高。应该结合该高校学生的特性,开展有针对性的艾滋病宣传教育活动,以此提高大学生HIV主动检测率。     

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.     

Use of Alternative Designs and Data Sources for Pediatric Trials

Abstract

Children are considered a vulnerable group and as such are granted additional protection as research subjects. Research projects using children as research subjects are justifiable if the answer to the scientific question of the study cannot be obtained by enrolling adult subjects (cf. scientific necessity). Thus, there is an ethical obligation to explore innovative analytical strategies that seek balance between the feasibility of conducting a trial and maximizing the utilization of data on efficacy and safety. On this note, there is enthusiasm for implementing some less popular but efficient alternative designs for confirmatory pediatric trials. Within the pediatric extrapolation paradigm, examples of such designs, other than purely based on pharmacokinetic/pharmacodynamic data, are described in this article along with their advantages and disadvantages. This article will also discuss how to incorporate alternative data sources in the analysis of pediatric clinical trials. A discussion of existing approaches and a road-map to their utilization will be provided. Real case examples on the use of the approaches are provided.     

luminal型乳腺癌患者戈舍瑞林用药依从性现状及影响因素分析

目的了解luminal型乳腺癌患者戈舍瑞林用药依从性情况，分析影响其依从性的相关因素。 方法根据纳入及排除标准，收集2015年1月至2017年12月重庆医科大学附属第一医院内分泌乳腺外科使用戈舍瑞林治疗的luminal型乳腺癌女性患者174例进行回顾性分析。中位随访时间16个月(范围：1～54个月)，完成随访154例，失访20例，失访率为11.5%(20/174)。采用问卷调查评价其用药依从性，使用χ²检验和Mann-Whitney U检验比较不同特征患者依从性的差异；用Logistic回归分析影响患者依从性的相关因素。将患者分为≤40岁(103例)和>40岁(51例)2个亚组，进行亚组分析。 结果在完成随访的154例患者中，依从性好82例(53.2%，82/154)，依从性差72例(46.8%，72/154)。≤40岁组患者中，55.3%(57/103)依从性好，而>40岁组患者中仅49.0%(25/51)依从性好。全部患者中，文化程度、医保类型、不良反应和是否了解疗程时间均与乳腺癌患者戈舍瑞林用药依从性有关(χ²＝13.586、13.042、7.880、14.251，P均<0.050)；Logistic回归分析结果显示：高中及以下学历、居民医保和不了解戈舍瑞林的疗程时间为影响依从性的危险因素(OR＝2.772，95%CI：1.243～6.183，P＝0.013；OR＝5.188，95%CI：1.383～19.465，P＝0.015; OR＝3.363，95%CI：1.645～6.878，P＝0.001)。亚组分析显示：文化程度、职业、医保类型和是否了解疗程时间是≤40岁患者戈舍瑞林用药依从性的影响因素(χ²＝15.992、5.978、7.701、10.376，P均<0.050)；不良反应及医保类型是>40岁患者用药依从性的影响因素(χ²＝4.763、7.471，P均<0.050)。Logistic回归分析表明：高中及以下文化程度和不了解疗程时间是≤40岁患者用药依从性的危险因素(OR＝5.126，95%CI：2.086～12.598，P<0.001; OR＝3.631, 95%CI：1.500～8.792，P＝0.004)；居民医保是>40岁患者用药依从性的危险因素(OR＝64.315，95%CI：2.513～1 646.042，P＝0.012)，不良反应是>40岁患者用药依从性的保护因素OR＝0.189，95%CI＝0.047～0.759，P＝0.019)。 结论luminal型乳腺癌患者戈舍瑞林用药依从性较差，文化程度、医保类型及是否了解疗程时间都可能影响患者的依从性。≤40岁组和>40岁组患者依从性有差异，且影响因素不同，建议对不同年龄患者用药采用不同的干预措施。     

The FABP12/PPARγ pathway promotes metastatic transformation by inducing epithelial‐to‐mesenchymal transition and lipid‐derived energy production in prostate cancer cells

Early stage localized prostate cancer (PCa) has an excellent prognosis; however, patient survival drops dramatically when PCa metastasizes. The molecular mechanisms underlying PCa metastasis are complex and remain unclear. Here, we examine the role of a new member of the fatty acid‐binding protein (FABP) family, FABP12, in PCa progression. FABP12 is preferentially amplified and/or overexpressed in metastatic compared to primary tumors from both PCa patients and xenograft animal models. We show that FABP12 concurrently triggers metastatic phenotypes (induced epithelial‐to‐mesenchymal transition (EMT) leading to increased cell motility and invasion) and lipid bioenergetics (increased fatty acid uptake and accumulation, increased ATP production from fatty acid β‐oxidation) in PCa cells, supporting increased reliance on fatty acids for energy production. Mechanistically, we show that FABP12 is a driver of PPARγ activation which, in turn, regulates FABP12''s role in lipid metabolism and PCa progression. Our results point to a novel role for a FABP‐PPAR pathway in promoting PCa metastasis through induction of EMT and lipid bioenergetics.

Abbreviations

AR

androgen receptor

ATP

adenosine triphosphate

CN

copy number

CPT1

carnitine palmitoyltransferase I

CS

citrate synthase

EMT

epithelial–mesenchymal transition

ET

electron transfer‐state

FABP

fatty acid‐binding protein

LD

lipid droplet

OA

oleic acid

PCa

prostate cancer

PPAR

peroxisome proliferator‐activated receptor

PPRE

peroxisome proliferator‐activated receptor response element

TZD

thiazolidinediones