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.     

HIV-negative children’s experiences and opinions towards parental HIV disclosure: a qualitative study in China

In HIV/AIDS research, few studies to date have evaluated ways to improve parental HIV disclosure practices using feedback from HIV-negative children who have recently experienced this event. We conducted semi-structured in-depth interviews with 20 children (aged 6–15) who were partially to fully aware of their parents’ HIV status in rural Guangxi, China. Of the 20 children, eight children who were of older age (11.38 years in average) endorsed parental HIV disclosure, five discouraged it and seven expressed uncertainty. Children’s different experiences and attitudes towards disclosure were seen to be associated with their family dynamics (especially the parent–child relationship), social support and care, experiences of stigma and discrimination, psychosocial suffering, comprehension of the disease and the children’s age. Our study contributes to building a child-centered comprehensive understanding for Chinese parental HIV disclosure. It is imperative that counselors and community advocates assess and help parents achieve optimal readiness preceding disclosure of their illness to their HIV-negative children.     

Decreased expression levels of DAL-1 and TOB1 are associated with clinicopathological features and poor prognosis in gastric cancer

PurposeWe previously demonstrated that the functional inactivation of DAL-1 and TOB1 promotes an aggressive phenotype in gastric cancer cells, but the links between both genes and the survival of patients with gastric cancer are unknown. Here, we investigated the correlations of the expression levels of DAL-1 and TOB1 with the progression of gastric cancer.MethodsA total of 270 patients who underwent resectable gastrectomy were included. The expression of DAL-1 and TOB1 was detected by immunohistochemistry.ResultsLow expression of DAL-1 in cancer tissue was significantly associated with tumor site (p < 0.05), histological grade (p < 0.01), depth of invasion (p < 0.05), lymph node metastasis status (p < 0.05), Lauren classification (p < 0.001), and clinical stage (p < 0.01). A lower level of TOB1 was observed in gastric cancer patients with diffuse type disease compared to patients with either intestinal or mixed type disease (p < 0.001). Additionally, Spearman’s correlation analysis revealed that decreased expression of DAL-1 was positively correlated with low TOB1 expression (r=0.304, p < 0.001). The survival analysis showed that low levels of DAL-1 and TOB1 were significantly associated with poor survival of gastric cancer patients (p <0.001 and p < 0.05, respectively).ConclusionThe downregulation of DAL-1 and TOB1 expression is associated with shorter survival of gastric cancer patients. Hence, DAL-1 and TOB1 may be considered potential novel markers for predicting the outcomes of patients with gastric cancer.     

Investigation of the mechanisms of Genkwa Flos hepatotoxicity by a cell metabolomics strategy combined with serum pharmacology in HL-7702 liver cells

1. To investigate Genkwa Flos hepatotoxicity, a cell metabolomics strategy combined with serum pharmacology was performed on human HL-7702 liver cells in this study.

2. Firstly, cell viability and biochemical indicators were determined and the cell morphology was observed to confirm the cell injury and develop a cell hepatotoxicity model. Then, with the help of cell metabolomics based on UPLC-MS, the Genkwa Flos group samples were completely separated from the blank group samples in the score plots and seven upregulated as well as two down-regulated putative biomarkers in the loading plot were identified and confirmed. Besides, two signal molecules and four enzymes involved in biosynthesis pathway of lysophosphatidylcholine and the sphingosine kinase/sphingosine-1-phosphate pathway were determined to investigate the relationship between Genkwa Flos hepatotoxicity and these two classic pathways. Finally, the metabolic pathways related to specific biomarkers and two classic metabolic pathways were analyzed to explain the possible mechanism of Genkwa Flos hepatotoxicity.

3. Based on the results, lipid peroxidation and oxidative stress, phospholipase A₂/lysophosphatidylcholine pathway, the disturbance of sphingosine-1-phosphate metabolic profile centered on sphingosine kinase/sphingosine-1-phosphate pathway and fatty acid metabolism might be critical participators in the progression of liver injury induced by Genkwa Flos.     

Health-Related Quality of Life in KEYNOTE-010: a Phase II/III Study of Pembrolizumab Versus Docetaxel in Patients With Previously Treated Advanced,Programmed Death Ligand 1–Expressing NSCLC

Introduction

In the phase II/III KEYNOTE-010 study (ClinicalTrials.gov, NCT01905657), pembrolizumab significantly prolonged overall survival over docetaxel in patients with previously treated, programmed death ligand 1–expressing (tumor proportion score ≥ 1%), advanced NSCLC. Health-related quality of life (HRQoL) results are reported here.

平肝定眩汤治疗肝阳上亢型后循环缺血性眩晕60例临床观察

目的:观察平肝定眩汤对肝阳上亢型后循环缺血性眩晕的疗效。方法:选取2017年6月-2018年10月烟台业达医院收治的后循环缺血性眩晕的患者120例,按随机数字表法分为治疗组和对照组。治疗组和对照组各60例,两组一般的资料经统计学方法,差异无统计学意义(P>0.05),具有可比性。两组均给予改善循环,控制血压、血糖,调节血脂,抗血小板聚集等基础治疗。治疗组给予平肝定眩汤,对照组给予平眩胶囊。两组疗程均为4周,观察两组患者治疗前后总体症状,脑血流速度、血脂、血糖等指标改善情况。采用SPSS 11.0统计学软件进行计算。结果:治疗组总有效率91.7%(55/60),对照组总有效率61.6%(37/60),两组疗效比较有统计学意义(P<0.05)。治疗组三酰甘油(Triglyceride,TG)、血清总胆固醇(Serum Total Cholesterol,TC)、HDL-C、LDL-C治疗后显著改善,与治疗前比较,差异有统计学意义(P<0.05);对照组TG及TC治疗前后差异有统计学意义(P<0.05),高密度脂蛋白胆固醇(High Density Liptein Cholesterol,HDL-C)及低密度脂蛋白胆固醇(Low Density Liptein Cholesterol,LDL-C)治疗前后比较,差异无统计学意义(P>0.05)。两组治疗后TC比较,差异有统计学意义(P<0.05)。两组治疗后空腹血糖(Fasting Plasma Glucose,GLU)明显降低(P<0.05),两组间的治疗后比较,差异无统计学意义(P>0.05)。治疗组治疗后椎动脉(Vertebral Artery,VA)、基底动脉(Basilarartery,BA)平均血流速度(Mean Blood Flow Velocity,VM)明显提高,与对照组治疗后相比较,差异具有统计学意义(P<0.05)。结论:平肝定眩汤治疗后循环缺血性眩晕在改善患者症状、降低血液黏稠度,改善脑血流状况方面疗效显著。