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.     

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.     

H型高血压患者舌面诊图像颜色特征参数分析＊

目的 分析H型高血压患者的舌面诊图像颜色参数特征，探讨H型高血压患者的舌诊、面诊变化规律。方法 运用上海中医药大学自行研制的Smart TCM-1型中医舌面一体仪，采集高血压患者舌面诊图像，提取特征参数，分析健康对照组、H型高血压组与非H型高血压组患者舌面颜色参数特征。结果 ①在舌色各项参数中，H型高血压组舌尖部R值、B值、V值均显著小于健康对照组（P < 0.01）；非H型高血压组舌尖部B值显著小于健康对照组（P < 0.01），S值较健康对照组显著增大（P < 0.05）；H型高血压组舌尖部R、V值均明显小于非H型高血压组（P < 0.05）。在舌苔各项参数中，H型高血压组舌中H值、V值均明显小于健康对照组（P < 0.05）；非H型高血压组舌中V值、舌右V值均显著小于健康对照组（P < 0.01）；H型高血压组舌中H值明显小于非H型高血压组（P < 0.05），右侧舌苔S值明显大于非H型高血压组（P < 0.05）。②H型高血压组面色参数鼻G值、下颌G值、口唇R值、口唇V值均明显小于健康对照组（P < 0.05）；非H型高血压组前额H值、目眶H值、脸颊H值、鼻H值、下颌H值、整体H值均明显大于健康对照组（P < 0.05）；H型高血压组前额H值、目眶G值、目眶H值、脸颊H值、鼻G值、鼻H值、下颌R值、下颌G值、下颌H值、下颌V值、口唇R值、口唇G值、口唇V值、整体R值、整体G值、整体H值、整体V值均明显小于非H型高血压组（P < 0.05）。结论 H型高血压患者苔色偏黄，以舌中部为主，且舌右侧黄苔积聚较明显；H型高血压患者面色为黄中带红，口唇、下颌部更为晦暗。H型高血压患者的舌、面诊特征参数的变化，与高血压病阳亢湿盛病机相符。     

Bayesian estimation of a random effects heteroscedastic probit model

Summary Bayesian analysis is given of a random effects binary probit model that allows for heteroscedasticity. Real and simulated examples illustrate the approach and show that ignoring heteroscedasticity when it exists may lead to biased estimates and poor prediction. The computation is carried out by an efficient Markov chain Monte Carlo sampling scheme that generates the parameters in blocks. We use the Bayes factor, cross‐validation of the predictive density, the deviance information criterion and Receiver Operating Characteristic (ROC) curves for model comparison.     

食管癌三维适形后程加速超分割放射治疗的疗效分析

目的评价三维适形后程加速超分割放射治疗食管癌的疗效及放疗反应、并发症。方法2002年2月至2004年5月,71例食管鳞癌随机分成两组,三维适形后程加速超分割组36例,食管病变上下外约4cm,前后、左右外约0.5~1cm作为PTV1,每次2GY,每周5次,DT40GY后,病变上下外约2cm,前后、左右外约0.5~1cm作为PTV2,每日2次,每次1.5GY,间隔4~6小时,总疗程6周,总剂量67GY/38次。非三维适形后程加速超分割组35例,时间、剂量、分割方式同适形组。所有病例均采用8MV-X外照射。结果1、2、3年的生存率和原发肿瘤的局控率,与非适形后程加速超分割比较,适形组明显提高,分别为88.9%、75%、63.9%比68.6%、51.4%、40%和86.1%、72.2%、58.3%比65.7%、48.5%、34.3%。适形组的急性放射反应明显低于非适形后程加速超分割组,两组有显著差别。结论本研究的初步结果表明食管癌适形后程加速超分割放射治疗的疗效优于非适形后程加速超分割组。     

腹腔镜手术治疗小儿卵巢肿瘤26例

目的探讨腹腔镜手术治疗小儿卵巢肿瘤的效果及安全性。方法2000年1月~2005年3月,我们对26例小儿卵巢肿瘤行腹腔镜手术。气管插管全麻或静脉复合麻醉,行卵巢肿瘤剥除术或一侧附件切除术。对直径<5 cm的肿瘤,在肿瘤的外侧缘线形电凝囊肿包膜;直径>5 cm的肿瘤,在其中部或距基底部3 cm处环形电凝囊肿包膜,钝性分离肿瘤与囊壁,完整剥出肿瘤,残余囊壁创面彻底电凝止血,不缝合。卵巢冠囊肿切除。影响术野的大卵巢囊肿,先穿刺吸净囊液,帽状电凝卵巢囊肿包膜一周,再剥出肿瘤。结果所有患儿卵巢肿瘤手术都在腹腔镜下完成,肿瘤剥除术24例,一侧附件切除2例。手术时间(50±20)m in,术中出血量(30±10)m l,术后住院2~4 d,无手术并发症,无伤口感染。24例随访1年,未见复发。结论腹腔镜手术治疗小儿卵巢肿瘤是一种安全、有效的手术方法。     

祛瘀消斑胶囊治疗不稳定型心绞痛及对其血浆Fib、DD的影响

目的　观察祛瘀消斑胶囊治疗不稳定型心绞痛及对其血浆Fib和DD水平的影响。方法　对 4 0例不稳定型心绞痛患者随机分为常规西药加祛瘀消斑胶囊治疗组 (治疗组 )和常规西药治疗组 (对照组 ) ,治疗组与对照组各 2 0例。采用相应药物治疗 4周后 ,观察 2组患者的临床疗效、心电图改善及硝酸酯类药物的停减率 ,以及血浆Fib、DD水平变化 ,并进行比较分析。结果　治疗组可显著改善心绞痛症状 ,与对照组比较有显著性差异 (P <0 .0 5 ) ,2组患者心电图改善情况及硝酸酯类药物减停率无显著性差异 (P >0 .0 5 )。治疗组降低Fib、DD水平 ,与对照组比较有显著性差异 (P <0 .0 5 )。 2组均未出现明显不良反应。结论　祛瘀消斑胶囊可显著降低不稳定型心绞痛患者Fib、DD水平 ,联合西药治疗不稳定型心绞痛 ,疗效优于单用西药 ,且安全可靠。