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.     

八段锦治疗神经根型颈椎病的系统评价与Meta分析

[目的] 系统评价八段锦治疗神经根型颈椎病的临床疗效。[方法] 计算机检索中国知网数据库（CNKI）、维普资讯中文科技期刊数据库（VIP）、万方数据库（Wan-fang）、中国生物医学文献数据库（SinoMed）、Web of science、Clinical Trials gov、Pubmed、EMBASE、CENTRAL、Cochrane Library，查找出八段锦治疗神经根型颈椎病的随机对照试验（RCT），检索时限均从建库至2019年7月1日。两名研究者按照纳入与排除标准独立进行文献筛选、资料提取和偏倚风险评估，应用RevMan 5.3软件对最后纳入的研究进行Meta分析。[结果] 最终纳入10个RCT，共843例患者。Meta分析结果显示：八段锦+常规治疗与常规治疗比较，其临床疗效的总有效率差异具有统计学意义[OR=4.19，95% CI（2.42，7.26），P<0.000 01]；八段锦+常规治疗与常规治疗+颈部“米”字操比较，其临床疗效的总有效率差异具有统计学意义[OR=3.41，95% CI（1.56，7.46），P=0.002]；八段锦+常规治疗与常规治疗比较，其疼痛视觉模拟评分法（VAS）评分差异具有统计学意义[MD=-1.90，95% CI（-1.97，-1.83），P<0.000 01]。[结论] 基于现有的研究，该系统评价显示，与常规治疗相比，八段锦+常规治疗在临床疗效总有效率、VAS评分方面有一定的治疗优势。与常规治疗+颈部“米”字操比较，八段锦+常规治疗在临床疗效的总有效率方面有一定的治疗优势。但由于纳入研究的质量不高，仍需要大样本、多中心、随机、双盲试验及试验参照CONSORT标准和STRICTA声明进行RCT研究。     

体外转染Cyclin A2基因对原代大鼠心肌细胞增殖的影响

目的探讨体外转染细胞周期素A2(Cyclin A2)基因对原代大鼠心肌细胞增殖的影响,为心脏再生提供细胞学依据。方法 SD乳鼠12只,分离、培养、鉴定原代乳鼠心肌细胞并分为3组,实验组:转染带有强化绿色荧光蛋白(GFP)和Cyclin A2基因的重组腺病毒(Ad-Cyclin A2-GFP);空病毒组:转染不含目的基因带有GFP的重组腺病毒(Ad-Null-GFP);阴性对照组:未做转染处理,仅加入等量的培养基。利用GFP示踪技术,评估原代心肌细胞转染效率;转染后的细胞继续体外培养3~5d,利用免疫荧光技术分别检测Cyclin A2、磷酸化组蛋白H3(H3P)、心肌肌钙蛋白-T(c Tn T)。结果 1.荧光GFP示踪表明原代心肌细胞的转染效率高达(97±0.74)%;2.免疫荧光标记显示,空病毒组和对照组结果相似;心肌细胞特异性标记蛋白c Tn T分布于细胞质,原代心肌细胞纯度高达(95±0.62)%;心肌细胞Cyclin A2主要在胞核内聚集,少数分布于细胞质。H3P为核蛋白在细胞核内分布。3.转染Cyclin A2后,实验组H3P阳性率明显高于空病毒组和对照组,差异具有统计学意义(P0.05);实验组可见大量多核细胞,以双核为主,伴少量3核细胞。结论腺病毒作为转染载体对原代心肌细胞有很好的侵染效率;Cyclin A2超表达促进原代心肌细胞形成双核。     

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.     

脉络学说营卫理论指导心律失常辨证论治

经脉包括经(气)络和血(脉)络,清代周学海《读医随笔》将气络末端称为"气之细络",脉络末端称为"血之细络"。心之气络涵盖心脏起搏与传导系统等广泛调控机制,心之脉络涵盖冠状动脉循环系统,心之气络与脉络相互协调,营卫相偕而行,共同维持心脏正常功能。各种致病因素导致营卫异常而发为心律失常,基于脉络学说营卫理论"损其心者,调其营卫"(《难经·十四难》)治疗原则指导心律失常辨证论治,同时充分结合现代致病因素和致病特点,分别选用调节卫气营血之方药,标本兼治,以期为临床诊疗提供有益借鉴。     

细胞因子白细胞介素-4对认知功能改善的研究进展

白细胞介素4(IL-4)是T辅助2(Th2)介导的免疫反应的基本免疫调节细胞因子,IL-4具有复杂的信号系统和多效的功能,但在脑组织中,诸多研究发现IL-4可在炎症中保护认知功能。该文总结了关于IL-4保护认知功能的证据及机制,以及在阿尔茨海默病、缺血性脑血管病以及手术后认知功能障碍中IL-4保护认知功能的途径及证据。     

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。