Closed loop stimulation helps with weaning from chronotropic incompetence-related ventilator dependence

Journal of Interventional Cardiac Electrophysiology -     

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.     

基于细胞因子的人参败毒散治疗新型冠状病毒肺炎(COVID-19)的网络药理学研究

目的从细胞因子角度,探究人参败毒散多成分、多靶点、多途径抗新型冠状病毒肺炎(COVID-19)的作用机制。方法应用中药系统药理分析平台(TCMSP)收集人参败毒散中活性化合物,结合药物靶点数据库收集细胞因子风暴相关靶点,利用Cytoscape构建"药材-化合物-疾病靶点"网络。通过String和DAVID数据库对靶点的互作网络、GO功能和KEGG通路进行分析。结果人参败毒散"药材-活性化合物-疾病靶点"网络包括10种药材,211个活性成分和151个疾病靶点。互作网络发现人参败毒散抑制细胞因子风暴治疗COVID-19的靶点可能包含STAT3、MAPK1、NFκB1、PIK3CA、MAPK3、TNF、CXCR4、VEGFA、IL-6、IL-2等。GO功能分析发现上述靶点在生物功能方面涉及趋化性、类固醇代谢过程等;在分子功能方面涉及血红素结合、铁离子结合、氧结合等;在细胞组成方面涉及细胞表面、细胞膜等。KEGG通路富集发现上述靶点参与查加斯病通路、HIF-1信号通路、肿瘤坏死因子信号通路等的调控。结论人参败毒散可能通过调节趋化性细胞因子,增加血氧饱和度,抑制STAT、MAPK、NFκB、PIK3K、IL-6等炎症相关信号通路,实现多成分-多靶点-多途径抑制细胞因子风暴形成的抗COVID-19作用。     

The impact of age on prognosis in patients with gastric cancer: experience in a tertiary care centre

BackgroundGastric cancer (GC) is a leading cause of cancer-related death in the world and most patients have advanced disease upon presentation. The effect of age on prognosis in GC is controversial. We aimed to determine the impact of age on survival in patients with GC.MethodsThis was a retrospective study of the medical records of Lebanese patients diagnosed with GC at the American University of Beirut Medical Center (AUBMC) between 2005 and 2014. Patients were divided into young (<65 years) and older groups (≥65 years). A multivariate analysis was done to determine the independent predictors of survival. Kaplan-Meier method was used for analysis of long-term survival outcomes.ResultsThe sample consisted of 156 patients. The mean age was 62.15 (SD 13.54). Most patients presented with stage 4 disease (62.2%) and poorly differentiated histology (66.4%). The most common symptoms were abdominal pain and weight loss. On bivariate analysis, advanced stage (P=0.02) and higher grade (P=0.04) were associated with increased mortality. Patients <65 years of age were significantly more likely to have poorly differentiated tumours, while patients ≥65 years had more comorbidities (P=0.001). The 5-year DFS were 35% and 37% for patients <65 years of age and ≥65 years of age, respectively (P=0.15).ConclusionsHigher grade and advanced stage are associated with worse survival in patients with GC, but age did not seem to have an impact. Screening high risk patients and early diagnosis are necessary to improve survival.     

Working the edges of Posthuman disability studies: theorising with disabled young people with life‐limiting impairments

This paper is built upon an assumption: that social theory can be generated through a meaningful engagement with a co‐researcher group of disabled young people. Our co‐researchers are theoretical provocateurs and theorists in their own right who, through their activism and writing, are challenging us to reconsider the meaning of life, death and disability. Their work on our funded Economic and Social Research Council (ESRC) project has enabled us to consider the promise and potential of humanist and posthuman epistemologies, theories, methodologies, interventions and activisms. The paper introduces the research, the authors of this paper (academics and co‐researchers) and then explores three layers of analysis that work the edges of posthuman thinking; sovereign and assembled selves; affects and desires; mourning and affirmation. We conclude by asserting that as a research team we are engaging with a DisHuman approach to theory and activism: one that blends the pragmatics of humanism with posthuman possibilities.     

Epidermal growth factor‐induced COX‐2 regulates metastasis of head and neck squamous cell carcinoma through upregulation of angiopoietin‐like 4

Epidermal growth factor receptor (EGFR) expression and activation are the major causes of metastasis in cancers such as head and neck squamous cell carcinoma (HNSCC). However, the reciprocal effect of EGF‐induced COX‐2 and angiopoietin‐like 4 (ANGPTL4) on HNSCC metastasis remains unclear. In this study, we revealed that the expression of ANGPTL4 is essential for COX‐2‐derived prostaglandin E₂ (PGE₂)‐induced tumor cell metastasis. We showed that EGF‐induced ANGPTL4 expression was dramatically inhibited with the depletion and inactivation of COX‐2 by knockdown of COX‐2 and celecoxib treatment, respectively. Prostaglandin E₂ induced ANGPTL4 expression in a time‐ and dose‐dependent manners in various HNSCC cell lines through the ERK pathway. In addition, the depletion of ANGPTL4 and MMP1 significantly impeded the PGE₂‐induced transendothelial invasion ability of HNSCC cells and the binding of tumor cells to endothelial cells. The induction of molecules involved in the regulation of epithelial‐mesenchymal transition was also dependent on ANGPTL4 expression in PGE₂‐treated cells. The depletion of ANGPTL4 further blocked PGE₂‐primed tumor cell metastatic seeding of lungs. These results indicate that the EGF‐activated PGE₂/ANGPTL4 axis enhanced HNSCC metastasis. The concurrent expression of COX‐2 and ANGPTL4 in HNSCC tumor specimens provides insight into potential therapeutic targets for the treatment of EGFR‐associated HNSCC metastasis.