非小细胞肺癌患者手术前后血清IL-18和sFas水平的变化

[目的]测定非小细胞肺癌(NSCLC)患者血清IL-18和sFas水平,并探讨手术对非小细胞肺癌患者血清IL-18和sFas的影响.[方法]采用酶联免疫吸附试验(ELASA)检测20例正常对照组和52例NSCLC患者手术前的血清IL-18和sFas水平,并比较48例NSCLC患者手术前后血清IL-18和sFas水平.[结果]NSCLC患者血清IL-18和sFas水平明显高于正常对照组(P＜0.01);血清IL-18和sFas水平与NSCLC的临床分期有关(P＜0.01),与肺癌患者病理类型无相关;NSCLC患者术后血清IL-18和sFas水平明显低于术前(P＜0.01).[结论]血清IL-18和sFas水平可能与NSCLC的发生发展有一定的关系,手术可以降低NSCLC患者血清IL-18和sFas水平,血清IL-18和sFas水平检测对NSCLC患者病情判断有一定的临床意义.     

Decreased Expression of CD95 (FAS/APO-1) on CD4+ T-lymphocytes from Participants with Autism

Although autism remains an enigmatic disease, there is mounting evidence that the immune system plays an important role in the pathogenesis. Immune system involvement is apparently widespread as numerous humoral and cellular abnormalities have been reported in both the innate and adaptive responses. Fas (CD95/APO-1) is a type I cell-surface protein from the TNF/NGF-R superfamily present on the surface of many immune related cells. Fas activation is instrumental in starting a complicated chain of events that results in programmed cell death (apoptosis) by DNA fragmentation. Preliminary data is presented, which indicate that subjects with austism have lower levels of Fas on their CD4⁺ helper T cells (p = .048) than have normal subjects. Data also indicates subjects with autism have significantly higher levels of soluble Fas (p = .01) than have normal subjects. A maturing individual must eliminate cells for proper morphogenesis to occur. Preliminary data suggest that faulty apoptosis may be involved in the pathogenesis of autism.     

Diet associated hepatic steatosis sensitizes to Fas mediated liver injury in mice

BACKGROUND/AIMS: Hepatic steatosis sensitizes the liver to injury and inflammation by unclear mechanisms. Because Fas has been linked to liver injury and inflammation, Fas expression and sensitization to Fas signaling was examined in models of hepatic steatosis. METHODS: Mice were fed a carbohydrate diet while control animals received standard chow. Sensitization to Fas was examined following administration of Jo2 antibody. For the in vitro experiments, HepG2 cells were incubated with or without a mixture of long chain fatty acids (2:1 oleate:palmitate). Sensitization of the cells to Fas was examined using the CH11 antibody. RESULTS: Mice fed a high caloric diet developed hepatic steatosis, hyperlipidemia, insulin resistance, and hyperleptinemia, all features of the human syndrome. Fas expression in hepatocytes was increased as compared to lean animals and was coupled to cytotoxic signaling. Indeed, hepatocyte apoptosis, liver injury and chemokine generation were all accentuated in obese animals following administration of Jo-2, a Fas agonist. Hep G2 cells cultured in the presence of free fatty acids also developed 'cellular steatosis', upregulated Fas expression and were more sensitive to apoptosis by a Fas agonist. CONCLUSIONS: Collectively, these data implicate Fas as a link between obesity associated fatty liver and increased susceptibility to liver damage.     

Overweight improves long-term survival in Japanese patients with asthma

BackgroundObesity is a risk factor for severe and difficult-to-treat asthma. However, the impact of different physiques on long-term outcomes is poorly understood. We aimed to investigate the correlation between obesity and asthma-associated long-term mortality in Japanese adults.MethodsFrom the data on 3146 individuals with air pollution-related respiratory diseases in the Omuta City Air Pollution-Related Health Damage Cohort Program, 697 adult patients with asthma were analyzed. Hazard ratios for long-term all-cause and respiratory disease -related mortality were compared in patients with different physiques using the Cox proportional hazard models. The classification of physiques was based on the WHO obesity criteria.ResultsOf the 697 patients, 439 died during the median observation period of 26.3 years. The number (% of total) of underweight, normal-weight, pre-obese, and obese class I–III individuals were 75 (10.8%), 459 (65.9%), 140 (20.1%), and 23 (3.3%), respectively. The Cox proportional hazard model (adjusted hazard ratio [95% confidence interval], P value) showed that pre-obese group had a significantly reduced risk for all-cause (0.65 [0.51 to 0.83], P < 0.05) and respiratory disease (0.55 [0.37 to 0.81], P < 0.05)-related mortality related to normal-weight group.ConclusionsOur cohort program demonstrated that being slightly overweight may reduce the risk of long-term mortality in patients with asthma. However, the influence of obesity on long-term outcomes remains unclear in asthma, because of the small number of obese patients included in our study. Our findings suggest that interventions, including nutrition and exercises, should be provided to Japanese patients with asthma.     

系统性红斑狼疮患者T细胞上Fas受体分子与疾病活动指数的相关性研究

目的通过定量流式细胞术检测系统性红斑狼疮(SLE)患者T淋巴细胞表面Fas受体的分子数,探讨SLE的发病机制及与疾病活动指数的相关性.方法对36例活动期SLE患者和18名正常人群采集外周血,采用Fas定量流式细胞试剂盒荧光染色,通过流式细胞仪对T淋巴细胞上表达Fas受体分子数和凋亡率进行检测.结果活动期SLE患者T细胞表面表达Fas受体分子数和凋亡率较正常人群明显上调(P＜0.01).活动期SLE患者T细胞表面Fas受体分子数与T细胞凋亡率和SLEDAI之间,具有明显的正相关(P＜0.01),抗dsDNA抗体阳性患者组T细胞表面Fas受体分子数较抗dsDNA抗体阴性组明显增高,差异具有统计学意义(P＜0.05).结论SLE患者T淋巴细胞表面Fas受体分子数上调,由Fas介导的T淋巴细胞凋亡加快,刺激机体产生抗dsDNA等多种自身抗体,可能是引起SLE免疫功能紊乱的主要原因.SLE患者T淋巴细胞表面Fas受体分子数与SLE的活动性呈正相关,是一较好的评价SLE疾病活动性的指标.     

Bile salt-induced hepatocyte apoptosis involves epidermal growth factor receptor-dependent CD95 tyrosine phosphorylation

BACKGROUND & AIMS: Hydrophobic bile acids induce CD95-dependent hepatocyte apoptosis. METHODS: The mechanisms of bile acid-induced CD95 activation were studied in 24-hour cultured rat hepatocytes, in situ-perfused rat livers, and livers from bile duct-ligated rats. RESULTS: Within 1 minute, the proapoptotic bile salts taurolithocholate-3-sulfate and glycochenodeoxycholate induced oxidative stress and EGF receptor (EGF-R) tyrosine phosphorylation followed by rapid c-Jun-N-terminal kinase (JNK) activation. Thereafter, EGF-R associated with CD95 with subsequent CD95 tyrosine phosphorylation, CD95 membrane targeting, and death-inducing signal complex (DISC) formation. All of these responses were also triggered by taurochenodeoxycholate except that DISC formation only occurred in the presence of phosphatidylinositol 3-kinase inhibitors. No activation of EGF-R or CD95 was observed with tauroursodeoxycholate or taurocholate. Taurolithocholate-3-sulfate-induced EGF-R phosphorylation was sensitive to N-acetylcysteine (NAC) and genistein, whereas CD95/EGF-R association was inhibited by NAC, JNK, or protein kinase C inhibition but not by AG1478. However, the latter compound as well as NAC, genistein, inhibition of JNK, or protein kinase C inhibited CD95 tyrosine phosphorylation, membrane trafficking, and DISC formation. CONCLUSIONS: Induction of apoptosis by hydrophobic bile salts involves EGF-R activation and EGF-R-dependent CD95 tyrosine phosphorylation, which triggers CD95 membrane targeting and Fas-associated death domain/caspase-8 recruitment. The latter step is apparently also controlled by phosphatidylinositol 3-kinase.     

A systematic review and meta-analysis of the COVID-19 associated liver injury

Introduction and ObjectivesThe novel coronavirus disease 2019 (COVID-19) has affected more than 5 million people globally. Data on the prevalence and degree of COVID-19 associated liver injury among patients with COVID-19 remain limited. We conducted a systematic review and meta-analysis to assess the prevalence and degree of liver injury between patients with severe and non-severe COVID-19.MethodsWe performed a systematic search of three electronic databases (PubMed/MEDLINE, EMBASE and Cochrane Library), from inception to 24^th April 2020. We included all adult human studies (>20 subjects) regardless of language, region or publication date or status. We assessed the pooled odds ratio (OR), mean difference (MD) and 95% confidence interval (95%CI) using the random-effects model.ResultsAmong 1543 citations, there were 24 studies (5961 subjects) which fulfilled our inclusion criteria. The pooled odds ratio for elevated ALT (OR = 2.5, 95%CI: 1.6-3.7, I² = 57%), AST (OR = 3.4, 95%CI: 2.3-5.0, I² = 56%), hyperbilirubinemia (OR = 1.7, 95%CI: 1.2-2.5, I² = 0%) and hypoalbuminemia (OR = 7.1, 95%CI: 2.1-24.1, I² = 71%) were higher subjects in critical COVID-19.ConclusionCOVID-19 associated liver injury is more common in severe COVID-19 than non-severe COVID-19. Physicians should be aware of possible progression to severe disease in subjects with COVID-19-associated liver injury.     

Association between serum chloride levels with mortality in incident peritoneal dialysis patients

Background and aimsLower serum chloride (Cl) levels have been associated with excess mortality in pre-dialysis chronic kidney disease patients. However, the relationship between serum Cl levels and clinical outcomes in continuous ambulatory peritoneal dialysis (CAPD) patients is unclear.Methods and resultsIn this retrospective cohort study, we enrolled 1656 eligible incident patients undergoing CAPD from 2006 to 2013, and followed until December 2018. Cox regression analyses were used to examine the association between baseline and time-varying serum Cl levels and mortality. During a median follow-up of 46 months, 503 patients (30.4%) died. In analyses of baseline serum Cl, the adjusted hazard ratios (HR) for tertile 1 (<100.0 mmol/L), tertile 2 (100.0–103.0 mmol/L) versus tertile 3 (>103.0 mmol/L) were 2.34 [95% confidence interval (CI) 1.43–3.82] and 1.73 (95% CI 1.24–2.42) for all-cause mortality, 2.86 (95% CI 1.47–5.56) and 1.90 (95% CI 1.19–3.02) for cardiovascular disease (CVD) mortality, respectively. And a linear relationship was observed between serum Cl and mortality. Further, the inverse association between serum Cl and CVD mortality was particularly accentuated in the patients who were ≥50 years or with a history of diabetes. Similarly, lower time-varying serum Cl levels were also associated with a significant increased risk of all-cause and CVD death.ConclusionLower serum Cl levels predicted higher risk of all-cause and CVD mortality in CAPD patients.     

Monocyte to high-density lipoprotein ratio and cardiovascular events in patients on peritoneal dialysis

Background and aimsThe monocyte to high-density lipoprotein cholesterol ratio (MHR) is associated with multiple cardiovascular diseases. However, the role of the MHR in predicting cardiovascular diseases in patients on peritoneal dialysis remains unclear.Methods and resultsEight hundred and eighty incident peritoneal dialysis patients were enrolled from November 1, 2005, to February 28, 2017, and followed until May 31, 2017. Primary outcomes were cardiovascular events. Using the X-tile program, these patients were divided into three groups according to the MHR. Kaplan–Meier method and Cox regressions were used for survival analysis. During a median follow-up period of 26 months (interquartile range: 12–39 months), 139 cardiovascular events were recorded. After multiple adjustment, the high MHR group was associated with a 1.97-fold increase in the cardiovascular events hazard compared to that of the low group in the overall population (hazard ratio: 1.97; 95% CI, 1.19–3.28; P = 0.009). Subgroup analysis demonstrated that the association between the MHR and a higher risk of cardiovascular events was strongest in the subgroup of patients with diabetes (P for interaction = 0.004). In this subgroup, the high MHR group was found to be associated with a higher risk of cardiovascular events compared to the low group (hazard ratio: 7.69; 95% CI, 2.76–21.47).ConclusionThis study suggests that the MHR is independently associated with the risk of cardiovascular events in patients undergoing peritoneal dialysis, and diabetes status can influence the association between the MHR and the risk of cardiovascular events.