Effect of cytotoxic T-lymphocyte antigen-4, TNF-alpha polymorphisms on osteosarcoma： evidences from a meta-analysis

Objective： Previous studies have investigated the role of cytotoxic T-lymphocyte antigen-4 （CTLA-4） and tumor necrosis factor-alpha （TNF-a） in carcinogenesis of osteosarcoma, but their results were inconsistent. We aimed to clarify the associations between CTLA-4, TNF-a polymorphism and osteosarcoma risk by using meta-analysis. Methods： We searched relevant studies without language restriction in PubMed, EMbase, Cochrane Library, Google Scholar databases, Chinese National Knowledge Infrastructure （CNKI） and conference literature in humans published prior to March 2013. The strengths of the associations between genetic variants and osteosarcoma risk were estimated by odds ratio （OR） with 95% confidence interval （95% CI）. Results： A total of seven studies with 1,198 osteosarcoma patients and 1,493 controls were selected. Four studies were eligible for CTLA-4 （1,003 osteosarcoma and 1,162 controls）, and three studies for TNF-a （195 osteosarcoma and 331 controls）. Pooled results showed that rs231775 polymorphism of CTLA-4 was associated with osteosarcoma risk （GG vs. AA： OR=1.63, 95% CI=1.24-2.13; GG ＋ GA vs. AA： OR=1.56, 95% CI=1.21-2.01; AA ＋ GA vs. GG： OR=0.83, 95% CI=0.71-0.97; G vs. A： OR=1.21, 95% CI=1.08-1.36）. No significant heterogeneity was observed across the studies. No significant associations were found between rs5742909 polymorphism of CTLA-4 or rs1800629 polymorphism of TNF-a and osteosarcoma risk. Conclusions： These results suggest that the rs231775 polymorphism of CTLA-4 may play an important role in carcinogenesis of osteosarcoma.     

三黄片对糖尿病患者血清超敏C反应蛋白及肿瘤坏死因子-a的影响

目的：探讨三黄片对糖尿病患者血清超敏C反应蛋白（hs-CRP）及肿瘤坏死因子-a（TNF-a）的影响。方法：将60例2型糖尿病患者随机分为糖尿病组和三黄片组,糖尿病组在控制血糖及血压的基础上对症治疗,三黄片组在糖尿病组治疗基础上加用三黄片4片,3次／d,口服。根据患者大便情况调整三黄片的用量,使大便保持在1～3次／d。4周后。测定两组患者血清hs-CRP及TNF-a的变化,并进行比较。结果：三黄片组与糖尿病相比,能明显抑制hs-CRP及TNF-a的升高（P〈0．05）。三黄片对糖尿病患者的血糖没有影响。结论：三黄片具有降低糖尿病患者血清TNF-a及hs-CRP的作用,推断其在“抗炎”层面上具有抗动脉硬化作用。     

多器官功能障碍综合症患者应用CRRT临床研究

目的观察连续性肾脏替代治疗（CRRT）对多器官功能障碍综合症（MODS）的临床疗效。方法将我科（ICU）2007～2010年收治的多器官功能障碍综合症30例给予连续静-静血液滤过（CVVH）方式治疗,治疗前后检测肾功能、电解质、二氧化碳结合率（CO2-CP）、血浆肿瘤坏死因子a（TNF-a）、白介素1β（IL-1β）水平的变化。结果治疗后血尿素氮（BUN）、肌酐（SCr）、血清磷、血浆TNF-a、IL-1β水平较前下降明显（P〈0.05）,血清钾、钠、氯、钙及二氧化碳结合率水平无显著变化。结论连续肾脏替代治疗能够有效救治多器官功能障碍综合症,毒素清除能力强,能显著清除炎症介质、能保持水电及酸碱平衡。     

依达拉奉对大鼠移植肾缺血再灌注损伤急性期的影响及作用

目的：观察在大鼠肾移植模型中依达拉奉对移植术后24h移植肾的影响及其作用。方法：36只雄性SD大鼠,随机分为3组：假手术组（A纽）、正常移植组（B组）、依达拉奉治疗移植纽（C组）,每组12只。B纽为左肾原位移植,C组为移植术后予依达拉奉（10mg·kg^-1）干预。观察移植术后24h各组血清肌酐、尿素氮、移植肾肿瘤坏死因子α（TNF—α）、白细胞介素1β（IL-1β）及移植肾损伤程度。结果：与B组比较,C组血清肌酐水平明显下降（301．75±27．53比242．73±30．21,P〈0．05）;TNF—α转录水平（0．36±0．02比0．29±0．04,P〈0．05）、表达水平（212．72±20．92比179．62±21．41,P〈0．05）及IL-1β表达水平均明显下降（44．82±10．21比32．21±9．17,P〈0．05）,肾组织损伤程度明显减轻（2．68±0．13比2．02±0．21,P〈0．05）。结论：依达拉奉能够抑制细胞因子TNF—α、IL-1β,改善大鼠同种异体移植肾功能。     

Does Sodium Intake Induce Systemic Inflammatory Response? A Systematic Review and Meta-Analysis of Randomized Studies in Humans

Experimental studies suggest that sodium induced inflammation might be another missing link leading to atherosclerosis. To test the hypothesis that high daily sodium intake induces systemic inflammatory response in humans, we performed a systematic review according to PRISMA guidelines of randomized controlled trials (RCTs) that examined the effect of high versus low sodium dose (HSD vs. LSD), as defined per study, on plasma circulating inflammatory biomarkers. Eight RCTs that examined CRP, TNF-a and IL-6 were found. Meta-analysis testing the change of each biomarker in HSD versus LSD was possible for CRP (n = 5 studies), TNF-a (n = 4 studies) and IL-6 (n = 4 studies). The pooled difference (95% confidence intervals) per biomarker was for: CRP values of 0.1(−0.3, 0.4) mg/L; TNF-a −0.7(−5.0, 3.6) pg/mL; IL-6 −1.1(−3.3 to 1.1) pg/mL. Importantly, there was inconsistency between RCTs regarding major population characteristics and the applied methodology, including a very wide range of LSD (460 to 6740 mg/day) and HSD (2800 to 7452 mg/day). Although our results suggest that the different levels of daily sodium intake are not associated with significant changes in the level of systemic inflammation in humans, this outcome may result from methodological issues. Based on these identified methodological issues we propose that future RCTs should focus on young healthy participants to avoid confounding effects of comorbidities, should have three instead of two arms (very low, “normal” and high) of daily sodium intake with more than 100 participants per arm, whereas an intervention duration of 14 days is adequate.     

辨证分型中药内服结合外治治疗溃疡性结肠炎的临床疗效及对免疫功能的影响

目的:探讨辨证分型中药内服结合外治法治疗溃疡性结肠炎的临床疗效及对免疫功能的影响。方法:选取2012年1月至2014年12月南京中医药大学附属医院南通市中医院脾胃专科门诊就诊的溃疡性结肠炎患者92例作为研究对象,根据中医证候分类标准分为大肠湿热型组(38例),脾虚湿蕴型组(32例),脾肾阳虚型组(22例),选择同期溃疡性结肠炎的患者40例为对照组,观察组予以辨证分型中药口服结合中药灌肠、耳穴埋籽等治疗,对照组予以美沙拉嗪口服,疗程约3个月。观察比较4组患者中医证候积分、SutherlandDAI积分、炎性反应指标、免疫学指标、疗效及安全性指标。结果:4组治疗前中医证候积分、SutherlandDAI积分差异无统计学意义(P0.05);与治疗前比较,大肠湿热型组、脾虚湿蕴型组、脾肾阳虚型组治疗后1个月、3个月中医证候积分、SutherlandDAI积分明显降低(P0.05);与对照组比较,大肠湿热型组、脾虚湿蕴型组、脾肾阳虚型组治疗后3个月中医证候积分、SutherlandDAI明显降低(P0.05);4组治疗前IgA、IgG、IgE、CRP、TNF-α、IL-8水平差异无统计学意义(P0.05);与治疗前比较,大肠湿热型组、脾虚湿蕴型组、脾肾阳虚型组治疗后1个月、3个月IgA、IgG、IgE、CRP、TNF-α、IL-8水平明显降低(P0.05);与对照组比较,大肠湿热型组、脾虚湿蕴型组、脾肾阳虚型组治疗后3个月IgA、IgG、IgE、CRP、TNF-α、IL-8水平明显降低(P0.05);中药内服结合外治法患者总有效率为91.30%,显著高于对照组总有效率。大肠湿热型组、脾虚湿蕴型组、脾肾阳虚型组总有效率分别为89.47%、90.63%、95.45%,大肠湿热型组最低,脾肾阳虚型组最高,但3组差异无统计学意义(P0.05);结论:辨证分型中药内服结合保留灌肠、耳穴埋籽外治疗法治疗溃疡性结肠炎临床疗效确切,可能与改善机体的免疫功能,控制炎性反应等有关,且安全简便,在临床上具有一定的可行性。     

Melatonin protects liver from intestine ischemia reperfusion injury in rats

AIM： To investigate the protective effect of melatonin on liver after intestinal ischemia-reperfusion injury in rats. METHODS： One hundred and fifty male Wistar rats, weighing 190-210 g, aged 7 wk, were randomly divided into melatonin exposure group, alcohol solvent control group and normal saline control group. Rats in the melatonin exposure group received intraperitoneal （IP） melatonin （20 mg/kg） 30 min before intestinal ischemia-reperfusion （IR）, rats in the alcohol solvent control group received the same concentration and volume of alcohol, and rats in the normal saline control group received the same volume of normal saline. Serum samples were collected from each group 0.5, 1, 6, 12, and 24 h after intestinal IR. Levels of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were measured with an auto-biochemical analyzer. Serum TNF-α was tested by enzyme-linked immunosorbent assay （ELISA）. Malondialdehyde （MDA） in liver was detected by colorimetric assay. Pathological changes in liver and immunohistochemical straining of ICAM-1 were observed under an optical microscope. RESULTS： The levels of ALT measured at various time points after intestinal IR in the melatonin exposure group were significantly lower than those in the other two control groups （P 〈 0.05）. The serum AST levels 12 and 24 h after intestinal IR and the ICAM-1 levels （%） 6, 12 and 24 h after intestinal IR in the melatonin exposure group were also significantly lower than those in the other two control groups （P 〈 0.05）. CONCLUSION： Exotic melatonin can inhibit the activity of ALT, AST and TNF-α, decrease the accumulation of MDA, and depress the expression of ICAM-1 in liver after intestinal IR injury, thus improving the liver function.     

TNF-α对血管内皮细胞VCAM-1诱导作用的研究

目的：探讨肿瘤坏死因子－α（ＴＮＦ－α）对血管内皮细胞ＶＣＡＭ－１表达的诱导作用。方法：通过血管内皮细胞培养,采用免疫组织化学方法分别观察不同浓度ＴＮＦ－α（０．２５０Ｕ．ｍＬ＾－１）２４小时内以及相同浓度（１００Ｕｍｌ＾－１）ＴＮＦ－μ０－α０－７２ｈ对内皮细胞ＶＣＡＭ－１表达的影响。结果：与对照组比较,ＴＮＦ－α对内皮细胞ＶＣＡＭ－１的诱导作用具有明显浓度与时间依赖性。结论：ＴＮＦ－α可诱导血     

酪-D-丙-甘-苯丙-D-亮(DADL)五肽的固相合成及对免疫功能的影响

用固相多肽合成法合成了脑啡肽衍生物DADL,一种δ受体选择性激动剂。实验观察发现DADL能直接促进小鼠脾淋巴细胞增殖,并有一定浓度依赖关系,与ConA和LPS无明显协同效应,此外DADL(l.0mg·kg^-1X6d)在体内能促进TNF-α的产生。体外高浓度时(10^-6～5Xl0^-6mol·L^-1)能促成LPS诱导的TNF-a的表达。上述结果表明,DADL与脑啡肽类似,有一定免疫调节作用。     

清热解毒化浊片对ETM兔肝组织CD14及TNF-α、IL-1表达的影响

目的：探讨清热解毒化浊片对内毒素血症（Endotoxemia,ETM）模型兔肝功能、肝组织CD14和血清肿瘤坏死因子-α（TNF-α）、白细胞介素-1（IL-1）的影响。方法将21只新西兰大耳白兔随机分为正常组、模型组、清热解毒化浊片组（清化组）,每组7只。将模型组及清化组兔沿耳缘静脉注射大肠杆菌内毒素（LPS,10μg/kg）,于造模后2 h干预,灌胃后2 h心脏采血检测家兔的肝功能、TNF-α和IL-α的变化,采肝脏组织检测CD14及观察肝脏病理形态。结果（1）与模型组比较,清化组ALT、AST上升（P＜0.05）,肝组织CD14表达及血清TNF-α、IL-1下降(P＜0.05);（2）模型组肝细胞排列结构紊乱,有炎性细胞浸润,且出现空泡样改变,清化组及正常组改变不明显。结论清热解毒化浊片能下调ETM模型兔CDl4、TNF-α和IL-1的表达,具有多靶点、多效应的干预作用,推测其有阻断早期LPS诱导信号通路的作用。