乳黄制剂对肝硬化模型大鼠肝组织脂多糖结合蛋白mRNA、CD14 mRNA及Toll样受体4 mRNA的影响

目的:研究乳黄制剂对肝硬化大鼠肝组织LBP(脂多糖结合蛋白)mRNA、CD14 mRNA、TLR4(Toll样受体-4)mRNA的影响.方法:SPF级雄性Wister大鼠88只随机分为6组:正常组、模型组、预防组、预防对照组、模型治疗组、模型治疗对照组.采用CCl4复合因素法制造肝硬化模型.用乳黄制剂进行预防和治疗,并与乳果糖对照药进行比较,分别检测大鼠肝组织LBP mRNA、CD14 mRNA、TLR4 mRNA的表达水平.结果:治疗组大鼠肝组织LBP mRNA、CD14 mRNA、TLR4 mRNA表达水平明显低于模型组(P＜0.05),预防组大鼠肝组织LBP mRNA、CD14 mRNA、TLR4 mRNA表达水平与正常组比较差异无显著性意义(P＞0.05).结论:乳黄制剂能有效抑制内毒素调节蛋白及其相关受体的表达,从而减少内毒素血症的发生.     

益生菌对肝硬化患者免疫功能的影响

肝硬化患者易发生多种感染，与免疫功能下降、肠道菌群紊乱有关。目的：观察口服微生态制剂对肝硬化患者细胞免疫功能、外周血单核细胞内毒素受体表达以及血清细胞因子和血浆内毒素水平的影响。方法：选取连续入院的肝硬化患者，予常规保肝治疗和口服微生态制剂4周，应用流式细胞术检测患者治疗前后外周血T细胞及其亚群和自然杀伤细胞、外周血单核细胞内毒素受体Toll样受体（TLR）4和CD14的表达。分别以酶联免疫吸附测定法和偶氮基质显色法检测细胞因子白细胞介素（IL）-1β、肿瘤坏死因子（TNF）-α、IL-10水平和血浆内毒素水平。结果：治疗前肝硬化患者外周血总T细胞（CD3）和CD4细胞数明显低于正常对照组（P〈0．05），微生态制剂治疗后CD3和CD4亚群显著升高（P〈0．05）。治疗前肝硬化患者外周血单核细胞内毒素受体TLR4和CD14的表达显著高于正常对照组（P〈0．01），微生态制剂治疗后CD14表达显著降低（P〈0．01），TLR4表达也呈下降的趋势，但差异无统计学意义。治疗前肝硬化患者血清IL-1β、TNF-α、IL-10水平显著高于正常对照组（P〈0．05），微生态制剂治疗后血清细胞因子和血浆内毒素水平均无明显改变。结论：肝硬化患者存在细胞免疫功能下降和慢性炎症状态，微生态制剂可改善患者免疫功能的紊乱。因此可将其作为一种慢性肝病的辅助治疗。     

单核细胞Toll样受体和髓样分化蛋白表达水平与T2DM神经病变患者炎症反应的关系

目的探讨单核细胞Toll样受体(TLR)4和髓样分化蛋白(MyD88)表达与2型糖尿病(T2DM)神经病变患者炎症反应的关系及作用机制。方法收集T2DM患者210例,其中无神经病变(TDM组)120例,伴周围神经病变(DPN组)90例;另选取同年龄段健康志愿者100名为对照组。单次抽取受试者空腹肘静脉血10 ml,梯度离心分离血清和血浆,分离单核细胞;RT-PCR法检测单核细胞中TLR4、陷窝蛋白-1 mRNA表达;Western印迹法检测TLR4、陷窝蛋白-1及其下游信号蛋白(MyD88、IκB、p-IκB)表达;酶联免疫吸附试验(ELISA)检测血浆中促炎因子〔白细胞介素(IL-6)、肿瘤坏死因子(TNF-α)〕水平。结果TDM组、DPN组血浆IL-6、TNF-α浓度均明显高于对照组,TDM组患者血浆IL-6、TNF-α浓度明显高于DPN组(P<0.05)。TDM组、DPN组患者TLR4、陷窝蛋白-1 mRNA相对表达量均明显高于对照组,TDM组患者TLR4、陷窝蛋白-1 mRNA相对表达量明显高于DPN组(P<0.05)。Spearman分析显示,TLR4 mRNA表达与血浆IL-6、TNF-α均呈显著正相关;TLR4 mRNA表达与陷窝蛋白-1 mRNA呈显著负相关。TDM组、DPN组患者陷窝蛋白-1、IκB蛋白相对表达量明显低于对照组,TLR4、MyD88、p-IκB蛋白相对表达量明显高于对照组(P<0.05);与TDM组相比,陷窝蛋白-1、IκB蛋白相对表达量明显减少,TLR4、MyD88、p-IκB蛋白相对表达量明显增加(P<0.05)。结论T2DM神经病变患者炎症状态与单核细胞TLR4、MyD88信号通路介导的炎症级联反应有关;陷窝蛋白-1表达下调与TLR4、MyD88信号通路异常活化有关。     

乙型肝炎肝硬化患者外周血单个核细胞Toll样受体2、4的表达

目的 探讨乙型肝炎(乙肝)肝硬化患者中Toll样受体(TLR)2、4表达与细胞因子的相关性.方法 采用随机数字表法随机收集35例乙肝肝硬化患者与35例健康对照者的静脉抗凝血.ELISA检测血TNF-α含量.分离两组外周血单个核细胞(PBMC),流式细胞仪检测PBMC表面TLR2、4表达.实时荧光定量PCR检测每份PBMC中TLR2、4 mRNA的表达水平.正态分布均数比较采用t检验和单因素方差分析,非正态分布数据采用Mann-Whitney U检验、Kruskal-Wallis H检验和Spearman相关分析.结果 肝硬化组的血TNF-α水平明显高于对照组(33.52 ng/L比6.07 ng/L,Z=6.584,P<0.01),且随着Child-Pugh评分的增加而升高.肝硬化组PBMC中TLR2阳性细胞率明显高于对照组(20.65%比12.04%,Z=-4.458,P<0.01),与血TNF-α水平存在正相关(r=0.448 3,P<0.05),且随着Child-Pugh评分的增加而升高.两组PBMC中TLR4阳性率差异无统计学意义.肝硬化组PBMC中TLR2/还原型磷酸甘油醛脱氢酶(GAPDH)mRNA表达水平明显高于对照组(0.234 2比0.043 1,Z=-6.83,P<0.01),与血TNF-α水平存在正相关(r=0.411 1,P<0.05),且随着Child-Pugh评分的增加而升高.两组PBMC中TLR4 mRNA表达水平差异无统计学意义.结论 肝硬化患者PBMC中TLR2表达水平明显增高,与血TNF-α水平及肝硬化的严重程度呈正比,但TLR4表达水平无明显变化,提示在乙肝肝硬化患者中,是TLR2而非TLR4在肝硬化的进展过程中具有重要作用.     

Toll样受体4在猪急性坏死性胰腺炎肠道组织中的表达及其意义

目的:探讨猪急性坏死性胰腺炎(acute necrotizing pancreatitis,ANP)回肠组织中Toll样受体4(Toll-like receptor4,TLR4)的表达及其意义.方法:选择太湖梅山猪,随机分成对照组(C,n=4)、急性坏死性胰腺炎组(ANP,n=4).诱导制备ANP模型.用分光光度法检测血清及回肠组织匀浆中二胺氧化酶(DAO)活性;动态比浊法检测血浆内毒素水平;RT-PCR检测回肠黏膜组织TLR4、TNF-α及IL-6mRNA表达.结果:ANP组回肠组织DAO水平明显低于C组,血清中DAO明显升高(P<0.05).ANP组血浆内毒素水平较C组明显升高(P<0.05);回肠黏膜组织TLR4、TNF-α、IL-6mRNA在C组表达非常低,ANP组表达明显增加;TLR4mRNA表达水平与肠黏膜DAO水平呈负相关(r=-0.762,P=0.028),与血浆内毒素呈正相关(r=0.778,P=0.023).结论:ANP时回肠组织内TLR4mRNA表达上调,可能与ANP肠黏膜屏障功能障碍有关;其可能机制与TLR4介导激活核转录因子NF-αB信号转导途径有关.     

系统性红斑狼疮外周血B淋巴细胞激活及TOLL样受体9表达

目的探讨系统性红斑狼疮(SLE)外周血单个核细胞(PBMCs)中B淋巴细胞的激活状态及TOLL样受体9(TLR9)表达水平。方法用流式细胞术测定25例SLE患者PBMC中CD19 B细胞及CD19 CD38 B细胞的比例。用反转录-聚合酶链反应(RT-PCR)半定量方法检测38例SLE患者PBMCs中TLR9mRNA的表达水平。分析TLR9mRNA的表达水平与SLE活动性指数(SLEDAI)的相关性。结果SLE患者PBMCs中CD19 B细胞和CD19 CD38 B细胞的百分数均高于正常对照组(P<0.01)。活动期SLE患者PBMCs的TLR9mRNA表达低于缓解组(P<0.01)及正常对照(P<0.01),缓解期和正常对照组相比,差异无统计学意义(P>0.05)。TLR9mRNA的表达与SLEDAI评分呈负相关。结论SLE患者PBMC中激活B细胞增多。活动期SLE患者PBMC的TLR9的表达水平降低,与SLEDAI呈负相关。TLR9可能参与SLE的病理发病过程。     

肝硬化患者外周血单核细胞表面TLR4和TLR2表达的临床意义

目的:探讨肝硬化患者外周血中单个核细胞(PBMC)表面Toll样受体4(Toll-likereceptor4,TLR4)、TLR2表达与肝硬化患者细菌感染的关系,观察抗生素治疗对TLR4与TLR2表达的影响.方法:采用三色荧光染色法,荧光素标记的抗TLR2/抗TLR4/抗CD14mAb对42例肝硬化患者及正常人的血液单核细胞表面TLR2、TLR4及CD14分子进行免疫荧光染色,应用流式细胞仪检测.结果:肝硬化腹水组TLR2和TLR4表达(n=30,TLR2,47.65±0.75;TLR4,22.28±0.80)与正常对照组(n=15,TLR2,24.40±2.77;TLR4,14.45±3.23)比较有显著性差异(P<0.05),肝硬化腹水患者治疗前(n=20,TLR2,47.79±0.76;TLR4,28.58±0.79)和治疗后(n=20,TLR2,17.22±2.48;TLR4,12.37±0.35)比较有显著性差异(P<0.05);肝硬化腹水患者与肝硬化无腹水患者组(n=12,TLR2,25.37±1.62;TLR4,14.81±0.29)比较有显著性差异(P<0.05);肝硬化无腹水患者组与正常对照组比较无显著性差异(P>0.05).结论:肝硬化腹水患者TLR4与TLR2的表达显著上调,抗生素治疗后显著下调.     

原发性免疫性血小板减少症患者血浆高迁移率族蛋白B1的表达及其与CD4+T淋巴细胞表面TLR4受体的关系

目的 检测原发性免疫性血小板减少症(ITP)患者血浆高迁移率族蛋白B1(HMGB1)、干扰素(IFN)-γ、白细胞介素(IL)4和CD4+T细胞表面Toll样受体4(TLR4)表达的变化,研究其在ITP发病中的意义.方法 采用酶联免疫吸附试验法(ELISA)检测24例ITP患者和20例正常人血浆中HMGB1、IFN-γ、IL-4的水平,利用流式细胞仪分析外周血CD4+T细胞表面TLR4受体的表达率,分析HMGB1与TLR4及IFN-γ、IL-4之间的关系.结果 ITP患者血浆HMGB1水平明显高于正常对照组(P＜0.05),IL-4水平明显低于正常对照组(P＜0.05),IFN-γ水平与正常对照组比较差异无统计学意义(P＞0.05);ⅡR4受体的表达明显高于正常对照组(P＜0.05);HMGB1与IL-4、TLR4水平呈正相关(P＜0.05),与IFN-γ水平呈负相关(P＜0.05).结论 ITP中存在血浆HMGB和CD4+T细胞表面TLR4受体的高表达,两者可能通过HMGB1/TLR4通路影响T淋巴细胞细胞因子的分泌.     

病毒性肝炎患者内毒素血症及外周血单核细胞Toll样受体4基因表达的研究

目的研究病毒性肝炎患者内毒素血症及外周血单核细胞内Toll样受体4(TLR4)mRNA的表达。方法采用鲎试剂法测定86例肝炎患者和11例对照组的血浆脂多糖(LPS)浓度,外周血单核细胞TLR4mRNA的表达用RT-PCR法检测。结果肝炎患者血浆LPS浓度均有不同程度的升高,高于对照组(P<0.05),重型肝炎组升高最显著,与其他各型肝炎比较差异有显著性(P<0.05);重型肝炎组单核细胞TLR4mRNA的表达升高最明显,与其他各型肝炎及对照组比较差异有显著性(P<0.05),其他各型肝炎与对照组比较差异不明显(P>0.05)。结论各型肝炎均存在内毒素血症,以重型肝炎最为显著,且重型肝炎患者外周血单核细胞内TLR4mRNA的表达水平最高,可能与肝细胞损伤相关。     

原发性非小细胞肺癌患者外周血中Th17的检测及其临床意义

目的通过检测非小细胞癌(NSCLC)患者与健康对照组外周血中Th17细胞及相关因子的表达水平,探讨其在NSCLC中的临床意义。方法流式细胞术检测外周血中Th17细胞占CD4+T淋巴细胞的比例;RT-PCR检测外周血单个核细胞(PBMC)中IL-17及孤独核受体γt(RORγt)mRNA的表达水平;酶联免疫吸附(ELISA)法检测外周血浆中IL-17的水平。结果 NSCLC患者外周血Th17细胞占CD4+T淋巴细胞的比例较对照组显著升高(P<0.01);PBMC中IL-17及RORγt mRNA表达水平显著高于对照组(P<0.01);外周血浆中IL-17的水平显著高于对照组(P<0.01)。不同病理类型之间Th17细胞比例、IL-17 mRNA及IL-17的表达水平无统计学差异(P>0.05)。Ⅲ期患者Th17细胞比例、IL-17 mRNA及IL-17的表达水平较Ⅰ^Ⅱ期患者显著增高(P<0.01)。结论 Th17细胞可能通过RORγt和IL-17参与NSCLC的发生,Th17相关指标对NSCLC的治疗及预后有指导意义。     

Treatment of patients with Eisenmenger's syndrome with Bosentan

We treated prospectively 14 patients with Eisenmenger's syndrome, with a mean age of 10 years, ranging from 3 to 18 years. Treatment continued for 12 months, and demonstrated a lasting symptomatic improvement, but no improvement in terms of mean saturation of oxygen over 24 hours. Exercise capacity, as judged by peak uptake of oxygen, worsened in the six patients able to perform a treadmill test. The symptomatic benefit from dual blockage of endothelin receptors in these patients may be due to mechanisms other than selective pulmonary vasodilatation alone.     

Satisfaction with ambulatory care of persons with AIDS

OBJECTIVE: To examine the relation of patient characteristics and site of care to the perception of ambulatory care quality by persons with AIDS (PWAs). DESIGN: Patient surveys and medical record review were used to determine PWAs’ perceptions of their ambulatory care, self-perceived health status, primary care relationships, sociodemographic characteristics, and severity of illness. SETTING: A public-hospital HIV clinic, an academic group practice, and a staff-model health maintenance organization (HMO) that together care for 20% of all Massachusetts PWAs. PATIENTS: All active patients as of February 12, 1990, and all new AIDS patients at each of the three sites during the subsequent 13 months. MEASUREMENTS AND MAIN BESULTS: The primary outcome measure was a six-item scale of patient-rated quality of care (PRQC), a newly developed measure that combined patients’ ratings of their physician care, nursing care, involvement in medical decisions, and overall quality of care. Multiple logistic regression was carried out with low PRQC (lowest quart He) as the dependent variable, to identify correlates of patient perceptions of poor quality. Patients who had a primary nurse were significantly less likely to have low PRQC scores (OR=0.50, 95% CI=0.26 to 0.97). Black patients and patients who used injection drugs were significantly more likely to rate their care in the lowest quartile (OR=2.22, 95% CI=1.04 to 4.78; and OR=2.43, 95% CI=1.13 to 5.23, respectively), as were those who had lower self-perceived health status, after controlling for confounders; no association was found by site or severity. CONCLUSIONS: These results show that primary nursing may be an important determinant of how PWAs rate the quality of their ambulatory care. Furthermore, PWAs who are black or who are injection drug users are less satisfied than are others with the quality of their ambulatory AIDS care. Presented in part at the annual meeting of the Society of General Internal Medicine, April 30, 1993, Arlington, Virginia. Supported by the Agency for Health Care Policy and Research, grant number HS06239.     

Experience with the treatment of patients with hypertrophic cardiomyopathy with obsidan and isoptin

Forty-five patients with hypertrophic cardiomyopathy were examined clinically and echocardiographically. The results of their treatment with obsidan and isoptin in relation to various types of central hemodynamic disorders are presented. The data have been obtained making it possible to treat patients differentially with regard to the form of the disease. The treatment of this category of patients requires the echocardiographic monitoring of the parameters of the central hemodynamics and myocardial contractility.     

分析老年糖尿病患者应用甘精胰岛素联合阿卡波糖治疗的效果

目的探讨甘精胰岛素联合阿卡波糖在老年糖尿病患者中的临床疗效。方法选取该院2018年7月—2019年7月收治的113例老年糖尿病患者作为研究对象,经随机数字表法,划分A组(n=56,阿卡波糖)和B组(n=57,甘精胰岛素+阿卡波糖),比较两组临床疗效、血糖指标。结果B组患者临床治疗总有效率显著高于A组;经治疗,B组患者空腹血糖(FBG)、餐后2 h血糖(2 hPG)、糖化血红蛋白(HbAlc)水平明显低于A组。两组之间比较差异有统计学意义(P<0.05)。结论在老年糖尿病患者中应用甘精胰岛素+阿卡波糖,临床疗效显著,使患者的空腹血糖、餐后2 h血糖、糖化血红蛋白等指标得到了明显改善,安全性强。     

Evaluation of atrial vulnerability with transoesophageal stimulation in patients with atrioventricular junctional: Comparison with patients with ventricular pre-excitation and with normal subjects

The aim of our work was to evaluate the inducibility of atrialfibrillation in a group of patients with atrioventricular junctionalreentrant tachycardia and to compare it with that of patientswith a Kent-type ventricular pre-excitation (Wolff-Parkinson-Whitesyndrome) and a control group. One hundred and twenty-five subjects were separated into groups.Group 1 comprised 49 Wolff-Parkinson-White patients, with amean age of 26.4, range 10.66 years; group 2, 51 patients withatrioventricular junctional reentrant tachycardia inducibleby transoesophageal atrial stimulation andlor clinically documented,with a mean age of 43.4, range 16–78 years; group 3, 25control subjects with a mean age of2.64, range 13–76 years. Each subject underwent atrial transoesophageal stimulation withthe following protocol: programmed atrial stimulation with 1and 2 stimuli during atrial pacing of 100. min^–1 and 150.min^–1; atrial stimulation for 10 s at a rate of 200–300–400–500–600.min^–1 with intervals of 10 s between stimulations, fivesuccessive ‘ramp-up’ atrial stimulations for 9 swith the rate increasing from 100 to 800. min^–1 with intervalsof 10 s between stimulations. The end point was the completionof the protocol or induction of sustained atrial fibrillation(>1 min). The chi-square test was used for statistical analysis. Our resultsshowed that in group 1 atrial fibrillation was induced in 27149patients (55.1%); this was sustained in 13149 (26.5%) and non-sustainedin 14149 (28.5%); in group 2, atrial fibrillation was inducedin 22151 patients (43.0%); it was sustained in 7151 (13.7%)and non-sustained in 15151 (29.4%); in group 3, sustained atrialfibrillation was not induced in any subject and in only onesubject was a non-sustained atrial fibrillation (4 s) induced. The chi-square test showed that group 2 vs group 1 were non-significant,while group 2 vs group 3 and group 1 vs group 3 were significant(P<0.003 and P<0.0007, respectively). Therefore group 2 patients showed a greater atrial vulnerabilityin comparison to the control subjects and a similar vulnerabilityto group 1 patients. It is possible that the greater atrialvulnerability in the patients of group 2 was due to the doublenodal pathway.     

Treatment of patients with thromboangiitis obliterans with cyclophosphamide.

This report describes a small, nonrandomized trial of cyclophosphamide in the treatment of patients with advanced thromboangiitis obliterans (TAO) with modest results. The rationale of the treatment was based on the immunopathogenesis of the disease, ie, autoimmune vasculitis of peripheral arteries. Twelve male patient volunteers with TAO were included for the trial. Diagnosis was based on the history of chronic smoking or tobacco chewing, clinical features of ischemia of peripheral vessels, radioarteriography showing arterial block, and characteristic histopathologic changes of affected arteries. Cyclophosphamide (400 mg) was given intravenously daily to the patients for 7 days followed by daily oral administration of 100 mg cyclophosphamide for another 7 weeks. Clinical conditions of the patients started to improve during the third week of the treatment and maximum benefit was noticed at the end of the treatment. There was significant decrease of intermittent claudication and twentyfold increase of claudication distance as well as relief of rest pain. Before starting treatment 6 patients had developed ulcers on their affected limbs; these healed completely in 2, partially healed in another 2, and showed no improvement in the remaining 2, who never stopped smoking. However, immunosuppressive therapy failed to show any improvement of arterial block, as evidenced by radioarteriography and any significant increase of skin temperature over the affected limbs. Nevertheless, histopathologic studies of biopsies taken from the diseased arteries after completion of therapy showed decreased influx of lymphocytes and plasma cells in the thrombi as well as in the arterial walls in comparison to the biopsies taken before the start of treatment. During the treatment the degree of immunosuppression was monitored by blood leukocyte and lymphocyte counts, which were kept between 4,000/mm3 and above 3,000/mm3 and not less than 500/mm3, respectively, indicating modest immunosuppression and no serious complications. All patients were followed up for 1 year. Only 2 patients, who resumed smoking, had relapse.