环磷酰胺联合糖皮质激素对SLE患者外周血白细胞GCR水平的影响

目的观察环磷酰胺联合糖皮质激素治疗系统性红斑狼疮（SLE）的疗效及机制。方法将同期收治的43例SLE患者随机分为观察组22例和对照组21例,两组均予糖皮质激素强的松口服或甲基强的松龙静滴,在此基础上观察组予环磷酰胺静滴。治疗后3个月观察两组疗效,并检测外周血白细胞糖皮质激素受体（GCR）水平。结果观察组完全缓解率明显高于对照组（P〈0．05）;两组治疗后外周血白细胞GCR水平均较治疗前升高,尤以观察组为著（P〈0．05）。结论环磷酰胺联合糖皮质激素可明显提高SLE完全缓解率,可能机制之一为提高外周血白细胞GCR水平。     

糖皮质激素受体在系统性红斑狼疮中的研究进展

系统性红斑狼疮（systemic lupus erythematosus，SLE）是自身免疫介导的，以免疫性炎症为突出表现的弥漫性结缔组织病。该病是结缔组织病中最易累及多脏器并引起严重脏器损害的常见疾病之一。糖皮质激素(glucocorticoids GC)为其首选治疗药物。GC 由肾上腺皮质束状带合成和分泌，受下丘脑-垂体-肾上腺轴的调节，具有调节碳水化合物、蛋白质、脂肪和水、盐、电解质的代谢,维持机体内环境平衡，以及抑制免疫、抗炎、抗休克、抗过敏等多项生理功能。其通过与糖皮质激素受体（glucocorticoid receptor GR）结合而发挥作用。现在研究表明糖皮质激素受体表达水平及基因多态性与SLE的发病、病情轻重及激素治疗效果相关。本文就此进行综述。     

系统性红斑狼疮患者骨髓CD34+细胞表面标志及与病情活动的相关性分析

目的研究系统性红斑狼疮(SLE)患者骨髓CD34+细胞表面标志的变化,了解SLE患者造血干细胞是否存在异常。方法应用流式细胞术CD45/SSC设门分析10例SLE患者和10例正常人骨髓CD34+细胞CD90、CD117、CD123、CD164、CD166、CD95(FAS)、FAS-L、人类白细胞抗原(HLA)-DR等表面分子的表达及其与病情活动指标的相关性。结果活动期SLE患者骨髓CD34+细胞比例(1.5±0.4)%,明显低于正常人(2.3±0.8)%,P<0.01;非活动期患者(2.0±0.4)%与正常人相比差异无统计学意义。SLE患者CD34+、CD95+的表达明显高于正常人[(48.3±10.6)%vs(24.3±11.1)%,P<0.05],患者CDl23和CDl66也明显高于正常人[(45±22)%vs(20±4)%,P<0.05];[(31±20)%vs(11±6)%,P<0.05]。其余表面标志的表达与正常人相比差异无统计学意义。CDl23表达率与患者外周血白细胞计数负相关(r=-0.700,P< 0.05),与SLE疾病活动指数(SLEDAI)评分无相关性。CD166表达与SLEDAI(r=0.472,P<0.05),血清C3 (r=-0.712,P<0.01),尿蛋白定量(24h)(r=0.558,P<0.05)显著相关。结论SLE患者骨髓CD34+细胞CD95、CDl23、CDl66的表达率增加,CDl23的表达率与外周血白细胞计数显著负相关:CDl66的表达率与SLEDAI评分、24h尿蛋白呈显著正相关,与血清C3呈显著负相关,CDl66可能是一个新的SLE疾病活动性标志。     

淋巴细胞趋化因子受体mRNA在系统性红斑狼疮患者外周血单个核细胞的表达

目的探讨淋巴细胞趋化因子受体(XCR1)mRNA在系统性红斑狼疮(SLE)患者外周血单个核细胞(PBMC)中的表达,及其与疾病的相关性。方法收集93例确诊的SLE患者和30名健康对照组,收集PBMC,提取RNA。应用反转录-聚合酶链反应(RT-PCR)方法检测研究对象XCR1mRNA表达水平。结果!"XCR1mRNA在PBMC中表达水平,患者组(1.57±0.84)与正常对照组(0.19±0.14),两者差异无统计学意义(P>0.05)。活动期(2.09±1.38)与对照组比较,两者差异有统计学意义(t=2.392,P=0.02);活动期与非活动期(0.31±0.24)比较,差异有统计学意义(t=3.091,P=0.003);非活动期与对照组比较,差异无统计学意义(P>0.05)。"#SLE患者组XCR1mRNA水平与疾病活动度评分(SLEDAI)关系:SLE患者组PBMC中XCR1mRNA表达水平与SLEDAI作直线相关性分析,XCR1mRNA水平与SLEDAI(r=0.540,t=5.445,P=0.000)呈正相关。"$SLE患者PBMC中XCR1mRNA表达与临床表现及实验室检查相关性:SLE抗SSA抗体阳性患者(17/68,1.4±1.2)比阴性患者(51/68,3.5±4.9),其XCR1mRNA表达水平降低,差异有统计学意义(t=2.78,P=0.007)。结论XCR1mRNA表达水平在PBMC中活动期SLE患者比非活动期及对照组增高,与疾病的活动性(SLEDAI)正相关,非活动期与对照组差异无统计学意义。SLE抗SSA抗体阳性患者比阴性患者,其XCR1mRNA表达水平降低,两组均较健康对照组增高。提示XCR1参与疾病的发展,与疾病的活动性相关,XCR1可能参与抗SSA抗体的形成过程,造成组织损伤。     

系统性红斑狼疮外周血单个核细胞生长激素受体和mRNA表达的研究

目的　探讨SLE患者外周血单个核细胞 (PBMC)的生长激素受体 (GHR)的表达与系统性红斑狼疮 (SLE)的关系。方法　采用放射性受体配基结合试验 (RLBA)及反转录 聚合酶链反应(RT PCR)研究外周血淋巴细胞GHR变化。结果　SLE活动期患者PBMC的GHR的特异性结合率 (SB) (3 4± 2 0 ) %、总结合率 (TB) (13 8± 5 7) %和静止期患者SB (1 3± 1 2 ) % ,TB (11 4±4 6 ) %均高于正常对照组SB (1 0± 1 0 ) % ,TB (8 3± 0 9) % (P <0 0 1) ;SLE活动期患者PBMC的mRNA的表达水平 (0 77± 0 6 6 )高于静止期患者 (0 4 5± 0 2 8) (P <0 0 5 )和正常对照组PBMC的mRNA的表达 (0 31± 0 2 2 ) (P <0 0 1)。结论　SLE患者PBMC的GHR高表达与SLE的病情活动性相关。     

多发性硬化患者糖皮质激素受体含量与疗效的关系

目的探讨多发性硬化(MS)患者外周血白细胞糖皮质激素受体(GR)含量与糖皮质激素的治疗效果关系。方法用放射免疫法和放射配体结合法测定25例MS患者的血浆皮质醇(F)含量和血白细胞GR含量。结果MS患者血浆F含量与正常对照组无明显差异,而血GR含量为(8635±1432)位点/细胞,明显高于正常对照组(5320±540)位点/细胞(P<0.01)。用常规大剂量激素治疗时,治疗前GR位点数高者［(9356±645)位点/细胞共18例］,疗效优于位点数低者［(6176±385)7例］。结论MS患者外周血白细胞GR增多,GR含量高者近期疗效较好,GR含量低者可加用超大剂量激素治疗,以提高疗效。     

糖皮质激素对系统性红斑狼疮CD4+Foxp3+T细胞水平的影响

目的 探讨糖皮质激素治疗对系统性红斑狼疮(SLE)患者外周血CD4+ Foxp3+ T细胞水平的影响以及CD4+Foxp3+T细胞与SLE疾病活动的相关性.方法 采用流式细胞术检测26例SLE患者和5名正常人外周血CD4+Foxp3+T细胞百分率,Spearman相关分析法分析CD4+Foxp3+T细胞与SLE疾病活动指标及糖皮质激素的相关性.结果 活动期SLE患者外周血CD4+Foxp3+T细胞百分率(2.4±1.6)%低于正常人(3.3±0.8)%,但差异无统计学意义;非活动期SLE患者外周血CD4+Foxp3+T细胞百分率(3.3±0.7)%与正常人比较差异无统计学意义.活动期SLE患者经糖皮质激素治疗后外周血CD4+Foxp3+T细胞(6.1±3.5)%较治疗前(3.9±2.4)%升高(P＜0.05).SLE患者外周血CD4+Foxp3+T细胞水平与年龄、病程、红细胞沉降率、尿蛋白定量(24 h)、血清补体C3浓度、血清抗双链DNA(anti-dsDNA)抗体水平及SLE疾病活动指数(SLEDAI)无相关性,但与糖皮质激素每日用量呈显著正相关(r=0.51,P＜0.05).结论 SLE患者外周血CD4+Foxp3+T细胞水平不能作为狼疮活动指标.糖皮质激素治疗可上调SLE患者外周血CD4+Foxp3+T细胞水平,CD4+Foxp3+T细胞水平上调可能是糖皮质激素治疗SLE有效的机制之一.     

系统性红斑狼疮患者外周血淋巴细胞穿孔素表达及糖皮质激素对穿孔素的影响

目的 研究系统性红斑狼疮(SLE)患者外周血淋巴细胞穿孔素(PF)表达与分布,PF水平与疾病活动的相关性,探讨PF在SLE发病机制中的作用,观察糖皮质激素治疗对PF表达的影响.方法 SLE活动期患者16例,健康对照者12名.用流式细胞仪检测外周血淋巴细胞PF、CD3、CD4或CD8表达,用直线相关分析PF水平与SLE疾病活动性评分(SLEDAI)的相关性;比较糖皮质激素治疗前后PF水平变化.结果 与健康对照组比较,SLE活动期患者组外周血PF+淋巴细胞的百分率显著增高(P<0.01),PF的平均荧光强度(PFMFI)增高(P<0.01),PF+CD8+CD3+淋巴细胞的百分率明显增加(P<0.01),差异均有统计学意义.SLE活动期患者外周血PP淋巴细胞百分率与SLEDAI呈正相关(r=0.673).经过短期大剂量糖皮质激素治疗,SLE活动期患者外周血淋巴细胞PF+细胞百分率和PFMFI都显著下降(P<0.05),差异有统计学意义.结论 SLE活动期患者PF高表达,主要分布于CD8+CD3+细胞;PF水平与SLE活动程度呈正相关;短期糖皮质激素治疗能够减少患者体内PF表达.     

糖皮质激素受体αβ和剪接因子SRp30c在系统性红斑狼疮的表达及意义

目的研究系统性红斑狼疮（SLE）糖皮质激素（GC）抵抗患者外周血单个核细胞（PBMC中糖皮质激素受体（GR）α、GRβ及剪接因子SRp30c的表达及其与临床指标的相关性，以探讨GC抵抗发生的可能机制。方法根据患者对GC反应的敏感程度分为GC抵抗组和GC敏感组，分别用反转录聚合酶链反应（RT-PCR）方法检测两组患者与健康人外周血PBMC中GRα、GRβ及剪接因子SRp30c的mRNA表达量；免疫细胞化学（ICC）方法测定外周血PBMC的GRα、GRβ蛋白水平的表达，并分析GR及SRp30c变化的意义及与各临床指标之间的关系。结果①SLE患者与正常对照者PBMC均有GRα、GRβ的mRNA及蛋白的表达，以GRα占大部分；②GC抵抗组GRβ和SRp30c的mRNA表达量均明显高于GC敏感组及正常对照组（P〈0．05），GC抵抗组GRβ阳性细胞数也明显高于GC敏感组及正常对照组（P〈0．05），但三组GRctmRNA表达量及阳性细胞数比较差异无统计学意义；③两组的临床指标中肾脏受累时间、尿蛋白定量（24h）、血浆白蛋白水平及SLE疾病活动指数（SLEDAI）评分差异有统计学意义（P〈0．05），但采用多因素Logistic回归分析后，显示只有GRα和SRp30c的mRNA表达量是GC抵抗发生的独立危险因素。结论GRβ及剪接因子SRp30c在GC抵抗的发生中可能发挥重要作用，检测患者外周血PBMC中GRβ及SRp30c的表达有可能预测患者对激素治疗的反应，给临床治疗提供进一步的依据。     

系统性红斑狼疮患者外周血单个核细胞白细胞介素-10受体水平的研究

目的探讨IL-10受体(IL-10R)在系统性红斑狼疮(SLE)发病机制中的作用及其临床意义。方法应用反转录-聚合酶链反应(RT-PCR)检测89例SLE患者和30名正常人外周血单个核细胞(PBMC)中IL-10RmRNA的表达水平;用酶联免疫吸附试验(ELISA)法检测血清中IL-10水平。结果①活动期SLE患者和非活动期SLE患者及正常人IL-10受体表达阳性率为100%。②PBMC中,IL-10RmRNA表达水平:活动期SLE患者(1组)为0.87±0.29,非活动期SLE患者(2组)为0.72±0.21,正常人(3组)为0.68±0.14。1组和2组间比较差异有统计学意义(P<0.05),1组和3组间比较差异有统计学意义(P<0.05),2组和3组间比较差异无统计学意义(P>0.05)。③血清中IL-10水平:1组和2组间比较差异无统计学意义(P>0.05),1组显著高于3组(P<0.05),2组显著高于3组(P<0.05)。活动期SLE患者和非活动期SLE患者血清中的IL-10水平与PBMC上的IL-10R的表达水平呈正相关(r=0.888,r=0.787,P<0.05)。结论IL-10及其受体的异常表达可能在SLE疾病活动和发展过程中起重要作用。检测SLE患者PBMC中IL-10受体的表达水平可作为疾病的活动性指标之一。     

Control of intraabdominal hemorrhage and shock: a comparison of fluid resuscitation, MAST, and balloon occlusion

Our study examined the efficacy of four treatment modalities in controlling hemorrhage and achieving hemodynamic stabilization in hemorrhagic shock: intravenous fluid replacement (IV); military antishock trousers used concomitantly with fluids (MAST); balloon occlusion at the level of the diaphragm with concomitant fluid replacement (balloon); and a combination of MAST inflation, balloon occlusion, and fluid resuscitation (MAST and balloon). Twenty-eight mongrel dogs were anesthetized, and the spleen was exposed and completely crushed. The abdomen was closed, and treatment was initiated and continued for four hours or until the dog died. For all conditions the hematocrit dropped during the course of the experiment; balloon occlusion was effective at slowing this drop (P less than .0001), but MAST had no statistically significant effect. Animals with balloons bled more slowly into the abdominal cavity than did animals in the other two groups (P less than .0001). MAST also were effective at slowing the bleeding (P less than .05). Of the balloon and the MAST and balloon dogs, all except one survived the entire four hours; this difference between balloon and nonballoon dogs is significant (P = .002). MAST did not have a statistically significant effect on survival. Perfusion pressure (PP) declined during the course of the experiment, and the balloon was effective at slowing this decline (P less than .0001); none of the other comparisons was statistically significant.     

Use of fab fragments of digoxin-specific antibodies in the therapy of massive digoxin poisoning

A case of massive digoxin ingestion with multiple arrhythmias, consisting of high grade A-V block and ventricular ectopy not responsive to lidocaine, is described. The arrhythmias ceased following administration of digoxin-specific Fab fragments. The patient improved and was transferred to the psychiatric unit.     

Comparison of intravenous and oral routes of theophylline loading in acute asthma

In a prospective, randomized clinical trial, 19 patients with an acute exacerbation of asthma were given a loading dose of aminophylline by the IV (n = 10) or oral route (n = 9) of administration following treatment with epinephrine. Plasma concentrations of theophylline were measured prior to giving the loading dose, and one, two, three, and 24 to 48 hours later. Therapeutic effectiveness was evaluated by analyzing spirometric measurements prior to giving the loading dose, and one, three, and 24 to 48 hours later. Side effects also were recorded. In the IV group, the mean peak plasma theophylline concentration was 15.1 micrograms/mL one hour after loading, and in the oral group the mean peak serum theophylline concentration was 14.2 micrograms/mL three hours after loading. There was no correlation between theophylline concentrations and normalized change in spirometric values. There was no significant difference in spirometric values between the IV and oral groups. Nausea was slightly more common in the IV group. We conclude that there is no therapeutic advantage to giving a loading dose of aminophylline by the IV route rather than orally in patients with mild-to-moderate exacerbation of asthma initially treated with epinephrine.     

Role of microRNA in regulation of myeloma-related angiogenesis and survival

Multiple myeloma (MM) is a malignant disease caused by clonal proliferation of plasma cells that result in monoclonal gammopathy and severe end organ damage. Despite the uniform clinical signs, the disease is very diverse in terms of the nature and sequence of the underlying molecular events. Multiple cellular processes are involved in helping the malignant cells to remain viable and maintain proliferative properties in the hypoxic microenvironment of the bone marrow. Specifically, the process of angiogenesis, triggered by the interactions between the malignant MM cells and the stroma cells around them, was found to be critical for MM progression. In this review we highlight the current understanding about the epigenetic regulation of the proliferation and apoptosis of MM cells and its dependency on angiogenesis in the bone marrow that is carried out by different microRNAs.     

安徽巢湖市丝虫病控制、消除历程和监测报告

【摘要】 目的  回顾并总结巢湖市丝虫病的流行、控制,以及消除丝虫病的历程。 方法  统计分析1970~1989年在该市采取以消灭传染源、切断传播途径为主的防治策略,以及展开大规模防治的各个阶段。 结果  1989年,采用分层整群抽样调查方法调查,微丝蚴率下降至0.032%,以行政村为单位,微丝蚴率已控制在1.0%以下,达到卫生部规定的基本消灭丝虫病标准;1991年,经省级调查考核,认定全市已达到卫生部规定的基本消灭丝虫病标准。1996年,省级审评确认已达到卫生部颁布的消灭丝虫病标准。经过10年的监测和跟踪治疗,到2005年,全市丝虫病病原学监测未查见微丝蚴阳性者,解剖镜检人房内淡色库蚊1 348只,蚊体内均未查见人体幼丝虫。 结论  巢湖市达到了消除丝虫病的标准。     

RNA-Seq在老年神经退行性疾病研究中的应用

阿尔茨海默病及帕金森病是老年人最常见的两种神经退行性疾病,但其发病机制及治疗是研究的热点。随着高通量测序技术的进步及成本的下降,RNA-Seq也成为神经退行性疾病机制研究及生物标志物发现的有力手段。RNA-Seq相对于microarray具有高灵敏度、高准确性、高重复性以及噪声低等优势,在阿尔茨海默病及帕金森病研究中有较为广泛的应用,包括检测差异表达基因,可变剪接、新长链非编码RNA预测分析和miRNAs调控等,但是容易受病理复杂性及样本等因素影响。目前阿尔茨海默病及帕金森病转录组研究相比于癌症等还不够深入,在临床诊断及治疗应用还面临较大挑战。但是随着新技术及新方法的发展,RNA-Seq将进一步推动神经退行性相关疾病的研究和临床转化。     

岳阳市城区小学生血吸虫病防治健康教育现状调查

目的 调查湖南省岳阳市城区小学生血吸虫病防治知识、行为现状及健康教育需求情况,为制定科学有效的小学生血吸虫病健康教育方案提供参考依据。方法 采用分层整群抽样方法,抽取岳阳市城区洞庭湖湖畔学校和中心城区学校各2所,每所再从五、六年级分别抽取2个班的学生,通过调查问卷了解小学生血吸虫病相关知识、预防行为及健康教育需求,并进行统计分析。结果 共调查湖畔小学353人、中心城区小学363人,两组学校小学生年龄、性别、年级构成差异无统计学意义（t=-0.494,χ²_性别=1.615,χ²_年级=2.152;P均>0.05）。学生血吸虫病防治知识总知晓率为42.60%（305/716）,其中,湖畔学校小学生血防知识知晓率（52.97%）高于中心城区（32.51%）,差异有统计学意义（χ²=30.661,P<0.05）;学生行为正确率为76.68%（549/716）,血防知识知晓组行为正确率（81.31%）高于不知晓组（71.24%）,差异有统计学意义（χ²=6.384,P<0.05）。学生血防知识主要来源于老师（47.49%）;91.90%的学生愿意了解更多的血防知识,最喜欢的血防知识学习方式是参加课外活动（50.42%）。结论 岳阳市城区小学生的血防知识知晓率及行为正确率偏低,对血吸虫病防治健康教育需求较高。建议针对学生开展形式多样的血防健康教育,以增强学生的血吸虫病防护意识,提高自我防护能力。     

Advanced Evaluation of the Freeze–Thaw Damage of Concrete Based on the Fracture Tests

This paper presents the results of an experimental program aimed at the assessment of the freeze–thaw (F–T) resistance of concrete based on the evaluation of fracture tests accompanied by acoustic emission measurements. Two concretes of similar mechanical characteristics were manufactured for the experiment. The main difference between the C1 and C2 concrete was in the total number of air voids and in the A300 parameter, where both parameters were higher for C1 by about 35% and 52%, respectively. The evaluation of the fracture characteristics was performed on the basis of experimentally recorded load–deflection and load–crack mouth opening displacement diagrams using two different approaches: linear fracture mechanics completed with the effective crack model and the double-K model. The results show that both approaches gave similar results, especially if the nonlinear behavior before the peak load was considered. According to the results, it can be stated that continuous AE measurement is beneficial for the assessment of the extent of concrete deterioration, and it suitably supplements the fracture test evaluation. A comparison of the results of fracture tests with the resonance method and splitting tensile strength test shows that all testing methods led to the same conclusion, i.e., the C1 concrete was more F–T-resistant than C2. However, the fracture test evaluation provided more detailed information about the internal structure deterioration due to the F–T exposure.     

欧洲儿童肝豆状核变性诊疗推荐意见简介

正肝豆状核变性(Wilson’s disease,WD)是常染色隐性遗传相关的铜代谢障碍性疾病,估计患病率为1:30000。该病是由于编码P型ATP酶的ATP7B基因突变,影响铜的分泌及排泄所致铜沉积。儿童肝豆状核变性的临床表现可以从无症状肝脏疾病到肝硬化或者肝衰竭,但是神经精神症状却非常少见。常规的检测方法包括血清铜蓝蛋白、24 h尿铜。最终的诊断需要基于症状、评估铜代谢的生化学检