系统性红斑狼疮外周血单个核细胞cFLIP-L mRNA和cFLIP-S mRNA表达的研究

目的 探讨系统性红斑狼疮(system lupus erythematosus,SLE)患者外周血单个核细胞(peripheral blood monouuclear cells,PBMC)中细胞型Fas相关死亡域样白介素-1β转换酶抑制蛋白(cFLIP)表达的意义.方法 应用半定量RT-PCR方法检测38例SLE患者和21名正常人PBMC中cFLIP-L mRNA和cFLIP-S mRNA的表达水平,并与SLE疾病活动指数(SLEDAI)评分进行相关性分析.结果 ① SLE患者PBMC中cFLIP-L mRNA和cFLIP-S mRNA表达水平均明显高于正常对照组(P＜0.01);SLE患者活动组cFLIP-L mRNA表达水平显著高于非活动组(P＜0.05),cFLIP-S mRNA表达水平在SLE患者活动组与非活动组之间没有显著性差异(P＞0.05). ② SLE患者cFLIP-L mRNA表达水平与SLEDAI评分呈正相关(r=0.423,P＜0.01);而cFLIP-S mRNA表达水平与SLEDAI评分无明显相关性(r=0.270,P＞0.05).结论 cFLIP-L mRNA和cFLIP-S mRNA可能在SLE发病机制中起重要作用.     

单核细胞骨调素的表达水平与狼疮肾炎

目的：研究骨调素（OPN）在狼疮性肾损害中的作用。方法：采用酶联免疫吸附试验（Ⅱ届A）检测了90例系统性红斑狼疮（SLE）患者、15例非SLE肾损害患者及30例对照血浆OPN的水平，应用半定量RT-PCR方法，测定以上各组外周血单个核细胞（PBMCs）OPN的表达。结果：狼疮处于疾病活动时PBMCs OPN mRNA表达上调，尤其是狼疮肾炎活动组患者PBMCs OPN mRNA表达增加最为显著（P〈0．01），PBMCs OPN mRNA表达不仅与总狼疮疾病活动指数评分呈正相关（r=0．532，P〈0．001），而且与狼疮疾病活动指数肾评分呈正相关（r=0．584，P〈0．001），而非狼疮肾脏疾病组仅低水平表达，与正常对照组水平相近似（P〉0．05）。狼疮活动组血清OPN水平较非活动组及正常对照组均明显升高（P〈0．01），但活动性狼疮肾炎组与无肾损伤组之间血清OPN水平的差异无显著性（P〉0．05）。结论：狼疮处于疾病活动时PBMCs OPN mRNA表达上调，并与狼疮肾炎的疾病活动情况密切相关。     

系统性红斑狼疮外周血Dicer和Ago2的表达

Dicer和Ago2是RNA干扰(RNAi)中重要的酶,本研究检测常见自身免疫病系统性红斑狼疮(SLE)、类风湿关节炎(RA)和强直性脊柱炎(AS)患者中Dicer和Ago2的表达水平并分析其与SLE临床特征的相关性。方法:采用实时荧光定量聚合酶链反应(real-time PCR)检测41例SLE、24例RA、13例AS患者和21例正常人外周血白细胞中Dicer和Ago2的表达水平,并分析其与SLE疾病活动指数(SLEDAI)、SLE肾脏损伤活动指数(renal-SLEDAI)及临床用药之间的相关性。结果显示,Dicer表达水平在SLE、RA和AS患者中较正常对照显著升高(P=0.0051;P<0.0001;P=0.0001),而Ago2表达水平仅在SLE患者中显著升高(P=0.0015)。Dicer表达水平在中度以上活动性SLE患者中较轻度以下活动性患者显著升高(P=0.032),并且与SLEDAI正相关(r=0.4075,P=0.0254),在狼疮肾炎患者中较无狼疮肾炎患者显著升高(P=0.0367),与renal-SLEDAI显著正相关(r=0.4014,P=0.0309),但Ago2表达水平与SLEDAI积分无明显相关性,且在狼疮肾炎患者中也无明显变化,不同量激素治疗组之间Dicer与Ago2均无显著差异。提示,Dicer和Ago2的表达水平在SLE患者中均显著升高且前者与SLEDAI积分、Renal-SLEDAI积分正相关,Dicer升高提示SLE活动及肾脏损害,可能参与SLE的发病。     

TLR9、IFN-α和BAFF水平与系统性红斑狼疮的相关性研究

目的检测系统性红斑狼疮(SLE)患者外周血单个核细胞(PBMCs)Toll样受体(TLR)-9 mRNA及血清干扰素(IFN)-α、B细胞活化因子(BAFF)水平,探讨TLR9与SLE疾病活动的关系及与IFN-α、BAFF在SLE发病中可能的相互作用。方法应用实时荧光定量聚合酶链反应(real-time PCR)检测40例SLE患者及20例健康对照者PBMCs中TLR9 mRNA水平;采用酶联免疫吸附法(ELISA)检测60例SLE患者及20例健康对照者血清IFN-α、BAFF水平。结果 1SLE患者外周血单个核细胞TLR9 mRNA表达水平较健康对照组上调(P0.05);TLR9 mRNA表达水平与SLE疾病活动指数(SLEDAI)、血沉(ESR)呈正相关(P0.01,P0.05);与补体3(C3)呈负相关(P0.05)。2SLE患者血清中BAFF、IFN-α水平高于健康对照(P均0.05);BAFF、IFN-α水平均与SLEDAI呈正相关(P0.05)。3SLE患者中抗ds-DNA抗体阳性者TLR9 mRNA、BAFF与IFN-α水平高于阴性者(P均0.05)。4SLE患者外周血单个核细胞TLR9mRNA表达水平与血清中BAFF、IFN-α水平正相关(P0.01);血清中BAFF与IFN-α呈正相关(P0.05)。结论 SLE患者外周血单个核细胞TLR9 mRNA表达上调,血清中BAFF、IFN-α分泌增加,均与疾病活动相关。SLE患者外周血单个核细胞TLR9 mRNA表达与血清IFN-α、BAFF水平之间及BAFF和IFN-α之间均呈显著正相关,提示TLR9、BAFF及IFN-α参与了人类SLE的发病过程并相互调控,在SLE疾病活动维持中起重要作用。     

系统性红斑狼疮患者外周血Th2型细胞因子受体水平的研究

目的探讨Th2型细胞因子受体(IL-4R、IL-6R、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.方法应用逆转录酶-聚合酶链反应(RT-PCR)检测89例SLE患者和30例正常人外周血单核细胞(PBMC)中IL-4R、IL-6R和IL-10R mRNA的表达水平;用ELISA法检测血清中IL-4、IL-6和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Th2型细胞因子受体阳性表达率为100%.②PBMC中,IL-4R mRNA表达水平活动期SLE患者(1组)为0.604±0.147,非活动期SLE患者(2组)为0.40±0.13,正常人(3组)为0.37±0.07;IL-6R mRNA表达水平1组为0.90±0.27,2组为0.52±0.11,3组为0.57±0.24;IL-10R mRNA表达水平1组为0.87±0.29,2组为0.72±0.21,3组为0.68±0.14.1组和2组间比较无显著性差异(P＜0.05),1组和3组间比较有显著性差异(P=0.00),2组和3组间比较无显著性差异(P＞0.05).③血清中IL-4、IL-6和IL-10水平1组显著高于2组和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-4水平与PBMC上的IL-4R的表达水平呈正相关(r=0.622和r=0.859,P＜0.05).活动期SLE患者和非活动期SLE患者血清中的IL-6水平与PBMC上的IL-6R的表达水平呈正相关(r=0.887和r=0.615,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和r=0.787,P＜0.05).结论Th2型细胞因子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Th2型细胞因子受体的表达水平可作为疾病的活动性指标之一.     

Toll 样受体7及Ⅰ型干扰素通路在系统性红斑狼疮中的作用研究

探讨Toll样受体7(TLR7)及Ⅰ型干扰素(IFN-α)通路在系统性红斑狼疮(SLE)发病中的作用.采用实时荧光定量PCR方法检测42例SLE患者和34例正常人外周血TLR7mRNA以及4个干扰素调节基因mRNA的表达水平,同时观察TLR7mRNA的表达量与SLE疾病活动相关指标和干扰素积分(IFN score)的关系.结果,SLE患者外周血TLR7mRNA的表达水平显著增高;TLR7mRNA的表达水平与SLEDAI积分,肾脏损伤指数、抗双链DNA(dsDNA)抗体、抗RNA相关抗体水平及干扰素积分呈正相关;与补体C3、C4、白细胞数呈负相关.TLR7-IFN-α通路可能参与了SLE的病理过程.     

系统性红斑狼疮外周血单个核细胞CD40L的表达增高

目的:了解系统性红斑狼疮(SLE)患者外周血单个核细胞(PBMCs)的白细胞分化抗原40配体(CD40L)表达,探讨其在发病中的作用。方法:分离SLE患者和正常人PBMCs,采用流式细胞术,检测其在正常状况和应用植物凝集素(PHA)及地塞米松(Dex)后,CD40L的表达水平,并进行比较;分析SLE患者CD40L的表达水平和狼疮活动指数(SLEDAI)的相关性。结果:活动期SLE患者PBMCs的CD40L阳性细胞百分率(%)明显高于对照组,且高于静止期SLE患者;应用PHA处理24h后,3组PBMC表达CD40L均明显增加,但活动期SLE患者增加更明显;应用地塞米松后,SLE患者(活动期和静止期)PBMCs的CD40L表达明显减少,对照组无明显改变;SLE患者(活动期和静止期)CD40L的表达水平和SLEDAI均呈明显正相关。结论:CD40L在SLE患者PBMCs的表达增加,和疾病活动度有关;其受PHA和Dex调控,在SLE发病和病程中起重要作用。     

系统性红斑狼疮患者血中sCD30L的变化及其临床意义

目的:通过检测系统性红斑狼疮(SLE)患者血清中可溶性CD30配体(sCD30L)的表达水平, 探讨其水平变化及在疾病发病中的作用.方法:选取符合1982年美国风湿病学会制定的SLE诊断标准的45例SLE患者, 另选20例健康人作对照, 采取双抗体夹心ELISA方法检测SLE组及对照组血清中的sCD30L的水平, 同时检测临床相关指标, 分析sCD30L在各组患者血中的变化及其与临床各指标的相关性.结果:SLE 血清sCD30L水平为(21.20±10.90)μg/L, 显著高于正常对照组水平;(6.45±1.17)μg/L, P<0.01].SLE血清sCD30L水平与ds-DNA, 尿α1, SLEDAI评分呈正相关(r=0.324, P<0.05;r=0.658, P<0.05;r=0.486, P<0.05), 特别是在SLEDAI评分大于10分和早期狼疮性肾炎的患者中相关性更强(r=0.508, P<0.01;r=0.715, P<0.01).SLE患者血清sCD30L水平明显升高, 其升高水平与ds-DNA, 尿α1, SLEDAI评分呈正相关.结论:sCD30L的表达异常可能是SLE 发病的重要环节, 在一定程度上反映疾病活动, 特别在早期狼疮性肾炎的发病及诊断中起重要作用.     

IL-17、干扰素-γ在红斑狼疮患者体内的表达及地塞米松对其的抑制作用

目的研究系统性红斑狼疮（SLE）患者血浆及外周血单个核细胞（PBMCs）中IL-17、IFN-γ的表达水平,探讨地塞米松对PBMC分泌IL-17和IFN-γ的影响。方法采用双抗体夹心酶联免疫吸附法（ELISA）测定SLE患者和健康对照者血浆及PBMCs培养上清液中IL-17、IFN-γ的表达水平。结果SLE患者组血浆IL-17、IFN-γ含量均高于健康对照组（t=d．96,P〈0．001;t=2．43,P〈0．05）,SLE活动组患者血浆IL-17水平明显高于非活动组（t=g．52,P〈0．005）;血浆IL-17水平与SLE疾病活动性指数（SLEDAI）、抗dsDNA抗体滴度呈正相关（r=0．681,0．492）,与补体C3、C4水平呈负相关（r=-0．529,-0．534）。无佛波酯（PMA）刺激条件下,SLE患者PBMCs培养上清液中细胞因子水平与对照组均无显著差异（t=0．06,P〉0．05）．力口人PMA刺激后,SLE患者PBMCs分泌IL—17的水平显著高于正常对照组（t=2．48,P〈0．05）;地塞米松可明显抑制PMA刺激后的PBMCs分泌IL-17和IFN-γ水平（t=3．72,3．34,P〈0．01）,且地塞米松对PBMCs分泌IL-17的抑制率更高。结论SLE患者体内细胞因子的表达水平存在明显异常,IL-17表达水平显著增高,且与疾病活动性有明显关联,地塞米松可明显抑制IL-17的表达,提示IL—17可能是治疗SLE的一个潜在的新靶点。     

SLE患者外周血单个核细胞中miR-148b、miR-152和靶基因dnmt1的表达及其临床意义

目的探讨系统性红斑狼疮(systemic lupus erythematosus,SLE)患者外周血单个核细胞中miR-148b、miR-152和其靶基因dnmt1的表达水平在发病机制中的作用以及与SLE实验室相关指标、临床疾病活动度的之间的关系。方法采用实时荧光定量PCR(quantitative real-time,qPCR)方法检测74例SLE患者和44例健康者的PBMCs中miR-148b、miR-152、dnmt1的表达水平,统计学分析其与SLE疾病活动度及SLE相关检验指标的关系。结果 miR-148b、miR-152在SLE患者PBMCs中的表达水平显著高于健康对照(P0.05),dnmt1在SLE患者PBMCs中的表达水平显著低于健康对照(P0.05)。除miR-148b在低活动组与健康对照组差异无统计学意义(P0.05)外,miR-148b、miR-152和dnmt1在其他各组中的表达差异均有统计学意义。miR-152与ESR正相关(r=0.443,P=0.027);dnmt1与ANA抗体(r=-0.576,P=0.001)及SLEDAI评分均为负相关(r=-0.408,P=0.038)。结论 miR-148b、miR-152和dnmt1在SLE的发病机制中扮演着重要角色,可能作为疾病活动的参考指标,有助于指导疾病治疗和预后评估,并为SLE的治疗带来更多靶点。     

Studies on the structure and function of the apolipoprotein(a) gene

Lp(a) is an LDL-like lipoprotein that is a major inherited risk factor for atherosclerosis. It is distinguished from Lp(a) by the addition of apolipoprotein(a). The gene structure of apolipoprotein(a) is homologous to plasminogen, and competition with plasminogen activity may account for some of the pathophysiology associated with Lp(a). Six highly related genes have now been identified, and at least four are found in close proximity in overlapping genomic clones. Studies have begun on the regulation of apolipoprotein (a) gene expression, and the human apolipoprotein(a) gene has been inserted into transgenic mice, where it leads to the development of arterial lesions.     

视觉诱发电位在诊断多发性硬化症中的应用

目的：探讨视觉诱发电位对多发性硬化症早期诊断的应用价值。方法：对多发性硬化症患行视觉诱发电位（VEP）检查。结果：多发性硬化症患常有视神经受累，经视觉诱发电位检测，P100波潜伏期均有不同程度延长，P100波振幅降低。结论：视觉诱发电位对多发性硬化症早期诊断有重要价值。     

骨质疏松症患者血清CT、Ca和P的水平观察

目的：为了研究血清降钙素（CT）、钙（Ca）和磷（P）的水平对激素引起男、女性骨质疏松症（OP）的影响。方法：放射免疫分析了血清CT的水平,生化法测定了血钙和血磷,发光免疫分析了性激素水平,并都做了相关性分析。结果：67例男性OP的血清Ca、P和E2均明显高于正常对照组（P均〈0.01）,而血清CT和T较正常对照组明显降低（P〈0.01）。在治疗前,60例女性OP患者血清Ca、P和T均明显高于正常对照组（P均〈0.01）,而血清CT和E2较正常对照组明显降低（P〈0.01）;治疗后女性OP患者血清CT和E2较治疗前明显增高,血清Ca、P和T明显降低,血清CT、E2和T较正常对照组接近（P均〉0.05）,而血清Ca和P较正常对照组仍增高（P〈0.05）。结论：由性激素引起的OP与血清CT、Ca、P和性激素相互之间存在着相关关系。在女性OP治疗时,以CT、E2和T水平为随访的最佳指导。     

Vacuum Ultraviolet Photolysis of Hydrocarbon Polymers

Summary: The wavelength‐dependent vacuum ultraviolet (VUV) photolysis of several polymers, low density polyethylene (LDPE), biaxially oriented poly(propylene) (BOPP), atactic polystyrene (PS), and poly(methyl methacrylate) (PMMA), was studied by irradiation in vacuum with the well‐characterized emissions from four different resonant or excimer VUV sources. These lamps comprise radiofrequency (r.f.) discharges in different noble gases, such as krypton, xenon (at low pressures, producing near‐monochromatic resonant line radiations), xenon excimer (at “high” pressure), and a deuterium/argon mixture (producing a broad‐band emission). VUV‐induced mass loss (ablation or etching) was monitored in situ by quartz crystal microbalance measurements. Following irradiation, samples were analysed by ATR‐FTIR and XPS, to evaluate near‐surface structural changes (e.g., creation of unsaturation, cross‐linking) resulting from the VUV‐initiated bond scissions and radical‐creation reactions. PMMA was the most readily ablatable polymer, whereas the mass loss of BOPP was higher than that of LDPE, regardless of the irradiation wavelength, λ. All polymers were found to form double bonds, with the exception of PS, which is rather stable, probably due to energy dissipation by fluorescence.

Formation of double bonds in a) vinyl‐, b) vinylidene‐, and c) vinylene‐like unsaturated groups, as a function of the radiation dose, D, for KrL (?), XeL (?), and D₂Ar‐irradiated (?) PMMA.     

New insights in the role of nucleoporins: A bridge leading to concerted steps from HIV-1 nuclear entry until integration

Human Immunodeficiency virus type 1 (HIV-1), as well as many other viruses that depend on nuclear entry for replication, has developed an evolutionary strategy to dock and translocate through the nuclear pore complex (NPC). In particular, the nuclear pore is not a static window but it is a dynamic structure involved in many vital cellular functions, as nuclear import/export, gene regulation, chromatin organization and genome stability. This review aims to shed light on viral mechanisms developed by HIV-1 to usurp cellular machinery to favor viral gene expression and their replication. In particular, it will be reviewed both what is known and what is speculated about the link between HIV translocation through the nuclear pore and the proviral integration in the host chromatin.     

Distribution of six neuropeptides in the nucleus tractus solitarii of the rat: an immunohistochemical analysis

Distribution of substance P-, [Leu]enkephalin-, cholecystokinin-8-, neurotensin-, avian pancreatic polypeptide- and gamma-melanocyte stimulating hormone-like immunoreactive structures were investigated in the nucleus tractus solitarii of the rat by means of the indirect immunofluorescence method. The density of the immunoreactive structures varied markedly according to neuropeptides or subnuclei, with the medial and commissural nuclei containing the highest density. This suggests that the peptides examined play a role in cardiovascular function. However, as seen in the substance P- and [Leu]enkephalin-like immunoreactive structures, these peptides were widely distributed in the nucleus tractus solitarii in addition to the commissural and medial nuclei; a high density of immunoreactive fibers in the ventral, dorsolateral and intermediate subnuclei. In addition to the immunoreactive fiber plexus, a group of immunoreactive cells was also identified in the subnuclei mentioned above. These findings strongly suggest that substance P- and [Leu]enkephalin-like immunoreactive structures are involved not only in cardiovascular function but also in other functions such as respiration, at least in the rat. Finally, the present study demonstrated that the area postrema, particularly its lateral portion, contains various neuropeptide-like structures, both neurons and fibers, substance P-, [Leu]enkephalin-, cholecystokinin-8- and neurotensin-like immunoreactive neurons and fibers, and avian pancreatic polypeptide- and gamma-melanocyte stimulating hormone-like immunoreactive fibers.     

仿生型BG-COL-HYA-PS复合支架细胞相容性

目的:研究仿生型BG-COL-PS-HYA复合支架材料与成骨细胞的相容性。方法:将小鼠胚胎成骨细胞种植于BG-COL-HYA-PS、BG-COL复合材料、58SBG支架上,用MTT法、ALP活性测定等观察细胞在材料中的生长情况。通过体外实验方法,观察其生物相容性。结果:成骨细胞在BG-COL-HYA-PS材料上能良好粘附、增殖,而在58SBG材料上粘附差、细胞逐渐死亡。MTT法结果显示:联合培养后,BG-COL-HYA-PS组的OD值为0.314±0.004,5天时达到0.621±0.002,分别为58SBG组的1.49倍和1.44倍,P<0.05。结论:仿生型BG-COL-PS-HYA复合支架具有天然骨分级结构和有良好的生物相容性,在诱导成骨细胞增殖方面性能优越,可作为骨组织工程支架材料,临床应用前景广阔。     

Dexamethasone attenuates LPS-induced changes in expression of urea transporter and aquaporin proteins,ameliorating brain endotoxemia in mice

Aim: AQP4 in the brain is involved in the occurrence and development of a variety of encephalopathy. AQPs family changes in kidney were accompanied by altered UTs family. The aim of this study was to observe AQP4 and UT-A3 expression in CNS and to explore their role in the pathogenesis of endotoxemia encephalopathy following peripheral LPS injection in mice. Methods: Endotoxemia was induced in C57Bl/6 mice by intraperitoneal injection of LPS. The expression of UT-A3 and AQP4 in brain were detected by Western blot and immunohistochemistry, the level of cytokines were detected by ELISA, and the content of LDH, AST/ALT, BUN and CREA were detected by colorimetric method. Results: As compared with the control group, in model group, the brain weight/ body weight ratio increased by 13%. Meanwhile, a 2.5 fold increase in LDH and a 1.2 fold increase in AST/ALT were found in peripheral serum (P < 0.05), and also, BUN and CREA increased 2.5 fold (P < 0.01). In addition to severe CNS injury in response to lipopolysaccharide, the contents of cytokines and the expression of AQP4 protein in hippocampal is increased (P < 0.05), while the expression of UT-A3 protein in the hippocampus and cortical astrocytes decreased (P < 0.05). And, in part, Dexa pretreatment attenuated those effects. Conclusions: In endotoxemia encephalopathy, AQPs and UTs which regulate the functions of cell membrane are both altered. We suggested that the molecular mechanisms of regulation in endotoxemia may provide a new strategy for clinical treatment of the disease and drug binding sites.     

植物血凝素（PHA）对小鼠骨髓粒—巨噬祖细胞的保护作用

以体外半固体琼脂培养方法,观察了PHA对小鼠骨髓CFU—GM的保护作用.结果显示 小鼠经腹腔往射PHA后,对小鼠CFU—GM的自杀率有明显提高,提示适量的PHA在体内可以促进小鼠CFU—GM增殖.使更多的CFU—GM由Go进入S期.我们发现4mg/kg三尖杉酯碱(Ha)明显抑制小鼠CFU—GM增殖,若先用PHA(30mg/kg处理小鼠,则可对抗上述剂量的Ha,使CFU—GM产率维持于对照组水平.提示PHA能有效地保护粒-巨噬系免受Ha的损害,     

New Complex Crystals of Chiral Poly(L‐lactic acid) and Different Tactic Poly(methyl methacrylate)

Based on evidence from differential scanning calorimetry (DSC), wide‐angle X‐ray diffraction (WAXD), and Fourier‐transform infrared (FTIR) spectroscopy, a new stereocomplex crystal (DSC T_m = 175 °C, with WAXD 2θ = 10.0° and 12.5°) is proven for the first time between structurally dissimilar chiral poly(L ‐lactic acid) (PLLA) and syndiotactic poly(methyl methacrylate) (sPMMA). There is a strong complexing capacity only between low molecular weight PLLA and sPMMA, in miscible state, at specific weight fractions (70:30). The complexing capacity is more significant when the mixtures are melt‐crystallized at T_c = 110 °C or lower, and the intensity of this complex can be further enhanced if it is annealed between 100 and 160 °C, below its T_m = 175 °C. The new complex crystal can be formed only between PLLA and sPMMA, but not with isotactic or atactic PMMA.