角膜共焦显微镜对于肌萎缩侧索硬化症小纤维神经病变的临床研究

目的通过角膜共焦显微镜(CCM)评价肌萎缩侧索硬化症患者小纤维病变情况及其诊断价值。方法肌萎缩侧索硬化症患者57例, 为2015年6月至2016年2月北京大学第三医院神经内科门诊和住院患者, 男性37例、女性20例, 年龄24～80(52±11)岁。健康对照组30名, 男性21名、女性9名, 年龄23～76(55±13)岁。采用CCM量化分析角膜神经纤维的角膜神经纤维长度(NFL), 神经分支密度(NBD), 神经纤维密度(NFD), 神经纤维弯曲度(NFT), 并同时进行接触性热痛诱发电位(CHEP), 皮肤交感反射(SSR)等检查。计量资料用xˉ±s或M(Q₁, Q₃)表示;计量资料符合正态分布者组间比较用t检验, 偏态分布计量资料可用秩和检验等非参数检验, 计数资料分析用χ2检验。多因素计量资料相关分析用简单相关分析。所有统计分析采用SPSS 12.0软件处理。结果肌萎缩侧索硬化症组角膜NFL、NFD均显著低于健康对照组[(12.2±4.4)mm/mm2比(15.1±4.5)mm/mm2, P=0.028;(50.8±24.0)个/mm...     

The clinical pattern differentiates ANCA-positive infective endocarditis patients from ANCA-associated vasculitis patients: a 23 years’ retrospective cohort study in China and follow-ups

Clinical Rheumatology - Patients with infective endocarditis (IE) may present rheumatic manifestations concurrent with various autoantibodies and thus mimic antineutrophil cytoplasmic antibody...     

系统性红斑狼疮中A20表达特点的研究

目的:了解系统性红斑狼疮(SLE)患者外周血中肿瘤坏死因子α诱导蛋白3(TNFAIP3,也称A20)、核因子κB(NF-κB)、黏膜相关淋巴瘤易位基因1(MALT1)及其转录本1(MALT1V1)的mRNA表达特点。方法:采用real-time PCR法检测21例SLE患者(其中合并硬皮症2例,合并类风湿关节炎1例,合并淋巴瘤1例)及31例健康人外周血单个核细胞(PBMC)中MALT1、A20、NF-κB和MALT1V1 mRNA的表达情况。结果:SLE样本中,A20 mRNA表达水平较健康人明显降低(P0.01),MALT1和NF-κB也较健康人降低(P0.01)。在健康人组,A20和NF-κB mRNA的表达水平未呈现明显相关性,MALT1和NF-κB则呈正相关(P0.05);而在SLE组中,A20和NF-κB mRNA则显示出显著正相关(P0.05),MALT1和NF-κB则不存在相关性。SLE中MALT1V1表达量显著低于正常人(P0.05),相关性研究还显示,健康人中A20和MALT1V1存在正相关关系(P0.01),在SLE中则不存在(P0.05)。结论:本研究首先提供了MALT1-A20-NF-κB通路在SLE中的表达特点。SLE患者异常低表达A20,这可能与患者低免疫耐受相关,其与NF-κB表达的正相关性情况可能与其它因素的调控有关,有待进一步证实。     

白细胞介素21在小鼠病毒性心肌炎中的表达及其与抗ANT抗体的相关性

目的:观察病毒性心肌炎(VMC)小鼠急性期不同时点白细胞介素21(IL-21)的表达及其与抗腺嘌呤核苷酸转位子(adenine nucleotide translocator,ANT)抗体的相关性,探究其在VMC发病中的作用及意义。方法:BALB/c小鼠腹腔注射柯萨奇病毒B3(CVB3)建立VMC模型,腹腔注射等量PBS的BALB/c小鼠作为对照组,在注射的第0、1、2、3、4和6周,应用荧光定量逆转录-聚合酶链反应(qRT-PCR)检测小鼠心肌组织中IL-21mRNA的表达、酶联免疫双夹心抗体法(ELISA)检测血清IL-21蛋白及抗ANT抗体的表达。结果:与对照组比较,VMC小鼠心肌组织中IL-21mRNA及血清中IL-21自1周开始高表达,2周时达峰值,并维持高表达至6周,各时点表达量均高于相应时点的对照组(P<0.05)。血清中抗ANT抗体在第1周时开始升高,2周时达峰值,维持高水平表达至第6周,除0周时点外,VMC小鼠与对照组小鼠比较差异均有统计学意义(P<0.05),Pearson相关分析显示,IL-21与抗ANT抗体存在相关性(r=0.88,P<0.01)。结论:IL-21在VMC小鼠心肌组织及外周血中高表达,并与血清抗ANT抗体呈正相关,提示IL-21参与VMC的发病过程。     

数值模拟松质骨中流动电势分布

目的对压力驱动下一种松质骨细观模型产生的流动电势进行数值模拟分析,了解流动电势在松质骨中的分布特点。方法根据电场和流体的控制方程,利用有限单元法计算该松质骨模型在一定压力下产生的稳态流动电势。结果松质骨模型中靠近固体表面的流动电势较大,约为43.4μV;而远离固体表面的流动电势较小,约为19.7μV。压力和Zeta电势对模型的流动电势影响比较大,并且呈线性增长的关系。离子数浓度较低时,离子数浓度对流动电势的影响较大;当离子数浓度较高时,离子数浓度对流动电势的影响很小。结论研究结果为利用电流、电磁场刺激等方法防治和治疗临床骨折、老年性骨质疏松及其他骨科疾病提供相关的理论依据。     

动态轴向压应变促进丝素蛋白支架内MC3T3-E1细胞成骨分化

目的 观察动态轴向压应变对三维丝素蛋白支架内成骨细胞成骨相关基因表达的影响。方法 应用动态力学加载仪对实验组小鼠胚胎成骨细胞MC3T3-E1加载动态轴向压应变（5%应变幅度,1 Hz,30 min/d,共21 d）,对照组细胞常规静置培养,不施加力学刺激。应用定量PCR检测细胞成骨基因碱性磷酸酶（ALP）、I型胶原（COLⅠ）、骨特异性转录因子（Runx2）、成骨相关转录因子（Osx）、骨钙蛋白（OCN） mRNA表达量。结果 成骨细胞在周期性轴向压应力刺激下,Runx2、Osx及COLⅠ表达分别增加280%、68.9%和79.6%,ALP及OCN表达也分别增加10.7%和26.9%。实验组成骨相关基因mRNA表达与对照组比较,差异具有统计学意义（P<0.05）。结论 成骨细胞复合丝素蛋白生物支架材料在周期性轴向压应力刺激下,成骨基因COLⅠ、Runx2、Osx及OCN表达明显上调,可能是生理状态下压应力刺激促进骨折愈合的重要机制之一。研究结果对于以力学信号为基础的细胞疗法修复骨缺损等疾病具有重要临床价值。     

慢性阻塞性肺疾病患者甲状腺激素水平变化的临床分析

目的 检测慢性阻塞性肺疾病(COPD)患者血清甲状腺激素水平的变化,并分析其临床意义.方法 应用化学发光微粒子免疫分析方法检测84例住院COPD患者急性发作时和好转出院2周后血清中TT3、TT4、FI3、FT4、高敏促甲状腺激素(sTSH),并与60名健康志愿者的甲状腺激素水平相互比较.结果 COPD患者的TT3、TT4、FT3、FT4水平明显低于对照组,sTSH高于对照组.在COPD组中TT3、FT3低于正常值的比例明显高于TT4和FT4.COPD患者出院2周后的甲状腺激素水平有一定程度的升高,但仍低于对照组.结论 COPD患者的甲状腺激素水平发生变化,多数表现为低T3综合征,可通过检测激素水平指导COPD患者的治疗和预测预后.     

Brain injury-associated biomarkers of TGF-beta1, S100B,GFAP, NF-L,tTG, AbetaPP,and tau were concomitantly enhanced and the UPS was impaired during acute brain injury caused by <Emphasis Type="Italic">Toxocara canis</Emphasis>in mice

Background  

Because the outcomes and sequelae after different types of brain injury (BI) are variable and difficult to predict, investigations on whether enhanced expressions of BI-associated biomarkers (BIABs), including transforming growth factor β1 (TGF-β1), S100B, glial fibrillary acidic protein (GFAP), neurofilament light chain (NF-L), tissue transglutaminases (tTGs), β-amyloid precursor proteins (AβPP), and tau are present as well as whether impairment of the ubiquitin-proteasome system (UPS) is present have been widely used to help delineate pathophysiological mechanisms in various BIs. Larvae of Toxocara canis can invade the brain and cause BI in humans and mice, leading to cerebral toxocariasis (CT). Because the parasitic burden is light in CT, it may be too cryptic to be detected in humans, making it difficult to clearly understand the pathogenesis of subtle BI in CT. Since the pathogenesis of murine toxocariasis is very similar to that in humans, it appears appropriate to use a murine model to investigate the pathogenesis of CT.     

Genetic association of vitamin D receptor polymorphisms with autoimmune hepatitis and primary biliary cirrhosis in the Chinese

BACKGROUND: Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are two autoimmune diseases of unknown etiology. Genetic factors appear to be involved in the pathogenesis of both diseases. Vitamin D has been shown to exert multiple immunomodulatory effects, which acts through its own receptor (VDR). Polymorphisms of VDR had been implicated in several autoimmune diseases. In the present study, the association between Chinese patients with AIH, PBC and the polymorphisms in exon 2, intron 8 and exon 9 of vitamin D receptor genes was studied. METHODS: Four candidate gene loci were investigated in 49 patients with AIH, 58 patients with PBC, and 160 healthy controls. The VDR polymorphisms were assessed by FokI, BsmI, ApaI, and TaqI endonuclease digestion after specific polymerase chain reaction (PCR) amplification. RESULTS: The result show a significant difference in FokI polymorphism between AIH patients and controls (chi(2) = 5.47, P = 0.019), and a significant association in BsmI polymorphisms between PBC patients and controls (chi(2) = 6.52, P = 0.01). Furthermore the distribution of FokI, BsmI, ApaI, and TaqI gene types differed between Chinese healthy controls and Caucasian healthy controls. CONCLUSION: It is suggested that there is a genetic link of VDR polymorphisms to autoimmune liver diseases such as AIH and PBC in Chinese patients. Further studies are needed to elucidate the mechanisms by which VDR polymorphisms contribute to the lose of immune tolerance in autoimmune diseases.     

Adenosine-mediated bronchoconstriction and lung inflammation in an allergic mouse model

In this study, we studied the role of adenosine on airway responsiveness and airway inflammation using an allergic mouse model. Mice were sensitized by two i.p. injections of ragweed and three consecutive ragweed aerosol challenges. It was found that inhalation of adenosine causes a dose-related bronchoconstriction in this model. Ragweed sensitized and challenged mice showed increased sensitivity to airway challenge to adenosine compared to control animals. Theophylline, a non-selective adenosine receptor antagonist, blocked adenosine-induced bronchoconstriction, but was unable to inhibit bronchoconstrictor response to methacholine. Mice systemically sensitized and airway challenged with allergen showed a marked airway inflammation manifesting increases in eosinophils, lymphocytes and neutrophils, and decrease in macrophages. Twenty-four hours after airway challenge with allergen, aerosolization of adenosine further potentiated the allergen-induced airway inflammation. Cells in bronchoalveolar lavage fluid after adenosine aerosolization increased by 3.07-fold as compared to control mice, and by 1.8-fold compared to ragweed sensitized and challenged mice. The increases in eosinophils, lymphocytes, and neutrophils caused by allergen were potentiated after adenosine challenge. Unexpectedly, macrophages significantly decreased after adenosine challenge. Theophylline attenuated adenosine-enhanced airway inflammation, but could not reverse allergen-induced airway inflammation. These findings suggested that specific adenosine receptors contribute to airway responsiveness and airway inflammation associated with this model of allergic asthma.