不同磷脂肽段诱导的实验性自身免疫性脑脊髓炎模型病理特征多样性的研究

目的:探索是否不同磷脂肽段可以诱导Lewis大鼠产生不同的病理学表现。方法:采用髓鞘碱性蛋白82-99(MBP82-99)、MBP68-86、髓鞘少突胶质细胞糖蛋白35-55(MOG35-55)免疫Lewis大鼠,每天进行神经功能评分。免疫后取各组大鼠大脑、小脑、脑干和脊髓组织,观察炎性细胞浸润部位和浸润程度、有无脱髓鞘和轴索损害。结果:MBP68-86和MBP82-99两组大鼠的大脑、脑干、小脑和脊髓组织均有炎性细胞浸润,脊髓炎症程度重于其他部位;MBP68-86和MBP82-99诱导的脊髓炎症程度无统计学差异;MOG35-55组大鼠仅脊髓组织受累,且炎症程度明显低于MBP组,其余各组未见炎性细胞浸润。各组大鼠神经组织均未见脱髓鞘和轴索受累。结论:不同磷脂肽段诱导Lewis大鼠神经组织炎性细胞浸润的分布和程度不同。     

军医大学各专业学员的典型人格类型分析

目的：调查军医大学不同专业学员人格类型的异同,寻找各专业的典型人格,为进一步探讨人格类型与专业的匹配情况,开展教育教学工作提供依据。方法：应用迈尔斯类型指标（ MBTI）量表,调查某军医大学所有在校学员的个性类型。结果：①不同专业学员在MBTI每个维度的百分比均有差异（χ2＝24．988,23．653,25．641,24．567;P均＜0．05）;②不同专业学员的16种人格类型比较均有统计学差异（χ2＝5．421,1．289,3．070,2．468,1．526,56．778,1．246,2．371,6．260,1．965,3．529,2．112,3．553,1．784,3．930,4．866;P均＜0．001））。其中ESFJ比例最高的是护理、海医学员（21．30％、19．8％）;ISTJ比例最高的是心理、药学、生物技术学员（23．1％、22．1％、18．2％）;INFP比例最高的是卫管、中医学员（24．2％、17．6％）;③不同专业学员8种偏好的标准化分数比较均有不同（F＝3．002,3．010,2．875,2．070,2．825,2．825,2．162,2．170;P均＜0．05）。结论：军医大学各专业学员大多有典型人格类型,存在一定相似性;要根据军医大学不同专业学员的个性特点进行针对性的教学。     

采用不同方法检测幽门螺杆菌的感染情况

目的 探讨几种不同方法检测幽门螺杆菌感染的临床效果,分析幽门螺杆菌感染与性别、年龄及疾病的相关性.方法 选取2012年8月至2014年8月在我院消化科门诊就诊的806例患者,分别采用尿素呼气试验法,免疫胶体金法以及病理组织切片染色镜检进行检测,以尿素呼气试验法作为金标准,比较免疫胶体金法与病理组织切片染色镜检法检测Hp的阳性预期值、阴性预期值、敏感度、特异性并比较不同性别、不同年龄及不同疾病Hp的感染率.结果 Hp检出率为37.5％,其中男性感染率为37.3％,女性为37.7％,差异无统计学意义(P＞0.05);随着年龄增长Hp感染率有升高趋势,差异有统计学意义(P＜0.05);确诊为慢性胃炎、消化性溃疡、胃息肉、胃癌的Hp感染率分别为48.6％、50.2％、21.6％、13.8％,慢性胃病的发生与幽门螺杆菌感染有一定的关联.免疫胶体金法以及病理组织切片染色镜检的敏感度分别为83.77％、93.05％,特异性分别为75.20％、83.53％,阳性预期值分别为66.93％、77.20％,阴性预期值为分别为88.55％、95.25％.结论 胶体金法适用于大批量的流行病学调查,病理组织切片染色镜检敏感性高,可作为Hp感染筛查的方法之一.Hp感染率与年龄、疾病种类相关,与性别无关,为幽门螺杆菌感染的流行病学资料提供依据.     

肥胖及2型糖尿病患者血清apelin水平及其相关因素分析

目的测定肥胖及新诊断2型糖尿病患者血清apelin水平，探讨apelin与体脂、糖、脂代谢、胰岛素抵抗等的相关性。方法62例2型糖尿病患者和72例正常糖调节（NGR）者按体重指数（BMI）≥25kg／m^2或〈25kg／m^2又各自分为超重／肥胖与正常体重亚组，采用放射免疫分析法检测空腹血清apelin水平，同时检测空腹血糖（FPG）、HbA1C、血脂各项指标及空腹胰岛素（FINS）水平，计算BMI和腰臀比，并以稳态模型计算胰岛素抵抗指数（HOMA-IR）。结果校正年龄及性别后，2型糖尿病组血清apelin水平高于NGR组[（317．9±99．6vs279．0±66．8）ng／L，P〈0．01]，2型糖尿病组和NGR组中的超重／肥胖者均高于非肥胖者[（354．0±114．4vs274．1±53．0）ng／L，（299．2±74．5vs252．8±48．9）ng／L，均P〈0．05]，且2型糖尿病超重／肥胖组明显高于NGR肥胖组（P〈0．01）；偏相关分析显示，空腹血清apelin与BMI、ln（HOMA-IR）、FPG、总胆固醇（TC）呈正相关（r=0．353，r=0．355，r=0．224，r=0．241，均P〈0．01），与腰围、收缩压呈正相关（r=0．263，r=0．183，P〈0．05）。多元逐步回归分析发现，BMI、ln（HOMA—IR）和TC是血清apelin的独立相关因素。结论血清apelin水平在肥胖和初发的2型糖尿病人群中升高，且与BMI、HOMA-IR及脂代谢相关，推测apelin可能参与构成胰岛素抵抗综合征的病理生理基础。     

Latent autoimmune hepatitis triggered during interferon therapy in patients with chronic hepatitis C

Interferon can induce autoantibodies and autoimmune reactions. This study reviewed the clinical, serological, and HLA phenotypical features of patients who developed autoimmune hepatitis during interferon therapy for chronic hepatitis C, analyzing their response to immunosuppressive treatment. The diagnosis of chronic hepatitis C was based on positivity for viral RNA and a liver biopsy specimen obtained before interferon treatment. Sera were tested for autoantibodies by indirect immunofluorescence assay. HLA typing was performed by applying a standard microlymphocytotoxicity method. Of 144 patients with chronic hepatitis C treated with interferon, 7 women deteriorated during treatment; serum transaminase, γ-globulin, and immunoglobulin G levels increased; and serum autoantibodies became positive. Interferon was interrupted, a diagnosis of autoimmune hepatitis was established, and immunosuppressive therapy was initiated. All patients responded to this treatment. The 7 patients had similar HLA typing to those with autoimmune hepatitis, with DR4 in 2 patients (67%) with type 2 autoimmune hepatitis, and with DR3 and DR52 in 2 (50%) and 4 (100%) patients, respectively, with type 1 autoimmune hepatitis; additionally, 5 patients (71%) had DQ2, and 4 (57%) had both DR52 and DQ2. In female patients with chronic hepatitis C, a genetic susceptibility to autoimmune hepatitis may exist, possibly triggered by immunostimulating effects during interferon therapy. Immunosuppressive treatment has been well tolerated and seems to be effective.     

Is β-cell failure in type 2 diabetes mellitus reversible?

BACKGROUND:

In the UK Prospective Diabetes Study (UKPDS), many subjects maintained glycemic goal (HbA_1c < 7.0%) at 9 years, showing that β-cell function was preserved and that the initial decline in β-cell function recovered with sulphonylureas. Moreover, obese subjects using high daily doses of insulin for several years rarely require insulin or oral hypoglycemic agents to maintain their glycemic goal following weight loss achieved by gastric bypass surgery. Thus, declining β-cell function during the course of type 2 diabetes mellitus (T2DM) is neither universal nor permanent.

OBJECTIVE:

To assess β-cell function in morbidly obese subjects before insulin withdrawal and on attaining the glycemic goal with weight loss and oral agents.

MATERIALS AND METHODS:

Serum C-peptide (CPEP) and glucose (G) concentrations were determined up to 180 min during an oral glucose tolerance test (OGTT) with 75 glucose in 10 obese men with T2DM, before insulin withdrawal, and on achieving the glycemic goal with metformin, glimepiride, and weight loss. Ten age-matched healthy men participated as controls. Cumulative responses (CR) of CPEP and G were calculated by adding differences between the level at each time-period during OGTT and fasting (F) concentration. β-Cell function was expressed as the FCPEP as well as the insulinogenic index (CRCPEP/CRG). Insulin sensitivity was determined as FCEP × FG.

RESULTS:

FCPEP was decreased, though still present, prior to insulin withdrawal. Moreover, on attaining the glycemic goal over 6-9 months, FCPEP, CRPEP/CRG, and FCPEP × FG improved markedly (P < 0.001).

CONCLUSION:

Decline in β-cell function in morbidly obese T2DM may not be progressive and is reversible on improving insulin sensitivity and on eliminating the inhibition by exogenous insulin.     

Interferon-γ secretion defects in haemophilia A patients receiving highly purified plasma-derived or recombinant factor VIII

The outcome of developing immune responses is influenced by interactions among a large and complex network of secreted cytokines. T-cell secretion of interferon-γ (IFN-γ), tumour necrosis factor α (TNF-α) and TNF-β, or lymphotoxin contributes to the development of cell-mediated immunity, whereas secretion of interleukin (IL)-4, IL-5 and IL-6 contributes to development of humoral immunity. Humoral immunity to factor VIII (FVIII) develops in approximately 25% of severe haemophilia A patients. The aim of our research was to understand the underlying immune response to FVIII in patients with FVIII inhibitors. We report a defect in IFN-γ secretion by peripheral blood mononuclear cells (PBMC) derived from haemophilia A patients, which was accompanied by a low level of mitogen-induced proliferation and a significant decrease in the percentage of natural killer (NK) cells. All of the observed defects were found in haemophilia A patients, both with and without FVIII inhibitors, who were free of viral infection and had been treated predominantly or exclusively with monoclonal antibody-purified or recombinant FVIII.     

Effects of AT1 receptor antagonist, losartan, on rat hepatic fibrosis induced by CCl(4)

AIM:To investigate effect of losartan, an AT1 receptor antagonist, on hepatic fibrosis induced by CCl(4); and to determine whether or not AT1 receptors are expressed on hepatic stellate cells. METHODS AND RESULTS:Fifty male Sprague-Dawley rats, weighing (180 plus minus20)g, were randomized into five groups (control group, model group, and three losartan treated groups), in which all rats were given the subcutaneous injection of 40% CCl(4)(every 3 days for 6 weeks) except for rats of control group. Rats of losartan-treated groups were treated with losartan (20 mg/kg, 10 mg/kg, 5 mg/kg, daily gavage). After 6 weeks liver tissue and serum samples of all rats were examined. Serum hyaluronic acid (HA), procollagen type III (PC III) were detected by radioimmunoassays. van Giesion collagen staining was used to evaluate the extracellular matrix of rats with liver fibrosis. The expression of AT1 receptors, transforming growth factor-beta (TGF-beta), and alpha-smooth muscle actinalpha-SMA) in liver tissue were determined by immunohistochemical techniques. Compared with model group, serum ALT and AST of losartan-treated groups were significantly reduced (italic>t = 4.20,P < 0.01 and italic>t = 4.57,P < 0.01). Serum HA and PC III also had significant differences (italic>t = 3.53,P<0.01 and t=2.20, P<0.05). The degree of fibrosis was improved by losartan and correlated with the expressions of AT1 receptors, TGF-beta, and alpha-SMA in liver tissue.CONCLUSION:AT1 receptor antagonist, losartan, could limit the progression of the hepatic fibrosis induced by CCl(4). The mechanism may be related to the decrease in the expression of AT1 receptors and TGF-beta, ameliorating the injury of hepatocytes; activation of local renin-angiotensin system might relate to hepatic fibrosis; and during progression of fibrosis, activated hepatic stellate cells might express AT1 receptors.     

Identification of new type 2B von Willebrand disease mutations: Arg543Gln, Arg545Pro and Arg578Leu

We report the identification in five patients (three families) affected with type 2B von Willebrand disease (VWD) of three heterozygous nucleotide substitutions at the codon for arginine 543, 545 and 578 of the mature von Willebrand factor (VWF) subunit resulting in a glutamine, proline and leucine substitution, respectively. These mutations are located in the A1 loop where prevalent type 2B mutations (Arg543Trp, Arg545Cys and Arg578Gln) have been already identified at the same positions. By in vitro mutagenesis of full-length cDNA of VWF and transient expression in Cos-7 cells, we have shown that the six corresponding mutated recombinant VWFs (Gln543, Trp543, Cys545, Pro545, Leu578 and Gln578 rVWF) exhibited quantitatively normal expression and normal multimeric pattern but increased ristocetin- and botrocetin-induced binding to platelets as compared with that for wild-type rVWF. The two mutations at position 545 induced the greatest reactivity for GPIb of corresponding rVWFs as compared to the two mutations at positions 543 and 578.