吡那地尔对高血压心脏结构和功能重构的影响

在等降压剂量下吡那地尔和赖诺普利可使４月龄自发性高血压大鼠的血压下降６．０￣８．０ｋＰａ，并接近同种属正常血压大刀瓣血压水平。     

基于贝叶斯多变量联合模型的体检人群脑卒中发病风险因素的纵向研究

背景 脑卒中是目前影响人类健康的主要公共卫生问题之一;健康体检纵向数据累积了大量的健康信息,由于缺失数据多、样本量小等诸多问题,导致其利用率低、重要信息未能得到充分挖掘,进而对常见慢性病的有效防控等工作带来一定困难。目的 基于贝叶斯多变量联合模型,探讨体检人群脑卒中发病风险因素,为慢性病风险因素分析提供新的方法。方法 本研究使用空军军医大学西京医院健康医学中心2008—2015年的体检资料。随访情况：以首次发生脑卒中为结局事件,发生结局事件立即停止随访;若未发生,到2015年体检信息收集完成后结束随访;体检间隔时间为1年。依据随访过程中是否发生脑卒中分为脑卒中组和非脑卒中组。纵向观察变量包括总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）、体质指数（BMI）和收缩压（SBP）。采用多因素Cox回归模型分析基线情况对脑卒中结局事件的影响;采用贝叶斯多变量联合模型,分析随访过程中TC、TG、LDL-C、HDL-C、BMI和SBP的纵向变化轨迹对脑卒中发病的影响。结果 本研究共纳入234例研究对象,1 581条纵向随访记录,平均随访时间为...     

明胶-聚乳酸载药纳米微球的制备及其体外释药研究

采用复合乳液—溶剂挥发法制得明胶—聚乳酸载五氟脲嘧啶(5—Fu)微球，以混合型乳化剂Tween—80：Span—80＝5：1—作为初乳乳化剂，O—羧甲基壳聚糖作为复乳乳化剂，考察了明胶—聚乳酸载药微球的制备条件对微球的成球性、药物包封率及体外释药的影响。结果表明乳化剂的选择、内部水相药物浓度和PLA分子量等均对载药微球的结构与性能产生影响，经优化条件得到了成球性和体外释放都比较好的载药微球。     

Application of phage display peptide library to autoimmune diabetes: identification of IA-2/ICA512bdc dominant autoantigenic epitopes

Autoantigenic epitope mapping represents a critical issue in autoimmune diseases. The islet tyrosine phosphatase-like protein IA-2/ICA512bdc is a major autoantigen in type 1 diabetes (IDDM), but the epitopes responsible for autoantibody binding have been only partially defined. The aim of our study was to identify ICA512bdc epitopes, and in particular mini-epitopes, utilizing a novel strategy for autoimmune diseases. The study was performed in three sequential steps: (1) construction of a lambda-phage surface-displayed ICA512bdc cDNA library with the methodology of tagged random priming with peptides displayed as a fusion to the C terminus of the capsid protein D; (2) affinity selection of the resulting library, followed by immunoscreening, enzyme-linked immunosorbent assay and sequence analysis of positive clones, and (3) radioimmunoprecipitation to detect autoantibodies to the selected clones. This strategy resulted in the identification of two epitopes (IA-2 residues 761 - 964 and 929 - 979), which were recognized by 100 % and 62.9 % ICA512bdc-positive IDDM patients, respectively. Interestingly, the larger clone was detected also by a proportion (16.7 %) of new onset ICA512bdc-negative patients, thus suggesting that this region contains not only the main autoantigenic repertoire of ICA512bdc molecule, but is able to detect IA-2 autoantibodies in even higher percentages of patients. In addition, this study showed the existence of multiple epitopes located in the C-terminal domain of the IA-2 protein, one of which is formed by the 50 C-terminal amino acids, and provided evidence that the strategy used represents a valid tool for identification of epitopes within autoantigenic molecules.     

Studies on mutants deficient in the photosystem I reaction centers in Chlamydomonas reinhardtii

Summary Genetic analysis of 25 nuclear mutants defective in the chlorophyll-protein complex CP1 was undertaken. The mutants belong to 13 complementation groups scattered throughout the nuclear genome. All these mutants lack the apoprotein of CP1 and, in addition, a specific set of six low molecular weight thylakoid polypeptides. System I particles obtained by treating WT thylakoid membranes with detergent specifically contain those polypeptides which the mutants lack. These observations suggest that a particular sub-structure of the thylakoid membrane associated with the photosystem I activity is missing from all 25 mutants studied, and that this general phenotype can result from mutation at any one of several unlinked Mendelian loci.     

用细胞酶联免疫吸附法筛选分泌抗人B细胞分化抗原单抗的杂交瘤

用活化的人Ｂ细胞株３Ｄ５细胞免疫ＢＡＬＢ／Ｃ小鼠，取小鼠脾脏细胞与ＳＰ２／０细胞融合，融合后细胞置甲基纤维素半固体培养基生长。以０．５％甲醛处理的３Ｄ５细胞和ＣＥＭ细胞包被酶细胞反应阳性而与ＣＥＭ细胞反应阴性的克隆。再经间接免疫荧光染色后，用流式细胞仪复测以上所得３３个阳性克隆，结果３Ｄ５阳性ＣＥＭ阴性者２７例，占８１．８２％，表明ＣＥＬＩＳＡ法是一个粗筛抗人Ｂ细胞分化抗原的简便有效方法。     

CD1d deficiency exacerbates inflammatory dermatitis in MRL-lpr/lpr mice

Mechanisms responsible for the development of autoimmune skin disease in humans and animal models with lupus remain poorly understood. In this study, we have investigated the role of CD1d, an antigen-presenting molecule known to activate natural killer T cells, in the development of inflammatory dermatitis in lupus-susceptible MRL-lpr/lpr mice. In particular, we have established MRL-lpr/lpr mice carrying a germ-line deletion of the CD1d genes. We demonstrate that CD1d-deficient MRL-lpr/lpr mice, as compared with wild-type littermates, have more frequent and more severe skin disease, with increased local infiltration with mast cells, lymphocytes and dendritic cells, including Langerhans cells. CD1d-deficient MRL-lpr/lpr mice had increased prevalence of CD4(+) T cells in the spleen and liver and of TCR alpha beta (+)B220(+) cells in lymph nodes. Furthermore, CD1d deficiency was associated with decreased T cell production of type 2 cytokines and increased or unchanged type 1 cytokines. These findings indicate a regulatory role of CD1d in inflammatory dermatitis. Understanding the mechanisms by which CD1d deficiency results in splenic T cell expansion and cytokine alterations, with increased dermal infiltration of dendritic cells and lymphocytes in MRL-lpr/lpr mice, will have implications for the pathogenesis of inflammatory skin diseases.     

抗汉坦病毒单克隆抗体F（ab‘）2的制备及其纯度和活性鉴定

利用木瓜蛋白酶分别制备了抗汉坦病毒鼠源性单克隆抗体（ｍＡｂ）３Ｇ１和３Ｄ８Ｆ（ａｂ′）２片段。通过ＷａｔｅｒＤＥＡＥ４０ＨＲ阴离子交换色谱柱纯化后，非还原型ＳＤＳＰＡＧＥ呈现单一条带，相对分子质量（Ｍｒ）约１０００００。两种Ｆ（ａｂ′）２片段均具有良好的血凝抑制活性、病毒中和活性及对汉坦病毒感染乳鼠的保护作用     

STAT3 couples with 14-3-3σ to regulate BCR signaling,B-cell differentiation,and IgE production

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Pleiotropic genomic variants at 17q21.31 associated with bone mineral density and body fat mass: a bivariate genome-wide association analysis

Osteoporosis and obesity are two severe complex diseases threatening public health worldwide. Both diseases are under strong genetic determinants as well as genetically correlated. Aiming to identify pleiotropic genes underlying obesity and osteoporosis, we performed a bivariate genome-wide association (GWA) meta-analysis of hip bone mineral density (BMD) and total body fat mass (TBFM) in 12,981 participants from seven samples, and followed by in silico replication in the UK biobank (UKB) cohort sample (N = 217,822). Combining the results from discovery meta-analysis and replication sample, we identified one novel locus, 17q21.31 (lead SNP rs12150327, {"type":"entrez-nucleotide","attrs":{"text":"NC_000017.11","term_id":"568815581"}}NC_000017.11:g.44956910G > A, discovery bivariate P = 4.83 × 10⁻⁹, replication P = 5.75 × 10⁻⁵) at the genome-wide significance level (ɑ = 5.0 × 10⁻⁸), which may have pleiotropic effects to both hip BMD and TBFM. Functional annotations highlighted several candidate genes, including KIF18B, C1QL1, and PRPF19 that may exert pleiotropic effects to the development of both body mass and bone mass. Our findings can improve our understanding of the etiology of osteoporosis and obesity, as well as shed light on potential new therapies.Subject terms: Genome-wide association studies, Gene expression profiling