聚集蛋白聚糖基因串联重复多态性和肥胖交互作用与中国北方男性腰椎间盘突出症易感性的关系

目的:探讨中国北方汉族男性人群聚集蛋白聚糖(Aggrecan)基因串联重复多态性(variable number of tandem repeat,VNTR)与肥胖的交互作用对腰椎间盘突出症(LDH)发病的影响.方法:收集2004年1月～2015年12月在中国医科大学附属第一医院骨科住院且符合纳入及排除标准的299例男...     

医用线性回归变量变换及诊断

本文运用近代回归分析的原理和方法，将残差图和偏回归杠杆图作为诊断回归模型缺陷的工具，利用变量变换使资料满足线性回归模型的基本要求。实例分析表明，这些方法在诊断模型缺陷。决定相应处理措施以及改进模型回归效果等方面均取得了满意效果。     

从人外周血淋巴细胞扩增抗体可变区基因的3种方法

介绍了从人外周血淋巴细胞（ＰＢＬ）以传统方法提取总ＲＮＡ再行反转录ＰＣＲ（ＲＴ－ＰＣＲ）、以Ｔｒｉｚｏｌ Ｒｅａｇｅｎｔ提取ＲＮＡ再行ＲＴ－ＰＣＲ以及细胞内直接ＲＴ－ＰＣＲ等３种方法扩增人抗体可变区（Ｖ区）基因的方法并作了比较。３种方法均扩增出了人抗体ＶＨ、Ｖκ、Ｖλ基因，从方法的简便及结果的可靠等方面综合考虑，作者推荐以Ｔｒｉｚｏｌ Ｒｅａｇｅｎｔ提取ＲＮＡ再行ＲＴ－ＰＣＲ扩增的方法。     

Antitumor efficacy of MUC1-derived variable epitope library treatments in a mouse model of breast cancer

The identification of novel targets for cancer immunotherapy and the development of new vaccine immunogens are subjects of permanent interest. MUC1 is an overexpressed antigen found in most tumors, and its overexpression correlates with poor prognosis. Many attempts to direct the immune response against MUC1 in tumor cells have failed, including several clinical trials. We have previously developed an innovative Variable Epitope Library (VEL) vaccine platform that carries massively substituted mutant variants of defined epitopes or epitope regions as an alternative to using wild-type peptide sequences-based immunogens. Here, two murine MUC1-derived epitopes equivalent to the previously tested in cancer immunotherapy human MUC1 regions were used to generate VELs. We observed that vaccination with the 23L VEL immunogens, encompassing the entire signal peptide region of MUC1, reduces the tumor area compared to the wild-type sequence treatment. Contrastingly, vaccination with the MUC1 signal peptide-derived predicted CD8⁺+ T cell epitope-based VEL, 9MUC1spL, showed similar tumor area reduction as the wild-type treatment; however, a decrease in lung metastasis after 9MUC1spL treatment was observed. In addition, vaccination induced a large pool of CD8⁺ T cells which recognized most variant epitopes from 9MUC1spL. Also, we generated MUC1 variable number tandem repeat (VNTR)-based VELs that reduced the metastatic burden when dendritic cells and M13 recombinant bacteriophages were used as vaccine carriers. Collectively, our data demonstrate the immunogenic and antitumor properties of MUC1 signal peptide- and VNTR-derived VEL immunogens.     

不同可变数目串联重复序列组合对中国流行结核分枝杆菌分辨力的评价研究

目的 在规范化的结核分枝杆菌（Mycobacterium tuberculosis,MTB）可变数目串联重复序列（variable number of tandem repeats,VNTR）基因分型的基础上,构建我国31个省（自治区、直辖市）VNTR数据库,每个省优化一套VNTR位点组合,为我国结核病预防控制策略的制定提供科学依据。方法 对2007－2008年全国结核病耐药性基线调查的4 116株MTB15位点VNTR（15-VNTR）基因分型。汉高指数（Hunter-Gaston Index,HGI）分析每个位点的分辨率。依据谱系流行特征,以分辨率高和稳定性强为原则,为各省设计一套VNTR优化组合（12-VNTR、10-VNTR、8-VNTR和5-VNTR）,采用HGI和成簇率进行评价。结果 完成了涵盖率为96.36%（3 966/4 116）MTB完整15-VNTR图谱。发现QUB11b、MIRU26等7个高分辨率位点;QUB26、MIRU16、Mtub21、QUB11b在部分地区遗传稳定性差。内蒙古自治区、重庆市、黑龙江省的最优组合为10-VNTR,其他各省的最佳组合为8-VNTR。结论 VNTR数据库的建立将推动全国范围MTB传染源的追踪;各省优化VNTR组合的推出有助于当地结核病疫情的监测和群体遗传学的研究。     

磁共振3D-SPACE在原发性三叉神经痛诊断中的应用

目的探讨MR变翻转角的三维快速自旋回波序列(3D-SPACE)对原发性三叉神经痛的应用价值。方法对39例原发性三叉神经痛患者于1.5T磁共振扫描仪上行3D-SPACE序列成像并多平面重建,分析患侧组与健侧组三叉神经与邻近血管关系。结果原发性三叉神经痛患侧组39侧神经,31例(31/39)表现为神经受压或移位;健侧39侧神经,25例(25/39)表现为神经血管关系阴性;健侧组与患侧组神经血管关系密切阳性率及三叉神经受压推移率的差异具有统计学意义(P0.05)。结论 3D-SPACE序列可以清晰显示三叉神经与邻近血管的关系,为临床治疗及决策提供更准确的影像学诊断依据。     

High-Dimensional Smoothing Splines and Application in Alzheimer’s Disease Prediction Using Magnetic Resonance Imaging

Abstract

Recent evidence has shown that structural magnetic resonance imaging (MRI) is an effective tool for Alzheimer’s disease (AD) prediction. While traditional MRI-based prediction uses images acquired at a single time point, a longitudinal study is more sensitive and accurate in detecting early pathological changes of the AD. Two main statistical difficulties arise in the longitudinal MRI-based analysis: (i) the inconsistent longitudinal scans among subjects (i.e., the different scanning time and the different total number of scans); (ii) the heterogeneous progressions of high-dimensional regions of interest (ROIs) in MRI. In this work, we propose a new feature selection and estimation method which can be applied to extract AD-related features from the heterogeneous longitudinal MRI. A key ingredient of our approach is a hybrid of the smoothing splines and the l₁-penalty. Smoothing splines can integrate information from heterogeneous progressions of ROIs and adapt to inconsistent scans of MRIs. The selection property of the l₁-penalty helps to select important ROIs related to AD. We introduce an efficient algorithm to perform the proposed method. Real data experiments on the Alzheimer’s Disease Neuroimaging Initiative database are provided to corroborate some advantages of the proposed method for AD prediction in longitudinal studies.