基于互信息研究的乳腺癌与阿尔茨海默症的免疫系统发病机理探寻

近年来,越来越多的流行病学研究显示多种癌症与阿尔茨海默症(AD)呈现负相关,但分子生物学机制尚不明确。从基因信号传导及调控网络构建方面研究这种负相关,将对两种疾病致病机理的探寻起重要作用。选取乳腺癌(BC)与AD进行对比研究。考虑到传统特征基因提取方法注重单个基因在不同样本中的表达差异而忽视基因之间的关联性,从基因之间的关联性出发,利用互信息(MI)首先提取两种疾病中共有的差异表达基因作为特征基因。在此基础上,鉴于网络成分分析(NCA)约束条件较强、运行时间过长等局限性,采用快速网络成分分析算法(FastNCA),推演出特征基因中转录因子的表达活性及其对靶基因的调控强度,并分别构建两种疾病的转录调控网络。实验结果表明,转录因子POLR2E、RFC5、THOC4、FBXO22、KPNA1、MYST3、PTBP1等在两种疾病中表达活性及调控作用相反,如转录因子RFC5的表达活性从健康到BC患病过程中由0.269降低至0.077,而从健康到AD患病过程中则由-0.430升高至0.307。通过分子生物学分析可知,它们所影响的调控关系及生物过程对BC及AD的致病起着关键作用,对两种疾病之间呈现负相关性机制的探寻具有重要意义。     

基于KPCA算法的阿尔茨海默症辅助诊断

阿尔茨海默症（AD）是一种起病隐匿、进行性发展的神经系统退行性疾病,利用磁共振成像和计算机技术对AD患者的辅助诊断是目前不断探索的新课题。本研究先对磁共振图像进行预处理和相关性分析,然后利用核主成分分析法（KPCA）对脑灰质图像进行特征提取,结合Adaboost算法进行分类,并与主成分分析法（PCA）进行对比试验。通过对AD神经影像学计划数据库中的116名AD患者、116名轻度认知障碍患者,以及117名正常对照的脑部功能磁共振成像进行的研究表明,利用机器学习能够很有效地辅助诊断AD脑部疾病,KPCA算法对图像进行特征提取比PCA 算法更加充分完备,分类结果更加精确,能够获得更好的AD辅助诊断结果。     

基于纹理分析的阿尔茨海默症及轻度认知功能障碍的分类研究

目的 利用脑MR图像中胼胝体的三维纹理特征对阿尔茨海默症患者（Alzheimer disease,AD）及轻度认知功能障碍（mild cognitive impairment,MCI）患者进行分类识别,以探索AD早期诊断新途径.方法 选取AD患者、MCI患者及健康对照者各l8例,采用灰度共生矩阵和游程长矩阵提取每位受试者胼胝体部位的三维纹理特征.通过筛选得到的纹理特征参量,利用BP神经网络建立识别模型,对AD患者、MCI患者和健康对照者进行分类识别,并对采用主成分分析、线性判别分析和非线性判别分析3种方法得到的识别结果进行比较.结果 使用神经网络模型的非线性判别分析的分类识别正确率最高.结论 利用三维纹理特征的神经网络模型可分类识别早期AD患者及MCI患者.     

长期卧床的阿尔茨海默症患者的护理体会

由于我国人口的老龄化,阿尔茨海默症(Alzheimer's disease,AD)患病人数逐步增加,已成为严重的社会问题和家庭问题。探讨最佳的护理模式,使阿尔茨海默症患者的护理质量高而有效,成为护理研究的热点。     

基于随机森林算法的阿尔茨海默症医学影像分类

为实现阿尔茨海默症(AD)的医学影像分类,辅助医生对患者的病情进行准确判断,本研究对采集的34名AD患者、35名轻度认知障碍患者和35名正常对照组成员的功能磁共振影像进行特征提取和分类,具体思路包括:首先利用皮尔逊相关系数计算脑区之间的功能连接,然后采用随机森林算法对被试不同脑区之间的功能连接进行重要性度量及特征选择,最后使用支持向量机分类器进行分类,利用十倍交叉验证估算分类准确率。实验结果显示,随机森林算法可以对功能连接特征进行有效分析,同时得到AD发病过程的异常脑区,基于随机森林和SVM建立的分类模型对AD、轻度认知障碍的识别具有较好的效果,分类准确率可达90.68%,相关结论可以为AD的早期临床诊断提供客观参照。 【关键词】阿尔茨海默症;功能磁共振成像;随机森林;特征选择     

基于sMRI的阿尔茨海默症分类影响因素研究

本研究提出基于三类解剖特征的SVM建模方法,探索样本、特征及算法选择三个因素,对阿尔茨海默症(AD)及其前驱阶段分类的重要性。该方法以三维重构s MRI后不同大脑区域的灰质体积、皮层表面积及其平均厚度三类特征作为SVM模型的输入参数,并采用十折交叉验证方法对AD患者、轻度认知损害患者和健康者进行分类识别,并与其他文献结果进行比较分析。实验结果表明,为了达到更高的分类准确率,选择合适的样本和特征,比选择算法更重要。此结论为未来AD的计算机辅助诊断研究工作提供了有益的指导。     

基于特征选择的阿尔茨海默症辅助诊断

阿尔茨海默症（AD）是一种在老年人中多发的脑部神经疾病,致病原因迄今未明,在疾病发展早期难以诊断。随着 计算机和人工智能技术的大力发展,利用磁共振成像（MRI）技术和机器学习方法辅助医生对AD进行辅助诊断不断取得 新的成果。本研究提出一种基于支持向量机递归特征消除（SVM-RFE）和线性判别分析（LDA）的AD辅助诊断方法。首 先对MRI图像进行预处理,获得90个大脑脑区的灰质体积;然后使用SVM-RFE和LDA相结合的方法,对90个大脑脑区 灰质体积进行特征选择;最后通过SVM进行分类。通过对来自于ADNI数据库中的34名AD、26名主观记忆衰退（SMC） 患者和50名正常被试（NC）的MRI图像分析,得到AD/NC、AD/SMC和NC/SMC的平均分类准确率分别为94.0%、100.0% 和93.6%。实验结果证明,本研究提出的方法可有效提取样本特征,辅助医生诊断AD。     

KPCA和Adaboost算法在阿尔茨海默症功能磁共振影像分类中的 应用

本研究的目的在于使用机器学习方法,对脑部功能磁共振成像数据进行分析与特征提取,完成对阿尔茨海默症 （AD）的辅助诊断与分析。首先对数据进行预处理与去除协变量,并从大脑全局特征出发,根据现有的自动解剖标记模 板,把每个被试的大脑分为116个脑区,通过提取每个脑区的时间序列,构建全脑功能连接矩阵,然后使用核主成分分析 法进行特征提取,最后用Adaboost算法进行分类。在对34名AD患者、35名轻度认知障碍患者和35名正常对照组的功能 磁共振成像数据进行的实验结果表明,利用静息态功能磁共振成像,同时结合机器学习的方法,能够有效地实现AD的正 确分类,准确率可以达到96%,该结果可以为AD患者的临床辅助诊断提供有效的判断依据。     

基于PiB PET图像感兴趣区域的阿尔茨海默症计算机辅助分析

阿尔兹海默症 (AD) 是一种不可逆的神经退行性疾病,PiB PET成像技术可用于AD的早期诊断。但是,目前临床基于PiB PET图像的AD诊断主要依靠医生视觉评估分析,其缺点为依赖医生经验且耗时,无法实现对患者病情的客观追踪,因此提出一种基于PiB PET图像的计算机辅助分析方法 (CAAD)实现AD诊断。使用基于阈值先验的3D格子玻尔兹曼技术分割ROIs,采用主成分分析 (PCA) 技术提取图像特征,最终采取基于支持向量机(SVM)多项式核模型对特征进行分类。通过对ADNI数据库和上海市华山医院PET中心的149个样本的PiB PET数据进行对比实验,该方法对于ROIs的分割后Dice系数平均准确率为91.53%±3.0%,最终对AD和正常老年组(HC)、轻度认知障碍组(MCI)和HC、AD/MCI和HC的分类准确率分别达到87.01%、93.04%和91.95%。与现有文献的AD计算机辅助诊断相比,所提出CAAD方法的准确率高出约10%。 实验结果表明,该方法能够很好地对AD、MCI和HC进行分类。     

阿尔茨海默病患者默认网络社团结构的分析

研究表明,默认网络(DMN)的功能失调与阿尔茨海默病有关。为进一步发现阿尔茨海默病患者大脑默认网络存在的异常连接结构,使用最小生成树方法构建无偏的脑网络,采用树层次聚类方法分析早期轻度认知障碍组(EMCI)、晚期轻度认知障碍组(LMCI)、阿尔茨海默病患者(AD)和健康对照者(NC) DMN社团结构的变化,并且对4种被试大脑网络中回直肌-眶部额上回、楔前叶-后扣带回的连接以及颞上回中心性进行差异分析。结果显示:DMN在NC和EMCI中分成5个社团,在LMCI中分成7个社团,但是在AD分成9个社团; LMCI和AD在回直肌-眶部额上回的连接存在显著差异(P=0. 048),LMCI和EMCI在楔前叶-后扣带回的连接存在显著差异(P=0. 042),LMCI和NC在楔前叶-后扣带回的连接存在显著差异(P=0. 016);颞上回介数中心性在AD组与LMCI组(P=0. 028)、LMCI组与NC组(P=0. 001)、EMCI组与NC组(P=0. 048)都存在显著差异。阿尔茨海默病患者随着病情的进展,DMN的结构逐渐分散,脑区之间的连接以及中心性发生变化,这些脑区主要包括海马、海马旁回、楔...     

基因表达系列分析技术研究进展

基因表达系列分析技术(SAGE)是一种新的基因表达分析技术,它可以大量获取全基因组范围基因表达的类别并量化分析。由于其克服了基因丰度的影响,SAGE在新基因的发现中具有独特的优点。同时,SAGE技术被成功应用于特异组织或细胞的转录组研究、mRNA群体间的全局化比较以及差异表达基因染色体分布的分析。文章主要述及了SAGE技术的原理、特点及其在应用上的最新进展。     

早老素1基因多态性与Alzheimer病的相关研究

目的探讨中国人群中早老素１（ＰＳ１）基因多态性与Ａｌｚｈｅｉｍｅｒ病（ＡＤ）的相关情况。方法应用聚合酶链式反应（ＰＣＲ）和限制性片段长度多态性（ＲＦＬＰ）方法,观察了５８例早发性ＡＤ患者、６５例迟发ＡＤ患者、１５７名正常人中的ＰＳ１多态性分布,并对ＡＤ与ＰＳ１基因的各等位基因和基因型进行关联分析。结果（１）早发ＡＤ患者中,ＰＳ１基因２／２型频率显著降低（Ｐ＜０．０５）;等位基因１频率显著升高,等位基因２频率显著降低（Ｐ＜０．０５）。迟发ＡＤ患者与正常对照之间不存在ＰＳ１等位基因和基因型分布的差异。（２）早发ＡＤ与ＰＳ１等位基因１正关联（ＲＲ＝２．２９,Ｐ＜０．０５）,与等位基因２（ＲＲ＝０．４４）和２／２基因型负关联（ＲＲ＝０．２３,Ｐ＜０．０５）;迟发ＡＤ与ＰＳ１各等位基因及等位基因型之间无明显关联。（３）ＡｐｏＥε４型、早发性及女性ＡＤ患者与ＰＳ１基因的相关性尤为显著。结论中国人群中ＰＳ１基因多态性可能仅与早发ＡＤ之间具有关联,而与迟发ＡＤ无关;这种关联具有年龄、性别差别     

Analysis of the Proteomic Profiling of Brain Tissue in Alzheimer's Disease

In proteome analysis, it is necessary to separate proteins as a first step prior to characterization. Thus, the overall performance of the analysis depends strongly on the separation tool, which is usually two-dimensional electrophoresis (2DE). We have utilized 2DE to begin characterization of the complex pathologic processes in Alzheimer''s disease (AD). In the present study, we show how a reliable 2-DE database of brain proteins in Alzheimer''s disease was created, improving reproducibility by using an immobilized pH gradient (IPG) for the first dimension gel electrophoresis. The recent progress in this field, and future prospects in this area are also discussed. Preparation of brain proteins into a suitable solubilized state enabled us to separate over 1000 well-defined protein spots in each 2-DE. A comparison of the density of the spots identified on the reference map between the AD and control group, showed that 5 protein spots were significantly increased, 28 spots were significantly decreased and 7 spots were specifically detected in AD. Two spots among those significantly increased and one spot among those significantly decreased were identified as GFAP related. It is hoped that comparative studies to identify, quantitate, and characterize the proteins differentially expressed in normal brain versus diseased brain will give insight into the mechanisms of pathogenesis and allow the development of a strategy to control both the etiology and course of the diseases.     

Up-regulated FHL1 Expression Maybe Involved in the Prognosis of Hirschsprung's Disease

Background: In a subset of patients with Hirschsprung''s disease (HSCR), gastrointestinal motor dysfunction persisted long after surgical correction. Gastrointestinal motility is achieved through the coordinated activity of the enteric nervous system, interstitial cells of Cajal, and smooth muscle (SMC) cells. Inhibition of four-and-a-half LIM protein-1 (Fhl1) expression by siRNA significantly decreases pulmonary artery SMCs migration and proliferation. Furthermore when up-expressing FHL1 in atrial myocytes, K (+) current density markedly increases, therefore changing myocytes'' response to an electrical stimulus. However whether FHL1 in colon SMCs (the final effector organ) influences intestinal motility in HSCR patients has not been clarified. Methods: FHL1 mRNA and protein expressions were analyzed in 32 HSCR colons and 4 normal colons. Results: Smooth muscle layers were thicken and disorganized in HSCR. FHL1 was expressed in the ganglion cells of the myenteric plexus, submucosa, as well as in the longitudinal and circular muscle layer of the ganglionic colon. FHL1 mRNA relative expression level in aganglionic colons was 1.06±0.49 (ganglionic colon relative expression level was 1) (P=0.44). FHL1 protein gray level relative to GAPDH in normal colons was 0.83±0.09. FHL1 expression level in ganglionic colon (1.66±0.30) or aganglionic colon (1.81±0.35) was significantly higher than that in normal colons (P=0.045 and P=0.041, respectively). Meanwhile, we found FHL1 expression in aganglionic colon was slightly stronger than that in ganglionic colon (P=0.036). Conclusion: These data suggested that up-regulated FHL1 in smooth muscle in HSCR might be associated with intestinal wall remodeling in HSCR and might be one of the risk factors for gastrointestinal motor dysfunction.     

Endothelin-Converting Enzyme-1 Promoter Polymorphisms and Susceptibility to Sporadic Late-Onset Alzheimer's Disease in a Chinese Population

Endothelin converting enzyme (ECE-1) is a candidate Alzheimer disease susceptibility gene. It was previously reported that western individuals homozygous for the C-338A polymorphism (AA) within the ECE1 gene promoter region are at reduced risk of developing late onset Alzheimer disease (LOAD). A further polymorphism, T-839G, is present within the ECE1 promoter region but a potential association with LOAD has not been studied. We therefore studied possible associations between these ECE1 polymorphisms and LOAD in a Chinese population. Subjects comprised 376 Chinese LOAD patients and 376 age- and sex-matched controls; all subjects were typed for the ECE1 C-338A and the T-839G polymorphisms. We report that the frequency of the 338A allele was decreased in LOAD patients compared to controls (adjusted OR =0.73; 95% CI=0.54–0.98; P=0.03). There was no significant association between T-839G genotype and LOAD, however the combined 839T/338A haplotype was significantly associated with decreased risk of LOAD (OR=0.73; 95% CI=0.57–0.93; P=0.01). This study argues that the ECE1 338A allele is protective against LOAD in a Chinese population.     

IL-23 Gene Expression in PBMCs of Patients with Coronary Artery Disease

Objective: Both adaptive and innate immune systems are involved in coronary artery disease (CAD). The aim of this study was to evaluate TH17 cytokines expression profiles in un-stimulated peripheral blood lymphocytes (PBMCs) of patients with coronary artery disease. Methods: Expression profiles of IL-17, IL-23, and TGF-β1 were determined in individuals with and without CAD using Real-time PCR. Results: A significant decrease in IL-23 gene expression in un-stimulated PBMCs of patients with CAD compared to those without CAD was found (p=0.003, OR=0.045, 95% CI: 0.006–0.355). Conclusion: Our data reinforce the potential role of the IL-23 as a critical regulatory molecule that bridges the innate and adaptive arms of the immune system in the complex mechanisms associated with the development of atherosclerosis.     

Colocalization and alteration of estrogen receptor-alpha and -beta in the hippocampus in Alzheimer's disease

The human hippocampus is severely affected in Alzheimer's disease (AD). Because postmenopausal estrogen use may decrease the risk and delay the onset and progression of AD, possibly by a direct action on the hippocampal neurons, we used fluorescence immunocytochemistry to examine the colocalization of estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta) in the hippocampus of elderly human controls and AD patients. Double-labeling cells (DLCs) of ERalpha and ERbeta can be divided into 3 types: double-cytoplasm-staining cells (DCCs), double-nucleus-staining cells (DNCs), and ERalpha nucleus-staining and ERbeta cytoplasm-staining cells (NCCs). There was no difference in the percentage of DLCs in total ERalpha-positive cells or in total ERbeta-positive cells in the CA1 to CA4 subfields of the hippocampus between controls and AD patients. Interestingly, the ratio of DNCs to the total ERalpha-positive cells (2.6% +/- 0.5%) or to the total ERbeta-positive cells (1.8% +/- 0.3%) in the CA1 subfield of the AD hippocampus was significantly decreased in comparison with controls (5.0% +/- 0.7% and 3.9% +/- 0.6%, respectively; P<0.001), suggesting that changes in the compartmentalization of these receptors could play a role in the pathogenesis of AD.     

早期和非早期类风湿关节炎患者外周血CD4+ T细胞基因表达差异

为了探讨早期、非早期类风湿关节炎(RA)患者与健康人外周血CD4+T细胞的基因表达差异。采集早期、非早期RA患者及健康人空腹静脉血,纯化得到CD4+T淋巴细胞,利用基因芯片检测和分析技术,探索早期、非早期RA患者与健康人外周血CD4+T淋巴细胞基因表达差异。结果:非早期与早期RA患者比较,外周血CD4+T淋巴细胞有83条基因表达存在显著性差异,其中上调3条,下调80条,主要涉及信号转导。与健康人比较,有45条基因异常表达,其中13条基因在RA的早期和非早期较正常对照组表达降低,30条在早期高表达;只有2条与早期与非早期比较差异表达的83条基因重复;差异基因涉及信号转导和免疫应答,以及相关的信号转导途径。早期与非早期RA患者外周血CD4+T淋巴细胞基因表达谱存在明显差异,与健康人比较的差异基因与RA早期和非早期比较的差异基因不一致。