基于极限学习机的阿尔兹海默病辅助诊断

阿尔兹海默病是一种渐进发展式的痴呆疾病, 其脑部随着病情发展逐渐出现萎缩。利用磁共振脑图像解剖学特征的变化, 提出一种使用极限学习机来诊断阿尔兹海默病以及轻度认知障碍的方法。采用FreeSurfer软件, 分析从ADNI数据库的818份磁共振图像中得到的脑部解剖学特征。首先对这些特征使用线性回归模型来估计正常衰老引起的萎缩因素, 并将其从特征中去除;随后采用极限学习机作为分类器, 使用处理后的特征来诊断阿尔兹海默病和轻度认知障碍。在实验过程中, 通过十折交叉验证来测试该方法的诊断准确率、敏感度、特异度和曲线下面积。通过100次实验求平均的方式计算得出, 该方法诊断阿尔兹海默病的准确率达到87.62%, 曲线下面积达到94.25%;诊断轻度认知障碍的准确率达到73.38%, 敏感度达到83.88%, 其中年龄矫正能有效提高轻度认知障碍诊断的准确率。实验结果表明, 该方法能有效诊断阿尔兹海默病和轻度认知障碍。     

阿尔兹海默病动物模型的研究进展

<正>阿尔兹海默病(Alzheimer’s disease,AD),是一种由神经系统变性引发的进行性痴呆,老年者发病率较高,亦称老年痴呆。临床表现以记忆障碍、认知功能障碍、精神症状以及人格、行为方面的异常为主。典型的三大病理特征为:神经原纤维缠结、老年斑以及神经元的广泛缺失[1]。AD的动物模型按产生原因大致分为两大类:一是自发性动物模型,即     

APOE和SORL1基因联合检测对阿尔兹海默病患者早期诊断的意义

目的探讨载脂蛋白E(APOE)和分拣蛋白相关受体L1基因(SORL1)基因联合检测对阿尔兹海默病(AD)患者早期诊断的临床意义。方法选择2017年10月-2018年10月我院神经内科收治的AD患者118例作为研究组,另选90例同期健康体检者作为对照组,采用qRT-PCR检测两组外周血白细胞中APOE和SORL1基因相对表达量,比较APOE、SORL1基因对AD联合诊断与单独诊断的效果。结果对照组APOE基因平均相对表达量明显低于研究组,差异有统计学意义(P<0.05);对照组APOE基因平均相对表达量明显低于研究组,差异有统计学意义(P<0.05);APOE、SORL1基因联合诊断效果明显优于单独诊断效果,差异有统计学意义(P<0.05)。结论 APOE和SORL1基因联合检测可互补二者单独应用时的不足,在阿尔兹海默病患者早期诊断中具有较好的应用价值,值得推广。     

基于统计学纹理特征的阿尔兹海默病MR图像研究

阿尔兹海默病（Alzheimer’s disease,AD）是一种老年神经系统退行性疾病。流行病学研究显示,在过去的50年里,AD的发病率增加了4倍,是目前威胁老年健康的重要疾病。对AD的影像学研究目前主要采用对图像上特征线、面积、体积测量的方法,还没有发现对AD具有特异性的影像学指标。本文尝试采用基于统计学理论的灰度共生矩阵、游程长矩阵的纹理分析方法提取AD患者MR图像上感兴趣区的纹理特征参数,通过筛选得到的参数,对AD患者和健康对照组进行分类识别,并对采用不同分类方法得到的识别结果进行比较。研究结果显示对统计学纹理特征参数使用非线性判别分析的分类方法得到的识别率最高达到90．12％。可以预见,此项研究对AD的早期诊断具有积极作用。     

N170在阿尔兹海默病中的应用现状

阿尔兹海默病(AD)患者存在面部感知障碍,N170可作为面孔刺激过程中大脑认知加工过程的标志物,利用事件相关电位评价AD患者的面孔识别和加工的缺陷是目前研究的热点,也是临床亟需解决的难点之一。本文就面孔识别的认知加工过程和事件相关电位表现特点以及AD患者的异常N170特征进行全面阐述,解析N170在AD患者中的研究现状,发现AD患者面孔识别的神经机制尚未有统一定论。提出未来医务人员应该进一步使用更敏感、统一的范式,揭示面孔识别的内隐神经心理学时间过程,更深层次地探究N170成为AD患者社会功能障碍的诊断、监测治疗进展的生物标志物证据。     

基于典型相关分析与双模态数据融合的抑郁症辅助诊断

为了充分提取抑郁症患者的磁共振影像信息,提高抑郁症的诊断准确率,本研究将功能磁共振图像与结构磁共振图像作为研究对象,提出一种双模态数据融合的抑郁症分类算法。首先构建4种不同尺度的功能脑网络,提取功能磁共振图像的数据特征,然后使用迁移学习处理的三维密集连接卷积神经网络,提取结构磁共振图像的数据特征,接着使用典型相关分析方法融合两种特征,最后使用支持向量机对融合特征进行分类,从而将受试者识别为健康者或抑郁症患者。实验结果表明,本文提出的方法可获得89.56%的分类准确率与95.48%的召回率,与单模态数据分类相比,基于双模态数据的分类方法具有更好的分类性能。此外,典型相关分析法可以有效融合双模态的图像特征。     

基于多模态特征融合的脑瘤图像分割方法

针对目前大多数医学图像分割方法难以对多模态图像进行特征融合进而完成精确分割任务的问题,提出一种基于编码器-解码器总体架构的多模态脑瘤图像特征融合策略。首先,编码阶段利用孪生网络对不同模态数据进行特征提取,孪生网络结构参数和权值共享的特性可有效减少网络参数量;其次,在进行特征提取的编码阶段加入级间融合,保留不同模态的共性特征的同时强调其互补特征;然后,在解码阶段引入密集跳跃连接思想,最大程度结合不同尺度特征图的低级细节和高级语义信息;最后,设计混合损失函数,在网络生成的预测图受真值图监督的同时让最高级特征融合图也受同倍下采样真值图的监督。所提方法在公开数据集BraTS2019上进行实验,并用图像分割常用的5种指标进行评估。在脑瘤及水肿区域分割任务中得到平均Dice系数为0.884,阳性预测率为0.870,灵敏度为0.898,豪斯多夫距离为3.917,平均交并比达到79.1%,与较先进的算法U-Net和PA-Net相比多项指标均有提升。实验结果说明,级间融合和层间跳跃连接的加入对多模态医学图像的分割效果有所提升,在医学上对脑肿瘤磁共振图像进行病变区域分割具有重要的应用价值和理论意义。     

基于多模态情绪识别的研究进展

情绪是对一系列主观认知经验的高度概括,对人类的发展意义重大。而在人机交互领域,情绪识别是实现机器智能化的关键一步。随着信息技术的发展,目前针对该领域的研究主要集中在基于神经生理模态、基于外在行为表现模态以及基于多模态的情绪识别。本文从以上角度出发,分别梳理了近年来情绪识别领域的发展进程和研究现状,并对未来的研究方向进行了展望。     

面向临床肿瘤诊疗决策的多模态医学影像融合

恶性肿瘤严重危害人类健康,早期诊断和有效治疗可降低致死率.借助在体和无创等优势,现代生物医学影像技术能为肿瘤诊疗提供大量有价值的结构和功能信息.由于肿瘤是一种多因素的发展型疾病,并且每种成像模态也都存在自身缺陷,单一时间点、单一模态的医学影像检查,无法揭示其本质、发生和发展过程.不同模态医学图像信息融合,可以实现信息互补和交叉验证,是揭示肿瘤机理、实现早期准确诊断和有效治疗的必然选择.本文在分析各模态成像技术特点的基础上,从配准、多模态医学图像融合方法和肿瘤诊疗中融合应用等3个方面分别进行综述,并指出了未来需要研究的问题.     

黄芩的化学成分及治疗阿尔兹海默病的研究进展

阿尔茨海默病是一种神经系统退行性疾病,中医称之为“痴呆”,其发病机制复杂,普遍认为主要有β-淀粉样蛋白（Aβ）过度沉积、神经炎症反应、Tau蛋白过度磷酸化等,目前临床还没有找到有效的治疗药物。黄芩的化学成分复杂,作用广泛,研究发现其主要有效成分黄酮类化合物黄芩苷、黄芩素等可改善神经退行性疾病,具有潜在的治疗阿尔兹海默病的发展前景。本文对黄芩的化学成分及治疗阿尔兹海默病的机制作一综述。     

脑电特征分析在阿尔茨海默症临床研究中的应用

阿尔茨海默症(AD)是典型的脑认知功能障碍性疾病,严重影响患者的工作与生活,如何早期诊断此类疾病,一直是人们关注的热点,也是一项有意义的研究。脑电信号包含的功能信息,在脑认知功能障碍的早期诊断中有着独特的优势。从AD的发病机理出发,总结AD的常规诊断方法,进一步阐述脑电特征分析方法,即脑电功率谱、脑诱发电位、脑电近似熵及脑电复杂度等在AD诊断中的应用研究现状,并进行展望。     

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...     

Initial Abdominal CT and Laboratory Findings Prior to Diagnosis of Crohn’s Disease in Children

PurposeTo identify initial abdominal computed tomography (CT) and laboratory findings prior to a diagnosis of Crohn’s disease (CD) in children.Materials and MethodsIn this retrospective study, patients (≤18 year-old) who were diagnosed with CD from 2004 to 2019 and had abdominal CT just prior to being diagnosed with CD were included in the CD group. Patients (≤18 years old) who were diagnosed with infectious enterocolitis from 2018 to 2019 and had undergone CT prior to being diagnosed with enterocolitis were included as a control group. We assessed the diagnostic performances of initial CT and laboratory findings for the diagnosis of CD using logistic regression and the area under the curve (AUC).ResultsIn total, 107 patients (50 CD patients, 57 control patients) were included, without an age difference between groups (median 13 years old vs. 11 years old, p=0.119). On univariate logistic regression analysis, multisegmental bowel involvement, mesenteric vessel engorgement, higher portal vein/aorta diameter ratio, longer liver longitudinal diameter, lower hemoglobin (≤12.5 g/dL), lower albumin (≤4 g/dL), and higher platelet (>320×10³/µL) levels were significant factors for CD. On multivariate analysis, multisegmental bowel involvement [odds ratio (OR) 111.6, 95% confidence interval (CI) 4.778–2605.925] and lower albumin levels (OR 0.9, 95% CI 0.891–0.993) were significant factors. When these two features were combined, the AUC value was 0.985 with a sensitivity of 96% and specificity of 100% for differentiating CD.ConclusionMultisegmental bowel involvement on CT and decreased albumin levels can help differentiate CD from infectious enterocolitis in children prior to a definite diagnosis of CD.     

阿尔茨海默病的早期诊断--认知与定量磁共振指标的作用

目的：(1)探讨阿尔茨海默病(AD)患者认知特点及磁共振成像(MRI)内颞叶结构定量成像特点；(2)拟提出指导AD临床诊断与鉴别诊断的认知指标与MRI定量指标。方法：选取52名AD患者为研究对象，27名血管性痴呆患者(VD)和35例年龄匹配的健康人为对照。采用阿尔茨海默病评定量表-认知部分(ADAS-Cog)、韦氏记忆量表-修订版(WMS-R)和简短心理状况检查(MMSE)评估认知功能。采用定量MRI测量内颞叶结构体积。结果：(1)AD患者学习与记忆、理解、语言、注意力和定向力等方面的障碍比VD患者和正常老人显著。(2)AD患者的海马结构、杏仁核及海马旁回的萎缩比VD患者和正常老人明显。(3)词语回忆、定向力、逻辑记忆等认知指标区分AD、VD和正常老人的总体准确性为83．3％。左侧侧脑室颞角和杏仁核海马复合体体积区分三组被试的准确性为77．1％。联合认知指标和MRI指标，诊断准确性为90．5％。结论：AD具有特征性认知改变和内颞叶结构萎缩．认知指标和内颞叶MRI定量指标对AD的鉴别诊断具有一定提示性意义。     

Apoptosis-Related Protein Expression in the Hippocampus in Alzheimer’s Disease

Recent research indicates that apoptotic mechanisms may be involved in cell death in Alzheimer’s disease (AD). We studied the expression of three members of the Bcl-2 protein family, Bcl-2, Bcl-x, and Bax, in a selection of senile and DS-related AD patients as well as in controls. These proteins are all associated with apoptotic mechanisms. In contrast to previous reports, neuronal Bcl-2 labeling was not detected in our cases, although there was some weak and inconsistent glial cell labeling. Neuronal Bcl-x expression was virtually absent in controls and the presence of the protein in AD patients was neither consistent nor specific. Some reactive glial cells were strongly labeled with the Bcl-x antibody. In contrast Bax, a protein that is believed to promote apoptosis, was widely expressed by neurones but was mainly present in areas other than CA1 in the hippocampus. Neuritic elements of some senile plaques were clearly and strongly labeled with this antibody, whereas neurofibrillary tangles and neuropil threads were not. Double labeling studies indicated that AT8-positive cells and neurites were never Bax-positive and vice versa. The possible implications of the different expression patterns are discussed in relation to neurone death in AD.     

The Angiotensin-Converting Enzyme Inhibitor Lisinopril Mitigates Memory and Motor Deficits in a Drosophila Model of Alzheimer’s Disease

The use of angiotensin-converting enzyme inhibitors (ACEis) has been reported to reduce symptoms of cognitive decline in patients with Alzheimer’s disease (AD). Yet, the protective role of ACEis against AD symptoms is still controversial. Here, we aimed at determining whether oral treatment with the ACEi lisinopril has beneficial effects on cognitive and physical functions in a Drosophila melanogaster model of AD that overexpresses the human amyloid precursor protein and the human β-site APP-cleaving enzyme in neurons. We found a significant impairment in learning and memory as well as in climbing ability in young AD flies compared to control flies. After evaluation of the kynurenine pathway of tryptophan metabolism, we also found that AD flies displayed a >30-fold increase in the levels of the neurotoxic 3-hydroxykynurenine (3-HK) in their heads. Furthermore, compared to control flies, AD flies had significantly higher levels of the reactive oxygen species (ROS) hydrogen peroxide in their muscle-enriched thoraces. Lisinopril significantly improved deficits in learning and memory and climbing ability in AD flies. The positive impact of lisinopril on physical function might be, in part, explained by a significant reduction in ROS levels in the thoraces of the lisinopril-fed AD flies. However, lisinopril did not affect the levels of 3-HK. In conclusion, our findings provide novel and relevant insights into the therapeutic potential of ACEis in a preclinical AD model.     

Efficacy and Safety of Anti-Tumor Necrosis Factor-Alpha Agents for Patients with Intestinal Behcet’s Disease: A Systematic Review and Meta-Analysis

PurposeIntestinal Behcet’s disease (BD) is a systemic autoimmune disease for which treatment options are limited. As a prospective therapeutic strategy for intestinal BD, anti-tumor necrosis factor-alpha (anti-TNF-α) agents have received increasing attention. In this study, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of anti-TNF-α agents for patients with intestinal BD.Materials and MethodsWe searched PubMed, Embase, and Cochrane Library databases up to July 1, 2021 and articles that met the eligibility criteria were further assessed. Pooled rates were synthesized by a randomized effects model using Stata software.ResultsEleven clinical trials covering 671 patients with intestinal BD were included. According to compositive data, the pooled rate for remission was 39% [95% confidence interval (CI) 26–52] in patients receiving anti-TNF-α agents. Intestinal symptoms were cured in 70% (95% CI 53–84) of the patients, and the rate for endoscopic healing was 65% (95% CI 52–78). Corticosteroid discontinuation was achieved in 43% (95% CI 28–58) of the patients, and the dose reduction of corticosteroid was 20.43 mg (95% CI 13.4–27.46). There were 239 adverse events and 80 serious adverse events during follow-up.ConclusionOur study indicated that anti-TNF-α agents may serve as an effective treatment with acceptable safety for patients with intestinal BD. However, more robust evidence from randomized controlled trials is urgently needed to assess the long-term efficacy and safety of anti-TNF-α agents for those patients.     

生物大分子特征谱在疾病诊断中的应用

疾病的不同阶段表达的生物大分子不同,并且随着疾病的发生和发展,生物大分子的表达谱也同时发生改变。这些变化的综合信息可以作为疾病相关的特征性生物大分子谱用于疾病诊断和预后评价。随着多种生物大分子组学技术的迅速发展,人们获得的疾病相关的生物大分子信息量不断扩大,从而实现利用生物大分子特征谱诊断疾病。     

Variability in the type and layer distribution of cortical Aβ pathology in familial Alzheimer’s disease

Familial Alzheimer''s disease (FAD) is caused by autosomal dominant mutations in the PSEN1, PSEN2 or APP genes, giving rise to considerable clinical and pathological heterogeneity in FAD. Here we investigate variability in clinical data and the type and distribution of Aβ pathologies throughout the cortical layers of different FAD mutation cases. Brain tissue from 20 FAD cases [PSEN1 pre‐codon 200 (n = 10), PSEN1 post‐codon 200 (n = 6), APP (n = 4)] were investigated. Frontal cortex sections were stained immunohistochemically for Aβ, and Nissl to define the cortical layers. The frequency of different amyloid‐beta plaque types was graded for each cortical layer and the severity of cerebral amyloid angiopathy (CAA) was determined in cortical and leptomeningeal blood vessels. Comparisons were made between FAD mutations and APOE4 status, with associations between pathology, clinical and genetic data investigated. In this cohort, possession of an APOE4 allele was associated with increased disease duration but not with age at onset, after adjusting for mutation sub‐group and sex. We found Aβ pathology to be heterogeneous between cases although Aβ load was highest in cortical layer 3 for all mutation groups and a higher Aβ load was associated with APOE4. The PSEN1 post‐codon 200 group had a higher Aβ load in lower cortical layers, with a small number of this group having increased cotton wool plaque pathology in lower layers. Cotton wool plaque frequency was positively associated with the severity of CAA in the whole cohort and in the PSEN1 post‐codon 200 group. Carriers of the same PSEN1 mutation can have differing patterns of Aβ deposition, potentially because of differences in risk factors. Our results highlight possible influences of APOE4 genotype, and PSEN1 mutation type on Aβ deposition, which may have effects on the clinical heterogeneity of FAD.