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Dysregulated N6-methyladenosine modification in peripheral immune cells contributes to the pathogenesis of amyotrophic lateral sclerosis

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Frontiers of Medicine 2024年第2期18卷 285-302页

作者： Di He Xunzhe Yang Liyang Liu Dongchao Shen Qing Liu Mingsheng Liu Xue Zhang liying cui Department of Neurology Peking Union Medical College Hospital(PUMCH)Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100730China Medical Doctor Program Chinese Academy of Medical Science and Peking Union Medical CollegeBeijing100730China McKusick-Zhang Center for Genetic Medicine State Key Laboratory of Medical Molecular BiologyInstitute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijing100730China Neuroscience Center Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100730China

Amyotrophic lateral sclerosis(ALS)is a progressive neurogenerative disorder with uncertain origins.Emerging evidence implicates N6-methyladenosine(m6A)modification in ALS pathogenesis.Methylated RNA immunoprecipitation sequencing(MeRIP-seq)and liquid chromatography–mass spectrometry were utilized for m6A profiling in peripheral immune cells and serum proteome analysis,respectively,in patients with ALS(n=16)and controls(n=6).The single-cell transcriptomic dataset(GSE174332)of primary motor cortex was further analyzed to illuminate the biological implications of differentially methylated genes and cell communication changes.Analysis of peripheral immune cells revealed extensive RNA hypermethylation,highlighting candidate genes with differential m6A modification and expression,including C-X3-C motif chemokine receptor 1(CX3CR1).In RAW264.7 macrophages,disrupted CX3CR1 signaling affected chemotaxis,potentially influencing immune cell migration in ALS.Serum proteome analysis demonstrated the role of dysregulated immune cell migration in ALS.Cell type-specific expression variations of these genes in the central nervous system(CNS),particularly microglia,were observed.Intercellular communication between neurons and glial cells was selectively altered in ALS CNS.This integrated approach underscores m6A dysregulation in immune cells as a potential ALS contributor.

关键词： amyotrophic lateral sclerosis N^(6)-methyladenosine epi-transcriptome proteome single cell RNA sequencing analysis CX3CR1

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Epigenome-wide DNA methylation study of whole blood in patients with sporadic amyotrophic lateral sclerosis

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Chinese Medical Journal 2022年第12期135卷 1466-1473页

作者： Zhengyi Cai Xinmiao Jia Mingsheng Liu Xunzhe Yang liying cui Department of Neurology Peking Union Medical College HospitalPeking Union Medical College and Chinese Academy of Medical SciencesBeijing 100730China Medical Research Center State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalPeking Union Medical College and Chinese Academy of Medical SciencesBejing 100730China Neuroscience Center Chinese Academy of Medical SciencesBeijing 100730China

Background:Epigenetics,and especially DNA methylation,contributes to the pathogenesis of sporadic amyotrophic lateral sclerosis(SALS).This study aimed to investigate the role of DNA methylation in SALS using whole blood of SALS patients.Methods::In total,32 SALS patients and 32 healthy controls were enrolled in this study.DNA was isolated from whole blood collected from the participants.DNA methylation profiles were generated using Infinium MethylationEPIC BeadChip.Results:We identified 34 significant differentially methylated positions(DMPs)in whole blood from SALS patients,compared with the healthy controls.Of these DMPs,five were hypermethylated and 29 were hypomethylated;they corresponded to 13 genes.For the DMPs,ATAD3B and BLK were hypermethylated,whereas DDO,IQCE,ABCB1,DNAH9,FIGN,NRP1,TMEM87B,CCSAP,ST6GALNAC5,MYOM2,and RUSC1-AS1 were hypomethylated.We also identified 12 differentially methylated regions(DMRs),related to 12 genes(NWD1,LDHD,CIS,IQCE,TNF,PDE1C,LGALS1,CSNK1E,LRRC23,ENO2,ELOVL2,and ELOVL2-AS1).According to data from the Kyoto Encyclopedia of Genes and Genomes database,DNAH9 and TNF are involved in the amyotrophic lateral sclerosis(ALS)pathway.Correlation analysis between clinical features and DNA methylation profiling indicated that the methylation level of ELOVL2 and ARID1B was positively associated with the age of onset(r=0.86,adjust P=0.001)and disease duration(r=0.83,adjust P=0.01),respectively.Conclusions:We found aberrant methylation in DMP-and DMR-related genes,implying that many epigenetic alterations,such as the hypomethylation of DNAH9 and TNF,play important roles in ALS etiology.These findings can be helpful for developing new therapeutic interventions.

关键词： Amyotrophic lateral sclerosis DNA methylation Differentially methylated positions Differentially methylated regions Whole blood

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Upper extremity motor function before and after the cerebrospinal fluid tap test in patients with idiopathic normal pressure hydrocephalus: A retrospective study

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中华医学杂志(英文版) 2024年第7期137卷 877-879页

作者： Liu Caiyan Wei Junji Dong Liling Mao Chenhui Li Jie Huang Xinying Hou Bo Feng Feng cui liying Gao Jing Department of Neurology Peking Union Medical College Hospital Chinese Academy of Medical Sciences Beijing 100730 China Department of Neurosurgery Department of Neurosurgery and Radiology

To the Editor:Idiopathic normal pressure hydrocephalus (iNPH) patients present disturbances in gait,cognition,and/or control of urination with neuroimaging characterized by enlargement of the cerebral ventricles.Typically,gait disturbance in iNPH patients is the initial and most prominent symptom,but motor impairments can also extend to upper extremity.

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A multicenter,randomized,double blind,placebo-controlled clinical trial of DL-3-n-butylphthalide in treatment of amyotrophic lateral sclerosis

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Chinese Medical Journal 2023年第3期136卷 354-356页

作者： Mingsheng Liu Xiaoli Yao Xusheng Huang Huifang Shang Dongsheng Fan Jia He liying cui the Chinese ALS Study Group Department of Neurology Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijing 100730China Department of Neurology The First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510006China Department of Neurology Chinese PLA General HospitalBeijing 100853China Department of Neurology West China HospitalSichuan UniversityChengduSichuan 610041China Department of Neurology Peking University Third HospitalBeijing 100191China Department of Health Statistics Faculty of Health ServiceNaval Medical UniversityShanghai 200433China 不详

To the Editor:DL-3-n-butylphthalide(NBP)is a synthetic drug based on a component extracted from seeds of Apium graveolens Linn.(Chinese celery).It reportedly has protective effects in amyotrophic lateral sclerosis(ALS)model mice.[1]A randomized,double-blind,placebocontrolled trial was performed at 19 ALS clinical centers of the Chinese ALS association.All patients provided written informed consent.The Ethics Committee of Peking Union Medical College Hospital approved the study protocol(No.S621)and all patients signed informed consent.All centers followed the same research protocol.

关键词： clinical amyotrophic protective

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轻质铝基熵合金:概述与未来趋势

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Science China Materials 2024年第1期67卷 31-46页

作者：崔立莹张展陈晓光 Department of Applied Science University of Quebec at Chicoutimi555boulevard de l’UniversiteSaguenay G7H 2B1QCCanada

新一代合金——高熵合金的出现,揭示了熵效应在合金设计中的重要意义.受这一概念的启发,轻质铝基熵合金这一概念被提出.随着对低密度结构材料的需求不断增加,这些新型合金在各种应用中具有巨大的潜力.本文综述了轻质铝基熵合金的发展背... 详细信息

新一代合金——高熵合金的出现,揭示了熵效应在合金设计中的重要意义.受这一概念的启发,轻质铝基熵合金这一概念被提出.随着对低密度结构材料的需求不断增加,这些新型合金在各种应用中具有巨大的潜力.本文综述了轻质铝基熵合金的发展背景、设计原理、制造方法、微观结构和力学性能、高温应用,及其发展前景.通过对当前研究的全面调查,本文重点研究分析了122种密度低于4.0 g cm-3的铝基熵合金.轻质铝基熵合金可以弥补传统铝和钛合金在机械性能和密度方面的差距.轻质铝基熵合金优异的热稳定性使其有望成为在高温下使用的结构材料.此外,本文还讨论了轻质铝基熵合金领域的未来发展趋势.机器学习作为有效计算工具,可以极大地提高合金的开发效率.

关键词：高温应用合金设计新型合金机器学习铝基计算工具高熵合金微观结构

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The Gold Coast criteria increases the diagnostic sensitivity for amyotrophic lateral sclerosis in a Chinese population

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Translational Neurodegeneration 2021年第3期10卷 359-366页

作者： Dongchao Shen Xunzhe Yang Yanying Wang Di He Xiaohan Sun Zhengyi Cai Jinyue Li Mingsheng Liu liying cui Department of Neurology Peking Union Medical College HospitalBeijing 100730China Neuroscience Center Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

Objectives:The aim of this study was to assess and compare the diagnostic utility of a new diagnostic criteria for amyotrophic lateral sclerosis(ALS),abbreviated as the‘Gold Coast Criteria’,with the revised El Escorial(rEEC)and Awaji criteria.Methods:Clinical and electrophysiological data of 1185 patients from January 2014 to December 2019 in the Peking Union Medical College Hospital ALS database were reviewed.The sensitivity of the Gold Coast criteria was compared to that of the possible rEEC and Awaji criteria(defined by the proportion of patients categorized as definite,probable,or possible ALS).Results:A final diagnosis of ALS was recorded in 1162 patients.The sensitivity of the Gold Coast criteria(96.6%,95%confidence interval[CI]=95.3%-97.5%)was greater than that of the rEEC(85.1%,95%CI=82.9%-87.1%)and Awaji(85.3%,95%CI=83.2%-87.3%).In addition,the sensitivity of the novel criteria maintained robust across subgroups,and the advantage was more prominent in limb-onset ALS patients and those who completed electromyographic tests.In those who did not achieve any of the rEEC diagnostic categories,the sensitivity of Gold Coast criteria was 84.4%.Conclusions:The current study demonstrated that the Gold Coast criteria exhibited greater diagnostic sensitivity than the rEEC and Awaji criteria in a Chinese ALS population.The application of the Gold Coast criteria should be considered in clinical practice and future therapeutic trials.

关键词： Amyotrophic lateral sclerosis Diagnostic criteria Gold Coast Sensitivity

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部分地区留守儿童教育现状调查

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未来与发展 2024年第1期48卷 27-33页

作者：吕红军崔丽英辽宁对外经贸学院高等教育研究院辽宁大连116052

文章以问卷调查法为主要研究方法对部分地区留守儿童的教育状况开展调研。数据显示,我国部分地区留守儿童精神状态积极向上、学习成绩呈正态分布、对未来充满期待、有正当的文化需求。女性留守儿童和男性留守儿童在学习成绩等方面无显... 详细信息

文章以问卷调查法为主要研究方法对部分地区留守儿童的教育状况开展调研。数据显示,我国部分地区留守儿童精神状态积极向上、学习成绩呈正态分布、对未来充满期待、有正当的文化需求。女性留守儿童和男性留守儿童在学习成绩等方面无显著性差异;同时,部分地区留守儿童在教育方面存在家庭教育缺失、学校教育内容单调、社会文化活动资源匮乏等问题。据此,文章提出提升留守儿童的家庭教育水平、发挥学校的育人核心作用、构建全方位的留守儿童教育新格局3个方面的建议,以期为提升留守儿童教育水平提供参考。

关键词：农村留守儿童教育

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神经科住院医师困难谈话技能培训课程初探

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中国卒中杂志 2024年第6期19卷 729-734页

作者：尹翮翔周立新姚明朱以诚崔丽英倪俊中国医学科学院北京协和医学院北京协和医院神经科北京100730

目的在神经科住院医师中开展困难谈话技能培训课程,探究困难谈话技能培训的可行性,并初步探索本课程的效果。方法在北京协和医院神经科住院医师中开展2次困难谈话技能培训课程,每月1次,每次2 h。课程主题均为与神经科临床实践相关的具... 详细信息

目的在神经科住院医师中开展困难谈话技能培训课程,探究困难谈话技能培训的可行性,并初步探索本课程的效果。方法在北京协和医院神经科住院医师中开展2次困难谈话技能培训课程,每月1次,每次2 h。课程主题均为与神经科临床实践相关的具体临床情景,包括:(1)告知坏消息;(2)与“困难”患者或家属沟通;(3)讨论不施行心肺复苏等抢救措施;(4)与家属讨论重症患者的临终关怀。采用情景模拟教学方法,邀请标准化病人和住院医师在教师指导下完成案例情景模拟,并进行医患沟通伦理知识、技能策略的学习。采用匿名在线调查评估住院医师对本课程的满意度,课程前后采用困难谈话技能自我评估问卷分析住院医师11个维度技能的改善情况。课程结束1年后使用医患沟通技能评价量表(set the stage,elicit information,give information,understand the patient’s perspective,and end the encounter;SEGUE)对部分住院医师的沟通能力进行考核。结果共有14位住院医师参加了困难谈话技能培训课程,12位(85.7%)完成了相关调查评估问卷。完成问卷的住院医师中9位(75.0%)为女性,10位(83.3%)为低年级住院医师(第一年或第二年住院医师)。总体而言,住院医师对本课程反响积极,所有完成问卷的住院医师均对课程表示满意;参与的住院医师在困难谈话技能自我评估问卷涉及的绝大多数维度上均有不同程度改善;4位住院医师完成SEGUE评估,3位获得A级评分。结论在神经科住院医师中使用基于真实病例的特定临床情景模拟来开展困难谈话技能培训课程是可行的,住院医师对课程满意度高且课程对其有积极影响,住院医师的困难谈话技能在培训后得到一定提升。

关键词：沟通技能困难谈话神经科住院医师培训模拟教学

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超声速火焰喷涂WC-10Co4Cr涂层对TC11钛合金耐磨性和耐蚀性的影响

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腐蚀与防护 2024年第6期45卷 68-74页

作者：张玉霖杨阳卢涛杨中娜崔丽颖王添逸徐志刚中海油田服务股份有限公司廊坊065201 中海油(天津)管道工程技术有限公司天津300452

采用超声速火焰喷涂(HVOF)工艺,在随钻仪器零件常用材料TC11钛合金表面制备金属陶瓷涂层WC-10Co4Cr,利用冲击试验机测量喷涂前后钛合金的冲击韧性,使用磨粒磨损试验机测定涂层的耐磨性,采用电化学测试分析涂层的耐蚀性。结果表明:HVOF... 详细信息

采用超声速火焰喷涂(HVOF)工艺,在随钻仪器零件常用材料TC11钛合金表面制备金属陶瓷涂层WC-10Co4Cr,利用冲击试验机测量喷涂前后钛合金的冲击韧性,使用磨粒磨损试验机测定涂层的耐磨性,采用电化学测试分析涂层的耐蚀性。结果表明:HVOF工艺对TC11钛合金的组织和性能影响较小,与未喷涂的钛合金相比,界面处基体的显微组织和显微硬度没有明显变化,冲击韧性稍有提高;HVOF工艺稳定可靠,涂层呈片层结构,致密度高,涂层的孔隙率为2.55%,硬度达到1400 HV,涂层主要由WC和W2C相组成,其与基体结合良好,为机械结合;金属陶瓷涂层能够显著改善钛合金的耐磨性和耐蚀性,喷涂涂层钛合金的磨损量是未喷涂钛合金的1.56%,喷涂涂层钛合金的磨损机制是磨粒磨损,未喷涂涂层钛合金磨损机制是磨粒磨损+黏着磨损。

关键词： TC11钛合金随钻仪器零件超声速火焰喷涂(HVOF) WC-10Co4Cr涂层组织与性能磨损

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Facilitative Effect of Awe on Cooperation:The Role of the Small-self and Self-other Inclusion

Facilitative Effect of Awe on Cooperation:The Role of the Sm...

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第二十四届全国心理学学术会议

作者： Qin Wu liying cui Xianguo Han Wen He Department of psychology Shanghai Normal University

Awe has been theorized as a kind of self-transcendence emotion that has an important impact on individual social behavior.Based on the self-transcendence of awe,this study examined how awe can increase small-self and self-other inclusion to facilitate cooperation among individuals across three studies(N=1,162).First,the relationship between awe,cooperative propensity,and the mediating role of small-self and self-other inclusion in the relationship was examined using questionnaires on trait levels(Study 1).Second,awe emotions were induced from the state level through behavioral experiments to verify the facilitative effect on cooperative behavior in multiple rounds of public goods dilemma(Study 2).Third,by adding the induction of negative awe to discuss the impact of different valence types of awe on cooperative behavior,and the mediating role of small-self and self-other inclusion was verified(Study 3).Results show that awe has a facilitative effect on cooperation,which provides strong evidence for the positive social effects of awe.

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