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Assessment of pathogenicity and functional characterization of APPL1 gene mutations in diabetic patients

World Journal of Diabetes 2024年第2期15卷 275-286页

作者： Ping Shi Yang Tian Feng Xu Lu-Na Liu wan-hong Wu Ying-Zhou Shi An-Qi Dai Hang-Yu Fang Kun-Xia Li Chao Xu Department of Endocrinology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250021Shandong ProvinceChina Department of Pediatric Yantai Yuhuangding Hospital Affiliated to Qingdao UniversityYantai 264099Shandong ProvinceChina

BACKGROUND Adaptor protein,phosphotyrosine interacting with PH domain and leucine zipper 1(APPL1)plays a crucial role in regulating insulin signaling and glucose metabolism.Mutations in the APPL1 gene have been associated with the development of maturity-onset diabetes of the young type 14(MODY14).Currently,only two mutations[c.1655T>A(p.Leu552*)and c.281G>A p.(Asp94Asn)]have been identified in association with this disease.Given the limited understanding of MODY14,it is imperative to identify additional cases and carry out comprehensive research on MODY14 and APPL1 mutations.AIM To assess the pathogenicity of APPL1 gene mutations in diabetic patients and to characterize the functional role of the APPL1 domain.METHODS Patients exhibiting clinical signs and a medical history suggestive of MODY were screened for the study.Whole exome sequencing was performed on the patients as well as their family members.The pathogenicity of the identified APPL1 variants was predicted on the basis of bioinformatics analysis.In addition,the pathogenicity of the novel APPL1 variant was preliminarily evaluated through in vitro functional experiments.Finally,the impact of these variants on APPL1 protein expression and the insulin pathway were assessed,and the potential mechanism underlying the interaction between the APPL1 protein and the insulin receptor was further explored.RESULTS A total of five novel mutations were identified,including four missense mutations(Asp632Tyr,Arg633His,Arg532Gln,and Ile642Met)and one intronic mutation(1153-16A>T).Pathogenicity prediction analysis revealed that the Arg532Gln was pathogenic across all predictions.The Asp632Tyr and Arg633His variants also had pathogenicity based on MutationTaster.In addition,multiple alignment of amino acid sequences showed that the Arg532Gln,Asp632Tyr,and Arg633His variants were conserved across different species.Moreover,in in vitro functional experiments,both the c.1894G>T(at Asp632Tyr)and c.1595G>A(at Arg532Gln)mutations were found to downregulate the expression of APP

关键词： Adaptor protein,phosphotyrosine interacting with PH domain and leucine zipper 1 Maturity-onset diabetes of the young Bioinformatics analysis Gene mutation Domain

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Online Nonstop Task Management for Storm-Based Distributed Stream Processing Engines

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Journal of Computer Science & Technology 2024年第1期39卷 116-138页

作者：张洲金培权谢希科王晓亮刘睿诚万寿红 School of Computer Science and Technology University of Science and Technology of ChinaHefei 230026China Key Laboratory of Electromagnetic Space Information Chinese Academy of SciencesHefei 230026China

Most distributed stream processing engines(DSPEs)do not support online task management and cannot adapt to time-varying data flows.Recently,some studies have proposed online task deployment algorithms to solve this problem.However,these approaches do not guarantee the Quality of Service(QoS)when the task deployment changes at runtime,because the task migrations caused by the change of task deployments will impose an exorbitant cost.We study one of the most popular DSPEs,Apache Storm,and find out that when a task needs to be migrated,Storm has to stop the resource(implemented as a process of Worker in Storm)where the task is deployed.This will lead to the stop and restart of all tasks in the resource,resulting in the poor performance of task migrations.Aiming to solve this problem,in this pa-per,we propose N-Storm(Nonstop Storm),which is a task-resource decoupling DSPE.N-Storm allows tasks allocated to resources to be changed at runtime,which is implemented by a thread-level scheme for task migrations.Particularly,we add a local shared key/value store on each node to make resources aware of the changes in the allocation plan.Thus,each resource can manage its tasks at runtime.Based on N-Storm,we further propose Online Task Deployment(OTD).Differ-ing from traditional task deployment algorithms that deploy all tasks at once without considering the cost of task migra-tions caused by a task re-deployment,OTD can gradually adjust the current task deployment to an optimized one based on the communication cost and the runtime states of resources.We demonstrate that OTD can adapt to different kinds of applications including computation-and communication-intensive applications.The experimental results on a real DSPE cluster show that N-Storm can avoid the system stop and save up to 87%of the performance degradation time,compared with Apache Storm and other state-of-the-art approaches.In addition,OTD can increase the average CPU usage by 51%for computation-intensive applications and reduce network communication costs by 88%f

关键词： distributed stream processing engine(DSPE) Apache Storm online task migration online task deployment

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Analysis of Preoperative Factors Influencing Hypoglossal-facial ‘Side’-to-side Neurorrhaphy for Facial Paralysis after Excision of Acoustic Neuroma

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Biomedical and Environmental Sciences 2020年第1期33卷 30-36页

作者： SU Di Ya wan hong LI De Zhi QIAO Hui SCHUMACHER Michael LIU Song Beijing Neurosurgical Institute and Beijing Key Laboratory of Central Nervous System Injury Capital Medical UniversityBeijing 100070China Dalian University Affiliated Xinhua Hospital Dalian 116000LiaoningChina Department of Neurosurgery and China National Clinical Research Center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China U 1195 INSERM and University Paris-Sud and University Paris Saclay94276 Le Kremlin-BicêtreFrance

Objective Hypoglossal nerve-facial nerve‘side’-to-side neurorrhaphy is a new method for the treatment of potential incomplete facial paralysis after acoustic neuroma.However,there are differences in postoperative outcomes among patients.This study analysed preoperative factors that may influence the treatment outcomes of neurorrhaphy.Methods We performed a retrospective study of 53 patients who were treated by neurorrhaphy for facial paralysis after acoustic neuroma resection.After a one-year follow-up period,the patients were divided into two groups according to facial functional outcome:better recovery or ordinary recovery.We analysed the following factors:gender,age,tumour size,and characteristics,tumour adhesion to the facial nerve,the duration of facial paralysis(DFP)and F wave appearance prior to neurorrhaphy(F wave).Results Univariate analysis showed significant differences between the two groups in DFP(P=0.0002),tumour adhesion to the facial nerve(P=0.0079)and F waves(P=0.0048).Logistic regression analysis of these factors also showed statistical significance with P values of 0.042 for the DFP,0.043 for F waves,and 0.031 for tumour adhesion to the facial nerve.Conclusions Tumour adhesion to the facial nerve,F waves appearance and DFP prior to neurorrhaphy are the predominant factors that influence treatment outcomes.

关键词： Facial nerve injury Nerve regeneration Preoperative factors analysis

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人的尊严:跨越普遍主义与相对主义之争的人权共识——纪念《维也纳宣言与行动纲领》通过30周年

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湘潭大学学报（哲学社会科学版） 2024年第3期48卷 67-71页

作者：张万洪肖思宇武汉大学法学院湖北武汉430072

普遍主义与相对主义在人权领域的争议由来已久,《世界人权宣言》尝试以全人类纲领性文件的形式,用尊严的名义统合多样性和差异。第一次开宗明义地指出人的尊严是人权共识的,则是近半个世纪之后的《维也纳宣言与行动纲领》。《维也纳宣... 详细信息

普遍主义与相对主义在人权领域的争议由来已久,《世界人权宣言》尝试以全人类纲领性文件的形式,用尊严的名义统合多样性和差异。第一次开宗明义地指出人的尊严是人权共识的,则是近半个世纪之后的《维也纳宣言与行动纲领》。《维也纳宣言与行动纲领》首次以国际性文件的形式确立了人的尊严作为跨越人权普遍主义与相对主义之争的人权共识。维也纳世界人权会议及《维也纳宣言与行动纲领》也成为用跨文化对话达成人权共识的生动展现。在未来,让人的尊严成为一个有内容、有厚度的人权基础概念是进一步努力的方向。

关键词：普遍主义人权观相对主义人权观人的尊严

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总体国家安全观下基层情指警务机制改革问题探究

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河南警察学院学报 2024年第2期33卷 80-86页

作者：万红河南警察学院指挥战术系河南郑州450046

当前地方市、县两级公安机关大力推进情指中心建设,初步构建了“情指牵头、警种合成、纵向贯通、集群攻坚”的警务新模式。但在改革中存在着机制模式与职能定位不够匹配、信息管理与合成作战需要不够匹配、科技支撑与实战指挥不够匹配... 详细信息

当前地方市、县两级公安机关大力推进情指中心建设,初步构建了“情指牵头、警种合成、纵向贯通、集群攻坚”的警务新模式。但在改革中存在着机制模式与职能定位不够匹配、信息管理与合成作战需要不够匹配、科技支撑与实战指挥不够匹配、民警专业化程度与实战任务不够匹配等问题。结合总体国家安全观贯彻需求,建议从加强顶层设计,统筹推进情指中心的权威化、监测预警系统的信息化、指挥体系的扁平化和队伍建设的专业化等路径完善地方情指部门运行机制,创新警务模式。

关键词：情指部门警务机制职能定位改革发展

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穴位不同层次和强度电刺激缓解肌肉炎性痛及对脊髓背角广动力神经元的抑制作用

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针刺研究 2024年第2期49卷 103-109页

作者：孙小月陈李圳万红叶王晓宇张知云宿杨帅于清泉曹婉萦景向红中国中医科学院针灸研究所北京100700

目的:观察在痛源局部穴区不同层次和强度电刺激的镇痛作用及对脊髓背角广动力(WDR)神经元诱发电活动的影响,为选择合理的电针刺激参数提供依据。方法:Wistar大鼠用于3部分实验。采用弗氏完全佐剂(CFA)建立腓肠肌炎性痛模型,造模后随机选... 详细信息

目的:观察在痛源局部穴区不同层次和强度电刺激的镇痛作用及对脊髓背角广动力(WDR)神经元诱发电活动的影响,为选择合理的电针刺激参数提供依据。方法:Wistar大鼠用于3部分实验。采用弗氏完全佐剂(CFA)建立腓肠肌炎性痛模型,造模后随机选取6只大鼠进行WDR神经元电活动多通道细胞外电生理记录,用于确定激活A-成分的电刺激阈值Ta和C-成分的电刺激阈值Tc,以此作为经皮穴位电刺激(TEAS)或电针的干预强度;选取36只大鼠随机分为正常组、模型组、TEAS-Ta组、TEAS-Tc组、EA-Ta组和EA-Tc组,每组6只,在痛源局部“承山”采用Ta或Tc强度的TEAS或电针干预,每次30 min,1次/d,连续3 d,采用小动物压痛测量仪检测大鼠腓肠肌的机械压痛阈值,Von Frey丝测量足底机械痛阈值;随机选择13只肌肉炎性痛大鼠用于观察Ta/Tc强度电针或TEAS“承山”即刻WDR神经元的反应性。结果:TEAS皮肤激活WDR神经元A-成分或C-成分的阈值分别为(2.43±0.57)mA和(7.00±1.34)mA,电针激活肌肉WDR神经元的A-成分或C-成分的阈值分别为(0.72±0.34)mA和(1.58±0.35)mA。大鼠腓肠肌注射CFA后腓肠肌和足底机械痛阈值较正常组明显降低(P<0.001),在“承山”给予TEAS-Ta、TEAS-Tc或EA-Ta干预后,其腓肠肌和足底机械痛阈值较模型组明显升高(P<0.05,P<0.001)。模型组大鼠伤害性电刺激诱发WDR神经元C-成分放电阈值较正常组降低(P<0.001);与模型组比较,TEAS-Ta、TEAS-Tc或EA-Ta干预后阈值明显升高(P<0.01)。TEAS-Ta、TEAS-Tc或EA-Ta即刻干预后,肌肉WDR神经元诱发放电频率较干预前明显降低(P<0.01,P<0.05)。EA-Tc对WDR神经元的诱发电活动和痛行为均无显著改善。结论:TEAS-Ta、TEAS-Tc或EA-Ta均可减轻肌肉炎性痛大鼠痛源局部及足底机械痛,并抑制WDR神经元的反应性,提示在痛源局部穴位的不同层次镇痛作用需要的电刺激强度不同。

关键词：电针刺激强度刺激层次经皮穴位电刺激广动力神经元肌肉炎性痛

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“立德树人”视角下高校公共体育课程思政建设的路径探索

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冰雪体育创新研究 2024年第3期 161-163页

作者：万虹湖南幼儿师范高等专科学校湖南常德415000

“立德树人”凝练了中国长期以来的育人愿望,是新时代教育的根本任务。公共体育课程是高校教育体系中的重要组成部分,在立德树人背景下也要加强与思政教育的合作,是贯彻“三全育人”以及落实立德树人任务的必要途径,也是实现高校公共体... 详细信息

“立德树人”凝练了中国长期以来的育人愿望,是新时代教育的根本任务。公共体育课程是高校教育体系中的重要组成部分,在立德树人背景下也要加强与思政教育的合作,是贯彻“三全育人”以及落实立德树人任务的必要途径,也是实现高校公共体育课程目的性与规律性统一的必然选择。

关键词：立德树人高校体育课程思政

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交叉扩散驱动的SI模型空间斑图

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物理学报 2024年第8期73卷 62-71页

作者：陆源杉肖敏万佑红丁洁蒋海军南京邮电大学自动化学院人工智能学院南京210023 新疆大学数学与系统科学学院乌鲁木齐830047

目前国内外关于SI模型空间格局的研究大多数局限在自扩散以及系统参数对斑图模式的影响,而关于交叉扩散对空间格局的演化机理研究成果较少.本文建立了一个具有自扩散和交叉扩散的空间流行病模型,研究了在有无自扩散驱动系统不稳定的情况... 详细信息

目前国内外关于SI模型空间格局的研究大多数局限在自扩散以及系统参数对斑图模式的影响,而关于交叉扩散对空间格局的演化机理研究成果较少.本文建立了一个具有自扩散和交叉扩散的空间流行病模型,研究了在有无自扩散驱动系统不稳定的情况下,交叉扩散对SI模型的稳定性、稳定速度以及斑图结构的影响.研究发现,在无自扩散驱动系统不稳定的情况下,引入交叉扩散能够激发Turing斑图的产生;在自扩散驱动系统不稳定的情况下,交叉扩散可以实现斑图结构的改变;对于SI模型的稳定速度,不论有无自扩散驱动系统不稳定,交叉扩散都影响了其到达稳定所需时间,且在不同的交叉扩散系数下,所需时间也不同.因此,交叉扩散对于SI模型的稳定性、稳定速度、斑图结构都有重要的影响.

关键词： Turing不稳定非线性发病率交叉扩散 Turing 斑图

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An Experimental Study on the Optimal Timing for the Repair of Incomplete Facial Paralysis by Hypoglossal-facial‘Side'-to-side Neurorrhaphy in Rats

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Biomedical and Environmental Sciences 2018年第6期31卷 413-424页

作者： wanG Bin Bin ZHANG Shao Dong FENG Jie LI Jun Hua LIU Song LI De Zhi wan hong Beijing Neurosurgical Institute Capital Medical UniversityBeijing 100050China Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijing 100050China

Objective To investigate the optimal timing for the repair of persistent incomplete facial paralysis by hypoglossal-facial ‘side＇-to-side neurorrhaphy in rats. Methods A total of 30 adult rats with crushed and bulldog-clamped facial nerve injury were randomly divided into 5 groups（n = 6 each） that were subjected to injury without nerve repair or with immediate repair, 2-week-delayed repair, 4-week-delayed repair, or 8-week-delayed repair. Three months later, the effects of repair in each rat were evaluated by facial symmetry assessment, electrophysiological examination, retrograde labeling, and axon regeneration measurement. Results At 3 months after injury, the alpha angle significantly increased in the group of rats with 4-week-delayed repair compared with the other four groups. Upon stimulation of the facial nerve or Pre degenerated nerve, the muscle action potentials MAPs were recorded in the whisker pad muscle, and the MAP amplitude and area under the curve in the 4-week-delayed repair group were significantly augmented at 3 months post-injury. Similarly, the number of retrograde-labeled motor neurons in the facial and hypoglossal nuclei was quantified to be significantly greater in the 4-week-delayed repair group than in the other groups, and a large number of regenerated axons was also observed. Conclusion The results of this study demonstrated that hemi HN-FN neurorrhaphy performed 4 weeks after facial nerve injury was most effective in terms of the functional recovery of axonal regeneration and activation of facial muscles.

关键词： Facial paralysis Hypoglossal-facial nerve anastomosis Nerve autograft Optimal time

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电子支气管镜肺泡灌洗治疗小儿重症肺炎的效果分析

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中国医疗器械信息 2024年第2期30卷 88-90页

作者：林婉鸿泉州市第一医院儿童重症监护室福建泉州362000

目的:分析在小儿重症肺炎中实施电子支气管镜肺泡灌洗治疗的效果。方法:选择2021年3月~2022年3月小儿重症肺炎病例98例,依据计算机表法分为对照组与观察组各49例,分别开展常规治疗、联合电子支气管镜肺泡灌洗治疗,期间记录炎症指标水平... 详细信息

目的:分析在小儿重症肺炎中实施电子支气管镜肺泡灌洗治疗的效果。方法:选择2021年3月~2022年3月小儿重症肺炎病例98例,依据计算机表法分为对照组与观察组各49例,分别开展常规治疗、联合电子支气管镜肺泡灌洗治疗,期间记录炎症指标水平、症状改善时间、动脉血气分析指标,调查治疗满意度。结果:经治疗后,观察组的炎症指标水平,症状改善时间,PCO_(2)水平显著低于对照组(P<0.05);观察组的PaO_(2),治疗满意度显著高于对照组(P<0.05)。结论:在重症肺炎小儿的治疗中联合电子支气管镜肺泡灌洗治疗,可以有效降低炎性水平、改善动脉血气,在提高临床疗效的同时,有效提升治疗满意度,临床意义积极。

关键词：电子支气管镜肺泡灌洗小儿重症肺炎效果

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