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DDX6通过调控CKMT1A mRNA稳定性促进鼻咽癌细胞增殖和迁移的机制研究

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中国癌症杂志 2024年第5期34卷 451-459页

作者：熊茄妍雷伟游波张振新谢海静单颖夏天周勇南通大学附属医院耳鼻咽喉头颈外科研究所江苏南通226001 南通大学医学院江苏南通226001 苏州大学附属第二医院耳鼻咽喉头颈外科江苏苏州215000 南通大学附属医院耳鼻咽喉头颈外科江苏南通226001

背景与目的:DDX是一类腺苷三磷酸(adenosine triphosphate,ATP)依赖的RNA解旋酶,与mRNA调控、肿瘤增殖及侵袭等密切相关。本研究旨在探讨DDX家族成员DDX6对CKMT1A mRNA稳定性的影响以及DDX6-CKMT1A轴对人鼻咽癌细胞CNE2增殖和迁移能力... 详细信息

背景与目的:DDX是一类腺苷三磷酸(adenosine triphosphate,ATP)依赖的RNA解旋酶,与mRNA调控、肿瘤增殖及侵袭等密切相关。本研究旨在探讨DDX家族成员DDX6对CKMT1A mRNA稳定性的影响以及DDX6-CKMT1A轴对人鼻咽癌细胞CNE2增殖和迁移能力的影响及其分子机制。方法:检索癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库中DDX6和CKMT1A在人头颈部鳞状细胞癌中的表达情况并进行相关性分析,利用蛋白质印迹法(Western blot)检测南通大学附属医院保存的人体鼻咽癌组织和正常鼻咽部组织中CKMT1A和DDX6的表达,本研究通过了南通大学附属医院伦理委员会的审查(编号:2022-L114)。利用transwell实验检测细胞迁移能力,采用EdU试剂盒检测细胞增殖能力,采用细胞集落形成实验检测克隆形成能力。转染慢病毒、质粒,构建南通大学附属医院保存的人源鼻咽癌细胞CNE2的shDDX6、sh-CKMT1A、sh-CKMT1A+sh-DDX6和oe-CKMT1A细胞模型,明确DDX6和CKMT1A表达水平对鼻咽癌细胞恶性生物学表型的影响。构建BALC/c裸小鼠皮下移植瘤模型,检测DDX6和CKMT1A在小鼠体内对鼻咽癌细胞成瘤性的影响。采用RNA稳定性实验检测敲除DDX6对CKMT1A mRNA的影响,进一步明确DDX6的分子机制。结果:人鼻咽癌组织中DDX6高表达,CKMT1A低表达,DDX6与CKMT1A表达呈负相关。DDX6通过破环CKMT1A mRNA稳定性,抑制CKMT1A蛋白质翻译。在CNE2细胞中,CKMT1A低表达可增强细胞迁移和增殖能力,高表达则抑制细胞迁移和增殖能力,而DDX6的敲除可逆转CKMT1A下调导致的恶性行为进展。在裸鼠皮下移植瘤模型中,低表达CKMT1A促进肿瘤细胞生长,低表达DDX6抑制肿瘤细胞生长,而同时敲除DDX6与CKMT1A能恢复单独敲低DDX6导致的抑制效果。结论:鼻咽癌细胞中DDX6通过破坏CKMT1A mRNA稳定性,负调控CKMT1A蛋白质翻译,增强鼻咽癌细胞增殖和迁移能力,从而促进鼻咽癌恶性进展。

关键词：鼻咽癌 CKMT1A DDX6 细胞增殖细胞迁移

2022年内蒙古自治区碘缺乏和适碘地区儿童和孕妇碘营养水平分析

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中华地方病学杂志 2024年第6期43卷 472-476页

作者：左媛媛张振欣乔佳楠贾海澄郭宏宇内蒙古自治区疾病预防控制中心(内蒙古自治区预防医学科学院)碘缺乏病防控科呼和浩特

目的掌握内蒙古自治区(简称内蒙古)碘缺乏和适碘地区8 ～ 10岁儿童和孕妇碘营养水平, 为碘缺乏病防治研究提供科学依据。方法 2022年3 - 7月, 对内蒙古12个盟市104个旗(县、市、区)的碘缺乏和适碘地区进行碘营养分析, 每个监测旗(县、... 详细信息

目的掌握内蒙古自治区(简称内蒙古)碘缺乏和适碘地区8 ～ 10岁儿童和孕妇碘营养水平, 为碘缺乏病防治研究提供科学依据。方法 2022年3 - 7月, 对内蒙古12个盟市104个旗(县、市、区)的碘缺乏和适碘地区进行碘营养分析, 每个监测旗(县、市、区)按东、西、南、北、中划分5个抽样片区, 每个片区抽取1个苏木(乡镇、街道), 每个苏木(乡镇、街道)抽取1所小学, 每所小学抽取8 ～ 10岁非寄宿学生40名, 对其中1/3学生进行甲状腺B超检查;每个监测旗(县、市、区)在所抽取的5个苏木(乡镇、街道)各抽取孕妇20名。采集儿童和孕妇家中食用盐盐样和一次随机尿样, 检测盐碘和尿碘含量。结果 2022年, 内蒙古碘缺乏和适碘地区8 ～ 10岁儿童甲状腺容积中位数为2.44 ml, 甲状腺肿大率(甲肿率)为1.89%(123/6 496), 不同盟市甲状腺容积和甲肿率比较, 差异均有统计学意义(H = 1 229.05, χ2 = 34.13, 均P < 0.001);12个盟市的碘盐覆盖率为98.51%(30 628/31 090), 合格碘盐食用率为94.42%(29 355/31 090), 盐碘中位数为22.80 mg/kg;儿童(n = 20 968)尿碘中位数为195.00 μg/L, 其中7个盟市的尿碘中位数处于碘适宜水平(100 ～ 199 μg/L), 5个盟市的尿碘中位数处于超适宜量水平(200 ～ 299 μg/L);孕妇(n = 10 122)尿碘中位数为168.00 μg/L, 除了巴彦淖尔市(149.18 μg/L), 其他11个盟市的尿碘中位数均处于碘适宜水平(150 ～ 249 μg/L)。结论内蒙古儿童和孕妇的总体碘营养均处于适宜水平, 但部分孕妇仍存在碘营养不足风险, 今后碘缺乏病防治重点应为特需人群的碘营养监测。

关键词：碘尿食用盐甲状腺

Public policies and conservation plans of historic urban landscapes under the sustainable heritage tourism milieu: discussions on the equilibrium model on Kulangsu Island, UNESCO World Heritage site

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Built Heritage 2023年第1期7卷 24-43页

作者： Long Zhao Yuan Li Na zhang zhenxin zhang School of Architecture and Civil Engineering Xiamen UniversityNo.422Siming South RoadXiamen 361005FujianChina Xiamen Key Laboratory of Integrated Application of Intelligent Technology for Architectural Heritage Protection Xiamen 361005China Department of Architecture Xiamen UniversityNo.422Siming South RoadXiamen 361005FujianChina School of Architecture Urban Planning Construction Engineering Polytechnic University of MilanPiazza Carlo D'Arco346100 MantuaLombardiaItaly

Purpose The tensions and threats in historic urban landscapes brought about by heritage tourism are still regional,global,general,and dynamic *** Kulangsu,there is an obvious problem in the connection between the current conservation plan and public *** a large extent,public policy cannot effectively,specifically,and flexibly respond to the dynamic problems in the implementation of the conservation plan,which seems insufficient concerning the effect of these conservation plans and public policies on promoting the adaptive reuse and sustainable tourism of the historic urban in Kulangsu heritage ***,giving more consideration to the combination of public policies and conservation plans of historic urban landscapes under the heritage tourism milieu,ensuring a balanced,sustainable,and integrated development pattern still calls for new discussions in achieving good performance of sustainable heritage *** study conceptually discusses the equilibrium model of historic urban landscapes with a range of strategies under a sustainable heritage tourism background and responds to the synthetic contradiction of the imbalances among public policy,conservation plans,and development ***/methodology/approach The study is based on a range of prepared desktop studies(public policy studies,conservation plans),field surveys,participant observations,and randomised interviews to respond to the insufficiency of the current *** This study discusses the equilibrium model of sustainable heritage tourism at heritage *** takes Kulangsu Island,a UNESCO World Heritage site in Southeast China,as an example to discuss the equilibrium model,which encompasses a convergent parallel framework and three dimensions concerning heritage management and *** equilibrium model of historic urban landscapes is a dynamic framework that integrates social,economic,environmental,and cultural concerns into a holistic collaborative framew

关键词： sustainable heritage tourism historic urban landscapes equilibrium model public policies conservation plans Kulangsu Island

Mortality of Dementia and Its Major Subtypes in Urban and Rural Communities of Beijing

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Biomedical and Environmental Sciences 2011年第5期24卷 483-490页

作者： WEN HongBo zhang zhenxin HUANG JueBin DUAN LeiLei WANG QingHua Department of Neurology Peking Union Medical College Hospital Chinese Academy of Medical Sciences Beijing100730 China

Objective To identify the mortality and epidemiological pattern of dementia and its various major subtypes among urban and rural senior residents in *** Based on Beijing＇s dementia prevalence survey among residents aged 55 years and above in 1997,respondents were selected by stratified multiple‐stage cluster sampling and 12 urban communities and 17 rural village communities were randomly sampled then follow‐up in *** regression was used to analyze relative risks controllingconfounding factors on deaths of dementia *** The mortality of dement patients in the 55‐64 age‐group was 0.82/100 person‐*** age‐standardized mortality of dement cases was 0.90/100 person‐*** mortality in the 65 and above age‐group was 1.44/100 person‐year,and the age‐standardized mortality was 1.56/100 person‐*** AD cases,the above two mortalities were 0.35/100 and 0.42/100 person‐year respectively,and among VaD cases,0.34/100 and 0.36/100 person‐year *** both AD and VaD cases,their mortality increased with ***,gender and age were more significant to survival of AD *** One major subtype of dementia,AD,among elderly urban and rural residents in Beijing,has a different mortality and epidemiological pattern from VaD.

关键词： Dementia Mortality Alzheimer's disease Vascular dementia

多场所实验室环境监测质量管理体系的构建与实践

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中国环境监测 2024年第3期40卷 27-33页

作者：彭刚华尹群康长安李晓燕张振欣蔡芹欧阳涛钟鸿雁陈宜夏新江西省生态环境监测中心江西南昌330000 中国环境监测总站国家环境保护环境监测质量控制重点实验室北京100012

在事业单位机构改革过程中,部分事业单位的法人资格被重组到上一级机构,而不再具有独立法人资格,其原有的CMA检验检测资质不复存在。撤并以后的环境监测机构各项业务如何融合开展,资质认定如何管理,多个实验室场所质量管理体系如何构建... 详细信息

在事业单位机构改革过程中,部分事业单位的法人资格被重组到上一级机构,而不再具有独立法人资格,其原有的CMA检验检测资质不复存在。撤并以后的环境监测机构各项业务如何融合开展,资质认定如何管理,多个实验室场所质量管理体系如何构建,是当前一些检验检测机构亟待解决的普遍性问题。为此,该研究在优化多场所实验室质量管理体系,制定科学、合理、全面、具备开放性和可拓展的多场所实验室质量管理体系文件方面进行了积极探索。以江西省生态环境监测中心“1+11”多场所实验室质量管理为例,结合江西省环境监测机构改革现状,兼顾资质认定有关法律法规要求,就环境监测多场所实验室提出了一套系统性的质量管理体系构建模式,希望为多场所检验检测机构的质量管理提供借鉴。

关键词：机构改革环境监测多场所实验室质量管理体系

Combination of Nitrogen-Rich Skeleton and Coordination Group:Synthesis of a High-Energy Primary Explosive Based on 1H-Tetrazole-5-Carbohydrazide

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Defence Technology（防务技术） 2024年第1期31卷 271-277页

作者： Tingwei Wang Zujia Lu Shu Bu Baolong Kuang Lu zhang zhenxin Yi Kun Wang Shunguan Zhu Jianguo zhang State Key Laboratory of Explosion Science and Technology Beijing Institute of TechnologyBeijing 100081China School of Chemical Engineering Nanjing University of Science and Technology200 Xiaolingwei StreetXuanwuNanjing 210094China Department of Chemistry Laboratory of Structure and Functional Regulation of Hybrid MaterialsAnhui UniversityMinistry of EducationHefei 230601China

The high energy coordination compounds Cu(TZCA)_(2)(ClO_(4))_(2)(ECCs-1) was prepared by 1H-tetrazole-5-carbohydrazide(TZCA) with a high energy skeleton and a strong coordination ability *** the same time,the reaction activity of the ligand was explored,and the single crystal structure of it and intermediate were *** structures of all substances were characterized by IR and *** the structure and composition of ECCs-1 are confirmed by ESP,AC,SEM and *** and chemical properties tests show that ECCs-1 has an acceptable thermal stability(T_(d)=177℃) and extremely sensitive mechanical stimulation(IS=1 J,FS=5 N).The comprehensive performance test results show that ECCs-1 has excellent initiation *** addition,the decomposition mechanism of ECCs-1 is explored from two aspects of experiment and theoretical calculation.

关键词： 1H-tetrazole-5-carbohydrazide Primary explosive Decomposition mechanism Coordination polymers Laser

Standardized Operational Protocol for Human Brain Banking in China

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Neuroscience Bulletin 2019年第2期35卷 270-276页

作者： Wenying Qiu Hanlin zhang Aimin Bao Keqing Zhu Yue Huang Xiaoxin Yan Jing zhang Chunjiu Zhong Yong Shen Jiangning Zhou Xiaoying Zheng Liwei zhang Yousheng Shu Beisha Tang zhenxin zhang Gang Wang Ren Zhou Bing Sun Changlin Gong Shumin Duan Chao Ma Department of Human Anatomy Histology and EmbryologyInstitute of Basic Medical SciencesNeuroscience CenterChinese Academy of Medical SciencesPeking Union Medical College Department of Neurobiology Zhejiang University School of Medicine Neurology Center Beijing Tiantan Hospital Affiliated to Beijing Capital Medical University and Central Brain BankNational Clinical Research Centre for Neurological Disorders Department of Human Anatomy and Neurobiology Xiangya School of MedicineCentral South University Department of Pathology Peking University Health Science Centre Department of Neurology Zhongshan HospitalFudan University School of Life Sciences University of Science and Technology of China Asia-Pacific Economic Cooperation Health Science Acad-emy/Institute of Population Research Peking University Beijing Tian Tan Hospital Capital Medical University Institute of Brain and Cognitive Sciences Beijing Normal University Xiangya Hospital Central South University Department of Neurology Peking Union Medical College Hospital Department of Neurology and Neuroscience Institute Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Department of Pathology Zhejiang University School of Medicine China Brain Bank Zhejiang University School of Medicine

With the progress of society, there is an increasing need to tackle disorders of the central nervous system. Human brain tissue, unlike animal tissues, is an irreplaceable resource for the study of neurological diseases (1)Aimed at scientific research and education, the roles of human brain tissue repositories are to acquire brain tissue from donors, prepare, process, and preserve collected samples,provide tissue to specific eligible facilities, and determine the characteristics of each tissue sample.

关键词： Standardized Brain Banking increasing

Efficacy and safety of rasagiline in Chinese patients with early Parkinson’s disease:a randomized, double-blind,parallel,placebo-controlled,fixed-dose study

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Translational Neurodegeneration 2018年第1期7卷 352-360页

作者： zhenxin zhang Jian Wang Shengdi Chen Chunfeng Liu Baorong zhang Rong Peng Shenggang Sun Xiangru Sun Gang Zhao Qiumin Qu Yansheng Li Suiqiang Zhu Xiaoping Pan Ming Shao Yanping Wang Peking Union Medical College Hospital BeijingChina Huashan Hospital Fudan UniversityShanghaiChina Ruijin Hospital Shanghai Jiaotong University School of MedicineShanghaiChina The Second Affiliated Hospital of Soochow University SuzhouChina The Second Affiliated Hospital School of MedicineZhejiang UniversityZhejiangHangzhouChina West China Hospital Sichuan UniversityChengduChina Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology WuhanChina Peking University First Hospital BeijingChina Xijing Hospital The First Affiliated Hospital of The Fourth Military Medical UniversityXi’anChina The First Affiliated Hospital of Xi’an Jiaotong University Xi’anChina Renji Hospital Shanghai Jiaotong University School of MedicineShanghaiChina Tongji Hospital of Tongji Medical College Huazhong University of Science and TechnologyWuhanChina Guangzhou First People’s Hospital School of MedicineSouth China University of TechnologyGuangzhouChina The First Affiliated Hospital of Guangzhou Medical University GuangzhouChina The Second Affiliated Hospital of Guangzhou Medical University GuangzhouChina

Background:Rasagiline is a monoamine oxidase-B inhibitor used for Parkinson’s disease(PD)treatment,but its effectiveness on Chinese patients is *** study aimed to evaluate the efficacy and safety of rasagiline monotherapy in Chinese patients with early ***:A 26-weeks,randomized,double-blind,placebo-controlled study has been performed at 15 sites in China and enrolled outpatients(≥35 years old)with idiopathic PD without a history of using any dopaminergic *** were randomized 1:1 to receive rasagiline 1 mg once daily or *** primary endpoint was the change of the Unified Parkinson’s Disease Rating Scale(UPDRS)total score from baseline to 26 weeks *** endpoints included changes in UPDRS subscale scores from part Ⅰ to Ⅲ.Health status was assessed with the PD Questionnaire(PDQ)-39 and EuroQol-Five-Dimension(EQ-5D)*** profile was collected until 30 weeks after ***:A total of 130 patients(n=65/group)were recruited,and 127(rasagiline,n=64;placebo,n=63)were included in the full analysis *** characteristics were comparable between the two *** decrease in the mean UPDRS total score was greater in the rasagiline group than in the placebo group(−3.18±0.95 vs.−0.18±0.98,P=0.025),and the mean UPDRS part I non-motor symptoms score(−0.54±0.15 vs.-0.08±0.15,P=0.003)were significantly decreased in the rasagiline group compared with placebo treated *** improvement trend was observed in the active treatment group for the subscales evaluation with parts Ⅱ and Ⅲ,while the difference to placebo was not statistically *** quality assessed by the EQ-5D visual analog scale improved in the rasagiline group but worsened in placebo treated *** overall incidence of treatment-emergent adverse events(AEs)was slightly lower in the rasagiline group(41.5%)than in the placebo group(46.2%).Conclusions:Rasagiline is effective,safe,and well tolerated as monotherapy for the

关键词： Parkinson’s disease Monoamine oxidase inhibitor Rasagiline Monotherapy China

Adjunct rasagiline to treat Parkinson’s disease with motor fluctuations:a randomized,double-blind study in China

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Translational Neurodegeneration 2018年第1期7卷 127-137页

作者： zhenxin zhang Ming Shao Shengdi Chen Chunfeng Liu Rong Peng Yansheng Li Jian Wang Suiqiang Zhu Qiumin Qu Xiaoying zhang Haibo Chen Xiangru Sun Yanping Wang Shenggang Sun Baorong zhang Jimei Li Xiaoping Pan Gang Zhao Department of Neurology Peking Union Medical College Hospital53 Dongdan N StDongchengBeijingChina Department of Neurology The First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina Department of Neurology Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiChina Department of Neurology The Second Affiliated Hospital of Soochow UniversitySuzhouChina Department of Neurology West China HospitalSichuan UniversityChengduChina Department of Neurology Renji HospitalShanghai Jiaotong University School of MedicineShanghaiChina Department of Neurology Huashan HospitalFudan UniversityShanghaiChina Department of Neurology Tongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Department of Neurology The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Department of Neurology Beijing HospitalBeijingChina Department of Neurology Peking University First HospitalBeijingChina Department of Neurology The Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina Department of Neurology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Department of Neurology The Second Affiliated hospital of Zhejiang University School of MedicineZhejiangHangzhouChina Department of Neurology Beijing Friendship HospitalCapital Medical UniversityBeijingChina Department of Neurology Guangzhou First People’s HospitalGuangzhouChina Department of Neurology Xijing HospitalThe First Affiliated Hospital of The Fourth Military Medical UniversityXi’anChina

Background:The use of adjunct rasagiline in levodopa-treated patients with Parkinson’s disease and motor fluctuations is supported by findings from large-scale clinical *** study is to investigate the efficacy and safety of adjunct rasagiline in Chinese patients with Parkinson’s disease,as a product registration ***:This 16-week,randomized,double-blind,parallel-group,multicenter,placebo-controlled study of rasagiline 1 mg/day included levodopa-treated patients with Parkinson’s disease and motor *** primary efficacy endpoint was mean change from baseline in total daily OFF time over 16 *** endpoints were Clinical Global Impressions–Improvement(CGI-I),and change in Unified Parkinson’s Disease Rating Scale(UPDRS)Activities of daily living(ADL)and Motor *** well-being(EQ-5D),and the frequency of adverse events were also ***:In total,324 levodopa-treated patients were randomized to rasagiline 1 mg/day(n=165)or placebo(n=159).Over 16 weeks,rasagiline statistically significantly reduced the mean[95% confidence interval]total daily OFF time versus placebo(−0.5 h[−0.92,−0.07];p=0.023).There were also statistically significant improvements versus placebo in CGI-I(−0.4 points[−0.61,−0.22];p<0.001),UPDRS-ADL OFF(−1.0 points[−1.75,−0.27];p=0.008),and UPDRS-Motor ON(−1.6 points[−3.05,−0.14];p=0.032)scores,as well as the EQ-5D utility index(p<0.05).Rasagiline was safe and well ***:In levodopa-treated Chinese patients with Parkinson’s disease and motor fluctuations,adjunct rasagiline 1 mg/day statistically significantly reduced OFF time,and improved daily function and overall well-being,versus *** with findings in other countries,adjunct rasagiline was proven efficacious and well tolerated in Chinese patients.

关键词： Parkinson’s disease Rasagiline Adjunct Motor fluctuations OFF time Quality of life China