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Positive Association Between Type 2 Diabetes Risk Alleles Near CDKAL1 and Reduced Birthweight in Chinese Han Individuals

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Chinese Medical Journal 2015年第14期128卷 1873-1878页

作者： Xiao-Fang Sun Xin-Hua Xiao zhen-Xin Zhang Ying Liu Tao Xu Xi-Lin Zhu Yun Zhang Xiao-Pan Wu Wen-hui Li Hua-Bing Zhang Miao Yu Department of Endocrinology Key Laboratory of Endocrinology Ministry of Health Peking Union Medical College Hospital Diabetes Research Center of Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100730 China Department of Endocrinology The Affiliated Hospital of Qingdao University Qingdao Shandong 266003 China Department of Neurology Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100730 China National Laboratory of Medical Molecular Biology Institute of Basic Medical Sciences Chinese Academy of Medical Sciences School of Basic Medicine Peking Union Medical College Beijing 100730 China Department of Epidemiology and Statistics Institute of Basic Medical Sciences Chinese Academy of Medical Sciences and School of Basic Medicine Peking Union Medical College Beijing 100730 China

Background： Fetal insulin hypothesis was proposed that the association between low birth weight and type 2 diabetes is principally genetically mediated. The aim of this study was to investigate whether common variants in genes CDKALI, HHEX, ADCY5, SRR, PTPRD that predisposed to type 2 diabetes were also associated with reduced birthweight in Chinese Han population.Methods： Twelve single nucleotide polymorphisms （rs7756992/rs10946398 in CDKAL1, rsl 111875 in HHEA; rs391300 in SRR, rs17584499 in PTPRD. rs1170806/rs9883204/rs4678017/rs9881942/rs7641344/rs6777397/rs6226243 in ADCY5） were genotyped in 1174 unrelated individuals born in Peking Union Medical College Hospital from 1921 to 1954 by TaqMan allelic discrimination assays, of which 645 had normal glucose tolerance, 181 had developed type 2 diabetes and 348 impaired glucose regulation. Associations of these 12 genetic variants with birthweight and glucose metabolism in later life were analyzed.Results： Birthweight was inversely associated with CDKAL 1-rs 10946398 （β = -41 g [95% confidence interval [CI]： -80, 3], P= 0.034）, common variants both associated with increased risk of impaired glucose metabolism and decreased insulin secretion index later in life. After adjusting for sex, gestational weeks, parity and maternal age, the risk allele of CDKAL1-rs7756992 was associated with reduced birthweight （β = 36 g [95% CI： -72, -0.2], P = 0.048）. The risk allele in SRR showed a trend toward a reduction ofbirthweight （P =0.085）. Conclusions： This study identified the association between type 2 diabetes risk variants in CDKAL 1 and birthweight in Chinese Hart individuals, and the carrier of risk allele within SRR had the trend of reduced birthweight. This demonstrates that there is a clear overlap between the genetics of type 2 diabetes and fetal growth, which proposes that lower birth weight and type 2 diabetes may be two phenotypes of one genotype.

关键词： Birthweight Chinese Han Genetic Polymorphisms Impaired Glucose Metabolism

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变电站多传感器数据融合远程安保预警系统

自动化与仪器仪表 2023年第2期 152-155,160页

作者：王振邱慧国网江苏省电力有限公司扬州供电分公司江苏扬州225009

无人值守变电站的日常安全平稳运行过程中,需要采用多种监控系统辅助,为提升变电站运行安全自动化水平,提出将多种传感器布设在变电站中,通过构建变电站多传感器数据融合远程安保预警系统,实现变电站智能安保。利用多种传感器及入侵信... 详细信息

无人值守变电站的日常安全平稳运行过程中,需要采用多种监控系统辅助,为提升变电站运行安全自动化水平,提出将多种传感器布设在变电站中,通过构建变电站多传感器数据融合远程安保预警系统,实现变电站智能安保。利用多种传感器及入侵信号监测终端,采集变电站内部的运行数据及变电站外部的入侵信息;在数据分析模块,利用支持向量机算法对所获得的变电站多传感器数据进行识别、划分及回归处理,得到周界环境、变压器等数据特征;将数据特征上传至中控层、发布预警指令等,实现变电站安保预警。实验结果表明,设计系统可以有效采集变电站运行信息,对运行异常信息发出准确预警,数据采集时间、系统响应时间均较短,可以满足现实需求,具有一定的应用价值。

关键词：多传感器变电站安防支持向量机深度分析数据融合

Distinctive Drug-resistant Mutation Profiles and Interpretations of HIV-1 Proviral DNA Revealed by Deep Sequencing in Reverse Transcriptase

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Biomedical and Environmental Sciences 2016年第4期29卷 239-247页

作者： YIN Qian Qian LI zhen Peng ZHAO Hai PAN Dong WANG Yan XU Wei Si XING hui FENG Yi JIANG Shi Bo SHAO Yi Ming MA Li Ying State Key Laboratory of Infectious Disease Prevention and Control National Center for AIDS/STD Control and Prevention (NCAIDS) Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases Chinese Center for Disease Control and Prevention State Key Laboratory of Infectious Disease Prevention and Control National Institute for Communicable Disease Control and Prevention Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases Chinese Center for Disease Control and Prevention Key Laboratory of Medical Molecular Virology (Ministries of Education and Health) Shanghai Medical College and Institute of Medical Microbiology Fudan University

Objective To investigate distinctive features in drug-resistant mutations （DRMs） and interpretations for reverse transcriptase inhibitors （RTIs） between proviral DNA and paired viral RNA in HIV-l-infected patients. Methods Forty-three HIV-l-infected individuals receiving first-line antiretroviral therapy were recruited to participate in a multicenter AIDS Cohort Study in Anhui and Henan Provinces in China in 2004. Drug resistance genotyping was performed by bulk sequencing and deep sequencing on the plasma and whole blood of 77 samples, respectively. Drug-resistance interpretation was compared between viral RNA and paired proviral DNA. Results Compared with bulk sequencing, deep sequencing could detect more DRMs and samples with DRMs in both viral RNA and proviral DNA. The mutations M1841 and M2301 were more prevalent in proviral DNA than in viral RNA （Fisher＇s exact test, P〈0.05）. Considering ＇majority resistant variants＇, 15 samples （19.48%） showed differences in drug resistance interpretation between viral RNA and proviral DNA, and 5 of these samples with different DRMs between proviral DNA and paired viral RNA showed a higher level of drug resistance to the first-line drugs. Considering ＇minority resistant variants＇, 22 samples （28.57%） were associated with a higher level of drug resistance to the tested RTIs for proviral DNA when compared with paired viral RNA. Conclusion Compared with viral RNA, the distinctive information of DRMs and drug resistance interpretations for proviral DNA could be obtained by deep sequencing, which could provide more detailed and precise information for drug resistance monitoring and the rational design of optimal antiretroviral therapy regimens.

关键词： HIV-1 drug-resistant mutation Drug-resistance interpretation Proviral DNA Viral RNA Deep sequencing

Implementation of MPEG-2 TS Transmission Based on CATV(HFC)

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The Journal of China Universities of Posts and Telecommunications 2000年第4期7卷 51-56页

作者： DU Jiang-hong XU zhong-yang XIONG Chun-shang DING hui WEI Zhi-gang ZHANG Ke-feng LIU Wei-zhong LIU zheng-lin Department of Electronics Science and Technology Huazhong University of Science and TechnologyWuhan 430074P.R.China

This paper suggests the method for MPEG 2 Transport Stream ( TS ) processing and transmitting over CATV (HFC ). An MPEG 2 TS Generator Card design is presented. The system configuration and the functions of the Generator Card are given. The design of hardware and software for the card and some issues are discussed. A practical system of the application of the MPEG 2 TS Generator Card is given. A satisfactory result has been achieved in the application.

关键词： MPEG-2 CATV(HFC) transmitting PCI bus

α-苯巯基-α-氨基乙酸乙酯类LSD1抑制剂的设计、合成及活性评价

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中国药学杂志 2023年第1期58卷 26-32页

作者：李中华秦婷婷王真真乔永辉胡锴苏运芳张宁宁张紫娟马金莲河南中医药大学中医药科学院郑州450046

目的设计构建α-苯巯基-α-氨基乙酸乙酯类组蛋白赖氨酸特异性去甲基化酶1(lysine specific demethylase 1,LSD1)抑制剂,并进行生物活性评价与计算机模拟研究。方法以乙醛酸乙酯、氨和芳基硫酚为原料,采用三组分一锅法构建α-苯巯基-α... 详细信息

目的设计构建α-苯巯基-α-氨基乙酸乙酯类组蛋白赖氨酸特异性去甲基化酶1(lysine specific demethylase 1,LSD1)抑制剂,并进行生物活性评价与计算机模拟研究。方法以乙醛酸乙酯、氨和芳基硫酚为原料,采用三组分一锅法构建α-苯巯基-α-氨基乙酸乙酯类小分子化合物。采用课题组构建的筛选平台,测试目标化合物在5和1μmol·L^(-1)浓度下对LSD1的抑制率,将活性最好的化合物测试其半数抑制浓度值(IC_(50)),并通过分子模拟研究其结合机制。利用稀释法评价抑制剂的可逆性,通过迁移(transwell)和蛋白质印迹(Western blot)试验评价抑制剂对肿瘤细胞的抗转移和上皮-间质转换(epithelial-mesenchymal transition,EMT)过程。结果共合成11个目标化合物,多数化合物具有很好的LSD1抑制活性。活性最好的化合物4j的IC_(50)值为0.28μmol·L^(-1),能够可逆性作用于LSD1,在细胞水平能通过抑制LSD1来提高H3K4me2的表达水平。此外,化合物4j能够抑制肺癌细胞H1299的转移能力和EMT过程。结论α-苯巯基-α-氨基乙酸乙酯类结构是一类结构新颖的LSD1抑制剂骨架,为进行后续结构优化和构效关系研究打下良好基础。

关键词：组蛋白赖氨酸特异性去甲基化酶1 酶抑制作用可逆性分子模拟抗肿瘤作用

A high-throughput model for screening anti-tumor agents capable of promoting polymerization of tubulin in vitro

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Acta Pharmacologica Sinica 2004年第6期25卷 73-80页

作者： Wei HU, hui DONG, Yue-zhong LI2, Xi-tao HU, Guan-jun HAN, Yin-bo QU State KeyLaboratory of Microbial Technology, School of Life Science, Shandong University, Ji-nan 250100, China 山东大学微生物技术国家重点实验室 Jinan 250100

AIM: To establish a high-throughput model for screening anti-tumor agents capable of promoting the polymeriza- tion of tubulin in vitro. METHODS: Tubulin was prepared in different purity for two screening steps. The first step was a high-throughput screening (HTS) for a set of 1500 samples using the GTP-containing tubulin and the end-reading method. The second step was performed on 119 hits from the first screening by a kinetic assay with GTP-lacking tubulin. RESULTS: The HTS for 1500 samples was accomplished in less than 3 h. From the screening, 108 samples were identified with >20 % promotion activity at 10 mg/L. Five of 108 were further confirmed by the kinetic assay using the purified tubulin subsequently. Three of the hit compounds were Epothilone A or its analogs, the other two compounds had new structures with a common pharmacophore for cytotoxic natural products that stabilize microtubules. In an MTT test, the five selected samples from the screening showed a minimal IC50 at0.28±0.06 nmol/Lto Helacells. CONCLUTION: The two-stepscreening methodis a high-throughtput, cost-effective, and efficient approach to identify microtubule-stabilizing agents.

关键词： antitumor drug screening assays tubulin polymerization promotor microtubules

Prevalence of Thyroid Nodules and Its Relationship with Iodine Status in Shanghai:a Population-based Study

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Biomedical and Environmental Sciences 2016年第6期29卷 398-407页

作者： SONG Jun ZOU Shu Rong GUO Chang Yi ZANG Jia Jie ZHU zhen Ni MI Ming HUANG Cui Hua YU hui Ting LU Xi RUAN Ye WU Fan Department of Nutrition Hygiene Shanghai Municipal Center for Disease Control and Prevention Department of Food Hygiene & Food-Borne Disease Control Shanghai Municipal Center for Disease Control and Prevention Department of Health Statistics Shanghai Municipal Center for Disease Control and Prevention Department of School Health Shanghai Municipal Center for Disease Control and Prevention Department of Diabetes Mellitus Control and Prevention Shanghai Municipal Center for Disease Control and Prevention

Objective This study was designed to evaluate the prevalence of thyroid nodules（TNs） and its relationship with urine iodine concentrations（UICs） after the regional rapid economic growth and lifestyle changes. Methods A cross-sectional survey was conducted in the general population aged 15-69 years. A questionnaire regarding general and personal characteristics and relevant information was administered. Ultrasonography of the thyroid was performed, and serum triiodothyronine（T3）, tetraiodothyronine（T4）, serum thyroid stimulating hormone（TSH）, free triiodothyronine（FT3）, free tetraiodothyronine（FT4）, thyroglobulin antibody（Tg Ab）, thyroid peroxidase antibody（TPOAb）, and TSH receptor antibody（TRAb） levels were measured for each individual subject. Results The prevalence rates of TNs in the whole population, females and males were 27.76%, 34.04%, and 21.60%, respectively. The prevalence of multiple nodules increased with age, whereas the prevalence peaks differed between males and females. The median UICs in the whole population and females with non-TNs were higher than those of subjects with TNs（P=0.0035, P=0.0068）. The median UICs in subjects with a single TN were higher than those in subjects with multiple TNs（P=0.0164, P=0.0127）. The result showed a U-shaped curve relationship between UIC and prevalence of TNs. The prevalence of TNs was the lowest when the UIC was 140-400 μg/L. Conclusion The prevalence of TNs was nearly 30% and increased with age. The relationship between UIC and prevalence of TNs is U-shaped, with an increase in risk when the UIC was 〈140 μg/L and 〉400 μg/L. Very low or high UIC levels need attention and correction.

关键词： Thyroid Nodules Prevalence Urine iodine Epidemiology

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我国金融业区域发展差异的空间统计分析

系统工程理论与实践 2014年第5期34卷 1171-1180页

作者：部慧梁小珍皮理北京航空航天大学经济管理学院北京100191

本文利用我国31个省(直辖市)1997 2009年的数据,度量了我国金融业的空间集聚情况,并对我国区域金融发展进行了全局Moran I检验、局部Moran I检验和Moran散点图分析,以探讨我国区域金融发展的空间相似性和动态演变.实证结果显示:从全局... 详细信息

本文利用我国31个省(直辖市)1997 2009年的数据,度量了我国金融业的空间集聚情况,并对我国区域金融发展进行了全局Moran I检验、局部Moran I检验和Moran散点图分析,以探讨我国区域金融发展的空间相似性和动态演变.实证结果显示:从全局上看我国金融业空间聚集性仍不显著,并不像经济增长已呈现显著的聚集性分布,经济集聚远远先于金融集聚;但是,我国某些相邻的省市间的金融发展具有一定的空间相似性,局部呈现出某种集聚性分布,即金融业发展在局部具有一定的辐射效应.

关键词：金融集聚空间统计分析 Moran I检验 Moran散点图

多层UV形瓦楞纸板的准静态轴向压溃模型研究

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包装工程 2022年第19期43卷 180-189页

作者：梁友珍王军范慧丽江南大学江苏无锡214122 江苏省先进食品装备制造技术重点试验室江苏无锡214122 耐帆包装工程(无锡)有限公司江苏无锡214028

目的对多层UV型瓦楞纸板轴向压溃后的变形机理和抗压性能进行探究,以助于多层瓦楞纸箱和缓冲包装的设计。方法采用理论分析和试验研究相结合的方式,对UV形多层瓦楞纸板轴向压溃后的平台应力进行理论建模和准静态试验研究。结果在UV形瓦... 详细信息

目的对多层UV型瓦楞纸板轴向压溃后的变形机理和抗压性能进行探究,以助于多层瓦楞纸箱和缓冲包装的设计。方法采用理论分析和试验研究相结合的方式,对UV形多层瓦楞纸板轴向压溃后的平台应力进行理论建模和准静态试验研究。结果在UV形瓦楞生产工艺的基础上,假设楞纸与相邻层之间的相互作用为面黏合;提出了一种新的折叠元件以及波纹芯的3种变形模式;此外,分别提出了五层瓦楞纸板和七层瓦楞纸板平台应力理论模型;多层瓦楞纸板平台应力的理论预测结果与试验结果吻合良好。结论所提出的多层UV形瓦楞纸板理论模型是有效的,这将有助于波纹结构刚度设计和参数选择,以满足不同的强度要求。

关键词： UV形多层瓦楞纸板面黏合轴向压溃平台应力能量吸收