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国产rhPTH1-34治疗绝经后骨质疏松症的有效性和安全性:随机对照、多中心临床研究

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中华骨质疏松和骨矿盐疾病杂志 2022年第2期15卷 135-141页

作者：李梅章振林林华程群屠重棋唐海游利郑淑慧徐勉金小岚余卫胡伟伟朱秀芬朱汉民石锐陈浩陈琳高尚聚杜鹃程莹夏维波中国医学科学院北京协和医学院北京协和医院内分泌科国家卫生健康委员会内分泌重点实验室北京100730 上海交通大学附属第六人民医院骨质疏松和骨病专科上海200233 南京大学医学院附属鼓楼医院骨科南京210008 复旦大学附属华东医院骨质疏松科上海200040 四川大学华西医院骨科成都610047 首都医科大学附属北京友谊医院骨科北京100050 上海市第一人民医院内分泌科上海200080 河北省人民医院骨科石家庄050051 昆明医科大学第二附属医院内分泌科昆明650101 中国人民解放军西部战区总医院内分泌科成都610083 中国医学科学院北京协和医学院北京协和医院放射科北京100730

目的以原研特立帕肽和鲑鱼降钙素为阳性对照,观察国产基因重组人甲状旁腺素氨基端1-34片段(recombinant human parathyroid hormone N-terminal 1-34 fragment,rhPTH1-34)治疗绝经后骨质疏松症的有效性和安全性。方法纳入绝经后骨质... 详细信息

目的以原研特立帕肽和鲑鱼降钙素为阳性对照,观察国产基因重组人甲状旁腺素氨基端1-34片段(recombinant human parathyroid hormone N-terminal 1-34 fragment,rhPTH1-34)治疗绝经后骨质疏松症的有效性和安全性。方法纳入绝经后骨质疏松症女性214例,按照1∶1∶1∶0.5比例,随机分为4组:rhPTH1-3420μg组(n=59)及40μg组(n=62)分别每天注射国产rhPTH1-3420及40μg;降钙素组(n=61)给予鼻喷鲑鱼降钙素200 IU;特立帕肽组(n=32)给予原研特立帕肽注射20μg/d;疗程均为24周。观察治疗前后腰椎(L1-4)和髋部骨密度(bone mineral density,BMD)的变化率,骨转换生化指标的变化率,包括血清Ⅰ型前胶原N-端肽(procollagen typeⅠN-terminal propeptide,P1NP)和Ⅰ型胶原交联C-末端肽(β-cross linked C-telopeptide of typeⅠcollagen,β-CTX),以及药物治疗的安全性。结果治疗24周后,rhPTH1-3420μg及40μg组L1-4 BMD较基线分别增加3.42%和4.82%,特立帕肽组L1-4 BMD增加3.66%(均P0.05)。国产及原研特立帕肽的疗效均优于鼻喷降钙素组。国产与原研rhPTH1-3420μg组治疗24周使血清P1NP分别升高534.22%和277.86%,使β-CTX水平分别升高247.88%和202.25%(均P<0.001),P1NP增幅大于β-CTX。国产与原研rhPTH1-34组的安全性较好。结论每天皮下注射20μg国产rhPTH1-34治疗24周能够显著提升腰椎BMD,促进骨形成,疗效及安全性与原研特立帕肽相当,且优于降钙素鼻喷剂。

关键词：甲状旁腺素氨基端1-34片段特立帕肽绝经后骨质疏松骨密度

黄粉虫纤溶活性蛋白酶(TFP)酶学性质以及红外光谱分析

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时珍国医国药 2011年第9期22卷 2061-2064页

作者：吴艳玲谭竹钧韩雅莉林非凡陈雅雄余磊汪威张丽广东工业大学轻工化工学院广东广州510006

目的研究黄粉虫纤溶活性蛋白(Tenebrio Fibrinolyric Proteins,TFP)的酶学性质及对其进行分类。方法以BAEE、BAPNA和酪蛋白为底物分别测TFP的Km值;分别研究PMSF和胰蛋白酶对TFP活性的影响。结果以BAEE和BAPNA为TFP底物,Km值分别为0.182 ... 详细信息

目的研究黄粉虫纤溶活性蛋白(Tenebrio Fibrinolyric Proteins,TFP)的酶学性质及对其进行分类。方法以BAEE、BAPNA和酪蛋白为底物分别测TFP的Km值;分别研究PMSF和胰蛋白酶对TFP活性的影响。结果以BAEE和BAPNA为TFP底物,Km值分别为0.182 mmol/L和1.138 mmol/L,表明TFP与BAEE亲和力最好,酯酶活力>酰胺酶活力>肽键酶活力。丝氨酸蛋白酶抑制剂PMSF能有效抑制TFP活性,而偏弱碱性环境下胰蛋白酶未降解TFP,胰蛋白酶与TFP红外结构图谱相似,可以初步证明TFP属于丝氨酸蛋白酶。结论黄粉虫纤溶活性蛋白酶的酯酶活力最好,属于丝氨酸蛋白酶。

关键词：黄粉虫纤溶活性蛋白 Km 丝氨酸蛋白酶胰蛋白酶红外光谱

Efficacy and safety of LY01005 versus goserelin implant in Chinese patients with prostate cancer: A multicenter, randomized, open-label, phase III, non-inferiority trial

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Chinese Medical Journal 2023年第10期136卷 1207-1215页

作者： Chengyuan Gu Zengjun Wang Tianxin lin Zhiyu liu weiqing han Xuhui Zhang Chao liang Hao liu Yang yu Zhenzhou Xu Shuang liu Jingen Wang linghua Jia Xin Yao Wenfeng liao Cheng Fu Zhaohui Tan Guohua He Guoxi zhu Rui Fan Wenzeng Yang Xin Chen Zhizhong liu liqiang Zhong Benkang Shi Degang Ding Shubo Chen Junli wei Xudong Yao Ming Chen Zhanpeng Lu Qun Xie Zhiquan Hu Yinhuai Wang Hongqian Guo Tiwu Fan Zhaozhao liang Peng Chen wei Wang Tao Xu Chunsheng li Jinchun Xing Hong liao Dalin He Zhibin Wu Jiandi yu Zhongwen Feng Mengxiang Yang Qifeng Dou Quan Zeng yuanwei li Xin Gou Guangchen Zhou Xiaofeng Wang Rujian zhu Zhonghua Zhang Bo Zhang Wanlong Tan Xueling Qu Hongliang Sun Tianyi Gan Dingwei Ye Department of Urology Fudan University Shanghai Cancer CenterShanghai 200032China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai 200032China Department of Urology The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China Department of Urology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouGuangdong 510120China Department of Urology The Second Affiliated Hospital of Dalian Medical UniversityDalianLiaoning 116023China Department of Urology The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityHunan Cancer CenterChangshaHunan 410013China Department of Urology First Hospital of Shanxi Medical UniversityTaiyuanShanxi 030000China Department of Urology Jiangxi Provincial People’s HospitalSchool of MedicineNanchang UniversityNanchangJiangxi 330006China Department of Urology Tianjin Medical University Cancer Institute and HospitalTianjin 300060China Department of Urology Cancer Hospital of China Medical UniversityLiaoning Cancer Hospital and InstituteShenyangLiaoning 110043China Department of Urology Inner Mongolia People’s HospitalHohhotInner Mongolia 010010China Department of Urinary Surgery Taizhou Hospital of Traditional Chinese MedicineTaizhouJiangsu 225300China Department of Urology Linfen People’s HospitalLinfenShanxi 041000China Department of Urology Zhengzhou Central Hospital Affiliated to Zhengzhou UniversityZhengzhouHenan 450006China Department of Urology The Affiliated Hospital of Hebei UniversityBaodingHebei 071000China Department of Urology Chifeng Municipal HospitalChifeng Clinical Medical College of Inner Mongolia Medical UniversityChifengInner Mongolia 024000China Department of Urology Baogang HospitalBaotouInner Mongolia 014010China Department of Oncology The Second People’s Hospital of YibinYibinSichuan 644000China Department of Urology Qilu Hospital of Shandong UniversityJinanShandong 250014China Department of Urology Henan Provincial People’s Hos

Background:LY01005(Goserelin acetate sustained-release microsphere injection)is a modified gonadotropin-releasing hormone(GnRH)agonist injected *** phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate ***:We conducted a randomized controlled,open-label,non-inferiority trial across 49 sites in *** study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three *** primary efficacy endpoints were the percentage of patients with testosterone suppression≤50 ng/dL at day 29 and the cumulative probability of testosterone≤50 ng/dL from day 29 to ***-inferiority was prespecified at a margin of-10%.Secondary endpoints included significant castration(≤20 ng/dL),testosterone surge within 72 h following repeated dosing,and changes in luteinizing hormone,follicle-stimulating hormone,and prostate specific antigen ***:On day 29,in the LY01005 and goserelin implant groups,testosterone concentrations fell below medical-castration levels in 99.3%(142/143)and 100%(140/140)of patients,respectively,with a difference of-0.7%(95%confidence interval[CI],-3.9%to 2.0%)between the two *** cumulative probabilities of maintaining castration from days 29 to 85 were 99.3%and 97.8%,respectively,with a between-group difference of 1.5%(95%CI,-1.3%to 4.4%).Both results met the criterion for *** endpoints were similar between *** treatments were ***01005 was associated with fewer injection-site reactions than the goserelin implant(0%vs.1.4%[2/145]).Conclusion:LY01005 is as effective as goserelin implants in reducing testosterone to castration levels,with a similar safety *** registration:***,NCT04563936.

关键词： Prostatic neoplasms LY01005 Gonadotropin-releasing hormone agonist Efficacy Safety

Dark matter direct search sensitivity of the PandaX-4T experiment

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Science China(Physics,Mechanics & Astronomy) 2019年第3期62卷 49-57页

作者： HongGuang Zhang Abdusalam Abdukerim wei Chen Xun Chen yunHua Chen XiangYi Cui BinBin Dong DeQing Fang ChangBo Fu Karl Giboni Franco Giuliani linHui Gu Xuyuan Guo ZhiFan Guo Ke han ChangDa He ShengMing He Di Huang XingTao Huang Zhou Huang Peng Ji XiangDong Ji Yonglin Ju Shaoli li Yao li Heng lin HuaXuan liu JiangLai liu yuGang Ma YaJun Mao KaiXiang Ni JinHua Ning XiangXiang Ren Fang Shi AnDi Tan AnQing Wang Cheng Wang Hongwei Wang Meng Wang QiuHong Wang SiGuang Wang Xiuli Wang XuMing Wang Zhou Wang MengMeng Wu ShiYong Wu JingKai Xia MengJiao Xiao Pengwei Xie BinBin Yan JiJun Yang Yong Yang ChunXu yu JuMin yuan JianFeng yue Dan Zhang Tao Zhang li Zhao QiBin Zheng JiFang Zhou Ning Zhou XiaoPeng Zhou Shanghai Key Laboratory for Particle Physics and Cosmology Institute of Nuclear and Particle Physics (INPC) (INPC) and School of Physics and AstronomyShanghai Jiao Tong University School of Physics and Technology Xinjiang University Shanghai Key Laboratory for Particle Physics and Cosmology Institute of Nuclear and Particle Physics (INPC) and School of Physics and AstronomyShanghai Jiao Tong University Yalong River Hydropower Development Company Ltd. Shanghai Institute of Applied Physics Chinese Academy of Sciences School of Mechanical Engineering Shanghai Jiao Tong University School of Physics and Key Laboratory of Particle Physics and Particle Irradiation(MOE)(MOE) Shandong University School of Physics Nankai University tsung-Dao Lee Institute School of Physics Peking University Department of Physics University of Maryland College Park School of Physics and Key Laboratory of Particle Physics and Particle Irradiation(MOE) Shandong University Center of High Energy Physics Peking University School of Medical Instrument and Food Engineering University of Shanghai for Science and Technology

The Panda X-4T experiment, a 4-ton scale dark matter direct detection experiment, is being planned at the China Jinping Underground Laboratory. In this paper we present a simulation study of the expected background in this experiment. In a 2.8-ton fiducial mass and the signal region between 1-10 keV electron equivalent energy, the total electron recoil background is found to be 4.9 × 10^(-5) kg^(-1) d^(-1) keV^(-1). The nuclear recoil background in the same region is 2.8 × 10^(-7) kg^(-1) d^(-1) keV^(-1). With an exposure of 5.6 ton-years, the sensitivity of Panda X-4 T could reach a minimum spin-independent dark matter-nucleon cross section of 6 × 10^(-48) cm^2 at a dark matter mass of 40 Ge V/c^2.

关键词： dark matter WIMPs direct detection xenon

Measurement of solar pp neutrino flux using electron recoil data from PandaX-4T commissioning run

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Chinese Physics C 2024年第9期48卷 1-7,300页

作者： Xiaoying Lu Abdusalam Abdukerim Zihao Bo wei Chen Xun Chen yunhua Chen Chen Cheng Zhaokan Cheng Xiangyi Cui Yingjie Fan Deqing Fang lisheng Geng Karl Giboni Xuyuan Guo Chencheng han Ke han Changda He Jinrong He Di Huang Junting Huang Zhou Huang Ruquan Hou yu Hou Xiangdong Ji Yonglin Ju Chenxiang li Jiafu li Mingchuan li Shuaijie li Tao li Qing lin Jianglai liu Congcong Lu lingyin Luo yunyang Luo Wenbo Ma yugang Ma Yajun Mao yue Meng Xuyang Ning Binyu Pang Ningchun Qi Zhicheng Qian Xiangxiang Ren Nasir Shaheed Xiaofeng Shang Xiyuan Shao Guofang Shen Manbin Shen lin Si Wenliang Sun Yi Tao Anqing Wang Meng Wang Qiuhong Wang Shaobo Wang Siguang Wang wei Wang Xiuli Wang Xu Wang Zhou Wang yuehuan wei Mengmeng Wu weihao Wu yuan Wu Mengjiao Xiao Xiang Xiao Kaizhi Xiong Binbin Yan Xiyu Yan Yong Yang Chunxu yu Ying yuan Zhe yuan Youhui yun Xinning Zeng Minzhen Zhang Peng Zhang Shibo Zhang Shu Zhang Tao Zhang wei Zhang Yang Zhang Yingxin Zhang yuanyuan Zhang li Zhao Jifang Zhou Ning Zhou Xiaopeng Zhou yubo Zhou Zhizhen Zhou Research Center for Particle Science and Technology Institute of Frontier and Interdisciplinary ScienceShandong UniversityQingdao 266237China Key Laboratory of Particle Physics and Particle Irradiation of Ministry of Education Shandong UniversityQingdao 266237China School of Physics and Astronomy Shanghai Jiao Tong UniversityKey Laboratory for Particle Astrophysics and Cosmology(MoE)Shanghai Key Laboratory for Particle Physics and CosmologyShanghai 200240China New Cornerstone Science Laboratory Tsung-Dao Lee InstituteShanghai Jiao Tong UniversityShanghai 200240China Shanghai Jiao Tong University Sichuan Research Institute Chengdu 610213China Jinping Deep Underground Frontier Science and Dark Matter Key Laboratory of Sichuan Province Liangshan 615000China Yalong River Hydropower Development Company Ltd.288 Shuanglin RoadChengdu 610051China School of Physics Sun Yat-Sen UniversityGuangzhou 510275China Sino-French Institute of Nuclear Engineering and Technology Sun Yat-Sen UniversityZhuhai 519082China Department of Physics Yantai UniversityYantai 264005China Key Laboratory of Nuclear Physics and Ion-beam Application(MOE) Institute of Modern PhysicsFudan UniversityShanghai 200433China School of Physics Beihang UniversityBeijing 102206China Beijing Key Laboratory of Advanced Nuclear Materials and Physics Beihang UniversityBeijing 102206China Peng Huanwu Collaborative Center for Research and Education Beihang UniversityBeijing 100191China Southern Center for Nuclear-Science Theory(SCNT) Institute of Modern PhysicsChinese Academy of SciencesHuizhou 516000China School of Mechanical Engineering Shanghai Jiao Tong UniversityShanghai 200240China Department of Physics University of MarylandCollege ParkMaryland 20742USA State Key Laboratory of Particle Detection and Electronics University of Science and Technology of ChinaHefei 230026China Department of Modern Physics University of Science and Technology of ChinaHefei 230026China School of Physics Peking UniversityBeijing 100871Ch

The proton-proton(pp)fusion chain dominates the neutrino production in the *** uncertainty of the predicted pp neutrino flux is at the sub-percent level,whereas that of the best measurement is O(10%).In this study,for the first time,we measure solar pp neutrinos in the electron recoil energy range from 24 to 144 keV using the PandaX-4T commissioning data with 0.63 tonne×year *** pp neutrino flux is determined as(8.0±3.9(stat)±10.0(syst))×1010 s^(-1)cm^(-2),which is consistent with the Standard Solar Model and existing measurements,corresponding to an upper flux limit of 23.3×10^(10)s^(-1)cm^(-2)at 90%C.L..

关键词： solar pp neutrino flux PandaX-4T electron recoil spectrum

艾灸督脉调控PI3K/Akt/mTOR信号通路增强APP/PS1双转基因AD小鼠自噬水平的研究

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中国针灸 2019年第12期39卷 1313-1319页

作者：张利达韩为朱才丰宋小鸽程卉杨坤秦晓凤张君宇桂林安徽中医药大学研究生院合肥230038 安徽中医药大学第二附属医院脑病科合肥230061 安徽中医药大学第二附属医院老年病科合肥230061 安徽中医药大学针灸经络研究所安徽中医药大学科研实验中心新安医学教育部重点实验室

目的:基于上游磷脂酰肌醇-3激酶(phosphoinositide 3-kinases,PI3K)/蛋白激酶B(protein kinase B,AKT)/哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)信号通路观察艾灸"百会""风府""大椎"穴对淀粉样前体蛋白/早老素1(amyloid precursor protein/presenili1,APP/PS1)双转基因阿尔茨海默病(Alzheimer’s disease,AD)小鼠脑内β-淀粉样蛋白(amyloidβ-peptide,Aβ)清除作用的影响。方法:将60只APP/PS1双转基因AD小鼠随机分为模型组、艾灸组、雷帕霉素组、艾灸+抑制剂组,每组15只,15只同龄同背景C57BL/6J雄性小鼠作为对照组。艾灸组小鼠实按灸"百会"、温和灸"风府"和"大椎",每次20 min,每日1次,治疗2周;雷帕霉素组用雷帕霉素(rapamycin)腹腔注射给药,2 mg·kg^-1·d^-1,治疗2周;艾灸+抑制剂组在艾灸组治疗基础上同时予以3-甲基腺嘌呤(3-methyladenine,3-MA)腹腔注射给药,1.5 mg·kg^-1·d^-1,治疗2周;对照组和模型组动物常规饲养2周,不进行任何干预。用免疫组化技术检测小鼠皮质和海马脑区Aβ1-42表达水平,透射电镜观察小鼠海马脑区自噬体的形成,免疫印迹法检测小鼠海马组织PI3K、Akt、p-Akt、mTOR、p-m TOR的蛋白表达。结果:与对照组比较,模型组皮质区和海马脑区Aβ1-42蛋白表达增多(P0.05),艾灸+抑制剂组皮质区和海马脑区Aβ1-42蛋白表达增多(P<0.01);与雷帕霉素组比较,艾灸+抑制剂组皮质区和海马脑区Aβ1-42蛋白表达增多(P<0.01)。模型组神经细胞胞质内自噬泡和细胞器减少;艾灸组自噬泡较多,可见不规则变形、萎缩的细胞器;雷帕霉素组可看到较多自噬泡,尚有变形的细胞器;艾灸+抑制剂组偶可观察到少量的自噬泡,可见较多变形、萎缩的细胞器。与对照组比较,模型组PI3K、Akt、p-Akt、m TOR、p-m TOR蛋白表达显著升高(P<0.01);与模型组比较,艾灸组、雷帕霉素组和艾灸+抑制剂组小鼠PI3K、Akt、p-Akt、mTOR、p-mTOR蛋白表达均明显下降(P<0.01);与艾灸组比较,雷帕霉素组小鼠PI3K、Akt、p-mTOR蛋白表达略有升高(P<0.01),艾灸+抑制剂组PI3K、Akt、p-Akt、mTOR、p-mTOR蛋白表达显著升高(P<0.01);与雷帕霉素组比较,艾灸+抑制剂组小鼠PI3K、Akt、p-Akt、mTOR、p-mTOR蛋白表达显著升高(P<0.01)。结论:艾灸督脉可加速自噬清除APP/PS1双转基因AD小鼠脑内的Aβ1-42蛋白异常沉积,其作用机制可能与艾灸督脉抑制PI3K/Akt/mTOR信号通路异常激活有关。

关键词：阿尔茨海默病艾灸督脉细胞自噬 β-淀粉样蛋白 PI3K/Akt/mTOR信号通路

The Jiao Tong University Spectroscopic Telescope Project

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Astronomical Techniques and Instruments 2024年第1期1卷 16-30页

作者： JUST Team Chengze liu Ying Zu Fabo Feng Zhaoyu li yu yu Hua Bai Xiangqun Cui Bozhong Gu Yizhou Gu Jiaxin han Yonghui Hou Zhongwen Hu hangxin Ji Yipeng Jing wei li Zhaoxiang Qi Xianyu Tan Cairang Tian Dehua Yang Xiangyan yuan Chao Zhai Congcong Zhang Jun Zhang Haotong Zhang Pengjie Zhang Yong Zhang Yi Zhao Xianzhong Zheng Qingfeng zhu Xiaohu Yang tsung-Dao Lee Institute Shanghai Jiao Tong UniversityShanghai 200240China Department of Astronomy School of Physics and AstronomyShanghai Jiao Tong UniversityShanghai 200240China Nanjing Institute of Astronomical Optics&Technology Chinese Academy of SciencesNanjing 210042China University of Chinese Academy of Sciences NanjingNanjing 211135China University of Chinese Academy of Sciences Beijing 101408China Lenghu Technology Innovation Industrial Park Management Committee Lenghu 817400China Shanghai Astronomical Observatory Chinese Academy of SciencesShanghai 200030China Department of Astronomy University of Science and Technology of ChinaHefei 230026China National Astronomical Observatories Chinese Academy of SciencesBeijing 100101China Purple Mountain Observatory Chinese Academy of SciencesNanjing 210023China

The Jiao Tong University Spectroscopic Telescope(JUST)is a 4.4-meter f/6.0 segmented-mirror telescope dedicated to spectroscopic *** JUST primary mirror is composed of 18 hexagonal segments,each with a diameter of 1.1 *** provides two Nasmyth platforms for placing science *** Nasmyth focus fits a field of view of 10′and the other has an extended field of view of 1.2°with correction optics.A tertiary mirror is used to switch between the two Nasmyth *** will be installed at a site at Lenghu in Qinghai Province,China,and will conduct spectroscopic observations with three types of instruments to explore the dark universe,trace the dynamic universe,and search for exoplanets:(1)a multi-fiber(2000 fibers)medium-resolution spectrometer(R=4000-5000)to spectroscopically map galaxies and large-scale structure;(2)an integral field unit(IFU)array of 500 optical fibers and/or a long-slit spectrograph dedicated to fast follow-ups of transient sources for multi-messenger astronomy;(3)a high-resolution spectrometer(R~100000)designed to identify Jupiter analogs and Earth-like planets,with the capability to characterize the atmospheres of hot exoplanets.

关键词： Astronomical instrumentation Optical telescopes Large-scale structure of the universe Redshift surveys Time domain astronomy Exoplanet astronomy

增塑剂邻苯二甲酸二丁酯低剂量与神经系统毒性效应的评估

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中国临床康复 2006年第8期10卷 76-78页

作者：朱才众熊鸿燕李亚斐张耀李莉林辉韩京许斌王思雄吴波马翔宇韩家信舒为群曹佳解放军第三军医大学军事预防医学院流行病学教研室重庆市400038 解放军第三军医大学军事预防医学院防原医学教研室全军复合伤研究所创伤烧伤与复合伤国家重点实验室重庆市400038 解放军第三军医大学军事预防医学院环境卫生学教研室重庆市400038 解放军第三军医大学军事预防医学院卫生毒理学教研室重庆市400038

目的:探讨增塑剂邻苯二甲酸二丁酯低剂量暴露对PC12细胞的毒性效应与作用机制,为接触人群产生远期效应的生物学检测提供参考评价指标。方法:体外培养神经细胞株PC12细胞,培养基分别含有12.5,25,50,100,200mg/L邻苯二甲酸二丁酯,作用24,4... 详细信息

目的:探讨增塑剂邻苯二甲酸二丁酯低剂量暴露对PC12细胞的毒性效应与作用机制,为接触人群产生远期效应的生物学检测提供参考评价指标。方法:体外培养神经细胞株PC12细胞,培养基分别含有12.5,25,50,100,200mg/L邻苯二甲酸二丁酯,作用24,48,72和96h后,用细胞计数细胞毒法检测细胞的存活和生长;椎虫蓝拒染法绘制生长曲线;乳酸脱氢酶释放检测细胞损伤程度;DNTB法测定谷胱苷肽过氧化物酶活性,丙二醛比色法测定丙二醛含量;DNA凝胶电泳检测神经细胞凋亡。结果:①细胞毒检测结果显示浓度在12.5～200mg/L的邻苯二甲酸二丁酯剂量暴露对PC12细胞株处理24～96h,对PC12细胞生长存在显著的抑制作用,并呈剂量-效应关系。各实验组在各时相点与对照组比较,差异有显著性(P<0.01)。②PC12细胞暴露于邻苯二甲酸二丁酯48h,乳酸脱氢酶释放增多,谷胱甘肽过氧化物酶活性降低,丙二醛含量增高;且随着邻苯二甲酸二丁酯的暴露剂量的上升乳酸脱氢酶浓度相应升高。而邻苯二甲酸二丁酯的暴露剂量的变化与谷胱甘肽过氧化物酶活性呈反比关系,与丙二醛含量呈正比关系。③DNA凝胶电泳结果显示实验组出现明显的DNA梯形条带。结论:不同剂量的邻苯二甲酸二丁酯暴露对PC12细胞的增殖具有显著的抑制作用,且在低剂量慢性暴露条件下对细胞产生以细胞凋亡为主的毒性效应;主要干扰神经细胞的DNA代谢,直接抑制PC12细胞生长,降低脂质过氧化物酶活性,产生氧化应激,诱导神经细胞凋亡。

关键词： PC12细胞剂量效应关系凋亡,细胞膜损伤增塑剂神经系统毒性效应邻苯二甲酸二丁酯

广西人工养殖牛蛙源嗜水气单胞菌的分离鉴定及致病力分析

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南方农业学报 2023年第1期54卷 303-314页

作者：肖双燕韦冬冬余庆刘明珠甘文林江建波何金钊韩书煜李鹏飞广西科学院广西渔业重大疫病防控与高效健康养殖产业技术工程研究中心/广西水产生物技术与现代生态养殖重点实验室/中国—东盟现代渔业产业技术转移示范中心广西南宁530007 南宁市水产畜牧兽医技术推广站广西南宁530199 广西水产技术推广站广西南宁530199

【目的】确定引起广西人工养殖牛蛙(Rana catesbeiana)发病死亡的病原菌,了解其致病性、组织病理学特征、耐药性及耐药基因的携带情况,为该病的临床诊断及合理预防提供科学依据。【方法】采用常规细菌分离纯化方法从患病牛蛙的病灶组织... 详细信息

【目的】确定引起广西人工养殖牛蛙(Rana catesbeiana)发病死亡的病原菌,了解其致病性、组织病理学特征、耐药性及耐药基因的携带情况,为该病的临床诊断及合理预防提供科学依据。【方法】采用常规细菌分离纯化方法从患病牛蛙的病灶组织中分离优势菌株,通过观察分离菌株的形态特征、生理生化特征和16S rRNA基因序列分析等对病原菌进行鉴定,以纸片扩散法测定其耐药性,通过PCR扩增分析其耐药基因和毒力基因携带情况,通过人工回归感染试验确定病原菌的致病性,并通过组织病理学探究牛蛙感染菌株后的组织特性。【结果】从患病牛蛙腿部分离得到1株优势菌株(编号NFAH-5),综合其形态学、生理生化特性、溶血特性及分子鉴定结果,确定为嗜水气单胞菌(Aeromonas hydrophila)。菌株NFAH-5对多西环素、多粘菌素B和庆大霉素等6种抗生素敏感,对头孢拉定、恩诺沙星和阿莫西林等12种抗生素已产生耐药性;经耐药基因PCR检测,发现该分离菌携带Ant(3″)-I、Intl1和parC等9种耐药基因,与耐药表型基本一致。毒力基因PCR检测结果显示,菌株NFAH-5携带Ser、aer、lip、exu、LuxS、act和aha等7种毒力基因。人工回归感染试验结果表明,菌株NFAH-5感染牛蛙的半数致死剂量(LD50)为1.55×10^(6)CFU/mL,感染后发病牛蛙表现四肢底侧充血发红,肝肿大呈红褐色或黄色,肠内空虚或有出血,肾充血发红,与自然发病牛蛙的症状相似。患病牛蛙的肝细胞发生变性,脾脏红、白髓质间很难辨出,可见大量血源性色素沉着物,肾小球萎缩,肾小管发生玻璃样变。【结论】嗜水气单胞菌是引起广西南宁人工养殖牛蛙发生红腿病的致病菌,结合农业农村部《水产养殖用药明白纸2022年2号》文件中批准使用的药物目录,建议选用敏感药物多西环素进行防治。

关键词：牛蛙嗜水气单胞菌致病性耐药性组织病理特征