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Insight-HXMT observations of the first binary neutron star merger GW170817

Science China(Physics,Mechanics & Astronomy) 2018年第3期61卷 26-33页

作者： TiPei li Shaolin Xiong ShuangNan Zhang FangJun Lu liMing Song XueLei cao Zhi Chang Gang Chen li Chen TianXiang Chen Yong Chen YiBao Chen YuPeng Chen Wei Cui WeiWei Cui JingKang Deng YongWei dong YuanYuan Du MinXue fu GuanHua Gao He Gao Min Gao MingYu Ge Yudong Gu Ju Guan ChengCheng Guo DaWei Han Wei Hu Yue Huang Jia Huo ShuMei Jia LuHua jiang WeiChun jiang Jing Jin YongJie Jin Bing li ChengKui li Gang li MaoShun li Wei li Xian li XiaoBo li XuFang li YanGuo li ZiJian li ZhengWei li XiaoHua liang JinYuan liao CongZhan liu Guoqing liu HongWei liu ShaoZhen liu XiaoJing liu Yuan liu YiNong liu Bo Lu XueFeng Lu Tao Luo Xiang Ma Bin Meng Yi Nang JianYin Nie Ge OU JinLu Qu Na Sai liang Sun Yin Tan lian Tao WenHui Tao Youli Tuo GuoFeng wang HuanYu wang Juan wang WenShuai wang YuSa wang XiangYang Wen BoBing WU Mei Wu GuangCheng Xiao He Xu YuPeng Xu linli Yan JiaWei Yang sheng Yang YanJi Yang AiMei Zhang ChunLei Zhang ChengMo Zhang Fan Zhang HongMei Zhang Juan Zhang Qiang Zhang Shu Zhang Tong Zhang Wei Zhang WanChang Zhang WenZhao Zhang Yi Zhang Yue Zhang YiFei Zhang YongJie Zhang Zhao Zhang Ziliang Zhang Haisheng Zhao Jianling Zhao XiaoFan Zhao ShiJie Zheng Yue Zhu YuXuan Zhu Changlin Zou Key Laboratory of Particle Astrophysics Institute of High Energy Physics Chinese Academy of Sciences Beijing 100049 China Department of Physics Tsinghua University Beijing 100084 China University of Chinese Academy of Sciences Chinese Academy of Sciences Beijing 100049 China Department of Astronomy Beijing Normal University Beijing 100088 China Department of Engineering Physics Tsinghua University Beijing 100084 China

Finding the electromagnetic （EM） counterpart of binary compact star merger, especially the binary neutron star （BNS） merger, is critically important for gravitational wave （GW） astronomy, cosmology and fundamental physics. On Aug. 17, 2017, Advanced liGO and Fermi/GBM independently triggered the first BNS merger, GW170817, and its high energy EM counterpart, GRB 170817A, respectively, resulting in a global observation campaign covering gamma-ray, X-ray, UV, optical, IR, radio as well as neutrinos. The High Energy X-ray telescope （HE） onboard Insight-HXMT （Hard X-ray Modulation Telescope） is the unique high-energy gamma-ray telescope that monitored the entire GW localization area and especially the optical counterpart （SSS17a/AT2017gfo） with very large collection area （M000 cm2） and microsecond time resolution in 0.2-5 MeV. In addition, Insight-HXMT quickly implemented a Target of Opportunity （TOO） observation to scan the GW localization area for potential X-ray emission from the GW source. Although Insight-HXMT did not detect any significant high energy （0.2-5 MeV） radiation from GW170817, its observation helped to confirm the unexpected weak and soft nature of GRB 170817A. Meanwhile, Insight-HXMT/HE provides one of the most stringent constraints （-10-7 to 104 erg/cm2/s） for both GRB170817A and any other possible precursor or extended emissions in 0.2-5 MeV, which help us to better understand the properties of EM radiation from this BNS merger. Therefore the observation of Insight-HXMT constitutes an important chapter in the full context of multi-wavelength and multi-messenger observation of this historical GW event.

关键词： GW170817 BNS merger gravitational wave electromagnetic counterpart

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Timing analysis of the black hole candidate EXO 1846–031 with Insight-HXMT monitoring

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Research in Astronomy and Astrophysics 2021年第3期21卷 193-204页

作者： He-Xin liu Yue Huang Guang-Cheng Xiao qing-Cui Bu Jin-Lu Qu Shu Zhang Shuang-Nan Zhang Shu-Mei Jia Fang-Jun Lu Xiang Ma lian Tao Wei Zhang li Chen li-Ming Song Ti-Pei li Yu-Peng Xu Xue-Lei cao Yong Chen Cong-Zhan liu Ce Cai Zhi Chang Gang Chen Tian-Xiang Chen Yi-Bao Chen Yu-Peng Chen Wei Cui Wei-Wei Cui Jing-Kang Deng Yong-Wei dong Yuan-Yuan Du Min-Xue fu Guan-Hua Gao He Gao Min Gao Ming-Yu Ge Yu-dong Gu Ju Guan Cheng-Cheng Guo Da-Wei Han Jia Huo Lu-Hua jiang Wei-Chun jiang Jing Jin Yong-Jie Jin ling-Da Kong Bing li Cheng-Kui li Gang li Mao-Shun li Wei li Xian li Xiao-Bo li Xu-Fang li Yang-Guo li Zheng-Wei li Xiao-Hua liang Jing-Yuan liao Bai-sheng liu Guo-qing liu Hong-Wei liu Xiao-Jing liu Yi-Nong liu Bo Lu Xue-Feng Lu Qi Luo Tao Luo Bin Meng Yi Nang Jian-Yin Nie Ge Ou Na Sai Ren-Cheng Shang Xin-Ying Song liang Sun Ying Tan You-li Tuo Chen wang Guo-Feng wang Juan wang ling-Jun wang Weng-Shuai wang Yu-Sa wang Xiang-Yang Wen Bai-Yang Wu Bo-Bing Wu Mei Wu Shuo Xiao Shao-lin Xiong He Xu Jia-Wei Yang sheng Yang Yan-Ji Yang Yi-Jung Yang Qi-Bin Yi Qian-qing Yin Yuan You Ai-Mei Zhang Cheng-Mo Zhang Fan Zhang Hong-Mei Zhang Juan Zhang Tong Zhang Wan-Chang Zhang Wen-Zhao Zhang Yi Zhang Yi-Fei Zhang Yong-Jie Zhang Yuan-Hang Zhang Yue Zhang Zhao Zhang Zhi Zhang Zi-liang Zhang Hai-sheng Zhao Xiao-Fan Zhao Shi-Jie Zheng Yao-Guang Zheng Deng-Ke Zhou Jian-Feng Zhou Yu-Xuan Zhu Ren-lin Zhuang Yue Zhu Key Laboratory of Particle Astrophysics Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China University of Chinese Academy of Sciences Chinese Academy of SciencesBeijing 100049China Institut fur Astronomie und Astrophysik Kepler Center for Astro and Particle PhysicsEberhard Karls Universität72076 TubingenGermany Department of Astronomy Beijing Normal UniversityBeijing 100088China Department of Astronomy Tsinghua UniversityBeijing 100084China Department of Physics Tsinghua UniversityBeijing 100084China Department of Engineering Physics Tsinghua UniversityBeijing 100084China Key Laboratory of Space Astronomy and Technology National Astronomical ObservatoriesChinese Academy of SciencesBeijing 100101China College of Physics Sciences&Technology Hebei UniversityBaoding 071002Hebei ProvinceChina

We present the observational results from a detailed timing analysis of the black hole candidate EXO 1846-031 during its outburst in 2019 with the observations of Insight-HXMT,NICER and *** outburst can be classified roughly into four different ***-C quasi-periodic oscillations(QPOs)observed by NICER(about 0.1-6 Hz)and Insight-HXMT(about 0.7-8 Hz)are also reported in this ***,we study various physical quantities related to QPO *** QPO rms-frequency relationship in the energy band 1-10 keV indicates that there is a turning pointing in frequency around2 Hz,which is similar to that of GRS 1915+105.A possible hypothesis for the relationship above may be related to the inclination of the source,which may require a high inclination to explain *** relationships between QPO frequency and QPO rms,hardness,total fractional rms and count rate have also been found in other transient sources,which can indicate that the origin of type-C QPOs is non-thermal.

关键词： X-ray binaries black hole candidate QPO EXO 1846–031

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医务人员视角下县乡村医务人员整合协作现状——以江苏省三县为例

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中国卫生政策研究 2018年第3期11卷 42-45页

作者：殷璇石金楼钱东福谷小丽王烨曹江翎南京医科大学医政学院江苏南京211166

目的:以江苏开展慢性病综合防控示范区建设的县城为例,借鉴DMIC整合医疗服务发展模型的9大维度对县、乡、村医务人员慢性病整合服务协作的工作现状进行分析,以期为医务人员跨机构慢性病协作提供改善方向。方法:采用典型抽样和多阶段随... 详细信息

目的:以江苏开展慢性病综合防控示范区建设的县城为例,借鉴DMIC整合医疗服务发展模型的9大维度对县、乡、村医务人员慢性病整合服务协作的工作现状进行分析,以期为医务人员跨机构慢性病协作提供改善方向。方法:采用典型抽样和多阶段随机抽样相结合,对278名医务人员进行问卷调查,并对结果进行统计学分析。结果:村医在整合协作工作中参与度最强,但人力年龄结构老化、文化程度低;县、乡、村医务人员均对开展跨机构协作工作表示高度认可,但实际协作水平低;县、乡、村连通的卫生信息平台尚未建立。

关键词：服务整合农村整合医疗服务发展模型

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Incidence and prognosis of olfactory and gustatory dysfunctions related to SARS-CoV-2 Omicron strain infection in China:A national multicenter survey of 35,566 individuals

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第2期10卷 113-120页

作者： Meng-Fan liu Rui-Xia Ma Xian-Bao cao Hua Zhang Shui-Hong Zhou Wei-Hong jiang Yan jiang Jing-Wu Sun Qin-Tai Yang Xue-Zhong li Ya-Nan Sun li Shi Min wang Xi-Cheng Song fu-Quan Chen Xiao-Shu Zhang Hong-Quan Wei Shao-qing Yu dong-dong Zhu Luo Ba Zhi-Wei cao Xu-Ping Xiao Xin Wei Zhi-Hong lin Feng-Hong Chen Chun-Guang Shan Guang-Ke wang Jing ye Shen-Hong Qu Chang-qing Zhao Zhen-lin wang Hua-Bin li Feng liu Xiao-Bo Cui sheng-Nan ye Zheng liu Yu Xu Xiao Cai Wei Huang Ru-Xin Zhang Yu-lin Zhao Guo-dong Yu Guang-Gang Shi Mei-Ping Lu Yang Shen Yu-Tong Zhao Jia-Hong Pei Shao-Bing Xie Long-Gang Yu ye-Hai liu Shao-Wei Gu Yu-Cheng Yang Lei Cheng Jian-Feng liu Graduate School of Beijing University of Chinese Medicine BeijingChina Department of Otorhinolaryngology Head and Neck Surgery China-Japan Friendship HospitalBeijingChina Department of Otorhinolaryngology Head and Neck Surgery The First People's Hospital of YinchuanYinchuanChina Department of Otorhinolaryngology The First People's Hospital of Yunnan ProvinceKunmingChina Department of Otorhinolaryngology The First Affiliated Hospital of Xinjiang Medical UniversityUrumqiChina Department of Otorhinolaryngology Head and Neck Surgery The First Affiliated Hospital of Zhejiang University School of MedicineHangzhouChina Department of Otorhinolaryngology Head and Neck Surgery Xiangya Hospital Central South UniversityChangshaChina Department of Otorhinolaryngology Head and Neck Surgery The Affiliated Hospital of Qingdao UniversityQingdaoChina Department of Otorhinolaryngology Head and Neck Surgery The First Affiliated Hospital of USTCHefeiChina Department of Otorhinolaryngology Head and Neck Surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina Department of Otorhinolaryngology Head and Neck Surgery Qilu Hospital of Shandong UniversityJinanChina Department of Otorhinolaryngology Head and Neck Surgery The Second Affiliated Hospital of Harbin Medical UniversityHarbinChina Department of Otolaryngology The Second Hospital of Shandong UniversityShandong UniversityJinanChina Department of Otorhinolaryngology Head and Neck Surgery Peking University People's HospitalBeijingChina Department of Otorhinolaryngology Head and Neck Surgery Yantai Yuhuangding HospitalQingdao UniversityYantaiChina Department of Otorhinolaryngology Head and Neck Surgery Xijing HospitalThe Fourth Military Medical UniversityXi'anChina Gansu Provincial Center for Disease Control and Prevention LanzhouChina Department of Otorhinolaryngology Head and Neck Surgery The First Affiliated Hospital of China Medical UniversityShenyangChina Department of Otorhinolaryngology Head and Neck Surgery Tongji Hospit

Objective:This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in ***:This study was conducted by 45 tertiary Grade-A hospitals in *** and offline questionnaire data were obtained from patients infected with COVID-19 between December 28,2022,and February 21,*** collected information included basic demographics,medical history,smoking and drinking history,vaccination history,changes in olfactory and gustatory functions before and after infection,and other postinfection symptoms,as well as the duration and improvement status of olfactory and gustatory ***:Complete questionnaires were obtained from 35,566 *** overall incidence of olfactory and taste dysfunction was 67.75%.Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste *** received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such *** infection,the average olfactory and taste VAS scores were 8.41 and 8.51,respectively;after infection,they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the *** median duration of dysosmia and dysgeusia was 15 and 12 days,respectively,with 0.5%of patients having symptoms lasting for more than 28 *** overall self-reported improvement rate was 59.16%.Recovery was higher in males,never smokers,those who received two or three vaccine doses,and those that had never experienced dental health issues,or chronic accompanying ***:The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in *** and prognosis are influenced by several factors,including sex,SARS-CoV-2 vaccination,history of head-facial trauma,nasal and oral health status,smoking and drinking history,and the persistence of accompanying symptoms.

关键词： epidemiologic studies incidence olfactory disorders prognosis SARS-CoV-2 taste disorders

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非综合征性耳聋人工耳蜗植入者的基因分析

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中华医学杂志 2007年第16期87卷 1093-1096页

作者：田永胜陈晓巍曹克利陈东野左瑾方福德中国医学科学院中国协和医科大学北京协和医院耳鼻咽喉科 100730 中国医学科学院中国协和医科大学基础所方福德实验室

目的研究连接蛋白26(Connexin26)基因(GJB2)突变和线粒体12S rRNA 基因突变在人工耳蜗植入的非综合征性耳聋患者中发生的几率及特性。方法选取100例接受人工耳蜗植入患者,语前聋为96例,语后聋为4例。自外周静脉血中提取总 DNA,进行 GJB... 详细信息

目的研究连接蛋白26(Connexin26)基因(GJB2)突变和线粒体12S rRNA 基因突变在人工耳蜗植入的非综合征性耳聋患者中发生的几率及特性。方法选取100例接受人工耳蜗植入患者,语前聋为96例,语后聋为4例。自外周静脉血中提取总 DNA,进行 GJB2基因和线粒体12S rRNA基因核苷酸 PCR,对扩增的基因片段进行测序,检测 GJB2基因突变和线粒体12S rRNA 基因突变。结果接受人工耳蜗植入的非综合征性耳聋病例中发现 GJB2基因突变率最高,为34%(34/100)。其突变类型主要为235delC,占27%;同时有氨基糖甙类药物使用史的16例病例中发现2例有线粒体12S rRNA 基因 A1555G突变,1例有线粒体12S rRNA 基因突变 delT961Cn。结论 GJB2基因突变在人工耳蜗植入的患者中发生率最高,235delC 是主要突变类型,有氨基糖甙类药物应用史的语后聋患者中线粒体12S rRNA 基因突变 A1555G 为常见突变形式。

关键词：耳蜗植入突变线粒体聋 GJB2

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黄河河南悬河段地下水环境健康评价

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人民黄河 2007年第12期29卷 1-2,5页

作者：曹剑峰李升姜纪沂冶雪艳曹东平苏玛莱吉林大学环境与资源学院吉林长春130026 防灾科技学院地震工程技术系河北三河065201 中国石化集团上海海洋石油局上海200120

根据水环境健康理论,探讨了地下水环境健康的概念,构建了包括目标层、准则层、指标层的地下水环境健康评价指标体系结构。根据指标层19个因子,建立了地下水环境健康评价标准。选取7个评价指标,采用灰色聚类法评价了黄河下游悬河段郑州... 详细信息

根据水环境健康理论,探讨了地下水环境健康的概念,构建了包括目标层、准则层、指标层的地下水环境健康评价指标体系结构。根据指标层19个因子,建立了地下水环境健康评价标准。选取7个评价指标,采用灰色聚类法评价了黄河下游悬河段郑州、开封、新乡、濮阳4个地区的地下水环境健康状态。结果显示,郑州、濮阳地区地下水环境处于不健康状态,新乡、开封地区处于亚健康状态。

关键词：水环境健康地下水环境评价指标体系评价标准灰色聚类法黄河河南悬河段

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A two edges sword:O6-methylguanine-DNA methyltransferase promoter methylation status associates with contrasting roles of YKL-40 in glioblastoma

A two edges sword:O6-methylguanine-DNA methyltransferase pro...

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第十三届中国医师协会神经外科医师年会

作者： Wei Zhang Wei-jun Chen Xiang Zhang Jian-nan Lv En-ming Kang Hiro Wakimoto Wei-dong cao Wei-ping liu Xiao-fan jiang Xiao-sheng He Luo-an fu Bing li Xi-tuan Ji Guang Chen qing-dong Guo Da-kuan Gao Wei lin Hai-ning Zhen Xing-gang Mao Huan Bian Takashi Tamiya Hua Han Department of Neurosurgery Xijing HospitalThe Fourth Military Medical University Department of Medical Genetics and Developmental Biology The Fourth Military Medical University Department of Neurosurgery Massachusetts General HospitalHarvard Medical SchoolBoston Department of Biochemistry and Molecular Biology The Fourth Military Medical University Department of Neurological Surgery Faculty of MedicineKagawa University

Inter-and intra-tumoral heterogeneity is a hallmark of glioblastoma(GBM)that facilitates recurrence and treatment *** only gene expression profiles or mutations but also epigenetic states dictate GBM biology.O-methylguanine-DNA methyltransferase(MGMT)promoter methylation is a significant prognostic marker for GBM patients’ survival,however,underlying mechanisms by which MGMT epigenetics impacts patient outcomes are not fully ***,using in vitro cultures and in vivo orthotopic models of IDH1/2-wild-type GBM stem-like cells(GSCs)we show that MGMT promoter methylation status,but not molecular subtypes of GBM,is tightly associated with contrasting roles of ***-40 promotes the RAS-MEK-ERK signaling pathway and stemness,chemoresistance and tumorigenicity in MGMT-unmethylated *** contrast,YKL-40 suppresses the RAS-MEK-ERK signaling pathway and the stem-like properties in MGMT-methylated *** study demonstrates previously underappreciated epigenetic status association with distinct functions of cancer-relevant genes,and supports the need of epigenome characterization into tumor stratification and targeted therapeutic development.

关键词： MGMT Methylation YKL-40 ERK Gliobalstoma

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IL-6在人胆管上皮细胞损伤修复中的作用

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中华消化外科杂志 2012年第5期11卷 471-475页

作者：蒋桂星崔云甫曹利平邰升钟翔宇王志东哈尔滨医科大学附属第二医院肝胆胰腺外科哈尔滨150086 浙江大学医学院附属第二医院普通外科浙江大学医学院附属第二医院普通外科杭州310009

目的探讨IL-6在人胆管上皮细胞（BECs）损伤修复中的作用机制。方法IL-6按浓度分为5组：0ng／L组，10ng／L组，50ng／L组，100ng／L组，1000ng／L组，将不同浓度的IL-6分别干预体外培养的BECs，并检测IL-6对转录激活子3（STAT3）磷酸化... 详细信息

目的探讨IL-6在人胆管上皮细胞（BECs）损伤修复中的作用机制。方法IL-6按浓度分为5组：0ng／L组，10ng／L组，50ng／L组，100ng／L组，1000ng／L组，将不同浓度的IL-6分别干预体外培养的BECs，并检测IL-6对转录激活子3（STAT3）磷酸化和三叶因子3（TFF3）表达的影响；将BECs分为未处理组、STAT3-RNAi组（细胞中转人STAT3RNAi腺病毒）和Control-RNAi组（细胞中转入空RNAi腺病毒），检测行干扰后，IL-6对TFF3表达的影响；分别用未处理组、STAT3-RNAi组、Control-RNAi组BECs制备体外损伤模型，观察IL-6、TFF3对各组细胞的影响。两组数据间比较采用Student’s t检验，多组间比较采用单因素方差或Sidak检验。结果添加IL-6的50ng／L组、100ng／L组、1000ng／L组磷酸化STAT3（P-STAT3）的表达水平分别为0．240±0．052、0．714±O．124、0．327±0．069，明显强于0 ng／L组的0．033±0．011（q=5．246，17．260，7．451，P〈0．05）。TFF3mRNA及其蛋白表达水平随着IL-6浓度的增高而显著增加（q=12．045，9．889，P〈0．05）；IL-6浓度为1000ng／L时，TFF3mRNA及其蛋白表达有所回落。行干扰后，STAT3-RNAi组BECsTFF3蛋白表达水平为0．037±0．005，明显低于Control-RNAi组的0．267±0．038和未处理组的0．301±0．042（q=12．135，13．929，P〈0．05）。体外损伤模型中，IL-6干预BECs12h后，STAT3-RNAi组BECs移行速度为（9．1±1．5）μm／h，慢于Control-RNAi组的（25．1±3．8）μm／h（q=7．737，P〈0．05）；而STAT3-RNAi组中加入外源性人重组TFF31g／L后，BECs移行速度为（39．2±4．7）μm／h，比Control-RNAi组显著提高（q=14．507，P〈0．05）。结论IL-6主要通过激活STAT3，继发上调TFF3表达，从而促进人胆管上皮细胞移行和损伤修复。

关键词：胆管上皮细胞损伤修复 IL-6 信号转导子和转录激活子3 三叶因子3

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Smad2基因在人脑胶质瘤的表达及其临床意义

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中华神经外科杂志 2011年第10期27卷 1064-1068页

作者：苏伟朱贵东刘福生姜中利金贵善柴奇曹泽聂秀涛北京市神经外科研究所首都医科大学附属北京天坛医院神经外科100050

目的探讨Smad2基因在人脑胶质瘤组织中的表达情况，与细胞增殖指数Ki一67及患者生存期的关系。方法对80例人脑胶质瘤组织标本，用免疫组化sP法检测Smad2、Ki一67的蛋白表达，逆转录聚合酶链反应法（RT—PCR）测定Smad2mRNA的转录水平。S... 详细信息

目的探讨Smad2基因在人脑胶质瘤组织中的表达情况，与细胞增殖指数Ki一67及患者生存期的关系。方法对80例人脑胶质瘤组织标本，用免疫组化sP法检测Smad2、Ki一67的蛋白表达，逆转录聚合酶链反应法（RT—PCR）测定Smad2mRNA的转录水平。Smad2蛋白表达情况与患者生存期的关系用Kaplan—Meier生存曲线表示，并采用log—rank方法分析。结果（1）Smad2蛋白在高级别胶质瘤（Ⅲ级和Ⅳ级）中表达水平较低级别胶质瘤（Ⅱ级）明显增高（P〈0．001）。（2）Smad2mRNA在高级别胶质瘤（Ⅲ级和Ⅳ级）中转录水平较低级别胶质瘤（Ⅱ级）增高（P〈0．05）。（3）Smad2蛋白阳性表达与Ki-67阳性表达呈正相关（r=0．812，P〈0．001）。（4）将所有患者分为Smad2高表达组和低表达组，两组间生存率差异有统计学意义（P〈0．05）。结论Smad2的转录和蛋白表达水平在恶性胶质瘤中显著增高，检测Smad2表达水平有利于脑胶质瘤的恶性程度判断及对患者预后的评估。

关键词：神经胶质瘤 Smad2 免疫组织化学逆转录聚合酶链反应预后

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重组人内皮抑素腺病毒注射液Ⅰ期临床耐受性试验

引用

癌症 2007年第8期26卷 856-860页

作者：曹烨李苏李鸿立李宇红张东生郭颖李晓玲林旭滨黄文林姜文奇华南肿瘤学国家重点实验室

背景与目的:血管生成抑制剂在抗肿瘤新生血管生成方面显示出良好的临床应用前景,已有多个I期临床试验研究人内皮抑素重组蛋白的安全性和抗瘤活性。本试验目的是确定携带人内皮抑素基因的重组腺病毒注射液(Ad-Es)的最大耐受剂量,并推荐... 详细信息

背景与目的:血管生成抑制剂在抗肿瘤新生血管生成方面显示出良好的临床应用前景,已有多个I期临床试验研究人内皮抑素重组蛋白的安全性和抗瘤活性。本试验目的是确定携带人内皮抑素基因的重组腺病毒注射液(Ad-Es)的最大耐受剂量,并推荐Ⅱ期临床试验的用量和用法。方法:设预试验组1例,1×1010病毒颗粒,单次瘤内注射。普通试验组遵循以一个自然对数级的1/2的方式递增,共14例,分三个剂量组:1×1011、5×1011、1×1012病毒颗粒/次,瘤内注射,每周1次,连续2周。结果:未观察到剂量限制性毒性,各受试者均显示出良好的耐受性。主要的不良事件为:局部反应和发热。其他不良反应有轻微的肝功能异常和流感样症状,如头痛、肌痛、乏力等。1例鼻咽癌放疗后鼻咽复发并颏下淋巴结转移的患者病情好转,12例病情稳定,2例出现进展。结论:人体对Ad-Es耐受性良好,晚期肿瘤患者使用1×1012病毒颗粒/次,瘤内注射,每周1次,连续2周,初步观察到Ad-Es的抗瘤活性。推荐Ⅱ期临床给药剂量为1.0×1012病毒颗粒/次,每周1次,连续4周。

关键词：重组人内皮抑素腺病毒 Ⅰ期临床试验恶性肿瘤耐受剂量

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