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Chinese Medical Journal 2006年第5期119卷 412-416页

作者： jin shu-xian yin kai-sheng bian tao sun pei-li Respiratory Department of Internal Medicine First Affiliated Hospital of Nanjing Medical University Nanjing 210029 China

Imiquimod is an imidazoquinoline derivative. Some studies have shown that imiquimod modulates the Th1/Th2 response by inducing the production of Th1 cytokines IFN-γ and interleukin （IL）-12. and by inhibiting Th2 cytokines IL-4 and IL-5. These data suggest that imiquimod has therapeutic appli . cations in atopic diseases such as allergic asthma that are associated with overexpression of Th2 cytokines.

关键词： asthma Th1/Th2 cell thymus and activation regulated chemokine imiquimod

10B-doped MCP detector developed for neutron resonance imaging at Back-n white neutron source

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Nuclear Science and Techniques 2024年第8期35卷 58-68页

作者： Qiang li li‑Jiao Wang jing‑Yu Tang xiang‑Biao Qiu Zhen Chen Mao‑Yuan Zhao Chang‑Jun Ning kai Pan Wei Xu tao li Su‑Peng Lu Han Yi Rui‑Rui Fan Chang‑Qing Feng Rong Zhang Xiao‑Yang sun Qi An Hao‑Fan Bai Jiang‑Bo Bai Jie Bao Ping Cao Qi‑Ping Chen Yong‑Hao Chen Zeng‑Qi Cui An‑Chuan Fan Fan‑Zhen Feng Min‑Hao Gu Chang‑Cai Han Zi‑Jie Han Guo‑Zhu He Yong‑Cheng He Yang Hong Yi‑Wei Hu Han‑Xiong Huang Wei Jiang Zhi‑Jie Jiang Zheng‑Yao jin ling Kang Bo li Gong li Xiao li Yang li Jie liu Rong liu shu‑Bin liu Yi‑Na liu Guang‑Yuan Luan Jie Ren Zhi‑Zhou Ren Xi‑Chao Ruan Zhao‑Hui Song Kang sun Zhi‑Xin Tan sheng‑Da Tang jin‑Cheng Wang Peng‑Cheng Wang Zhao‑Hui Wang Zhong‑Wei Wen Xiao‑Guang Wu Xuan Wu Cong Xia Yong‑Ji Yu Guo‑Hui Zhang Hang‑Chang Zhang lin‑Hao Zhang Qi‑Wei Zhang xian‑Peng Zhang Yu‑liang Zhang Yue Zhang Zhi‑Yong Zhang Zhi‑Hao Zhou Ke‑Jun Zhu Chong Zou Institute of High Energy Physics Chinese Academy of Sciences(CAS)Beijing 100049China Spallation Neutron Source Science Center Dongguan 523803China State Key Laboratory of Particle Detection and Electronics Institute of High Energy Physics Chinese Academy of SciencesBeijing 100049China Dongguan Songshan Lake Future School Dongguan 523808China School of Nuclear Science and Technology University of Science and Technology of ChinaHefei 230027China State Key Laboratory of Particle Detection and Electronics University of Science and Technology of ChinaHefei 230026China North Night Vision Science and Technology(Nanjing)Research Institute Co.Ltd Nanjing 211106China Department of Modern Physics University of Science and Technology of ChinaHefei 230026China State Key Laboratory of Nuclear Physics and Technology School of PhysicsPeking UniversityBeijing 100871China Institute of Modern Physics Fudan UniversityShanghai 200433China Key Laboratory of Nuclear Data China Institute of Atomic EnergyBeijing 102413China China Academy of Engineering Physics Institute of Nuclear Physics and ChemistryMianyang 621900China USTC archaeometry lab University of Science and Technology of ChinaHefei 230026China Northwest Institute of Nuclear Technology Xi’an 710024China University of Chinese Academy of Sciences Beijing 100049China China Shipbuilding Trading Co. LtdBeijing 100044China

Neutron resonance imaging(NRI)has recently emerged as an appealing technique for neutron *** complexity surpasses that of conventional transmission imaging,as it requires a high demand for both a neutron source and ***,the progression of NRI technology has been sluggish since its inception in the 1980s,particularly considering the limited studies analyzing the neutron energy range above *** white neutron source(Back-n)at the China Spallation Neutron Source(CSNS)provides favorable beam conditions for the development of the NRI technique over a wide neutron energy range from eV to ***-sensitive microchannel plates(MCP)have emerged as a cutting-edge tool in the field of neutron detection owing to their high temporal and spatial resolutions,high detection efficiency,and low *** this study,we report the development of a 10B-doped MCP detector,along with its associated electronics,data processing system,and NRI experiments at the *** heavy elements such as gold,silver,tungsten,and indium can be easily identified in the transmission images by their characteristic resonance peaks in the 1–100 eV energy range;the more difficult medium-weight elements such as iron,copper,and aluminum with resonance peaks in the 1–100 keV energy range can also be *** particular,results in the neutron energy range of dozens of keV(Aluminum)are reported here for the first time.

关键词： Neutron resonance imaging 10B doped MCP detector White neutron source Sample nuclide identification

Treatment of allergic airway inflammation and hyperrespon-siveness by imiquimod modulating transcription factors T-bet and GATA-3

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Chinese Medical Journal 2006年第8期119卷 640-648页

作者： bian tao yin kai-sheng jin shu-xian ZHANG Xi-long ZHOU jin-yong MA Xiu-qin HU jing-jing DE Wei Department of Respiratory Medicine First Affiliated Hospital of Nanjing Medical University Nanjing 210029 China

Background Imiquimod is an imidazoquinoline, which class of compounds are known to have antiviral and antitumoural properties. In recent studies, it was shown that imiquimod modulates the T helper cell type Th1/Th2 response by inducing the production of Thl cytokines like IFN-γ, and by inhibiting the Th2 cytokines like interleukin （IL）-4. Several investigators have shown that T-bet and GATA-3 are master Thl and Th2 regulatory transcription factors. This study investigated whether irniquimod treatment inhibited airway inflammation by modulating transcription factors T-bet and GATA-3. Methods Thirty-six male SD rats were randomly divided into a control group, an asthmatic group, and an imiquimod group, which was exposed to an aerosol of 0.15% imiquimod. Twenty-four hours after the last ovalbumin （OVA） challenge, airway responsiveness was measured and changes in airway histology were observed. The concentrations of IL-4, IL-5 and IFN-γ in bronchoalveolar lavage fluid （BALF） and serum were measured by enzyme linked immunosorbent assay （EliSA）. The rnRNA expressions of IL-4, IL-5, IFN-γ, T-bet and GATA-3 in lung and in CD4^＋ T cells were determined by reverse transcription polymerase chain reaction （RT-PCR）. The protein expressions ofT-bet and GATA-3 were measured by Western blot. Results It was demonstrated that imiquimod 1） attenuated OVA induced airway inflammation; 2） diminished the degree of airway hyperresponsiveness （AHR）; 3） decreased the Th2 type cytokines and increased Thl type cytokines mRNA and protein levels; 4） modulated the Th1/Th2 reaction by inhibiting GATA-3 production and increasing T-bet production. Conclusion Imiquimod treatment inhibits OVA induced airway inflammation by modulating key master switches GATA-3 and T-bet that result in committing T helper cells to a Thl phenotype.

关键词： asthma T-bet GATA-3 imiquimod

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咪喹莫特治疗哮喘作用机制的实验研究

南京医科大学学报（自然科学版） 2006年第5期26卷 346-350,355页

作者：金淑贤殷凯生卞涛孙培莉南京医科大学第一附属医院呼吸科江苏南京210029

目的:观察咪喹莫特对小鼠哮喘模型气道炎症和肺组织Th2型胸腺和活化调节趋化因子(thymusandactivationregulatedchemokine,TARC)和其受体CCR4表达的影响。方法:建立哮喘模型,自第14天雾化吸入OVA前0.5h,干预组分别雾化吸入咪喹莫特30mi... 详细信息

目的:观察咪喹莫特对小鼠哮喘模型气道炎症和肺组织Th2型胸腺和活化调节趋化因子(thymusandactivationregulatedchemokine,TARC)和其受体CCR4表达的影响。方法:建立哮喘模型,自第14天雾化吸入OVA前0.5h,干预组分别雾化吸入咪喹莫特30min及腹腔注射地塞米松。OVA雾化结束后24h,每组小鼠眼球摘除采血收集血清,采用酶联免疫吸附法测定血清中TARC水平;收集肺泡灌洗液进行细胞计数和分类;HE染色观察肺组织炎症改变;用免疫组化方法检测肺组织CCR4和TARC的表达;用逆转录-聚合酶链反应半定量检测肺组织IL-4、IFN-γ、CCR4和TARCmRNA表达水平。结果:①哮喘小鼠HE染色可见气道上皮不完整,黏膜下有大量的炎细胞浸润,以淋巴细胞为主。地塞米松组和咪喹莫特组炎症程度减轻。②哮喘组小鼠支气管肺泡灌洗液(BALF)中细胞总数及各种炎症细胞较正常组显著增加,咪喹莫特治疗组的嗜酸性粒细胞、单核细胞和淋巴细胞比哮喘组明显减少。③哮喘组小鼠血清TARC水平较正常组升高,咪喹莫特治疗组小鼠血TARC水平较哮喘组降低,与正常组比较差异无显著性。④CCR4和TARC均在气道上皮细胞表达,咪喹莫特和地塞米松治疗组能减少CCR4和TARC的表达。⑤哮喘组小鼠肺组织IL-4、CCR4和TARCmRNA表达较正常组增强,咪喹莫特和地塞米松治疗组小鼠肺组织IL-4、CCR4和TARCmRNA表达较哮喘组降低,比正常组表达增加。结论:雾化吸入咪喹莫特可在一定程度上减轻哮喘小鼠的气道炎症,抑制肺组织CCR4和TARC蛋白和mRNA的过度表达。

关键词：哮喘 CCR4 胸腺和活化调节趋化因子咪喹莫特

CEPC Technical Design Report

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Radiation Detection Technology and Methods 2024年第1期8卷 I0003-I0016,1-1091页

作者： Waleed Abdallah Tiago Carlos Adorno de Freitas Konstantin Afanaciev Shakeel Ahmad Ijaz Ahmed Xiaocong Ai Abid Aleem Wolfgang Altmannshofer Fabio Alves Weiming An Rui An Daniele Paolo Anderle Stefan Antusch Yasuo Arai Andrej Arbuzov Abdesslam Arhrib Mustafa Ashry Sha Bai Yu Bai Yang Bai Vipul Bairathi Csaba Balazs Philip Bambade Yong Ban Tripamo Bandyopadhyay Shou-Shan Bao Desmond P.Barber Ayse Bat Varvara Batozskaya Subash Chandra Behera Alexander Belyaev Michele Bertucci Xiao-Jun Bi Yuanjie Bi Tianjian bian Fabrizio bianchi Thomas Biekotter Michela Biglietti Shalva Bilanishvili Deng Binglin Denis Bodrov Anton Bogomyagkov Serge Bondarenko Stewart Boogert Maarten Boonekamp Marcello Borri Angelo Bosotti Vincent Boudry Mohammed Boukidi Igor Boyko Ivanka Bozovic Giuseppe Bozzi Jean-Claude Brient Anastasiia Budzinskaya Masroor Bukhari Vladimir Bytev Giacomo Cacciapaglia Hua Cai Wenyong Cai Wujun Cai Yijian Cai Yizhou Cai Yuchen Cai Haiying Cai Huacheng Cai Lorenzo Calibbi Junsong Cang Guofu Cao Jianshe Cao Antoine Chance Xuejun Chang Yue Chang Zhe Chang Xinyuan Chang Wei Chao Auttakit Chatrabhuti Yimin Che Yuzhi Che Bin Chen Danping Chen Fuqing Chen Fusan Chen Gang Chen Guoming Chen Hua-Xing Chen Huirun Chen jinhui Chen Ji-Yuan Chen kai Chen Mali Chen Mingjun Chen Mingshui Chen Ning Chen Shanhong Chen Shanzhen Chen Shao-Long Chen Shaomin Chen Shiqiang Chen Tianlu Chen Wei Chen xiang Chen Xiaoyu Chen Xin Chen Xun Chen Xurong Chen Ye Chen ying Chen Yukai Chen Zelin Chen Zilin Chen Gang Chen Boping Chen Chunhui Chen Hok Chuen Cheng Huajie Cheng Shan Cheng Tongguang Cheng Yunlong Chi Pietro Chimenti Wen Han Chiu Guk Cho Ming-Chung Chu Xiaotong Chu Ziliang Chu Guglielmo Coloretti Andreas Crivellin Hanhua Cui Xiaohao Cui Zhaoyuan Cui Brunella D'Anzi ling-Yun Dai Xinchen Dai Xuwen Dai Antonio De Maria Nicola De Filippis Christophe De La Taille Francesca De Mori Chiara De Sio Elisa Del Core shuangxue Deng Wei-Tian Deng Zhi Deng Ziyan Deng Bhupal Dev Tang Dewen Biagio Di Micco Ran Ding Siqin Dingl Yadong Ding Haiyi Dong Jianin AGH University of Science and Technology Faculty of Physics and Applied Computer ScienceKrakow Anhui University HefeiAnhui Applied Physics Department Federal Urdu University of ArtsScience and TechnologyIslamabad Banaras Hindu University Institute of ScienceVaranasi Bandirma Onyedi Eylul University Bandirma Beihang University Beijing Beijing Computational Science Research Center Beijing Beijing Conveyi LTD Beijing Beijing Glass Research Institute Co. LtdBeijing Beijing Institute of Technology Beijing Beijing Normal University Beijing Brown University ProvidenceRI Budker Institute of Nuclear Physics Novosibirsk Cadi Ayyad University Laboratory of Fundamental and Applied PhysicsPolydisciplinary FacultyMarrakech Cairo University Giza Center for Theory and Computation National Tsing Hua UniversityHsinchu Central China Normal University WuhanHubei Central South University ChangshaHunan Centro de Fisica Teorica de Particulas Universidade Tecnica de LisboaLisboa Chengdu kaitengSifang Digital Radio&TV Equipment Co. LtdChengduSichuan China academy of engineering physics MianyangSichuan China building materials academy Beijing China Center of Advanced Science and Technology Beijing China Institute of Atomic Energy Beijing China Jiliang University HangzhouZhejiang China Nuclear Instrument CO. LTDBeijing China University of Geosciences Beijing China University of Geosciences WuhanHubei China University of Mining and Technology XuzhouJiangsu China West Normal University NanchongSichuan Chongqing University Department of PhysicsChongqing Chulalongkorn University Bangkok City University of Hong Kong Department of PhysicsHong Kong Cockcroft Institute Daresbury Cornell University IthacaNY CPPM(AMU/IPhU&CNRS/INP) Marseille Dalian Minzu University DalianLiaoning Dalian University of Technology Department of PhysicsDalian Deutsches Elektronen-Synchrotron DESY Hamburg Dzhelepov Laboratory of Nuclear Problems of Joint Institute for Nuclear Research(DLNP jinR) Dubna East China University Of Science And Technol

The Circular Electron Positron Collider(CEPC)is a large scientific project initiated and hosted by China,fostered through extensive collaboration with international *** complex comprises four accelerators:a 30 GeV linac,a 1.1 GeV Damping Ring,a Booster capable of achieving energies up to 180 GeV,and a Collider operating at varying energy modes(Z,W,H,and tt).The linac and Damping Ring are situated on the surface,while the subterranean Booster and Collider are housed in a 100 km circumference underground tunnel,strategically accommodating future expansion with provisions for a potential Super Proton Proton Collider(SPPC).The CEPC primarily serves as a Higgs *** its baseline design with synchrotron radiation(SR)power of 30 MW per beam,it can achieve a luminosity of 5×10^(34)cm^(-2)s^(-1)per interaction point(IP),resulting in an integrated luminosity of 13 ab^(-1)for two IPs over a decade,producing 2.6 million Higgs *** the SR power to 50 MW per beam expands the CEPC's capability to generate 4.3 million Higgs bosons,facilitating precise measurements of Higgs coupling at sub-percent levels,exceeding the precision expected from the HL-LHC by an order of *** Technical Design Report(TDR)follows the Preliminary Conceptual Design Report(Pre-CDR,2015)and the Conceptual Design Report(CDR,2018),comprehensively detailing the machine's layout,performance metrics,physical design and analysis,technical systems design,R&D and prototyping efforts,and associated civil engineering ***,it includes a cost estimate and a preliminary construction timeline,establishing a framework for forthcoming engineering design phase and site selection *** is anticipated to begin around 2027-2028,pending government approval,with an estimated duration of 8 *** commencement of experiments and data collection could potentially be initiated in the mid-2030s.

关键词： initiated exceeding precise

地塞米松对致敏性哮喘小鼠肺组织CCR3和Eotaxin表达的影响

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中国现代医学杂志 2006年第8期16卷 1140-1144,1148页

作者：金淑贤殷凯生卞涛南京医科大学第一附属医院呼吸内科江苏南京210029

目的观察地塞米松对小鼠哮喘模型气道炎症和肺组织CC型趋化因子Eotaxin和受体CCR3表达的影响。方法建立哮喘模型,自第14天雾化吸入OVA前0.5h,干预组分别雾化吸入咪喹莫特30min及ip地塞米松。OVA雾化结束后24h,每组小鼠眼球摘除采血收集... 详细信息

目的观察地塞米松对小鼠哮喘模型气道炎症和肺组织CC型趋化因子Eotaxin和受体CCR3表达的影响。方法建立哮喘模型,自第14天雾化吸入OVA前0.5h,干预组分别雾化吸入咪喹莫特30min及ip地塞米松。OVA雾化结束后24h,每组小鼠眼球摘除采血收集血清。采用酶联免疫吸附法测定血清、支气管肺泡灌洗液及肺组织匀浆中Eotaxin水平:收集肺泡灌洗液进行细胞计数和分类;H-E染色观察肺组织炎症改变;用免疫组化方法检测肺组织Eotaxin和CCR3的表达;用Westernblot方法测定肺组织CCR3表达;用逆转录-聚合酶链反应半定量检测肺组织IL-4、IFN-γ、Eotaxin、和CCR3mRNA表达水平。结果H-E染色可见地塞米松组小鼠气道炎症程度减轻;地塞米松治疗组嗜酸性粒细胞、单核细胞和淋巴细胞比哮喘组明显减少;哮喘组小鼠血清和肺组织匀浆Eotaxin水平较正常组升高,地塞米松治疗组小鼠较哮喘组下降;Eotaxin、CCR3均在气道上皮细胞表达,哮喘组小鼠气道上皮细胞Eotaxin、CCR3较正常组增加,地塞米松治疗组较哮喘组减轻;哮喘组小鼠肺组织EotaxinCCR3和IL-4mRNA表达较正常组增强,地塞米松治疗组小鼠肺组织Eotaxin、CCR3和IL-4mRNA表达较哮喘组降低。结论地塞米松减轻哮喘小鼠的气道炎症与抑制哮喘小鼠肺组织Eotaxin、CCR3蛋白和mRNA的过度表达有关。

关键词：哮喘 Eotaxin 巨噬细胞衍生的趋化因子(MDC) 胸腺和活化调节趋化因子(TARC) 咪喹莫特

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咪喹莫特治疗支气管哮喘作用机制的实验研究

中华结核和呼吸杂志 2007年第7期30卷 509-517页

作者：殷凯生金淑贤卞涛吴巧珍王祥姚欣南京医科大学第一附属医院呼吸科 210029

目的研究新型免疫调节剂咪喹莫特对支气管哮喘(简称哮喘)的治疗作用,探讨其可能的作用机制。方法 (1)40只 BALB/c 小鼠(每组10只)和48只 SD 大鼠(每组12只)分为对照组、哮喘组、咪喹莫特组和地塞米松组,建立大鼠和小鼠哮喘模型。用卵清... 详细信息

目的研究新型免疫调节剂咪喹莫特对支气管哮喘(简称哮喘)的治疗作用,探讨其可能的作用机制。方法 (1)40只 BALB/c 小鼠(每组10只)和48只 SD 大鼠(每组12只)分为对照组、哮喘组、咪喹莫特组和地塞米松组,建立大鼠和小鼠哮喘模型。用卵清白蛋白激发前吸入0.15%咪喹莫特混悬液5 ml。末次激发后24 h 观察肺组织炎症及测定气道反应性;用逆转录-聚合酶链反应(RT-PCR)法测定肺组织中白细胞介素4(IL-4)、γ干扰素(IFN-γ)、嗜酸粒细胞活化趋化因子(eotaxin)、巨噬细胞衍生趋化因子(MDC)、胸腺和活化调节趋化因子(TARC)、T-bet、GATA-3、信息转导转录激活子6(STAT_6)mRNA 的表达;用酶联免疫吸附试验(EliSA)法测定血清中 eotaxin、MDC、TARC 及支气管肺泡灌洗液中 IL-4和 IFN-γ浓度;用 Western blot 法测定肺组织中 T-bet、GATA-3、STAT_6蛋白水平;(2)分离和培养致敏大鼠气管旁淋巴结细胞(PBLN),分为空白对照组、阳性对照组、地塞米松组和药物1～3组,测定不同时间点各组细胞上清液中 IL-4、IFN-γ蛋白和细胞的 mRNA表达;(3)分离和培养致敏小鼠的脾脏 T 淋巴细胞,用流式细胞仪测定经咪喹莫特刺激后不同时间点细胞内 IL-4、IFN-γ水平;(4)培养致敏大鼠 CD_4^+T 淋巴细胞,测定经咪喹莫特干预后 T-bet、GATA-3mRNA 和蛋白的表达水平。结果用同等剂量氯化乙酰胆碱(20、40、80、160μg/ml)激发时平均呼气阻力哮喘组分别为(6.26±0.85)、(11.55±3.09)、(28.74±5.94)、(3710.83±197.49)cm H_2O·ml^(-1)·s^(-1)(1 cm H_2O=0.098 kPa),咪喹莫特组分别为(1.34±0.16)、(3.47±0.49)、(9.29±1.27)、(25.22±5.44)cm H_2O·ml^(-1)·s^(-1),两组相同剂量比较差异有统计学意义(D 值分别为88.98、56.00、45.00、108.00,P 均<0.01);哮喘组大鼠气道壁和肺组织中嗜酸粒细胞(EOS)、淋巴细胞、管壁面积/支气管管腔内周长(WA/Pi)、支气管平滑肌面积/支气管管腔内周长(ASM/Pi)分别为(26.0±1.6)、(45.2±3.2)个/mm^2、12.0±1.4、6.7±0.6,咪喹莫特组分别为(12.4±2.9)、(24.2±3.7)个/mm^2、9.2±0.6、4.0±0.5,两组比较差异有统计学意义(D 和 q 值分别为193.00、16.92、185.50、7.66,P 均<0.01);哮喘组肺组织中 T-bet mRNA 和蛋白表达量分别为0.08±0.12、0.18±0.06,咪喹莫特组分别为0.48±0.08、0.48±0.17,两组比较差异有统计学意义(D 值分别为120.96、177.98,P 均<0.01);哮喘组肺组织中 GATA-3 mRNA 和蛋白表达量分别为1.56±0.28、2.25±0.74,咪喹莫特组分别为0.54±0.14、0.50±0.14,两组比较差异有统计学意义(D 值分别为166.96、310.97,P 均<0.01);空白对照组24、48 h 时 PBLN 细胞培养液中 IL-4、IFN-γ分别为(0±0、0±0、22±5、31±5)pg/ml。随着培养时间的延长,药物2组24、48 h 时 IL-4、IFN-γ水平分别为(23±5)、(39±11)、(149±31)、(154±28)pg/ml,药物3组24、48 h 时IL-4、IFN-γ水平分别为(25±6)、(40±12)、(166±30)、(158±31)pg/ml,与阳性对照组[(43±13)、(56±12)、(100±22)、(112±33)pg/ml)]比较差异有统计学意义(药物2、3组24、48 h 时 IL-4的 D 值分别为9.90、8.79、8.80、8.10;药物2、3组24、48 h 时 IFN-γ的 q 值分别为4.80、6.40、3.95、4.31,P 均<0.05);哮喘组小鼠 BALF 中细胞总数及 EOS 分别为(8.7±1.4)×10~6/L、(29.80±7.00)%,咪喹莫特组为(4.1±1.3)×10~6/L、(8.90±2.40)%,两组比较差异有统计学意义(q 值分别为16.40、7.40,P 均<0.05);哮喘组小鼠血清 eotaxin、MDC 和 TARC 水平分别为(593±41)、(170±20)、(221±25)pg/ml,咪喹莫特组分别为(501±76)、(84±13)、(163

关键词：哮喘咪喹莫特

咪喹莫特对小鼠哮喘模型气道炎症和STAT6表达的影响

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第四军医大学学报 2006年第6期27卷 548-552页

作者：金淑贤殷凯生卞涛陈子庆南京医科大学第一附属医院呼吸内科江苏南京210029 南京医科大学第一附属医院中心实验室

目的观察咪喹莫特对小鼠哮喘模型气道炎症和肺组织信号转导与转录激活因子1(STAT1)和STAT6表达的影响.方法建立哮喘模型,自14d时雾化吸入OVA前0.5h,干预组分别雾化吸入咪喹莫特30min及ip地塞米松.OVA雾化结束后24h取左上叶肺组织做HE染... 详细信息

目的观察咪喹莫特对小鼠哮喘模型气道炎症和肺组织信号转导与转录激活因子1(STAT1)和STAT6表达的影响.方法建立哮喘模型,自14d时雾化吸入OVA前0.5h,干预组分别雾化吸入咪喹莫特30min及ip地塞米松.OVA雾化结束后24h取左上叶肺组织做HE染色观察肺组织炎症改变;收集肺泡灌洗液进行细胞计数和分类;用免疫组化和West blot方法检测肺组织STAT1和STAT6的表达;用逆转录-聚合酶链反应半定量检测肺组织STAT1,STAT6,IL-4,eotaxin和IFN-γmRNA表达水平.结果①HE染色示地塞米松组和咪喹莫特组小鼠肺组织炎症程度较哮喘小鼠减轻.②哮喘组小鼠BALF中细胞总数及各种炎症细胞较正常组显著增加,咪喹莫特治疗组嗜酸性粒细胞、淋巴细胞比哮喘组明显减少(P<0.01).③STAT1和STAT6均在气道上皮细胞表达,哮喘组肺组织STAT1和STAT6表达较正常组增强,咪喹莫特组STAT1表达与哮喘组无明显区别,较正常组增加.④哮喘组小鼠肺组织STAT1,STAT6,eotaxin,IL-4mRNA表达较正常组增强(P<0.01),IFN-γmRNA表达减少,咪喹莫特组STAT1mRNA表达与哮喘组无明显区别,STAT6,eotaxin和IL-4mRNA的表达较哮喘组降低,较正常组增加,IFN-γmRNA表达较哮喘组增加,但低于正常组.结论雾化吸入咪喹莫特可在一定程度上减轻哮喘小鼠的气道炎症,抑制肺组织STAT6蛋白和mRNA的过度表达.

关键词：哮喘信号转导与转录激活因子1 信号转导与转录激活因子6 咪喹莫特

支气管哮喘大鼠转录因子T-bet/GATA-3失衡表达与气道炎症的关系

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中华结核和呼吸杂志 2006年第3期29卷 176-180页

作者：卞涛殷凯生金淑贤孟自力周锦勇马秀琴胡静静德伟南京医科大学第一附属医院呼吸科 210029 南京医科大学生化实验室

目的探讨支气管哮喘(简称哮喘)转录因子T-bet/GATA-3表达量比值的变化及其与气道炎症的关系。方法24只雄性SD大鼠按随机数字表法分为对照组、哮喘组,每组12只。用动物肺功能仪测定大鼠气道反应性;用苏木精-伊红染色观察气道病理改变;用... 详细信息

目的探讨支气管哮喘(简称哮喘)转录因子T-bet/GATA-3表达量比值的变化及其与气道炎症的关系。方法24只雄性SD大鼠按随机数字表法分为对照组、哮喘组,每组12只。用动物肺功能仪测定大鼠气道反应性;用苏木精-伊红染色观察气道病理改变;用酶联免疫吸附测定(EliSA)法检测大鼠支气管肺泡灌洗液(BALF)中白细胞介素4(IL-4)、IL-5、γ干扰素(IFN-γ)含量;用逆转录-聚合酶链反应(RT-PCR)测定法检测肺组织中IL-4、IL-5、IFNγ-、T-bet和GATA-3 mRNA的表达水平;用免疫印迹(W estern b lot)法检测肺组织T-bet和GATA-3蛋白的表达水平。结果用同等剂量氯化乙酰胆碱(20、40、80、160μg/m l)激发时平均呼气阻力哮喘组分别为(6.26±0.85)、(11.55±3.09)、(28.74±5.94)、(3 710.83±197.49)cm H2O.m l-1.s-1,对照组分别为(1.51±0.18)、(2.15±0.36)、(6.08±1.06)、(37.17±6.12)cm H2O.m l-1.s-1,两组不同激素剂量比较差异有统计学意义(P均<0.01);肺组织中嗜酸粒细胞(EOS)、淋巴细胞数,管壁面积/支气管管腔内周长(WA/P i)和支气管平滑肌面积/支气管管腔内周长(ASM/P i)哮喘组分别为(26.0±1.6)个/mm2、(45.2±3.2)个/mm2、12.0±1.4、6.7±0.6,对照组分别为(2.9±1.2)个/mm2、(8.8±1.8)个/mm2、6.4±0.8、2.7±0.5,两组比较差异有统计学意义(P均<0.01);BALF中IL-4、IL-5和IFN-γ含量哮喘组为(23.4±0.7)pg/m l、(24.8±0.5)pg/m l和(21.7±1.1)pg/m l,对照组为(9.3±0.3)pg/m l、(12.5±0.3)pg/m l、(65.8±2.1)pg/m l,两组比较差异有统计学意义(P均<0.01);肺组织中IL-4、IL-5和IFN-γmRNA表达水平哮喘组分别为2.260±0.210、0.510±0.100、0.100±0.020,对照组分别为0.060±0.020、0.160±0.020、0.850±0.260,两组比较差异有统计学意义(P均<0.01)。肺组织中T-bet/GATA-3 mRNA表达量比值对照组为0.73±0.32,哮喘组为0.06±0.09,两组比较差异有统计学意义(P<0.01);肺组织中T-bet/GATA-3蛋白表达量比值哮喘组为0.09±0.04,对照组为0.75±0.25,两组比较差异有统计学意义(P<0.01)。两组大鼠T-bet/GATA-3蛋白表达量比值与20、40、80μg/m l氯化乙酰胆碱激发时的呼气阻力呈负相关(r分别=-0.959、-0.919、-0.943,P均<0.01);与EOS数、淋巴细胞数呈负相关(r=-0.832、-0.831,P均<0.01);与WA/P i、ASM/P i呈负相关(r=-0.837、-0.863,P均<0.01);与BALF中IL-4和IL-5含量呈负相关(r=-0.921、-0.920,P均<0.01);与IFN-γ含量呈正相关(r=0.934,P<0.01);与肺组织中IL-4、IL-5mRNA表达水平呈负相关(r=-0.964、-0.931,P均<0.01);与IFN-γmRNA表达呈正相关(r=0.983,P<0.01)。结论转录因子T-bet/GATA-3失衡表达与气道炎症密切相关,能客观反应哮喘免疫失衡,很可能是哮喘气道炎症形成的重要原因之一。

关键词：哮喘转录因子 T淋巴细胞气道炎症白细胞介素类

Association of Overlapped and Un-overlapped Comorbidities with COVID-19 Severity and Treatment Outcomes: A Retrospective Cohort Study from Nine Provinces in China

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Biomedical and Environmental Sciences 2020年第12期33卷 893-905页

作者： MA Yan ZHU Dong Shan CHEN Ren Bo SHI Nan Nan liU Si Hong FAN Yi Pin WU Gui Hui YANG Pu Ye BAI Jiang Feng CHEN Hong CHEN li ying FENG Qiao GUO Tuan Mao HOU Yong HU Gui Fen HU Xiao Mei HU Yun Hong HUANG jin HUANG Qiu Hua HUANG Shao Zhen JI liang jin Hai Hao LEI Xiao li Chun Yan li Min Qing li Qun Tang li xian Yong liU Hong De liU jin Ping liU Zhang MA Yu Ting MAO Ya MO liu Fen NA Hui WANG jing Wei SONG Fang li sun sheng WANG Dong Ting WANG Ming Xuan WANG Xiao Yan WANG yin Zhen WANG Yu Dong WU Wei WU Lan Ping XIAO Yan Hua XIE Hai Jun XU Hong Ming XU Shou Fang XUE Rui Xia YANG Chun YANG kai Jun YUAN sheng li ZHANG Gong Qi ZHANG jin Bo ZHANG lin Song ZHAO shu Sen ZHAO Wan ying ZHENG kai ZHOU ying Chun ZHU Jun Teng ZHU Tian Qing ZHANG Hua Min WANG Yan Ping WANG Yong Yan 无 Institute of Basic Research in Clinical Medicine China Academy of Chinese Medical SciencesBeijing 100700China Centre for Health Management and Policy Research School of Public HealthCheeloo College of MedicineShandong UniversityJinan 250012ShandongChina Institute of Information on Traditional Chinese Medicine China Academy of Chinese Medical SciencesBeijing 100700China Department of Tuberculosis The Public Health Clinical Center of ChengduChengdu 610066SichuanChina Department of Infectious Disease Shaanxi Infectious Disease HospitalXi'an 610113ShaanxiChina Department of Infectious Disease Yulin Chinese Medicine HospitalYulin 719000ShaanxiChina President's Office The First Hospital of QiqiharQiqihar 161005HeilongjiangChina Department of Traditional Chinese Medicine Shangluo Central HospitalShangluo 726000ShaanxiChina Department of Traditional Chinese Medicine The People's Hospital of QitaiheQitaihe 154603HeilongjiangChina Department of Scientific Research Xianyang Central HospitalXianyang 712000ShaanxiChina Department of traditional Chinese medicine The First Affiliated Hospital of Anhui University of Traditional Chinese MedicineHefei 230012AnhuiChina Department of Infectious Disease Heping Hospital Affiliated to Changzhi Medical CollegeChangzhi 046000ShanxiChina Department of Traditional Chinese Medicine Langfang Hospital of Chinese MedicineLangfang 065000HeibeiChina Department of Traditional Chinese Medicine Xingtai Hospital of Chinese MedicineXingtai 054001HeibeiChina Department of Traditional Chinese Medicine The People's Hospital of Guangxi Zhuang Autonomous RegionNanning 168600GuangxiChina Department of Traditional Chinese Medicine The First People'sHospital of FangchenggangFangchenggang 538001GuangxiChina Department of Traditional Chinese Medicine Mianyang Hospital of Traditional Chinese MedicineMianyang 621000SichuanChina Department of Traditional Chinese Medicine Liuzhou People's HospitalLiuzhou 545006GansuChina Department of Traditional Chinese Medici

Objective Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains *** A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients’ medical records. Multivariable logistic regression models were used to estimate the odds ratio(OR) and 95% confidence interval(95% CI) of the associations between comorbidities(cardiometabolic or non-cardiometabolic diseases), clinical severity, and treatment outcomes of *** Overall, 158(13.6%) patients were diagnosed with severe illness and 32(2.7%) had unfavorable outcomes. Hypertension(2.87, 1.30–6.32), type 2 diabetes(T2 DM)(3.57, 2.32–5.49),cardiovascular disease(CVD)(3.78, 1.81–7.89), fatty liver disease(7.53, 1.96–28.96), hyperlipidemia(2.15, 1.26–3.67), other lung diseases(6.00, 3.01–11.96), and electrolyte imbalance(10.40, 3.00–26.10)were independently linked to increased odds of being severely ill. T2 DM(6.07, 2.89–12.75), CVD(8.47,6.03–11.89), and electrolyte imbalance(19.44, 11.47–32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission(5.46,3.25–9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes(6.58, 1.46–29.64) within two *** Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.

关键词： Comorbidities COVID-19 Severity Gender Age Treatment outcome