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控轧控冷条件下Q345中厚板的生产工艺研究

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钢铁 2005年第5期40卷 32-37页

作者：朱伏先李艳梅刘彦春张苏渊易敏刘晶志轧制技术及连轧自动化国家重点实验室(东北大学) 辽宁沈阳110004 首钢集团总公司技术研究院北京100041 首钢集团总公司中板厂北京100041

通过试验模拟和实机轧制试验,对传统Q345钢的静态再结晶行为、应变累积效应和晶粒细化机制等进行研究,分析了影响中厚钢板显微组织和力学性能的主要因素。结合首钢中板厂3500mm机组的特点,确定出Q345中厚钢板的TMCP生产工艺。实践表明... 详细信息

通过试验模拟和实机轧制试验,对传统Q345钢的静态再结晶行为、应变累积效应和晶粒细化机制等进行研究,分析了影响中厚钢板显微组织和力学性能的主要因素。结合首钢中板厂3500mm机组的特点,确定出Q345中厚钢板的TMCP生产工艺。实践表明该工艺可使钢板的平均组织晶粒度达到10～12级,带状组织降至1.5级以下。

关键词： Q345钢中厚钢板 TMCP 再结晶

Q345钢奥氏体再结晶行为对组织和性能的影响

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东北大学学报（自然科学版） 2005年第6期26卷 566-569页

作者：朱伏先刘彦春李艳梅王国栋东北大学轧制技术及连轧自动化国家重点实验室辽宁沈阳110004

利用热模拟试验和实验轧机轧制试验,对Q345中厚钢板轧制过程中的奥氏体再结晶行为及应变累积效应等进行研究,讨论分析了再结晶行为对钢板组织和性能的影响规律,确定了奥氏体再结晶区和部分再结晶区道次变形量的控制原则,指出在880～820... 详细信息

利用热模拟试验和实验轧机轧制试验,对Q345中厚钢板轧制过程中的奥氏体再结晶行为及应变累积效应等进行研究,讨论分析了再结晶行为对钢板组织和性能的影响规律,确定了奥氏体再结晶区和部分再结晶区道次变形量的控制原则,指出在880～820℃的精轧温度区间内增加待温厚度有利于晶粒细化·研究成果已在首钢中板厂3500mm机组的工业生产中得到实际应用,使钢板的平均组织晶粒度达到10～12级;带状组织降至1 5级以下·

关键词： Q345钢中厚钢板奥氏体再结晶应变累积效应 TMCP工艺晶粒细化

Postoperative chemotherapy with S-1 plus oxaliplatin versus S-1alone in locally advanced gastric cancer(RESCUE-GC study): a protocol for a phase Ⅲ randomized controlled trial

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Chinese Journal of Cancer Research 2017年第2期29卷 144-148页

作者： xiang Hu lin Chen Yian Du Biao Fan Zhaode Bu Xin Wang Yingjiang Ye Zhongtao zhang Gang Xiao Fei li Qingsi He Guoli li xian Shen Bin Xiong liming zhu Jiwei liui lian liu Tao Wu Jing Zhou Jun zhang Gang Zhao Xulin Wang Pin liang Xinxin Wang yan zhang Xiaojiang Wu Ji zhang Xin Ji xianglong Zong Tao fu ziyu Jia Jiafu Ji Department of Gastrointestinal Surgery the First Affiliated Hospital of Dalian Medical University Dalian 116011 China Deparunent of General Surgery Chinese People's Liberation Army General Hospital Beijing 100853 China Department of Abdominal Surgery Zhejiang Cancer Hospital Hangzhou 310022 China Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Center of Gastrointestinal Surgery Peking University Cancer Hospital & Institute Beijing 100142 China Department of General Surgery Peking University First Hospital Beijing 100034 China Department of Gastrointestinal Surgery Peking University People's Hospital Beijing 100044 China Department of General Surgery Beijing Friendship Hospital Capital Medical University Beijing 100050 China Department of General Surgery Beijing Hospital Beijing 100730 China Department of General Surgery Xuanwu Hospital Capital Medical University Beijing 100053 China Department of General Surgery Qilu Hospital of Shandong University Jinan 250012 China Department of General Surgery Nanjing General Hospital Nanjing 210002 China Department of Gastrointestinal Surgery the First Affiliated Hospital of Wenzhou Medical University Wenzhou 325000 China Department of Oncology Zhongnan Hospital of Wuhan University Wuhan 430071 China Department of Medical Oncology Zhejiang Cancer Hospital Hangzhou 310022 China Department of Medical Oncology the First Affiliated Hospital of Dalian Medical University Dalian 116011 China Department of Chemotherapy Qilu Hospital of Shandong University Jinan 250012 China

Background： The ACTS-GC study had shown postoperative adiuvant therapy with S-1 improved survival of patients with locally advanced gastric cancer. Addition of oxaliplatin to S-1 is considered to be acceptable as one of the treatment options for gastric cancer patients after radical gastrectomy with D2 lymph node excision. Methods： We have commenced a randomized phase III trial in December 2016 to evaluate S-I plus oxaliplatin compared with S-1 alone in the adjuvant setting for locally advanced gastric cancer. A total of 564 patients will be accrued from 13 Chinese institutions in two years. The primary endpoint is 3-year relapse-free survival. The secondary endpoints are 5-year overall survival, proportion of patients who complete the postoperative chemotherapy and incidence of adverse events. Ethic and dissemination： The trial has been approved by the institutional review board of each participating institution and it was activated on December, 2016. The enrollment will be finished in December, 2018. Patient＇s follow-up will be ended until December, 2023. Trial registration： ***, identifier： NCT02867839. Registered on August 4, 2016.

关键词： Locally advanced gastric cancer S-1 plus oxaliplatin randomized phase HI trial

Amplitude analysis of the decays D^(0)→π^(+)π^(−)π^(+)π^(−)and D^(0)→π^(+)π^(−)π^(0)π^(0)

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Chinese Physics C 2024年第8期48卷 6-33页

作者： M.Ablikim M.N.Achasov P.Adlarson O.Afedulidis X.C.Ai R.Aliberti A.Amoroso Q.An Y.Bai O.Bakina I.Balossino Y.Ban H.-R.Bao V.Batozskaya K.Begzsuren N.Berger M.Berlowski M.Bertani D.Bettoni F.Bianchi E.Bianco A.Bortone I.Boyko R.A.Briere A.Brueggemann H.Cai X.Cai A.Calcaterra G.F.Cao N.Cao S.A.Cetin J.F.Chang W.L.Chang G.R.Che G.Chelkov C.Chen C.H.Chen Chao Chen G.Chen H.S.Chen M.L.Chen S.J.Chen S.L.Chen S.M.Chen T.Chen X.R.Chen X.T.Chen Y.B.Chen Y.Q.Chen Z.J.Chen Z.Y.Chen S.K.Choi X.Chu G.Cibinetto F.Cossio J.J.Cui H.L.Dai J.P.Dai A.Dbeyssi R.E.de Boer D.Dedovich C.Q.Deng Z.Y.Deng A.Denig I.Denysenko M.Destefanis F.De Mori B.Fang S.S.Fang W.X.Fang Y.Fang Y.Q.Fang R.Farinelli L.Fava F.Feldbauer G.Felici C.Q.Feng J.H.Feng Y.T.Feng K.Fischer M.Fritsch C.D.fu J.L.fu Y.W.fu H.Gao Y.N.Gao yang Gao S.Garbolino I.Garzia P.T.Ge Z.W.Ge C.Geng E.M.Gersabeck B.Ding X.X.Ding Y.Ding Y.Ding J.Dong L.Y.Dong M.Y.Dong X.Dong M.C.Du S.X.Du Z.H.Duan P.Egorov Y.H.Fan J.Fang JA.Gilman K.Goetzen L.Gong W.X.Gong W.Gradl S.Gramigna M.Greco M.H.Gu Y.T.Gu C.Y.Guan Z.L.Guan A.Q.Guo L.B.Guo M.J.Guo R.P.Guo Y.P.Guo A.Guskov J.Gutierrez K.L.Han T.T.Han X.Q.Hao F.A.Harris K.K.He K.L.He F.H.Heinsius C.H.Heinz Y.K.Heng C.Herold T.Holtmann P.C.Hong G.Y.Hou X.T.Hou Y.R.Hou Z.L.Hou B.Y.Hu H.M.Hu J.F.Hu T.Hu Y.Hu G.S.Huang K.X.Huang L.Q.Huang X.T.Huang Y.P.Huang T.Hussain F.H\"olzken N.H\"usken N.in der Wiesche M.Irshad J.Jackson S.Janchiv J.H.Jeong Q.Ji Q.P.Ji W.Ji X.B.Ji X.L.Ji Y.Y.Ji X.Q.Jia Z.K.Jia D.Jiang H.B.Jiang P.C.Jiang S.S.Jiang T.J.Jiang X.S.Jiang Y.Jiang J.B.Jiao J.K.Jiao Z.Jiao S.Jin Y.Jin M.Q.Jing X.M.Jing T.Johansson S.Kabana N.Kalantar-Nayestanaki X.L.Kang X.S.Kang M.Kavatsyuk B.C.Ke V.Khachatryan A.Khoukaz R.Kiuchi O.B.Kolcu B.Kopf M.Kuessner X.Kui A.Kupsc W.K\"uhn J.J.Lane P.Larin L.Lavezzi T.T.Lei Z.H.Lei H.Leithoff M.Lellmann T.Lenz C.li C.li C.H.li cheng li D.M.li F.li G.li H.li H.B.li H.J.li H.N.li Hui li J.R.li J.S.li K.li L.J.li L.K.li Lei li M.H.li P.R.li Q.M.li Q.X.li R.li S.X.li T.li W.D.li W.G.li X.li X.H.li X.L.li X.Y.li Y Institute of High Energy Physics Chinese Academy of SciencesBeijing 100049China Beihang University Beijing 100191China Bochum Ruhr-University D-44780 BochumGermany Budker Institute of Nuclear Physics SB RAS(BINP) Novosibirsk 630090Russia Carnegie Mellon University PittsburghPennsylvania 15213USA Central China Normal University Wuhan 430079China Central South University Changsha 410083China China Center of Advanced Science and Technology Beijing 100190China China University of Geosciences Wuhan 430074China Chung-Ang University Seoul06974Republic of Korea COMSATS University Islamabad Lahore CampusDefence RoadOff Raiwind Road54000 LahorePakistan fudan University Shanghai 200433China GSI Helmholtzcentre for Heavy Ion Research GmbH D-64291 DarmstadtGermany Guangxi Normal University Guilin 541004China Guangxi University Nanning 530004China Hangzhou Normal University Hangzhou 310036China Hebei University Baoding 071002China Helmholtz Institute Mainz Staudinger Weg 18D-55099 MainzGermany Henan Normal University Xinxiang 453007China Henan University Kaifeng 475004China Henan University of Science and Technology Luoyang 471003China Henan University of Technology Zhengzhou 450001China Huangshan College Huangshan 245000China Hunan Normal University Changsha 410081China Hunan University Changsha 410082China Indian Institute of Technology Madras Chennai 600036India Indiana University BloomingtonIndiana 47405USA INFN Laboratori Nazionali di Frascati INFN Laboratori Nazionali di FrascatiI-00044FrascatiItaly INFN Laboratori Nazionali di Frascati INFN Sezione di PerugiaI-06100PerugiaItaly INFN Laboratori Nazionali di Frascati University of PerugiaI-06100PerugiaItaly INFN Sezione di Ferrara INFN Sezione di FerraraI-44122FerraraItaly INFN Sezione di Ferrara University of FerraraI-44122FerraraItaly Inner Mongolia University Hohhot 010021China Institute of Modern Physics Lanzhou 730000China Institute of Physics and Technology Peace Avenue 54BUlaanbaatar 13330Mongolia Instituto de A

Using e^(+)e^(−)annihilation data corresponding to an integrated luminosity of 2.93 fb^(−1)taken at the center-of-mass energy√s=3.773 GeV with the BESIII detector,a joint amplitude analysis is performed on the decays D^(0)→π^(+)π^(−)π^(+)π^(−)and D^(0)→π^(+)π^(−)π^(0)π^(0)(non-η).The fit fractions of individual components are obtained,and large interferences among the dominant components of the decays D^(0)→a_(1)(1260)π,D^(0)→π(1300)π,D^(0)→ρ(770)ρ(770),and D^(0)→2(ππ)_(S)are observed in both *** the obtained amplitude model,the CP-even fractions of D^(0)→π^(+)π^(−)π^(+)π^(−)and D^(0)→π^(+)π^(−)π^(0)π^(0)(non-η)are determined to be(75.2±1.1_(stat).±1.5_(syst.))%and(68.9±1.5_(stat).±2.4_(syst.))%,*** branching fractions of D^(0)→π^(+)π^(−)π^(+)π^(−)and D^(0)→π^(+)π^(−)π^(0)π^(0)(non-η)are measured to be(0.688±0.010_(stat.)±0.010_(syst.))%and(0.951±0.025_(stat.)±0.021_(syst.))%,*** amplitude analysis provides an important model for the binning strategy in measuring the strong phase parameters of D^(0)→4πwhen used to determine the CKM angleγ(ϕ_(3))via the B^(−)→DK^(−)decay.

关键词： BESIII D^(0)meson decays amplitude analysis CP-even fraction

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

XELOX doublet regimen versus EOX triplet regimen as first-line treatment for advanced gastric cancer:An open-labeled,multicenter,randomized,prospective phase III trial(EXELOX)

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Cancer Communications 2022年第4期42卷 314-326页

作者： Xiao-Dong zhu Ming-zhu Huang Yu-Sheng Wang Wan-Jing Feng Zhi-Yu Chen Yi-fu He Xiao-Wei zhang Xin liu Chen-Chen Wang Wen zhang Jie-Er Ying Jun Wu Lei yang yan-Ru Qin Jian-Feng Luo Xiao-Ying Zhao Wen-Hua li Zhe zhang li-Xin Qiu Qi-Rong Geng Jian-ling Zou Jie-Yun zhang Hong Zheng Xue-Feng Song Shu-Sheng Wu cheng-yan zhang Zhe Gong Qin-Qin liu Xiao-Feng Wang Qi Xu Qi Wang Jian-mei Ji Jian Zhao Wei-Jian Guo Department of Gastrointestinal Medical Oncology Fudan University Shanghai Cancer CenterShanghai 200032P.R.China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai 200032P.R.China Department of Gastroenterology Shanxi Cancer HospitalTaiyuanShanxi 030013P.R.China Department of Medical Oncology The First Affiliated HospitalDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230031P.R.China Department of Abdominal Medical Oncology Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital)Institute of Cancer and Basic Medicine(IBMC)Chinese Academy of SciencesHangzhouZhejiang 310005P.R.China Department of Medical Oncology The First People’s Hospital of ChangzhouChangzhouJiangsu 213004P.R.China Department of Gastroenterology Nantong Tumor HospitalNantongJiangsu 226006P.R.China Department of Oncology Zhengzhou University First Affiliated HospitalZhengzhouHenan 450052P.R.China Department of Biostatistics School of Public HealthFudan UniversityShanghai 200032P.R.China Department of medical oncology Cancer Hospital of Fudan UniversityMinhang BranchShanghai 200032P.R.China

Background:There is no consensus on whether triplet regimen is better than doublet regimen in the first-line treatment of advanced gastric cancer(AGC).We aimed to compare the efficacy and safety of oxaliplatin plus capecitabine(XELOX)and epirubicin,oxaliplatin,plus capecitabine(EOX)regimens in treating ***:This phase III trial enrolled previously untreated patients with AGC whowere randomly assigned to receive the XELOXor *** primary endpoint was non-inferiority in progression-free survival(PFS)for XELOX as compared with EOX on an intention-to-treat ***:Between April 10,2015 andAugust 20,2020,448AGCpatientswere randomized to receive XELOX(n=222)or EOX(n=226).The median PFS(mPFS)was 5.0 months(95%confidence interval[CI]=4.5-6.0 months)in the XELOX arm and 5.5 months(95%CI=5.0-6.0 months)in the EOX arm(hazard ratio[HR]=0.989,95%CI=0.812-1.203;P_(non-inferiority)=0.003).There was no significant difference inmedian overall survival(mOS)(12.0 vs.12.0months,P=0.384)or objective response rate(37.4%vs.45.1%,P=0.291)between the two *** patients with poorly differentiated adenocarcinoma and liver metastasis,the EOX arm had a significantly longer mOS(P=0.021)and a trend of longer mPFS(P=0.073)than the XELOX *** rate of grade 3/4 adverse events(AEs)was 42.2%(90/213)in the XELOX arm and 72.5%(156/215)in the EOX arm(P=0.001).The global health-related quality of life(QoL)score was significantly higher in the XELOX arm than in the EOX arm during ***:This non-inferiority trial demonstrated that the doublet regimen was as effective as the triplet regimen and had a better safety profile and QoL as a first-line treatment for AGC ***,the triplet regimen might have a survival advantage in patients with poorly differentiated adenocarcinoma and liver metastasis.

关键词： Advanced gastric cancer chemotherapy XELOX doublet regimen EOX triplet regimen noninferiority quality of life phase III trial

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含铌微合金化热轧多相钢的控轧控冷工艺

钢铁研究学报 2010年第8期22卷 41-44页

作者：郑东升朱伏先李艳梅东北大学轧制技术及连轧自动化国家重点实验室辽宁沈阳110004

通过热轧试验研究了两阶段轧制+层流冷却、空冷、超快冷的TMCP工艺对高硅铌钢、高硅Nb-Ti钢、低硅Nb-Ti钢显微组织和力学性能的影响。结果表明,控轧控冷后的试验钢含有铁素体、贝氏体、马氏体以及少量残余奥氏体的混合组织。在控轧控冷... 详细信息

通过热轧试验研究了两阶段轧制+层流冷却、空冷、超快冷的TMCP工艺对高硅铌钢、高硅Nb-Ti钢、低硅Nb-Ti钢显微组织和力学性能的影响。结果表明,控轧控冷后的试验钢含有铁素体、贝氏体、马氏体以及少量残余奥氏体的混合组织。在控轧控冷工艺参数相近的情况下,高硅铌钢、高硅Nb-Ti钢、低硅Nb-Ti钢的抗拉强度依次减小,其伸长率和强塑积依次增大。低硅Nb-Ti钢的伸长率和强塑积分别达到了41%、25 256 MPa.%的最大值。

关键词：铌微合金钢热轧多相钢控轧控冷工艺

空冷弛豫对铌微合金化热轧多相钢组织性能的影响

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钢铁 2011年第4期46卷 70-75页

作者：郑东升朱伏先李艳梅陈炳张东北大学轧制技术及连轧自动化国家重点实验室辽宁沈阳110819

研究了铌微合金化试验钢控冷过程空冷弛豫温度对其组织和力学性能的影响,结合金相、电镜观察以及XRD技术分析了弛豫过程铁素体组织的演变、基体中的应变诱导析出行为以及组织中的残余奥氏体量变化。结果表明,轧后采用弛豫+超快冷的控冷... 详细信息

研究了铌微合金化试验钢控冷过程空冷弛豫温度对其组织和力学性能的影响,结合金相、电镜观察以及XRD技术分析了弛豫过程铁素体组织的演变、基体中的应变诱导析出行为以及组织中的残余奥氏体量变化。结果表明,轧后采用弛豫+超快冷的控冷工艺可以得到含有铁素体、贝氏体和残余奥氏体的多相组织,弛豫终止温度显著影响铁素体晶粒尺寸、铁素体量以及铁素体基体上的沉淀析出量。随着弛豫终止温度的降低,试验钢的屈服强度和抗拉强度呈降低趋势,而屈强比均保持在0.7左右的较低水平。当弛豫终止温度为720℃时,试验钢的抗拉强度、伸长率和强塑积分别达到820 MPa,37.5%和30.750 GPa.%的最大值。

关键词：铌微合金钢热轧多相钢弛豫显微组织力学性能

Neuroprotectants attenuate hypobaric hypoxia-induced brain injuries in cynomolgus monkeys

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Zoological Research 2020年第1期41卷 3-19页

作者： Pei zhang Jie-Si Chen Qi-Ye li Long-xiang Sheng Yi-Xing Gao Bing-Zheng Lu Wen-Bo zhu Xiao-Yu Zhan Yuan li Zhi-Bing Yuan Gang Xu Bi-Tao Qiu Min yan Chun-Xue Guo You-Qiong Wang Yi-Jun Huang Jing-Xia zhang fu-Yu liu Zhong-Wei Tang Sui-Zhen lin David NCooper Huan-Ming yang Jian Wang Yu-Qi Gao Wei Yin Guo-Jie zhang Guang-mei yan State Key Laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China BGI-Shenzhen ShenzhenGuangdong 518083China Section for Ecology and Evolution Department of BiologyUniversity of CopenhagenCopenhagen DK-2100Denmark Department of Pharmacology Zhongshan School of MedicineSun Yat-Sen UniversityGuangzhouGuangdong 510080China Institute of Medicine and Hygienic Equipment for High Altitude Region College of High Altitude Military MedicineThird Military Medical UniversityChongqing 400038China Key Laboratory of High Altitude Medicine of People's liberation Army Chongqing 400038China Key Laboratory of High Altitude Environmental Medicine Third Military Medical UniversityMinistry of EducationChongqing 400038China School of Pharmaceutical Sciences Sun Yat-Sen UniversityGuangzhouGuangdong 510006China Guangzhou Cellprotek Pharmaceutical Co.Ltd. GuangzhouGuangdong 510663China Institute of Medical Genetics School of MedicineCardiff UniversityCardiff CF144XNUK James D.Watson Institute of Genome Sciences HangzhouZhejiang 310058China Department of Biochemistry Zhongshan School of MedicineSun Yat-Sen UniversityGuangzhouGuangdong 510080China Center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunmingYunnan 650223China China National Genebank BGI-ShenzhenShenzhenGuangdong 518120China

Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily using non-primate animal models that are genetically distant to humans, thus hindering the development of disease treatment. Here, we report that cynomolgus monkeys (Macaca fascicularis) exposed to acute HH developed human-like HH syndrome involving severe brain injury and abnormal behavior. Transcriptome profiling of white blood cells and brain tissue from monkeys exposed to increasing altitude revealed the central role of the HIF-1 and other novel signaling pathways, such as the vitamin D receptor (VDR) signaling pathway, in co-regulating HH-induced inflammation processes. We also observed profound transcriptomic alterations in brains after exposure to acute HH, including the activation of angiogenesis and impairment of aerobic respiration and protein folding processes, which likely underlie the pathological effects of HH-induced brain injury. Administration of progesterone (PROG) and steroid neuroprotectant 5α-androst-3β,5,6β-triol (TRIOL) significantly attenuated brain injuries and rescued the transcriptomic changes induced by acute HH. functional investigation of the affected genes suggested that these two neuroprotectants protect the brain by targeting different pathways, with PROG enhancing erythropoiesis and TRIOL suppressing glutamate-induced excitotoxicity. Thus, this study advances our understanding of the pathology induced by acute HH and provides potential compounds for the development of neuroprotectant drugs for therapeutic treatment.

关键词： Acute hypobaric hypoxia Cynomolgus monkeys Brain injury Neuroprotectant Gene regulatory networks