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CHES: A Space-borne Astrometric Mission for the Detection of Habitable Planets of the Nearby Solar-type Stars

Research in Astronomy and Astrophysics 2022年第7期22卷 32-59页

作者： Jiang-Hui Ji hai-Tao Li Jun-Bo zhang Liang Fang Dong Li Su Wang Yang Cao Lei Deng Bao-Quan Li Hao Xian Xiao-Dong Gao Ang zhang Fei Li Jia-Cheng Liu Zhao-Xiang Qi Sheng {3. Ya-Ning Liu Guo Chen Ming-Tao Li yao Dong Zi Zhu CAS Key Laboratory of Planetary sciences Purple Mountain ObservatoryChinese Academy of SciencesNanjing 210023China School of Astronomy and Space Science University of Science and Technology of ChinaHefei 230026China Key Laboratory of Electronics and Information Technology for Space Systems National Space Science CenterChinese Academy of SciencesBeijing 100190China University of chinese academy of sciences Beijing 100049China institute of Optics and Electronics Chinese Academy of SciencesChengdu 610209China Key Laboratory on Adaptive Optics Chinese Academy of SciencesChengdu 610209China Key Laboratory of Science and Technology on Space Optoelectronic Precision Measurement Chinese Academy of SciencesChengdu 610209China Innovation academy for Microsatellites of chinese academy of {3. Shanghai 201306China School of Astronomy and Space Science Nanjing UniversityNanjing 210046China Shanghai Astronomical Observatory Chinese Academy of SciencesShanghai 200030China

The Closeby Habitable Exoplanet Survey(CHES) mission is proposed to discover habitable-zone Earth-like planets of nearby solar-type stars(~10 pc away from our solar system) via microarcsecond relative *** major scientific objectives of CHES are:to search for Earth Twins or terrestrial planets in habitable zones orbiting100 FGK nearby stars;further to conduct a comprehensive survey and extensively characterize nearby planetary *** primary payload is a high-quality,low-distortion,high-stability *** optical subsystem is a coaxial three-mirror anastigmat(TMA) with a 1.2 m-aperture,0°.44 × 0°.44 field of view and 500 nm-900 nm working wave *** camera focal plane is composed of a mosaic of 81 scientific CMOS detectors each with4 k × 4 k *** heterodyne laser interferometric calibration technology is employed to ensure microarcsecond level(1 μas) relative astrometry precision to meet the requirements for detection of Earth-like *** CHES satellite operates at the Sun-Earth L2 point and observes all the target stars for 5 *** will offer the first direct measurements of true masses and inclinations of Earth Twins and super-Earths orbiting our neighbor stars based on microarcsecond astrometry from *** will definitely enhance our understanding of the formation of diverse nearby planetary systems and the emergence of other worlds for solar-type stars,and finally provide insights to the evolution of our own solar system.

关键词： Astrometry and Celestial Mechanics planets and satellites:detection planets and satellites:terrestrial planets stars:solar-type

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基于功率合成技术的166 GHz大功率源研制

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红外与毫米波学报 2018年第5期37卷 608-612页

作者：孟进张德海蒋长宏姚常飞中国科学院国家空间科学中心微波遥感重点实验室北京100190 南京信息工程大学电子与信息工程学院江苏南京210044

冰云探测对于提高天气预报准确性、监测极端天气现象等具有重要的意义.考虑到冰云粒子尺寸、形状分布等因素,利用太赫兹频段被动遥感仪器能更好地解决冰云探测的难题. 664 GHz作为一个重要的探测频点,其接收机射频前端主要包括664 GHz... 详细信息

冰云探测对于提高天气预报准确性、监测极端天气现象等具有重要的意义.考虑到冰云粒子尺寸、形状分布等因素,利用太赫兹频段被动遥感仪器能更好地解决冰云探测的难题. 664 GHz作为一个重要的探测频点,其接收机射频前端主要包括664 GHz二次谐波混频器、3.2 GHz二倍频器以及166 GHz大功率源.作者在太赫兹二倍频设计的基础上,利用两路功率合成技术实现166 GHz大功率源,目的是提供给后级的3.2 GHz二倍频器足够的输入功率,从而能够驱动谐波混频器工作.实验结果表明,上述大功率源在164~172 GHz频率范围内输出功率大于46m W;在168 GHz处有最大输出功率59 m W.以上研究有效解决了本振链路中G波段输出功率不足的问题,为研制更高频段的太赫兹系统提供了技术支撑.

关键词：功率合成技术二倍频大功率源

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Paired quasi-periodic pulsations of hard X-ray emission in a solar flare

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Science China(Physics,Mechanics & Astronomy) 2023年第5期66卷 195-206页

作者： hai-Sheng Zhao Dong Li Shao-Lin Xiong Yan-Qiu zhang Yang Su Wei Chen Yi Zhao Xiao-Bo Li Jia-Cong Liu Wen-Xi Peng Rui Qiao Xin-Qiao Li Xiang-Yang Wen Li-Ming Song Shi-Jie zheng Xin-Ying Song Xiao-Yun Zhao Yue Huang Shuang-Nan zhang Shuo Xiao Ce Cai zheng-Hua An Can Chen Gang Chen Wei Chen Yan-Qi Du Min Gao Ke Gong Dong-Ya Guo Zhi-Wei Guo Jian-Jian He Bin Li Chao Li Chao-Yang Li Gang Li Jian-Hui Li Lu Li Qing-Xin Li Yan-Guo Li jing Liang Xiao-Hua Liang jin-Yuan Liao Xiao-jing Liu Ya-Qing Liu Qi Luo Xiang Ma Bin Meng Ge Ou Dong-Li Shi jing-Yan Shi Gong-xing Sun Xi-Lei Sun You-Li Tuo Chen-Wei Wang Hui Wang jin Wang jin-Zhou Wang Ping Wang Wen-Shuai Wang Hong Wu Sheng-Lun Xie Yan-Bing Xu Yu-Peng Xu Wang-Chen Xue Sheng Yang Min yao Jian-Ying Ye Qi-Bin Yi Chao-Yue zhang Da-Li zhang Fan zhang Fei zhang Hong-Mei zhang Kai zhang Peng zhang Xiao-Lu zhang zhen zhang Guo-Ying Zhao Shi-Yi Zhao Chao zheng xing Zhou Yue Zhu Key Laboratory for Particle Astrophysics Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China Purple Mountain Observatory Chinese Academy of SciencesNanjing 210023China University of chinese academy of sciences Beijing 100049China Department of Astronomy Beijing Normal UniversityBeijing 100875China School of Computing and Artificial Intelligence Southwest Jiaotong UniversityChengdu 611756China Physics and Space Science College China West Normal UniversityNanchong 637002China Key Laboratory of Stellar and Interstellar Physics and Department of Physics Xiangtan UniversityXiangtan 411105China institute of Astrophysics Central China Normal UniversityWuhan 430079China School of Physics Changchun University of Science and TechnologyChangchun 130022China College of Physics and Engineering Qufu Normal UniversityQufu 273165China College of Physics sciences&Technology Hebei UniversityBaoding 071002China

We investigate high time resolution data obtained by the Gravitational wave high-energy Electromagnetic Counterpart All-sky Monitor(GECAM)during the flare event on 2022 April 21 at 01:52 *** subpeaks with durations of 4-6 s have been detected in the hard X-ray precursor phase,and the key feature is that they appear in pairs and seem like double-peak *** subpeaks are rarely observed in hard X-ray band and confirmed by the microwave obtained by Nobeyama Radio Polarimeters(NoRP)and Radio Solar Telescope Network(RSTN).While an exponential function can describe the continuum component of the time profile from the precursor to part of the impulsive *** periods of quasi-periodic pulsations(QPPs)are detected to be about 7.3.and 12.8 s for the precursor and impulsive phase,respectively,with at least 95%confidence *** paired QPPs are assumed to be double-peak QPPs and then the scenario of current loop coalescence model is found to be in good agreement with our *** precursor phase can be interpreted as the oscillating coalescence of two islands,while the impulsive phase can be interpreted as more islands to coalesce one by one to form larger islands.

关键词： solar flare QPPs loop coalescence circular-ribbon flare

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Cell atlas of CCl_(4)-induced progressive liver fibrosis reveals stage-specific responses

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Zoological Research 2023年第3期44卷 451-466页

作者： Peng-Cheng Guo jing Zuo Ke-Ke Huang Guang-yao Lai Xiao zhang Juan An jin-Xiu Li Li Li Liang Wu Yi-Ting Lin Dong-Ye Wang Jiang-Shan Xu Shi-Jie Hao Yang Wang Rong-hai Li Wen Ma Yu-Mo Song Chang Liu Chuan-Yu Liu zhen Dai Yan Xu Amar Deep Sharma Michael Ott Qing Ou-Yang Feng Huo Rong Fan Yong-Yin Li jin-Lin Hou Giacomo Volpe Long-Qi Liu Miguel A.Esteban Yi-Wei Lai State Key Laboratory for Zoonotic Diseases Key Laboratory for Zoonosis Research of Ministry of EducationInstitute of ZoonosisCollege of Veterinary MedicineJilin UniversityChangchunJilin 130062China BGI-Hangzhou HangzhouZhejiang 310012China BGI-Shenzhen ShenzhenGuangdong 518083China Key Laboratory of Biological Targeting Diagnosis Therapy and Rehabilitation of Guangdong Higher Education InstitutesFifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong 510799China Laboratory of Integrative Biology Guangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouGuangdong 510530China Joint School of Life sciences Guangzhou Institutes of Biomedicine and Health and Guangzhou Medical UniversityGuangzhouGuangdong 510530China School of Life sciences Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230026China College of Life sciences University of Chinese Academy of SciencesBeijing 100049China Guangzhou institutes of Biomedicine and Health Chinese Academy of SciencesGuangzhouGuangdong 510530China Biotherapy Centre Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China Department of Gastroenterology Hepatology and EndocrinologyHannover Medical SchoolHannover 30625Germany Department of Hepatobiliary Surgery and Liver Transplant Center General Hospital of Southern Theater CommandGuangzhouGuangdong 510010China Department of Infectious Diseases Nanfang HospitalSouthern Medical UniversityGuangdong Provincial Key Laboratory of Viral Hepatitis ResearchGuangzhouGuangdong 510515China Hematology and Cell Therapy Unit IRCCS-Istituto Tumori‘Giovanni Paolo II’Bari 70124Italy institute of Experimental Hematology Hannover Medical SchoolHannover 30625Germany

Chronic liver injury leads to progressive liver fibrosis and ultimately cirrhosis,a major cause of morbidity and mortality ***,there are currently no effective anti-fibrotic therapies available,especially for latestage patients,which is partly attributed to the major knowledge gap regarding liver cell heterogeneity and cellspecific responses in different fibrosis *** reveal the multicellular networks regulating mammalian liver fibrosis from mild to severe phenotypes,we generated a single-nucleus transcriptomic atlas encompassing 49919nuclei corresponding to all main liver cell types at different stages of murine carbon tetrachloride(CCl_(4))-induced progressive liver *** analysis distinguished the sequential responses to injury of hepatocytes,hepatic stellate cells and endothelial ***,we reconstructed the cell-cell interactions and gene regulatory networks implicated in these *** integrative analyses uncovered previously overlooked aspects of hepatocyte proliferation exhaustion and disrupted pericentral metabolic functions,dysfunction for clearance by apoptosis of activated hepatic stellate cells,accumulation of pro-fibrotic signals,and the switch from an anti-angiogenic to a pro-angiogenic program during CCl_(4)-induced progressive liver *** dataset thus constitutes a useful resource for understanding the molecular basis of progressive liver fibrosis using a relevant animal model.

关键词： Liver fibrosis Toxicity Single-cell and single-nucleus RNA-sequencing Hepatocytes Hepatic stellate cells Angiogenesis Cell-cell interactions Gene regulatory networks

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The Homo sapiens Cave hominin site of Mulan Mountain,Jiangzhou District,Chongzuo,Guangxi with emphasis on its age

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chinese Science Bulletin 2009年第21期54卷 3848-3856页

作者： jin ChangZhu PAN WenShi zhang YingQi CAI YanJun XU QinQi TANG ZhiLu WANG Wei WANG Yuan LIU jinYi QIN DaGong R. Lawrence Edwards CHENG {3. Key Laboratory of Evolutionary Systematics of Vertebrates Institute of Vertebrate Paleontology and Paleoanthropology (IVPP) Chinese Academy of Sciences Beijing 100044 China School of Life sciences Peking University Beijing 100871 China institute of Earth Environment Chinese Academy of Sciences Xi'an 710075 China Natural History Museum of Guangxi Zhuang Autonomous Region Nanning 530012 China Department of geology and geophysics University of Minnesota Minneapolis MN 55455 USA

One of the most hotly debated and frontal issues in paleoanthropology focuses on the origins of modern humans. Recently, an incomplete hominin mandible with a distinctly weaker mental protuberance than modern human and a great variety of coexisting fossil mammals were unearthed from the Homo sapiens Cave of Mulan Mountain, Chongzuo, Guangxi. The mammalian fauna from the Homo sapiens Cave characterized by the combination of Elephas kiangnanensis, first occurring Elephas maixmus, and Megatapirus augustus, and strikingly different from the Early Pleistocene Gigantopithecus fauna and the Middle Pleistocene Ailuropoda-Stogodon fauna of South China could be regarded as an early representive of the typical Asian elephant fauna. Faunal analysis, biostratigraphic correlation, and, most importantly, U-series dating all consistently support an estimate of ca. 110 ka for the age of the fossil Homo sapiens and coexisting mammalian fauna, that is, the early Late Pleistocene. The fauna is mainly made up of tropical-subtropical elements, but grassland elements have a much greater variety than forest elements, which probably indicates a drier climate at that time. This discovery of early Homo sapiens at the Mulan Mountain will play a significant role in the study of the origin and its environmental background of modern humans.

关键词：早期智人木兰人族广西年龄现代人类起源哺乳动物化石哺乳动物群

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Native Medicinal Plant Richness Distribution Patterns and Environmental Determinants of Xinjiang, Northwest China

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chinese Herbal Medicines 2015年第1期7卷 45-53页

作者： Li-ping Li Ben-gang zhang Pei-gen Xiao Zhao zhang yao-dong Qi Xiao-{3. Li Guo-ping Wang hai-tao Liu Key Laboratory of Bioactive Substances and Resources Utilization of chinese Herbal Medicine (Peking Union Medical College) Ministry of Education Institute of Medicinal Plant Development Chinese Academy of Medical Sciences Peking Union Medical College Xinjiang institute of chinese Materia Medica and Ethical Materia Medica

Objective To comprehensively map the distribution patterns of native medicinal plants of Xinjiang Uygur Autonomous Region, China; To find the environmental determinants and to give suggestions for the conservation planning of medicinal plants in Xinjiang region. Methods Firstly, we compiled the distribution data of native medicinal plants at a county level in Xinjiang region, including the source plants of chinese Materia Medica （CMM）, Uygur Medicine （UM）, and Kazak Medicine （KM）; Secondly, we divided the distribution data into grid with a resolution of 0.1~ x 0.1~ and overlaid it on the topography and climate data in Arcgis 10.0; Finally, we analyzed the correlations of medicinal plant richness and environmental variables with ordinary least square （OLS） regressions and partial regressions. Results UM has more non-native species in Xinjiang region than KM. The species richness of medicinal plants is high in Altay Mountains, western Tianshan Mountains, and part of Kunlun Mountains. The richness of medicinal plants is highly correlated with the vascular plant species richness and climate, and further, the independent effects of vascular plant species richness are higher than the independent effects of climate. The whole plant, root ＆ rhizome, and seed ＆ fruit are more frequently used than stem and leaf for CMM in Xinjiang region. Conclusion The distribution patterns of medicinal plants are concordant with vascular plant species, which could be carefully considered in the conservation planning of this region. Taking full advantage of current nature reserves is a low-costing approach to the conservation of medicinal plants although they were not originally established for medicinal plant protection. Nevertheless, it is urgent to further study the distributions and protection status of medicinal plants in the nature reserves of Xinjiang region.

关键词： chinese Materia Medica distribution diversity Kazak Medicine Traditional chineseMedicine Uygur Medicine Xinjiang Uygur Autonomous Region

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The Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST)

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Research in Astronomy and Astrophysics 2012年第9期12卷 1197-1242页

作者： Xiang-Qun Cui Yong-Heng Zhao yao-Quan Chu Guo-Ping Li Qi Li Li-Ping zhang Hong-Jun Su zheng-Qiu yao Ya-Nan Wang Xiao-zheng {3. Xin-Nan Li Yong-Tian Zhu Gang Wang Bo-Zhong Gu A-Li Luo Xin-Qi Xu zhen-Chao zhang Gen-Rong Liu Hao-Tong zhang De-Hua Yang Shu-Yun Cao hai-Yuan Chen Jian-Jun Chen Kun-Xin Chen Ying Chen Jia-Ru Chu Lei Feng Xue-Fei Gong Yong-Hui Hou Hong-Zhuan Hu Ning-Sheng Hu Zhong-Wen Hu Lei Jia Fang-Hua Jiang Xiang Jiang Zi-Bo Jiang Ge jin Ai-Hua Li Yan Li Ye-Ping Li Guan-QunLiu Zhi-Gang Liu Huo-Ming Shi zheng-Hong Tang Qing-Sheng Tao Xiang-Yan Yuan Chao Zhai jing zhang Yan-Xia zhang Yong zhang Ming Zhao Fang Zhou Guo-Hua Zhou Jie Zhu Si-Cheng Zou National Astronomical Observatories Chinese Academy of Sciences Beijing 100012 China yzhao @ *** Nanjing institute of Astronomical Optics and Technology National Astronomical ObservatoriesChinese Academy of Sciences Nanjing 210042 China University of Science and Tecfinologyof China Hefei 230026 China Shanghai Astronomical Observatory Chinese Academy of Sciences Shanghai 200030 China institute of Architecture Design and Research Chinese Academy of Sciences Beijing 100190China

The Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST, also called the Guo Shou jing Telescope) is a special reflecting Schmidt telescope. LAMOST’s special design allows both a large aperture (effective aperture of 3.6 m–4.9 m) and a wide field of view (FOV) (5°). It has an innovative active reflecting Schmidt configuration which continuously changes the mirror’s surface that adjusts during the observation process and combines thin deformable mirror active optics with segmented active optics. Its primary mirror (6.67m×6.05 m) and active Schmidt mirror (5.74m×4.40 m) are both segmented, and composed of 3. and 24 hexagonal sub-mirrors respectively. By using a parallel controllable fiber positioning technique, the focal surface of 1.75 m in diameter can accommodate 4000 optical fibers. Also, LAMOST has 16 spectrographs with 3. CCD cameras. LAMOST will be the telescope with the highest rate of spectral acquisition. As a national large scientific project, the LAMOST project was formally proposed in 1996, and approved by the chinese government in 1997. The construction started in 2001, was completed in 2008 and passed the official acceptance in June 2009. The LAMOST pilot survey was started in October 2011 and the spectroscopic survey will launch in September 2012. Up to now, LAMOST has released more than 480 000 spectra of objects. LAMOST will make an important contribution to the study of the large-scale structure of the Universe, structure and evolution of the Galaxy, and cross-identification of multiwaveband properties in celestial objects.

关键词： techniques: wide field telescope - active optics - multi fiber - spectroscopy survey - data reduction

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Effect and Mechanism of hai Tong-pi Decoction Ointment on Antiinflammation and Analgesia by Transcutaneous Administration in Mice

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Journal of hainan Medical University 2022年第16期28卷 13-20页

作者： LI Fa-jie GU jin-yu zhang-Yue SHEN Shuo yao yao WAN Tian-hao XIA Di zhang Qing Wang jing Hospital China Academy of Chinese Medical SciencesBeijing 100102China institute of Basic Research in Clinical Medicine China Academy of Chinese Medical SciencesBeijing 100700China institute of chinese Materia Medica China Academy of Chinese Medical SciencesBeijing 100700China

Objectve:To investigate the effect and mechanism of hai Tongpi decoction ointment on analgesic and anti-inflammatory effects in mice after transdermal ***:The hot plate method and the acetic acid writhing experiment were used to verify the analgesic effect of hai tong-pi extract on pain model mice;the xylene-induced auricular swelling model and the carrageenan-induced right foot swelling model were used,combined with the ELISA method to determine the analgesic *** levels of TNF-α,IL-1βand IL-6 in the serum of mice were ***-inflammatory effect of haitongpi Tang decoction ointment on inflammation model ***:In terms of analgesia,compared with the model group,both the treatment group 1 and the treatment group 2 can significantly prolong the hot plate pain threshold and the latency of the writhing response(P1),and the effect of process 1 is more obvious(P1),indicating that the acute inflammation model was successfully established in the *** with the model group,both the process group 1 and the process group 2 can significantly reduce the swelling degree and swelling rate of the mice feet(P1 group was more significant(P1βand IL-6 in the model group were significantly increased(P1).Compared with the process group 2,the process group 1 had a more significant decrease in the content of IL-1β(P0.05).Conclusion:The hai tong-pi decoction ointment prepared by two diff

关键词： hai Tong-pi decoction ointment Anti-inflammation Analgesia interleukin-1β Tumor necrosis factor

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Site testing campaign for the Large Optical/infrared Telescope of China:overview

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Research in Astronomy and Astrophysics 2020年第6期20卷 81-95页

作者： Lu Feng jin-Xin Hao Zi-Huang Cao jin-Min Bai Ji Yang Xu Zhou Yong-Qiang yao jin-Liang Hou Yong-Heng Zhao Yu Liu Teng-Fei Song Li-Yong Liu Jia Yin Hua-Lin Chen Chong Pei Ali Esamdin Lu Ma Chun-hai Bai Peng Wei jing Xu Guang-Xin Pu Guo-Jie Feng Xuan zhang Liang Ming Abudusaimaitijiang Yisikandee Jian-Rong Shi Jian Li Yuan Tian zheng Wang Xia Wang Xiao-Jun Jiang Jian-Feng Wang Jian-Feng Tian Yan-Jie Xue Jian-Sheng Chen jing-yao Hu Zhi-Xia Shen Yun-Ying Jiang National Astronomical Observatories Chinese Academy of SciencesBeijing 100101China Yunnan Observatories Chinese Academy of SciencesKunming 650216China Xinjiang Astronomical Observatory Chinese Academy of SciencesUrumqi 830011China Shanghai Astronomical Observatory Chinese Academy of SciencesShanghai 200030China Nanjing institute of Astronomical Optics&Technology Chinese Academy of SciencesNanjing 210042China Purple Mountain Observatory Chinese Academy of SciencesNanjing 210033China University of chinese academy of sciences Beijing 100049China

The Large Optical/infrared Telescope(LOT)is a ground-based 12 m diameter optical/infrared telescope which is proposed to be built in the western part of China in the next *** on satellite remote sensing data,along with geographical,logistical and political considerations,three candidate sites were chosen for ground-based astronomical performance *** sites include:Ali in Tibet,Daocheng in Sichuan and Muztagh-ata in *** until now,all three sites have continuously collected data for two *** this paper,we will introduce this site testing campaign,and present its monitoring results obtained during the period between March 2017 and March 2019.

关键词： techniques telescope-site testing

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PI3./AKT信号通路与HER2阳性乳腺癌患者总生存时间的相关性及验证分析

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解放军医学杂志 2018年第3期43卷 217-223页

作者：李慧李春晓南鹏王婷王劲松张竞尧窦娜马飞王海娟钱海利詹启敏国家癌症中心/中国医学科学院北京协和医学院肿瘤医院分子肿瘤学国家重点实验室北京100021 国家癌症中心/中国医学科学院北京协和医学院肿瘤医院肿瘤内科北京100021

目的分析并验证与HER2阳性乳腺癌患者总生存时间相关的关键分子靶点。方法首先,从TCGA数据库中分别下载Ⅰ/Ⅱ期和Ⅲ/Ⅳ期HER2阳性乳腺癌患者生存时间及转录组数据,将Ⅰ/Ⅱ期患者根据总生存时间分为2年和8.5年两组,先利用edgeR软件包分... 详细信息

目的分析并验证与HER2阳性乳腺癌患者总生存时间相关的关键分子靶点。方法首先,从TCGA数据库中分别下载Ⅰ/Ⅱ期和Ⅲ/Ⅳ期HER2阳性乳腺癌患者生存时间及转录组数据,将Ⅰ/Ⅱ期患者根据总生存时间分为2年和8.5年两组,先利用edgeR软件包分析两组乳腺癌患者的差异基因,随后对差异基因进行KEGG通路富集;将Ⅲ/Ⅳ期患者根据总生存时间分为2年和7年两组,利用edgeR软件包分析差异基因并对其进行KEGG通路富集;最后分析与Ⅰ/Ⅱ期和Ⅲ/Ⅳ期HER2阳性乳腺癌患者总生存时间均相关的共同调控通路。其次,利用KMplot(Kaplan-Meier plotter)数据库验证KEGG富集通路关键节点基因及其他基因与HER2阳性乳腺癌患者总生存时间之间的相关性。最后,利用HER2阳性乳腺癌细胞系BT474验证KEGG富集通路与抗HER2治疗耐药之间的相关性。结果在Ⅰ/Ⅱ期HER2阳性乳腺癌患者中,总生存时间2年者PI3./AKT信号通路处于上调差异基因富集信号通路的第9位,而在Ⅲ/Ⅳ期总生存时间2年者中,PI3./AKT信号通路位于上调差异基因富集信号通路的第2位。在Ⅰ/Ⅱ期与Ⅲ/Ⅳ期总生存时间均2年的患者共同上调的差异基因中,PI3./AKT信号通路被富集于第1位。在PI3./AKT通路中,PI3.和AKT(关键节点基因)、CFAP221和COL4A6(通路其他基因)高表达的患者总生存时间短于低表达患者。细胞验证实验显示,PI3.抑制剂能够增强HER2小分子抑制剂对HER2阳性乳腺癌细胞系BT474的生长抑制作用。结论 PI3./AKT通路过度激活与HER2阳性乳腺癌患者总生存时间短相关,并与HER2阳性乳腺癌细胞抗HER2治疗耐药相关。

关键词： TCGA数据库 PI3./AKT信号通路 HER2阳性乳腺癌

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