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The activity and immune dynamics of PD-1 inhibition on high-risk pulmonary ground glass opacity lesions:insights from a single-arm,phase II trial

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2202-2214页

作者： Bo Cheng Caichen Li Jianfu Li Longlong Gong Peng Liang Ying Chen Shuting Zhan Shan Xiong Ran Zhong Hengrui Liang Yi Feng Runchen wang haixuan wang Hongbo Zheng Jun Liu Chengzhi Zhou Wenlong Shao Yuan Qiu Jiancong Sun Zhanhong Xie Zhu Liang Chenglin Yang Xiuyu Cai Chunxia Su Wei wang Jianxing He Wenhua Liang Department of Thoracic Surgery and Oncology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Institute of Respiratory HealthState Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhouChina Medical Department Genecast Biotechnology Co.LtdWuxiChina Department of Radiation Oncology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina Department of Respiratory Medicine the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Institute of Respiratory HealthState Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhouChina Department of Cardiothoracic Surgery Affiliated Hospital of Guangdong Medical UniversityZhanjiangChina Department of Thoracic Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenChina Department of VIP Inpatient Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaSun Yat-sen UniversityGuangzhouChina Department of Medical Oncology Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghaiChina

Immune checkpoint inhibitors targeting the programmed cell death-1(PD-1)protein significantly improve survival in patients with advanced non-small-cell lung cancer(NSCLC),but its impact on early-stage ground-glass opacity(GGO)lesions remains *** is a single-arm,phase II trial(NCT04026841)using Simon’s optimal two-stage design,of which 4 doses of sintilimab(200 mg per 3 weeks)were administrated in 36 enrolled multiple primary lung cancer(MPLC)patients with persistent high-risk(Lung-RADS category 4 or had progressed within 6 months)*** primary endpoint was objective response rate(ORR).T/B/NK-cell subpopulations,TCR-seq,cytokines,exosomal RNA,and multiplexed immunohistochemistry(mIHC)were monitored and compared between responders and ***,two intent-to-treat(ITT)lesions(pure-GGO or GGO-predominant)showed responses(ORR:5.6%,2/36),and no patients had progressive disease(PD).No grade 3-5 TRAEs *** total response rate considering two ITT lesions and three non-intent-to-treat(NITT)lesions(pure-solid or solid-predominant)was 13.9%(5/36).The proportion of CD8^(+)T cells,the ratio of CD8^(+)/CD4^(+),and the TCR clonality value were significantly higher in the peripheral blood of responders before treatment and decreased over ***,the mIHC analysis showed more CD8^(+)T cells infiltrated in ***,responders’cytokine concentrations of EGF and CTLA-4 increased during *** exosomal expression of fatty acid metabolism and oxidative phosphorylation gene signatures were down-regulated among ***,PD-1 inhibitor showed certain activity on high-risk pulmonary GGO lesions without safety *** effects were associated with specific T-cell re-distribution,EGF/CTLA-4 cytokine compensation,and regulation of metabolism pathways.

关键词： lesions metabolism doses

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Three doses of prototypic SARS-CoV-2 inactivated vaccine induce cross-protection against its variants of concern

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Signal Transduction and Targeted Therapy 2022年第3期7卷 909-917页

作者： Tianhong Xie Shuaiyao Lu Zhanlong He Hongqi Liu Junbin wang Cong Tang Ting Yang Wenhai Yu Hua Li Yun Yang Hao Yang Lei Yue Yanan Zhou Fengmei Yang Zhiwu Luo Yanyan Li Hong Xiang Yuan Zhao Jie wang haixuan wang Runxiang Long Dexuan Kuang Wenjie Tan Xiaozhong Peng Qihan Li Zhongping Xie Institute of Medical Biology Chinese Academy of Medicine Sciences&Peking Union Medical CollegeYunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases650118 KunmingChina The NHC Key Laboratory of Biosafety National Institute for Viral Disease Control and PreventionChina CDC102206 BeijingChina

Variants are globally emerging very quickly following pandemic prototypic *** evaluate the cross-protection of prototypic SARS-CoV-2 vaccine against its variants,we vaccinated rhesus monkeys with three doses of protot... 详细信息

关键词： doses globally protection

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Asian,regional,and national burdens of respiratory tract cancers and associated risk factors from 1990 to 2019:A systematic analysis for the global burden of disease study 2019

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Chinese Medical Journal Pulmonary and Critical Care Medicine 2023年第4期1卷 249-258页

作者： Ran Zhong Xiuyu Cai Jianfu Li Peiling Chen Runchen wang Xinting Li Feng Li Shan Xiong Caichen Li Huiting wang Yang Xiang Shuting Zhan Ziwen Yu haixuan wang Chunyan Li Lixuan Lin Wenhai Fu Xin Zheng Shen Zhao Kang Zhang Jianxing He Department of Thoracic Surgery and Oncology The First Affiliated Hospital of Guangzhou Medical UniversityState Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory HealthGuangzhouGuangdong 510000China Guangzhou Medical University GuangzhouGuangdong 510000China Department of Medical Oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdong 510050China The First People Hospital of Zhaoqing ZhaoqingGuangdong 526000China Center for Biomedicine and Innovations Faculty of MedicineMacao University of Science and TechnologyMacao 999078China

Background:Respiratory cancer is the leading cause of cancer-related deaths worldwide,but its statistics vary between the East and *** study aimed to estimate the burdens of tracheal,bronchus,and lung(TBL)cancer and larynx cancer and their attributable risks from 1990 to 2019 in Asia,and at regional and national ***:This research evaluated the incidence,mortality,years lived with disability,years of life lost,and disability-adjusted life years(DALYs)for respiratory tract cancers using the Global Burden of Diseases,Injuries,and Risk Factors Study(GBD)2019 ***-standardized rates were calculated for TBL cancer from 1990 to 2019,adjusted for smoking and socio-demographic index(SDI).Deaths from TBL cancer and larynx cancer attributable to each risk factor were estimated for 33 Asian ***:The age-standardized incidence and death rates for TBL cancer in Asia declined from 2010 to 2019,while the incidence rate of larynx cancer *** was the leading specific risk factor for deaths from both TBL and larynx *** burden of TBL cancer in Asian countries was influenced by SDI and smoking,particularly among males in Central ***,DALYs,and incidences of larynx cancer in East Asia had not changed significantly over the past 30 years,but showed slight downward trends in males and both sexes combined,and an upward trend in females in recent ***:The past decade saw increases in numbers of incident cases and deaths from TBL cancer and larynx cancer in *** and smoking were the main factors influencing the disease burden of TBL cancer in Asian *** study highlights the need for tailored cancer control programs to address the burden of respiratory tract cancers in different Asian countries.

关键词： Tracheal,bronchus,and lung(TBL)cancer Larynx cancer Smoking Socio-demographic index Global burden of diseases,injuries,and risk factors study(GBD) Asia

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Histones released by NETosis enhance the infectivity of SARS-CoV-2 by bridging the spike protein subunit 2 and sialic acid on host cells

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Cellular & Molecular Immunology 2022年第5期19卷 577-587页

作者： Weiqi Hong Jingyun Yang Jun Zou Zhenfei Bi Cai He Hong Lei Xuemei He Xue Li Aqu Alu Wenyan Ren Zeng wang Xiaohua Jiang Kunhong Zhong Guowen Jia Yun Yang Wenhai Yu Qing Huang Mengli Yang Yanan Zhou Yuan Zhao Dexuan Kuang Junbin wang haixuan wang Siyuan Chen Min Luo Ziqi Zhang Tiangi Lu Li Chen Haiying Que Zhiyao He Qiu Sun Wei wang Guobo Shen Guangwen Lu Zhiwei Zhao Li Yang Jinliang Yang Zhenling wang Jiong Li Xiangrong Song Lunzhi Dai Chong Chen Jia Geng Maling Gou Lu Chen Haohao Dong Yong Peng Canhua Huang Zhiyong Qian Wei Cheng Changfa Fan Yuquan Wei Zhaoming Su Aiping Tong Shuaiyao Lu Xiaozhong Peng Xiawei Wei Laboratory of Aging Research and Cancer Drug Targeting State Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityNo.17Block 3Southern Renmin RoadChengduSichuan610041China National Kunming High-level Biosafety Primate Research Center Institute of Medical BiologyChinese Academy of Medical Sciences and Peking Union Medical CollegeYunnanChina Westvac Biopharm Co. Ltd.No.618Fenghuang RoadShuangliu DistrictChengduSichuanChina Division of Animal Model Research Institute for Laboratory Animal ResourcesNational Institutes for Food and Drug Control102629BeijingChina State Key Laboratory of Medical Molecular Biology Department of Molecular Biology and BiochemistryInstitute of Basic Medical SciencesMedical Primate Research CenterNeuroscience CenterChinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijingChina

Neutrophil extracellular traps(NETs)can capture and kill viruses,such as influenza viruses,human immunodeficiency virus(HIV),and respiratory syncytial virus(RSV),thus contributing to host *** to our expectation,we show here that the histones released by NETosis enhance the infectivity of SARS-CoV-2,as found by using live SARS-CoV-2 and two pseudovirus systems as well as a mouse *** histone H3 or H4 selectively binds to subunit 2 of the spike(S)protein,as shown by a biochemical binding assay,surface plasmon resonance and binding energy calculation as well as the construction of a mutant S protein by replacing four acidic amino *** acid on the host cell surface is the key molecule to which histones bridge subunit 2 of the S ***,histones enhance cell-cell ***,treatment with an inhibitor of NETosis,histone H3 or H4,or sialic acid notably affected the levels of sgRNA copies and the number of apoptotic cells in a mouse *** findings suggest that SARS-CoV-2 could hijack histones from neutrophil NETosis to promote its host cell attachment and entry process and may be important in exploring pathogenesis and possible strategies to develop new effective therapies for COVID-19.

关键词： COVID-19 SARS-CoV-2 neutrophil extracellular traps histones sialic acid

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人力资源结构性矛盾下我国教育供给侧改革路径

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闽江学院学报 2023年第4期44卷 88-94页

作者：王海轩郭焱浙江大学能源工程学院浙江杭州310027 福州市人力资源和社会保障局福建福州350026

近年来,我国社会经济迅猛发展,人才市场的需求与教育体系人才供给的结构性失衡不断加剧,在高校毕业生就业难的同时,劳动市场却面临严峻的人才短缺问题。高等教育应将教育体系的人才供给嵌入社会经济发展,直面我国高等教育、职业教育人... 详细信息

近年来,我国社会经济迅猛发展,人才市场的需求与教育体系人才供给的结构性失衡不断加剧,在高校毕业生就业难的同时,劳动市场却面临严峻的人才短缺问题。高等教育应将教育体系的人才供给嵌入社会经济发展,直面我国高等教育、职业教育人才供给失衡现状,在人力资源结构性矛盾下,要从规模控制、顶层设计和结构优化三个有效路径实现我国高等教育、职业教育供给侧改革。

关键词：人力资源教育供给侧改革高等教育职业教育

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断裂岩石排替压力预测方法的改进及其应用

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石油与天然气地质 2024年第3期45卷 866-872页

作者：徐海轩李江海北京大学地球与空间学学院北京100871 造山带与地壳演化教育部重点实验室北京100871

为了解决目前断裂岩石排替压力预测方法尚存在的问题,以便更准确、科学地反映地下实际情况,根据断裂岩石和围岩排替压力与压实成岩程度之间的正相关关系,利用断裂岩石与相同埋深围岩排替压力之比应等于断裂岩石与相同埋深围岩压实成岩... 详细信息

为了解决目前断裂岩石排替压力预测方法尚存在的问题,以便更准确、科学地反映地下实际情况,根据断裂岩石和围岩排替压力与压实成岩程度之间的正相关关系,利用断裂岩石与相同埋深围岩排替压力之比应等于断裂岩石与相同埋深围岩压实成岩程度之比的关系,推导出了断裂岩石与相同埋深围岩排替压力之间关系,进而改进了目前断裂岩石排替压力的预测方法。利用该方法预测海拉尔盆地贝尔凹陷呼和诺仁背斜带F1断裂在大磨拐河组一段下亚段区域性泥岩盖层内的断裂岩石排替压力,结果表明改进后方法的预测结果明显小于改进前方法的预测结果,更符合F1断裂处南屯组二段油气仅分布在构造高部位的实际情况。改进后的断裂岩石排替压力预测方法适用于碎屑岩含油气盆地张性断裂在脆性地层中的断裂岩石排替压力预测。

关键词：围岩盖层排替压力断裂岩石海拉尔盆地

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二级齿轮非线性动态特性同伦摄动法分析

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振动与冲击 2024年第8期43卷 89-97,108页

作者：荀超吴海轩王云龙南京工程学院机械工程学院南京211167

考虑时变啮合刚度、脱齿、各级齿轮啮合间的耦合关系,建立了二级齿轮传动机构的刚柔混合模型,采用同伦超越摄动法分析了机构的非线性动态特性,得到了二级齿轮机构主共振、超谐共振和亚谐共振的频响表达式。与多尺度法不同,同伦法的分析... 详细信息

考虑时变啮合刚度、脱齿、各级齿轮啮合间的耦合关系,建立了二级齿轮传动机构的刚柔混合模型,采用同伦超越摄动法分析了机构的非线性动态特性,得到了二级齿轮机构主共振、超谐共振和亚谐共振的频响表达式。与多尺度法不同,同伦法的分析精度不受脱齿程度的影响。与数值积分结果的对比表明,在脱齿率达到30%以上时,同伦法较多尺度法具有明显的计算精度优势。该研究为复杂齿轮传动机构的非线性动态特性分析提供了更为精确的理论分析方法。

关键词：多级齿轮同伦摄动法脱齿非线性动态特性

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The olfactory route is a potential way for SARS-CoV-2 to invade the central nervous system of rhesus monkeys

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Signal Transduction and Targeted Therapy 2021年第5期6卷 1614-1624页

作者： Li Jiao Yun Yang Wenhai Yu Yuan Zhao Haiting Long Jiahong Gao Kaiyun Ding Chunxia Ma Jingmei Li Siwen Zhao haixuan wang Haiyan Li Mengli Yang Jingwen Xu Junbin wang Jing Yang Dexuan Kuang Fangyu Luo Xingli Qian Longjiang Xu Bin Yin Wei Liu Hongqi Liu Shuaiyao Lu Xiaozhong Peng National Kunming High-Level Biosafety Primate Research Center Institute of Medical BiologyChinese Academy of Medical Sciences and Peking Union Medical CollegeKunmingYunnanChina State Key Laboratory of Medical Molecular Biology Department of Molecular Biology and BiochemistryInstitute of Basic Medical SciencesMedical Primate Research CenterNeuroscience CenterChinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijingChina Department of Anatomy Institute of Basic Medical SciencesChinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijingChina

Neurological manifestations are frequently reported in the COVID-19 *** of SARS-CoV-2 remains to be *** this study,we explored the mechanisms of SARS-CoV-2 neurotropism via our established non-human primate model of *** rhesus monkey,SARS-CoV-2 invades the CNS primarily via the olfactory ***,viruses rapidly spread to functional areas of the central nervous system,such as hippocampus,thalamus,and medulla *** infection of SARS-CoV-2 induces the inflammation possibly by targeting neurons,microglia,and astrocytes in the ***,SARS-CoV-2 infects neuro-derived SK-N-SH,glial-derived U251,and brain microvascular endothelial cells in *** our knowledge,this is the first experimental evidence of SARS-CoV-2 neuroinvasion in the NHP model,which provides important insights into the CNS-related pathogenesis of SARS-CoV-2.

关键词： invasion inflammation system

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Distinct profiles of Gastrointestinal Microbiota and Metabolites in Rhesus Monkeys Infected with SARS-CoV-2 or Variants

Distinct profiles of Gastrointestinal Microbiota and Metabol...

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第十六届中国实验动物科学年会

作者： Hongyu Chen Junbin wang Kaiyun Ding Jingwen Xu Yun Yang Cong Tang Yanan Zhou Wenhai Yu haixuan wang Qing Huang Bai Li Dexuan Kuang Daoju Wu Zhiwu Luo Jiahong Gao Yuan Zhao Jiansheng Liu Xiaozhong Peng Shuaiyao Lu Hongqi Liu Institute of Medical biology Chinese Academy of Medical Sciences and Peking Union Medical School (IMBCAMS&PUMC) Institute of Basic Medical Sciences IMBCAMS&PUMC Institute of Laboratory Animals Science IMBCAMS&PUMC

Background Accumulating evidences demonstrate that gastrointestinal(GI)infection is involved in pathogenesis of *** of GI microbiota is documented in feces of COVID-19 patients and animal models of SARS-CoV-2 *** evolution of SARS-CoV-2 leads to appearance of distinct viral ***,profiles of GI microbiota and their contribution to infections of SARS-CoV-2 and variants remain to be *** Rhesus monkeys were infected with SARS-CoV-2 or its variants of concern(VOCs),followed by an integrative analysis of histopathology,microbiome and inflammatory responses in fragments of GI *** Five tested strains of SARS-CoV-2 formed two distinct *** viral cluster of Alpha,Beta and Delta(ABD) cause more severe infection and histopathology in both respiratory and gastrointestinal tissues than the cluster of Proto and Omicron(PO).Distinct profile of GI microbiome was observed between two ***,high abundance of potentially pathogenic pathogens,specially Spirocheta,was sequenced in small and large intestines of ABD viral strain infected *** analysis showed that ABD viral strains were positively correlated with infection and immunity-associated metabolites or pathways whereas PO viral strains had negative ***,tryptophanase was upregulated in ABD viral infection,and fatty acid biosynthesis was negatively correlated with PO viral *** analysis of fragments in GI tract showed that ABD viral strains had negative correlations with anti-viral and inhibiting viral binding pathways,including RIG-like receptor signaling pathway that was positively correlated with PO viral ***-and immune-related genes showed lower expressions in ABD virus-infected animals compared with those in PO virus-infected *** contrast,the top five upregulated genes,associated with cancer,inflammation and tight junction,had higher expressions in in ABD virus-infect

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培养选拔优秀年轻干部的新部署新要求——学习习近平在中央党校(国家行政学院)中青班开班式上的讲话

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理论视野 2021年第12期262卷 42-45页

作者：王海璇洪向华

习近平高度重视新时代培养选拔年轻干部工作,结合不同的主题内容对年轻干部队伍建设作出了五次重要论述。这些讲话深刻阐明了选拔优秀年轻干部的重大意义,提出培养选拔优秀年轻干部的新问题新要求,各内容之间严谨连贯、相辅相成,是统一... 详细信息

习近平高度重视新时代培养选拔年轻干部工作,结合不同的主题内容对年轻干部队伍建设作出了五次重要论述。这些讲话深刻阐明了选拔优秀年轻干部的重大意义,提出培养选拔优秀年轻干部的新问题新要求,各内容之间严谨连贯、相辅相成,是统一的科学体系。它深刻反映了党的年轻干部队伍建设的一般规律,为锻造党和国家事业发展的生力军提供了科学的方法,是新时代年轻干部成长和培养选拔工作的根本遵循。

关键词：习近平年轻干部中青干部培训班

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