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Expert consensus on management of metabolic disease in Chinese liver transplant recipients

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World Journal of Gastroenterology 2020年第27期26卷 3851-3864页

作者： Tian Shen Li zhuang xiao-dong sun xiao-sheng qi Zhi-Hui Wang Rui-dong Li wen-Xiu Chang jia-Yin yang yang yang Shu-Sen Zheng xiao Xu Department of Hepatobiliary and Pancreatic Surgery The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina Department of Hepatobiliary and Pancreatic Surgery Shulan(Hangzhou)HospitalHangzhou 310003Zhejiang ProvinceChina Department of Hepatobiliary and Pancreas Surgery The First HospitalJilin UniversityChangchun 130021Jilin ProvinceChina Department of General Surgery Shanghai First People's HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200080China Department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina Department of General Surgery and Liver Transplant Center Huashan HospitalFudan UniversityShanghai 200040China Department of Nephrology Tianjin First Center HospitalTianjin 300384China Department of Liver Surgery and Liver Transplantation Center West China Hospital of Sichuan UniversityChengdu 610041Sichuan ProvinceChina Department of Hepatic Surgery and Liver Transplantation Center The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630Guangdong ProvinceChina

Metabolic disease,including diabetes mellitus,hypertension,dyslipidemia,obesity,and hyperuricemia,is a common complication after liver transplantation and a risk factor for cardiovascular disease and *** development of metabolic disease is closely related to the side effects of ***,optimization of the immunosuppressive regimen is very important for the prevention and treatment of metabolic *** Chinese Society of Organ Transplantation has developed an expert consensus on the management of metabolic diseases in Chinese liver transplant recipients based on recent *** is placed on the risk factors of metabolic diseases,the effect of immunosuppressants on metabolic disease,and the prevention and treatment of metabolic diseases.

关键词： Liver transplantation Metabolic disease Diabetes mellitus Hypertension Dyslipidemia Hyperuricemia Obesity Immunosuppressive agents Consensus

Optimized valence state of Co and Ni in high-entropy alloy for high active-stable OER

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Rare Metals 2023年第11期42卷 3607-3613页

作者： Zhi-jia zhang Jun-Peng Guo Shi-Hao sun qi sun Yu-wen Zhao Yi-Fang zhang Zhen-yang Yu Chun-sheng Li Yan sun Meng-Meng zhang Yong jiang School of Materials Science and Engineering State Key Laboratory of Separation Membrane and Membrane ProcessesTiangong UniversityTianjin300387China School of Electronic and Information Engineering Institute of Quantum Materials and DevicesTiangong UniversityTianjin300387China School of Mechanical Engineering Tiangong UniversityTianjin300387China School of Chemistry and Life Sciences Key Laboratory of Advanced Electrode Materials for Novel Solar Cells for Petroleum and Chemical Industry of ChinaSuzhou University of Science and TechnologySuzhou215009China

High entropy alloy(HEA)exhibits potential water-splitting properties but are limited by the high energy consumption from ***,the complex atomic distribution endows the electronic structure regulation of HEA to remain ***,the nanoporous NiCuMnCoFe(np-NCMCF)HEA was prepared by the high-energy ball milling coupled with de-alloying *** introduced Fe markedly increases the proportion of Ni^(3+)and Co^(3+).

关键词： alloy alloying entropy

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

The In-Flight Realtime Trigger and Localization Software of GECAM

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Research in Astronomy and Astrophysics 2024年第10期24卷 11-24页

作者： xiao-Yun Zhao Shao-Lin Xiong Xiang-yang wen Xin-qiao Li Ce Cai Shuo xiao qi Luo wen-Xi Peng dong-Ya Guo Zheng-Hua An Ke Gong Jin-Yuan Liao Yan-qiu zhang Yue Huang Lu Li Xing wen Fei zhang Jing Duan Chen-Wei Wang dong-Li Shi Peng zhang qi-Bin Yi Chao-yang Li Yan-Bing Xu xiao-Hua Liang Ya-qing Liu Da-Li zhang Xi-Lei sun Fan zhang Gang Chen Huan-Yu Wang sheng yang xiao-Jing Liu Min Gao Mao-Shun Li Jin-Zhou Wang Xing Zhou Yi Zhao Wang-Chen Xue Chao Zheng jia-Cong Liu Xing-Bo Han Jin-Ling qi jia Huang Ke-Ke zhang Can Chen Xiong-Tao yang dong-Jie Hou Yu-Sa Wang Rui qiao Xiang Ma xiao-Bo Li Ping Wang Xin-ying Song Li-Ming Song Shi-Jie Zheng Bing Li Hong-Mei zhang Yue Zhu Wei Chen jian-jian He Zhen zhang Jin Hou Hong-Jun Wang Yan-Chao Hao Xiang-Yu Wang Zong-Yuan yang Zhi-Long wen Zhi Chang Yuan-Yuan Du Rui Gao xiao-Fei Lan Yan-Guo Li Gang Li Xu-Fang Li Fang-Jun Lu Hong Lu Bin Meng Feng Shi Hui Wang Hui-Zhen Wang Yu-Peng Xu jia-Wei yang Xue-Juan yang Shuang-Nan zhang Chao-Yue zhang Cheng-Mo zhang Zhi-Cheng Tang Cheng Cheng 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 School of Information Science and Technology Southwest Jiaotong UniversityChengdu 611756China Key Laboratory of Stellar and Interstellar Physics and Department of Physics Xiangtan UniversityXiangtan 411105China Physics and Space Science College China West Normal UniversityNanchong 637002China Department of Astronomy Beijing Normal UniversityBeijing 100875China Innovation Academy for Microsatellites of CAS Shanghai 201203China Changchun University of Science and Technology Changchun 130022China Chinese Academy of Sciences South America Center for Astronomy National Astronomical ObservatoriesCASBeijing 100101China

Realtime trigger and localization of bursts are the key functions of GECAM,an all-sky gamma-ray monitor launched on 2020 December *** developed a multifunctional trigger and localization software operating in the CPU of the GECAM Electronic *** onboard software has the following features:high trigger efficiency for real celestial bursts with a suppression of false triggers caused by charged particle bursts and background fluctuation,dedicated localization algorithm optimized for both short and long bursts,and low time latency of the trigger information which is downlinked through the Global Short Message Communication service of the global BeiDou navigation *** paper provides a detailed description of the design and development of the trigger and localization software system for *** covers the general design,workflow,the main functions,and the algorithms used in the *** paper also includes on-ground trigger tests using simulated gamma-ray bursts generated by a dedicated X-ray tube,as well as an overview of the performance for real celestial bursts during its in-orbit operation.

关键词： telescopes instrumentation:detectors methods:observational

SAPT:a synchrotron-based proton therapy facility in Shanghai

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Nuclear Science and Techniques 2023年第10期34卷 36-46页

作者： Man-Zhou zhang De-Ming Li Li-Ren Shen Hai-Rong zhang Zhi-Ling Chen Han-wen Du Ming Gu Rui Li De-Kang Liu Yue-Hu Pu Jun-Feng Yu jian-Feng Chen Chu Chen Chun-Long Guo Hao Guo Ge-yang jiang Zhi-qiang jiang Lin Jin wen-Jing Li Xiu-Fang Li Ye Lin Ming Liu Yong-Hao Liu Ya-Juan Liu Ming Lv qing-Ru Mi Lian-Hua Ouyang Wei-Guo Shi Hang Shu qi-sheng Tang Kun Wang Zhi-Shan Wang Jun Wu xiao-Bing Wu jia-qiang Xu wen-Zhen Xu Chong-Xian Yin Cheng Yu Ren-Xian Yuan qi-Bing Yuan Hai-Qun zhang Miao zhang wen-Zhi zhang Li-ying Zhao Wei-Min Zhou Shou-Xian Fang Xi-dong sun Zhen-Tang Zhao Shanghai Institute of Applied Physics Chinese Academy of SciencesShanghai 201800China Shanghai Advanced Research Institute Chinese Academy of SciencesShanghai 201204China APACTRON Particle Equipment Co. Ltd.Shanghai 201815China The Institute of High Energy Physics Chinese Academy of SciencesBeijing 100049China

Because of its excellent dose distribution,proton therapy is becoming increasingly popular in the medical application of cancer treatment.A synchrotron-based proton therapy facility was designed and constructed in *** synchrotron,beam delivery system,and other technical systems were commissioned and reached their expected *** a clinical trial of 47 patients was finished,the proton therapy facility obtained a registration certificate from the National Medical Products *** characteristics of the accelerator and treatment systems are described in this article.

关键词： Proton therapy Synchrotron Slow extraction Gantry Beam delivery system

Frontiers in high entropy alloys and high entropy functional materials

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Rare Metals 2024年第10期43卷 4639-4776页

作者： wen-Tao zhang Xue-qian Wang Feng-qi zhang xiao-Ya Cui Bing-Bing Fan jia-Ming Guo Zhi-Min Guo Rui Huang wen Huang Xu-Bo Li Meng-Ru Li Yan Ma Zhi-Hua Shen Yong-Gang sun De-zhuang Wang Fei-yang Wang Li-qiang Wang Nan Wang Tian-Li Wang Wei Wang xiao-yang Wang Yi-Han Wang Fu-Jie Yu Yu-Zhen Yin Ling-Kun zhang Yi zhang jian-yang zhang qi Zhao Yu-Ping Zhao Xin-dong Zhu Yasir Sohail Ya-Nan Chen Tao Feng qi-Long Gao Hai-Yan He Yong-jiang Huang Zeng-Bao jiao Hua Ji Yao jiang qiang Li xiao-Ming Li Wei-Bing Liao Huai-Jun Lin Hui Liu qi Liu qing-Feng Liu Wei-Di Liu Xiong-Jun Liu yang Lu Yi-Ping Lu wen Ma Xue-Fei Miao Jie Pan qing Wang Hong-Hui Wu Yuan Wu Tao yang Wei-Ming yang qian Yu Jin-Yu zhang Zhi-Gang Chen Liang Mao yang Ren Bao-Long Shen Xun-Li Wang Zhe jia He Zhu Zhen-Duo Wu Si Lan School of Materials Science and Engineering Nanjing University of Science and TechnologyNanjing 210094China jiangsu Key Laboratory for Advanced Metallic Materials School of Materials Science and EngineeringSoutheast UniversityNanjing 211189China Department of Physics City University of Hong KongHongKong 999077China School of Materials Science and Engineering Tianjin UniversityTianjin 300072China School of Physics and Microelectronics Zhengzhou UniversityZhengzhou 450001China Department of Mechanical Engineering Research Institute for Advanced ManufacturingThe Hong Kong Polytechnic UniversityHong Kong 100872China Center of Electron Microscopy and State Key Laboratory of Silicon Materials School of Materials Science and EngineeringZhejiang UniversityHangzhou 310027China Key Laboratory of Solidification Control and Digital Preparation Technology(Liaoning Province) School of Materials Science and EngineeringDalian University of TechnologyDalian 116024China Institute of Advanced Wear&Corrosion Resistance and Functional Materials Jinan UniversityGuangzhou 510632China School of Mechanics and Civil Engineering China University of Mining and TechnologyXuzhou 221116China School of Physical Sciences Great Bay UniversityDongguan 523000China School of Materials Science and Engineering Harbin Institute of TechnologyHarbin 150001China State Key Laboratory of Materials-Oriented Chemical Engineering College of Chemical EngineeringNanjing Tech UniversityNanjing 211816China Beijing Advanced Innovation Center for Materials Genome Engineering Research Institute for Carbon NeutralityUniversity of Science and Technology BeijingBeijing 100083China Department of Mechanical Engineering The University of Hong KongHong Kong 999077China School of Computing Macquarie UniversitySydney 2113Australia Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province College of Physics and Optoelectronic EngineeringShenzhen UniversityShenzhen 518060China State Key Laborato

Owing to their exceptional properties,high-entropy alloys(HEAs)and high-entropy materials have emerged as promising research areas and shown diverse ***,the recent advances in the field are comprehensively reviewed,organized into five *** first section introduces the background of HEAs,covering their definition,significance,application prospects,basic properties,design principles,and *** subsequent section focuses on cutting-edge high-entropy structural materials,highlighting developments such as nanostructured alloys,grain boundary engineering,eutectic systems,cryogenic alloys,thin films,micro-nano-lattice structures,additive manufacturing,high entropy metallic glasses,nano-precipitate strengthened alloys,composition modulation,alloy fibers,and refractory *** the following section,the emphasis shifts to functional materials,exploring HEAs as catalysts,magneto-caloric materials,corrosion-resistant alloys,radiation-resistant alloys,hydrogen storage systems,and materials for ***,the review encompasses functional high-entropy materials outside the realm of alloys,including thermoelectric,quantum dots,nanooxide catalysts,energy storage materials,negative thermal expansion ceramics,and high-entropy wave absorption *** paper concludes with an outlook,discussing future directions and potential growth areas in the *** this comprehensive review,researchers,engineers,and scientists may gain valuable insights into the recent progress and opportunities for further exploration in the exciting domains of high-entropy alloys and functional materials.

关键词： High entropy alloys Cutting-edge structural materials Cutting-edgefunctional materials

Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma(CHANCE001)

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Signal Transduction and Targeted Therapy 2023年第3期8卷 1198-1207页

作者： Hai-dong Zhu Hai-Liang Li Ming-sheng Huang Wei-Zhu yang Guo-wen Yin Bin-Yan Zhong Jun-Hui sun Zhi-Cheng Jin jian-jian Chen Nai-jian Ge wen-Bin Ding wen-Hui Li Jin-Hua Huang Wei Mu Shan-Zhi Gu jia-Ping Li Hui Zhao Shu-Wei wen Yan-Ming Lei Yu-sheng Song Chun-Wang Yuan Wei-dong Wang Ming Huang Wei Zhao jian-Bing Wu Song Wang Xu Zhu jian-Jun Han Wei-Xin Ren Zai-Ming Lu wen-Ge Xing Yong Fan Hai-Lan Lin Zi-Shu zhang Guo-Hui Xu wen-Hao Hu qiang Tu Hong-ying Su Chuan-sheng Zheng Yong Chen Xu-Ya Zhao Zhu-Ting Fang qi Wang Jin-Wei Zhao Ai-Bing Xu jian Xu qing-Hua Wu Huan-zhang Niu jian Wang Feng Dai Dui-Ping Feng qing-dong Li Rong-Shu Shi jia-Rui Li Guang yang Hai-Bin Shi jian-Song Ji Yu-E Liu Zheng Cai Po yang yang Zhao xiao-Li Zhu Li-Gong Lu Gao-Jun Teng Center of Interventional Radiology&Vascular Surgery Department of RadiologyZhongda HospitalMedical SchoolSoutheast UniversityNanjing 210009China Department of Minimally invasive Intervention The Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhou 450008China Department of Interventional Radiology the Third Affiliated HospitalSun Yat-Sen UniversityGuangzhou 510630China Department of Interventional Radiology Union Hospital of Fujian Medical UniversityFuzhou 350001China Department of Interventional Radiology Jiangsu Cancer Hospital&Jiangsu Institute of Cancer Research&The Affiliated Cancer Hospital of Nanjing Medical UniversityNanjing 210009China Department of Interventional Radiology The First Affiliated Hospital of Soochow UniversitySoochow UniversitySuzhou 215006China Hepatobiliary and Pancreatic Interventional Treatment Center Division of Hepatobiliary and Pancreatic SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Interventional Radiology Eastern Hospital of Hepatobiliary SurgeryNavy Medical University(Second Military Medical University)Shanghai 200438China Department of Interventional Radiology Nantong First People’s HospitalNantong 226001China Department of Interventional Radiology Yancheng Third People’s HospitalYancheng 224008China Department of Minimally Invasive Interventional Therapy Sun YatSen University Cancer CenterGuangzhou 510060China Department of Vascular Surgery Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China. Department of Interventional Radiology Hunan Cancer HospitalChangsha 410031China Department of Interventional Oncology The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080China Department of Interventional Radiology The Hospital of Nantong UniversityNantong 226001China Department of Interventional Therapy Shanxi Tumor HospitalTaiyuan 030001China Department of Interventional Radiology Tibet Autonomous Region People’s

There is considerable potential for integrating transarterial chemoembolization(TACE),programmed death-(ligand)1(PD-[L]1)inhibitors,and molecular targeted treatments(MTT)in hepatocellular carcinoma(HCC).It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world *** this nationwide,retrospective,cohort study,826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT(combination group,n=376)or TACE monotherapy(monotherapy group,n=450)were included from January 2018 to May *** primary endpoint was progression-free survival(PFS)according to modified *** secondary outcomes included overall survival(OS),objective response rate(ORR),and *** performed propensity score matching approaches to reduce bias between two *** matching,228 pairs were included with a predominantly advanced disease *** PFS in combination group was 9.5 months(95%confidence interval[CI],8.4-11.0)versus 8.0 months(95%CI,6.6-9.5)(adjusted hazard ratio[HR],0.70,P=0.002).OS and ORR were also significantly higher in combination group(median OS,19.2[16.1-27.3]vs.15.7 months[13.0-20.2];adjusted HR,0.63,P=0.001;ORR,60.1%vs.32.0%;P<0.001).Grade 3/4 adverse events were observed at a rate of 15.8%and 7.5%in combination and monotherapy groups,*** results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS,OS,and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice,with an acceptable safety profile.

关键词： hepatocellular targeted matching

Safety and efficacy of meplazumab in healthy volunteers and COVID-19 patients: a randomized phase 1 and an exploratory phase 2 trial

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Signal Transduction and Targeted Therapy 2021年第6期6卷 1845-1855页

作者： Huijie Bian Zhao-Hui Zheng Ding Wei Aidong wen Zheng zhang jian-qi Lian wen-Zhen Kang Chun-qiu Hao Jing Wang Rong-Hua Xie Ke dong Jie-Lai Xia Jin-Lin Miao wen Kang Guoquan Li Di zhang Mingru zhang Xiu-Xuan sun Likun Ding Kui zhang Junfeng jia Jin Ding Zhiqin Li Yanyan jia Lin-Na Liu Zhe zhang Zhao-Wei Gao Hong Du Na Yao qing Wang Ke Wang Jie-Jie Geng Bin Wang Ting Guo Ruo Chen Yu-Meng Zhu Li-Juan Wang qian He Rui-Rui Yao ying Shi Xiang-Min yang jian-sheng Zhou Yi-Nan Ma Ya-Tao Wang Xue Liang Fei Huo Zhe Wang yang zhang Xu yang Ye zhang Lu-Hua Gao Ling Wang xiao-Chun Chen Hao Tang Shuang-Shuang Liu qing-Yi Wang Zhi-Nan Chen Ping Zhu National Translational Science Center for Molecular Medicine and Department of Cell Biology Fourth Military Medical UniversityXi'anChina Department of Clinical Immunology Xijing HospitalFourth Military Medical UniversityXi'anChina Department of Pharmacy Xijing HospitalFourth Military Medical UniversityXi'anChina Center for Infectious Diseases Tangdu HospitalFourth Military Medical UniversityXi'anChina Department of Nuclear Medicine Xijing HospitalFourth Military Medical UniversityXi'anChina department of Clinical Diagnosis Tangdu HospitalFourth Military Medical UniversityXKanChina College of Military Preventive Medicine Fourth Military Medical UniversityXi'anChina Department of Pharmaceutics Tangdu HospitalFourth Military Medical UniversityXi'anChina Department of Pathology Fourth Military Medical UniversityXi'anChina jiangsu Pacific Meinuoke Biopharmaceutical Co.Ltd ChangzhouChina Department of Foreign Languages Fourth Military Medical UniversityXi'anChina

Recent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)*** CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 *** is a humanized anti-CD147 IgG_(2) monoclonal antibody,which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019(COVID-19)***,we conducted a randomized,double-blinded,placebo-controlled phase 1 trial to evaluate the safety,tolerability,and pharmacokinetics of meplazumab in healthy subjects,and an open-labeled,concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 *** phase 1 study,59 subjects were enrolled and assigned to eight cohorts,and no serious treatment-emergent adverse event(TEAE)or TEAE grade≥3 was *** serum and peripheral blood Cmax and area under the curve showed non-linear pharmacokinetic *** obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each *** biodistribution study indicated that meplazumab reached lung tissue and maintained>14 days stable with the lung tissue/cardiac blood-pool ratio ranging from 0.41 to *** the exploratory phase 2 study,17 COVID-19 patients were enrolled,and 11 hospitalized patients were involved as concurrent *** meplazumab treatment significantly improved the discharged(P=0.005)and case severity(P=0.021),and reduced the time to virus negative(P=0.045)in comparison to the control *** results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.

关键词： patients dosage phase

Efficacy and safety of sirolimus early conversion protocol in liver transplant patients with hepatocellular carcinoma:A single-arm, multicenter, prospective study

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Hepatobiliary & Pancreatic Diseases International 2022年第2期21卷 106-112页

作者： Ren-Yi Su sun-Bin Ling qiao-Nan Shan Xu-Yong Wei Rui Wang Chang-Ku jia Li zhuang Tian Shen Li-Min Ding Zhi-Dan Xu Lai-Bang Luo Li-Bo sun Guang-Ming Li Tai-Shi Fang Nan jiang Kun zhang Zhao-Jie Su Zhi-Hai Peng Ren Lang Tao jiang qiang He Lin-Sen Ye yang yang Yu-Ting He wen-Zhi Guo Liu-Gen Lan Xu-Yong sun dong Chen Zhi-Shui Chen Da-Wei Zhou Shao-Jun Ye qi-Fa Ye Min Tian jian-Hua Shi Bo Wang jiang Liu qian Lu Wei Rao Jin-Zhen Cai Tao Lv jia-Yin yang Pu-Sen Wang Lin Zhong Jing-sheng Ma qi-Gen Li sheng-dong Wu Chang-jiang Lu Cai-De Lu dong-Hua zhang Xuan Wang Zi-qiang Li Mu-jian Teng Jun-Jie Li wen-Tao jiang jian-Hua Li Quan-Bao zhang Ning-qi Zhu Zheng-Xin Wang Kang He qiang Xia Shao-Hua Song Zhi-Ren Fu Wei qiu Guo-Yue Lv Rui-Peng Song Ji-Zhou Wang Zheng Wang jian Zhou Gang Chen ying-Peng Zhao Li Li Ze-Min Hu qi-Jie Luo Zhong-Zhou Si Bin Xie xiao-Shun He Zhi-Yong Guo Shu-Sen Zheng xiao Xu Department of Hepatobiliary and Pancreatic Surgery The Center for Integrated Oncology and Precision MedicineAffiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhou 310006China NHC Key Laboratory of Combined Multi-organ Transplantation Hangzhou 310003China Department of Hepatobiliary and Pancreatic Surgery Shulan(Hangzhou)HospitalZhejiang Shuren University School of MedicineHangzhou 310022China Department of Hepatobiliary and Pancreatic Surgery The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Transplantation Jiangxi Provincial People’s Hospital Affiliated to Nanchang UniversityNanchang 330006China Liver Transplantation Center Beijing You’an HospitalCapital Medical UniversityBeijing 100069China Department of Hepatic Surgery National Clinical Research Center for Infectious DiseaseShenzhen Third People’s HospitalThe Second Affiliated Hospital of Southern University of Science and TechnologyShenzhen 518112China Department of General Surgery Xiang’an Hospital of Xiamen UniversityXiamen 361000China Deartment of Hepatobiliary and Pancreaticosplenic Surgery Beijing Chaoyang HospitalCapital Medical UniversityBeijing 100020China Department of Hepatic Surgery and Liver Transplantation Center The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of Liver Transplantation The Second Affiliated Hospital of Guangxi Medical UniversityNanning 530000China Institute of Organ Transplantation Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Institute of Hepatobiliary Diseases of Wuhan University Transplant Center of Wuhan UniversityHubei Key Laboratory of Medical Technology on TransplantationZhongnan Hospital of Wuhan UniversityWuhan 430071China Department of Hepatobiliary Surgery The First Affiliated Hos

Mammalian target of rapamycin(m TOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant(LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival(RFS) in hepatocellular carcinoma(HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specifc for the frst 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefts for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data.

关键词： Sirolimus Immunosuppressive agents Hepatocellular carcinoma Liver transplantation Conversion