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Expression of CXCL12-CXCR4 in osteosarcoma and its correlation with angiogenesis

Oncology and translational Medicine 2017年第6期3卷 254-259页

作者： Lu Han Yangyang Shen Wenhua Zhao Baoyong Sun Xin Zhang Kai Cui Lei Zhou Sheng Li School of Medicine and Life Sciences University of Jinan-Shandong Academy of Medical Sciences Jinan 250117 China Department of Hepatobiliary Surgery Shandong Academy of Medical Sciences Shandong Cancer Hospital affiliated to Shandong University Jinan 250117 China Department of Anesthesiology Shandong Academy of Medical Sciences Shandong Cancer Hospital affiliated to Shandong University Jinan 250117 China Department of Tumor Minimally Invasive Surgery Qianfo Hill Hospital of Shandong Province Jinan 250014 China Department of Bone & Soft Tissue Surgery Shandong Academy of Medical Sciences Shandong Cancer Hospital affiliated to Shandong University Jinan 250117 China Shandong Institute of Pharmaceutical research Jinan 250062 China Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders Qingdao University Qingdao 266071 China

Objective The expression of CXCL12(stromal cell-derived factor-1)-CXCR4(chemokine receptors-4) in osteosarcoma and its role in angiogenesis were *** The expression of CXCR4 and CXCL12 in 40 cases of osteosarcoma was detected by immunohistochemistry and real-time fluorescence quantitative *** expression of CD34 in osteosarcoma was detected by *** image analysis was performed to measure microvessel density(MVD).Additionally,the relationship between CXCL12 and CXCR4 expression and MVD of osteosarcoma and pulmonary metastasis were *** The positive rates of CXCL12 and CXCR4 protein expression in osteosarcoma were 40.0%(16/40) and 60.0%(24/40),*** quantitative real-time PCR indicated that the expression level of CXCR4 m rna in pulmonary metastatic osteosarcoma was higher than that in nonpulmonary metastatic osteosarcoma(P non-pulmonary metastatic osteosarcoma(P < 0.01).Conclusion The expression level of CXCR4 was significantly associated with pulmonary metastasis and angiogenesis of osteosarcoma.

关键词： osteosarcoma stromal cell-derived factor-1 (CXCL12) chemokine receptors-4 (CXCR4) angiogenesis pulmonary metastatics

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Genomic stability at the coding regions of the multidrug transporter gene ABCB1: insights into the development of alternative drug resistance mechanisms in human leukemia cells

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Cancer Drug Resistance 2020年第4期3卷 959-979页

作者： Kevin G.Chen George E.Duran Mark J.Mogul Yan C.Wang Kevin L.Ross Jean-Pierre Jaffrézou Lyn M.Huff Kory R.Johnson Tito Fojo Norman J.Lacayo Branimir I.Sikic Division of Oncology Department of MedicineStanford University School of MedicineStanfordCA 94305USA Current Address:NIH Stem Cell Unit National Institute of Neurological Disorders and StrokeNational Institutes of HealthBethesdaMD 20892USA Current Address:Medical Affairs U.S. Servier PharmaceuticalsBostonMA 02210USA Current Address:Ross BioPharm Group Rocky PointNY 11778USA Current Address:French National Centre for Scientific research Paris 75016France Medicine Branch National Cancer InstituteNational Institutes of HealthBethesdaMD 20892USA Current Address Laboratory of Cell BiologyNational Cancer InstituteNational Institutes of HealthBethesdaMD 20892USA Intramural IT and Bioinformatics Program National Institute of Neurological Disorders and StrokeNational Institutes of HealthBethesdaMD 20892USA Current Address:Herbert Irving Comprehensive Cancer Center Columbia University Medical Center/New York-Presbyterian HospitalNew YorkNY 10032USA Division of Pediatric Hematology-Oncology-Stem Cell Transplantation and Cancer Biology Stanford University School of Medicine and Stanford Cancer InstitutePalo AltoCA 94305USA

Aim:Despite considerable efforts to reverse clinical multidrug resistance(MDR),targeting the predominant multidrug transporter ABCB1/P-glycoprotein(P-gp)using small molecule inhibitors has been unsuccessful,possibly due to the emergence of alternative drug resistance ***,the non-specific P-gp inhibitor cyclosporine(CsA)showed significant clinical benefits in patients with acute myeloid leukemia(AML),which likely represents the only proof-of-principle clinical trial using several generations of MDR ***,the mutational mechanisms that may underlie unsuccessful MDR modulation by CsA are not elucidated because of the absence of CsA-relevant cellular *** this study,our aims were to establish CsA-resistant leukemia models and to examine the presence or absence of ABCB1 exonic mutations in these models as well as in diverse types of human cancer samples including ***:Drug-resistant lines were established by stepwise drug co-selection and characterized by drug sensitivity assay,rhodamine-123 accumulation,[3H]-labeled drug export,ABCB1 cDNA sequencing,and rnase protection *** genomic stability of the ABCB1 coding regions was evaluated by exome sequencing analysis of variant allele frequencies in human ***,the mutational spectrum of ABCB1 was further assessed in diverse types of cancer samples including AMLs in the Cancer Genome Atlas(TCGA)at the National Cancer ***:We report the development of two erythroleukemia variants,RVC and RDC,which were derived by stepwise co-selection of K562/R7 drug-resistant leukemia cells with the etoposide-CsA and doxorubicin-CsA drug combinations,***,both RVC and RDC cell lines,which retained P-gp expression,showed altered multidrug-resistant phenotypes that were resistant to CsA ***,no mutations were found in the ABCB1 coding regions in these variant cells even under long-term stringent drug ***,ABCB1

关键词： Cancer leukemia multidrug resistance ABCB1 P-glycoprotein cyclosporine mutation

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CTNS Molecular Genetics Profile in a Portuguese Cystinosis Population

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Open Journal of Genetics 2018年第4期8卷 91-100页

作者： Filipa Ferreira Ines Leal David Sousa Teresa Costa Conceicao Mota Ana Marta Gomes Daniela Lopes Maria do Carmo Macario Isabel Tavares Helena Pinto Joao Paulo Oliveira Rita Magrico Celia Carmona Sonia Ramos Raquel Neiva Ana Marcao Laura Vilarinho Newborn Screening Metabolism and Genetics UnitHuman Genetics DepartmentNational Institute of Health Dr Ricardo JorgePortoPortugal Centro Hospitalar Lisboa Norte Hospital de Santa MariaLisboaPortugal Centro Hospitalar Universitario do Porto PortoPortugal Centro Hospitalar Vila Nova de Gaia EspinhoPortugal Centro Hospitalar Universitario de Coimbra CHUCCoimbraPortugal Servico de Genetica Medica Centro Hospitalar de Sao JoaoPortoPortugal Unidade de Genetica Faculdade de Medicina da Universidade do PortoPortoPortugal I3S—Instituto de Investigacao e Inovacao em Saude PortoPortugal Servico de Nefrologia do Hospital Garcia de Orta AlmadaPortugal research and Development Unit Department of Human GeneticsNational Institute of Health Dr Ricardo JorgePortoPortugal

Background: Cystinosis is a multisystemic autosomal recessive deficiency of the lysosomal membrane transporter protein (cystinosin) caused by mutations in CTNS gene. Objective: This study summarizes the Portuguese experience in the diagnosis and management of patients with this rare disease over the past few years and reports recurrent mutations in the CTNS gene. Methods: Unrelated patients from different pediatric and adult hospitals all over Portugal with non-nephrotic proteinuria, hypercalciuria, hypokalemia impaired proximal reabsorption of amino acids, glycosuria and hypophosphatemia, suggestive of a Fanconi syndrome and ocular problems, were studied. Intra-leukocyte cystine levels were determined and molecular analysis was performed, to determine the presence or absence of the 57-kb deletion in CTNS, followed by direct sequencing of the coding exons of CTNS. Results: From 1998 to 2017, twenty-one cystinotic patients were biochemically diagnosed. From the remaining seventeen (four deceased), eleven were studied for CTNS gene. Five out of eleven patients were homozygous for the 57-kb deletion (10/22;45.5%), and other five were compound heterozygous for this variant (15/22;68.2%). The other mutations found were p.Q128X (c.721 C>T;2/22), p.S139F (c.755 C>T;4/22) and c.18-21delGACT (p.T7FfsX7;1/22). All of these seventeen cystinotic patients are in treatment. Approximately 84% are adults, 16% are young children, and 54.5% are kidney transplant recipient. Conclusions: The authors would like to emphasize the importance of first screening for the 57-kb deletion since it is very common in our population. This genetic study is the first in our country and it could be the basis for future genetic counseling in Portuguese population.

关键词： Cystinosis CTNS Gene Mutational Spectrum Kidney Failure 57-kb Deletion

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Xenografting of human umbilical mesenchymal stem cells from Wharton’s jelly ameliorates mouse spinocerebellar ataxia type 1

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translational Neurodegeneration 2019年第1期8卷 359-371页

作者： Pei-Jiun Tsai Chang-Ching Yeh Wan-Jhen Huang Ming-Yuan Min Tzu-Hao Huang Tsui-Ling Ko Pei-Yu Huang Tien-Hua Chen Sanford P.C.Hsu Bing-Wen Soong Yu-Show Fu Institute of Anatomy and Cell Biology School of MedicineNational Yang-Ming UniversityTaipeiTaiwanRepublic of China Trauma Center Department of SurgeryVeterans General HospitalTaipeiTaiwanRepublic of China Department of Critical Care Medicine Veterans General HospitalTaipeiTaiwanRepublic of China Department of Obstetrics and Gynecology Veterans General HospitalTaipeiTaiwanRepublic of China Institute of Clinical Medicine National Yang-Ming UniversityTaipeiTaiwanRepublic of China Department of Obstetrics and Gynecology National Yang-Ming UniversityTaipeiTaiwanRepublic of China Department of Life Science National Taiwan UniversityTaipeiTaiwanRepublic of China School of Medicine I-Shou UniversityKaohsiungTaiwanRepublic of China Institute of Physiology School of MedicineNational Yang-Ming UniversityTaipeiTaiwanRepublic of China Division of General Surgery Department of SurgeryVeterans General HospitalTaipeiTaiwanRepublic of China Department of Neurosurgery Neurological InstituteTaipei Veterans General HospitalTaipeiTaiwanRepublic of China School of Medicine National Yang-Ming UniversityTaipeiTaiwanRepublic of China Department of Neurology Shuang Ho Hospitaland Taipei Neuroscience InstituteTaipei Medical UniversityTaipeiTaiwanRepublic of China Department of Neurology Taipei Veterans General HospitalTaipeiTaiwanRepublic of China Brain research Center National Yang-Ming UniversityTaipeiTaiwanRepublic of China Department of Anatomy and Cell Biology School of MedicineNational Yang-Ming UniversityNo.155Sec.2Li-Nung StreetTaipei 112TaiwanRepublic of China

Background:Spinocerebellar ataxia type 1(SCA1)is an autosomal dominant neurodegenerative disorder caused by the expansion of CAG repeats in ATXN1 gene resulting in an expansion of polyglutamine repeats in the ATXN1 ***,there has yet been any effective treatment so far for *** study investigated the feasibility of transplanting human umbilical mesenchymal stem cells(HUMSCs)into transgenic SCA1 mice containing an expanded uninterrupted allele with 82 repeats in the ATXN1-coding ***:106 human umbilical mesenchymal stem cells were transplanted into the cerebella at 1 month of ***:HUMSCs displayed significant ameliorating effects in SCA1 mice in terms of motor behaviors in balance beam test and open field test as compared with the untransplanted SCA1 *** transplantation effectively reduced the cerebellar atrophy,salvaged Purkinje cell death,and alleviated molecular layer *** studies showed higher amplitudes of compound motor action potentials as indicated by increasing neuronal-muscular response strength to stimuli after stem cell *** 5 months after transplantation,HUMSCs scattering in the mice cerebella remained viable and secreted cytokines without differentiating into neuronal or glia ***:Our findings provide hope for a new therapeutic direction for the treatment of SCA1.

关键词： Umbilical mesenchymal stem cells Cell transplantation SCA1

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糖尿病肾病NLRP3炎症小体活化的分子调控机制及中药的干预作用

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中国中药杂志 2020年第1期45卷 7-13页

作者：王文文韩文贝万毅刚涂玥刘不悔刘莹露吴薇 YEE Hong-yun 房其军姚建南京中医药大学中西医结合鼓楼临床医学院中医科江苏南京210008 温州市中西医结合医院肾内科浙江温州325000 南京大学医学院附属鼓楼医院中医科江苏南京210008 南京中医药大学针灸推拿学院·养生康复学院中医养生学教研室江苏南京210023 南京中医药大学附属医院肾内科江苏南京210029 Division of Molecular Signaling Department of Advanced Biomedical ResearchInterdisciplinary Graduate School of Medicine and EngineeringUniversity of YamanashiYamanashi 409-3898

在糖尿病肾病(diabetic nephropathy,DN)进展的过程中,Nod样受体蛋白3(Nod-like receptor protein3,NLRP3)炎症小体活化与DN肾损伤密切相关。其特征是组分蛋白——NLRP3、凋亡相关斑点样蛋白(apoptosis-associated speck-like protien,ASC)、胱冬肽酶(caspase)-1前体表达水平和结合水平的改变以及下游的效应蛋白——caspase-1,白介素(interleukin,IL)-1β,IL-18表达水平的升高,此外,还有相关炎症介质的释放。NLRP3炎症小体活化的分子调控机制涉及多条信号通路的激活,如活性氧(reactive oxygen species,ROS)/硫氧还蛋白互作蛋白(thioredoxin-interacting protein,TXNIP)通路、核因子(nuclear factor,NF-κB)通路、核转录因子E-2相关因子-2(nuclear factor erythroid-related factor 2,Nrf2)通路、长链非编码rna(long non-coding rna,lncrna)通路以及丝裂原激活蛋白激酶(mitogen-activated protein kinases,MAPKs)通路等。更为重要的是,激酶类的调节因子,如未有丝分裂曲霉相关蛋白激酶7(never in mitosis aspergillus-related kinase 7,Nek7)在上游可与NLRP3靶向结合而直接激活NLRP3炎症小体。一些中药提取物(槲皮素、姜黄素、千金藤素、胡椒碱以及红景天苷)和中药经典复方(乌梅丸)等可以通过多种途径干预NLPR3炎症小体而改善DN炎症性肾损伤。因此,基于NLRP3炎症小体活化的分子调控机制而精准揭示抗炎性中药或中药复方延缓DN进展的作用靶点是今后的发展方向之一。

关键词：糖尿病肾病 NLRP3炎症小体中药分子机制信号通路

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MAFG-AS1/MAFG正反馈环通过拮抗铁死亡增加膀胱癌的顺铂耐药性

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Science Bulletin 2021年第17期66卷 1773-1788,M0004页

作者：向亮曾庆海刘建业肖梦卿何东张群谢丹邓敏华朱煜星刘彦孛昊刘晓明周鸣熊炜周艳宏周建大李晓辉曹科 Department of Oncology Third Xiangya Hospital of Central South UniversityChangsha 410013China Department of Dermatology Third Xiangya Hospital of Central South UniversityChangsha 410013China Department of Urology Third Xiangya Hospital of Central South UniversityChangsha 410013China Department of Respiratory The Second People’s Hospital of Hunan ProvinceChangsha 410007China Department of Radiotherapy The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080China Department of Pathology Sun Yat-sen University Cancer CenterGuangzhou 510060China Department of Urology Sun Yat-sen University Cancer CenterGuangzhou 510060China Department of Plastic Surgery Third Xiangya Hospital of Central South UniversityChangsha 410013China Institute of Reproductive and Stem Cell Engineering Central South UniversityChangsha 410083China Department of Gastroenterology Third Xiangya Hospital of Central South UniversityChangsha 410013China Cancer research Institute and Key Laboratory of Carcinogenesis of the Chinese Ministry of Health Central South UniversityChangsha 410078China Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples Changsha 410205China Department of Pharmaceutical Chemistry School of Pharmaceutical SciencesCentral South UniversityChangsha 410013China

促进铁死亡可以降低肿瘤细胞对顺铂的耐药性,长链非编码rna(lnc rna)参与铁死亡的调控,但lnc rna在调控铁死亡介导的膀胱癌顺铂耐药性中的作用尚不清楚.本研究通过体内外实验,综合运用Ch IP、CO-IP、Ch IRP、PRM-MS等实验及多种生物信... 详细信息

促进铁死亡可以降低肿瘤细胞对顺铂的耐药性,长链非编码rna(lnc rna)参与铁死亡的调控,但lnc rna在调控铁死亡介导的膀胱癌顺铂耐药性中的作用尚不清楚.本研究通过体内外实验,综合运用Ch IP、CO-IP、Ch IRP、PRM-MS等实验及多种生物信息学技术探究了lnc rna MAFG-AS1调控铁死亡影响膀胱癌顺铂耐药性的作用及具体机制.研究结果发现活化的MAFG-AS1/MAFG正反馈环可通过拮抗铁死亡增加膀胱癌的顺铂耐药性.MAFG-AS1和MAFG可作为膀胱癌的潜在治疗新靶点及化疗敏感性评估标志物.

关键词：顺铂耐药性体内外实验化疗敏感性膀胱癌 MAF 生物信息学技术铁死亡

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Reconstructing the phytogeny of new world monkeys(platyrrhini):evidence from multiple non-coding loci

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Current Zoology 2019年第5期65卷 579-588页

作者： Xiaoping WANG Burton K.LIM Nelson TING Jingyang HU Yunpeng LIANG Christian ROOS Li YU State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan Yunnan UniversityKunmingChina School of Life Sciences Yunnan UniversityKunmingChina epartm ent of Natural History Royal Ontario MuseumTorontoONCanada Department of Anthropology and Institute of Ecology and Evolution University of OregonEugeneOregonUSA State Key Laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of SciencesKunmingChina Kunming College of Life Science University of Chinese Academy of SciencesKunmingChina Gene Bank of Primates and Primate Genetics Laboratory German Primate CenterLeibniz Institute for Primate ResearchKellnerwegGottingenGermany

Among mammalian phylogenies,those characterized by rapid radiations are particularly *** New World monkeys(NWMs,Platyrrhini)comprise 3 families and 7 subfamilies,which radiated within a relatively short time ***,their phylogenetic relationships are still largely *** the present study,56 nuclear non-coding loci,including 33 introns(INs)and 23 intergenic regions(IGs),from 20 NWM individuals representing 18 species were used to investigate phylogenetic relationships among families and *** the 56 loci,43 have not been used in previous NWM *** applied concatenation and coalescence tree-inference methods,and a recently proposed question-specific approach to address NWM *** results indicate incongruence between concatenation and coalescence methods for the IN and IG ***,a consensus was reached with a single tree topology from all analyses of combined INs and IGs as well as all analyses of question-specific loci using both concatenation and coalescence methods,albeit with varying degrees of statistical *** detail,our results indicated the sister-group relationships between the families Atelidae and Pitheciidae,and between the subfamilies Aotinae and Callithrichinae among *** study provides insights into the disputed phylogenetic relationships among NWM families and subfamilies from the perspective of multiple non-coding loci and various tree-inference ***,the present phylogenetic framework needs further evaluation by adding more independent sequence data and a deeper taxonomic ***,our work has important implications for phylogenetic studies dealing with rapid radiations.

关键词： coalescence concatenation non-coding nuclear genes primates phylogenetics

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Analysis of single nucleotide polymorphisms in the region of CLDN2-MORC4 in relation to inflammatory bowel disease

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World Journal of Gastroenterology 2013年第30期19卷 4935-4943页

作者： Jan Sderman Elisabeth Norén Malin Christiansson Hanna Bragde Raphaele Thiébaut Jean-Pierre Hugot Curt Tysk Colm A O'Morain Miquel Gassull Yigael Finkel Jean-Frédéric Colombel Marc Lémann Sven Almer Division of Medical Diagnostics Ryhov County Hospital55185 JnkpingSweden Department of Clinical and Experimental Medicine Linkping University58183 LinkpingSweden INSERM U843Université Paris DiderotHpital Robert Debré75019 ParisFrance Université ParisDiderot Sorbonne Paris-Cité UMR84375018 ParisFrance Assistance Publique-Hopitaux de Paris Hopital Robert Debré75019 ParisFrance Division of Gastroenterology Department of MedicineUniversity HospitalSchool of Health and Medical Sciencesrebro University70185 rebroSweden School of Health and Medical Sciences rebro University70185 rebroSweden Department of Gastroenterology Adelaide and Meath HospitalTallaghtDublin 24Ireland Trinity College Dublin College GreenDublin 2Ireland Health Sciences research Institute Germans Trias i Pujol08916 BadalonaSpain Department of Gastroenterology Sachs' Children's HospitalSdersjukhuset11861 StockholmSweden EPIMAD group Registre EPIMADService d'Epidémiologie et de Santé PubliqueHpital CalmetteCentre Hospitalier Universitaire de Lille59037 LilleFrance Icahn School of Medicine at Mount Sinai New YorkNY 10029United States GETAID group Groupe d'Etude Thérapeutiques des Affections Inflammatoires DigestivesService de gastroentérologieHpital Saint Louis75010 ParisFrance Department of Gastroenterology UHL County Council of stergtland58185 Link pingSweden Division of Gastroenterology Karolinska InstitutetDepartment of Gastroenterology and HepatologyKarolinska university hospital14186 StockholmSweden

AIM:To investigate a possible genetic influence of claudin(CLDN)1,CLDN2 and CLDN4 in the etiology of inflammatory bowel ***:Allelic association between genetic regions of CLDN1,CLDN2 or CLDN4 and patients with inflammatory bowel disease,Crohn's disease(CD)or ulcerative colitis were investigated using both a casecontrol study approach(one case randomly selected from each of 191 Swedish inflammatory bowel disease families and 333 controls)and a family-based study(463 non-Swedish European inflammatory bowel disease-families).A nonsynonymous coding single nucleotide polymorphism in MORC4,located on the same linkage block as CLDN2,was investigated for association,as were two novel CLDN2 single nucleotide polymorphism markers,identified by ***:A single nucleotide polymorphism marker(rs12014762)located in the genetic region of CLDN2 was significantly associated to CD(case-control allelic OR = 1.98,95%CI:1.17-3.35,P = 0.007).MORC4 was present on the same linkage block as this CD *** the case-control approach,a significant association(case control allelic OR = 1.61,95%CI:1.08-2.41,P = 0.018)was found between CD and a nonsynonymous coding single nucleotide polymorphism(rs6622126)in *** association between the CLDN2 marker and CD was not replicated in the familybased *** colitis was not associated to any of the single nucleotide polymorphism ***:These findings suggest that a variant of the CLDN2-MORC4 region predisposes to CD in a Swedish population.

关键词： Crohn’s disease Genetic predisposition Inflammatory bowel disease Single nucleotide polymorphism Tight junctions

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Efficacy and Safety of All-oral Emitasvir and Sofosbuvir in Patients with Genotype 1b HCV Infections without Cirrhosis

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Journal of Clinical and translational Hepatology 2020年第3期8卷 255-261页

作者： Huiying Rao Xingxiang Yang Youwen Tan Qin Ning Daokun Yang Jiefei Wang Yongfeng Yang Sujun Zheng Dongliang Yang Jinlin Hou Qing Xie Caiyan Zhao Lunli Zhang Xiaorong Mao Tong Sun Lang Bai Fuchun Zhang Jinglan Jin Yingren Zhao Maorong Wang Wen Xie Yingjie Ma Jun Quan Xuebing Yan Ping An Feng Lin Jidong Jia Xiaoxuan Hu Zuojiong Gong Jie Wu Yongping Chen Zhansheng Jia Minghua Lin Guiqiang Wang Yueyong Zhu Yingjun Zhang Hongming Xie Lin Luo Qingyun Ren Rui Huang Lai Wei Peking University People’s Hospital Peking University Hepatology InstituteNational Clinical Research Center for Infectious DiseaseBeijing Key Laboratory of Hepatitis C and Immunotherapy for Liver DiseasesBeijing International Cooperation Base for Science and Technology on NAFLD DiagnosisBeijingChina Department of Infectious Diseases Sichuan Provincial People’s HospitalChengduSichuanChina Department of Hepatology The Third People’s Hospital of ZhenjiangZhenjiangJiangsuChina Department of Infectious Diseases Tongji HospitalTongji Medical College Huazhong University of Science and TechnologyWuhanHubeiChina Department of Infectious Diseases The First Affiliated Hospital of Xinxiang Medical CollegeXinxiangHenanChina Shanghai Public Health Clinical Center ShanghaiChina Department of Hepatology The Second Hospital of NanjingNanjingJiangsuChina Center of Artificial liver Beijing Youan HospitalCapital Medical UniversityBeijingChina Department of Infectious Disease Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiChina Department of Infectious Diseases Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdongChina Department of Infectious Diseases Ruijin Hospital Affiliated to Shanghai Jiaotong University School of MedicineShanghaiChina Department of Infectious Diseases The Third Hospital of Hebei Medical UniversityShijiazhuangHebeiChina Department of Infectious Diseases The First Affiliated Hospital of Nanchang UniversityNanchangJiangxiChina Department of Infectious Diseases The First Hospital of Lanzhou UniversityLanzhouGansuChina Department of Infectious Diseases Wuxi Fifth People’s HospitalWuxiJiangsuChina Infectious Diseases Center West China HospitalSichuan UniversityChengduSichuanChina Department of Hepatology Guangzhou Eighth People’s HospitalGuangzhouGuangdongChina Department of Hepato-Biliary-Pancreatic Diseases The First Hospital of Jilin UniversityChangchunJilinChina Department of Infectious Diseases Xi’an Ji

Publications>Journals>Journal of Clinical and translational Hepatology>Article Full Text ORIGINAL ARTICLE OPEN ACCESS Efficacy and Safety of All-oral Emitasvir and Sofosbuvir in Patients with Genotype 1b HCV Infections without Cirrhosis Huiying Rao1,Xingxiang Yang2,Youwen Tan3,Qin Ning4,Daokun Yang5,Jiefei Wang6,Yongfeng Yang7,Sujun Zheng8,Dongliang Yang9,Jinlin Hou10,Qing Xie11,Caiyan Zhao12,Lunli Zhang13,Xiaorong Mao14,Tong Sun15,Lang Bai16,Fuchun Zhang17,Jinglan Jin18,Yingren Zhao19,Maorong Wang20,Wen Xie21,Yingjie Ma22,Jun Quan23,Xuebing Yan24,Ping An25,Feng Lin26,Jidong Jia27,Xiaoxuan Hu28,Zuojiong Gong29,Jie Wu30,Yongping Chen31,Zhansheng Jia32,Minghua Lin33,Guiqiang Wang34,Yueyong Zhu35,Yingjun Zhang*,36,Hongming Xie36,Lin Luo36,Qingyun Ren36,Rui Huang1 and Lai Wei*,37 Author information Journal of Clinical and translational Hepatology 2020;8(3):255-261DOI:10.14218/JCTH.2020.00031 Abstract Background and Aims:Emitasvir is a new type of hepatitis C virus(HCV)nonstructural protein 5A(NS5A)inhibitor,and the data of phase 2 trial has shown emitasvir-sofosbuvir to have good safety and *** conducted this phase 3 trial to further verify the efficacy and ***:We evaluated the antiviral activity and safety of a 12-week regimen of emitasvir phosphate(100 mg)combined with sofosbuvir(400 mg)once daily in non-cirrhotic patients with genotype 1 HCV *** primary endpoint was a sustained virological response at 12 weeks(SVR12)after the end of ***:Of the 362 patients enrolled in the trial,39.8%were male,99.2%had HCV genotype 1b,0.8%had genotype 1a and 79.8%were treatment-naï*** average age was 47.2 *** patients completed the treatment and *** 3 patients with genotype 1a achieved *** genotype 1b treatment-naïve patients experienced virologic *** rate of SVR12 was 99.7%(358/359),and SVR24 was 99.4%(357/359)in genotype ***,36.2%had resistance-associated substitutions(RASs)in NS5A and 98.3%had RASs in

关键词： Hepatitis C virus Genotype 1 Direct acting antivirals Emitasvir Sofosbuvir Combination treatment

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