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Sex biased expression of hormone related genes at early stage of sex differentiation in papaya flowers

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Horticulture Research 2021年第1期8卷 2082-2094页

作者： Juan Liu Li-Yu Chen Ping Zhou Zhenyang Liao Hai Lin Qingyi Yu Ray Ming FAFU and UIUC Joint Center for genomics and Biotechnology Key Laboratory of GeneticsBreeding and Multiple Utilization of CropsMinistry of EducationFujian Provincial Key Laboratory of Haixia Applied Plant Systems BiologyCollege of Life ScienceFujian Agriculture and Forestry UniversityFuzhou 350002 FujianChina Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture Chinese Academy of SciencesWuhan Botanical GardenWuhan 430074China Texas A&M AgriLife Research Center at Dallas Texas A&M University SystemDallasTX 75252USA Department of Plant Pathology&Microbiology Texas A&M UniversityCollege StationTX 77843USA Department of Plant Biology School of Integrative BiologyUniversity of Illinois at Urbana-ChampaignUrbanaIL 61801USA

Sex types of papaya are controlled by a pair of nascent sex chromosomes,but molecular genetic mechanisms of sex determination and sex differentiation in papaya are still *** performed comparative analysis of transcriptomic profiles of male and female floral buds at the early development stage before the initiation of reproductive organ primordia at which there is no morphological difference between male and female flowers.A total of 1734 differentially expressed genes(DEGs)were identified,of which 923 showed female-biased expression and 811 showed male-biased *** annotation revealed that genes related to plant hormone biosynthesis and signaling pathways,especially in abscisic acid and auxin pathways,were overrepresented in the *** factor binding motifs,such as MYB2,GAMYB,and AP2/EREBP,were enriched in the promoters of the hormone-related DEGs,and transcription factors with those motifs also exhibited differential expression between sex *** these DEGs,we also identified 11 genes in the non-recombining region of the papaya sex chromosomes and 9 genes involved in stamen and carpel *** results suggested that sex differentiation in papaya may be regulated by multiple layers of regulation and coordination and involved transcriptional,epigenetic,and phytohormone ***,especially ABA and auxin,transcription factors,and genes in the non-recombination region of the sex chromosome could be involved in this *** findings may facilitate the elucidation of signal transduction and gene interaction in sex differentiation of unisexual flowers in papaya.

关键词： expression flowers papaya

APOE-mediated suppression of the lncRNA MEG3 protects human cardiovascular cells from chronic inflammation

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Protein & Cell 2023年第12期14卷 908-913页

作者： Hongkai Zhao Kuan Yang Yiyuan Zhang Hongyu Li Qianzhao ji Zeming Wu Shuai Ma Si Wang Moshi Song Guang-Hui Liu Qiang Liu Weiqi Zhang Jing Qu Division of Life Sciences and Medicine School of Life SciencesUniversity of Science and Technology of ChinaHefei 230001China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Universityof Chinese Academy of Sciences Beijing100049China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing100101China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China Advanced Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical University.Beijing100053China Aging Translational Medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China Aging Biomarker Consortium Beijing 100101China 12Division of Life Sciences and Medicine Institute on Aging and Brain DisordersThe First Affiliated Hospital of USTCHefei National Laboratory for Physical Sciences at the MicroscaleUniversity of Science and Technology of ChinaHefei 230026China Neurodegenerative Disease Research Center University of Science and Technology of ChinaHefei 230026China CAS Key Laboratory of Brain Function and Disease University of Science and Technology of ChinaHefei 230026China Center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunming 650201China

Dear Editor,Cardiovascular diseases(CVDs)are the leading cause of death ***,diagnosing and treating CVD remains at the forefront for clinicians while identifying targetable disease mechanisms in preclinical models are focus areas for researchers and drug developers(Cai et al.,2022a).The polymorphic protein apolipoprotein E(APOE),central to lipid transport and metabolism,is well-recognized for the role of its isoforms as important predictors for human cardiovascular disorders and neurodegenerative diseases(Tudorache et al.,2017).Plasma APOE is generated primarily from liver hepatocytes,accounting for around 75%of the APOE production from the whole body(Getz and Reardon,2009),and plays important functional roles in monocytes/macrophages,adipocytes,and the central nervous system(Kockx et al.,2018).However,despite the fact that APOE is widely expressed in different mammalian cells,studies on the functional roles of APOE mostly focus on its extracellular secreted form,and the specific effects of APOE,particularly intracellular form in cell types closely related to human cardiovascular diseases are therefore still poorly understood.

关键词： cardiovascular metabolism

Pangenome of water caltrop reveals structural variations and asymmetric subgenome divergence after allopolyploidization

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Horticulture Research 2023年第11期10卷 168-179页

作者： Xinyi Zhang Yang Chen Lingyun Wang Ye Yuan Mingya Fang Lin Shi Ruisen Lu Hans Peter Comes Yazhen Ma Yuanyuan Chen Guizhou Huang Yongfeng Zhou Zhaisheng Zheng Yingxiong Qiu Systematic and Evolutionary Botany and Biodiversity Laboratory College of Life SciencesZhejiang UniversityHangzhou310058ZhejiangChina CAS Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture Wuhan Botanical GardenChinese Academy of SciencesWuhan430074HubeiChina Provincial Key Laboratory of Characteristic Aquatic Vegetable Breeding and Cultivation Jinhua Academy of Agricultural Sciences(Zhejiang Institute of Agricultural Machinery)Jinhua321000ZhejiangChina Jiaxing Academy of Agricultural Sciences Jiaxing314016ZhejiangChina Institute of Botany Jiangsu Province and Chinese Academy of SciencesNanjing 210014JiangsuChina Department of Environment&Biodiversity Salzburg UniversitySalzburg5020Austria State Key Laboratory of Tropical Crop Breeding Shenzhen BranchGuangdong Laboratory of Lingnan Modern AgricultureKey Laboratory of Synthetic BiologyMinistry of Agriculture and Rural AffairsAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhen 518124GuangdongChina

Water caltrop(Trapa spp.,Lythraceae)is a traditional but currently underutilized non-cereal ***,we generated chromosome-level genome assemblies for the two diploid progenitors of allotetraploid ***(4x,AABB),i.e.,diploid ***(2x,AA)and Trapa incisa(2x,BB).In conjunction with four published(sub)genomes of Trapa,we used gene-based and graph-based pangenomic approaches and a pangenomic transposable element(TE)library to develop Trapa genomic *** pangenome displayed substantial gene-content variationwith dispensable and private gene clusters occupying a large proportion(51.95%)of the total cluster sets in the six(sub)*** of presence-absence variation(PAVs)identified 40453 PAVs associated with 2570 genes specific to A-or B-lineages,of which 1428were differentially expressed,andwere enriched in organ development process,organic substancemetabolic process and response to *** genome analyses showed that the allotetraploid *** underwent asymmetric subgenome divergence,with the B-subgenome being more dominant than the *** factors,including PAVs,asymmetrical amplification of TEs,homeologous exchanges(HEs),and homeolog expression divergence,together affected genome evolution after ***,this study sheds lights on the genome architecture and evolution of Trapa,and facilitates its functional genomic studies and breeding program.

关键词： divergence evolution structural

Mutations in foregut SOX2^+ cells induce efficient proliferation via CXCR2 pathway

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Protein & Cell 2019年第7期10卷 485-495页

作者： Tomoaki Hishida Eric Vazquez-Ferrer Yuriko Hishida-Nozaki Ignacio Sancho-Martinez Yuta Takahashi Fumiyuki Hatanaka Jun Wu Alejandro Ocampo Pradeep Reddy Min-Zu Wu Laurie Gerken Reuben J. Shaw Concepcion Rodriguez Esteban Christopher Benner Hiroshi Nakagawa Pedro Guillen Garcia Estrella Nunez Delicado Antoni Castells Josep M. Campistol Guang-Hui Liu Juan Carlos Izpisua Belmonte Gene Expression Laboratory Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Advaneed Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric Disorders Xuanwu Hospital Capital Medical University Beijing 100053 China National Laboratory of Biomacromolecules CAS Center for Excellence in Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China University of the Chinese Academy of Sciences Beijing 100049 China Insitute for Stem Cell and Regeneration Chinese Academy of Sciences Beijing 100101 China Beijing Institute for Brain Disorder Beijing 100069 China Universidad Catolica San Antonio de Murcia Campus de los Jeronimos 135 Guadalupe 30107 Spain Molecular and Cell Biology Laboratory Dulbecco Center for Cancer Research Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Howard Hughes Medical Institute Dulbecco Center for Cancer Research Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Integrative genomics Core Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Division of Gastroenterology Department of Medicine Perelman School of Medicine University of Pennsylvania Philadelphia PA 19104 USA Abramson Cancer Center University of Pennsylvania Philadelphia PA 19104 USA Department of Traumatology and Research Unit Clinica CEMTRO Av. Ventisquero de la Condesa 42 Madrid 28035 Spain Gastroenterology Department Hospital Clinic University of Barcelona IDIBAPS CIBEREHD Barcelona 08036 Spain

Identification of the precise molecular pathways involved in oncogene-induced transformation may help us gain a better understanding of tumor initiation and promotion. Here, we demonstrate that SOX2^+ foregut epithelial cells are prone to oncogenic transformation upon mutagenic insults, such as Kras^G12D and p53 deletion. GFP-based lineage-tracing experiments indicate that SOX2^+ cells are the cells-of-origin of esophagus and stomach hyperplasia. Our observations indicate distinct roles for oncogenic KRAS mutation and P53 deletion. p53 homozygous deletion is required for the acquisition of an invasive potential, and Kras^G12D expression, but not p53 deletion, suffices for tumor formation. Global gene expression analysis reveals secreting factors upregulated in the hyperplasia induced by oncogenic KRAS and highlights a crucial role for the CXCR2 pathway in driving hyperplasia. Collectively, the array of genetic models presented here demonstrate that stratified epithelial cells are susceptible to oncogenic insults, which may lead to a better understanding of tumor initiation and aid in the design of new cancer therapeutics.

关键词： Sox2 tumor CXCR2 stratified epithelia

Epidemiological Survey of Hemoglobinopathies Based on Next-Generation Sequencing Platform in Hunan Province,China

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Biomedical and Environmental Sciences 2023年第2期36卷 127-134页

作者： XI Hui LIU Qin XIE Dong Hua ZHOU Xu TANG Wang Lan TANG De Guo ZENG Chun Yan WANG Qiong NIE Xing Hui PENG Jin Ping GAO Xiao Ya WU Hong Liang ZHANG Hao Qing QIU Li FENG Zong Hui WANG Shu Yuan ZHOU Shu Xiang HE Jun ZHOU Shi Hao ZHOU Fa Qun ZHENG Jun Qing WANG Shun Yao CHEN Shi Ping ZHENG Zhi Fen MA Xiao Yuan FANG Jun Qun LIANG Chang Biao WANG Hua NHC Key Laboratory of Birth Defect for Research and Prevention Hunan Provincial Maternal and Child Health Care HospitalChangsha 410028HunanChina Yongzhou Hospital for Maternal and Child Health Care Yongzhou 425000HunanChina Changde Hospital for Maternal and Child Health Care Changde 415099HunanChina Hengyang Hospital for Maternal and Child Health Care Hengyang 421009HunanChina Shaoyang Hospital for Maternal and Child Health Care Shaoyang 422001HunanChina Yiyang Hospital for Maternal and Child Health Care Yiyang 413099HunanChina Yueyang Hospital for Maternal and Child Health Care Yueyang 414021HunanChina Center of Prenatal Diagnosis Chenzhou No.1 People’s HospitalChenzhou 423099HunanChina Loudi Hospital for Maternal and Child Health Care Loudi 417599HunanChina Huaihua Hospital for Maternal and Child Health Care Huaihua 418099HunanChina Xiangtan Hospital for Maternal and Child Health Care Xiangtan 411104HunanChina Zhuzhou Hospital for Maternal and Child Health Care Zhuzhou 412008HunanChina Changsha Hospital for Maternal and Child Health Care Changsha 410007HunanChina Xiangxi Tujia and Miao Autonomous Prefecture Hospital for Maternal and Child Health Care Jishou 416000HunanChina Zhang Jiajie Centre for maternal and child health family planning services Zhangjiajie 427299HunanChina BGI genomics BGI-ShenzhenShenzhen 518083GuangdongChina Clinical Laboratory of BGI Health BGI-ShenzhenShenzhen 518083GuangdongChina BGI-Wuhan Clinical Laboratories BGI-ShenzhenWuhan 430074HubeiChina SEBIA Representative Office Shanghai 200001China

Objective This study was aimed at investigating the carrier rate of,and molecular variation in,α-andβ-globin gene mutations in Hunan *** We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan *** screening was performed,and molecular parameters were *** The overall carrier rate of thalassemia was 7.1%,including 4.83%forα-thalassemia,2.15%forβ-thalassemia,and 0.12%for bothα-andβ-*** highest carrier rate of thalassemia was in Yongzhou(14.57%).The most abundant genotype ofα-thalassemia andβ-thalassemia was-α^(3.7)/αα(50.23%)andβ^(IVS-Ⅱ-654)/β^(N)(28.23%),***α-globin mutations[CD108(ACC>AAC),CAP+29(G>C),Hb Agrinio and Hb Cervantes]and sixβ-globin mutations[CAP+8(C>T),IVS-Ⅱ-848(C>T),-56(G>C),beta nt-77(G>C),codon 20/21(-TGGA)and Hb Knossos]had not previously been identified in ***,this study provides the first report of the carrier rates of abnormal hemoglobin variants andα-globin triplication in Hunan Province,which were 0.49%and 1.99%,*** Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan *** results should facilitate genetic counselling and the prevention of severe thalassemia in this region.

关键词： Thalassemia Carrier rate Molecular spectrum Abnormal hemoglobin variants α-globin triplication

Single-nucleus profiling unveils a geroprotective role of the Foxo3 in primate skeletal muscle aging

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Protein & Cell 2023年第7期14卷 499-514页

作者： Ying Jing Yuesheng Zuo Yang Yu Liang Sun Zhengrong Yu Shuai Ma Qian Zhao Guoqiang Sun Huifang Hu Jingyi Li Daoyuan Huang Lixiao Liu Jiaming Li Zijuan Xin Haoyan Huang Juan Carlos Izpisua Belmonte Weiqi Zhang Si Wang Jing Qu Guang-Hui Liu State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Advanced Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China University of Chinese Academy of Sciences Beijing 100049China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China China National Center for Bioinformation Beijing 100101China Aging Translational Medicine Center Intemational Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China Department of Obstetrics and Gynecology Center for Reproductive MedicinePeking University Third HospitalBeijing 100191China The Key Laboratory of Geriatrics Beijing Institute of GeriatricsInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing Hospital/National Center of Gerontology of National Health CommissionBeijing 100730China Clinical Stem Cell Research Center Peking University Third HospitalBeijing 100191China Department of Orthopaedics Peking University First HospitalBeijing 100034China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China Sino-Danish Center for Education and Research Beijing 101408China Altos Labs Inc.San DiegoCA 94022USA The Fifth People's Hospital of Chongqing Chongqing 400062China

Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia,and increases the risk of many aging-related metabolic ***,we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging.A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types,indicating a higher susceptibility of skeletal muscle fiber to *** found a downregulation of Foxo3 in aged primate skeletal muscle,and identi-fied FOxo3 as a hub transcription factor maintaining skeletal muscle *** the establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model,we revealed that silence of Foxo3 accelerates human myotube senescence,whereas genetic activation of endogenous FOxO3 alleviates human myotube ***,based on a combination of monkey skeletal muscle and human myotube aging research models,we unraveled the pivotal role of the FOxO3 in safeguarding primate skeletal muscle from aging,providing a comprehensive resource for the development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-relateddisorders.

关键词： single-nucleus RNA sequencing primate aging skeletal muscle FOxO3

Evolutionary genomics of structural variation in the tea plant,Camellia sinensis

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Tropical Plants 2022年第1期1卷 2-12页

作者： Shuai Chen Jingping Fang Yibin Wang Pengjie Wang Shengcheng Zhang Zhenyang Liao Hong Lu Xingtan Zhang Shenzhen Branch Guangdong Laboratory for Lingnan Modern AgricultureGenome Analysis Laboratory of the Ministry of AgricultureAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhen 518120China College of Life Science Center of Engineering Technology Research for Microalgae Germplasm Improvement of FujianSouthern Institute of OceanographyFujian Normal UniversityFuzhou 350117FujianChina

Structural variants(SVs)are a type of genetic variation that contribute substantially to phenotypic diversity and *** study of SVs will help us understand the influence of SVs associated with tea quality and stress resistance and provide new insight into tea plant breeding improvement and genetic ***,SVs have not been thoroughly discovered in the tea plant ***,we constructed a large-scale SV map across a population of 107 resequenced genomes,including both ancient and cultivated tea plants.A total of 44,240 highconfident SVs were identified,including 34,124 DEL(deletions),4,448 DUP(duplications),2,503 INV(inversions),544 INS(insertions)and 2,621 TRA(translocations).In total,12,400 protein-coding genes were overlapped with SVs,of which 49.5%were expressed in all five tea *** analysis of phylogenetic relationships and population structure in tea plants showed a consistent evolutionary history with the SNP-based *** also identified SVs subject to artificial selection and found that genes under domestication were enriched in metabolic pathways involving theanine and purine alkaloids,biosynthesis of monoterpenoid,phenylpropanoid,fatty acid,and isoflavonoid,contributing to traits of agronomic interest in tea *** addition,a total of 27 terpene synthase(TPS)family genes were selected during *** results indicate that these SVs could provide extensive genomic information for tea quality improvement.

关键词： structural thoroughly plant

Biological and Molecular Components for Genetically Engineering Biosensors in Plants

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BioDesign Research 2022年第1期2022卷 19-37页

作者： Yang Liu Guoliang Yuan Md MahmudulHassan Paul E.Abraham Julie C.Mitchell Daniel Jacobson Gerald A.Tuskan Arjun Khakhar June Medford Cheng Zhao Chang-Jun Liu Carrie A.Eckert Mitchel J.Doktycz Timothy J.Tschaplinski Xiaohan Yang Biosciences Division Oak Ridge National LaboratoryOak RidgeTennessee37831USA The Center for Bioenergy Innovation Oak Ridge National LaboratoryOak RidgeTennessee37831USA Department of Genetics and Plant Breeding Patuakhali Science and Technology UniversityDumkiPatuakhali8602Bangladesh Departmentof Biology Colorado State UniversityFort CollinsColorado80523USA Shenzhen Branch Guangdong Laboratory for Lingnan Modern AgricultureKey Laboratory of Synthetic BiologyMinistry of Agriculture and Rural AffairsAgricultural Genomics Institute at ShenzhenChinese A cademy of Agriculural SciencesShenzhen 518120China Biology Department Brookhaven National LaboratoryUptonNew York 11973USA

Plants adapt to their changing environments by sensing and responding to physical,biological,and chemical *** to their sessile lifestyles,plants experience a vast array of external stimuli and selectively perceive and respond to specific *** repurposing the logic circuitry and biological and molecular components used by plants in nature,genetically encoded plant-based biosensors(GEPBs)have been developed by directing signal recognition mechanisms into carefully assembled outcomes that are easily *** allow for in vivo monitoring of biological processes in plants to facilitate basic studies of plant growth and *** are also useful for environmental monitoring,plant abiotic and biotic stress management,and accelerating design-build-test-learn cycles of plant *** the advent of synthetic biology,biological and molecular components derived from alternate natural organisms(e.g.,microbes)and/or de novo parts have been used to build *** this review,we summarize the framework for engineering different types of *** then highlight representative validated biological components for building plant-based biosensors,along with various applications of plant-based biosensors in basic and applied plant science ***,we discuss challenges and strategies for the identification and design of biological components for plant-based biosensors.

关键词： Plants Molecular monitoring

Safety and efficacy of thalidomide in patients with transfusiondependentβ-thalassemia:a randomized clinical trial

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Signal Transduction and Targeted Therapy 2021年第12期6卷 3723-3729页

作者： Jiang-Ming Chen Wei-Jian Zhu Jie Liu Gui-Zhen Wang Xiao-Qin Chen Yun Tan Wei-Wei Xu Li-Wei Qu Jin-Yan Li Huan-Ju Yang Lan Huang Ning Cai Wei-Da Wang Ken Huang Jian-Quan Xu Guo-Hui Li Sheng He Tian-Ying Luo Yi Huang Song-Hua Liu Wen-Qiang Wu Qi-Yang Lu Mei-Guang Zhou Shu-Ying Chen Rong-Lan Li Mei-Ling Hu Ying Huang Jin-Hua Wei Jun-Min Li Sai-Juan Chen Guang-Biao Zhou Department of Hematology Wuzhou Gongren HospitalWuzhou 543001 GuangxiChina Department of Hematology Zhuhai People’s Hospital(Zhuhai Hospital Affiliated with Jinan University)Zhuhai 541000 GuangdongChina State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Reproductive Medicine The First Affiliated Hospital of Hebei North UniversityZhangjiakou 075000 HebeiChina State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineMedical Oncology DepartmentSun Yat-Sen University Cancer CenterGuangzhou 510060 GuangdongChina State Key Laboratory of Medical genomics Shanghai Institute of HematologyNational Research Center for Translational MedicineRuijin Hospital Affiliated with Shanghai Jiao Tong University School of MedicineShanghai 200025China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of Sciences&University of Chinese Academy of SciencesBeijing 100101China Department of Pediatrics Affiliated Hospital of Youjiang Medical University for NationalitiesBaise City 533000 GuangxiChina Department of Hematology Yulin Guinan HospitalYulin 537005 GuangxiChina Department of neurology Wuzhou Gongren HospitalWuzhou 543001 GuangxiChina Guangxi Key Laboratory of Basic Research on Birth Defects Prevention and Treatment Guangxi Zhuang Autonomous Region Women and Children Health Care HospitalNanning 530000 GuangxiChina Department of Hematology Guigang People’s HospitalGuigang 537100 GuangxiChina Department of Hematology Hospital of Traditional Chinese Medicine of Wuzhou CityWuzhou 543002 GuangxiChina Department of Hematology Wuzhou Red Cross HospitalWuzhou 543002 GuangxiChina Department of Hematology Hechi People’s HospitalHechi City 547000 GuangxiChina

Thalidomide inducesγ-globin expression in erythroid progenitor cells,but its efficacy on patients with transfusion-dependentβ-thalassemia(TDT)remains *** this phase 2,multi-center,randomized,double-blind clinical trial,we aimed to determine the safety and efficacy of thalidomide in TDT patients.A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks,followed by an extension phase of at least 36 *** primary endpoint was the change of hemoglobin(Hb)level in the *** secondary endpoints included the red blood cell(RBC)units transfused and adverse *** the placebo-controlled period,Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0(range,2.5 to 37.5)g/L,whereas Hb in patients treated with placebo did not significantly *** the 12 weeks,the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4±5.0 U and 10.3±6.4 U,respectively(P<0.001).Adverse events of drowsiness,dizziness,fatigue,pyrexia,sore throat,and rash were more common with thalidomide than *** the extension phase,treatment with thalidomide for 24 weeks resulted in a sustainable increase in Hb concentrations which reached 104.9±19.0 g/L,without blood *** increase in Hb concentration and reduction in RBC transfusions were associated with nonβ0/β0 and HBS1L-MYB(rs9399137 C/T,C/C;rs4895441 A/G,G/G)*** results demonstrated that thalidomide is effective in patients with TDT.

关键词： transfusion patients thalidomide