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

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

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3D-printed cell-free PCL-MECM scaffold with biomimetic micro-structure and micro-environment to enhance in situ meniscus regeneration

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Bioactive Materials 2021年第10期6卷 3620-3633页

作者： Weimin Guo Mingxue Chen Zhenyong Wang Yue Tian Jinxuan Zheng Shuang Gao Yangyang Li Yufeng Zheng Xu Li Jingxiang Huang Wei Niu Shuangpeng Jiang Chunxiang Hao Zhiguo Yuan Yu Zhang Mingjie Wang Zehao Wang Jiang Peng Aiyuan Wang Yu Wang Xiang Sui Wenjing Xu Libo Hao Xifu Zheng Shuyun Liu Quanyi Guo Department of Orthopaedic Surgery First Affiliated HospitalSun Yat-sen UniversityNo.58 Zhongshan Second RoadYuexiu DistrictGuangzhouGuangdong510080People’s Republic of China Institute of Orthopedics The First Medical CenterChinese PLA General HospitalBeijing Key Lab of Regenerative Medicine in OrthopedicsKey Laboratory of Musculoskeletal Trauma&War Injuries PLA.No.28 Fuxing RoadHaidian DistrictBeijing 100853People’s Republic of China Department of Orthopedic Surgery Beijing Jishuitan HospitalFourth Clinical College of Peking UniversityNo.31 Xinjiekou East StreetXicheng DistrictBeijing100035People’s Republic of China Department of Orthodontics Guanghua School of StomatologyGuangdong Provincial Key Laboratory of StomatologySun Yat-sen UniversityNo.56 Linyuan Xi RoadYuexiu DistrictGuangzhouGuangdong 510055People’s Republic of China Center for Biomaterial and Tissue Engineering Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijing100871People’s Republic of China Department of Materials Science and Engineering College of EngineeringPeking UniversityBeijing 100871People’s Republic of China Musculoskeletal Research Laboratory Department of Orthopaedics and TraumatologyInnovative Orthopaedic Biomaterial and Drug Translational Research LaboratoryLi Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong KongPeople’s Republic of China Institute of Anesthesiology The First Medical CenterChinese PLA General HospitalNo.28 Fuxing RoadHaidian DistrictBeijing 100853People’s Republic of China Department of Orthopedic Surgery First Affiliated HospitalDalian Medical UniversityNo.222 Zhongshan RoadXigang DistrictDalian 116011China

Despite intensive effort was made to regenerate injured meniscus by cell-free strategies through recruiting endogenous stem/progenitor cells,meniscus regeneration remains a great challenge in *** this study,we found decellularized meniscal extracellular matrix(MECM)preserved native meniscal collagen and glycosaminoglycans which could be a good endogenous regeneration guider for stem ***,MECM significantly promoted meniscal fibrochondrocytes viability and proliferation,increased the expression of type II collagen and proteoglycans in ***,we designed 3D-printed polycaprolactone(PCL)scaffolds which mimic the circumferential and radial collagen orientation in native *** these two advantages together,a micro-structure and micro-environment dually biomimetic cell-free scaffold was *** cell-free PCL-MECM scaffold displayed superior biocompatibility and yielded favorable biomechanical capacities closely to native ***,neo-menisci were regenerated within PCL-MECM scaffolds which were transplanted into knee joints underwent medial meniscectomy in rabbits and sheep *** staining confirmed neo-menisci showed meniscus-like heterogeneous *** scores showed PCL-MECM scaffold could protect articular cartilage well,and knee X-ray examination revealed same *** magnetic resonance imaging(MRI)scanning also showed some neo-menisci in PCL-MECM scaffold *** conclusion,PCL-MECM scaffold appears to optimize meniscus *** could represent a promising approach worthy of further investigation in preclinical applications.

关键词： 3D printing Cell-free Decellularization Biomimetic scaffold Meniscus regeneration

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Disruption of KDM4C-ALDH1 A3 feed-forward loop inhibits sternness,tumorigenesis and chemoresistance of gastric cancer stem cells

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Signal Transduction and Targeted Therapy 2021年第10期6卷 2975-2977页

作者： Tingyuan Lang Jia Xu Lei Zhou Zhiqi Zhang Xinli Ma Jiayi Gu Jingshu Liu Yunzhe Li Dongyan Ding Jiangfeng Qiu Ddepartment of Gynecologic Oncology Chongqing University Cancer HospitalSchool of MedicineChongqing UniversityChongqingPeople's Republic of China Department of Gastrointestinal Surgery Renji Hospital Shanghai Jiao Tong University School of MedicineShanghaiPeople's Republic of China Singapore Eye Research Institute The AcademiaSingaporeSingapore Department of Ophthalmology Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore Ophthalmology and Visual Sciences Academia clinical Program Duke-NUS Medical SchoolSingaporeSingapore Department of General Surgery Shanghai Fourth People's Hospital Affiliated to Tongji University School of MedicineShanghaiPeople's Republic of China

Dear Editor,Gastric cancer(GC)is a considerable global health burden;the median survival of advaneed GC is less than 1 year.^(1)Cancer stem cells(CSCs),a small population of cancer cells with stem cell-like properties,are the major cause of treatme nt failure,in eluding GC,2 however,the mechanisms underlying stemness maintenanee of GC stem cells(GCSCs)are still poorly understood.

关键词： cancer Gastric Cancer

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Transdifferentiation of pancreatic α-cells into insulinsecreting cells: From experimental models to underlying mechanisms

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World Journal of Diabetes 2014年第6期5卷 847-853页

作者： Jieli Lu Rami Jaafer Rémy Bonnavion Philippe Bertolino Chang-Xian Zhang Sino-French Life Science and Genomic Center the E-Institute of ShanghaiShanghai Institute of Endocrine and Metabolic DiseasesRuijin HospitalShang-hai Jiao Tong University Shanghai clinical Center for Endocrine and Metabolic Diseases Ruijin HospitalShanghai Jiao Tong University Inserm U1052 Cancer Research Centre of Lyon CNRS UMR5286 Cancer Research Centre of Lyon Cancer Research Centre of Lyon Université de Lyon

Pancreatic insulin-secreting β-cells are essential regulators of glucose metabolism. New strategies are cur-rently being investigated to create insulin-producing β cells to replace deficient β cells, including the differentiation of either stem or progenitor cells, and the newly uncovered transdifferentiation of mature non-β islet cell types. However, in order to correctly drive any cell to adopt a new β-cell fate, a better understanding of the in vivo mechanisms involved in the plasticity and biology of islet cells is urgently required. Here, we review the recent studies reporting the phenomenon of transdifferentiation of α cells into β cells by focusing on the major candidates and contexts revealed to be involved in adult β-cell regeneration through this process. The possible underlying mechanisms of transdifferentiation and the interactions between several key factors involved in the process are also addressed. We propose that it is of importance to further study the molecular and cellular mechanisms underlying α- to β-cell transdifferentiation, in order to make β-cell regeneration from α cells a relevant and realizable strategy for developing cell-replacement therapy.

关键词： α-cell β-cell Transdifferentiation Diabetes mellitus Cell-replacement therapy

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细胞移植治疗脊髓损伤（英文）

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中华神经外科疾病研究杂志 2017年第3期16卷 216-216页

作者： Assinck P Duncan GJ Hilton BJ plemel JR Tetzlaff W International Collaboration on Repair Discoveries University of British Columbia Graduate Program in Neuroscience University of British Columbia Department of Zoology University of British Columbia Department of clinical Neurosciences and the Hotchkiss Brain Institute University of Calgary Department of Surgery University of British Columbia

Spinal cord injury can lead to severe motor,sensory and autonomic ***,there is no effective treatment for the injured *** transplantation of Schwann cells,neural stem cells or progenitor cells,olfactory ensheathing cells,oligodendrocyte precursor cells and mesenchymal stem cells has been investigated as potential therapies for spinal cord ***,little is known about the mechanisms through which these individual cell types promote repair and functional *** five most commonly proposed mechanisms include neuroprotection,immunomodulation,axon regeneration,neuronal relay formation and myelin regeneration.A better understanding of the mechanisms whereby these cells promote functional improvements,as well as an appreciation of the obstacles in implementing these therapies and effectively modeling spinal cord injury,will be important to make cell transplantation a viable clinical option and may lead to the development of more targeted therapies.

关键词：期刊编辑工作英文摘要

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The Identity of Human Tissue-Emigrant CD8+T cells

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四川生理科学杂志 2020年第4期42卷 426-426页

作者： Marcus Buggert Department of Microbiology Perelman School of Medicine University of Pennsylvania Philadelphia PA USA Institute for Immunology Perelman School of Medicine University of Pennsylvania Philadelphia PA USA Center for Infectious Medicine Department of Medicine Huddinge Karolinska Institutet Karolinska University Hospital Huddinge Stockholm Sweden Genome Analysis Core Vaccine Research Center National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda MD USA Neuroimmunology Unit Montreal Neurological Institute McGill University Montreal QC Canada Division of Human Genetics Children’s Hospital of Philadelphia Philadelphia PA USA Vaccine and Gene Therapy Institute and Oregon National Primate Research Center Oregon Health & Science University Beaverton OR USA Division of Surgery Department of Clinical Science Intervention and Technology Karolinska Institutet Stockholm Sweden Division of Infection and Immunity Cardiff University School of Medicine Cardiff UK Human Immunology Section Vaccine Research Center National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda MD USA Center for Lymphatic Disorders Department of Radiology Perelman School of Medicine University of Pennsylvania Philadelphia PA USA

Lymphocyte migration is essential for adaptive immune ***,our current understanding of this process is rudimentary,because most human studies have been restricted to immunological analyses of blood and various *** address this knowledge gap,we used an integrated approach to characterize tissue-emigrant lineages in thoracic duct lymph(TDL).The most prevalent immune cells in human and non-human primate efferent lymph were T *** CD8+T cell subsets with effector-like epigenetic and transcriptional signatures were clonotypically skewed and selectively confined to the intravascular circulation,whereas non-cytolytic CD8+T cell subsets with stem-like epigenetic and transcriptional signatures predominated in tissues and ***,these anatomically distinct gene expression profiles were recapitulated within individual clonotypes,suggesting parallel differentiation programs independent of the expressed antigen *** collective dataset provides an atlas of the migratory immune system and defines the nature of tissue-emigrant CD8+T cells that recirculate via TDL.

关键词： signature collective Human

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Evaluation of biodegradable electric conductive tube-guides and mesenchymal stem cells

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World Journal of stem cells 2015年第6期7卷 956-975页

作者： Jorge Ribeiro Tiago Pereira Ana Rita Caseiro Paulo Armada-da-Silva Isabel Pires Justina Prada Irina Amorim Sandra Amado Miguel Franca Carolina Goncalves Maria Ascensao Lopes Jose Domingos Santos Dina Morais Silva Stefano Geuna Ana Lúcia Luís Ana Colette Maurício Departmento de Clínicas Veterinárias and+UPVet Instituto de Ciencias Biomedicas de Abel Salazar(ICBAS)and Centro de Estudos de Ciencia Animal(CECA)Instituto de CienciasTecnologias e Agroambiente da Universidade do Porto(ICETA)Rua de Jorge Viterbo Ferreira4050-313 PortoPortugal Centro Interdisciplinar de Estudo de Performance Humana(CIPER) Faculdade de Motricidade Humana(FMH)Universidade de Lisboa(UL)Estrada da Costa1499-002 Cruz QuebradaDafundoPortugal CECAV and Departamento de Ciencias Veterinárias Universidade de Trás-os-Montes e Alto Douro(UTAD)5001-801 Vila RealPortugal Departmento de Patologia e de Imunologia Molecular Instituto de Ciencias Biomedicas de Abel SalazarRua de Jorge Viterbo Ferreira4050-313 PortoPortugal Instituto Português de Patologia e Imunologia Molecular da Universidade do Porto(IPATIMUP) Rua Dr.Roberto Frias s/n4200-465 PortoPortugal UIS-Ipl:Unidade de Investigacao em Saúde da Escola Superior de Saúde de Leiria Instituto Politécnico de Leiria2411-901 LeiriaPortugal CEMUC Departamento de Engenharia Metalúrgica e MateriaisFaculdade de Engenharia da Universidade do Porto(FEUP)Rua Dr.Roberto Frias4200-465 PortoPortugal Biosckin Molecular and Cell Therapies S.A.Tec MaiaRua Engenheiro Frederico Ulrich 26504470-605 MaiaPortugal Neuroscience Institute of the Cavalieri Ottolenghi Foundation and Department of clinical and Biological Sciences University of Turin

AIM: To study the therapeutic effect of three tubeguides with electrical conductivity associated to mesenchymal stem cells(MSCs) on neuro-muscular regeneration after ***: Rats with 10-mm gap nerve injury were tested using polyvinyl alcohol(PVA), PVA-carbon nanotubes(CNTs) and MSCs, and PVA-polypyrrole(PPy). The regenerated nerves and tibialis anterior muscles were processed for stereological studies after 20 wk. The functional recovery was assessed serially for gait biomechanical analysis, by extensor postural thrust, sciatic functional index and static sciatic functionalindex(SSI), and by withdrawal reflex latency(WRL). In vitro studies included cytocompatibility, flow cytometry, reverse transcriptase polymerase chain reaction and karyotype analysis of the MSCs. Histopathology of lung, liver, kidneys, and regional lymph nodes ensured the biomaterials biocompatibility. RESULTS: SSI remained negative throughout and independently from treatment. Differences between treted groups in the severity of changes in WRL existed, showing a faster regeneration for PVA-CNTs-MSCs(P < 0.05). At toe-off, less acute ankle joint angles were seen for PVA-CNTs-MSCs group(P = 0.051) suggesting improved ankle muscles function during the push off phase of the gait cycle. In PVA-PPy and PVA-CNTs groups, there was a 25% and 42% increase of average fiber area and a 13% and 21% increase of the "minimal Feret's diameter" respectively. Stereological analysis disclosed a significantly(P < 0.05) increased myelin thickness(M), ratio myelin thickness/axon diameter(M/d) and ratio axon diameter/fiber diameter(d/D; g-ratio) in PVA-CNT-MSCs group(P < 0.05). CONCLUSION: Results revealed that treatment with MSCs and PVA-CNTs tube-guides induced better nerve fiber regeneration. Functional and kinematics analysis revealed positive synergistic effects brought by MSCs and PVA-CNTs. The PVA-CNTs and PVA-PPy are promising scaffolds with electric conductive properties, bio- and cytocompatible th

关键词： Nerve regeneration Neurotmesis Tubeguides Mesenchymal stem cells Carbon nanotubes Functional assessment Gait biomechanical analysis Histomorfometry Polyvinyl alcohol

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研究神经胶质细胞的新兴技术

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神经损伤与功能重建 2020年第10期15卷 F0003-F0003页

作者： Hélène Hirbec Nicole Déglon Lynette C Foo Inbal Goshen Jaime Grutzendler Emilie Hangen Tirzah Kreisel Nathalie Linck Julien Muffat Sara Regio Sybille Rion Carole Escartin 杜一星 Institute for Functional Genomics(IGF) University of MontpellierCNRSINSERMMontpellierFrance Laboratory of Neurotherapies and Neuromodulation Department of Clinical NeuroscienceLausanne University HospitalUniversity of LausanneLausanneSwitzerland Laboratory of Neurotherapies and Neuromodulation Neuroscience Research CenterLausanne University Hospital and University of LausanneLausanneSwitzerland Neuroimmunology and Neurodegeneration Section The Neuroscience and Rare Diseases Discovery and Translational AreaF.Hoffman-La RocheBaselSwitzerland Edmond and Lily Safra Center for Brain Sciences The Hebrew University of JerusalemJerusalemIsrael Department of Neurology Yale University School of MedicineNew HavenConnecticutUSA Department of Neuroscience Yale University School of MedicineNew HavenConnecticutUSA Commissariatà l'Energie Atomique et aux Energies Alternatives Département de la Recherche FondamentaleInstitut de Biologie François JacobMIRCenFontenay-aux-RosesFrance Centre National de la Recherche Scientifique Neurodegenerative Diseases LaboratoryUniversitéParis-SudUniversitéParis-SaclayUMR 9199Fontenay-aux-RosesFrance Program in Neurosciences and Mental Health The Hospital for Sick Childrenand Department of Molecular GeneticsThe University of TorontoTorontoCanada 不详

大脑的发育、生理功能和病理与神经元和不同类型的神经胶质细胞(如星形胶质细胞、小胶质细胞、少突胶质细胞和少突胶质细胞的前体细胞等)之间的相互作用密切相关。研究脑功能及其功能障碍,除了神经元之外,还需要对不同类型的神经胶质细... 详细信息

大脑的发育、生理功能和病理与神经元和不同类型的神经胶质细胞(如星形胶质细胞、小胶质细胞、少突胶质细胞和少突胶质细胞的前体细胞等)之间的相互作用密切相关。研究脑功能及其功能障碍,除了神经元之外,还需要对不同类型的神经胶质细胞进行研究。近年来,多项技术突破使“神经胶质科学家”能够解决新的具有挑战性的生物学问题。这些技术发展使得以中/高含量工作流研究特定细胞类型的作用成为可能,并在保存完好的环境中对其相互作用进行精细的分析。本综述阐明了几种可能揭示神经胶质细胞在特定脑功能或疾病中作用的尖端实验方法。这些实验方法包括高级细胞培养,诱导多能干细胞(iPSC)衍生的人神经胶质细胞,病毒载体,原位胶质细胞成像,光学遗传学和化学遗传学方法,以及高内涵分子分析。本文还阐述了某些技术的临床转化,通过特定的脑成像方法以监控患者的神经胶质细胞。本文亦讨论了每种技术的优点,缺陷和未来发展,并提供了选定的示例以说明现在如何可以解决特定的“胶质生物学”问题。

关键词：神经胶质细胞少突胶质细胞小胶质细胞星形胶质细胞脑功能细胞培养细胞类型脑成像

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