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Celastrus orbiculatus Extract Inhibits Immune Inflammatory Thrombotic State of B-Lymphoma

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Chinese Journal of Integrative Medicine 2024年第11期30卷 1018-1026页

作者： ZHU Miao SHI Qing-qing NI Jun WU Wei SUN Xing SUN Mei XU Kai-lin LIU Yan-qing GU Jian GU Hao Department of hematology Clinical Medical Col ege Yangzhou University Yangzhou Institute of hematology Department of hematology The Affiliated Hospital of Xuzhou Medical University Department of Oncology The Affiliated Hospital of Yangzhou University Yangzhou University Department of Neurology The Affiliated Brain Hospital of Nanjing Medical University

Objective:To investigate the inhibitory effect of Celastrus orbiculatus extracts（COE） on the proliferation of lymphoma cells and the immune regulation ability on inflammation and thrombophilia in ***:The 38B9 lymphoma cells were treated with COE（160μg/mL） and CTX（25 μmol/L）.The apoptosis rate and cell cycle of each group were detected by flow *** secretion of inflammatory factors,including interleukin（IL）-6,IL-10,and tumor necrosis factor α（TNF-α）,in cell supernatant was detected by enzyme-linked immunosorbent assay（ELISA）.In vivo,BALB/c mice were subcutaneously injected with 38B9 lymphoma cells to establish lymphoma ***(3 mg·kg-1·d-1) and CTX(40 mg-kg-1·d-1) were administered to the model mice,*** expression of plasma inflammatory factors（IL-6,IL-10 and TNF-α） and thrombus indexes,including D-dimer（D-D）,von Willebrand factor（vWF） and tissue factor（TF）,were detected by ELISA before tumor bearing（1 d）,after tumor formation（14 d） and after intervention（21 d）.PicoGreen dsDNA was used to detect the level of serum neutrophil extracellular traps（NETs）.Flow cytometry was used to detect the expression of platelet activation marker calcium-dependent lectin-like receptor 2（CLEC-2）.The tumor growth and survival of mice were ***:The 38B9 lymphoma cells were apoptotic after the intervention of COE and *** ratio of G2-M phase cells decreased in COE intervented cells compared with the control cells（P<0.05）,and S phase cells decreased in CTX intervented cells（P<0.05）.Also,the secretion level of IL-6 was significantly reduced after COE or CTX intervention（P<0.05）,and IL-10 was significantly increased（P<0.05）.Furthermore,the tumor mass was reduced,and the median survival time was longer in COE and CTX intervented tumor-bearing mice than in nonintervented *** significantly lower levels of TNF-α,IL-6,NETs,TF,DD and CLEC-2,as well as higher IL-10 were observed in COE and CTX treatment mice in comparision with the control mice（P

关键词： Celastrus orbiculatus extract immune regulation lymphoma murine lymphoma cells proliferation inhibition thrombotic state tumor inflammation

Azacitidine maintenance therapy for blastic plasmacytoid dendritic cell neoplasm allograft: A case report

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World Journal of clinical Cases 2024年第1期12卷 136-141页

作者： Li-Li Tao Hui-Ting Wen Zi-Yi Wang Juan Cheng Li Zhao Department of hematology The First Clinical Medical CollegeLanzhou UniversityLanzhou 730000Gansu ProvinceChina Department of hematology The First Hospital of Lanzhou UniversityLanzhou 730000Gansu ProvinceChina

BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare,highly invasive malignant *** is no universally accepted standard of care because of its rarity and the dearth of prospective *** is still challenging for some patients to achieve persistent clinical remission or cure,despite the success of allogeneic hematopoietic stem cell transplantation(allo-HSCT),indicating that there is still a significant recurrence *** report a case of prevention of BPDCN allograft recurrence by azacitidine maintenance therapy and review the relevant *** SUMMARY We report a 41-year-old man with BPDCN who was admitted to hospital due to skin sclerosis for>5 mo’*** was diagnosed by combined clinical assessment and laboratory *** diagnosis,the patients underwent induction consolidation chemotherapy to achieve the first complete remission,followed by bridging ***-transplantation,azacitidine(75 mg/m2 for 7 d)was administered as maintenance therapy,with repeat administration every 4–6 wk and appropriate extension of the chemotherapy *** 10 cycles,the patient has been disease free for 26 mo after *** assessments of bone marrow morphology,minimal residual disease,full donor chimerism,Epstein–Barr virus,and cytomegalovirus all yielded normal results with no abnormalities *** Azacitidine may be a safe and effective maintenance treatment for BPDCN following transplantation because there were no overt adverse events during the course of treatment.

关键词： Blastic plasmacytoid dendritic cell neoplasm Azacitidine Allogeneic hematopoietic stem cell transplantation Maintenance therapy Case report

Haploidentical hematopoietic cell transplantation with or without an unrelated cord blood unit for adult acute myeloid leukemia:a multicenter,randomized,open-label,phase 3 trial

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2669-2678页

作者： Biqi Zhou Jia Chen Tianhui Liu Yishan Ye Yanming Zhang Yiyang Ding Hong Liu MingQing Zhu Xiao Ma Xiaoli Li Longfei Zhao Zhihong Lin He Huang Yang Xu Depei Wu National clinical Research Center for Hematologic Diseases Jiangsu Institute of HematologyThe First Affiliated Hospital of Soochow UniversitySuzhouChina Institute of Blood and Marrow Transplantation Collaborative Innovation Center of HematologySoochow UniversitySuzhouChina Bone Marrow Transplantation Center The First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangChina Department of hematology The Affiliated Huai’an Hospital of Xuzhou Medical University and The Second People’s Hospital of Huai’anHuai’anChina Soochow Hopes hematology Hospital SuzhouChina Department of hematology Hygeia Suzhou Yongding HospitalSuzhouChina

Coinfusion of unrelated cord blood(UCB)units in haploidentical hematopoietic cell transplantation(haplo-HCT)(haplo-cord HCT)for hematopoietic malignancies showed promising results in previous reports,but the efficiency of haplo-cord HCT in acute myeloid leukemia(AML)still lacks sufficient *** multicenter,randomized,phase 3 trial(*** NCT03719534)aimed to assess the efficacy and safety of haplo-cord HCT in AML patients.A total of 268 eligible patients aged 18-60 years,diagnosed with measurable residual disease in AML(excluding acute promyelocytic leukemia),with available haploidentical donors and suitable for allotransplantation,were randomly allocated(1:1)to receive haplo-cord HCT(n=134)or haplo-HCT(n=134).The 3-year overall survival(OS)was the primary endpoint in this *** median follow-up was 36.50 months(IQR 24.75-46.50).The 3-year OS of Haplo-cord HCT group was better than haplo-HCT group(80.5%,95%confidence interval[CI]:73.7-87.9 vs.67.8%95%CI 60.0-76.5,p=0.013).Favorable progression-free survival(70.3%,95%CI 62.6-78.8 vs.57.6%,95%CI 49.6-67.0,p=0.012)and cumulative incidence of relapse(12.1%,95%CI 12.0-12.2 vs.30.3%,95%CI 30.1-30.4,p=0.024)were observed in haplo-cord HCT *** 3-4 adverse events(AEs)within two years posttransplantation in the two groups were ***-cord HCT patients exhibited a faster cumulative incidence of neutrophil recovery(p=0.026)and increased T-cell reconstitution in the early period ***-cord HCT can improve OS in AML patients without excessive AEs,which may exert additional benefits for recipients of haplo-HCT.

关键词： hematopoietic acute phase

Embracing the age of artificial intelligence:paradigm shifts,opportunities,and challenges in the treatment of acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

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Science China(Life Sciences) 2024年第6期67卷 1302-1304页

作者： Zhuo-Yu An Xiao-Hui Zhang Peking University People’s Hospital Peking University Institute of HematologyBeijing 100044China Collaborative Innovation Center of hematology Peking UniversityBeijing 100044China Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation Beijing 100044China National clinical Research Center for Hematologic Disease Beijing 100044China

Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is an important medical development in treating hematological ***,the risk of acute graft-versus-host disease(a GVHD)severely limits its use.a GVHD is a sev... 详细信息

关键词： hematopoietic graft artificial

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Towards a blood ecosystem approach to dissect systemic diseases

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Science China(Life Sciences) 2024年第7期67卷 1528-1531页

作者： Hong Wang Tao Cheng State Key Laboratory of Experimental hematology Haihe Laboratory of Cell EcosystemNational Clinical Research Center for Blood DiseasesInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China Tianjin Institutes of Health Science Tianjin 301600China

Systemic diseases,in contrast to localized ailments,exert widespread effects and can impact the entire *** of systemic diseases encompass autoimmune disorders,infectious diseases,metabolic disorders,and chronic conditions like *** diseases often entail intricate interactions among diverse organs,tissues,and physiological systems,influenced by a myriad of factors.

关键词： diseases organs autoimmune

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Identification of TNFRSF1A as a novel regulator of carfilzomib resistance in multiple myeloma

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Oncology Research 2024年第2期32卷 325-337页

作者： JIE ZHAO XUANTAO YANG HAIXI ZHANG XUEZHONG GU Department of hematology The First People’s Hospital of Yunnan ProvinceYunnan Province Clinical Research Center for Hematologic DiseaseYunnan Province Clinical Center for Hematologic DiseaseKunming650032China Department of Pathology The First People’s Hospital of Yunnan ProvinceKunming650032China

Multiple myeloma(MM)is a hematological tumor with high mortality and recurrence *** is a new-generation proteasome inhibitor that is used as the first-line therapy for ***,the development of drug resistance is a pervasive obstacle to treating ***,elucidating the drug resistance mechanisms is conducive to the formulation of novel therapeutic *** elucidate the mechanisms of carfilzomib resistance,we retrieved the GSE78069 microarray dataset containing carfilzomib-resistant LP-1 MM cells and parental MM *** gene expression analyses revealed major alterations in the major histocompatibility complex(MHC)and cell adhesion *** upregulation of the tumor necrosis factor(TNF)receptor superfamily member 1A(TNFRSF1A)gene was accompanied by the downregulation of MHC genes and cell adhesion ***,to investigate the roles of these genes,we established a carfilzomib-resistant cell model and observed that carfilzomib resistance induced TNFRSF1A overexpression and TNFRSF1A silencing reversed carfilzomib resistance and reactivated the expression of cell adhesion ***,TNFRSF1A silencing suppressed the tumorigenesis of MM cells in immunocompetent mice,indicating that TNFRSF1A may lead to carfilzomib resistance by dampening antitumor ***,our results indicated that TNFRSF1A overexpression conferred carfilzomib resistance in MM cells and suppressed the expression of MHC genes and cell adhesion *** suppression of MHC genes and cell adhesion molecules may impair the interaction between immune cells and cancer cells to impair antitumor *** studies are warranted to further investigate the signaling pathway underlying the regulatory role of TNFRSF1A in MM cells.

关键词： Multiple myeloma Carfilzomib Drug resistance Major histocompatibility complex TNFRSF1A

LATS1 Promotes B-ALL Tumorigenesis by Regulating YAP1 Phosphorylation and Subcellular Localization

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Current Medical Science 2024年第1期44卷 81-92页

作者： Feng ZHANG Mohammed Awal Issah Hai-ying FU Hua-rong ZHOU Ting-bo LIU Jian-zhen SHEN Fujian Provincial Key Laboratory on hematology Fujian Medical Center of HematologyFujian Institute of HematologyClinical Research Center for Hematological Malignancies of Fujian ProvinceFujian Medical University Union HospitalFuzhou 350001China Tamale Technical University Faculty of Allied Health and Pharmaceutical SciencesDepartment of Medical Laboratory TechnologyTamale NS-011-2000Ghana Department of hematology The Third Affiliated People's Hospital of Fujian University of Traditional Chinese MedicineThe Third People's Hospital of Fujian ProvinceFuzhou 350122China

Objective YAP1 plays a dual role as an oncogene and tumor suppressor gene in several tumors;differentiating between these roles may depend on the YAP1 phosphorylation *** specific function of YAP1 in B cell acute lymphoblastic leukemia(B-ALL),however,is currently ***,in the present study,the role of YAP1 in B-ALL was investigated using relevant cell lines and patient *** The effects of shRNA-mediated knockdown on YAP1 and LATS1 levels in the NALM6 and MOLT-4 cell lines were examined using Western blotting,quantitative real-time polymerase chain reaction,flow cytometry,immunostaining,and nude mouse subcutaneous tumorigenesis *** expression levels of Hippo pathway-related molecules before and after verteporfin(VP)treatment were compared using RNA-Seq to identify significant Hippo pathway-related genes in NALM6 *** Patients with ALL showing high YAP1 expression and low YAP1-Ser127 phosphorylation levels had worse prognoses than those with low YAP1 protein expression and high YAP1-Ser127 phosphorylation ***1-Ser127 phosphorylation levels were lower in NALM6 cells than in MOLT-4 and control cells;YAP1 was distributed in the nuclei in NALM6 *** of YAP1 inhibited MOLT-4 and NALM6 cell proliferation and arrested the NALM6 cell cycle in the G0/G1 *** and after VP treatment,the expression of the upstream gene LATS1 was upregulated;its overexpression promoted YAP1-Ser127 ***,YAP1 was distributed in the *** LATS1 may downregulate YAP1-Ser127 phosphorylation and maintain B-ALL cell function;thus,VP,which targets this axis,may serve as a new therapeutic method for improving the outcomes for B-ALL patients.

关键词： acute lymphoblastic leukemia large tumor suppressor kinase 1 phosphorylation RNA-Seq Yesl-associated protein

Effects of different concentrations of nicotinamide on hematopoietic stem cells cultured in vitro

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World Journal of Stem Cells 2024年第2期16卷 163-175页

作者： Yan Ren Yan-Ni Cui Hong-Wei Wang The Second clinical Medical College Shanxi Medical UniversityTaiyuan 030001Shanxi ProvinceChina Department of hematology The Second Hospital of Shanxi Medical UniversityTaiyuan 030001Shanxi ProvinceChina Department of hematology Key Laboratory of Molecular Diagnosis and Treatment of Blood Diseases in Shanxi ProvinceTaiyuan 030001Shanxi ProvinceChina

BACKGROUND In vitro expansion to increase numbers of hematopoietic stem cells(HSCs)in cord blood could improve clinical efficacy of this vital ***(NAM)can promote HSC expansion ex vivo,but its effect on hematopoietic stem and progenitor cells(HSPCs,CD34^(+)CD38)and functional subtypes of HSCs-shortterm repopulating HSCs(ST-HSCs,CD34^(+)CD38CD45RACD49f^(+))and long-term repopulating HSCs(LT-HSCs,CD34^(+)CD38CD45RACD49f^(+)CD90^(+))is not yet *** a sirtuin 1(SIRT1)inhibitor,NAM participates in regulating cell adhesion,polarity,migration,proliferation,and ***,SIRT1 exhibits dual effects by promoting or inhibiting differentiation in different tissues or *** propose that the concentration of NAM may influence proliferation,differentiation,and SIRT1 signaling of *** To evaluate the effects and underlying mechanisms of action of different concentrations of NAM on HSC proliferation and *** CD34^(+)cells were purified from umbilical cord blood using MacsCD34 beads,and cultured for 10-12 d in a serum-free medium supplemented with cytokines,with different concentrations of NAM added according to experimental *** cytometry was used to detect phenotype,cell cycle distribution,and apoptosis of the cultured ***-time polymerase chain reaction was used to detect the transcription levels of target genes encoding stemness-related factors,che mokines,components of hypoxia pathways,and antioxidant ***-dihydro-fluorescein diacetate probes were used to evaluate intracellular production of reactive oxygen species(ROS).Determination of the effect of different culture conditions on the balance of cytokine by cytometric bead *** Compared with the control group,the proportion and expansion folds of HSPCs(CD34^(+)CD38)incubated with 5 mmol/L or 10 mmol/L NAM were significantly increased(all P<0.05).The ST-HSCs ratio and fold expansion of the 5 mmol/L NAM group were significantly

关键词： Hematopoietic stem cells Nicotinamide Concentration Proliferation Differentiation Sirtuin 1

Acquired immune thrombotic thrombocytopenic purpura(TTP)associated with inactivated COVID-19 vaccine CoronaVac

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Frontiers of Medicine 2024年第4期18卷 744-751页

作者： Zhangbiao Long Suyu Jiang Honglei Xin Lu Zhang Ruinan Lu Fengqi Liu Yong Xu Linv Wang Jun Wang Xuezhong Zhang Hui Liao Jinning Shi Xue Yan Xiang Zhu Ruonan Shao Zijian Li Yilin Zhu Han Yan Jiao Wu Chao Fang Xiaodong Xi Xiaofeng Shi Department of hematology The First Affiliated Hospital of Anhui Medical UniversityHefei230022China Department of hematology The Second Affiliated Hospital of Nanjing Medical UniversityNanjing210003China Department of hematology The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjing210029China Department of hematology Nanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing210008China Department of hematology The Affiliated Hospital of Nanjing University of Chinese MedicineThe First Clinical Medical College of Nanjing University of Chinese MedicineNanjing210009China Department of hematology Zhongda Hospital of Southeast UniversityNanjing210044China Department of hematology Nanjing First HospitalNanjing Medical UniversityNanjing210006China Department of hematology The Air Force Hospital of Eastern Theater commandNanjing210016China Department of hematology Jiangning Hospital Affiliated of Nanjing Medical UniversityNanjing211199China Department of hematology Nanjing Hospital of Chinese MedicineNanjing210006China Department of Pharmacology School of Basic MedicineTongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious DiseasesHuazhong University of Science and TechnologyThe Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei ProvinceWuhan430030China Shanghai Institute of hematology State Key Laboratory of Medical GenomicsRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200025China

Corona virus disease 2019(COVID-19)due to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has affected the whole *** thrombotic thrombocytopenic purpura(TTP)has been reported after administration of mRNA-or adenoviral vector-based COVID-19 vaccines,including ***2-S,BNT162b2,mRNA-1273,and ChAdOx1 ***,whether inactivated vaccines,such as CoronaVac,could cause TTP and whether the symptoms in TTPs caused by inactivated vaccines are different from previously reported cases are *** this study,two cases were *** cases developed TTP after the second CoronaVac vaccination shot,but not the *** demonstrated symptoms of fever,neurological abnormalities,renal dysfunction,thrombocytopenia,and *** patients achieved complete remission through several sessions of plasma exchanges and immune *** incidence of TTP in Nanjing area was *** number of patients with TTP was 12 in 2019,6 in 2020,16 in 2021,and 19 in *** the authors’knowledge,this report is the first report of TTP associated with inactivated COVID-19 vaccine(CoronaVac).The rarity and delayed onset may be due to the relatively milder immune response caused by the inactivated vaccines than mRNA-based *** plasma exchange is a vital treatment for CoronaVac-related TTP,similar to activated vaccine-related TTP.

关键词： thrombotic thrombocytopenia purpura(TTP) corona virus disease 2019(COVID-19) CoronaVac acute respiratory syndrome coronavirus 2(SARS-CoV-2) vaccine