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Genes & Diseases 2024年第2期11卷 550-553页

作者： Jing Tang Yue li Jiazhu Wu Haorui Shen Hua Yin Jinhua liang li Wang jianyong li Yi Xia Wei Xu Department of Hematology The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingJiangsu 210029China Key Laboratory of Hematology of Nanjing Medical University NanjingJiangsu 210029China Collaborative Innovation Center for Cancer Personalized Medicine NanjingJiangsu 210029China

PR/SET domain 1(PRDM1)gene is located on chromosome 6q21,encoding the B lymphocyte-induced maturation protein 1(BliMP1).1 It is reported that loss of PRDM1 function is exacerbated in activated B-cell-like(ABC)-diffuse large B cell lymphoma(DLBCL)and associated with inferior survival.However,it remains unclear what leads to PRDM1 inactivation and the drug resistance mechanism caused by abnormal inactivation of PRDM1.We investigated the contribution of PRDM1 gene as a prognosis and potential therapeutic target for ABC-DLBCL patients and further clarified the possible mechanism of PRDM1 abnormal inactivation.We first proposed that TP53 could regulate PRDM1 by histone ubiquitination modification at the post-transcriptional level.

关键词： PRDM1 TP53 therapeutic

Genotyping on circulating tumor DNA improves mutation detection rate in high-risk diffuse large B-cell lymphoma

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Genes & Diseases 2024年第4期11卷 116-119页

作者： Yi Xia li Wang Jinhua liang Haorui Shen Jiazhu Wu Hua Yin Yue li Huayuan Zhu jianyong li Wei Xu Department of Hematology The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingJiangsu 210029China Key Laboratory of Hematology of Nanjing Medical University NanjingJiangsu 210029China Collaborative Innovation Center for Cancer Personalized Medicine NanjingJiangsu 210029China

Diffuse large B-cell lymphoma(DLBCL)is the most common lymphoma with heterogeneous clinical outcomes.Patients who are primarily refractory to the frontline therapy or relapse less than 12 months after diagnosis have an extremely dismal prognosis.The heterogeneous clinical outcomes of DLBCL patients result from variable genetic profiles.

关键词： lymphoma diagnosis clinical

Influence of Mass Ratio of Resin and Stabilizer on Mechanical Properties of Mo Fiber-reinforced Granite Polymer Composite

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Journal of Wuhan University of Technology(Materials Science) 2024年第4期39卷 912-920页

作者：张超任秀华 BA Dongzhe ZHANG Jianhua li jianyong GUO Mengnan GAO Yinghao WANG Guixin li Jiayang School of Mechanical and Electronic Engineering Shandong Jianzhu UniversityJinan 250101China Key Laboratory of High Efficiency and Clean Mechanical Manufacture Ministry of Education of ChinaSchool of Mechanical EngineeringShandong UniversityJinan 250061China

Because inferior mechanical strength of granite polymer composite(GPC)has become the main drawback limiting its application and popularization,Mo fibers were added into(GPC)to improve its mechanical strength.Mechanical properties of matrix materials with different mass ratio of resin and stabilizer(MRRS)were investigated systematically.The influences of MRRS on interface bonding strength of Mo fiber-matrix,wettability and mechanical strength of GPC were discussed,respectively,and the theoretical calculation result of MRRS k was obtained,with the optimal value of k=4.When k=4,tensile strength,tensile strain and fracture stress of the cured resin achieve the maximum values.But for k=7,the corresponding values reach the minimum.With the increase of MRRS k,surface free energy of the cured resin first increases and then decreases,while contact angles between Mo sample and matrix have displayed the opposite trend.Wettability of resin to Mo fiber is the best at k=4.Pulling load of Mo fiber and interface bonding strength appear the maximum at k=4,followed by k=5,k=3 the third,and k=7 the minimum.When k=4,mechanical properties of Mo fiber-reinforced GPC are optimal,which is consistent with the result of theoretical calculation.This study is of great significance to get better component formulas of Mo fiber reinforced GPC and to improve its application in machine tools.

关键词： polymer composite fiber mechanical strength interface bonding

Phase Ⅰ study of CBM.CD19 chimeric antigen receptor T cell in the treatment of refractory diffuse large B-cell lymphoma in Chinese patients

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Frontiers of Medicine 2022年第2期16卷 285-294,F0004页

作者： Lei Fan li Wang Lei Cao Huayuan Zhu Wei Xu jianyong li Department of Hematology Pukou CLL CenterJiangsu Province HospitalThe First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China

Anti-CD 19 chimeric antigen receptor(CAR)T cell therapy has shown impressive efficacy in treating B-cell malignancies.A single-center phase I dose-escalation study was conducted to evaluate the safety and efficacy of T cells transduced with CBM.CD19 CAR,a second-generation anti-CD19 CAR bearing 4-1BB costimulatory molecule,for the treatment of patients with refractory diffuse large B-cell lymphoma(DLBCL).Ten heavily treated patients with refractory DLBCL were given CBM.CD19 CAR-T cell(C-CAR011)treatment.The overall response rate was 20%and 50%at 4 and 12 weeks after the infusion of C-CAR011,respectively,and the disease control rate was 60%at 12 weeks after infusion.Treatment-emergent adverse events occurred in all patients.The incidence of cytokine release syndrome in all grades and grade^3 was 90%and 0,respectively,which is consistent with the safety profile of axicabtagene ciloleucel and tisagenlecleucel.Neurotoxicity or other dose-limiting toxicides was not observed in any dose cohort of C-CAR011 therapy.Antitumor efficacy was apparent across dose cohorts.Therefore,C-CAR011 is a safe and effective therapeutic option for Chinese patients with refractory DLBCL,and further large-scale clinical trials are warranted.

关键词： CAR-T cell therapy refractory diffuse large B-cell lymphoma cytokine release syndrome dose-limiting toxicity

Overexpression of c-Myc-dependent heterogeneous nuclear ribonucleoprotein A1 promotes proliferation and inhibits apoptosis in NOTCH1-mutated chronic lymphocytic leukemia cells

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Chinese Medical Journal 2022年第8期135卷 920-929页

作者： Yixin Zou Hanning Tang Yi Miao Huayuan Zhu li Wang Lei Fan Jianxin Fu Wei Xu jianyong li Yi Xia department of Hematology The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingJiangsu 210029China Key Laboratory of Hematology of Nanjing Medical University NanjingJiangsu 210029China Collaborative Innovation Center for Cancer Personalized Medicine NanjingJiangsu 210029China Pukou CLL Center NanjingJiangsu 210000China

Background: NOTCH1 mutation is an essential molecular biologic aberration in chronic lymphocytic leukemia (CLL). CLL patients withNOTCH1 mutation have shown an unfavorable survival and a poor response to chemoimmunotherapy. This study aims to present the mechanisms of adverse prognosis caused byNOTCH1 mutation from the perspective of the splicing factor heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1).Methods: The microarray data in Gene Expression Omnibus datasets were analyzed by bioinformatics and the function of hnRNPA1 was checked by testing the proliferation and apoptosis of CLL-like cell lines. Afterward, quantitative reverse transcription-polymerase chain reaction and Western blotting were applied to explore the relationship among NOTCH1, c-Myc, and hnRNPA1.Results: RNA splicing was found to play a vital part inNOTCH1-mutated CLL cells;hence, hnRNPA1 was selected as the focus of this study. Higher expression of hnRNPA1 validated in primaryNOTCH1-mutated CLL samples could promote proliferation and inhibit apoptosis in CLL. The expression of hnRNPA1 increased when NOTCH1 signaling was activated by transfection with NOTCH1 intracellular domain (NICD)-overexpressed adenovirus vector and declined after NOTCH1 signaling was inhibited by NOTCH1-shRNA. Higher expression of c-Myc was observed in NICD-overexpressed cells and hnRNPA1 expression was downregulated after applying c-Myc inhibitor 10058-F4. Moreover, in NICD-overexpressed cells, hnRNPA1 expression decreased through c-Myc inhibition.Conclusion: Overexpression of c-Myc-dependent hnRNPA1 could promote proliferation and inhibit apoptosis inNOTCH1- mutated CLL cells, which might partly account for the poor prognosis of patients withNOTCH1 mutation.

关键词： Chronic lymphocytic leukemia NOTCH1 mutation c-Myc Heterogeneous nuclear ribonucleoprotein A1

Chinese expert consensus on oral drugs for the treatment of mature B-cell lymphomas (2020 edition)

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Frontiers of Medicine 2022年第5期16卷 815-826页

作者： Suning Chen Weili Zhao jianyong li Depei Wu on behalf of Lymphoid Disease Group,Chinese Society of Hematology,Chinese Medical Association National Clinical Research Center for Hematologic Diseases Suzhou 215006China Jiangsu Institute of Hematology the First Affiliated Hospital of Soochow UniversitySuzhou 215006China Shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China Department of Hematology The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalCollaborative Innovation Center for Cancer Personalized MedicineNanjing 210029China

Oral drugs such as ibrutinib play an important role in the treatment of mature B-cell lymphoma(BCL)due to their reliable efficacy,manageable safety,high accessibility,and convenience for use.Still,no guidelines or consensus focusing on oral drug therapies for BCL is available.To provide a reference of oral agent-based treatment for mature BCL,a panel of experts from the Lymphocyte Disease Group,Chinese Society of Hematology,Chinese Medical Association conducted an extensive discussion and reached a consensus on oral drugs for Chinese BCL patients on the basis of the current application status of oral drugs in China,combined with the latest authoritative guidelines in the world and current research reports.This consensus reviewed the application of oral drugs in the treatment of BCL and the latest research and provided appropriate recommendations on the use of oral drugs for indolent or aggressive BCL patients.With the deepening of research and the development of standardized clinical applications,oral medications will bring better treatment to BCL patients,enabling more patients to benefit from them.

关键词： B-cell lymphoma oral drug targeted therapy immunotherapy COVID-19 pandemic

Mechanical Characteristics Analysis of 3D-printing Novel Chiral Honeycomb Array Structures Based on Functional Principle and Constitutive Relationship

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Journal of Bionic Engineering 2023年第5期20卷 1917-1929页

作者： Ruiyao liu Guofeng Yao Zezhou Xu Xue Guo jianyong li Zhenglei Yu Ping liang Zhihui Zhang Chunyang Han Department of Mechanics School of Mechanical and Aerospace EngineeringJilin UniversityChangchun130022China Key Laboratory of Bionic Engineering of Ministry of Education Jilin UniversityChangchun130022China State Key Laboratory of Automotive Simulation and Control Jilin UniversityChangchun130022China Changchun Institute of Optics Fine Mechanics and PhysicsChinese Academy of SciencesChangchun130022China

Four novel chiral honeycomb structures inspired by the biological arrangement shape are designed.The functional principle is raised to solve the large deformation of bio-inspired structures and the structural constitutive model is proposed to explain the quasi-static mechanical properties of chiral honeycomb array structures and honeycomb structures.Simulation and experiment results verify the accuracy of theoretical analysis results and the errors are all within 15%.In structural mechanical properties,Equidimensional Chiral Honeycomb Array Structure(ECHS)has excellent mechanical properties.Among ECHS,Small-sized Column Chiral Honeycomb Array Structure(SCHCS)has the best properties.The bearing capacity,specific energy absorption,and specific strength of SCHCS are more than twice as much as the others in this paper.The chiral honeycomb array structure has the best mechanical properties at a certain size.In the structural design,the optimal size model should be obtained first in combination with the optimization algorithm for the protection design.

关键词： Bionic Gradient sizes Function principle Constitutive model The global simulated annealing optimization algorithm

Chidamide-BEAC plus autologous stem cell transplantation in high-risk non-Hodgkin lymphoma:a phase II clinical trial

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Chinese Medical Journal 2023年第12期136卷 1491-1493页

作者： Yi Xia li Wang Kaiyang Ding Jiazhu Wu Hua Yin Maogui Hu Haorui Shen Jinhua liang Ruize Chen Yue li Huayuan Zhu jianyong li Wei Xu Department of Hematology The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingJiangsu 210029China Key Laboratory of Hematology of Nanjing Medical University NanjingJiangsu 210029China Collaborative Innovation Center for Cancer Personalized Medicine NanjingJiangsu 210029China Department of Hematology The First Affiliated Hospital of USTC Anhui Provincial HospitalHefeiAnhui 230001China National Clinical Research Center for Hematologic Diseases The First Affiliated Hospital of Soochow UniversitySuzhouJiangsu 215000China

To the Editor:Non-Hodgkin lymphoma(NHL)is a common type of hematological malignancy.Although the development of targeted therapies has improved the survival of patients with aggressive NHL,autologous hematopoietic stem cell transplantation(HSCT)remains indispensable.There is no standard conditioning regimen for autologous stem cell transplantation(ASCT).

关键词： autologous lymphoma NHL

Characteristics and prognostic value of extramedullary chromosomal abnormalities in extramedullary myeloma

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Chinese Medical Journal 2022年第20期135卷 2500-2502页

作者： Yuan Xia Yu Shi Zhi Chen Jue Zhang Yu Zhu Rui Guo Run Zhang Qinglin Shi jianyong li lijuan Chen Department of Hematology The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China Department of Hematology The Affiliated Taizhou People's Hospital of Nanjing Medical UniversityTaizhouJiangsu 225300China Department of Hematology Jiangsu Province HospitalNanjingJiangsu 210029China

To the Editor:Multiple myeloma(MM),the second most common hematological malignancy,is caused by clonal proliferation of plasma cells and presents characteristics including anemia,bone pain,renal insufficiency,and hypercalcemia.The adhesion of myeloma cells to the bone marrow(BM)microenvironment results in the mainly intramedullary involvement of MM,and sometimes,however,plasma cells can disseminate and infiltrate into extramedullary(EM)sites.

关键词： medullary myeloma involvement

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原发纵隔大B细胞淋巴瘤的治疗进展

中华血液学杂志 2024年第1期45卷 98-102页

作者：陈吕雯李建勇范磊南京医科大学第一附属医院江苏省人民医院血液科南京210029

原发纵隔大B细胞淋巴瘤(PMBCL)是一种起源于胸腺的侵袭性B细胞淋巴瘤。具有不同于非特指型弥漫大B细胞淋巴瘤的临床和生物学特征,PMBCL好发于年轻女性,通常表现为前纵隔巨大肿块,大多数患者就诊时处于Ⅰ~Ⅱ期,目前尚无标准的PMBCL预后... 详细信息

原发纵隔大B细胞淋巴瘤(PMBCL)是一种起源于胸腺的侵袭性B细胞淋巴瘤。具有不同于非特指型弥漫大B细胞淋巴瘤的临床和生物学特征,PMBCL好发于年轻女性,通常表现为前纵隔巨大肿块,大多数患者就诊时处于Ⅰ~Ⅱ期,目前尚无标准的PMBCL预后评分系统。PMBCL治疗多采用免疫化疗,但最佳一线治疗方案尚无定论,并且放疗的地位存在争议,PET-CT指导治疗的价值有待进一步证实。复发/难治PMBCL预后较差,PD-1抑制剂、维布妥昔单抗和CAR-T细胞等新型疗法有助于改善此类患者生存。

关键词：弥漫大B细胞淋巴瘤前纵隔免疫化疗原发纵隔大B细胞淋巴瘤一线治疗方案年轻女性复发/难治指导治疗