多发性骨髓瘤(multiple myeloma,MM)是一种不可治愈的血液系统恶性肿瘤,尽管新型蛋白酶体抑制剂、免疫调节剂及CD38单抗等药物的应用显著延长了患者的生存时间,但复发耐药仍难以避免。细胞免疫治疗,特别是嵌合抗原受体(chimeric antigen...多发性骨髓瘤(multiple myeloma,MM)是一种不可治愈的血液系统恶性肿瘤,尽管新型蛋白酶体抑制剂、免疫调节剂及CD38单抗等药物的应用显著延长了患者的生存时间,但复发耐药仍难以避免。细胞免疫治疗,特别是嵌合抗原受体(chimeric antigen receptor,CAR)T细胞疗法的快速发展,极大程度的改变了复发/难治性(relapsed/refractory,R/R)MM患者的治疗现状。FDA目前已批准了2款靶向B细胞成熟抗原(B cell maturation antigen,BCMA)的CAR-T细胞产品,使其用于既往接受过4线及以上治疗的R/R MM患者。随着临床研究的不断深入,靶向GPRC5D(G protein-coupled receptor C class Group 5 member D,G蛋白偶联受体C类第5组成员D)的CAR-T细胞治疗也显示出其独特的优势。除了应用于难治复发的患者,多项临床试验支持CAR-T在MM中治疗线数的前移。本文就CAR-T细胞治疗在MM中开展的关键性临床研究展开综述,旨在为临床应用提供参考。展开更多
The Saccostrea mordax Gould,1850 is a typical intertidal species,whose genetic differentiation is influenced by various factors,including geological and climatic changes.To explore the genetic structure and historical...The Saccostrea mordax Gould,1850 is a typical intertidal species,whose genetic differentiation is influenced by various factors,including geological and climatic changes.To explore the genetic structure and historical population characteristics of Saccostrea mordax,we sequenced the mitochondrial cytochrome c oxidase subunit I(COI)gene from 58 specimens sampled from four locations in the western Pacific.Additionally,103 individuals from the Persian Gulf and western Pacific(from databases)were included for phylogenetic analysis.The Bayesian Inference tree showed that all specimens were divided into two clades,i.e.,the Persian Gulf population and the western Pacific population.Spatial molecular variance analysis indicated significant genetic differentiation between the two populations,and isolation by distance analysis revealed a positive correlation between genetic differentiation and geographic distance.Neutrality tests and Bayesian Skyline Plot suggested that both populations underwent expansions during the late Pleistocene.This study revealed the population history of Saccostrea mordax and described a new lineage,Saccostrea mordax lineage D,providing a foundation for understanding oyster biodiversity formation and genetic resource conservation.展开更多
文摘多发性骨髓瘤(multiple myeloma,MM)是一种不可治愈的血液系统恶性肿瘤,尽管新型蛋白酶体抑制剂、免疫调节剂及CD38单抗等药物的应用显著延长了患者的生存时间,但复发耐药仍难以避免。细胞免疫治疗,特别是嵌合抗原受体(chimeric antigen receptor,CAR)T细胞疗法的快速发展,极大程度的改变了复发/难治性(relapsed/refractory,R/R)MM患者的治疗现状。FDA目前已批准了2款靶向B细胞成熟抗原(B cell maturation antigen,BCMA)的CAR-T细胞产品,使其用于既往接受过4线及以上治疗的R/R MM患者。随着临床研究的不断深入,靶向GPRC5D(G protein-coupled receptor C class Group 5 member D,G蛋白偶联受体C类第5组成员D)的CAR-T细胞治疗也显示出其独特的优势。除了应用于难治复发的患者,多项临床试验支持CAR-T在MM中治疗线数的前移。本文就CAR-T细胞治疗在MM中开展的关键性临床研究展开综述,旨在为临床应用提供参考。
基金Supported by the Key R&D Program of Shandong Province(No.2023CXGC010411)the National Key R&D Program of China(Nos.2023YFD2400800,2022YFD2401301,2022FY100304)+2 种基金the National Natural Science Foundation of China(Nos.42076092,41906083,41776179)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB42000000)the Earmarked Fund for Modern Agro-industry Technology Research System(No.CARS-47)。
文摘The Saccostrea mordax Gould,1850 is a typical intertidal species,whose genetic differentiation is influenced by various factors,including geological and climatic changes.To explore the genetic structure and historical population characteristics of Saccostrea mordax,we sequenced the mitochondrial cytochrome c oxidase subunit I(COI)gene from 58 specimens sampled from four locations in the western Pacific.Additionally,103 individuals from the Persian Gulf and western Pacific(from databases)were included for phylogenetic analysis.The Bayesian Inference tree showed that all specimens were divided into two clades,i.e.,the Persian Gulf population and the western Pacific population.Spatial molecular variance analysis indicated significant genetic differentiation between the two populations,and isolation by distance analysis revealed a positive correlation between genetic differentiation and geographic distance.Neutrality tests and Bayesian Skyline Plot suggested that both populations underwent expansions during the late Pleistocene.This study revealed the population history of Saccostrea mordax and described a new lineage,Saccostrea mordax lineage D,providing a foundation for understanding oyster biodiversity formation and genetic resource conservation.