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 enhancement of perpendicular magnetic anisotropy(PMA)is critical for the continuous growth of magnetic memory density.Material systems that possess high interfacial PMA typically involve strong spin-orbit coupling...The enhancement of perpendicular magnetic anisotropy(PMA)is critical for the continuous growth of magnetic memory density.Material systems that possess high interfacial PMA typically involve strong spin-orbit coupling(SOC)or transition metal/oxide interfaces.In contrast,the role of 3d light metals in enhancing the interfacial PMA has been less investigated.This study demonstrated that the insertion of a few atomic Cr layers into Pt/Co/Pt/Ta heterostructures with Cr between the 1 atomic Pt layer and the 3 nm Ta overlayer enhanced the effective PMA energy(K_(eff))by a factor of 4.First-principles calculations revealed that the underlying mechanism originated from Cr-Pt d-orbital hybridization,leading to a corresponding orbital redistribution and significantly increasing the magnetic anisotropy energy.The progressive reduction in the spin-orbit torque(SOT)efficiency with increasing Cr thickness might stem from the enhanced orbital Rashba–Edelstein effect at the Pt/Cr interface.Furthermore,the wedging of a few atomic Cr layers caused the robust field-free SOT switching of perpendicular magnetization,which was due to the lateral PMA gradients enabled by the strong dependence of the PMA on the Cr thickness.The results provide a method for interfacial PMA enhancement by d-orbital hybridization of 3d–5d electrons and an alternative to field-free SOT switching towards low-power and high-density memory applications.展开更多
嵌合抗原受体T细胞(chimeric antigen receptor T cells,CAR-T)的出现使得多发性骨髓瘤(multiple myeloma,MM)患者的治疗进入了一个新的阶段,但大多数患者都难逃原发耐药或疾病复发的不良结局。G蛋白偶联受体C类5组成员D(G protein-coup...嵌合抗原受体T细胞(chimeric antigen receptor T cells,CAR-T)的出现使得多发性骨髓瘤(multiple myeloma,MM)患者的治疗进入了一个新的阶段,但大多数患者都难逃原发耐药或疾病复发的不良结局。G蛋白偶联受体C类5组成员D(G protein-coupled receptor class C group 5 member D,GPRC5D)是目前MM患者的一个有前景的治疗靶点,与GPRC5D CAR-T相关的Ⅰ期临床研究也都显示出较高的反应率和疗效。文章将对现有的靶向GPRC5D CAR-T细胞最新研究进行综述,旨在通过总结讨论目前不同GPRC5D CAR-T细胞治疗复发难治性MM的研究现状,对今后的临床治疗提供更多参考。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 “Pioneer” and “Leading Goose” R&D Program of Zhejiang Province (Grant No.2022C01053)the National Natural Science Foundation of China (Grant No.62293493)the Natural Science Foundation of Zhejiang Province,China (Grant No.LQ21A050001)。
文摘The enhancement of perpendicular magnetic anisotropy(PMA)is critical for the continuous growth of magnetic memory density.Material systems that possess high interfacial PMA typically involve strong spin-orbit coupling(SOC)or transition metal/oxide interfaces.In contrast,the role of 3d light metals in enhancing the interfacial PMA has been less investigated.This study demonstrated that the insertion of a few atomic Cr layers into Pt/Co/Pt/Ta heterostructures with Cr between the 1 atomic Pt layer and the 3 nm Ta overlayer enhanced the effective PMA energy(K_(eff))by a factor of 4.First-principles calculations revealed that the underlying mechanism originated from Cr-Pt d-orbital hybridization,leading to a corresponding orbital redistribution and significantly increasing the magnetic anisotropy energy.The progressive reduction in the spin-orbit torque(SOT)efficiency with increasing Cr thickness might stem from the enhanced orbital Rashba–Edelstein effect at the Pt/Cr interface.Furthermore,the wedging of a few atomic Cr layers caused the robust field-free SOT switching of perpendicular magnetization,which was due to the lateral PMA gradients enabled by the strong dependence of the PMA on the Cr thickness.The results provide a method for interfacial PMA enhancement by d-orbital hybridization of 3d–5d electrons and an alternative to field-free SOT switching towards low-power and high-density memory applications.
文摘目的探索人工智能辅助压缩感知(artificial intelligence-assisted compressed sensing,ACS)技术加速颅内血管壁高分辨率三维T1加权黑血成像(three-dimensional T1-weighted black blood imaging,3D T1_HRVWI)的可行性,并与临床常规采用的并行采集技术(parallel imaging,PI)进行对比分析。方法前瞻性纳入47例脑血管疾病患者,行ACS加速(实验组)和PI加速(对照组)的3D T1_HRVWI扫描。客观比较ACS组和PI组的序列扫描时长、图像中血管壁的信噪比以及相对于血管腔的对比噪声比,主观评估两组图像总体质量、颅内血管显示情况及病灶诊断价值,并进行统计分析。结果相较于PI 3D T1_HRVWI,ACS 3D T1_HRVWI的扫描时长缩短43%;ACS 3D T1_HRVWI图像中颈内动脉、基底动脉、椎动脉、大脑前动脉、大脑中动脉、大脑后动脉血管壁的信噪比均显著升高(P<0.001);两组图像的总体质量评分和颅内血管的显示评分均未见显著差异(P>0.05);两组图像的病灶诊断价值相当(P>0.05)。结论ACS技术实现了3D T1_HRVWI序列更快的采集速度,同时保持了较好的成像质量,为开发兼顾扫描效率与诊断精度的脑血管影像扫描方案提供了循证依据,在脑血管疾病的精准诊断中展现出重要价值。
文摘嵌合抗原受体T细胞(chimeric antigen receptor T cells,CAR-T)的出现使得多发性骨髓瘤(multiple myeloma,MM)患者的治疗进入了一个新的阶段,但大多数患者都难逃原发耐药或疾病复发的不良结局。G蛋白偶联受体C类5组成员D(G protein-coupled receptor class C group 5 member D,GPRC5D)是目前MM患者的一个有前景的治疗靶点,与GPRC5D CAR-T相关的Ⅰ期临床研究也都显示出较高的反应率和疗效。文章将对现有的靶向GPRC5D CAR-T细胞最新研究进行综述,旨在通过总结讨论目前不同GPRC5D CAR-T细胞治疗复发难治性MM的研究现状,对今后的临床治疗提供更多参考。
