In order to understand the effect of gradual changes in photoperiod on immune function, adult female Siberian hamsters (Phodopus sungorus) were randomly divided into the control group (12L:12D, Con, n = 11) and the sh...In order to understand the effect of gradual changes in photoperiod on immune function, adult female Siberian hamsters (Phodopus sungorus) were randomly divided into the control group (12L:12D, Con, n = 11) and the shortening day length group (SD, n = 11), in which day length was reduced from 12:12 h to 8:16 h light-dark cycle at the pace of half an hour every week. Meanwhile the winter immunoenhancement hypothesis, which holds that animals’ immune function would be enhanced in winter or winter-like conditions, was tested. Gradual shortening day length had no effect on body mass and body composition including wet carcass mass, the subcutaneous, retroperitoneal, mesenteric and total body fat masses in Siberian hamsters. The masses of liver and small intestine with contents were higher in the SD group than in the Con group, however other organ masses such as brain, heart, kidney and so on did not differ between the two groups. Phytohemagglutinin (PHA) response after 24 h of PHA injection was enhanced by the shortening photoperiod, which supported the winter immunoenhancement hypothesis. The masses of spleen and thymus, white blood cells, bacteria killing capacity indicative of innate immunity were not affected, which did not support this hypothesis. In summary, gradually decrease in day length increased cellular immunity, but had no effect on other immunological parameters in Siberian hamsters.展开更多
With the maturity and development of 5G field,Mobile Edge CrowdSensing(MECS),as an intelligent data collection paradigm,provides a broad prospect for various applications in IoT.However,sensing users as data uploaders...With the maturity and development of 5G field,Mobile Edge CrowdSensing(MECS),as an intelligent data collection paradigm,provides a broad prospect for various applications in IoT.However,sensing users as data uploaders lack a balance between data benefits and privacy threats,leading to conservative data uploads and low revenue or excessive uploads and privacy breaches.To solve this problem,a Dynamic Privacy Measurement and Protection(DPMP)framework is proposed based on differential privacy and reinforcement learning.Firstly,a DPM model is designed to quantify the amount of data privacy,and a calculation method for personalized privacy threshold of different users is also designed.Furthermore,a Dynamic Private sensing data Selection(DPS)algorithm is proposed to help sensing users maximize data benefits within their privacy thresholds.Finally,theoretical analysis and ample experiment results show that DPMP framework is effective and efficient to achieve a balance between data benefits and sensing user privacy protection,in particular,the proposed DPMP framework has 63%and 23%higher training efficiency and data benefits,respectively,compared to the Monte Carlo algorithm.展开更多
Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-c...Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-cell products and advances in CAR T cell therapy,CAR T cells are expected to be used in a growing number of cases.However,CAR T-cell-associated toxicities can be severe or even fatal,thus compromising the survival benefit from this therapy.Standardizing and studying the clinical management of these toxicities are imperative.In contrast to other hematological malignancies,such as acute lymphoblastic leukemia and multiple myeloma,anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features,most notably local cytokine-release syndrome(CRS).However,previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL.Consequently,we developed this consensus for the prevention,recognition,and management of these toxicities,on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions.This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management,and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS.展开更多
To the Editor:After chimeric antigen receptor T(CAR-T)cell therapy,over 90%of patients experience either mild or severe cytopenia,with the prevalence of Grades 3–4 neutropenia ranging from 53%to 94.3%.[1,2]Granulocyt...To the Editor:After chimeric antigen receptor T(CAR-T)cell therapy,over 90%of patients experience either mild or severe cytopenia,with the prevalence of Grades 3–4 neutropenia ranging from 53%to 94.3%.[1,2]Granulocyte colony-stimulating factor(G-CSF),known for its ability to enhance the proliferation and differentiation of neutrophils,has been extensively employed for the prevention and treatment of neutropenia in various contexts.However,its application in patients with refractory/relapsing B-cell acute lymphoblastic leukemia(R/R B-ALL)after CAR-T cell therapy remains a topic of debate.[3]Several studies have suggested that G-CSF may exert anti-inflammatory effects by modulating the release of inflammatory factors,such as interleukin-12(IL-12),TNF-α,and IFN-γ,or by influencing the differentiation of T-cell subsets.[4]However,other researchers have posited that G-CSF could exacerbate cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)through the augmentation of antigen-presenting cell function.展开更多
To the Editor:Chimeric antigen receptor(CAR)-T-cell therapy has made considerable breakthroughs in the treatment of lymphoma and myeloma,but the lack of suitable or specific targets for acute myelocytic leukemia(AML)h...To the Editor:Chimeric antigen receptor(CAR)-T-cell therapy has made considerable breakthroughs in the treatment of lymphoma and myeloma,but the lack of suitable or specific targets for acute myelocytic leukemia(AML)has limited the progress of CAR-T-cell therapy in the clinical treatment of AML.Cluster of differentiation(CD)312,a member of the adhesion G protein-coupled receptor family,is highly expressed in acute myeloid leukemia and absent in normal hematopoietic stem cells(HSCs),[1]making it a potential target antigen for CART-cell therapy.In this study,we assessed the expression of CD312 in AML cell lines and patients and constructed anti-CD312 CAR-T cells,which showed excellent antitumor activity and safety in vitro and in vivo.Notably,CD312 CAR-T cells exhibited no significant off-target effects,suggesting their potential as an effective and safe treatment strategy for AML.展开更多
Clinical question What are the recommendations for the timing,dosage,and usage of corticosteroids during cytokine release syndrome(CRS)caused by chimeric antigen receptor(CAR)-T cell therapy for hematologic malignancies?
文摘In order to understand the effect of gradual changes in photoperiod on immune function, adult female Siberian hamsters (Phodopus sungorus) were randomly divided into the control group (12L:12D, Con, n = 11) and the shortening day length group (SD, n = 11), in which day length was reduced from 12:12 h to 8:16 h light-dark cycle at the pace of half an hour every week. Meanwhile the winter immunoenhancement hypothesis, which holds that animals’ immune function would be enhanced in winter or winter-like conditions, was tested. Gradual shortening day length had no effect on body mass and body composition including wet carcass mass, the subcutaneous, retroperitoneal, mesenteric and total body fat masses in Siberian hamsters. The masses of liver and small intestine with contents were higher in the SD group than in the Con group, however other organ masses such as brain, heart, kidney and so on did not differ between the two groups. Phytohemagglutinin (PHA) response after 24 h of PHA injection was enhanced by the shortening photoperiod, which supported the winter immunoenhancement hypothesis. The masses of spleen and thymus, white blood cells, bacteria killing capacity indicative of innate immunity were not affected, which did not support this hypothesis. In summary, gradually decrease in day length increased cellular immunity, but had no effect on other immunological parameters in Siberian hamsters.
基金supported in part by the National Natural Science Foundation of China under Grant U1905211,Grant 61872088,Grant 62072109,Grant 61872090,and Grant U1804263in part by the Guangxi Key Laboratory of Trusted Software under Grant KX202042+3 种基金in part by the Science and Technology Major Support Program of Guizhou Province under Grant 20183001in part by the Science and Technology Program of Guizhou Province under Grant 20191098in part by the Project of High-level Innovative Talents of Guizhou Province under Grant 20206008in part by the Open Research Fund of Key Laboratory of Cryptography of Zhejiang Province under Grant ZCL21015.
文摘With the maturity and development of 5G field,Mobile Edge CrowdSensing(MECS),as an intelligent data collection paradigm,provides a broad prospect for various applications in IoT.However,sensing users as data uploaders lack a balance between data benefits and privacy threats,leading to conservative data uploads and low revenue or excessive uploads and privacy breaches.To solve this problem,a Dynamic Privacy Measurement and Protection(DPMP)framework is proposed based on differential privacy and reinforcement learning.Firstly,a DPM model is designed to quantify the amount of data privacy,and a calculation method for personalized privacy threshold of different users is also designed.Furthermore,a Dynamic Private sensing data Selection(DPS)algorithm is proposed to help sensing users maximize data benefits within their privacy thresholds.Finally,theoretical analysis and ample experiment results show that DPMP framework is effective and efficient to achieve a balance between data benefits and sensing user privacy protection,in particular,the proposed DPMP framework has 63%and 23%higher training efficiency and data benefits,respectively,compared to the Monte Carlo algorithm.
基金supported by funds from the National Natural Science Foundation of China(Grant Nos.81830002,81830004,82070168,and 32070951)the Translational Research grant of NCRCH(Grant No.2020ZKZC04)National Key R&D Program of China(Grant No.2021YFA1100800)。
文摘Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-cell products and advances in CAR T cell therapy,CAR T cells are expected to be used in a growing number of cases.However,CAR T-cell-associated toxicities can be severe or even fatal,thus compromising the survival benefit from this therapy.Standardizing and studying the clinical management of these toxicities are imperative.In contrast to other hematological malignancies,such as acute lymphoblastic leukemia and multiple myeloma,anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features,most notably local cytokine-release syndrome(CRS).However,previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL.Consequently,we developed this consensus for the prevention,recognition,and management of these toxicities,on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions.This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management,and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS.
基金supported by grants from the General Project of the National Natural Science Foundation of China(No.81970180)the Science and Technology Project of Tianjin Municipal Health Committee(No.TJWJ2022QN030)+7 种基金the Key projects of Tianjin Applied Basic Research and Multi-Investment Fund(No.21JCZDJC01240)the Science and Technology Project of Tianjin Municipal Health Committee(No.TJWJ2022XK018)Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJYXZDXK-056B)Tianjin Municipal Natural Science Foundation(No.22JCQNJC00820)Tianjin Health Research Project(No.TJWJ2023QN027)Tianjin Health Bureau Project(No.ZC20074)Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJWJ2023XK010)Henan Provincial Youth and Middle-aged Health Science and Technology Talents Excellent Youth Program(No.20230273).
文摘To the Editor:After chimeric antigen receptor T(CAR-T)cell therapy,over 90%of patients experience either mild or severe cytopenia,with the prevalence of Grades 3–4 neutropenia ranging from 53%to 94.3%.[1,2]Granulocyte colony-stimulating factor(G-CSF),known for its ability to enhance the proliferation and differentiation of neutrophils,has been extensively employed for the prevention and treatment of neutropenia in various contexts.However,its application in patients with refractory/relapsing B-cell acute lymphoblastic leukemia(R/R B-ALL)after CAR-T cell therapy remains a topic of debate.[3]Several studies have suggested that G-CSF may exert anti-inflammatory effects by modulating the release of inflammatory factors,such as interleukin-12(IL-12),TNF-α,and IFN-γ,or by influencing the differentiation of T-cell subsets.[4]However,other researchers have posited that G-CSF could exacerbate cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)through the augmentation of antigen-presenting cell function.
基金supported by grants from the General Project of the National Natural Science Foundation of China(No.81970180)the Science and Technology Project of Tianjin Municipal Health Committee(No.TJWJ2022QN030)+6 种基金the Key Projects of Tianjin Applied Basic Research and Multi-Investment Fund(No.21JCZDJC01240)the Science and Technology Project of Tianjin Municipal Health Committee(No.TJWJ2022XK018)the Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJYXZDXK-056B)the Tianjin Municipal Natural Science Foundation(No.22JCQNJC00820)the Tianjin Health Research Project(No.TJWJ2023QN027)the Tianjin Health Bureau Project(No.ZC20074)the Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJWJ2023XK010).
文摘To the Editor:Chimeric antigen receptor(CAR)-T-cell therapy has made considerable breakthroughs in the treatment of lymphoma and myeloma,but the lack of suitable or specific targets for acute myelocytic leukemia(AML)has limited the progress of CAR-T-cell therapy in the clinical treatment of AML.Cluster of differentiation(CD)312,a member of the adhesion G protein-coupled receptor family,is highly expressed in acute myeloid leukemia and absent in normal hematopoietic stem cells(HSCs),[1]making it a potential target antigen for CART-cell therapy.In this study,we assessed the expression of CD312 in AML cell lines and patients and constructed anti-CD312 CAR-T cells,which showed excellent antitumor activity and safety in vitro and in vivo.Notably,CD312 CAR-T cells exhibited no significant off-target effects,suggesting their potential as an effective and safe treatment strategy for AML.
基金supported by grants from the National Natural Science Foundation of China(Nos.82270233,81830004 and 82070168)National Natural Science Foundation of China Youth Science Foundation Project(No.82200246)+2 种基金Translational Research Grant of NCRCH(No.2020ZKZC04)National Key R&D Program of China(No.2021YFA1100800)Shanghai Municipal Health Commission(No.2020CXJQ02).
文摘Clinical question What are the recommendations for the timing,dosage,and usage of corticosteroids during cytokine release syndrome(CRS)caused by chimeric antigen receptor(CAR)-T cell therapy for hematologic malignancies?
