Molecular Therapy最新文献_第6页

High-dimensional temporal mapping of CAR T cells reveals phenotypic and functional remodeling during manufacturing. CAR - T细胞的高维时间图谱揭示了制造过程中的表型和功能重塑。

IF 12.4 1区医学

Molecular Therapy Pub Date : 2025-04-30 DOI: 10.1016/j.ymthe.2025.04.006

Amaia Cadinanos-Garai,Christian L Flugel,Anson Cheung,Enzi Jiang,Alix Vaissié,Mohamed Abou-El-Enein

{"title":"High-dimensional temporal mapping of CAR T cells reveals phenotypic and functional remodeling during manufacturing.","authors":"Amaia Cadinanos-Garai,Christian L Flugel,Anson Cheung,Enzi Jiang,Alix Vaissié,Mohamed Abou-El-Enein","doi":"10.1016/j.ymthe.2025.04.006","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.04.006","url":null,"abstract":"Despite the notable success of chimeric antigen receptor (CAR) T cell therapies in hematological malignancies, clinical outcomes remain variable, making it critical to understand how manufacturing influences product composition and function. We developed a 36-marker spectral flow cytometry panel enabling integrated profiling of phenotypic, metabolic, and functional attributes across CAR T cell production. Mid-expansion products (day 5) retained stem-like, metabolically active CD4+ Th1 subsets with high proliferative capacity, whereas prolonged culture (day 10) enriched terminally differentiated CD8+ Tc1 cells and NK-like T cell populations. CAR+ and CAR- T cells showed similar differentiation trajectories, suggesting that culture conditions may have a larger impact on phenotypic remodeling than CAR integration. Upon antigen encounter and restimulation, day 5 and day 10 products showed comparable cytotoxicity, while differing in their activation and checkpoint profiles. Cryopreservation modestly affected stem cell memory, activation, and metabolic markers but preserved overall phenotype and cytotoxic function. These findings establish a high-dimensional framework for mapping CAR T cell dynamics to support manufacturing optimization and next-generation cell therapy design.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"8 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clinical applications of exon skipping antisense oligonucleotides in neuromuscular diseases. 外显子跳跃反义寡核苷酸在神经肌肉疾病中的临床应用。

IF 12.4 1区医学

Molecular Therapy Pub Date : 2025-04-29 DOI: 10.1016/j.ymthe.2025.04.038

Laia Torres-Masjoan,Sara Aguti,Haiyan Zhou,Francesco Muntoni

{"title":"Clinical applications of exon skipping antisense oligonucleotides in neuromuscular diseases.","authors":"Laia Torres-Masjoan,Sara Aguti,Haiyan Zhou,Francesco Muntoni","doi":"10.1016/j.ymthe.2025.04.038","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.04.038","url":null,"abstract":"Four exon skipping antisense oligonucleotides (ASOs) have been approved by the US Food and Drug Administration (FDA) for the treatment of Duchenne muscular dystrophy (DMD), including eteplirsen, golodirsen, viltolarsen and casimersen. Current data from long-term real-world usage of these ASOs suggests a broad safety profile and a delay in the muscle deterioration. Nevertheless, the exon skipping efficacy and dystrophin protein production of these ASOs are limited, suggesting the need of more efficient ASOs. Over the past decade, many studies have focused on improving ASOs efficacy by incorporating novel chemical modifications or bioconjugations of a variety of moieties including peptides or antibodies to increase their cellular uptake by muscle cells, their endosomal escape, and nuclear import to boost therapeutic efficacy. Many of these newly developed exon skipping ASOs have been studied in clinical trials in DMD patients, and early findings suggest clear improvements in molecular efficacy compared to the earlier version of ASOs, although the safety track record may not be the same as the first generation compounds. Here, we summarise the recent preclinical and clinical developments of ASOs and discuss the future challenges of exon skipping therapies for DMD and other neuromuscular diseases.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"21 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Engineering TME-gated inducible CAR-T cell therapy for solid tumors. 工程tme门控诱导CAR-T细胞治疗实体肿瘤。

IF 12.4 1区医学

Molecular Therapy Pub Date : 2025-04-29 DOI: 10.1016/j.ymthe.2025.04.037

Huong T X Nguyen,Byung-Gyu Kim,Jay T Myers,Hao Yan,Satendra Kumar,Saada Eid,Wei Wang,Alex Y Huang,Fu-Sen Liang

{"title":"Engineering TME-gated inducible CAR-T cell therapy for solid tumors.","authors":"Huong T X Nguyen,Byung-Gyu Kim,Jay T Myers,Hao Yan,Satendra Kumar,Saada Eid,Wei Wang,Alex Y Huang,Fu-Sen Liang","doi":"10.1016/j.ymthe.2025.04.037","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.04.037","url":null,"abstract":"Autonomous \"living drug\" Chimeric Antigen Receptor (CAR)-T cell therapy has revolutionized cancer medicine. However, concerns about on-target off-tumor T cell activation and resulting toxicities require advanced precise regulatory control systems for CAR-T. Here, we present a novel strategy using a genetic \"AND\" gate that integrates chemically-induced proximity (CIP) and tumor-activated prodrug approaches to generate the next generation CAR-T cell, namely TME-iCAR-T cell, that are capable of sensing multiple tumor-specific characteristics (i.e., tumor antigens and tumor microenvironment (TME) signals) to precisely execute therapeutic functions within the TME. This design was built on the abscisic acid (ABA)-based CIP and its associated reactivity-based caging/sensing technology. Hypoxia-responsive small molecule prodrugs were developed by conjugating ABA with different nitroaromatic derivatives, which render ABA inactive until the unique sensing moieties are removed by specific cancer signals in the TME. We demonstrated that TME-iCAR-T cells respond specifically to the chosen tumor signal combination in vitro and resulted in remarkable cancer signals-restricted activation and cytotoxicity to cancer cells. We also showed their controllability and antitumor efficacy in vivo using a xenograft prostate tumor model. Our highly modular multi-criteria control system in CAR-T represents a new promising strategy to enhance the tumor selectivity and safety of future cell-based immunotherapies.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"224 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

BIN1 gene replacement reverts BIN1-related centronuclear myopathy. BIN1基因替代可恢复与BIN1相关的中央核肌病。

IF 12.4 1区医学

Molecular Therapy Pub Date : 2025-04-29 DOI: 10.1016/j.ymthe.2025.04.036

Jacqueline Ji,Quentin Giraud,Nadège Diedhiou,Eva Lipkow,Coralie Spiegelhalter,Jocelyn Laporte

{"title":"BIN1 gene replacement reverts BIN1-related centronuclear myopathy.","authors":"Jacqueline Ji,Quentin Giraud,Nadège Diedhiou,Eva Lipkow,Coralie Spiegelhalter,Jocelyn Laporte","doi":"10.1016/j.ymthe.2025.04.036","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.04.036","url":null,"abstract":"Centronuclear myopathies (CNM) are severe genetic disorders characterized by generalized muscle weakness associated with organelle mispositioning in myofibers. Most CNM cases are caused by mutations in proteins involved in membrane remodeling, including amphiphysin 2 (BIN1). There is no treatment and the pathological mechanisms are not understood. Here, we aimed to cure the Bin1-CNM mouse model (Bin1mck-/-) via an adeno-associated virus (AAV)-based gene replacement strategy. Early systemic exogenous BIN1 expression efficiently prevented disease progression. Moreover, BIN1 expression after disease onset reverted all disease signs four weeks after treatment, including motor defects, muscle weakness, muscle and myofibers hypotrophy, kyphosis, nuclei and mitochondria misposition, and altered T-tubules network. We then validated the most efficient construct combining a myotropic AAV serotype with the muscle BIN1 isoform. The rescue correlated with normalization of autophagy and excitation-contraction coupling markers. Cellular and in vivo investigations revealed that different BIN1 natural isoforms shared similar beneficial effects. Artificial constructs coding for separated protein domains rescued different CNM hallmarks. Only the muscle-specific BIN1 isoform combined the different cellular functions of BIN1 on membrane tubulation and dynamin (DNM2) regulation necessary for a full rescue. Overall, this study validates BIN1 gene replacement as a promising strategy to cure BIN1-related centronuclear myopathy.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"11 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Perspectives and open questions in vision restoration with vMCO-010. vMCO-010在视力恢复中的应用前景与问题。

IF 12.4 1区医学

Molecular Therapy Pub Date : 2025-04-24 DOI: 10.1016/j.ymthe.2025.04.017

Moritz Lindner

引用次数: 0

Age sensitive response of systemic AAV-mediated gene therapy in a newly characterized feline model of mucolipidosis II. aav介导的全体性基因治疗在一种新特征的猫粘脂病模型中的年龄敏感反应。

IF 12.4 1区医学

Molecular Therapy Pub Date : 2025-04-24 DOI: 10.1016/j.ymthe.2025.04.030

Nettie K Pyne,Jessica Bagel,Charles Shyng,Patricia Odonnell,Keiko Miyadera,Jennifer Srnak,Gary Swain,Jill P Pesayco,G Diane Shelton,Charles-Antoine Assenmacher,Patricia Dickson,Joshua Stern,Heather Flanagan-Steet,Steven J Gray,Allison M Bradbury

{"title":"Age sensitive response of systemic AAV-mediated gene therapy in a newly characterized feline model of mucolipidosis II.","authors":"Nettie K Pyne,Jessica Bagel,Charles Shyng,Patricia Odonnell,Keiko Miyadera,Jennifer Srnak,Gary Swain,Jill P Pesayco,G Diane Shelton,Charles-Antoine Assenmacher,Patricia Dickson,Joshua Stern,Heather Flanagan-Steet,Steven J Gray,Allison M Bradbury","doi":"10.1016/j.ymthe.2025.04.030","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.04.030","url":null,"abstract":"Mucolipidosis II (MLII) is a lysosomal storage disorder caused by mutations in GNPTAB and loss of mannose 6-phosphate-dependent targeting of lysosomal enzymes. Affected children exhibit cognitive deficits, skeletal dysplasia and cardio-pulmonary disease with death typically occurring before ten. A naturally occurring feline model of MLII results from a nonsense mutation in GNPTAB; cats develop elevated lysosomal enzyme activities, growth retardation, skeletal deformities, blindness, cardiomegaly, and die prematurely. Most LSDs exhibit central nervous system disease, which is a primary contributor to morbidity and mortality. Therefore, we evaluated nervous system disease in feline MLII. MLII cats lived to approximately 5 months of age, had impairments in hearing and sensory nerve conduction, hydrocephalus, and increased expression of lysosomal associated membrane protein 1. Quantification of cytokines and chemokines revealed dysregulation, elucidating potential pathomechanisms and non-invasive biomarkers. We then evaluated adeno-associated virus (AAV)-mediated gene therapy. MLII cats were treated with AAV9 encoding feline GNPTAB. High dose AAV9-fGNPTAB intervention in the first week of life was fatal; however, delaying treatment to 4 weeks was tolerated. Correction was not complete, however, the highest dose resulted in greatest correction of ophthalmic, skeletal, and cardiac disease associated with MLII.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"9 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143885497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Truncated complement factor H Y402 gene therapy rescues C3 glomerulonephritis. 截断补体因子hy402基因治疗C3型肾小球肾炎。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-04-24 DOI: 10.1016/j.ymthe.2025.04.035

Lindsey A Chew, Daniel Grigsby, C Garren Hester, Joshua Amason, W Kyle McPherson, Edward J Flynn, Meike Visel, Christopher R Starr, John G Flannery, Tylor R Lewis, Catherine Bowes Rickman

{"title":"Truncated complement factor H Y402 gene therapy rescues C3 glomerulonephritis.","authors":"Lindsey A Chew, Daniel Grigsby, C Garren Hester, Joshua Amason, W Kyle McPherson, Edward J Flynn, Meike Visel, Christopher R Starr, John G Flannery, Tylor R Lewis, Catherine Bowes Rickman","doi":"10.1016/j.ymthe.2025.04.035","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.04.035","url":null,"abstract":"There are no effective therapies for patients with dry age-related macular degeneration (AMD) or C3 glomerulonephritis (C3G). Unfortunately, past efforts to treat C3G using exogenous human complement factor H (CFH) found limited success due to immune rejection of a foreign protein response. AMD research has also faced myriad challenges, including the absence of an ideal therapeutic target and difficulties with treatment delivery in certain preclinical models. In pursuit of an AMD therapy to overcome these obstacles, we ultimately capitalized on parallels in complement dysregulation between AMD and C3G. Here, we investigate the potential for CFH supplementation as a strategy to rescue C3G. Our findings demonstrate restored inhibition of complement's alternative pathway and long-term reversal of disease without immune rejection using adeno-associated virus (AAV)-mediated delivery of truncated CFH (tCFH) in a Cfh-/- mouse model of C3G. We tested three different tCFH vectors and found significant differences in their relative transduction efficiency and therapeutic efficacy. These discoveries motivate the development of AAV-mediated tCFH replacement therapy for patients with C3G while simultaneously demonstrating proof of concept for AAV-mediated tCFH gene augmentation therapy for patients with AMD.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Response: Promise and open questions of optogenetic vision restoration by MCO. 回应：MCO光遗传视力恢复的前景和悬而未决的问题。

IF 12.4 1区医学

Molecular Therapy Pub Date : 2025-04-24 DOI: 10.1016/j.ymthe.2025.04.018

Samarendra K Mohanty,Santosh Mahapatra,Subrata Batabyal,Michael Carlson,Gayatri Kanungo,Ananta Ayyagari,Kissaou Tchedre,Joel A Franco,Michael Singer,Samuel Barone,Sai Chavala,Vinit B Mahajan

引用次数: 0

ErbB2/HER2-targeted CAR-NK cells eliminate breast cancer cells in an organoid model that recapitulates tumor progression. 在一个再现肿瘤进展的类器官模型中，ErbB2/ her2靶向CAR-NK细胞消除乳腺癌细胞。

IF 12.4 1区医学

Molecular Therapy Pub Date : 2025-04-24 DOI: 10.1016/j.ymthe.2025.04.033

Jasmin Röder,Tijna Alekseeva,Anne Kiefer,Ines Kühnel,Maren Prüfer,Congcong Zhang,Malena Bodden,Sebastian Rosigkeit,Anja Waldmann,Torsten Tonn,Ernesto Bockamp,Stefan Stein,Winfried S Wels

{"title":"ErbB2/HER2-targeted CAR-NK cells eliminate breast cancer cells in an organoid model that recapitulates tumor progression.","authors":"Jasmin Röder,Tijna Alekseeva,Anne Kiefer,Ines Kühnel,Maren Prüfer,Congcong Zhang,Malena Bodden,Sebastian Rosigkeit,Anja Waldmann,Torsten Tonn,Ernesto Bockamp,Stefan Stein,Winfried S Wels","doi":"10.1016/j.ymthe.2025.04.033","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.04.033","url":null,"abstract":"Chimeric antigen receptor-engineered NK cells hold promise for adoptive cancer immunotherapy. In one such approach, the ErbB2 (HER2)-specific CAR-NK cell line NK-92/5.28.z is under investigation as an off-the-shelf therapy in a phase I trial in glioblastoma patients. To evaluate activity of NK-92/5.28.z cells against ErbB2-positive breast cancer, here we developed an organoid model derived from CKP mice that allows conditional activation of oncogenic driver mutations. Expression of ErbB2 and Cre recombinase in CKP mammary epithelial cells induced malignant transformation, with the resulting EC-CKP cells characterized by neoplastic morphology, loss of p53 and constitutive activation of the MAP kinase pathway. NK-92/5.28.z cells demonstrated potent CAR-mediated cytotoxicity against EC-CKP organoids, with tumor cell lysis dependent on exposure time and organoid size. In vivo passaging of EC-CKP organoids revealed cellular plasticity and induced an EMT phenotype associated with increased resistance to standard therapies. Importantly, NK-92/5.28.z cells retained high and specific cytotoxicity against these breast cancer cells in vitro and in an aggressive organoid-based in vivo mouse model that reflects advanced-stage disease. Our data highlight the therapeutic potential of NK-92/5.28.z cells against ErbB2-positive breast cancer, supporting their further development toward clinical application.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"9 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143885484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A novel tolerogenic antigen-specific vaccine induces VISTA-enriched regulatory T cells and protects against arthritis in DRB1*04:01 mice. 一种新的耐受性抗原特异性疫苗诱导富含vista的调节性T细胞，并对DRB1*04:01小鼠的关节炎有保护作用。

IF 12.4 1区医学

Molecular Therapy Pub Date : 2025-04-24 DOI: 10.1016/j.ymthe.2025.04.034

Laura Romero-Castillo,Rajan Kumar Pandey,Bingze Xu,Christian M Beusch,Ana Oliveira-Coelho,Kejsi Zeqiraj,Carolin Svensson,Zhongwei Xu,Huqiao Luo,Outi Sareila,Pierre Sabatier,Changrong Ge,Lei Cheng,Vilma Urbonaviciute,Alexander Krämer,Cecilia Lindgren,Sabrina Haag,Johan Viljanen,Roman A Zubarev,Jan Kihlberg,Anna Linusson,Harald Burkhardt,Rikard Holmdahl

{"title":"A novel tolerogenic antigen-specific vaccine induces VISTA-enriched regulatory T cells and protects against arthritis in DRB1*04:01 mice.","authors":"Laura Romero-Castillo,Rajan Kumar Pandey,Bingze Xu,Christian M Beusch,Ana Oliveira-Coelho,Kejsi Zeqiraj,Carolin Svensson,Zhongwei Xu,Huqiao Luo,Outi Sareila,Pierre Sabatier,Changrong Ge,Lei Cheng,Vilma Urbonaviciute,Alexander Krämer,Cecilia Lindgren,Sabrina Haag,Johan Viljanen,Roman A Zubarev,Jan Kihlberg,Anna Linusson,Harald Burkhardt,Rikard Holmdahl","doi":"10.1016/j.ymthe.2025.04.034","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.04.034","url":null,"abstract":"Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation, cartilage damage and bone erosion. Despite improvements with the introduction of biological disease-modifying anti-rheumatic drugs (DMARDs), RA remains an incurable life-lasting disease. Advancements in peptide-based vaccination may open new avenues for treating autoimmune diseases, including RA, by inducing immune tolerance while maintaining normal immune function. Previously we have already demonstrated the efficacy of a potent vaccine against RA, consisting of the mouse major histocompatibility complex class II (Aq) protein bound to the immunodominant type II collagen peptide COL2259-273, which needed to be galactosylated at position 264. To translate the vaccine to humans and to further enhance vaccine efficacy, we modified the glycine residue at position 265 and conjugated it with the human DRB1*04:01 molecule. Remarkably, this modified vaccine (named DR4-AL179) provided robust effectiveness in suppressing arthritis in DRB1*04:01-expressing mice without the need for galactosylation at position 264. DR4-AL179 vaccination induces tolerance involving multiple immunoregulatory pathways, including the activation of VISTA-positive nonconventional regulatory T cells, which contribute to a potent suppressive response preventing arthritis development in mice. This modified RA vaccine offers a novel therapeutic potential for human autoimmune diseases.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"19 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143885482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0