Molecular Therapy最新文献_第5页

A singular base-editing platform for polyfunctional multiplex engineering of immune cells. 免疫细胞多功能复合工程的奇异碱基编辑平台。

IF 11.4 1区医学

Molecular Therapy Pub Date : 2026-10-07 Epub Date: 2026-07-18 DOI: 10.1016/j.ymthe.2026.07.033

Joseph G Skeate, Nicholas J Slipek, Walker S Lahr, Shambojit Roy, Bryce J Wick, Bibekananda Kar, Jae-Woong Chang, Erin M Stelljes, Alexandria K Gilkey, Prateek P Thenge, Miechaleen D Diers, Joshua B Krueger, Ethan M Niemeyer, Cara-Lin Lonetree, Mitchell G Kluesner, Jason B Bell, Kendell Clement, Paolo P Provenzano, Branden S Moriarity, Beau R Webber

{"title":"A singular base-editing platform for polyfunctional multiplex engineering of immune cells.","authors":"Joseph G Skeate, Nicholas J Slipek, Walker S Lahr, Shambojit Roy, Bryce J Wick, Bibekananda Kar, Jae-Woong Chang, Erin M Stelljes, Alexandria K Gilkey, Prateek P Thenge, Miechaleen D Diers, Joshua B Krueger, Ethan M Niemeyer, Cara-Lin Lonetree, Mitchell G Kluesner, Jason B Bell, Kendell Clement, Paolo P Provenzano, Branden S Moriarity, Beau R Webber","doi":"10.1016/j.ymthe.2026.07.033","DOIUrl":"10.1016/j.ymthe.2026.07.033","url":null,"abstract":"Current methods to engineer antigen-specific receptors rely on randomly integrating vectors or double-strand-break-induced targeted integration, both of which pose safety risks. To implement an all-in-one tool for multiplex knockout (KO) and knockin (KI), we expand the use of base editor nickase activity to stimulate homology-directed repair (HDR) and insert clinically relevant chimeric antigen receptors (CARs) into specific loci. Through a novel single-guide RNA design strategy and a DNA template delivered by a recombinant adeno-associated virus, we enhanced the efficiency of ABE8e-stimulated HDR in human T cells. By combining KI of CD19, CD33, or mesothelin-targeting CARs with >95% quadplex gene KO (B2M/CD3E/PDCD1/CISH), we achieve single-step generation of highly functional off-the-shelf CAR T cell products with enhanced function. Importantly, we found no detectable translocations or significant off-target edits and demonstrated efficacy against multiple cancer lines and a suppressive 3D spheroid culture model. This efficient engineering process of \"Iterative Nicking for Synchronous Engineered Reprogramming of T cells\" (INSERT) establishes a safe, simplified platform for advanced therapeutic CAR T engineering.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":"5858-5871"},"PeriodicalIF":11.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development of recombinant anti-TLR2 antibodies and PLGA nanoparticle-based gene therapy for the treatment of neuropathic pain. 重组抗tlr2抗体和PLGA纳米颗粒基因治疗神经性疼痛的研究进展。

IF 11.4 1区医学

Molecular Therapy Pub Date : 2026-10-07 Epub Date: 2026-07-29 DOI: 10.1016/j.ymthe.2026.07.046

Subeen Lee, Jaekyung Jeon, Hyunji Lee, Ellane Eda Barcelon, Jinpyo Hong, Sung Joong Lee

{"title":"Development of recombinant anti-TLR2 antibodies and PLGA nanoparticle-based gene therapy for the treatment of neuropathic pain.","authors":"Subeen Lee, Jaekyung Jeon, Hyunji Lee, Ellane Eda Barcelon, Jinpyo Hong, Sung Joong Lee","doi":"10.1016/j.ymthe.2026.07.046","DOIUrl":"10.1016/j.ymthe.2026.07.046","url":null,"abstract":"Neuroinflammation is a key contributor to neuropathic pain, with microglial Toll-like receptor 2 (TLR2) playing a central role in initiating and sustaining proinflammatory responses. However, existing TLR2-targeting antibodies are limited by poor delivery to the central nervous system and short-lived efficacy. We developed a non-viral gene therapy strategy using biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) to deliver recombinant anti-TLR2 antibody genes. High-affinity nanobody and single-chain variable fragment candidates were selected through phage display screening and shown to suppress TLR2-dependent signaling both in vitro and in vivo. In mouse models of neuropathic pain, a single intrathecal administration of PLGA-NP-encapsulated antibody genes produced robust and sustained analgesia, accompanied by reduced glial activation and proinflammatory cytokine expression. These findings demonstrate a modular NP-based platform for sustained antibody expression in the central nervous system and establish its potential for the treatment of chronic pain driven by innate immune activation.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":"5922-5944"},"PeriodicalIF":11.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Repurposing triamterene to target CLIC1 in glioblastoma stem cells: A new opportunity for an old drug? 利用曲安霉素靶向胶质母细胞瘤干细胞中的CLIC1：老药的新机遇？

IF 11.4 1区医学

Molecular Therapy Pub Date : 2026-10-07 Epub Date: 2026-09-25 DOI: 10.1016/j.ymthe.2026.09.010

Shubha Gururaja Rao, Aviana R Smith, Harpreet Singh

引用次数: 0

Capless self-amplifying mRNA vaccine induces dose-sparing protective immunity against HPAI clade 2.3.4.4 H5 virus in mice. 无帽自扩增mRNA疫苗诱导小鼠对HPAI分支2.3.4.4 H5病毒的剂量节约保护性免疫

IF 11.4 1区医学

Molecular Therapy Pub Date : 2026-10-07 Epub Date: 2026-07-29 DOI: 10.1016/j.ymthe.2026.07.047

Beom Kyu Kim, Ji-Hyun Park, Won-Suk Choi, Sol Oh, Se Hee An, Gi Chan Lee, Santosh Chokkakula, Chang-Ung Kim, Ju Hwan Jeong, Seong Cheol Min, Dong Gyu Lee, Ju Ryeong Lee, Sun-Woo Yoon, Doo-Jin Kim, Timothy J Mahony, Richard J Webby, Young Ki Choi, Yun Hee Baek, Min-Suk Song

{"title":"Capless self-amplifying mRNA vaccine induces dose-sparing protective immunity against HPAI clade 2.3.4.4 H5 virus in mice.","authors":"Beom Kyu Kim, Ji-Hyun Park, Won-Suk Choi, Sol Oh, Se Hee An, Gi Chan Lee, Santosh Chokkakula, Chang-Ung Kim, Ju Hwan Jeong, Seong Cheol Min, Dong Gyu Lee, Ju Ryeong Lee, Sun-Woo Yoon, Doo-Jin Kim, Timothy J Mahony, Richard J Webby, Young Ki Choi, Yun Hee Baek, Min-Suk Song","doi":"10.1016/j.ymthe.2026.07.047","DOIUrl":"10.1016/j.ymthe.2026.07.047","url":null,"abstract":"Self-amplifying mRNA (samRNA) vaccines can induce potent immune responses at lower doses than conventional non-replicating mRNA vaccines; however, large RNA size and manufacturing considerations associated with 5' capping remain important challenges. Here, we developed a capless samRNA (CLsamRNA) vaccine platform derived from a Coxsackievirus B5 replicon that uses internal ribosome entry site-mediated cap-independent translation. Systematic optimization of key genetic elements enhanced antigen expression from the CLsamRNA backbone. Using reporter RNAs, LNP-formulated CLsamRNA showed rapid early expression and RNA amplification, with expression kinetics distinct from VEEV-based saRNA and nucleoside-modified mRNA comparators. When encoding the hemagglutinin antigen of highly pathogenic avian influenza clade 2.3.4.4 H5 viruses, CLsamRNA induced potent immune responses after LNP formulation. In mouse models, CLsamRNA induced potent neutralizing antibody responses, cross-reactive activity against clade 2.3.4.4b H5N1 virus, Th1-skewed humoral immunity, and strong antigen-specific cellular immune responses. CLsamRNA also elicited platform-specific early inflammatory and lymph node immune gene signatures associated with antigen presentation, costimulation, and cellular immune priming. Notably, a minimal 0.01-μg dose of CLsamRNA conferred complete protection against lethal H5N8 influenza virus challenge in BALB/c mice. These findings support CLsamRNA as a distinct cap-independent RNA vaccine platform with dose-sparing protective efficacy against highly pathogenic avian influenza H5 viruses.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":"6007-6027"},"PeriodicalIF":11.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dysregulated proline metabolism contributes to retinal fibrosis in neovascular AMD: Therapeutic potential of prolyl-4-hydroxylase inhibition. 脯氨酸代谢失调导致新生血管性AMD视网膜纤维化：脯氨酸-4-羟化酶抑制的治疗潜力。

IF 11.4 1区医学

Molecular Therapy Pub Date : 2026-10-07 Epub Date: 2026-07-29 DOI: 10.1016/j.ymthe.2026.07.044

Yue Zeng, Ting Zhang, Elisa Cornish, So-Ra Lee, Michelle Yam, Mark Eminhizer, Jingwen Zeng, Jialing Zhang, Shaoxue Zeng, Azhar Dzulhadj B Arafah, Xian Wei, Jinliang Yang, Meidong Zhu, Andrew Chang, Meixia Zhang, Jianhai Du, Ling Zhu, Mark C Gillies

{"title":"Dysregulated proline metabolism contributes to retinal fibrosis in neovascular AMD: Therapeutic potential of prolyl-4-hydroxylase inhibition.","authors":"Yue Zeng, Ting Zhang, Elisa Cornish, So-Ra Lee, Michelle Yam, Mark Eminhizer, Jingwen Zeng, Jialing Zhang, Shaoxue Zeng, Azhar Dzulhadj B Arafah, Xian Wei, Jinliang Yang, Meidong Zhu, Andrew Chang, Meixia Zhang, Jianhai Du, Ling Zhu, Mark C Gillies","doi":"10.1016/j.ymthe.2026.07.044","DOIUrl":"10.1016/j.ymthe.2026.07.044","url":null,"abstract":"Subretinal fibrosis, a major cause of irreversible vision loss in neovascular age-related macular degeneration (nAMD), is driven by excessive deposition of extracellular matrix such as collagens. While proline metabolism is known to play a critical role in collagen biosynthesis and fibrosis, its involvement in subretinal fibrosis remains unclear. Here, we characterized the progression of fibrovascular lesions in JR5558 mice, observing significant molecular alterations as early as 4 weeks of age and phenotypic changes by 8 weeks. Transcriptomic and metabolomic analyses revealed elevated levels of 4-hydroxyproline, an essential component of collagen, alongside significant alterations of other fibrosis-related pathways. P4HA1, a catalytic subunit of prolyl-4-hydroxylase essential for 4-hydroxyproline biosynthesis, was prominently expressed in fibrotic lesions in retinas of JR5558, laser-induced murine models and human eyes with nAMD. Targeting P4HA1 with the small-molecule inhibitor diethyl pythiDC significantly attenuated fibrovascular lesion expansion in the JR5558 mouse model and reduced collagen turnover in human retinal pigment epithelium cells. Treatment responses in JR5558 mice were lesion cluster dependent, with the combination of diethyl pythiDC with aflibercept showing selective antifibrotic benefit in moderate lesion cluster. These findings support a potential role of proline metabolism, particularly proline hydroxylation, in subretinal fibrosis. Inhibiting P4HA1 with diethyl pythiDC inhibited fibrosis in the models we studied, highlighting a potential therapeutic strategy.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":"6111-6133"},"PeriodicalIF":11.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Retinal ganglion cell-derived vesicles: A new path to neuroprotection. 视网膜神经节细胞来源的囊泡：神经保护的新途径。

IF 11.4 1区医学

Molecular Therapy Pub Date : 2026-10-07 Epub Date: 2026-09-01 DOI: 10.1016/j.ymthe.2026.08.030

Kun-Che Chang

引用次数: 0

Therapy-induced IGF1R signaling as an actionable vulnerability in oncolytic virotherapy. 治疗诱导的IGF1R信号作为溶瘤病毒治疗的可操作脆弱性。

IF 11.4 1区医学

Molecular Therapy Pub Date : 2026-10-07 Epub Date: 2026-09-05 DOI: 10.1016/j.ymthe.2026.08.032

Alexandra A Miller, Tae Jin Lee, Ji Young Yoo

引用次数: 0

Unlocking extracellular vesicle-mediated efficient DNA delivery for long-lasting transgene expression. 解锁细胞外囊泡介导的高效DNA传递，实现持久的转基因表达。

IF 11.4 1区医学

Molecular Therapy Pub Date : 2026-10-07 Epub Date: 2026-08-11 DOI: 10.1016/j.ymthe.2026.08.018

Melissa Tan, Yumi Kawamura, Carol Wang, Ryan Schneider, George Richards, Odom Seng, William Eagen, Dean Lee, Evonne Ip, Desmond Wai Loon Chin, Wei Zhong Leong, Walter Goh, Harwin Sidik, Trinh T T Tran, Ozan Alkan, Qin Yu, Ronne Yeo, Don Haut, Tenzin Gocha, Minh T N Le, Waqas Muhammad Usman

{"title":"Unlocking extracellular vesicle-mediated efficient DNA delivery for long-lasting transgene expression.","authors":"Melissa Tan, Yumi Kawamura, Carol Wang, Ryan Schneider, George Richards, Odom Seng, William Eagen, Dean Lee, Evonne Ip, Desmond Wai Loon Chin, Wei Zhong Leong, Walter Goh, Harwin Sidik, Trinh T T Tran, Ozan Alkan, Qin Yu, Ronne Yeo, Don Haut, Tenzin Gocha, Minh T N Le, Waqas Muhammad Usman","doi":"10.1016/j.ymthe.2026.08.018","DOIUrl":"10.1016/j.ymthe.2026.08.018","url":null,"abstract":"Achieving efficient DNA delivery for sustained transgene expression while minimizing immune response remains a significant challenge in gene therapy. Here, we conduct an in-depth characterization of red blood cell-derived extracellular vesicles (RBCEVs) and evaluate their potential as DNA delivery vehicles targeting specific cell types. We aim to achieve stable, prolonged transgene expression, minimizing the need for frequent treatments. Proteomic analysis shows that RBCEVs closely resemble red blood cells in protein content with over 90% of lumen proteins composed of hemoglobin family proteins. Biodistribution of RBCEVs in non-human primates indicates predominant liver accumulation, highlighting the liver's potential as a biofactory organ for RBCEV-mediated gene therapies. In mice, systemic administration of RBCEVs loaded with luciferase plasmids achieves stable, long-lasting luciferase expression, maintained throughout a 13-months monitoring period. RBCEV-mediated delivery of therapeutic human factor IX plasmids produces durable factor IX protein levels in bloodstream. RBCEVs can also co-deliver two plasmids simultaneously. Incorporating heavy- and light-chain antibody constructs into RBCEVs enables sustained expression of Herceptin antibodies in circulation. Further utilization of cell-specific promoters enhances transgene expression and concomitantly reduces undesired immune responses. These results highlight RBCEVs as a safe, scalable, and versatile DNA delivery platform for achieving sustained transgene expression in gene therapy.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":"5970-5992"},"PeriodicalIF":11.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Triple-AAV intein-mediated gene therapy ameliorates dystrophic phenotype in MDC1A mice. 三重AAV介素介导的基因治疗改善MDC1A小鼠的营养不良表型。

IF 11.4 1区医学

Molecular Therapy Pub Date : 2026-10-07 Epub Date: 2026-07-29 DOI: 10.1016/j.ymthe.2026.07.045

Núria Rafel-Millan, Carles Bayod-Girón, Maria Pallarès-Masmitjà, Cristina Fernández-Avilés, Keilisa Figuereo-Moya, Ángel Edo, Miguel Chillón, Miquel Vila-Perelló, Silvia Frutos, Marc Güell

{"title":"Triple-AAV intein-mediated gene therapy ameliorates dystrophic phenotype in MDC1A mice.","authors":"Núria Rafel-Millan, Carles Bayod-Girón, Maria Pallarès-Masmitjà, Cristina Fernández-Avilés, Keilisa Figuereo-Moya, Ángel Edo, Miguel Chillón, Miquel Vila-Perelló, Silvia Frutos, Marc Güell","doi":"10.1016/j.ymthe.2026.07.045","DOIUrl":"10.1016/j.ymthe.2026.07.045","url":null,"abstract":"Several therapies using adeno-associated viruses (AAVs) as a gene delivery tool have received marketing approval in the past. However, potential applications of AAVs are limited by their restricted gene packaging capacities (<4.7 kb). Many monogenic diseases are caused by large complex genes with hundreds of pathogenic variants that exceed AAV capacity. Merosin-deficient congenital muscular dystrophy type 1A is a severe monogenic recessive disease caused by the absence of functional copies of the LAMA2 gene. To date, no treatment options are available, with the most promising approach being gene replacement therapy to provide a functional copy. The LAMA2 coding sequence, spanning 9.3 kb, encodes laminin-α2, a subunit of the trimeric protein Laminin-211 found in the basement membrane of skeletal muscle cells and Schwann cells. Efforts have been focused on gene or protein replacement along with basement membrane engineering. Here, we exploit the ability of inteins to reconstitute full-length protein in a scarless manner. Using a combination of three AAVs, each encoding one fragment of the laminin-α2 protein flanked by a short split intein, resulted in the complete reconstitution of Laminin-α2 and an improvement of the histopathological features of the dy2j dystrophic mouse model.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":"5697-5709"},"PeriodicalIF":11.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A helicase-fused Cas9 improves large-size fragment knockin. 解旋酶融合Cas9改善大片段敲入。

IF 11.4 1区医学

Molecular Therapy Pub Date : 2026-10-07 Epub Date: 2026-07-29 DOI: 10.1016/j.ymthe.2026.07.049

Duowei Zhao, Xiangjie Zhao, Yuhang Gao, Sujie Yang, Xiaochen Guo, Caiyan Zhang, Chuanpei Li, Chengda Zhang, Huan Tian, Qianqian Xu, Zhi Yin, Zhonghua Liu, Jun Song

{"title":"A helicase-fused Cas9 improves large-size fragment knockin.","authors":"Duowei Zhao, Xiangjie Zhao, Yuhang Gao, Sujie Yang, Xiaochen Guo, Caiyan Zhang, Chuanpei Li, Chengda Zhang, Huan Tian, Qianqian Xu, Zhi Yin, Zhonghua Liu, Jun Song","doi":"10.1016/j.ymthe.2026.07.049","DOIUrl":"10.1016/j.ymthe.2026.07.049","url":null,"abstract":"Homologous recombination (HR)-mediated large-size fragment knockin (ls-KI) remains inefficient in mammalian cells, even with the assistance of CRISPR-Cas9. We hypothesized that adding DNA helicase activity to CRISPR-Cas9 could enhance ls-KI efficiency. To test this, we fused MCM5, a subunit of the eukaryotic MCM2-7 helicase complex, to the N terminus of spCas9. The resulting fusion protein, termed MCCas, markedly increased knockin rates across multiple loci in different human cell lines, significantly outperforming spCas9. Remarkably, MCCas enabled efficient ls-KI with donor templates of up to 10 kb in size. MCCas-mediated ls-KI, in comparison to those mediated by spCas9, is also associated with reduced frequencies of on-target and off-target insertion and deletion (indel) events. Mechanistic investigations revealed that MCCas-mediated ls-KI relies on the canonical HR pathway, as inhibition of key processes such as end resection and strand invasion abolished the enhancement. To further validate its application, we employed MCCas to knock in the human ACE2 (hACE2) coding sequence to the rabbit genome. Consistent with our findings in human cells, MCCas led to a more than 2-fold increase in ls-KI rates in rabbit embryos compared to spCas9. Collectively, our results establish MCCas as a promising gene-editing tool with enhanced ls-KI capacity.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":"6153-6162"},"PeriodicalIF":11.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0