Molecular Therapy最新文献_第2页

Targeting human plasma cells using small molecule regulated BCMA CAR T cells eliminates circulating antibodies in humanized mice.

IF 12.1 1区医学

Molecular Therapy Pub Date : 2024-12-12 DOI: 10.1016/j.ymthe.2024.12.018

Yuchi Honaker, David Gruber, Chester Jacobs, Rene Yu-Hong Cheng, Shivani Patel, Christopher Zavala Galvan, Iram F Khan, Kevin Zhou, Karen Sommer, Alexander Astrakhan, Peter J Cook, Richard G James, David J Rawlings

{"title":"Targeting human plasma cells using small molecule regulated BCMA CAR T cells eliminates circulating antibodies in humanized mice.","authors":"Yuchi Honaker, David Gruber, Chester Jacobs, Rene Yu-Hong Cheng, Shivani Patel, Christopher Zavala Galvan, Iram F Khan, Kevin Zhou, Karen Sommer, Alexander Astrakhan, Peter J Cook, Richard G James, David J Rawlings","doi":"10.1016/j.ymthe.2024.12.018","DOIUrl":"https://doi.org/10.1016/j.ymthe.2024.12.018","url":null,"abstract":"Pathogenic long-lived plasma cells (LLPCs) secrete autoreactive antibodies, exacerbating autoimmune diseases and complicating solid organ transplantation. Targeted elimination of the autoreactive B-cell pool represents a promising therapeutic strategy, yet current treatment modalities fall short in depleting mature plasma cells. Here, we demonstrate that chimeric antigen receptor (CAR) T cells, targeting BCMA utilizing a split-receptor design, offer a controlled and effective therapeutic strategy against LLPCs. Dimerizing agent-regulated immune-receptor complex (DARIC) T cells demonstrated robust rapamycin-dependent targeting of tumor and plasma cells. Notably, in humanized mouse models, DARIC-T cells regulated peripheral human immunoglobulin levels through specific elimination of human LLPCs from the bone marrow. Furthermore, DARIC constructs were efficiently integrated into the T-cell receptor α constant (TRAC) locus while maintaining potent antigen-specific cytotoxicity. These findings underscore the potential of split-receptor CAR T cells in autoimmune and transplant medicine, highlighting their versatility in applications beyond oncology.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824330","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

IL-1ra and CCL5, but not IL-10, are promising targets for treating SMA astrocyte-driven pathology. IL-1ra和CCL5，而非IL-10，是治疗SMA星形胶质细胞驱动的病理学的有希望的靶点。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2024-12-12 DOI: 10.1016/j.ymthe.2024.12.016

Reilly L Allison, Cecelia C Mangione, Mya Suneja, Jessica Gawrys, Brendan M Melvin, Natalya Belous, Megan LaCroix, Matthew Harmelink, Barrington G Burnett, Allison D Ebert

{"title":"IL-1ra and CCL5, but not IL-10, are promising targets for treating SMA astrocyte-driven pathology.","authors":"Reilly L Allison, Cecelia C Mangione, Mya Suneja, Jessica Gawrys, Brendan M Melvin, Natalya Belous, Megan LaCroix, Matthew Harmelink, Barrington G Burnett, Allison D Ebert","doi":"10.1016/j.ymthe.2024.12.016","DOIUrl":"https://doi.org/10.1016/j.ymthe.2024.12.016","url":null,"abstract":"Spinal muscular atrophy (SMA) is a pediatric genetic disorder characterized by the loss of spinal cord motor neurons. Although the mechanisms underlying motor neuron loss are not clear, current data suggest that glial cells contribute to disease pathology. We have previously found that SMA astrocytes drive microglial activation and motor neuron loss potentially through the upregulation of NFkB-mediated pro-inflammatory cytokines. In this study, we tested the ability of neutralizing C-C motif chemokine ligand 5 (CCL5) while increasing either interleukin 10 (IL-10) or IL-1 receptor antagonist (IL-1ra) to reduce the pro-inflammatory phenotype of SMA astrocytes. While IL-10 was ineffective, IL-1ra ameliorated SMA astrocyte-driven glial activation and motor neuron loss in iPSC-derived cultures in vitro. In vivo AAV5 delivered IL-1ra overexpression and miR-30 shRNA knockdown of CCL5 had modest but significant improvements on lifespan, weight gain, motor neuron number, and motor function of SMNΔ7 mice. Together these data identify IL-1ra and CCL5 as possible therapeutic targets for SMA and highlight the importance of glial-targeted therapeutics for neurodegenerative disease.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823920","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 small TAT-TrkB peptide prevents BDNF receptor cleavage and restores synaptic physiology in Alzheimer's disease. 一种小的 TAT-TrkB 肽能防止 BDNF 受体裂解并恢复阿尔茨海默病的突触生理机能。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2024-12-12 DOI: 10.1016/j.ymthe.2024.12.005

João Fonseca-Gomes, Tiago Costa-Coelho, Mafalda Ferreira-Manso, Sara Inteiro-Oliveira, Sandra H Vaz, Nuno Alemãn-Serrano, Henrique Atalaia-Barbacena, Leonor Ribeiro-Rodrigues, Rita M Ramalho, Rui Pinto, Hugo Vicente Miranda, Sara R Tanqueiro, Carolina de Almeida-Borlido, Maria João Ramalho, Catarina Miranda-Lourenço, Rita F Belo, Catarina B Ferreira, Vera Neves, Diogo M Rombo, Ricardo Viais, Juzoh Umemori, Ivo C Martins, André Jerónimo-Santos, António Caetano, Nuno Manso, Petra Mäkinen, Mikael Marttinen, Mari Takalo, Michael Bremang, Ian Pike, Annakaisa Haapasalo, Joana A Loureiro, Maria Carmo Pereira, Nuno C Santos, Tiago F Outeiro, Miguel A R B Castanho, Adelaide Fernandes, Mikko Hiltunen, Carlos B Duarte, Eero Castrén, Alexandre de Mendonça, Ana M Sebastião, Tiago M Rodrigues, Maria José Diógenes

引用次数: 0

Critical role of TPRN rings in the stereocilia for hearing.

IF 12.1 1区医学

Molecular Therapy Pub Date : 2024-12-12 DOI: 10.1016/j.ymthe.2024.12.004

Jieyu Qi, Fangzhi Tan, Liyan Zhang, Yinyi Zhou, Ziyu Zhang, Qiuhan Sun, Nianci Li, Yuan Fang, Xin Chen, Yunhao Wu, Guisheng Zhong, Renjie Chai

引用次数: 0

mRNA-LNPs induce immune activation and cytokine release in human whole blood assays across diverse health conditions. mRNA-LNPs 可在人体全血检测中诱导免疫激活和细胞因子释放，适用于各种健康状况。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2024-12-12 DOI: 10.1016/j.ymthe.2024.12.019

Hong-My Nguyen, Kristin E Alexander, Mark Collinge, James C Hickey, Thomas A Lanz, Jin Li, Mark J Sheehan, Leah C Newman, Mitchell Thorn

{"title":"mRNA-LNPs induce immune activation and cytokine release in human whole blood assays across diverse health conditions.","authors":"Hong-My Nguyen, Kristin E Alexander, Mark Collinge, James C Hickey, Thomas A Lanz, Jin Li, Mark J Sheehan, Leah C Newman, Mitchell Thorn","doi":"10.1016/j.ymthe.2024.12.019","DOIUrl":"https://doi.org/10.1016/j.ymthe.2024.12.019","url":null,"abstract":"RNA medicines have become a promising platform for therapeutic use in recent years. Understanding the immunomodulatory effects of novel mRNA-LNPs is crucial for future therapeutic development. An in vitro whole blood assay was developed to assess the impact of mRNA-LNPs on immune cell function, cytokine release, and complement activation. mRNA-LNPs significantly increased CD69 expression on T cells and natural killer (NK) cells, and CD80/CD86 on myeloid subsets, in a dose-dependent fashion. Furthermore, mRNA-LNPs elicited a robust release of pro-inflammatory cytokines, including TNF-α, IL-1β, MCP-1, IL-6, and IP-10, indicating a potent immune response. Notably, mRNA-LNPs stimulate early cytokine production prior to triggering immune cell activation, suggesting a temporal and biological relationship. Moreover, mRNA-LNPs induce complement activation via the alternative pathway, as evidenced by increased serum sC5b-9, C3a, and Bb which can amplify the inflammatory response and potentially impact safety. In vitro effects of mRNA-LNPs in whole blood of healthy human donors were compared to those from disease cohorts including systemic lupus erythematosus (SLE), type 2 diabetes mellitus (T2DM), and cancer donors. The differences in mRNA-LNPs effects on samples from healthy and diseased populations may impact therapeutic efficacy or toxicity, indicating a need for tailoring LNPs for specific target populations.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823944","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

CD137-expressing Regulatory T Cells in Cancer and Autoimmune Diseases.

IF 12.1 1区医学

Molecular Therapy Pub Date : 2024-12-11 DOI: 10.1016/j.ymthe.2024.12.010

Kang Yi Lee, Yu Mei, Haiyan Liu, Herbert Schwarz

{"title":"CD137-expressing Regulatory T Cells in Cancer and Autoimmune Diseases.","authors":"Kang Yi Lee, Yu Mei, Haiyan Liu, Herbert Schwarz","doi":"10.1016/j.ymthe.2024.12.010","DOIUrl":"https://doi.org/10.1016/j.ymthe.2024.12.010","url":null,"abstract":"Regulatory T cells (Tregs) are essential for maintaining immune homeostasis, with critical roles in preventing aberrant immune responses that occur in autoimmune diseases and chronic inflammation. Conversely, the abundance of Tregs in cancer is associated with impaired anti-tumour immunity, and tumour immune evasion. Recent work demonstrates that CD137, a well-known costimulatory molecule for T cells, is highly expressed on Tregs in pathological conditions, while its expression is minimal or negligible on peripheral Tregs. The expression of CD137 marks Tregs with potent immunosuppressive phenotype that foster cancer progression and are protective against certain autoimmune diseases. Hence CD137 has emerged as a marker for Tregs. However, several important questions still remain regarding the expression and function of CD137 in Tregs. Here, we provide an overview of our current knowledge of Treg mechanisms of action, with a focus on the role of CD137 in modulating Treg activity. We also explore the implications of CD137+ Tregs in both cancer and autoimmune diseases, emphasizing the significance of targeting these cells for therapeutic intervention in these conditions.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818758","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

Modified human mesenchymal stromal/stem cells restore cortical excitability after focal ischemic stroke in rats.

IF 12.1 1区医学

Molecular Therapy Pub Date : 2024-12-11 DOI: 10.1016/j.ymthe.2024.12.006

Barbara Klein, Agnieszka Ciesielska, Patricia Morán Losada, Anna Sato, Sajita Shah-Morales, Jeremy B Ford, Bryan Higashikubo, Dale Tager, Alexander Urry, Juliane Bombosch, Wei-Cheng Chang, Yaisa Andrews-Zwilling, Bijan Nejadnik, Zuha Warraich, Jeanne T Paz

{"title":"Modified human mesenchymal stromal/stem cells restore cortical excitability after focal ischemic stroke in rats.","authors":"Barbara Klein, Agnieszka Ciesielska, Patricia Morán Losada, Anna Sato, Sajita Shah-Morales, Jeremy B Ford, Bryan Higashikubo, Dale Tager, Alexander Urry, Juliane Bombosch, Wei-Cheng Chang, Yaisa Andrews-Zwilling, Bijan Nejadnik, Zuha Warraich, Jeanne T Paz","doi":"10.1016/j.ymthe.2024.12.006","DOIUrl":"https://doi.org/10.1016/j.ymthe.2024.12.006","url":null,"abstract":"Allogeneic modified bone marrow-derived mesenchymal stromal/stem cells (hMSC-SB623 cells) are in clinical development for the treatment of chronic motor deficits after traumatic brain injury and cerebral ischemic stroke. However, their exact mechanisms of action remain unclear. Here, we investigated the effects of this cell therapy on cortical network excitability, brain tissue and peripheral blood at a chronic stage after ischemic stroke in a rat model. One month after focal cortical ischemic stroke, hMSC-SB623 cells or the vehicle solution were injected into the peri-stroke cortex. Starting one-week post-treatment, cortical excitability was assessed ex vivo. hMSC-SB623 cell transplants reduced stroke-induced cortical hyperexcitability, restoring cortical excitability to control levels. Histology of brain tissue revealed an increase of factors relevant to neuroregeneration and synaptic and cellular plasticity. Whole-blood RNA sequencing and serum protein analyses showed that intracortical hMSC-SB623 cell transplantation reversed effects of stroke on peripheral blood factors known to be involved in stroke pathophysiology. Our findings demonstrate that intra-cortical transplants of hMSC-SB623 cells correct stroke-induced circuit disruptions even at the chronic stage, suggesting broad utility as a therapeutic for neurological conditions with network hyperexcitability. Additionally, the transplanted cells exert far-reaching immunomodulatory effects whose therapeutic impact remains to be explored.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818770","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

Debulking Influenza and Herpes Simplex virus strains by a wide-spectrum anti-viral protein formulated in clinical grade chewing gum.

IF 12.1 1区医学

Molecular Therapy Pub Date : 2024-12-10 DOI: 10.1016/j.ymthe.2024.12.008

Henry Daniell, Yuwei Guo, Rahul Singh, Uddhab Karki, Rachel J Kulchar, Geetanjali Wakade, Juha-Matti Pihlava, Hamid Khazaei, Gary H Cohen

{"title":"Debulking Influenza and Herpes Simplex virus strains by a wide-spectrum anti-viral protein formulated in clinical grade chewing gum.","authors":"Henry Daniell, Yuwei Guo, Rahul Singh, Uddhab Karki, Rachel J Kulchar, Geetanjali Wakade, Juha-Matti Pihlava, Hamid Khazaei, Gary H Cohen","doi":"10.1016/j.ymthe.2024.12.008","DOIUrl":"https://doi.org/10.1016/j.ymthe.2024.12.008","url":null,"abstract":"Lack of Herpes Simplex Virus (HSV) vaccine, low vaccination rates of Influenza viruses, waning immunity and viral transmission after vaccination underscore the need to reduce viral loads at their transmission sites. Oral virus transmission is several orders of magnitude higher than nasal transmission. Therefore, in this study, we evaluated neutralization of viruses using a natural viral trap protein (FRIL) formulated in clinical-grade chewing gum. FRIL is highly stable in the lablab bean powder (683 days) and in chewing gum (790 days), and fully functional (794 days) when stored at ambient temperature. They passed the bioburden test with no aerobic bacteria, yeasts/molds, with minimal moisture content (1.28-5.9%). Bean gum extracts trapped HSV-1/HSV-2 75-94% in a dose-dependent manner through virus self-aggregation. Mastication simulator released >50% release of FRIL within 15 minutes of chewing the bean gum. In plaque reduction assays, >95% neutralization of H1N1 and H3N2 required ∼40mg/mL, HSV-1 160mg/mL, and HSV-2 74 mg/mL of bean gum for 1,000 copies/mL virus particles. Therefore, a 2000 mg bean gum tablet has more than adequate potency for clinical evaluation and is safe with no detectable levels of glycosides. These observations augur well for evaluating bean gum in human clinical studies to minimize virus infection/transmission.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813515","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

Targeting Viral Suppressor of RNAi confers anti-coronaviral activity.

IF 12.1 1区医学

Molecular Therapy Pub Date : 2024-12-10 DOI: 10.1016/j.ymthe.2024.12.009

Jiyao Chen, JingFang Mu, Kangping Zhou, Yuming Zhang, Jieling Zhang, Ting Shu, Weijuan Shang, Yujie Ren, Xi-Qiu Xu, Leike Zhang, Shuai Yuan, Dingyu Zhang, Kun Cai, Yang Qiu, Xi Zhou

{"title":"Targeting Viral Suppressor of RNAi confers anti-coronaviral activity.","authors":"Jiyao Chen, JingFang Mu, Kangping Zhou, Yuming Zhang, Jieling Zhang, Ting Shu, Weijuan Shang, Yujie Ren, Xi-Qiu Xu, Leike Zhang, Shuai Yuan, Dingyu Zhang, Kun Cai, Yang Qiu, Xi Zhou","doi":"10.1016/j.ymthe.2024.12.009","DOIUrl":"https://doi.org/10.1016/j.ymthe.2024.12.009","url":null,"abstract":"Infections caused by coronaviruses are persistent threats to human health in recent decades, necessitating the development of innovative anti-coronaviral therapies. RNA interference (RNAi) is a conserved cell-intrinsic antiviral mechanism in diverse eukaryotic organisms, including mammals. To counteract, many viruses encode viral suppressors of RNAi (VSRs) to evade antiviral RNAi, implying that targeting VSRs could be a promising strategy to develop antiviral therapies. Here, we designed a series of peptides specifically targeting the SARS-CoV-2-encoded VSR, nucleocapsid (N) protein. Among these peptides, one designated GL directly interacts with N protein and inactivates its VSR activity, which unlocks a potent RNAi response and effectively inhibits SARS-CoV-2 replication. Moreover, GL exhibited RNAi-dependent antiviral effects not only against various SARS-CoV-2 variants, including Delta, Omicron BA.5, XBB and JN.1, but also against other coronaviruses such as HCoV-229E, HCoV-OC43 and mouse hepatitis virus. The in vivo anti-coronaviral activity of GL was also confirmed. Our findings indicate that the VSR-targeting peptide GL has the potential to be further developed as a broad-spectrum anti-coronaviral treatment, highlighting the functional importance and therapeutic potential of antiviral RNAi.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813526","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

Combination with oxaliplatin improves abscopal effect of oncolytic virotherapy through reorganization of intratumoral macrophages.

IF 12.1 1区医学

Molecular Therapy Pub Date : 2024-12-10 DOI: 10.1016/j.ymthe.2024.12.007

Kyoko Tomita, Midori Yamashita, Kentaro Ikegami, Yoshiko Shimizu, Nobuaki Amino, Shinsuke Nakao

{"title":"Combination with oxaliplatin improves abscopal effect of oncolytic virotherapy through reorganization of intratumoral macrophages.","authors":"Kyoko Tomita, Midori Yamashita, Kentaro Ikegami, Yoshiko Shimizu, Nobuaki Amino, Shinsuke Nakao","doi":"10.1016/j.ymthe.2024.12.007","DOIUrl":"https://doi.org/10.1016/j.ymthe.2024.12.007","url":null,"abstract":"Intratumoral administration is a widely used method for oncolytic virotherapy, as it enables immediate access of virus particles to the target tumor and potentially lead suppression of untreated distant tumors via in situ vaccination. However, because the injection volume and concentration of the virus solution are physically limited, the dose level cannot be increased. Additionally, efficacy in distant tumors needs improvement to prolong patient survival. Here, we demonstrate benefit of oxaliplatin, with detailed mechanisms revealed through transcriptome analysis, which may provide a solution for the crucial deficiencies of oncolytic virotherapy. In virus-injected tumors, oxaliplatin improved virus retention through suppression of type-I interferons. In distant virus-naïve tumors, oxaliplatin induced alteration in the intratumoral macrophage characteristics, leading to the chemotaxis and recruitment of activated T cells and subsequently inducing an inflammatory state in the non-injected tumors. Our findings can be a trigger to change the therapeutic paradigm of oncolytic virotherapy for patients with systemic metastases.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813514","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