Cytotherapy最新文献

{"title":"The next innovations in chimeric antigen receptor T cell immunotherapies for cancer","authors":"Kusala Anupindi ,&nbsp;Julia Malachowski ,&nbsp;Isabella Hodson ,&nbsp;Daniel Zhu ,&nbsp;Carl H. June ,&nbsp;Bruce L. Levine","doi":"10.1016/j.jcyt.2025.05.010","DOIUrl":"10.1016/j.jcyt.2025.05.010","url":null,"abstract":"<div><div>Chimeric antigen receptor (CAR) T cell therapy has transformed cancer treatment and the field of immunotherapy. Although CAR T cell therapy has demonstrated considerable clinical success for the treatment of B cell malignancies, expanding its therapeutic efficacy and accessibility for other hematological malignancies and solid tumors remains a challenge. Key limitations include manufacturing constraints and therapeutic hurdles, such as CAR T cell persistence, proliferation, tumor trafficking and treatment-related toxicities. To overcome the unique challenges associated with CAR T cell therapy, novel technological advancements in CAR design, delivery, and T cell functionality can be leveraged. This review will explore three innovative approaches: gene editing and silencing, armoring strategies and <em>in vivo</em> CAR gene delivery. These approaches are all aimed at enhancing the accessibility and therapeutic efficacy of CAR T cell therapy in hematological malignancies.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 7","pages":"Pages 795-811"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Considerations for manufacturing of cell and gene medicines for clinical development","authors":"Mark W. Lowdell","doi":"10.1016/j.jcyt.2024.11.015","DOIUrl":"10.1016/j.jcyt.2024.11.015","url":null,"abstract":"<div><div>The global changes from 2001 that elevated substantially modified cell therapies to the definition of “medicinal product” have been the catalyst for the dramatic expansion of the field to its current and future commercial success. Europe was the first to incorporate human somatic cells into drug legislation with the medicines directive of 2001 (2001/83/EC), which led to the development of the term “advanced therapy medicinal products” (ATMPs) to cover all substantially modified products, tissue-engineered products and somatic cells that are not substantially modified but that are used non-homologously. For convenience, I use the term “ATMPs” throughout this review. The transition from “cell therapy” to “cellular medicine” coincided with changes in clinical trial legislation in Europe and, subsequently, across many drug jurisdictions throughout the world. As medicines, there is a clear path through multiple phases of trials and associated requirements for compliance with the good practice standards of drug development, and manufacturability is central to this development.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 7","pages":"Pages 874-883"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dark NKnight rising: a current perspective on NK cell and CAR-NK cell therapy","authors":"Joseph R. Caporale ,&nbsp;Meisam Naeimi Kararoudi ,&nbsp;Margaret G. Lamb ,&nbsp;Dean A. Lee","doi":"10.1016/j.jcyt.2025.04.064","DOIUrl":"10.1016/j.jcyt.2025.04.064","url":null,"abstract":"<div><div>Natural killer (NK) cell therapy began decades ago with administration of small doses of minimally-characterized cells known as cytokine-induced or lymphokine-activated killer cells (CIK or LAK, respectively). Methods and conditions that enabled the broad adoption of T cell therapies have often been less effective for NK cells, but in the last 15 years, new NK-specific advances in selection, differentiation, and <em>ex vivo</em> expansion hav e made possible the infusion of large doses of pure and potent NK cell products. Also, NK cells have been more resistant to the genetic modification approaches utilized for engineering T cells, but in the last 5 years several robust approaches for NK cell modification have advanced to the clinic. Thus, a tremendous surge in NK cell clinical trials has been seen recently. Here, we present a focused perspective on the key developments in NK cell therapy that differentiate it from T cell therapies and discuss areas that are key to their clinical and commercial success- both current advancements and hurdles that remain to be addressed.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 7","pages":"Pages 812-825"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"iPSC-based cell replacement therapy: from basic research to clinical application","authors":"Jun Takahashi","doi":"10.1016/j.jcyt.2025.01.015","DOIUrl":"10.1016/j.jcyt.2025.01.015","url":null,"abstract":"<div><div>The advancement of induced pluripotent stem cell (iPSC) technology has revolutionized regenerative medicine, enabling breakthroughs in disease modeling, drug discovery, and cell replacement therapies. This review examines the progression of iPSC-based regenerative medicine, focusing on cell replacement therapy and mechanisms like the Replacement Effect, which is crucial for long-term tissue regeneration. Using Parkinson's disease as a key example, it discusses the induction of midbrain dopaminergic neurons from iPSCs and the importance of precise signaling for safety and efficacy. By demonstrating the integration and safety of these cells, animal studies have paved the way for clinical trials. This review highlights the need for strategic collaboration among stakeholders—regulatory authorities, research and medical staff, and industry—to ensure successful clinical applications. iPSC technology's ongoing evolution holds significant promise for broader therapeutic applications and improved patient outcomes.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 7","pages":"Pages 835-842"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subscription information","authors":"","doi":"10.1016/S1465-3249(25)00755-8","DOIUrl":"10.1016/S1465-3249(25)00755-8","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 7","pages":"Page A4"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144563361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoimmune FK binding protein 12-knockout CD19 CAR T cells achieve deep tissue B-cell depletion and control Nalm6 tumors in immunosuppressed humanized mice.","authors":"Xiaomeng Hu, Andrew McAlister, Jeremy Kinder, Adam Johnson, Kathy White, Carolin B Caruso, Chenyan Wang, Ron Basco, Corie Gattis, Annabelle Friera, Tobias Deuse, Sonja Schrepfer","doi":"10.1016/j.jcyt.2025.06.013","DOIUrl":"https://doi.org/10.1016/j.jcyt.2025.06.013","url":null,"abstract":"<p><p>Autologous chimeric antigen receptor (CAR) T-cell therapy in solid-organ transplant recipients on life-long systemic immunosuppression has so far been disappointing. The mTOR inhibitors tacrolimus (Tac) and rapamycin (Rapa) are among the most common immunosuppressive drugs. While they prevent organ allograft rejection, they also suppress the efficacy and persistence of the CAR T-cell product. A reduction in immunosuppression is usually recommended before leukapheresis and after infusion of the final CAR therapeutic to facilitate CAR T-cell activity. However, this reduction jeopardizes allograft survival and multiple graft failures have been reported. Here, we report the engineering of allogeneic, human CD19 CAR T cells that are resistant to mTOR inhibitors through the knockout of FK-binding protein 12 (FKBP-KO). Both HLA-replete WT-FKBP-KO and hypoimmune (HLA class I- and II-depleted and CD47-overexpressing, HIP) CD19 CAR T cells maintained effective in vitro killing capacity of benign human B cells and malignant Nalm6 tumor cells when incubated with high Tac and Rapa concentrations. CAR T cells without the FKBP-KO failed to kill both targets in the presence of Tac or Rapa. HIP-FKBP-KO CAR T cells were able to fully evade cytotoxicity from primed allogeneic T cells, natural killer (NK cells), and macrophages. When injected into immunosuppressed Nalm6-bearing humanized mice, only the HIP-FKBP-KO CAR T cells achieved persistence and deep tissue depletion of CD19⁺ cells over a 25-day study period, whereas the WT-FKBP-KO CAR T cells diminished in number and efficacy. Allogeneic HIP-FKBP-KO CAR T cells may treat post-transplant lymphoproliferative disease effectively in solid organ transplant recipients maintained on immunosuppression.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of ATLG on CD4⁺ T-cell reconstitution after HSCT in children: a detailed immune profiling study.","authors":"Marco M Sindoni, Anita Toso, Francesca Limido, Cristina Bugarin, Tiziana Villa, Sarah Bonte, Yvan Saeys, Chiara Buracchi, Giulia Prunotto, Virginia Meda Spaccamela, Mathias Hauri, Oscar Maglia, Simona Sala, Domenico Gaspari, Grazia Fazio, Andrea Biondi, Adriana Balduzzi, Silvia Nucera, Giuseppe Gaipa","doi":"10.1016/j.jcyt.2025.06.009","DOIUrl":"https://doi.org/10.1016/j.jcyt.2025.06.009","url":null,"abstract":"<p><strong>Introduction: </strong>Graft versus host disease (GvHD) prophylaxis impacts on post-hematopoietic stem cell transplantation (HSCT) immune reconstitution (IR). Specifically, anti-T lymphocyte globulin (ATLG) delays CD4⁺ T cell reconstitution. However, the mechanism by which ATLG alters the composition of CD4⁺ T-cell compartments remains elusive.</p><p><strong>Aims: </strong>Dissect the impact of ATLG on CD4⁺ T cells by integrating advanced and highly standardized flow cytometric panels, unsupervised clustering analysis, machine learning approaches, and molecular biology techniques.</p><p><strong>Results: </strong>We analyzed post-HSCT IR in 94 pediatric patients with a machine learning approach. ATLG exposure resulted in the most relevant variable affecting CD4⁺ T-cell counts. Severe combined immunodeficiency/recent thymic emigrant (SCID/RTE) and CD4 PERISCOPE EuroFlow antibody panels were applied to a sub-cohort of patients with acute lymphoblastic leukemia. Unsupervised clustering analysis showed that in the first months, post-HSCT CD4⁺ naïve T cells and RTEs were significantly reduced in ATLG-treated compared to no-ATLG patients, including haploidentical graft recipients receiving post-transplant cyclophosphamide. In no-ATLG patients, there was a significant contribution of residual recipient-derived cells to the RTE compartment, whereas in ATLG-treated patients RTEs were of donor origin. In addition, in no-ATLG patients, early RTEs and CD4⁺ T-cell counts correlated with infused CD3⁺ T cells/kg. Bone marrow and T-cell receptor excision circle (TREC) analysis showed that ATLG treatment does not affect early T-cell maturation. In vitro testing showed increased differentiation of naïve/RTE CD4⁺ into effector subsets upon ATLG exposure, confirmed by flow cytometry and RNA sequencing.</p><p><strong>Discussion: </strong>Our data show that ATLG induces concomitant differentiation and depletion of the peripheral CD4⁺ naïve/RTE T-cell compartment. Together, these findings suggest that naïve T-cell reconstitution after ATLG is delayed since it only relies on thymic maturation, differently from no-ATLG treated patients.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144644011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing gene-editing platforms to improve the viability of rare-disease therapeutics: key insights from a 2024 Scientific Exchange hosted by ARM, ISCT, and Danaher.","authors":"Fyodor Urnov, Sadik Kassim, Kiran Musunuru, David Liu, Ann Lee, Luis Barrera, Pam Stetkiewicz, Julianne Bruno, Matthew Hewitt, Troy Lister, Harry Malech, Lindsay Gasch, Matt Diver, Nicholas Gertler, Felix Grignon, Audrey Le, Michael Lehmicke, Vanessa Almendro-Navarro, Josephine Lembong","doi":"10.1016/j.jcyt.2025.06.010","DOIUrl":"10.1016/j.jcyt.2025.06.010","url":null,"abstract":"<p><p>Rare-disease therapeutics face viability challenges due to small patient populations and drug-development and regulatory frameworks that were not developed to address rapidly progressive or quickly fatal conditions. Because the majority of rare diseases are genetic in nature, gene-editing modalities offer substantial promise. This Scientific Exchange, co-hosted by the Alliance for Regenerative Medicine, the International Society for Cell and Gene Therapy, and Danaher Corporation in November 2024, set out to address the challenge of realizing the full promise of gene editing for rare-disease therapies by advancing platforms that leverage stable and reusable processes or components to develop multiple therapies. Through multi-stakeholder engagement and discussions of case studies in CRISPR/Cas nuclease, base, and prime editing, 4 key opportunities emerged that deliver value by holding platform elements constant and/or streamlining development steps: (1) consistent delivery vehicle; (2) consistent manufacturing; (3) benefit-risk appropriate quality requirements; and (4) expansive clinical trial designs. Together, these opportunities could yield up to 5-fold efficiency gains and result in substantial value creation for patients, regulators, and developers, potentially decreasing the time required to dose patients with a new gene-editing therapy from years down to 6 months.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical manufacture of CRISPR/Cas9-based cytokine-induced SH2 protein knock-out tumor-infiltrating lymphocytes for gastrointestinal cancers.","authors":"Matthew J Johnson, Darin Sumstad, Timothy D Folsom, Nicholas J Slipek, Anthony P DeFeo, Molly Growe, Diane Kadidlo, Bharat Thyagarajan, Timothy K Starr, Emil Lou, Modassir Choudhry, Branden S Moriarity, Beau R Webber, David H McKenna","doi":"10.1016/j.jcyt.2025.06.007","DOIUrl":"https://doi.org/10.1016/j.jcyt.2025.06.007","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;The prognosis of stage IV gastrointestinal (GI) carcinomas is poor with a 15% five-year survival rate for colorectal carcinomas. To improve efficacy of tumor infiltrating lymphocytes (TIL), we isolated mutation-reactive autologous TIL and employed CRISPR/Cas9 to knockout (KO) the intracellular checkpoint protein CISH, which has been shown to enhance T cell expansion, functional avidity, and cytokine polyfunctionality, with consequent durable regression of established tumors in an animal model.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials & methods: &lt;/strong&gt;TIL cultures were initiated from resected tumor fragments and maintained for six weeks before harvest and cryopreservation. Candidate neoantigens were nominated by exome sequencing and peptides were used to identify mutation reactive (MR) TIL. Selected MR TIL were thawed and allowed to recover for 24-36 h in media with 10% AB serum, 6000 IU/mL IL-2, and 5 ng/mL IL-7 and IL-15 followed by stimulation with plate-bound anti-CD3/soluble anti-CD28 for 4 days. CISH KO was performed by electroporation of Cas9 mRNA and chemically modified single guide RNA. Between 5 -7.5 million viable cells were added to each 100 cm&lt;sup&gt;2&lt;/sup&gt; G-Rex vessel containing 600 mL expansion media (with allogeneic feeder MNC:TIL = 100:1) and incubated for 6-8 days. Cultures were evaluated and split according to cell concentration criteria (and dose cohort) and incubated for an additional 6-8 days. On day 14, all of the cells were harvested, washed with buffer and cryopreserved (5% DMSO). Lot release testing included: viability, %CD3+, cytology review, Gram stain, sterility, endotoxin, mycoplasma, and interferon gamma (IFN-γ) production. Additional testing included DNA sequencing to determine genomic CISH editing efficiency and a Western blot for determination of CISH protein loss.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Patients with GI cancers (colon [10], rectal [8], pancreatic [1], and esophageal [1]) underwent tumor collection. Nineteen of 22 tumor biopsies sampled from 20 patients total proceeded to KO/expansion. Final TIL product results (mean [SD], median [range]) were: viable count (x 10&lt;sup&gt;10&lt;/sup&gt;) -3.25 (3.67), 1.95 (0.018-12.40); viable TIL fold expansion -327.1 (364.8), 153.1 (8-1454); % viability - 76 (13), 78 (43-92); % CD3 -94.4 (5.4), 95.8 (78.6-99.4); % CISH KO efficiency - 75 (29), 87 (0-96); % editing efficiency - 59.9 (24.8), 66.9 (0.4-86). Viability fell below 70% for five TIL products. All other lot release testing has met specification. Thirteen patients have received TIL; six patients were not treated due to disease progression prior to anticipated infusion.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The translation of CRISPR/Cas9-based CISH KO MR TIL from the basic research lab to current good manufacturing practices The (cGMP) facility was successful, allowing for optimized, large-scale expansion in support of a first-in-human clinical trial to treat patients with metastatic GI cancers (ClinicalTria","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144651124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping the European landscape and specificity of ATMPs guidance.","authors":"Aurélie Mahalatchimy, Valentin Roby, Julie Véran, Christian Chabannon, Florence Sabatier","doi":"10.1016/j.jcyt.2025.06.008","DOIUrl":"https://doi.org/10.1016/j.jcyt.2025.06.008","url":null,"abstract":"&lt;p&gt;&lt;p&gt;A good amount of guidance has been issued by various national and international organizations in addition to the global regulation of Advanced Therapy Medicinal Products (ATMPs) at the European Union (EU) level. These include regulatory, technical, and scientific documents (mainly, but not only, guidelines), which aim to support the operability of the European pharmaceutical legislative framework. Guidance documents are highly necessary, especially in a rapidly evolving field such as ATMPs in which scientific achievements may translate quickly into therapeutic innovations. They provide the needed flexibility and adaptation that the legislative level could never afford to the same extent when considering the usual delays for revision, adoption, and application of binding legislative acts such as the ATMPs Regulation or the European Directives on medicinal products. This has led to the early adoption of guidance documents in the field of gene and cell therapy, the first of which appeared in the 1990s. However, with this early adoption comes complexity and difficult readability due to the accumulation of new soft law rules in the wake of new scientific findings and hard law regulations. Our study provides the first comprehensive analysis of guidance produced and currently applicable in the field of ATMPs and its relationship with categorization of biological medicinal products. We base our analysis on the collection of available guidance documents from the websites of the most active institutions in the production of guidance on ATMPs applicable within the European Union. We also obtained relevant material via the search engines of those websites by using a list of keywords corresponding to ATMPs or their subcategories. Our search resulted in a collection of 126 guidance documents applicable to ATMPs from July 1990 to September 8, 2023. We found that the distribution of current ATMP guidance mainly comes from the European Medicines Agency (EMA) and the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use regarding their sources, and are mainly guidelines regarding their types. This demonstrates that for the majority of currently applicable ATMP guidance documents, there is no overlap with other categories of biologicals, indicating that they are strictly specific to ATMPs. Our data indicate that the overlap between ATMPs and other biologicals essentially deals with the active substance and finished products among transversal categories and with biotechnologicals among various types of biological medicinal products. We discuss these results in light of their usefulness in regard to medical and socioeconomic actors of biotherapies. Finally, we conclude that the singularity of ATMPs is quite well reflected through their guidance landscape with a high number and diversity of documents. Although the overlap of guidance applicable to biologicals is important and could be anticipated based on the common ","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}