Clinical and experimental immunology最新文献

{"title":"Dysregulated complement activation in COVID-19: The Role of Soluble Complement Inhibitors.","authors":"Stef van der Meulen, Haiyu Wang, Saskia Nugteren, Frederique Ponchel, Anna H E Roukens, Cilia R Pothast, Mirjam H M Heemskerk, Kyra A Gelderman, Jeroen C J Eikenboom, Bernard M van den Berg, Wendy Stam, Coert Margadant, Simone A Joosten, Leendert A Trouw","doi":"10.1093/cei/uxag064","DOIUrl":"https://doi.org/10.1093/cei/uxag064","url":null,"abstract":"<p><p>In viral infections, complement activation can contribute to viral clearance, but excessive activation, as observed in severe COVID-19, may drive immunopathology. While much is known about complement-activating factors in COVID-19, insight into the role of endogenous complement inhibitors remains limited. We performed a longitudinal analysis within the BEAT-COVID cohort, comprising hospitalized patients with SARS-CoV-2 infection admitted to the intensive care unit (ICU) or ward, and age-matched healthy controls. Serum levels of the complement activation marker soluble membrane attack complex (sC5b-9) and soluble inhibitors C1-Inhibitor (C1-INH), C4b-Binding Protein (C4BP), Factor H, and Factor I were measured by ELISA. In vitro endothelial complement sensitivity was assessed by flow cytometry. Soluble inhibitors were also measured in a cohort of patients with long COVID. Patients admitted to the ICU showed elevated sC5b-9 levels compared to patients admitted to the ward and controls, correlating with disease severity, length of hospitalization, and need for mechanical ventilation, but not mortality. Unexpectedly, levels of all soluble complement inhibitors were elevated, particularly in patients admitted to the ICU. Factor H levels positively correlated with sC5b-9. Endothelial cells pre-incubated with serum from patients admitted to the ICU became more susceptible to complement attack. In patients with long COVID, Factor H and C4BP levels remained elevated compared to pre-pandemic healthy controls. Severe COVID-19 is characterized by extensive complement activation despite elevated circulating inhibitor levels, suggesting impaired local complement regulation at the cell surface, potentially amplified by overwhelming systemic activation, rather than inhibitor deficiency.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191717","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":"Precision targeting and alternative effector cells: Revolutionizing CAR-based therapy for T-cell malignancies.","authors":"Yingtong Chen, Shuang Gao, Shuozi Liu, Ping Yang, Hongmei Jing","doi":"10.1093/cei/uxag060","DOIUrl":"https://doi.org/10.1093/cei/uxag060","url":null,"abstract":"<p><p>T-cell malignancies are highly heterogeneous and associated with high relapse rate and poor prognosis. While chimeric antigen receptor-T (CAR-T) cell therapy has achieved remarkable success in relapsed or refractory B-cell malignancies, its application in T-cell malignancies remains limited. Key challenges include shared surface antigen expression among CAR-T cells, normal T cells, and malignant T cells, leading to fratricide and T-cell aplasia, and the risk of tumor cell contamination during CAR-T manufacturing. This review summarizes recent advances in CAR-based therapies for T-cell malignancies, focusing on clinical translation barriers, emerging solutions, and future directions. We highlight promising target antigens under preclinical and clinical investigation, as well as alternative effector platforms, including natural killer (NK) cells, NKT cells, γδ T cells, and macrophages, that hold potential as next-generation CAR-expressing cellular therapeutics.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104527","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":"Diagnosing primary immunodeficiencies using protein-based screening assays.","authors":"M Ferro, M Selby, M Davis, K Gilmour","doi":"10.1093/cei/uxag062","DOIUrl":"https://doi.org/10.1093/cei/uxag062","url":null,"abstract":"<p><p>Primary immunodeficiencies (PIDs), now more commonly referred to as inborn errors of immunity (IEIs), are a diverse group of inherited conditions characterized by immune system defects, leading to recurrent infections, immune dysregulation, and autoimmune symptoms. Early diagnosis is crucial for effective management and treatment. This document explores the role of protein-based assays in diagnosing and characterizing IEIs. Protein-based assays, including enzyme-linked immunosorbent assay (ELISA), flow cytometry, and immunoblotting, have significantly advanced the identification and understanding of IEI. These assays enable rapid screening and functional analysis of immune proteins, providing critical insights into the phenotypic manifestations of genetic mutations. ELISA technology allows for the detection of specific antigens or antibodies, while flow cytometry facilitates the analysis of multiple cell populations and their functional states. Immunoblotting remains valuable for detecting protein expression and identifying truncated or non-functional proteins. This review highlights case studies demonstrating the application of these assays in diagnosing conditions such as X-linked lymphoproliferative syndrome type 2 (XLP2), activated phosphoinositide 3-kinase delta syndrome (APDS), Severe Combined Immunodeficiency (SCID) and Wiskott-Aldrich syndrome (WAS). It also discusses the importance of functional assays in confirming the pathogenicity of genetic variants of unknown significance (VUS) and guiding targeted genetic analysis. Overall, protein-based assays are essential tools in the diagnostic workflow for IEI, enabling timely and accurate diagnosis, guiding therapeutic decisions, and monitoring patient outcomes post-treatment, including hematopoietic stem cell transplantation (HSCT) and gene therapy.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103556","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":"Epitope-Specific Thyroid Peroxidase Antibodies Reveal Functional Heterogeneity Within a Patient-Derived Monoclonal Repertoire.","authors":"Yingxue Wang, XinYi Liu, Hui Ye, Nan Li, Huayu Zhong, Lihong Nie, Xiaomin Zhang, Xin Luo","doi":"10.1093/cei/uxag054","DOIUrl":"https://doi.org/10.1093/cei/uxag054","url":null,"abstract":"<p><strong>Introduction: </strong>Thyroid peroxidase (TPO) autoantibodies are defining features of autoimmune thyroid disease (AITD), yet the relationship between epitope specificity and antibody function remains incompletely understood.</p><p><strong>Methods: </strong>In this study, we generated patient-derived human monoclonal anti-TPO antibodies from a single donor with AITD (T-011) and characterized their competition-defined epitope relationships, reporter-based Fcγ receptor activity, and direct effects on TPO enzymatic function.</p><p><strong>Results: </strong>Although the antibodies exhibited comparable FcγRIIIa reporter activation, FcγRIIa reporter responses varied according to epitope specificity. Notably, TPO036 demonstrated enhanced FcγRIIa reporter signaling and, following conversion to an F(ab')2 format, competitively inhibited Fc-mediated reporter activation. Direct TPO activity assays demonstrated that representative antibodies produced either no or only minimal inhibition of TPO enzymatic activity under the conditions tested. These findings indicate that competition-defined anti-TPO antibody groups within a single-donor repertoire can exhibit distinct functional profiles, particularly with respect to Fc-mediated reporter responses, without evidence of broad inhibition of TPO catalytic activity.</p><p><strong>Conclusion: </strong>Overall, our results support the existence of intra-individual, epitope-associated functional heterogeneity among anti-TPO antibodies and provide a proof-of-concept foundation for future studies evaluating epitope-targeted and Fc-modulating strategies in physiologically relevant models.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896367","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":"Immunometabolism crosstalk between regulatory T cells and glucose homeostasis of type 1 diabetes.","authors":"Masoume Nodehi, Ziba Veisi Malekshahi, Ramin Rahimnia, Javad Verdi, Nasim Vousooghi, Iman Seyhoun","doi":"10.1093/cei/uxag020","DOIUrl":"10.1093/cei/uxag020","url":null,"abstract":"<p><p>Type 1 diabetes mellitus (T1D) is an autoimmune disease that is associated with the loss of pancreatic β cells. Regulatory T cells (Tregs) play a critical role in the maintenance of immune tolerance; however, the number and function of Tregs have been found to be compromised in T1D. Genetic changes in FOXP3, as well as the role of hyperglycaemia and the accumulation of advanced glycation end products, have been proposed as potential mechanisms for the dysfunction of Tregs. However, the current understanding suggests that the role of the metabolic reprogramming associated with hyperglycaemia is more likely to be a potential mechanism for the instability of Tregs rather than a well-established primary mechanism for the development of T1D. Several therapeutic strategies have been explored in experimental models for the management of autoimmune diseases associated with Tregs dysfunction. These include the administration of low-dose interleukin-2, metformin, and dietary or microbiome-based therapies. These therapies have been found to modulate the immune system; however, the efficacy of these therapies for the management of T1D is to be established. In the present review article, the current understanding of the role of the interrelationship between hyperglycaemia, metabolic reprogramming, and Tregs-mediated immune tolerance in the pathogenesis of type 1 diabetes is reviewed.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":"220 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13193186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147986913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PD-1 engagement and circulating Th17 effector activity during secukinumab treatment in plaque psoriasis.","authors":"Mengmeng Zhang, Xujiao Feng, Kexiang Yan, Jiaqing Zhou, Lei Shen, Zhenghua Zhang","doi":"10.1093/cei/uxag037","DOIUrl":"10.1093/cei/uxag037","url":null,"abstract":"<p><p>Plaque psoriasis (PP) is a chronic immune-mediated inflammatory disease driven by dysregulation of the IL-23/Th17/IL-17 axis. Although IL-17A-targeted biologics achieve robust clinical efficacy, the systemic immune remodeling accompanying successful treatment remains incompletely understood. We performed longitudinal immune profiling in seven patients with PP before treatment and after achieving a 90% reduction in the Psoriasis Area and Severity Index (PASI 90) following secukinumab therapy. Circulating T-cell subsets, programmed cell death protein 1 (PD-1)-expressing populations, cutaneous lymphocyte antigen-positive (CLA+) T cells, and plasma cytokines were analyzed by flow cytometry and multiplex assays. Ex vivo responses to the PD-1 agonist peresolimab were further evaluated in an independent cohort. At baseline, patients exhibited reduced frequencies of regulatory T cells compared with healthy controls. Following PASI 90, circulating Th17 and Th2 cell frequencies increased despite minimal sustained changes in plasma cytokine levels, suggesting dissociation between effector T-cell expansion and soluble inflammatory mediators during IL-17A blockade. Circulating CD4+CLA+ T cells were partially restored, and treatment was accompanied by increased frequencies of PD-1-expressing CD4+ T-cell subsets, which were inversely associated with disease activity over time. Ex vivo PD-1 engagement selectively suppressed IL-17A-producing CD4+ T cells while largely preserving IFN-γ production. These findings suggest that clinical improvement during IL-17A blockade is accompanied by coordinated immune remodeling rather than generalized systemic immunosuppression and that PD-1 signaling may contribute to restraining Th17 effector function during therapeutic response.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13344862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148351035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of C1 inhibitor subcutaneously in the UK: insights from a national real-world retrospective study.","authors":"Ky-Lyn Tan, Moira Thomas, Anthony D Dorr, Lorena Lorenzo, Michael Tarzi, Malini Bhole, Efrem Eren, Xi Ying Soo, Sadia Noorani, Emily Zinser, Patrick F K Yong","doi":"10.1093/cei/uxag055","DOIUrl":"10.1093/cei/uxag055","url":null,"abstract":"","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13583499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Depletion and recovery of IgG following treatment with an anti-FcRn antibody and IdeS in pigtail macaques.","authors":"Kara M Rzasa, Joanna Zikos, Toni Penney, Faith R Schiro, Lara A Doyle-Meyers, Pyone P Aye, Ronald S Veazey, James A Hoxie, Nicholas J Maness, Diogo M Magnani, Margaret E Ackerman","doi":"10.1093/cei/uxag029","DOIUrl":"10.1093/cei/uxag029","url":null,"abstract":"<p><p>Antibodies are central players in adaptive immunity, providing protection against a wide array of pathogens through mechanisms such as neutralization, opsonization, recruitment of effector immune cells, complement activation, and engagement. However, in other contexts, these same effector functions can contribute to immunopathology, particularly when antibodies are developed against self-antigens, resulting in autoimmunity. Understanding the role antibodies play in preventing or causing disease is often supported by studies in model systems wherein manipulation of immunoglobulin G (IgG) levels can be used as an experimental tool. Here, we report in simian immunodeficiency virus (SIV) infected pigtail macaques (Macaca nemestrina) the capacity of two orthogonal strategies to systemically deplete IgG: treatment with a primatized neonatal Fc receptor blocking antibody (anti-FcRn) modelled on rozanolixizumab that restricts IgG rescue and recycling, and administration of the IgG protease IdeS that cleaves the Fc domain. Under the conditions evaluated, we observed more rapid and effective, although not necessarily more durable, IgG depletion mediated by IdeS, reducing levels by 74.1-95.1%, compared with a lesser reduction of 31.3-66.9% with anti-FcRn treatment. We observed a similar degree of depletion, comparable kinetics of rebound among SIV antigen-specific fractions as total IgG, but differential balance among IgG subclasses following treatment in some cases. In sum, this study in a non-human primate model describes the efficacy and downstream impacts of new tools to modify humoral immune states, providing insight into the balance between protective and pathological effects of IgG antibodies.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13248873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147980922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Severity-associated changes in ICOS, CD27, CD127, and CLA expression and expansion of virus-specific T cells in acute dengue.","authors":"Heshan Kuruppu, Malithi De Silva, Chathumini Dissanayake, Radanee Rathnapriya, Ananda Wijewickrama, Damayanthi Idampitiya, Lakshmanane Premkumar, Chandima Jeewandara, Graham Ogg, Gathsaurie Neelika Malavige","doi":"10.1093/cei/uxag049","DOIUrl":"10.1093/cei/uxag049","url":null,"abstract":"<p><p>Currently, the role of dengue virus-specific T-cell responses in disease pathogenesis and protection is not well understood, including potential differences in individuals with obesity. We sought to investigate the functionality and phenotype of T cells in patients with acute dengue fever (DF) or dengue haemorrhagic fever (DHF). T-cell function was assessed in paired samples (first sample on ≤4 days and second 5-6 days since onset of illness) in patients with DF (n = 50) and DHF (n = 12), using 109 peptides representing CD8+ epitopes and 90 peptides targeting CD4+ T-cell epitopes. Phenotypic analysis was performed in patients with DF (n = 21) and DHF (n = 21), recruited between days 6 and 8 since onset of illness, using multicolor flow cytometry. The frequency of ex vivo IFNγ ELISpot responses to both the CD4+ and CD8+ peptide pools significantly increased from first (F) to second (S) time point in patients with DF (P < 0.0001) but not with DHF. The frequency of ex vivo IFNγ ELISpot responses to CD4+ (P = 0.001) and CD8+ peptide pools (P = 0.0002) also significantly increased from the F to S in lean patients but not in obese patients. Cutaneous lymphocyte-associated antigen (CLA) expression was significantly higher in the CD8+ T-cell subset in patients with DF and DHF compared to healthy controls, and these differences were most significant in CD8+ CD45RA- T cells. CD8+ CD45RA-CLA+ T cells consisted of >50% of the T cells in 9/21 patients with DHF, with 92.7% expressing CD38. CLA expression was highest in the CD8+ CD45RA- T cells in obese individuals, which was significantly higher compared to lean individuals (P = 0.01). CD27 and CD127 were both significantly downregulated in patients with DHF compared to DF, with ICOS expression being significantly higher in CD8+ T cells in DHF. Patients with DHF and obese individuals had impaired T-cell functionality compared to patients with DF and lean individuals, with an expansion of activated, skin-homing CD8+ T cells exhibiting downregulation of CD27 and CD127. Our data suggest a contributory role of dysfunctional skin-homing T cells in disease pathogenesis, meriting further investigation.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13564389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD137 deficiency patients: two new patients and review of the literature.","authors":"Zehra Genc Ozbay, Busra Kocali, Deniz Ilgun Gurel, Ismail Yaz, Baris Ulum, Dilek Aktas, Ece Ozogul, Elif Soyak Aytekin, Saliha Esenboga, Aysegul Uner, Baris Kuskonmaz, Deniz Cagdas","doi":"10.1093/cei/uxag021","DOIUrl":"10.1093/cei/uxag021","url":null,"abstract":"<p><p>CD137 (4-1BB, TNFRSF9) plays a crucial role in T-cell activation, proliferation, and antiviral immunity. Biallelic TNFRSF9 variants cause CD137 deficiency, a rare inborn error of immunity characterized by Epstein-Barr virus (EBV)-induced hemophagocytic lymphohistiocytosis (HLH) and lymphoproliferation/malignancy. In this study, we aimed to characterize the clinical, immunological, and genetic spectrum of CD137 deficiency to provide insights into patient management. We recruited two patients carrying the same homozygous large deletion encompassing exons 1-6 of the TNFRSF9 gene and reviewed previously reported cases. The genetic defect was identified by whole-exome sequencing and confirmed by multiplex ligation-dependent probe amplification. Reported variants included missense, splice-site, and frameshift variants, large deletions, and compound heterozygous variants. A total of 14 patients, including the two newly reported cases, exhibited recurrent sinopulmonary infections and EBV viremia. HLH occurred in four patients (28.5%), including both newly reported patients, while lymphoma developed in seven patients (50%). Most patients were of Middle Eastern origin, and parental consanguinity was documented in 12 of 14 patients (85%). Hematopoietic stem cell transplantation (HSCT) was performed in 35.7% (5/14) of patients, with a median age of 9 years (range, 7-17 years) among four reported cases. All transplanted patients were alive at the last follow-up, whereas mortality occurred exclusively among non-transplanted patients, including EBV-positive cases. These findings expand the phenotypic and mutational spectrum of CD137 deficiency and highlight the importance of incorporating copy number variant analysis into exome-based diagnostic pipelines when conventional single-nucleotide variant analysis is inconclusive. HSCT remains the only potentially curative treatment, and early molecular diagnosis is essential to enable timely consideration of HSCT and to mitigate life-threatening EBV-driven immunopathology.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":"220 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13180749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147962601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}