Xenotransplantation最新文献

{"title":"Xenotransplantation: A Bibliometric Analysis of Current Trends.","authors":"Hamzeh Feras Alshahwan, Saif Yamin, Layan Ababneh, Abdullah Alhalbouni, Muna Rommaneh, Omar Ismail, Badi Rawashdeh","doi":"10.1111/xen.70046","DOIUrl":"https://doi.org/10.1111/xen.70046","url":null,"abstract":"<p><p>Xenotransplantation, the transplantation of organs or tissues between species, offers a promising solution to the organ donor shortage. This study examines the research landscape of the field, identifying key trends, influential studies, and leading contributors. A search of the Scopus database on June 24, 2024, focused on solid-organ xenotransplantation publications. Articles were analyzed using Vosviewer, Bibliometrix, and Microsoft Excel. The analysis included 1072 articles with 26 066 citations, reflecting substantial impact in transplantation research. The average citations per document were 24.32, with an annual publication growth rate of 7.63%. Key sources included Xenotransplantation, Transplantation, and Transplantation Proceedings. Cooper was the most influential author, and Harvard Medical School was the leading institution. The United States dominated in publication output and citations. The most cited article, by Hering et al. (2006), had 458 citations. The study highlights the significant growth and increasing attention to xenotransplantation, with ongoing trials emphasizing its potential. This analysis provides insights into the field's progress and serves as a guide for future translational research to advance xenotransplantation toward clinical application.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"32 2","pages":"e70046"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144039918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Religious Perspectives Regarding the Ethical Issues Associated With Clinical Xenotransplantation.","authors":"Daniel J Hurst, Mansur Ali, Samuel M Brown, Joris Gielen, Komal Kashyap, Terri Laws, John Loike, Renzo Pegoraro, Jonah Rubin, Martha Stebbins, Andrew T Walker, Syed Shabih Haider Zaidi, Richard N Pierson, Emanuele Cozzi","doi":"10.1111/xen.70036","DOIUrl":"https://doi.org/10.1111/xen.70036","url":null,"abstract":"<p><strong>Background: </strong>As xenotransplantation advances toward clinical trials, viewpoints from various segments of society are continually needed to engage the public and to inform the prospective clinical trials. As the majority of the world's population identifies with a religious tradition, religious perspectives regarding the ethical issues associated with clinical xenotransplantation are an important element to take into account.</p><p><strong>Methods: </strong>At the 2024 Congress of The Transplantation Society in Istanbul, Türkiye, a group of religious scholars from Catholicism, The Church of Jesus Christ of Latter-day Saints, Hinduism, Shia Islam, Judaism, Protestant Christianity, and the African American religious traditions met together to discuss viewpoints toward xenotransplantation from their respective religious tradition. Additional contributions were received from representatives from the American Anglican Episcopal Church and Sunni Islam faith traditions.</p><p><strong>Results: </strong>Each speaker presented viewpoints on the ethical issues associated with clinical xenotransplantation from their own religious perspective. Common issues that were raised include the treatment and stewardship of animals, xenozoonotic infection and other risks, while religious dictums of particular relevance for each faith tradition were noted.</p><p><strong>Conclusion: </strong>Overall, none of the participants considered xenotransplantation to be impermissible within their religious tradition. Yet, it is important to note that persons of religious faith may come to different conclusions from their coreligionists about the permissibility of xenotransplantation as a personal choice or as spokespersons for others of their faith. Additional empirical viewpoint data from each religious tradition will be helpful to further inform normative views and measure the impact of public education. As xenotransplantation continues to advance to the clinic, continued exploration of religious perspectives is needed to best support individual decision-making and optimize patient-centered care.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"32 2","pages":"e70036"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12005069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection of Anti-Non-α-Gal Xenoreactive Antibodies in Human Blood Products.","authors":"Joseph M Ladowski, Meghan Hu, Janghoon Yoon, Zheng Chen, Stuart Knechtle, Annette M Jackson, Jean Kwun","doi":"10.1111/xen.70034","DOIUrl":"10.1111/xen.70034","url":null,"abstract":"<p><strong>Background: </strong>Surgical bleeding is a risk in any solid organ transplant, and is commonly addressed with the transfusion of human blood products to replace or supplement coagulation factors. It is unknown if these blood products would harm xenotransplanted pig organs in human recipients demonstrating coagulopathy. The aim of this study was to investigate in vitro if blood products such as fresh frozen plasma (FFP) or cryoprecipitate (cryo) contain xenoantibodies capable of cytotoxicity to GTKO pig cells.</p><p><strong>Methods: </strong>We obtained 12 individual single-donor (7 FFP and 5 cryo) blood products from our institution's blood bank for testing. Peripheral blood mononuclear cells (PBMCs) were obtained from a GTKO/hCD55 pig for use as target cells. We performed a series of flow cytometry crossmatch (FCXM) and complement-dependent cytotoxicity (CDC) assays.</p><p><strong>Results: </strong>We found that all the tested blood products contained some degree of IgM and IgG xenoantibody. Tests using a 1:50 dilution revealed a significant decrease in IgM xenoantibody binding, but an increase in the detection of IgG binding. Multiple preparations were capable of GTKO PBMC cytotoxicity but the level of antibody binding and cell death varied by preparation.</p><p><strong>Conclusions: </strong>Both FFP and cryo contain IgM and IgG non-galactose-α-1,3-galactose (αGal) xenoantibodies capable of killing GTKO PBMCs, though the level varies by preparation. Although some centers utilize a genetic background with mutations in the three enzymes responsible for the known xenoantigens, others are investigating the GTKO pig as a potential option. These results suggest that a center pursuing a human xenotransplantation study with a GTKO genetic background should pre-screen blood products prior to administration.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"32 2","pages":"e70034"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12013840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment of Presumptive Rejection After Orthotopic Pig-to-Baboon Cardiac Xenotransplantation.","authors":"Chace B Mitchell, Sarah J Neal, Joe H Simmons, Sriram Chitta, David K C Cooper, David C Cleveland, John D Cleveland","doi":"10.1111/xen.70044","DOIUrl":"https://doi.org/10.1111/xen.70044","url":null,"abstract":"<p><strong>Background: </strong>Significant progress has been made in the long-term survival of non-human primates after orthotopic gene-edited pig cardiac xenotransplantation. However, to our knowledge, there are no reports of the successful reversal of an acute rejection episode in such an experiment. We present evidence suggesting that rejection can be reversed with corticosteroids and complement inhibition.</p><p><strong>Methods: </strong>Orthotopic transplantation of a pig heart (with 69 gene-edits) was carried out in a baboon. The immunosuppressive regimen was based on CD40/CD154 T cell co-stimulation pathway blockade and rapamycin. Cardiac function remained excellent until Day 162, when there were increases in heart rate, ventricular septal wall thickness, left ventricular end-diastolic pressures (LVEDP), and troponin level, which were associated with a low serum level of rapamycin (<4 ng/mL). Anti-rejection treatment was begun with an increase in rapamycin dosage, steroid bolus therapy, two doses of a C1-esterase inhibitor, and an extra dose of the anti-CD154mAb.</p><p><strong>Results: </strong>There was a rapid correction of all hemodynamic parameters, and the troponin T level (which had risen to 139 ng/L) returned to pre-rejection levels. Ventricular septal thickness and LVEDP returned to pre-rejection levels after treatment. The baboon remains well with normal graft function. Baseline heart rate remains faster than before the rejection episode.</p><p><strong>Conclusions: </strong>As we transition to the clinical application of gene-edited pig cardiac xenotransplantation, the ability to treat rejection is of vital importance. The optimal treatment for rejection remains uncertain but we suggest that systemic complement inhibition is important.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"32 2","pages":"e70044"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dendritic Cells in Xenotransplantation: Shaping the Cellular Immune Response Toward Tolerance.","authors":"Gisella L Puga Yung, Tom Wakley, Athanasios Kouklas, Jörg D Seebach","doi":"10.1111/xen.70037","DOIUrl":"https://doi.org/10.1111/xen.70037","url":null,"abstract":"<p><p>The molecular barriers that cause acute xenograft rejection have been identified and addressed by generating genetically modified (GM) animals, knocked out for specific xenoantigens (xenoAgs), and expressing regulatory molecules for both complement and coagulation pathways among others. The focus of xenotransplantation research now lies in delayed xenograft rejection. Dendritic cells (DC) are a specific subpopulation of professional antigen-presenting cells (APC) that play a crucial role in the context of organ transplantation. DCs, originating from both the xenograft and the recipient, have the capacity to present xenoAgs to the recipient's immune system via their respective major histocompatibility complex (MHC) molecules leading to rejection. These processes are known as direct and indirect presentation, respectively. However, under certain microenvironmental conditions, DC develops into anti-inflammatory regulatory cells that can induce immunological tolerance. The purpose of this review is to summarize current knowledge on the general characteristics and functions of DC from species relevant to xenotransplantation, specifically humans, non-human primates (NHP), and pigs. It will also cover the process of xenoAg presentation, different methods for generating DC with regulatory properties in vitro, and finally, discuss the current strategies for using regulatory DC to improve xenograft acceptance by inducing tolerance.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"32 2","pages":"e70037"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12005074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Defect in Sensing Human Thrombin by Porcine Endothelial Protease-Activated Receptor-1: Molecular Incompatibility Between Porcine PAR-1 and Human Thrombin.","authors":"Thi Xoan Hoang, Ju-Young Bang, Vinh Phuoc Nguyen, Phu Chi Vu, Ik Jin Yun, Hee Jung Kang, Jae Young Kim","doi":"10.1111/xen.70041","DOIUrl":"https://doi.org/10.1111/xen.70041","url":null,"abstract":"<p><p>Xenotransplantation, the transplantation of organs from pigs to humans, presents significant challenges due to immune rejection, which is driven by molecular incompatibilities between species. This study investigates the compatibility between human thrombin and porcine protease-activated receptor-1 (PAR-1), a key regulator of both coagulation and inflammatory responses. Human thrombin activates PAR-1 in human vascular endothelial cells, but our results demonstrate that human thrombin does not effectively activate PAR-1 in porcine vascular endothelial cells due to differences in amino acid sequences, particularly at the thrombin cleavage site and the Hir domain. Protein-protein docking analysis further reveals that porcine PAR-1 forms less stable interactions with human thrombin compared to human PAR-1, resulting in reduced activation. This molecular incompatibility likely contributes to impaired nitric oxide (NO) production, endothelial dysfunction, and increased inflammation, which are critical for the survival of transplanted organs. Additionally, experiments using the PAR-1 inhibitor vorapaxar (Vor) show that inhibiting PAR-1 signaling can suppress inflammatory cytokine and chemokine expression in co-cultures of human macrophages and porcine endothelial cells. These findings suggest that selective PAR-1 inhibitors or targeted therapies regulating thrombin-PAR-1 signaling may improve the success rate of xenotransplantation. However, further in vivo studies are needed to validate these findings and explore therapeutic interventions targeting thrombin-PAR-1 interactions to enhance xenograft survival.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"32 2","pages":"e70041"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12005063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combinatorial Decellularization as a Better Approach to Porcine Liver Extracellular Matrix Scaffold Fabrication With Preserved Bioactivity: A Comparative Evaluation.","authors":"Jesna Puthiya Veettil, Devika Sasikumar Lolitha, Umashankar Payanam Ramachandra","doi":"10.1111/xen.70031","DOIUrl":"10.1111/xen.70031","url":null,"abstract":"<p><p>Soft tissue repair patches of decellularized extracellular matrices (ECM) with inherently preserved structural components and biomacromolecules are desirable in regenerative applications. This study characterizes three detergent-based decellularization methods to fabricate acellular porcine liver matrices to remove antigenic determinants without compromising the structural integrity, glycosaminoglycans (GAG) content, and bound growth factors within the resulting ECM. Three detergents chosen for decellularization were sodium dodecyl sulfate (SDS), SDS with sodium deoxycholate (SDS+SDC-combinatorial method), and triton X-100 followed by SDS. Combinatorial detergent decellularization effectively removed cellular components and retained intact collagenous structure with minimal residual DNA and protein. It also preserved significantly higher amounts of GAG, HGF, and bFGF. TX100 decellularization was highly destructive with the least preservation of GAG and GFs. The SDS method showed an intermediate level of preservation of biomolecules. The correlation obtained between GAG and GFs revealed quantification of GAG to be an indirect way of estimating the bound GFs preserved within the ECM. In vitro experiments revealed the non-cytotoxic nature of the scaffolds. The study revealed that, among the three methods of decellularization, the ECM scaffold fabricated by combinatorial detergent decellularization is extremely promising to be used as a soft tissue repair patch with inherent bioactive molecules for scaffold-based regenerative therapies.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"32 2","pages":"e70031"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Attitudes Toward Renal Xenotransplantation in a Muslim Country: Analysis of Specific Subgroups.","authors":"Mustafa Karaaslan, Muhammed Emin Polat, Mehmet Emin Sirin, Kazim Ceviz, Alp Bardakci, Mecit Celik, Mehmet Yilmaz, Erkan Olcucuoglu","doi":"10.1111/xen.70042","DOIUrl":"https://doi.org/10.1111/xen.70042","url":null,"abstract":"<p><p>Renal transplantation is the optimal treatment for end-stage kidney disease, but the rising demand for organs necessitates exploring alternative graft sources, including xenotransplantation. This study evaluated attitudes toward xenotransplantation among different social groups in a Muslim country. A structured survey assessing demographics, religiosity levels, attitudes toward xenotransplantation, and the influence of religious authorities was completed by 988 participants: 376 clergy members (38.1%), 206 physicians (20.9%), 162 dialysis patients and their relatives (16.4%), and 244 individuals from other groups (24.7%). Significant sociodemographic differences were observed in gender, marital status, and education (p < 0.001). Physicians and dialysis patients/relatives were likelier to support living donor transplantation (48.5%, 67.3%), whereas clergy members often reported no opinion (44.9%). Favorable attitudes toward xenotransplantation were the highest among physicians (66%) and dialysis patients/relatives (67.3%). When the animal was specified as a pig, 73.1% of the Clergy group exhibited unfavorable attitudes. However, this group significantly changed their opinion after the favorable fatwa issued by the religious authority. Logistic regression identified male gender, lower religiosity, and higher education as predictors of favorable attitudes, with physicians and dialysis patients/relatives demonstrating the strongest associations compared to clergy. To infer, collaboration between religious and scientific authorities is essential to address concerns and emphasize the potential benefits of xenotransplantation.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"32 2","pages":"e70042"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"International Xenotransplantation Association (IXA) Position Paper on Infectious Disease Considerations in Xenotransplantation.","authors":"Jay A Fishman, Joachim Denner, Linda Scobie","doi":"10.1111/xen.70001","DOIUrl":"10.1111/xen.70001","url":null,"abstract":"<p><p>Clinical xenotransplantation has the potential to address shortages of human organs for patients with end-stage organ failure. Advances in genetic engineering, immunosuppressive regimens, and infectious disease diagnostics have improved prospects for clinical xenotransplantation. Management of the infectious risks posed by clinical xenotransplantation requires biosecure breeding and validated methods for microbiological surveillance of source animals and recipients. Novel infection control protocols may complement biosafety requirements. Infectious risks in xenotransplantation include both known human pathogens common to immunosuppressed organ recipients and from porcine organisms or xenozoonoses for which the clinical manifestations are less well defined and for which microbial assays and therapies are more limited. Some pig-specific organisms do not infect human cells but have systemic manifestations when active within the xenograft. The human risk posed by porcine endogenous retroviruses (PERV) is uncertain. There are no documented transmissions of PERV in humans and swine are available with inactivated genomic PERV loci. Metagenomic sequencing will complement more traditional diagnostic tools in the detection of any unknown pathogens in xenotransplantation recipients. Such data are required for the development of protocols for donor and recipient microbiological surveillance, infection control, and antimicrobial therapies that will enhance the safety of clinical xenotransplantation.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"32 2","pages":"e70001"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Desensitization With Proteasome Inhibition and Costimulation Blockade Modulates the Xenoreactive Humoral Response in Nonhuman Primate Xenotransplantation.","authors":"Brendan P Lovasik, Abraham J Matar, Jakob Habib, David A Faber, Cynthia P Breeden, Alton B Farris, A Joseph Tector, Andrew B Adams","doi":"10.1111/xen.70045","DOIUrl":"https://doi.org/10.1111/xen.70045","url":null,"abstract":"<p><strong>Introduction: </strong>\"Delayed\" antibody-mediated xenograft rejection is one of the most important obstacles to clinical application of pig organ xenografts. The aim of this study was to assess the impact of a structured desensitization regimen including proteasome inhibition and next-generation costimulation blockade on xenoreactive antibodies.</p><p><strong>Methods: </strong>Rhesus macaques with moderate-high pre-treatment xenoreactive antibody titers (N = 2) were selected. Recipients received twice-weekly carfilzomib (20 mg/m²), anti-CD154 (20 mg/kg) every other week, and CD4 and CD20 lymphocyte cell depletion. Bone marrow was acquired to assess plasma cell depletion in response to proteasome inhibition. A flow cytometry-based xenoreactive crossmatch assay was performed to assess levels of circulating xenoreactive antibodies.</p><p><strong>Results: </strong>The desensitization regimen resulted in a >50% depletion of CD38+CD27+ bone marrow plasma cells; these changes were progressive over the duration of the desensitization treatment period. The desensitization strategy and plasma cell depletion resulted in a progressive reduction in anti-pig IgG antibodies. Following xenotransplantation, both desensitized recipients demonstrated superior graft survival to a highly xenoreactive recipient (MST 30 days vs. 6 days), but neither desensitized recipient experienced prolonged graft survival.</p><p><strong>Conclusions: </strong>A structured desensitization regimen including proteasome inhibition and costimulation blockade results in plasma cell depletion and resultant reduction in circulating xenoreactive anti-pig IgG antibodies, with a modest improvement in xenograft survival. This desensitization regimen has promise for pig-to-NHP xenotransplant models.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"32 2","pages":"e70045"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}