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{"title":"Chimeric antigen receptor T cells in treatment-refractory DAGLA antibody-associated encephalitis.","authors":"Tobias Hegelmaier, Denise Wolleschak, Vaia Pappa, Jonathan Wickel, Christian Geis, Ramona Miske, Alexander Duscha, Christiane Desel, Martin Böttcher, Alexandra Neyazi, Simon Faissner, Jeremias Motte, Ralf Gold, Dominic Borie, Georg Schett, Dimitrios Mougiakakos, Aiden Haghikia","doi":"10.1016/j.medj.2025.100776","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100776","url":null,"abstract":"<p><strong>Background: </strong>Autoimmune encephalitides are a heterogeneous group of autoantibody-associated central nervous system disorders. The clinical course of autoimmune encephalitides can be life threatening, and treatment can be challenging.</p><p><strong>Objective: </strong>This report describes a case of treatment-refractory, anti-diacylglycerol lipase alpha (DAGLA) antibody-associated autoimmune encephalitis successfully treated with chimeric antigen receptor (CAR) T cells.</p><p><strong>Methods: </strong>Treatment was done by single intravenous infusion of fully human, second-generation CAR T cells (KYV-101) targeting CD19 and depleting B cells. Clinical response was measured by International Cooperative Ataxia Rating Scale and Clinical Assessment Scale in Autoimmune Encephalitis scores. Autoantibodies against DAGLA were measured by a recombinant cell-based indirect immunofluorescence assay in the serum and the cerebrospinal fluid and confirmed by staining of primary murine neurons and brain sections.</p><p><strong>Findings: </strong>A 36-year-old man developed rapidly progressing generalized myoclonus, cerebellar head tremor, vertical binocular nystagmus, and tetraparesis despite treatment with pulse glucocorticoid therapy, plasma exchange, and rituximab. Anti-DAGLA antibodies were positive in the indirect immunofluorescence assay, in serum and cerebrospinal fluid, and reacted with neurons and brain sections. Due to his severe clinical condition and treatment refractoriness, the patient received a single infusion of autologous anti-CD19 CAR T cells. Clinical scores improved significantly after treatment, and anti-DAGLA antibody levels in serum and cerebrospinal fluid diminished. Oligoclonal bands in the cerebrospinal fluid were initially positive and became negative after CAR T cell therapy.</p><p><strong>Conclusion: </strong>The report highlights the therapeutic potential of anti-CD19 CAR T cell therapy in severe, treatment-refractory autoimmune encephalitis.</p><p><strong>Funding: </strong>There was no external funding for the treatment or the data generated.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100776"},"PeriodicalIF":12.8,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144709204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbiota-derived metabolites: Key modulators of cancer immunotherapies.","authors":"Markus Perl, Matthias A Fante, Konstantin Herfeld, Julian N Scherer, Hendrik Poeck, Erik Thiele Orberg","doi":"10.1016/j.medj.2025.100773","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100773","url":null,"abstract":"<p><p>The human gut microbiome shapes local and systemic immune responses and influences cancer immunotherapy outcomes. Microbial metabolites, including short-chain and branched-chain fatty acids, bile acids, tryptophan derivatives, and others, influence anti-tumor immunity by modulating immune cells, tumor growth, and the tumor microenvironment. These metabolites impact the efficacy of immune checkpoint inhibitors, allogeneic stem cell transplantation, chimeric antigen receptor T cell therapies, and immune-related adverse events. However, interindividual microbiome variability, antibiotic exposure, and the context-dependent pro- and anti-inflammatory effects of metabolites present significant challenges for clinical translation. Microbiome-based therapies, including live biotherapeutic products, dietary modifications (such as prebiotics), and synthetic metabolite compounds (postbiotics), are being developed for use in combination with immunotherapy. This review outlines how metabolites influence immunotherapy outcomes and discusses translational approaches to harness them for clinical practice. Future research should focus on validating metabolite-based biomarkers and tailoring metabolite-based interventions to enhance efficacy and reduce toxicity across different immunotherapies.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100773"},"PeriodicalIF":12.8,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aldosterone synthase inhibition in mineralocorticoid blockade: From hypertension to cardiovascular and kidney disease.","authors":"Jonathan W Cunningham, Carolyn S P Lam","doi":"10.1016/j.medj.2025.100772","DOIUrl":"10.1016/j.medj.2025.100772","url":null,"abstract":"<p><p>The Advance-HTN trial demonstrated that lorundrostat, an aldosterone synthase inhibitor, effectively reduced 24-h systolic blood pressure by 8 mm Hg in resistant hypertension, with manageable hyperkalemia.¹ These findings support further research into aldosterone synthase inhibitors as promising alternatives to mineralocorticoid receptor antagonists for resistant hypertension management.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 7","pages":"100772"},"PeriodicalIF":12.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144620808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of DV in HER2-negative and HER2-low locally advanced or metastatic urothelial carcinoma: Results of a phase 2 study.","authors":"Xieqiao Yan, Juan Li, Huayan Xu, Yiqiang Liu, Li Zhou, Siming Li, Xiaowen Wu, Bixia Tang, Zhihong Chi, Chuanliang Cui, Lu Si, Lili Mao, Bin Lian, Xuan Wang, Rong Duan, Caili Li, Jianmin Fang, Jun Guo, Xinan Sheng","doi":"10.1016/j.medj.2025.100637","DOIUrl":"10.1016/j.medj.2025.100637","url":null,"abstract":"<p><strong>Background: </strong>Human epidermal growth factor receptor 2 (HER2) has emerged as a new target for metastatic urothelial carcinomas (mUCs). Disitamab vedotin (DV), an anti-HER2 antibody-drug conjugate (ADC), demonstrates a promising efficacy in patients with HER2-positive mUC. However, the role of DV in HER2-negative and HER2-low mUCs remains unknown.</p><p><strong>Methods: </strong>Patients with HER2-negative and HER2-low (immunohistochemistry [IHC] 0 or 1+) mUCs who received ≥1 line of systemic chemotherapy were included. Patients received 2 mg/kg DV intravenously once every 2 weeks. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety.</p><p><strong>Findings: </strong>Nineteen patients with UC were enrolled from September 2019 to December 2021. The median age was 64.0 years. 15 patients (79%) had visceral metastases. HER2 IHC 0 and 1+ were detected in 6 and 13 patients, respectively. As of September 30, 2022, the confirmed ORR was 31.6% (95% confidence interval [CI]: 12.6, 56.6), and the disease control rate was 94.7% (18/19). The median PFS and OS were 5.5 (95% CI: 3.9, 5.7) and 16.4 (6.8, 26.8) months, respectively. Common treatment related adverse events were mostly grade 1 or 2, including leukopenia (52.6%) and hypoesthesia (47.4%).</p><p><strong>Conclusions: </strong>This is the first exploratory trial demonstrating substantial anti-tumor activity and a manageable safety profile using a HER2-targeting agent in patients with HER2-low mUC. This study was registered at ClinicalTrials.gov (ClinicalTrials.gov: NCT04073602).</p><p><strong>Funding: </strong>The study was funded by the Natural Science Foundation of China, the Natural Science Foundation of Tibet Autonomous Region, the Beijing Xisike Clinical Oncology Research Foundation, and RemeGen, Ltd.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100637"},"PeriodicalIF":12.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conformational ligand-directed targeting of calcium-dependent receptors in acute trauma.","authors":"Renata Pasqualini, Christopher Markosian, Daniela I Staquicini, Andrey S Dobroff, Esteban Dodero-Rojas, Paul C Whitford, E Magda Barbu, Julianna K Bronk, Marina Cardó-Vila, Dawn R Christianson, Emmanuel Dias-Neto, Wouter H P Driessen, Liliana Guzman-Rojas, Serena Marchiò, Diana N Nunes, Francislon S de Oliveira, Michael G Ozawa, Bettina Proneth, Roberto Rangel, Tracey L Smith, Glauco R Souza, Fernanda I Staquicini, Fenny H F Tang, Wallace B Baze, João C Setubal, John W Burns, Michael A Dubick, Juri G Gelovani, Andriy I Batchinsky, Jon E Mogford, Charles E Wade, John B Holcomb, Stephen K Burley, José N Onuchic, Wadih Arap","doi":"10.1016/j.medj.2025.100638","DOIUrl":"10.1016/j.medj.2025.100638","url":null,"abstract":"<p><strong>Background: </strong>Trauma is a leading cause of mortality, but injury-specific molecular targets remain largely unknown. We hypothesized that distinctive yet unrecognized tissue targets accessible to circulating ligands might emerge during trauma, thereby underscoring a trauma-related proteome.</p><p><strong>Methods: </strong>We screened a peptide library to discover targets in a porcine model of major trauma: compound femur fracture with hemorrhagic shock. Bioinformatics yielded conserved motifs, and candidate receptors were affinity purified. In silico and in vitro approaches served to investigate possible associations between candidate receptors and calcium, a major component of skeletal muscle and bone. In vivo homing and molecular imaging (PET/MRI and SPECT/CT) studies of the most promising ligand peptide candidate were performed in the porcine model and were also confirmed in a corresponding rat model of major trauma. Optical methodologies and molecular dynamics simulations served to explore the molecular attributes of the ligand-receptor binding.</p><p><strong>Findings: </strong>Nearly all molecular targets of the selected ligand peptides were calcium-dependent proteins, which become accessible upon trauma. We validated specific binding of homing peptides to these receptors in injured tissues, including CLRGFPALVC:CASQ1, CSEIGVRAC:HSP27, and CRQRPASGC:CALR. Notably, we determined that ligand peptide CRQRPASGC targets an injury-specific calcium-facilitated conformation of calreticulin, enabling specific molecular imaging of trauma.</p><p><strong>Conclusions: </strong>We conceptually propose the term \"traumome\" for the functional receptor repertoire that becomes readily amenable for ligand-directed targeting upon major trauma. These preclinical findings pave the way toward clinic-ready targeted theragnostic approaches in the setting of trauma.</p><p><strong>Funding: </strong>Major funding was provided by the Defense Advanced Research Projects Agency (DARPA).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100638"},"PeriodicalIF":12.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144561338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"When UV1 cancer vaccine meets immune checkpoint blockade: Positive immune response but negative clinical outcome.","authors":"Guo Zhao, Shuhang Wang, Ning Li","doi":"10.1016/j.medj.2025.100664","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100664","url":null,"abstract":"<p><p>Brandt et al. present findings from the phase 2 FOCUS trial evaluating UV1 vaccine combined with pembrolizumab in PD-L1-positive recurrent/metastatic head and neck squamous cell carcinoma. While UV1 elicited human telomerase reverse transcriptase-specific T cell responses in 86% of patients, clinical outcomes showed no improvement over pembrolizumab monotherapy.¹ This discordance between immune activation and therapeutic efficacy underscores the necessity for further disease understanding and vaccine design in the future.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 7","pages":"100664"},"PeriodicalIF":12.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144620811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reaching for the summit in pulmonary arterial hypertension with sotatercept: Results of the ZENITH study.","authors":"Robin Condliffe, David G Kiely","doi":"10.1016/j.medj.2025.100750","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100750","url":null,"abstract":"<p><p>The ZENITH study recently reported significant benefits from treatment with sotatercept, an activin signaling inhibitor, in patients with pulmonary arterial hypertension.¹ In this Viewpoint, we discuss the findings and implications of this study in the context of the previous PULSAR and STELLAR trials.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 7","pages":"100750"},"PeriodicalIF":12.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144620809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Theranostic methodology for ex vivo donor lung rehabilitation.","authors":"Meghan R Pinezich, John D O'Neill, Brandon A Guenthart, Jinho Kim, Olaia F Vila, Stephen P Ma, Ya-Wen Chen, Ahmed E Hozain, Aravind Krishnan, Moeed Fawad, Katherine M Cunningham, Holly M Wobma, Julie Van Hassel, Hans-Willem Snoeck, Matthew Bacchetta, Gordana Vunjak-Novakovic","doi":"10.1016/j.medj.2025.100644","DOIUrl":"10.1016/j.medj.2025.100644","url":null,"abstract":"<p><strong>Background: </strong>About 80% of donor lungs are not utilized for transplantation. Cross-circulation of ex vivo lungs with a support swine enables the rehabilitation of donor lungs that are initially deemed unsuitable for transplantation. Robust therapeutic and diagnostic modalities are needed for ex vivo lung rehabilitation; however, no standardized \"theranostic\" methodology has been reported.</p><p><strong>Methods: </strong>Ex vivo lungs (n = 23; 17 injured and 6 controls) with multi-focal contusion (n = 6, human), gastric aspiration injury (n = 8, swine), ischemia-reperfusion injury (n = 3, swine), or no injury (n = 6, swine) were used to develop a therapeutic and diagnostic (theranostic) methodology for ex vivo lung rehabilitation during cross-circulation. Airway (bronchoscopic, nebulized), intravascular, and transpleural access enabled sample collection and therapeutic delivery. Diagnostic modalities included non-invasive imaging, functional testing, and molecular assays. Therapeutic modalities included bronchoalveolar lavage, surfactant replacement, recruitment maneuvers, and cell/organoid delivery. Real-time tracking of delivered cells was performed via fluorescence and bioluminescence imaging.</p><p><strong>Findings: </strong>Diagnostic assessments revealed tissue-, cell-, and molecular-level insights at global and regional scales of ex vivo lungs during cross-circulation, which informed therapeutic management and interventions to recover donor lungs. Mesenchymal stromal cells and lung organoids were delivered bronchoscopically and transpleurally, tracked non-invasively during cross-circulation, and observed to localize within the parenchyma.</p><p><strong>Conclusions: </strong>Application of a theranostic methodology during cross-circulation enabled real-time ex vivo lung assessment and rehabilitation across a variety of lung injuries to help increase clinical utilization of donor lungs in the future.</p><p><strong>Funding: </strong>NIH (P41 EB027062, R01HL120046, U01HL134760), CFF (VUNJAK23XX0).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100644"},"PeriodicalIF":12.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of anti-PD-1 therapy with severe radiation-induced oral mucositis: A retrospective cohort study and validation in the CONTINUUM trial.","authors":"Shi-Qian Zou, Cheng-Long Huang, Jing-Jing Zhang, Zhe Li, Xiao-Tang Xiao, Yi-Zhe Cheng, Jia-Yi Shen, Dong-Hong Wu, Jia-Wei Lv, Ling-Long Tang, Ying Sun, Ji-Bin Li, Xu Liu, Jun Ma, Wen-Fei Li, Yu-Pei Chen","doi":"10.1016/j.medj.2025.100770","DOIUrl":"10.1016/j.medj.2025.100770","url":null,"abstract":"<p><strong>Background: </strong>The association of immune checkpoint inhibitors (ICIs) with radiation-induced oral mucositis (RIOM), a common and debilitating complication that affects the treatment tolerance of head and neck cancer patients, remains unclear.</p><p><strong>Methods: </strong>In this multicenter retrospective cohort study, 840 eligible patients with locoregionally advanced nasopharyngeal carcinoma (NPC) were included, with propensity score matching (PSM) creating two comparison groups based on the receipt of anti-programmed cell death 1 (anti-PD-1) therapy. Additionally, individual patient data from 197 NPC patients in the CONTINUUM trial (NCT03700476) were used for validation.</p><p><strong>Findings: </strong>One-to-one PSM created 215 pairs of patients (ICI group, 215; control group, 215). Although the incidence of severe RIOM was similar between the ICI (n = 92, 42.8%) and control groups (n = 93, 43.3%), multivariable logistic regression revealed that ICI-treated patients with younger age (<45 years), receiving induction chemotherapy (IC) regimens with docetaxel, cisplatin, and 5-fluorouracil/capecitabine (TPF/X) or docetaxel and cisplatin (TP), or with a pre-radiotherapy neutrophil-to-lymphocyte ratio (NLR) ≥2.5 were at an increased risk of severe RIOM. The established nomogram demonstrated excellent performance for predicting severe RIOM risk (concordance index: 0.721 in the ICI group and 0.722 in the CONTINUUM trial).</p><p><strong>Conclusions: </strong>Anti-PD-1 therapy did not generally increase the incidence of severe RIOM in NPC patients; however, it significantly raised the risk in those under 45 years of age, those receiving TPF/X or TP during IC, or those with a pre-radiotherapy NLR ≥2.5. The established nomogram enables tailored monitoring and intervention strategies for severe RIOM, enhancing management during immunotherapy.</p><p><strong>Funding: </strong>National Key Research and Development Program of China (2021YFA0909800).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100770"},"PeriodicalIF":12.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144620807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinician-artificial intelligence collaboration: A win-win solution for efficiency and reliability in atrial fibrillation diagnosis.","authors":"Peng Zhang, Fan Lin, Fei Ma, Yuting Chen, Yuhang Liu, Xiaoli Feng, Siyi Fang, Haowei Zhang, Shuna Xiao, Xiangli Yang, Dun Li, Dao Wen Wang, Xiaoyun Yang, Qiang Li","doi":"10.1016/j.medj.2025.100668","DOIUrl":"10.1016/j.medj.2025.100668","url":null,"abstract":"<p><strong>Background: </strong>Given the biases and ethical concerns of AI models, the fully automatic diagnosis of diseases in clinical settings is challenging. In contrast, clinician-AI collaboration is considered essential to ensure the validity and reliability of utilizing AI models in clinical practice. However, effective strategies for clinician-AI collaboration remain largely unexplored.</p><p><strong>Methods: </strong>This study proposed a three-step general clinician-AI collaboration pipeline aimed at improving disease diagnosis efficiency: first, utilizing large real-world clinical datasets to evaluate and clarify clinicians' diagnostic strengths/weaknesses; second, developing an AI model to complement clinicians' weakness in disease diagnosis; and finally, proposing a clinician-AI collaboration strategy to leverage the strengths of both AI and clinicians. The effectiveness of this pipeline was validated through a study focusing on clinical paroxysmal atrial fibrillation (PAF) detection, utilizing 24-h Holter recordings from over 30,000 patients.</p><p><strong>Findings: </strong>In PAF detection, clinicians alone required a significant amount of time to identify the data and still overlooked 13.7% of PAF patients but successfully identified all non-atrial fibrillation (AF) patients. Conversely, AI alone rarely missed PAF patients but misidentified 23.3% of non-AF patients as having PAF. After implementing the proposed clinician-AI collaboration strategy, all patients were correctly identified, and clinicians' workload was reduced by 76.7%.</p><p><strong>Conclusions: </strong>This study improves both the efficiency and reliability of PAF detection, bridging the gap between AI model development and its clinical application, thereby effectively promoting the application of AI models in clinical AF screening.</p><p><strong>Funding: </strong>This study was supported in part by the National Natural Science Foundation of China.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100668"},"PeriodicalIF":12.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}