Comprehensive Physiology最新文献

{"title":"Heart-Lung Interactions in Pulmonary Hypertension due to Heart Failure With Preserved Ejection Fraction.","authors":"Pratima Prabala, Farhan Raza, Naomi C Chesler","doi":"10.1002/cph4.70168","DOIUrl":"10.1002/cph4.70168","url":null,"abstract":"<p><p>Pulmonary hypertension associated with heart failure with preserved ejection fraction (PH-HFpEF) is a common and high-risk clinical condition characterized by the convergence of pulmonary vascular dysfunction and right ventricular (RV) stress. Despite its prevalence, the pathophysiological mechanisms of development and progression of PH-HFpEF remain largely unknown. Consequently, there are no current therapies that target PH-HFpEF other than optimization of treatment for HFpEF and some limited adaptation of therapies for pulmonary artery hypertension (PAH). This review examines PH-HFpEF through the lens of heart-lung interactions, integrating evidence across hemodynamic, molecular, and cellular scales. We highlight how chronic venous pressure overload, impaired pulmonary vascular reserve, and increased pulsatile load reshape RV afterload and contribute to RV-pulmonary arterial uncoupling, particularly during physiological stress such as exercise. We further discuss how endothelial dysfunction, context-dependent signaling pathways, and systemic comorbidities modify pulmonary vascular remodeling and RV adaptation in ways that differ from PAH. Emerging roles for extracellular vesicles and other circulating mediators as vehicles of cardiopulmonary signaling are considered, alongside current experimental and clinical tools for studying these processes. By examining physiological and molecular insights in parallel, this review identifies key gaps in disease modeling, phenotyping, and mechanistic understanding, while emphasizing the need for approaches that link cardiopulmonary function to underlying biology. Such strategies are essential for advancing disease phenotyping and developing targeted therapies for PH-HFpEF.</p>","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"16 3","pages":"e70168"},"PeriodicalIF":6.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13178418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147947927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Lung-Liver Axis in Pulmonary Arterial Hypertension.","authors":"Navneet Singh, Jordan Lawson, Ashok Ragavendran, Somanshu Banerjee, Andy Hon, Alejandro Vega, Jason Hong, Christopher J Mullin, Mandy Pereira, Allyson Sherman-Roe, Alexander T Jorrin, Tiffaney Cayton, Gregory Fishbein, James R Klinger, William M Oldham, Rui-Sheng Wang, Zhiyu Dai, Michael Fallon, Elizabeth O Harrington, Olin D Liang, Soban Umar, Corey E Ventetuolo","doi":"10.1002/cph4.70171","DOIUrl":"10.1002/cph4.70171","url":null,"abstract":"<p><p>The liver's contribution to pulmonary arterial hypertension (PAH) pathogenesis remains unclear. We hypothesized that the liver promotes inflammatory injury to the pulmonary endothelium. PAH patients without liver disease with pulmonary artery endothelial cell (PAEC) biopsies were included. Unsupervised CART analysis of liver serologies identified subclinical dysfunction clusters; machine-learning models informed differential expression and protein-protein interaction network assembly. PAEC transcriptomes were compared to liver and lung data from monocrotaline and Sugen-Hypoxia rats. Liver fibrosis was assessed in rat and human PAH livers. Among 25 PAH patients (76% female, median age 61 [30-84] years), CART identified clusters distinguished by Model for End-Stage Liver Disease Sodium (MELD-Na) ≥ 12, which was associated with higher Fibrosis-4 scores and higher pulmonary vascular resistance (ß = 0.5 Wood units per point increase in MELD-Na, 95% CI 0.2-0.8, p = 0.005) after adjustment for right atrial pressure. Subjects with MELD-Na ≥ 12 had decreased 6-min walk distance (353 [120-576] m vs. 411 [300-600] m, p = 0.03). In comparing the two clusters, a protein-protein interaction network analysis identified IL-6 as the primary hub of a transcriptional module enriched for leukocyte chemotaxis and myeloid leukocyte migration (all FDR < 0.05) among the High-MELD-Na group. Rat livers demonstrated immune activation and a trend toward increased fibrosis (20.8 vs. 16.6% area stained, p = 0.09), and human PAH livers without liver disease showed an intermediate fibrotic phenotype between controls and portopulmonary hypertension, though this did not reach statistical significance. Our observations support a lung-liver axis in PAH even in the absence of liver disease, warranting further study.</p>","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"16 3","pages":"e70171"},"PeriodicalIF":6.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13178415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147947978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wenxin Granules Prevent Ibrutinib-Associated Atrial Fibrillation Through Restoring Redox Balance and Calcium Homeostasis.","authors":"Xinyu Yang, Hao Yang, Na An, Fan Yang, Linke Jiao, Donghua Yang, Jie Zhao, Yonghong Gao, Yanwei Xing, Hongcai Shang","doi":"10.1002/cph4.70154","DOIUrl":"10.1002/cph4.70154","url":null,"abstract":"<p><strong>Background: </strong>Ibrutinib, a frontline therapy for chronic lymphocytic leukemia (CLL), has been associated with an approximately 10-fold increased risk of atrial fibrillation (AF) during treatment. Wenxin Granules, as a multi-component and multi-target drug, exert therapeutic effects on AF.</p><p><strong>Methods: </strong>We conducted electrophysiological studies in ibrutinib-treated mice models to assess AF inducibility and the therapeutic efficacy of Wenxin Granules. Through network pharmacology screening, we identified potential molecular targets of Wenxin Granules. Subsequent proteomic analysis revealed specific targets through which Wenxin Granules may prevent ibrutinib-associated AF. These targets were further validated in mice model experiments.</p><p><strong>Results: </strong>Our study demonstrates that Wenxin Granules treatment in mice significantly reduces AF inducibility, shortens AF duration, and attenuates pathological cardiac remodeling, including left atrial (LA) enlargement and myocardial fibrosis (p < 0.05). Through comprehensive analysis integrating proteomics with network pharmacology-predicted molecular targets, we systematically screened and identified 25 core therapeutic targets of Wenxin Granules, which are primarily associated with oxidative stress and calcium protein-related signaling pathways. The ibrutinib treatment group demonstrated significantly elevated expression of reactive oxygen species (ROS)-related proteins, including NOX2, NOX4, p22-phox, and XO. Additionally, ibrutinib substantially increased the expression of ox-CaMKII, p-CaMKII (Thr-286), and p-RyR2 (Ser2814), resulting in enhanced abnormal sarcoplasmic reticulum (SR) Ca²⁺ release, altered mitochondrial structures, and atrial fibrosis. Notably, Wenxin Granules administration reduced the expression of these proteins (p < 0.05).</p><p><strong>Conclusions: </strong>These findings demonstrate that Wenxin Granules can ameliorate the occurrence and progression of AF induced by ibrutinib treatment, thereby laying the groundwork for further research and potential clinical applications in AF therapy.</p>","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"16 3","pages":"e70154"},"PeriodicalIF":6.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxysterols as Endogenous Lipid Toxins and Toxic Signaling Mediators in Chronic Disease.","authors":"Arin Natania S","doi":"10.1002/cph4.70162","DOIUrl":"10.1002/cph4.70162","url":null,"abstract":"<p><p>Oxysterols, oxygenated derivatives of cholesterol, have emerged as critical regulators of metabolic homeostasis and interorgan communication. Generated via enzymatic and oxidative pathways, they function as ligands for nuclear receptors such as liver X receptors (LXRs) and modulators of GPCR signaling. Through these mechanisms, oxysterols integrate lipid metabolism with glucose regulation, inflammation, and immune responses across key metabolic organs, including liver, adipose tissue, brain, and pancreas. Notably, the oxysterol-LXR axis coordinates cholesterol flux with insulin sensitivity and glycemic control, while dysregulated oxysterol accumulation promotes cellular stress and chronic disease. These insights position oxysterols as promising therapeutic targets in metabolic disorders.</p>","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"16 3","pages":"e70162"},"PeriodicalIF":6.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leptin in Obesity-Related Heart Failure: Pathophysiological Mechanisms and Therapeutic Implications.","authors":"Xuemin Li, Weiguo Wang, Yibo Zhang, Pengfei Ding, Xuewen Li","doi":"10.1002/cph4.70189","DOIUrl":"10.1002/cph4.70189","url":null,"abstract":"<p><p>Obesity is a major and potentially modifiable risk factor for heart failure (HF); however, the biological mediators linking excess adiposity to adverse cardiac remodeling and HF progression remain incompletely defined. Among adipose-derived factors, leptin has emerged as a candidate mediator because of its associations with neurohormonal activation, vascular dysfunction, inflammation, oxidative stress, and myocardial remodeling. This review synthesizes contemporary evidence regarding the role of leptin in the pathophysiology of obesity-related heart failure and examines its clinical and translational ramifications. Data indicate that hyperleptinemia and leptin resistance may facilitate HF progression via interconnected mechanisms, including sympathetic nervous system activation, dysregulation of the renin-angiotensin-aldosterone system, endothelin-1 and reactive oxygen species signaling, diminished nitric oxide bioavailability, endothelial dysfunction, and myocardial hypertrophy and fibrosis. These pathways may be particularly pertinent to obesity-related HF phenotypes characterized by diastolic dysfunction and detrimental remodeling. Leptin may facilitate biomarker-driven phenotyping and risk stratification, especially in obesity-related heart failure with preserved ejection fraction (HFpEF). Nonetheless, the majority of mechanistic evidence is sourced from animal and cellular studies, with substantial human data still lacking. Taken together, current evidence supports leptin as a mechanistically informative biomarker candidate in obesity-related HF, particularly HFpEF, rather than as an established causal mediator or therapeutic target.</p>","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"16 3","pages":"e70189"},"PeriodicalIF":5.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial Dysfunction and Its Role in Ferroptosis: Molecular Mechanisms and Therapeutic Targets.","authors":"Jiaxin Yang, Rongli Guan, Zhiyin Tang, Sheng Yang, Hai Zhao, Fan Yang","doi":"10.1002/cph4.70202","DOIUrl":"10.1002/cph4.70202","url":null,"abstract":"<p><p>Ferroptosis is an iron-dependent, lipid peroxidation-driven form of regulated cell death, characterized morphologically by mitochondrial shrinkage, increased membrane density, and diminished cristae. As a central regulator of cellular energy metabolism, redox homeostasis, and iron handling, mitochondria are closely implicated in ferroptotic signaling. Mitochondrial dysfunction may contribute to the initiation and progression of ferroptosis through multiple interrelated mechanisms. Mitochondrial metabolic reprogramming (e.g., abnormal glutaminolysis and tricarboxylic acid cycle disturbances) is associated with elevated reactive oxygen species (ROS) production, whereas impaired mitochondrial quality control-including imbalanced fission-fusion dynamics and defective mitophagy-may further amplify oxidative stress and modulate cellular sensitivity to ferroptosis. This review summarizes current evidence supporting the molecular interplay between mitochondrial dysfunction and ferroptosis, and addresses the pathological implications of the mitochondria-ferroptosis axis in multiple disease contexts, including cancer drug resistance, neurodegenerative disorders, and ischemia-reperfusion injury. We also highlight potential therapeutic strategies targeting this axis, such as mitochondria-targeted antioxidants, iron chelators, and modulators of key mitochondrial quality control proteins. Deepened understanding of mitochondria-ferroptosis crosstalk may provide a rational theoretical basis for the development of novel precision therapies for ferroptosis-associated diseases.</p>","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"16 3","pages":"e70202"},"PeriodicalIF":6.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148307407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crosstalk Between Probiotics and Host Immunity: Antimicrobial Peptides-Mediated Health Benefits.","authors":"Shuanshan Ren, Muhammad Asif Arain, Atique Ahmed Behan, Lingling Wang","doi":"10.1002/cph4.70197","DOIUrl":"https://doi.org/10.1002/cph4.70197","url":null,"abstract":"<p><p>The intricate crosstalk between probiotics and the host immune system is increasingly recognized as a central determinant of mucosal integrity, resistance to infection, and systemic homeostasis. This narrative review synthesizes current evidence identified through comprehensive searches of major scientific databases, including PubMed, Scopus, and Web of Science, using targeted keywords related to probiotics, antimicrobial peptides (AMPs), and immune modulation. Emerging evidence indicates that, beyond their traditional metabolic roles, probiotics exert significant immunomodulatory effects through the induction and regulation of AMPs, including bacteriocins, defensins, lysozymes, and cathelicidins. Mechanistically, probiotics activate key host signaling pathways, stimulating epithelial and immune cells to enhance AMP expression. These peptides exhibit broad-spectrum antimicrobial activity by disrupting microbial membranes, inhibiting quorum sensing, and excluding pathogens, thereby strengthening mucosal barrier function and maintaining microbial homeostasis. Additionally, host immune signaling further promotes probiotic colonization and AMPs biosynthesis, establishing a tightly regulated bidirectional feedback mechanism. This review aims to highlight the current evidence on the bidirectional crosstalk between probiotics and host immunity, with particular emphasis on AMPs-mediated mechanisms underlying mucosal protection, immune modulation, and pathogen resistance.</p>","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"16 3","pages":"e70197"},"PeriodicalIF":6.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148263638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Redox Regulation and Mitochondrial Neuroprotection in Ischemic Stroke: The Emerging Role of DJ-1 (PARK7).","authors":"Nila Ganamurali, Alexander Ravikumar, Sandhya Saravanan, Sarvesh Sabarathinam","doi":"10.1002/cph4.70182","DOIUrl":"10.1002/cph4.70182","url":null,"abstract":"<p><p>Ischemic stroke remains a leading cause of global mortality and long-term disability, driven largely by oxidative stress, mitochondrial dysfunction, and inflammatory cascades. DJ-1 (PARK7), a redox-sensitive protein originally implicated in Parkinson's disease, has emerged as a critical neuroprotective regulator in cerebral ischemia. Oxidation of its cysteine-106 residue enables DJ-1 to stabilize mitochondrial function, suppress reactive oxygen species, and activate Nrf2-dependent antioxidant defenses. DJ-1 deficiency markedly exacerbates infarct size and neuronal vulnerability, whereas its activation confers robust neuroprotection. This review highlights DJ-1 as a promising redox-responsive therapeutic target for limiting ischemic brain injury.</p>","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"16 3","pages":"e70182"},"PeriodicalIF":6.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148013916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sensing and Communicating β-Cell Stress in the Context of T1D Etiology: New Opportunities for Therapeutic Impact.","authors":"Diana Esparza, Chathurani S Jayasena, Tijana Jovanovic-Talisman, Debbie C Thurmond","doi":"10.1002/cph4.70198","DOIUrl":"10.1002/cph4.70198","url":null,"abstract":"<p><p>Type 1 diabetes (T1D) has traditionally been viewed as an immune-driven disease. However, evidence from pre-onset T1D individuals suggests that pancreatic β-cells show reduced metabolic gene expression and stress responses before substantial immune entry. In this review, we examine how chronically stressed β-cells are detectable in a reshaped local microenvironment prior to overt immune cell infiltration, a period defined as a \"pre-immune\" niche. During this period, pre-onset β-cells exhibit early extracellular matrix (ECM) remodeling capabilities, endoplasmic reticulum and Golgi stress, a shift in their soluble-factor secretome and extracellular outputs, including release of extracellular vesicles with distinct cargo. Loss of the double C2-like domain containing protein B (DOC2B), a regulator of vesicle trafficking and membrane fusion, may contribute to these processes. Beyond its canonical role in regulated insulin exocytosis, DOC2B negatively regulates cytokine-induced CXCL10 expression in β-cells via inhibition of IKKβ-STAT1 signaling, and its loss increases activation of these pathways. DOC2B loss in cancer models promotes the formation of filopodia, protrusive structures capable of ECM engagement for matrix metalloproteinase-mediated degradation; similarly, we consider whether changes in β-cells could influence maladaptive interactions with the peri-islet matrix during early T1D. Together, these concepts position DOC2B as a potential additional point of β-cell vulnerability; further study may help guide early biomarker development and inform long-term strategies for intercepting T1D before clinical onset.</p>","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"16 3","pages":"e70198"},"PeriodicalIF":6.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13276439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148270303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-21-5p Protects Embryonic Growth and Heart Function During Developmental Hypoxia by Dampening HIF Responses and Altering Gene Expression.","authors":"Bernardo J Krause, Ximena Calle, Ranya V Kumar, Youguo Niu, Oriana Ramirez-Herrera, Damariz Gonzalez, Barbara Bernal, Sage G Ford, Rachael C Crew, Anna L K Cochrane, German A Arenas, Alex Di Genova, Dino A Giussani","doi":"10.1002/cph4.70173","DOIUrl":"10.1002/cph4.70173","url":null,"abstract":"<p><p>Fetal hypoxia is a common complication of pregnancy and increases the cardiovascular risk in offspring, contributing to a significant burden on life-long health. Preventative strategies against its adverse effects have focused on targeting oxidative stress, but not epigenetic mechanisms. Since miRNA-21-5p downregulation contributes to fetal growth restriction (FGR) and cardiovascular impairment, we tested the hypothesis that miR-21 upregulation during developmental hypoxia is protective. The hypothesis was tested adopting an integrative approach, combining gene expression and transcript variant usage, profiling of neonatal rat cardiomyocytes (NRC) exposed to hypoxia and miR-21-5p mimic, and in vivo assessment of the effects of miR-21-5p on growth and cardiac function in hypoxic chicken embryos. In NRC, hypoxia resulted in 385 differentially expressed genes (DEG) relative to normoxia (FDR < 0.05; DEG; 142 down- and 243 up-regulated). In vitro miR-21-5p improved cell survival, completely dampened hypoxia-responsive genes, modified transcript isoform usage of key cardiac transcripts (i.e., Sfpq and Lgr4), attenuated apoptotic signaling, and shifted gene networks toward improved Ca²⁺ handling, β-adrenergic and PI3K-related pathways. In vivo miR-21-5p administration during incubation prevented asymmetric FGR, protected systolic and diastolic function, and normalized cardiac sympathetic dominance in hypoxic chicken embryos. These data suggest that miR-21-5p exerts post-transcriptional control, linking hypoxia sensing to effectors of cardiomyocyte survival and function, as well as protecting against FGR and cardiac dysfunction in development during chronic hypoxia. This work supports the significant translational potential of miRNA-21 not only as a biomarker, but also as a therapeutic target in high-risk pregnancy.</p>","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"16 3","pages":"e70173"},"PeriodicalIF":6.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13178401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147947964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}