Acta Pharmacologica Sinica最新文献

{"title":"Selumetinib promotes coronary collateral circulation by inducing M2-like macrophage polarization following myocardial infarction.","authors":"Ke-Chuan Lin, Wei He, Dan Wang, Mei-Lian Yao, Jing Chen, Mei-Fang Chen, Guo-Gang Zhang, Chuan-Chang Li, Ling-Ping Zhu, Yong-Ping Bai","doi":"10.1038/s41401-025-01508-8","DOIUrl":"10.1038/s41401-025-01508-8","url":null,"abstract":"<p><p>Coronary collateral circulation (CCC) construction could be a practical therapeutic strategy for patients following myocardial infarction (MI), yet effective therapeutic drugs remain scarce. In this study we conducted database federation analyses to identify FDA-approved drugs that could promote CCC after MI injury. By comparing the differentially expressed genes in peripheral blood mononuclear cells (PBMCs) from two public gene profiles: one comparing patients with good versus poor CCC, and another with good versus poor heart function, the overlapped genes were analyzed using CMap, a popular resource designed for FDA approved drug. As a result, selumetinib emerged as a potential therapeutic drug to facilitate CCC formation. In MI mouse model induced by permanent ligation of left anterior descending (LAD) coronary artery, administration of selumetinib (2.5 mg/kg, i.p.) at the indicated time-points significantly enhanced CCC by promoting the polarization of macrophages from the pro-inflammatory M1-like phenotype to the pro-angiogenic M2-like phenotype, which was confirmed by 3D visualization through micro-CT imaging and immunofluorescent staining. We demonstrated that selumetinib (5 μM) promoted THP-1 differentiated into M2-like phenotype in vitro, and increased VEGFA secretion. Selumetinib-treated macrophages significantly enhanced in vitro angiogenesis of HUVECs in cocultured assay. We found that selumetinib (2.5 and 5 μM) dose-dependently inhibited the expression of the RIT1 in THP-1 derived M1 macrophage; knockdown of RIT1 significantly polarized M2-like phenotype via the MAPK/ERK1/2 signaling pathway, which was equal to the efficiency of selumetinib. In rescued experiments, specific overexpression of RIT1 in macrophage by injecting with targeting F4/80 promoter AAV9 in mice, could block the M2-like phenotype shifts and CCC formation by selumetinib. Finally, honokiol, a MAPK/ERK1/2 agonist was able to reverse the effects of selumetinib on CCC in mice with MI. In conclusion, selumetinib possesses therapeutic potential for induction of CCC formation after MI.</p>","PeriodicalId":6942,"journal":{"name":"Acta Pharmacologica Sinica","volume":" ","pages":"1905-1919"},"PeriodicalIF":6.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PYRCR alleviates myocardial ischemia/reperfusion injury in mice via inhibiting DRG2-mediated cardiomyocyte pyroptosis.","authors":"Xin-Zhe Chen, Hong-Fei Xu, Xue-Mei Zhao, Fu-Hai Li, Jia-Hao Ren, Lu-Yu Zhou, Cui-Yun Liu, Yu-Qin Wang, Su-Min Yang, Fang Liu, Yu-Hui Zhang, Kun Wang, Xiang-Qian Gao","doi":"10.1038/s41401-025-01604-9","DOIUrl":"https://doi.org/10.1038/s41401-025-01604-9","url":null,"abstract":"<p><p>Circular RNAs (circRNAs) are a distinct class of endogenous RNAs characterized by their covalently closed circular structure. CircRNAs play crucial regulatory roles in various biological processes and pathogenesis. In this study we investigated the role of circRNAs in cardiomyocyte pyroptosis and underlying mechanisms. Ischemia/reperfusion (I/R)-induced myocardial injury was induced in mice by ligation of the left anterior descending coronary artery (LAD). Neonatal mouse cardiomyocytes were subjected to hypoxia/reoxygenation (H/R) assault. By using circRNA microarray, we found that the expression levels of a pyroptosis-related circRNA (designated PYRCR) were markedly decreased in H/R-exposed cardiomyocytes and I/R-injured mouse hearts. Overexpression of PYRCR inhibited cardiomyocyte pyroptosis, attenuated I/R-induced myocardial infarction and ameliorated cardiac function in mice. By RNA pull-down assays coupled with MS analysis followed by molecular validation, we identified developmental regulated GTP-binding protein 2 (DRG2) as the direct downstream target of PYRCR. Cardiac-specific DRG2 knockout mice displayed attenuated pyroptosis and enhanced cardiac function following I/R injury compared to DRG2^fl/fl controls. DRG2 directly bound to dynamin-related protein 1 (Drp1), the master regulator of mitochondrial fission, and enhanced its protein stability and expression. Importantly, PYRCR competitively disrupted the DRG2-Drp1 interaction, thereby suppressing DRG2-mediated Drp1 expression and subsequently reducing mitochondrial fission, cardiomyocyte pyroptosis, and myocardial damage. In conclusion, we demonstrate that PYRCR, a novel pyroptosis-related circRNA, protects against I/R-induced myocardial injury through the DRG2-mediated modulation of Drp1 activity, offering promising new therapeutic strategies for preventing cardiac damage mediated by cardiomyocyte pyroptosis.</p>","PeriodicalId":6942,"journal":{"name":"Acta Pharmacologica Sinica","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SAAINT-DB: a comprehensive structural antibody database for antibody modeling and design.","authors":"Xiaoqiang Huang, Jun Zhou, Shuang Chen, Xiaofeng Xia, Y Eugene Chen, Jie Xu","doi":"10.1038/s41401-025-01608-5","DOIUrl":"https://doi.org/10.1038/s41401-025-01608-5","url":null,"abstract":"<p><p>Antibody (Ab) structures and antibody-antigen (Ag) interactions (AAIs) are essential for understanding immune recognition and designing Ab therapeutics. While existing structural Ab databases provide valuable insights, they still face limitations in data accuracy, completeness, and/or update frequency. Here, we present SAAINT-parser, a computational workflow for rapid, accurate, and robust extraction of Ab and AAI information from the Protein Data Bank (PDB). SAAINT-parser features precise detection of Ab chains, accurate pairing of Ab chains, and reliable identification of AAIs. The resulting SAAINT-DB, last updated on May 1, 2025, contains 19,128 data entries from 9757 PDB structures, offering a comprehensive and up-to-date resource. Detailed analyses highlight the advantages of SAAINT-DB over the widely used SAbDab in terms of data accuracy and completeness. Furthermore, SAAINT-DB provides nearly twice as many non-redundant, manually curated Ab-Ag binding affinity entries as SAbDab. To support Ab-related research and benefit the broader scientific community, we provide open access to SAAINT-parser, the SAAINT-DB summary file, unprocessed PDB structures, and SAAINT-parser-processed structure models at https://github.com/tommyhuangthu/SAAINT .</p>","PeriodicalId":6942,"journal":{"name":"Acta Pharmacologica Sinica","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the distinct activation mechanisms of neuromedin B receptor through multiple replica molecular dynamics simulations and Markov state modeling.","authors":"Nuan Li, Ming-Yuan Yang, Ming-Yang Zhang, Ning Liu, Ai-Wu Zhou, Zong-Tao Chai, Shao-Yong Lu","doi":"10.1038/s41401-025-01603-w","DOIUrl":"https://doi.org/10.1038/s41401-025-01603-w","url":null,"abstract":"<p><p>Neuromedin B receptor (NMBR) is a prototypical class A G protein-coupled receptor (GPCR) that plays a crucial role in histamine-independent itch transmission. However, the mechanisms underlying NMBR's selectivity and activation remain poorly understood. Herein, we utilized multiple replica molecular dynamics simulations, Markov state model (MSM), and community network analysis to explore how NMBR interacts with its two orthosteric ligands namely NMB30 and GRP(14-27) and the distinct activation mechanisms of NMBR. Our findings revealed distinct binding modes for these two ligands, highlighting the significance of the C-terminal dumbbell structure of peptides in ligand positioning and interaction with the \"toggle switch\" residue W279^6.48. Moreover, MSM analysis of the NMBR-GRP(14-27) complex revealed that the active conformation of the receptor appeared for less than half of the simulation time, confirming GRP(14-27) as a weak agonist of NMBR. Additionally, community network analysis identified community 8 as a connector between the orthosteric pocket and the intracellular end of NMBR, suggesting that ligand binding patterns may further influence the extent of receptor activation through allosteric regulation. Collectively, our study not only paves the way for the development of antipruritic therapy, but also provides valuable insights for future studies on GPCR activation.</p>","PeriodicalId":6942,"journal":{"name":"Acta Pharmacologica Sinica","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A rat Satb1 truncation causes neurodevelopmental abnormalities recapitulating the symptoms of patients with SATB1 mutations.","authors":"Zhi-Bin Hu, Wei-Tang Liu, Yi-Wei Li, Ling Hu, Ying Huang, Xi-Yue Liu, Qiong Zhang, Yu-Bing Wang, Jia-Yin Chen, Ze-Xuan Li, Si-Xin Tu, Li Zhao, Ning-Ning Song, Oded Klavir, Yu-Qiang Ding","doi":"10.1038/s41401-025-01588-6","DOIUrl":"https://doi.org/10.1038/s41401-025-01588-6","url":null,"abstract":"<p><p>The special AT-rich sequence binding protein 1 (SATB1) has been linked to neurodevelopmental disorders (NDDs) including developmental delay, intellectual disabilities (ID) and autism spectrum disorder (ASD). But the underlying biological mechanisms are still not fully understood. In this study we generated a rat model with a truncated Satb1 protein. We showed that Satb1 mutant caused growth retardation, microcephaly, altered ultrasonic vocalization and delayed neurobehavioral development in mutant pups as well as social and cognitive behavior deficits in adult mutants, mimicking the typical clinical characteristics of SATB1-associated NDDs. Injection of a GABAergic enhancer clonazepam (0.04 mg/kg, i.p.) effectively alleviated the abnormal social and cognitive behaviors in Satb1 mutant rats. Finally, RNA sequencing analysis further revealed a potential role of Satb1 in a cortical transcriptional regulatory network associated with NDDs including ID and ASD. Our results confirm the crucial roles of SATB1 in the pathogenesis of NDDs and provide insights into treatment strategies for SATB1-associated NDDs.</p>","PeriodicalId":6942,"journal":{"name":"Acta Pharmacologica Sinica","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota-derived butyrate prevents aortic dissection via GPR41.","authors":"Huan-Xin Yang, Bing-Xin Wang, Xiao-Liang Dong, Jia Sun, Zeng-Li Miao, Li-Long Pan","doi":"10.1038/s41401-025-01592-w","DOIUrl":"https://doi.org/10.1038/s41401-025-01592-w","url":null,"abstract":"<p><p>Aortic dissection (AD) is a life-threatening condition with high morbidity. Its underlying pathogenesis remains poorly understood, yielding limited therapeutic options. In this study, we investigated the role of gut microbiota and its metabolite, butyrate, in AD development. Experimental AD was established in 3-week-old mice by administering of β-aminopropionitrile monofumarate (BAPN, 1 g·kg^-1·d^-1) in drinking water for 4 weeks. Microbiota composition analysis was conducted on fecal samples from of the mice. AD mice exhibited significant alterations in gut microbiota composition in particular a decrease in butyrate-producing bacteria, accompanied by markedly reduced serum and fecal butyrate levels. Supplementation with exogenous butyrate (200 mg·kg^-1·d^-1, i.g., for 4 weeks) significantly attenuated the progression of AD by enhancing the expression of vascular smooth muscle cell (SMC) contractile markers. Moreover, butyrate alleviated AD-associated SMC phenotypic switching by suppressing NADPH oxidase 4 expression, thereby reducing reactive oxygen species production. Notably, the protective effects of butyrate were abolished in G-protein-coupled receptor 41 (GPR41) knockout mice, but not in GPR109A knockout mice, highlighting the critical role of GPR41 in mediating its therapeutic effects. These results provide new insights into the pathogenesis of AD and suggest that targeting gut microbiota and its metabolites, such as butyrate, may offer a promising strategy.</p>","PeriodicalId":6942,"journal":{"name":"Acta Pharmacologica Sinica","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum amyloid A3 aggravates bleomycin-induced pulmonary fibrosis through Krüppel-like factor 6-dependent interlukin-36α expression.","authors":"Xin-Yi Yang, Ying Liu, Wen Li, Hui-Xing Li, Yu-Wen Zhong, Yu-Han Cao, Tian-Yi Liu, A-Jing Xu, Wei Gu, Qing Liang, Feng Qian, Lei Sun","doi":"10.1038/s41401-025-01596-6","DOIUrl":"https://doi.org/10.1038/s41401-025-01596-6","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease; however, effective clinical treatments for IPF are lacking. High serum amyloid A (SAA) expression in serum is closely related to the severity of pulmonary fibrosis, but the underlying mechanisms remain incompletely understood. This study found that the expression of endogenous SAA3 was significantly induced in mice with bleomycin-induced fibrosis. Saa3 deletion alleviated pulmonary fibrosis in mice. Additionally, recombinant IL-36α treatment aggravated fibrosis in bleomycin-induced Saa3^-/- mice. Furthermore, SAA3 could induce the expression of IL-36α in macrophages through the NF-κB pathway and transcription factor Krűppel-like factor 6 (KLF6). Also, the Klf6 knockdown alleviated severe lung fibrosis after recombinant SAA3 treatment. In conclusion, our study suggested that SAA3 aggravated bleomycin-induced pulmonary fibrosis by inducing IL-36α expression in macrophages through the NF-κB-KLF6 pathway. It provides new theoretical bases and potential therapeutic targets for treating fibrosis-related diseases.</p>","PeriodicalId":6942,"journal":{"name":"Acta Pharmacologica Sinica","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginsenoside (20)S-APPT induces ferroptosis in hepatocellular carcinoma and cholangiocarcinoma by targeting FSP1.","authors":"Fan-Yu Liu, Yuan-Jie Yang, Xue-Long Wang, Yan Hong, Xiao-Peng Ou-Yang, Lu Chang, Nan-Lin Zhu, Ao Huang, Min-Min Zhang, Jia Liu, Mei-Yu Geng, Ai-Jun Shen","doi":"10.1038/s41401-025-01589-5","DOIUrl":"https://doi.org/10.1038/s41401-025-01589-5","url":null,"abstract":"<p><p>Triggering ferroptosis has recently been recognized as a promising approach for cancer treatment. However, current ferroptosis inducers, such as glutathione peroxidase 4 (GPX4) inhibitors, face limitations in terms of druggability and safety. In this study, we performed a phenotypic screen of a 180-compound natural product library and identified (20S)-protopanaxatriol ((20)S-APPT), a ginsenoside derivative, as a potent ferroptosis inducer with a favorable safety profile both in vitro and in vivo. We demonstrated that (20)S-APPT induced ferroptosis by targeting the plasma membrane-localized CoQ₁₀ oxidoreductase FSP1. FSP1 inhibition promoted ACSL4-dependent arachidonic acid oxidation and mitochondrial ROS production, thereby increasing ferroptosis. Intriguingly, we revealed that FSP1 inhibition alone was sufficient to trigger ferroptosis in a subset of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) cells. Furthermore, the combined inhibition of FSP1 and γ-glutamylcysteine synthetase (GCS) synergistically induced ferroptosis in otherwise resistant cancer cells while sparing noncancerous cells. These results establish a previously unrecognized role for FSP1 in driving ferroptosis and highlight the therapeutic potential of cotargeting FSP1 and GCS in HCC and CCA.</p>","PeriodicalId":6942,"journal":{"name":"Acta Pharmacologica Sinica","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Receptor tyrosine kinase inhibitor tivozanib regulates cell state plasticity and restores MITF dependency in BRAF wild-type melanoma.","authors":"Yan-Ni Ma, Xu-Hui Ma, Mei-Ling Hao, Rui-Xin Liu, Yang Zheng, Jie Yang, Xiang-Yu Chen, Yi-Nan Chen, Sheng-Nan Zheng, Yan-Jie Zhang, Ming Lei, Min Jiang, Wei Guo, Han-Lin Zeng","doi":"10.1038/s41401-025-01599-3","DOIUrl":"https://doi.org/10.1038/s41401-025-01599-3","url":null,"abstract":"<p><p>While combination BRAF/MEK inhibition has improved survival in BRAF^V600 mutant melanoma, targeted therapies for BRAF^WT melanoma remain limited. Microphthalmia transcription factor (MITF), a lineage-specific transcription factor that regulates melanocyte proliferation and melanin synthesis, represents a promising melanoma-specific drug target. In this study, we evaluated TT-012, a recently identified MITF dimerization specific inhibitor, and surprisingly found that most BRAF^WT melanoma lines were resistant to TT-012 due to low MITF transcriptional activity and reduced dependency on MITF for proliferation. High-throughput drug screen identified tivozanib, an FDA-approved drug targeting VEGFR and other receptor tyrosine kinases (RTKs), which sensitized cells to TT-012. Mechanistically, tivozanib induced cell state transition from MITF^low to MITF^high state via VEGFR2 inhibition followed by NF-κB pathway activation, restoring MITF transcriptional activity and growth dependency. The combination of tivozanib and TT-012 synergistically inhibited melanoma growth both in vitro and in vivo, underscoring its potential as a novel therapeutic strategy for BRAF^WT melanoma.</p>","PeriodicalId":6942,"journal":{"name":"Acta Pharmacologica Sinica","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic enzyme-associated protein-protein interactions (mPPIs) in cancer: potential vulnerability for cancer treatment?","authors":"Yu-Ting Tang, Tian-Yi Chen, Zi-Yi Liu, Ming-Yu Luo, Miao-Miao Gong, Ying Shen","doi":"10.1038/s41401-025-01601-y","DOIUrl":"10.1038/s41401-025-01601-y","url":null,"abstract":"<p><p>Cancer metastasis and drug resistance are intricately linked processes that drive cancer progression and poor prognosis. One of the hallmarks of cancer is metabolic reprogramming, which evolves at various stages of tumor metastasis and drug resistance progression. This reprogramming involves the dysregulation of metabolic enzymes, which not only regulate the metabolic status in cancer cells, but also play multifunctional roles through influencing downstream signaling networks, acting as protein kinases, post-translational modifications and multiple biological processes, thereby exacerbating cancer malignancy. This review focuses on the metabolic enzyme-associated protein-protein interactions (mPPIs) during tumor metastasis and therapeutic resistance, and discusses the roles of key enzymes in glycolysis, the serine synthesis pathway, the pentose phosphate pathway, the glucuronate pathway and the sorbitol pathway. Understanding the distinct multifunctionality of these metabolic enzymes is crucial for gaining valuable insights into cancer pathogenesis and identifying potential therapeutic vulnerability to combat metastatic progression and overcome therapy resistance.</p>","PeriodicalId":6942,"journal":{"name":"Acta Pharmacologica Sinica","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}