Thrombosis and haemostasis最新文献

{"title":"Inhibitor Formation in the Era of Novel Haemophilia Treatment-A Humanized Mouse Model to Answer Our Questions?","authors":"Lize F D van Vulpen, Simon C Mastbergen","doi":"10.1055/a-2551-8561","DOIUrl":"10.1055/a-2551-8561","url":null,"abstract":"","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573741","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":"Hyperfibrinolysis Is Associated With Complement Activation Following Trauma.","authors":"Christopher D Barrett, Elizabeth Maginot, Ernest E Moore, Collin M White, Hunter B Moore, Isabella M Bernhardt, Trace Moody, James G Chandler, Flobater I Gawargi, Reynold Henry, Dominik Draxler, Martin Schreiber, Robert Medcalf, Angela Sauaia","doi":"10.1055/a-2565-2449","DOIUrl":"https://doi.org/10.1055/a-2565-2449","url":null,"abstract":"<p><strong>Background: </strong>Complement is activated after trauma, but the activation mechanism is unknown. Plasmin can directly activate C3 and C5, and four distinct fibrinolytic phenotypes have now been recognized after injury - hyperfibrinolysis, fibrinolysis shutdown, hypofibrinolysis, and non-pathologic/physiologic.</p><p><strong>Objectives: </strong>We set out to investigate whether a relationship between complement activation and fibrinolysis was present in adult trauma patients (n=56).</p><p><strong>Methods: </strong>Rapid and tPA-challenged thromboelastography (TEG) were performed in the emergency department with IRB approval, and plasma obtained for C3a, C4a, C5a, Ba, sC5b-9, Factor I, Factor H, active PAI-1, alpha-2 antiplasmin (A2AP), plasmin-antiplasmin complex (PAP), and tPA activity measurement via multiplex, ELISA and activity assays. Data were analyzed using ANOVA and Spearman's correlations. Significance was set at p<0.05.</p><p><strong>Results: </strong>C3a and sC5b-9 were significantly higher in patients with hyperfibrinolysis than with physiologic or hypofibrinolysis (p<0.05). Elevations in C3a, C4a, and SC5b9, along with depletion of Factors H and I, were significantly associated with massive transfusion within 6 hours and post-injury death. There were significant positive correlations between multiple markers of fibrinolysis and complement activation markers, and significant negative correlations with Factors H and I. Significant negative correlations between fibrinolytic inhibitors and complement activation were also observed.</p><p><strong>Conclusions: </strong>Our findings suggest that fibrinolysis may play a direct role in complement activation in trauma through plasmin-mediated cleavage of C3 and C5.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711331","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":"Homophilic interactions of platelet F11R/JAM-A with its surface-bound counterpart facilitate thrombus formation.","authors":"Piotr Kamola, Boguslawa Luzak, Patrycja Przygodzka, Cezary Watala, Moro O Salifu, Anna Babinska, Tomasz Przygodzki","doi":"10.1055/a-2565-9496","DOIUrl":"https://doi.org/10.1055/a-2565-9496","url":null,"abstract":"<p><strong>Background: </strong>F11Receptor/Junctional Adhesion Molecule-A (F11R/JAM-A) is a transmembrane protein expressed in endothelial cells, epithelial cells and in blood platelets. In blood platelets F11R/JAM-A participates in adhesion of platelets under static conditions, suppresses the activation of the platelet αIIbβ3 integrin and was shown to activate blood platelets as soluble form via homophilic interaction.</p><p><strong>Objectives: </strong>The purpose of presented study was to evaluate whether F11R/JAM-A is involved in platelet adhesion under flow conditions and in thrombus formation.</p><p><strong>Methods: </strong>F11R/JAM-A contribution to platelet adhesion under flow conditions was assessed using flow chamber assay. Monoclonal antibodies and recombinant F11R/ JAM-A were used to assess the effects of F11R/JAM-A blockade on platelet aggregation and thrombus formation using total thrombus formation analysis system. Effects of F11R/JAM-A blockade on thrombus formation in vivo were evaluated in murine models of carotid artery injury.</p><p><strong>Results: </strong>F11R/JAM-A was not capable of capturing flowing blood platelets alone but enhanced platelet adhesion to fibrinogen under flow conditions. Blocking of F11R/JAM-A homophilic interactions with specific monoclonal antibodies or with recombinant F11R/JAM-A impaired thrombus formation in vitro in human blood and in vivo in the models of thrombosis in mice.</p><p><strong>Conclusion: </strong>Interactions of F11R/JAM-A located on flowing platelets with its surface-bound counterpart enhance platelets binding to fibrinogen under high shear-stress conditions. Blocking of these homophilic interactions compromises thrombus formation. While previously published studies pointed at a significant role of soluble F11R/JAM-A in priming platelets during thrombus formation, our results highlight the role of surface-bound F11R/JAM-A in this process.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711328","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":"Modifications of the Prothrombin Active Site S4 Subpocket Confer Resistance to Dabigatran.","authors":"Viola J F Strijbis, Ka Lei Cheung, Dejvid Veizaj, Tessa Rutten, Boris de Bruin, Pieter H Reitsma, Daniël Verhoef, Mettine H A Bos","doi":"10.1055/a-2537-6037","DOIUrl":"10.1055/a-2537-6037","url":null,"abstract":"<p><p>Direct anticoagulants inhibit coagulation serine proteases by reversibly engaging their active site with high affinity. By modifying the S4 active site subpocket of factor (F)Xa, we introduced inhibitor resistance while preserving catalytic activity. Given the homology between FXa and thrombin in active site architecture and direct anticoagulant binding, we have targeted the S4 subsite to introduce inhibitor resistance in (pro)thrombin.Recombinant prothrombin variants were generated in which I174 was substituted or sequence R92-N98 was exchanged with that of human kallikrein-3.Specific prothrombin clotting activity of the variants was 6-fold (intrinsic clotting) to 10-fold (extrinsic clotting) reduced relative to wild-type prothrombin. Further analyses revealed that modification of the S4 subsite hampers fibrinogen and thrombomodulin-mediated protein C conversion by thrombin. Consistent with this, the thrombin variants displayed a reduced catalytic efficiency toward the peptidyl substrate used in thrombin generation assessments. The variants displayed a 2-fold reduced sensitivity for dabigatran relative to wild-type prothrombin, while argatroban inhibition was unaffected. Analyses using a purified component system revealed an up to 24-fold and 4-fold reduced IC₅₀ for inhibition of thrombin by dabigatran and argatroban, respectively. Molecular dynamics (MD) simulations of both dabigatran-bound and unbound (apo) modified thrombin variants indicated these to comprise a larger inhibitor binding pocket relative to wild-type thrombin and display reduced inhibitor binding. As a net effect, (pro)thrombin variants with S4 subsite modifications supported detectable fibrin formation at therapeutic dabigatran concentrations.Our findings provide proof-of-concept for the engineering of thrombin variants that are resistant to direct thrombin inhibitors by modulating the S4 subsite.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143410848","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":"Optimal Long-term Antiplatelet Regimen for Patients with High Ischaemic and Bleeding Risks After Percutaneous Coronary Intervention.","authors":"Jeong Yoon Jang, Ga-In Yu, Jongwha Ahn, Jae-Suck Bae, Yun-Ho Cho, Min-Gyu Kang, Jin-Sin Koh, Young-Hoon Jeong, Sang Yeup Lee, Byeong-Keuk Kim, Hyung Joon Joo, Do-Sun Lim, Kiyuk Chang, Young Bin Song, Sung Gyun Ahn, Jung-Won Suh, Jung Rae Cho, Ae-Young Her, Jee-Hoon Kang, Hyo-Soo Kim, Moo Hyun Kim, Eun-Seok Shin, Yongwhi Park","doi":"10.1055/a-2499-5458","DOIUrl":"10.1055/a-2499-5458","url":null,"abstract":"<p><p>To assess an optimal long-term antiplatelet strategy in patients at both high ischaemic and bleeding risks after percutaneous coronary intervention (PCI).Patients at high risks of both ischaemia and bleeding were eligible for inclusion. We excluded patients with any ischaemic and major bleeding complications during the mandatory period of dual antiplatelet therapy (DAPT). Clinical outcomes were evaluated in three groups of regimens, namely, clopidogrel monotherapy (CLPD), aspirin monotherapy (ASA), and DAPT group. The primary endpoint was a composite of all-cause death, myocardial infarction, stroke, or major bleeding for 12-month follow-up period. To balance characteristics according to antiplatelet strategies, stabilized inverse probability treatment weighting (IPTW) was conducted. After IPTW adjustment, CLPD group (<i>N</i> = 916) showed significantly lower rate of primary endpoint than DAPT group (<i>N</i> = 949) (hazard ratio [HR] = 2.09, 95% confidence interval [CI] = 1.22-3.60, <i>p</i> = 0.008), but there was no statistical difference between CLPD and ASA groups (<i>N</i> = 838) (HR = 1.46, 95% CI = 0.83-2.54, <i>p</i> = 0.187). Clinical benefits of CLPD over DAPT was mainly driven by the lower incidence of ischemic events (HR = 2.51, 95% CI 1.37-4.61; <i>p</i> = 0.003). Incidence of major bleeding did not differ among groups, but there was an increased bleeding tendency in DAPT group compared to CLPD group (HR = 2.51, 95% CI = 0.85-7.41, <i>p</i> = 0.096).For patients at high bleeding and ischaemic risk, especially undergoing complex PCI, clopidogrel monotherapy demonstrated a significant net clinical benefit compared to DAPT. Clopidogrel monotherapy showed numerical reductions of bleeding and ischaemic event rates compared to aspirin monotherapy.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808212","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":"Impact of Obesity and Overweight on Heparin Dosing and Clinical Outcomes in Pediatric Patients with Venous Thromboembolism.","authors":"Alexandra Larouche, Valérie Dollo, Gabriel Mercier, Narcisse Singbo, Chantal Éthier, Marie-Christine Boulanger, Marie-Claude Pelland-Marcotte","doi":"10.1055/a-2544-6183","DOIUrl":"https://doi.org/10.1055/a-2544-6183","url":null,"abstract":"<p><p>Dosing guidance for anticoagulation, the mainstay of venous thromboembolism (VTE) treatment, is lacking for obese children. We aimed to compare unfractionated heparin (UFH) and low-molecular-weight heparins (LMWH) dosing requirements and clinical outcomes between obese/overweight and nonobese children.This monocentric retrospective cohort study included patients aged < 18 years old receiving anticoagulation for VTE. The outcomes were: (1) number of dose adjustments to reach therapeutic levels, (2) variation from initial dose, (3) thrombotic progression/recurrence, and (4) clinically relevant bleeding. Characteristics and dosing requirements of obese/overweight and nonobese children were compared using Pearson chi-square, Fisher exact, and Wilcoxon Mann-Whitney tests. Kaplan-Meier estimator compared the cumulative incidence of thrombotic recurrence/progression and clinically relevant bleeding between groups.We included 212 patients (median age: 6.2 years, 23.6% obese/overweight) having 258 anticoagulation encounters (LMWH: 82.6%, UFH: 17.4%). Most children had therapeutic levels following one dosage (66.7% in obese/overweight vs. 51.8% in nonobese, <i>p</i> = 0.201). Dosing requirements significantly differed between obese/overweight and nonobese children (average increase from initial dose: 3.2 vs. 11.3%, <i>p</i> < 0.001). In obese/overweight children, 11.1% of patients required ≥ 10% dose reduction versus 2.1% in nonobese children (<i>p</i> < 0.001). The cumulative incidence of thrombotic progression/recurrence was comparable between groups (obese/overweight: 12.0%, nonobese: 10.5%, <i>p</i> = 0.786). Similarly, clinically significant bleeding was rare for both groups (obese/overweight: 2.0%, nonobese: 3.1%, <i>p</i> = 0.609).In children treated for VTE, obesity/overweight was associated with lower anticoagulation requirements. Further prospective work is urgently needed to explore alternate regimens, such as dose capping, reduced initial dosing, or the use of fat-free mass.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701646","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":"Identifying Risk Factors for Left Ventricular Thrombus in Patients with Ischemic Left Ventricular Aneurysm Using Cardiac MRI.","authors":"Yanfang Wu, Hui Wang, Zhiyan Wang, Chang Hua, Ran Xiong, Hao Fu, Qiang Lv, Lei Xu, Xin Du, Jianzeng Dong","doi":"10.1055/a-2536-8739","DOIUrl":"10.1055/a-2536-8739","url":null,"abstract":"<p><p>Ischemic left ventricular (LV) aneurysm is associated with LV thrombus and subsequent embolic events. However, there is currently no evidence-based recommendation for anticoagulation in these patients.To determine the characteristics of LV aneurysms associated with a high risk of thrombus formation.This retrospective study included all hospitalized patients with ischemic LV aneurysm who underwent cardiac magnetic resonance (CMR) from September 2015 to June 2023. Baseline characteristics and CMR parameters were compared between patients with and without LV thrombus. Factors associated with LV thrombus were identified using univariable and multivariable logistic regression analyses.Among the 317 patients included in this study, 88 (27.8%) had LV thrombus. Patients with LV thrombus demonstrated a higher prevalence of heart failure, lower left ventricular ejection fraction, and greater volume, mass, and global extent of late gadolinium enhancement (LGE). They also exhibited distinct LV aneurysm characteristics, such as a larger maximum transverse dimension (maximum width), a wider aneurysm neck, and a higher aneurysm shape index (ratio of maximum length to neck width). Multivariable logistic regression analyses identified aneurysm neck width (OR 1.33 per 5 mm, 95% CI 1.00-1.77, <i>P</i> = 0.047), shape index (OR 1.63 per 20%, 95% CI 1.23-2.16, <i>P</i> = 0.001), and LGE global extent of >50% (OR 6.58, 95% CI 3.04-14.27, <i>P</i> < 0.001) as significant predictors of LV thrombus.A wider aneurysm neck, a higher aneurysm shape index, and LGE global extent >50% are associated with LV thrombus in patients with ischemic LV aneurysm.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399962","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":"Stress, Partner Violence, and Coagulopathy: Unmasking New Triggers for Venous Thromboembolism.","authors":"Eva Soler-Espejo, Vanessa Roldán, Francisco Marín","doi":"10.1055/a-2520-8725","DOIUrl":"10.1055/a-2520-8725","url":null,"abstract":"","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053682","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":"Safety and Efficacy of Factor Xa Inhibitors in Atrial Fibrillation Patients on Dialysis: Evidence from Four Randomized Controlled Trials.","authors":"Wulamiding Kaisaier, Yili Chen, Gregory Y H Lip, Chen Liu, Wengen Zhu","doi":"10.1055/a-2544-7919","DOIUrl":"10.1055/a-2544-7919","url":null,"abstract":"<p><p>Atrial fibrillation (AF) is prevalent in dialysis-dependent patients, who face higher risks of thromboembolism and bleeding. Although vitamin K antagonists (VKAs) are commonly used for anticoagulation, the benefits of factor Xa (FXa) inhibitors over VKAs in this population are unclear. This systematic review aims to compare the efficacy and safety of VKAs and FXa inhibitors based on randomized controlled trials (RCTs). We conducted a systematic search of PubMed and Embase for RCTs comparing FXa inhibitors and VKAs up to November 2024. The primary safety outcome was major bleeding, and the primary efficacy outcome was stroke or systemic embolism (SSE). Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using random-effects models. This meta-analysis included 486 dialysis-dependent AF patients from 4 RCTs, with a median follow-up of 26 weeks to 1.88 years. FXa inhibitors were associated with a reduced risk of major bleeding compared to VKAs (RR = 0.64, 95% CI = 0.42-0.99; <i>p</i> = 0.04), but no significant difference in SSE (RR = 0.46, 95% CI = 0.20-1.02; <i>p</i> = 0.06). FXa inhibitors also showed a significantly lower risk of intracranial bleeding (RR = 0.40, 95% CI = 0.17-0.96; <i>p</i> = 0.04), but no differences in other outcomes, including gastrointestinal bleeding, hemorrhagic stroke, ischemic stroke, acute coronary syndrome, and mortality. This systematic review and meta-analysis suggest that FXa inhibitors may offer a safer alternative to VKAs for AF patients on dialysis, with a lower risk of bleeding and similar risks of stroke and mortality.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493622","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":"Long-Chain Polysaturated Fatty Acid in Atrial Fibrillation-Associated Stroke: Lipidomic-GWAS Study.","authors":"Youngae Jung, Beomsu Kim, Chi Kyung Kim, Hong-Hee Won, Su-Hyun Chae, Kyungmi Oh, Min-Jeong Shin, Geum-Sook Hwang, Woo-Keun Seo","doi":"10.1055/a-2504-0903","DOIUrl":"10.1055/a-2504-0903","url":null,"abstract":"<p><p>This study aimed to explore the relationship between lipidomic domains, particularly free fatty acids (FFAs), and the presence of atrial fibrillation (AF) in patients with acute stroke, and to identify mechanisms of AF-associated stroke through genetic studies.A total of 483 stroke patients without AF (<i>n</i> = 391) and with AF (<i>n</i> = 92) were selected from a prospectively collected stroke registry. Lipidomic profiling was conducted, and the lipid components associated with AF were explored using fold-change analyses and clustering. Genotyping was conducted through trait comparison. Colocalization was also performed.Among the lipidomic domains, the free fatty acid (FFA) class was positively associated with AF. Long-chain fatty acids with 14 to 24 carbons and unsaturated FFAs distinguished AF. Clustering analysis based on FFAs revealed differences in AF proportion across groups. Genome-wide association study (GWAS) identified two loci associated with clustered groups of FFA metabolites: near MIR548F3 associated with FFA 20:1, FFA 20:2, FFA 22:5, and FFA 22:6; and near RPL37A associated with FFA 22:5 and FFA 22:6. These loci were associated with increased fibrinogen levels. In the GWAS for the FFA metabolite, quantitative trial locus analysis, loci near rs28456 and rs3770088, and FFA 20:4-QTLs were co-localized with the eQTLs of <i>FADS2</i>, a gene involved in the peroxisome proliferator-activated receptor gamma-related signaling pathway, in the whole blood, left ventricle, and atrial appendage tissue.Elevated FFA levels, especially those of long-chain unsaturated FFAs, are strongly associated with AF-associated stroke. This relationship is regulated by the peroxisome proliferator-activated receptor (PPAR) gamma-related signaling pathway.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855535","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}