Thrombosis and haemostasis最新文献

{"title":"Monocyte Subsets in Cardiovascular Disease: A Biomarker Perspective.","authors":"Michael Hristov, Christian Weber","doi":"10.1055/a-2348-5697","DOIUrl":"10.1055/a-2348-5697","url":null,"abstract":"<p><p>Endothelial dysfunctions together with a dysregulated immune response and lipid accumulation are important confounding factors in the onset and chronic development of atherosclerosis. Recently, a large body of data has emerged on the sequential involvement of different immune cell types, including monocytes, in the pathology of this disease. In this condensed review, we aim to highlight some of the recent basic research and clinical findings on monocyte subsets published since our joint European Society of Cardiology consensus document, and re-evaluate their potential relevance as surrogate biomarkers in coronary artery disease.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141427694","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":"Risk of Major Bleeding with Antiplatelet and/or Anticoagulation Therapy in Inherited Factor XI Deficiency: Insights from Real-World Observations.","authors":"Shanni Vaismann, Nili Stein, Liat Dizengoff, Amir Warwar, Shoshan Perek, Ibraheem Zoabi, Walid Saliba, Meir Preis","doi":"10.1055/a-2347-4338","DOIUrl":"10.1055/a-2347-4338","url":null,"abstract":"","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421098","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":"Heterozygous Prothrombin Mutation-Associated Thrombophilia.","authors":"Xi Wu, Lei Li, Zhengjing Lu, Xiaobo Hu, Yeling Lu, Yu Liu, Guanqun Xu, Qiulan Ding, Xuefeng Wang, Wenman Wu, Peipei Jin, Jing Dai","doi":"10.1055/a-2350-8338","DOIUrl":"10.1055/a-2350-8338","url":null,"abstract":"<p><strong>Background: </strong> Venous thromboembolism (VTE) is predisposed by thrombotic mutations in patients with hereditary thrombophilia. Although prothrombin deficiencies caused by homozygous or compound heterozygous mutations are associated with bleeding diathesis, rare cases have shown a correlation between heterozygous prothrombin mutations and thrombosis.</p><p><strong>Materials and methods: </strong> We surveyed genetic variants involved in thrombosis and hemostasis in 347 patients with unprovoked VTE or having a positive family history of thrombosis. For patients identified with heterozygous prothrombin mutations, we conducted family investigations and performed a thrombin generation test (TGT) to elucidate the thrombotic risk. Novel mutants were expressed and subjected to functional assays to clarify the underlying thrombotic mechanisms.</p><p><strong>Results: </strong> Heterozygous prothrombin mutations were identified in 3.5% of patients (12/347), including three novel mutations Phe382Ser, Phe382Leu, and Asp597Tyr found in one patient each, as well as previously reported Arg541Trp mutation in four patients and Arg596Gln mutation in five patients. A total of 42 mutation carriers were identified within the 12 pedigrees, among whom 64.3% (27/42) had experienced thrombotic events. TGT results demonstrated hypercoagulability for carriers of the five mutations, with Arg596Gln showing the highest thrombin generation potential followed by Arg541Trp. The Phe382-associated mutations severely impaired thrombomodulin-binding ability of thrombin, resulting in obviously reduced protein C (PC) activation. The Asp597Tyr mutation exhibited a mild reduction in both inactivation by antithrombin and PC activation reactions.</p><p><strong>Conclusion: </strong>The presence of heterozygous prothrombin mutations represents a potential genetic predisposition for VTE. All thrombosis-associated mutations potentiate coagulation activity by either conferring antithrombin resistance and/or impairing PC pathway activity.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141447174","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":"Antithrombotic Prophylaxis with Rivaroxaban in Patients with Prehospital COVID-19: A Meta-analysis of Two Placebo-Controlled Trials.","authors":"Judith Hsia, Alex C Spyropoulos, Gregory Piazza, Stephen Weng, Michael W Dunne, Concetta Lipardi, Elliot S Barnathan, Marc P Bonaca","doi":"10.1055/a-2216-5848","DOIUrl":"10.1055/a-2216-5848","url":null,"abstract":"<p><strong>Background: </strong> We conducted a prespecified meta-analysis of two randomized, placebo-controlled trials of rivaroxaban 10 mg daily in prehospital patients with acute coronavirus disease 2019 (COVID-19). Individually, the trials had limited power to detect a treatment effect due to recruitment stopping ahead of plan.</p><p><strong>Material and methods: </strong> The statistical analysis plan for the meta-analysis was finalized before unblinding of PREVENT-HD, the larger of the two trials. Pooled risk ratios and pooled risk differences along with the two-sided 95% confidence intervals were calculated using random-effect models.</p><p><strong>Results: </strong> Rivaroxaban did not reduce the occurrence of either the primary prespecified endpoint, a composite of symptomatic arterial and venous thromboembolism, myocardial infarction, ischemic stroke, acute limb ischemia, all-cause hospitalization, and all-cause mortality (risk difference: 0.0044; 95% confidence interval: -0.0263, 0.0175; <i>p</i> = 0.69 for pooled risk difference) or the secondary endpoint of all-cause hospitalization (<i>p</i> = 0.76). Although thrombotic events were infrequent, pooled analysis did reveal that rivaroxaban reduced arterial and venous thrombotic events (placebo 6 events, rivaroxaban 0 events; pooled risk difference: -0.0068; 95% confidence interval: -0.0132, -0.0006; <i>p</i> = 0.03). In the pooled studies, only one major bleeding event was observed in a rivaroxaban-allocated patient with no critical site or fatal bleeding events.</p><p><strong>Conclusion: </strong> Although this meta-analysis does not support antithrombotic prophylaxis with rivaroxaban in a broad prehospital population with acute COVID-19, the prevention of arterial and venous thrombotic events among rivaroxaban-allocated patients is consistent with the known thromboprophylactic effect of the drug in medically ill patients.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"649-655"},"PeriodicalIF":5.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11199042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138300097","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":"Glycosaminoglycans: Participants in Microvascular Coagulation of Sepsis.","authors":"Nanxi Li, Ruolin Hao, Peng Ren, Jingya Wang, Jiahui Dong, Tong Ye, Danyang Zhao, Xuan Qiao, Zhiyun Meng, Hui Gan, Shuchen Liu, Yunbo Sun, Guifang Dou, Ruolan Gu","doi":"10.1055/a-2250-3166","DOIUrl":"10.1055/a-2250-3166","url":null,"abstract":"<p><p>Sepsis represents a syndromic response to infection and frequently acts as a common pathway leading to fatality in the context of various infectious diseases globally. The pathology of severe sepsis is marked by an excess of inflammation and activated coagulation. A substantial contributor to mortality in sepsis patients is widespread microvascular thrombosis-induced organ dysfunction. Multiple lines of evidence support the notion that sepsis induces endothelial damage, leading to the release of glycosaminoglycans, potentially causing microvascular dysfunction. This review aims to initially elucidate the relationship among endothelial damage, excessive inflammation, and thrombosis in sepsis. Following this, we present a summary of the involvement of glycosaminoglycans in coagulation, elucidating interactions among glycosaminoglycans, platelets, and inflammatory cells. In this section, we also introduce a reasoned generalization of potential signal pathways wherein glycosaminoglycans play a role in clotting. Finally, we discuss current methods for detecting microvascular conditions in sepsis patients from the perspective of glycosaminoglycans. In conclusion, it is imperative to pay closer attention to the role of glycosaminoglycans in the mechanism of microvascular thrombosis in sepsis. Dynamically assessing glycosaminoglycan levels in patients may aid in predicting microvascular conditions, enabling the monitoring of disease progression, adjustment of clinical treatment schemes, and mitigation of both acute and long-term adverse outcomes associated with sepsis.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"599-612"},"PeriodicalIF":5.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11199054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139502633","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":"Novel Insights into the Aortic Mechanical Properties of Mice Modeling Hereditary Aortic Diseases.","authors":"Nicolo Dubacher, Kaori Sugiyama, Jeffrey D Smith, Vanessa Nussbaumer, Máté Csonka, Szilamér Ferenczi, Krisztina J Kovács, Sylvan M Caspar, Lisa Lamberti, Janine Meienberg, Hiromi Yanagisawa, Mary B Sheppard, Gabor Matyas","doi":"10.1055/s-0044-1787957","DOIUrl":"10.1055/s-0044-1787957","url":null,"abstract":"<p><strong>Objective: </strong> Hereditary aortic diseases (hADs) increase the risk of aortic dissections and ruptures. Recently, we have established an objective approach to measure the rupture force of the murine aorta, thereby explaining the outcomes of clinical studies and assessing the added value of approved drugs in vascular Ehlers-Danlos syndrome (vEDS). Here, we applied our approach to six additional mouse hAD models.</p><p><strong>Material and methods: </strong> We used two mouse models (<i>Fbn1C1041G</i> and <i>Fbn1mgR</i> ) of Marfan syndrome (MFS) as well as one smooth-muscle-cell-specific knockout (SMKO) of <i>Efemp2</i> and three CRISPR/Cas9-engineered knock-in models (<i>Ltbp1</i>, <i>Mfap4</i>, and <i>Timp1</i>). One of the two MFS models was subjected to 4-week-long losartan treatment. Per mouse, three rings of the thoracic aorta were prepared, mounted on a tissue puller, and uniaxially stretched until rupture.</p><p><strong>Results: </strong> The aortic rupture force of the SMKO and both MFS models was significantly lower compared with wild-type mice but in both MFS models higher than in mice modeling vEDS. In contrast, the <i>Ltbp1</i>, <i>Mfap4</i>, and <i>Timp1</i> knock-in models presented no impaired aortic integrity. As expected, losartan treatment reduced aneurysm formation but surprisingly had no impact on the aortic rupture force of our MFS mice.</p><p><strong>Conclusion: </strong> Our read-out system can characterize the aortic biomechanical integrity of mice modeling not only vEDS but also related hADs, allowing the aortic-rupture-force-focused comparison of mouse models. Furthermore, aneurysm progression alone may not be a sufficient read-out for aortic rupture, as antihypertensive drugs reducing aortic dilatation might not strengthen the weakened aortic wall. Our results may enable identification of improved medical therapies of hADs.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477499","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":"Anticoagulation in Patients with Mechanical Heart Valves: Less Is More?","authors":"Daniela Poli, Alessandro Squizzato, Alberto Tosetto","doi":"10.1055/s-0044-1786176","DOIUrl":"10.1055/s-0044-1786176","url":null,"abstract":"","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"625-627"},"PeriodicalIF":5.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140852861","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":"Inverse Association of Lipoprotein(a) on Long-Term Bleeding Risk in Patients with Coronary Heart Disease: Insight from a Multicenter Cohort in Asia.","authors":"Peizhi Wang, Deshan Yuan, Xueyan Zhao, Pei Zhu, Xiaogang Guo, Lin Jiang, Na Xu, Zhifang Wang, Ru Liu, Qingsheng Wang, Yan Chen, Yongzhen Zhang, Jingjing Xu, Zhenyu Liu, Ying Song, Zheng Zhang, Yi Yao, Yingqing Feng, Xiaofang Tang, Xiaozeng Wang, Runlin Gao, Yaling Han, Jinqing Yuan","doi":"10.1055/s-0043-1771188","DOIUrl":"10.1055/s-0043-1771188","url":null,"abstract":"<p><strong>Background: </strong> Lipoprotein(a), or Lp(a), has been recognized as a strong risk factor for atherosclerotic cardiovascular disease. However, the relationship between Lp(a) and bleeding remains indistinct, especially in the secondary prevention population of coronary artery disease (CAD). This investigation aimed to evaluate the association of Lp(a) with long-term bleeding among patients with CAD.</p><p><strong>Methods: </strong> Based on a prospective multicenter cohort of patients with CAD consecutively enrolled from January 2015 to May 2019 in China, the current analysis included 16,150 participants. Thus, according to Lp(a) quintiles, all subjects were divided into five groups. The primary endpoint was bleeding at 2-year follow-up, and the secondary endpoint was major bleeding at 2-year follow-up.</p><p><strong>Results: </strong> A total of 2,747 (17.0%) bleeding and 525 (3.3%) major bleeding were recorded during a median follow-up of 2.0 years. Kaplan-Meier survival analysis showed the highest bleeding incidence in Lp(a) quintile 1, compared with patients in Lp(a) quintiles 2 to 5 (<i>p</i> < 0.001), while the incidence of major bleeding seemed similar between the two groups. Moreover, restricted cubic spline analysis suggested that there was an L-shaped association between Lp(a) and 2-year bleeding after adjustment for potential confounding factors, whereas there was no significant association between Lp(a) and 2-year major bleeding.</p><p><strong>Conclusion: </strong> There was an inverse and L-shaped association of Lp(a) with bleeding at 2-year follow-up in patients with CAD. More attention and effort should be made to increase the clinician awareness of Lp(a)'s role, as a novel marker for bleeding risk to better guide shared-decision making in clinical practice.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"684-694"},"PeriodicalIF":5.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11199048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9868182","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":"Platelet-Derived TGF-β1 Promotes Deep Vein Thrombosis.","authors":"Sixuan Zhang, Yingying Li, Jie Zhang, Yueyue Sun, Xiang Chu, Xiang Gui, Huan Tong, Yangyang Ding, Wen Ju, Mengdi Xu, Zhenyu Li, Lingyu Zeng, Kailin Xu, Jianlin Qiao","doi":"10.1055/a-2235-7485","DOIUrl":"10.1055/a-2235-7485","url":null,"abstract":"<p><strong>Background: </strong> Transforming growth factor-β1 (TGF-β1) modulates multiple cellular functions during development and tissue homeostasis. A large amount of TGF-β1 is stored in platelet α-granules and released upon platelet activation. Whether platelet-derived TGF-β1 plays a role in venous thrombosis remains unclear. This study intends to assess the role of platelet-derived TGF-β1 in the development of venous thrombosis in mice.</p><p><strong>Material and methods: </strong> TGF-β1^flox/flox and platelet-specific TGF-β1^-/- mice were utilized to assess platelet function in vitro, arterial thrombosis induced by FeCl₃, tail bleeding time, prothrombin time (PT), activated partial thromboplastin time (APTT), and deep vein thrombosis induced through ligation of the inferior vena cava (IVC). The IVC sample was collected to measure accumulation of neutrophils, monocytes, and the formation of neutrophil extracellular traps (NETs) by immunofluorescence staining.</p><p><strong>Results: </strong> TGF-β1 deficiency in platelets did not affect the number of circulating platelets, platelet aggregation, adenosine triphosphate release, and integrin αIIbβ3 activation. Meanwhile, TGF-β1 deficiency did not alter the arterial thrombus formation, hemostasis, and coagulation time (PT and APTT), but significantly impaired venous thrombus formation, inhibited the recruitment and accumulation of neutrophils and monocytes in thrombi, as well as reduced formation of NETs and platelet-neutrophil complex. In addition, adoptive transfer of TGF-β1^flox/flox platelets to TGF-β1^-/- mice rescued the impaired venous thrombus formation, recruitment of leukocytes and monocytes, as well as the NETs formation.</p><p><strong>Conclusion: </strong>In conclusion, platelet-derived TGF-β1 positively modulates venous thrombus formation in mice, indicating that targeting TGF-β1 might be a novel approach for treating venous thrombosis without increasing the risk of bleeding.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"641-648"},"PeriodicalIF":5.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139049349","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":"Endothelial LAT1 (SLC7A5) Mediates S-Nitrosothiol Import and Modulates Respiratory Sequelae of Red Blood Cell Transfusion In Vivo.","authors":"Hongmei Zhu, Richard L Auten, Augustus Richard Whorton, Stanley Nicholas Mason, Cheryl B Bock, Gary T Kucera, Zachary T Kelleher, Aaron T Vose, Tim J McMahon","doi":"10.1055/s-0044-1782182","DOIUrl":"10.1055/s-0044-1782182","url":null,"abstract":"<p><strong>Background: </strong> Increased adhesivity of red blood cells (RBCs) to endothelial cells (ECs) may contribute to organ dysfunction in malaria, sickle cell disease, and diabetes. RBCs normally export nitric oxide (NO)-derived vascular signals, facilitating blood flow. S-nitrosothiols (SNOs) are thiol adducts formed in RBCs from precursor NO upon the oxygenation-linked allosteric transition in hemoglobin. RBCs export these vasoregulatory SNOs on demand, thereby regulating regional blood flow and preventing RBC-EC adhesion, and the large (system L) neutral amino acid transporter 1 (LAT1; SLC7A5) appears to mediate SNO export by RBCs.</p><p><strong>Methods: </strong> To determine the role of LAT1-mediated SNO import by ECs generally and of LAT1-mediated SNO import by ECs in RBC SNO-dependent modulation of RBC sequestration and blood oxygenation in vivo, we engineered LAT1^fl/fl; Cdh5-Cre⁺ mice, in which the putative SNO transporter LAT1 can be inducibly depleted (knocked down, KD) specifically in ECs (\"LAT1^ECKD\").</p><p><strong>Results: </strong> We show that LAT1 in mouse lung ECs mediates cellular SNO uptake. ECs from LAT1^ECKD mice (tamoxifen-induced LAT1^fl/fl; Cdh5-Cre⁺) import SNOs poorly ex vivo compared with ECs from wild-type (tamoxifen-treated LAT1^fl/fl; Cdh5-Cre^-) mice. In vivo, endothelial depletion of LAT1 increased RBC sequestration in the lung and decreased blood oxygenation after RBC transfusion.</p><p><strong>Conclusion: </strong> This is the first study showing a role for SNO transport by LAT1 in ECs in a genetic mouse model. We provide the first direct evidence for the coordination of RBC SNO export with EC SNO import via LAT1. SNO flux via LAT1 modulates RBC-EC sequestration in lungs after transfusion, and its disruption impairs blood oxygenation by the lung.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"656-668"},"PeriodicalIF":5.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11199053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140190108","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}