Thrombosis and haemostasis最新文献

{"title":"Diabetic Microvascular Disease and Risk of Peripheral Artery Disease, Foot Ulcer, Leg Infection, and Amputation.","authors":"Fu-Shun Yen, Yu-Hsin Yen, Yao-Min Hung, James Cheng-Chung Wei, Fuu-Jen Tsai, Yu-Tung Hung, Heng-Jun Lin, Chii-Min Hwu, Chih-Cheng Hsu","doi":"10.1055/a-2661-2537","DOIUrl":"https://doi.org/10.1055/a-2661-2537","url":null,"abstract":"<p><p>Patients with diabetes are at risk for developing peripheral artery disease, foot ulcer, and amputation. We conducted this study to compare the risk of peripheral artery disease, foot ulcer, and amputation between patients with type 2 diabetes with and without microvascular disease.We identified 1,013,154 patients aged 18 to 80 years and newly diagnosed with type 2 diabetes between January 1, 2008, and December 31, 2018, as the study participants. Cox proportional hazard models were used to compare the risk of diabetic foot disease between patients with and without diabetic kidney disease, diabetic retinopathy, and diabetic neuropathy.Patients with more types of microvascular disease were associated with a further increased risk of peripheral artery disease, foot ulcer, leg infection, and amputation compared to those without microvascular disease (p for trend <0.001). Patients with diabetic retinopathy were associated with a significantly increased risk of peripheral artery disease (aHR [95% CI] 1.12 [1.08, 1.16]), foot ulcer (1.50 [1.28, 1.75]), and amputation (2.53 [1.59, 4.01]) compared to those without microvascular disease. Individuals with diabetic neuropathy had a significantly higher risk of peripheral artery disease (1.27 [1.24, 1.29]), foot ulcer (1.27 [1.16, 1.40]), and leg infection (1.16 [1.12, 1.21]) compared to those without microvascular disease.This nationwide cohort study showed that patients with type 2 diabetes and microvascular disease were associated with a higher risk of peripheral artery disease, foot ulcer, leg infection, and amputation than those without microvascular disease.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790048","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":"Integrin β3E726 Regulates the Switch Between Platelet Spreading and Clot Retraction by Interfering Gα13/RhoA Pathway.","authors":"Jie Peng, Yichen Liu, Yilin Zhu, Honglei Xin, Yun Wang, Bing Xiao, Tiantian Li, Rong Huang, Jing'an Liu, Ruonan Shao, Zijian Li, Jiao Wu, Han Yan, Yongqiu Di, Zijie Gan, Yifei Ma, Jianhua Mao, Shuai Chen, Jiansong Huang, Chao Fang, Xiaodong Xi, Xiaofeng Shi","doi":"10.1055/a-2664-7955","DOIUrl":"10.1055/a-2664-7955","url":null,"abstract":"<p><p>Platelet spreading and clot retraction, albeit both mediated by integrin outside-in signaling, lead to platelet shape changes in two opposite directions. The mechanisms by which these processes are regulated are not fully understood. Our previous study found that E726Q mutation in β3 integrin caused impaired spreading in Chinese hamster ovary (CHO) cells on immobilized fibrinogen.The current study further utilized knock-in mice bearing the β3^E726Q mutation to explore the underlying mechanisms whereby the E⁷²⁶ residue differentially influences platelet spreading and clot retraction.Compared to wild type (WT) platelets, β3^E726Q platelets displayed similar level of β3 expression but partially impaired fibrinogen binding associated with attenuated responses in platelet aggregation and P-selectin exposure. Notably, β3^E726Q mutation resulted in defective platelet spreading but accelerated clot retraction concomitant with increased clot density. Functionally, β3^E726Q mice displayed prolonged bleeding time and defective thrombogenesis in vitro and in vivo. Further mechanistic study showed that in β3^E726Q platelets the activities of RhoA and Rac1 were significantly enhanced following thrombin stimulation, possibly due to reduced binding of Gα13 to the β3 cytoplasmic tail.Taken together, the β3E⁷²⁶ is a potential novel regulatory site that influences the direct interaction of β3 cytoplasmic tail with Gα13 and therefore the activity of downstream RhoA, a molecular switch that shifts platelet spreading into clot retraction.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144733419","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":"Hepatic Apolipoprotein M Suppresses Hepatocyte Secretion of Prothrombin by Upregulating Arid5B.","authors":"Makoto Kurano, Baasanjav Uranbileg, Yutaka Yatomi","doi":"10.1055/a-2664-8170","DOIUrl":"10.1055/a-2664-8170","url":null,"abstract":"<p><p>Apolipoprotein M (ApoM) is a minor apolipoprotein bound to HDL, which carries sphingosine 1-phosphate (S1P), a potent lipid mediator.Since HDL has been proposed to possess pleiotropic effects, including an anti-thrombotic effect, we investigated the association between ApoM and coagulopathy.ApoM overexpression suppressed and ApoM knockout accelerated the decrease in platelet counts, but ApoM overexpression accelerated and ApoM knockout suppressed the prolongation of prothrombin time and activated partial thromboplastin time in a murine lipopolysaccharide-induced model of sepsis. ApoM decreased the plasma/culture-medium prothrombin levels and increased the hepatic/cellular prothrombin levels in mice and HepG2 cells, a hepatocyte cell line. S1P receptor knockdown did not inhibit prothrombin secretion by HepG2 cells.An RNA-sequence-based approach suggested that Arid5B was involved in these effects of ApoM. Arid5B knockdown increased the culture-medium prothrombin level but decreased cellular prothrombin level. ApoM upregulated Arid5B, and Arid5B knockdown antagonized the inhibitory effect of ApoM on prothrombin secretion. Hepatic ApoM suppresses hepatocyte prothrombin secretion independent of S1P receptors, by upregulation of Arid5B.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144733418","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":"802-813"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","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":"Dabigatran Attenuates the Binding of Thrombin to Platelets-A Novel Mechanism of Action.","authors":"Tomas L Lindahl, Aishwarya Prasanna Kumar, Teresia Hallström, Ahmed Al-Hashimi, Anna du Rietz, Elena Arlaman, Kajsa Uvdal, Ankit S Macwan","doi":"10.1055/a-2483-0107","DOIUrl":"10.1055/a-2483-0107","url":null,"abstract":"<p><p>Thrombin is a multifunctional regulatory enzyme of the haemostasis and has both pro- and anticoagulant roles. It has, therefore, been a main target for drug discovery over many decades. Thrombin is a serine protease and possesses two positively charged regions called exosites, through which it is known to bind to many substrates. Dabigatran is a thrombin inhibitor and is widely used as an oral anticoagulant for the antithrombotic treatment of atrial fibrillation and venous thromboembolism. The mechanism by which dabigatran inhibits thrombin is the blockage of the active site, however, its effect on thrombin binding to its substrates has not been studied thoroughly and is thus poorly understood.The effect of dabigatran on thrombin binding to platelets was evaluated by flow cytometry using fluorescently labelled thrombin and washed platelets. Further, to confirm the results we utilized modern techniques for biomolecular binding studies, microscale thermophoresis (MST) and surface plasmon resonance (SPR), which validated the results.Dabigatran inhibited thrombin binding to platelets as analysed by flow cytometry. The inhibition was dose dependent with IC50 of 118 nM which was slightly lower than for inhibition of platelet activation and is close to the clinically relevant plasma concentration of dabigatran. MST and SPR also confirmed inhibitory effect of dabigatran on thrombin binding to platelets.Apart from blocking the active site, dabigatran also inhibits thrombin binding to platelets. Since thrombin has numerous functions beyond the cardiovascular system, this finding may have important implications.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"747-756"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12283142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142717070","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":"Multidisciplinary Expert Guidance for the Management of Severe Bleeding on Oral Anticoagulation: An Algorithm for Practicing Clinicians.","authors":"Siraj Mithoowani, Tammy Bungard, Lana Castellucci, Mark Crowther, Kerstin de Wit, Dar Dowlatshahi, Nauzer Forbes, Katie Lin, Deborah M Siegal","doi":"10.1055/a-2464-2887","DOIUrl":"10.1055/a-2464-2887","url":null,"abstract":"<p><p>Bleeding complications associated with oral anticoagulant (OAC) frequently lead to emergency department visits and hospitalization. Short-term all-cause mortality after severe bleeding is substantial ranging from approximately 10% for gastrointestinal bleeding (the most frequent single site) to approximately 50% for intracranial bleeding. A protocol for multidisciplinary approach to bleeding is needed to (i) ensure rapid identification of patients at risk of adverse outcomes, (ii) optimize delivery of supportive measures, (iii) treat the source of bleeding, and (iv) administer anticoagulant reversal or hemostatic therapies judiciously for patients most likely to benefit. We convened a multidisciplinary panel of experts (emergency medicine, gastroenterology, general internal medicine, hematology, neurology, pharmacy, thrombosis) to review the literature and provide practical guidance including a corresponding algorithm for use at the point of care to assist clinicians in the management of patients with acute severe OAC-related bleeding.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"717-732"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12283145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605509","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":"Real-Time Imaging of Platelet-Initiated Plasma Clot Formation and Lysis Unveils Distinct Impacts of Anticoagulants.","authors":"Yuko Suzuki, Nitty S Mathews, Hideto Sano, Nanami Morooka, Naoki Honkura, Tetsumei Urano","doi":"10.1055/a-2497-4213","DOIUrl":"10.1055/a-2497-4213","url":null,"abstract":"<p><p>Fibrinolysis is spatiotemporally well-regulated and greatly influenced by activated platelets and coagulation activity. Our previous real-time imaging analyses revealed that clotting commences on activated platelet surfaces, resulting in uneven-density fibrin structures, and that fibrinolysis initiates in dense fibrin regions and extends to the periphery. Despite the widespread clinical use of direct oral anticoagulants (DOACs), their impact on thrombin-dependent activation of thrombin-activatable fibrinolysis inhibitor (TAFI) and fibrinolysis remains unclear. Here, we investigated the effects of different DOACs on the TAFI-mediated inhibition of fibrinolysis.Using human platelet-containing plasma, we performed turbidimetric assays, thrombin generation assays, and confocal laser scanning microscopy to assess the effects of anticoagulants on fibrinolysis.Activated platelets-prolonged plasma clot lysis time, shortened by activated TAFI inhibitor (TAFIaI), positively correlated with the amount of thrombin generated. Rivaroxaban (an activated factor X inhibitor) and dabigatran (a direct thrombin inhibitor) dose-dependently shortened lysis time comparably. The highest concentration of DOACs showed no further shortening of lysis time with TAFIaI. The fibrin network structures initiated by activated platelets and the localization of fluorescently labeled plasminogen were unique for these two drugs. Rivaroxaban maintained an uneven fibrin network but promoted faster plasminogen accumulation and fibrinolysis from outside dense fibrin regions. Conversely, dabigatran resulted in a more even fibrin network, with fibrinolysis starting from the activated platelets and propagating to the periphery. Visualizing and analyzing the patterns of fibrin network formation, plasminogen accumulation, and fibrinolysis provide new insights into the specific impact of anticoagulants on coagulation and fibrinolysis.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"766-778"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12283144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955477","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":"Optimizing Use of Antithrombotics and Overcoming Therapeutic Inertia: Lessons from the AEGIS Trial.","authors":"Giulio Francesco Romiti","doi":"10.1055/a-2622-8652","DOIUrl":"10.1055/a-2622-8652","url":null,"abstract":"","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"744-746"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267283","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":"Validity of Diagnosis of Disseminated Intravascular Coagulation Based on International Classification of Diseases Coding in a Claims Database.","authors":"Yutaka Umemura, Kazuma Yamakawa, Hirotaka Mori, Kohji Okamoto, Jun Oda, Satoshi Fujimi","doi":"10.1055/a-2453-7920","DOIUrl":"10.1055/a-2453-7920","url":null,"abstract":"<p><p>Accuracy in diagnoses recorded using the International Classification of Diseases (ICD) coding is the most important element ensuring the foundation of research using real-world data analyses.To evaluate the validity of ICD coding for diagnoses of disseminated intravascular coagulation (DIC) using the International Society on Thrombosis and Haemostasis (ISTH) overt DIC criteria and the Japanese Association for Acute Medicine (JAAM) DIC criteria as reference standards.This retrospective observational study included adult hospitalized patients diagnosed as having diseases potentially causing DIC extracted from a part of a large-scale database in Japan. The index test was a diagnosis of DIC based on the ICD-10 codes. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated using ISTH overt DIC criteria and JAAM-2 DIC criteria as the reference standards. We also conducted subgroup analyses according to the underlying diseases.We included 84,300 patients in this study. In the overall study population, sensitivity, specificity, PPV, and NPV of the ICD-based diagnosis for ISTH criteria were 26.28, 98.10, 35.12, and 97.14%, respectively. In subgroup analyses according to the underlying disease, sensitivity ranged from 9.48 to 52.08%, and specificity ranged from 96.94 to 99.47%. The accuracy of the ICD-based diagnosis for JAAM-2 criteria was similar to that for ISTH criteria.Identification of DIC patients using ICD-10 codes had relatively low sensitivity but very high specificity for DIC diagnostic criteria. Approximately 65% of patients identified by ICD coding are likely to meet the JAAM-2 DIC criteria.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"757-765"},"PeriodicalIF":4.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547629","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":"Distinct Role of GRK3 in Platelet Activation by Desensitization of G Protein-Coupled Receptors.","authors":"Preeti K Chaudhary, Sanggu Kim, Satya P Kunapuli, Soochong Kim","doi":"10.1055/a-2442-9031","DOIUrl":"10.1055/a-2442-9031","url":null,"abstract":"<p><p>Many platelet agonists mediate their cellular effects through G protein-coupled receptors (GPCRs) to induce platelet activation, and GPCR kinases (GRKs) have been demonstrated to have crucial roles in most GPCR functions in other cell types. Here, we investigated the functional role of GRK3 and the molecular basis for the regulation of GPCR desensitization by GRK3 in platelets.We used mice lacking GRK3 as well as β-arrestin2, which has been shown to be important in GPCR function in platelets.Platelet aggregation and dense granule secretion induced by 2-MeSADP, U46619, thrombin, and AYPGKF were significantly potentiated in both GRK3 -/- and β-arrestin2 -/- platelets compared with wild-type (WT) platelets, whereas non-GPCR agonist collagen-induced platelet aggregation and secretion were not affected. We have previously shown that GRK6 is not involved in the regulation of G_q-coupled 5HT_2A and G_z-coupled α_2A adrenergic receptors. Interestingly, in contrast to GRK6, platelet aggregation induced by costimulation of serotonin and epinephrine, which activate 5-HT_2A and α_2A adrenergic receptors, respectively, was significantly potentiated in GRK3 -/- platelets, suggesting that GRK3 is involved in general GPCR regulation. In addition, platelet aggregation in response to the second challenge of adenosine diphosphate was restored in GRK3 -/- platelets, whereas restimulation of the agonist failed to induce aggregation in WT platelets, confirming that GRK3 contributes to general GPCR desensitization. Furthermore, 2-MeSADP- and AYPGKF-induced AKT and ERK phosphorylation were significantly potentiated in GRK3 -/- platelets. Finally, GRK3 -/- mice showed shorter tail bleeding times compared with WT, indicating that GRK3 -/- mice is more susceptible to hemostasis.GRK3 plays a crucial role in the regulation of platelet activation through general GPCR desensitization in platelets.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"779-790"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475430","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}