Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis最新文献

{"title":"Understanding of the roles of CD4 + CD25 + T cells and Tregs in development of anti-FVIII in hemophilia A: insights for inhibitor development prevention.","authors":"Emre Akkaya, Basak S Koc, Umut C Kucuksezer, Aysenur Kokoglu, Esin Cetin Aktas, Gunnur Deniz, Sema Genc, Bulent Zulfikar","doi":"10.1097/MBC.0000000000001393","DOIUrl":"10.1097/MBC.0000000000001393","url":null,"abstract":"<p><p>Hemophilia A, characterized by factor VIII (FVIII) deficiency, can be managed with factor replacement therapy. However, FVIII-neutralizing antibodies developed in people with hemophilia A (PwH) can reduce treatment efficacy. This study investigated the impact of FVIII inhibitors on immunity in PwH. Twenty PwH (with the presence and absence of inhibitors) and 10 healthy individuals have participated. CD4 + , CD4 + CD25 + , Treg cell percentages, proliferation levels, and cytokine levels in cell-culture supernatants were evaluated. An increased CD4 + CD25 + T-cell subset was noted in PwH without inhibitors. CD4 + and CD4 + CD25 + T cells showed increased proliferation, while Treg cells had decreased proliferation in PwH without inhibitors compared to controls. With rFVIII added to cell culture, CD4 + CD25 + proliferation decreased and Treg proliferation increased in PwH with inhibitors, while it remained unchanged in other groups. IL-10 was reduced in both PwH groups. TGF-β was decreased in PwH with inhibitors compared to those without inhibitors. IL-10/TGF-β ratio was reduced in both PwH groups compared to controls. rFVIII in culture conditions significantly reduced TNF-α only in PwH with inhibitors, while TGF-β was decreased in PwH without inhibitors and healthy controls. Monitoring T-cell immunity in PwH before anti-FVIII antibody development may improve treatment success and help prevent antibodies and related complications.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"371-380"},"PeriodicalIF":1.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145357478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of HLA alleles involved in immune thrombotic thrombocytopenic purpura patients from Turkey: Erratum.","authors":"","doi":"10.1097/MBC.0000000000001387","DOIUrl":"https://doi.org/10.1097/MBC.0000000000001387","url":null,"abstract":"","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":"36 7","pages":"347"},"PeriodicalIF":1.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platelet aggregation response in children with infantile haemangioma under propranolol treatment.","authors":"Havva Özüm Kolsuz, Zeynep Canan Özdemir, Özcan Bör","doi":"10.1097/MBC.0000000000001383","DOIUrl":"10.1097/MBC.0000000000001383","url":null,"abstract":"<p><p>Infantile haemangioma is characterized by the proliferation of immature endothelial cells. A small portion requires treatment. Beta blockers are a good treatment option; however, it has been shown that beta blockers cause a decrease in the aggregation response of platelets. Twenty healthy children and 20 children with a diagnosis of infantile haemangioma who were started on propranolol treatment were included in the study. All patients were given propranolol 1 mg/kg/day in two doses. Haemangioma size, appearance features, blood count parameters and percentage of the maximal amplitude of platelets were compared before treatment and at the first month of treatment. The percentage of the maximal amplitude was determined using the light transmission aggregometry method. A total of 23 haemangiomas were detected. The mean size of haemangioma at the first month after treatment (2.46 cm) was statistically significantly lower than before treatment (2.65 cm) ( P  < 0.05). A lighter shade was noticeable in six of 23 (26.1%) haemangiomas. The number of patients whose swelling decreased (13 patients, 68.4%) was significantly greater than the number whose swelling did not decrease (six patients, 31.6%) ( P  < 0.05). There was no difference in blood count parameters and percentage of the maximal amplitude of platelets between groups ( P  > 0.05, for all). When 1 mg/kg/day propranolol was given to children with infantile haemangioma, it was shown that propranolol was effective in the response to treatment even after 1 month of treatment, and there was no change in the blood count parameters and platelet aggregation response.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"323-327"},"PeriodicalIF":1.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The efficacy, safety, and pharmacokinetics of N8-GP in previously treated Chinese patients with haemophilia A: results from the phase 3b pathfinder10 study.","authors":"Runhui Wu, Yun Chen, Wenqian Li, Jing Sun, Feng'e Yang, Xiaojing Zeng, Zeping Zhou, Xiaolei Bao, Xiaoyan Li, Marek Stanislaw Zak, Renchi Yang","doi":"10.1097/MBC.0000000000001386","DOIUrl":"10.1097/MBC.0000000000001386","url":null,"abstract":"<p><strong>Introduction: </strong>N8-GP (turoctocog alfa pegol) is a recombinant, glycoPEGylated, extended half-life FVIII replacement product approved for treatment of haemophilia A (HA).</p><p><strong>Aim: </strong>The pathfinder10 (NCT05082116) multicentre, open-label, nonrandomised, single-arm phase 3b trial investigated N8-GP efficacy, safety, and pharmacokinetics in previously treated Chinese patients.</p><p><strong>Methods: </strong>Patients (≥12 years) with severe HA, FVIII activity <1%, ≥150 exposure days to FVIII products, and no FVIII inhibitors (≥0.6 BU) or history were enrolled and received 50 IU/kg N8-GP prophylaxis every four days for ≥28 weeks. Bleeding episodes were treated with 20-75 IU/kg N8-GP. The primary endpoint was the number of treatment-requiring bleeding episodes (spontaneous, traumatic). Secondary endpoints included haemostatic effect, inhibitor rate, FVIII trough activity, and pharmacokinetics.</p><p><strong>Results: </strong>Thirty-six patients completed the trial. During 12 months pretrial, 17 (47%) patients received a mixture of episodic and prophylactic regimens, and 1 (3%) episodic treatment only, and the mean (SD) and median number of bleeding episodes during prophylaxis were 11.0 (11.1) and 5.0. During N8-GP prophylaxis, mean (95% CI) and median ABR were 2.55 (1.24; 5.23) and 0.00. No bleeds were reported in 25/36 patients (69.4%). The haemostatic success rate for bleed treatment was 94.8% (73.2; 99.2). Most bleeds (49/52; 94.2%) were treated with ≤2 injections; 42/52 (80.8%) needed 1 injection. Mean FVIII activity trough level (predose) was 3.3 IU/dl (2.6; 4.3), mean postdose recovery 126.1 IU/dl (116.9; 136.0), N8-GP terminal half-life 19.9 h (18.6, 21.2), 30 min IR 2.28 (IU/dl)/(IU/kg) (2.05, 2.52), and AUC (0-96 h) (single dose) 31.8 h*(IU/ml) (28.9; 34.9). No inhibitors or safety concerns were identified.</p><p><strong>Conclusion: </strong>N8-GP appeared safe and efficacious in previously treated Chinese patients with severe HA.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"309-317"},"PeriodicalIF":1.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12517726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144839756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factor VIII beyond haemophilia: a hidden regulator of venous thrombosis and endothelial dysfunction.","authors":"Anusha Prasannan, Kaliyamurthi Venkatachalam, Ambika Binesh","doi":"10.1097/MBC.0000000000001385","DOIUrl":"10.1097/MBC.0000000000001385","url":null,"abstract":"<p><p>Factor VIII (FVIII), a critical cofactor protein traditionally acknowledged for its deficiency in haemophilia A (HA), has been attracting interest for its substantial role in vascular disease. Recent data highlights its essential role beyond haemostasis, in the development of venous thrombosis (VT) and endothelial dysfunction influenced by genetic and acquired factors. This review summarizes the biology, synthesis, and activation of FVIII, emphasizing its role in thrombin generation and endothelial dysfunction. FVIII is implicated in inflammatory and thrombotic disorders, such as COVID-19, sepsis, and cancer-associated thrombosis. Although anticoagulant medication indirectly reduces elevated FVIII levels, direct intervention is constrained by the associated bleeding risks. Novel approaches like RNA interference, gene editing, and endothelial-specific modulation might offer compelling opportunities for the regulation of FVIII. This study highlights the potential of FVIII as a diagnostic and therapeutic target in thrombosis by integrating molecular insights with clinical data, hence promoting future precision-based therapies.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"335-346"},"PeriodicalIF":1.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144791710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and clinical characterization of factor VII deficiency: insights from 34 Turkish patients.","authors":"Tahir Atik, Basak Durmus Ozen, Esra Isik, Enise Avci Durmusalioglu, Nazan Sarper, Canan Albayrak, Alphan Kupesiz, Melike Sezgin Evim, Mehmet Azizoglu, Davut Albayrak, Funda Tayfun Kupesiz, Gulen Tuysuz Kintrup, Ekrem Unal, Alper Ozcan, Kaan Kavakli, Ferda Ozkinay","doi":"10.1097/MBC.0000000000001381","DOIUrl":"10.1097/MBC.0000000000001381","url":null,"abstract":"<p><strong>Background: </strong>Factor VII (FVII) deficiency is a rare autosomal recessive bleeding disorder caused by pathogenic variants in the F7 gene. Clinical manifestations vary widely, ranging from asymptomatic cases to severe bleeding episodes, including gastrointestinal bleeding and intracranial hemorrhage.</p><p><strong>Objective: </strong>This study aims to evaluate the clinical and molecular characteristics of Turkish patients diagnosed with FVII deficiency and explore genotype-phenotype correlations.</p><p><strong>Methods: </strong>A cohort of 34 patients with FVII deficiency was examined. Clinical symptoms were documented, and genetic analysis of the F7 gene was performed to identify pathogenic variants.</p><p><strong>Results: </strong>A total of 16 different variants were identified, including four novel variants: c.-5_4delTCinsCA, c.686T>C (p.Leu229Pro), c.728T>C (p.Ile243Thr), c.733delA (p.Thr245ProfsTer20). Monoallelic variants were found in 50% of patients, while biallelic pathogenic variants were detected in 20.6%. No pathogenic variants were identified in 29.4% of the patients. There was a poor correlation between FVII activity levels and clinical severity.</p><p><strong>Conclusion: </strong>This study highlights the importance of molecular diagnostics in the management of FVII deficiency, providing valuable insights into genotype-phenotype relationships. Our findings contribute to the understanding of the genetic diversity and clinical spectrum of FVII deficiency, particularly within the Turkish population.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"303-308"},"PeriodicalIF":1.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144763024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in nanotechnology for synthetic polymer hemostats: navigating precision hemostasis.","authors":"Shaohan Luo, Jie Shi, Qi Lv","doi":"10.1097/MBC.0000000000001378","DOIUrl":"10.1097/MBC.0000000000001378","url":null,"abstract":"<p><p>Traumatic hemorrhage poses a significant medical challenge to humanity, which is one of the primary causes of patient mortality. Rapid and effective hemostasis is crucial for saving lives, however, traditional hemostatic methods exhibiting numerous limitations, such as unstable hemostatic effects, complex operations, and potential complications. In recent years, with the rapid development of nanotechnology, significant progress has been made in the nanotechnological optimization of synthetic polymer hemostats, providing new avenues for navigating precision hemostasis. This paper reviews the advancements in nanotechnology for synthetic polymer hemostats, including the development and application of novel hemostatic materials such as nanoparticles, nanofibers, and self-assembling nanopeptides, as well as the potential applications of these materials in precision hemostasis. Additionally, the challenges faced by nanotechnology in the field of hemostasis and future directions for development are discussed, in order to provide guidance for clinicians and scientist.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"328-334"},"PeriodicalIF":1.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High agreement between one-stage clot-based and chromogenic factor VIII activity assays.","authors":"Radhiya Al Buraidi, Muntadhar Al Moosawi, Karima Al Falahi, Bader Al Rawahi, Johnny Mahlangu, Murtadha Al-Khabori","doi":"10.1097/MBC.0000000000001384","DOIUrl":"10.1097/MBC.0000000000001384","url":null,"abstract":"<p><strong>Introduction: </strong>A number of gene therapy studies have shown discrepancies between the one-stage and chromogenic factor VIII (FVIII) assays. Studies comparing the two assays are of small sample size. We aimed to compare the one-stage clot-based assay with the chromogenic assay in measuring FVIII activity in blood sample in a single tertiary academic centre.</p><p><strong>Methods: </strong>This is a single-centre retrospective study conducted at Sultan Qaboos University Hospital. Both assays performed FVIII measurements at the SQUH from March 2009 to March 2018. A total of 3623 samples from a range of haematologic conditions had both assays performed.</p><p><strong>Results: </strong>The median age of all patients was 26 years (IQR: 17-37). The mean FVIII activity by one-stage clot-based and chromogenic assays were 1.2 IU/ml (SD: 0.6) and 1.2 IU/ml (SD: 0.5), respectively. Bland-Altman analysis showed excellent agreement with a very minimal bias of -0.0034. High baseline FVIII activity and the diagnosis predicted disagreement between the two assays ( P values < 0.001). Positive ANA and FVIII inhibitor had no impact on the disagreement ( P value = 0.2 and 0.7, respectively). A subgroup analysis of samples with FVIII activity of <0.4 IU/ml showed 21.1% discrepancy with the majority (75.8%) of samples showing overestimated results by the OSA.</p><p><strong>Conclusion: </strong>One-stage clot-based and chromogenic FVIII assays showed excellent agreement for measuring FVIII activity.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"318-322"},"PeriodicalIF":1.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and efficacy of thrombolytic interventions in the treatment of intermediate and high-risk pulmonary embolism.","authors":"Logan D Johnson, J Chase Cole, Michael J Erdman, Leela Krishna Teja Boppana, Nimeh Najjar, Elizabeth A Shald, Kirsten V Busey, Kelsey L Stilley, Jason A Ferreira","doi":"10.1097/MBC.0000000000001375","DOIUrl":"10.1097/MBC.0000000000001375","url":null,"abstract":"<p><strong>Background: </strong>Intermediate to high-risk pulmonary embolism management is controversial in the absence of hemodynamic instability. Anticoagulation with systemic thrombolysis is commonly employed in these patients, and alternative interventional therapies when contraindications to thrombolysis are present. No comparative evidence exists between systemic alteplase, tenecteplase and catheter directed thrombolysis (CDT) and practice continues to be clouded by this lack of literature.</p><p><strong>Research question: </strong>Does systemic alteplase, tenecteplase or CDT have better safety or efficacy outcomes in the treatment of intermediate to high-risk pulmonary embolism?</p><p><strong>Study design and methods: </strong>This was a retrospective, multicenter study including patients 18-90 years old with an acute presentation of intermediate-high risk PE receiving systemic or directed thrombolysis with therapeutic anticoagulation. The primary outcome was major bleeding complications within 72 h of treatment. Secondary outcomes included minor bleeding, hemodynamic decompensation, 28-day ventilator-free days, mortality and length of stay.</p><p><strong>Results: </strong>The primary outcome was significantly higher with tenecteplase and US-CDT when compared to alteplase (alteplase 10.9% vs. tenecteplase 31.1%, P  = 0.004; US-CDT 21.4%, P  = 0.03). After propensity matching, tenecteplase was associated with a higher rate of major bleeding ( P  = 0.13) while US-CDT showed a significantly higher risk of complications ( P  = 0.04). This was supported by multivariate logistic regression with alteplase vs. US-CDT (odds ratio 0.07; 95% confidence interval 0.01, 0.3). Tenecteplase receipt was not associated with different rates of hemodynamic decompensation or mortality compared to alteplase while US-CDT had significantly lower rates, likely secondary to acuity of illness.</p><p><strong>Interpretation: </strong>Alteplase was associated with the lowest risk of major bleeding, but with variable disease severities. Selection of agent for the treatment of PE continues to require analysis of patient-specific hemodynamics and disease severity.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"253-260"},"PeriodicalIF":1.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rosa Centifolia L. effect on hemostasis: a multifaceted study combining in-vitro, in-vivo, and in-silico investigations of molecular mechanisms.","authors":"Omayma El Meziouy, Moulay Hfid Youssoufi, Ali Berraaouan, Fatima Zahra Lafdil, Sergey Shityakov, Abdelkhaleq Legssyer, Abderrahim Ziyyat, Khalil Azzaoui, Hassane Mekhfi","doi":"10.1097/MBC.0000000000001379","DOIUrl":"10.1097/MBC.0000000000001379","url":null,"abstract":"<p><p>Thrombus formation is a major cause of cardiovascular disease-related death. Traditional medicine has long utilized plants for therapeutic purposes. The aqueous extract of Rosa centifolia L., commonly used in Moroccan folk medicine, was investigated for its potential anticoagulant and antioxidant properties. The study assessed platelet aggregation inhibition, bleeding time, antioxidant activity, and coagulation parameters, including activated partial thromboplastin time (aPTT), prothrombin time (PT), and fibrinogen concentration. Platelet aggregation was induced using thrombin, ADP, arachidonic acid, and collagen. Antioxidant activity was evaluated using the FRAP and β-carotene assays. Phytochemical analysis identified the presence of phenols, flavonoids, and tannins. Additionally, computational molecular docking was performed to analyze the interaction between prostaglandin G/H synthase 1 (COX-1) and kaempferol. The aqueous extract significantly inhibited platelet aggregation and prolonged bleeding time, particularly at 1 mg/ml, where it also extended aPTT. Antioxidant activity was confirmed through FRAP and β-carotene assays. Computational docking of kaempferol with COX-1 generated 10 binding modes, demonstrating favorable binding affinities and validating the docking protocol using the co-crystallized diclofenac structure. The findings suggest that Rosa centifolia L. exhibits anticoagulant and antioxidant properties, supporting its potential therapeutic application in preventing oxidative stress and thrombosis-related disorders.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"268-278"},"PeriodicalIF":1.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144629297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}