Blood Coagulation & Fibrinolysis最新文献

{"title":"Generation and characterization of zebrafish f9l mutant confirmed that f9l is f10 like gene.","authors":"Sanchi Dhinoja, Jabila Mary, Ayah Al Qaryoute, Anthony De Maria, Pudur Jagadeeswaran","doi":"10.1097/MBC.0000000000001337","DOIUrl":"https://doi.org/10.1097/MBC.0000000000001337","url":null,"abstract":"<p><strong>Aim: </strong>This study aimed to create an f9l mutant zebrafish using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) and characterize its coagulation properties to investigate its functional similarity to human FX and explore the potential synergy between f9l and f10.</p><p><strong>Methods: </strong>Three gRNAs targeting exon 8 encoded by the catalytic domain of the f9l gene were injected into 300 single-cell zebrafish embryos using CRISPR/Cas9 technology. DNA from the resulting adults was extracted from tail tips, and PCR was used to detect indels. The identified founder mutant was bred to homozygosity, and functional assays, kinetic Russel viper venom time, bleeding assay in adults, and venous laser injury on larvae were conducted to assess its hemostatic function. Additionally, f10 was knocked down in f9l homozygous embryos using f10 antisense morpholinos to study their interaction by monitoring its survival.</p><p><strong>Results: </strong>DNA from 60 adults was screened for indels, resulting in a fish with a heritable complex mutation involving one insertion and two deletions in exon 8. The f9l homozygous mutants exhibited impaired F10 activity, mild bleeding after mechanical injury, and developmental deformities in early larval stages. The caudal vein thrombosis assay showed variable occlusion times, indicating a bleeding phenotype with incomplete penetrance. Knocking down f10 in f9l homozygous embryos resulted in 50% mortality within five dpf, compared to f9l homozygous embryos injected with control morpholinos.</p><p><strong>Conclusion: </strong>In summary, we generated f9l knockout and showed it is a paralog to f10. We also found a synergy between f9l and f10 genes, highlighting its importance in hemostasis.</p>","PeriodicalId":8992,"journal":{"name":"Blood Coagulation & Fibrinolysis","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is the combination of two automated rapid assays for diagnosis of heparin-induced thrombocytopenia necessary?","authors":"Erika Jani, Margherita Bozzola, Elmar Marco Zagler, Massimo Daves","doi":"10.1097/MBC.0000000000001327","DOIUrl":"10.1097/MBC.0000000000001327","url":null,"abstract":"<p><p>Heparin-induced thrombocytopenia (HIT) is an immune-mediated condition characterized by a decrease in platelet count and an increased thrombotic risk. HIT event is caused by antiplatelet factor/heparin (PF4/H) antibodies that can activate the platelets. The diagnosis of HIT is based on a clinical evaluation and laboratory results. Aim of our study was to evaluate whether the combined use of two rapid assays for diagnosis of HIT provides a diagnostic advantage over the use of a single automate assay. We extracted from the laboratory informatic system all the determinations requested for the detection of antibodies against heparin/PF4 complexes from July 2020 to June 2024 (n. 229). In our laboratory, total antibodies against heparin/PF4 complex [HemosIL HIT-Ab-(PF4-H), Instrumentation Laboratory] and IgG Ab (HemosIL AcuStar HIT-IgG, Instrumentation Laboratory) are measured simultaneously with two different instruments. Two hundred six samples tested negative for both methods, 23 samples tested positive for at least one method and nine samples tested positive for both methods. The grade of concordance between the two assays shows a weighted Kappa of 0.536 (moderate agreement). No sample tested positive only for IgG-Ab. The sensitivity of HIT-Ab-(PF4-H) was 1, whereas the specificity was 0.95. For the HIT-IgG (PF4-H) method, sensibility and specificity were 0.77 and 1, respectively. Our results suggest that performing these two tests simultaneously does not provide additional useful information in patients with suspicion of HIT. The total Ab assay seems to be sufficient, as it shows higher sensitivity although at the expense of lower specificity.</p>","PeriodicalId":8992,"journal":{"name":"Blood Coagulation & Fibrinolysis","volume":" ","pages":"362-364"},"PeriodicalIF":1.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanism analysis of a family with hereditary coagulation FXI deficiency caused by compound heterozygous mutations.","authors":"Yuan Chen, Manlin Zeng, Ke Zhang, Longying Ye, Shuting Jiang, Kaiqi Jia, Lihong Yang, MingShan Wang","doi":"10.1097/MBC.0000000000001330","DOIUrl":"https://doi.org/10.1097/MBC.0000000000001330","url":null,"abstract":"<p><strong>Objective: </strong>The purpose of this study was to determine the molecular basis of a Chinese family with factor XI (FXI) deficiency.</p><p><strong>Methods: </strong>The qRT-PCR was used to detect the transcription of F11 mRNA in transfected cells. ELISAs and western blot were used to detect the expression of FXI protein in culture media and lysates.</p><p><strong>Results: </strong>Genetic analysis revealed that the proband carried a heterozygous nonsense mutation c.1107C>A (p.Tyr351stop) in exon 10 and a heterozygous missense mutation c.1562A>G (p.Tyr503Cys) in exon 13. The expression study revealed that p.Tyr351stop mutation resulted in the degradation of F11 mRNA. The p.Tyr503Cys mutation, however, had no effects on biosynthesis and secretion of FXI protein, but it had affected the catalytic activity of FXI.</p><p><strong>Conclusion: </strong>The inherited FXI deficiency of this family is related to nonsense mutation p.Tyr351stop and missense mutation p.Tyr503Cys.</p>","PeriodicalId":8992,"journal":{"name":"Blood Coagulation & Fibrinolysis","volume":"35 8","pages":"372-378"},"PeriodicalIF":1.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Variation among venous thromboembolism risk assessment tools for postcesarean patients: a retrospective cohort study.","authors":"Alshaima Fraoug Eltayeb Ahmed, Seeba Zachariah, Amal Hassan Ismail, Caitlin M Gibson","doi":"10.1097/MBC.0000000000001325","DOIUrl":"10.1097/MBC.0000000000001325","url":null,"abstract":"<p><p>Venous thromboembolism (VTE) risk in pregnant women is four to five-fold higher than in nonpregnant women, and the risk of VTE is an additional four-fold higher after Cesarean section compared to normal vaginal delivery. Recommendations regarding anticoagulant prophylaxis are inconsistent across international guidelines, and VTE remains one of the leading causes of maternal morbidity and mortality. This study aimed to compare the need for postcesarean anticoagulation for VTE prophylaxis based on three major guidelines and our own institutional protocol. It was a retrospective cohort study that reviewed the medical records of patients who underwent a cesarean section at a tertiary-level care hospital in the United Arab Emirates (UAE). The need for anticoagulation was assessed using clinical tools from the American College of Obstetricians and Gynecologists (ACOG), Royal College Obstetricians and Gynecologists (RCOG), American College of Chest Physicians (ACCP), and the study site hospital protocol. A total of 1134 postcesarean women, aged 18-55 years, were included in the study. Most patients (87%) were at moderate risk for VTE. According to the study site hospital tool, 90.7% qualified for anticoagulant prophylaxis, while the ACOG, RCOG, and ACCP tools indicated that 0.5, 90.9, and 36.7% qualified, respectively. Enoxaparin was the primary anticoagulant used in 95% of cases. Only one patient developed VTE during the follow-up period. Anticoagulation needs assessment tools vary extensively in their estimations, highlighting the need for a uniform tool across multiple societies to establish a consistent standard of care and guide the development of evidence-based, site-specific protocols.</p>","PeriodicalId":8992,"journal":{"name":"Blood Coagulation & Fibrinolysis","volume":" ","pages":"357-361"},"PeriodicalIF":1.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel γ-chain mutation p.Asp318His in a Chinese family with dysfibrinogenemia.","authors":"Haiyue Zhang, Weifeng Shen","doi":"10.1097/MBC.0000000000001329","DOIUrl":"10.1097/MBC.0000000000001329","url":null,"abstract":"<p><strong>Background: </strong>Congenital dysfibrinogenemia is characterized by reduced fibrinogen activity, but normal immunoreactive fibrinogen levels. Here, we present a novel case with an elevated risk of thrombosis.</p><p><strong>Methods: </strong>Coagulation assays, gene analysis, in silico tools, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), fibrin polymerization, thrombin generation assay, and electron microscopy scanning were utilized to elucidate the pathogenic mechanism.</p><p><strong>Results: </strong>The proband manifested with a normal immunologic fibrinogen (2.13 g/l) but reduced functional fibrinogen (0.39 g/l). Subsequent genetic analysis unveiled a novel heterozygous mutation, c.1030G>C (p.Asp318His), in the γ-chain D domain of fibrinogen, which was highly conserved in homologous species and led to enhanced thrombin generation capability. The ability of the proband's fibrinogen to polymerize was significantly impaired, with decreased final turbidity. Scanning electron microscopy indicated that the fibers of the proband were thinner than normal, with smaller pores. Thromboelastography (TEG) results demonstrated prolonged K time, decreased angle value, and a normal confidence interval value in the proband.</p><p><strong>Conclusion: </strong>We present a novel case displaying the γAsp318His mutation, which resulted in dysfibrinogenemia.</p>","PeriodicalId":8992,"journal":{"name":"Blood Coagulation & Fibrinolysis","volume":"35 8","pages":"365-371"},"PeriodicalIF":1.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel SERPINC1 c.119G>A (p.Cys40Tyr) mutation with variable clinical expression in an Indian family.","authors":"Kranti Patil, Asha Shah, Gurpreet Saini, Shreyas Tawde, Shruti Kharat, Fiza Jivani, Aniket Kamble, Shrimati Shetty","doi":"10.1097/MBC.0000000000001333","DOIUrl":"10.1097/MBC.0000000000001333","url":null,"abstract":"<p><p>Hereditary antithrombin (AT) deficiency due to mutations in SERPINC1 is known to be the most severe form of thrombophilia. We report three members in a family with hereditary AT deficiency with a novel mutation in exon 2 of SERPINC1, that is c.119 G>A (p.Cys40Tyr). Two brothers presented with acute pulmonary thromboembolism (PTE) at 18 and 21 years of age, whereas their 58-year-old father did not have any thrombotic episode till date. The in-silico prediction of the variant was found to be highly damaging by PolyPhen-2, SIFT and MutationTaster. Clinical exome sequencing did not show any strong coinherited thrombophilia genes, except SERPINE1 -844 G>A variant in homozygous state in the two affected brothers as compared to the father who was heterozygous for this variant. The additive effect of SERPINE1 variant in the clinical expression in two siblings cannot be ruled out, in the absence of any other known environmental triggering factors.</p>","PeriodicalId":8992,"journal":{"name":"Blood Coagulation & Fibrinolysis","volume":"35 8","pages":"379-381"},"PeriodicalIF":1.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"4-Factor prothrombin complex concentrates and factor VIII inhibitor bypass activity use in cardiac surgery.","authors":"Ashley N Budd, Suraj D Parulkar, Louanne M Carabini, Robert J McCarthy","doi":"10.1097/MBC.0000000000001335","DOIUrl":"https://doi.org/10.1097/MBC.0000000000001335","url":null,"abstract":"<p><strong>Objectives: </strong>The objective of this study was to compare total thromboembolic complications between 4-factor prothrombin complex concentrate (4F-PCC) with factor VIII inhibitor bypassing activity (FEIBA) when utilized during cardiac surgery.</p><p><strong>Design: </strong>A quasi-experimental analysis of retrospective data from consecutive patients.</p><p><strong>Setting: </strong>A tertiary care university hospital.</p><p><strong>Participants: </strong>Patients undergoing cardiac surgery with cardiopulmonary bypass.</p><p><strong>Interventions: </strong>Patients received either 4F-PCC or FEIBA after discontinuation of cardiopulmonary bypass and reversal of heparin with protamine.</p><p><strong>Measurements and main results: </strong>Medical records were reviewed for thromboembolic events (stroke, arterial or venous thrombosis, pulmonary embolism, myocardial infarction), acute kidney injury, ischemic bowel, death, duration of intensive care unit and hospital stay, clinical and surgical characteristics and blood product utilization. A comparison of the clinical and surgical variables demonstrated a mean effect size of 0.33 imbalance between groups that was reduced to 0.18 after propensity score weighting. The propensity scores weighted analysis found an incidence of composite thromboembolic events of 39% in the 4F-PCC (n = 90) and 47% in the FEIBA (n = 50) group, difference -8 (-24% to 12%), P = 0.13. Individual thromboembolic events, acute kidney injury, ischemic bowel, mortality, and length of intensive care unit or hospital stay was not different among groups. Patients who received FEIBA had greater chest tube drainage and received more cryoprecipitate intraoperatively. Patients who received 4F-PCC received more fresh frozen plasma transfusions postoperatively.</p><p><strong>Conclusions: </strong>Among cardiac surgery patients, there was no difference in thromboembolic events between patients who received 4F-PCC or FEIBA when used as an adjunct to blood product administration.</p>","PeriodicalId":8992,"journal":{"name":"Blood Coagulation & Fibrinolysis","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of eosinophil counts and megakaryocyte nuclei for distinction of acute and chronic immune thrombocytopenic purpura.","authors":"Kubra Cilesiz, Ulker Kocak, Zuhre Kaya, Idil Yenicesu","doi":"10.1097/MBC.0000000000001328","DOIUrl":"https://doi.org/10.1097/MBC.0000000000001328","url":null,"abstract":"<p><strong>Objective: </strong>Immune thrombocytopenic purpura (ITP), the most common cause of thrombocytopenia, is clinically classified as acute and chronic. This study aimed to distinguish between acute/chronic ITP parameters examined at diagnosis via complete blood count (CBC), peripheral blood (PB) and bone marrow aspirate (BMA) smears. It would also contribute to early treatment options, cost-effective policies, and the life quality of patients.</p><p><strong>Methods: </strong>This study consisted of 304 ITP patients aged under 18 years diagnosed and followed up between 1982-2018. Differences between acute and chronic groups were compared by eosinophilia, megakaryocytes (MKs), and megakaryocyte nuclei. Diagnostic scales were created using simple parameters both to guide the distinction between acute and chronic ITP as well as for the prediction of the chronic progression of the patients at diagnosis.</p><p><strong>Results: </strong>Of the patients in this study, 71% had acute and 29% had chronic ITP. In CBC and PB smears, eosinophil and lymphocyte counts were higher in acute whereas neutrophil counts were higher in chronic ITP patients. Eosinophil counts in the BMA were also significantly higher in acute ITP patients. There was no significant difference in MK counts. However, the mean number of MK nuclei was higher in acute ITP patients.</p><p><strong>Conclusion: </strong>Comparison analyses between acute/chronic ITP with the methods developed for the first time are low-cost and promising. Using only eosinophil percentages in the CBC and PB smear, we could identify acute cases by 100%. Further studies including the integration of our study and clinical risk scoring models would contribute to the diagnosis and treatment process of ITP.</p>","PeriodicalId":8992,"journal":{"name":"Blood Coagulation & Fibrinolysis","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clot waveform analysis in hemophilia carriers.","authors":"Eya Drissi, Fatma Ben Lakhal, Ons Ghali, Sarra Fekih Salem, Wijden El Borgi, Lina Thabet, Kaouther Zahra, Emna Gouider","doi":"10.1097/MBC.0000000000001331","DOIUrl":"https://doi.org/10.1097/MBC.0000000000001331","url":null,"abstract":"<p><p>In recent years, there has been a growing interest in the activated partial thromboplastin time clot waveform analysis (APTT-CWA), which reflects clot formation. It was mainly studied in hemophilia and disseminated intravascular coagulation. The aim of this study was to evaluate the usefulness of APTT-CWA in hemophilia carriers. This was a cross-sectional study including hemophilia carriers and healthy women volunteers. Bleeding assessment was performed using the ISTH-BAT. Laboratory assessment included APTT, APTT-CWA and FVIII:C or FIX:C. Thirty-two hemophilia carriers and 30 women as a control group were recruited. APTT was prolonged in 14 carriers and none of controls. Tmax 1 and Tmax 2 were significantly prolonged in hemophilia carriers compared to controls. Max 1 and Max 2 were significantly lower in carriers. Using ROC analysis, APTT-CWA parametrs cut-offs showed good sensitivity and specificity in discriminating between carriers and controls. When comparing bleeders and nonbleeders carriers, a significant difference was noted in Max 2, Min 2, Tmax 1 and Tmax 2. No correlation was found between APTT and bleeding score, nor between FVIII:C and Max 1. A positive significant correlation of FVIII:C with Max 2 was found. A negative and significant correlation of FVIII:C with Tmax 1, Tmax 2 and Min 2 was noticed. The APTT-CWA seems to be a good tool to evaluate bleeding tendency or detecting coagulation factor deficiency. Additional research efforts are warranted to explore the potential of APTT-CWA for identifying hemophilia carriers.</p>","PeriodicalId":8992,"journal":{"name":"Blood Coagulation & Fibrinolysis","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The determination of euglobulin clot lysis time reference intervals in Beckton Dickinson and Kima 3.2% sodium citrate coagulation tubes.","authors":"Ivona Kuktić, Ante Pašalić, Ognjen Čančarević, Edvard Galić, Andrea Saračević, Vanja Radišić Biljak","doi":"10.1097/MBC.0000000000001334","DOIUrl":"https://doi.org/10.1097/MBC.0000000000001334","url":null,"abstract":"<p><p>Enhanced fibrinolysis or hyperfibrinolysis may lead to life-threatening blood loss, while reduced activity may contribute to thrombosis. Euglobulin clot lysis time (ECLT) is a manual method that measures plasma fibrinolytic activity and is considered the gold standard. However, the data on reference interval is scarce and outdated. We have employed one-sided reference interval (>3 h) since the implementation of ECLT in our laboratory; therefore, we aimed to establish reliable ECLT reference interval and to explore the possible preanalytical influence of different blood collection tubes on the established ECLT reference interval. Establishing a reference interval for fibrinolysis was performed according to CLSI EP28-A3c guidelines by employing a posteriori direct sampling technique. The predefined exclusion criteria included a history of malignant or hepatobiliary disease, a history of deep vein thrombosis/pulmonary embolism (DVT/PE), an acute inflammatory state at the time of the venipuncture. We collected vein blood samples in Vacutest plastic coagulation tubes (Kima, Italy) and Vacutainer glass coagulation tubes (Beckton Dickinson, USA) containing 0.109 mol/l buffered trisodium citrate as an anticoagulant at a blood-to-anticoagulant ratio 9 : 1. We calculated two-sided reference interval and presented as 2.5th and 97.5th percentiles. ECLT values did not differ between sexes or the types of tubes enrolled in the study (P = 0.8979). The established reference interval ranged from 130 to 297 min for the KIMA Vacutest tube and from 120 to 292 min for the BD Vacutainer tube. The established ECLT reference interval differed significantly from the currently used cut-off value in our laboratory, thus enabling the assessment of hyperfibrinolysis by employing double-sided reference interval.</p>","PeriodicalId":8992,"journal":{"name":"Blood Coagulation & Fibrinolysis","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}