HaemostasisPub Date : 1999-01-01DOI: 10.1159/000022494
J Amiral
{"title":"Diagnostic approach of phospholipid-dependent antibodies. State-of-the art lecture.","authors":"J Amiral","doi":"10.1159/000022494","DOIUrl":"https://doi.org/10.1159/000022494","url":null,"abstract":"<p><p>Recent scientific developments enable to better understand the strong heterogeneity of assay methods for phospholipid (PLP)-dependent antibodies, measured as lupus anticoagulant (LA) or as anti-PLP antibodies (APA). These latter are actually targeted at complexes of beta(2)-glycoprotein I (beta2GPI) and anionic PLP and also react with insolubilized beta2GPI alone in some patients. Although APA present little species specificity for beta2GPI, some of them bind preferentially to complexes of human beta2GPI and PLP. LAs are diagnosed with screening assays (dPT, dRVVT, KCT, APTT); their sensitivity is dependent on the concentration and type of PLPs used. They are either beta2GPI or prothrombin dependent. Based on the antibody-neutralizing capacity of PLP preparations (such as hexagonal phase phosphatidylethanolamine) or their bypassing activity, confirmatory assays enable to confirm LA. LAs and APAs bind to different epitopes on beta2GPI or its complexes with PLP. Major characteristics of APA assays are: the capture antigen (PLPs, beta2GPI source); its optimization and density on micro-ELISA plates; the efficacy of postcoating saturation; the animal serum used for saturation and diluent; the second antibody which must avoid nonspecific interactions; the calibrators proposed and their reference to international standards; the cutoff between the normal and the pathological ranges; the assay sensitivity and overall specificity for APAs. New optimized assays have been developed to meet these criteria. They are designed with PLP-coated plates, saturated first with immunoglobulin-free human serum as a source of beta2GPI, then with goat serum also used in diluent. The cutoff value is determined with at least 200 normal plasma samples (mean + 3 standard deviations or 99th percentiles) and plasma samples from patients without APAs. This approach offers both optimized specificity and sensitivity for testing APAs, along with a good standardization and it helps to measure the true APAs associated with pathology.</p>","PeriodicalId":12910,"journal":{"name":"Haemostasis","volume":"29 2-3","pages":"135-49"},"PeriodicalIF":0.0,"publicationDate":"1999-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000022494","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21485696","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}
HaemostasisPub Date : 1999-01-01DOI: 10.1159/000022507
I Tornai, Z Boda, A Schlammadinger, A Juhasz, N Cauwenberghs, H Deckmyn, J Harsfalvi
{"title":"Acquired Bernard-Soulier syndrome: a case with necrotizing vasculitis and thrombosis.","authors":"I Tornai, Z Boda, A Schlammadinger, A Juhasz, N Cauwenberghs, H Deckmyn, J Harsfalvi","doi":"10.1159/000022507","DOIUrl":"https://doi.org/10.1159/000022507","url":null,"abstract":"<p><p>We describe a patient with positive antinuclear antibodies, polyclonal gammopathy and high level of circulating immunocomplexes, resulting in vascular purpura. In addition, the patient had a slightly prolonged bleeding time and an isolated defect of ristocetin-induced platelet aggregation (RIPA) in platelet-rich plasma (PRP). The patient's plasma also inhibited RIPA in normal PRP and in normal platelet suspension. The activity and multimeric structure of plasmatic von Willebrand factor showed no alteration. We could demonstrate an autoantibody against platelet membrane glycoprotein (GP) Ib, using an ELISA-type assay. These data suggest an acquired Bernard-Soulier syndrome. We suggest that the patient had an immunocomplex-mediated leukocytoclastic vasculitis accompanied by production of antinuclear autoantibodies as well as the presence of an autoantibody against GPIb. The titer of the anti-GPIb antibody, however, was too low to induce significant platelet-type bleeding tendency, only laboratory alterations were found. Moreover, in a later stage of her disease, she developed a severe necrotizing vasculitis which was followed by a deep venous thrombosis.</p>","PeriodicalId":12910,"journal":{"name":"Haemostasis","volume":"29 4","pages":"229-36"},"PeriodicalIF":0.0,"publicationDate":"1999-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000022507","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21555069","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}
HaemostasisPub Date : 1999-01-01DOI: 10.1159/000022491
M Samama, G Gerotziafas, J Conard, M Horellou, I Elalamy
{"title":"Clinical aspects and laboratory problems in hereditary thrombophilia.","authors":"M Samama, G Gerotziafas, J Conard, M Horellou, I Elalamy","doi":"10.1159/000022491","DOIUrl":"https://doi.org/10.1159/000022491","url":null,"abstract":"<p><p>Hereditary thrombophilia is a multifactorial disease which is mono- or plurigenic and its clinical expression is associated with a heterogeneous expression. Factor V (FV) Leiden and FII gene mutations are more frequent than antithrombin, and protein C and S deficiencies. All thrombophilias are not the same. Heterozygous carriers of FV Leiden or FII gene mutation have a weaker risk of venous thrombosis. The mean age at the first episode is older in the former and higher rate of recurrences is observed in the latter. The cosegregation of mutations significantly increases the risk of thrombosis. Both mutations have a geographic and ethnic distribution in relation with a gene founder effect. Clinical expression consists of deep or superficial venous thrombosis with or without pulmonary embolism, thromboses at unusual sites (e.g. cerebral, portal, mesenteric) or with an increased incidence of fetal loss and abortion. A precipitating cause is present in more than 50% of patients. The risk pf arterial thromboses seems to be restricted to some protein S and FII gene mutations. Laboratory diagnosis strategy should be oriented by careful selection of patients and preanalytical variables should be considered. It is highly probable that other unindentified gene mutations are, at least partly, other causes of the heterogeneous expression of hereditary thrombophilia.</p>","PeriodicalId":12910,"journal":{"name":"Haemostasis","volume":"29 2-3","pages":"76-99"},"PeriodicalIF":0.0,"publicationDate":"1999-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000022491","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21485767","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}
HaemostasisPub Date : 1999-01-01DOI: 10.1159/000022504
F Araújo, A Santos, V Araújo, I Henriques, F Monteiro, E Meireles, I Moreira, D David, M J Maciel, L M Cunha-Ribeiro
{"title":"Genetic risk factors in acute coronary disease.","authors":"F Araújo, A Santos, V Araújo, I Henriques, F Monteiro, E Meireles, I Moreira, D David, M J Maciel, L M Cunha-Ribeiro","doi":"10.1159/000022504","DOIUrl":"https://doi.org/10.1159/000022504","url":null,"abstract":"<p><strong>Objective: </strong>We investigate whether each of the following: HPA-1, Factor V Leiden, prothrombin gene variant and the methylene tetrahydrofolate reductase gene (MTHFR) mutation, are risk factors for acute coronary disease in Portuguese patients.</p><p><strong>Material and methods: </strong>100 blood donors and 52 patients with an established diagnosis of myocardial infarction or unstable angina were evaluated for genetic risk factors, by determining HPA-1 genotype, Factor V Leiden, Prothrombin 20210 variant and MTHFR mutation.</p><p><strong>Results: </strong>We found a prevalence of 2.0% for Factor V Leiden, 5.0% for the Prothrombin 20210 variant and 66% for the MTHFR mutation in blood donors. These values are similar to those found in the patients (1.9, 3.8 and 58%, respectively). We found that 28/100 controls had the PI(A2) polymorphism, a frequency statistically different from that in the patients (23/52). This difference was even more pronounced in patients less than 60 years old (27/96 vs. 13/24).</p><p><strong>Conclusion: </strong>Factor V Leiden, Prothrombin 20210 variant and MTHFR mutation do not seem to represent risk factors for acute coronary disease. However, the PI(A2) polymorphism could have a role in the pathogenesis of this disease. The presence of multiple genetic factors, more than single ones, could influence the development and outcome of myocardial infarction and unstable angina. Larger studies are needed in order to have a better insight into the pathophysiological mechanisms of this disease, along with its prevention and the development of new treatments.</p>","PeriodicalId":12910,"journal":{"name":"Haemostasis","volume":"29 4","pages":"212-8"},"PeriodicalIF":0.0,"publicationDate":"1999-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000022504","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21555066","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}
HaemostasisPub Date : 1999-01-01DOI: 10.1159/000022514
H Minowa, Y Takahashi, T Tanaka, K Naganuma, S Ida, I Maki, A Yoshioka
{"title":"Four cases of bleeding diathesis in children due to congenital plasminogen activator inhibitor-1 deficiency.","authors":"H Minowa, Y Takahashi, T Tanaka, K Naganuma, S Ida, I Maki, A Yoshioka","doi":"10.1159/000022514","DOIUrl":"https://doi.org/10.1159/000022514","url":null,"abstract":"<p><p>Congenital plasminogen activator inhibitor-1 (PAI-1) deficiency is an extremely rare disorder characterized by a bleeding diathesis that begins in childhood due to hyperfibrinolysis as a result of decreased PAI-1 activity. We now present 4 unrelated pediatric cases of congenital PAI-1 deficiency. All 4 patients had a history of recurrent episodes of subcutaneous bleeding beginning in early childhood. These episodes were characterized by abnormal prolonged bleeding after trauma, tooth extraction, and surgical procedures, as well as by rebleeding following initial hemostasis. The 2 female patients both had symptoms compatible with hypermenorrhea. The family history was positive in 2 of the 4 patients. Hemostatic screening studies in all 4 patients revealed no abnormalities. Testing for factor XIII antigen, von Willebrand factor antigen, ristocetin cofactor activity, alpha(2)-plasmin inhibitor (alpha2PI) activity, and plasminogen activity was normal. The euglobulin lysis times were shortened in all cases as compared with those in normal control subjects. None of the patients had elevated tissue plasminogen activator (tPA) antigen levels, but PAI activity was markedly decreased in all cases. Three of the patients also had reduced levels of PAI-1 antigen. There tended to be a reduction in tPA-PAI-1 complex in all cases. In addition, 2 patients had elevated PIC (plasmin-alpha2PI complex). Tourniquet tests were performed in 2 patients, with no appreciable rise in PAI-1 activity or PAI-1 antigen levels. The administration of tranexamic acid clearly improved hemorrhagic symptoms in these patients. We considered PAI-1 deficiency to be the likely etiology of the congenital bleeding diatheses in these 4 cases.</p>","PeriodicalId":12910,"journal":{"name":"Haemostasis","volume":"29 5","pages":"286-91"},"PeriodicalIF":0.0,"publicationDate":"1999-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000022514","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21604573","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}
HaemostasisPub Date : 1999-01-01DOI: 10.1159/000022509
M Monreal, B Oller, N Rodriguez, J Vega, T Torres, P Valero, G Mach, A E Ruiz, J Roca
{"title":"Infusion phlebitis in post-operative patients: when and why.","authors":"M Monreal, B Oller, N Rodriguez, J Vega, T Torres, P Valero, G Mach, A E Ruiz, J Roca","doi":"10.1159/000022509","DOIUrl":"https://doi.org/10.1159/000022509","url":null,"abstract":"<p><strong>Background: </strong>The most common complication of intravenous therapy is infusion phlebitis. This study was done to prospectively assess its frequency in a series of consecutive patients who will undergo surgery, and to identify which variables may predict an increased risk for phlebitis.</p><p><strong>Patients and methods: </strong>400 consecutive patients who will undergo surgery in a general surgery department were included. Only the first catheter, inserted the day before surgery, was taken into account. Eighteen variables (from the infusion, the catheter and from the patient) were prospectively evaluated for their contribution to the occurrence of phlebitis.</p><p><strong>Results: </strong>60/400 patients (15%) developed phlebitis, and most of them needed insertion of a further catheter. The univariate analysis showed that patients who developed phlebitis were older, and their pre-operative levels of both blood haemoglobin and neutrophil cound were significantly higher than those in patients who did not develop phlebitis. However, the multivariate analysis only confirmed the association with blood haemoglobin levels: the risk of phlebitis sharply increased in the patients with the highest haemoglobin levels. As to the influence of time on phlebitis development, there was a significant decrease in the day-specific risk, from the 5th day on.</p><p><strong>Comments: </strong>In our series, blood haemoglobin levels were found to be the only variable associated to a higher risk of phlebitis. Besides, in contrast with the recommendations by the Centers for Disease Control, no significant increase in the day-specific risk of phlebitis was found. Thus, a guideline to select the type of catheter to be inserted in an individual patient is suggested.</p>","PeriodicalId":12910,"journal":{"name":"Haemostasis","volume":"29 5","pages":"247-54"},"PeriodicalIF":0.0,"publicationDate":"1999-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000022509","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21604588","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}
HaemostasisPub Date : 1999-01-01DOI: 10.1159/000022495
S Coccheri, G Palareti, B Cosmi
{"title":"Oral anticoagulant therapy: efficacy, safety and the low-dose controversy.","authors":"S Coccheri, G Palareti, B Cosmi","doi":"10.1159/000022495","DOIUrl":"https://doi.org/10.1159/000022495","url":null,"abstract":"<p><p>The issue of optimal duration of oral anticoagulant therapy after a first episode of venous thromboembolism is still unresolved. However, recent data suggest that short (6 weeks to 3 months), intermediate (3- 6 months) or indefinite-term anticoagulant therapy should be adopted on the basis of the classification of patients into low-, intermediate- and high-recurrence-risk groups, respectively. Oral anticoagulants have been shown to effectively prevent cardioembolic stroke in nonvalvular atrial fibrillation. Recent data seem to suggest that their safety can be ameliorated with adequate risk stratification on the basis of clinical and echocardiographic features. After unstable angina and non-Q-wave myocardial infarction, oral anticoagulant therapy (INR range 2-3) combined with aspirin has been shown to be advantageous over aspirin alone, although at the cost of a slight increase in bleeding. Bleeding complications are major drawbacks of oral anticoagulant therapy thus limiting their generalized adoption in recognized indications. To sharply reduce the bleeding risk and need of laboratory control, the low- or fixed-dose oral anticoagulant approach has been evaluated. In primary prevention and in low or low-to-moderate thrombotic risk, minidose warfarin treatment has been shown to be advantageous. In secondary prevention, and in patients at high risk for recurrent venous or arterial thrombotic events, standard range (INR 2-3) or higher level of anticoagulation is needed.</p>","PeriodicalId":12910,"journal":{"name":"Haemostasis","volume":"29 2-3","pages":"150-65"},"PeriodicalIF":0.0,"publicationDate":"1999-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000022495","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21485697","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}
HaemostasisPub Date : 1999-01-01DOI: 10.1159/000022501
T Taka, E Okano, J Seki, J Yamamoto
{"title":"Effects of clopidogrel on platelet activation and coagulation of non-anticoagulated rat blood under high shear stress.","authors":"T Taka, E Okano, J Seki, J Yamamoto","doi":"10.1159/000022501","DOIUrl":"https://doi.org/10.1159/000022501","url":null,"abstract":"<p><p>Clopidogrel is a new thienopyridine derivative similar to ticlopidine, which inhibits adenosine diphosphate-induced platelet aggregation. The in vitro effects of clopidogrel on shear-induced platelet activation and coagulation were assessed after oral administration to rats, by subjecting non-anticoagulated blood to haemostatometry. Clopidogrel significantly inhibited shear-induced platelet activation and coagulation 2 h after administration at doses of 7.5 and 15 mg/kg. Both ticlopidine (200 mg/kg) and aspirin (200 mg/kg) inhibited shear-induced platelet activation, but not coagulation. The peak inhibition of plaetelet activation by clopidogrel occurred 2 h after oral administration, but significant inhibition persisted even after 24 h. These results suggest that clopidogrel could be a more potent antithrombotic agent than ticlopidine or aspirin, and also that ADP plays an important role in shear-induced platelet activation.</p>","PeriodicalId":12910,"journal":{"name":"Haemostasis","volume":"29 4","pages":"189-96"},"PeriodicalIF":0.0,"publicationDate":"1999-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000022501","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21555167","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}
HaemostasisPub Date : 1999-01-01DOI: 10.1159/000022513
P Ferroni, S Basili, M Vieri, F Martini, G Labbadia, A Bellomo, P P Gazzaniga, C Cordova, C Alessandri
{"title":"Soluble P-selectin and proinflammatory cytokines in patients with polygenic type IIa hypercholesterolemia.","authors":"P Ferroni, S Basili, M Vieri, F Martini, G Labbadia, A Bellomo, P P Gazzaniga, C Cordova, C Alessandri","doi":"10.1159/000022513","DOIUrl":"https://doi.org/10.1159/000022513","url":null,"abstract":"<p><p>Plasma soluble P-selectin (sP-selectin), beta-thromboglobulin (beta-TG), von Willebrand Factor (vWF), prothrombin factor 1+2 (F1+2), IL-6 and IL-1beta levels were analyzed in 35 consecutive patients with polygenic type IIa hypercholesterolemia (HC) and 35 age- and sex-matched healthy subjects. sP-selectin (p < 0.005), beta-TG (p < 0.05) and IL-1beta (p < 0.02) levels were higher in HC patients than healthy subjects whereas no significant difference was observed for vWF. sP-selectin directly correlated with beta-TG (p < 0.05) and IL-1beta levels (p < 0.005), but not with the other variables analyzed. A direct correlation was observed between F1+2 and IL-6 (p < 0.05), total cholesterol (p < 0.05) or LDL cholesterol (p < 0.05). We conclude that HC is associated with an increase of plasma sP-selectin levels, and that sP-selectin may be considered as a marker of in vivo platelet activation in type IIa polygenic HC. The correlations observed among the variables analyzed in the study suggest that proinflammatory cytokines might play a role in the prothrombotic state often associated with HC.</p>","PeriodicalId":12910,"journal":{"name":"Haemostasis","volume":"29 5","pages":"277-85"},"PeriodicalIF":0.0,"publicationDate":"1999-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000022513","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21604571","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}
HaemostasisPub Date : 1999-01-01DOI: 10.1159/000022505
G Azaceta, S Romero, J A Moreno, A Vaquerizo, T Olave, C Lorente, J M Azcona, M Gutiérrez
{"title":"Hemorheological profile in chronic venous insufficiency after surgery.","authors":"G Azaceta, S Romero, J A Moreno, A Vaquerizo, T Olave, C Lorente, J M Azcona, M Gutiérrez","doi":"10.1159/000022505","DOIUrl":"https://doi.org/10.1159/000022505","url":null,"abstract":"<p><p>In recent years, there have been rheological abnormalities reported in chronic venous insufficiency (CVI), mainly an increase of erythrocyte aggregability (EA), which probably take part in the pathophysiology of the disease. The aim of this study was to analyze the hemorheological profile after stripping in 45 patients suffering from CVI. Follow-up included laboratory tests on the 7th, 60th and 180th day after surgery. EA was assessed with a photometric aggregometer (MA1, Myrenne) in stasis and low shear (3 s(-1)). The results show an increase of EA on the 7th day after surgery (p<0.001). Two and 6 months later, EA values returned to those found prior to surgery. The plasma fibrinogen level changes in a way parallel to EA. The association between rheological disturbances and thrombogenesis is well known, so the hyperaggregability found supports the antithrombotic prophylaxis in the early postsurgical period. On the other hand, the hemorheological abnormalities persist after stripping, so postsurgical treatment to inhibit EA may be beneficial.</p>","PeriodicalId":12910,"journal":{"name":"Haemostasis","volume":"29 4","pages":"219-24"},"PeriodicalIF":0.0,"publicationDate":"1999-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000022505","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21555067","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}