Predictors of Bleeding from Esophageal Varices: The Role of Factor VII and von Willebrand Factor (vWF)

Objectives: Bleeding from gastroesophageal varices is the most serious and life-threatening complication of cirrhosis and accounts for 10% of all cases of bleeding from the upper GI tract. It is essential to identify and treat those patients at the highest risk because each episode of variceal hemorrhage carries a 20 percent to 30 percent risk of death, and up to 70 percent of patients who do not receive treatment die within one year of the initial bleeding episode. The aim of this study is to determine the clinical predictors of bleeding esophageal varices and study the role of F VII (factor VII) and vWF (von willebrand factor) in predicting bleeding in patients with eosphogeal varices. Methods: A case control study was done on all patients with esophageal varices admitted at Sohag and Qena faculty of medicine hospitals from January 2012 to August 2013. Various clinical, laboratory and endoscopic variables were tested to determine the predictors of esophageal bleeding. Results: Among 300 patients with esophageal varices, 80 percent was due to hepatitis C virus (HCV), 18 percent was due to hepatitis B virus (HBV), and 2 percent had both HCV and HBV. As an etiologic factor for their liver disease, hemoglobin was 10.12 ± 2.26 g/l, platelet count 135.55 ± 65.94 × l09/l, prothrombin time 14.1 ± 0.92 second, albumin 2.88 ± 0.71 g/dl, ALT 48.25 ± 24.15 u/l, total bilirubin 1.92 ± 1.36 mg/dl. Factor VII was 27.4 ± 8.92 percent and vWF was 188.33 ± 13.66 IU/dl. Splenomegaly was reported 79.6 percent, 90.3 percent had ascites. 35 percent had grade III esophageal varices, 29 percent had four-column esophageal varices on endoscopy, 13.7 percent had concomitant gastric varices and 38.3 percent had portal hypertensive gastropathy. Platelet count, presence of red color sign, the number of columns of esophageal varices, presence of portal gastropathy on eosphagogastroduodenoscopy (EGD) showed a significant positive correlation with bleeding. There is a significant decrease of FVII and a significant increase of vWF in bleeding group in comparison with non bleeding group. Conclusion: Thrombocytopenia, presence of encephalopathy and endoscopic findings of large varices, presence of red color sign, and portal hypertensive gastropathy were found to be predictors of esophageal variceal bleeding. Increase of vWF and decrease of FVII are laboratory predictors of esophageal variceal bleeding.

改良墨汁灌注法与von Willebrand factor免疫荧光法在大鼠视网膜微血管形态显示中的对比研究

目的:比较改良墨汁灌注法与von Willebrand factor(vWf)免疫荧光法在大鼠视网膜微血管形态显示方面的异同。方法:成年健康SD大鼠随机分成vWf免疫荧光显色组和改良墨汁灌注组。改良墨汁灌注组分两步灌注明胶墨汁40 ml。vWf免疫荧光显色组常规灌注生理盐水40 ml。视网膜行铺片和切片,观察vWf免疫荧光法和改良的墨汁灌注法显示的微血管形态;两组视网膜切片还进行NeuN、Parvalbumin和GFAP的免疫组织化学显色。结果:vWf免疫荧光法能充分显示视网膜铺片周围部的微血管,但对铺片中央部和切片的微血管显示不良;改良墨汁灌注法能充分显示大鼠视网膜铺片和切片的微血管,用此方法灌注的视网膜切片的NeuN、Parvalbumin和GFAP免疫组织化学效果均与正常视网膜相似。结论:改良墨汁灌注法在大鼠视网膜微血管形态显示中优于vWf免疫荧光法,且能在同一切片上准确显示血管与神经元/胶质细胞的空间关系。

固相基质表面von Willebrand Factor抗体的固定化研究

以丝素蛋白膜和聚乳酸膜为基质,采用辉光放电等离子体处理技术和共价交联的方法对vonWillebrand factor(vWf)抗体进行了固定化研究。利用抗体过剩法和酶联免疫实验对固定化效率进行了评价,固定化抗体的活性采用体外凝血时间(APTT,TT和PT)测定进行检测。结果显示固定化效率最高可以达到23.88%,酶联免疫实验均显示阳性,APTT、TT项有明显延长,有的还超出了仪器的测量范围,由此说明,通过这种方法可以有效地对vWf抗体进行共价固定化。本研究拓宽了抗体固定化技术的应用范围,为血管性假血友病的早期快速诊断仪器或试剂盒的研制打下技术基础,同时为其它凝血因子抗体相关的生物材料研究与开发提供一种新思路。

重度创伤性颅脑损伤后凝血功能障碍患者血浆α2-抗纤溶酶、vWF及ET-1水平及其影响因素分析

目的探讨重度创伤性颅脑损伤(TBI)后凝血功能障碍患者血浆α2-抗纤溶酶(α2-AP)、血管性血友病因子(vWF)及内皮素-1(ET-1)水平变化及影响因素。方法回顾性分析2021年1月—2022年12月南阳市第一人民医院神经外科和新乡市中心医院神经外科收治的106例重度TBI患者。其中男性58例,女性48岁;年龄32~60岁,平均43.7岁。根据TBI后24 h内是否发生凝血功能障碍分为凝血正常组(74例)和凝血障碍组(32例)。比较两组重度TBI患者临床资料和入院次日清晨的凝血功能指标及血浆α2-AP、vWF、ET-1水平;Pearson相关性分析重度TBI后凝血功能障碍患者血浆α2-AP、vWF、ET-1水平与凝血功能指标的关系;Logistic回归性分析影响重度TBI患者发生凝血功能障碍的危险因素;受试者工作特征(ROC)曲线分析血浆α2-AP、vWF、ET-1水平对重度TBI患者发生凝血功能障碍的预测价值。结果两组患者年龄、入院GCS、入院头部最高AIS和入院时平均MAP比较,差异有统计学意义[(45.4±5.7)岁vs.(42.8±4.2)岁、(6.7±1.1)分vs.(7.2±0.9)分、(4.6±0.8)分vs.(3.7±0.6)分、(84.1±11.2)mmHg vs.(91.0±9.7)mmHg],P<0.05。凝血障碍组TBI患者PT、APTT和INR等凝血功能指标水平和血浆α2-AP、vWF、ET-1水平高于凝血正常组,纤维蛋白原(FIB)水平低于凝血正常组[(27.9±3.4)s vs.(12.0±1.9)s、(66.4±5.8)s vs.(36.2±2.3)s、1.6±0.2 vs.1.0±0.1、(67.8±8.2)mg/L vs.(19.3±2.4)mg/L、(162.5±24.6)%vs.(94.8±10.4)%、(65.1±5.2)mg/L vs.(41.6±3.9)mg/L、(2.6±0.3)g/L vs.(3.9±0.5)g/L,差异有统计学意义(P<0.05)。Pearson相关性分析,重度TBI后凝血功能障碍患者血浆α2-AP、vWF、ET-1与PT呈强正相关(r=0.723、0.528、0.586,P<0.05),与APTT呈强正相关(r=0.646、0.572、0.585,P<0.05),与INR呈强正相关(r=0.592、0.507、0.548,P<0.05),与FIB呈强负相关(r=-0.653、-0.672、-0.526,P<0.05);Logistic回归分析显示,入院时GCS降低(OR=2.593,95%CI:1.018~6.606,P<0.05)、α2-AP水平升高(OR=3.019,95%CI:1.107~8.236,P<0.05)和vWF水平升高(OR=2.729,95%CI:1.028~7.243,P<0.05)为重度TBI患者发生凝血功能障碍的相关危险因素;ROC曲线显示,α2-AP、vWF、ET-1预测重度TBI患者发生凝血功能障碍的AUC分别为0.887(95%CI:0.805~0.969,P<0.05)、0.828(95%CI:0.734~0.922,P<0.05)和0.807(95%CI:0.695~0.918,P<0.05),联合检测的AUC为0.912(95%CI:0.854~0.970,P<0.05),灵敏度为91.67%,特异度为87.14%。结论重度TBI后凝血功能障碍患者血浆α2-AP、vWF和ET-1水平均显著升高,其中血浆α2-AP、vWF水平升高为重度TBI患者发生凝血功能障碍的相关危险因素。

Plasma von Willebrand factor level as a prognostic indicator of patients with metastatic colorectal carcinoma

AIM: To evaluate the correlations of plasma von Willebrand factor (vWF) level with the distant metastasis and prognosis of patients with colorectal cancer. METHODS: A total of 86 patients with histologically confirmed metastatic colorectal cancers receiving treatment at Taipei Veterans General Hospital were enrolled. All patients had measurable metastatic lesions and life expectancies of more than 3 mo. Plasma vWF levels were measured by immuno-turbidimetric assay and compared with results from 40 non-metastatic colorectal cancer patients and 22 healthy controls. Patients with metastatic colorectal cancer were divided into two groups according to serum vWF levels and the differences between these two groups were analyzed using x2 test. Data on age, gender, performance status, location of primary tumor, extent of metastasis, site of metastases, histological differentiation, serum CEA and plasma vWF levels were analyzed to determine association with survival. Survival curves were constructed by Kaplan-Meier product limit method and the data was analyzed using log-rank test on a microcomputer. Multivariate analysis using the Cox's proportional hazards regression model was then performed to determine the independent prognostic indicators among all of the possible variables.RESULTS: Colorectal cancer patients were identified as having significantly higher plasma vWF concentrations than healthy controls (P＜0.05). Moreover, higher vWF plasmalevels were associated with advanced tumor stage (P＜0.05) and the presence of multiple metastases (P = 0.014).Patients with lower vWF plasma levels (≤ 160%) survived significantly longer than those with a higher plasma vWF level (log-rank test, P = 0.0043). By multivariate analysis,plasma vWF levels (P＜0.001), the extent of metastasis (P = 0.012), and the performance status (P = 0.014)were identified as independent prognostic factors. CONCLUSION: Our data indicates that high plasma vWF concentrations correlate with advanced diseases and significantly poor prognosis of patients with metastatic colorectal carcinoma. It may serve as a potential biological marker of disease progression in these patients.

Von Willebrand Factor Antigen and ADAMTS13 Activity Assay in Pregnant Women and Severe Preeclamptic Patients

The present study examined von Willebrand factor (vWF) levels and ADAMTS13 activity in pregnant and severe preeclamptic women in order to shed light on the prothrombotic state in severe preeclampsia.Thirty healthy women of childbearing age,22 second trimester pregnant women,30 third trimester pregnant women and 10 severe preeclamptic patients were recruited in this study.ADAMTS13 activity was determined by the FRETS-vWF73 assay and vWF antigen (vWF:Ag) levels by an enzyme-linked immunosorbent assay.The results showed that there were statistically significant differences in plasma vWF antigen levels between the severe preeclamptic and third trimester pregnant women,between third and second trimester pregnant women (P【0.05).The third trimester pregnant women had significantly lower plasma ADAMTS13 activity than second trimester pregnant women (P【0.05).Nevertheless,no significant differences in plasma ADAMTS13 activity were found between severe preeclamptic patients and the third trimester pregnant women (P】0.05).In conclusion,plasma ADAMTS13 activity is normal in severe preeclampsia despite the increased vWF:Ag levels.Prothrombotic state is involved in the pathogenesis of severe preeclampsia,as a result of endothelial injury.

von Willebrand factor antigen as a therapeutic target of portal hypertension in cirrhosis

Increased thrombotic potential within the liver sinusoids due to local endothelial production of von Willebrand factor antigen macromolecules could represent an additional therapeutic target of portal hypertension in patients with cirrhosis. In this case, anti-inflammatory and antithrombotic drugs could modulate portal pressure by preventing the formation of intrahepatic platelet-induced microthrombi.

Clinical significance of plasma D-dimer and von Willebrand factor levels in patients with ulcer colitis

AIM: To investigate the levels of D-dimer(DD) and vonWillebrand factor(vWF) and the relationship between DDand vWF in ulcerative colitis(UC) patients.METHODS: A total of 29 plasma specimens were obtainedfrom patients with ulcerative colitis (male 13, female 16),aged 21-47 years (33 + 11). Disease activity was assessed byTruelove-Writeria. Patients with a score of above 5 wereregarded as having active colitis. Twenty healthy people(male 12, female 8),aged 19-53 years(31 + 14), ssrved asnormal controls. Blood samples were taken from anantecubital vein puncture. Blood(1.8 mL) was injected intothe tubes containing sodium citrate (0. 13 mmol/L). Theplasma was obtained by centrifugation at 3000 r@ min-1 for 10min, and stored at -80 ℃ until assayed by ELISA.RESULTS: The mean plasma levels of DD and vWF in activeUC patients were significantly higher than those of thecontrols(0.69+0.41 vs0.27+0.11, P＜0.01;143+46 vs103 + 35, P ＜ 0.01 ). The mean plasma levels of DD in thepatients with active disease were higher than those withinactive disease(0. 69 + 0. 41 vs 0.48+0.29, P＜0.05). Thelevls of v WF were not different between active and inactivepatients. DD levels were positively related to vWF levels( r =0.574, P ＜ 0. 01 ). There was no significant differencebetween levels of DD and vWF and the scope of disease cndsex of the patients.CONCLUSION: vWF is an important feature and a goodmarker of UC; intravascular thrombus and endothelial celldysfunction were found in UC patients; and the combinedtest of DD and vWF is helpful to distinguish the activity ofthe UC patients.

Levels and activities of von Willebrand factor and metalloproteinase with thrombospondin type-1 motif, number 13 in inflammatory bowel diseases

AIM To evaluate the levels of von Willebrand factor(VWF) and metalloproteinase with thrombospondin type-1 motif, number 13(ADAMTS13) in inflammatory bowel disease(IBD) and correlate them with the disease activity.METHODS Consecutive patients with IBD aged 18 years or older were enrolled in the study. Forty-seven patients with ulcerative colitis(UC), 38 with Crohn's disease(CD), and 50 healthy controls were included. The white blood cell count, haematocrit, platelet count, fibrinogen, partial activated thromboplastin time, C-reactive protein, albumin, VWF antigen level(VWF:Ag), VWF ristocetin cofactor activity(VWF:RCo), VWF collagen-binding activity(VWF:CB), and ADAMTS13 antigen level(ADAMTS13:Ag) and activity(ADAMTS13act) were measured. The following ratios were assessed: V W F : R C o/V W F : A g, V W F : C B/V W F : A g, V W F : A g/ADAMTS13 act, and ADAMTS13act/ADAMTS13:Ag. RESULTS Compared to controls, the odds ratio(OR) of an elevated VWF: Ag > 150% was 8.7(95%CI: 2.7-28.1) in the UC group and 16.2(95%CI: 4.8-54.0) in the CD group. VWF:CB was lower in UC patients, and active CD was associated with a higher VWF: RCo(+38%). The ORs of VWF:CB/VWF:Ag < 0.7(a marker of acquired von Willebrand syndrome) in the UC and CD groups were 11.9(95%CI: 4.4-32.4) and 13.3(95%CI: 4.6-38.1), respectively. Active UC was associated with lower ADAMTS13:Ag(-23%) and ADAMTS13act(-20%) compared to UC in remission. Patients with active CD had a 15% lower ADAMTS13 act than controls. The activity of UC, but not that of CD, was inversely correlated with ADAMTS13:Ag(r =-0.76) and ADAMTS13act(r =-0.81). CONCLUSION Complex VWF-ADAMTS13-mediated mechanisms disturb haemostasis in IBD. A reduced WVF:CB is a risk factor for bleeding, while a lower ADAMTS13 level combined with an elevated VWF:Ag could predispose one to thrombosis.

ADAMTS13 and von Willebrand factor are useful biomarkers for sorafenib treatment efficiency in patients with hepatocellular carcinoma

BACKGROUND Many advanced hepatocellular carcinoma(HCC) patients are receiving sorafenib treatment. Sorafenib reportedly improves overall survival(OS) significantly in patients with HCC. Prediction of sorafenib response and prognosis in patients with HCC receiving sorafenib treatment are important due to the potentially serious side effects of sorafenib. A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13(ADAMTS13) and von Willebrand factor(VWF) are associated with the pathophysiology of liver cirrhosis and HCC through their roles in hypercoagulability; they are also associated with angiogenesis via vascular endothelial growth factor(VEGF). The imbalance between ADAMTS13 and VWF was associated with prognosis of various cancers in patients undergoing chemotherapy.AIM To investigate ADAMTS13 and VWF as potential biomarkers for sorafenib response and prognosis in patients with HCC receiving sorafenib treatment.METHODS Forty-one patients with HCC receiving sorafenib treatment were included in this study. The initial daily sorafenib dose was 400 mg in all patients. ADAMTS13 activity(ADAMTS13:AC), VWF antigen(VWF:Ag), VEGF levels were determined by enzyme-linked immunosorbent assay. Univariate andmultivariate analyses were used to determine predictive factors for sorafenib response and prognosis in patients with HCC receiving sorafenib treatment.RESULTS ADAMTS13:AC was significantly higher in patients with stable disease(SD),partial response(PR), and complete response(CR) than in those with progressive disease(PD)(P < 0.05). In contrast, VWF:Ag and the VWF:Ag/ADAMTS13:AC ratio were significantly lower in patients with SD, PR, and CR than in those with PD(P < 0.05 for both). Multivariate analysis showed that the VWF:Ag/ADAMTS13:AC ratio was the only predictive factor for sorafenib response and ADAMTS13:AC was the only prognostic factor in patients with HCC receiving sorafenib treatment. The patients with a low ADAMTS13:AC(<78.0) had significantly higher VEGF levels than those with a high ADAMTS13:AC(≥ 78.0)(P < 0.05).CONCLUSION The VWF:Ag/ADAMTS13:AC ratio and ADAMTS13:AC are potentially useful biomarkers for sorafenib response and prognosis, respectively, in patients with HCC receiving sorafenib treatment.

Effect of Tongmai Jiangzhi Oral Liquid (通脉降脂口服液) on Serum P-selectin, von Willebrand Factors and D-Dimer in Patients with Atherosclerosis

Objective: To explore the role of cytokines on the pathogenesis of atherosclerosis, and the effect of Tongmai Jiangzhi oral liquid (通脉降脂口服液,TMJZ) on cytokines through observing serum P-se-lectins (Ps), von Willebrand (vWF), and D-dimer (D-D) in atherosclerosis (AS) patients. Methods: Sixty-three AS patients were randomly divided into the treated group (n = 33, treated with TMJZ, 10 ml each time, three times a day) and the control group (n = 30, treated with Lovastatin, 10 mg, once daily). The levels of serum lipids (enzymatic methods), Ps, vWF, and D-D were measured before and after 8 weeks of treatment. Results: Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), apo-protein B-100 (apoB-100) were significantly decreased (P<0.05 or P< 0.01) and high-density lipoprotein cholesterol (HDL-C) was significantly raised (P<0.05) after TMJZ treatment. Serum Ps, vWF, and D-D also declined (P<0.05) after treatment. There was no significant difference between the treated and the control groups in these parameters except serum HDL-C level. Conclusion: TMJZ has good therapeutic effect in regulating serum lipids, improving endothelial cell function, inhibiting activation of platelets, and preventing the disturbance of blood coagulation/fibrinolysis function in patients with AS.

Elevated plasma von Willebrand factor levels in patients with active ulcerative colitis reflect endothelial perturbation due to systemic inflammation

AIM: To evaluate the plasma von Willebrand factor (vWF) levels in patients with ulcerative colitis (UC) and to investigate their relationship with disease activity,systemic inflammation and coagulation activation.METHODS: In 46 patients with ulcerative colitis (active in 34 patients), clinical data were gathered and plasma vWF levels, markers of inflammation (ESR, CRP, and fibrinogen) and thrombin generation (TAT, F1+2, and D-dimers) were measured at baseline and after 12 wk of treatment. Plasma vWF levels were also determined in 52 healthy controls (HC). The relationship of plasma vWF levels with disease activity, disease extent, response to therapy, acute-phase reactants (APRs) and coagulation markers (COAGs) was assessed.RESULTS: The mean plasma vWF concentrations were significantly higher in active UC patients (143.38±63.73%) than in HC (100.75±29.65%, P = 0.001)and inactive UC patients (98.92±43.6%, P = 0.031).ESR, CRP and fibrinogen mean levels were significantly higher in active UC patients than in inactive UC patients,whereas there were no significant differences in plasma levels of D-dimers, F1+2, and TAT. UC patients with raised APRs had significantly higher mean plasma vWF levels than those with normal APRs (144.3% vs 96.2%,P = 0.019), regardless of disease activity. Although the mean plasma vWF levels were higher in UC patients with raised COAGs than in those with normal COAGs,irrespective of disease activity, the difference was not significant (141.3% vs 118.2%, P = 0.216). No correlation was noted between plasma vWF levels and disease extent. After 12 wk of treatment, significant decreases of fibrinogen, ESR, F1+2, D-dimers and vWF levels were noted only in UC patients with clinical and endoscopic improvement.CONCLUSION: Our data indicate that increased plasma vWF levels correlate with active ulcerative colitis and increased acute-phase proteins. Elevated plasma vWF levels in ulcerative colitis possibly reflect an acutephase response of the perturbed endothelium due to inflammation. In UC patients, plasma vWF levels may be another useful marker of disease activity or response to therapy.

Reliability of Plasma Von Willebrand Factor Antigen in Prediction of Esophageal Varices in Patients with Liver Cirrhosis

Background: Bleeding esophageal varices (OVs) due to portal hypertension are one of the major complications with high mortality in liver cirrhosis. So, early detection and management are mandatory. Aim: To evaluate the role of Von Willebrand factor (VWF) in predicting the presence of OVs. Patients and Methods: 62 patients with liver cirrhosis representing different Child-Pugh classes were included. The diagnosis of liver cirrhosis was based on the combination of clinical, laboratory and US examinations. All included patients underwent the following investigations: complete blood count, liver function tests (ALT, AST, serum bilirubin, albumin and total protein, prothrombin time (PT) and concentration (PC), INR and serum alkaline phosphatase), serum creatinine, Von Willebrand factor antigen (VWF-Ag) measurement and abdominal US. Upper endoscopic evaluation was done to detect presence or absence of varices (esophageal or gastric) and/or PHG. Results: 38 males and 24 females with their mean age (46 ± 12 years old) were included. Plasma Von Willebrand factor-Ag level was significantly higher in patients with OVs than those without varices (P value = 0.000). Also, its level was significantly higher in patients with higher grade of OVs, G3 than those with G1 or G2 (P value = 0.000). Patients with large OVs including those with G2 and G3 showed significantly higher values of VWF than those with small OVs (NO and G1) (P value = 0.000). VWF was independent predictor for detecting the presence of OVs with good sensitivity (90), specificity (77.3) and accuracy (85.5) at a cutoff value of 1.74 U/ml. Also it was an independent predictor for detecting the presence of large OVs with good sensitivity (91.2), specificity (85.7) and accuracy (88.7) at a cutoff value of 2.16 U/ml. Conclusion: VWF-Ag could be used as a non invasive laboratory independent predictor for the detection of OVs.

Role of von Willebrand factor levels in the prognosis of stage Ⅳ colorectal cancer: Do we have enough evidence?

TO THE EDITOR Cancer patients usually present a prothrombotic condition.Several clotting-related proteins, such as yon Willebrand factor (vWF), presenting higher plasma concentrations in these patients, may play a key role in this process. Moreover,some of those proteins are currently being characterized as response rate and overall survival markers in metastatic colorectal cancer (MCRC). In this comment article, we discuss the last piece of evidence that supports the use of vWF as a prognostic indicator in MCRC patients, provided by a paper recently published by Wang et al., in the World Journal of Gastroenterology. Summarizing, although vWF should be seriously considered as potential future prognostic and predictive indicator in colorectal cancer, more dynamic and better designed studies in longer series of patients should be conducted before standardizing its universal use among these patients.

Comments on:Perioperative von Willebrand factor dynamics are associated with liver regeneration and predict outcome after liver resection

Recentlythearticle"PerioperativevonWillebrandfactordynamics are associated with liver regeneration and predict outcome afterliver resection" was published in Hepatology[1].Prof.Starlinger et al. aimed to assess the association of von Willebrand factor (vWF) levels and clinical outcome in patients with liver cancers post-liverresection(LR).Basedonthemechanismthatplatelets accumulation in the liver may promote liver regeneration after partial LR in mice, they found the vWF-dependent pattern of platelets accumulationduringliverregenerationinpatientsaftersurgery.

von Willebrand Factor and von Willebrand Disease

von Willebrand factor (vWF) is an important compound in the human plasma. which is synthesized by endotlrelial cells and also by megakaryocytes. The gene for vWF is located near the tip of the short arm of chromosome 12, being approximately 180 kb in length and consisting of 52 exons separated by 51 introns. The mature vWF subunit consists of 2 050 amino acid residues with molecular weight of about 250 ku. In plasma vWF appears as various multimers. vWF has two well-characterized functions.

Physical Models for Interactions Between Single Von Willebrand Factor A1 Domain and GPIbα

Von Willebrand Factor(VWF)is a concatameric glycoprotein that plays a key role in rapid hemostasis and thrombosis.VWF has different functional domains that can bind to various molecules such as collagen,hemostatic factorⅧ,integrin,and platelet glycoprotein lbα(GPlbα)to achieve multiple biological functions.During hemostasis,the A1 domain of VWF binds to GPIbαwhere platelets accumulate in the injured vascular endothelium.Due to forces generated by the hemodynamic gradient flow,the relations of bond-dissociation rates versus forces show that the lifetime of molecular bond has multiple states under the external force.We processed the experimental data of receptor-ligand in a single molecule obtained from optical tweezers by two different methods,including a Dudko-Hummer-Szabo equation,and another method combining force4ime history and force induced bond rupture.Then we used a recently developed physical equation regarding protein unfolding rate to fit our results.The lifetime of the bond between A1 and GPlbαobtained by the above mentioned two methods shows a'three-stage'change upon gradually increasing the external force.When the external force was below 8 pN,the lifetime of the bond deceased as the external force increased,which is a typical expression of a catch bond.The lifetime of the bond started to increase when the external force increased from 8 to 11 pN,and then decrease again when the external force increased to above 11 pN.Kim et al.used different processing methods and proposes a'flex-bond'model:the lifetime of the bond will decrease as the external force increases,then suddenly increase to a peak,and continue to decrease with the increase of force.A recently developed model based on the structural-elastic properties of molecules fits our data well,indicating that the bond formed by Al and GPlbαhas a catch-bond phenomenon in a certain interval of external forces,and a flex bond in other force intervals.In conclusion,A1-GPIbαbond will have a'slip-catch-slip'bond tendency.Our result provides a alternative understanding about the role of Al-GPlbαinteractions in the mechanism of hemostasis.

Genome-Wide Analysis of von Willebrand Factor A Gene Family in Rice for Its Role in Imparting Biotic Stress Resistance with Emphasis on Rice Blast Disease

von Willebrand factor A(vWA)genes are well characterized in humans except for few BONZAI genes,but the vWA genes are least explored in plants.Considering the novelty and vital role of vWA genes,this study aimed at characterization of vWA superfamily in rice.Rice genome was found to have 40 vWA genes distributed across all the 12 chromosomes,and 20 of the 40 vWA genes were unique while the remaining shared large fragment similarities with each other,indicating gene duplication.In addition to vWA domain,vWA proteins possess other different motifs or domains,such as ubiquitin interacting motif in protein degradation pathway,and RING finger in protein-protein interaction.Expression analysis of vWA genes in available expression data suggested that they probably function in biotic and abiotic stress responses including hormonal response and signaling.The frequency of transposon elements in the entire 3K rice germplasm was negligible except for 9 vWA genes,indicating the importance of these genes in rice.Structural and functional diversities showed that the vWA genes in a blast-resistant rice variety Tetep had huge variations compared to blast-susceptible rice varieties HP2216 and Nipponbare.qRT-PCR analysis of vWA genes in Magnaporthe oryzae infected rice tissues indicated OsvWA9,OsvWA36,OsvWA37 and OsvWA18 as the optimal candidate genes for disease resistance.This is the first attempt to characterize vWA gene family in plant species.

寻常型银屑病患者血清TARC、vWF水平与病情严重程度的相关性

目的 检测并分析寻常型银屑病(PV)患者血清胸腺和活化调节趋化因子(TARC)、血管性血友病因子(vWF)水平及与病情严重程度的相关性。方法 选取2020年2月至2022年2月沧州市人民医院收治的74例PV患者(PV组),以本院同期42例健康体检者为对照组。根据病情严重程度将PV患者分为轻中度组(40例)和重度组(34例)。收集患者临床资料,采用ELISA法检测血清TARC、vWF、TNF-α和IL-8水平。比较不同病情严重程度PV患者血清TARC、vWF、TNF-α、IL-8水平及临床指标的差异。采用Pearson相关分析PV患者血清TARC、vWF与临床指标的相关性。采用logistic回归分析重度PV发生的影响因素。采用ROC曲线评估血清TARC、vWF对重度PV的诊断效能。结果 PV组血清TARC、vWF水平均高于对照组,差异均有统计学意义(均P<0.05)。重度组PV患者血清TARC、vWF、WBC、中性粒细胞计数、ESR、银屑病皮损面积和严重程度评分(PASI)、超敏C反应蛋白(hs-CRP)、TNF-α、IL-8均高于轻中度组,差异均有统计学意义(均P<0.05)。PV组患者血清TARC、vWF水平与ESR、hs-CRP、PASI评分、TNF-α、IL-8均呈显著正相关(均P<0.05)。血清TARC、vWF水平升高是重度PV发生的独立危险因素。血清TARC、vWF联合诊断发生重度PV的AUC为0.903,显著高于TARC和vWF单独诊断的0.823和0.807(均P<0.05)。血清TARC、vWF联合诊断发生重度PV的灵敏度和特异度为0.878和0.753。结论 PV患者血清TARC、vWF水平升高。两者与PV病情严重程度呈正相关,血清TARC、vWF联合检测有助于评估PV疾病严重程度。