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

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. METHODSConsecutive 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: VWF:RCo/VWF:Ag, VWF:CB/VWF:Ag, VWF:Ag/ADAMTS13act, and ADAMTS13act/ADAMTS13:Ag. RESULTSCompared 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 ADAMTS13act 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). CONCLUSIONComplex 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.

Spontaneous intramural duodenal hematoma in type 2B von Willebrand disease

Intramural duodenal hematoma is a rare cause of a proximal gastrointestinal tract obstruction.Presentation of intramural duodenal hematoma most often occurs following blunt abdominal trauma in children,but spontaneous non-traumatic cases have been linked to anticoagulant therapy,pancreatitis,malignancy,vasculitis and endoscopy.We report an unusual case of spontaneous intramural duodenal hematoma presenting as an intestinal obstruction associated with acute pancreatitis in a patient with established von Willebrand disease,type 2B.The patient presented with abrupt onset of abdominal pain,nausea,and vomiting.Computed tomography imaging identified an intramural duodenal mass consistent with blood measuring 4.7 cm×8.7 cm in the second portion of the duodenum abutting on the head of the pancreas.Serum lipase was 3828 units/L.Patient was managed conservatively with bowel rest,continuous nasogastric decompression,total parenteral nutrition,recombinant factorⅧ(humateP)and transfusion.Symptoms resolved over the course of the hospitalization.This case highlights an important complication of an inherited coagulopathy.

Changing insights in the diagnosis and classification of autosomal recessive and dominant von Willebrand diseases 1980-2015

The European Clinical Laboratory and Molecular(ECLM) criteria define 10 distinct Willebrand diseases(VWD) recessive type 3, severe 1, 2C and 2N; dominant VWD type 1 secretion/clearance defect, 2A, 2B, 2E, 2M and 2D; and mild type 1 VWD(usually carriers of recessive VWD). Recessive severe 1 and 2C VWD are characterized by secretion and multimerization defects caused by mutations in the D1-D2 domain. Recessive 2N VWD is a mild hemophilia due to D'-FVIII-von Willebrand factor(VWF) binding site mutations. Dominant 2E VWD caused by heterozygous missense mutations in the D3 domain is featured by a secretion-clearancemultimerization VWF defect. Dominant VWD type 2M due to loss of function mutations in the A1 domain is characterized by decreased ristocetin-induced platelet aggregation and VWF RCo, normal VWF multimers and VWF CB, a poor response of VWF RCo and good response of VWF CB to desmopressin(DDAVP). Dominant VWD type 2A induced by heterozygous mutations in the A2 domain results in hypersensitivity of VWF for proteolysis by ADAMTS13 into VWF degradationproducts, resulting in loss of large VWF multimers with triplet structure of each individual VWF band. Dominant VWD type 2B due to a gain of function mutation in the A1 domain is featured by spontaneous interaction between platelet glycoprotein Ib(GPIb) and mutated VWF A1 followed by increased proteolysis with loss of large VWF multimers and presence of each VWF band. A new category of dominant VWD type 1 secretion or clearance defect due to mutations in the D3 domain or D4-C1-C5 domains consists of two groups Those with normal or smeary pattern of VWF multimers.

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.

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.

Autoimmune Diseases and Acquired Von Willebrand Disease in Two Cases of Progeria

Ammar A., a 23-year-old male patient, who lives in Babylon, Haswa District, and his mother describes symptoms of growth retardation, skin changes, hair changes early graying and alopecia. These manifestation started early during his childhood period. There is canseguanity between the patient’s mother & father also one of the patient’s sister has similar illness and one male brother died few months following his birth. We admit the patient to hospital due acute pulmonary infection in Jan 2009, which is controlled after a course of antibiotic and after 5 months he develops generalised mucocuteneous bullous eruption which shows partial response to oral prednisolone 2 mg/Kg. The patient has normal IQ and he is in the secondary school and he has normal blood picture and the only abnormal biochemical abnormalities is mild hyperlipidemia Serum cholestrol of 5.8 mmol/L and Serum Triglyceride of 260 mg/dl. Ammar’s Sister Qawthar A., who has a similar phenotypic manifestations, presented skin vitiligo and hepatosplenomegaly associated with sever anemia and jaundice and her presentation suggestive of autoimmune haemolytic anemia improved following blood transfusion, corticosteroid and azothioprim. In February 2014 Ammer presented with multiple and diffuse cuteneous ecchymymosis with markedly prolonged PTT and slightly proloned bleeding time highly consistent with acquired Von Willebrand’s disease. In conclusion premature aging is a predisposing factor for disturbed immunity and development of autoimmune diseases.

Pseudohemophilia of Erik von Willebrand caused by homozygous one nucleotide deletion in exon 18 of the VW-factor gene

The original description of a novel severe bleeding disorder as"Hereditary Pseudohemophilia"by Erik von Willebrand can currently be labelled as von Willebrand disease(VWD)type 3.VWD type 3 is autosomal recessive caused by homozygous or double heterozygous null mutations in the von Willebrand factor(VWF)gene and typically characterized by prolonged bleeding time and APTT,FⅧ:C levels below 2%,undetectable VWF:Ag,VWF:RCo and VWF:CB and absence of ristocetin induced platelet aggregation(RIPA).Autosomal recessive von Willebrand disease type 3 VWD with virtual complete VWF deficiency are homozygous or compound heterozygous for two null alleles(gene deletions,stop codons,frame shift mutations,splice site mutations,and absence of m RNA).Reports on severerecessive VWD compound heterozygous for a null allele and a missense mutation and homozygous or double heterozygous for missense mutations are associated with very low but measurable FⅧand VWF:Ag and should be reclassified as severe recessive type 1 VWD.Homozygous missense or compound missense/null mutations related to recessive severe type 1 VWD have been indentified in the VWF prosequence D1 and D2domains,the D4,B1-3,C1-2 domains,and only a very few in the dimmerization site(D3 domain).The detection of even tiny amounts of VWF:Ag after desmopressin acetate(DDAVP)or in hidden sites like platelets allows the differentiation between patients with VWD type 3 and homozygous or double heterozygous recessive severe type 1.Carriers of a null allele related to VWD type 3 or a missense mutation related with severe recessive type 1 VWD may present with mild VWD with low penetrance of bleeding in particular when associated with blood group O.Heterozygous obligatory carriers(OC)of a null mutation or a missense mutation related to recessive VWD type 3 or severe type 1both present with asymptomatic or mild VWD type 1 in particular when associated with blood group O.The response to DDAVP of OC of either a nonsense or a missense mutation appears to be abnormal and diagnostic with a 3-times higher response of FⅧ:C as compared to VWF:Ag.In contrast,the responses to DDAVP of FⅧ:C and VWF:Ag are equally good in individuals with low VWF levels related to blood group O and a normal VWF gene and protein(pseudo-VWD).These observations are completely in line with and extend the original observations of von Willebrand in a large family with VWD type 3 and asymptomatic or mild true type1 VWD in OC.

冠心病患者细胞间粘附分子-1、P-选择素和von Willebrand因子的表达

探讨细胞间粘附分子－１（ＩＣＡＭ－１）、Ｐ－选择素（Ｐ－ｓｅｌｅｃｔｉｎ）．ｖｏｎＷｉｌｌｅｂｒａｎｄ因子（ｖＷＦ）在冠心病中的表达特点和临床意义。方法用酶联免疫吸附法（ＥＬＩＳＡ）检测２８例稳定性心绞痛患者（ＳＡ）、２３例不稳定性心绞痛患者（ＵＡ）和２０例心肌梗死患者（ＡＭＩ）血中ＩＣＡＭ－１、Ｐ－ｓｅｌｅｃｔｉｎ、ｖＷＦ的表达。结果冠心病患者血中ＩＣＡＭ－１、Ｐ－ｓｅｌｅｃｔｉｎ和ｖＷＦ的表达较正常组增高，且在ＵＡ组中的表达高于ＳＡ组，ＡＭＩ组的表达高于ＵＡ组。除Ｐ－ｓｅｌｅｃｔｉｎ在ＳＡ组与正常组间差别不显著外，其余均差异显著（Ｐ＜０．０１）。ＩＣＡＭ－１和ｖＷＦ在ＳＡ、ＵＡ及ＡＭＩ组均呈正相关。结论ＩＣＡＭ－１、Ｐ－ｓｅｌｅｃｔｉｎ和ｖＷＦ在不同类型冠心病患者有不同的增加，表明它们与冠心病的发生、发展及临床严重程度密切相关。

von Willebrand因子与稳定冠心病

早期大量研究揭示了von Willebrand因子的生物学特点、结构和功能,近期研究发现von Willebrand因子可能在稳定冠心病发病、剪切力机制诱导血小板聚集、血栓形成,以及药物和介入治疗(包括支架置入等)方面有重要作用。

冠心病患者C反应蛋白、丙二醛与von Willebrand因子检测及辛伐他汀干预后的变化

目的 检测各型冠心病患者外周血炎症标志物C反应蛋白 (CRP)、丙二醛 (MDA)与vonWillebrand因子(vWF)以及辛伐他汀对冠心病患者调脂以外的作用。方法 血脂正常的冠心病患者 14 0例 ,其中稳定性心绞痛(SAP) 4 0例 ,不稳定性心绞痛 (UAP) 5 0例 ,急性心肌梗死 (AMI) 5 0例。每种病例随机分为两组 ,一组为辛伐他汀治疗组 ,一组为常规治疗组 ;正常对照组 2 0例。分别于入院时及治疗后 1周两次检测上述标志物。结果 三组病例的CRP、MDA、vWF均显著高于对照组 (P <0 .0 0 1) ,AMI组显著高于SAP及UAP组 (P <0 .0 0 1) ;辛伐他汀治疗组可以使三种指标显著下降 (P <0 .0 5 )。结论 炎症反应、氧化应激及血管内皮损伤在冠心病的发病机制及进展中起重要作用 ,辛伐他汀可以抑制炎症反应、氧化应激 ,修复内皮从而稳定病变进展。

Von Willebrand因子在先天性心脏病肺动脉高压中的表达及意义

目的 探讨VonWillebrand因子 (VWF)在先天性心脏病 (简称先心病 )室间隔缺损 (简称室缺 )伴肺动脉高压 (简称肺高压 )中的表达及其临床意义。方法 应用酶联免疫吸附双抗体夹心法检测 1 5例先心病室缺伴肺高压患者血浆中VWF的表达 ,并与先心病室缺无肺高压的患者作对照。结果 伴肺高压的先心病患者血浆中的VWF水平显著高于无肺高压的先心病患者(P <0 .0 5 )。结论 VWF与先心病室缺伴肺高压的发生、发展有着密切关系。

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.

Acquired von Willebrand Syndrome in a Male with Systemic Lupus Erythematosus Presented with Mucocutaneous Bleeding and Treated with rFVIIa

Background: Systemic lupus erythematosis (SLE) is a disorder with multiple organ involvement. Haematological abnormalities have been addressed in it, but acquired von Willebrand syndrome is a rarer phenomenon in current disease. The Case: We report acquired von Willebrand syndrome and SLE in a man with brown rash on face, gingival bleeding, easy bruising and epistaxis and laboratory finding of decreased complement, high level of anti-nuclear antibody and anti-DNA. These findings confirmed the diagnosis of SLE. He underwent kidney biopsy and experienced severe pain at the site of biopsy, but the ultra-sonography evaluation showed small sub capsular haematoma at the site of biopsy. During the next 48 hours, gradually APTT prolongation was continued and haematocrit dropped. In spite of FFP infusion and taking tranexamic acid every eight hours, there wasn’t any improvement in haemostatic condition. He received Methylprednisolone and Cyclophosphamid pulses. The patient underwent surgery to roll out vascular complication, but there wasn’t any vascular problem. On the third day, recombinant activated factor VII was infused every two hours until oozing was stopped.

非透析2型糖尿病肾病患者病情严重程度的影响因素分析

目的:探讨非透析2型糖尿病肾病(DKD)患者病情严重程度的影响因素。方法:选取2020年1月—2022年3月海军安庆医院收治的86例非透析2型DKD患者为研究对象,收集患者性别,年龄,体质量指数(BMI),糖尿病病程,高血压分级,入院第2天总胆固醇(TC)、甘油三酯(TG)、空腹血糖、糖化血红蛋白(HbA1c)、尿白蛋白肌酐比值(UACR)、估算肾小球滤过率(eGFR)以及血清超敏C反应蛋白(hs-CRP)、同型半胱氨酸(Hcy)、血管性血友病因子(vWF)水平等资料。根据eGFR对研究对象进行分组,eGFR≥60 m L/(m i n·1.73 m^(2))为A组,eGFR 30~<60 mL/(min·1.73 m^(2))为B组,eGFR<30 mL/(min·1.73 m^(2))为C组,采用多因素Logistc回归分析非透析2型DKD患者病情严重程度的危险因素。结果:单因素分析结果显示,三组受试者间性别、年龄、BMI、高血压分级、TC、TG比较,差异无统计学意义(P>0.05),而糖尿病病程、空腹血糖、HbA1c、UACR以及血清hs-CRP、Hcy、vWF水平比较,差异具有统计学意义(P<0.05);多因素logistic回归分析结果显示,年龄[OR=1.022,95%CI:(1.011,1.033),P<0.001]、糖尿病病程[OR=1.315,95%CI:(1.082,1.591),P=0.013]、高血压分级[OR=1.091,95%CI:(0.994,1.218),P=0.030]、UACR[OR=1.085,95%CI:(1.003,1.162),P=0.022],以及血清hs-CRP[OR=1.031,95%CI:(1.011,1.057),P=0.017]、Hcy[OR=1.018,95%CI:(0.913,1.149),P<0.001]、vWF[OR=1.016,95%CI:(1.011,1.023),P<0.001]水平是非透析2型DKD患者eGFR低的影响因素。结论:非透析2型DKD患者病情严重程度与年龄、糖尿病病程、高血压分级、UACR以及血清hs-CRP、Hcy、vWF水平密切相关。

1例c.1117C>T/c.7288-9T>G复合杂合突变所致血管性血友病家系的发病机制分析

目的探讨1例血管性血友病(vWD)家系的诊断及发病机制。方法家系收集。收集北京大学第一医院就诊的先证者及其家系成员(共4人),检测活化部分凝血活酶时间(APTT)、血管性血友病因子抗原(vWF:Ag)和活性(vWF:Ac)、凝血因子Ⅷ活性(FⅧ:C)、vWF瑞斯托霉素辅因子(vWF:RCo),进行瑞斯托霉素诱导血小板聚集试验(RIPA)、vWF胶原结合(vWF:CB)试验,对先证者及其家系成员进行诊断。提取先证者及其家系成员外周血基因组DNA,进行全外显子测序,分析vWF基因突变,采用生物信息分析工具进行基因突变位点致病性分析,探讨先证者发病机制。结果先证者(Ⅲ_(1))的APTT轻度延长、FⅧ:C正常、vWF:Ag、vWF:Ac、vWF:RCo和vWF:CB明显减低,1.0 mg/mL和1.25 mg/mL的RIPA无明显聚集;父亲(Ⅱ_(3))的APTT、FⅧ:C、vWF:Ag、vWF:Ac和vWF:CB均正常,vWF:RCo轻度减低;母亲(Ⅱ_(4))的APTT、FⅧ:C、vWF:Ag、vWF:RCo和vWF:CB均正常,vWF:Ac明显减低;哥哥(Ⅲ_(2))的APTT、FⅧ:C均正常,vWF:Ag、vWF:Ac、vWF:RCo及vWF:CB均不同程度减低;父亲(Ⅱ_(3))、母亲(Ⅱ_(4))和哥哥(Ⅲ_(2))的1.0 mg/mL RIPA均无明显聚集。基因分析显示先证者(Ⅲ_(1))存在vWF基因c.7288-9T>G和c.1117C>T复合杂合突变,其父亲(Ⅱ_(3))存在vWF基因c.7288-9T>G杂合突变;母亲(Ⅱ_(4))和哥哥(Ⅲ_(2))存在vWF基因c.1117C>T杂合突变。结论先证者为2A型vWD,其vWF基因c.1117C>T和c.7288-9T>G杂合突变可能是导致该先证者发病的原因。

冠心病中医证型与血浆vWF、Ps、hs-CRP、FIB、TXB_2、6-keto-PG_(1α)关系的临床研究

目的:探讨血浆v WF、Ps、hs-CRP、FIB、TXB2、6-keto-PGF1α与冠心病中医证型的关系。方法:将152例冠心病患者辨证分为心血瘀阻、痰阻心脉、阴寒凝滞、心肾阴虚、气阴两虚、阳气虚衰,测定血浆v WF、Ps、hs-CRP、FIB、TXB2、6-keto-PGF1α值。结果:心血瘀阻、痰阻心脉、心肾阴虚、气阴两虚4型血浆v WF、Ps、FIB、TXB2水平明显升高,心血瘀阻、痰阻心脉2型高于心肾阴虚、气阴两虚2型,心血瘀阻、痰阻心脉、心肾阴虚、气阴两虚4型血浆6-keto-PGF1α水平明显降低,心肾阴虚、气阴两虚证型2型低于心血瘀阻和痰阻心脉2型。各证型血浆hs-CRP水平比较差异无统计学意义。结论:提示心肾阴虚、气阴两虚两型病机为炎症损伤血管内皮,心血瘀阻、痰阻心脉是炎症损伤血管内皮基础上,抗血栓能力下降,导致动脉粥样硬化。

初诊2型糖尿病ET-1、NO、vWF含量与血管内皮功能改变之间的关系

目的:探讨临床初诊2型糖尿病(T2DM)患者血浆内皮素-1(ET-1)、氧化亚氮(NO)和血管性假血友病因子(vWF)含量的变化及其与血管内皮功能之间的关系。方法:分别检测66例临床初诊T2DM、30例健康者血浆中ET-1、NO和vWF;用彩色多普勒超声仪测定血管内皮依赖性舒张功能,并进行统计分析。结果:T2DM组空腹血糖(FBG)和三酰甘油(TG)、低密度胆固醇(LDL-c)高于正常对照组(P<0.05);T2DM组ET-1、vWF均增高(P<0.05),两组NO水平比较无统计学差异(P>0.05);T2DM组反应性充血引起的肱动脉内径较对照组上升,但无统计学意义(P>0.05);T2DM组反应性充血引起的肱动脉内径变化率较对照组下降,有统计学意义(P<0.05);相关分析显示,ET-1、vWF与反应性充血后肱动脉内径的变化率呈负相关(P<0.05)。结论:临床初诊T2DM患者存在ET-1、vWF水平增高和内皮依赖性血管舒张功能障碍;内皮细胞标志物ET-1、vWF可反映内皮依赖性血管舒张功能。

老年2型糖尿病合并非酒精性脂肪肝患者血清vWF、sST2水平与胰岛素抵抗及肝功能的相关性分析

目的探究老年2型糖尿病(T2DM)合并非酒精性脂肪肝(NAFLD)患者血清血管性血友病因子(vWF)、可溶性生长刺激因子2(sST2)水平与胰岛素抵抗及肝功能的相关性。方法选取2020年4月至2022年4月我院收治的116例确诊为老年T2DM合并NAFLD患者为患病组,根据肝功能等级,将其分为A级组(41例)、B级组(39例)和C级组(36例);根据是否存在胰岛素抵抗,将其分为抵抗组(42例)和非抵抗组(74例)。选取我院同期收治的单纯T2DM患者116例作为对照组。比较各组血清vWF、sST2水平;多因素Logistic回归分析老年T2DM合并NAFLD的影响因素;受试者工作特征(ROC)曲线分析血清vWF、sST2水平对T2DM合并NAFLD的诊断价值。结果患病组肥胖人数占比、HOMA-IR评分、BMI、饮酒史人数占比、低密度脂蛋白胆固醇、总胆固醇、三酰甘油、vWF、sST2水平均高于对照组,而总胆红素低于对照组(P<0.05);随着肝功能等级增加,血清vWF、sST2水平逐渐升高(P<0.05);抵抗组血清vWF、sST2水平高于非抵抗组(P<0.05)。饮酒史、低密度脂蛋白胆固醇、总胆固醇、三酰甘油、HOMA-IR、vWF、sST2为老年T2DM合并NAFLD的独立危险因素,总胆红素为独立保护因素(P<0.05)。血清vWF、sST2水平诊断T2DM合并NAFLD的曲线下面积(AUC)分别为0.870、0.866,截断值分别为24.05 ng/ml、20.28 ng/ml,二者联合诊断的AUC为0.940,二者联合诊断优于各指标单独诊断(Z_(二者联合-vWF)=2.056、Z_(二者联合-sST2)=2.417,P=0.040、0.016)。结论老年T2DM合并NAFLD患者血清vWF、sST2水平均上调,且vWF、sST2与胰岛素抵抗及肝功能密切相关,二者联合对老年T2DM合并NAFLD具有较高的诊断价值。

子痫前期患者血清MAPK1、TNF-α及vWF水平及其与病情严重程度的关系

目的分析子痫前期患者血清丝裂原活化蛋白激酶1(MAPK1)、肿瘤坏死因子α(TNF-α)及血管性血友病因子(vWF)水平及其与病情严重程度的关系。方法纳入100例子痫前期患者及70例健康孕妇(对照组),根据病情严重程度将子痫前期患者分为重度组46例及轻度组54例。比较3组孕妇的常规指标(血清肌酐及尿素水平、血压、24 h尿蛋白含量)及血清TNF-α、MAPK1、vWF水平。结果重度组和轻度组的血清肌酐和尿素水平、收缩压、舒张压、24 h尿蛋白含量,以及血清TNF-α、MAPK1、vWF水平高于对照组,且重度组的上述指标高于轻度组(P<0.05)。结论子痫前期患者血清MAPK1、TNF-α及vWF水平升高,且与患者病情严重程度密切相关。检测以上指标或许有助于提高子痫前期的早期诊断率。

川崎病急性期中性粒细胞胞外诱捕网与血管损伤的相关研究

目的观察中性粒细胞胞外诱捕网(NETs)形成在川崎病(KD)急性期中的变化,探讨其参与KD血管损伤的可能和相关药物的保护机制。方法留取2022年1月—2023年6月东莞市妇幼保健院收治的40例KD患儿静脉注射丙种球蛋白前、后与对照组40例健康同龄儿童血样,对外周血中性粒细胞计数和酶联免疫吸附试验法检测的血浆中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和循环游离DNA(cfDNA)、LL-37、脱氧核糖核酸酶Ⅰ(DNaseⅠ),以及血管性血友病因子(vWF)、内皮细胞微粒(EMPs)及血小板衍生微粒(PDMP)水平进行比较并分析。结果KD急性期患儿外周血中中性粒细胞计数和TNF-α、IL-6以及NETs主要成分cfDNA和LL-37水平增高,DNaseⅠ水平下降,丙种球蛋白治疗后恢复,且与对照组相比无统计学差异;同时血浆中vWF、EMPs和PDMP也均增高,丙种球蛋白治疗后下降,与对照组相比无统计学差异;有冠状动脉扩张者KD急性期的中性粒细胞计数、TNF-α、cfDNA及vWF、EMPs、PDMP较无冠状动脉扩张者高,DNaseⅠ则较之低;相关分析提示,NETs主要成分cfNDA与EMPs、vWF及PDMP水平呈正相关,与DNaseⅠ水平呈负相关。结论KD急性期存在NETs过表达和DNaseⅠ降解能力下降与患者病情相关,动态监测cfDNA在早期诊断和病情严重程度评估中有一定临床价值;NETs可能参与了KD的血管炎症内皮损伤-凝血轴反应;提示丙种球蛋白通过减少NETs损伤途径发挥一定药理保护作用。