NLRP3: A promising therapeutic target for autoimmune diseases.

NLRP3, a member of nucleotide-binding domain-(NOD) like receptor family, can be found in large varieties of immune and non-immune cells. Upon activation, the NLRP3, apoptosis-associated speck-like protein (ASC) and pro-caspase-1 would assemble into a multimeric protein, called the NLRP3 inflammasome. Then the inflammasome promotes inflammation (through specific cleavage and production of bioactive IL-1ß and IL-18) and pyroptotic cell death. Previous studies have indicated the importance of NLRP3 in regulating innate immunity. Recently, numerous studies have revealed their significance in autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc) and inflammatory bowel disease (IBD). In this review, we will briefly discuss the biological features of NLRP3 and summarize the recent progression of the involvement of NLRP3 in the development and pathogenesis of autoimmune diseases, as well as its clinical implications and therapeutic potential.

Open and Endovascular Management of Severe Cerebral Ischemia in Takayasu's Arteritis.

BACKGROUND: Severe cerebral ischemia in patients with Takayasu's arteries was caused by occlusion of most supra-aortic arteries. Arterial revascularization is necessary to decrease the incidence of stroke and improve the quality of life but may be complicated with multiple occlusive lesions and inflammation condition of this disease. This study was to assess options and long-term outcomes of surgical and endovascular treatment. METHODS: Twenty-nine patients with severe cerebral ischemic symptoms underwent surgical or endovascular treatment from January 1991 to July 2015. Demographic characteristics, surgical and endovascular procedures, and follow-up outcomes were reviewed. Risk factors associated with primary patency of surgical treatment and assisted primary patency of endovascular treatment was identified by Cox regression analyses. RESULTS: There were 29 patients with a median age of 24 (range 9-37 years), 9 in active and 20 in inactive phase. Seventeen patients underwent a variety of bypass procedures. Fourteen endovascular procedures were performed in 12 patients. No death occurred within 30 days after both procedures. Complications within 30 days after bypass included stroke in 1 patient, infection in 2 patients, and heart failure in 1 patient. Nine patients developed brain hyperperfusion after bypass. Transient hemiplegic paralysis occurred in 1 patient during dilation of the carotid artery. During a median follow-up time of 41 months, primary and secondary patency rate of bypass at 1 and 3 years was 93.75% and 100% and 87.5% and 100%, respectively. Assisted primary and secondary patency rate of endovascular treatment at 1 and 3 years was 85.71% and 92.86% and 68.18% and 75.66%, respectively. There was no independent risk factor associated with either primary patency of surgical treatment or assisted primary patency of endovascular treatment. Disease activity was independent risk factor associated with combined rate of primary patency of surgical treatment and assisted primary patency of endovascular treatment (HR: 0.17, 95% CI: 0.03-0.93, P = 0.04). CONCLUSIONS: Bypass is the preferred treatment in majority of patients with good long-term patency, even has a higher propensity for postoperative complications. Endovascular treatment should be preserved for short lesions in inappropriate or high-risk surgical patients but needs more reintervention and close monitoring of lesion for better outcomes. Long-term patency of surgical and endovascular treatment is related with disease activity. Combination of surgical or endovascular treatment and medical therapy may improve the efficacy of interventions.

Incidence and Risk Factors of Deep Venous Thrombosis in Asymptomatic Iliac Vein Compression: A Prospective Cohort Study.

BACKGROUND: Deep vein thrombosis (DVT) may be associated with iliac vein compression. Up to now, the majority of data has come from a retrospective study about the correlation between DVT and iliac vein compression. This prospective study was to determine the incidence of DVT in individuals with iliac vein compression and identify risk factors predictive of DVT. METHODS: A total of 500 volunteers without symptoms of venous diseases of lower extremities and overt risk factors of deep venous thrombosis between October 2011 and September 2012 in Shijitan Hospital were enrolled in this cohort study. All the participants underwent contrast-enhanced abdominal computed tomography (CT) to evaluate iliac vein compression. Baseline demographic information and degree of iliac vein compression were collected. They were categorized into ≥50% or <50% iliac vein compression group. Ultrasound examination was performed to screen DVT at the time of CT examination and 3, 6, 9, and 12 months after the examination. Primary event was DVT of ipsilateral lower extremity. Correlation between DVT and iliac vein compression was estimated by multivariate Logistic regression after adjusting for age, gender, malignancy, surgery/immobilization, chemotherapy/hormonal therapy, and pregnancy. RESULTS: In 500 volunteers, 8.8% (44) had ≥50% iliac vein compression and 91.2% (456) had <50% iliac vein compression. Ipsilateral DVT occurred in six volunteers including two in iliofemoral vein, two in popliteal vein, and two in calf vein within 1 year. Univariate analysis showed that the incidence of DVT was 6.8% in ≥50% compression group, significantly higher than that in <50% compression group (0.7%) (χ2 = 12.84, P = 0.01). Patients with malignancy had significantly higher incidence of DVT than those without malignancy (χ2 = 69.60,P< 0.01). Multivariate Logistic regression indicated that iliac vein compression and malignancy were independent risk factors of DVT. After adjustment for malignancy, patients with ≥50% iliac vein compression had 10-fold increased risk of developing DVT (adjusted relative risk [RR] = 10.162, 95% confidence interval [CI]: 1.149-89.865, P = 0.037). In subgroup analysis, patients with malignancy and ≥50% iliac vein compression had 12-fold increased the risk of DVT than those without malignance and ≥50% compression (RR = 12.389, 95% CI: 2.327-65.957, P = 0.003). CONCLUSIONS: Iliac vein compression is common, but the incidence of DVT is low. Only individuals with ≥50% iliac vein compression or compression combined with other risk factors might have significantly increased the risk of DVT. Further study is recommended to improve prevention strategies for DVT in significant iliac vein compression.

[A prospective randomized control clinical trial about clopidogrel combined with warfarin versus clopidogrel alone in the prevention of restenosis after femoral-popliteal artery angioplasty].

OBJECTIVE: Using two antithrombotic treatment (clopidogrel vs. clopidogrel combined warfarin) strategies after femoral-popliteal artery angioplasty prospectively, to evaluate which strategy is more effective for the restenosis prevention. METHODS: Totally 50 patients referred for endovascular treatment (including the percutaneous transluminal angioplasty (PTA) and stent implantation) of the superficial femoral artery and popliteal artery from January 2008 to May 2009 were randomly divided into clopidogrel group (group A, 25 cases, 30 limbs) and clopidogrel plus warfarin group (group B, 25 cases, 33 limbs) before operation. Clinical outcomes and restenosis rate of the target lesions were evaluated at 3, 6 and 12 months after operation. RESULTS: Totally 88 patients were screened for participation in the study, 56 patients were included after the follow-up of 12 months. At 3 months, the rates of restenosis were 16.7% in group A and 18.2% in group B (χ² = 0.025, P = 0.874). At 6 months, the accumulated restenosis rates were 36.7% in group A and 36.4% in group B (χ² = 0.001, P = 0.98). At 12 months, the accumulated restenosis rates were 53.3% in group A and 42.4% in group B (χ² = 0.75, P = 0.387). Analysis for the critical limb ischemia sub-group showed that follow-up of 12 months, the accumulated restenosis rate was 8/10 in group A and 6/12 in group B (χ² = 1.023, P = 0.312). CONCLUSION: The clopidogrel alone treatment for PTA or PTA plus stent implantation of femoral popliteal artery has no statistically significant difference in comparison with the clopidogrel combined warfarin treatment in terms of the cumulative vascular restenosis rate at 3, 6, 12 months postoperatively.

[Preliminary study on differential expression of plasma proteins of patients with Takayasu's arteritis in different stage].

OBJECTIVES: To investigate differential expression of plasma proteins of patients with Takayasu's arteritis to screen disease-related or phase-related proteins or biomarkers. METHODS: From March, 2005 to January, 2006, Plasma of 20 patients with acute Takayasu's arteritis, 20 patients with chronic Takayasu's arteritis, and 20 healthy people as control were collected. Plasma proteins were profiled by two-dimensional electrophoresis. Spots of differential expression were screened by computerized map analysis and identified by matrix assisted laser desorption/ionization time of flight-mass spectrometry. Circulation levels of parts of differential expression proteins were investigated by Elisa in each subject. RESULTS: Fourteen differential expression proteins were identified, including serum amyloid A, serum amyloid P, fibrinogen, complement C3c, C7, C4 binding protein, factor H related protein-1, immunoglobin, alpha-acid glycoprotein, RAG1 protein, alpha1-microglobin, apolipoprotein A-I, A-IV, transthyretin, haptoglobin. Proteins related to acute and chronic phase were serum amyloid A, fibrinogen, transthyretin, haptoglobin; Circulation levels of Serum amyloid A (SAA) and Complement C4 binding protein (C4BP) were significantly increased in active TA patients comparing to that in inactive TA patients and in controls (SAA: 95.9 vs 49.2, P = 0.009 and 23.9 mg/L, P = 0.001, respectively; C4BP: 88.5 vs 61.7, P = 0.023 and 32.6 mg/L, P < 0.001, respectively). CONCLUSIONS: Acute phase proteins and immune proteins may possible be markers for diagnosis and activity of Takayasu's arteritis, Complement activity, complement modulation protein and antibody production may be involved in immune mechanism of Takayasu's arteritis. Further study of these proteins may be helpful to elucidate the pathologic mechanism of Takayasu's arteritis.

[The study of Chinese optimal anticoagulant range of warfarin for venous thromboembolism].

OBJECTIVE: The aim of trial is to observe the Chinese bleeding frequency and frequency of recurrent VTE in different international normalized ratio (INR) range of warfarin for venous thromboembolism (VTE) including deep venous thrombosis (DVT) and pulmonary embolism (PE), and to search optimal INR range. METHODS: We conducted a randomized, double-blind cohort trial, in which 180 patients were assigned to apply warfarin in a target INR of 1.50 to 1.99 (group A), a target INR of 2.00 to 2.50 (group B) or a target of INR of 2.51 to 3.00 (group C). Every group had respectively 60 patients. After they had completed warfarin therapy to be stability kept with those target INR range for two or more weeks, this study would be begun to observe the bleeding frequency and frequency of recurrent VTE. RESULTS: There was significant difference in recurrent VTE frequency between Group A (8.3%) and BC (1.7%, P = 0.042). The minor bleeding frequency of Group A, B and C is respectively 8.3%, 18.3% and 6.7% (P = 0.089). The moderate bleeding frequency of Group A and BC is respectively 3.3% and 7.5% (P = 0.341), and large bleeding frequency of them is respectively 0% and 3.3% (P = 0.303). To patients whose age above 62 year, major bleeding episode occurred respectively in 1 patient assigned to INR of 1.5-2.5 and in three patients assigned to Group C (hazard ratio, 12. 600; 95 percent confidence interval, 1.183-134.238). CONCLUSION: Warfarin therapy in INR of 2.0-3.0 is more effective than INR of 1.5-1.99 for the long-term prevention of recurrent VTE. And warfarin regimen in INR of 2.0-3.0 does not increase the risk of major bleeding either. So to general Chinese, INR ought to be recommended in 2.0-3.0. To patients whose age above 62 year, INR ought to be recommended between 2.0 to 2.5.

[The relationship between peripheral arterial disease and coronary artery disease and stroke in arterial sclerosis].

OBJECTIVE: The purpose of the study was to investigate the relationship between peripheral arterial disease (PAD) and coronary artery disease or stroke in Chinese. At the same time, investigate the prevalence of symptoms, include cold, numb, pain, intermittent claudication and ulcer, then investigate the relationship between abnormal ABI and them. METHODS: Hospitalized patients in department of cardiology, neurology and vascular were enrolled from March 2006 to December 2007 consecutively. ABI was measured and the disease history was collected. Elective Fraction (EF), cardioangiography of coronary artery, and ultrasound examination of cervical artery were recorded too to analyze the relationship between them and ABI. The degree of cold, numb, pain, intermittent claudication and ulcer were recorded in patients with PAD, to analyze the relationship between the prevalence and ABI. RESULTS: In 132 patients of department of cardiology, the prevalence of ABI < 0.9 was 29.5%, In 124 patients of department of neurology, the prevalence of ABI < 0.9 was 17.7%. When ABI decreased, the EF decreased too, and the disease of coronary artery and cervical artery became more serious. In patients of vascular department, when ABI decreased, the symptoms of cold, numb, pain, intermittent claudication and ulcer aggravated. CONCLUSIONS: In Chinese, in patients with coronary artery disease, the prevalence of PAD is 29.5%, and in patients with stroke the prevalence of PAD is 17.7%. 7.2% patients have these three disease. PAD has relationship with the severity of these two diseases. In patients with PAD, the symptoms will aggravate when ABI decreased. When ABI < 0.4, the symptoms all aggravate significantly.