Kallikrein-kinin system consists of kininogen , kallikrein, bradykinin and kinin .Kinins, derived from kininogen by tissue kallikrein , play their biological effects via bradykinin 1/2 receptors or protease activated receptors .Existing researches suggest that kinins exert various effects through different intracellular and mitochondrial signal pathways such as MAPK , PI3K/Akt/GSK3 be-ta, NO, JAKs/STATs.This review aims to elucidate the roles and the intracellular signal pathways of KKS in different diseases .

Objective To study the association of V249I and T280M polymorphisms of fractalkine receptor CX3CR1 with carotid artery stenosis (CAS). Methods 318 patients with CAS diagnosed using color Doppler ultrasound criteria were studied and compared with 292 subjects without CAS. V249I and T280M polymorphic genotypes of CX3CR1 were determined by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and sequencing analysis. Results The genotypes of MM and TM were associated with reduced risk of CAS,the frequency of genotype MM + TM in the two groups being 22. 6% and 31.2% respectively ( OR = 0. 646, 95% CI 0. 451-0. 928, P = 0. 017), the frequency of M allele was significantly lower in patients with CAS than in those without CAS ( 13.8% and 19. 2% respectively, OR = 0. 677, 95%CI 0.499--0. 918,P=0. 010). No differences were observed in the Ⅱ, Ⅵ, or VV genotype, the frequency of genotype Ⅱ + Ⅵ in the two groups being 39. 0% and 43.8% respectively ( OR = 1. 012, 95% CI 0. 731-1. 403 ,P = 0. 940), the frequency of Ⅰ allele was significantly lower in patients with CAS than in those without CAS (28. 6% and 32. 7% respectively, OR = 0. 842, 95% CI 0. 660-1. 076, P = 0. 034). The genotypes of Ⅱ and Ⅵ in patients with stable plaques were more frequent than in vulnerable plaques( OR = 0. 610, 95% CI 0. 387-0. 962, P = 0. 033 ). Multiple Logistic regression analysis revealed that the genotypes of MM and TM were an independent risk factor for CAS ( OR = 1. 847,95% CI 1. 091- 3. 127 ,P = 0. 022). Conclusion The genotypes of MM and TM are independent risk factors for carotid artery stenosis, and the genotypes of Ⅱ and Ⅵ are associated with the stability of carotid artery plaques.

Transcranial Doppler (TCD) is a non-invasive,convenient and inexpensive method for cerebral hemodynamic assessment widely used in clinical practice.Monitoring of cerebrovascular reserve capacity with TCD can provide relevant information for clinical decision making in the treatment of carotid stenosis.During carotid angioplasty and stenting,TCD can be used to evaluate effect of stenting on hemodynamics,and predict major complications,particularly postoperative hyperperfusion.

In recent years, multicenter studies have confirmed that intra-arterial thrombolysis is an effective approach in the treatment of acute cerebral infarction. This article reviews the study status quo of the time window, pretreatment assessment, and selection of patients and drugs for intra-arterial thrombolysis.

Objective:To investigate neuroprotection of calcitriol in LPS-induced rat systemic inflammation and underlying mechanism. Methods:Adult male Sprague-Dawley rats were randomized into three groups: blank group(6 rats),calcitriol group [23 rats,4?g/(kg?d)?14d] and control group [23 rats,fat milk,4ml/(kg?d)?14d].46 rats were induced systemic inflammation by intraperitoneal injection of LPS(10mg/kg) on day 14th,1 hour after the administration.On post-injection 3,6,9 hour,36 rats were anesthetized to death and obtained rat brain tissue to detect activity of NF-?B by EMSA and to assess TNF-?,IL-10 concentration by ELISA.HE staining was used to determine brain injury. Results:LPS effectively activated NF-?B,enhanced TNF-? expression,induced sporadic neurons damage in brain in the control group and in time-dependent,compared with blank group rats.Calcitriol significantly down-regulated NF-?B activity,TNF-? expression but enhanced IL-10 expression at all time point evaluated,compared with the control group rats. Conclusion:Intraperitoneal injection of LPS can induce brain damage,Calcitriol modulate the inflammatory-antiinflammatory cytokine balance by downregulating activation of NF-?B,reducing over express of TNF-? and elevating IL-10 concentration.

Vascular smooth muscle cell (VSMC) proliferation and migation play important roles in the occurrence and development of atherosclerosis and restenosis after intravascular stenting.The studies in recent years have shown that kallikrein-kinin system (KKS) is closely correlated with VSMC proliferation and migration in cytokines and transduction pathways.Therefore,investigating the roles of KKS in the VSMC proliferation and migation process has great significance in clinical prevention and treatment of atherosclerosis and restenosis after intravascular stenting.

Objective To investigate the rate and the time of generalization from childhood ocular myasthenia gravis (OMG),and the preventive effect of prednisone on the progression of OMG to generalized myasthenia of gravis (GMG).Methods Retrospective study of medical data from 978 childhood patients with OMG and 1359 adult patients with OMG during a follow-up period of 1--28 years (mean 7.5 years) who were diagnosed and treated in Affiliated Hospital of Qingdao Medical College from 1977 to 2005.Results The generalized rate of childhood OMG and adult OMG was 13.0% (127/978) and 67.2% (913/1359) respectively (χ2=674.17,P < 0.01).Of 127 childhood OMG patients who had become generalized form,74 patients (58.3%) developed generalized form in the first 2 years from the onset; Of 913 adult OMG patients who had become generalized form,763 patients (83.6%) did (χ2=45.39,P < 0.01) .Of 456 childhood OMG patients treated with prednisone,only 5 patients (1.1%) became generalized form; 0f522 childhood OMG patients never treated with prednisone,122 patients (23.4%) developed the generalized form (χ2=104.9,P < 0.01).Conclusions The rate of generalization of childhood OMG is significantly decreased than that of adult OMG.The frequency of generalization of childhood OMG in the first 2 years from the onset is significantly lowered than adult OMG.Prednisone does reduce the chance of generalization from childhood OMG.

Objective There is little research focusing on the expression and function of bradykinin 1 receptor ( B1R ) and bradykinin 2 receptor ( B2R) after cerebral ischemia/reperfusion on the basis of diabetes .The aim of this study was to compare the ex-pression difference and function change of B 1R and B2R in non-dia-betic and diabetic rats . Methods The cerebral ischemia/reperfu-sion model was established on 41 non-diabetic and type 2 diabetic rats, the weight and the biochemical index were measured on these two types of rats .8 non-diabetic rats and 8 diabetic rats were respec-
tively assigned to two groups according to random number tables:control group and I/R 24 h group, 4 in each group.Real-time PCR was performed to observe the expressions of two receptors at 24 h after reperfusion .Then, 33 non-diabetic rats and 33 diabetic rats were randomly divided into 4 groups respectively, including sham group (n=6), saline group (n=9), B1R antagonist group (n=9) and B2R antagonist group (n=9).At 24 hours after cerebral I/R, neurological deficiency was evaluated by neurological severity scores ( NSS);infarct volume was observed by TTC staining;cell apoptosis was determined by TUNEL staining;neuron degeneration was de-tected by Fluoro-Jade C staining. Results Glucoses of diabetics at 3, 7, 14 d after model establishment [(23.45 ±5.01), (23.71 ±4.87), (22.72 ±4.11) mmol/L] were obviously elevated compared with non-diabetics [(5.77 ±0.75), (6.05 ±0.69), (7.15 ±1.09) mmol/L];blood cholesterin [(4.59 ±3.43) mmol/L] and insulin [(67.26 ±12.02) pmol/L] at 14 d after model establishment were evidently incresaed in comparison to those in non-diabetics [(1.58 ±0.37) mmol/L, (25.34 ±4.88) pmol/L] (P<0.05), while no significant difference was found in the blood triglyceride of diabetics between them (P>0.05).Compared with non-diabetics, diabetics suffered from more apparent up-regulation of B1R mRNA (P<0.01) but relatively less B2R mRNA (P<0.05) at 24 h after I/R.NSS score, infarction volume, damaged and apoptotic cells in B2R antagonis-treated non-diabetic rats at 24 h after I/R conspicuously decreased compared with saline-treated non-daibetic rats.Those indicators in B1R antagonis-treated diabeics were strikingly lessened compared with saline-treated daibetics . Conclusion I/R induced distinct up-regulation of B2R mRNA in non-diabetics and inhibiton of B 2R effectively ameliorated the infarct volume and cell injury after I/R in non-diabetics; I/R induced more notable up-regulation of B1R mRNA in diabetics and B1R antagonist exerted neuroprotective effects instead of B 2R antagonist af-ter I/R in diabetics.

Objective To compare the clinical efficacy and angiographic outcomes of balloon dilation angioplasty,balloon-expandable stent implantation and self-expanding stent implantation in the treatment of intracranial arterial stenosis.Methods The patients with intracranial arterial stenosis who met the indications of surgical intervention treated with balloon dilatation angioplasty and stent placement were selected from Nanjing Stroke Registry Program.According to the different interventional procedures,the patients were divided into the balloon expandable stenting goup,the self-expanding stents group and the balloon dilatation angioplasty group.The success rate of surgery,the perioperative complication rate and the significant residual stenosis rate were compared among the three groups.The clinical and angiographic assessments were performed through 1-,3-,6-,12- and 24-month regular outpatient or inpatient follow-up after procedure.The incidences of ischemic stroke and/or death and restenosis within 2 years were compared.Multivariate Cox proportional hazards analysis was used to analyze the risk factors for recurrent ischemic stroke and/or death and restenosis.Results A total of 183 patients with 192 stenoses performed balloon dilatation angioplasty or stenting,in which 92 were in the balloon expandable stenting goup,42 were in the self-expanding stents goup and 49 in the balloon dilatation angioplasty group.Their preoperative stenosis rates were 80.2 ±12.8％ 、76.3 ± 11.9％ and 89.7 ± 10.2％,respectively (F =15.863,P =0.000).There were no significant differences in other baseline data.The success rates of surgery in the balloon expandable stenting group,self-expanding stents group and balloon dilatation angioplasty group were 96.7％,95.2％ and 91.8％,respectively (x2 =1.646,P =0.439).The perioperative complication rates were 6.5％,14.3％ and 10.2％,respectively (Fisher exact test,P=0.334).The imaging follow-up showed that the restenosis rate in the balloon dilatation angioplasty group was 48.5％.Although it was high than 27.7％ in the balloon expandable stenting group and 34.8％ in the self-expanding stents group,there were no significant differences (x2 =4.176,P =0.124).Multivariate Cox proportional hazards analysis showed that balloon dilatation angioplasty was an independent risk factor for restenosis after procedure (hazard ratio 2.490,95％ confidence interval 1.247- 4.969,P=0.010).Conclusions Compared to the balloon expandable stenting,the balloon dilatation angioplasty is more likely to have restenosis,but it is not associated with the risks of postoperative recurrent ischemic stroke and/or death.

Objective:To analyze the independent and comprehensive effects of the sites and mechanisms of middle cerebral artery(MCA)occlusion on cerebral infarction patterns and the National Institutes of Health Stroke Scale (NIHSS)scores andto investigate the possible related mechanisms and their potential values to the selection of patieras for thrombolysis.Methods:Sixty-six patients with new cerebral infarction caused by MCA occlusion were enrolled.The sites of MCA occlusion were classified into the origin of the MCA(type Ⅰ),the MCA trunk distal to the lenticulostriate arteries(type Ⅱ)and the branches of the MCA(type Ⅲ):the mechanisms of cerebral infection were categorized as thrombotic and embolic.Cerebral infarction lesion patterns were determined according to diffusion-weighted image(DWI).NIHSS scores were evaluated within 24 hours after stroke onset.The independent and comprehensive effects of the sites and mechanisms of MCA occlusion on cerebral infarction lesion patterns and the NIHSS were analyzed.Results:Cerebral infarction involved a larger range and NIHSS scores were higher in patients with occlusion at the origin of MCA and embolic occlusion of the MCA trunk distal to the lenticulostriate arteries.The analysis of the combination of the sites and mechanisms of occlusion could conduct further stratification for patients with cerebral infarction caused by MCA occlusion compared with univariate analysis.Conclusion:The analysis of the combination of the sites and mechanisms of occlusion better stratifies patients with cerebral infarction caused by MCA occlusion.It may be help to select patients for thrombolytic therapy.