AIM: To investigate the effects of angiotensin Ⅱ (AngⅡ) and valsartan on the expression of AngⅡ type 1 receptor (AT 1), AngⅡ type 2 receptor (AT 2) and endothelial nitric oxide synthase (eNOS) and the synthesis of nitric oxide (NO) in human umbilical vein endothelial cells (HUVECs, ECV304 cells). METHODS: Human umbilical vein endothelial cells (HUVECs) were incubated by Ang Ⅱ or valsartan for various periods. The expression of AT 1/AT 2, eNOS and the production of NO were detected. Potential mechanism of the above effects was explored by using the relevant inhibitors of the signal molecules and antioxidants. RESULTS: Both AngⅡ and valsartan significantly inhibited the mRNA and the protein expression of AT 1 in HUVECs. The combination of the two drugs caused more significantly inhibitory effects. AngⅡ showed a slightly promotive effect at first and a significantly inhibitory effect afterward on the expression of eNOS and synthesis of NO in HUVECs. MAPK inhibitor reversed the promotive effect whereas valsartan and antioxidant vitamine C significantly reversed the inhibitory effect. CONCLUSION: Valsartan can downregulate the expression of AT 1 in HUVECs. Long time action of AngⅡcan significantly inhibit the expression of eNOS and synthesis of NO in endothelial cells, while valsartan can significantly reverse this inhibitory effect.

Increased plasma total homocysteine (tHcy) and high sensitivity C-reactive protein (hsCRP) levels are independent risk factors for cardiovascular disease. However, the predictive value of tHcy in combination with hsCRP in patients with stroke is not known. To determine the relationship between tHcy and hsCRP, we enrolled 291 patients with first-onset stroke (196 ischemic and 95 hemorrhagic). Plasma tHcy and hsCRP levels were measured and subsequent vascular events and deaths were determined over a 5-year period. Using the arbitrary cutoff for tHcy (<18 μmol/L and ≥18 μmol/L) and hsCRP (<1 mg/L, 1-3 mg/L and >3 mg/L), the patients were divided into 6 groups. Survival analysis showed that the probability of death or new vascular events during a 5-year follow-up increased according to tHcy and hsCRP levels (P<0.01). The relative risk (RR) of death or new vascular events was 4.67 (95% CI, 1.96 to 11.14, P=0.001) in patients with high tHcy (≥18 μmol/L) and hsCRP (>3 mg/L) compared with those with low tHcy (<18 μmol/L) and hsCRP (<1 mg/L). The increased tHcy level (≥18 μmol/L) combined with increased hsCRP level (>3 mg/L) was still significantly associated with the risk of death or new vascular events (RR, 4.10, 95% CI, 1.61 to 10.45, P=0.003) even when adjusted for other risk factors at inclusion. The combination of increased tHcy and hsCRP levels had a stronger predictive value than increased hsCRP alone or increased tHcy level alone. Further studies are required to evaluate the potential decrease in risks associated with lowering both Hcy and hsCRP levels in patients that present with both increased tHcy and hsCRP.

AIM:Cytochrome P450 epoxygenase 2J2 and epoxyeicosatrienoic acids ( EETs) are known to protect against cardiac hypertrophy and heart failure, which involve activation of 5′-AMP-activated protein kinase ( AMPK) and Akt.Although the functional roles of AMPK and Akt are well established , the significance of crosstalk between them in the development of cardiac hypertrophy and anti -hy-pertrophy of CYP2J2 and EETs remains unclear .Here, we investigated whether CYP 2J2 and its metabolites EETs protected against cardiac hypertrophy by activating AMPKα2 and Akt1.Moreover, we tested whether EETs enhanced crosstalk between AMPKα2 and phosphorylated Akt1 ( p-Akt1), and stimulated the nuclear translocation of p-Akt1, to exert their anti-hypertrophic effects. METHODS:The recombinant rAAV9 vector was coupled to CYP2J2 and the rAAV9-CYP2J2 construct was injected into the caudal vein of AMPKα2-/-and littermate control mice .AMPKα2 -/-and littermate control mice that overexpressed CYP 2J2 in heart were treated with angiotensin II (Ang II) for 2 weeks.Hemodynamic and cardiac functions were also evaluated after 14 days of infusion with Ang II or saline.RESULTS:Interestingly, the overexpression of CYP2J2 suppressed cardiac hypertrophy , including decreased heart size, cross sectional area of cardiomyocytes , markers of cardiac hypertrophy [ brain natriuretic peptide ( BNP) ,β-myosin heavy chain (β-MHC) and skeletal muscle α-actin (ACTA1)] and increased levels of atrial natriuretic peptide (ANP) in the heart tissue and plasma of wild-type mice but not AMPKα2 -/-mice.Measurement of left ventricular ejection fraction and fractional shortening showed that CYP2J2 overexpression prevented Ang II-induced ventricular systolic dysfunction in mice .Moreover, an Ang II-induced reduction in cardiac function, demonstrated by decreased dp/dtmax and dp/dtmin, was prevented by overexpression of CYP2J2.Mechanistically, the CYP2J2 metabolites 11,12-EET activated AMPKα2 to induce the nuclear translocation of p-Akt1, which increased production of ANP and thereby inhibited the development of cardiac hypertrophy .Furthermore , by co-immunoprecipitation analysis , we found that full-length Akt1 and an Akt1 fragment containing amino acids 150-408, which constitute the protein kinase domain , but not other frag-ments of Akt1, bind to the AMPKγ1 subunit.AMPKα2β2γ1 and p-Akt1 interact through the direct binding of the AMPKγ1 subunit to the Akt1 protein kinase domain.This interaction was enhanced by 11,12-EET.CONCLUSION:Our studies reveal a novel mechanism in which CYP2J2 and EETs enhanced Akt1 nuclear translocation through interaction with AMPKα2β2γ1 and protect against cardiac hy-pertrophy and suggest that overexpression of CYP 2J2 might have clinical potential to suppress cardiac hypertrophy and heart failure .

AIM: To study the effect of tissue kallikrein gene (HK) treatment on blood pressure in type 2 diabetic rats and its mechanism. METHODS: Male Wistar rats were injected with low dose streptozotocin and fed with diets enriched in fat and sugar to form type 2 diabetic model. Recombinant adeno-associated viral vectors (rAAV)-mediated HK gene (HK group) or LacZ gene (LacZ group) was introduced to the diabetic rats. The systolic blood pressure was measured every 2 weeks. The acetylcholine (Ach)-dependent vasodilation response, the synthesis of nitric oxide (NO), the expression of endothelin-1 (ET-1) and endothelin-A receptor (ET_A-R) in the aorta were detected. RESULTS: (1) Systolic blood pressure was significantly higher in diabetic rats than that in normal control rats. In HK group, systolic blood pressure was significantly reduced within 2 weeks after injection with rAAV?HK, reached near normal levels at 4 weeks and kept until the experiments ended (16 weeks). (2) In LacZ group, Ach-dependent vasodilation response of isolated aorta was markedly decreased than that in HK group (P

Objective To analyze relationship between the gene polymorphism of CYP4F2 and essential hypertension (EH) in China's Han population. Methods 189 EH patients and 187 age-matched controls were used to analysis G20597A polymorphism site of CYP4F2 gene with polymerase chain-restriction fragment length polymorphisms. Results There was no difference of neither genotype nor allele of CYP4F2 (G20597A) between EH and controls through stratified analysis on gender. CYP4F2 gene 20597 G allele carriers had significant association with EH for male in China (81.6% vs 71.3% , P =0.019) , but not with female. After adjustment for cardiovascular risk factors (including smoking, TC, age, genetype, BMI) , the hazard ratio for incident EH in male with CYP4F2 20597GG increased about 2. 689 than that with CYP4F2 20597GA and 20597AA. Conclusion CYP4F2 20597G allele has significant association with male EH, and CYP4F2 20597GG may be an independent predictor of EH for male in china's Han population.

BACKGROUND:There is controversy on the treatment of old femoral neck fracture with hemiarthroplasty.
OBJECTIVE:To observe the clinical effect of cementless hemiarthroplasty in the treatment of old femoral neck fracture, and to compare with total hip arthroplasty.
METHODS:A retrospective analysis was performed on the clinical data of 23 old femoral neck fracture patients treated by artificial joint replacement from January 2009 to June 2010. Among the 23 patients, 11 cases were treated with cementless hemiarthroplasty, and 12 cases were treated with total hip arthroplasty. The time for off-bed activity, Harris score and the incidence of perioperative complications were compared between cementless total hip arthroplasty and hemiarthroplasty.
RESULTS AND CONCLUSION:Al the patients were fol owed-up for 12-18 months. The active straight leg raising angle, time for off-bed activity, incidence of early postoperative complications and Harris score at 1 week after treatment of the cementless hemiarthroplasty group were better than those of the total hip arthroplasty group;there were no significant differences in Harris score at 6 weeks, 3 and 6 months between two groups;the incidence of forward hip pain of the cementless hemiarthroplasty group was higher than that of the total hip arthroplasty group. So, we general y think that cementless hemiarthroplasty has better short-term effect in the treatment of old femoral neck fracture, but the long-term integrated efficacy needs to be further identified.

Objective To observe the effects of diammonium glycyrrhizinate (DG) on arrhythmia induced by acute myocardial ischemia-reperfusion injury.Methods Electrocardiogram of lead Ⅱwas examined on the myocardial ischemia-reperfusion model,which was induced by the 10 min of ligation of left descending coronary artery and then 30 min of reperfusion in rats.Myocardial malondialdehyde (MDA) content,superoxide dismutase (SOD) activity and adenosine triphosphatase (ATPase),and serum lactate dehydrogenase (LDH) and creatine phosphokinase (CK) levels were measured.Results As compared with the model,DG significantly reduced the incidence of ventricular arrhythmia and its score (P

AIM:to investigate the effects of extract of ginkgo biloba (EGB) on human tubular epithelial-mesenchymal transition induced by transforming growth factor-?1.METHODS: HK2 cells were induced to epithelial-mesenchymal transition by transforming growth factor-?1 (TGF-?1, 10 ?g/L). EGB was added into the medium of HK2 cells 2 h before TGF-?1 was added. The expressions of E-cadherin, ?-smooth muscle actin (?-SMA), NADPH oxidase p67phox and superoxide dismutase (SOD) were determined by Western blotting. Malondialdehyde (MDA) in the mediums of HK2 cells was detected. RESULTS: EGB significantly attenuated the downregulation of E-cadherin, the upregulation of ?-SMA and p67phox, the downregulation of SOD and the upregulation of MDA in HK2 cells induced by TGF-?1.CONCLUSION: EGB significantly attenuates human tubular epithelial-mesenchymal transition induced by TGF-?1, and its underlying mechanism is that EGB attenuates the upregulation of p67phox and the downregulation of SOD induced by TGF-?1.

OBJECTIVE To study the relationship between allergic rhinitis and asthma. METHODS A total of 1526 cases of allergic rhinitis were investigated to elucidate the relationship between allergic rhinitis (A R )a n d b r o n c h i a l a s t h m a (B A ). T h e allergopharma allergic abstraction was used to detect the allergens with the skin prick test. RESULTS Among the AR patients , 43.8 % were complicated with BA. In patients with AR and BA, 52.3 % suffered from AR initially and 36.5 % suffered from BA initially. 42.4 % of the AR cases and 61.7 % of the AR with BA cases had a positive family history. In addition,30.7 % of the AR cases were complicated with allergic dermatitis. CONCLUSION The results suggested that atopic individuals with asthma or rhinitis had a tendency to develop total airway inflammation. Allergic rhinitis was also related to other allergic diseases. The skin prick test showed that the Dermatophagoides pteronyssinus was the commonest allergen in AR patients.

AIM: To investigate whether endogenous endothelium-derived hyperpolarizing factors(EHDFs) produced by CYP epoxygenases BM3?F87V,2C11OR or CYP2J2 transfection was able to protect endothelial cells against apoptosis induced by tumor necrosis factor alpha.METHODS: Three or four passages of cultured bovine aortic endothelial cells(BAECs) were transfected with epoxygenases or the empty vector(pCB6).Cell viability was detected by MTT assay.Apoptosis of transfected endothelial cells was evaluated by DNA ladder assay,flow cytometry and morphological observations under fluorescence microscopy.RESULTS: Overexpression of CYP epoxygenases BM3?F87V,2C11OR,CYP2J2 increased cell viability respectively observed by MTT assay.The percentage of cells undergoing apoptosis was decreased in 2C11OR-,BM3F87V-or 2J2-transfected cells compared to the vector as evaluated by DNA fragment assay,flow cytometry analysis and morphological observations under fluorescence microscopy.CONCLUSION: Overexpression of CYP epoxygenases BM3?F87V,2C11OR or 2J2 increases cell viability and protects endothelial cells against TNF-?-induced apoptosis.These findings suggest new targets to investigate the endothelium-associated disorders and provide novel therapeutic strategies to treat them by modulating cytochrome P450 epoxygenases.