Association of nicotinamide adenine dinucleotide phosphate oxidase p22phox gene 549C>T polymorphism with coronary artery disease.

BACKGROUND: The p22phox is a critical component of the superoxide-generating vascular nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Several polymorphisms in p22phox gene are studied for their association with cardiovascular diseases. However, no publication is available to assess the relation of 549C > T polymorphism in p22phox gene to coronary artery disease (CAD) risk. This study was to investigate the effect of the p22phox gene 549C > T polymorphism on CAD risk. METHODS: Hospital-based case-control study was conducted with 297 CAD patients and 343 healthy persons as the control group. Polymerase chain reaction and pyrosequencing using PSQ 96 MA Pyrosequencer (Biotage AB) were used to detect the polymorphisms. Multiple Logistic regression model was used to adjust the potential confounders and to estimate odds ratio (OR) with 95% confidence intervals (CIs). RESULTS: The observed genotype frequencies of this polymorphism obeyed the Hardy-Weinberg equilibrium in both cases (P = 0.439) and controls (P = 0.668). The frequency of mutant genotypes (TT + CT) in cases (41.08%) was higher than that in controls (36.73%) with an OR = 1.20 (95%CI = 0.87-1.65). After the adjustment of the potential confounders, there was a significant association of the mutant genotypes with increased risk of CAD (OR = 1.57, 95%CI = 1.01-2.46, P = 0.047). CONCLUSIONS: The mutant genotypes of the p22phox gene 549C > T polymorphism had a significant effect on the increased risk of CAD in this studied population.

Ethyl pyruvate reduces mortality in an endotoxin-induced severe acute lung injury mouse model.

BACKGROUND: Ethyl pyruvate (EP) was recently identified as an experimental therapeutic agent in a wide variety of model systems for inflammation-mediated tissue and cellular injury. OBJECTIVE: To evaluate the effect of ethyl EP on improving the survival in mice with LPS-induced acute lung injury (ALI). METHODS: ALI was induced by administering lipopolysaccharide (LPS) intratracheally. The mice were treated intraperitoneally (i.p.) with 100, 50 and 10 mg/kg EP immediately before intratracheal instillation of LPS, and 100 mg/kg EP was administered 0, 12, 24 and 48 hours after induction of ALI. The mortality rate was recorded and analyzed by the Kaplan-Meier method. Serum tumor necrosis factor (TNF)-alpha, interleukin (IL) -6 and IL-1 beta were measured in bronchial alveolar lavage fluid using an enzyme-linked immunosorbent assay. High-mobility group box 1 levels were measured by Western immunoblotting. RESULTS: Treatment with EP significantly inhibited the release of HMGB1, TNF-alpha, IL-6 and IL-1beta into bronchoalveolar lavage (BAL) fluids of ALI mice, and reduced the permeability index of the injured lung. High EP doses reduced the mortality from ALI and the permeability index (100 mg/kg and 50 mg/kg EP versus control; P < 0.0001). Early administration of high-dose EP significantly increased survival rate (0, 12 and 24 h versus control; P < 0.0001, P < 0.0001 and P = 0.01 respectively by log-rank test). There was no survival advantage when EP was initiated at 48 h. CONCLUSION: Ethyl pyruvate improves survival and reduces the lung permeability index in mice with LPS-induced ALI.

Serum high mobility group box protein 1 as a clinical marker for non-small cell lung cancer.

AIM: The role of high mobility group box protein 1 (HMGB1) in non-small cell lung cancer (NSCLC) is unknown. We investigated the contributions of HMGB1 in NSCLC, and analyze the correlation between HMGB1 and clinicopathologic outcomes. PATIENTS AND METHODS: A total of 145 patients with diagnosed NSCLC, and 77 patients with diagnosed chronic obstructive pulmonary disease (COPD) (51 chronic bronchitis and 26 obstructive pulmonary emphysema), and 49 healthy volunteers were enrolled from January 2005 through July 2008. HMGB1 levels were analyzed by Western blot analysis. RESULTS: The mean value of serum HMGB1 levels in 145 patients with lung cancer was 76.1+/-37.0ng/ml and was significantly higher than those in 77 COPD patients (39.8+/-10.8ng/ml), and 49 healthy control (7.7+/-6.1ng/ml, p<0.0001, respectively); The serum HMGB1 levels were 30.2+/-5.9ng/ml, 60.9+/-22.5ng/ml, 99.0+/-23.1ng/ml and 133.4+/-18.9ng/ml in patients with NSCLC of TNM stage I, II, III, and IV. There were significant differences among four groups (p<0.0001). Moreover, the significant positive correlation between the levels of serum HMGB1 and the size of tumor (r=0.799, p<0.001); The serum HMGB1 levels were 57.2+/-28.8ng/ml in patients with NSCLC before operation, and 26.5+/-14.7ng/ml one month after operation (p<0.0001). CONCLUSIONS: Our study suggests that HMGB1 may be a useful clinical marker for evaluating the NSCLC progression and is of potential prognostic value.

[Study on the risk factors of hypertension among rural residents in mid-west areas of Shandong province, using the classification tree analysis methodology].

OBJECTIVE: To explore the risk factors of hypertension and risk population for adults aged > or = 25 in the mid-western rural areas of Shandong province and to provide evidence for development of intervention measure. METHODS: Subjects aged > or = 25 were selected by multi-stage stratified random sampling method. All participants were interviewed with a standard questionnaire and physically examined on height, weight, waist circumference, blood pressure and fasting plasma glucose (FPG). Classification tree analysis was employed to determine the risk factors of hypertension and high risk populations related to it. RESULTS: The major risk factors of hypertension would include age, abdominal obesity, overweight or obesity, family history and high blood sugar. The major populations at high risk would include populations as: a) being elderly, b) at middle-age but with: high blood sugar or with abdominal obesity/overweight, or with family history, c) people at middle-age but with family history and abdominal obesity. Through classification tree analysis, sensitivity, specificity and overall correct rates were 71.87%, 66.38% and 68.79%, respectively on 'learning sample' while 70.70%, 65.84% and 67.97% respectively on 'testing sample'. CONCLUSION: Efforts on both weight and blood sugar reduction were common prevention measures for general population. Different kinds of prevention and control measures should be taken according to different risk factors existed in the targeted high-risk population of hypertension. Community-based prevention and control for hypertension measures should be integrated when targeting the population at high risk.

Chemoembolization combined with radiofrequency ablation for patients with hepatocellular carcinoma larger than 3 cm: a randomized controlled trial.

CONTEXT: Transarterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) therapy has been used for patients with large hepatocellular carcinoma tumors, but the survival benefits of combined treatment are not known. OBJECTIVE: To compare rates of survival of patients with large hepatocellular carcinoma tumors who received treatment with TACE combined with RFA therapy (TACE-RFA), TACE alone, and RFA alone. DESIGN, SETTING, AND PATIENTS: Randomized controlled trial conducted from January 2001 to May 2004 among 291 consecutive patients with hepatocellular carcinoma larger than 3 cm at a single center in China. INTERVENTION: Patients were randomly assigned to treatment with combined TACE-RFA (n = 96), TACE alone (n = 95), or RFA alone (n = 100). MAIN OUTCOME MEASURES: The primary end point was survival and the secondary end point was objective response rate. RESULTS: During a median 28.5 months of follow-up, median survival times were 24 months in the TACE group (3.4 courses), 22 months in the RFA group (3.6 courses), and 37 months in the TACE-RFA group (4.4 courses). Patients treated with TACE-RFA had better overall survival than those treated with TACE alone (hazard ratio [HR], 1.87; 95% confidence interval [CI], 1.33-2.63; P < .001) or RFA (HR, 1.88; 95% CI, 1.34-2.65; P < .001). In a preplanned substratification analysis, survival was also better in the TACE-RFA group than in the RFA group for patients with uninodular hepatocellular carcinoma (HR, 2.50; 95% CI, 1.42-4.42; P = .001) and in the TACE-RFA group than the TACE group for patients with multinodular hepatocellular carcinoma (HR, 1.99; 95% CI, 1.31-3.00; P < .001). The rate of objective response sustained for at least 6 months was higher in the TACE-RFA group (54%) than with either TACE (35%; rate difference, 0.19; 95% CI, 0.06-0.33; P = .009) or RFA (36%; rate difference, 0.18; 95% CI, 0.05-0.32; P = .01) treatment alone. CONCLUSION: In this patient group, TACE-RFA was superior to TACE alone or RFA alone in improving survival for patients with hepatocellular carcinoma larger than 3 cm. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00479050.

[Association between G894T mutation in endothelial nitric oxide synthase gene and premature coronary heart disease].

OBJECTIVE: To assess the association between G894T (Glu298Asp) mutation in exon 7 of the endothelial nitric oxide synthase gene and premature coronary heart disease (P-CHD). METHODS: Hospital-based case-control study was conducted. Newly-diagnosed CHD patients were recruited as study subjects. 132 CHD patients diagnosed at/before age 55 for males and 65 for females were assigned to P-CHD case group with other 172 CHD patients as the control group. Polymerase chain reaction with Ban II restriction enzyme digestion was performed to detect the G894T mutation. RESULTS: G894T mutant genotypes in P-CHD group (TT, GT and GG frequencies were 6.06%, 20.45% and 73.48%, respectively) were significant higher than those in control group (TT, GT and GG frequencies were 1.74%, 11.63% and 86.63%, respectively) (P = 0.01). Mutant T allele frequency in P-CHD group was also significantly higher than that in control group (16.29% versus 7.56%, P = 0.001, OR = 2.38, 95% CI: 1.38 - 4.16). Stepwise multiple logistic regression analysis at 0.05 significant level with sex, smoking, alcohol drinking, and overweight covariates indicated that G894T mutation also having significant effect on P-CHD (P = 0.01, OR = 2.25, 95% CI: 1.19 - 4.26). CONCLUSION: This study suggested that G894T mutation in endothelial nitric oxide synthase gene might serve as a major risk factor to the pathogenesis of P-CHD in this study population.

Characterization of Orientia tsutsugamushi strains isolated in Shandong Province, China by immunofluorescence and restriction fragment length polymorphism (RFLP) analyses.

In order to identify the characteristics of the Sta56 gene of the 23 isolates of Orientia (O.) tsutsugamushi isolated in Shandong Province, indirect immunofluorescence assay (IFA) was used to identify the gene type of 23 strains O. tsutsugamushi isolated from scrub typhus patients, chigger mites, and rodents. Restriction fragment length polymorphism (RFLP) analysis was also used to analyze the restriction profiles of the Sta56 gene PCR amplification products of the 23 isolated strains of the O. tsutsugamushi; the results were compared with those acquired by nested PCR. By IFA, 21 of the 23 isolates belonged to the Gilliam type, and 2 to the Karp type. Using RFLP analysis, 21 strains had similar restriction profiles to the Japan Kawasaki strain, but they had no restriction site Hha I, and thus had some difference in gene sequence compared with the Japan Kawasaki strain. The other 2 strains had similar restriction profiles to Karp. These results were identical to that acquired by nested-PCR. In Shandong Province, the gene types of epidemic O. tsutsugamushi strains were similar to the Japan Kawasaki type, but had some differences in gene sequence. In addition, Karp also existed.

[Relationship between mutation of exon G894 T of endothelial nitric oxide synthase gene and overweight to essential hypertension].

OBJECTIVE: To explore the relationship between the 7th exon G894T mutation of endothelial nitric oxide synthase (eNOS) gene and overweight in patients with essential hypertension. METHODS: Totally, 116 patients with essential hypertension taking no medications and 136 normotensives were selected from a steel workers as study subjects. Polymerase chain reaction and restriction fragment length polymorphism were performed to detect mutation of the 7th exon G894T. Additive model was used to analyze interaction between G894T mutation and overweight on hypertension. Population attributable risk percent (PAR%) for them, etiologic fraction, was applied to their contribution to hypertension. RESULTS: There was a positive interaction between G894T mutation and overweight on essential hypertension, with an index of interaction of 1.99 and attributable interaction percent of 30.76%. Their pure attributable interaction percent was 36.38%. Multiple logistic regression analysis showed that there still was positive interaction between G894T mutation and overweight on essential hypertension, adjusted for age, sex, smoking and alcohol drinking. Index of their attributable interaction was 2.85, with attributable interaction percent of 39.97%, also adjusted for the above-mentioned factors. Their pure attributable interaction percent was 46.49% and PAR% was estimated as about 15% under certain condition. CONCLUSIONS: Interaction between mutation of the 7th exon G894T of eNOS gene and overweight played an important role in essential hypertension of the studied population. Control of body weight in the population with both G894T mutation and overweight could markedly decrease their risk of hypertension.

[Effects of G894T mutation in the endothelial nitric oxide synthase gene on blood pressure].

OBJECTIVE: To analyze the association between G894T (Glu298Asp) mutation at exon 7 in the endothelial nitric oxide synthase gene and essential hypertension. METHODS: One hundred and sixteen essential hypertensives without taking hypertensive medication and 136 normotensives screened from health workers in a steel factory were selected as subjects in this study. Polymerase chain reaction (PCR) and Ban II restriction enzyme digestion were performed to detect the G894T mutation. RESULTS: G894T mutation was significantly associated with essential hypertension. The T allele frequency in essential hypertensive group was significantly higher than that in normotensive group (16.0% versus 8.8%, P = 0.019, OR = 1.96, 95% CI: 1.14 - 3.37). The levels of systolic blood pressure and diastolic blood pressure in the G894T mutant genotypes were all significantly elevated in hypertensive, normotensive, and the total subjects (P < 0.05). After adjusting factors as age, sex, smoking, alcohol drinking, body mass index, triglyceride, serum total cholesterol, serum high density lipoprotein cholesterol by analysis of multiple covariance, significant positive effect of the G894T mutant genotypes on blood pressure in the total subjects (P < 0.01) was noticed. CONCLUSION: This study suggested that the G894T mutation in the endothelial nitric oxide synthase gene might serve as a major risk factor of essential hypertension in this study population.