首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 15 毫秒
1.
Nitric oxide generated by the vascular endothelial nitric oxide synthase (eNOS) plays an important role in the regulation of vascular structure/function and blood pressure. However, information is scant regarding the influence of G894T polymorphism of the eNOS gene on arterial wall thickness in asymptomatic young adults. This aspect was examined for G894T polymorphism in 661 White and Black subjects, aged 25 to 43 years (73.2% White; 39.5% male). Arterial vascular changes were assessed by common carotid intima-media thickness (IMT) using B-mode ultrasonography. The variant T allele frequency of G894T was significantly higher in Whites compared with Blacks (0.339 vs. 0.102; P < .0001). In bivariate analysis, adjusted for gender, age, mean arterial blood pressure, and/or race, carotid IMT was marginally lower in carriers vs. non-carriers of T allele in Whites (P = .07), but significantly lower for the total number of subjects (P = .04). In multivariable regression analysis, adjusted for gender, age, mean arterial pressure, body mass index (BMI), low-density lipoprotein cholesterol, triglycerides/high-density lipoprotein cholesterol ratio, homeostasis model assessment of insulin resistance, smoking, and race (in the total sample), the variant allele was independently associated with lower carotid IMT in both the White subjects (P = .04), and total sample (P = .03). These results suggest that the allelic variation of G894T polymorphism of the eNOS gene beneficially influences vascular changes as measured by carotid IMT in asymptomatic young adults.  相似文献   

2.
The Framingham risk score (FRS), developed in a white cohort aged 30-74 years, is increasingly used in the early risk identification for coronary artery disease (CAD). This study examines the relationship between FRS and carotid artery intima-media thickness (IMT), a surrogate marker of coronary atherosclerosis, in black and white individuals aged 20-37 years. Five hundred seventeen young adults (aged 20-37 years; 71% white, 39% male) enrolled in the Bogalusa Heart Study had carotid artery ultrasonography. Age, gender, systolic blood pressure, total cholesterol to HDL cholesterol ratio, cigarette smoking habit, type 2 diabetes, and left ventricular hypertrophy (LVH) were used to calculate FRS. Results indicated a significant, positive linear relationship between tertiles of FRS and IMT of the common, bulb, and internal carotid segments in blacks and whites alike. In a multivariate analysis including FRS, race, BMI, parental history of CAD, stroke, type 2 diabetes, or hypertension, logtriglycerides, loginsulin, alcohol consumption (ml/week), and regular physical activity, the FRS was independently associated with all three carotid segments. Further, the FRS as a main predictor variable explained relatively more of the variance in the IMT of the carotid bulb (9%) than in the common (5%) or internal (3%) carotid segments. These results support the use of FRS in both white and black young adults and underscore the importance of prevention and control of multiple risk factors in youth.  相似文献   

3.
Decreased arterial elasticity, an independent risk factor for cardiovascular (C-V) disease, is associated with C-V risk factors in middle-aged and older individuals. However, information is limited in this regard in young adults. This aspect was examined in a community-based sample of 516 black and white subjects aged 25-38 years (71% white, 39% male). The common carotid artery elasticity was measured from M-mode ultrasonography as Peterson's elastic modulus (Ep) and relative wall thickness-adjusted Young's elastic modulus (YEM). Blacks and males had higher Ep (P < 0.05); males had higher YEM (P < 0.0001); and blacks had higher wall thickness (P < 0.01). For the entire sample adjusted for race and gender both Ep and YEM correlated significantly (P < 0.05-0.0001) with age, BMI, waist, systolic and diastolic blood pressures, heart rate, product of heart rate and pulse pressure, triglycerides, total cholesterol to HDL cholesterol ratio, insulin and glucose. In a multivariate regression model that included hemodynamic variables, systolic blood pressure, product of heart rate and pulse pressure, age, triglycerides, BMI, and male gender (for YEM only) were independent correlates of Ep (R2 = 0.38) and YEM (R2 = 0.25). When the hemodynamic variables were excluded from the model, age, triglycerides, BMI, black race (Ep only), male gender, parental history of hypertension, HDL cholesterol (inverse association), and insulin (marginal significance) remained independent correlates of Ep (R2 = 0.20) and YEM (R2 = 16). Both Ep and YEM increased (P for trend P < 0.0001) with increasing number of independent continuous risk factors (defined as values above or below the age, race, and gender-specific extreme quintiles) that were retained in the regression models. The observed increasing arterial stiffness (or decreased elasticity) with increasing number of risk factors related to insulin resistance syndrome in free-living, asymptomatic young adults has important implications for prevention.  相似文献   

4.
BACKGROUND: Femoral artery intima-media thickness (IMT), like carotid IMT, is a surrogate indicator of atherosclerotic coronary and peripheral vascular diseases in middle-aged and older adults. This study examined the cardiovascular disease risk profile of asymptomatic young adults with increased femoral artery IMT. METHODS: Femoral artery IMT was measured by B-mode ultrasonography in 1080 black and white subjects (aged 24-43 years; 71% white, 43% male) enrolled in the Bogalusa Heart Study. Individuals in the top (n=54) versus bottom fifth (n=54) percentiles distribution of femoral IMT were compared for traditional cardiovascular risk factors profile. Univariate analysis compared the two groups, t-tests and chi tests were performed. RESULTS: The top and bottom fifth percentiles of IMT differed with respect to age (P<0.001), systolic blood pressure (P<0.05), diastolic blood pressure (P<0.05), total cholesterol (P<0.01), low-density lipoprotein (LDL) cholesterol (P<0.001), non-high-density lipoprotein (HDL) cholesterol (P<0.01) and smoking status (P<0.01). In terms of prevalence of clinically defined traditional risk factors, individuals at the top versus bottom fifth percentile of IMT distribution had significantly higher prevalence of high LDL cholesterol (>OR=130 mg/dL), non-HDL cholesterol (>OR=160 mg/dL), and cigarette smoking. The odds ratio for individuals with three or more risk factors versus no risk factors having IMT in the top fifth percentile was 4.7 (P=0.01). CONCLUSION: The observed adverse effect of cardiovascular risk factors on IMT of femoral artery, a surrogate measure of coronary and peripheral atherosclerosis, in asymptomatic young individuals underscores the need for risk factors profiling in early life. These observations have important implications in preventive medicine.  相似文献   

5.
Femoral artery intima-media thickness (IMT), like carotid IMT, is a surrogate indicator of atherosclerotic coronary and peripheral vascular diseases in middle-aged and older adults. Although risk factors for coronary artery disease are also associated with increased IMT, especially as measured in carotid arteries, there is a paucity of information with respect to the femoral artery in this regard in the asymptomatic, younger adult population. This study examined the impact of multiple risk factors on the common femoral artery IMT as measured by B-mode ultrasonography in 1,080 black and white subjects aged 24 to 43 years (71% white and 43% men) enrolled in the Bogalusa Heart Study. Femoral IMT showed gender difference (men more than women, p = 0.001), but no racial difference. In a multivariate model, systolic blood pressure, age, male gender, cigarette smoking, and total cholesterol/high-density lipoprotein cholesterol ratios related independently, in that order, to IMT. Mean IMT increased with an increasing number of risk factors defined as values above the age-, race-, and gender-specific 75th percentile of systolic blood pressure, waist circumference, total cholesterol/high-density lipoprotein cholesterol ratio, and insulin along with smoking status (p for trend = 0.003), with respective mean IMT values of 0.66, 0.69, 0.73, and 0.79 mm for 0, 1 to 2, 3, and 4 to 5 risk factors. The odds ratio for patients with >/=3 risk factors versus no risk factors having IMT in the top fifth percentile was 4.7 (p = 0.01). The observed adverse trend of increasing femoral IMT with an increasing number of risk factors in free-living, asymptomatic young subjects underscores the need for multiple risk factors profiling in early life. Further, ultrasonography of the femoral artery in conjunction with multiple risk factor profiling can be helpful in risk stratification.  相似文献   

6.
Although risk factors for coronary artery disease are also associated with increased carotid artery intima-media thickness (IMT) as measured by B-mode ultrasonography in middle-aged and older persons, information on the impact of multiple risk factors on the IMT of different segments of the carotid artery in young adults is limited. This relation was examined in a sample of 518 black and white subjects (mean age 32 years; 71% white, 39% male) enrolled in the Bogalusa Heart Study. IMT was thicker and more skewed in the bulb compared with other carotid segments. Race differences (blacks more than whites) were noted for the common carotid (p <0.001) and carotid bulb (bifurcation) IMT (women only, p <0.001). Men had a greater IMT in the common carotid (p <0.05), internal carotid (p <0.05), and carotid bulb (whites only, p <0.001). In a multivariate analysis, systolic blood pressure, race, age, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol weree entered into a model in that order and accounted for the 16.7% variance in the common carotid IMT; age, systolic blood pressure, HDL cholesterol, LDL cholesterol, race, and insulin levels explained the 19.4% variance in the carotid bulb IMT. Gender and body mass index (BMI) accounted for the 4.7% variance in the internal carotid IMT. Increases in IMT with increasing number of risk factors (cigarette smoking, higher total cholesterol to HDL cholesterol ratio, higher systolic blood pressure, greater waist circumference, and higher insulin level) were noted for the common carotid and carotid bulb segments (p for trend <0.001 for both). The observed deleterious trend of increasing IMT at different carotid segments with increasing number of risk factors in free-living, asymptomatic young subjects underscores the importance of profiling multiple risk factors early in life. Ultrasonography of carotid arteries, especially at the bifurcation, may be helpful along with measurements of risk factors for evaluation of asymptomatic atherosclerotic disease.  相似文献   

7.
8.
IntroductionGender divergence on the impact of multiple cardiovascular risk factors on the femoral artery intima-media thickness (IMT) has not been studied in a biracial (black-white) community-based asymptomatic young adults.MethodsFemoral IMT was measured by B-mode ultrasonography in 1080 individuals (age, 24–43 years; 71% white; 43% men) enrolled in the Bogalusa Heart Study.ResultsFemoral IMT showed a gender difference (men > women; P = 0.001), but no racial difference. In a multivariate model, age, cigarette smoking, systolic blood pressure and total cholesterol to high-density lipoprotein cholesterol ratio related independently, in that order, to IMT in women, and age and low-density lipoprotein cholesterol in men. In women, mean IMT increased with increasing number of risk factors defined as values above the age-, race- and gender-specific 75th percentile of systolic blood pressure, waist circumference, total cholesterol to high-density lipoprotein cholesterol ratio and insulin along with positive smoking status (P for trend = 0.001), with respective mean IMT (mm) values of 0.61, 0.65, 0.72 and 0.77, for 0, 1 to 2, 3 and 4 to 5 risk factors. There was no such significant trend in men.ConclusionsAlthough men versus women had thicker IMT, the observed increasing trend of femoral IMT with increasing number of risk factors in asymptomatic young women suggests that women may be relatively more susceptible to the burden of multiple risk factors.  相似文献   

9.
10.
OBJECTIVE: Although obese children are at increased risk for coronary heart disease in later life, it is not clear if this association results from the persistence of childhood obesity into adulthood. We examined the relation of adiposity at various ages to the carotid intima-media thickness (IMT) at age 35 y. DESIGN: Prior to the determination of IMT by B-mode ultrasound, subjects (203 men, 310 women) had, on average, six measurements of body mass index (BMI) and triceps skinfold thickness (TSF) between the ages of 4 and 35 y. Mixed regression models for longitudinal data were used to assess the relation of these characteristics to adult IMT. RESULTS: Overall, adult IMT was associated with levels of both BMI and TSF (P<0.001), with the magnitudes of the associations with childhood adiposity comparable to those with adult levels of BMI and TSF. Furthermore, adult obesity modified the association between childhood adiposity and IMT: high IMT levels were seen only among overweight (BMI > or =95th percentile) children who became obese (BMI > or =30 kg/m2) adults (P<0.01 for linear trend). In contrast, IMT levels were not elevated among (1) overweight children who were not obese in adulthood, or among (2) thinner children who became obese adults. CONCLUSIONS: These results emphasize the adverse, cumulative effects of childhood-onset obesity that persists into adulthood. Since many overweight children become obese adults, the prevention of childhood obesity should be emphasized.  相似文献   

11.
Paraoxanase (PON 1), a high-density lipoprotein-associated enzyme, exerts an antiatherogenic effect by protecting low-density lipoproteins (LDL) against oxidation. A common polymorphism at codon 192(Q/R) of the PON 1 gene has been shown to be associated with an adverse lipoprotein profile and increased coronary artery disease (CAD) risk. However, these observations are based mostly on case-control studies involving relatively older adults. This study examined the frequency and phenotypic (lipoprotein variables) effect of the Q192R variant in a community-based sample of 1786 black and white young adults (mean age: 32.5 years; 69% white, 44% males). In addition, the genotypic effect of this polymorphism on ultrasonographically measured carotid artery intima-media thickness (IMT), a surrogate measure of CAD risk, was examined in a subsample of 436 young adults (mean age: 32.6 years; 70% white, 42% male). The frequency of the variant allele (R192) was higher in blacks than in whites (0.668 versus 0.297, P <0.001). After adjusting for age, sex, body mass index, and smoking status, the R versus Q allele was associated with increased HDL cholesterol in whites (P=0.041), whereas the opposite was true in blacks (P=0.008). Neither the Q nor the R allele was associated with LDL cholesterol and triglycerides in both races. The genotypic effect on the carotid IMT adjusted for the covariates including lipoprotein variables was not apparent in whites or blacks. However, among whites, the carotid IMT was lower in carriers (QR + R) versus non-carriers (QQ) of the variant allele among females (P=0.008) and non-smokers (P=0.026). In addition, the variant allele negated the adverse positive relationship between the carotid IMT and triglycerides among whites (P=0.212 for carriers versus P <0.001 for non-carriers). These results indicate a differential effect of the Q192R variant on HDL cholesterol in whites versus blacks and a beneficial interaction effect of the variant allele with individual's sex, smoking status or triglyceride levels on the carotid IMT among whites.  相似文献   

12.
The authors' aim was to determine reference values and predictors for carotid intima-media thickness (CIMT) in the Bogalusa Heart Study. Carotid ultrasound images from 1203 young adults (mean age 36 years; 30% black, 43% male) were reviewed. Age-, sex-, and race-specific CIMT percentiles were estimated using multivariable regression. Nomograms of CIMT quartiles for persons aged 25 to 40 years are provided in 5-year increments. CIMT was thickest in the carotid bulb and increased linearly with age, most rapidly in the bulb. With age, composite CIMT increased most slowly in white women and more rapidly in white men and black women. Systolic blood pressure (P<.001) was the strongest predictor of composite CIMT. Male sex, total to high-density lipoprotein cholesterol ratio, and age independently predicted CIMT in all segments. This report may be used to help plan epidemiologic investigations and clinical trials investigating atherosclerosis and its changes with interventions.  相似文献   

13.
AIM: To study putative associations of the ecNOS 4 a/b polymorphism with carotid artery intima-media thickness (IMT) and diabetic complications in young type-1 diabetic patients. METHODS: Study participants were 147 type-1 diabetic patients (56 men and 91 women), mean age 30.1 +/- 6.6 years (range 14 - 44), with a diabetes duration of 13.1 +/- 8.1 years. HbA1c, albuminuria, and lipid status were assessed by standard laboratory techniques, the ecNOS 4 a/b genotype was determined by polymerase chain reaction with subsequent polyacrylamide gel electrophoresis. The patients were categorized according to the presence or absence of hypertension, nephropathy and retinopathy. The IMT, which can be used to estimate early stages of arteriosclerosis, was measured by high-resolution ultrasonography. RESULTS: The ecNOS genotypes were distributed as follows: 7.5 % a/a, 30.6 % a/b, and 61.9 % b/b. The IMT values did not differ between the patients with various ecNOS genotypes (a/a: 0.62 +/- 0.13; a/b: 0.63 +/- 0.21; b/b: 0.63 +/- 0.13; all: 0.63 +/- 0.15 mm). The prevalence of retinopathy was significantly higher in patients with the b/b genotype (odds ratio: 2.4 vs. a/a+a/b; 95 % CI, 1.1 - 5.3). CONCLUSIONS: Our results do not support the hypothesis that the ecNOS 4 a/b polymorphism interacts with the development of early carotid arteriosclerosis in young type-1 diabetic patients, but they give grounds to assume that in these patients it could influence the occurence of diabetic retinopathy.  相似文献   

14.
BACKGROUND: The adverse association between blood pressure and carotid artery intima-media thickness (IMT), a surrogate measure of subclinical atherosclerosis, is well-known. However, whether the G-6A polymorphism of the angiotensinogen (AGT) gene, a candidate gene of hypertension and vascular remodeling, modulates this relationship is unknown. METHODS: In 662 white and black subjects aged 25 to 43 years (73.4% white, 39.7% male), common carotid IMT was measured by B-mode ultrasonography. RESULTS: The variant A-6 allele frequency was higher in blacks than in whites (0.850 v 0.448, P < .0001). In a bivariate analysis, there were no differences in mean arterial blood pressure and common carotid IMT between carriers and noncarriers of the G allele in whites, blacks, or the total sample, after adjusting for gender, age, and race. In a multivariable regression analysis that included the status of the G allele (carriers versus noncarriers) along with gender, age, mean arterial blood pressure, body mass index, LDL cholesterol, triglycerides:HDL cholesterol ratio, homeostasis model assessment of insulin resistance, smoking, and race (in the total sample), mean arterial blood pressure was significantly and adversely associated with common carotid IMT in whites, blacks, and the total sample. This adverse positive relationship between mean arterial blood pressure and common carotid IMT was noted among noncarriers but not carriers of the G allele (comparison of slopes, P = .02) in the total sample. Although the interaction was not significant (P = .2 and P = .05 in whites and blacks, respectively), a trend similar to that in the total sample was found in both races. CONCLUSIONS: In a recessive manner, the genetic variant (G-6A) of the AGT gene modulates the association between blood pressure and carotid IMT in young adults.  相似文献   

15.
Objective Nitric oxide (NO) inhibits thrombus formation, vascular contraction, and smooth muscle cell proliferation. We investigated whether NO release is enhanced after endothelial NO synthase (eNOS) gene transfer in atherosclerotic human carotid artery ex vivo. Methods and Results Western blotting and immunohistochemistry revealed that transduction enhanced eNOS expression; however, neither nitrite production nor NO release measured by porphyrinic microsensor was altered. In contrast, transduction enhanced NO production in non-atherosclerotic rat aorta and human internal mammary artery. In transduced carotid artery, calcium-dependent eNOS activity was minimal and did not differ from control conditions. Vascular tetrahydrobiopterin concentrations did not differ between the experimental groups.Treatment of transduced carotid artery with FAD, FMN, NADPH, L-arginine, and either sepiapterin or tetrahydrobiopterin did not alter NO release. Superoxide formation was similar in transduced carotid artery and control. Treatment of transduced carotid artery with superoxide dismutase (SOD), PEG-SOD, PEG-catalase did not affect NO release. Conclusions eNOS transduction in atherosclerotic human carotid artery results in high expression without any measurable activity of the recombinant protein. The defect in the atherosclerotic vessels is neither caused by cofactor deficiency nor enhanced NO breakdown. Since angioplasty is performed in atherosclerotic arteries,eNOS gene therapy is unlikely to provide clinical benefit.  相似文献   

16.
Genetic susceptibility is considered an important predictor of coronary artery disease (CAD) and its risk factors. This study was conducted to assess the hypothesis that parental CAD, a surrogate measure of genetic susceptibility, increases the vulnerability of the arterial wall to adverse effects of the metabolic syndrome and the aging process in asymptomatic young adults. The study cohort consisted of 1,073 black and white subjects (29.1% black, 43.7% male) aged 25 to 44 years. Carotid intima-media thickness (IMT) of the common carotid, carotid bulb, and internal carotid segments was measured using B-mode ultrasound. Subjects with parental CAD had greater composite (average of 3 segments) carotid IMT (0.839 vs 0.802 mm, p = 0.04) and a higher prevalence of the metabolic syndrome (20.7% vs 13.3%, p <0.01) compared with those without such a history. Furthermore, the association of the metabolic syndrome with composite, carotid bulb, and internal carotid IMT was significantly stronger in subjects with parental CAD than those without such a history (p = 0.022, p = 0.032, and p = 0.035 for comparison of slopes, respectively). After adjusting for race, gender, and the metabolic syndrome components, only internal carotid IMT showed significantly more increase with age in subjects with parental CAD compared with those without such a history (regression coefficient: beta = 0.014 vs beta = 0.006, p = 0.010 for comparison of slopes). In conclusion, parental CAD amplifies the adverse effects of the metabolic syndrome and aging on carotid artery IMT, especially internal carotid IMT, in asymptomatic young adults. These findings reinforce the value of using family history of CAD in risk assessment algorithm.  相似文献   

17.
It has been established that childhood cardiovascular (CV) risk factors are predictive of adulthood vascular changes as measured by carotid intima-media thickness (IMT). However, whether this relationship is race- and gender-specific is not known. This aspect was examined in a black-white cohort of 868 adults (29% blacks, 42% males) aged 25-44 years who were examined at least twice in childhood for traditional CV risk factors with an average follow-up period of 26.4 years. The average value of the two earliest childhood measurements was used as the childhood value, standardized to age, race, and gender-specific z-score. Carotid IMT was measured by B-mode ultrasonography. The mean of the maximum carotid IMT readings of three right and three left far walls for common, bulb and internal segments was used. In univariate analysis, significant correlates of adulthood carotid IMT (standardized to age-, race- and gender-specific z-score) were, in the order of decreasing magnitude, triglyceride and LDL cholesterol in white males; systolic blood pressure, LDL cholesterol, and body mass index (BMI) in white females; systolic blood pressure in black males; BMI and systolic blood pressure in black females. In multivariate regression analysis, significant predictors of carotid IMT were triglycerides and LDL cholesterol in white males; systolic blood pressure and LDL cholesterol in white females; systolic blood pressure in black males; and BMI and LDL cholesterol in black females. In conclusion, the predictability of childhood CV risk factors for increased carotid IMT in adulthood varies by race and gender. The prevention implications of these findings need further investigation.  相似文献   

18.
19.
BACKGROUND: Coronary artery spasm plays an important role in the pathogenesis of vasospastic angina, and contributes to the development of several acute coronary syndromes. Endothelial nitric oxide synthase (ecNOS) catalyzes the synthesis of nitric oxide, which regulates vascular tone, and may be related to coronary vasospasm. The present study investigated whether coronary spasm is related to particular polymorphisms of the ecNOS gene. METHODS AND RESULTS: Spasm provocation by serial infusions of acetylcholine was performed on 165 patients who were clinically suspected of having angina. In both study patients and healthy controls (n=400), genomic polymorphisms of the ecNOS gene were determined by using polymerase chain reaction. Quantitative luminal diameter measurements of the 3 major coronary arteries were initially obtained before and after acetylcholine injection, and then after isosorbide dinitrate injection, by using a computer-assisted analysis system. Logistic multiple regression analysis identified the a/a or a/b genotype in intron 4 of ecNOS (NOS4a: p=0.0431, odds ratio (OR) 2.43) and diabetes mellitus (p=0.0060, OR 4.88) as significant predictors of coronary spasm. In the patients with NOS4a, both the induced and spontaneous contractions were augmented. CONCLUSION: The present study results indicated that NOS4a could be a good marker for coronary artery spasm.  相似文献   

20.
BACKGROUND: Cardiovascular (CV) risk factors are associated with abnormalities in vascular function and structure. Arterial distensibility decreases with age and extent of arteriosclerosis. Mediators of arteriosclerosis may affect segments of the vascular tree differently, and information is limited on vascular changes of the brachial artery. Therefore, we explored the effect of multiple CV risk factors on brachial artery distensibility (BrachD). METHODS: A cross-sectional study of CV risk factors and BrachD was performed in an ongoing epidemiologic study (the Bogalusa Heart Study). Data were collected on 803 young adults (42% male, 72% white, aged 19 to 37 years) including BrachD measured by pulse waveform analysis (DynaPulse 2000A, Pulse Metric, Inc.) CV risk factors (anthropometric, hemodynamic, and metabolic variables) were considered abnormal if ranked in the highest age-, ethnicity-, and sex-specific quartile for this population (lowest quartile for HDL). RESULTS: BrachD was significantly lower in African American than in white subjects (6.33% v 6.76% Delta/mm Hg, P < .005). An inverse linear relationship was noted between BrachD and number of CV risk factors clustering in an individual (P < .0001 trend analysis). CONCLUSIONS: In young adults, increasing numbers of adverse CV risk factors is associated with decreased brachial artery distensibility. Noninvasive brachial artery function measures are useful in measuring subclinical arteriosclerotic vascular changes.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号