According to previous literature, venous hypoxia and the hypoxia‑inducible factor (HIF) pathway may contribute to the pathogenesis of varicose veins (VVs). It is widely accepted that the circadian locomotor output cycles kaput (CLOCK) gene affects nucleotide excision repair, DNA damage checkpoints and apoptosis in mammalian organisms; however, the expression levels of CLOCK in varicose veins remain to be elucidated. The aim of the present study was to detect the expression of the circadian clock gene in initial and advanced varicose lesions and analyze the correlation between the CLOCK gene, HIF‑1α, and its target gene, vascular endothelial growth factor (VEGF), in VVs. Sections of the great saphenous veins (GSVs) were obtained from patients undergoing ligation and stripping for VVs (n=70) and a control group undergoing coronary artery bypass grafting with GSV harvest (n=11). All VV patients had incompetent GSVs, according to color flow duplex scanning. C‑class VVs were determined according to the clinical‑etiology‑anatomy‑pathophysiology classification for venous diseases following physical examination of the patients with VV. Reverse transcription‑quantitative polymerase chain reaction was used to determine the expression levels of the CLOCK gene, HIF‑1α and VEGF. Immunohistochemical analysis was also performed. The patients with VVs were divided into those with initial varicose lesions (C3 and C4) and advanced varicose lesions (C5 and C6). In total, 21 of the patients had C3 lesions, 23 had C4 lesions, 14 had C5 lesions and 12 had C6 chronic venous disease. The expression of the CLOCK gene was significantly higher in the VV lesions of the GSV, compared with the normal GSVs (P<0.0001). The same trend was found in the expression levels of HIF‑1α and its target gene, VEGF, in the VV lesions (P=0.003 and P<0.0001, respectively). Subgroup analysis revealed that the expression levels of the CLOCK gene, HIF‑1α and VEGF were significantly higher in the advanced stage varicose lesions, compared with the initial varicose lesions (P<0.0001, P=0.0014 and P<0.0001, respectively). However, no statistically significant difference was identified in the expression levels of the aforementioned genes in the C3 and C4 lesions. The results demonstrated that the expression gene levels of CLOCK, HIF‑1α and its target gene, VEGF, increased significantly in advanced stage varicose lesions. Therefore, upregulation of the CLOCK gene in the vessel walls of veins may be involved in the pathogenesis of VVs and the progression of venous disease.

(1) Background: Epidemiological studies on the relationship between serum copper and hypertension are contradictory. We assessed the relationship between serum copper and blood pressure among adults in the United States. (2) Methods: We divided hypertension into two categories: treated hypertension and untreated hypertension. Linear or logistic regression analysis was applied to investigate the association between serum copper concentrations and blood pressure levels. (3) Results: As compared to quartile 1, the odds ratios (ORs) for untreated hypertension in quartiles 2, 3, and 4 were 1.02 (0.74–1.42), 1.23 (0.88–1.72), and 1.08 (0.74–1.58), respectively, in multivariable analysis (all p > 0.05). In non-hypertension, as compared with quartile 1, the β (95% CI) of systolic blood pressure for quartiles 2, 3, and 4 was −0.92 (−2.07–0.23), −0.05 (−1.30–1.20), and −0.48 (−1.83–0.88), respectively, in multivariable analysis (all p > 0.05). As compared to quartile 1, the ORs for treated hypertension in quartiles 2, 3, and 4 were 1.36 (0.88–2.10), 1.35 (0.87–2.09), and 1.56 (0.98–2.47), respectively, upon multivariable analysis including antihypertensive medication use as a covariate (all p > 0.05). Furthermore, 1SD increase in serum copper was non-significantly associated with 1.16 (0.97–1.37)-fold increased risk of hypertension in multivariable analysis (p = 0.096). (4) Conclusion: In the present study, we discovered that the serum copper concentration was not related with hypertension or blood pressure levels. Antihypertensive drug use may distort the correlation between copper and blood pressure levels. Information on antihypertensive drug use may be taken into account when identifying new risk factors for hypertension.

Background: This study aimed to investigate the association between abdominal aortic calcification (AAC) and coronary heart disease (CHD) in essential hypertension (EH). Methods: This study included patients diagnosed with EH during the 2013–2014 NHANES survey cycle. The study cohort was categorized into the following four groups based on their AAC-24 score: no AAC (0); mild AAC (1–4); moderate AAC (5–15); and severe AAC (16–24). Logistic regression models were used to assess the association between AAC and CHD. Restricted cubic spline curves (RCS) were used to explore possible nonlinear relationships between AAC and CHD. Results: The prevalence of CHD was found to be higher in the moderate AAC and severe AAC groups than in the group without AAC (40.1% versus 30.9%, 47.7% versus 30.9%). On a continuous scale, the fully adjusted model showed a 7% increase in the risk of CHD prevalence per score increase in AAC [OR (95% CI) = 1.07 (1.03–1.11)]. On a categorical scale, the fully adjusted model showed the risk of CHD prevalence in EH patients with moderate AAC and severe AAC was 2.06 (95%CI, 1.23–3.45) and 2.18 (1.09–5.25) times higher than that in patients without AAC, respectively. The RCS curve suggested a dose-response linear relationship between AAC and CHD. Conclusion: These findings highlight that in patients with EH, a higher severity of AAC is associated with a higher risk of CHD prevalence.

Objective: Hypertension is a major risk factor for myocardial infarction. However, the association between the dietary oxidative balance score and myocardial infarction risk among individuals with hypertension remains unclear. This study aimed to investigate the relationship between dietary oxidative balance score and the risk of myocardial infarction in hypertensive adults. Methods: In this cross-sectional study, we analyzed data from 14,137 hypertensive participants in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Dietary oxidative balance score was calculated based on the intake of 16 dietary components, including 14 antioxidants and two pro-oxidants. Logistic regression models were used to assess the association between dietary oxidative balance score and myocardial infarction, and restricted cubic splines were applied to explore potential nonlinear relationships. Results: A significant inverse association was observed between dietary oxidative balance score and myocardial infarction risk. In the fully adjusted model, each one-point increase in dietary oxidative balance score was associated with a 2.4% reduction in the odds of myocardial infarction (OR: 0.976; 95% CI: 0.966–0.985). Compared to the lowest tertile, participants in the highest dietary oxidative balance score tertile had a 28.9% lower risk of myocardial infarction (OR: 0.711; 95% CI: 0.609–0.831). Although nonlinearity was not statistically significant, a threshold effect was observed, with the most pronounced risk reduction at lower dietary oxidative balance score levels. Conclusion: Higher dietary oxidative balance score values were associated with a reduced risk of myocardial infarction in hypertensive patients. These findings suggest that dietary patterns emphasizing oxidative balance may serve as an effective strategy for myocardial infarction prevention in high-risk populations.

PDF file, 53KB, Activity of SL-176 Combined with Trastuzumab.

PDF file, 53KB, Activity of SL-176 Combined with Trastuzumab.