Substantial data from preclinical studies have revealed the biphasic effects of statins on cardiovascular angiogenesis. Although some have reported the anti‐angiogenic potential of statins in malignant tumors, the underlying mechanism remains poorly understood. The aim of this study is to elucidate the mechanism by which simvastatin, a member of the statin family, inhibits tumor angiogenesis. Simvastatin significantly suppressed tumor cell‐conditioned medium‐induced angiogenic promotion in vitro, and resulted in dose‐dependent anti‐angiogenesis in vivo. Further genetic silencing of hypoxia‐inducible factor‐1α (HIF‐1α) reduced vascular endothelial growth factor and fibroblast growth factor‐2 expressions in 4T1 cells and correspondingly ameliorated HUVEC proliferation facilitated by tumor cell‐conditioned medium. Additionally, simvastatin induced angiogenic inhibition through a mechanism of post‐transcriptional downregulation of HIF‐1α by increasing the phosphorylation level of AMP kinase. These results were further validated by the fact that 5‐aminoimidazole‐4‐carboxamide ribonucleotide reduced HIF‐1α protein levels and ameliorated the angiogenic ability of endothelial cells in vitro and in vivo. Critically, inhibition of AMPK phosphorylation by compound C almost completely abrogated simvastatin‐induced anti‐angiogenesis, which was accompanied by the reduction of protein levels of HIF‐1α and its downstream pro‐angiogenic factors. These findings reveal the mechanism by which simvastatin induces tumor anti‐angiogenesis, and therefore identifies the target that explains the beneficial effects of statins on malignant tumors.

Objective This meta-analysis aimed to update knowledge about the association between the SLC4A7 variant rs4973768 and breast cancer incidence. Methods Studies were identified from relevant digital databases. Fixed- or random-effects models were used to calculate odds ratios and 95% confidence intervals. Statistical Q and I2 tests and sensitivity analyses were used to detect interstudy heterogeneity and test the statistical stability of overall estimates, respectively. Egger’s tests were applied to detect publication bias among included studies. In silico analysis was used to ascertain increased expression of SLC4A7 mRNA in rs4973768 with the mutant allele. Trial sequential analysis was used to calculate the study’s sample size. Results The overall odds ratios reflected a positive correlation between the SLC4A7 rs4973768 polymorphism and susceptibility to breast cancer in five genetic comparisons of alleles T and C, and tests revealed significant heterogeneity in the allele comparison. After stratification by ethnicity, heterogeneity in Asian and White populations substantially decreased (Ph = 0.984, I2 = 0%) and remained stable (Ph = 0.083, I2 = 46.3%), respectively. The mutant allele was associated with increased expression of SLC4A7 mRNA in rs4973768. The cumulative z curve indicated that our conclusions were robust. Conclusions Our updated consequence shows that the SLC4A7 rs4973768 polymorphism is associated with increased breast cancer risk.

IntroductionThis study aimed to investigate the outcome of hybrid endovenous laser ablation (EVLA, 1470 nm) and radiofrequency ablation (RFA) procedures for varicose veins (VVs).Material and methodsWe retrospectively analyzed the clinical data of patients from July 2019 to December 2020. Eighty-four patients (121 limbs) underwent hybrid EVLA procedure, and 108 patients (151 limbs) underwent RFA procedure. The outcomes, venous clinical severity score (VCSS), chronic venous disease quality-of-life questionnaire (CIVIQ-20) score and recurrence at 1, 6, and 12 months were collected.ResultsNo differences in complications or 24-h pain scores were noted between the two procedures, but a lower dosage of foam sclerosant was used in EVLA procedure than in RFA procedure (P<0.02). The postoperative VCSS and CIVIQ-20 scores in two groups were significantly decreased compared with the scores before the procedure, and no differences in scores were noted between the two procedures at 1 month. However, the VCSS and CIVIQ-20 scores for EVLA procedure were significantly better than those for RFA procedure at 6 and 12 months (P<0.05). Both procedures showed a similar great saphenous vein closure rate at 12 months. The EVLA procedure showed lower rates of overall recurrence (4.96% vs. 14.57%, OR: 3.27, 95% CI: 1.33-8.00, P=0.01) and recurrence below the knee (4.13% vs. 11.92%, OR: 3.14; 95% CI: 1.18-8.35, P=0.02). Moreover, the patient satisfaction score was greater for EVLA procedure than RFA procedure (P<0.02).ConclusionsThe hybrid EVLA (1470 nm) procedure reduces VV recurrence below the knee and results in better quality-of-life scores.