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Objective:To investigate whether it is by regulating interleukin 1β ( IL-1β) gene expression that androgen receptor (AR) in macrophages affects hyperphosphate-induced vascular smooth muscle cell calcification. Methods:The chromatin immunoprecipitation (ChIP) experiment was used to determine whether AR was bound to the androgen receptor element (ARE) sequence of IL-1β promoter in THP-1 cells. Whether the AR regulated IL-1β gene expression was detected by luciferase assay experiments. AR of THP-1 cells was silenced and transfected by lentivirus with vector or shRNA. Flow cytometry was used to select positive transfected cells THP-1ARsc (control) and THP-1ARsi (AR silencing) with fluorescent markers. Western blotting was used to detect AR protein levels of THP-1ARsc (control) and THP-1ARsi cells (AR silencing in monocytes). Macrophages MФARsc (control) or MФARsi (AR silencing) were induced by 50 ng/ml phorbol ester. Enzyme-linked immunosorbent assay was used to detect IL-1β expression levels of MФARsc or MФARsi conditioned medium. The human aortic smooth muscle cells (HASMC) were cultured in MФARsc or MФARsi conditioned medium with phosphate (2.5 mmol/L final concentration of sodium dihydrogen phosphate), and Alizarin red S staining was used to analyze HASMC calcification degree. Western blotting was used to detect the expression levels of RUNX2 (osteoblast marker) and SM22α (HASMC marker), and neutralization assay was performed to test IL-1β-mediating effect of macrophages AR on HASMC calcification. Results:AR was bound to ARE sequence of IL-1β promoter and regulated IL-1β gene expression. The expression level of IL-1β protein in conditioned medium of MФARsi cells decreased significantly compared to MФARsc cells ( P<0.001). Compared with MФARsc conditioned medium group, HASMC calcium deposition in MФARsi conditioned medium group decreased significantly, RUNX2 protein decreased and SM22α protein increased (all P<0.05). The degree of HASMC calcification in the MФARsi conditioned medium+IgG antibody group decreased than that in the MФARsc conditioned medium+IgG antibody group significantly, and the degree of HASMC calcification in the MФARsc conditioned medium+IL-1β antibody group decreased significantly than that in the MФARsc conditioned medium+IgG antibody group; while the degree of HASMC calcification in the MФARsi conditioned medium+IgG antibody group and MФARsi conditioned medium+IL-1β antibody group decreased than that in the MФARsc conditioned medium+IL-1β antibody group (all P<0.05). Conclusions:Macrophage AR regulates IL-1β expression by binding to ARE sequence within IL-1β promoter, and IL-1β mediates the effect of macrophage AR on hyperphosphate-induced HASMC calcification.
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Objective:To evaluate the efficacy and safety of warfarin in the treatment of atrial fibrillation (AF) in patients with maintenance hemodialysis (MHD).Methods:Studies on evaluating efficacy and safety of warfarin in maintenance hemodialysis patients with AF were searched in CNKI, Wanfang Database of Chinese Academic Journals, PubMed, Embase and Cochrane databases from January 2001 to October 2021. The data were extracted independently by two reviewers. Meta-analysis was performed with RevMan 5.2.Results:Twelve relevant studies were included, involving 30 488 patients, 7 276 in the warfarin group and 23 212 in the control group. Meta-analysis showed that warfarin had no significant efficacy for treatment of AF in patients with maintenance hemodialysis, and there was no difference in the incidence of stroke( RR=1.10, 95%CI:0.82-1.48, P=0.52)between two groups; subgroup analysis showed that there was no significant effect on ischemic stroke or hemorrhagic stroke( RR=1.06,95% CI:0.80-1.42, P=0.67; RR=1.55,95% CI:0.93-2.58, P=0.09). There was no significant difference in mortality between the two groups( RR=1.09,95% CI:0.86-1.39, P=0.48). Meanwhile, the risk of bleeding in warfarin group was higher than that in control group( RR=1.32,95% CI:1.11-1.58, P=0.002). Conclusions:Warfarin has no significant effect on the incidence of stroke and mortality, while it increases the risk of bleeding in AF patients with maintenance hemodialysis So it is not recommended to use warfarin treatment for AF in patients with maintenance hemodialysis.
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Objective To obtain the information of therapies with beta blocker in patients with heart failure in our hospital. Methods 408 hospitalized cases in 2004 and 213 outpatients from April to July in 2005 with chronic heart failure from the cardiology department were collected. Results In hospitalized cases,of 54.9% patients were prescribed beta blocker,and only 4% of them arrived at target dosage and 24.9% of them arrived at half of target dosage. 86.1% of them were given metoprolol. The maximum dosage was (54.25?34.26) mg/d,the mean was equal to the 36.17% of target dosage. Among outpatients,77.5% were taken beta blocker,and only 2.5% of them reached the target dosage and 26.6% of them reached half of target dosage; and 89.7% of them were frequently given the metoprolol,the average dosage was up to 35% of the target dosage. Conclusions There was a great gap between the clinical practice and guideline of beta blocker therapy in patients with chronic heart failure. The prescribed dose of beta blocker was lower than the target dosage.