Objective:To explore the effects of microRNA-126 (miR-126) on the proliferation of human myeloid leukemia mononuclear cells (THP-1)-derived macrophages in high glucose environment and the regulatory role of miR-126 in periodontitis with diabetes.Methods:THP-1 cells were cultured in vitro and 5 &mu;g/L phorbol-12-myristate-13-acetate was applied to induce THP-1 cells differentiating into macrophages for 48 h in low glucose culture medium (5.5 mmol/L). THP-1-derived macrophages were then cultured with low glucose, medium glucose (15 mmol/L) or high glucose (25 mmol/L) media respectively. The proliferation of THP-1-derived macrophages was detected by cell counting kit-8 (CCK-8) method and the expressions of miR-126 and proliferation-associated factors were detected by quantitative real time PCR (qRT-PCR). The miR-126 mimic or inhibitor was transfected into THP-1-derived macrophages for 72 h. The proliferation of cells was detected by CCK-8 method and the expressions of miR-126 or proliferation-associated factors were detected by qRT-PCR. Results:Increasing glucose concentration decreased the proliferation of THP-1-derived macrophages (day 7, A values in low, medium and high glucose groups were 0.369±0.014, 0.214±0.009 and 0.200±0.010, respectively, P<0.01) as well as the survival rate ( P<0.05), promoted the expression of miR-126, B-cell lymphoma-2 (Bcl-2)-associated X protein (BAX) and caspase-3 ( P<0.05), and suppressed Bcl-2, phosphoinositol-3 kinase regulatory subunit 2 (PIK3R2) expression ( P<0.05). After the miR-126 mimic was transfected in cells in low glucose medium for 72 h, compared with negative control (1.005±0.118), the expression of miR-126 significantly increased (2 980.227±170.431, P<0.05), and the proliferation of THP-1 derived macrophages decreased (negative control: 1.816±0.013, mimic group: 1.310±0.048, P<0.01), the level of BAX and caspase-3 significantly increased ( P<0.01, P<0.05), PIK3R2 and Bcl-2 significantly decreased ( P<0.05, P<0.01). After the miR-126 inhibitor was transfected in cells cultured in high glucose medium for 72 h, compared with negative control (0.723±0.133), the proliferation of inhibitor group increased (0.984±0.049, P<0.05), the level of BAX and caspase-3 significantly decreased ( P<0.01, P<0.05), PIK3R2 and Bcl-2 significantly increased ( P<0.01, P<0.05). Conclusions:High glucose condition can inhibit the proliferation of THP-1-derived macrophages and increase the expression of miR-126. MiR-126 can inhibit the proliferation of THP-1-derived macrophages in high glucose environment through up-regulating the expression of BAX and caspase-3 and down-regulating the expression of PIK3R2 and Bcl-2.

OBJECTIVE To systematically evaluate the clinical efficacy of dapagliflozin in the treatment of heart failure with diabetes mellitus type 2. METHODS The clinical trials of dapagliflozin in the treatment of heart failure with diabetes mellitus type 2 were searched in Embase, PubMed, Web of Science, Cochrane Library, VIP, CNKI and Wanfang databases from the establishment of the database to March 18, 2022. The RevMan 5.3 software was used for meta-analysis, and the TSA 0.9 software was used for sequential analysis. RESULTS The 31 RCT studies meeting the criteria were finally included, involving 2 906 patients. Meta-analysis showed that compared with the control group, the experimental group significantly improved LVEF[MD=4.43, 95% CI(3.35, 5.50), P<0.000 01], total effective rate[MD=4.19, 95%CI(2.52, 6.99), P<0.000 01], and reduced NT-proBNP[MD=–451.84, 95%CI(–608.09, –295.60), P<0.000 01], LVEDD[MD=–2.74, 95%CI(–3.67, –1.82), P<0.000 01, Hb1ac[MD=–0.88, 95%CI(–1.19, –0.57), P<0.000 01], FPG[MD=–1.10, 95%CI(–1.45, –0.75), P<0.000 01], 2hPG[MD=–2.52, 95%CI(–3.37, –1.66), P<0.000 01] and the incidence of adverse reactions[MD=0.63, 95%CI(0.47, 0.83), P=0.001]. Sequential analysis showed that the effect of dapagliflozin on LVEF in patients with heart failure with type 2 diabetes was accurate, and the possibility of excluding false positive was possible. CONCLUSION The treatment of heart failure with diabetes mellitus type 2 with good efficacy and safety is achieved by dapagliflozin, but it still needs to be included in more high-quality RCT studies for further demonstration.