[Effects of Dapagliflozin on contrast-induced acute kidney injury in patients with type 2 diabetes mellitus underwent percutaneous coronary intervention].

Objective: To investigate the effect of Dapagliflozin, sodium-glucose cotransporter 2 inhibitor (SGLT2i), on contrast-induced acute kidney injury (CIAKI) in patients with type 2 diabetes mellitus (T2DM) after percutaneous coronary intervention(PCI). Methods: A cohort study. The clinical data of 366 patients with coronary heart disease combined with T2DM who underwent PCI in the Department of Cardiology, Tianjin University Chest Hospital, from June 2021 to June 2022 were retrospectively analyzed, including 218 males and 148 females, aged (64.6±11.0) years old. According to whether the patients had used Dapagliflozin or not, the selected patients were divided into SGLT2i group(n=124) and control group(n=242). The changes in cardiac indicators, renal function, and inflammatory response indicators before and 72 hours after PCI treatment were analyzed and compared between the two groups. The incidence rate of CIAKI in the two groups was analyzed, and the influencing factors of CIAKI were analyzed by multivariate logistic regression. The major adverse cardiac events (MACE) were recorded during the follow-up period of the two groups, and Kaplan-Meier survival analysis and log-rank test were used to compare the differences in MACE occurrence between the two group. Results: The left ventricular ejection fraction (LVEF) of the SGLT2i group was lower than that of the control group, and the proportion of patients with LVEF<45% and CIAKI risk score were higher than those of the control group, with statistical significance (all P<0.05). 72 h after PCI treatment, ß-2 Microglobulin(ß-2MG), cystatin-C(Cys-C), and neutrophil gelatinase-associated lipocalin (NGAL) in both groups were all increased compared to those before PCI treatment, with statistical significance (all P<0.05).ß-2MG, Cys-C, and NGAL in SGLT2i group were all lower than those in the control group, with statistical significance(all P<0.05).The levels of interleukin-6(IL-6), hypersensitive C-reactive protein (hs-CRP), and malondialdehyde in both groups of patients increased compared to preoperative levels, while the levels of superoxide dismutase (SOD) decreased compared to preoperative levels, with statistical significance (all P<0.05). The levels of IL-6, hs-CRP, and malondialdehyde in the SGLT2i group were lower than those in the control group, while SOD was higher than that in the control group, with statistical significance (all P<0.05). Among all patients included, 34 cases experienced CIAKI (9.8%), and the incidence of CIAKI in the SGLT2i group was lower than that in the control group [4.8% (6/124) vs 11.6% (28/242),P=0.037]. Multivariate logistic regression analysis showed that the use of dapagliflozin was a protective factor for CIAKI in T2DM patients receiving PCI treatment (OR=0.321, 95%CI: 0.127-0.816, P=0.017). After a follow-up of 14.0 (12.0, 16.2) months, the incidence of MACE in SGLT2i group was lower than that in the control group (7.3% vs 12.8%, P=0.048). Conclusions: Dapagliflozin may reduce the risk of CIAKI and MACE in T2DM patients after PCI treatment. Its mechanism may be related to the anti-inflammatory and antioxidant effects of SGLT2i.

Rational design and latest advances of codelivery systems for cancer therapy.

Current treatments have limited effectiveness in treating tumors. The combination of multiple drugs or treatment strategies is widely studied to improve therapeutic effect and reduce adverse effects of cancer therapy. The codelivery system is the key to realize combined therapies. It is necessary to design and construct different codelivery systems in accordance with the variable structures and properties of cargoes and vectors. This review presented the typical design considerations about codelivery vectors for cancer therapy and described the current state of codelivery systems from two aspects: different types of vectors and collaborative treatment strategies. The commonly used loading methods of cargoes into the vectors, including physical and chemical processes, are discussed in detail. Finally, we outline the challenges and perspectives about the improvement of codelivery systems.

LINC00511 accelerates the proliferation of cardiomyocytes after myocardial ischemia/reperfusion injury by absorbing miRNA-515-5p.

OBJECTIVE: The aim of this study was to clarify the role of LINC00511 in regulating the proliferative ability of cardiomyocytes undergoing ischemia/reperfusion (I/R) injury by absorbing miRNA-515-5p. MATERIALS AND METHODS: Adult male C57BL/6 mice were subjected to I/R injury, and I/R model was constructed in vivo. Primary cardiomyocytes were isolated from 1-2 days-old male mice and treated with H2O2 to establish the I/R model in vitro. The relative expression level of LINC00511 was determined after ligation of the anterior descending coronary artery (LAD) in mice or H2O2 induction in primary cardiomyocytes for different time points, respectively. The regulatory effect of LINC00511 on the viability of H2O2-treated cardiomyocytes was assessed. Subsequently, the interaction between LINC00511 and miRNA-515-5p was evaluated by Dual-Luciferase Reporter Gene Assay. Furthermore, the viability and 5-Ethynyl-2'-deoxyuridine (EdU)-positive rate influenced by LINC00511/miRNA-515-5p were examined. RESULTS: LINC00511 was gradually downregulated with the prolongation of I/R procedures in mice or H2O2 treatment in primary cardiomyocytes. The overexpression of LINC00511 significantly elevated the viability and EdU-positive rate in H2O2-treated cardiomyocytes. LINC00511 could bind to miRNA-515-5p. Meanwhile, there was a negative correlation between the levels of LINC00511 and miRNA-515-5p. In addition, the overexpression of miRNA-515-5p reversed the promoting effect of LINC00511 on the proliferative ability of H2O2-treated cardiomyocytes. CONCLUSIONS: LINC00511 accelerates the proliferation of cardiomyocytes after I/R by targeting miRNA-515-5p.

[A meta-analysis on the association between genetic polymorphisms of osteoprotegerin and cardiovascular disease].

Objective: To explore the association between genetic polymorphisms of rs2073617T/C (950T/C) and rs2073618G/C(1181G/C) in the osteoprotegerin gene and cardiovascular disease with meta-analysis. Methods: A computer-based search for the study of relationship between genetic polymorphisms of rs2073617T/C and rs2073618G/C in the osteoprotegerin gene and cardiovascular disease were performed in electronic databases including China National Knowledge Infrastructure(CNKI), China Biomedical Literature Database, Wanfang Database, Chinese Journal Full-text Database, Embase, PubMed, and Cochrane Library, supplemented by manual search, from the beginning of library to February 28, 2017. The quality of the included studies were assessed by the Newcastle-Ottawa Scale (NOS) scoring system. Data were analyzed using STATA 12.0 software. Results: Eleven clinical case-control studies that enrolled 2 115 patients with cardiovascular disease and 1 467 healthy subjects were included.The results indicated that osteoprotegerin gene polymorphisms of rs2073617T/C and rs2073618G/C might be closely associated with the susceptibility to cardiovascular disease(rs2073617T/C allele model: OR=0.79, 95%CI 0.73-0.87, P=0.001;rs2073618G/C M allele and W allele: OR=0.83, 95%CI 0.74-0.92, P=0.001). The osteoprotegerin gene polymorphisms of rs2073617T/C and rs2073618G/C were significantly related to the incidence of coronary artery disease and acute coronary syndrome(coronary artery disease allele model: OR=0.83, 95%CI 0.75-0.92, P=0.001; acute coronary syndrome allele model: OR=0.73, 95%CI 0.62-0.85, P<0.001). However, there was no significant correlation between the genetic polymorphisms of these two sites and the lesion vessel number of coronary artery (rs2073617T/C allele model:OR=1.00, 95%CI 0.81-1.24, P=0.985;rs2073618G/C allele model:OR=0.98, 95%CI 0.80-1.21, P=0.626). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and polymerase chain reaction-ligase detection reaction(PCR-LDR) evidenced the association between osteoprotegerin gene polymorphisms and cardiovascular disease(allele model: OR=0.79, 95%CI 0.72-0.86, P<0.001), but no obvious relationship was found with fluorogenic quantitative detection and molecularprobe(allele model: OR=0.86, 95%CI 0.65-1.12, P=0.263). Conclusion: This meta-analysis indicates that the osteoprotegerin gene polymorphisms of rs2073617T/C and rs2073618G/C may be closely related to the increased risk of cardiovascular disease.

[Effect of probucol on preventing contrast-induced nephropathy in patients undergoing percutaneous coronary intervention].

Objective: To investigate the preventive effect, possible mechanism and safety of probucol on contrast-induced nephropathy (CIN) after percutaneous coronary intervention (PCI) in patients with coronary heart disease (CHD). Methods: A total of 641 patients with coronary heart disease were consecutively enrolled from Department of Cardiology, in Tianjin Chest Hospital, Tianjin TEDA International Cardiovascular Hospital, Tianjin First Central Hospital, Tianjin Fourth Central Hospital. They were randomly divided into probucol group (n=321) and control group (n=320). The probucol group was given oral probucol 500 mg twice daily for day 0 to day 3 after PCI; the control group was given only conventional therapy. All patients were given intravenous drip 0.9% sodium chloride solution before 12 to 24 hours of operation. The levels of serum creatinine (Scr), blood urea nitrogen (BUN), evaluate glomerular filtration rate (eGFR), cystatin C (Cys-C), and high-sensitivity C-reactive protein (hs-CRP), neutrophil gelatinase associated lipocalin (NGAL), superoxide dismutase (SOD) and glutathione (GSH) were measured before and 72 h after the PCI operation in both groups. The incidence rates of CIN, the adverse events during hospitalization and postoperative 14-day follow-up were recorded in two groups. Results: There was no statistically significantly difference in the levels of Scr, BUN, eGFR, Cys-C, hs-CRP, NGAL, SOD and GSH between the two groups before PCI (P>0.05). The levels of serum Scr, BUN, Cys-C, hs-CRP, NGAL, SOD and GSH after operation in the two groups were higher than those before the operation (P<0.05). The levels of hs-CRP and NGAL in the probucol group were lower than those in the control group [(10±4) vs (11±4)mg/L, (25±8)vs (34±7)U/ml, P<0.05]. The levels of eGFR, SOD and GSH in probucol group were higher than those in control group [(80±27) vs (72±26) ml·min(-1)·1.73 m(-2,) (67±9) vs (58±8)U/ml, (4.6±0.9) vs (3.9±0.8)U/ml, P<0.05]. The incidence of CIN was 4.0% in the probucol group and 10.9% in the control group, and the difference was statistically significant (P<0.05, χ(2)=-3.31). Multivariate Logistic regression analysis showed that probucol was an independent protective factor for CIN (OR=0.334, 95%CI 0.172-0.648, P=0.001). There were no adverse events such as myasthenia gravis, abnormal liver function and cardiovascular events during the hospitalization and 14-day follow-up. Conclusions: Probucol can reduce the incidence of contrast-induced nephropathy after PCI. The protection mechanism is related with its anti-inflammatory and anti-oxidative stress effects, and it has good safety.

Could torasemide be a prophylactic agent of contrast induced acute kidney injury? A review about this field.

Contrast Induced Acute Kidney Injury (CI-AKI), due to the use of contrast media in radiographic procedures, is the leading cause of acute renal failure in hospitalized patients, and is associated with prolonged in-hospital stay and increased morbidity, mortality, and costs. However only peri-procedural hydration is now used universally as its preventive strategy. Some studies indicates that renin-angiotensin-aldosterone system (RAAS) is possibly responsible for the development of contrast-induced nephrotoxicity through mediating abnormalities of renal perfusion and other mechanisms. And torasemide, known as loop diuretics, could inhibit RAAS through its anti-aldosteronergic function. Therefore, speculation about torasemide's prevention of CI-AKI could be firmly made. Intravenously administrated torasemide would be promising as a future prophylactic agent, possibly in combination with other strategies such as adequate peri-procedural hydration and other renal protective agents, in the prevention of CI-AKI. In this context, we review the background and the role of RAAS on the development of CI-AKI, and discuss the pharmacologic individuality of torasemide on RAAS and torasemide's preventive effect on CI-AKI.