Ziliang Ye

The effect of alprostadil on preventing contrast-induced nephropathy for percutaneous coronary intervention in diabetic patients: A systematic review and meta-analysis.

Background:At present, there are a lot of research about the effect of Alprostadil on preventing contrast-induced nephropathy for percutaneous coronary intervention (PCI) in diabetic patients, but the clinical efficacy is not consistent, so we conduct this study and therefore determine the dominant strategy for the treatment of PCI in diabetic patients based on the best evidence currently. Methods:An electronic database search was conducted in MEDLINE, Embase, Cochrane library, CBM, CNKI, VIP, and WanFang to retrieve randomized controlled trial (RCT) comparing Alprostadil versus hydration on preventing CIN for PCI in diabetic patients. Reference lists of relevant articles were also screened manually to retrieve additional ones. Two investigators independently assessed the eligibility of retrieved articles using predefined inclusion and exclusion criteria. All characteristics as well as outcome variables including incidence of CIN, blood urea nitrogen (BUN), cystatin C (CysC), glomerular filtration rate (GFR), serum creatinine (Scr), serum beta 2-microspheres (&bgr;2-MG) presented in each included study were extracted. Heterogeneity was thought to be significant when I2 > 50%. All of the meta-analytic procedures were performed by using Review Manager software, version 5.3. Results:Finally, data from 8 articles including 969 patients were included into this meta-analysis, among them, 487 patients in the experience group, and 482 patients in the control group. Meta analysis showed that the incidence of CIN in the experimental group was significantly lower than that in the control group (OR = 0.28,95%CI[0.18,0.42]). The incidence of adverse reactions in the experimental group was significantly lower than that in the control group (OR = 0.46,95%CI[0.24,0.85]). The BUN of 24 hours, 48 hours, and 72 hours in the experimental group were significantly lower than that of control group (MD = –0.77, 95%CI [−1.22, –0.32]; MD = –1.38, 95%CI [−1.83,–0.92]; MD = –2.43, 95%CI [−2.68,–2.19], respectively). The CysC of 24 hours, 48 hours, and 72 hours in the experimental group were significantly lower than that of control group (MD = –0.30, 95%CI [−0.40, –0.21]; MD = –0.54, 95%CI [−0.68,–0.41]; MD = –0.49, 95%CI [−0.63, –0.35], respectively). The GFR of 24 hours, 48 hours, and 72 hours in the experimental group were significantly higher than that of control group (MD = 7.86, 95%CI [4.44, 11.29], MD = 18.23, 95%CI [13.76,22.69], MD = 12.81, 95%CI [8.51,17.11], respectively). The Scr of 24 hours, 48 hours, and 72 hours in the experimental group were significantly lower than that of control group (MD = –9.09, 95%CI [−12.67, –5.51], MD = –19.14, 95%CI [−23.61, –14.66], MD = –6.50, 95%CI [−8.29, –4.71], respectively). The &bgr;2-MG of 24 hours, 48 hours, and 72 hours in the experimental group were significantly lower than that of control group (MD = –0.12, 95%CI [−0.27, 0.03], MD = –0.55, 95%CI [−0.71, –0.39], MD = –0.50, 95%CI [−0.60, –0.39], respectively). Conclusion:Our result suggested that comparing with conventional Hydration, Alprostadil can significantly reduce the incidence of CIN, adverse reaction, and protect renal function in PCI in diabetic patients. Due to the limitations of the quality and quantity of the articles, this conclusion still needs further research to confirm.

The clinical effect of nicorandil on perioperative myocardial protection in patients undergoing elective PCI: A Systematic Review and Meta-Analysis

Many scholars have studied the effect of nicorandil on perioperative myocardial protection in patients undergoing elective percutaneous coronary intervention (PCI), but results are inconsistent. Therefore, we performed this meta-analysis. Finally, 16 articles, including 1616 patients, were included into this meta-analysis. Meta-analysis results showed that: (1) Nicorandil can reduce the level of CK-MB after PCI, including at 6 hours, 12 hours, 18 hours and 24 hours. (2) Nicorandil can reduce the level of TnT after PCI, including at 6 hours, 12 hours, 18 hours and 24 hours. (3) Nicorandil can reduce the incidence of adverse reactions after PCI. (4) Nicorandil cannot reduce the level of MVP after PCI, including at 12 hours and 24 hours. (5) Subgroup analysis showed that nicorandil can reduce CK-MB and TnT level at 24 hours after PCI for Chinese’s population (P < 0.05), but can not reduce CK-MB and TnT level at 24 hours after PCI for non Chinese’s population (P > 0.05). Our meta-analysis indicate that nicorandil can reduce myocardial injury and reduce the incidence of adverse reaction caused by PCI for Chinese’s population, but is not obvious for non Chinese’s population. However, this conclusion still needs to be confirmed in the future.

Effects of the TLR4/Myd88/NF-κB Signaling Pathway on NLRP3 Inflammasome in Coronary Microembolization-Induced Myocardial Injury

Background/Aims: Coronary microembolization (CME) is a common complication of acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI); Myocardial inflammation, caused by CME, is the main cause of cardiac injury. TLR4/MyD88/NF-κB signaling plays an important role in the development of myocardial inflammation, but its effects on CME remain unclear. To assess the cardiac protective effects of TAK-242 (TLR4 specific inhibitor) on CME-induced myocardial injury, and explore the underlying mechanism. Methods: Cardiac function, serum c-troponin I level, microinfarct were examined by cardiac ultrasound, myocardial enzyme assessment, HBFP staining. The levels of TLR4/MyD88/NF-κB signaling and NLRP3 inflammasome pathway were detected by ELISA, qRT-PCR and western blot. Results: The results showed inflammatory responses in the myocardium after CME, with increased expression levels of pro-inflammatory factors TNF-α, IL-1β and IL-18. Meanwhile, TLR4/MyD88/NF-κB signaling and the NLRP3 inflammasome were involved in the inflammatory process. TAK-242 administration before CME effectively inhibited the inflammatory response in the rat myocardium after CME and reduced myocardial injury, mainly by inhibiting TLR4/ MyD88/NF-κB signaling and reducing NLRP3 inflammasome activation. In addition, in vitro assays with neonatal rat cardiomyocytes further confirmed that TLR4/MyD88/NF-κB signaling was significantly activated in the inflammatory response of LPS-induced cardiomyocytes, via activation of the NLRP3 inflammasome. Inhibition of TLR4/MyD88/NF-κB signaling resulted in increased survival of cardiomyocytes mainly by reducing the release of inflammatory cytokines and decreasing NLRP3 inflammasome activation. Conclusions: TLR4/MyD88/NF-κB signaling participates in the inflammatory response of the myocardium after CME, activating the NLRP3 inflammasome, promoting the inflammatory cascade, and aggravating myocardial injury. Blocking TLR4/MyD88/NF-κB signaling may help reduce myocardial injury and improve cardiac function after CME.

Role of high mobility group A1/nuclear factor-kappa B signaling in coronary microembolization-induced myocardial injury

OBJECTIVE Coronary microembolization (CME) is a common complication in percutaneous coronary intervention (PCI). Local myocardial inflammation caused by CME is the major cause of progressive cardiac dysfunction. High mobility group A1 (HMGA1)/nuclear factor-kappa B (NF-κB) signaling plays an important role in the development and progression of inflammation, but its role in CME remains unclear. This study evaluated the effect of HMGA1/NF-κB signaling on CME-induced myocardial inflammation and cardiac dysfunction. METHODS Forty Sprague-Dawley rats were randomly divided into four groups: sham, CME, CME + HMGA1 small interfering RNA (HMGA1 siRNA), and CME + scrambled siRNA (control siRNA) groups, with 10 animals each. The CME model group was established by clamping the ascending aorta and injecting microspheres through the left ventricular apex for embolization, and the sham group was established by injecting the same amount of normal saline. The HMGA1 siRNA group was injected with HMGA1 siRNA transfection complexes into the tail vein 72 h before CME modeling, and the control siRNA group was caudally injected with the same amount of scrambled siRNA 72 h before CME modeling. Twelve hours after the operation, cardiac function, serum c-troponin I level, and microinfarct size were examined. The levels of HMGA1, NF-κB p65, TNF-α, and IL-1β were detected. RESULTS Myocardial dysfunction, enhanced serum c-troponin I, and microinfarct were induced following CME. Moreover, CME induced an increased expression of HMGA1, NF-κB p65, TNF-α, and IL-1β. The HMGA1 siRNA reversed these effects by CME, while the scrambled siRNA had no effect. CONCLUSIONS HMGA1/NF-κB signaling is involved in CME-induced myocardial inflammation. Inhibition of HMGA1/NF-κB signaling attenuated the CME-induced myocardial injury and improved cardiac function, suggesting a new potential target for the prevention and treatment of CME-induced myocardial injury.

Role of TLR4/MyD88/NF-κB signaling pathway in coronary microembolization-induced myocardial injury prevented and treated with nicorandil

Coronary microembolization (CME) is a common complication during the treatment of acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI). Nicorandil can be used to prevent myocardial injury after PCI to reduce the incidence of coronary no-reflow and slow flow, and play a role in myocardial protection, suggesting that its mechanism may be related to the inhibition of CME-induced inflammation of cardiomyocytes. However, the specific mechanism remains unclear. This study investigated the myocardial protective effects of nicorandil pretreatment on CME-induced myocardial injury and the specific mechanism of its inhibition of myocardial inflammation. An CME rat model exhibited CME-induced myocardial inflammation and the elevation of serum tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-1β based on echocardiography, myocardial enzyme detection, hematoxylin and eosin (HE) and hematoxylin-basic fuchsin-picric acid (HBFP) stainings, ELISA, quantitative real-time PCR, and western blotting. Nicorandil treatment seven days before CME induction effectively inhibited myocardial inflammation, ameliorated myocardial injury, and improved cardiac function, mainly by inhibiting Toll-like receptor 4 (TLR4)-mediated myeloid differentiation primary response protein 88 (MyD88)-dependent nuclear factor-kappa B (NF-κB) signaling. Rat neonatal cardiomyocyte experiments further confirmed that nicorandil ameliorated lipopolysaccharide (LPS)-induced myocardial inflammation and improved cardiomyocyte survival. The specific mechanisms mainly involved the inhibition of TLR4/MyD88/NF-κB signaling and the reduction of the inflammatory cytokines TNF-α and IL-1β released from cardiomyocytes. In summary, nicorandil significantly protected cardiomyocytes from CME-induced myocardial injury mainly by inhibiting TLR4/MyD88/NF-κB signaling, thereby reducing the onset of CME-induced myocardial inflammation. This could be one of the important mechanisms for reducing postoperative myocardial injury via PCI-preoperative prophylactic treatment with nicorandil.

Effect of Dipeptidyl Peptidase-4 Inhibitors on Heart Failure: A Network Meta-Analysis

BACKGROUND Previous meta-analyses evaluating the effectiveness of individual dipeptidyl peptidase-4 (DPP-4) inhibitors on the risk of heart failure (HF) were limited because of the small number of trials with direct comparisons between two treatments. METHODS A Bayesian network meta-analysis was performed to investigate the relationship between DPP-4 inhibitors and the risk of HF in patients with type-2 diabetes mellitus. The primary outcome was the occurrence of HF or hospital admission for HF. RESULTS Fifty randomized controlled trials were identified. Relative to placebo, no increased risk of HF events was seen for vildagliptin (risk ratio [RR] 0.71; 95% confidence interval [CI] 0.25-1.68), sitagliptin (RR 0.86; CI 0.43-1.57), or saxagliptin (RR 0.84; 95% CI 0.33-1.61), but alogliptin was associated with a higher risk of HF (RR 2.13; 95% CI 1.06-6.26). Vildagliptin and sitagliptin were associated with a significantly decreased risk of HF compared with alogliptin. Vildagliptin had the highest probability to be the safest option with regard to the risk of HF (49.18%), followed by saxagliptin (26.56%), sitagliptin (20.76%), linagliptin (0.25%), and alogliptin (0.12%). A statistically significant inconsistency was noted in some comparisons. CONCLUSIONS The risk of HF needs to be taken into account when prescribing DPP-4 inhibitors. Evidence suggests that vildagliptin may be the least harmful agent with regard to the risk of HF. However, a statistically significant inconsistency was identified in the Bayesian network meta-analysis. Therefore, further studies are warranted to evaluate the cardiovascular safety of DPP-4 inhibitors.

Clinical effect of trimetazidine on prevention of contrast-induced nephropathy in patients with renal insufficiency: An updated systematic review and meta-analysis

Background: With the continuous development of cardiac interventional medicine, the incidence of contrast-induced nephropathy (CIN) is increasing every year, which is a serious threat to peoples physical and mental health. Trimetazidine (TMZ) is a type of anti-ischemic drug developed in recent years, which can significantly reduce the incidence of CIN. At present, a systematic review and meta-analysis was conducted to evaluate the clinical effect of TMZ on prevention of CIN in patients with renal insufficiency. However, the study did not include patients from other countries and speaking different languages. So we conducted this study to update the previous meta-analysis that investigated the effects of TMZ on prevention of CIN in patients with renal insufficiency, and provided some theoretical reference for clinical. Methods: By searching PubMed, Embase, the Cochrane Library, Web of Science, CBM, CNKI, VIP database, and Wang Fang database for randomized controlled trial, which is comparing TMZ versus conventional hydration for prevention of CIN. Two researchers independently screened literature, and then evaluated the quality of literature and extracted the relevant data. Stata 11.0 software was used for statistical analysis. Results: Finally, this updated review showed that 3 studies that were not included in the previous meta-analysis were included in our study (3 articles were published in the Chinese Journal, 1 study for CIN, 1 study for CIN, serum creatinine (Scr), and superoxide dismutase, 1 study for CIN and Scr), and 1 outcome (Scr) reflecting the change of renal function was additionally included in our study. Of the 932 studies, 6 randomized controlled trials met the criteria, including 377 patients in TMZ group and 387 patients in control group. This meta-analysis for all studies showed that TMZ can significantly reduce the incidence of CIN (relative risk 0.27, 95% confidence interval [CI] 0.16, 0.46, P = 0.000), and can decrease the level of Scr after operation, including Scr of postoperative 24 hours (standardized mean difference [SMD] −0.30, 95% CI −0.51, −0.09, P = 0.005), Scr of postoperative 48 hours (SMD −0.66, 95% CI −1.23, −0.10, P = 0.022), and Scr of postoperative 7 days (SMD −0.74, 95% CI −1.36, −0.11, P = 0.021). However, the Scr of postoperative 72 hours between TMZ group and control group has no statistical significance (P = 0.362). Conclusion: Our study showed that when comparing with conventional hydration, TMZ can significantly reduce the incidence of CIN and the level of postoperative Scr. Therefore, we could suggest that TMZ was superior to conventional hydration for the treatment of CIN in patients with renal insufficiency. However, due to the restriction of quality and number of included articles, it still needs to carry out multicenter, randomized, double-blind clinical trials to confirm this conclusion in the future.

Pinocembrin protects endothelial cells from oxidized LDL-induced injury

HighlightsPinocembrin inhibits the induction of VCAM‐1, ICAM‐1, and E‐selectin by ox‐LDL.Pinocembrin ameliorates ox‐LDL‐induced attachment of monocytes to endothelial cells.Pinocembrin suppresses ox‐LDL induced production of pro‐inflammatory cytokines.Pinocembrin attenuates ox‐LDL induced production of ROS in HAECs.Pinocembrin inhibits ox‐LDL‐induced activation of p38 and IKK&agr;/I&kgr;B&agr;/NF‐&kgr;B signaling. Abstract Oxidized low‐density lipoprotein (ox‐LDL) is a major risk factor for atherosclerosis and often causes injury to vascular endothelial cells. We found that pinocembrin, a natural antioxidant found in honey and certain herbs, protects human aortic endothelial cells (HAECs) from ox‐LDL‐induced injury. Pinocembrin suppresses the expression of pro‐inflammatory vascular adhesion molecules (VCAM‐1, ICAM‐1 and E‐selectin) and cytokines (TNF‐&agr;, IL‐1&bgr;, and IL‐8), as well as ROS production induced by ox‐LDL. Pinocembrin potently inhibits the attachment of monocytes to HAEC cells. Mechanistically, pinocembrin suppresses activation of the MAPK kinase p38 and NF‐&kgr;B pathways in the context of ox‐LDL. Our data indicate that pinocembrin is a promising versatile natural compound that can protect endothelial cells from injury.

Effect of ligustrazine on preventing contrast-induced nephropathy in patients with unstable angina

Objective Our purpose was to assess the effect of ligustrazine in the prevention of contrast-induced nephropathy (CIN) in patients with unstable angina (UA). Methods 148 patients with UA undergoing coronary angiography and/or percutaneous coronary intervention (PCI) were selected for observation; the patients were divided into a control group (group A, n=74) and a ligustrazine group (group B, n=74). Group A was given routine treatment, while group B was given routine treatment combined with ligustrazine. Serum creatinine (Scr), cystatin C and glomerular filtration rate (eGFR) concentrations were measured before and 1 day, 2 days and 3 days after treatment, and the incidence of contrast-induced nephropathy (CIN) and major cardiovascular events (MACE) were observed in both groups. Results The Scr, Cystatin C and eGRF levels in group B were better than in group A after 1 day (OR: 2.64, 95% CI: 2.47-4.98; OR: 2.66, 95% CI: 2.62-5.77; OR: 4.02, 95% CI: 3.02-5.53, respectively), 2 days (OR: 3.58, 95% CI: 2.41-4.92; OR: 2.92, 95% CI: 2.83-5.02; OR: 3.28, 95% CI: 3.24-5.14, respectively) and 3 days of treatment (OR: 3.26, 95% CI: 2.17-4.35; OR: 2.85, 95% CI: 2.26-4.02; OR: 3.19, 95% CI: 2.53-4.34, respectively). The incidence of CIN (9.26% vs 16.67%) and MACE (7.41% vs 18.51%) of group B were significantly lower than in group A (P<0.05). Conclusions Our study suggests that ligustrazine can reduce CIN and MACE in patients with UA when undergoing coronary angiography and/or PCI.

Relationship between circulating miRNA-30e and no-reflow phenomenon in STEMI patients undergoing primary coronary intervention

Abstract To investigate the relationship between miRNA-30e level in circulation and no-reflow phenomenon in patients with acute ST-segment elevation myocardial infarction (STEMI) during primary percutaneous coronary intervention (pPCI). A total of 255 consecutive patients with STEMI undergoing pPCI were enrolled in this study. These patients were divided into two groups according to the occurrence of reflow during pPCI, namely normal-reflow group with 214 cases and no-reflow group with 41 cases. The plasma levels of miRNA-30e were quantified using real-time quantitative polymerase chain reaction. The plasma levels of miRNA-30e were significantly lower in the no-reflow group as compared to the normal-reflow group (p < .05). Also, miRNA-30e was positively correlated with left ventricular ejection fraction (LVEF) and negatively correlated with hs-CRP levels (p < .05). Multivariate logistic regression analyses indicated that the plasma level of miRNA-30e (OR = 0.732, 95% CI 0.674–0.851, p = .034), hs-CRP (OR = 1.353, 95% CI 1.129–1.635, p = .012) and Killip class ≥2 at admission (OR = 1.263, 95% CI 1.023–1.532, p = .027), were independent risk factors for no-reflow during pPCI. When plasma miRNA-30e level was used as the test variable, the area under the curve was 0.914 (p < .05) by ROC curve analysis. Lower miRNA-30e levels at admission are associated with no-reflow in STEMI patients undergoing pPCI and may play an important role in the pathogenesis of no-reflow. Plasma miRNA-30e level was an independent predictor of no-reflow during pPCI in patients with STEMI. Therefore, early detection of plasma miRNA-30e level can be a preliminary assessment for risk of no-reflow during pPCI.