Catalpol alleviates myocardial ischemia reperfusion injury by activating the Nrf2/HO-1 signaling pathway.

PURPOSE: Myocardial ischemia/reperfusion injury (MI/RI) is a major problem in the clinical treatment of ischemic cardiomyopathy, and its specific underlying mechanisms are complicated and still unclear. A number of studies have indicated that the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxidase-1(HO-1) signaling pathway might serve as an important target for the management of MI/RI. Catalpol is a kind of iridoid glucoside that has been found to exhibit diverse anti-inflammatory and antioxidant properties. This study was aimed at investigating the role of Catalpol in targeting MI/RI and its related mechanisms in an oxygen-glucose deprivation/reoxygenation (OGD/R) model in vitro and a preclinical ischemia/reperfusion (I/R) model. METHODS: This study using both in vitro and in vivo models investigated the possible role and underlying mechanisms used by Catalpol for modulating of MI/RI. The potential effects of Catalpol on the viability of cardiomyocytes were measured by cell counting kit-8 (CCK-8) assays. The phenotypes of myocardial injury, oxidative stress and inflammation markers were measured by western blot, immunofluorescence, enzyme-linked immunosorbent assay (ELISA) etc. Nrf2/HO-1 signaling pathway was detected by immunofluorescence and western blot analysis. RESULTS: We found that Catalpol significantly suppressed the process of MI/RI and protected OGD/R-treated cardiomyocytes by inhibiting the various markers of inflammation and suppressing oxidative stress. Additionally, mechanistically it was also demonstrated that Catalpol could effectively activate Nrf2/HO-1 signaling pathway to suppress the damage caused by inflammation and oxidative stress in MI/RI. CONCLUSION: In summary, the findings suggest that Catalpol exerted significant cardioprotective effects following myocardial ischemia, possibly through the activation of the Nrf2/HO-1 signaling pathway.

Comparison of single-port, multi-port video-assisted thoracoscopic and open lobectomy for children: a single-center experience.

PURPOSE: The feasibility of single-port video-assisted thoracic surgery (SPVATS) for pediatric lobectomy has not been clearly established. We compared the feasibilities of single-port (SP), multi-port (MP) VATS and open lobectomy (OL) for surgical treatment of children with lung disease. METHODS: In this study, we retrospectively analyzed and compared data for 22,19 and 30 pediatric lung disease patients who had been subjected to SP, MP and OL, respectively. These procedures were performed between March, 2012 and August, 2020 at the Second Affiliated Hospital of Wenzhou Medical University. Perioperative clinical indicators were analyzed. RESULTS: Compared to OL, SP was associated with lower intraoperative blood loss (p = 0.008), lower postoperative thoracic drainage volume (p = 0.041), shorter chest drainage duration (p = 0.002) and hospital stay (p = 0.001). Operation time (p = 0.437), volume of estimated blood loss (p = 0.979), conversion rate to thoracotomy (p = 0.861), total thoracic drainage volume (p = 0.824), duration of chest tube drainage (p = 0.543), length of hospital stay (p = 0.812) and incidences of postoperative complications were comparable in MP and SP groups. CONCLUSION: SPVATS is a safe and feasible approach for lobectomy in pediatrics, with comparable postoperative clinical outcomes to MPVATS and better outcomes relative to OL. However, studies with large sample sizes in multicenter should be performed to verify our findings.

Outcomes of Surgical Repair of Total Anomalous Pulmonary Venous Drainage: Role of Primary Sutureless Technique.

To evaluate the surgical outcomes of total anomalous pulmonary venous drainage focusing on survival, postoperative and pulmonary venous obstruction. Further investigate the role of primary sutureless technique in patients with preoperative pulmonary venous obstruction. Consecutive patients underwent total anomalous pulmonary venous drainage repair in our institution during Jan 2000 to Dec 2019 were enrolled into this retrospective analysis. Since 2016, sutureless repair was regularly applied in patients with preoperative pulmonary venous obstruction. All patients with preoperative pulmonary venous obstruction referred before 2016 had underwent traditional repair. A total of 95 patients were included. During follow-up time of 85 months, main endpoints were documented in 21 patients, including 9 (9.5%) early deaths, 3 (2.3%) late deaths and 9 (9.5%) postoperative pulmonary venous obstructions. Preoperative pulmonary venous obstruction was presented in 26 (27.4%) patients with more emergent surgery (14/26 vs 3/69, P < 0.001) was required. Main endpoints occurred more in patients with preoperative pulmonary venous obstruction (4/26 vs 5/69, P = 0.004). Patients experienced sutureless technique had a lower incidence of postoperative PVO at follow-up (0/11 versus 4/11, P = 0.045). Outcomes of surgical repair for total anomalous venous drainage are satisfactory. However, preoperative pulmonary venous obstruction may be accompanying unfavorable early deaths and postoperative pulmonary venous obstruction. Propensity matching analysis showed that sutureless technique was benefit for postoperative pulmonary venous obstruction without longer cardiopulmonary bypass and aortic cross-clamp time.

The role of dendritic cells regulated by HMGB1/TLR4 signalling pathway in myocardial ischaemia reperfusion injury.

Inflammatory response plays an important role in ischaemia reperfusion injury (IRI) through a variety of inflammatory cells. Apart from neutrophils, macrophages and lymphocytes, the role of dendritic cells (DCs) in IRI has been noticed. The study was aimed at investigating whether the high-mobility group protein box-1/toll like receptor 4 (HMGB1/TLR4) signalling pathway regulate the migration, adhesion and aggregation of DCs to the myocardium, induce DCs activation and maturation, stimulate the expression of surface costimulatory molecules and participate in myocardial IRI. In vivo, migration, adhesion, and aggregation of DCs was enhanced; the expression of peripheral blood DCs CD80 and CD86, myocardial adhesion molecules were increased; and the infarct size was increased during myocardial ischaemia reperfusion injury myocardial ischemic/reperfusion injury (MI/RI). These responses induced by MI/RI were significantly inhibited by HMGB1 specific neutralizing antibody treatment. Cellular experiments confirmed that HMGB1 promoted the release of inflammatory cytokines through TLR4/MyD88/NF-κB, upregulated CD80 and CD86 expression, mediated the damage of cardiomyocytes and accelerated the apoptosis. Our results indicate that DCs activation and maturation, stimulate the expression of surface costimulatory molecules by promoting the release of inflammatory factors through NF-κB pathway and participate in myocardial IRI.

Microarray analysis reveals a potential role of lncRNA expression in remote ischemic preconditioning in myocardial ischemia-reperfusion injury.

The challenge to avoid or reduce cardiopulmonary bypass-related injuries in cardiovascular surgery remains a major issue. Remote ischemic preconditioning (RIPC) remains a promising strategy whose clinical applications appear to be significantly more realistic and extensive as compared with other conservative or surgical strategies. However, considering its underlying mechanism(s) are still unclear, novel ideas and methods must be explored to enhance its potential in clinical applications. Long noncoding RNAs (LncRNAs) are a kind of RNAs that have been implicated in the occurrence and development of cardiovascular diseases. The differently expressed LncRNAs and their biological effects during RIPC have not been explored previously. In this study, mouse and human LncRNA microarrays were used to investigate the expression signatures of LncRNAs and mRNAs in the myocardial tissue after RIPC. Therafter, homology comparisons were used to screen homologous genes from differentially expressed LncRNAs. Competing endogenous RNA (ceRNA) mechanism analysis were employed to find the matching relationship among homologous LncRNA, mRNA and microRNA. 554 differentially expressed mouse LncRNAs (281 up-regulated/273 down-regulated) and 1392 differentially expresssed human LncRNAs (635 up-regulated/757 down-regulated) were selected for further analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to quantify these LncRNAs, homology comparison and ceRNA mechanism analysis provided a pair of homologous LncRNAs (ENST00000574727 & ENSMUST00000123752) for further research investigation. Overall, in this study, a number of differentially expressed LncRNAs were identified which may play an important role the regulation of both inflammation and cell proliferation. The findings may thus unveil the mystery of RIPC and discover a novel protective mechanism for the mitigation of cardiovascular ischemia-reperfusion disease.

Comparison of extracardiac conduit and lateral tunnel for functional single-ventricle patients: A meta-analysis.

OBJECTIVE: This study aims to assess and compare the early and long-term effects of extracardiac conduit (EC) and lateral tunnel (LT) in patients with a functional single ventricle through meta-analysis. DESIGN: A systematic search was performed in PubMed, Embase, Cochrane Library, CNKI, VIP, CBM, and WanFang databases for papers that were published until August 1, 2016. Cochrane systematic review method was used for paper screening and information retrieve, and RevMan 5.3 software was applied for the meta-analysis. RESULTS: Data for 10 studies with a total of 3814 patients were retrieved. The advantages of EC comparing to LT include: lower 30 day postsurgery supraventricular arrhythmia incidence (Relative Risk [RR] = 0.31 [0.17, 0.55], P < .001), lower protein loss enteropathy incidence (RR = 0.33 [0.11, 0.96], P = .04), and requiring no cardiopulmonary bypass. However, the chest drainage time was longer (mean difference [MD] = 1.99 [1.83, 2.15], P < .001) in EC. There were no significant differences in early postoperative mortality, long-term mortality, long-term arrhythmia, Fontan takedown, ventilator-assisted ventilation, ICU stay, thrombosis, pleural effusion, and pericardial effusion between EC and LT. CONCLUSIONS: EC had a lower incidence of supraventricular arrhythmia (30 days after operation) and the rate of protein losing enteropathy than LT, and requiring no cardiopulmonary bypass. These show that EC has an advantage over the LT in patients with a functional single ventricle.