TRIM16 exerts protective function on myocardial ischemia/reperfusion injury through reducing pyroptosis and inflammation via NLRP3 signaling.

Myocardial infarction is still a leading cause of morbidity and mortality worldwide, but its pathogenesis has not been fully understood. In the study, we attempted to explore the effects of E3 ligase tripartite motif 16 (TRIM16) on myocardial ischemia-reperfusion (MI/R) injury in vivo and in vitro, and the underlying mechanisms. We identified that TRIM16 was indeed a potent regulator during MI/R progression in murine models and surprisingly showed a negative correlation with the concentrations of cardiac pro-inflammatory cytokines. Adenoviral vectors encoding GFP or TRIM16 (Ad-TRIM16) were subjected to mice through direct injection into the left ventricular (LV). We found that Ad-TRIM16 significantly reduced the infarct size, and improved the cardiac function and structure compared with the Ad-GFP mice after MI/R operation. More studies indicated that TRIM16 over-expression strongly meliorated nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and associated inflammatory response in hearts of MI/R-induced mice, which were validated in hypoxia/reoxygenation (H/R)-exposed primary cardiomyocytes in vitro. In particular, MI/R operation led to cardiac pyroptosis by increasing the cleavage of Caspase-1 and Gasdermin D (GSDMD), while being considerably abrogated upon TRIM16 over-expression. Mechanistically, TRIM16 interacted with NLRP3 and promoted the K48-linked polyubiquitination of NLRP3, ultimately promoted its degradation. Together, we identified TRIM16 as a novel E3 ubiquitin ligase for NLRP3, which played an essential role in modulating its expression, and subsequently influenced inflammatory response and pyroptosis in MI/R murine model, confirming that TRIM16 may be a potential therapeutic target for myocardial infarction.

Kawasaki disease: multiple giant coronary aneurysms intervention and pacemaker implantation due to complete heart block-a case report.

Early intravenous immunoglobulin (IVIG) is the standard treatment for Kawasaki disease (KD) to reduce the incidence of coronary aneurysms. Patients with atypical presentation or who live in a rural area are less likely to receive treatment in the early stage of presentation and are more likely to develop severe complications. There is little consensus on how to treat coronary aneurysms effectively in the acute or subacute stage especially when giant aneurysms develop that compromise cardiac function. This case study is of a 19-month-old girl who initially was not treated as KD and developed multivessel giant coronary artery aneurysms (CAAs) (>8 mm), acute myocardial infarction, and complete heart block despite late intravenous IVIG administration. Multiple attempts of percutaneous coronary intervention (PCI) failed to open the occlusion in the right artery; therefore, bradycardia persisted. The girl received a permanent pace-maker and was doing well at 12-month follow up.

Evaluation of the prognostic value of the metastatic lymph node ratio for gastric cancer.

BACKGROUND: The aim of this study was to investigate the prognostic value of metastatic lymph node (LN) ratio (LNR) compared with pathologic node (pN) category. METHODS: Three hundred ninety-nine patients with gastric cancer with R0 resection were reviewed. LNR, pN, and the number of retrieved LNs were evaluated in node-positive groups with ≥15 or <15 LNs resected and a node-negative group, respectively, by univariate and multivariate analyses. Associations of pN and LNR with the number of retrieved LNs were determined using Spearman's rank correlation test. RESULTS: LNR and pN were correlated with overall survival. For the node-positive group with ≥15 LNs retrieved, pN and LNR were independent prognostic factors, with the hazard ratio higher for LNR; neither was correlated with the number of retrieved LNs. For the group with <15 LNs retrieved, LNR but not pN was an independent prognostic factor, with LNR uncorrelated with the number of LNs retrieved. For the node-negative group, the number of LNs retrieved retained an independent prognostic factor. CONCLUSIONS: LNR is an independent prognostic factor in node-positive patients with gastric cancer with R0 resection, and it is uninfluenced by the number of LNs retrieved. It may be superior to pN.