Alkylation Repair Homolog 5 Regulates N(6)-methyladenosine (m6A) Methylation of Mitsugumin 53 to Attenuate Myocardial Infarction by Inhibiting Apoptosis and Oxidative Stress.

ABSTRACT: N(6)-methyladenosine (m6A) methylation modification is involved in the progression of myocardial infarction (MI). In this study, we investigated the effects of demethylase alkylation repair homolog 5 (ALKBH5) on cell apoptosis and oxidative stress in MI. The ischemia/reperfusion (I/R) injury mouse model and hypoxia/reoxygenation (H/R) cell model were established. The levels of ALKBH5 and mitsugumin 53 (MG53) were measured by quantitative real-time polymerase chain reaction, immunohistochemical, and immunofluorescence analysis. Apoptosis was evaluated by TUNEL assay, flow cytometry, and western blot. Oxidative stress was assessed by antioxidant index kits. Methylation was analyzed by RNA binding protein immunoprecipitation (RIP), MeRIP, and dual-luciferase reporter assay. We observed that ALKBH5 and MG53 were highly expressed in MI. Overexpression of ALKBH5 inhibited H/R-induced cardiomyocyte apoptosis and oxidative stress in vitro, and it inhibited I/R-induced collagen deposition, cardiac function, and apoptosis in vivo. ALKBH5 could bind to MG53, inhibit m6A methylation of MG53, and increase its mRNA stability. Silencing of MG53 counteracted the inhibition of apoptosis and oxidative stress induced by ALKBH5. In conclusion, ALKBH5 suppressed m6A methylation of MG53 and inhibited MG53 degradation to inhibit apoptosis and oxidative stress of cardiomyocytes, thereby attenuating MI. The results provided a theoretical basis that ALKBH5 is a potential target for MI treatment.

2022 CMICS Expert Consensus on the Management of Isolated Tricuspid Regurgitation after Left-Sided Valve Surgery.

Tricuspid regurgitation (TR) may occur late after left-sided valve surgery (LSVS). Isolated tricuspid regurgitation after left-sided valve surgery (iTR-LSVS) refers to isolated TR without significant lesions in the mitral and/or aortic position late after mitral and/or aortic replacement or repair. Severe TR has a negative impact on long-term prognosis and requires surgical or transcatheter treatment. However, there is no clear recommendation on when and how intervention should be performed for patients with iTR-LSVS in the current guidelines for the management of valvular heart disease. The historically high operative mortality may be reduced by current minimally invasive techniques and transcatheter therapy. To further understand iTR-LSVS, standardize the treatment, improve the prognosis, and promote the collaboration, the Chinese Minimally Invasive Cardiovascular Surgery Committee (CMICS) wrote this expert consensus on the management of iTR-LSVS from the aspects of etiology, preoperative evaluation, indications for intervention, surgical treatment, transcatheter therapy, and postoperative management.

Application of Machine Learning Algorithms to Predict New-Onset Postoperative Atrial Fibrillation and Identify Risk Factors Following Isolated Valve Surgery.

BACKGROUND: New-onset postoperative atrial fibrillation (POAF) is the most common complication after valvular surgery, but its etiology and risk factors are incompletely understood. This study investigates the benefits of machine learning methods in risk prediction and in identifying relative perioperative variables for POAF after valve surgery. METHODS: This retrospective study involved 847 patients, who underwent isolated valve surgery from January 2018 to September 2021 in our institution. We used machine learning algorithms to predict new-onset postoperative atrial fibrillation and to select relatively important variables from a set of 123 preoperative characteristics and intraoperative information. RESULTS: The support vector machine (SVM) model demonstrated the best area under the receiver operating characteristic (AUC) value of 0.786, followed by logistic regression (AUC = 0.745) and the Complement Naive Bayes (CNB) model (AUC = 0.672). Left atrium diameter, age, estimated glomerular filtration rate (eGFR), duration of cardiopulmonary bypass, New York Heart Association (NYHA) class III-IV, and preoperative hemoglobin were high-ranked variables. CONCLUSIONS: Risk models based on machine learning algorithms may be superior to traditional models, which were primarily based on logistic algorithms to predict the occurrence of POAF after valve surgery. Further prospective multicenter studies are needed to confirm the performance of SVM in predicting POAF.

Bioinformatic-based Identification of Genes Associated with Aortic Valve Stenosis.

BACKGROUND: Aortic valve stenosis (AS) disease is the most common valvular disease in developed countries. The pathology of AS is complex, and its main processes include calcification of the valve stroma and involve genetic factors, lipoprotein deposition and oxidation, chronic inflammation, osteogenic transition of cardiac valve interstitial cells, and active valve calcification. The aim of this study was to identify potential genes associated with AS. METHODS: Three original gene expression profiles (GSE153555, GSE12644, and GSE51472) were downloaded from the Gene Expression Omnibus (GEO) database and analyzed by GEO2R tool or 'limma' in R to identify differentially expressed genes (DEGs). Functional enrichment was analyzed using the ClusterProfiler package in R Bioconductor. STRING was utilized for the Protein-Protein Interaction (PPI) Network construct, and tissue-specific gene expression were identified using BioGPS database. The hub genes were screened out using the Cytoscape software. Related miRNAs were predicted in Targetscan, miWalk, miRDB, Hoctar, and TarBase. RESULTS: A total of 58 upregulated genes and 20 downregulated genes were screened out, which were mostly enriched in matrix remodeling and the immune system process. A module was thus clustered into by PPI network analysis, which mainly involved in Fc gamma R-mediated phagocytosis, Osteoclast differentiation. Ten genes (IBSP, NCAM1, MMP9, FCGR3B, COL4A3, FCGR1A, THY1, RUNX2, ITGA4, and COL10A1) with the highest degree scores were subsequently identified as the hub genes for AS by applying the CytoHubba plugin. And hsa-miR-1276 was finally identified as potential miRNA and miRNA-gene regulatory network was constructed using NetworkAnalyst. CONCLUSIONS: Our analysis suggested that IBSP, NCAM1, MMP9, FCGR3B, COL4A3, FCGR1A, THY1, RUNX2, ITGA4, and COL10A1 might be hub genes associated with AS, and hsa-miR-1276 was potential miRNA. This result could provide novel insight into pathology and therapy of AS in the future.

Using machine learning and liquid crystal droplets to identify and quantify endotoxins from different bacterial species.

Detection and quantification of bacterial endotoxins is important in a range of health-related contexts, including during pharmaceutical manufacturing of therapeutic proteins and vaccines. Here we combine experimental measurements based on nematic liquid crystalline droplets and machine learning methods to show that it is possible to classify bacterial sources (Escherichia coli, Pseudomonas aeruginosa, Salmonella minnesota) and quantify concentration of endotoxin derived from all three bacterial species present in aqueous solution. The approach uses flow cytometry to quantify, in a high-throughput manner, changes in the internal ordering of micrometer-sized droplets of nematic 4-cyano-4'-pentylbiphenyl triggered by the endotoxins. The changes in internal ordering alter the intensities of light side-scattered (SSC, large-angle) and forward-scattered (FSC, small-angle) by the liquid crystal droplets. A convolutional neural network (Endonet) is trained using the large data sets generated by flow cytometry and shown to predict endotoxin source and concentration directly from the FSC/SSC scatter plots. By using saliency maps, we reveal how EndoNet captures subtle differences in scatter fields to enable classification of bacterial source and quantification of endotoxin concentration over a range that spans eight orders of magnitude (0.01 pg mL-1 to 1 µg mL-1). We attribute changes in scatter fields with bacterial origin of endotoxin, as detected by EndoNet, to the distinct molecular structures of the lipid A domains of the endotoxins derived from the three bacteria. Overall, we conclude that the combination of liquid crystal droplets and EndoNet provides the basis of a promising analytical approach for endotoxins that does not require use of complex biologically-derived reagents (e.g., Limulus amoebocyte lysate).

Left atrial appendage exclusion is effective in reducing postoperative stroke after mitral valve replacement.

OBJECTIVE: This study aimed to evaluate the role of surgical left atrial appendage (LAA) exclusion in the prevention of stroke after mitral valve replacement (MVR). METHODS: We retrospectively reviewed clinical data of 860 patients who received MVR in our center from January 2008 to January 2013. The patients were randomly assigned to two surgical groups, namely LAA exclusion group (n = 521) and LAA nonexclusion group (n = 339) according to whether concurrent surgical exclusion of the LAA was to be undertaken or not before surgery in a blind fashion. MVR was performed by two experienced surgeons. The LAA was explored during the operation and mural thrombus removed in all cases. The LAA was left intact in nonocclusion group whereas the neck of the LAA was closed with a two-layer continued suture in exclusion group. The incidence of early postoperative ischemic stroke between the two groups was compared. RESULTS: The patients' age was 53 ± 12 years, with 48.1% male and 67.9% with rheumatic disease. Mural thrombosis was seen in 18.8% of the patients and atrial fibrillation (AF) coexisted in 62.4%. All operations were successfully performed and no difference was noted in in-hospital mortality, re-exploration for bleeding, and other major complications between the two groups. The incidence of ischemic stroke in LAA exclusion group was significantly lower than in nonexclusion group (0.6% vs. 2.7%, p = .011). The subgroup multivariate analysis showed that LAA exclusion significantly reduced the risk of postoperative stroke in patients with AF (odds ratio [OR] = 0.070, 95% confidence interval [CI]: 0.006-0.705, p = .025) but not in non-AF patients (OR = 1.902, 95% CI: 0.171-21.191, p = .601). CONCLUSIONS: Concurrent LAA exclusion during MVR is a safe and effective way to reduce postoperative ischemic stroke, particularly in patients with AF.

The Pacopexy procedure for left ventricular aneurysm: a 10-year clinical experience.

PURPOSE: To evaluate our 10-year clinical experience of performing the Pacopexy procedure for left ventricular aneurysm (LVA). METHODS: Between January, 1998 and November, 2015, a cohort of 92 patients with LVA underwent surgery to reshape the left ventricle. Fifty-seven patients underwent the Dor procedure and 35 underwent the Pacopexy procedure to emphasize the conical shape, whereby patch placement followed an oblique trajectory between the left ventricular apex and the septum below the aortic valve. RESULTS: The early-mortality rate was 4.34% (4/92; n = 2 in each group). The 10-year survival rate was 70.4 ± 7.9% in the Pacopexy group vs 41.7 ± 7.2% in the Dor group (p < 0.05), and the rate of freedom from hospital re-admission for heart failure (HF) or cardiac death was 60.0 ± 8.6% vs 28.8 ± 6.8%, respectively (p < 0.05). The Dor procedure and left ventricular end systolic volume index (LVESVI) ≥ 60 ml/m2 were strongly and significantly associated with long-term mortality and hospital re-admission for HF. CONCLUSIONS: The Pacopexy procedure is a reproducible surgical option for the treatment of LVA. The improved configuration achieved by the Pacopexy procedure has resulted in good long-term survival and a high degree of freedom from re-admission for HF in patients with advanced LVA.

Minimally Invasive Isolated Tricuspid Valve Redo Surgery Has Better Clinical Outcome: A Single-Center Experience.

BACKGROUND: Reoperation for isolated tricuspid valve (TV) surgery is considered a high-risk procedure. The optimal surgical approach is controversial. We analyzed our experience with isolated TV redo surgery performed either through thoracoscopic approach (thoracoscopic group), right thoracotomy (thoracotomy group), or median sternotomy (sternotomy group). METHODS: We retrospectively analyzed all patients with previous cardiac surgery who underwent redo-TV procedure through thoracoscopic approach (n = 33), right lateral thoracotomy approach (n = 14), or sternotomy (n = 72). RESULTS: All patients successfully underwent elective surgery, with no intraoperative conversion or death occurring. 69% and 31% of patients received valve replacement and valvuloplasty, respectively. After operation, one patient in the sternotomy group received reoperation for bleeding, while another patient received valve replacement surgery 2 weeks after operation due to heart failure caused by valvuloplasty failure. No obvious complications occurred in the minimally invasive groups. The overall success rate of valve repair during 1-year follow-up was 99.2%. CONCLUSION: Minimally invasive, isolated TV surgery as reoperation can be safe and may improve clinical outcome.

Severe Left Main Coronary Stenosis Due to Aortic Bioprosthesis Implantation: A Case Report.

Coronary artery ostial stenosis is a common but life-threatening complication that usually presents right after valve implantation, especially in transcatheter aortic valve implantation (TAVI) procedure. However, as reported in our case, it may also have a late delayed presentation in valve replacement through median sternotomy. Here, we present a rare case of one patient who underwent percutaneous coronary intervention (PCI) for severe stenosis of the left main (LM) coronary artery six months after Mosaic aortic bioprosthesis implantation.

Progress in Treatment of Myocardial Injury in Patients with 2019-nCoV: A Chinese Experience.

Since December 2019, the 2019 novel coronavirus (2019-nCoV) infection began to appear in Hubei Province of China and gradually spread to other provinces and other countries. The virus has the characteristics of strong transmission capacity, diverse clinical manifestations, long incubation period, and latent infection, thus posing a serious threat to human life safety and health. With the increasing number of cases and the continuous enrichment of clinical data, 2019-nCoV-infected patients have received more and more attention regarding myocardial injury related to virus infection besides typical respiratory system manifestations. According to the published data, we summarize the myocardial injury manifestations, characteristics, effects on disease condition, and prognosis of 2019-nCoV-infected patients and discuss the possible injury mechanism, treatment methods, and future research directions.

Red Blood Cell Distribution Width Predicts Postoperative Death of Infective Endocarditis.

Infectious endocarditis (IE) is a rare disease with high mortality rate. Recently, red cell distribution width (RDW) has drawn special attention for predicting cardiovascular disease. This study aims to explore the relationship between RDW value and postoperative death of IE patients.Clinical records of patients with definite IE from Chinese People's Liberation Army General Hospital department of cardiovascular surgery were collected and analyzed. Clinical, echocardiographic, and biochemical variables were evaluated along with RDW.Results: A total of 158 consecutive IE patients (mean age 47.0 ± 16.3 years, male 61.4%) were enrolled in this study. According to receiver operating characteristic (ROC) curve analysis, the optimal RDW cutoff value for predicting mortality was 15.45% (area under the curve 0.913, P < 0.001). A total of 28 patients (17.8%) died postoperatively; of these, 89.3% had RDW value >15.45%. Binary regression analysis showed that aging, multiple valvular involved, valvular vegetation formation, pulmonary hypertension, and high RDW are strong predictors of postoperative death. Multiple regression analysis revealed that high RDW value was independent predictors of postoperative mortality in patients with IE (ß: 3.704, 95% confidence interval (95%CI): 2.729-604.692, P < 0.05).IE has a high inhospital mortality rate, and increased RDW is an independent predictor of postoperative death in these patients.

Surgery for Patients with Radiation-Induced Constrictive Pericarditis.

Radiation-induced heart disease (RIHD) is a major side effect of chest radiation therapy (RT). Most changes of pericardium will occur within a few weeks after receiving chest RT, while most of them will take decades or more to become constrictive pericarditis. Pericardiectomy is an effective treatment method. Here, we report 2 cases of radiation pericarditis after chest RT at our center.

From intermolecular interactions to structures and properties of a novel cocrystal explosive: a first-principles study.

By employing a first-principles method, we conducted a thorough study on a novel cocrystal explosive 1 : 1 NTO : TZTN and gained insight into the interaction-structure-property interrelationship. Mulliken bond orders, Hirshfeld surfaces, intermolecular binding energies, packing coefficients, and oxygen balance were calculated to analyze the intermolecular interactions and structures of the cocrystal explosive. The cocrystallization of NTO and TZTN molecules enhances the intermolecular binding force, which drives the synthesis of the cocrystal. However, the cocrystallization decreases the molecular packing density along the closest packed directions, which reduces the density by 10.5% and deteriorates the oxygen balance. All of these lead to a reduction in the detonation performance compared to NTO explosives. We have also proposed a new method to evaluate the impact sensitivity according to the lattice dynamics calculation. The cocrystal explosive has a lower impact sensitivity than TZTN but higher than NTO, which agrees well with experiments.