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.

Efficacy analysis of clinical serological indicators in the diagnosis of postoperative periprosthetic joint infection in patients with rheumatoid arthritis or osteoarthritis.

PURPOSE: To investigate the incidence of periprosthetic joint infection (PJI) in patients with rheumatoid arthritis (RA) or osteoarthritis (OA) after primary joint arthroplasty; to analyze the optimal cut-off values of clinical serum markers C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and D-dimer for the diagnosis of PJI in RA patients; and to explore their diagnostic efficacy and clinical significance. METHODS: Clinical data of 15,702 patients with RA (578) or OA (15,124) who underwent total joint arthroplasty from 2013 to 2021 were retrospectively analyzed. Serum CRP, ESR, and D-dimer were recorded for each patient, and subject characteristic curves were used to determine the optimal threshold values of CRP, ESR, and D-dimer for RA-PJI and OA-PJI and to compare the areas under the curves to assess the diagnostic efficacy of the optimal threshold values of serologic indices for RA-PJI. RESULTS: The five year incidence of PJI was 6.92% in RA patients and 0.67% in OA patients. The optimal thresholds of CRP, ESR, and D-dimer for the diagnosis of RA-PJI were respectively 13.85 mg/L, 33.02 mm/h, and 796.50 ng/mL. The sensitivities of the optimal thresholds were respectively 67.6%, 62.2%, and 56.8%, and the specificities were 74.7%, 60.4%, and 74.4%. CONCLUSION: RA patients have a higher incidence of PJI than OA patients. The optimal thresholds for CRP, ESR, and d-dimer for the diagnosis of PJI were higher in RA patients than in OA patients, but the sensitivity and specificity of the diagnosis were not as good as in OA patients.

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.

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.

Mid-term clinical outcomes of totally endoscopic repair for mitral regurgitation in Barlow's disease.

OBJECTIVE: This study aimed to confirm the safety and feasibility of totally endoscopic repair for mitral regurgitation (MR) in Barlow's disease. METHODS: From June 2018 to December 2022, 21 consecutive Barlow's disease patients (aged 33 ± 12 years; 57.1% male) underwent totally endoscopic mitral valve (MV) repair with leaflets folding, multiple artificial chordae implantation and ring annuloplasty. The safety and feasibility of this technique was evaluated by its mid-term clinical outcomes. RESULTS: There was no operative death or complications. The mean cardiopulmonary bypass (CPB) time was 190 ± 41 (128-267) min, and the aortic cross-clamp time was 145 ± 32 (66-200) min. The average number of artificial chordae implantation was 2.9 ± 0.7 (1-4) pairs. The mean MV coaptation length was 1.4 ± 0.3 (0.8-1.8) cm, and the median transvalvular gradient was 1 [interquartile range (IQR), 1-2] mmHg. During a median follow-up time of 24 (IQR, 10-38) months, all patients showed persistent effective valve function with no significant MR or systolic anterior motion. CONCLUSIONS: Totally endoscopic repair was a safe, effective, and reproducible procedure with satisfied mid-term clinical outcomes for MR in Barlow's disease. However, further randomized and long-term follow-up studies were warranted to determine its clinical effects.

The value of sequential application of hydrogen peroxide, povidone-iodine and physiological saline in reducing postoperative infections after total knee arthroplasty: A prospective, randomized, controlled study.

BACKGROUND: Currently, in the field of total joint arthroplasty (TJA), there are no studies that have demonstrated the value of the sequential application of hydrogen peroxide, povidone-iodine, and physiological saline during the surgical procedure in decreasing postoperative infections in total knee arthroplasty (TKA), and in decreasing the incidence of periprosthetic joint infections (PJI) in particular. This study aimed to assess the efficacy of the sequential application of hydrogen peroxide, povidone-iodine, and physiological saline in reducing postoperative infections in TKA. METHODS: The study prospectively included 4743 patients, with Group A (2371, 49.9%) receiving sequential intraoperative application of hydrogen peroxide, povidone-iodine, and physiological saline irrigation of the incision, and Group B (2372, 50.1%) receiving intraoperative application of physiological saline irrigation of the incision only, to collect the patients' baseline data and clinical characteristics, and to statistically assess the incidence of superficial infections and the PJI during the follow up period to evaluate the clinical value of the study. RESULTS: The baseline levels of patients in Groups A and B were comparable. There were 132 (2.8%) lost visits during the study period. The incidence of superficial infections within 30 days after surgery was 0.22% in Group A and 1.17% in Group B, the difference between the two groups was statistically significant (P = 0.007). The incidence of PJI was 0.17% in Group A and 1.26% in Group B, the difference between the two groups was statistically significant (P = 0.0121). CONCLUSION: Sequential application of hydrogen peroxide, povidone-iodine, and physiological saline to irrigate incision in TKA can significantly reduce the incidence of postoperative superficial infections and PJI. The scientific and rational application of this therapy intraoperatively greatly reduces the incidence of PJI and postoperative superficial infections, which is of great benefit to the patient's prognosis.

Clinical effect of total thoracoscopic mitral valve surgery combined with atrial fibrillation radiofrequency ablation in patients with different left atrium diameter-a single center prospective observational cohort study.

Background: Mitral valve surgery combined with atrial fibrillation (AF) radiofrequency ablation (AFRA) is recommended as the first-line strategy for valvular disease-related AF. There are relatively few reports on the effect of AFRA combined with total thoracoscopic mitral valve surgery. This article aimed to analyze the clinical data and prognostic outcomes of patients with diverse left atrium diameter (LAD) (>50 or ≤50 mm) who underwent total thoracoscopic mitral valve surgery combined with AFRA. Methods: We conducted a prospective analysis of patients who underwent AFRA from January 2021 to June 2022 in the Department of Cardiovascular Surgery at the Chinese PLA General Hospital. The inclusion criteria were: (I) aged 40-70 years; (II) diagnosed with valvular heart disease and concomitant long-term persistent AF (>1 year); (III) patients who underwent total thoracoscopic mitral valve surgery; (IV) with a left ventricular end-diastolic diameter of ≤70 mm; (V) with a LAD ≤65 mm; and (VI) left ventricular ejection fraction (LVEF) ≥50%. The included patients were assigned to group A and B depend up on the LAD. All patients were followed up at 3 and 6 months timepoints postoperatively. The prime endpoint was the recovery rate of sinus rhythm. Results: There were 24 cases in group A (LAD >50 mm) and 16 cases in group B (LAD ≤50 mm). The two groups exhibited no statistical differences in terms of age, gender proportion, preoperative comorbidities, AF duration, preoperative heart function, and type of valve disease (P>0.05). The LAD, pulmonary artery pressure, and left ventricular diameter of group A were significantly greater than those of group B (P<0.05). There were no new cerebrovascular incidents during the perioperative and follow-up periods. The sinus rhythm conversion rates in group A after surgery and at 6 months were 75% and 66.7%, respectively; meanwhile, both of these values were 87.5% in group B, and the difference between the groups was statistically significant (P<0.05). Conclusions: Total thoracoscopic mitral valve surgery with AFRA is more effective in maintaining sinus rhythm in patients with LAD ≤50 mm than in those with LAD >50 mm without increased risk of adverse events. Further studies are warranted to validate our findings.

Totally endoscopic surgical resection for a blood cyst originated from mitral valve: a case report.

BACKGROUND: Intracardiac blood cysts are very rare primary cardiac tumors. Blood cysts originated from the mitral valve represent a minority of cases, and previous cases have been mainly treated with conventional surgery through median sternotomy. When the tumor involves heart valves and histopathological diagnosis remains unknown preoperatively, minimally invasive surgical resection of an intracardiac tumor can be challenging, especially through an endoscopic approach. We herein present the first case of successful surgical resection for a rare mitral valve originated blood cyst in a minimally invasive, totally thoracoscopic approach. CASE PRESENTATION: An apparently healthy 38-year-old male presented to his local hospital with six months history of palpitation and exertional dyspnea. Transthoracic echocardiography showed a mobile round cystic mass inside the left ventricle, attached to the anterolateral papillary muscle and chordae tendineae of the mitral valve. The local doctor diagnosed an intracardiac tumor and suggested a surgical resection through median sternotomy. However, the patient refused to have a sternotomy. He was then referred to us seeking minimally invasive surgery. We assessed the location, appearance and relationship to nearby structures of the tumor with echocardiography, and made a diagnosis of a suspected primary cystic intracardiac tumor. Since we had enough experience of totally endoscopic mitral surgery, our surgical plan was to resect the tumor in the aid of thoracoscopy, and manage the possible deformation and dysfunction of the cardiac structure if necessary. Using femoro-femoral cannulation and cardiopulmonary bypass, we successfully resected the tumor through a thoracoscopic approach in a closed chest, and well preserved the subvalvular structure and valvular function. Postoperative recovery was quick and uneventful. Pathologic diagnosis confirmed a simple blood cyst. CONCLUSIONS: Surgical resection is warranted for symptomatic cases of intracardiac blood cysts. With prudent preoperative diagnosis and comprehensive surgical plan, we believe the thoracoscopic approach is a safe, curative and viable alternative for complete resection of cardiac valvular tumors.

Thoracoscopic-Assisted Repair of Perivalvular Leakage of Prosthetic Mitral Valve.

Perivalvular leakage (PVL) after valve replacement is an awkward complication, and is liable to recur if re-replacement of a prosthetic valve is attempted. A 58-year-old male patient received initial mitral valve replacement 17 years earlier and recently developed PVL in mitral position. In this case we attempted an alternative way to repair mitral PVL through a mini-thoracotomy with thoracoscopic assistance without valve re-replacement surgery. The patient recovered uneventfully and was discharged on the day 7 after operation. Echocardiography revealed no regurgitation or new PVL developing during the 3 months follow-up.

Early clinical outcomes of thoracoscopic mitral valvuloplasty: a clinical experience of 100 consecutive cases.

BACKGROUND: We reported our experience of 100 consecutive cases of thoracoscopic mitral valvuloplasty in the early period. METHODS: Between September 2017 and December 2019, 100 consecutive cases (aged 49.2±14.7 years; 56% male) of thoracoscopic mitral valvuloplasty had been completed in our institution. The safety and feasibility of this technique was evaluated by its early clinical outcomes. RESULTS: Mitral valve (MV) repair was performed by means of Carpentier techniques, including leaflet folding in 5 cases, cleft suture in 10, commissuroplasty in 15 including 2 commissurotomy, edge to edge in 1, artificial chordae implantation in 76 cases with an average of 2.5±1.6 (1 to 4) pairs, and prosthetic annuloplasty in all cases. Intraoperative transoesophageal echocardiography (TEE) revealed no mitral regurgitation (MR) in 95 cases and a mild in 2 cases with all coaptation length more than 5 mm. The rest 3 cases with moderate or more MR were successfully reconstructed during a second pump-run. The average cardiopulmonary bypass (CPB) time was 164.4±51.0 min and aortic clamping time was 119.7±39.1 min, and the latest 10 cases were 140.2±45.3 and 96.3±25.4 min, respectively (P<0.05). There was only one operative death from avulsion of left atrial suture after operation and 2 intraoperative re-exploration through a conversion to sternotomy for bleeding. Severe MR was observed in 2 patients 3 months after operation, and MV replacement (MVR) was performed through median sternotomy. CONCLUSIONS: Totally thoracoscopic mitral valvuloplasty was technically feasible, safe, effective, and reproducible in clinical practice after crossing the learning curve.

Short-term and mid-term effects of radiofrequency ablation in mitral valve surgery in patients with different left atrial sizes.

BACKGROUND: To evaluate the efficacy of atrial fibrillation radiofrequency ablation (AFRA) in patients with chronic valvular atrial fibrillation (AF) with different left atrial sizes [left atrial diameter (LAD) >45 or ≤45 mm]. METHODS: Between May 2016 and January 2019, 264 patients who underwent cardiac operations with modified bipolar AFRA in the Department of Cardiovascular Surgery, PLA General Hospital, were enrolled. The clinical data of the patients were analysed, and inclusion and exclusion criteria were implemented. A propensity score was given for two groups of different left atrial sizes: group A (75 patients with LAD >45 mm) and group B (75 patients with LAD ≤45 mm). Preoperative general data, operative indicators, postoperative mortality, complications, and sinus rhythm recovery were analysed and compared between the two groups. RESULTS: The rates of sinus rhythm recovery in group A (LAD >45 mm) at 1 week, 6 months, 1 year, and 2 years after surgery were 84.0%, 81.33%, 73.33%, and 69.33%, respectively, compared with 90.67.0%, 88.00%, 86.67%, and 84.00% at 1 week, 6 months, 1 year, and 2 years after surgery, respectively, in group B (LAD ≤45 mm). The difference between the two groups was statistically significant at the two points in time of 1 year, and 2 years (P<0.05). Warfarin anticoagulation, the standard therapy, was applied after surgery. No new cerebrovascular events occurred in either group during short- and medium-term postoperative follow-up. CONCLUSIONS: Mitral valve surgery using improved Cox-Maze IV bipolar radiofrequency ablation was effective in treating chronic long-term persistent valvular AF and had an excellent sinus rhythm recovery rate. However, the larger the LAD, the less likely a patient was to maintain sinus rhythm as time passed after surgery.

Comparison of clinical outcomes between robotic and thoracoscopic mitral valve repair.

BACKGROUND: To compare the clinical outcomes and hospital cost of robotic versus thoracoscopic approaches to mitral valve plasty (MVP). METHODS: We retrospectively analyzed patients who received minimal invasive MVP between 2007 January and 2020 January at our department. The basic characteristics, echocardiography, surgical data, postoperative adverse events and hospital cost of the patients were collected. The primary outcomes of this study were direct hospital cost and 30-day outcomes, including the operative time, complications, and length of hospital stay. RESULTS: A total of 234 patients received minimally invasive MVP by using robotic (n=121) and thoracoscopic (n=113) technique respectively. The overall 30-day mortality rate was 0.9% (n=2), with no significant difference between two groups. The cardiopulmonary bypass time and aorta clamping time in thoracoscopic group were longer than that in robotic group (153.2±25.6 vs. 123.8±34.9 min and 111.8±23.0 vs. 84.9±24.3 min, P<0.001). The intraoperative blood transfusion rate (52.2% vs. 64.5%) and ICU time (2.8±2.3 vs. 3.6±2.7 days, all P<0.05) of the thoracoscopic group were lower than those in the robotic group. The adjusted hospital and operating room cost of the thoracoscopic group were significant lower ($18,208.4±$4,429.1 vs. $35,674.3±$4,936.1 and $9,038.3±$2,171.7 vs. $18,655.1±$2,558.3, all P<0.001). CONCLUSIONS: Both robotic and thoracoscopic approach for MVP are safe and reliable. Robotic technique has shorter operation time, while thoracoscopic technique has more advantages in blood transfusion rate, postoperative ventilation time, ICU duration and hospitalization expenses.

[Mechanism of AMPK regulating GLUT4 gene expression in skeletal muscle cells].

AMP-activated protein kinase, AMPK, is responsible for regulation of exercise-induced GLUT4 gene expression in skeletal muscle. But the molecular mechanisms for this regulation and key protein in this signaling pathway are obscure. There has been growing recognition that histone acetylation probably represents a central mechanism for regulation of gene transcription, and recent studies showed that numerous gene expressions are regulated by nucleosomal histone acetylation, which is modulated through histone acetyltransferases (HATs) and histone deacetylases (HDACs). So we have a hypothesis that the AMPK regulates GLUT4 gene through recruiting HDACs. Skeletal muscle cells cultured with normal (5 mmol/L) and high (20 mmol/L) glucose concentration were incubated with AICAR, and then total and nuclear AMPKalpha2, HDAC5 protein and GLUT4 mRNA were measured. The results show that the AICAR activated AMPKalpha2, reduced nuclear HDAC5,and increased GLUT4 mRNA in skeletal muscle cells; in contrast, the effect evoked by AICAR was blunted in cultured skeletal muscle cells with high glucose. Therefore, the changes of GLUT4 gene expression under different glucose concentration are closely related to the changes of AMPKalpha2 and HDAC5 protein in skeletal muscle cells. This result demonstrates that HDAC5 plays an important role in regulating GLUT4 gene transcription by AMPK signaling pathway skeletal muscle cells.