Successful one-stage surgical repair in a rare adult patient with berry syndrome.

BACKGROUND: Berry syndrome is a rare congenital cardiac malformation, herein we report an adult male patient who was successfully repaired by one-stage surgery. CASE DESCRIPTION: 18-year-old male patient presenting symptoms of chest tightness and shortness for over a year presented to outpatient clinic in our department to have corrective procedure heart. CTA revealed an Aortopulmonary Window (APW) type III, measuring 4.6 cm in maximum diameter. The right pulmonary artery originated from the ascending aorta, and the pulmonary trunk exhibited dilation with dimensions of 8.3 cm × 5.7 cm × 5.9 cm. Additional findings included Interrupted Aortic Arch (IAA) type A, intact ventricular septum, and Patent Ductus Arteriosus (PDA). Echocardiography showed bidirectional shunt at the level of APW in severe pulmonary hypertension. The right heart catheterization indicated a mean pulmonary artery pressure of 70mmHg and a pulmonary artery resistance of 5 Wood units. We evaluated after two weeks of treatment with epoprostenol at a rate of 20 ng/(kg. min) and found a significant improvement in pulmonary-artery pressure. Finally, we communicated with the patient's family and decided to proceed with the procedure. CONCLUSIONS: For complex cardiovascular malformations, the ideal treatment strategy must be tailored to the characteristics of the patient to provide maximum efficacy and safety.

Noncoding RNA Lipotherapeutics: A Promising Breakthrough in Pulmonary Hypertension Treatment.

Pulmonary Hypertension (PH) is a complex cardiovascular disorder characterized by elevated blood pressure in the pulmonary arteries. Current therapeutic approaches for PH have limitations in addressing the underlying molecular mechanisms. This article explores the potential of noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), delivered through Lipid-Based Nanoparticles (LNPs) as a novel treatment strategy. These ncRNAs play critical roles in regulating vascular function and are implicated in PH pathogenesis. LNPs provide a promising method for the efficient and targeted delivery of ncRNAs. Advances in LNP technology, including the incorporation of R8 peptide modification, have shown promise in enhancing the delivery and efficacy of ncRNAs in PH models. Challenges such as biocompatibility, toxicity, and precise targeting must be addressed as these therapies move toward clinical application. The potential of personalized medicine and the integration of artificial intelligence in LNP design are discussed as prospects. In conclusion, ncRNA lipotherapeutics delivered via LNPs offer a transformative approach to treating PH, potentially leading to more effective management and improved patient outcomes in the future. However, continued research and clinical trials are necessary to fully realize their therapeutic potential in the field of PH treatment.

Prognostic Value of Left Ventricular Global Longitudinal Strain for Major Adverse Cardiovascular Events in Patients with Aortic Valve Disease: A Meta-Analysis.

INTRODUCTION: Valvular heart disease is one of the most common heart diseases. It is characterized by abnormal function or structure of the heart valves. There may be no clinical symptoms in the early stages. Clinical symptoms of arrhythmia, heart failure, or thromboembolic events may occur in the late stages of the disease, such as palpitation after activities, breathing difficulties, fatigue, and so on. Aortic valve disease is a major part of valvular heart disease. The main treatment for aortic valve disease is valve replacement or repair surgery, but it is extremely risky. Therefore, a rigorous prognostic assessment is extremely important for patients with aortic valve disease. The global longitudinal strain is an index that describes the deformation capacity of myocardium. There is evidence that it provides a test for systolic dysfunction other than LVEF (left ventricular ejection fraction) and provides additional prognostic information. METHOD: Search literature published between 2010 and 2023 on relevant platforms and contain the following keywords: "Aortic valve disease," "Aortic stenosis," "Aortic regurgitation," and "longitudinal strain" or "strain." The data is then extracted and collated for analysis. RESULTS: A total of 15 articles were included. The total population involved in this study was 3,678 individuals. The absolute value of LVGLS was higher in the no-MACE group than in the MACE group in patients with aortic stenosis (Z = 8.10, p < 0.00001), and impaired LVGLS was a risk factor for MACE in patients with aortic stenosis (HR = 1.14, p < 0.00001, 95% CI: 1.08-1.20). There was also a correlation between impaired LVGLS and aortic valve surgery in patients with aortic valve disease (HR = 1.16, p < 0.0001, 95% CI: 1.08-1.25) or patients with aortic valve regurgitation (HR = 1.21, p = 0.0004, 95% CI: 1.09-1.34). We also found that impaired LVGLS had no significant association between LVGLS and mortality during the period of follow-up in patients with aortic valve stenosis (HR = 1.08, 95% CI: 0.94-1.25, p = 0.28), but it was associated with mortality in studies of prospective analyses (HR = 1.34, 95% CI: 1.02-1.75, p = 0.04). CONCLUSIONS: Impaired LVGLS correlates with major adverse cardiovascular events in patients with aortic valve disease, and it has predictive value for the prognosis of patients with aortic valve disease.

The Function of Circular RNAs in Myocardial Ischemia-Reperfusion Injury: Underlying Mechanisms and Therapeutic Advancement.

Myocardial ischemia reperfusion injury (MIRI) represents a prevalent and severe cardiovascular condition that arises primarily after myocardial infarction recanalization, cardiopulmonary bypass surgery, and both stable and unstable angina pectoris. MIRI can induce malignant arrhythmias and heart failure, thereby increasing the morbidity and mortality rates associated with cardiovascular diseases. Hence, it is important to assess the potential pathological mechanisms of MIRI and develop effective treatments. The role of circular RNAs (circRNAs) in MIRI has increasingly become a topic of interest in recent years. Moreover, significant evidence suggests that circRNAs play a critical role in MIRI pathogenesis, thereby representing a promising therapeutic target. This review aimed to provide a comprehensive overview of the current understanding of the role of circRNAs in MIRI and discuss the mechanisms through which circRNAs contribute to MIRI development and progression, including their effects on apoptosis, inflammation, oxidative stress, and autophagy. Furthermore, the potential therapeutic applications of circRNAs in MIRI treatment, including the use of circRNA-based therapies and modulation of circRNA expression levels, have been explored. Overall, this paper highlights the importance of circRNAs in MIRI and underscores their potential as novel therapeutic targets.

PDHA1 Alleviates Myocardial Ischemia-Reperfusion Injury by Improving Myocardial Insulin Resistance During Cardiopulmonary Bypass Surgery in Rats.

OBJECTIVE: Cardiopulmonary bypass (CPB) is a requisite technique for thoracotomy in advanced cardiovascular surgery. However, the consequent myocardial ischemia-reperfusion injury (MIRI) is the primary culprit behind cardiac dysfunction and fatal consequences post-operation. Prior research has posited that myocardial insulin resistance (IR) plays a vital role in exacerbating the progression of MIRI. Nonetheless, the exact mechanisms underlying this phenomenon remain obscure. METHODS: We constructed pyruvate dehydrogenase E1 α subunit (PDHA1) interference and overexpression rats and used ascending aorta occlusion in an in vivo model of CPB-MIRI. We devised an in vivo model of CPB-MIRI by constructing rat models with both pyruvate dehydrogenase E1α subunit (PDHA1) interference and overexpression through ascending aorta occlusion. We analyzed myocardial glucose metabolism and the degree of myocardial injury using functional monitoring, biochemical assays, and histological analysis. RESULTS: We discovered a clear downregulation of glucose transporter 4 (GLUT4) protein content expression in the CPB I/R model. In particular, cardiac-specific PDHA1 interference resulted in exacerbated cardiac dysfunction, significantly increased myocardial infarction area, more pronounced myocardial edema, and markedly increased cardiomyocyte apoptosis. Notably, the opposite effect was observed with PDHA1 overexpression, leading to a mitigated cardiac dysfunction and decreased incidence of myocardial infarction post-global ischemia. Mechanistically, PDHA1 plays a crucial role in regulating the protein content expression of GLUT4 on cardiomyocytes, thereby controlling the uptake and utilization of myocardial glucose, influencing the development of myocardial insulin resistance, and ultimately modulating MIRI. CONCLUSION: Overall, our study sheds new light on the pivotal role of PDHA1 in glucose metabolism and the development of myocardial insulin resistance. Our findings hold promising therapeutic potential for addressing the deleterious effects of MIRI in patients.

Bone marrow mesenchymal stem cell-derived exosomes carrying E3 ubiquitin ligase ITCH attenuated cardiomyocyte apoptosis by mediating apoptosis signal-regulated kinase-1.

BACKGROUND: Bone marrow mesenchymal stem cell (BMSC)-derived exosomes have been verified to perform an effective role in treating acute myocardial infarction (MI). Herein, we aimed to investigate the role of BMSC-derived exosomes carrying itchy E3 ubiquitin ligase (ITCH) in MI and the underlying mechanism involved. METHODS: BMSCs were isolated from rat bone marrow and exosomes were extracted using ultra-high speed centrifugation. Exosomes uptake by cardiomyoblasts was determined by PKH-67 staining. Rat cardiomyoblast cell line H9C2 was stimulated by hypoxia, as in vitro model. H9C2 cell apoptosis was determined by flow cytometry. Cell viability was examined by cell counting kit-8 assay. Western blotting was performed to determine the expression of ITCH, apoptosis signal-regulated kinase-1 (ASK1), and apoptotic-related protein cleaved-caspase 3 and Bcl-2. Ubiquitination assay was employed to measure the levels of ASK1 ubiquitination. RESULTS: Exosomes derived from BMSCs were endocytosed by H9C2 cardiomyoblasts. BMSC-Exo downregulated cleaved-caspase 3 expression, upregulated Bcl-2 expression, further suppressed H9C2 cell apoptosis under hypoxia treatment, meanwhile the expression of ASK1 was downregulated, and similar effects were observed in BMSC-cultured supernatant (BMSC-S). However, these effects were reversed by exosome inhibitor GW4869. BMSC-derived exosomes enhanced ASK1 ubiquitination and degradation. Mechanically, exosomes of ITCH-knockdown BMSCs promoted H9C2 cell apoptosis and upregulated ASK1 expression. Overexpression of ITCH enhanced ASK1 ubiquitination and degradation. Further, the protein expression of ASK1 and cleaved-caspase 3 was upregulated and Bcl-2 protein expression was downregulated. ITCH-knockdown BMSC exosomes increased cardiomyoblast apoptosis. CONCLUSION: BMSC-derived exosomes carrying ITCH suppressed cardiomyoblast apoptosis, promoted cardiomyoblast viability, and improved myocardial injury in AMI by mediating ASK1 ubiquitination.

Insulin reduces pyroptosis-induced inflammation by PDHA1 dephosphorylation-mediated NLRP3 activation during myocardial ischemia-reperfusion injury.

BACKGROUND: Previous studies proved that pyrin domain-containing protein 3 (NLRP3)-induced pyroptosis plays an important role in Myocardial ischemia-reperfusion injury (MIRI). Insulin can inhibit the activation of NLRP3 inflammasome, although the exact mechanism remains unclear. The aim of this study was to determine whether insulin reduces NLRP3-induced pyroptosis by regulating pyruvate dehydrogenase E1alpha subunit (PDHA1) dephosphorylation during MIRI. METHODS: Rat hearts were subject to 30 min global ischemia followed by 60 min reperfusion, with or without 0.5 IU/L insulin. Myocardial ischemia-reperfusion injury was evaluated by measuring myocardial enzymes release, Cardiac hemodynamics, pathological changes, infarct size, and apoptosis rate. Cardiac aerobic glycolysis was evaluated by measuring ATP, lactic acid content, and pyruvate dehydrogenase complex (PDHc) activity in myocardial tissue. Recombinant adenoviral vectors for PDHA1 knockdown were constructed. Pyroptosis-related proteins were measured by Western blotting analysis, immunohistochemistry staining, and ELISA assay, respectively. RESULTS: It was found that insulin significantly reduced the area of myocardial infarction, apoptosis rate, and improved cardiac hemodynamics, pathological changes, energy metabolism. Insulin inhibits pyroptosis-induced inflammation during MIRI. Subsequently, Adeno-associated virus was used to knock down cardiac PDHA1 expression. Knockdown PDHA1 not only promoted the expression of NLRP3 but also blocked the inhibitory effect of insulin on NLRP3-mediated pyroptosis in MIRI. CONCLUSIONS: Results suggest that insulin protects against MIRI by regulating PDHA1 dephosphorylation, its mechanism is not only to improve myocardial energy metabolism but also to reduce the NLRP3-induced pyroptosis.

Case Report: Surgical management of idiopathic pulmonary aneurysms and review surgical approaches.

Idiopathic pulmonary aneurysm is a clinically rare condition characterized by an unknown etiology and episodic occurrence. Despite its rarity, idiopathic pulmonary artery aneurysm poses potential risks to patients. Currently, there is a lack of established clinical guidelines and consensus regarding its management, leading to ongoing controversies in treatment strategies. Particularly, the optimal approach for addressing the main pulmonary artery, its branches, and the pulmonary artery valve remains uncertain. A 57-year-old female patient presented with chest pain and tightness, leading to the diagnosis of idiopathic pulmonary artery aneurysm after excluding other potential causes. Subsequently, she underwent surgical treatment. However, during the surgery, the pulmonary artery wall was found to be extremely weak, prompting us to employ a surgical approach involving the utilization of autologous vessel wrapping with artificial grafts. By summarizing almost all surgical treatment strategies reported in recent years, including the management of pulmonary artery vessels and the pulmonary valve, we have developed a treatment flow chart. This flowchart serves as a valuable guide for the management of future cases presenting similar challenges, offering clinicians valuable insights and evidence-based recommendations.

TIPE2-modified human amnion-derived mesenchymal stem cells promote the efficacy of allogeneic heart transplantation through inducing immune tolerance.

BACKGROUND: Immune rejection of heart transplantation has been regarded as the biggest challenge encountered by a patient suffering from end-stage heart disease. The transplantation of human amnion-derived mesenchymal stem cells (hAD-MSCs) has exhibited promising application prospects in organ transplantation. However, its persistent unsatisfactory tolerance has limited the widespread application of this technology. We aim to investigate the role of tumor necrosis factor-α-induced protein-8 like-2 (TIPE2)-mediated hAD-MSCs in immune tolerance in heart transplantation and its molecular regulatory mechanisms. METHODS: This project detected the effect of TIPE2 on immune tolerance by constructing an allogeneic heart transplantation mouse model through which TIPE2-overexpressed hAD-MSCs were injected into recipients. The fluorescence distribution of TIPE2-hAD-MSCs in mice was observed by a small animal in vivo imaging system. Pathological changes of the transplanted heart were detected by hematoxylin and eosin (HE) staining. Flow cytometry was performed to detect the content of cardiac lymphocytes. The expression of immune-induced related factors was measured by quantitative real-time PCR (qRT-PCR) and western blot assays. RESULTS: TIPE2-hAD-MSCs protected myocardial tissue structures, reduced the spleen and thymus indexes in recipient mice, minimized the content of cardiac lymphocytes, reduced expressions of ERK, p38, and IFN-γ, and elevated expressions of both IL-10 and TGF-ß, markedly improving the survival time and survival rates of recipient mice. CONCLUSIONS: TIPE2-hAD-MSCs induce immune tolerance and improve the survival rates of allogeneic heart transplantation in mice. This study is expected to offer an ideal source and target of cells for organ transplantation.

Fabrication of Novel Printable Electrically Conductive Adhesives (ECAs) with Excellent Conductivity and Stability Enhanced by the Addition of Polyaniline Nanoparticles.

Electrically conductive adhesives (ECAs) are one of the low temperature bonding materials. It can be used to replace toxic Sn-Pb solder. The key issue for the application of ECAs is how to improve their electrical properties. In the present study, we develop an effective method to promote the electrical properties of ECAs by addition of polyaniline (PANI) nanoparticles. PANIs were synthesized via a facile one-step chemical oxidative polymerization method. After adding 0.5 wt% PANI nanoparticles, the conductivity of ECAs increased dramatically by an order of magnitude. The bulk resistivity of 8.8 × 10-5 Ω·cm is achieved for 65 wt% silver fillers with 0.5 wt% PANIs loaded ECAs. Besides, this improvement has no negative effect on the shear strength and the aging life of ECAs. Moreover, the use of PANIs not only lowers the percolation threshold of ECAs, but also reduces the cost and improves the bonding reliability. Finally, PANIs enhanced ECAs patterns were successfully printed by a stencil printing method, which proved their potential applications in replacing conventional solder pastes and printing functional circuits.

Capsaicin is beneficial to hyperlipidemia, oxidative stress, endothelial dysfunction, and atherosclerosis in Guinea pigs fed on a high-fat diet.

Capsaicin has anti-inflammatory and antioxidant effects, as well as some benefits on the cardiovascular system. The exact effects of capsaicin on atherosclerosis are poorly understood. To investigate the effects of capsaicin on hyperlipidemia and atherosclerosis in guinea pigs fed on a high-fat diet, as well as its potential mechanisms. Guinea pigs (n = 48) were randomly divided into six groups (n = 8/group): normal diet (control); high fat diet (model); model + low-dose capsaicin (2.5 mg/kg); model + moderate-dose capsaicin (5 mg/kg); model + high-dose capsaicin (10 mg/kg), and model + simvastatin (1.5 mg/kg) (positive control). After 14 weeks, serum lipids, apolipoprotein B100, malondialdehyde (MDA), superoxide dismutase (SOD), nitric oxide (NO), and endothelin-1 were measured. Aortic atherosclerotic lesions were histologically examined. eNOS and iNOS were assessed by immunohistochemistry. The model group developed severe dyslipidemia and associated histologic changes and endothelial dysfunction. All doses of capsaicin decreased total cholesterol, triglycerides, low-density lipoprotein cholesterol, and apolipoprotein B-100, and increased high-density lipoprotein cholesterol (all P < 0.05). Capsaicin alleviated the plaque area (-17.9-70.5%), plaque area to intima ratio (-18.0-73.6%), and intima thickness (-20.5-83.6%) (all P < 0.05). Capsaicin decreased MDA (-45.5-76.1%), ET-1 (-19.6-51.6%), and average gray value (AGV) of eNOS (-10.9-48.8%), and increased SOD activity (+31.7-76.1%), NO (+11.2-36.8%), and AGV of iNOS (+6.8-+93.0%) (all P < 0.05). Similar changes were observed with simvastatin. Capsaicin is beneficial to hyperlipidemia and atherosclerosis in guinea pigs fed on a high-fat diet. Reduced oxidative stress and endothelial dysfunction were involved in these benefits. This could represent a novel approach to prevent cardiovascular diseases.

Efficacy of minimally invasive transthoracic closure of atrial and ventricular septal defects / 中国胸心血管外科临床杂志

@#Objective     To evaluate the efficacy and safety of transthoracic minimally invasive occlusion operation for the treatment of congenital atrial and ventricular septal defects. Methods     The clinical data of 88 patients who underwent surgical occlusion operation from December 2015 to February 2017 were summarized. There were 52 males and 36 females, aged 6.8±7.5 years ranging from 1.6 to 24.0 years. All the patients were followed up by ultrasound and electrocardiogram at postoperative 3, 6 and 12 months. The efficacy of minimally invasive thoracotomy was analyzed by statistical methods. Results     The patients were followed up for 3-15 (6.8±2.3) months, and the follow-up rate was 92.0%. Ultrasound showed occluder fixed well and no residual shunt, valve regurgitation, thrombosis or other complications occurred. The heart was reduced, the ejection fraction was greater than 55%, and heart function rating for all patients was grade Ⅰ. Conclusion     Transthoracic mini-invasive surgical occlusion of atrial and ventricular septal defects is safe and effective. The short and middle-term effect is satisfying. It can be widely used in clinical, but multi-center and long-term follow-up and assessment still need to be carried out.

[Myocardial protective effect of L-carnitine in cardioplegia solution on patients undergoing heart valve replacement operation].

OBJECTIVE: To investigate the myocardial protective effect of L-carnitine as an ingredient of cardiac arresting solution in the process of heart valve replacement operation. METHODS: 69 cases undergoing heart valve replacement with cardiopulmonary bypass (CPB), 47 males and 22 females, aged 48.17 +/- 14.22 (16 approximately 74 years), were divided into 3 groups: test group I (n = 22, 12 g/L L-carnitine was put in the St. Thomas II cold crystal cardiac arresting liquid), test group II (n = 24, 6 g/L L-carnitine was put in the St. Thomas II cold crystal cardiac arresting liquid), and control group (n = 23, no L-carnitine was put in the St. Thomas II cold crystal cardiac arresting liquid). Before operation, 20 minutes after the beginning of shunt, after the finish of shunt, and 8 hours, one day, 3 days, and 7 days after operation venous blood was drawn to test the serum cardial tropnin I (cTnI), aspartate transaminase, lactate dehydrogenase, creatine kinase (CK) and CK-MB isozyme. Heart color ultrasonography was conducted to test the cardiac index (CI) and left heart ejecting fraction (EF) one day before operation and 7 days after operation. Before shunt and by the end of intracardiac procedure a bit of myocardial tissue was taken to undergo electron microscopy. The amounts of vaso-active drugs, such as dopamine and dobutamine, used postoperatively, and the postoperative cardiac auto-rebeating rate were recorded. RESULTS: The Amounts of vaso-active drugs used after operation was 329 +/- 54 mg in the test group I and 339 +/- 47 mg in the test group II, both significantly less than in the control group (669 +/- 56 mg, both P < 0.01) without a significant difference between the 2 test groups. Since the end of CPB to 3 days after operation, the serum levels of cTnI, aspartate transaminase, lactate dehydrogenase, CK and CK-MB isozyme were significantly lower in the 2 test groups than in the control group (P < 0.05 or P < 0.01). The serum level of cTnI in test group I was significantly lower than in the test group II (5.71 +/- 1.14 ng/ml vs 7.87 +/- 1.89 ng/ml 1 day postoperatively (P < 0.05), and 5.01 +/- 0.89 ng/ml vs 7.53 +/- 1.43 ng/ml 3 days postoperatively (P < 0.05). The postoperative cardiac auto-rebeating rate was 87.9% in the test group I and 74.3% in the test group II, both significantly higher than that in the control group (45.7%, P < 0.05 and P < 0.01). Heart color ultrasonogram showed that 7 days postoperatively the CI index was 2.86 +/- 0.55 and 2.74 +/- 0.56 in the 2 test groups, significantly higher than that in the control group (2.11 +/- 0.35, both P < 0.05), and the left heart EF were 64.3 +/- 8.6 and 59.1 +/- 6.7 in the 2 test groups, both significantly higher than that in the control group (51.7 +/- 4.9, both P < 0.05). Electron microscopy showed only slight swelling of mitochondria in the cardial cell and the myocardial fiber was intact by the end of operation in the 2 test groups without significant difference between these 2 groups, however, in the control group swelling of mitochondria with vesicle formation, fissure of part of mitochondrial ridges, and disappearance of glycogen particles were found. CONCLUSION: Antegrade coronary perfusion of L-carnitine has a good protective effect on myocardium and is worth spreading for heart valve replacement patients with cardiopulmonary bypass.