ultrasound-guided-induced-pluripotent-stem-cell-derived-cardiomyocyte

Ultrasound-Guided Induced Pluripotent Stem Cell-Derived Cardiomyocyte Implantation in Myocardial Infarcted Mice

The key objective of cell therapy after myocardial infarction (MI) is to effectively enhance the cell grafted rate, and human induced pluripotent stem ...

Central South University

Ferroptosis plays a key role in the death of cells including cardiomyocytes, and it is related to a variety of cardiac diseases. However, the role of ferroptosis-related genes (FRGs) in coronary artery disease (CAD) is not well characterized. We downloaded CAD-related information and FRGs from the gene expression omnibus (GEO) database and Ferroptosis Database (FerrDb) respectively. A total of 10 CAD-related DE-FRGs were obtained, which were closely linked to autophagy regulation and immune response. Subsequently, CA9, CBS, CEBPG, HSPB1, SLC1A4, STMN1 and TRIB3 among the 10 DE-FRGs were identified as marker genes by LASSO and SVM-RFE algorithms, which had tolerable diagnostic capabilities. Subsequent functional enrichment analysis showed that these marker genes may play a corresponding role in CAD by participating in the regulation of immune response, amino acid metabolism, cell cycle and multiple pathways related to the pathogenesis of CAD. Furthermore, a total of 58 drugs targeting 7 marker genes had been obtained. On the contrary, the ceRNA network revealed a complex regulatory relationship based on the marker genes. Also, CIBERSORT analysis showed that the changes in the immune microenvironment of CAD patients may be related to CBS, HSPB1 and CEBPG. We developed a diagnostic potency and provided an insight for exploring the mechanism for CAD. Before clinical application, further research is needed to test its diagnostic value for CAD.

Genetic analysis of potential biomarkers and therapeutic targets in ferroptosis from coronary artery disease.

To build a guideline for the individual treatment of Tetralogy of Fallot (TOF) with major aortopulmonary collaterals (MAPCAs) and tentatively establish the occlusion index of MAPCAs.

Clinical Study to Individual Treatment for Major Aortopulmonary Collaterals of Tetralogy of Fallot.

Endomyocardial fibrosis (EMF) is a neglected cardiovascular disease of poverty which carries a poor prognosis with no specific treatment affecting mainly children and young adults. Here, we report our 10-year experience in the therapeutic management and surgical treatment for EMF.

Endomyocardial fibrosis.

The pursuit of a clearer understanding of the pathogenesis of atrial fibrillation (AFib) and the development of new technology has resulted in a surge of interest in the surgical ablation for AFib. Here, we report our 8-year experience in the surgical treatment and management of AFib alongside, evaluating the cost-effectiveness in southern Mainland China over a 1-year follow-up.

Evaluating the cost-effectiveness of catheter ablation of atrial fibrillation.

 The purpose of this study was to report our experience in the surgical reconstruction of the right ventricular outflow tract in double outlet right ventricle with a major coronary artery crossing the right ventricular outflow tract in the presence of mirror image-dextrocardia.  From January 2005 to December 2019, 19 double outlet right ventricle patients (median age 4 years) with mirror image-dextrocardia and a major coronary artery crossing the right ventricular outflow tract received surgical repair. An autologous pericardial patch was used to enlarge the right ventricular outflow tract in four patients without pulmonary stenosis and three patients with mild pulmonary stenosis. A valved bovine jugular venous conduit was added to a hypoplastic native pathway in nine patients, among which six patients with moderate pulmonary stenosis received small-sized bovine jugular venous conduit implantation (diameter ≤ 16 mm). In comparison, a large-sized bovine jugular venous conduit (diameter >16 mm) was adopted in a total of three patients with severe pulmonary stenosis. Finally, three patients with preoperative pulmonary hypertension (mean pulmonary artery pressure ≥40 mmHg) did not undergo further intervention of right ventricular outflow tract due to the adequate outflow tract blood flow.  There was no hospital mortality. One patient with sub-pulmonary ventricular septal defect and concomitant severe pulmonary hypertension died from respiratory failure 11 months after the operation. Kaplan-Meier survival was 94% at 5, 10 years. Within a mean echocardiographic follow-up of 6.9 ± 3.6 years, a total of two patients received reintervention due to valvular stenosis of the bovine jugular venous conduit (pressure gradient > 50 mmHg at 4 and 9 years) after surgical operation. Actuarial freedom from reoperation was 90 and 72% at 5 and 10 years, respectively. During the last echocardiographic follow-up phase, all the survivors were in NYHA class I.  Double outlet right ventricle with mirror image-dextrocardia is a rare and complicated congenital cardiac malformation. Surgical reconstruction of the right ventricular outflow tract should be individualized based on the degree of pulmonary stenosis and the specific anatomical features of each patient. Reconstructing the pulmonary artery using the various sizes of valved bovine jugular venous conduit is a safe and effective surgical method.

Individualized Surgical Reconstruction of the Right Ventricle Outflow Tract in Double Outlet Right Ventricle With Mirror Image-Dextrocardia.

Local recurrence (LR) is clinical challenge in the treatment of esophageal squamous cell carcinoma (ESCC). The current study aimed to determine the optimal re-irradiation dose for local recurrent esophageal squamous cell carcinoma (LRESCC) following radical (chemo) radiotherapy.

A re-irradiation dose of 55-60 Gy improves the survival rate of patients with local recurrent esophageal squamous cell carcinoma after radiotherapy.

Cardiovascular disease (CVD) is the leading cause of death in the global population, accounting for about one-third of all deaths each year. Notably, with CVDs, myocardial damages result from myocardial infarction (MI) or cardiac arrhythmias caused by interrupted blood flow. Significantly, in the process of MI or myocardial ischemic-reperfusion (I/R) injury, both regulated and non-regulated cell death methods are involved. The critical factor for patients' prognosis is the infarct area's size, which determines the myocardial cells' survival. Cell therapy for MI has been a research hotspot in recent years; however, exosomes secreted by cells have attracted much attention following shortcomings concerning immunogens. Exosomes are extracellular vesicles containing several biologically active substances such as lipids, nucleic acids, and proteins. New evidence suggests that exosomes play a crucial role in regulating cell death after MI as exosomes of various stem cells can participate in the cell damage process after MI. Hence, in the review herein, we focused on introducing various cell-derived exosomes to reduce cell death after MI by regulating the cell death pathway to understand myocardial repair mechanisms better and provide a reference for clinical treatment.

Cell Death and Exosomes Regulation After Myocardial Infarction and Ischemia-Reperfusion.

China has the largest population of patients with epilepsy worldwide, which imposes a heavy burden on the public and health care systems. Several epidemiological surveys on epilepsy have been performed in China. Although these surveys grossly describe the prevalence and gap in treatment of epilepsy, the status of epilepsy centers is unclear. The number of epilepsy centers has increased substantially in recent decades. Therefore, a nationwide investigation of the scale and distribution, personnel, equipment, and epilepsy care capacity of each epilepsy center is of great value.

Epilepsy centers in China: Current status and ways forward.

 We investigated the potency of cardiac repair based on echocardiography-guided multiple percutaneous left ventricular intramyocardial injection of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) after myocardial infarction (MI).  Mice with surgically induced MI were randomly divided into three groups ( = 8 in each group) and subjected to echocardiography-guided percutaneous left ventricular infarcted border injection of hiPSC-CMs (single dose; 10 μl 3 × 10 cells) or repeated injections of hiPSC-CMs at post-MI weeks 1 and 2 (multiple doses). The sham group of animals underwent all surgical procedures necessary for MI induction except for ligation. Then 4 weeks after MI, heart function was measured with transthoracic echocardiography. Engraftment was evaluated through the detection of human-specific cardiac troponin T. Infarct size and collagen volume were calculated with Sirius Red/Fast Green staining. Angiogenesis was evaluated with isolectin B4 staining. Cardiac remodeling was evaluated from the cardiomyocyte minimal fiber diameter in the infarcted border zone. Apoptosis was detected  TdT-mediated dUTP Nick-End Labeling (TUNEL) staining in cardiomyocytes from the infarcted border zone.  No mice died after echocardiography-guided percutaneous left ventricular intramyocardial injection. hiPSC-CMs were about nine-fold higher in the multiple-dose group at week 4 compared to the single-dose group. Multiple-dose transplantation was associated with significant improvement in left ventricular function, infarct size, angiogenesis, cardiac remodeling, and cardiomyocyte apoptosis.  Echocardiography-guided multiple percutaneous left ventricular intramyocardial injection is a feasible, satisfactory, repeatable, relatively less invasive, and effective method of delivering cell therapy. The delivery of hiPSC-CMs indicates a novel therapy for MI.

Cardiac Repair With Echocardiography-Guided Multiple Percutaneous Left Ventricular Intramyocardial Injection of hiPSC-CMs After Myocardial Infarction.

 The study aims to establish a new method in the Tetralogy of Fallot (ToF) called the pulmonary valve bi-orifice method (pulmonary annular sparing with an individualized autologous pericardial patch; thus, two orifices are formed at the level of the pulmonary valve annulus) to reconstruct the right ventricular outflow tract (RVOT).  A retrospective analysis of 128 TOF patients from October 2009 to June 2018 with severe pulmonary valve dysplasia who underwent transvalvular annular patch (TAP) procedure (control group) or an individualized pulmonary valve bi-orifice procedure (observation group) were studied. The RVOT for each patient in the observation group was individually reconstructed per the patient's weight and the size of the autologous pulmonary valve using the bi-orifice method; however, increasing the cross-sectional area of the pulmonary valve annulus without destroying its integrity. The result was then compared to the control group, where TAP procedures were applied to evaluate the short to mid-term outcome(s). An  simulation test was used to verify the anti-regurgitation mechanism of the new method.  The  simulation test indicated that the anti-regurgitation mechanism was completed by the pericardial patch and the autologous pulmonary valve movement toward each other. Thus, for clinical applications, patients in both groups were compared. The results showed no significant differences in cardiopulmonary bypass and aortic cross-clamp time, mechanical ventilation, and ICU and post-operative residence between the two groups. During the follow-up period (3- to 12-years), 14 patients in the observation group had mild regurgitation after surgery (22.2%), while 10 patients had moderate pulmonary regurgitation (15.8%) with no right ventricular (RV) dilation. On the other hand, 22 patients (39.6%) had moderate to severe regurgitation in the control group, while left pulmonary artery stenosis occurred in one patient. In the control group, six patients (9.2%) with severe RV dilation were reoperated.  Individualized pulmonary valve bi-orifice procedure is a safe and excellent method for reconstructing RVOT in ToF.

Clinical Application of Individualized Pulmonary Bi-Orifice for the Reconstruction of Right Ventricular Outflow Tract in Tetralogy of Fallot.

The study aims to evaluate the feasibility and effectiveness of an individualized procedure for right ventricular outflow tract (RVOT) reconstruction in pulmonary atresia with ventricular septal defect (PA-VSD).

Individualized right ventricular outflow tract reconstruction using autologous pulmonary tissue in situ for the treatment of pulmonary atresia with ventricular septum defect.

Article	Year
Genetic analysis of potential biomarkers and therapeutic targets in ferroptosis from coronary artery disease. Journal of cellular and molecular medicine\| PubMed ID: 35152560	2022
Clinical Study to Individual Treatment for Major Aortopulmonary Collaterals of Tetralogy of Fallot. BioMed research international\| PubMed ID: 31223611	2019
Endomyocardial fibrosis. Cardiovascular diagnosis and therapy\| PubMed ID: 32420101	2020
Evaluating the cost-effectiveness of catheter ablation of atrial fibrillation. Cardiovascular diagnosis and therapy\| PubMed ID: 33224744	2020
Individualized Surgical Reconstruction of the Right Ventricle Outflow Tract in Double Outlet Right Ventricle With Mirror Image-Dextrocardia. Frontiers in pediatrics\| PubMed ID: 33681097	2021
A re-irradiation dose of 55-60 Gy improves the survival rate of patients with local recurrent esophageal squamous cell carcinoma after radiotherapy. Radiation oncology (London, England)\| PubMed ID: 34103059	2021
Cell Death and Exosomes Regulation After Myocardial Infarction and Ischemia-Reperfusion. Frontiers in cell and developmental biology\| PubMed ID: 34179002	2021
Epilepsy centers in China: Current status and ways forward. Epilepsia\| PubMed ID: 34510417	2021
Cardiac Repair With Echocardiography-Guided Multiple Percutaneous Left Ventricular Intramyocardial Injection of hiPSC-CMs After Myocardial Infarction. Frontiers in cardiovascular medicine\| PubMed ID: 34805322	2021
Clinical Application of Individualized Pulmonary Bi-Orifice for the Reconstruction of Right Ventricular Outflow Tract in Tetralogy of Fallot. Frontiers in cardiovascular medicine\| PubMed ID: 34901232	2021
Individualized right ventricular outflow tract reconstruction using autologous pulmonary tissue in situ for the treatment of pulmonary atresia with ventricular septum defect. Reviews in cardiovascular medicine\| PubMed ID: 35345252	2022

Xun Wu

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