a-preclinical-model-orthotopic-heart-transplantation-bama-miniature

A Preclinical Model of Orthotopic Heart Transplantation in Bama Miniature Pigs Using Biatrial Technique

Although significant progress has been made in heart transplantation, issues such as graft preservation, primary graft dysfunction, cardiac allograft ...

Chinese Academy of Medical Sciences and Peking Union Medical College

Affiliated Cardiovascular Hospital of Kunming Medical University

This study aimed to identify factors that affect the prognosis of children with pulmonary valve atresia and intact ventricular septum treated with transthoracic balloon dilation of the pulmonary valve. The study included 148 participants who were followed up for 5 years. Of these, 10 died, while 138 survived. Independent sample t-test and χ2 test were used to analyze clinical data of children in the death and survival groups. It was found that height, weight, body surface area, arterial oxygen saturation, degree of tricuspid regurgitation, pulmonary valve cross valve pressure difference, ICU length of stay, length of stay, reoperation intervention, and complications were statistically significant (P<0.05). ROC curve analysis of the measurement indicators with statistically significant differences showed that height, weight, body surface area, arterial oxygen saturation, ICU length of stay, and length of stay had AUCs ranging from 0.723 to 0.870. Logistic regression analysis revealed that the degree of tricuspid regurgitation, pulmonary valve cross valvular pressure difference, ICU length of stay, reoperation intervention, and complications were independent risk factors that affect the prognosis of patients with PA/IVS undergoing transthoracic balloon dilation of pulmonary valve. The study proposed a nomogram prediction model using R language software 4.0 "rms" package, which was validated using calibration curve and decision curve. The model had a C-index of 0.667 (95% CI: 0.643-0.786) and high degree of fit. This study provides clinicians with a prediction model to identify children with poor prognosis after treatment with transpulmonary valve balloon dilatation.           .

Influencing factors of prognosis in children with pulmonary atresia with intact ventricle septum after transthoracic balloon dilation of pulmonary valve and construction of a nomograph prediction model.

The modified Morrow operation for hypertrophic obstructive cardiomyopathy (HOCM) in children has a favorable outcome, but some children still have a poor prognosis after the procedure. In this study, the authors aimed to investigate the application of cardiac computed tomography (CCT) to construct a three-dimensional (3D) model of the left ventricle (LV) and analyze the association between hypertrophy in different parts of the LV and poor prognosis.

Left ventricular posterior wall hypertrophy leads to poor prognosis of hypertrophic obstructive cardiomyopathy in children: a cohort study.

Left ventricular septal myotomy provides a favorable prognosis for children with hypertrophic obstructive cardiomyopathy (HOCM). However, some children still suffer from recurrent left ventricular outflow tract obstruction (LVOTO) after surgery. Poor prognosis exists for HOCM caused by PTPN11 mutation. Therefore, the aim of this study was to determine the clinical features of recurrent obstruction in children with HOCM caused by pathogenic mutations in the PTPN11 gene.

Genetic variations in PTPN11 lead to a recurrent left ventricular outflow tract obstruction phenotype in childhood hypertrophic cardiomyopathy.

Myocarditis, a leading cause of sudden cardiac death and heart transplantation, poses significant treatment challenges. The study of clinical samples from myocarditis patients reveals a correlation between the pathogenesis of myocarditis and cardiomyocyte mitochondrial DNA (mtDNA). During inflammation, the concentration of mtDNA in cardiomyocytes increases. Hence, it is hypothesized that the combined clearance of mtDNA and its downstream STING pathway can treat myocarditis. However, clearing mtDNA is problematic. An innovative mtDNA scavenger is introduced, Nanosweeper (NS), which utilizes its nanostructure to facilitate the transport of NS-mtDNA co-assemblies for degradation, achieving mtDNA clearance. The fluorescent mtDNA probe on NS, bound to functional peptides, enhances the stability of NS. NS also exhibits robust stability in human plasma with a half-life of up to 10 hours. In a murine myocarditis model, NS serves as a drug delivery vehicle, targeting the delivery of the STING pathway inhibitor C-176 to the myocardium. This approach synergistically modulates the cGAS-STING axis with NS, effectively attenuating myocarditis- associated inflammatory cascade. This evaluation of NS in porcine models corroborated its superior biosafety profile and cardiac targeting capability. This strategic approach of targeted mtDNA clearance couple with STING pathway inhibition, significantly augments therapeutic efficacy against myocarditis, outperforming the conventional drug C-176, indicating its clinical potential.

An Injectable Multifunctional Nanosweeper Eliminates Cardiac Mitochondrial DNA to Reduce Inflammation.

Low family socio-economic status is a known factor that can contribute to increased mortality for patients with cardiovascular disease. However, in developing countries, the prognostic impact of socio-economic level on pediatric HTx is unclear.

Impact of family socio-economic status on the prognosis of heart transplantation in children.

Allograft valves offer significant advantages in valve replacement; however, their limited availability from cadaveric or brain-dead donors presents a considerable challenge. This study aims to share our experience in harvesting and preserving Allograft valves from heart transplant recipients, addressing this shortage and streamlining the process. Allograft valves were harvested from patients who underwent heart transplants at our center from October 2007 to October 2022. After sampling of the allograft for quality control, allograft valves were cryopreserved and thawed before implantation. Allograft valves were used in 60 patients who had pulmonary valve replacement (PVR) in or after repaired Tetralogy of Fallot (TOF). Patient data were collected and statistically analyzed. The age of donors was 39.0 ± 186.0 years while the median age of recipients was 5.1 years (interquartile range, 1.5-12.1). After a median follow-up of 2.6 years (interquartile range, 1.0-6.9), the freedom from all-cause mortality was 94.0%, 89.5%, and 89.5% at 5, 10, and 15 years, respectively. Adverse clinical outcomes, occurred in 24 patients (40.0%), while freedom is 64.9%, 53.4%, and 31.7% for 5, 10, and 15 years. Allograft valves bicuspidized (odds ratio, 75.085; 95% confidence interval, 10.100-558.202, P < 0.001) and early postoperative regurgitation (odds ratio, 9.946; 95% confidence interval, 1.034-95.706, P = 0.047) were considered independent risk factors for adverse clinical outcomes. Our study presents our approach to harvesting and preserving allograft valves from heart transplant recipients, demonstrating favorable short to mid-term outcomes when utilized in allograft valves for patients with or after repaired TOF. We recommend vigilant monitoring of early postoperative regurgitation, as it may signal a poor prognosis, and we strongly advise against bicuspidized the implanted allograft valves.

Allograft valves harvesting and preservation technique for enhanced performance.

Xenotransplantation offers a transformative solution to the global organ shortage crisis. However, the survival of xenografts remains limited despite various proposed strategies. In this study, we present an endothelial cell protection strategy that extends graft survival through the  construction of biomimetic glycan-enriched nanofibers. These biomimetic glycan-enriched molecules specifically target integrin αβ and form a polysaccharide-structured nanofiber network on the vascular endothelial surface. This network protects endothelial cells without compromising their normal physiological functions. The constructed biomimetic glycan-enriched layer significantly increased the xenograft survival by 1.64-fold compared to the untreated groups. This work introduces a novel strategy to enhance the survival of heart xenografts.

In Situ Biomimetic Glycocalyx Layer Protects Endothelial Damage in Xenotransplantation.

N-methyladenosine (mA), the most abundant internal RNA modification in humans, regulates most aspects of RNA processing. Prostate cancer is characterized by widespread transcriptomic dysregulation; therefore, we characterized the mA landscape of 162 localized prostate tumors with matched DNA, RNA and protein profiling. mA abundance varied dramatically across tumors, with global patterns emerging via complex germline-somatic cooperative regulation. Individual germline polymorphisms regulated mA abundance, cooperating with somatic mutation of cancer driver genes and mA regulators. The resulting complex patterns were associated with prognostic clinical features and established the biomarker potential of global and locus-specific mA patterns. Tumor hypoxia dysregulates mA profiles, bridging prior genomic and proteomic observations. Specific mA sites, such as those in VCAN, drive disease aggression, associating with poor outcomes, tumor growth and metastasis. mA dysregulation is thus associated with key events in the natural history of prostate cancer: germline risk, microenvironmental dysregulation, somatic mutation and metastasis.

The landscape of N-methyladenosine in localized primary prostate cancer.

Hypertrophic cardiomyopathy (HCM) is the common cause of sudden cardiac death in young people and is characterized by cardiac hypertrophy. Non-HCM caused left ventricular hypertrophy (LVH) is more common in the population, especially in people with hypertension, obesity, and diabetes. In order to identify high-risk populations, a screening technique that can rapidly differentiate between HCM and LVH patients should be developed. Plasma metabolomics may help develop useful biomarkers for the disease diagnosis. We performed a comprehensive plasma metabolomic analysis on a total of 720 individuals, included 441 HCM patients, 160 LVH patients, and 119 normal controls (NC) (derivation cohort = 368, validation cohort = 352). Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to construct discriminant models based on metabolomics, and the result showed significant changes in plasma metabolic profiling among the HCM, LVH, and NC. The prospective diagnostic biomarkers for HCM patients have been examined using variable importance in projection, fold change, and FDR. Acylcarnitines efficiently distinguished HCM and LVH patients, with a C14:0-carnitine AUC of 0.937 shown by the reiver operator characteristic (ROC) curve analysis. The biomarkers for the diagnosis of HCM patients was verified in another independent validation cohort. This study is the largest plasma metabolomics analysis of Chinese Han patients with HCM, finding biomarkers that can be used to distinguish between HCM from LVH patients. These results highlight the great potential value of plasma metabolic profiling analysis on HCM diagnoses.

Comprehensive plasma metabolomics profiling develops diagnostic biomarkers of obstructive hypertrophic cardiomyopathy.

Restrictive cardiomyopathy (RCM) is a rare cardiac disease characterized by impaired ventricular filling and relaxation, with preserved systolic function. This study investigates the genetic basis of RCM and its impact on clinical outcomes, particularly heart transplantation (HTx).

MYH7 Mutations in Restrictive Cardiomyopathy.

The diagnostic value of serum metabolomics in congenital heart disease has been proven. The difference of serum metabolomics between children with hypertrophic obstructive cardiomyopathy (HOCM) and normal children is unknown.

Comparison of plasma metabolic profiling between children with hypertrophic obstructive cardiomyopathy and healthy controls.

This study aimed to evaluate the long-term outcomes of aortic valve (AV) function and identify predictors of significant aortic regurgitation (SAR) and left ventricular outflow tract obstruction (LVOTO) recurrence following surgical repair of discrete membranous subaortic stenosis (DMSS) in pediatric patients and to develop a scoring model for long-term management.

Article	Year
Influencing factors of prognosis in children with pulmonary atresia with intact ventricle septum after transthoracic balloon dilation of pulmonary valve and construction of a nomograph predi... Biotechnology & genetic engineering reviews\| PubMed ID: 37154016	2024
Left ventricular posterior wall hypertrophy leads to poor prognosis of hypertrophic obstructive cardiomyopathy in children: a cohort study. International journal of surgery (London, England)\| PubMed ID: 38905490	2025
Genetic variations in PTPN11 lead to a recurrent left ventricular outflow tract obstruction phenotype in childhood hypertrophic cardiomyopathy. The Journal of thoracic and cardiovascular surgery\| PubMed ID: 38936599	2025
An Injectable Multifunctional Nanosweeper Eliminates Cardiac Mitochondrial DNA to Reduce Inflammation. Advanced healthcare materials\| PubMed ID: 39811901	2025
Impact of family socio-economic status on the prognosis of heart transplantation in children. BMC public health\| PubMed ID: 39871244	2025
Allograft valves harvesting and preservation technique for enhanced performance. Cell and tissue banking\| PubMed ID: 40038126	2025
In Situ Biomimetic Glycocalyx Layer Protects Endothelial Damage in Xenotransplantation. Nano letters\| PubMed ID: 40062533	2025
The landscape of N-methyladenosine in localized primary prostate cancer. Nature genetics\| PubMed ID: 40128621	2025
Comprehensive plasma metabolomics profiling develops diagnostic biomarkers of obstructive hypertrophic cardiomyopathy. Biomarker research\| PubMed ID: 40188144	2025
MYH7 Mutations in Restrictive Cardiomyopathy. JACC. Advances\| PubMed ID: 40286359	2025
Comparison of plasma metabolic profiling between children with hypertrophic obstructive cardiomyopathy and healthy controls. Cardiovascular endocrinology & metabolism\| PubMed ID: 40297477	2025
The Fate of Aortic Valve after Surgical Repair for Discrete Membranous Subaortic Stenosis in Pediatric Patients. The Journal of thoracic and cardiovascular surgery\| PubMed ID: 40436333	2025

Shun Liu

Biography

JoVE Journal Publications

Other Publications