A rare inflammatory myofibroblastic tumor appearing both inside and outside the heart.

BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is an uncommon cardiac tumor that primarily affects infants, children, and young adults. While complete surgical resection generally leads to a favorable prognosis, accurate diagnostic tests remain limited. CASE PRESENTATION: We describe the case of a 26-year-old female who had a dual tumor inside and outside the heart and was misdiagnosed by echocardiography and MRI. We also review 71 cases of cardiac IMTs from the literature regarding their epidemiology, clinical presentation, and outcome. CONCLUSION: Early detection of this rare disorder is essential for optimal surgical management.

Comparison between the modified Blalock-Taussig shunt and right ventricular outflow tract stent in the palliative treatment for tetralogy of Fallot. / 改良Blalock-Taussigåˆ†æµæœ¯ä¸Žå³å¿ƒå®¤æµå‡ºé“æ”¯æž¶æ¤å ¥æœ¯å§‘æ¯æ€§æ²»ç–—æ³•æ´›å››è”ç—‡çš„æ¯”è¾ƒ.

OBJECTIVES: For patients with tetralogy of Fallot (TOF) who are not suitable candidates for primary corrective surgery or have a high surgical risk, transcatheter right ventricular outflow tract (RVOT) stent implantation is considered a safe and effective palliative intervention. This study aims to investigate the therapeutic outcomes of RVOT stent implantation in neonates and infants with TOF in comparison with the modified Blalock-Taussig shunt (mBTS) and to compare the impact of the 2 palliative interventions on arterial oxygen saturation and pulmonary artery development in pediatric patients. METHODS: Clinical data of 32 patients with TOF admitted to the Second Xiangya Hospital of Central South University from March 2011 to March 2021 were retrospectively collected. The patients were divided into an mBTS group (undergoing mBTS, n=15) and a stent implantation group (undergoing RVOT stenting, n=17) according to the surgical procedures. The 2 groups were assessed and compared in the surgical-related arterial oxygen saturation, postoperative complication rate, mortality rate, and re-intervention rate. The development of the patients' main pulmonary artery, right pulmonary artery, and left pulmonary artery was assessed by z-scores according to echocardiographic results. RESULTS: The children in the stent implantation group were younger and less weighed compared with the mBTS group (both P<0.05). Compared with the preoperative period, children in the stent implantation group had significantly higher arterial oxygen saturation [(75±17)% vs (96±3)%, P=0.026]; z-scores of pulmonary trunk [(-2.82±1.27) points vs (0.86±0.77) points, P=0.014], right pulmonary artery [(-1.88±0.59) points vs (-0.28±0.71) points, P=0.011], and left pulmonary artery [(-2.34±0.36) points vs (-1.67±0.36) points, P=0.036] were significantly increased. However, there were no significant differences in arterial oxygen saturation and pulmonary artery z-scores between pre- and post-mBTS procedures (all P>0.05). CONCLUSIONS: RVOT stent would have good surgical outcomes used in TOF patients with low weight and severe comorbidities. It also leads to an higher postoperative oxygen saturation and better promotion of pulmonary artery growth with RVOT stent compared to mBTS.

Case Report: Successful surgical management of a challenging primary cardiac angiosarcoma.

Primary cardiac tumors are exceptionally rare, with malignant tumor occurrences ranging from 0.0017% to 0.28%. Among these, primary cardiac angiosarcoma (PCA) stands as the most prevalent malignancy, primarily impacting the right cardiac system. In this case report, we present the instance of a 44-year-old woman who recently exhibited acute chest discomfort and was subsequently diagnosed with a microangiosarcoma within the right atrium and superior vena cava. Diagnostic modalities including chest x-rays, CT, MRI, and PET-CT were instrumental in pinpointing the tumor's location and nature. Surgical excision followed by pathological and immunological examinations confirmed the diagnosis. The patient's recovery post-surgery has been encouraging, with successful follow-up chemoradiotherapy administered. Despite advancements, devising optimal strategies for enhancing patient survival and quality of life in angiosarcoma cases remains a pressing research challenge.

RNA modification in cardiovascular disease: implications for therapeutic interventions.

Cardiovascular disease (CVD) is the leading cause of death in the world, with a high incidence and a youth-oriented tendency. RNA modification is ubiquitous and indispensable in cell, maintaining cell homeostasis and function by dynamically regulating gene expression. Accumulating evidence has revealed the role of aberrant gene expression in CVD caused by dysregulated RNA modification. In this review, we focus on nine common RNA modifications: N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), N7-methylguanosine (m7G), N4-acetylcytosine (ac4C), pseudouridine (Ψ), uridylation, adenosine-to-inosine (A-to-I) RNA editing, and modifications of U34 on tRNA wobble. We summarize the key regulators of RNA modification and their effects on gene expression, such as RNA splicing, maturation, transport, stability, and translation. Then, based on the classification of CVD, the mechanisms by which the disease occurs and progresses through RNA modifications are discussed. Potential therapeutic strategies, such as gene therapy, are reviewed based on these mechanisms. Herein, some of the CVD (such as stroke and peripheral vascular disease) are not included due to the limited availability of literature. Finally, the prospective applications and challenges of RNA modification in CVD are discussed for the purpose of facilitating clinical translation. Moreover, we look forward to more studies exploring the mechanisms and roles of RNA modification in CVD in the future, as there are substantial uncultivated areas to be explored.

Case report: Surgical management of a rare right coronary artery fistula with a giant pseudoaneurysm compressing the pulmonary vein in a young patient.

Congenital coronary artery fistula (CAF) represents a remarkable rarity within the realm of cardiovascular anomalies, characterized by an aberrant connection between coronary arteries and either cardiac chambers or major vessels. Clinical manifestations of CAFs often remain unspecified or may even be entirely absent, posing diagnostic challenges. Notably, patients harboring substantial CAFs may exhibit symptoms such as palpitations, chest tightness, and dyspnea. Although right-sided congenital CAFs are relatively prevalent, the occurrence of a CAF accompanied by a colossal pseudoaneurysm imposing compression upon the pulmonary vein is an exceedingly rare phenomenon. This exceptional case report delineates a singular fistula originating from the right coronary artery, extending its course to the right atrium, and remarkably featuring a substantial pseudoaneurysm exerting compression upon the right superior pulmonary vein. Therapeutic intervention encompassed surgical closure of the proximal artery and excision of the pseudoaneurysm, underscoring the complexity and criticality of managing such intricate cardiac anomalies to ensure optimal patient outcomes.

Cardioprotective effect of epigallocatechin gallate in myocardial ischemia/reperfusion injury and myocardial infarction: a meta-analysis in preclinical animal studies.

This meta-analysis aims to determine the efficacy of Epigallocatechin gallate (EGCG) in the treatment of myocardial ischemia-reperfusion injury (MIRI) and summarize the mechanisms involved. Literature from six databases including Web of Science, PubMed, Embase, China National Knowledge Infrastructure (CNKI), Wan-Fang database, and VIP database (VIP) were systematically searched. All the analysis were conducted by R. Twenty-five eligible studies involving 443 animals were included in this meta-analysis. The results indicated that compared to controls, EGCG exerts a cardioprotective effect by reducing myocardial infarct size (SMD = -4.06; 95% CI: -5.17, -2.94; P < 0.01; I2 = 77%). The funnel plot revealed publication bias. Moreover, EGCG significantly improves cardiac function, serum myocardial injury enzyme, and oxidative stress levels in MIRI animal models. This meta-analysis demonstrates that EGCG exhibits therapeutic promise in animal models of MIRI. However, further validation is still needed in large animal models and large clinical studies.

Cardioprotective effect of curcumin on myocardial ischemia/reperfusion injury: a meta-analysis of preclinical animal studies.

Objective: This meta-analysis aimed to determine the efficacy of curcumin in preventing myocardial ischemia/reperfusion (I/R) injury in animal models. Methods: Studies published from inception to January 2023 were systematically searched in databases including PubMed, Web of Science, Embase, China's National Knowledge Infrastructure (CNKI), Wan-Fang database, and VIP database (VIP). The SYRCLE's RoB tool was used to determine methodological quality. Sensitivity analysis and subgroup analysis were performed when there was high heterogeneity. Publication bias was assessed using a funnel plot. Results: Thirty-seven studies involving 771 animals were included in this meta-analysis with methodology quality scores ranging from 4 to 7. The results indicated that curcumin treatment significantly improved myocardial infarction size standard mean difference (SMD) = -5.65; 95% confidence interval (CI): 6.94, -4.36; p < 0.01; I2 = 90%). The sensitivity analysis for infarct size showed that the results were stable and reliable. However, the funnel plot was asymmetric. The subgroup analysis included species, animal model, dose, administration, and duration. The results showed that the subgroup dose was statistically significant between subgroups. In addition, curcumin treatment improved cardiac function, myocardial injury enzymes, and oxidative stress levels in animal models of myocardial I/R injury. The funnel plot revealed that there is publication bias for creatine kinase and lactate dehydrogenase. Finally, we performed a meta-analysis of inflammatory cytokines and apoptosis index. The results showed that curcumin treatment downregulated serum inflammatory cytokine levels and myocardial apoptosis index. Conclusion: This meta-analysis suggests that curcumin has excellent potential for the treatment of myocardial I/R injury in animal models. However, this conclusion needs to be further discussed and verified in large animal models and human clinical trials. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022383901.

MKI67 as a potential diagnostic biomarker in pulmonary hypertension.

Background: Right heart failure results from advanced pulmonary hypertension (PH) and has a poor prognosis. There are few available treatments for right heart failure. Pulmonary artery remodeling, including changes in pulmonary artery endothelial cells to endothelial-mesenchymal cells, and aberrant fibroblast and pulmonary artery smooth muscle cell (PASMC) proliferation, are characteristics of the pathophysiological process of PH. As a result, the clinical situation requires novel PH diagnostic and treatment targets. Methods: Monocrotaline was used to create an animal model of PH, and lung tissue was removed for transcriptome sequencing. The targets with the highest differences were chosen for transfection after possible targets were identified using bioinformatic techniques and confirmed by qPCR to examine their function in hypoxic PASMCs. Results: After sequencing 781 differentially expressed mRNAs, we compared them with the GEO dataset and found 43 differentially expressed genes. We chose the top three scores for further study and verification and discovered that MKI67, a crucial element of the cell cycle that regulates PASMC proliferation, had the greatest effect. After suppressing MKI67 in PASMCs, both cell proliferation and migration decreased. Conclusion: Several potential targets were chosen for this study, and MKI67 was found to play a regulatory role in cell migration and proliferation. This implies that PH can be diagnosed and treated using MKI67.

Case Report: Mycobacterium senegalense Infection After Cholecystectomy.

Background: Mycobacterium senegalense is a non-tuberculous mycobacterium and is found everywhere in the environment. However, M. senegalense infection in human is extremely rare, especially in immunocompetent individuals. It is difficult to detect M. senegalense infection because its symptoms are non-specific, and routine diagnostic tests are less sensitive. It is also resistant to commonly used antibiotics. Here, we report the first case of M. senegalense infection after laparoscopic cholecystectomy in China. Case Presentation: A 55-year-old man was admitted because of repeated infections at multiple incision sites for more than 1 year. Although routine diagnostic test results were negative, metagenomic next-generation sequencing (mNGS) identified DNA sequences of M. senegalense in tissue samples from incision sites. The presence of M. senegalense was further confirmed by polymerase chain reaction and capillary electrophoresis. After 60 days of quadruple therapy with clarithromycin, moxifloxacin, rifampicin, and oxycycline, the patient's wound healed. Conclusion: We believe the case findings contribute to the limited amount of knowledge about M. senegalense infection and raises awareness that this infection can result in poor wound healing, even in an immunocompetent host. Owing to a lack of early, precise diagnosis, it is difficult to treat M. senegalense infections. Based on our findings, mNGS is a sensitive diagnostic test for M. senegalense infections.

Identification of altered exosomal microRNAs and mRNAs in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by decreased memory and cognitive functions. Exosomes carry a variety of important information such as proteins, lipids, DNA and RNA of mother cells. It is reported that exosomes play critical roles in nervous system physiology and neurodegenerative diseases. However, the functions of exosomes in AD progression are not fully elucidated. In this study, we detected the expression pattern of mRNAs and miRNAs in exosomes derived from the AD and health mice. A total of 1320 mRNAs and 29 miRNAs were differentially expressed in exosomes between the two groups. Subsequently, the downregulation of Chi3l1 and upregulation of Rhog in AD mice were verified by qRT-PCR. Meanwhile, the downregulation of miR-148a-5p and upregulation of miR-27a-5p in AD group were also tested by qRT-PCR. The functions of differentially expressed mRNAs and potential target genes of miRNAs were determined by GO and KEGG analysis. According to the ceRNA hypothesis, we established an integrated ceRNA network of circRNA-lncRNA-miRNA-mRNA. In conclusion, exosomal lncRNAs, mRNAs, circRNAs and miRNAs were identified to participate in the progression of AD which might be possible biomarkers and therapeutic targets for AD.

Successful management of a rare case of juvenile giant right ventricular myxoma.

Primary cardiac tumors are extremely uncommon in young children and infants. Cardiac myxoma are typically found in the atria, predominately in the left atrium, with relatively few found on the right side, such as in the right ventricle or pulmonary artery. Numerous significant complications, including sudden death, can result from obstruction of the main pulmonary artery trunk and right ventricular outflow tract. Here, we describe the case of a 14-year-old Chinese girl diagnosed with a right ventricular myxoma located in the right ventricle and extended into the main pulmonary trunk. Complete resection of the myxoma and histological confirmation were performed.

Atrial fibrillation and electrophysiology in transgenic mice with cardiac-restricted overexpression of FKBP12.

Cardiomyocyte-restricted overexpression of FK506-binding protein 12 transgenic (αMyHC-FKBP12) mice develop spontaneous atrial fibrillation (AF). The aim of the present study is to explore the mechanisms underlying the occurrence of AF in αMyHC-FKBP12 mice. Spontaneous AF was documented by telemetry in vivo and Langendorff-perfused hearts of αMyHC-FKBP12 and littermate control mice in vitro. Atrial conduction velocity was evaluated by optical mapping. The patch-clamp technique was applied to determine the potentially altered electrophysiology in atrial myocytes. Channel protein expression levels were evaluated by Western blot analyses. Spontaneous AF was recorded in four of seven αMyHC-FKBP12 mice but in none of eight nontransgenic (NTG) controls. Atrial conduction velocity was significantly reduced in αMyHC-FKBP12 hearts compared with NTG hearts. Interestingly, the mean action potential duration at 50% but not 90% was significantly prolonged in αMyHC-FKBP12 atrial myocytes compared with their NTG counterparts. Consistent with decreased conduction velocity, average peak Na+ current ( INa) density was dramatically reduced and the INa inactivation curve was shifted by approximately +7 mV in αMyHC-FKBP12 atrial myocytes, whereas the activation and recovery curves were unaltered. The Nav1.5 expression level was significantly reduced in αMyHC-FKBP12 atria. Furthermore, we found increases in atrial Cav1.2 protein levels and peak L-type Ca2+ current density and increased levels of fibrosis in αMyHC-FKBP12 atria. In summary, cardiomyocyte-restricted overexpression of FKBP12 reduces the atrial Nav1.5 expression level and mean peak INa, which is associated with increased peak L-type Ca2+ current and interstitial fibrosis in atria. The combined electrophysiological and structural changes facilitated the development of local conduction block and altered action potential duration and spontaneous AF. NEW & NOTEWORTHY This study addresses a long-standing riddle regarding the role of FK506-binding protein 12 in cardiac physiology. The work provides further evidence that FK506-binding protein 12 is a critical component for regulating voltage-gated sodium current and in so doing has an important role in arrhythmogenic physiology, such as atrial fibrillation.

A Child with Lung Hypoplasia, Congenital Heart Disease, Hemifacial Microsomia, and Inguinal Hernia: Ipsilateral Congenital Malformations.

A 3-year-old Chinese boy was diagnosed with ipsilateral congenital malformations: right lung hypoplasia, dextroversion of heart, atrial septal defect, hepatic vein drainage directly into the right atrium, facial asymmetry, right microtia and congenital deafness, and indirect inguinal hernia. He underwent indirect inguinal hernia repair at the age of 2. Although without any facial plastic surgery performed, he underwent a repair of atrial septal defect and recovered uneventfully. At 6-month follow-up, the patient was free from any symptom of dyspnea; his heart function returned to the first grade.

A novel variant in TBX20 (p.D176N) identified by whole-exome sequencing in combination with a congenital heart disease related gene filter is associated with familial atrial septal defect.

Congenital heart disease (CHD) is the leading cause of birth defects, and its etiology is not completely understood. Atrial septal defect (ASD) is one of the most common defects of CHD. Previous studies have demonstrated that mutations in the transcription factor T-box 20 (TBX20) contribute to congenital ASD. Whole-exome sequencing in combination with a CHD-related gene filter was used to detect a family of three generations with ASD. A novel TBX20 mutation, c.526G>A (p.D176N), was identified and co-segregated in all affected members in this family. This mutation was predicted to be deleterious by bioinformatics programs (SIFT, Polyphen2, and MutationTaster). This mutation was also not presented in the current Single Nucleotide Polymorphism Database (dbSNP) or National Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project (ESP). In conclusion, our finding expands the spectrum of TBX20 mutations and provides additional support that TBX20 plays important roles in cardiac development. Our study also provided a new and cost-effective analysis strategy for the genetic study in small CHD pedigree.

Fkbp1a controls ventricular myocardium trabeculation and compaction by regulating endocardial Notch1 activity.

Trabeculation and compaction of the embryonic myocardium are morphogenetic events crucial for the formation and function of the ventricular walls. Fkbp1a (FKBP12) is a ubiquitously expressed cis-trans peptidyl-prolyl isomerase. Fkbp1a-deficient mice develop ventricular hypertrabeculation and noncompaction. To determine the physiological function of Fkbp1a in regulating the intercellular and intracellular signaling pathways involved in ventricular trabeculation and compaction, we generated a series of Fkbp1a conditional knockouts. Surprisingly, cardiomyocyte-restricted ablation of Fkbp1a did not give rise to the ventricular developmental defect, whereas endothelial cell-restricted ablation of Fkbp1a recapitulated the ventricular hypertrabeculation and noncompaction observed in Fkbp1a systemically deficient mice, suggesting an important contribution of Fkbp1a within the developing endocardia in regulating the morphogenesis of ventricular trabeculation and compaction. Further analysis demonstrated that Fkbp1a is a novel negative modulator of activated Notch1. Activated Notch1 (N1ICD) was significantly upregulated in Fkbp1a-ablated endothelial cells in vivo and in vitro. Overexpression of Fkbp1a significantly reduced the stability of N1ICD and direct inhibition of Notch signaling significantly reduced hypertrabeculation in Fkbp1a-deficient mice. Our findings suggest that Fkbp1a-mediated regulation of Notch1 plays an important role in intercellular communication between endocardium and myocardium, which is crucial in controlling the formation of the ventricular walls.