Del nido versus conventional blood cardioplegia in patients with obstructive hypertrophic cardiomyopathy.

BACKGROUND: Myocardial protection is essential in cardiac surgery with cardiopulmonary bypass The Del Nido cardioplegia which was initially used in pediatric cardiac surgery, has been increasingly used in adult cardiac surgery recently. However, no literature has reported the efficacy of DNC in hypertrophic obstructive cardiomyopathy. METHODS: This retrospective study involved elective patients who underwent extended surgical myectomy with or without concomitant cardiac surgical procedures between September 2017 and June 2022. Patients were distributed into two groups, the DNC and the CBC group. The primary outcome was high-sensitivity cardiac troponin I (hs-TnI) and creatine kinase-MB (CK-MB) levels at the 0, 1, and 2 postoperative days. The secondary outcomes contained: intraoperative LVEF, return to spontaneous rhythm; postoperative myocardial infarction, worsening or deteriorating of EF, mechanical circulatory support; new-onset atrial fibrillation; mechanical ventilation duration; intensive care unit hours; in-hospital days. RESULTS: Fifty-nine patients were included and divided into the CBC (n = 15) and the DNC group (n = 44). There was no statistical difference in patients' demographics and preoperative parameters between the two groups. No in-hospital mortality. The total cardioplegia volume [21.93(18.36,26.07) vs. 25.68(23.17,37.12), p = 0.012] and infusion times [1(1,1) vs. 2(2,3), p = 0.000] were less and the incidence of return to spontaneous rhythm after declamping was higher in the DNC group [97.7% vs. 73.3%, p = 0.013]. Postoperative hs-TnI and CK-MB levels were comparable between the two groups. A longer DNC infusion interval was associated with higher levels of CK-MB on postoperative day 1 and day 2 (p = 0.009 and p = 0.011, respectively). CONCLUSIONS: The use of DNC in extended surgical myectomy procedure was as safe and effective as CBC. However, DNC infusion interval over 60 minutes was associated with increased postoperative CK-MB levels.

LncRNA SENCR overexpression attenuated the proliferation, migration and phenotypic switching of vascular smooth muscle cells in aortic dissection via the miR-206/myocardin axis.

BACKGROUND AND AIMS: Smooth muscle and endothelial cell-enriched migration/differentiation-associated lncRNA (SENCR) has been reported to be associated with some cardiovascular diseases; however, its function and exact molecular mechanism in aortic dissection (AD) remain undefined. Thus, we investigated the effects of SENCR on AD and its potential mechanisms. METHODS AND RESULTS: SENCR expression in aortic media specimens from AD patients was detected by quantitative real-time PCR (qPCR). The roles of SENCR in vascular smooth muscle cell (VMSC) proliferation and migration as well as in the regulation of contractile phenotype genes were studied using CCK-8, wound healing, Transwell, qPCR and Western blot assays. Dual-luciferase reporter assays were performed to identify the regulatory correlation between SENCR, miR-206 and myocardin. Furthermore, mouse AD models were constructed with ApoE-/- mice, and the effect of upregulated SENCR on phenotypic switching in the AD model was detected using hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) assays. SENCR overexpression inhibited VSMC proliferation, migration and synthetic phenotype-related gene expression; decreased miR-206 expression; increased myocardin expression; and suppressed rupture of the aortic media in mice. SENCR knockdown had the opposite effects. Our results further suggested that miR-206 upregulation could reverse the inhibitory roles of SENCR upregulation and that myocardin upregulation could restore the function of SENCR upregulation in VSMCs. Dual-luciferase reporter assays confirmed that SENCR regulated miR-206, which directly targeted myocardin in VSMCs. CONCLUSION: SENCR overexpression suppressed VMSC proliferation and migration, maintained the contractile phenotype and suppressed aortic dilatation via the miR-206/myocardin axis.

miR-335-5p regulates the proliferation, migration and phenotypic switching of vascular smooth muscle cells in aortic dissection by directly regulating SP1.

Uncontrolled proliferation, migration and phenotypic switching of vascular smooth muscle cells (VSMCs) are important steps in the development and progression of aortic dissection (AD). The function and potential mechanism of miR-335-5p in the pathogenesis of AD are explored in this study. Specifically, the biological function of miR-335-5p is explored in vitro through CCK-8, Transwell, immunofluorescence, EdU, wound-healing, RT-qPCR and western blotting assays. In addition, an AD model induced by angiotensin II is used to investigate the function of miR-335-5p in vivo. A dual-luciferase assay is performed to verify the targeting relationship between miR-335-5p and specificity protein 1 (SP1). Experiments involving the loss of SP1 function are performed to demonstrate the function of SP1 in the miR-335-5p-mediated regulation of human aortic-VSMCs (HA-VSMCs). AD tissues and platelet-derived growth factor BB (PDGF-BB)-stimulated HA-VSMCs show significant downregulation of miR-335-5p expression and upregulated SP1 expression. Overexpression of miR-335-5p effectively suppresses cell proliferation, migration and synthetic phenotype markers and enhances contractile phenotype markers induced by PDGF-BB treatment. Additionally, SP1 is identified as a target gene downstream of miR-335-5p, and its expression is negatively correlated with miR-335-5p in AD. Upregulation of SP1 partially reverses the inhibitory effect of miR-335-5p on HA-VSMCs, whereas the downregulation of SP1 has the opposite effect. Furthermore, Ad-miR-335-5p clearly suppresses aorta dilatation and vascular media degeneration in the AD model. Our results suggest that miR-335-5p inhibits HA-VSMC proliferation, migration and phenotypic switching by negatively regulating SP1, and indicate that miR-335-5p may be a potential therapeutic target in AD.

Altered Lung Microbiome and Metabolome Profile in Children With Pulmonary Arterial Hypertension Associated With Congenital Heart Disease.

Backgrounds: Pulmonary arterial hypertension (PAH) is characterized by progressive pulmonary vascular functional and structural changes, resulting in increased pulmonary vascular resistance and eventually right heart failure and death. Congenital Left-to-Right shunts (LTRS) is one type of congenital heart disease (CHD) and PAH associated with the congenital Left-to-Right shunt (PAH-LTRS) is a severe disease in children. However, changes in the lung microbiome and their potential impact on PAH-LTRS have not been not fully studied. We hypothesized that lung microbiota and their derived metabolites have been disturbed in children with PAH-LTRS, which might contribute to the progression and outcomes of PAH-LTRS. Methods: In this study, 68 age- and sex-matched children of three different groups (patients with PAH-LTRS cohort, patients with LTRS but have no pathologic features of PAH cohort, and healthy reference cohort) were enrolled in the current study. Bronchoalveolar lavage fluid samples from these participants were conducted for multi-omics analysis, including 16S rRNA sequencing and metabolomic profiling. Data progressing and integration analysis were performed to identify pulmonary microbial and metabolic characteristics of PAH-LTRS in children. Results: We found that microbial community density was not significantly altered in PAH-LTRS based on α-diversity analysis. Microbial composition analysis indicated phylum of Bacteroidetes was that less abundant while Lactobacillus, Alicycliphilus, and Parapusillimonas were significantly altered and might contribute to PAH in children with LTRS. Moreover, metabolome profiling data showed that metabolites involved in Purine metabolism, Glycerophospholipid metabolism, Galactose metabolism, and Pyrimidine metabolism were also significantly disturbed in the PAH-LTRS cohort. Correlation analysis between microbes and metabolites indicated that alterations in the microbial composition from the lung microbiota could eventually result in the disturbance in certain metabolites, and might finally contribute to the pathology of PAH-LTRS. Conclusion: Lung microbial density was not significantly altered in patients with PAH-LTRS. Composition analysis results showed that the relative microbiome abundance was different between groups. Metabolome profiling and correlation analysis with microbiota showed that metabolome also altered in children with PAH-LTRS. This study indicated that pulmonary microbes and metabolites disturbed in PAH-LTRS could be potentially effective biomarkers and provides valuable perspectives on clinical diagnosis, treatment, and prognosis of pediatric PAH-LTRS.

SSR-Sequencing Reveals the Inter- and Intraspecific Genetic Variation and Phylogenetic Relationships among an Extensive Collection of Radish (Raphanus) Germplasm Resources.

Raphanus has undergone a lengthy evolutionary process and has rich diversity. However, the inter- and intraspecific phylogenetic relationships and genetic diversity of this genus are not well understood. Through SSR-sequencing and multi-analysis of 939 wild, semi-wild and cultivated accessions, we discovered that the European wild radish (EWR) population is separated from cultivated radishes and has a higher genetic diversity. Frequent intraspecific genetic exchanges occurred in the whole cultivated radish (WCR) population; there was considerable genetic differentiation within the European cultivated radish (ECR) population, which could drive radish diversity formation. Among the ECR subpopulations, European primitive cultivated radishes (EPCRs) with higher genetic diversity are most closely related to the EWR population and exhibit a gene flow with rat-tail radishes (RTRs) and black radishes (BRs)/oil radishes (ORs). Among Asian cultivated radishes (ACRs), Chinese big radishes (CBRs) with a relatively high diversity are furthest from the EWR population, and most Japanese/Korean big radishes (JKBRs) are close to CBR accessions, except for a few old Japanese landraces that are closer to the EPCR. The CBR and JKBR accessions are independent of RTR accessions; however, phylogenetic analysis indicates that the RTR is sister to the clade of CBR (including JWR), which suggests that the RTR may share the most recent common ancestry with CBRs and JWRs. In addition, Japanese wild radishes (JWRs), (namely, R. sativus forma raphanistroides) are mainly scattered between CBRs and EPCRs in PCoA analysis. Moreover, JWRs have a strong gene exchange with the JKBR, OR and RTR subpopulations. American wild radishes (AWRs) are closely related to European wild and cultivated radishes, and have a gene flow with European small radishes (ESRs), suggesting that the AWR developed from natural hybridization between the EWR and the ESR. Overall, this demonstrates that Europe was the origin center of the radish, and that Europe, South Asia and East Asia appear to have been three independent domestication centers. The EPCR, AWR and JWR, as semi-wild populations, might have played indispensable transitional roles in radish evolution. Our study provides new perspectives into the origin, evolution and genetic diversity of Raphanus and facilitates the conservation and exploitation of radish germplasm resources.