Midterm Outcome of Valve Repair for Rheumatic Mitral Stenosis: 6-year Experience in a Single Mid-Volume Cardiac Center.

OBJECTIVES: Previous studies have reported satisfactory long-term results of mitral valve (MV) repair for rheumatic mitral disease. However, the effects of this procedure in isolated rheumatic mitral stenosis remain unclear. In addition, protective effects of MV repair on cardiac function have not been verified in rheumatic MV disease. This study retrospectively evaluated early mortality and mid-term results of MV repair for isolated rheumatic mitral stenosis in a mid-volume cardiac centre, and explored the effects of this procedure on cardiac function. METHODS: Between January 2015 and May 2021, 360 patients with isolated rheumatic mitral stenosis and combined (concomitant) atrial fibrillation (AF) underwent MV repair (100 patients) or MV replacement (260 patients). Perioperative characteristics were compared between the two groups and a regression analysis for early mortality and mid-term left ventricular ejection fraction was conducted. In addition, mid-term survival was compared between the two groups. RESULTS: Baseline characteristics of the two groups were balanced after matching. Compared with patients in the replacement group, patients with MV repair had a lower occurrence of postoperative hypotension and AF. There was no difference in early mortality or mid-term survival between the two groups. However, MV repair was associated with a higher mid-term left ventricular ejection fraction. During follow-up, four thromboembolic events and four haemorrhagic events occurred in the replacement group. No blood coagulation-related complications occurred in the repair group. CONCLUSION: Mitral valve repair for isolated rheumatic mitral stenosis and concomitant AF was feasible in a mid-volume cardiac centre, with satisfactory perioperative results and mid-term outcomes. Furthermore, this procedure preserved mid-term left ventricular systolic function.

Global, Regional, and National Burdens of Ischemic Heart Disease Attributable to Smoking From 1990 to 2019.

Background This study was conducted to estimate the distribution of and changes in the global disease burden of ischemic heart disease attributable to smoking between 1990 and 2019. Methods and Results Data used in this study come from the GBD 2019 (Global Burden of Disease Study 2019). Age-standardized rates and estimated annual percentage change of age-standardized rates were used to describe this burden and its changing trend. Pearson's correlation coefficient was used to evaluate the correlation between the sociodemographic index and changing trend. From 1990 to 2019, the burden of ischemic heart disease attributable to smoking has shown a downward trend globally; estimated annual percentage changes of age-standardized mortality rates and age-standardized disability-adjusted life-years rates were -2.012 (95% CI, -2.068 to -1.956) and -1.907 (95% CI, -1.975 to -1.838). Nineteen countries experienced an increase in disease burden, and the changes in 17 countries were not statistically significant. In addition, this burden was higher in men and older age groups. Estimated annual percentage change of the age-standardized rates of this burden were negatively correlated with the sociodemographic index. Conclusions Although the burden of ischemic heart disease attributable to smoking has decreased in >80% of countries or regions in the past 30 years, it has remained a significant issue in low- and middle-income countries, particularly among men and elderly populations. Therefore, active tobacco control measures, focusing on key populations, are required to reduce the associated burden of ischemic heart disease, especially in those countries or regions with increasing prevalence and disease burden.

Impact of induction therapy on cytomegalovirus infection and post-transplant outcomes in pediatric heart transplant recipients receiving routine antiviral prophylaxis.

OBJECTIVES: Induction therapy has been increasingly used in pediatric heart transplantation. This study evaluated the impact of anti-thymocyte globulin (ATG) versus basiliximab as induction therapy on post-transplant cytomegalovirus (CMV) infection, rejection at 1 year, coronary allograft vasculopathy (CAV), and mortality in pediatric heart transplant recipients receiving antiviral prophylaxis. RESULTS: Of the 96 patients (age < 18 years) analyzed, 46 (47.9%) patients received basiliximab, and 50 (52.1%) received ATG. Median follow-up was 3.0 (IQR, 1.7-4.9) years with 32.3% reporting CMV infection. The ATG group, as compared with the basiliximab group, had similar incidences of CMV infection (36% vs. 28.3%, p = .418), CMV viremia (22% vs. 19.6%, p = .769), and CMV-positive tissue biopsy (30% vs. 22%, p = .486). The ATG group had lower incidences of rejection at 1 year (16% vs. 36.9%, p = .022) and CAV (4% vs. 23.9%, p = .006) with no difference in mortality (8% vs. 15.2%, p = .343), compared with the basiliximab group. Multivariate analysis showed that induction with ATG was associated with a lower risk of rejection at 1 year (OR, .31; 95% CI, .09-.94; p = .039) with no impact on the incidences of CMV infection (HR, 2.06; 95% CI, .54-7.89; p = .292), CAV (HR, .30; 95% CI, .04-2.58; p = .275), and mortality (HR, .39; 95% CI, .09-1.82; p = .233) compared to basiliximab induction. DISCUSSION AND CONCLUSIONS: In conclusion, induction with ATG was associated with reduction in risk of rejection at 1 year with no effects on CMV infection, CAV, and mortality in pediatric heart transplant recipients with universal antiviral prophylaxis compared with basiliximab induction therapy.

The diagnostic significance of integrating m6A modification and immune microenvironment features based on bioinformatic investigation in aortic dissection.

Purpose: The aim of this study was to investigate the role of m6A modification and the immune microenvironment (IME) features in aortic dissection (AD) and establish a clinical diagnostic model for AD based on m6A and IME factors. Methods: GSE52093, GSE98770, GSE147026, GSE153434, and GSE107844 datasets were downloaded from the GEO database. The expression of 21 m6A genes including m6A writers, erasers, readers, and immune cell infiltrates was analyzed in AD and healthy samples by differential analysis and ssGSEA method, respectively. Both correlation analyses between m6A genes and immune cells were conducted by Pearson and Spearman analysis. XGboost was used to dissect the major m6A genes with significant influences on AD. AD samples were classified into two subgroups via consensus cluster and principal component analysis (PCA) analysis, respectively. Among each subgroup, paramount IME features were evaluated. Random forest (RF) was used to figure out key genes from AD and healthy shared differentially expressed genes (DEGs) and two AD subgroups after gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Finally, we constructed an AD diagnostic model combining important m6A regulatory genes and assessed its efficacy. Results: Among 21 m6A genes, WTAP, HNRNPC, and FTO were upregulated in AD samples, while IGF2BP1 was downregulated compared with healthy samples. Immune cell infiltrating analysis revealed that YTHDF1 was positively correlated with γδT cell level, while FTO was negatively correlated with activated CD4+ T cell abundance. FTO and IGF2BP1 were identified to be crucial genes that facilitate AD development according to the XGboost algorithm. Notably, patients with AD could be classified into two subgroups among which 21 m6A gene expression profiles and IME features differ from each other via consensus cluster analysis. The RF identified SYNC and MAPK1IP1L as the crucial genes from common 657 shared common genes in 1,141 DEGs between high and low m6A scores of AD groups. Interestingly, the AD diagnostic model coordinating SYNC and MAPK1IP1L with FTO and IGF2BP1 performed well in distinguishing AD samples. Conclusion: This study indicated that FTO and IGF2BP1 were involved in the IME of AD. Integrating FTO and IGF2BP1 and MAPK1IP1L key genes in AD with a high m6A level context would provide clues for forthcoming AD diagnosis and therapy.

Intrinsic left ventricular impairment in Marfan syndrome: A systematic review and meta-analysis.

BACKGROUND: Intrinsic cardiac impairment in Marfan syndrome (MFS) has been explored in many clinical studies; however, their results have been inconsistent. This meta-analysis aimed to assess the difference in cardiac structure and function between Marfan patients and healthy individuals, and to verify the hypothesis of intrinsic cardiac impairment in MFS. METHODS: Electronic searches for studies were performed in the PubMed, Embase, and Cochrane Library databases. Nine studies with 490 patients with MFS and 478 controls were included in the analysis. Age and sex were strictly matched between Marfan patients and healthy controls in every study. RESULTS: There was no difference in the left ventricular end systolic diameter index (mean difference [MD]: 0.33; 95% confidence interval [CI]: (-0.24, 0.89); p = 0.26) and left ventricular end diastolic diameter index (MD: 0.18; 95% CI: [-0.47, 0.83]; p = 0.58) between Marfan patients and controls. Marfan patients showed larger left ventricular end systolic volume index (MD: 2.62; 95% CI: [0.27, 4.97]; p = 0.03) and left ventricular end diastolic volume index (MD: 4.16; 95% CI: [2.70, 5.63]; p < 0.01) than the control group. Furthermore, Marfan patients showed a lower left ventricular ejection fraction than healthy people (MD: -2.59%; 95% CI: [-4.64%, -0.54%]; p = 0.01). CONCLUSIONS: Intrinsic cardiac impairment was observed in MFS. MFS patients showed the larger left ventricular volume and poorer left ventricular function than matched controls. Considering the potentially adverse impact on cardiac function, intrinsic cardiac impairment in MFS should be considered during the cardiac surgery.

The lncRNA H19/miR-675 axis regulates myocardial ischemic and reperfusion injury by targeting PPARα.

Increasing evidence has indicated that lncRNAs and miRNAs play important roles in the pathogenesis of myocardial ischemic and reperfusion (I/R) injury. This study investigated the potential roles and underlying molecular mechanisms of lncRNA H19 and H19-derived miR-675 in regulating myocardial I/R injury in vitro and in vivo. The results showed that expression of H19 and H19-derived miR-675 was upregulated in cardiomyocytes exposed to oxygen-glucose deprivation and reperfusion. Knockdown of H19 increased cell viability, reduced cell apoptosis, decreased inflammatory cytokines (IL-1ß, TNF-α and IL-6), inhibited oxidative stress, downregulated p-IκB-α and p-p65, and upregulated expression of Nrf2 and HO-1. All of these effects were partly reversed by overexpression of miR-675. Furthermore, we found that PPARα was a target gene of miR-675 and that H19 negatively regulated PPARα expression via miR-675. By inhibiting PPARα, the biological effects of miR-675 or H19 inhibition on cellular functions (apoptosis, inflammation and oxidative stress) were at least partially reversed. Moreover, knockdown of H19 significantly reduced infarct size, increased left ventricular systolic pressure, and decreased left ventricular end-diastolic pressure in a mouse model of myocardial I/R. Taken together, these data indicate that H19 inhibition protects the heart against myocardial I/R injury, which may be partly attributed to regulation of the miR-675/PPARα axis.

Overexpression of CLEC18B Associates With the Proliferation, Migration, and Prognosis of Glioblastoma.

C-type lectin domain family 18 member B (CLEC18B), encoding a superfamily of CLEC, has been found to be expressed in some of cancer cells, which possibly indicates it associated with cancer. However, the defined functional characterizations of CLEC18B in glioblastoma multiforme (GBM) progression still remain unclear. To this end, clinical relevance of CLEC18B expression with GBM patients' prognosis was analyzed both in The Cancer Genome Atlas dataset of 174 tissues and 40 GBM tumor tissues collected from our hospital by using the Kaplan-Meier survival and the Cox proportional hazard model. The role of CLEC18B in GBM was determined by loss-of-function assay using small interfering RNA approach in vitro. Functional and signaling analyses were also performed to understand how CLEC18B facilitated the aggressiveness of GBM at molecular and cellular levels using Cell Counting Kit-8 assay, wound-healing, transwell, and Western blot analyses. Results from our analyses showed that CLEC18B was markedly elevated in both GBM tissues and cells, and exhibited strong inverse correlation with overall survival in GBM patients. Moreover, CLEC18B was identified as an independent predictor of patient survival. Functionally, knockdown of CLEC18B inhibited the growth, migration, and invasion of GBM cells. Mechanistic studies revealed that silencing of CLEC18B resulted in downregulation of Wnt/ß-catenin signaling activity. Collectively, our findings provide clinical, molecular, and cellular evidence of CLEC18B as a promising prognostic biomarker and therapeutic target for GBM.

Original Research: Adipose-derived stem cells from younger donors, but not aging donors, inspire the host self-healing capability through its secreta.

Adipose-derived stem cells demonstrate promising effects in promoting cutaneous wound healing, but the mechanisms are still not well defined and contradictory views are still debatable. In the present research, we established a mouse cutaneous wound model and investigated the effects of adipose-derived stem cells in wound healing. Adipocyte, adipose-derived stem cells, and epidermal keratinocyte stem cells were isolated from younger and aged donors according to the standard protocol. The conditioned medium either from adipose-derived stem cells or from adipocytes was used to treat epidermal keratinocyte cells. The results showed that adipocytes or adipose-derived stem cells isolated from younger donors demonstrated mild advantage over those cells isolated from aging donors. Adipose-derived stem cells showed stronger stimuli than adipocytes, and the adipose-derived stem cells or adipocytes from younger donors enabled to support higher growth rate of keratinocyte stem cells. The invasion of vasculature was observed at day 10 after posttransplantation in the mice bearing the keratinocyte stem cells or combination of keratinocyte stem cells with adipose-derived stem cells; however, simply inoculating keratinocyte stem cells from aging donors did not result in vasculature formation. Adipose-derived stem cells isolated from younger donors were able to inspire the host's self-healing capabilities, and age-associated factors should be taken into consideration when designing a feasible therapeutic treatment for skin regeneration.

The Tumor Suppressive Role of MiRNA-509-5p by Targeting FOXM1 in Non-Small Cell Lung Cancer.

BACKGROUND/AIMS: Deregulation of microRNAs (miRNAs) expression is a frequent event in cancer development and progression. Recent studies have implied that abnormal expression of miRNAs is frequently observed in non-small cell lung cancer (NSCLC). Here, we examined the levels and biological functions of miR-509-5p in NSCLC. METHODS: The levels of miR-509-5p were measured by real-time quantitative PCR (RT-PCR) in NSCLC cell lines and NSCLC tissues along with adjacent normal tissues. Cell viability was analyzed by MTT and colony formation assay. Cell migration and invasion were evaluated by transwell and wound healing assay. In addition, we predicted the putative targets of miR-509-5p by bioinformatics analyses. Moreover, by luciferase-reporter assay, we analyzed the relationship between miR-509-5p and the target in NSCLC cells. RESULTS: miR-509-5p expression was significantly reduced in NSCLC tissues compared with adjacent normal tissues. In addition, miR-509-5p decreased cell proliferation, migration and invasive capability of NSCLC cells. Moreover, we found that FOXM1 was a putative target of miR-509-5p. Enforced miR-509-5p expression in NSCLC cells reduced both mRNA and protein levels of FOXM1. Furthermore, dual-luciferase reporter assay showed miR-509-5p could bind to the 3' untranslational regions of FOXM1 mRNA. Furthermore, overexpression of FOXM1 reversed cell viability, migration, invasion and vimentin levels suppressed by miR-509-5p mimics in H1299 cells. CONCLUSIONS: miR-509-5p exerts tumor-suppressive effects by attenuating FOXM1 in NSCLC. Collectively, these findings provide further evidence that miR-509-5p may be considered as a novel and potential target for the diagnosis, prognosis and treatment of NSCLC.