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.

Integrated Bioinformatics Analysis Reveals Key Candidate Genes and Cytokine Pathways Involved in COVID-19 After Rhinovirus Infection in Asthma Patients.

BACKGROUND Rhinovirus (RV) is the most common pathogen involved in asthma, and COVID-19, caused by SARS-COV-2, may be more severe in asthma patients. Here, we applied integrated bioinformatics to identify potential key genes and cytokine pathways after RV infection in asthma, and analyzed changes in angiotensin-converting enzyme 2 (ACE2), the cellular receptor of SARS-COV-2. MATERIAL AND METHODS The gene expression profile dataset GSE149273 was downloaded from NCBI-GEO, which included 90 samples of non-infected, RVA, and RVC. Differentially expressed genes (DEGs) were identified using t tests in the limma R package, and subsequently investigated by GO, KEGG, and DO analysis. Moreover, the expression of ACE2 and the proportion of immune cells were further analyzed to determine the effects of RV on cytokines. RESULTS A total of 555 DEGs of RVA and 421 of RVC were identified. There were 415 DEGs in RVA and RVC, of which 406 were upregulated and 9 were downregulated. The functional enrichment analysis showed that most DEGs were obviously enriched in cytokines, and were mainly enriched in "influenza" and "hepatitis C, chronic". In addition, the expression of ACE2 increased significantly and the proportion of immune cytokines significantly changed after RV infection. Our results suggest that RV can activate the cytokine pathway associated with COVID-19 by increasing ACE2. CONCLUSIONS The DEGs and related cytokine pathways after asthma RV infection identified using integrated bioinformatics in this study elucidate the potential link between RV and COVID-19.

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.

Diagnostic Value of Fractional Exhaled Nitric Oxide and Small Airway Function in Differentiating Cough-Variant Asthma from Typical Asthma.

Purpose: To explore the diagnostic value of fractional exhaled nitric oxide (FeNO), small airway function, and a combined of both in differentiating cough-variant asthma (CVA) from typical asthma (TA). Methods: A total of 206 asthma subjects, including 104 CVA and 102 TA, were tested for pulmonary function, bronchial provocation test and FeNO. The correlation between FeNO, small airway function and other pulmonary indicators was analyzed by single correlation and multiple regression analysis. The receiver operating characteristic (ROC) curve was established to evaluate the diagnostic efficiency of FeNO, small airway function, and their combination and to predict the optimal cut-off point. Results: All the respiratory function parameters and small airway function indicators in TA group were significantly different from those in CVA group, and FeNO value was significantly higher than that in CVA group. In addition, the area under the ROC curve (AUC) was estimated to be 0.660 for FeNO, 0.895 for MMEF75%/25%, 0.873 for FEF50%, 0.898 for FEF25%, 0.695 for Fres, 0.650 for R5-R20, and 0.645 for X5. The optimal cut-off points of FeNO, MMEF75%/25%, FEF50%, FEF25%, Fres, R5-R20 and X5, were 48.50 ppb, 60.02%, 63.46%, 45.26%, 16.63 Hz, 0.38 kPa·L-1·s-1, and -1.32, respectively. And the AUC of FeNO combined with small airway function indexes FEF25%, Fres, R5-R20, and X5 were prior than single indicators. Conclusion: FeNO and small airway function indexes might have great diagnostic value for differentiating CVA from TA. The combination of FeNO and FEF25%, Fres, R5-R20, and X5 provided a significantly better prediction than either alone.

Comparison of the efficacy and safety of thoracic endovascular aortic repair with open surgical repair and optimal medical therapy for acute type B aortic dissection: A systematic review and meta-analysis.

BACKGROUND: Current treatment approaches for acute type B aortic dissection (TBAD) are diversified. Thoracic endovascular aortic repair (TEVAR) as an effective and convenient intervention has been adopted extensively. However, the superior efficacy and safety of TEVAR have not yet been well evaluated. This meta-analysis was designed to comprehensively compare the efficacy and safety of TEVAR with open surgical repair and optimal medical therapy for acute type B aortic dissection. METHODS: A systematic search of PubMed, Embase, Cochrane Library and Web of Science up to April 1, 2020 was conducted for relevant studies that compared the efficacy of TEVAR and other conventional interventions in the treatment of TBAD. The primary outcomes were early mortality and midterm or long term survival. The secondary outcomes included early complications and other late outcomes. Two reviewers assessed trial quality and extracted the data independently. All statistical analyses were performed using the standard statistical procedures provided in Review Manager 5.2. RESULTS: A total of 18 studies including 12,789 patients were identified. 30-day/in-hospital mortality was significantly lower in TBAD patients with TEVAR than open surgical repair (OSR), with a pooled OR of 0.54 (95% CI 0.43-0.68; P < 0.00001). Compared with optimal medical therapy (OMT), TEVAR experienced lower incidence of long-term death (≥5-yr mortality), with a pooled OR of 0.46 (95% CI 0.24-0.86; P = 0.02). However, no significant difference between TEVAR and OSR or OMT in long-term survival was found. Compared with OSR, lower incidence of cardiac and pulmonary complications as well as shorter length of stay were observed in TEVAR. Compared with OMT, TEVAR showed higher rate of paraplegia or paraparesis, higher complete thrombosis of the false lumen, as well as longer length of ICU stay. CONCLUSIONS: Our analysis shows that TEVAR may be favorable in reducing 30-day/in-hospital mortality (than OSR) and long-term mortality (than OMT). TEVAR experienced equal efficacy with OSR and OMT in long-term survival. TEVAR showed higher rate of paraplegia or paraparesis, higher complete thrombosis of the false lumen, as well as longer length of ICU stay than OMT; and lower incidence of cardiac and pulmonary complications as well as shorter length of stay than OSR. However, TEVAR indicated similar incidence of other complications and outcomes with OSR and OMT. Further studies especially randomized clinical trials are needed to comprehensively compare the efficacy TEVAR.

Exposure to ozone impacted Th1/Th2 imbalance of CD4+ T cells and apoptosis of ASMCs underlying asthmatic progression by activating lncRNA PVT1-miR-15a-5p/miR-29c-3p signaling.

This investigation attempted to elucidate whether lncRNA PVT1-led miRNA axes participated in aggravating ozone-triggered asthma progression. One hundred and sixty-eight BALB/c mice were evenly divided into saline+air group, ovalbumin+air group, saline+ozone group and ovalbumin+ozone group. Correlations were evaluated between PVT1 expression and airway smooth muscle function/inflammatory cytokine release among the mice models. Furthermore, pcDNA3.1-PVT1 and si-PVT1 were, respectively, transfected into CD4+T cells and airway smooth muscle cells (ASMCs), and activities of the cells were observed. Ultimately, a cohort of asthma patients was recruited to estimate the diagnostic performance of PVT1. It was demonstrated that mice of ovalbumin+ozone group were associated with higher PVT1 expression, thicker trachea/airway smooth muscle and smaller ratio of Th1/Th2-like cytokines than mice of ovalbumin+air group and saline+ozone group (P<0.05). Moreover, pcDNA3.1-PVT1 significantly brought down Th1/Th2 ratio in CD4+ T cells by depressing miR-15a-5p expression and activating PI3K-Akt-mTOR signaling (P<0.05). The PVT1 also facilitated ASMC proliferation by sponging miR-29c-3p and motivating PI3K-Akt-mTOR signaling (P<0.05). Additionally, PVT1 seemed promising in diagnosis of asthma, with favorable sensitivity (i.e. 0.844) and specificity (i.e. 0.978). Conclusively, lncRNA PVT1-miR-15a-5p/miR-29c-3p-PI3K-Akt-mTOR axis was implicated in ozone-induced asthma development by promoting ASMC proliferation and Th1/Th2 imbalance.

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.

Regulatory T cells were recruited by CCL3 to promote cryo-injured muscle repair.

Skeletal muscle injury is a common symptom in daily life. After injury, a distinct population of regulatory T cells (Tregs) will infiltrate skeletal muscle in acute and chronic injury sites. However, the mechanism by which Tregs rapidly accumulate to the site of acute injury remains unclear. BALB/c mice were used to establish a cryo-injured model. Percentage of Tregs in the normal and cryo-injured tissues was detected on different days by flow cytometry. Then, the major factors that contribute to the repair of skeletal muscle by Tregs and the chemokines associated with the chemotaxis of Tregs in the paired muscle were analyzed by qRT-PCR. Finally, Tregs were sorted out by magnetic beads and the transwell analysis was performed in vitro. Compared to the normal muscle, the proportion of Tregs was dramatically-increased in the cryo-injured muscle on day 4. These Tregs produced high level of repair related factors such as amphiregulin (Areg), IL-10 and TGF-ß in the cryo-injured muscle. In addition, we found that CCL3, CCL4, CCL5 were the main chemokines that highly expressed in the injured skeletal muscle compared to the normal skeletal muscle. Simultaneously, their receptors CCR1 and CCR5 were highly expressed on Tregs in cryo-injured muscle compared with the normal muscle. Transwell analysis showed CCL3 can significantly chemotize Tregs and the antibody of CCR1 could reverse the chemotaxis in vitro. These results suggest that Tregs in the cryo-injured muscle play a pivotal role that can promote the regeneration of skeletal muscle and CCL3 may serve as the key chemokine to recruit Tregs to the injury sites.