Association study of FLT4 and HYDIN single nucleotide polymorphisms with atrial septal defect susceptibility in the Han Chinese population of Southwest China.

BACKGROUND: Atrial septal defect (ASD) is a common form of congenital heart disease. Although several genes related to ASD have been found, the genetic factors of ASD remain unclear. This study aimed to evaluate the correlation between 10 candidate single nucleotide polymorphisms (SNPs) and sporadic atrial septal defects. METHODS: Based on the results of 34 individual whole exome sequences, 10 candidate SNPs were selected. In total, 489 ASD samples and 420 normal samples were collected. The 10 SNPs in the case group and the control group were identified through Snapshot genotyping technology. The χ2-test and unconditional regression model were used to evaluate the relationship between ASD and each candidate SNP. Haploview software was used to perform linkage disequilibrium and haplotype analysis. RESULTS: The χ2 results showed that the FLT4 rs383985 (P = 0.003, OR = 1.115-1.773), HYDIN rs7198975 (P = 0.04621, OR = 1.003-1.461), and HYDIN rs1774266 (P = 0.04621, OR = 1.003-1.461) alleles were significantly different between the control group and the case group (P < 0.05). Only the association with the FLT4 polymorphism was statistically significant after adjustment for multiple comparisons. CONCLUSION: These findings suggest that a possible molecular pathogenesis associated with sporadic ASD is worth exploring in future studies.

Identification of ferroptosis-related key genes associated with immune infiltration in sepsis by bioinformatics analysis and in vivo validation.

OBJECTIVES: Sepsis is a life-threatening infectious disease in which an immune inflammatory response is triggered. The potential effect of ferroptosis-related genes (FRGs) in inflammation of sepsis remained unclear. We focused on identifying and validating core FRGs and their association with immune infiltration in blood from currently all patients with sepsis. METHODS: All current raw data of septic blood were obtained from Gene Expression Omnibus. After removing the batch effect merging into a complete dataset and obtaining Diferentially expressed genes (DEGs). Common cross-talk genes were identified from DEGs and FRGs. WGCNA, GO, KEGG, PPI, GESA, ROC curves, and LASSO regression analysis were performed to indentify and validate key genes based on external septic datasets. Infiltrated immune cells in 2 hub genes (MAPK14 and ACSL4) were conducted using CIBERSORT algorithm and Spearman correlation analysis. Further, the expressions of 2 core FRGs were verified in the LPS-induced ALI and cardiac injury sepsis mice. RESULTS: MAPK14 and ACSL4 were identified, mostly enriched in T cell infiltration through NOD-like receptor signaling pathway according to the high or low 2 hub genes expression. The upregulated 2 ferroptosis-related genes were validated in LPS-induced ALI and cardiac injury mice, accompanied by upregulation of the NLRP3 pathway. CONCLUSION: MAPK14 and ACSL4 could become robustly reliable and promising biomarkers for sepsis by regulating ferroptosis through the NLRP3 pathway, which is mainly associated with T-cell infiltration.

Synergistic Enhancement of Isoforskolin and Dexamethasone Against Sepsis and Acute Lung Injury Mouse Models.

Background: Sepsis is initiated by the dysfunctional response of the host immune system to infection. Septic shock and acute lung injury (ALI) are the main etiology of death caused by sepsis. Glucocorticoids, which are commonly used in clinic to antagonize the inflammatory response of sepsis, may cause serious side effects. Isoforskolin (ISOF) from the plant Coleus forskohlii stimulates adenylyl cyclase, increases the cAMP level and inhibits inflammatory response. The aim of this study was to investigate the synergistic effect of ISOF with dexamethasone (DEX) to prevent and ameliorate septic inflammation. Methods: Lipopolysaccharide (LPS) of 30 and 5 mg/kg (iv.) was used to induce sepsis and ALI mice model respectively in vivo. BEAS-2B cells stimulated by LPS were applied as cell model in vitro. The cumulative survival of mice with LPS-induced sepsis and the histopathological changes of lungs in mice with acute lung injury were observed, and the secretion of pro-inflammatory cytokines was analyzed by ELISA. The expression of RGS2 in BEAS-2B cells was detected by immunoblotting assay and PCR. Results: In the sepsis mice model, ISOF (10 mg/kg) combined with DEX (10 mg/kg.) (ip.) pretreatment significantly increased mice survival rate from 33.3% to 58.3%, which was significantly higher than that of ISOF or DEX treated alone. In the ALI mice model, ISOF, DEX pretreatment alone and combined application attenuated pulmonary pathological changes in ALI mice. Furthermore, ISOF, DEX alone or combined administration decreased MPO, MDA, IL-6, and IL-8 levels, while significantly synergistic effects were observed in the combined treatment group compared with ISOF or DEX alone. In BEAS-2B cells, combined pretreatment with ISOF and DEX significantly decreased the expression of IL-8 and increased the expression of RGS2. Conclusion: The results indicated that ISOF in combination with DEX synergistically improves survival rate and attenuates ALI in mice model through anti-inflammatory and antioxidant effects.

Roles of TRPV4 in Regulating Circulating Angiogenic Cells to Promote Coronary Microvascular Regeneration.

To clarify the mechanisms underlying TRPV4 regulating angiogenesis by enhancing the activity of CACs, we detected the angiogenesis ability of HUVEC co-cultured with CACs, the effects of ILK on TRPV4 expression and CACs activity, and the impacts of TRPV4 agonist or inhibitor on cardio-protection of AMI rats with or without CAC transplantation. ILK overexpression or TRPV4 agonist promoted the angiogenesis in HUVEC co-cultured with CACs. ILK overexpression or activation upregulated TRPV4 expression in CACs, while TRPV4 agonist stimulation also regulated ILK expression. TRPV4 agonist effectively improved the myocardial function of AMI rats. Moreover, this effect could be strengthened when combined with CAC transplantation, as CAC transplantation dramatically upregulated the expression of ILK and TRPV4 in heart tissues of AMI rats. Thus, the application of TRPV4 agonist may maintain the activity of CACs to promote angiogenesis and microcirculation reconstruction in the area of myocardial infarction and substantially improve the therapeutic effect.

Bi-atrial or left atrial ablation of atrial fibrillation during concomitant cardiac surgery: A Bayesian network meta-analysis of randomized controlled trials.

OBJECTIVE: Surgical ablation of atrial fibrillation (AF) has become a routine procedure during concomitant cardiac surgery, however, the extension of lesion sets remain controversial. We sought to compare the relative benefit and risk of different lesion sets through a Bayesian network meta-analysis (NMA). METHODS: Pubmed, Embase, and Cochrane Trials databases were searched for randomized controlled trials (RCTs) comparing the rhythm outcome of AF patients undergoing pulmonary vein isolation (PVI), left atrial Maze (LAM), bi-atrial Maze (BAM), or no ablation during concomitant cardiac surgery. An NMA was conducted to explore the difference of over 1 year AF freedom as well as risks for early mortality and permanent pacemaker implantation (PPMI). RESULTS: A total of 2031 patients of 19 RCTs were included. PVI, LAM, and BAM (OR [95% Cr.I]: 5.02 [2.72, 10.02], 7.97 [4.93, 14.29], 8.29 [4.90, 14.86], p < .05) demonstrated higher freedom of AF compared with no ablation, however, no significant difference of rhythm outcome was found among the three ablation strategies based on the random-effects model. BAM was associated with an increase in early mortality when compared with no ablation (OR [95% Cr.I]: 4.08 [1.23, 17.30], p < .05), while none of the remaining comparisons reached statistical difference in terms of early mortality and PPMI. CONCLUSION: Bi-atrial ablation is not superior to left atrial ablation strategies in reducing AF recurrence for un-selected surgical patients. BAM has a higher risk of early mortality than no ablation, but no difference was found between bi-atrial and left atrial ablation in regard to early mortality and PPMI based on the current evidence.

Assessment of Use and Fit of Face Masks Among Individuals in Public During the COVID-19 Pandemic in China.

Importance: Face masks are recommended to prevent transmission of coronavirus disease 2019 (COVID-19); however, there is scarce evidence on their protection efficacy and ways to improve it. Objective: To determine the proportion of improper face mask use, the factors associated with face mask protection efficacy, and ways to improve efficacy. Design, Setting, and Participants: This population-based cross-sectional study was conducted in China from July to August 2020 in 5 kinds of public places. Participants included convenience samples of individuals wearing face masks and able to taste the check solution. Exposures: Demographic and socioeconomic characteristics, including sex, age, and education level; information on face mask model and the worn duration was recorded. Main Outcomes and Measures: The main outcome as airtightness, assessed by detecting face-to-face mask gaps, movement of cotton fiber placed at the face mask edges, and using a qualitative fit test with a bitter solution spray. Masks were further assessed for whether sealing the upper face mask edge with an adhesive tape strip was associated with improved face mask airtightness. Results: Among 6003 face mask wearers enrolled, the mean (SD) age of participants was 31.1 (13.7) years, and 3047 participants (50.8%) were female. The first qualitative fit test found air leakage in 2754 participants (45.9%; 95% CI, 44.6%-47.1%), which was mostly attributable to gaps at the upper face mask edge. After sealing the upper face mask edge with an adhesive tape strip, 69.7% (95% CI, 68.0%-71.5%) of masks that had exhibited leakage became airtight in the second qualitative fit test, and the rate of airtightness reached 96.2% (95% CI, 95.4%-96.8%) in a third qualitative fit test after new surgical face masks with tape on the upper edge were provided to those who had not converted initially. The tape was well tolerated; overall, 6 participants (1.2%) reported a rash and 24 participants (5.8%) reported significant discomfort. Conclusions and Relevance: In this study of face mask fit among participants in China, although most people used face masks in public places, compromised protection due to suboptimal airtightness was common. The simple approach of sealing the upper edge of the face mask with an adhesive tape strip was associated with substantially improved its airtightness.

Tianma Formula Alleviates Dementia via ACER2-Mediated Sphingolipid Signaling Pathway Involving Aß.

OBJECTIVE: To reveal the molecular mechanism of the antagonistic effect of traditional Chinese medicine Tianma formula (TF) on dementia including vascular dementia (VaD) and Alzheimer's disease (AD) and to provide a scientific basis for the study of traditional Chinese medicine for prevention and treatment of dementia. METHOD: The TF was derived from the concerted application of traditional Chinese medicine. We detected the pharmacological effect of TF in VaD rats. The molecular mechanism of TF was examined by APP/PS1 mice in vivo, Caenorhabditis elegans (C. elegans) in vitro, ELISA, pathological assay via HE staining, and transcriptome. Based on RNA-seq analysis in VaD rats, the differentially expressed genes (DEGs) were identified and then verified by quantitative PCR (qPCR) and ELISA. The molecular mechanisms of TF on dementia were further confirmed by network pharmacology and molecular docking finally. RESULTS: The Morris water maze showed that TF could improve the cognitive memory function of the VaD rats. The ELISA and histological analysis suggested that TF could protect the hippocampus via reducing tau and IL-6 levels and increasing SYN expression. Meanwhile, it could protect the neurological function by alleviating Aß deposition in APP/PS1 mice and C. elegans. In the RNA-seq analysis, 3 sphingolipid metabolism pathway-related genes, ADORA3, FCER1G, and ACER2, and another 5 nerve-related genes in 45 key DEGs were identified, so it indicated that the protection mechanism of TF was mainly associated with the sphingolipid metabolism pathway. In the qPCR assay, compared with the model group, the mRNA expressions of the 8 genes mentioned above were upregulated, and these results were consistent with RNA-seq. The protein and mRNA levels of ACER2 were also upregulated. Also, the results of network pharmacology analysis and molecular docking were consistent with those of RNA-seq analysis. CONCLUSION: TF alleviates dementia by reducing Aß deposition via the ACER2-mediated sphingolipid signaling pathway.

Different effects of additional ganglion plexus ablation on catheter and surgical ablation for atrial fibrillation: a systemic review and meta-analysis.

The effect of ganglion plexus (GP) ablation in addition to pulmonary veins isolation (PVI) for atrial fibrillation (AF) remained controversial between the catheter and surgical-based studies. Eleven studies (five randomized controlled trials and six nonrandomized studies) of 1750 patients were included in a meta-analysis to elucidate the incremental benefit of additional GP ablation in patients undergoing catheter or surgical ablation. Risk ratios were calculated for freedom from AF or AT recurrence after a single procedure. Additional GP ablation was associated with a better rhythm outcome for patients undergone catheter ablation but did not seem to increase freedom from AF/AT for surgical patients. Both paroxysmal and non-paroxysmal AF showed a positive outcome comparing additional GP ablation with PVI alone.

[Mechano-electric Feedback and Atrial Fibrillation].

Atrial fibrillation is a common and refractory atrial arrhythmia.Changes of atrial mechanical circumstances are closely related to the occurrence and maintenance of atrial fibrillation.Mechanical factors can increase the automaticity,slow conduction velocity and shorten the effective refractory period of the atrium by causing electrical and structural remodeling,and eventually increase the inducibility of atrial fibrillation.The intracellular calcium level,function and structure of cytoskeleton,local renin-angiotensin system,integrin and mitogen-activated protein kinases(MAPKs)pathway might take part in the process.Here we analyze and review the underlining mechano-electric feedback process of atrial fibrillation and its related research in order to provide a theoretical basis for further research and elucidating of the mechanical mechanism of atrial fibrillation.