Exploring Ferroptosis-Associated Gene Signatures as Diagnostic and Therapeutic Targets for Sepsis-Induced Cardiomyopathy.

BACKGROUND: Sepsis-induced cardiomyopathy (SICM) is a severe complication of sepsis associated with high mortality rates. Despite its significance, the molecular mechanisms underlying SICM remain poorly understood, particularly the role of ferroptosis - a form of iron-dependent programmed cell death. METHODOLOGY: This study analyzed the GSE79962 dataset from the Gene Expression Omnibus, containing cardiac gene expression profiles from SICM patients and controls. A list of ferroptosis-related genes (FRGs) was retrieved from the FerrDb. We used the limma package in R for differential expression analysis, setting an adjusted P-value cutoff of <0.05 and a log2-fold change threshold of ±1 to identify differentially expressed ferroptosis-related genes (DE-FRGs). We applied machine learning algorithms for biomarker identification, including least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine with recursive feature elimination (SVM-RFE), implemented via the glmnet and e1071 packages in R, respectively. Gene set enrichment analysis (GSEA) was conducted using the GSEA package to investigate the biological pathways related to key DE-FRGs. RESULTS: After differential expression analysis, we identified 145 DE-FRGs. Functional enrichment analyses underscored the involvement of these genes in critical biological processes and pathways, such as lipid metabolism and insulin resistance. Machine learning approaches pinpointed five key DE-FRGs (NCOA4, GABARAPL1, GJA1, CISD1, CP), with strong predictive potential for SICM. Further analyses, including the construction of a ceRNA network, revealed intricate post-transcriptional regulatory mechanisms that may influence the expression of these key genes. CONCLUSIONS: Our findings highlight the central role of ferroptosis in SICM and identify potential biomarkers and therapeutic targets that could help refine diagnostic and treatment strategies. This study advances our understanding of the molecular underpinnings of SICM and sets the stage for future research aimed at mitigating this severe sepsis complication.

ITGAM: A Pivotal Regulator in Macrophage Dynamics and Cardiac Function During Sepsis-Induced Cardiomyopathy.

BACKGROUND: Sepsis-induced cardiomyopathy (SIC) is a critical complication arising from sepsis characterized by reversible myocardial dysfunction. Despite the increasing attention to SIC in research, the underlying molecular mechanisms remain poorly comprehended. METHODS: In this study, we utilized bioinformatics to analyze RNA-sequencing (RNA-seq) and single-cell RNA-sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database to identify key immune cell populations and molecular markers associated with SIC. Our experimental approach combined in vitro and in vivo studies to investigate the roles of integrin alpha M (ITGAM) and intracellular adhesion molecule-1 (ICAM-1) in macrophage recruitment and phenotypic polarization, as well as their impact on cardiac function during SIC. RESULTS: The bioinformatics analysis disclosed significant alterations in gene expression and immune cell composition within the cardiac tissue during SIC, where macrophages emerged as the predominant immune cell type. Notably, ITGAM was identified as a key regulatory molecule that modulates macrophage function, driving the pathogenesis of SIC through its influence on the recruitment and functional reprogramming of these cells. In vitro experiments revealed that lipopolysaccharide (LPS) stimulation triggered an upregulation of ITGAM in macrophages and ICAM-1 in endothelial cells, underscoring their critical roles in immune cell mobilization and intercellular communication. The strategic administration of ITGAM-neutralizing antibodies to SIC mice resulted in a marked decrease in macrophage infiltration within the cardiac tissue, which was initially associated with an improvement in cardiac function. However, this intervention paradoxically resulted in an increased mortality rate during the later phases of SIC, underscoring the complex and dualistic function of ITGAM. CONCLUSION: This study provides new insights into the complex dynamics of immune cells within the cardiac environment during SIC, with a particular emphasis on the modulatory role of ITGAM in shaping macrophage behavior. The findings shed light on the reversible nature of myocardial dysfunction in SIC and emphasize the importance of targeted therapeutic strategies for the effective management of SIC.

Association of urinary bisphenol A levels with heart failure risk in U.S. adults from the NHANES (2003-2016).

Introduction: Although heart failure (HF) has been linked to bisphenol A (BPA), few studies have investigated the cut-off values for the effects of urinary BPA levels on heart failure risk. The association between urinary BPA levels and HF prognosis has not been investigated. Methods: This study included 11,849 adults over 20 years old using information from the National Health and Nutrition Examination Survey (NHANES), which was conducted from 2003 to 2016. The relationship between urinary BPA levels and the risk of HF was determined via a multivariable logistic regression model, and restricted cubic spline (RCS) methods were used to determine the cut-off for the effect of BPA levels on HF risk. Based on the available NT-proBNP concentration data from the NHANES (2003-2004), multivariable linear regression was applied to determine the linear association between the NT-proBNP concentration and urinary BPA concentration. Results: The results revealed a positive correlation between a urinary BPA concentration in the fourth quartile and the occurrence of heart failure [OR 1.49, 95% CI (1.09, 2.04), p = 0.012]. A one-unit increase (1 ng/mg creatinine) in the ln-transformed BPA concentration was linked to a 15% increase in the incidence of HF [OR 1.15, 95% CI (1.03, 1.29), p = 0.014]. The cut-off urinary BPA concentration for HF risk was 1.51 ng/mg creatinine. There was a positive correlation between urinary BPA and NT-proBNP concentrations [ß = 0.093, 95% CI (0.014, 0.171), p = 0.02] in males, but there was no linear association [ß = 0.040, 95% CI (-0.033, 0.113), p = 0.283] in females. Discussion: Increased urinary BPA levels are linked to an increased risk of heart failure and poor prognosis. There is a significant increase in the risk of heart failure if the urinary concentration of BPA exceeds 1.51 ng/mg creatinine.

N, P and C removal simultaneously and microbial population numbers in a cyclic activated sludge system treating village and township domestic wastewater by altering the cycle times.

It was necessary to research an efficient treatment process suitable for township domestic wastewater. In this paper, the performance of the cyclic activated sludge system (CASS) system for simultaneous carbon (C), nitrogen (N) and phosphorus (P) removal was investigated by changing the operation cycle of the CASS reactor. Four operating conditions were set up, T1, T2, T3 and T4, with cycle times of 6, 8, 12 and 8 h (with carbon source), respectively. The results showed that the CASS system had good simultaneous removal of C, N and P. The highest removal rates of COD, TN, NH4+ -N and TP were 87.69, 72.99, 98.60 and 98.38%, respectively, at a cycle time of 8 h. The TN removal rate could be increased to 82.51% after the addition of carbon source. Microbial community analysis showed that Proteobacteria, Bacteroidetes and Candidatus Saccharibacteria were the main phylum-level bacteria. Their presence facilitated the effectiveness of the CASS process for nitrogen removal and phosphorus removal. Functional analysis of genes revealed that the abundance values of genes associated with C, N and P metabolism were higher when the treatment was effective.

Genome-wide analysis of RNA-binding proteins co-expression with alternative splicing events in mitral valve prolapse.

Objectives: We investigated the role and molecular mechanisms of RNA-binding proteins (RBPs) and their regulated alternative splicing events (RASEs) in the pathogenesis of mitral valve prolapse (MVP). Methods: For RNA extraction, we obtained peripheral blood mononuclear cells (PBMCs) from five patients with MVP, with or without chordae tendineae rupture, and five healthy individuals. High-throughput sequencing was used for RNA sequencing (RNA-seq). Differentially expressed genes (DEGs) analysis, alternative splicing (AS) analysis, functional enrichment analysis, co-expression of RBPs, and alternative splicing events (ASEs) analysis were conducted. Results: The MVP patients exhibited 306 up-regulated genes and 198 down-regulated genes. All down- and up-regulated genes were enriched in both Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Furthermore, MVP was closely associated with the top 10 enriched terms and pathways. In MVP patients, 2,288 RASEs were found to be significantly different, and four suitable RASEs (CARD11 A3ss, RBM5 ES, NCF1 A5SS, and DAXX A3ss) were tested. We identified 13 RNA-binding proteins (RBPs) from the DEGs and screened out four RBPs (ZFP36, HSPA1A, TRIM21, and P2RX7). We selected four RASEs based on the co-expression analyses of RBPs and RASEs, including exon skipping (ES) of DEDD2, alternative 3' splice site (A3SS) of ETV6, mutually exclusive 3'UTRs (3pMXE) of TNFAIP8L2, and A3SS of HLA-B. Furthermore, the selected four RBPs and four RASEs were validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and showed high consistency with RNA sequencing (RNA-seq). Conclusion: Dysregulated RBPs and their associated RASEs may play regulatory roles in MVP development and may therefore be used as therapeutic targets in the future.

High­risk pathological subtype associated FAM83A­AS1 promotes malignancy and glycolysis of lung adenocarcinoma via miR­202­3p/HK2 axis.

According to the diverse cellular morphology, lung adenocarcinoma (LUAD) was classified into five pathological subtypes, referred to as follows: High­risk group (micropapillary and solid), intermediate­risk group (acinar and papillary) and low­risk group (epidic). Nevertheless, little is known about the biological function of long non­coding RNA (lncRNA) in the molecular determination of LUAD histologic patterns. Screening the transcriptional expression data from TCGA­LUAD, the differentially expressed lncRNA across the divergent pathological subtypes were explored. Pan­cancer analysis revealed the characteristic of FAM83A­AS1, which was also confirmed in the LUAD tissues. The function of FAM83A­AS1 was uncovered through the in vitro assays. RNA immunoprecipitation and dual­luciferase reporter assays were performed to explore the molecular mechanisms of FAM83A­AS1. In the present study, it was identified that the expression of FAM83A­AS1 was increased from the low­risk group to the high, which was associated with a poorer prognosis and higher risk of recurrence. Pan­cancer analysis revealed that FAM83A­AS1 was positively correlated with high tumor mutational burden. Additionally, FAM83A­AS1 promoted cell migration, invasion and growth of LUAD cancer cells. Mechanistically, FAM83A­AS1 sponged miR­202­3p to regulate the expression of hexokinase II (HK2) in post­transcription, which facilitated the malignancy and glycolysis. The present study uncovered the biological roles of FAM83A­AS1/miR­202­3p/HK2 axis in regulating malignancy and glycolysis of LUAD, which provided novel avenues to addressing the determination of histologic patterns.

Maternal Serum tRNA-Derived Fragments (tRFs) as Potential Candidates for Diagnosis of Fetal Congenital Heart Disease.

BACKGROUND: Congenital heart disease (CHD) is one of the most predominant birth defects that causes infant death worldwide. The timely and successful surgical treatment of CHD on newborns after delivery requires accurate detection and reliable diagnosis during pregnancy. However, there are no biomarkers that can serve as an early diagnostic factor for CHD patients. tRNA-derived fragments (tRFs) have been reported to play an important role in the occurrence and progression of numerous diseases, but their roles in CHD remains unknown. METHODS: High-throughput sequencing was performed on the peripheral blood of pregnant women with an abnormal fetal heart and a normal fetal heart, and 728 differentially expressed tRFs/tiRNAs were identified, among which the top 18 tRFs/tiRNAs were selected as predictive biomarkers of CHD. Then, a quantitative reverse transcriptase polymerase chain reaction verified the expression of tRFs/tiRNAs in more clinical samples, and the correlation between tRFs/tiRNAs abnormalities and CHD was analyzed. RESULTS: tRF-58:74-Gly-GCC-1 and tiRNA-1:35-Leu-CAG-1-M2 may be promising biomarkers. Through further bioinformatics analysis, we predicted that TRF-58:744-GLy-GCC-1 could induce CHD by influencing biological metabolic processes. CONCLUSIONS: Our results provide a theoretical basis for the abnormally expressed tRF-58:74-Gly-GCC-1 in maternal peripheral blood as a new potential biomarker for the accurate diagnosis of CHD during pregnancy.

Functional analysis of differently expressed ferroptosis-related genes in patients with mitral valve prolapse.

Background: The prevalence of mitral valve prolapse (MVP) in heart valvular diseases is globally increasing. However, the understanding of its etiology and pathogenesis is limited. So far, the relationship between ferroptosis-related genes and long non-coding RNAs (lncRNAs) in MVP remains unexplored. This study investigates the potential pathogenesis of ferroptosis-related genes in MVP and provides a therapeutic target for the disease. Methods: Blood samples from patients with MVP and healthy volunteers were collected for transcriptomic sequencing to analyze the expression of ferroptosis-related differentially expressed genes (DEGs) and differentially expressed long non-coding RNAs (DElncRNAs Co-expression network of ferroptosis-related DEGs and DElncRNAs. Furthermore, this work conducted GO and KEGG enrichment analyses. Results: CDKN2A, SLC1A4, ATF3, and other core genes related to the mitral valve prolapse were screened out. CDKN2A, SLC1A4, and ATF3 genes were at the core position of the network, regulated by numerous lncRNAs. Notably, these genes are primarily involved in the extracellular region and p53 signaling pathway. Conclusion: In summary, CDKN2A, SLC1A4, and ATF3 regulate the pathophysiological process of MVP and are potential therapeutic targets.

Aortic valve repair for the treatment of rheumatic aortic valve disease: a systematic review and meta-analysis.

Valvuloplasty for rheumatic aortic valve disease remains controversial. We conducted this study to explore whether aortic valvuloplasty is appropriate for the rheumatic population. A comprehensive search was conducted, and 7 eligible retrospective studies were identified from PubMed, Embase, Medline and Cochrane (up to April 7, 2020) according to the inclusion and exclusion criteria. The data for hospital mortality, 5-year survival, 5-year reoperation, aortic insufficiency grade (AIG) and aortic valve gradient (AVG) were extracted by 2 independent reviewers and were analysed to evaluate the safety and availability of aortic valvuloplasty for rheumatic patients. The heterogeneity of the results was estimated using the Q test and I2 statistics. The fixed pooling model was used when I2 ≤ 50%; otherwise, the random pooling model was selected. 7 articles with 418 patients were included. The pooled hospital mortality, 5-year survival and 5-year reoperation rates were 3.2%, 94.5% and 9.9%, respectively. The heterogeneities of the weighted mean differences (WMD) values of the AIG and AVG between preoperation and postoperation were extremely high (I2 = 81.5%, p < 0.001 in AIG, I2 = 97.6%, p = 0.003 in AVG). Subgroup analysis suggested that the AIG and AVG were improved by 3.03 grades (I2 = 0%, p < 0.001) and 3.16 mmHg (I2 = 0%, p < 0.001) in the European group, respectively. In the Asian group, the AIG and AVG were improved by 2.57 grades (I2 = 0%, p < 0.001) and 34.39 mmHg (I2 = 0%, p < 0.001), respectively. Compared with the values at discharge, the AIG was increased by 0.15 grades (I2 = 0%, p = 0.031) and the AVG was still decreased by 2.07 mmHg (I2 = 0%, p = 0.031) at the time of follow up. Valvuloplasty is safe and effective to treat rheumatic aortic insufficiency and stenosis, and the duration of maintenance required to improve stenosis was longer than that of insufficiency.

Comparison of catheter and surgical ablation of atrial fibrillation: A systemic review and meta-analysis of randomized trials.

OBJECTIVE: To compare both the beneficial and adverse effects of catheter ablation (CA) and surgical ablation (SA) on patients with atrial fibrillation (AF). METHODS: We searched MEDLINE and 4 additional databases for randomized controlled trials that compared CA with SA. Following data extraction, we conducted a meta-analysis to estimate the efficacy and safety of CA relative to SA. The primary end point of this study was the absence of AF during a 12-month follow-up period without the use of antiarrhythmic drugs. RESULTS: Seven trials comparing SA with CA met the inclusion criteria for efficacy outcome assessments. Following the meta-analysis, we obtained a summary odds ratio (OR) of achieving success 1 year after CA relative to SA was 0.37:1 (95% confidence interval [CI], 0.20-0.69). The result was robust in the subgroup analysis. CA was associated with a greater incidence of femoral vascular complications (OR, 5.81; 95% CI, 1.03-32.71), but a lower incidence of pneumothorax (OR, 0.09; 95% CI, 0.01-0.74) than SA. Statistically significant differences in the other safety outcomes were not observed between CA and SA. CONCLUSIONS: SA confers a moderate advantage over CA in 1-year efficacy outcomes and may be safely performed by experienced surgeons.

Surgical ablation supplemented by ethanol injection for ventricular tachycardia refractory to percutaneous ablation.

BACKGROUND: A combination of endocardial and epicardial approaches has improved the overall success rate of ventricular tachycardia (VT) ablation in patients with cardiomyopathy. However, the origins of some VTs are truly intramural or close to coronary arteries, which makes this combined strategy either prone to failure or too risky. OBJECTIVES: This observational study aimed to explore the feasibility and efficacy of direct epicardial ablation combined with intramural ethanol injection via surgical approach for inaccessible intramural VTs or VTs too close to coronary arteries. METHODS: In four canines ventricular lesions produced by direct epicardial injection of ethanol were assessed. Six consecutive patients with recurrent VT refractory to catheter endocardial and epicardial RF ablation and that remained inducible after surgical epicardial mapping and RF ablation were included. Ethanol was injected by needle at the epicardial RF ablation sites. The primary outcome was freedom of sustained VT determined by device interrogation and periodical 24-h holter recordings subsequently. RESULTS: In an animal study, the lesions were homogenous and increased in size with the volume of ethanol injected. In all six patients, ethanol injection at the target sites in the anterior or lateral left ventricle abolished inducible VT. Over a median follow-up of 22 months (range, 6-65), all patients remained free of sustained VT. One patient died of pulmonary infection one year after the procedure. CONCLUSIONS: A hybrid strategy of surgical ablation combined with intramural ethanol injection is feasible and effective in patients with multiple failed percutaneous ablation attempts.

Tocilizumab for treating COVID-19: a systemic review and meta-analysis of retrospective studies.

OBJECTIVES: COVID-19 has become a global epidemic, and effective therapies have not been discovered up to now. We conducted this study to explore the effectiveness and safety of tocilizumab recently used for treating COVID-19. METHOD: A comprehensive search was conducted (up to September 27, 2020), and 19 eligible records were identified according to the inclusion and exclusion criteria. The data of the studies were extracted by 2 independent reviewers and were analyzed to evaluate the safety and availability of tocilizumab for treating COVID-19. RESULTS: Thirteen retrospective case-control studies (n = 2285 patients) and 6 retrospective single-armed studies (n = 208) were retrieved in this study. In the comparison of tocilizumab treatment group (TCZ) and standard treatment group (ST), significant associations with a lower risk of admission to ICU, use of ventilation, and mortality (OR, 95% CI: 0.53, 0.26~1.09; 0.66, 0.46~0.94; 0.44, 0.36~0.55) were found in the tocilizumab treatment group. What is more, patients treated with tocilizumab had better clinical improvement compared with the patients treated with ST (OR, 1.24; 95% CI, 0.96~1.62). After taking tocilizumab, the patients had lower C-reactive protein (CRP), white blood cell count (WBC), aspartate aminotransferase (AST) (WMD, 95% CI: - 99.66, - 156.24~- 43.09; - 0.95, - 1.8~- 0.11; - 12.58, - 18.88~-6.29) but higher troponin (WMD, 7.61; 95% CI, 3.06~12.15) than before. In addition, tocilizumab did not have significant influence on patients' neutrophil count (Neut), lymphocyte count (Lymp), platelet count (Plt), alanine aminotransferase (ALT), and creatine (WMD, 95% CI: - 0.29, - 2.91~2.33; 0.42, - 0.23~1.07; 5.2, - 2.85~13.25; 22.49, - 2.73~47.7; - 44.78, - 93.37~3.81). CONCLUSION: Tocilizumab may have potential effectiveness to treat COVID-19 according to the results of this study. However, more large-scale studies are needed for more accurate conclusions.

MiR-889 promotes cell growth in human non-small cell lung cancer by regulating KLF9.

Currently, non-small cell lung cancer (NSCLC) is still the most common malignancy worldwide. Although miR-889 has been reported to play an important role in various malignancies, the physiological function of miR-889 in NSCLC remains unknown. This paper places emphasis on the influence of miR-889 on the development and progression of non-small cell lung cancer. To detect the expression level of miR-889 in NSCLC tissues and cell lines, quantitative real-time polymerase chain reaction (qRT-PCR) assay and In Situ Hybridization (ISH) were adopted in this study. Cell proliferation and colony forming ability were examined by Cell Counting Kit-8 (CCK-8) and colony formation assays. Furthermore, transwell experiments were conducted to determine the influence of miR-889 on migration. KLF9 expression was evaluated by qRT-PCR and Western blotting. First, miR-889 expression was increased in the cancer tissues of non-small cell lung cancer patients (n = 40) compared with adjacent tissues. Subsequently, knockdown of miR-889 significantly inhibited cell proliferation and migration, while overexpression of miR-889 had the opposite effect. KLF9 may be a potential target of miR-889. In addition, upregulation of miR-889 promotes tumorigenesis in vitro, and KLF9 protein levels are also reduced. The current study suggests that miR-889 may play a potential therapeutic role for NSCLC by targeting KLF9 to control NSCLC proliferation and migration.

Effect of eNOS on Ischemic Postconditioning-Induced Autophagy against Ischemia/Reperfusion Injury in Mice.

Autophagy is involved in the development of numerous illnesses, including ischemia/reperfusion (I/R). Endothelial nitric oxide synthase (eNOS) participates in the protective effects of ischemic postconditioning (IPostC). However, it remains unclear whether eNOS-mediated autophagy serves as a critical role in IPostC in the hearts of mice, in protecting against I/R injury. In the present study, the hearts of mice with left anterior descending coronary artery ligation were studied as I/R models. H9c2 cells underwent exposure to hypoxia/reoxygenation (H/R) and were examined as in vitro model. IPostC reduced mice myocardial infarct size and improved the structure of the heart. IPostC increased the formation of autophagosomes and increased the phosphorylation of eNOS and adenosine monophosphate-activated protein kinase (AMPK). Autophagy and eNOS inhibition suppressed the cardioprotective effects of IPostC. AMPK or eNOS inhibition abolished the improvement effect of IPostC on autophagy. AMPK inhibition decreased eNOS phosphorylation in the heart. Additionally, H9c2 cells suffering hypoxia were used as in vitro model. Autophagy or eNOS inhibition abolished the protective effects of hypoxic postconditioning (HPostC) against H/R injury. AMPK and eNOS inhibition/knockout decreased autophagic activity in the HPostC group. These results indicated that IPostC protects the heart against I/R injury, partially via promoting AMPK/eNOS-mediated autophagy.

B-type Natriuretic Peptide and Other Risk Factors for Predicting Postoperative Atrial Fibrillation after Thoracic Surgery.

BACKGROUND: Postoperative atrial fibrillation (POAF) is associated with increased morality rate, prolonged hospitalization, and reduced long-term survival after surgery. Thus, prediction of POAF is important to assess surgical risk and provide prophylaxis. METHODS: It was a prospective study of 207 consecutive patients who underwent a routine preoperative laboratory testing before thoracic surgery from October 2016 to May 2017. Comprehensive data were collected. Then stepwise multivariate logistic regression analysis was adopted to identify significant risk factors associated with POAF from various variables. RESULTS: As results, three variables as follows: male gender, open thoracotomy, and B-type natriuretic peptide (BNP) exceeding 59 pg/mL were considered as independent risk factors associated with POAF (p < 0.05). CONCLUSION: In patients undergoing noncardiac thoracic surgery, we found that an elevated preoperative BNP level (with the level of 59 pg/mL as a cutoff), male gender, and open-chest surgeries were significant risk factors for POAF. The identification of patients who are prone to develop POAF will provide prevention strategies to reduce this complication.

Association between polyfluoroalkyl chemical concentrations and leucocyte telomere length in US adults.

Exposure to some environmental chemicals is reportedly associated with the leucocyte telomere length (LTL), but the effects of the non-occupational exposure to polyfluoroalkyl chemical (PFCs) on the LTL are not well understood. Using data from 773 participants in the National Health and Nutrition Examination Survey (NHANES) conducted in 1999-2000, we analysed the association between blood PFC concentrations and LTL. Coefficients (betas) and 95% confidence intervals (CIs) for the blood PFC concentrations in association with the LTL were estimated using multivariate linear regression models after adjustment for age, gender, race, body mass index (BMI), poverty income ratio, educational level, white blood cell count, C-reactive protein and other PFCs. The results identified a strong positive association between the blood perfluorooctane sulfonic acid (PFOS) concentration and LTL in adults, and no associations were found between the LTL and other PFCs. In the linear regression models, each increment of one standard deviation (SD) in the base-10-logarithm-transformed PFOS concentration was associated with a 21-bp increase in the LTL in the fully adjusted model (P = 0.033). Moreover, serum PFOS was associated with the LTL mainly in females and individuals aged 40-50, as demonstrated by stratified analyses. These results provide epidemiological evidence showing that environment-related levels of serum PFOS are positively associated with the LTL in adults.

Total endoscopic repair of atrial septal defect under on-pump beating heart.

BACKGROUND: We previously reported the techniques for total endoscopic atrial septal defect (ASD) repair on hearts arrested with cardioplegia through three small incisions in the chest wall without aid of a surgical robotic system. The optimal results motivated us to use total thoracoscopic technology for ASD on perfused beating hearts. METHODS: From 2010 to 2017, 161 patients with a mean age of 28.31±12.34 years who underwent non-robotically assisted total thoracoscopic closure for ASD were included in this study, and those patients were also divided into two groups, including group A and group B. In group A, 115 patients underwent the procedure on beating hearts without aorta cross-clamped; in group B, 46 patients underwent the procedure on hearts arrested with cardioplegia with aorta cross-clamped. Cardiopulmonary bypass (CPB) was peripherally achieved as well. RESULTS: Total thoracoscopic ASD closures were successfully performed without in-hospital mortality or other serious complications in all patients of both groups. Dacron or bovine patches were used in 81 and 32 patients in the two groups, respectively. Duration of operation, duration of CPB, aorta cross-clamped time, duration of mechanical ventilation, the length of intensive care unit (ICU) and post-operative hospital stay in group A, were all shorter than those in group B (P<0.05). There was no statistically significant difference in blood transfusion during operation or post-operation thoracic drainage. During follow-up, echocardiograms at 3, 30, 90 and 365, showed no residual shunt or tricuspid regurgitation. CONCLUSIONS: Total thoracoscopic closure of ASD without assistance of a surgical robotic system on beating heart is safe and feasible and can be used as a therapeutic option for ASD, and by using the mentioned technique, less injuries are applied to patients.

MiR-155 inhibits proliferation and invasion by directly targeting PDCD4 in non-small cell lung cancer.

BACKGROUND: MicroRNAs are often abnormally expressed in human non-small cell lung cancer (NSCLC) and are thought to play a critical role in the emergence or maintenance of NSCLC by binding to its target messenger RNA. We assessed the effects of miR-155 on cell proliferation and invasion to elucidate the role played by miR-155/PDCD4 in NSCLC. METHODS: Quantitative reverse transcription-PCR, Western blotting, and cell counting kit-8, luciferase, and transwell invasion assays were conducted on a normal human bronchial epithelial cell line (BEAS-2B) and three NSCLC cell lines (SPC-A-1, A549, and H2170). RESULTS: We confirmed that miR-155 was upregulated, while PDCD4 messenger RNA and protein levels were downregulated in NSCLC cell lines. miR-155 negatively regulated PDCD4 at both transcriptional and post-transcriptional levels. Moreover, PDCD4 was forecast as an assumed target of miR-155 using bioinformatic methods and we demonstrated that PDCD4 was a direct target of miR-155 using luciferase reporter assays. Furthermore, PDCD4 overexpression could restrain NSCLC proliferation and invasion induced by miR-155. CONCLUSION: Our results collectively demonstrate that miR-155 exerts an oncogenic role in NSCLC by directly targeting PDCD4.