S-Nitrosylation of Septin2 Exacerbates Aortic Aneurysm and Dissection by Coupling the TIAM1-RAC1 Axis in Macrophages.

BACKGROUND: S-Nitrosylation (SNO), a prototypic redox-based posttranslational modification, is involved in cardiovascular disease. Aortic aneurysm and dissection are high-risk cardiovascular diseases without an effective cure. The aim of this study was to determine the role of SNO of Septin2 in macrophages in aortic aneurysm and dissection. METHODS: Biotin-switch assay combined with liquid chromatography-tandem mass spectrometry was performed to identify the S-nitrosylated proteins in aortic tissue from both patients undergoing surgery for aortic dissection and Apoe-/- mice infused with angiotensin II. Angiotensin II-induced aortic aneurysm model and ß-aminopropionitrile-induced aortic aneurysm and dissection model were used to determine the role of SNO of Septin2 (SNO-Septin2) in aortic aneurysm and dissection development. RNA-sequencing analysis was performed to recapitulate possible changes in the transcriptome profile of SNO-Septin2 in macrophages in aortic aneurysm and dissection. Liquid chromatography-tandem mass spectrometry and coimmunoprecipitation were used to uncover the TIAM1-RAC1 (Ras-related C3 botulinum toxin substrate 1) axis as the downstream target of SNO-Septin2. Both R-Ketorolac and NSC23766 treatments were used to inhibit the TIAM1-RAC1 axis. RESULTS: Septin2 was identified S-nitrosylated at cysteine 111 (Cys111) in both aortic tissue from patients undergoing surgery for aortic dissection and Apoe-/- mice infused with Angiotensin II. SNO-Septin2 was demonstrated driving the development of aortic aneurysm and dissection. By RNA-sequencing, SNO-Septin2 in macrophages was demonstrated to exacerbate vascular inflammation and extracellular matrix degradation in aortic aneurysm. Next, TIAM1 (T lymphoma invasion and metastasis-inducing protein 1) was identified as a SNO-Septin2 target protein. Mechanistically, compared with unmodified Septin2, SNO-Septin2 reduced its interaction with TIAM1 and activated the TIAM1-RAC1 axis and consequent nuclear factor-κB signaling pathway, resulting in stronger inflammation and extracellular matrix degradation mediated by macrophages. Consistently, both R-Ketorolac and NSC23766 treatments protected against aortic aneurysm and dissection by inhibiting the TIAM1-RAC1 axis. CONCLUSIONS: SNO-Septin2 drives aortic aneurysm and dissection through coupling the TIAM1-RAC1 axis in macrophages and activating the nuclear factor-κB signaling pathway-dependent inflammation and extracellular matrix degradation. Pharmacological blockade of RAC1 by R-Ketorolac or NSC23766 may therefore represent a potential treatment against aortic aneurysm and dissection.

Mitochondrial GSNOR Alleviates Cardiac Dysfunction via ANT1 Denitrosylation.

BACKGROUND: The cardiac-protective role of GSNOR (S-nitrosoglutathione reductase) in the cytoplasm, as a denitrosylase enzyme of S-nitrosylation, has been reported in cardiac remodeling, but whether GSNOR is localized in other organelles and exerts novel effects remains unknown. We aimed to elucidate the effects of mitochondrial GSNOR, a novel subcellular localization of GSNOR, on cardiac remodeling and heart failure (HF). METHODS: GSNOR subcellular localization was observed by cellular fractionation assay, immunofluorescent staining, and colloidal gold particle staining. Overexpression of GSNOR in mitochondria was achieved by mitochondria-targeting sequence-directed adeno-associated virus 9. Cardiac-specific knockout of GSNOR mice was used to examine the role of GSNOR in HF. S-nitrosylation sites of ANT1 (adenine nucleotide translocase 1) were identified using biotin-switch and liquid chromatography-tandem mass spectrometry. RESULTS: GSNOR expression was suppressed in cardiac tissues of patients with HF. Consistently, cardiac-specific knockout mice showed aggravated pathological remodeling induced by transverse aortic constriction. We found that GSNOR is also localized in mitochondria. In the angiotensin II-induced hypertrophic cardiomyocytes, mitochondrial GSNOR levels significantly decreased along with mitochondrial functional impairment. Restoration of mitochondrial GSNOR levels in cardiac-specific knockout mice significantly improved mitochondrial function and cardiac performance in transverse aortic constriction-induced HF mice. Mechanistically, we identified ANT1 as a direct target of GSNOR. A decrease in mitochondrial GSNOR under HF leads to an elevation of S-nitrosylation ANT1 at cysteine 160 (C160). In accordance with these findings, overexpression of either mitochondrial GSNOR or ANT1 C160A, non-nitrosylated mutant, significantly improved mitochondrial function, maintained the mitochondrial membrane potential, and upregulated mitophagy. CONCLUSIONS: We identified a novel species of GSNOR localized in mitochondria and found mitochondrial GSNOR plays an essential role in maintaining mitochondrial homeostasis through ANT1 denitrosylation, which provides a potential novel therapeutic target for HF.

Endothelial HDAC1-ZEB2-NuRD Complex Drives Aortic Aneurysm and Dissection Through Regulation of Protein S-Sulfhydration.

BACKGROUND: Aortic aneurysm and aortic dissection (AAD) are life-threatening vascular diseases, with endothelium being the primary target for AAD treatment. Protein S-sulfhydration is a newly discovered posttranslational modification whose role in AAD has not yet been defined. This study aims to investigate whether protein S-sulfhydration in the endothelium regulates AAD and its underlying mechanism. METHODS: Protein S-sulfhydration in endothelial cells (ECs) during AAD was detected and hub genes regulating homeostasis of the endothelium were identified. Clinical data of patients with AAD and healthy controls were collected, and the level of the cystathionine γ lyase (CSE)/hydrogen sulfide (H2S) system in plasma and aortic tissue were determined. Mice with EC-specific CSE deletion or overexpression were generated, and the progression of AAD was determined. Unbiased proteomics and coimmunoprecipitation combined with mass spectrometry analysis were conducted to determine the upstream regulators of the CSE/H2S system and the findings were confirmed in transgenic mice. RESULTS: Higher plasma H2S levels were associated with a lower risk of AAD, after adjustment for common risk factors. CSE was reduced in the endothelium of AAD mouse and aorta of patients with AAD. Protein S-sulfhydration was reduced in the endothelium during AAD and protein disulfide isomerase (PDI) was the main target. S-sulfhydration of PDI at Cys343 and Cys400 enhanced PDI activity and mitigated endoplasmic reticulum stress. EC-specific CSE deletion was exacerbated, and EC-specific overexpression of CSE alleviated the progression of AAD through regulating the S-sulfhydration of PDI. ZEB2 (zinc finger E-box binding homeobox 2) recruited the HDAC1-NuRD complex (histone deacetylase 1-nucleosome remodeling and deacetylase) to repress the transcription of CTH, the gene encoding CSE, and inhibited PDI S-sulfhydration. EC-specific HDAC1 deletion increased PDI S-sulfhydration and alleviated AAD. Increasing PDI S-sulfhydration with the H2S donor GYY4137 or pharmacologically inhibiting HDAC1 activity with entinostat alleviated the progression of AAD. CONCLUSIONS: Decreased plasma H2S levels are associated with an increased risk of aortic dissection. The endothelial ZEB2-HDAC1-NuRD complex transcriptionally represses CTH, impairs PDI S-sulfhydration, and drives AAD. The regulation of this pathway effectively prevents AAD progression.

Phenylacetyl glutamine (PAGln) enhances cardiomyocyte death after myocardial infarction through ß1 adrenergic receptor.

This study aims to explore the roles of phenylacetyl glutamine (PAGln) on myocardial infarction (MI) pathogenesis. Here, using targeted metabolomics analysis, it was found that the plasma metabolite PAGln was upregulated in coronary artery disease (CAD) patients and MI mice and could be an independent risk factor for CAD. In vivo and in vitro functional experiments revealed that PAGln pretreatment enhanced MI-induced myocardial injury and cardiac fibrosis, as evident by the increased infarct size, cardiomyocyte death, and the upregulated expression of cardiac fibrosis markers (Col1a1 and α-SMA). Combined with RNA-sequencing analysis and G protein-coupled receptor (GPCR) inhibitor, we found that the GPCR signaling activation is essential for PAGln-mediated effects on cardiomyocyte death. Furthermore, drug affinity responsive target stability and cellular thermal shift assay demonstrated that PAGln could interact with ß1-adrenergic receptor (AR). Moreover, ß1-AR blocker treatment indeed extended the cardiac remodeling after PAGln-enhanced MI. These results suggest that PAGln might be a potential therapeutic target for extending the cardiac remodeling window in MI patients that signals via ß1-AR.

Prediction of acute kidney injury incidence following acute type A aortic dissection surgery with novel biomarkers: a prospective observational study.

BACKGROUND: Acute kidney injury (AKI) is a prevalent complication following acute type A aortic dissection (ATAAD) surgery and is closely associated with unfavorable prognostic outcomes. Hence, the development of a robust and efficient diagnostic approach to identify high-risk patients is of paramount importance. METHODS: We conducted a prospective study involving 328 patients who underwent ATAAD surgery at our institution, comprising three distinct cohorts. In addition, 52 patients undergoing alternative cardiopulmonary surgeries and 37 healthy individuals were enrolled as control groups. Employing proteomic analysis, we initially identified plasma proteins potentially linked to AKI occurrence within the plasma proteomic cohort. Subsequent validation was performed in an independent cohort. Utilizing predictors derived from multivariate logistic regression analysis, a nomogram was meticulously formulated and its efficacy was validated in the model construction cohort. RESULTS: Proteomics revealed significant elevation of plasma levels of S100A8/A9, pentraxin 3 (PTX3), and chitinase 3-like 1 (CHI3L1) immediately post-surgery in patients who developed ATAAD surgery-associated AKI (ASA-AKI). Receiver operating characteristic (ROC) curves demonstrated impressive predictive performance of S100A8/A9, PTX3, and CHI3L1 at 0 h post-surgery, yielding area under the curve (AUC) values of 0.823, 0.786, and 0.803, respectively, for ASA-AKI prediction. Furthermore, our findings exhibited positive correlations between plasma levels of S100A8/A9, PTX3, CHI3L1, and urinary neutrophil gelatinase-associated lipocalin (NGAL) at 0 h post-surgery, along with correlations between plasma S100A8/A9, CHI3L1 levels, and the Cleveland Clinic score. A logistic regression model incorporating plasma S100A8/A9, PTX3, CHI3L1 levels, urinary NGAL levels, and the Cleveland Clinic score facilitated the construction of a predictive nomogram for ASA-AKI. This nomogram demonstrated robust discriminative ability, achieving an AUC of 0.963 in the model construction cohort. CONCLUSIONS: Our study underscored the augmentation of plasma S100A8/A9, PTX3, and CHI3L1 levels immediately post-surgery in patients developing ASA-AKI. The incorporation of these three biomarkers, in conjunction with the Cleveland Clinic score and NGAL, into a nomogram demonstrated commendable predictive efficacy. This presents a practical tool for identifying patients at an elevated risk of AKI following ATAAD surgery.

Smooth Muscle Overexpression of PGC1α Attenuates Atherosclerosis in Rabbits.

[Figure: see text].

Dietary betaine intake and risk of mortality in patients with coronary artery disease: the prospective Guangdong Coronary Artery Disease Cohort.

This study is designed to explore the association between dietary betaine intake and risk of all-cause and cardiovascular death in patients with coronary artery diseases (CAD). In this cohort study, 1292 patients with CAD were followed up for a median of 9·2 years. Baseline dietary betaine intake was collected using a paper-based semi-quantitative FFQ and assessed according to the US Department of Agriculture (USDA) database and the data of betaine in common foods. Cox proportional hazards regression models were used to analyse the association between dietary betaine intake and risks of all-cause and cardiovascular mortality. During the follow-up periods, 259 deaths recorded in 1292 participants, of which 167 died of CVD. Patients in the highest tertile of dietary betaine intake had a lower risk of all-cause (P = 0·007) and cardiovascular death (P < 0·001) than those in the lowest tertile after adjusting for age and sex, traditional cardiovascular risk factors and other potential confounders. After further adjusting for plasma methionine metabolites and vitamins, hazard ratio across tertiles of dietary betaine intake were 1·00, 0·84 and 0·72 for all-cause mortality (Pfor trend = 0·124), and 1·00, 0·77 and 0·55 for cardiovascular mortality (Pfor trend = 0·021). Higher dietary betaine intake was associated with a decreased risk of cardiovascular death after fully adjustment for cardiovascular risk factors, other potential confounders and plasma methionine metabolites and vitamins. However, the association between dietary betaine intake and risk of all-cause mortality was not statistically significant after further adjusting for plasma methionine metabolites and vitamins.

The low-dose colchicine in patients after non-CABG cardiac surgery: a randomized controlled trial.

BACKGROUND: Recent high-quality trials have shown that the anti-inflammatory effects of colchicine reduce the risk of cardiovascular events in patients suffering post-myocardial infarction and chronic coronary disease. The effect of colchicine in patients undergoing non-coronary artery bypass grafting (non-CABG) with cardiopulmonary bypass remains unclear. We aim to evaluate the effect of colchicine on myocardial protection in patients who underwent non-CABG cardiac surgery. METHOD: Patients were randomly assigned to colchicine or placebo groups starting 72 h before scheduled cardiac surgery and for 5 days thereafter (0.5 mg daily).The primary outcome was the level of cardiac troponin T (cTnT) at postoperative 48 h. The secondary outcomes included troponin I (cTnI) and creatine kinase-MB (CK-MB), inflammatory biomarkers (procalcitonin and interleukin-6, etc.), and adverse events (30-day mortality, stroke, ECMO and IABP use, etc.). RESULTS: A total of 132 patients underwent non-CAGB cardiac surgery, 11were excluded because of diarrhea (n = 6) and long aortic cross-clamp time > 2 h (n = 5), 59 were assigned to the colchicine group and 62 to the placebo group. Compared with the placebo group, cTnT (median: 0.3 µg/L, IQR 0.2-0.4 µg/L vs. median: 0.4 µg/L, IQR 0.3-0.6 µg/L, P < 0.01), cardiac troponin I (median: 0.9 ng/ml, IQR 0.4-1.7 ng/ml vs. median: 1.3 ng/ml, IQR 0.6-2.3 ng/ml, P = 0.02), CK-MB (median: 1.9 ng/ml, IQR 0.7-3.2 ng/ml vs. median: 4.4 ng/ml, IQR 1.5-8.2 ng/ml, P < 0.01), and interleukin-6 (median: 73.5 pg/ml, IQR 49.6-125.8 pg/ml vs. median: 101 pg/ml, IQR 57.5-164.7 pg/ml, P = 0.048) were significantly reduced in colchicine group at postoperative 48 h. For safety evaluation, the colchicine (n = 65) significantly decreased post-pericardiotomy syndrome (3.08% vs. 17.7%, P < 0.01) and increased the rate of diarrhea (9.23% vs. 0, P = 0.01) compared with the placebo group (n = 62). No significant difference was observed in other adverse events between the two groups. CONCLUSION: A short perioperative course of low-dose colchicine was effective to attenuate the postoperative biomarkers of myocardial injury and inflammation, and to decrease the postoperative syndrome compared with the placebo. Trial registration ChiCTR2000040129. Registered 22nd Nov. 2020. This trial was registered before the first participant was enrolled. http://www.chictr.org.cn/showproj.aspx?proj=64370 .

Dexmedetomidine as an anesthetic adjunct is associated with reduced complications and cardiac intensive care unit length of stay after heart valve surgery.

BACKGROUND: We sought to explore the relationship between dexmedetomidine as an anesthetic adjuvant in cardiac surgery and postoperative complications and length of stay (LOS) in the cardiac intensive care unit (CICU). METHODS: We conducted a retrospective study of patients aged 18 years and older who underwent heart valve surgery between October 2020 and June 2022. The primary endpoint of the study was major postoperative complications (cardiac arrest, atrial fibrillation, myocardial injury/infarction, heart failure) and the secondary endpoint was prolonged CICU LOS (defined as LOS > 90th percentile). Multivariate logistic regression analysis was performed for variables that were significant in the univariate analysis. RESULTS: A total of 856 patients entered our study. The 283 patients who experienced the primary and secondary endpoints were included in the adverse outcomes group, and the remaining 573 were included in the prognostic control group. Multivariate logistic regression analysis revealed that age > 60 years (odds ratio [OR], 1.68; 95% confidence interval [CI], 1.23-2.31; p < 0.01), cardiopulmonary bypass (CPB) > 180 min (OR, 1.62; 95% CI, 1.03-2.55; p = 0.04) and postoperative mechanical ventilation time > 10 h (OR, 1.84; 95% CI, 1.35-2.52; p < 0.01) were independent risk factors for major postoperative complications; Age > 60 years (OR, 3.20; 95% CI, 1.65-6.20; p < 0.01), preoperative NYHA class 4 (OR, 4.03; 95% CI, 1.74-9.33; p < 0.01), diabetes mellitus (OR, 2.57; 95% CI, 1.22-5.41; p = 0.01), Intraoperative red blood cell (RBC) transfusion > 650 ml (OR, 2.04; 95% CI, 1.13-3.66; p = 0.02), Intraoperative bleeding > 1200 ml (OR, 2.69; 95% CI, 1.42-5.12; p < 0.01) were independent risk factors for prolonged CICU length of stay. Intraoperative use of dexmedetomidine as an anesthetic adjunct was a protective factor for major complications (odds ratio, 0.51; 95% confidence interval, 0.35-0.74; p < 0.01) and prolonged CICU stay. (odds ratio, 0.37; 95% confidence interval, 0.19-0.73; p < 0.01). CONCLUSIONS: In patients undergoing heart valve surgery, age, duration of cardiopulmonary bypass, and duration of mechanical ventilation are associated with major postoperative complication. Age, preoperative NYHA classification 4, diabetes mellitus, intraoperative bleeding, and RBC transfusion are associated with increased CICU length of stay. Intraoperative use of dexmedetomidine may improve such clinical outcomes.

"Drum Tower Hospital" strategy for acute type A aortic dissection with coma.

OVERVIEW: Acute type A aortic dissection (ATAAD) with persistent coma is a life-threatening condition associated with high mortality and poor neurological outcomes. The optimal timing for surgical intervention in these patients remains uncertain, and many patients are not eligible for surgery due to their poor prognosis. DESCRIPTION: In this case, a 53-year-old man with hypertension presented to the emergency department in a coma that had lasted for 9 hours. The patient was diagnosed with ATAAD and underwent the "Drum Tower Hospital" strategy, which involved preoperative assessments, including computed tomography angiography (CTA) and quantitative electroencephalogram (qEEG) monitoring. Surgical interventions, such as emergency stenting and aortic replacement, were performed to restore blood flow and repair the aorta. Postoperative monitoring, including qEEG, showed improvements in brain function. Despite the patient experiencing hemiplegia and a neurological deficit, the "Drum Tower Hospital" strategy, guided by comprehensive brain assessments, showed promise in managing ATAAD with coma. However, further research is needed to establish effective treatment strategies for these patients. Overall, ATAAD with persistent coma is a critical condition with limited treatment options. The "Drum Tower Hospital" strategy, supported by multimodal brain assessment, offers a potential approach to improve outcomes in these patients.

Luteolin alleviates ischemia/reperfusion injury-induced no-reflow by regulating Wnt/ß-catenin signaling in rats.

The no-reflow phenomenon induced by ischemia-reperfusion (I/R) injury seriously limits the therapeutic value of coronary recanalization and leads to a poor prognosis. Previous studies have shown that luteolin (LUT) is a vasoprotective factor. However, whether LUT can be used to prevent the no-reflow phenomenon remains unknown. Positron emission tomography perfusion imaging, performed to detect the effects of LUT on the no-reflow phenomenon in vivo, revealed that LUT treatment was able to reduce the no-reflow area in rat I/R models. In vitro, LUT was shown to reduce the hypoxia-reoxygenation injury-induced endothelial permeability and apoptosis. The levels of malondialdehyde, reactive oxygen species and NADPH were also measured and the results indicated that LUT could inhibit the oxidative stress. Western blot analysis revealed that LUT protected endothelial cells from I/R injury by regulating the Wnt/ß-catenin pathway. Overall, we concluded that the use of LUT to minimize I/R induced microvascular damage is a feasible strategy to prevent the no-reflow phenomenon.

MicroRNA-29b reduces myocardial ischemia-reperfusion injury in rats via down-regulating PTEN and activating the Akt/eNOS signaling pathway.

Reperfusion may cause injuries to the myocardium in ischemia situation, which is called ischemia/reperfusion (I/R) injury. The study aimed to explore the roles of microRNA-29b (miR-29b) in myocardial I/R injury. Myocardial I/R injury rat model was established. Differentially expressed miRNAs between the model rats and the sham-operated rats were analyzed. miR-29b expression in myocardial tissues was measured. Gain-of-function of miR-29b was performed, and then the morphological changes, infarct size, myocardial function, oxidative stress, and the cell apoptosis in myocardial tissues were detected. The target relation between miR-29b and PTEN was detected through bio-information prediction and dual luciferase reporter gene assay. Activation of Akt/eNOS signaling was detected. H9C2 cells were subjected to hypoxia/reoxygenation treatment to perform in vitro experiments. I/R rats presented severe inflammatory infiltration, increased infarct size and cell apoptosis, increased oxidative stress and decreased myocardial function. miR-29b was downregulated in I/R rats, and up-regulation of miR-29b reversed the above changes. miR-29b directly bound to PTEN, and overexpression of miR-29b reduced PTEN expression level and increased the protein levels of p-Akt/Akt and p-eNOS/eNOS. In vivo results were confirmed in in vitro experiments. This study provided evidence that miR-29b could alleviate the myocardial I/R injury in vivo and in vitro by inhibiting PTEN expression and activating the Akt/eNOS signaling pathway.

The evaluation of levosimendan in patients with acute myocardial infarction related ventricular septal rupture undergoing cardiac surgery: a prospective observational cohort study with propensity score analysis.

STUDY OBJECTIVE: The purpose of the present study was to evaluate the efficacy of levosimendan in patients with acute myocardial infarction related ventricular septal rupture (AMI-VSR) underwent cardiac surgery. DESIGN: Prospective observational cohort study with propensity score analysis. PATIENTS: There were 261 patients with AMI-VSR in our study. After 1:1 propensity matching, 106 patients (53 levosimendan and 53 control) were selected in the matched cohort. INTERVENTIONS: None. MEASUREMENTS: Patients who received levosimendan were assigned to the levosimendan group (n = 164). The patients who were not received were levosimendan assigned to the control group (n = 97). The levosimendan was initiated immediately after cardiopulmonary bypass. Then, it has been maintained during the postoperative 3 days. The poor outcomes were identified as follows: death and postoperative complications (postoperative stroke, low cardiac output syndromeneeded mechanical circulatory support after surgery, acute kidney injury (≥ stage III), postoperative infection or septic shock, new developed atrial fibrillation or ventricular arrhythmias). MAIN RESULTS: Before matching, the control group had more length of ICU stay (6.69 ± 3.90 d vs. 5.20 ± 2.24 d, p < 0.001) and longer mechanical ventilation time (23 h, IQR: 16-53 h vs. 16 h, IQR: 11-23 h, p < 0.001). Other postoperative outcomes have not shown significant differences between two groups. After matching, no significant difference was found between both groups for all postoperative outcomes. The Kaplan-Meier survivul estimate and log-rank test showed that the 90-day survival had no significant differences between two groups before and after matching. CONCLUSION: Our study found that a low-dose infusion of levosimendan in AMI-VSR patients underwent surgical repair did not associated with positively affect to postoperative outcomes.

Identification of risk factors for postoperative stage 3 acute kidney injury in patients who received surgical repair for acute type A aortic dissection.

BACKGROUND: Acute kidney injury (AKI) is a serious complication that often occurred after acute type A aortic dissection (ATAAD) surgery. Previous studies proved that the Kidney Disease Improving Global Outcomes (KDIGO) defined stage 3 AKI was associated with lower long-term survival rate. However, the risk factors for developing stage 3 AKI had not been identified. The aim of the study was to explore the risk factors for developing KDIGO stage 3 after ATAAD operation. METHODS: This study included 993 patients who received ATAAD operation from 2014 to 2019 at the Nanjing Drum Tower Hospital. Postoperative AKI was diagnosed according to the KDIGO criteria. Multivariate logistic regression analyses were applied to identify risk factors for stage 3 AKI. Kaplan-Meier survival analyses and Cox proportional hazards regression model were conducted to explore the association between different AKI stages and postoperative survival rate. RESULTS: The mean age of all enrolled patients was 53.0 ± 13.1 years. A total of 236 (23.8%) patients suffered postoperative stage 3 AKI including 165 patients who required renal replacement therapy. Advanced age (odds ratio [OR] 1.031; 95% confidence interval [CI] 1.005-1.057; P = 0.018), prolonged cardiopulmonary bypass (CPB) duration (OR 1.010; 95% CI 1.002-1.018; P = 0.013), and higher drainage volume 24 h after surgery (OR 1.000; 95% CI 1.000-1.001; P = 0.033) were identified as independent risk factors for developing stage 3 AKI. In addition, our result showed that the mortality rate was correlated significantly with the severity of AKI defined by KDIGO criteria and the Cox regression analysis showed that only stage 3 AKI, but not stage 1 and 2, was an independent risk factor for mortality (Hazard ratio 10.365, 95% CI 4.208 to 25.528; P < 0.001) after adjusting for important confounding factors. CONCLUSIONS: Our study suggested that stage 3 postoperative AKI was significantly associated with decreased postoperative survival rate after ATAAD surgery. Advanced age, increased CPB duration and drainage volume 24 h after surgery were identified as risk factors for developing stage 3 AKI.

LncRNA KCNQ1OT1 Participates in Ox-LDL-Induced Proliferation/Apoptosis Imbalance in Vascular Smooth Muscle Cells by Regulating the MiR-196a-5p/FOXO1 Axis.

Backgroud The present study aimed to investigate the function and regulatory mechanisms of lncRNA KCNQ1OT1 in vascular smooth muscle cells under oxidation low lipoprotein stimulation. Methods RNA sequencing was used to detect transcriptome changes of vascular smooth muscle cells treated with oxidation low lipoprotein. KCNQ1OT1, miR-196a-5p, and FOXO1 expression levels in VSMCs after oxidation low lipoprotein treatment were assessed using qRT-PCR and western blotting. RNA immunoprecipitation, RNA pull-down, and dual-luciferase reporter assay were used to confirm the interaction among lncRNA KCNQ1OT1, miR-196a-5p, and FOXO1. The functions of KCNQ1OT1, miR-196a-5p, and FOXO1 were analyzed by CCK-8 and flow cytometry. The serum samples of high fat-feeding mice and atherosclerosis patients were collected, and the levels of KCNQ1OT1 and miR-196a-5p were analyzed. Results In vitro expression of KCNQ1OT1 and FOXO1 decreased in VSMCs treated with oxidation low lipoprotein, accompanied by overexpression of miR-196a-5p. As a ceRNA, KCNQ1OT1 positively regulated FOXO1 and imparted a negative regulatory effect on miR-196a-5p. Interference KCNQ1OT1/miR-196a-5p/FOXO1 could change roliferation/apoptosis imbalance in VSMCs under oxidation low lipoprotein stimulation. Higher levels of KCNQ1OT1 and lower levels of miR-196a-5p can be found in the thoracic aorta tissues of high fat-feeding mice and serum samples from individuals with carotid atherosclerosis. Conclusion Aberrant expression of KCNQ1OT1/miR-196a-5p/FOXO1 pathway mediated oxidation low lipoprotein-induced proliferation/apoptosis imbalance in VSMCs.

Cooperative phenomenon of vapochromism and proton conduction of luminescent Pt(ii) complexes for the visualisation of proton conductivity.

The luminescent and proton conductive Pt(ii) complex [PtCl(tpy-o-py)]Cl and its HCl adduct [PtCl(tpy-o-pyH)]Cl2 (o-Pt and o-Pt·HCl, respectively; tpy-o-py = 2,2':6',2''-terpyridine-6',2'''-pyridine) were synthesised and their crystal structures, vapochromic behaviour, and proton conduction, were investigated and compared to those of the para isomers [PtCl(tpy-p-py)]Cl and [PtCl(tpy-p-pyH)]Cl2 (p-Pt and p-Pt·HCl, respectively; tpy-p-py = 2,2':6',2''-terpyridine-4',4'''-pyridine). X-ray structure analysis revealed that the intermolecular metallophilic (PtPt) interaction was negligible in o-Pt but effective in o-Pt·HCl. Reversible transformation between o-Pt and o-Pt·HCl coupled with significant colour and luminescence changes was achieved by four different external stimuli, namely: exposure of o-Pt to humid HCl gas to form o-Pt·HCl, heating, exposure to MeOH vapour, and finally drying in air to regenerate the original o-Pt. The intraligand π-π* orange emission observed for o-Pt exhibited negligible dependence on the relative humidity (RH). Conversely, o-Pt·HCl exhibited red metal-metal-to-ligand charge-transfer (MMLCT) phosphorescence at 725 nm, originating from effective intermolecular Pt-Pt interactions, and interesting vapochromic behaviour that was dependent on the RH. Notably, o-Pt·HCl presented higher conductivity than the p-Pt·HCl isomer at RH < 80%. This trend was reversed at RH values > 80%, probably owing to the second water-adsorption-induced transformation of p-Pt·HCl. The cooperative phenomenon between the proton conduction and vapochromic behaviour observed for both o-Pt·HCl and p-Pt·HCl should allow the visualisation of the proton-conducting pathway, without the need for a bulk electrode, via the absorption and emission colours at both macroscopic and microscopic levels.

LncRNA NEAT1 acts as a key regulator of cell apoptosis and inflammatory response by the miR-944/TRIM37 axis in acute lung injury.

Acute lung injury (ALI), a common complication of sepsis, is characterized by the impairment and injury of pulmonary function. The nuclear factor kappa-B (NF-κB) pathway is activated in ALI. Tripartite motif-containing 37 (TRIM37) can activate the NF-κB pathway and is closely associated with inflammation. The purpose of our study is to reveal the role of TRIM37 in ALI. The present study revealed that TRIM37 presented high levels in lung tissues of ALI mice, and knockdown of TRIM37 alleviated lipopolysaccharide (LPS)-induced lung injury, inflammatory response, and cell apoptosis in vivo. In addition, knockdown of TRIM37 inhibited the inflammatory response, and cell apoptosis of LPS-treated WI-38 cells. Mechanistically, miR-944 was identified to bind with and negatively regulate TRIM37. Furthermore, NEAT1 was indicated to act as a competitive endogenous RNA to promote TRIM37 expression by sequestering miR-944. Detailly, NEAT1 bound with miR-944, negatively modulated miR-944 expression, and positively modulated TRIM37 expression. The rescue assays suggested that overexpression of TRIM37 rescued the influence of NEAT1 knockdown on cell apoptosis and inflammatory response. Overall, NEAT1 facilitated cell apoptosis and inflammatory response of WI-38 cells by the miR-944/TRIM37 axis in sepsis-induced ALI, implying that NEAT1 may provide a novel insight for the treatment of sepsis-induced ALI.

Risk factors for mortality in patients undergoing continuous renal replacement therapy after cardiac surgery.

BACKGROUND: To investigate the risk factors for mortality in patients with acute kidney injury requiring continuous renal replacement therapy (AKI-CRRT) after cardiac surgery. METHODS: In this retrospective study, patients who underwent AKI-CRRT after cardiac surgery in our centre from January 2015 to January 2020 were included. Univariable and multivariable analyses were performed to identify the risk factors for in-hospital mortality. RESULTS: A total of 412 patients were included in our study. Of these, 174 died after AKI-CRRT, and the remaining 238 were included in the survival control group. Multivariable logistic regression analysis revealed that EuroSCORE > 7 (odds ratio [OR], 3.72; 95% confidence interval [CI], 1.92-7.24; p < 0.01), intraoperative bleeding > 1 L (OR, 2.14; 95% CI, 1.19-3.86; p = 0.01) and mechanical ventilation time > 70 h (OR, 5.03; 95% CI, 2.40-10.54; p < 0.01) were independent risk factors for in-hospital mortality in patients who had undergone AKI-CRRT. Our study also found that the use of furosemide after surgery was a protective factor for such patients (odds ratio, 0.48; 95% confidence interval, 0.25-0.92; p = 0.03). CONCLUSIONS: In summary, the mortality of patients with AKI-CRRT after cardiac surgery remains high. The EuroSCORE, intraoperative bleeding and mechanical ventilation time were independent risk factors for in-hospital mortality. Continuous application of furosemide may be associated with a better outcome.

Clinical outcomes of postoperative extracorporeal membrane oxygenation support in Stanford type a aortic dissection.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) support may be considered to reduce mortality but survival and clinical outcomes are uncertain after Stanford type A Aortic dissection (TAAD). We analyzed the data of TAAD patients with postoperative ECMO support in our institution to investigate clinical outcomes. METHODS: In this retrospective cohort study, all clinical data of TAAD patients with postoperative ECMO support from January 2013 to October 2019 in our institution were harvested. Cases with redo or incomplete records were excluded. RESULTS: 22 cases were enrolled, 18 male and 4 female. The mean age was52.85±10.91 years. 20 patients underwent VA-ECMO treatment and 2 patients received VV-ECMO support. The support time was92.54±78.71 hours. 9 patients were successfully weaned from ECMO. 30-day in-hospital survival rate was 27.27 % (6/22). The follow-up duration is from 5 to 74 months. The median follow-up time is 35 months. Only four patients were still alive at the end of the follow-up period. CONCLUSIONS: The mortality of TAAD patients with postoperativesevere circulatory and respiratory dysfunctions is high. ECMO would be considered as a valuable contribution to save lives. But more experience needs to be accumulated to improve clinical outcome.

Preoperative monocyte-to-HDL-cholesterol ratio predicts early recurrence after radiofrequency maze procedure of valvular atrial fibrillation.

BACKGROUND: Monocyte-to-high-density lipoprotein (M/H) ratio has emerged as a novel cardiovascular prognostic biomarker. We aimed to evaluate the prognostic values of M/H with early recurrence in persistent valvular atrial fibrillation (AF) patients after radiofrequency (RF) maze procedure. METHODS: We retrospectively analyzed 131 consecutive persistent AF patients with valvular heart diseases who were followed up 3 months after RF maze procedure. Their clinical data were recorded. Logistic regression analyses were performed for significant predictors. Receiver operating characteristic analysis was used for validation with corresponding area under the curve. RESULTS: 70 (53.4%) patients experienced early recurrence after procedure. Patients with early recurrence were older, have longer AF duration history, larger left atria diameter (LAD), higher plasma C-reactive protein (CRP), lower triglycerides (TG), lower cholesterol (TC), increased monocyte counts, lower HDL cholesterol, and increased M/H ratio. In multivariate analysis, age (OR 1.1 95% CI 1.0-1.1 P = .003), LAD (OR 2.1, 95%CI 1.2-3.5, P = .006), TG (OR 0.35, 95% CI 0.15-0.84, P = .019), M/H (OR 6.1, 95% CI 2.9-13.0, P < .001) were significantly independent predictors of AF early recurrence. M/H ratio demonstrated a significant predictive value (AUC = 0.77, sensitivity 89.0%, specificity 54%). Further, there was a positive correlation of M/H ratio with CRP and white blood cell. CONCLUSION: Preoperative M/H ratio was an independent risk factor of AF early recurrence following RF maze operation. M/H ratio should be considered in prediction of early recurrence for valvular AF patients.