FTO represses NLRP3-mediated pyroptosis and alleviates myocardial ischemia-reperfusion injury via inhibiting CBL-mediated ubiquitination and degradation of ß-catenin.

Cardiac ischemia/reperfusion (I/R) injury is a complicated pathological event, which has close association with pyroptosis. This study uncovered the regulatory mechanisms of fat mass and obesity-associated protein (FTO) in NLRP3-mediated pyroptosis during cardiac I/R injury. H9c2 cells were stimulated with oxygen-glucose deprivation/reoxygenation (OGD/R). Cell viability and pyroptosis were detected by CCK-8 and flow cytometry. Western blotting or RT-qPCR was performed to analyze target molecule expression. NLRP3 and Caspase-1 expression was observed by immunofluorescence staining. IL-18 and IL-1ß production was detected by ELISA. The total m6A and m6A level of CBL was determined by dot blot assay and methylated RNA immunoprecipitation-qPCR, respectively. The interaction between IGF2BP3 and CBL mRNA was confirmed by RNA pull-down and RIP assays. The protein interaction between CBL and ß-catenin and ß-catenin ubiquitination were evaluated by Co-IP. Myocardial I/R model was established in rats. We determined infarct size by TTC staining and pathological changes by H&E staining. LDH, CK-MB, LVFS, and LVEF were also assessed. FTO and ß-catenin were down-regulated, while CBL was up-regulated by OGD/R stimulation. FTO/ß-catenin overexpression or CBL silencing restrained OGD/R-induced NLRP3 inflammasome-mediated pyroptosis. CBL repressed ß-catenin expression via ubiquitination and degradation. FTO reduced the mRNA stability of CBL by inhibiting m6A modification. CBL-mediated ubiquitination and degradation of ß-catenin were involved in FTO-induced pyroptosis inhibition during myocardial I/R injury. FTO inhibits NLRP3-mediated pyroptosis to attenuate myocardial I/R injury via repressing CBL-induced ubiquitination degradation of ß-catenin.

A nomogram for prediction of early mortality in patients undergoing cardiac surgery for infective endocarditis: a retrospective single-center study.

OBJECTIVE: Despite advancements in surgical techniques, operations for infective endocarditis (IE) remain associated with relatively high mortality. The aim of this study was to develop a nomogram model to predict the early postoperative mortality in patients undergoing cardiac surgery for infective endocarditis based on the preoperative clinical features. METHODS: We retrospectively analyzed the clinical data of 357 patients with IE who underwent surgeries at our center between January 2007 and June 2023. Independent risk factors for early postoperative mortality were identified using univariate and multivariate logistic regression models. Based on these factors, a predictive model was developed and presented in a nomogram. The performance of the nomogram was evaluated through the receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis (DCA). Internal validation was performed utilizing the bootstrapping method. RESULTS: The nomogram included nine predictors: age, stroke, pulmonary embolism, albumin level, cardiac function class IV, antibotic use <4weeks, vegetation size ≥1.5 cm, perivalvular abscess and preoperative dialysis. The area under the ROC curve (AUC) of the model was 0.88 (95%CI:0.80-0.96). The calibration plot indicated strong prediction consistency of the nomogram with satisfactory Hosmer-Lemeshow test results (χ2 = 13.490, p = 0.142). Decision curve analysis indicated that the nomogram model provided greater clinical net benefits compared to "operate-all" or "operate-none" strategies. CONCLUSIONS: The innovative nomogram model offers cardiovascular surgeons a tool to predict the risk of early postoperative mortality in patients undergoing IE operations. This model can serve as a valuable reference for preoperative decision-making and can enhance the clinical outcomes of IE patients.

Bed nuclei of the stria terminalis: A key hub in the modulation of anxiety.

The bed nuclei of the stria terminalis (BST) is recognised as a pivotal integrative centre for monitoring emotional valence. It is implicated in the regulation of diverse affective states and motivated behaviours, and decades of research have firmly established its critical role in anxiety-related behavioural processes. Researchers have recently intricately dissected the BST's dynamic activities, its connection patterns and its functions with respect to specific cell types using multiple techniques such as optogenetics, in vivo calcium imaging and transgenic tools to unmask the complex circuitry mechanisms that underlie anxiety. In this review, we principally focus on studies of anxiety-involved neuromodulators within the BST and provide a comprehensive architecture of the anxiety network-highlighting the BST as a key hub in orchestrating anxiety-like behaviour. We posit that these promising efforts will contribute to the identification of an accurate roadmap for future treatment of anxiety disorders.

PKD1 participates in the processing of aortic dissection via regulating vascular smooth muscle cell contraction and MAPK signaling.

Aortic Dissection (AD) is a cardiovascular emergency with high mortality, of which one feature is the phenotypic switch of vascular smooth muscle cells (VSMCs). Transient Receptor Potential Channel Interacting (PKD1) has been regarded as one regulator as well as one biomarker for AD. However, multiple candidate pathways were reported though which PKD1 regulates AD in previous study, a comprehensive insight is still absent. In this study, we compared the AD and normal samples in transcriptome scale, and detected 717 PKD1-related differential expressed genes, which enriched in mitogen-activated protein kinase (MAPK) signal transduction (AD tissue preference) and VSMC contraction pathway (normal tissue preference). Furthermore, we also found two important functional hub genes in PKD1 regulation, JUN and ACTN2, and established a carnal-miRNA-mRNA network. Our study demonstrated the co-regulation of muscle development and signal transduction in AD's progression, and also provided the genetic basis for the following mechanism research with AD.

Potential biomarkers of aortic dissection based on expression network analysis.

BACKGROUND: Aortic dissection (AD) is a rare disease with severe morbidity and high mortality. Presently, the pathogenesis of aortic dissection is still not completely clear, and studying its pathogenesis will have important clinical significance. METHODS: We downloaded 28 samples from the Gene Expression Omnibus (GEO) database (Accession numbers: GSE147026 and GSE190635), including 14 aortic dissection samples and 14 healthy controls (HC) samples. The Limma package was used to screen differentially expressed genes. The StarBasev2.0 tool was used to predict the upstream molecular circRNA of the selected miRNAs, and Cytoscape software was used to process the obtained data. STRING database was used to analyze the interacting protein pairs of differentially expressed genes under medium filtration conditions. The R package "org.hs.eg.db" was used for functional enrichment analysis. RESULTS: Two hundred genes associated with aortic dissection were screened. Functional enrichment analysis was performed based on these 200 genes. At the same time, 2720 paired miRNAs were predicted based on these 200 genes, among which hsa-miR-650, hsa-miR-625-5p, hsa-miR-491-5p and hsa-miR-760 paired mRNAs were the most. Based on these four miRNAs, 7106 pairs of circRNAs were predicted to be paired with them. The genes most related to these four miRNAs were screened from 200 differentially expressed genes (CDH2, AKT1, WNT5A, ADRB2, GNAI1, GNAI2, HGF, MCAM, DKK2, ISL1). CONCLUSIONS: The study demonstrates that miRNA-associated circRNA-mRNA networks are altered in AD, implying that miRNA may play a crucial role in regulating the onset and progression of AD. It may become a potential biomarker for the diagnosis and treatment of AD.

E3 ubiquitin ligase HECW1 promotes the metastasis of non-small cell lung cancer cells through mediating the ubiquitination of Smad4.

Lung cancer is the leading cause of cancer-related death globally. Ubiquitin modification plays a crucial role in the regulation of gene expression, and is closely associated with cancer pathogenesis. The aim of our study was to clarify the role and mechanisms of action for HECT, C2 and WW domain containing E3 ubiquitin protein ligase 1 (HECW1) in non-small cell lung cancer (NSCLC). Herein, we demonstrate that the expression of HECW1 was significantly increased in NSCLC cell lines and tissues. Upregulation of HECW1 markedly enhanced the proliferation of NSCLC cells, whereas downregulation of HECW1 significantly inhibited proliferation. Moreover, the expression levels of HECW1 positively correlated with the migration and invasiveness of NSCLC cells. Upregulation or downregulation of HECW1 only affected the protein expression levels of SMAD family member 4 (Smad4), but had no effect on the mRNA expression levels. Furthermore, after treatment with MG-132, the relative protein level of Smad4 significantly increased in NSCLC cells. HECW1 promoted the proliferation, migration, and invasiveness of NSCLC cells by inducing the ubiquitination and degradation of Smad4, thus our data provide a novel target for NSCLC treatment.

LncRNA AFAP1-AS1 promotes osteoblast differentiation of human aortic valve interstitial cells through regulating miR-155/SMAD5 axis.

AIM: Degenerative calcific aortic valve disease (DCAVD) is a common valve disease characterized by massive calcium deposits in the aortic valve. Osteoblast differentiation of valve interstitial cells (VICs) is responsible for the formation of calcific nodules. This study aims to explore the function and underlying mechanism of long non-coding RNA (lncRNA) AFAP1-AS1 (actin filament-associated protein 1 antisense RNA 1) in the pathogenesis of DCAVD. METHODS: AFAP1-AS1, miR-155 and mRNA levels were detected by qRT-PCR. Protein levels were measured by Western blot. Calcification deposition was examined by Alizarin Red staining. The interaction between AFAP1-AS1 and miR-155, as well as miR-155 and SMAD5 was evaluated using luciferase reporter assay. RESULTS: AFAP1-AS1 expression was increased both in calcified aortic valves from DCAVD patients and after osteogenic induction in human VICs. Furthermore, AFAP1-AS1 overexpression promoted osteogenic differentiation of VICs, whereas AFAP1-AS1 knockdown inhibited osteogenic differentiation. Mechanistically, AFAP1-AS1 acted as a sponge for miR-155 to elevate SMAD5 expression. Further functional assays revealed that miR-155 mimic and SMAD5 silencing effectively reversed AFAP1-AS1-promoted osteogenic differentiation of VICs. CONCLUSION: Collectively, AFAP1-AS1 promotes osteogenic differentiation of VICs, at least in part, by sponging miR-155 to upregulate SMAD5. This study sheds new light on lncRNA-directed therapeutics in DCAVD.

WWP2 ameliorates acute kidney injury by mediating p53 ubiquitylation and degradation.

E3 ubiquitin ligase gene, WWP2, is associated with acute kidney injury (AKI). This research was conducted to explore the role of WWP2 in AKI. AKI cell model was produced in human renal proximal tubular epithelial cell line (HK-2) by ischemia-reperfusion (IR) injury. CCK8 and flow cytometry assay were performed to explore the influence of WWP2 overexpression on cell proliferation and apoptosis of IR-induced HK-2 cells. Quantitative real-time PCR and immunoblotting (IB) were performed to assess the gene and protein expression. Then, the influence of WWP2 on p53 ubiquitylation and degradation was estimated by immunoprecipitation assay. Our data indicated that WWP2 was down-regulated and p53 was up-regulated in IR-induced HK-2 cells. WWP2 overexpression promoted proliferation and inhibited apoptosis of IR-induced HK-2 cells. And WWP2 interacted with p53 and regulated p53 ubiquitylation and degradation. Furthermore, the influence of WWP2 on cell proliferation and apoptosis was rescued by MG132 (proteasome inhibitor) treatment. In conclusion, our work described for the first time the role of WWP2 in AKI, showing that WWP2 ameliorated AKI by mediating p53 ubiquitylation and degradation. Moreover, the study offers some important insights into the occurrence of AKI and WWP2 may be a novel target of AKI treatment. SIGNIFICANCE OF THE STUDY: Our data elaborates that WWP2 has protective effect against AKI by mediating p53 ubiquitylation and degradation. Thus, WWP2 might be a therapeutic target for AKI.

A case of abdominal bleeding after mitral valvuloplasty assisted by da Vinci robotic surgery.

A 66-year-old female patient was admitted with abdominal bleeding as an unexpected complication of robotic surgery. Assessments included the patient's medical history, physical examination, laboratory data, and abdominal ultrasound scan results. In our case, laparotomy revealed an injury to the diaphragm and liver of the patient caused by the previous robotic surgery. In conclusion, although abdominal bleeding is a rare condition, it should be taken into consideration as a complication of robotic cardiac surgery.

LncRNA NRON alleviates atrial fibrosis via promoting NFATc3 phosphorylation.

The aim of this study was to explore the role of NRON in the atrial fibrosis. The expression of NRON in atrial tissue was detected using qRT-PCR. The protein levels of collagen I, collagen III, NFATc3 and p-NFATc3 were determined by western blot. Immunohistochemistry assay were performed to observe expression and distribution of collagen I in atrial tissues. The atrial fibroblasts were authenticated by vimentin/troponin immunofluorescence staining. Fibroblast proliferation was detected by CCK-8 assay. The morphological changes of cardiac tissue were observed by HE staining. Myocardial fibrosis was detected by masson staining. NRON expression was significantly downregulated in atrial tissues of AF. NRON suppressed fibroblast proliferation; expression of collagen I and collagen III; activation of NFATc3 and nucleu import. NRON promoted p-NFATc3 expression and alleviated atrial fibrosis in vivo. Our data indicated that NRON alleviates atrial fibrosis via promoting NFATc3 phosphorylation.

The Predictive Value of Potential Hematological Biomarkers in Acute Coronary Syndrome.

BACKGROUND: To explore the predictive value of potential hematological biomarkers in acute coronary syndrome (ACS). METHODS: A total of 309 patients suffering ACS from June 2014 to June 2016 in The First Affiliated Hospital of Anhui Medical University were enrolled. The clinical data was studied retrospectively. All patients were divided into 3 groups based on the presence of elevated ST-segment including UA (150), STEMI (159), and NSTEMI (100). The association between potential hematological biomarkers of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), white blood cell count (WBC), monocyte percentage (MO), and platelet width (PLW) and outcome of ACS including cTnI, occlusion of coronary artery, emergent PCI, and 30-day mortality was performed. RESULTS: Mean ± standard deviation was used to describe quantitative data of normal distribution. Inter-group comparison was performed by t or chi-square test and non-parametric test. M (P25, P75) was used to describe quantitative data of skewed distribution. Non-parametric tests revealed, except for PLW, there was significance between NLR, PLR, MO, and WBC and emergent PCI as well as 30-day mortality (p < 0.05). Multivariate logistic regression revealed that NLR was the best predictive factor of 30-day mortality. Meanwhile, it was found that the association between NLR, PLR, WBC, and cTnI was significant (p < 0.05). CONCLUSIONS: NLR is a useful and available factor in predicting outcome of ACS and more significant when combined with PLR, MO, and WBC.

Nicotinamide Phosphate Transferase (NAMPT) Increases in Plasma in Patients with Acute Coronary Syndromes, and Promotes Macrophages to M2 Polarization.

Atherosclerosis is an inflammatory disease; monocytes and macrophages play an important role in the progression of this disease. However, the mechanisms are not fully understood yet. Nicotinamide phosphate transferase (NAMPT) is the rate limiting enzyme in the synthesis of NAD, but extracellular NAMPT shows the characteristics of cytokines/adipokines, suggesting that it may be a link between metabolism and inflammation. In this study, we compared the expression levels of the NAMPT/NAD+/Sirt1 signaling pathway as well as NAMPT, CRP and IL-6 in the peripheral blood mononuclear cell (PBMC), and plasma in patients with acute coronary syndromes and healthy subjects, and analyzed their association with macrophage polarization. The relationship between eNAMPT and iNAMPT and the polarization of macrophages was analyzed by NAD+, NAMPT blocker, and neutralizing antibody treatment. The results showed that the expression of the NAMPT/NAD+/Sirt1 signaling pathway was up-regulated in the peripheral blood of patients with ACS. Inhibition of iNAMPT expression can reduce M1 polarization; however, there was no significant effect on eNAMPT secretion and M2 polarization. Neutralizing eNAMPT by neutralizing antibodies can reduce M2 polarization and decrease the expression levels of IL-10, IL-13, IL-4 and IL-1ra. The addition of NAD+ in the cell culture supernatant had no significant effect on the polarization of M1 but increased the M2 polarization and the expression levels of IL-10 and IL-1ra. Our findings suggested that NAMPT is involved in the pathogenesis of atherosclerosis; the increased expression of eNAMPT in ACS patients may play a protective role by the up regulation of the NAMPT/NAD+/Sirt1 signaling pathway.

Cutting edge: Ubiquitin-specific protease 4 promotes Th17 cell function under inflammation by deubiquitinating and stabilizing RORγt.

RORγt is a key transcription factor that controls the development and function of inflammatory Th17. The mechanisms that regulate RORγt stability remain unclear. We report that Th17 cells highly express the deubiquitinase ubiquitin-specific protease (USP)4, which is essential for maintaining RORγt and Th17 cell function. Inhibition of the catalytic activity of USP4 with vialinin A, a compound derived from Chinese traditional medicine, dampened Th17 differentiation. USP4 interacted and deubiquitinated K48-linked polyubiquitination of RORγt, thereby promoting RORγt function and IL-17A transcription. Interestingly, TGF-ß plus IL-6 enhanced USP4-mediated deubiquitination of RORγt. Moreover, USP4 and IL-17 mRNA, but not RORγt mRNA, were significantly elevated in CD4(+) T cells from patients with rheumatic heart disease. Thus, USP4 could be a novel therapeutic target for the treatment of Th17-modulated autoimmune diseases.

Tumor necrosis factor alpha-stimulated gene-6 (TSG-6) inhibits the inflammatory response by inhibiting the activation of P38 and JNK signaling pathway and decreases the restenosis of vein grafts in rats.

This study aims to explore the effects of tumor necrosis factor alpha-stimulated gene-6 (TSG-6) on vascular inflammatory response and vascular injury in grafted vein wall of rats and its possible mechanism. Vascular grafting model was established by modified cuff. The effect of TSG-6 on the inflammatory response and vascular injury of vein graft was investigated. The activation of mast cells and macrophages after LPS stimulation was observed by lentivirus-mediated upregulation or downregulation of TSG-6 expression. The results showed that rhTSG-6 treatment could significantly inhibit the proliferation of venous bridge, decrease macrophage infiltration and smooth muscle cell proliferation. The expression levels of TNF-α and IL-1 in treated group were significantly lower than that of untreated group (P < 0.05), while the expression of IL-10 in treated group were significantly higher than that of untreated group (P < 0.05). The expression levels of P38, p-P38, JNK and p-JNK in venous bridge of rats were significantly lower than those of untreated rats (P < 0.05), while there was no significant difference in the expression level of ERK and p-ERK (P > 0.05). TSG-6 could inhibit the proliferation of mast cells and macrophages and the release of inflammatory cytokines by down regulating the expression levels of P38, p-P38, JNK and p-JNK. TSG-6 can inhibit the inflammatory response of transplanted vein grafts in rats and reduce vascular injury by downregulation of P38 and JNK signaling pathway.

Long non-coding RNA FGD5 antisense RNA 1 targets Baculovirus inhibitor 5 via microRNA-497-5p to alleviate calcific aortic valve disease.

Calcific aortic valve disease (CAVD) is featured by thickening and calcification of the aortic valve. Osteoblast differentiation is a crucial step in valve calcification. Long non-coding RNAs (LncRNAs) participate in the osteogenic differentiation of mesenchymal cells. However, the character of lncRNA FGD5 antisense RNA 1 (FGD5-AS1) in CAVD is uncertain. After collection of human aortic valve tissue samples, detection of FGD5-AS1, microRNA (miR)-497-5p and Baculovirus inhibitor 5 (BIRC5) was conducted. Valve mesenchymal cells were isolated from CAVD patients and induced to differentiate to osteoblasts, and transfected with FGD5-AS1, miR-497-5p and BIRC5 plasmids. Detection of the alkaline phosphatase activity was after osteogenic induction of human aortic valve interstitial cells (hAVICs); Detection of the degree of calcium nodules and osteoblast differentiation markers (RUNX2 and OPN) was conducted. After establishment of a mouse model of CAVD, detection of the thickness of aortic valve leaflets, and the degree of calcification of the valve leaflets, and evaluation of echocardiographic parameters were implemented. Experimental data manifested in CAVD patients, lncRNAFGD5-AS1 and BIRC5 were reduced, but miR-497-5p was elevated; Enhancing lncRNA FGD5-AS1 or repressing miR-497-5p mitigated CAVD by restraining osteogenic differentiation; LncRNA FGD5-AS1 sponged miR-497-5p to target BIRC5; Repressive BIRC5 turned around the therapeutic action of elevated FGD5-AS1 or depressed miR-497-5p on hAVICs; Enhancive FGD5-AS1 in vivo was available to reduce ApoE-/- mouse CAVD induced via high cholesterol diet. All in all, lncRNAFGD5-AS1 targets BIRC5 via miR-497-5p to alleviate CAVD.

STUB1 is acetylated by KAT5 and alleviates myocardial ischemia-reperfusion injury through LATS2-YAP-ß-catenin axis.

Myocardial ischemia-reperfusion injury (MIRI) is involved in the pathogenesis of multiple cardiovascular diseases. This study elucidated the biological function of lysine acetyltransferase 5 (KAT5) in cardiomyocyte pyroptosis during MIRI. Oxygen-glucose deprivation/reoxygenation and left anterior descending coronary artery ligation were used to establish MIRI models. Here we show, KAT5 and STIP1 homology and U-box-containing protein 1 (STUB1) were downregulated, while large tumor suppressor kinase 2 (LATS2) was upregulated in MIRI models. KAT5/STUB1 overexpression or LATS2 silencing repressed cardiomyocyte pyroptosis. Mechanistically, KAT5 promoted STUB1 transcription via acetylation modulation, and subsequently caused ubiquitination and degradation of LATS2, which activated YAP/ß-catenin pathway. Notably, the inhibitory effect of STUB1 overexpression on cardiomyocyte pyroptosis was abolished by LATS2 overexpression or KAT5 depletion. Our findings suggest that KAT5 overexpression inhibits NLRP3-mediated cardiomyocyte pyroptosis to relieve MIRI through modulation of STUB1/LATS2/YAP/ß-catenin axis, providing a potential therapeutic target for MIRI.

Comparative analysis of robotically-assisted versus conventional sternotomy approach in left atrial myxoma resection: A single-center retrospective observational study.

BACKGROUND: Minimally invasive surgery has emerged as a favorable alternative to conventional surgery for various cardiac conditions. This study aimed to compare the perioperative outcomes and follow-up results of the robotic approach versus the sternotomy approach for left atrial myxoma (LAM) resection. METHOD: We retrospectively analyzed the perioperative outcomes and follow-up results of 94 patients who underwent left atrial myxoma resection using either the sternotomy approach (n = 64) or the robotic approach (n = 30) at our center between January 2017 and April 2023. Multiple linear regressions were employed to examine the actual impact of the surgical approach on perioperative outcomes while controlling for potential confounding factors. RESULTS: There were no in-hospital deaths or follow-up deaths in the robotic group. Univariate analyses revealed that robotic LAM resection had a longer cardiopulmonary bypass (CPB) time (99.93 ± 22.30 vs. 76.28 ± 24.92, P < 0.001), longer aortic clamping time (57.80 ± 20.27 vs. 47.89 ± 18.10, P = 0.019), reduced postoperative drainage (P < 0.001), shorter mechanical ventilation time (P = 0.005), shorter postoperative bed-stay time (P < 0.001), shorter postoperative hospitalization time (P = 0.040), and higher hospital costs (P = 0.001) compared to the sternotomy group. After adjusting for baseline characteristics in a multiple regression model, a longer CPB time (B = 28.328; CI, 18.609-38.047; P < 0.001), longer aortic clamping time (B = 11.856; CI, 4.069-19.644; P = 0.003), reduced postoperative drainage (B = -200.224; CI, -254.962- -145.486; P < 0.001), shorter mechanical ventilation time (B = -3.429; CI, -6.562- -0.295; P = 0.032), shorter postoperative bed-stay time (B = -2.230; CI, -3.267- -1.193; P < 0.001), shorter postoperative hospitalization time (B = -1.998; CI, -3.747- -0.250; P = 0.026), and higher hospital costs (B = 2096.866, P = 0.002) were found in the robotic group. Furthermore, the robotic group exhibited a faster return to exercise compared to the sternotomy group (Log-Rank χ2 = 34.527, P < 0.001). CONCLUSION: Both the robotic and sternotomy approaches are viable and safe options for LAM resection. However, despite the higher costs, longer CPB time, and longer aortic clamping time associated with robotic LAM resection, this technique was correlated with reduced postoperative drainage and faster postoperative recovery compared to the sternotomy technique.

Risk factors for prolonged postoperative ICU stay in the patients with Stanford type A aortic dissection.

OBJECTIVE: To investigate the independent risk factors for postoperative prolonged ICU stay in patients with Stanford type A aortic dissection (TAAD) and assess the clinical outcomes of prolonged ICU stay. METHOD: The clinical data of 100 patients with TAAD admitted to the Department of Cardiovascular Surgery, First Affiliated Hospital of Anhui Medical University from December 2018 to September 2022 were retrospectively collected and analyzed. Patients were divided into two groups, based on the postoperative ICU stay (7 days as the threshold), regular ICU stay group (< 7 days) and prolonged ICU stay group (≥ 7 days). First, preoperative and intraoperative materials were collected for univariate analysis. Then, the significant variables after univariate analysis were analyzed using logistic regression, and the final independent risk factors for prolonged ICU stay were determined. Meanwhile, the postoperative clinical outcomes were analyzed with the aim of assessing the clinical outcomes due to prolonged ICU stay. RESULTS: There were 65 and 35 patients in the regular ICU stay group and the prolonged ICU stay group, respectively. In accordance with the result of univariate analysis in the two groups, emergency surgery (χ2 = 13.598; P < 0.001), preoperative urea nitrogen (t = 3.006; P = 0.004), cardiopulmonary bypass (CPB) time (t = 2.671; P = 0.001) and surgery time (t = 2.630; P = 0.010) were significant. All significant variates were analyzed through logistic regression, and it was found that emergency surgery (OR = 0.192; 95% CI: 0.065-0.561), preoperative urea nitrogen (OR = 0.775; 95% CI: 0.634-0.947) and cardiopulmonary time (OR = 0.988; 95% CI: 0.979-0.998) were independent risk factors for prolonged postoperative ICU stay. The Receiver Operating Characteristic (ROC) curves of these three factors were also effective in predicting postoperative prolonged ICU stay (Emergency surgery, AUC = 0.308, 95% CI: 0.201-0.415; Preoperative urea nitrogen, AUC = 0.288, 95% CI: 0.185-0.392; cardiopulmonary time, AUC = 0.340, 95% CI: 0.223-0.457). Moreover, compared with a single factor, the predictive value of combined factors was more significant (AUC = 0.810, 95% CI: 0.722-0.897). For the comparison of postoperative data in the two groups,, compared with the regular ICU stay group, the incidence of adverse events in the prolonged ICU stay group increased significantly, including limb disability of limbs (χ2 = 22.182; P < 0.001), severe organ injury (χ2 = 23.077; P < 0.001), tracheotomy (χ2 = 17.582; P < 0.001), reintubation (χ2 = 28.020; P < 0.001), 72 h tracheal extubation after surgery (χ2 = 29.335; P < 0.001), 12 h consciousness recovery after surgery (χ2 = 18.445; P < 0.001), ICU re-entering (χ2 = 9.496; P = 0.002) and irregular discharging (χ2 = 24.969; P < 0.001). CONCLUSION: Emergency surgery, preoperative urea nitrogen, and CPB time are risk factors for postoperative prolonged ICU stay after TAAD surgery. Furthermore, prolonged ICU stay is associated with worse clinical outcomes. Hence, a reasonable strategy should be adopted proactively focusing on the risk factors to shorten ICU stays and improve clinical outcomes.

The cGAS-STING pathway in cardiovascular diseases: from basic research to clinical perspectives.

The cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase-stimulator of interferon genes (cGAS-STING) signaling pathway, an important component of the innate immune system, is involved in the development of several diseases. Ectopic DNA-induced inflammatory responses are involved in several pathological processes. Repeated damage to tissues and metabolic organelles releases a large number of damage-associated molecular patterns (mitochondrial DNA, nuclear DNA, and exogenous DNA). The DNA fragments released into the cytoplasm are sensed by the sensor cGAS to initiate immune responses through the bridging protein STING. Many recent studies have revealed a regulatory role of the cGAS-STING signaling pathway in cardiovascular diseases (CVDs) such as myocardial infarction, heart failure, atherosclerosis, and aortic dissection/aneurysm. Furthermore, increasing evidence suggests that inhibiting the cGAS-STING signaling pathway can significantly inhibit myocardial hypertrophy and inflammatory cell infiltration. Therefore, this review is intended to identify risk factors for activating the cGAS-STING pathway to reduce risks and to simultaneously further elucidate the biological function of this pathway in the cardiovascular field, as well as its potential as a therapeutic target.

Small nucleolar RNA host gene 18 controls vascular smooth muscle cell contractile phenotype and neointimal hyperplasia.

AIMS: Long non-coding RNA (LncRNA) small nucleolar RNA host gene 18 (SNHG18) has been widely implicated in cancers. However, little is known about its functional involvement in vascular diseases. Herein, we attempted to explore a role for SNHG18 in modulating vascular smooth muscle cell (VSMC) contractile phenotype and injury-induced neointima formation. METHODS AND RESULTS: Analysis of single-cell RNA sequencing and transcriptomic datasets showed decreased levels of SNHG18 in injured and atherosclerotic murine and human arteries, which is positively associated with VSMC contractile genes. SNHG18 was upregulated in VSMCs by TGFß1 through transcription factors Sp1 and SMAD3. SNHG18 gene gain/loss-of-function studies revealed that VSMC contractile phenotype was positively regulated by SNHG18. Mechanistic studies showed that SNHG18 promotes a contractile VSMC phenotype by up-regulating miR-22-3p. SNHG18 up-regulates miR-22 biogenesis and miR-22-3p production by competitive binding with the A-to-I RNA editing enzyme, adenosine deaminase acting on RNA-2 (ADAR2). Surprisingly, we observed that ADAR2 inhibited miR-22 biogenesis not through increasing A-to-I editing within primary miR-22, but by interfering with the binding of microprocessor complex subunit DGCR8 to primary miR-22. Importantly, perivascular SNHG18 overexpression in the injured vessels dramatically up-regulated the expression levels of miR-22-3p and VSMC contractile genes, and prevented injury-induced neointimal hyperplasia. Such modulatory effects were reverted by miR-22-3p inhibition in the injured arteries. Finally, we observed a similar regulator role for SNHG18 in human VSMCs and a decreased expression level of both SNHG18 and miR-22-3p in diseased human arteries; and we found that the expression level of SNHG18 was positively associated with that of miR-22-3p in both healthy and diseased human arteries. CONCLUSION: We demonstrate that SNHG18 is a novel regulator in governing VSMC contractile phenotype and preventing injury-induced neointimal hyperplasia. Our findings have important implications for therapeutic targeting snhg18/miR-22-3p signalling in vascular diseases.