METTL3 attenuates ferroptosis sensitivity in lung cancer via modulating TFRC.

Overexpression of methyltransferase-like 3 (METTL3) is significantly correlated with the malignancy of lung cancer (LC). In the present study, we demonstrated that METTL3 had higher levels in LC tissues relative to normal tissues. METTL3 showed superior sensitivity and specificity for diagnosis and identification of LC functions. In addition, silencing METTL3 resulted in enhanced ferroptosis sensitivity, whereas overexpression of METTL3 exhibited the opposite effect. Inhibition of METTL3 impeded LC growth in cell-derived xenografts. Further exploratory studies found that METTL3 stimulated the low expression of transferrin receptor (TFRC), which was critical for ferroptosis sensitization in LC cells induced by silenced METTL3, as silencing of TFRC caused a decrease in negative regulators of ferroptosis (FTH1 and FTL) in METTL3 knockdown A549 and PC9 cells. Finally, we confirmed that METTL3 attenuation effectively maintained the stability of TFRC mRNA. In conclusion, we reported a novel mechanism of METTL3 desensitization to ferroptosis via regulating TFRC, and an appropriate reduction of METTL3 might sensitize cancer cells to ferroptosis-based therapy.

FOXP1­induced DUSP12 alleviates vascular endothelial cell inflammation and oxidative stress injury induced by ox­LDL via MAP3K5 signaling pathway.

Atherosclerosis (AS) is a type of chronic inflammatory disease and the main pathological basis of cardiovascular and cerebrovascular diseases, which seriously threaten the health of patients. The dual specificity phosphatase 12 (DUSP12) protein is known as regulator of inflammatory diseases. Nonetheless, at present, there are only a few reports on the regulatory role of DUSP12 in AS. Human umbilical vein endothelial cells (HUVECs) were induced using oxidized low-density lipoprotein (ox-LDL). Subsequently, cell transfection experiments were performed to overexpress DUSP12 in ox-LDL-induced HUVECs. Cell Counting Kit-8, TUNEL western blotting, 2',7'-dichlorofluorescein diacetate assays, ELISA and other techniques were used to measure cell viability, apoptosis, inflammation, oxidative stress and endothelial function-related indicators. Subsequently, the relationship between DUSP12 and Forkhead box P1 (FOXP1) was predicted using the JASPAR database and verified using luciferase reporter and chromatin immunoprecipitation assays. Finally, the regulatory mechanism was investigated by simultaneously overexpressing DUSP12 and knocking down FOXP1 in ox-LDL-induced HUVECs and MAP3K5-related proteins of the DUSP12 downstream pathway were measured by western blotting. The expression of DUSP12 in ox-LDL-induced HUVECs was significantly decreased. Overexpression of DUSP12 inhibited apoptosis, inflammation and oxidative stress damage and alleviated endothelial dysfunction in ox-LDL-induced HUVECs. FOXP1 promoted the transcription of DUSP12. Moreover, FOXP1 alleviated ox-LDL-induced apoptosis, inflammation and oxidative stress damage in HUVECs by regulating the expression of DUSP12, probably acting through the MAP3K5 pathway. Collectively, the present study revealed that FOXP1-induced DUSP12 alleviated vascular endothelial cell inflammation and oxidative stress injury in ox-LDL-induced HUVECs via the MAP3K5 signaling pathway, which might shed novel insights into the targeted treatment for AS in the clinic.

Comprehensive comparative analysis of the prognostic impact of systemic inflammation biomarkers for patients underwent cardiac surgery.

Background: Inflammation plays an integral role in the development of cardiovascular disease, and few studies have identified different biomarkers to predict the prognosis of cardiac surgery. But there is a lack of reliable and valid evidence to determine the optimal systemic inflammatory biomarkers to predict prognosis. Methods: From December 2015 and March 2021, we collected 10 systemic inflammation biomarkers among 820 patients who underwent cardiac surgery. Time-dependent receiver operating characteristic curves (ROC) curve at different time points and C-index was compared at different time points. Kaplan-Meier method was performed to analyze overall survival (OS). Cox proportional hazard regression analyses were used to assess independent risk factors for OS. A random internal validation was conducted to confirm the effectiveness of the biomarkers. Results: The area under the ROC of lymphocyte-to-C-reactive protein ratio (LCR) was 0.655, 0.620 and 0.613 at 1-, 2- and 3-year respectively, and C-index of LCR for OS after cardiac surgery was 0.611, suggesting that LCR may serve as a favorable indicator for predicting the prognosis of cardiac surgery. Patients with low LCR had a higher risk of postoperative complications. Besides, Cox proportional hazard regression analyses indicated that LCR was considered as an independent risk factor of OS after cardiac surgery. Conclusion: LCR shows promise as a noteworthy representative among the systemic inflammation biomarkers in predicting the prognosis of cardiac surgery. Screening for low LCR levels may help surgeons identify high-risk patients and guide perioperative management strategies.

A novel insight into the key gene signature associated with the immune landscape in the progression of sarcopenia.

Sarcopenia is an age-related skeletal muscle disorder that causes falls, disability and death in the elderly, but its exact mechanism remains unknown. In this study, we merged three GEO datasets into the expression profiles of 118 samples and screened 22 differentially expressed genes (DEGs) as candidate genes. Pathway analysis demonstrated that the functional enrichment of DEGs is mainly in the cellular response to insulin stimulus, PPAR signaling pathway and other metabolism-related pathways. Then, we identified six key genes by machine learning, which were confirmed to be closely associated with sarcopenia by bioinformatics analysis. It was experimentally verified that SCD1 exhibits the most substantial alterations in the progression of sarcopenia with disturbed lipid metabolism and myosteatosis. In addition, the immune microenvironment of sarcopenia was found to be affected by these key genes, with Th17 cells down-regulated and NK cells up-regulated. Sarcopenic patients consequently presented a more significant systemic inflammatory state with higher CAR (p = 0.028) and PAR (p = 0.018). For the first time, we identified key genes in sarcopenia with high-throughput data and demonstrated that key genes can regulate the progression of sarcopenia by affecting the immune microenvironment. Among them, SCD1 may influence lipid metabolism and myosteatosis process. Screening of key genes and analyzing of immune microenvironment provide a more accurate target for treating sarcopenia.

Prognostic implications of Global Leadership Initiative on Malnutrition-defined malnutrition in older patients who underwent cardiac surgery in China.

BACKGROUND: The proportion of older patients who are candidates for cardiac surgery is increasing. Growing evidence has shown that malnutrition is associated with a poor prognosis after cardiac surgery. The present study aimed to investigate the prognostic implications of malnutrition defined by the Global Leadership Initiative on Malnutrition in older patients who underwent cardiac surgery. METHODS: From November 2015 to January 2021, 401 older patients who underwent cardiac surgery were retrospectively enrolled and evaluated using the Global Leadership Initiative on Malnutrition criteria. The perioperative characteristics and clinical outcomes were collected. The independent risk factors for postoperative complications and overall survival were analyzed. RESULTS: The prevalence of Global Leadership Initiative on Malnutrition-defined malnutrition was 22.7% in this study. Patients with Global Leadership Initiative on Malnutrition-defined malnutrition had higher risks of postoperative complications (65.9% vs 49.7%, P = .006) and poor overall survival (68.1% vs 83.9%, P = .0019). Global Leadership Initiative on Malnutrition-defined malnutrition was also related to a longer postoperative hospital stay and prolonged intensive care stay. Five factors were identified as independent risk factors for overall survival: Global Leadership Initiative on Malnutrition-defined malnutrition (P = .009), chronic heart failure (P = .007), atrial fibrillation (P = .029), operative time (P < .001) and hemoglobin (P = .044). CONCLUSION: We demonstrated the prognostic implications of Global Leadership Initiative on Malnutrition-defined malnutrition in older patients who underwent cardiac surgery for the first time. This study highlights the necessity of using the Global Leadership Initiative on Malnutrition assessment in the comprehensive preoperative risk assessment of cardiac surgery.

Thoracic sarcopenia predicts clinical outcomes in patients undergoing coronary artery bypass grafting: A 6-year cohort study.

BACKGROUND: The relationship between thoracic sarcopenia and clinical outcomes in patients underwent coronary artery bypass grafting (CABG) is unclear. This study aims to evaluate whether thoracic sarcopenia has a satisfactory prognostic effect on adverse outcomes after CABG. METHODS: From December 2015 to May 2021, 338 patients who underwent isolated CABG at our institution were recruited in this study. Skeletal muscle area at T12 level acquired by chest computed tomography (CT) was normalized to assess thoracic sarcopenia. Univariate and multivariate analyses were performed to evaluate the risk factors of postoperative complications and overall survival (OS). RESULTS: The prevalence of thoracic sarcopenia in patients underwent CABG was 13.02%. The incidence of total major complication was significantly higher in thoracic sarcopenia group (81.8% vs 61.9%, p = 0.010). Thoracic sarcopenic patients also had longer postoperative hospital stays (p = 0.047), intensive care unit (ICU) stays (p = 0.001), higher costs (p = 0.001) and readmission rates within 30 days of discharge (18.2% vs 4.4%, p = 0.001). Patients without thoracic sarcopenia showed significantly higher OS at the 2-year follow-up period (93.9% vs 72.7%, p<0.001). Multivariate analyses demonstrated that thoracic sarcopenia was significantly and independently associated with postoperative complications and long-term OS after CABG. CONCLUSION: Thoracic sarcopenia is an effective clinical predictor of adverse postoperative complications and long-term OS in patients underwent CABG. Thoracic sarcopenia based on chest CT should be included in preoperative risk assessment of CABG.

Only transesophageal echocardiography guided patent foramen ovale closure: A single-center experience.

Background: An increasing number of studies have proved that patent foramen ovale (PFO) occlusion could reduce the incidence of recurrent stroke more than drug therapy alone under certain conditions. Which is the "best" guidance technique still remains to be discussed. Methods: A single center retrospective study enrolled 120 patients (mean age 52.51 ± 14.29 years) who underwent PFO closure between April 2019 and March 2021. 87 patients (72.5%) had suffered cryptogenic stroke (CS) at least one time, and 24 patients (20%) had repetitive episodes of hemicrania unsourced. 65 patients were in the transesophageal echocardiography (TEE) guidance group (T-group), and the other 55 patients were in the angiographic guidance group (A-group). Results: There were no significant differences in crucial clinical characteristics between the two groups. In T-group, the procedural success rate was higher (100% vs. 92.7%, P = 0.028), and the procedural time was shorter (23.15 ± 13.87 vs. 25.75 ± 7.19, P = 0.001). No difference was detected in the procedural complication rate. Follow-up were performed at least 12 months. At 12 months, new atrial fibrillation occurred in 1 patient (1.5%) in the T-group and in 1 patient (1.8%) in the A-group (P = 0.905). Residual shunt occurred in 1 patient (1.5%) in the T-group and in 3 patients (5.5%) in the A-group (P = 0.236). Recurrent cerebral ischemia occurred in 2 patient (3.1%) in the T-group and in 2 patients (3.6%) in the A-group (P = 0.865). Conclusion: The use of only intra-procedural TEE guidance for PFO closure is safe and effective. The whole procedure can be performed without fluoroscopy and contrast medium. The short and medium follow-up results are satisfactory, especially in the residual shunt.

Prognostic significance of postoperative loss of skeletal muscle mass in patients underwent coronary artery bypass grafting.

Background: Increasing life expectancy of coronary artery bypass grafting (CABG) remains to be the major concern of cardiac surgeons. However, few studies have investigated the effect of postoperative skeletal muscle index (SMI) loss on prognosis. This study aims to evaluate the prognostic role of postoperative SMI loss ≥ 5% after CABG, in order to develop a novel nomogram to predict overall survival (OS). Methods: Patients underwent CABG via midline sternotomy from December 2015 to March 2021 were recruited in this study. Preoperative and postoperative 3 months chest computed tomography (CT) images were compared to assess changes in SMI at T12 level. Based on this, patients were classified into the presence or absence of SMI loss ≥ 5%. The association between postoperative SMI loss ≥ 5% and OS was then analyzed by the Kaplan-Meier curves and Cox model. A novel nomogram incorporating independent clinical prognostic variables was also developed. Results: The study enrolled 506 patients receiving CABG, of whom 98 patients experienced T12 SMI loss ≥ 5% and had a significantly worse OS (P < 0.0001). Multivariate regression analysis showed that T12 SMI per cent change (%T12 SMI-change) was an independent prognostic factor for OS (HR = 0.809, 95% CI = 0.749-0.874). The nomogram incorporating %T12 SMI-change with other variables was accurate for predicting OS. Besides, we also found that postoperative oral nutritional supplement (ONS) can rescue T12 SMI loss. Conclusion: Postoperative SMI loss can predict survival outcome after CABG. The nomogram incorporating changes in SMI provides a superior performance than existing systems.

Construction of ultrasound-responsive urokinase precise controlled-release nanoliposome applied for thrombolysis.

Urokinase is widely used in the dissolution of an acute pulmonary embolism due to its high biocatalytic effect. However, how to precisely regulate its dose, avoid the side effects of hemolysis or ineffective thrombolysis caused by too high or too low a dose, and seize the golden time of acute pulmonary embolism are the key factors for its clinical promotion. Therefore, based on the precise design of a molecular structure, an ultrasonic-responsive nanoliposome capsule was prepared in this paper. Singlet oxygen is continuously generated under the interaction of the ultrasonic cavitation effect and the sonosensitizer protoporphyrin, and the generated singlet oxygen will break the thiol acetone bond between the hydrophilic head and the hydrophobic tail of the liposome, and the lipid The body structure disintegrates rapidly, and the urokinase encapsulated inside is rapidly released, down-regulating the expression of fibrinogen in the body, and exerting a thrombolytic function. The in vitro and in vivo results show that the smart urokinase nanoliposomes prepared by us have sensitive and responsive cytocompatibility to ultrasound and good in vivo thrombolytic properties for acute pulmonary embolism, which provides a new strategy for clinical acute pulmonary embolism thrombolysis.

Prognostic Effect of Thoracic Sarcopaenia on Short- and Long-Term Clinical Outcomes in Patients Who Underwent Cardiac Valve Surgery.

BACKGROUND: As the proportion of elderly patients increases, higher incidence of malnutrition is found among patients with valvular heart disease. Sarcopaenia is one of the main manifestations of malnutrition. Studies have shown the certain predictive effect of sarcopaenia on the clinical outcome in different cases. This study aims to clarify the impact of computed tomography (CT)-derived thoracic sarcopaenia on clinical outcomes of patients who underwent cardiac valve surgery. METHODS: The clinical data of 216 patients who underwent cardiac valve surgery from December 2015 to June 2020 were retrospectively collected. Skeletal muscle mass at 12th thoracic vertebra level was measured to diagnose thoracic sarcopaenia. Postoperative complications and follow-up data were collected. Medium follow-up was 3.2 years. RESULTS: The prevalence of thoracic sarcopaenia was 16.7% in this study. The incidence of total complications and in-hospital mortality were higher in thoracic sarcopaenia group (p=0.024 and p=0.014, respectively). Multivariate analysis revealed that thoracic sarcopaenia is a significant predictor for postoperative complications (OR 2.319; 95% CI 1.003-5.366; p=0.049). Decreased long-term survival was observed in patients with thoracic sarcopaenia. Thoracic sarcopaenia (HR 4.178; 95% CI 2.062-8.465; p<0.001) was determined to be an independent risk factor for late mortality. CONCLUSION: Thoracic sarcopaenia defined by chest CT was independently associated with higher incidence of postoperative complications and long-term mortality. Routine preoperative evaluation of thoracic sarcopaenia deserves further consideration to enhance the predictive performance for operation risk.

Development and Validation of Global Leadership Initiative on Malnutrition for Prognostic Prediction in Patients Who Underwent Cardiac Surgery.

The Global Leadership Initiative on Malnutrition (GLIM) has achieved a consensus for the diagnosis of malnutrition in recent years. This study aims to determine the prognostic effect of the GLIM after cardiac surgery. A total of 603 patients in the training cohort and 258 patients in the validation cohort were enrolled in this study. Perioperative characteristics and follow-up data were collected. A nomogram based on independent prognostic predictors was developed for survival prediction. In total, 114 (18.9%) and 48 (18.6%) patients were defined as being malnourished according to the GLIM criteria in the two cohorts, respectively. Multivariate regression analysis showed that GLIM-defined malnutrition was an independent risk factor of total complication (OR 1.661, 95% CI: 1.063-2.594) and overall survival (HR 2.339, 95% CI: 1.504-3.637). The c-index was 0.72 (95% CI: 0.66-0.79) and AUC were 0.800, 0.798, and 0.780 for 1-, 2-, and 3-year survival prediction, respectively. The calibration curves of the nomogram fit well. In conclusion, GLIM criteria can efficiently identify malnutrition and has a prognostic effect on clinical outcomes after cardiac surgery. GLIM-based nomogram has favorable performance in survival prediction.

F-box and WD repeat-containing protein 7 ameliorates angiotensin II-induced myocardial hypertrophic injury via the mTOR-mediated autophagy pathway.

Myocardial hypertrophy is a common heart disease that is closely associated with heart failure. The expression of F-box and WD repeat-containing protein 7 (FBW7) is significantly downregulated in angiotensin (Ang) II-induced cardiac fibroblasts, suggesting that it may possess an important function in cardiac development. The present study attempted to explore the role of FBW7 in Ang II-induced myocardial hypertrophic injury and its associated mechanism of action. Reverse transcription-quantitative PCR and western blotting were used to determine the expression levels of FBW7 in Ang II-induced H9C2 cells. The expression levels of autophagy-related and mTOR signaling pathway-related proteins were detected using western blotting. Cell viability was assessed using the Cell Counting Kit-8 assay. The apoptosis rate of H9C2 cells was detected using TUNEL assay and western blotting. Cellular hypertrophy and fibrosis were assessed using phalloidin staining and western blotting. Levels of inflammatory factors were examined using ELISA and western blotting, whereas levels of oxidative stress-related markers were detected by corresponding kits. The results indicated that FBW7 expression was downregulated in Ang II-induced H9C2 cells. FBW7 upregulation enhanced the expression levels of autophagy-related proteins and activated mTOR-mediated cellular autophagy. FBW7 overexpression promoted the cell viability, inhibited Ang II-induced apoptosis, cellular hypertrophy and fibrosis in H9C2 cells via the autophagic pathway, as well as inflammation and oxidative stress. Overall, the data indicated that FBW7 overexpression ameliorated Ang II-induced hypertrophic myocardial injury via the mTOR-mediated autophagic pathway.

Distribution of FFRCT in single obstructive coronary stenosis and predictors for major adverse cardiac events: a propensity score matching study.

BACKGROUND: Fractional flow reserve derived from computed tomography (FFRCT) has been demonstrated to improve identification of lesion-specific ischemia significantly compared with coronary computed tomography angiography (CCTA). It remains unclear whether the distribution of FFRCT values in obstructive stenosis between patients who received percutaneous coronary intervention (PCI) or not in routine clinical practice, as well as its association with clinical outcome. This study aims to reveal the distribution of FFRCT value in patients with single obstructive coronary artery stenosis and explored the independent factors for predicting major adverse cardiac events (MACE). METHODS: This was a retrospective study of adults with non-ST-segment elevation acute coronary syndrome undergoing FFRCT assessment by using CCTA data from January 1, 2016 to December 31, 2020. Propensity score matching (PSM) method was used to account for patient selection bias. The risk factors for predicting MACE were evaluated by a Cox proportional hazards regression analysis. RESULTS: Overall, 655 patients with single obstructive (≥ 50%) stenosis shown on CCTA were enrolled and divided into PCI group (279 cases) and conservative group (376 cases) according to treatment strategy. The PSM cohort analysis demonstrated that the difference in history of unstable angina, Canadian Cardiovascular Society Class (CCSC) and FFRCT between PCI group (188 cases) and conservative group (315 cases) was statistically significant, with all P values < 0.05, while the median follow-up time between them was not statistically significant (24 months vs. 22.5 months, P = 0.912). The incidence of MACE in PCI group and conservative group were 14.9% (28/188) and 23.5% (74/315) respectively, P = 0.020. Multivariate analysis of Cox proportional hazards regression revealed that history of unstable angina (adjusted odds ratio (adjOR), 3.165; 95% confidence interval (CI), 2.087-4.800; P < 0.001), FFRCT ≤ 0.8 (OR, 1.632;95% CI 1.095-2.431; P = 0.016), and PCI therapy (OR 0.481; 95% CI 0.305-0.758) were the independent factors for MACE. CONCLUSIONS: History of unstable angina and FFRCT value of ≤ 0.8 were the independent risk factors for MACE, while PCI therapy was the independent protective factor for MACE.

Single-Stage Pulmonary Resection via a Combination of Single Hookwire Localization and Video-Assisted Thoracoscopic Surgery for Synchronous Multiple Pulmonary Nodules.

Purpose: To retrospectively analyze the incidence and predictors of complications related to hookwire localization in patients with single and multiple nodules, and to evaluate the usefulness of a single-stage surgical method of single hookwire localization combined with video-assisted thoracoscopic surgery (VATS) in synchronous multiple pulmonary nodules (SMPNs). Methods: A total of 200 patients who underwent computed tomography (CT)-guided hookwire localization and subsequent VATS resection were enrolled in this study. For each patient, only 1 indeterminate nodule was implanted with a hookwire. There were 145 patients in the single-nodule group (Group S) and 55 in the multiple-nodule group (Group M). Univariate and binary logistic regression analyses were used to assess incidence and predictors of complications associated with hookwire localization. Results: The technical success rate of hookwire implantation was 97.5%. The incidence of pneumothorax and hookwire dislodgement was 17.0% and 2.5%, respectively. Binary logistic regression analysis showed that 1 transpleural puncture through the pleura (odds ratio [OR] = 0.433, P = .033) was the only independent protective factor for pneumothorax, and pneumothorax (OR = 26.114, P < .01) was the only independent risk factor for dislodgement. The volume of blood loss during VATS was significantly higher in group M than in group S, and the time of postoperative hospitalization was significantly longer in group M than in group S. About 44 patients in group M with additional 58 nodules without localization had undergone direct surgical resection simultaneously, and bilateral surgery was performed in 13 patients (29.5%). The intrathoracic recurrence rate was 4.8% during follow-up CT. Conclusion: Single-stage surgery via an approach of single hookwire localization combined with VATS is feasible and safe for SMPNs.

S100A1 as a potential biomarker for the diagnosis of patients with acute aortic dissection.

OBJECTIVE: Acute aortic dissection (AAD) is a common life-threatening cardiovascular disease. This retrospective study was conducted to analyze the plasma concentration of S100A1 and its diagnostic value for AAD through receiver operating characteristic (ROC) curve and logistic regression analyses. METHODS: Seventy-eight patients with AAD and 77 healthy controls were included, and the relevant clinical data for each group were collected. According to the Stanford classification, the AAD patients were divided into types A and B. The plasma levels of S100A1, D-dimer, hypersensitive C-reactive protein, and cardiac troponin T were detected by enzyme-linked immunosorbent assays. RESULTS: The S100A1 concentrations in the healthy control, Stanford A, and Stanford B groups were 0.7 ± 0.6, 4.9 ± 2.6, and 3.5 ± 2.2 ng/mL, respectively. The concentration of S100A1 was increased in patients with AAD complicated with aortic regurgitation, pericardial effusion, or in-hospital death. ROC curve analysis showed that the area under the curve was 0.89. Logistic regression analysis revealed that the S100A1 level was an important risk factor for the development of AAD. CONCLUSION: Plasma S100A1 is significantly elevated in patients with AAD, and its concentration has potential clinical value for diagnosing AAD.

ATF3: a novel biomarker for the diagnosis of acute kidney injury after cardiac surgery.

BACKGROUND: To investigate the expression of ATF3 in the blood and urine of adult patients undergoing cardiopulmonary bypass (CPB) surgery and to identify the changes during the perioperative period of CPB, and to determine whether ATF3 can be used as a biological marker for the early diagnosis of acute kidney injury (AKI). METHODS: We prospectively studied 83 patients who underwent elective CPB (ECB). Relevant clinical information was collected. Blood and urine samples were collected preoperatively (T0) and at 2 h (T1), 6 h (T2), 12 h (T3), 24 h (T4), and 48 h (T5) after surgery, and grouped according to the occurrence of AKI. The changes in ATF3 levels were observed, and the accuracy of the diagnosis of AKI was compared through receiver operating characteristic (ROC) curve analysis. Factors influencing the expression of ATF3 at baseline were also analyzed. RESULTS: A total of 83 adult patients undergoing cardiac surgery with CPB were included, and 42 of them developed AKI. The levels of serum ATF3 (sATF3) in the AKI group were significantly higher than those in the non-AKI group 24 h after surgery, and the difference was statistically significant (662.62±204.72 vs. 586.93±175.87; P=0.0345). Urinary ATF3 (uATF3) increased significantly 6 h after surgery, and the area under the ROC curve (AUC) for diagnosing AKI 12 h after surgery was 0.691 (95% CI: 0.576-0.807). When uATF3 was higher than 1,216 pg/mL, the sensitivity and specificity for the diagnosis of AKI were 0.43 and 0.85, respectively. On the other hand, the preoperative expression of ATF3 was negatively correlated with the preoperative creatinine level, but not affected by the patient's age, weight, gender, preoperative cardiac function, preoperative blood routine examination and liver function. CONCLUSIONS: ATF3 can be expressed early in the blood and urine of patients after CPB and can be used as a diagnostic marker for AKI after CPB in adult patients.

Association between serum S100A1 level and Global Registry of Acute Coronary Events score in patients with non-ST-segment elevation acute coronary syndrome.

Objective Acute coronary syndrome (ACS) is associated with several clinical syndromes, one of which is acute non-ST-segment ACS (NSTE-ACS). S100A1 is a calcium-dependent regulator of heart contraction and relaxation. We investigated the association between the serum S100A1 level and the Global Registry of Acute Coronary Events (GRACE) risk score in patients with NSTE-ACS and the potential of using the serum S100A1 level to predict the 30-day prognosis of NSTE-ACS. Methods The clinical characteristics of 162 patients with NSTE-ACS were analyzed to determine the GRACE score. The serum S100A1 concentration was determined using fasting antecubital venous blood. The patients were divided into different groups according to the serum S100A1 level, and the 30-day NSTE-ACS prognosis was evaluated using Kaplan-Meier analysis. Results The serum S100A1 levels differed significantly among the groups. Correlation analysis showed that the serum S100A1 level was positively correlated with the GRACE score. Kaplan-Meier analysis revealed that the number of 30-day cardiac events was significantly higher in patients with an S100A1 level of >3.41 ng/mL. Conclusions S100A1 is a potential biomarker that can predict the progression of NSTE-ACS and aid in its early risk stratification and prognosis.

Salidroside Protects Against Advanced Glycation End Products-Induced Vascular Endothelial Dysfunction.

BACKGROUND Salidroside, the major active compound in Rhodiola, has been reported to provide beneficial effects on cardiovascular diseases, but its effects on diabetes-induced vascular endothelial dysfunction are less known. Here, we examined the protective effects of salidroside on endothelial function in diabetes and explored the potential underlying mechanism. MATERIAL AND METHODS First, we assessed the endothelium-dependent relaxation response to acetylcholine, with or without salidroside treatment, in aortas isolated from Sprague-Dawley rats. Then, cell viability, oxidative biomarkers, and protein expression were tested to determine the effect of salidroside treatment on human umbilical vein endothelial cells (HUVECs) in vitro. RESULTS Advanced glycation end product (AGE)-induced endothelial dysfunction was significantly improved by salidroside treatment (P<0.05), as shown by a reduced relaxation response to the vasodilator acetylcholine. Further, incubation with salidroside restored NO levels and reduced reactive oxygen species formation in AGE-stimulated HUVECs in a concentration-dependent manner (P<0.05). We also showed that nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase 1 (HO-1) and nuclear factor kappa B (NF-κB) signaling was critical for the salidroside-mediated beneficial regulation. CONCLUSIONS Our results demonstrate that salidroside protects against AGE-induced endothelial dysfunction, and its effects may be in part attributed to the induction of HO-1 and attenuation of phosphorylated NF-κB p65.

Pathogenic mechanism of a catecholaminergic polymorphic ventricular tachycardia causing-mutation in cardiac calcium release channel RyR2.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a condition that is characterized by an abnormal heart rhythm in response to physical or emotional stress. The majority CPVT patients carry mutations in the RYR2 gene that encodes the calcium release channel/ryanodine receptor (RyR2) in cardiomyocytes. The pathogenic mechanisms that account for the clinical phenotypes of CPVT are still elusive. We have identified a de novo mutation, A165D, from a CPVT patient. We found that CPVT phenotypes are recapitulated in A165D knock-in mice. The mutant RyR2 channels enhanced sarcoplasmic reticulum Ca2+ release, triggered delayed afterdepolarization in cardiomyocytes. Structural analysis revealed that the A165D mutation is located in a loop that is involved in inter-subunit interactions in the RyR2 tetrameric structure, it disrupted conformational stability of the RyR2, which favored a closed-to-open state transition, resulting in a leaky channel. The loop also harbors several other CPVT mutations, which suggests a common pathogenic molecular mechanism of CPVT-causing mutations. Our data illustrated disease-relevant functional defects and provide a deeper mechanistic understanding of a life-threatening cardiac arrhythmia.

Total Endovascular Repair of Post-dissection Aortic Arch Aneurysm With Chimney Technique.

Open surgery remains the standard procedure for treatment of aortic arch pathologies. However, total endovascular repair can be a safe option for patients who are poor candidates for surgery because of compromised physiology. We report the case of a 63-year-old man with a post-dissection aortic arch aneurysm. We repaired the aneurysm using thoracic endovascular aortic repair (TEVAR) and used the chimney technique to reconstruct the supra-aortic branches. The patient is doing well after 12-month follow-up, demonstrating that TEVAR with the chimney technique can be used successfully for the treatment of post-dissection arch aneurysm.