Serum Free Fatty Acid Concentration Predicts ARDS after Off-Pump CABG: A Prospective Observational Study.

BACKGROUND: Free fatty acids (FFAs) are established risk factors for various cardiovascular and metabolic disorders. Elevated FFAs can trigger inflammatory response, which may be associated with the occurrence of acute respiratory distress syndrome (ARDS) in cardiac surgery. In this prospective study, we aimed to investigate the association between circulating FFA and the incidence of ARDS, as well as the length of ICU stay, in patients undergoing off-pump coronary artery bypass grafting (CABG). METHODS: We conducted a single-center, prospective, observational study among patients undergoing off-pump CABG. The primary endpoint was the occurrence of ARDS within 6 days after off-pump CABG. Serum FFA were measured at baseline and 24 h post-procedure, and the difference (Δ-FFA) was calculated. RESULTS: A total of 180 patients were included in the primary analysis. The median FFA was 2.3 mmol/L (quartile 1 [Q1]-Q3, 1.4-3.2) at baseline and 1.5 mmol/L (Q1-Q3, 0.9-2.3) 24 h after CABG, with a Δ-FFA of 0.6 mmol/L (Q1-Q3, -0.1 to 1.6). Patients with elevated Δ-FFA levels had a significantly higher ARDS occurrence (55.6% vs. 22.2%; P < 0.001). Elevated Δ-FFA after off-pump CABG correlated with a significantly lower PaO2/FiO2 ratio, prolonged mechanical ventilation, and extended length of ICU stay. The area under the curve (AUC) of Δ-FFA for predicting ARDS (AUC, 0.758; 95% confidence interval, 0.686-0.831) significantly exceeded the AUC of postoperative FFA (AUC, 0.708; 95% CI 0.628-0.788; P < 0.001). CONCLUSIONS: Elevated Δ-FFA levels correlated with ARDS following off-pump CABG. Monitoring FFA may assist in identifying high-risk patients for ARDS, facilitating timely interventions to improve clinical outcomes.

The role of FPR2-mediated ferroptosis in formyl peptide-induced acute lung injury against endothelial barrier damage and protective effect of the mitochondria-derived peptide MOTS-c.

BACKGROUND: Acute lung injury (ALI) has garnered significant attention in the field of respiratory and critical care due to its high mortality and morbidity, and limited treatment options. The role of the endothelial barrier in the development of ALI is crucial. Several bacterial pathogenic factors, including the bacteria-derived formyl peptide (fMLP), have been implicated in damaging the endothelial barrier and initiating ALI. However, the mechanism by which fMLP causes ALI remains unclear. In this study, we aim to explore the mechanisms of ALI caused by fMLP and evaluate the protective effects of MOTS-c, a mitochondrial-derived peptide. METHODS: We established a rat model of ALI and a human pulmonary microvascular endothelial cell (HPMVEC) model of ALI by treatment with fMLP. In vivo experiments involved lung histopathology assays, assessments of inflammatory and oxidative stress factors, and measurements of ferroptosis-related proteins and barrier proteins to evaluate the severity of fMLP-induced ALI and the type of tissue damage in rats. In vitro experiments included evaluations of fMLP-induced damage on HPMVEC using cell activity assays, assessments of inflammatory and oxidative stress factors, measurements of ferroptosis-related proteins, endothelial barrier function assays, and examination of the key role of FPR2 in fMLP-induced ALI. We also assessed the protective effect of MOTS-c and investigated its mechanism on the fMLP-induced ALI in vivo and in vitro. RESULTS: Results from both in vitro and in vivo experiments demonstrate that fMLP promotes the expression of inflammatory and oxidative stress factors, activates ferroptosis and disrupts the vascular endothelial barrier, ultimately contributing to the development and progression of ALI. Mechanistically, ferroptosis mediated by FPR2 plays a key role in fMLP-induced injury, and the Nrf2 and MAPK pathways are involved in this process. Knockdown of FPR2 and inhibition of ferroptosis can attenuate ALI induced by fMLP. Moreover, MOTS-c could protect the vascular endothelial barrier function by inhibiting ferroptosis and suppressing the expression of inflammatory and oxidative stress factors through Nrf2 and MAPK pathways, thereby alleviating fMLP-induced ALI. CONCLUSION: Overall, fMLP disrupts the vascular endothelial barrier through FPR2-mediated ferroptosis, leading to the development and progression of ALI. MOTS-c demonstrates potential as a protective treatment against ALI by alleviating the damage induced by fMLP.

Risk factors analysis and survival prediction model establishment of patients with lung adenocarcinoma based on different pyroptosis-related gene subtypes.

BACKGROUND: Lung adenocarcinoma (LUAD) is a common cancer with a poor prognosis. Pyroptosis is an important process in the development and progression of LUAD. We analyzed the risk factors affecting the prognosis of patients and constructed a nomogram to predict the overall survival of patients based on different pyroptosis-related genes (PRGs) subtypes. METHODS: The genomic data of LUAD were downloaded from the TCGA and GEO databases, and all data were filtered and divided into TCGA and GEO cohorts. The process of data analysis and visualization was performed via R software. The data were classified based on different PRGs subtypes using the K-means clustering method. Then, the differentially expressed genes were identified between two different subtypes, and risk factors analysis, survival analysis, functional enrichment analysis, and immune cells infiltration landscape analysis were conducted. The COX regression analysis was used to construct the prediction model. RESULTS: Based on the PRGs of LUAD, the patients were divided into two subtypes. We found the survival probability of patients in subtype 1 is higher than that in subtype 2. The results of the logistics analysis showed that gene risk score was closely associated with the prognosis of LUAD patients. The results of GO analysis and KEGG analysis revealed important biological processes and signaling pathways involved in the differentially expressed proteins between the two subtypes. Then we constructed a prediction model of patients' prognosis based on 13 genes, including IL-1A, P2RX1, GSTM2, ESYT3, ZNF682, KCNF1, STK32A, HHIPL2, GDF10, NDC80, GSTA1, BCL2L10, and CCR2. This model was strongly related to the overall survival (OS) and also reflects the immune status in patients with LUAD. CONCLUSION: In our study, we examined LUAD heterogeneity with reference to pyroptosis and found different prognoses between the two subtypes. And a novel prediction model was constructed to predict the OS of LUAD patients based on different PRGs signatures. The model has shown excellent predictive efficiency through validation.

The mitochondrial-derived peptide MOTS-c suppresses ferroptosis and alleviates acute lung injury induced by myocardial ischemia reperfusion via PPARγ signaling pathway.

Acute lung injury (ALI) is a life-threatening complication of cardiac surgery that has a high rate of morbidity and mortality. Epithelial ferroptosis is believed to be involved in the pathogenesis of ALI. MOTS-c has been reported to play a role in regulating inflammation and sepsis-associated ALI. The purpose of this study is to observe the effect of MOTS-c on myocardial ischemia reperfusion (MIR)-induced ALI and ferroptosis. In humans, we used ELISA kits to investigate MOTS-c and malondialdehyde (MDA) levels in patients undergoing off-pump coronary artery bypass grafting (CABG). In vivo, we pretreated Sprague-Dawley rats with MOTS-c, Ferrostatin-1 and Fe-citrate(Ⅲ). We conducted Hematoxylin and Eosin (H&E) staining and detection of ferroptosis-related genes in MIR-induced ALI rats. In vitro, we evaluated the effect of MOTS-c on hypoxia regeneration (HR)-induced mouse lung epithelial-12 (MLE-12) ferroptosis and analyzed the expression of PPARγ through western blotting. We found that circulating MOTS-c levels were decreased in postoperative ALI patients after off-pump CABG, and that ferroptosis contributed to ALI induced by MIR in rats. MOTS-c suppressed ferroptosis and alleviated ALI induced by MIR, and the protective effect of MOTS-c- was dependent on PPARγ signaling pathway. Additionally, HR promoted ferroptosis in MLE-12 cells, and MOTS-c inhibited ferroptosis against HR through the PPARγ signaling pathway. These findings highlight the therapeutic potential of MOTS-c for improving postoperative ALI induced by cardiac surgery.

Risk Factors Analysis and Prediction Model Establishment of Intestinal Metaplasia or Dysplasia in Patients With Chronic Atrophic Gastritis: A Multi-Center Retrospective Study.

Objective: To investigate the risk factors and construct a prediction model of chronic atrophic gastritis (CAG) patients with intestinal metaplasia or dysplasia. Method: The clinical data of 450 patients with CAG who were diagnosed and treated in the Department of Gastroenterology of the Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine from June 2016 to February 2022 were collected. Single and multiple factors logistic regression analysis were used to explore the risk factors of intestinal metaplasia or dysplasia in patients of training cohort. Then, we constructed a model to predict the onset of intestinal metaplasia or dysplasia based on the data of training cohort, following which we tested the model in an external validation cohort of 193 patients from a local university teaching hospital. The ROC curve, calibration curve, and decision curve analysis were used to evaluate the accuracy of the prediction model. Result: Helicobacter pylori (H. pylori, HP) infection, pepsinogen I, gastrin-17, and the number of lesions were found to be independent rick factors of the model. The liner prediction model showed excellent predictive value in both training cohort and validation cohort. Conclusion: HP infection, pepsinogen I, gastrin-17, and the number of lesions are independent risk factors for intestinal metaplasia or dysplasia in patients with CAG. The prediction model constructed based on these factors has a high accuracy and excellent calibration, which can provide a great basis for condition assessment and individualized treatment of the patients.

Prediction of Short-Term Mortality With Renal Replacement Therapy in Patients With Cardiac Surgery-Associated Acute Kidney Injury.

Objective: We aimed to: (1) explore the risk factors that affect the prognosis of cardiac surgery-associated acute kidney injury (CS-AKI) in patients undergoing renal replacement therapy (RRT) and (2) investigate the predictive value of the Acute Physiology and Chronic Health Evaluation (APACHE) III score, Sequential Organ Failure Assessment (SOFA) score, and Vasoactive-Inotropic Score (VIS) for mortality risk in patients undergoing RRT. Methods: Data from patients who underwent cardiac surgery from January 2015 through February 2021 were retrospectively reviewed to calculate the APACHE III score, SOFA score, and VIS on the first postoperative day and at the start of RRT. Various risk factors influencing the prognosis of the patients during treatment were evaluated; the area under the receiver operating characteristics curve (AUCROC) was used to measure the predictive ability of the three scores. Independent risk factors influencing mortality were analyzed using multivariable binary logistic regression. Results: A total of 90 patients were included in the study, using 90-day survival as the end point. Of those patients, 36 patients survived, and 54 patients died; the mortality rate reached 60%. At the start of RRT, the AUCROC of the APACHE III score was 0.866 (95% CI: 0.795-0.937), the VIS was 0.796 (95% CI: 0.700-0.892), and the SOFA score was 0.732 (95% CI: 0.623-0.842). The AUCROC-value of the APACHE III score on the first postoperative day was 0.790 (95% CI: 0.694-0.885). After analyzing multiple factors, we obtained the final logistic regression model with five independent risk factors at the start of RRT: a high APACHE III score (OR: 1.228, 95% CI: 1.079-1.397), high VIS (OR: 1.147, 95% CI: 1.021-1.290), low mean arterial pressure (MAP) (OR: 1.170, 95% CI: 1.050-1.303), high lactate value (OR: 1.552, 95% CI: 1.032-2.333), and long time from AKI to initiation of RRT (OR: 1.014, 95% CI: 1.002-1.027). Conclusion: In this study, we showed that at the start of RRT, the APACHE III score and the VIS can accurately predict the risk of death in patients undergoing continuous RRT for CS-AKI. The APACHE III score on the first postoperative day allows early prediction of patient mortality risk. Predictors influencing patient mortality at the initiation of RRT were high APACHE III score, high VIS, low MAP, high lactate value, and long time from AKI to the start of RRT.

Potential Clinical Value of Biomarker-Guided Emergency Triage for Thoracic Aortic Dissection.

Aim: Thoracic aortic dissection (TAD) is a high-risk vascular disease. The mortality rate of untreated TADs in 24 h was as high as 50%. Thus, rapid diagnosis of TAD in the emergency department would get patients to the right treatments to save their lives. Methods: We profiled the proteome of aortic tissues from TAD patients using a label-free quantification proteomics method. The differentially expressed proteins were screened and subjected to bioinformatics analysis. Candidate biomarkers were selected and validated in independent serum samples using enzyme-linked immunosorbent assays (ELISAs). The diagnostic values were further predicted via receiver operating characteristic (ROC) curve analysis. Results: A total of 1,141 differentially expressed proteins were identified in aortic tissues from 17 TAD patients and eight myocardial infarction (MI) patients. Six proteins were selected as candidate biomarkers for ELISAs in an independent training set of 20 serum samples (TAD = 10, MI = 10). Of these proteins, four with a P-value < 0.01 were further validated in another independent set of 64 serum samples (TAD = 32, MI = 32) via ELISAs. ITGA2, COL2A1, and MIF had P-values < 0.0001, and their areas under the curve (AUCs) were 0.801 (95% CI: 0.691-0.911), 0.773 (95% CI: 0.660-0.887), and 0.701 (95% CI: 0.574-0.828), respectively. Conclusion: ITGA2, COL2A1, and MIF were identified as promising biomarkers for discriminating TAD from emergency patients with severe chest pain. Biomarker-guided emergency triage could further shorten the time for patients to get more effective treatments.