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Background: Elderly acute kidney injury (AKI) occurring in the intensive care unit (ICU), particularly when caused or accompanied by sepsis, is linked to extended hospital stays, increased mortality rates, heightened prevalence of chronic diseases, and diminished quality of life. This study primarily utilizes a comprehensive critical care database to examine the correlation of albumin corrected anion gap (ACAG) levels with short-term prognosis in elderly patients with AKI caused or accompanied by sepsis, thus assisting physicians in early identification of high-risk patients. Methods: This study utilized data from the Medical Information Mart for Intensive Care IV (MIMIC-IV, v2.0) database. The patient population was divided into death and survival groups based on a 14-day prognosis. Subsequently, the entire population was further categorized into a normal ACAG group (12–20 mmol/L) and a high ACAG group (> 20 mmol/L) based on ACAG levels. The LASSO regression cross-validation method was employed to identify significant risk factors for inclusion in multivariate Cox regression analyses. A restricted cubic spline (RCS) was then employed to visually represent the correlation between ACAG levels and the risk of mortality in patients. Kaplan–Meier curves were utilized to plot the cumulative survival rates at 14 and 30 days for both patient groups. The robustness of the findings was subsequently evaluated through subgroup analyses. Results: Our study identified a total of 3741 eligible subjects, revealing higher all-cause mortality rates at both 14-day and 30-day intervals in the high ACAG group compared to the normal ACAG group (χ2 = 87.023, P < 0.001; χ2 = 90.508, P < 0.001). Cox regression analysis further demonstrated that an elevated ACAG on ICU admission independently posed a risk factor for both 14- and 30-day prognosis within this population. In addition, the analysis conducted using RCS revealed a non-linear association between the levels of ACAG and the risk of mortality at both 14 and 30 days in the patient cohort (χ2 = 18.220, P < 0.001; χ2 = 18.360, P < 0.001). The application of Kaplan–Meier analysis demonstrated a statistically significant decrease in cumulative survival rates among individuals with high ACAG levels (P < 0.001). Subgroup analyses indicated that ACAG levels interacted with cerebrovascular disease and acute pancreatitis on 14-day mortality (P < 0.05 for interaction). Conclusion: Elevated ACAG levels at ICU admission are an independent risk factor for poor short-term prognosis, correlating with increased all-cause mortality at 14 and 30 days in elderly patients with AKI caused or accompanied by sepsis. This highlights the importance of monitoring ACAG in critically ill patients to identify those at higher risk of adverse outcomes early. [ABSTRACT FROM AUTHOR]

The primary objective was to examine the association between the lactate/albumin ratio (LAR) and the prognosis of patients with acute kidney injury (AKI) undergoing continuous renal replacement therapy (CRRT). Utilizing the Medical Information Mart for Intensive Care IV (MIMIC-IV, v2.0) database, we categorized 703 adult AKI patients undergoing CRRT into survival and non-survival groups based on 28-day mortality. Patients were further grouped by LAR tertiles: low (< 0.692), moderate (0.692-1.641), and high (> 1.641). Restricted cubic splines (RCS), Least Absolute Shrinkage and Selection Operator (LASSO) regression, inverse probability treatment weighting (IPTW), and Kaplan-Meier curves were employed. In our study, the patients had a mortality rate of 50.07% within 28 days and 62.87% within 360 days. RCS analysis revealed a non-linear correlation between LAR and the risk of mortality at both 28 and 360 days. Cox regression analysis, which was adjusted for nine variables identified by LASSO, confirmed that a high LAR (>1.641) served as an independent predictor of mortality at these specific time points (p < 0.05) in AKI patients who were receiving CRRT. These findings remained consistent even after IPTW adjustment, thereby ensuring a reliable and robust outcome. Kaplan-Meier survival curves exhibited a gradual decline in cumulative survival rates at both 28 and 360 days as the LAR values increased (log-rank test, χ2 = 48.630, p < 0.001; χ2 = 33.530, p < 0.001). A high LAR (>1.641) was found to be an autonomous predictor of mortality at both 28 and 360 days in critically ill patients with AKI undergoing CRRT. [ABSTRACT FROM AUTHOR]

To explore the relationship between lactate-to-albumin ratio (LAR) at ICU admission and prognosis in critically ill patients with acute kidney injury (AKI). A retrospective analysis was conducted. Patients were divided into low (<0.659) LAR and high LAR (≥0.659) groups. Least absolute shrinkage and selection operator regression analysis was conducted to select variables associated with the 30-day prognosis. Cox regression analyses were performed to assess the association between LAR and mortality. Kaplan-Meier curves were plotted to compare cumulative survival rates between high and low LAR groups. Subgroup analysis was employed to assess the stability of the results. ROC curve was used to determine the diagnostic efficacy of LAR on prognosis. A nonlinear relationship was observed between LAR and the risk of 30-day and 360-day all-cause mortality in AKI patients (p < 0.001). Cox regulation showed that high LAR (≥ 0.659) was an independent risk factor for 30-day and 360-day all-cause mortality in patients with AKI (p < 0.001). The Kaplan-Meier survival curves demonstrated a noteworthy decrease in cumulative survival rates at both 30 and 360 days for the high LAR group in comparison to the low LAR group (p < 0.001). Subgroup analyses demonstrated the stability of the results. ROC curves showed that LAR had a diagnostic advantage when compared with lactate or albumin alone (p < 0.001). High LAR (≥0.659) at ICU admission was an independent risk factor for both short-term (30-day) and long-term (360-day) all-cause mortality in patients with AKI. [ABSTRACT FROM AUTHOR]

Epstein‒Barr virus (EBV) regulates the expression of host genes involved in functional pathways for viral infection and pathogenicity. Long noncoding RNAs (lncRNAs) have been found to be important regulators of cellular biology. However, how EBV affects host biological processes via lncRNAs remains elusive. Eukaryotic initiation factor 4A3 (EIF4A3) was recently identified as an essential controller of cell fate with an unknown role in EBV infection. Here, the expression of lncRNA brain cytoplasmic 200 (BC200) was shown to be significantly upregulated in EBV‐infected cell lines. RNA immunoprecipitation and RNA pulldown assays confirmed that BC200 bound to EIF4A3. Moreover, BC200 promoted EIF4A3 expression at the protein level but not at the mRNA level. Mechanistically, BC200 stabilized the EIF4A3 protein by impeding the K48‐linked polyubiquitination of the K195 and K198 residues of EIF4A3. In addition, RNA‐seq analysis of EBV‐positive cells with knockdown of either BC200 or EIF4A3 revealed that a broad range of cellular genes were differentially regulated, particularly those related to virus infection and immune response pathways. This study is the first to reveal the key residues involved in EIF4A3 polyubiquitination and elucidate the novel regulatory role of EBV in host gene expression via the BC200/EIF4A3 axis. These results have implications for the pathogenesis and treatment of EBV‐related diseases. [ABSTRACT FROM AUTHOR]

Aims: Acute myocardial infarction (AMI) is a cardiovascular disease with high morbidity and mortality. We collected patients with AMI from the Medical Information Mart for Intensive Care IV (v2.0) database and explored the association between serum albumin‐corrected anion gap (ACAG) level and mortality in patients with AMI. Methods and results: Data of adult patients with AMI were collected. According to the 360 day prognosis, patients were divided into survival and non‐survival groups. Based on the ACAG level, patients were then divided into normal and high ACAG groups. Cox hazard proportional models and restricted cubic splines (RCSs) were used to investigate the correlation between ACAG and mortality. Kaplan–Meier curves were created to compare the cumulative survival rates between the high and normal ACAG groups. The receiver operating characteristic (ROC) curve was used to analyse the predictive value of ACAG for the prognosis of patients with AMI. Sensitivity and subgroup analyses were conducted to revalidate the results. Finally, 1783 patients were included. Elevated ACAG (>20 mmol/L) was significantly associated with 30 and 360 day mortality (P < 0.001). Adjusted for multiple confounding factors, the Cox proportional hazard analysis showed that elevated ACAG (>20 mmol/L) was an independent risk factor of increased all‐cause mortality in patients with AMI (hazard ratio 1.423, 95% confidence interval 1.206–1.678, P < 0.001). RCS analysis further showed that there was a non‐linear trend relationship between ACAG and the risk of all‐cause mortality at 30 and 360 days (χ2 = 10.750, P = 0.013; χ2 = 13.960, P = 0.003). Kaplan–Meier survival curves showed that the 30 and 360 day cumulative survival rates of patients with AMI were significantly lower (log‐rank test, χ2 = 98.880, P < 0.001; χ2 = 105.440, P < 0.001) in the high ACAG group. ROC curve analysis showed that the area under the curve (AUC) of ACAG was 0.651, while the AUC of anion gap (AG) was 0.609, indicating that ACAG had a higher predictive value for 360 day mortality than AG. When combined with Sequential Organ Failure Assessment score, the predictive performance of ACAG for 360 day mortality was better, with an AUC of 0.699. Sensitivity and subgroup analyses were conducted suggesting the stability of our results. Conclusions: Elevated serum ACAG (≥20 mmol/L) is an independent risk factor for short‐term and long‐term mortality in critically ill patients with AMI, and it may assist clinicians and nurses identifying high‐risk patients. [ABSTRACT FROM AUTHOR]

IntroductionAtherosclerosis is the major cause of cardiovascular disease (CVD), and macrophages play a central role in progression of atherosclerosis (1, 2). In the early stage of atherosclerosis, macrophages take up [...], Acetaldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme detoxifying acetaldehyde and endogenous lipid aldehydes; previous studies suggest a protective role of ALDH2 against cardiovascular disease (CVD). Around 40% of East Asians carrying the single nucleotide polymorphism (SNP) ALDH2 rs671 have an increased incidence of CVD. However, the role of ALDH2 in CVD beyond alcohol consumption remains poorly defined. Here we report that ALDH2/LDLR double knockout (DKO) mice have decreased atherosclerosis compared with LDLR-KO mice, whereas ALDH2/APOE-DKO mice have increased atherosclerosis, suggesting an unexpected interaction of ALDH2 with LDLR. Further studies demonstrate that in the absence of LDLR, AMPK phosphorylates ALDH2 at threonine 356 and enables its nuclear translocation. Nuclear ALDH2 interacts with HDAC3 and represses transcription of a lysosomal proton pump protein ATP6V0E2, critical for maintaining lysosomal function, autophagy, and degradation of oxidized low-density lipid protein. Interestingly, an interaction of cytosolic LDLR C-terminus with AMPK blocks ALDH2 phosphorylation and subsequent nuclear translocation, whereas ALDH2 rs671 mutant in human macrophages attenuates this interaction, which releases ALDH2 to the nucleus to suppress ATP6V0E2 expression, resulting in increased foam cells due to impaired lysosomal function. Our studies reveal a novel role of ALDH2 and LDLR in atherosclerosis and provide a molecular mechanism by which ALDH2 rs671 SNP increases CVD.