Background: Glycolysis is a pivotal process in metabolic reprogramming of tumorigenesis. Previous research has indicated that lncRNAs might play crucial roles in glycolysis of various tumors. However, the function of lncRNAs in glycolysis of pancreatic cancer has not been fully elucidated. Methods: Bio-information analyses were applied to reveal the potential glycolysis-associated lncRNA. RT-PCR and fluorescence in situ hybridization (FISH) assays were applied to detect the expression of antisense RNA1 of DICER1 (DICER1-AS1) in pancreatic cancer tissues and cell lines. Gain- and loss-of-function experiments were performed to evaluate the roles of DICER1-AS1 in glycolysis and tumorigenesis of PC. Mechanistic experiments including luciferase reporter assay, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (ChIP) were employed to uncover the downstream targets and regulatory mechanism of DICER1-AS1 in glycolysis of PC. Results: Bio-information analysis indicated that DICER1-AS1 was downregulated in PC and negatively correlated with glycolytic genes expression. Meanwhile, overexpression of DICER1-AS1 inhibited glycolysis, proliferation, and metastasis of PC cells both in vitro and in vivo. Mechanistically, DICER1-AS1 promoted transcription of its sense gene DICER1 by recruiting transcriptional factor YY1 to the DICER1 promoter. Meanwhile, DICER1 promoted maturation of miR-5586-5p which consequently inhibited glycolytic gene expression including LDHA, HK2, PGK1, and SLC2A1. Notably, enhanced interaction between N6-methyladenosine (m6A) reader YTHDF3 and DICER1-AS1 led to degradation of DICER1-AS1 in response to glucose depletion. Moreover, our data revealed that YTHDF3 was a critical target for miR-5586-5p, by which forming a negative feedback with DICER1-AS1 to regulate glycolysis of PC. Conclusion: Our results implicate a negative feedback of m6A reader YTHDF3 and glycolytic lncRNA DICER1-AS1 is involved in glycolysis and tumorigenesis of PC.

Background: Serum creatinine (Cr) and albumin (Alb) are important predictors of mortality in individuals with various diseases, including acute pancreatitis (AP). However, most previous studies have only examined the relationship between single Cr or Alb levels and the prognosis of patients with AP. To our knowledge, the association between short- and long-term all-cause mortality in patients with AP and the blood creatinine to albumin ratio (CAR) has not been investigated. Therefore, this study aimed to evaluate the short- and long-term relationships between CAR and all-cause mortality in patients with AP.Methods: We conducted a retrospective study utilizing data from the Medical Information Market for Intensive Care (MIMIC-IV) database. The study involved analyzing various mortality variables and obtaining CAR values at the time of admission. The X-tile software was used to determine the optimal threshold for the CAR. Kaplan-Meier (K-M) survival curves and multivariate Cox proportional hazards regression models were used to assess the relationship between CAR and both short- and long-term all-cause mortality. The predictive power, sensitivity, specificity, and area under the curve (AUC) of CAR for short- and long-term mortality in patients with AP after hospital admission were investigated using Receiver Operating Characteristic analysis. Additionally, subgroup analyses were conducted.Results: A total of 520 participants were included in this study. The CAR ideal threshold, determined by X-tile software, was 0.446. The Cox proportional hazards model revealed an independent association between CAR≥0.446 and all-cause mortality at 7-day (d), 14-d, 21-d, 28-d, 90-d, and 1-year (y) before and after adjustment for confounders. K-M survival curves showed that patients with CAR≥0.446 had lower survival rates at 7-d, 14-d, 21-d, 28-d, 90-d, and 1-y. Additionally, CAR demonstrated superior performance, with higher AUC values than Cr, Alb, serum total calcium, Glasgow Coma Scale, Systemic Inflammatory Response Syndrome score, and Sepsis-related Organ Failure Assessment score at 7-d, 14-d, 21-d, 28-d, 90-d, and 1-y intervals. Subgroup analyses showed that CAR did not interact with a majority of subgroups.Conclusion: The CAR can serve as an independent predictor for short- and long-term all-cause mortality in patients with AP. This study enhances our understanding of the association between serum-based biomarkers and the prognosis of patients with AP.

Background: The endothelial activation and stress index (EASIX) serves as a dependable and efficient surrogate marker for endothelial dysfunction, which plays an essential role in the pathophysiology of acute pancreatitis (AP). Hence, we investigated the prognostic value of EASIX in AP.Methods: This was a retrospective study, using patient information obtained from the Medical Information Market for Intensive Care-IV (MIMIC-IV) database. EASIX was calculated using lactate dehydrogenase, serum creatinine, and platelet counts obtained during the first measurement within 24 h of admission. Patients were grouped into three cohorts based on log2-transformed EASIX. The main endpoint of the study was 28-day all-cause mortality (ACM) in AP patients, with the secondary endpoint being 90-day ACM. The relationship between EASIX and prognosis in patients with AP was evaluated using Cox proportional hazards models, Kaplan–Meier curves, restricted cubic spline (RCS) curves, and subgroup analyses. Receiver operating characteristic (ROC) curves were constructed to evaluate the predictive performance of EASIX compared to other indicators.Results: The study cohort comprised 620 patients in total. Multivariate Cox proportional hazards analysis indicated that an increased log2 (EASIX) was linked to a higher risk of 28-day ACM in AP patients (HR, 1.32; 95% CI: 1.14–1.52; p < 0.001). The risk of 28-day ACM was higher in Tertiles 2 and 3 compared with Tertile 1 [(HR, 2.80; 95% CI: 1.21–6.45); (HR, 3.50; 95% CI: 1.42–8.66)]. Comparable findings were noted for 90-day ACM. Kaplan–Meier curves demonstrated that patients with elevated log2 (EASIX) had lower 28- and 90-day survival rates. The RCS curves suggested a non-linear relationship between log2 (EASIX) and 28- and 90-day ACM. ROC curves indicated that log2 (EASIX) was not inferior to sequential organ failure assessment and systemic inflammatory response syndrome scores in predicting the prognosis of patients with AP. Subgroup analyses demonstrated no interaction between log2 (EASIX) and any subgroup.Conclusion: Elevated EASIX levels were significantly correlated with a heightened risk of 28- and 90-day ACM in AP patients.

Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) is characterized by a violent cytokine storm-driven inflammation and is associated with a predisposition to severe disease. The treatment strategy for HTG-AP consists mainly of conventional symptomatic and lipid-lowering treatments. For early-stage HTG-AP, blood purification (BP) can rapidly and effectively reduce serum triglyceride and inflammatory cytokine levels, block the development of systemic inflammatory response syndrome, and improve patient outcomes. Currently, the primary modalities for BP in patients with HTG-AP include plasma exchange, hemoperfusion, and hemofiltration. When using BP to treat patients with HTG-AP, a comprehensive analysis incorporating the elevated lipid levels and severity of the patient’s condition contributes to the selection of different treatment modes. Moreover, the timing of the treatment is also imperative. Early intervention is associated with a better prognosis for patients with HTG-AP requiring lipid-lowering treatment.

The endothelial activation and stress index (EASIX) can predict endothelial intricacies as well as survival in distinct clinical circumstances. Accordingly, we hypothesize that EASIX may also serve as a predictor for stroke prevalence and mortality outcomes-all-cause mortality (ACM) and cardiovascular mortality (CVM) due to stroke. To validate our hypothesis, we deployed the National Health and Nutrition Examination Survey data. This cohort study employed 1999–2018 NHANES data. To evaluate EASIX effects on stroke risk, weighted logistic regression models were deployed. Meanwhile, we utilized the weighted Cox proportional hazards model for the calculation of hazard ratios (HRs) and 95% confidence intervals (CI) for mortality outcomes. The Kaplan-Meier curves were utilized, seeking the assessment of the interplay between the EASIX and both ACM and CVM among stroke patients. Using restricted cubic spline (RCS) curves, the potential non-linear or linear relations were investigated between the EASIX and both stroke prevalence and mortality outcomes. Subgroup analyses were performed to further assess the interconnection that existed between the EASIX and both stroke presence and its mortality outcomes. Interaction tests between covariates were also performed. Assessment of diagnostic value was done via receiver operating characteristic (ROC) curves. The area under the curve (AUC) was measured to estimate the EASIX predictive values for stroke prevalence and mortality outcomes. Of 43,853 participants, 1674 had a stroke; among them, there were (743/1671, 44.46%) ACM and 225 (13.46%) CVM. After full adjustment, EASIX was positively related to the likelihood of having a stroke (odds ratio [OR] = 1.16, 95% CI: 1.07–1.25). Unlike participants whose EASIX was in the lowest quartile (Q1), those in other quartiles (Q3/Q4) had an increased likelihood of having a stroke (OR = 1.34, 95% CI: 1.04–1.74; OR = 1.54, 95% CI 1.20–1.96, correspondingly). During a median follow-up of 71 months, Cox regression analysis manifested a positive interplay between EASIX and ACM (HR = 1.30, 95% CI: 1.17–1.44) and CVM (HR = 1.29, 95% CI: 1.06–1.58). The results showcased a non-linear interplay between EASIX and stroke presence and mortality outcomes. Additionally, subgroup analysis indicated no significant interactions between EASIX and any categorical covariates for CVM. Nervelessness, significant interaction effects existed between EASIX and the prevalence of stroke in categorical covariates such as hypertension, diabetes, and coronary heart disease (CHD; P < 0.001), as well as between EASIX and ACM in the categorical covariate of gender (P = 0.03). The ROC curves illustrated that the cutoff value of EASIX for stroke incidence and CVM was 0.56, and 0.58 for ACM, with an AUC of 0.663 (95% CI: 0.649–0.677) for stroke prevalence, as well as for ACM with an AUC of 0.620 (95% CI: 0.595–0.649) and for CVM with an AUC of 0.587 (95% CI: 0.549–0.626). The EASIX demonstrated a positive non-linear association with the prevalence and mortality outcomes amongst individuals at the age of 20 years and older who experienced a stroke, as identified in the NHANES dataset. Heightened EASIX scores were significantly related to an escalated risk of both stroke prevalence and mortality outcomes. Collectively, EASIX may be a valuable biomarker for assessing mortality risks in stroke patients and stroke prevalence. Looking forward, implementing EASIX in primary care settings could facilitate the early screening of endothelial function, thereby identifying high-risk patients and guiding appropriate referrals for specialized medical care. This approach can promote patient outcomes and reduce mortality rates among those who have suffered a stroke. Nevertheless, further validation in diverse countries and among various ethnic groups is necessary.

Patients with liver cirrhosis face high infection risks due to immune dysfunction and hospital-related factors, increasing mortality rates when sepsis occurs. While various biomarkers predict outcomes in cirrhosis, few are accessible and reliable. This study addresses the gap by evaluating the prognostic potential of the lactate-to-albumin ratio (LAR). We retrospectively analyzed data from patients with cirrhosis and sepsis who were admitted to the intensive care unit at Beth Israel Deaconess Medical Center between 2008 and 2022. LAR was calculated from the ratio obtained from the first measurement taken within 24 h of admission. The optimal LAR threshold was determined using R statistical software. Kaplan-Meier analysis was used to compare mortality risks between two patient groups, while multivariate Cox proportional hazards regression models were used to assess the association between LAR and mortality risk in patients with cirrhosis and concomitant sepsis. A restricted cubic spline (RCS) was used to explore potential dose-response relationships between LAR and mortality. Receiver operating characteristic (ROC) analyses were used to assess the predictive ability, sensitivity, and specificity of LAR for all-cause mortality in patients with cirrhosis and combined sepsis, and the area under the curve (AUC) was calculated. Finally, subgroup analyses were performed to assess the relationship between LAR and prognosis across different populations. A total of 1731 patients were included in the study. The optimal LAR threshold was identified as 1.0 using R statistical software. Kaplan-Meier analysis indicated that patients with higher LAR levels had a higher risk of 14-day, 28-day, and 90-day all-cause mortality (all log-rank P < 0.001). Multivariate Cox proportional hazards models indicated independent associations between higher LAR levels and all-cause mortality at 14-day, 28-day, and 90-day before and after adjusting for confounders. RCS analysis revealed a nonlinear association between LAR and short- and long-term all-cause mortality in patients with cirrhosis and sepsis. ROC curve analysis showed that although the predictive value of LAR for the prognosis of patients with cirrhosis combined with sepsis was slightly inferior to that of the Model for End-Stage Liver Disease score, it was significantly better than that of lactate, albumin, and the Sequential Organ Failure Assessment. Subgroup analyses showed no significant interactions between LAR and any specific subgroup. LAR has good predictive value for the prognosis of patients with cirrhosis and sepsis.