Long non-coding RNA NRAV in the 12q24.31 risk locus drives gastric cancer development through glucose metabolism reprogramming.

Long non-coding RNAs (lncRNAs) serve as vital candidates to mediate cancer risk. Here, we aimed to identify the risk single-nucleotide polymorphisms (SNPs)-induced lncRNAs and to investigate their roles in gastric cancer (GC) development. Through integrating the differential expression analysis of lncRNAs in GC tissues and expression quantitative trait loci analysis in normal stomach tissues and GC tissues, as well as genetic association analysis based on GC genome-wide association studies and an independent validation study, we identified four lncRNA-related SNPs consistently associated with GC risk, including SNHG7 [odds ratio (OR) = 1.16, 95% confidence interval (CI): 1.09-1.23], NRAV (OR = 1.11, 95% CI: 1.05-1.17), LINC01082 (OR = 1.16, 95% CI: 1.08-1.22) and FENDRR (OR = 1.16, 95% CI: 1.07-1.25). We further found that a functional SNP rs6489786 at 12q24.31 increases binding of MEOX1 or MEOX2 at a distal enhancer and results in up-regulation of NRAV. The functional assays revealed that NRAV accelerates GC cell proliferation while inhibits GC cell apoptosis. Mechanistically, NRAV decreases the expression of key subunit genes through the electron transport chain, thereby driving the glucose metabolism reprogramming from aerobic respiration to glycolysis. These findings suggest that regulating lncRNA expression is a crucial mechanism for risk-associated variants in promoting GC development.

Association between Albumin-Corrected Anion Gap and Mortality in Patients with Cardiogenic Shock.

Background: Cardiogenic shock (CS) is a critical illness with a high mortality rate in clinical practice. Although some biomarkers have been found to be associated with mortality in patients suffering from CS in previous studies. The albumin-corrected anion gap (ACAG) has not been studied in depth. Our study aimed to explore the relationship between ACAG and mortality in patients with CS. Methods: All baseline data was extracted from Medical Information Mart for Intensive Care-IV version: 2.0 (MIMIC-IV). According to the prognosis at 30 days of follow-up, they were divided into survivors and non-survivors groups. The survival curves between the two groups were drawn using the Kaplan-Meier method and the log-rank test. Valid factors were selected using the least absolute shrinkage and selection operator (LASSO) logistic analysis model. Analysis was performed to investigate the relationship between mortality and all enrolled patients using restricted cubic spline (RCS) and Cox proportional hazards models. Receiver operating characteristic (ROC) curves were used to assess the predictive ability of ACAG. Evaluation of final result stability using sensitivity analysis. Results: 839 cases were selected to meet the inclusion criteria and categorized into survivors and non-survivors groups in the final analysis. The ACAG value measured for the first time at the time of admission was selected as the research object. Kaplan-Meier (K-M) survival curves showed that cumulative 30- and 90-day survival decreased progressively with elevated ACAG (p < 0.001), and multifactorial Cox regression analyses showed ACAG to be an independent risk factor for increased 30- and 90-day mortality in patients suffering from CS (p < 0.05). RCS curves revealed that all-cause mortality in this group of patients increased with increasing ACAG ( χ 2 = 5.830, p = 0.120). The ROC curve showed that the best cutoff value for ACAG for predicting 30-day mortality in patients with CS was 22.625, with a sensitivity of 44.0% and a specificity of 74.7%. The relationship between ACAG and CS short-term mortality remained stable in all sensitivity analyses (All p < 0.05). Conclusions: The ACAG is an independent risk factor for 30- and 90-day mortality in CS patients and predicts poor clinical outcomes in CS patients. According to our study, elevated ACAG at admission, especially when ACAG > 20 mmol/L, was an independent predictor of all-cause mortality in CS.

Clinical significance of the lactate-to-albumin ratio on prognosis in critically ill patients with acute kidney injury.

OBJECTIVE: To explore the relationship between lactate-to-albumin ratio (LAR) at ICU admission and prognosis in critically ill patients with acute kidney injury (AKI). METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Risk prediction models for successful discontinuation in acute kidney injury undergoing continuous renal replacement therapy.

Continuous renal replacement therapy (CRRT) is a commonly utilized treatment modality for individuals experiencing severe acute kidney injury (AKI). The objective of this research was to construct and assess prognostic models for the timely discontinuation of CRRT in critically ill AKI patients receiving this intervention. Data were collected retrospectively from the MIMIC-IV database (n = 758) for model development and from the intensive care unit (ICU) of Huzhou Central Hospital (n = 320) for model validation. Nine machine learning models were developed by utilizing LASSO regression to select features. In the training set, all models demonstrated an AUROC exceeding 0.75. In the validation set, the XGBoost model exhibited the highest AUROC of 0.798, leading to its selection as the optimal model for the development of an online calculator for clinical applications. The XGBoost model demonstrates significant predictive capabilities in determining the discontinuation of CRRT.

The correlation between albumin-corrected anion gap and prognosis in patients with acute myocardial infarction.

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.

Construction and evaluation of the functional polygenic risk score for gastric cancer in a prospective cohort of the European population.

BACKGROUND: A polygenic risk score (PRS) derived from 112 single-nucleotide polymorphisms (SNPs) for gastric cancer has been reported in Chinese populations (PRS-112). However, its performance in other populations is unknown. A functional PRS (fPRS) using functional SNPs (fSNPs) may improve the generalizability of the PRS across populations with distinct ethnicities. METHODS: We performed functional annotations on SNPs in strong linkage disequilibrium (LD) with the 112 previously reported SNPs to identify fSNPs that affect protein-coding or transcriptional regulation. Subsequently, we constructed an fPRS based on the fSNPs by using the LDpred2-infinitesimal model and then analyzed the performance of the PRS-112 and fPRS in the risk prediction of gastric cancer in 457,521 European participants of the UK Biobank cohort. Finally, the performance of the fPRS in combination with lifestyle factors were evaluated in predicting the risk of gastric cancer. RESULTS: During 4,582,045 person-years of follow-up with a total of 623 incident gastric cancer cases, we found no significant association between the PRS-112 and gastric cancer risk in the European population (hazard ratio [HR] = 1.00 [95% confidence interval (CI) 0.93-1.09], P = 0.846). We identified 125 fSNPs, including seven deleterious protein-coding SNPs and 118 regulatory non-coding SNPs, and used them to construct the fPRS-125. Our result showed that the fPRS-125 was significantly associated with gastric cancer risk (HR = 1.11 [95% CI, 1.03-1.20], P = 0.009). Compared to participants with a low fPRS-125 (bottom quintile), those with a high fPRS-125 (top quintile) had a higher risk of incident gastric cancer (HR = 1.43 [95% CI, 1.12-1.84], P = 0.005). Moreover, we observed that participants with both an unfavorable lifestyle and a high genetic risk had the highest risk of incident gastric cancer (HR = 4.99 [95% CI, 1.55-16.10], P = 0.007) compared to those with both a favorable lifestyle and a low genetic risk. CONCLUSION: These results indicate that the fPRS-125 derived from fSNPs may act as an indicator to measure the genetic risk of gastric cancer in the European population.

Elevated albumin corrected anion gap is associated with poor in-hospital prognosis in patients with cardiac arrest: A retrospective study based on MIMIC-IV database.

Background: Cardiac arrest(CA) is one of the most leading causes of death. Most of the indicators which used to predict the prognosis of patients with CA are not recognized. Previous studies have suggested that albumin corrected anion gap (ACAG) is associated with recovery of spontaneous circulation in patients with CA, but the predictive value of ACAG for prognosis has not been investigated. This study aims to explore the relationship between ACAG and prognosis during hospitalization in patients with CA. Methods: The baseline data of adult patients with CA hospitalized in the intensive care unit (ICU) from 2008 to 2019 in the American Intensive Care Database (MIMIC-IV, version v2.0) were collected. According to the in-hospital prognosis, patients were divided into survival and non-survival group. Based on the criteria of ACAG level in the previous literature, patients enrolled were divided into normal ACAG (12-20 mmol/L) and high ACAG (>20 mmol/L) group. The basic information of patients during hospitalization were compared and analyzed between the two groups with propensity score matching (PSM). The Kaplan-Meier method was used to compare the cumulative survival rates of normal ACAG and high ACAG groups before and after matching. Restricted cubic spline (RCS) method and multivariate COX proportional hazards regressions were used to analyze whether elevated ACAG was associated with all-cause mortality during hospitalization. Results: A total of 764 patients were included. A matched cohort (n = 310) was obtained after PSM analysis. The mortality rate before and after matching in the high ACAG group was higher than that in the normal ACAG group (χ 2 = 25.798; P < 0.001; χ 2 = 6.258; P = 0.012) The Kaplan-Meier survival analysis before and after matching showed that the cumulative survival rate of the high ACAG group was lower (P < 0.05). RCS analysis showed that ACAG had a non-linear relationship with the risk of in-hospital all-cause mortality (χ 2 = 6.060, P < 0.001). Multivariate COX regression analysis before and after PSM suggested that elevated ACAG was an independent risk factor for all-cause mortality in patients with CA during hospitalization (P < 0.01). Conclusions: Elevated ACAG is associated with increased all-cause mortality in patients with CA during hospitalization, it can be an independent risk factor for poor prognosis in patients with CA and remind clinicians to pay more attention to these patients.

[Clinical study of SS syrup in treating xerostomia].

OBJECTIVE: To compare the clinical efficacy of SS syrup, a Chinese medicine, and pilocarpine in treating patients with xerostomia. METHODS: Thirty-eight patients conformed to the inclusive criteria were randomly divided into two groups, they were treated by SS syrup (SS group) and pilocarpine (control group) respectively. Three indexes, i.e. questionnaire of dryness in mouth, total static salivary flow and dynamic salivary flow, before treatment, 1, 2 and 4 weeks after treatment were recorded and statistically analyzed. RESULTS: Significant difference was shown in the 3 indexes in the SS group between before treatment and 1, 2 and 4 weeks after treatment (P < 0.05), while in the control group significant difference was shown between before treatment and 1, 2, and 4 weeks after treatment except for total dynamic salivary flow after I weck treatment (P < 0.05). CONCLUSION: SS syrup, which has no adverse reaction, no contraindication, could be taken chronically, and shows good efficacy in improving the symptoms of xerostomia.

[The diagnostic value of magnetic resonance sialography for chronic obstructive parotitis].

PURPOSE: To evaluate the diagnostic value of magnetic resonance sialography (MRS) for chronic obstructive parotitis (COP). METHODS: 18 patients with COP underwent both conventional sialography and MRI sialography. A new magnetic resonance technique was applied. In addition to the usually performed T1 and T2 cross-sectional sequence, a heavy T2-weighted sequence (TR=4000 msec,TE=250 msec)was performed that allowed depiction of the fluid-filled parotid duct system. The MRI sialographic findings were compared with that of conventional sialography. The overall accuracy of diagnosis and ductal stenosis were assessed. RESULTS: The main duct of the parotid gland as well as primary branching ducts could be reliably depicted. Compared with the conventional sialography, the diagnostic accuracy of MRS was 94.4%(17/18) and stenosis diagnosis reached 100%(17/17). CONCLUSIONS: Initial experience indicates that magnetic resonance sialography can be applied successfully to investigate the duct system of the parotid gland. It is completely noninvasive and a promising alternative to radiographic sialography.