Construction and evaluation of a mortality prediction model for patients with acute kidney injury undergoing continuous renal replacement therapy based on machine learning algorithms.

BACKGROUND: To construct and evaluate a predictive model for in-hospital mortality among critically ill patients with acute kidney injury (AKI) undergoing continuous renal replacement therapy (CRRT), based on nine machine learning (ML) algorithm. METHODS: The study retrospectively included patients with AKI who underwent CRRT during their initial hospitalization in the United States using the medical information mart for intensive care (MIMIC) database IV (version 2.0), as well as in the intensive care unit (ICU) of Huzhou Central Hospital. Patients from the MIMIC database were used as the training cohort to construct the models (from 2008 to 2019, n = 1068). Patients from Huzhou Central Hospital were utilized as the external validation cohort to evaluate the models (from June 2019 to December 2022, n = 327). In the training cohort, least absolute shrinkage and selection operator (LASSO) regression with cross-validation was employed to select features for constructing the model and subsequently established nine ML predictive models. The performance of these nine models on the external validation cohort dataset was comprehensively evaluated based on the area under the receiver operating characteristic curve (AUROC) and the optimal model was selected. A static nomogram and a web-based dynamic nomogram were presented, with a comprehensive evaluation from the perspectives of discrimination (AUROC), calibration (calibration curve) and clinical practicability (DCA curves). RESULTS: Finally, 1395 eligible patients were enrolled, including 1068 patients in the training cohort and 327 patients in the external validation cohort. In the training cohort, LASSO regression with cross-validation was employed to select features and nine models were individually constructed. Compared to the other eight models, the Lasso regularized logistic regression (Lasso-LR) model exhibited the highest AUROC (0.756) and the optimal calibration curve. The DCA curve suggested a certain clinical utility in predicting in-hospital mortality among critically ill patients with AKI undergoing CRRT. Consequently, the Lasso-LR model was the optimal model and it was visualized as a common nomogram (static nomogram) and a web-based dynamic nomogram (https://chsyh2006.shinyapps.io/dynnomapp/). Discrimination, calibration and DCA curves were employed to assess the performance of the nomogram. The AUROC for the training and external validation cohorts in the nomogram model was 0.771 (95%CI: 0.743, 0.799) and 0.756 (95%CI: 0.702, 0.809), respectively. The calibration slope and Brier score for the training cohort were 1.000 and 0.195, while for the external validation cohort, they were 0.849 and 0.197, respectively. The DCA indicated that the model had a certain clinical application value. CONCLUSIONS: Our study selected the optimal model and visualized it as a static and dynamic nomogram integrating clinical predictors, so that clinicians can personalized predict the in-hospital outcome of critically ill patients with AKI undergoing CRRT upon ICU admission.

Relationship between nausea and vomiting and physical activity in patients with lung cancer undergoing first chemotherapy.

Objective: Nausea and vomiting are the distressing and debilitating side effects of chemotherapy. This study explores the relationship between the degree of nausea and vomiting and physical activity in patients with lung cancer during the first chemotherapy cycle. Design: A total of 107 patients with lung cancer who received platinum drugs during chemotherapy in a hospital in Shanghai, China, in 2023 were involved in this study. Data were collected with medical record system and self-reported questionnaires.Questionnaires included the International Physical Activity Questionnaire (IPAQ) and Index of Nausea, Vomiting, and Retching (INVR). IPAQ was used before chemotherapy; INVR was used on the second and sixth day of chemotherapy, followed by the analysis of the correlation between physical activity status and degree of nausea and vomiting during chemotherapy. The influencing factors of nausea and vomiting during chemotherapy in patients with lung cancer were analyzed using logistic regression analysis. Results: More than half of the patients experienced nausea, vomiting or retching related symptoms after chemotherapy, and the proportion of moderate to high physical activity was 50.5%. Univariate analysis showed that the degree of nausea and vomiting was influenced by factors such as age, gender, and history of drinking (P < 0.05). The degree of nausea and vomiting was negatively correlated with physical activity (P < 0.05). The multivariate linear analysis showed that gender, history of drinking, and moderate and high physical activity are contributing factors to nausea and vomiting during chemotherapy (P < 0.05). Conclusion: Moderate and high physical activity before chemotherapy is a protective factor for nausea and vomiting in patients with lung cancer. Physical activity can not only improve the degree of nausea and vomiting in patients with lung cancer but also reduce the incidence in these patients during the first chemotherapy cycle.

LncRNA BC200 promotes the development of EBV-associated nasopharyngeal carcinoma by competitively binding to miR-6834-5p to upregulate TYMS expression.

Nasopharyngeal carcinoma (NPC) is closely related to Epstein-Barr virus (EBV) infection. Long noncoding RNAs (lncRNAs) play important roles in cancers. However, the molecular mechanism underlying the roles of lncRNAs in EBV-associated NPC remains largely unclear. In this study, we confirmed that the expression of the lncRNA brain cytoplasmic 200 (BC200) was significantly increased in EBV-infected NPC cells and tissues. BC200 facilitated the growth and migration of NPC cells, suggesting that it participated in NPC progression by functioning as an oncogene. Mechanistically, BC200 was found to act as a ceRNA by sponging and inhibiting miR-6834-5p. Thymidylate synthetase (TYMS), whose high expression was reported to be an independent indicator of poor prognosis in NPC via an unknown mechanism, was identified as a target gene of miR-6834-5p in the present study. BC200 upregulated TYMS expression in a manner that depends on miR-6834-5p. TYMS was abnormally upregulated in EBV-positive NPC cells and tissues, and its ectopic expression contributed to the proliferation and migration of NPC cells. This study highlights the role of lncRNA BC200, which is upregulated by EBV, in promoting the development of NPC, suggesting that BC200-mediated ceRNA network may be valuable biomarkers for the diagnosis and treatment of EBV-associated NPC.

Association between lactate/albumin ratio and prognosis in critically ill patients with acute kidney injury undergoing continuous renal replacement therapy.

BACKGROUND: 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). METHODS: 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. RESULTS: 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). CONCLUSION: 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.

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.

Correlation between Lactate Dehydrogenase to Albumin Ratio and the Prognosis of Patients with Cardiac Arrest.

Background: Cardiac arrest (CA) is a common event in the intensive care unit (ICU), which seriously threatens the prognosis of patients. Therefore, it is crucial to determine a simple and effective clinical indicator to judge the prognosis of patients after a CA for later treatments. The purpose of this study was to investigate the relationship between the lactate dehydrogenase to albumin ratio (LAR) and the prognosis of patients after a CA. Methods: The clinical data of participants was obtained from the Medical Information Mart for Intensive Care IV (MIMIC-IV, v2.0; 2008 to 2019). According to the 30-day prognosis, patients were divided into a survivors group (n = 216) and a non-survivors group (n = 304). The optimal LAR threshold was determined using restricted cubic spline (RCS), which divided patients into a high LAR group ( ≥ 15.50, n = 257) and a low LAR group ( < 15.50, n = 263). The ICU hospitalization and 30-day accumulative survival curves of the two groups were plotted following the Kaplan-Meier survival analysis. Multivariate Cox regression was used to analyze the relationship between the LAR and the prognosis of CA patients. Receiver operating characteristic (ROC) curves were drawn to evaluate the predictive efficacy of the LAR on 30-day all-cause mortality, and sensitivity analysis was used to check the reliability of the findings. Results: A total of 520 patients with CA were enrolled and the 30-day mortality was 58.46%. The LAR in the non-survivors group was higher than in the survivors group. The RCS showed a linear trend relationship between the LAR and the mortality risk in patients during their ICU stay and 30 days; moreover, as the LAR increased, so did the risk of mortality. The Kaplan-Meier survival curve showed that compared with the low LAR group, the cumulative survival rates of ICU hospitalization and 30 days were lower in the high LAR group among CA patients (p < 0.001). Multivariate Cox regression analysis showed that an elevated LAR ( ≥ 15.50) was an independent risk factor for mortality during ICU stay and 30 days (p < 0.005). ROC analysis suggested that the LAR was superior to the sequential organ failure assessment (SOFA) score in predicting the 30-day all-cause mortality in CA patients (area under the curve (AUC) = 0.676, 95% confidence interval [CI]: 0.629-0.723). To verify the reliability of our findings, we performed sensitivity analyses and found that the findings were reliable. Conclusions: An elevated LAR might be a predictor of mortality in patients following a CA during ICU hospitalization and 30 days, thereby it can be used to provide a reference for the clinical management of these patients.

Unveiling the overlooked threat: antibiotic resistance in groundwater near an abandoned sulfuric acid plant in Xingyang, China.

Groundwater near a sulfuric acid plant in Xingyang, Henan, China was sampled from seven distinct sites to explore the prevalence of antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs). Results showed that genes aadA, blaCTX-M, tetA, qnrA, and sul1 were detected with 100% frequency followed by aac(6')-Ib (85.71%), ermB (85.71%), and tetX (71.42%). Most abundant ARGs were sul1 in LSA2 (1.15 × 1011 copies/mL), tetA in LSA6 (4.95 × 1010 copies/mL), aadA in LSA2 (4.56 × 109 copies/mL), blaCTX-M in LSA4 (1.19 × 109 copies/mL), and ermB in LSA5 (1.07 × 109 copies/mL). Moreover, in LSA2, intl1 as a marker of class 1 integron emerged as the most abundant gene as part of MGE (2.25 × 1011 copies/mL), trailed by ISCR1 (1.57 × 109 copies/mL). Environmental factors explained 81.34% of ARG variations, with a strong positive correlation between the intl2 and blaCTX-M genes, as well as the ISCR1 gene and qnrA, tetA, intl2, and blaCTX-M. Furthermore, the intI1 gene had a strong positive connection with the aadA, tetA, and sul1 genes. Moreover, the aac(6')-Ib gene was associated with As, Pb, Mg, Ca, and HCO3-. The intl2 gene was also shown to be strongly associated with Cd. Notably, network analysis highlighted blaCTX-M as the most frequently appearing gene across networks of at least five genera. Particularly, Lactobacillus, Plesiomonas, and Ligilactobacillus demonstrated correlations with aadA, qnrA, blaCTX-M, intI2, and ISCR1. Based on 16S rRNA sequencing, the dominant phyla were Proteobacteria, Firmicutes, Bacteroidota, Acidobacteriota, and Actinobacteriota, with dominant genera including Pseudomonas, Ligilactobacillus, Azoarcus, Vogesella, Streptococcus, Plesiomonas, and Ferritrophicum. These findings enhance our understanding of ARG distribution in groundwater, signaling substantial contamination by ARGs and potential risks to public health.

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.

The association between albumin-corrected calcium and prognosis in patients with cardiac arrest: a retrospective study based on the MIMIC-IV database.

BACKGROUND: Cardiac arrest (CA) is one of the leading causes of death globally, characterized by high incidence and mortality. It is of particular significance to determine the prognosis of patients with CA early and accurately. Therefore, we aim to investigate the correlation between albumin-corrected calcium (ACC) and the prognosis in patients diagnosed with CA. METHODS: We retrospectively collected data from medical information mart for intensive care IV database. Patients were divided into two groups (survival and non-survival groups), according to the 90-day prognosis. In the Restricted cubic spline (RCS) analysis, the cut-off values (8.86 and 10.32) were obtained to categorize patients into three groups: low ACC group (< 8.86), moderate ACC group (8.86-10.32), and high ACC group (> 10.32). The least absolute shrinkage and selection operator with a ten-fold cross-validation regression analysis was performed to identify variables linked to the mortality. The inverse probability treatment weighting (IPTW) was used to address the confounding factors, and a weighted cohort was generated. RCS, Kaplan-Meier curve, and Cox regression analyses were used to explore the relationship between ACC and the mortality. Sensitivity analysis was employed to validate the stability of the results. RESULTS: Cut-off values for ACC of 8.86 and 10.32 were determined. RCS analyses showed that there was an overall non-linear trend relationship between ACC and the risk of 90-day and 360-day mortalities. After IPTW adjustment, compared to the moderate ACC group, the 90-day and 360-day mortalities in the high ACC group were higher (P < 0.05). The Cox analyses before and after IPTW adjustment showed that both low ACC and high ACC group were independent risk factors for 90-day and 360-day all-cause mortality in patients with CA (P < 0.05). The results obtained from sensitivity analyses indicated the stability of the findings. The Kaplan-Meier survival curves indicated that 90- and 360-day cumulative survival rates in the low ACC and high ACC groups were lower than that in the moderate ACC group (χ2 = 11.350, P = 0.003; χ2 = 14.110, P = 0.001). CONCLUSION: Both low ACC (< 8.86) and high ACC groups (> 10.32) were independent risk factors for 90-day and 360-day all-cause mortality in patients with CA (P < 0.05). For those CA patients with high and low ACC, it deserved the attention of clinicians.

The Antitumor Effects of α-Linolenic Acid.

α-linolenic acid (ALA), which is a member of the n-3 polyunsaturated fatty acid (n-3 PUFA) family, has often been ignored due to a lack of information. ALA has gradually attracted increased attention due to its nutritional and medicinal advantages. Studies have shown that ALA exerts beneficial effects on a variety of diseases, including cancer. In this review, we summarize the antitumor effects of ALA in the context of cell biology, including the inhibition of proliferation, the induction of apoptosis, the inhibition of metastasis and angiogenesis, and antioxidant effects. In addition, studies have shown that ALA can be used as a drug carrier or exert positive clinical effects when combined with drugs. Therefore, the use of ALA in clinical treatments is very promising and valuable.

The relationship between lactate dehydrogenase to albumin ratio and all-cause mortality during ICU stays in patients with sepsis: A retrospective cohort study with propensity score matching.

Background: Sepsis is a prevalent and severe medical condition which is frequently observed in the intensive care unit (ICU). Although numerous biomarkers have been identified to predict the prognosis of sepsis, the lactate dehydrogenase to albumin ratio (LDH/ALB ratio) has not been extensively investigated. The principal objective of this study is to assess the relationship between LDH/ALB ratio and all-cause mortality in patients with sepsis. Methods: This study included all adult critically ill patients with sepsis from the Medical Information Mart for Intensive Care IV (MIMIC-IV, version 2.0) database. Propensity score matching (PSM) analysis was conducted to mitigate bias, and Kaplan-Meier curves were performed to evaluate the cumulative survival across different groups. The association between the LDH/ALB ratio and mortality was examined through restricted cubic spline (RCS) analysis and Cox regression analysis. The robustness of the findings was confirmed through subgroup analyses. Additionally, the prognostic capability of the LDH/ALB ratio was further evaluated using receiver operating characteristic (ROC) curve analysis. Results: There were 6059 adult patients with sepsis enrolled in the final analysis. RCS revealed a non-linear relationship between the LDH/ALB ratio and an increased risk of ICU all-cause mortality (χ2 = 46.900, P < 0.001). Following PSM analysis, 1553 matched pairs were obtained. As comparison to the low LDH/ALB ratio group, the mortality rate in the high LDH/ALB ratio group was significantly higher (P < 0.001). Kaplan-Meier curves, both before and after PSM, revealed that the ICU cumulative survival rate for patients with sepsis was significantly lower in the high LDH/ALB ratio group compared to the low LDH/ALB ratio group (χ2 = 93.360, P < 0.001; χ2 = 14.400, P < 0.001). Even after adjusting for a range of potential confounders, multivariate Cox regression analysis indicated that an elevated LDH/ALB ratio was a significant predictor of all-cause mortality in these patients. ROC curve analysis demonstrated that the LDH/ALB ratio had an area under the ROC curve (AUC) of 0.688 for predicting ICU mortality, with a sensitivity of 69.2% and a specificity of 58.6%. Conclusions: An elevated LDH/ALB ratio (≥10.57) was associated with all-cause mortality in critically ill patients with sepsis, and it might serve as a prognostic marker. Clinicians should pay closer attention to sepsis patients presenting with an LDH/ALB ratio of 10.57 or higher.

The Global Environmental Impacts of China's Accession to the WTO: A 20-Year Review.

Robust empirical assessments of the long-term cumulative global effects of free trade and economic globalization on the environment are limited. This account fills this gap by constructing a dynamic computable general equilibrium model to estimate the environmental effects of a milestone in the recent history of trade liberalization: China's 20-year World Trade Organization (WTO) accession. The modeling shows that China's accession could have resulted in an increase in the global cumulative greenhouse gases (GHGs), sulfur dioxide (SO2), and nitrogen oxide (NOx) emissions by roughly 14,000 Mt CO2-eq, 64 Mt, and 46 Mt, respectively. The global production scale effect contributed to most of these estimated increases. The regional total output composition effect also caused higher emissions. Meanwhile, the sectoral output composition effect helped reduce total emissions to a limited extent. Fortunately, a package of emission abatement measures led to a decrease in emission factors and a drop in the global cumulative emissions of GHGs, SO2, and NOx. The findings suggest that to enjoy the free trade and economic globalization benefits and minimize the induced emission increases, it is vitally important to systemically reduce emissions across the entire economy and nurture a low-carbon trade regime.

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.

IFIT3 inhibits Epstein-Barr virus reactivation via upregulating innate immunity.

Epstein-Barr virus (EBV), a member of the γ-herpesvirus family, can establish latent infection in B lymphocytes and certain epithelial cells after primary infection. Under certain circumstances, EBV can enter into lytic replication. However, the regulation of EBV latent-lytic infection remains largely unclear. The important immune molecule, interferon-induced protein with tetratricopeptide repeats 3 (IFIT3), was upregulated in EBV latently infected cells. When the lytic replication of EBV was induced, the expression of IFIT3 was further increased. In turn, IFIT3 overexpression dramatically inhibited the lytic replication of EBV, while IFIT3 knockdown facilitated EBV lytic replication. Moreover, upon the lytic induction, the ectopic IFIT3 expression promoted the activation of the interferon (IFN) pathway, including the production of IFN-stimulated genes (ISGs), IFNB1, and the phosphorylation of IFN-regulatory factor 3 (IRF3). In contrast, the depletion of IFIT3 led to decreased ISGs and IFNB1 expression. Mechanically, IFIT3 inhibited EBV lytic replication through IFN signaling. This study revealed that the host innate immune-related factor IFIT3 played an important role in regulating EBV latent-lytic homeostasis. The results implied that EBV has evolved well to utilize host factors to maintain latent infection.

Association between anion gap and all-cause mortality of critically ill surgical patients: a retrospective cohort study.

BACKGROUND: There are few widely accepted and operationally feasible models for predicting the mortality risk of patients in surgical intensive care unit (SICU). Although serum anion gap (AG) is known to be correlated with severe metabolic acidosis, no investigations have been reported about the association between AG level and the outcome during hospitalization in SICU. This study aimed to explore the predictive power of AG for 90-day all-cause mortality in SICU. METHODS: Data of the eligible patients in SICU from 2008 to 2019 was obtained from the Medical Information Mart for Intensive Care IV version 2.0 (MIMIC-IV v2.0) database. Baseline clinical data of the selected patients was compared in different groups stratified by the outcome during their admission via univariate analysis. Restricted cubic spline (RCS) was drawn to confirm the relationship of AG and the short-term mortality. Kaplan-Meier survival curve was plotted in different AG level groups. Univariate and multivariate Cox analyses were performed, and Cox proportional-hazards models were built to investigate an independent role of AG to predict 90-day all-cause mortality risk in SICU. Receiver operating characteristics (ROC) curves analysis was performed to evaluate the predictive value of AG on the 90-day prognosis of patients. RESULTS: A total of 6,395 patients were enrolled in this study and the 90-day all-cause mortality rate was 18.17%. Univariate analysis showed that elevated serum AG was associated with higher mortality (P < 0.001). RCS analysis indicated a positively linear relationship between serum AG and the risk of 90-day all-cause mortality in SICU (χ2 = 4.730, P = 0.193). Kaplan-Meier survival analysis demonstrated that low-AG group (with a cutoff value of 14.10 mmol/L) had a significantly higher cumulative survival rate than the counterpart of high-AG group (χ2 = 96.370, P < 0.001). Cox proportional-hazards models were constructed and confirmed the independent predictive role of AG in 90-day all-cause mortality risk in SICU after adjusting for 23 confounding factors gradually (HR 1.423, 1.246-1.625, P < 0.001). In the further subgroup analyses, a significant interaction was confirmed between AG and sepsis as well as surgery on the risk for the 90-day mortality. The ROC curve showed that the optimal cut-off value of AG for predicting 90-day mortality was 14.89 with sensitivity of 60.7% and specificity of 54.8%. The area under curve (AUC) was 0.602. When combined with SOFA score, the AUC of AG for predicting 90-day prognosis was 0.710, with a sensitivity and specificity of 70% and 62.5% respectively. CONCLUSIONS: Elevated AG (≥ 14.10 mmol/L) is an independent risk factor for predicting severe conditions and poor prognosis of critical ill surgical patients.

Association between serum anion gap and all-cause mortality in patients with acute myocardial infarction: A retrospective study based on MIMIC-IV database.

Background: Although previous studies have reported that many biomarkers can determine the prognosis of patients with acute myocardial infarction (AMI), serum anion gap (AG) has not been well studied. We aimed to investigate the association between serum AG and mortality in patients with AMI. Methods: Adult patients first admitted to the ICU and diagnosed with AMI from 2008 to 2019 in the MIMIC-IV database were included. Patients were divided into the survival and non-survival groups based on 30-day and 90-day outcomes. According to the AG value (15.12 mmol/L) with a hazard ratio of 1 in the restricted cubic spline (RCS) analysis, patients were further divided into high and low AG groups. The Kaplan-Meier survival curve was plotted, and all-cause mortality was compared between the high and low groups using the log-rank test. Multivariate Cox regression analysis and RCS analysis were constructed to assess the relationship between AG and recent all-cause mortality in patients with AMI. Results: 4446 patients were enrolled. The 30-day and 90-day mortality rates in the high AG group (25.53%, 31.75%) were higher than that in the low AG group (9.73%, 14.01%, P < 0.001) independently. The Kaplan-Meier curve showed that the 30-day and 90-day cumulative survival rates were lower in the high AG group than that in the low AG group (P < 0.001). RCS analysis showed that there was a non-linear relationship between AG and the risk of 90-day all-cause mortality in patients with AMI (χ2 = 18.680 P < 0.001). When AG was 15.12 mmol/L, its HR was about 1. Multivariable Cox regression analysis confirmed that increased AG was associated with higher 30-day and 90-day mortality. Conclusion: Elevated serum AG (≥15.12 mmol/L) is an independent predictor for short-term mortality in patients with AMI, and it may provide a basis for clinicians to identify patients with poor prognosis as early as possible.

TIPE2 deficiency prolongs mouse heart allograft survival by facilitating immature DCs-induced Treg generation.

It has been reported that deletion of tumor necrosis factor-α-induced protein-8 like 2 (TNFAIP8L2, TIPE2) facilitates the activation of T-cell receptors. However, the role of TIPE2 in T-cell-mediated acute transplant rejection remains unclear. To illustrate the underlying cellular mechanisms, we transplanted BALB/c hearts into C57BL/6 wild-type (WT) or C57BL/6 mice deficient for TIPE2 (TIPE2-/-) and found that TIPE2-/- recipient mice showed significantly prolonged survival of heart allografts and suppressed maturation of CD11c+ dendritic cells (DCs), which largely abolished the activation and proliferation of alloreactive T cells and their cytotoxic activity. TIPE2-/- DCs increased CD4+CD25+Foxp3+CD127- regulatory T cells (Tregs)generation, likely by inhibiting DCs maturation and CD80 and CD86 expression. Administration of anti-CD25 abolished the allograft survival induced by TIPE2 deficiency. Moreover, TIPE2 deficiency increased IL-10 production in T cells and in recipient serum and allografts. Mechanistic studies revealed that TIPE2-/- restrained the maturation of DCs via inhibition of PI3K/AKT phosphorylation during alloantigen stimulation. Taken together, TIPE2 deficiency in recipient mice inhibited acute rejection by increasing Tregs generated by immature DCs. Thus, TIPE2 could be a therapeutic target for suppressing rejection in organ transplantation.

Evaluation of the knowledge, awareness, and attitudes toward epilepsy among general practitioners in Eastern China.

OBJECTIVE: We aimed to assess the knowledge, awareness, and attitudes toward epilepsy among general practitioners (GPs) from community health service centers (CHCs) in Hangzhou, Eastern China. METHODS: One hundred twenty three GPs working at CHCs participated in this cross-sectional study in 2022. A custom-built electronic questionnaire, which comprised four domains, including 12 items for general condition data, 10 items for awareness (including first aid), a 16-item scale for attitudes, and 6 items for demographic data, was administered to the GPs. Descriptive statistics, the Mann-Whitney U test, the Kruskal-Wallis H test, and Spearman's rank correlation analysis were used to analyze the non-normal distribution of the data set. RESULTS: The GPs' average score on the awareness of epilepsy section was 18.14 ± 3.34 (aggregate score: 34), the first aid knowledge of epilepsy section scored 4.89 ± 1.54 (aggregate score: 7), and the epilepsy attitude section scored 62.28 ± 10.15 (aggregate score: 80). Age (rs = 0.218, P = 0.015), professional title (rs = 0.215, P = 0.017), and length of service (rs = 0.240, P = 0.008) correlated significantly with mean awareness of epilepsy scores. Age (rs = -0.234, P = 0.009) and educational background (rs = 0.199, P = 0.028) correlated significantly with attitudes toward epilepsy. Furthermore, when GPs faced newly diagnosed people with epilepsy (PWE), a referral was usually recommended (89.43%) and some would give Chinese traditional treatment (13.01%). In addition, the difficulties the GPs encountered in managing included PWE rarely appearing in the community (82.93%), the community lacking corresponding medical equipment (82.11%), and GPs lacking epilepsy-related experience (73.17%). CONCLUSION: The awareness and attitudes of GPs toward epilepsy in the CHCs were suboptimal. General practitioners age, professional title, length of service, and educational background influenced awareness and attitudes toward PWE. Effective public intervention programs, epilepsy training based on National Guidelines, and referral routes need to improve in China to enhance the care of PWE.

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.

Epstein-Barr Virus Synergizes with BRD7 to Conquer c-Myc-Mediated Viral Latency Maintenance via Chromatin Remodeling.

Epstein-Barr virus (EBV) switches between latent and lytic phases in hosts, which is important in the development of related diseases. However, the underlying mechanism of controlling the viral biphasic life cycle and how EBV mediates this regulation remain largely unknown. This study identified bromodomain-containing protein 7 (BRD7) as a crucial host protein in EBV latent infection. Based on the chromatin immunoprecipitation (ChIP) sequencing of endogenous BRD7 in Burkitt lymphoma cells, we found that EBV drove BRD7 to regulate cellular and viral genomic loci, including the transcriptional activation of c-Myc, a recently reported regulator of EBV latency. Additionally, EBV-mediated BRD7 signals were enriched around the FUSE (far-upstream sequence element) site in chromosome 8 and the enhancer LOC108348026 in the lgH locus, which might activate the c-Myc alleles. Mechanically, EBV-encoded nuclear antigen 1 (EBNA1) bound to BRD7 and colocalized at promoter regions of the related genes, thus serving as cofactors for the maintenance of viral latency. Moreover, the disruption of BRD7 decreased the c-Myc expression, induced the BZLF1 expression, and reactivated the lytic cycle. Our findings reveal the unique role of BRD7 to synergize with EBV in maintaining the viral latency state via chromatin remodeling. This study paves the way for understanding the new molecular mechanism of EBV-induced chromatin remodeling and latent-lytic switch, providing novel therapeutic candidate targets for EBV persistent infection. IMPORTANCE When establishing persistent infection in most human hosts, EBV is usually latent. How the viral latency is maintained in cells remains largely unknown. c-Myc was recently reported to act as a controller of the lytic switch, while whether and how EBV regulates it remain to be explored. Here, we identified that BRD7 is involved in controlling EBV latency. We found that EBV-mediated BRD7 was enriched in both the normal promoter regions and the translocation alleles of c-Myc, and disruption of BRD7 decreased c-Myc expression to reactivate the lytic cycle. We also demonstrated that EBV-encoded EBNA1 bound to and regulated BRD7. Therefore, we reveal a novel mechanism by which EBV can regulate its infection state by coordinating with host BRD7 to target c-Myc. Our findings will help future therapeutic intervention strategies for EBV infection and pathogenesis.