New insights of DsbA-L in the pathogenesis of metabolic diseases.

Metabolic diseases, such as obesity, diabetes mellitus, and non-alcoholic fatty liver disease (NAFLD), are abnormal conditions that result from disturbances of metabolism. With the improvement of living conditions, the morbidity and mortality rates of metabolic diseases are steadily rising, posing a significant threat to human health worldwide. Therefore, identifying novel effective targets for metabolic diseases is crucial. Accumulating evidence has indicated that disulfide bond A oxidoreductase-like protein (DsbA-L) delays the development of metabolic diseases. However, the underlying mechanisms of DsbA-L in metabolic diseases remain unclear. In this review, we will discuss the roles of DsbA-L in the pathogenesis of metabolic diseases, including obesity, diabetes mellitus, and NAFLD, and highlight the potential mechanisms. These findings suggest that DsbA-L might provide a novel therapeutic strategy for metabolic diseases.

Association of mean RDW values and changes in RDW with in-hospital mortality in ventilator-associated pneumonia (VAP): Evidence from MIMIC-IV database.

INTRODUCTION: Ventilator-associated pneumonia (VAP) is a hospital-acquired infection with high mortality, and remains a challenge for clinical treatment. Red blood cell distribution width (RDW) was associated with worse outcomes in several diseases. The purpose of this study was to investigate the relationship between mean RDW values, changes in RDW (delta RDW), and in-hospital mortality among patients with VAP. METHODS: In the present study, we enrolled 1266 VAP patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. All patients were categorized into low group, medium group, and high group according to tertiles of mean RDW values. The primary outcome was all-cause in-hospital mortality. Univariate logistic regression analysis, multivariate logistic regression analysis, and restricted cubic spline (RCS) curve were performed to determine the association between mean RDW values and in-hospital mortality in VAP. Moreover, RCS curve was plotted to explore the dose-response relationship between delta RDW and in-hospital mortality in VAP. RESULTS: Among the VAP patients included in the study, the in-hospital mortality was 20.85% with 264 non-survivors and 1002 survivors. The non-survivors exhibited significantly higher mean RDW values and delta RDW values compared to survivors. Multivariate logistic regression analysis indicated that mean RDW values were positively associated with in-hospital mortality in VAP after adjusting for relevant covariates. The RCS curve demonstrated a dose-response relationship between mean RDW and the mortality in VAP. Moreover, a linear relationship was observed between delta RDW and in-hospital mortality in VAP. CONCLUSION: Higher mean RDW values were significantly associated with an increased risk of in-hospital mortality in VAP. Additionally, a linear relationship was found between delta RDW values and in-hospital mortality. These findings suggest that RDW can be used to identify high-risk patients with poorer outcomes in VAP.

Association between manganese exposure in heavy metals mixtures and the prevalence of sarcopenia in US adults from NHANES 2011-2018.

Environmental pollution is identified as an essential risk factor for sarcopenia. However, the effect of manganese (Mn) exposure on the prevalence of sarcopenia is not assessed. Our study investigated the correlation between blood Mn concentration and sarcopenia risk in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. Three statistical methods were used to assess these correlations. Mediation analysis was performed to explore the role of inflammation in Mn exposure-induced sarcopenia. Of the 4957 individuals enrolled in this study, 398 (8 %) were diagnosed with sarcopenia. We found a positive association between the log10 Mn concentration and the prevalence of sarcopenia in the logistic regression model. Moreover, heavy metals mixtures were positively correlated with the prevalence of sarcopenia, with Mn identified as the main contributor to this association in the weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models. Furthermore, inflammation mediated the relationship between Mn exposure and the prevalence of sarcopenia, explaining 7.29 % of the effect (odds ratio: 0.03, 0.19, P = 0.002). Thus, our study results revealed that excessive Mn exposure is a contributing factor for sarcopenia. More prospective studies are required to examine the association between Mn exposure and the prevalence of sarcopenia.

Association of serum phosphate and changes in serum phosphate with 28-day mortality in septic shock from MIMIC-IV database.

This study aimed to investigate the relationship between serum phosphate levels, changes in serum phosphate levels, and 28-day mortality in patients with septic shock. In this retrospective study, data were collected from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database between 2008 and 2019. Patients were divided into three groups according to the tertiles of serum phosphate levels. Kaplan-Meier curves and log-rank test analyses were used for survival analysis. Multivariate logistic regression, and restricted cubic spline (RCS) curve were used to explore the association between serum phosphate, delta serum phosphate levels and 28-day mortality. In total, 3296 patients with septic shock were included in the study, and the 28-day mortality was 30.0%. Serum phosphate levels were significantly higher in the non-survivor group than in the survivor group. The Kaplan-Meier curves showed significant differences among the three groups. Multivariate logistic regression analysis and the RCS curve showed that serum phosphate levels were independently and positively associated with the 28-day mortality of septic shock. Non-survivors had higher delta serum phosphate levels than survivors. Survival analysis showed that patients with higher delta serum phosphate levels had higher 28-day mortality. A non-linear relationship was detected between delta serum phosphate and 28-day mortality with a point of inflection at - 0.3 mg/dL. Serum phosphate levels were positively and independently associated with 28-day mortality in septic shock. Delta serum phosphate level was a high-risk factor for patients with septic shock.

Association between ethylene oxide exposure and prevalence of COPD: Evidence from NHANES 2013-2016.

BACKGROUND: Environmental exposures are major risk factors for chronic obstructive pulmonary disease (COPD). Ethylene oxide (EO) is a ubiquitous organic compound and adversely affects human health. However, it remains unknown whether EO exposure increases the risk of COPD. This study aimed to explore the association between EO exposure and the prevalence of COPD. METHODS: In this cross-sectional study, 2243 participants were analyzed from the National Health and Nutrition Examination Survey (NHANES) between 2013 and 2016. Participants were classified into four groups according to quartiles of log10-transformed hemoglobin adducts of EO (HbEO) levels. HbEO levels were measured using the modified Edman reaction and high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). Logistic regression, restricted cubic spline regression model, and subgroup analysis were used to assess whether EO exposure was associated with the risk of COPD. A multivariate linear regression model was used to investigate the correlation between HbEO levels and inflammatory factors. A mediating analysis was conducted to estimate whether inflammatory factors were involved in the effects of HbEO on the prevalence of COPD. RESULTS: Participants with COPD had higher HbEO levels than those without COPD. Log10-transformed HbEO levels were associated with an increased risk of COPD after adjusting for all covariates. [Q4 vs. Q1 in model II: OR = 2.15, 95 % CI: 1.20-3.85, P = 0.010, P for trend = 0.009]. Moreover, a nonlinear J-shaped relationship was observed between HbEO levels and the risk of COPD. Furthermore, HbEO levels were positively correlated with inflammatory cells. In addition, white blood cells and neutrophils mediated the relationship between HbEO and the prevalence of COPD with mediated proportions of 10.37 % and 7.55 %, respectively. CONCLUSION: These findings indicate that EO exposure has a J-shaped association with the risk of COPD. Inflammation is a key mediator involved in the effects of EO exposure on COPD.