Background: Blood urea nitrogen to albumin ratio (BAR) has been implicated in predicting outcomes of various inflammatory-related diseases. However, the predictive value of BAR in long-term mortality in patients with acute myocardial infarction (AMI) has not yet been evaluated. Methods: In this retrospective cohort study, the patients were recruited from the Medical Information Mart for Intensive Care III (MIMIC III) database and categorized into two groups by a cutoff value of BAR. Kaplan–Meier (K-M) analysis and Cox proportional hazard model were performed to determine the predictive value of BAR in long-term mortality following AMI. In order to adjust the baseline differences, a 1:1 propensity score matching (PSM) was carried out and the results were further validated. Results: A total of 1827 eligible patients were enrolled. The optimal cutoff value of BAR for four-year mortality was 7.83 mg/g. Patients in the high BAR group tended to have a longer intensive care unit (ICU) stay and a higher rate of one-, two-, three- and four-year mortality (all p< 0.001) compared with those in the low BAR group. K-M curves indicated a significant difference in four-year survival (p< 0.001) between low and high BAR groups. The Cox proportional hazards model showed that higher BAR (> 7.83) was independently associated with increased four-year mortality in the entire cohort, with a hazard ratio (HR) of 1.478 [95% CI (1.254– 1.740), p< 0.001]. After PSM, the baseline characteristics of 312 pairs of patients in the high and low BAR groups were well balanced, and similar results were observed in K-M curve (p=0.003). Conclusion: A higher BAR (> 7.83) was associated with four-year mortality in patients with AMI. As an easily available biomarker, BAR can predict the long-term mortality in AMI patients independently.

Genome-wide association studies have recently illuminated that WDFY4 is genetically associated with systemic lupus erythematosus (SLE) susceptibility in various ethnic groups. Despite strong genetic evidence suggesting a role of WDFY4 in SLE pathogenesis, its functional relevance is largely unknown. In this study, we generated Wdfy4 B lymphocyte conditional knockout (Wdfy4-CKO) mice and found that loss of Wdfy4 led to a decrease in number of total B cells and several subpopulations of B cells in the periphery and a defect in the transition from the pro– to pre–B cell stage in bone marrow. Also, Wdfy4-CKO mice showed impaired Ab responses as compared with controls when challenged with Ag. SLE phenotypes were effectively alleviated in Wdfy4-CKO mice, with significantly diminished pristane-elicited production of autoantibodies and glomerulonephritis. Genetic silencing of WDFY4 in B cells increased lipidation of LC3 independent of p62 and Beclin1, which are essential proteins of canonical autophagy. Our in vivo and in vitro data suggest that WDFY4 facilitates noncanonical autophagic activity. Our findings provide a novel functional link underlying the mechanism of SLE in which WDFY4 influences B cell fate via noncanonical autophagy.

The genetic association of orosomucoid-like 3 (ORMDL3) with an array of immunoinflammatory disorders has been recently unraveled in multiple ethnic groups, and functional exploration has received attention of the particular relevance of this gene in endoplasmic reticulum stress, lipid metabolism, and inflammatory response. In this study, we demonstrated the upregulation of ORMDL3 in both patients with systemic lupus erythematosus and lupus mice compared with controls. By establishing ORMDL3 knockout mice (Ormdl3^−/−), we showed that silencing Ormdl3 in vivo significantly decreased the proportions of mature B lymphocytes and transitional 2B cells in spleen and B1a cells from abdominal cavity perfusion fluid, the secretion of IgG and IgM, and the expression of Baff. Additionally, knockdown of Ormdl3 augmented the apoptosis of total splenic cells and splenic CD19⁺ B cells but did not affect B cell proliferation and cell cycle. Subsequently, we in vitro and in vivo demonstrated that ORMDL3 potentially mediates the autophagy via the ATF 6–Beclin1 autophagy pathway, and it facilitates the survival of splenic B cells via promoting autophagy and suppressing apoptosis. Taken together, we uncovered a role of ORMDL3 in fine-tuning B cell development and survival, besides highlighting a potential mechanism by which ORMDL3 regulates autophagy via ATF6 pathway.

The complications of atherosclerosis such as coronary and cerebrovascular disease, are the most prevalent causes of mortality and morbidity worldwide. A single nucleotide polymorphism (SNP) rs1883832 (-1C/T) in CD40 gene has been recently suggested to contribute to the susceptibility to atherosclerosis in Chinese population; however, previous genetic association studies yielded inconsistent results. A meta-analysis of eligible studies reporting the association between rs1883832 and atherosclerosis in Chinese population was carried out. Pooling 7 eligible case-control studies involving 2129 patients and 1895 controls demonstrated a significant association between rs1883832 and atherosclerosis under dominant model [odds ratio (OR) = 1.631, 95% confidence interval [CI] [1.176, 2.260] in Chinese population with evident heterogeneity. Meta-regression analysis indicated that the heterogeneity could be completely explained by disease category. In subgroup analysis, rs1883832 conferred ORs of 2.866 (C/C versus T/T, 95%CI [2.203, 3.729]) and 1.680 (C/T versus T/T, 95%CI [1.352, 2.086]) for coronary artery disease (CAD) under co-dominant model without heterogeneity. Similar results were obtained for acute coronary syndrome (ACS) (C/C versus T/T, 3.674, 95%CI [2.638, 5.116]; C/T versus T/T, 1.981, 95%CI [1.483, 2.646]). The other genetic models including dominant, recessive and additive models, yielded consistent results without heterogeneity for CAD and ACS, respectively. However, a protective role was found for C allele in ischemic stroke (IS) under recessive model (0.582, 95%CI [0.393, 0.864]) and additive model (0.785, 95%CI [0.679, 0.909]) with reduced heterogeneity. This meta-analysis provided evidence of association of rs1883832 C allele with an overall increased risk of atherosclerosis but distinct effect of C allele on CAD (including ACS) and IS in Chinese population, respectively.

Introduction: ETS1 is a negative regulator of the Th17 differentiation gene and plays a central role in the pathogenesis of autoimmune diseases. We aimed to investigate whether polymorphisms in ETS1 confer susceptibility to ankylosing spondylitis (AS) in Han Chinese. Methods: We selected seven single nucleotide polymorphisms (SNPs) within ETS1 based on HapMap data and previous genome-wide association study. Genotyping involved the TaqMan method in 1,015 patients with AS and 1,132 healthy controls from Shandong Province, and 352 AS patients and 400 healthy controls from Ningxia, a northwest region in China. Gene expression was determined by real-time PCR. Results: The SNP rs1128334 was strongly associated with AS (odds ratio 1.204, 95% confidence interval 1.06-1.37; P = 0.005). This association was confiexrmed in the Ningxia population (P = 0.015). Carriers of the haplotype TAT for rs12574073, rs1128334 and rs4937333 were associated with increased risk of AS and haplotype CGC with reduced risk as compared to controls. In addition, ETS1 expression was lower in AS patients than controls. The risk allele A of rs1128334 and haplotype A-T of rs1128334 and rs4937333 were associated with decreased expression of ETS1. Conclusions: Common variants in ETS1 may contribute to AS susceptibility in Han Chinese people.

Background: This study examined the role of blood urea nitrogen-to-albumin ratio (BAR) in predicting long-term mortality in patients undergoing coronary artery bypass grafting (CABG).Methods: In this retrospective cohort study, patients undergoing CABG were enrolled from the Medical Information Mart for Intensive Care III (MIMIC III) database. Patients were divided into the three groups according to the optimal cutoff values of BAR determined by X-tile software. The survival curve was constructed by the Kaplan–Meier method and multivariate Cox regression analysis was performed to explore the independent prognostic factors of 1- and 4-year mortality after CABG. The receiver operating characteristic (ROC) curves and the areas under the ROC curves (AUCs) were calculated to estimate the accuracy of BAR in predicting the outcomes. Subgroup analyses were also carried out.Results: A total of 1,462 patients at 4-year follow-up were included, of which 933, 293, and 236 patients were categorized into the group 1 (≤ 6.45 mg/g), group 2 (>6.45 and ≤ 10.23 mg/g), and group 3 (>10.23 mg/g), respectively. Non-survivors showed an increased level of BAR at both 1- (p < 0.001) and 4-year (p < 0.001) follow-up compared with the survivors. The patients with a higher BAR had a higher risk of 1- and 4-year mortality following CABG (33.05 vs. 14.33 vs. 5.14%, p < 0.001 and 52.97 vs. 30.72 vs. 13.08%, p < 0.001, respectively). Cox proportional hazards regression model suggested a higher BAR as an independent risk factor of 1-year mortality (HR 3.904; 95% CI 2.559–5.956; P < 0.001) and 4-year mortality (HR 2.895; 95% CI 2.138–3.921; P < 0.001) after adjusting for confounders. Besides, the receiver operating characteristic (ROC) curves showed the better predictive ability of BAR compared to other grading scores at both 1- (0.7383, 95% CI: 0.6966–0.7800) and 4-year mortality (0.7189, 95% CI: 0.6872–0.7506). Subgroup analysis demonstrated no heterogeneous results of BAR in 4-year mortality in particular groups of patient.Conclusion: This report provided evidence of an independent association between 1- and 4-year mortality after CABG and BAR. A higher BAR was associated with a higher risk of long-term mortality and could serve as a prognostic predictor in patients following CABG.