Identification the role of necroptosis in rheumatoid arthritis by WGCNA network.

Rheumatoid arthritis (RA) is the predominant manifestation of inflammatory arthritis, distinguished by an increasing burden of morbidity and mortality. The intricate interplay of genes and signalling pathways involved in synovial inflammation in patients with RA remains inadequately comprehended. This study aimed to ascertain the role of necroptosis in RA, as along with their associations with immune cell infiltration. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were employed to identify central genes for RA. In this study, identified total of 28 differentially expressed genes (DEGs) were identified in RA. Utilising WGCNA, two co-expression modules were generated, with one module demonstrating the strongest correlation with RA. Through the integration of differential gene expression analysis, a total of 5 intersecting genes were discovered. These 5 hub genes, namely fused in sarcoma (FUS), transformer 2 beta homolog (TRA2B), eukaryotic translation elongation factor 2 (EEF2), cleavage and polyadenylation specific factor 6 (CPSF6) and signal transducer and activator of transcription 3 (STAT3) were found to possess significant diagnostic value as determined by receiver operating characteristic (ROC) curve analysis. The close association between the concentrations of various immune cells is anticipated to contribute to the diagnosis and treatment of RA. Furthermore, the infiltration of immune cells mentioned earlier is likely to exert a substantial influence on the initiation of this disease.

The Association Between Rheumatoid Arthritis and Atrial Fibrillation: Epidemiology, Pathophysiology and Management.

Atrial fibrillation (AF) is the most common cardiac arrhythmia with a significant increase in morbidity and mortality worldwide. Rheumatoid arthritis (RA), as a systemic inflammatory disease, affecting 0.5-1.0% of the adult population, is associated with increased incidence of cardiac arrhythmias such as AF. Several epidemiologic studies find that the risk of AF is increased in RA when compared with the general population. Other studies are inconsistent. Considering that inflammation plays an important role in AF, RA may be involved in the occurrence and development of AF. This review summarizes the epidemiology, pathophysiology, and management of AF in patients with RA.

The Effect of TNF-α on CHD and the Relationship between TNF-α Antagonist and CHD in Rheumatoid Arthritis: A Systematic Review.

Tumor necrosis factor-alpha (TNF-α) plays an important role in coronary heart disease (CHD), a chronic inflammatory process. Meanwhile, this pro-inflammatory factor is also involved in the pathogenesis of autoimmune diseases such as rheumatoid arthritis (RA). Patients with RA correspond to a higher risk of CHD. TNF-α antagonist, one of the main treatments for RA, may reduce the risk of CHD in patients with RA. This review summarizes the pathogenesis of TNF-α in CHD and discusses the relationship between TNF-α antagonist and CHD in patients with RA.

LDHA promotes osteoblast differentiation through histone lactylation.

Osteoblast cells tend to metabolize glucose to lactate via aerobic glycolysis during osteogenic differentiation. However, the function of lactate in this process is still elusive. As a newly discovered protein posttranslational modification, lactate-derived histone lactylation has been found to play important roles in gene regulation and have profound effects on diverse biological processes. Here, we found that the expression of lactate dehydrogenase A (LDHA), intracellular lactate, and histone lactylation levels were all gradually increased during osteogenic differentiation. Knockdown of LDHA impaired the formation of mineralized nodules and ALP activity. RNA-sequencing and subsequent validation experiments showed that JunB expression was decreased in LDHA knockdown cells. Mechanistically, knockdown of LDHA decreased histone lactylation mark enrichment on JunB promoter, and exogenous lactate treatment rescued this effect. Our study revealed a non-canonical function of lactate during osteogenic differentiation.

[Correlation of IgG Levels at Initial Diagnosis with Clinical Efficacy and Prognosis in 66 Patients with IgG Multiple Myeloma].

OBJECTIVE: To explore the IgG levels of newly diagnosed IgG-type multiple myeloma (MM) patients and analyze the relationship between the IgG levels and clinical efficacy and prognosis. METHODS: The clinical data of 66 newly diagnosed IgG-type MM patients in our hospital from September 2012 to October 2018 were collected. These 66 patients were divided into group A (IgG≤64 g/L, n=41), and group B (IgG ＞64 g/L, n=25), then the MM patients in 2 groups were divided into 2 subgroups thalidomide (TM)-treated group (n=35) and bortezomib (BTZ)-treated group (n=25) according to therapeutic regimens. The climical efficacy, PFS and OS time as well as the factors affecting prognosis of patients were compared and analyzed. RESULTS: The overall response rate (ORR) and CR+VGPR rate in group A were better than those in group B (P=0.008, P=0.036), the ORR of BTZ-treated group in group B was significantly better than that of TM-treated group (P=0.028), while the ORR of TM-treated group in group A was better than that of TM-treated group in group B (P=0.048), the CR+VGPR rate was better than that of TM-treated group in group B (P＜0.05). The number of patients with high risk cytogenetics (HRC) in group B was much more than that in group A (P=0.022). Spearman correlation analysis showed that serum IgG levels negatively correlated with albumin (r=-0.449，P=0.000) and hemoglobin (r=-0.608，P=0.000), and positively correlated with bone marrow plasma cells (r=0.328，P=0.007). Survival analysis showed that the PFS in group A was significantly better than that in group B (P=0.015), and the OS in group A was better than that in group B (P=0.049), but there was no significant difference in PFS and OS between TM group and BTZ group (PFS: P=0.695, OS: P=0.3250). Cox multivariate regression analysis showed that the ≥VGPR and standard-risk cytogenetics were independent prognostic factors for PFS and OS. CONCLUSION: IgG＞64g/L in patients with newly diagnosed IgG-type MM is a poor prognostic factor affecting PFS and OS. The higher level of serum IgG at the initial diagnosis, the higher the risk of HRCs, and the worse clinical efficacy and prognosis of patients.

Long non-coding RNA ANGPTL1-3 promotes multiple myeloma bortezomib resistance by sponging miR-30a-3p to activate c-Maf expression.

Multiple Myeloma (MM) is a malignant hematological disease characterized by monoclonal proliferation of plasma cells in the bone marrow. In recent years, the widespread use of new drugs based on bortezomib (Btz) has significantly improved the remission rate of MM patients. However, drug resistance and disease relapse occur within a few years and MM is still considered to be an incurable disease. The amplification of the long arm of chromosome 1 is one of the most common genetic abnormalities in MM patients. Here, we found that long non-coding RNA ANGPTL1-3 which located in 1q region was overexpressed in MM. Lnc-ANGPTL1-3 expression was correlated with MM International Staging System (ISS) and overall survival. Notably, knockdown of lnc-ANGPTL1-3 increased Btz sensitivity of MM cells. Following exploration revealed that lnc-ANGPTL1-3 competitively interacted with miR-30a-3p to c-Maf, a transcription factor which was reported to be associated with Btz resistance. Taken together, our findings demonstrate that lnc-ANGPTL1-3/miR-30a-3p/c-Maf axis plays a critical role in MM Btz resistance.