Effect of the immune cells and plasma metabolites on rheumatoid arthritis: a mediated mendelian randomization study.

Background: Increasing evidence indicates a close relationship between alterations in human immune cells and plasma metabolites with Rheumatoid Arthritis (RA). However, limited studies have left the causal relationships behind these links unclear. Methods: A bidirectional Mendelian Randomization (MR) study was conducted, combined with mediation analysis, using data from genome-wide association study database covering 731 immune cell phenotypes and 1,400 plasma metabolite traits to explore their causal relationships with RA and potential mediating effects. The primary method used for MR analysis was inverse-variance weighted and False Discovery Rate (FDR) correction was applied to verify the robustness of our results. Results: HLA DR on CD33- HLA DR+ (myeloid cell group) (OR, 1.422; 95% CI, 1.194-1.694; P < 0.001; PFDR = 0.012) increased the risk of developing RA. CD19 on IgD+ CD38- naive (B cell group) (OR, 0.969; 95% CI, 0.954-0.985; P < 0.001; PFDR = 0.021) reduced the risk of developing RA. RA was a risk factor for HLA DR on CD14- CD16+ monocytes (monocyte group) (OR, 1.242; 95% CI, 1.102-1.401; P < 0.001; PFDR = 0.047). RA was a protective factor for memory B cell %lymphocyte (B cell group) (OR, 0.861; 95% CI, 0.795-0.933; P < 0.001; PFDR = 0.050), CD4+ CD8dim T cell %lymphocyte (TBNK group) (OR, 0.802; 95% CI, 0.711-0.904; P < 0.001; PFDR = 0.043), CD4+ CD8dim T cell %leukocyte (TBNK group) (OR, 0.814; 95% CI, 0.726-0.913; P < 0.001; PFDR = 0.046), CD24 on IgD+ CD24+ B cells (B cell group) (OR, 0.857; 95% CI, 0.793-0.927; P < 0.001; PFDR = 0.038), and CD24 on unswitched memory B cells (B cell group) (OR, 0.867; 95% CI, 0.797-0.942; P < 0.001; PFDR = 0.050). Increasing levels of docosatrienoate (22:3n3) (OR, 0.886; 95% CI, 0.838-0.936; P < 0.001; PFDR = 0.023) significantly reduced the risk of developing RA. The mediating effect of plasma metabolites in this context was not established. Conclusion: This study provides genetic evidence for the intricate relationships between immune cells, plasma metabolites, and RA, highlighting the potential mechanisms involved. This will contribute to future directions in precision medicine and research.

Exploring the potential causal relationship between gut microbiota and heart failure: A two-sample mendelian randomization study combined with the geo database.

OBJECTIVE: In recent years, researchers have observed a potential association between alterations in gut microbiota and the onset and progression of heart failure. Nevertheless, the causal relationship between gut microbiota and heart failure remains a topic of controversy. This study employed a two-sample Mendelian randomization approach to investigate the causal link between gut microbiota and heart failure. METHOD: We extracted single nucleotide polymorphism (SNPs) data for heart failure (ebi-a-gcst009541) and gut microbiota from the publicly available genome-wide association analysis (GWAS) summary database. The primary analytical method employed was inverse variance weighting (IVW), complemented by validation using MR-PRESSO, weighted median, and MR pleiotropic residual methods. Additionally, gene pleiotropy (MR-Egger), heterogeneity testing, and a "leave-one-out" analysis were conducted to assess the robustness of the findings. Utilizing the limma package, differentially expressed genes (DEGs) from the Gut Microbiota datasets (GSE3586, GSE5406) and Heart Failure datasets (GSE47908, GSE87466) sourced from the Gene Expression Omnibus (GEO) were curated. Subsequent enrichment analysis was conducted using the Cluster Profiler and GO plot packages to validate the MR analysis outcomes. RESULTS: The results of our analysis revealed seven distinct bacterial groups in the intestines that exhibited associations.with.the.risk.of.heart.failure. These.included.class.negativicutes (P = 0.02,OR:1.11,95%CI:1.02,1.21), gene.eubacterium.eligensgroup (P = 0.02,OR:1.10,95%CI:1.01,1.20),gene.eubacteriummoxidoreducensgroup (P = 0.01,OR:1.10,95%CI:1.02,1.19),Order.selenium (P = 0.02,OR:1.11,95%CI:1.02,1.21), gene.familyxiiiucg001 (P = 0.03,OR=1.09.95%CI:1.01,1.19), gene.familyxiiiad3011group (P = 0.03,OR:0.92,95%CI:0.86,0.99), and.gene.anaerostipes (P = 0.00,OR:0.87,95%CI:0.80,0.94). Nevertheless, upon conducting reverse causal MR analysis, no evidence of a causal relationship between heart failure and the aforementioned seven gut microbiota groups was found.Bioinformatics analysis reveals shared DEGs between gut microbiota and heart failure. CONCLUSION: This Mendelian randomization study represents the first endeavor to explore the causal relationship between specific gut microbiota and heart failure. The findings suggest a significant correlation between these seven specific gut microbiota groups and the risk of heart failure, potentially offering valuable insights for heart failure prevention and control efforts.

Corrigendum to "Efficacy Comparison of Five Different Acupuncture Methods on Pain, Stiffness, and Function in Osteoarthritis of the Knee: A Network Meta-Analysis".

[This corrects the article DOI: 10.1155/2018/1638904.].

Efficacy Comparison of Five Different Acupuncture Methods on Pain, Stiffness, and Function in Osteoarthritis of the Knee: A Network Meta-Analysis.

The principal objective of this present study was to compare the effects of different acupuncture methods on pain, stiffness, and physical function for osteoarthritis of the knee by the pairwise and network meta-analysis (NMA). A network meta-analysis of randomized controlled trials (RCTs) was searched from three English databases and one Chinese database until January 2018. A pairwise meta-analysis was performed with a random effects model. Then we carried out the NMA within a Bayesian framework. Mean difference (MD) and its 95% confidence interval (CI) were calculated by R 3.4.1, Stata 14.0, and RevMan 5.3 software to assess the relief of pain, the effectiveness for stiffness, and physical function recovery. Node-splitting method was used to calculate the inconsistency. Rank probabilities were assessed and clustered by the surface under the cumulative ranking curve (SUCRA). 16 trials mostly researched short-term effectiveness and showed that fire needle and electro-acupuncture were statistically significant to decrease WOMAC pain and physical function scores when compared with other treatments, but there was no significant difference in stiffness calculations. Our NMA demonstrated that acupuncture with heat pain or electrical stimulation might be suggested as the better choices in all acupuncture methods to osteoarthritis of the knee.