This study aims to clarify the genetic associations between Sjögren’s Disease (SD) and cardiovascular disease (CVD) outcomes, and to conduct an in-depth exploration of specific pleiotropic susceptibility genes. We performed two-sample and multivariable Mendelian randomization (MR) analysis to investigate the association between SD and the risk of ischemic heart disease (IHD) and stroke. Linkage disequilibrium score regression (LDSC) and Bayesian co-localization analyses were employed to assess the genetic associations between traits. Cross-phenotype analyses were employed to identify shared variants and genes, followed by a Transcriptome-Wide Association Study (TWAS) and Multi-marker Analysis of Genomic Annotation (MAGMA) based on Multi-Trait Analysis of GWAS (MTAG) results. To validate the pleiotropic genes, we further analyzed tissue-specific differentially expressed genes (DEGs) related to SD using RNA sequencing data. The two-sample and multivariable MR analyses revealed that SD confers a genetic vulnerability to IHD and stroke. LDSC and co-localization analyses indicated a strong genetic linkage between SD and CVDs. Cross-phenotype analyses identified 38 and 37 pleiotropic single nucleotide polymorphisms (SNPs) for SD-Stroke and SD-IHD, respectively, primarily located within the MHC class region on 6p21.32:33 loci. Additionally, TWAS and MAGMA analyses identified pleiotropic genes located outside the MHC regions—seven associated with stroke (UHRF1BP1, SNRPC, BLK, FAM167A, ARHGAP27, C8orf12, and PLEKHM1) and two associated with IHD (UHRF1BP1 and SNRPC). Proxy variants within these genes in SD suggested an increased causal risk for stroke or IHD. Co-localization analysis further reinforced that SD and stroke share significant SNPs within the loci of FAM167A, BLK, C8orf12, SNRPC, and UHRF1BP1. DEG analysis revealed a significant up-regulation of the identified genes in SD-specific tissues. SD appears genetically predisposed to an increased risk of CVDs. Moreover, this research not only identified pleiotropic genes shared between SD and CVDs, but also, for the first time, detected key gene expressions that elevate CVD risk in SD patients—findings that may offer promising therapeutic targets for patient management.

QianghuoErhuang Decoction (QED) is an effective recipe in treating rheumatoid arthritis. The present study aimed to explore the effects of QED on Treg and Th17 in adjuvant arthritis (AA) model. The study included 6 group rats: normal control group, AA group, AA + methotrexate (MTX) group, AA + high, moderate, and low dose QED groups. The arthritis score was significantly decreased in the MTX and high-dose QED groups compared with the AA group on days 24 and 28 (P < 0.01), respectively. The synovial tissue inflammation was attenuated by histological observation, and the proliferation of splenocytes was significantly inhibited in MTX and high-dose QED groups (P < 0.01). High-dose QED can up-regulated the percentage of Treg cells (P < 0.01) and down-regulated the percentage of Th17 cells (P < 0.05). Notably, the serum levels of IL-6, IL-17 and TNF-α were significantly decreased, while TGF-β levels were apparently elevated compared with AA group (P < 0.05, P < 0.01). Interestingly, moderate and low-dose QED had no such similar effects. In summary, high-dose QED had a therapeutic effect against adjuvant arthritis and regulated the related cytokine levels in serum. The underlying mechanism might be mediated via restoration of the imbalance in CD4⁺ T lymphocyte subsets, Treg/Th17.

BACKGROUND:Sinomenine hydrochloride is an alkaloid that is extracted from the Chinese herbal plant Sinomenium acutum, and is used as a herbal medicine in the treatment or rheumatic disease. This report is the first to describe a case of sinomenine hy...