Rheumatoid arthritis (RA) is a chronic autoimmune disorder that is diagnosed mainly on the basis of patient signs, symptoms, and laboratory indices. However, the exact causes of RA are unclear. Moreover, there is a lack of any method of dynamically evaluating the efficacy of the medication administered to treat RA. Here, we applied a random walk model to reveal the compatibility among the various constituents of traditional Chinese medicine and evaluate their therapeutic efficacy against RA. Drugs commonly used to treat RA were investigated using cluster analysis. The association rule analysis was applied to identify compatibilities among the constituents. A random walk model was developed to evaluate drug efficacy based on an in‐house database comprising the clinical records of 9,408 RA patients. Frequently administered medicines were combined into three correlated sets. The evaluation based on the random walk method showed that the drug combination improved ESR, CRP, C3, C4, and IgA more effectively than any single drug. The present study demonstrated that the TCM constituents complement each other and various combinations of them produce different therapeutic effects on RA treatment.

Objective. This study aimed to ascertain the immuno-inflammatory molecular targets of Xinfeng capsules (XFC) in the treatment of ankylosing spondylitis (AS) based on data mining, network pharmacology, and molecular docking. Methods. The efficacy of XFC in the treatment of AS was assessed by clinical data mining. Network pharmacology was utilized to establish a network of the targets for XFC active ingredients in the treatment of AS. The binding mode and affinity of XFC active ingredients to the key targets for AS were predicted using molecular docking. Results. XFC significantly diminished immuno-inflammatory indicators of AS. In total, 208 targets of XFC were obtained from the TCMSP database and 629 disease targets of AS were screened from the GeneCards database, which were intersected to yield 57 targets of XFC in the treatment of AS. Protein-protein interaction, gene ontology, and Kyoto genome encyclopedia analyses showed that XFC might activate TNF and NF-κB signaling pathways. Quercetin, kaempferol, triptolide, and formononetin had free binding energies<-9kcal/mol to inflammatory targets (TNF and PTGS2) in the molecular docking analysis of XFC-active ingredients, indicating that TNF and PTGS2 might be the targets of the action of XFC. Conclusions. Collectively, XFC had a significant therapeutic effect on AS. Specifically, the active ingredients of XFC, including quercetin, kaempferol, triptolide, and formononetin, inhibited the inflammatory response in AS by downregulating TNF and PTGS2 in the TNF and NF-κB signaling pathways.

Radix Salvia miltiorrhiza (RSM) is widely used for the clinical improvement of inflammatory diseases. However, the actions of RSM in the treatment of ankylosing spondylitis (AS) have not been fully explored. Therefore, this study was designed to use retrospective clinical data mining approach to understand the effects of RSM on AS‐related immuno‐inflammatory processes, use network pharmacology to predict therapeutic targets of RSM, and to further investigate the pharmacological molecular mechanism in vitro. RSM treatment has a long‐term correlation with the improvement of AS‐related immuno‐inflammatory indicators through computational models. We established protein‐protein interaction networks, conducted KEGG analysis to enrich significant TNF pathways, and finally obtained three core targets of RSM in the treatment of AS, namely, prostaglandin endoperoxide synthase 2 (PTGS2), interleukin‐6 (IL‐6), and tumor necrosis factor‐alpha (TNF‐alpha). Screening of RSM active ingredients with node degree greater than 20 yielded cryptotanshinone and tanshinone IIA, and previous studies have reported their anti‐inflammatory effects. In vitro, both cryptotanshinone and tanshinone IIA significantly inhibited the expressions of PTGS2, IL‐6, and TNF‐α in peripheral blood mononuclear cells in AS patients. In conclusion, cryptotanshinone and tanshinone IIA, which are the active components of RSM, may inhibit the activation of TNF signaling pathway in AS patients by downregulating the expression of PTGS2, IL‐6, and TNF‐α. These findings illustrate that RSM may be a promising therapeutic candidate for AS, but further validation is required.

Background. Ankylosing spondylitis (AS) has a high disability rate, and an early diagnosis is difficult. Objectives. To explore the possible functions and underlying mechanism of circular RNAs Homo sapiens (hsa)_circ_0003307 in ankylosing spondylitis. Materials and methods. The hsa_circ_0003307 expression levels were investigated in the peripheral blood mononuclear cells (PBMCs) of 30 AS patients and 30 healthy controls (HC) using quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis. Primary fibroblast-like synoviocytes (FLS) were separated from synovial tissues, established as cell lines and cultured for subsequent cell experiments involving transfection with different vectors. The qRT-PCR analysis was used for evaluating the levels of hsa_circ_0003307 in AS-FLS. Phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway-related protein levels were measured using western blotting and immunofluorescence. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory cytokines. Spearman's correlation analysis was used to assess the correlation between hsa_circ_0003307 and clinical characteristics. Results. The expression level of hsa_circ_0003307 was significantly high in AS patients and was positively associated with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Bath Ankylosing Spondylitis Functional Index (BASFI). We found that hsa_circ_0003307 overexpression could promote the activation of the PI3K/AKT pathway and expression of inflammatory cytokines - tumor necrosis factor alpha (TNF-alpha) and TNF-alpha-induced protein 2 ( TNFAIP2). However, hsa_circ_ 0003307 knockdown reduced the expression of TNF-alpha and TNFAIP2. Conclusions. The expression level of hsa_circ_0003307 was associated with inflammatory response, and it was revealed that hsa_circ_0003307 knockdown could reduce the inflammatory response of AS by regulating the PI3K/AKT pathway.