Objective. To evaluate whether traditional Chinese medicine compound preparations (TCMCPs) are associated with rheumatoid arthritis- (RA-) related complications (including readmission, Sjogren’s syndrome, surgical treatment, and all-cause death) in patients with RA. Methods. Clinical outcome data were retrospectively collected from patients with RA discharged from the Department of Rheumatology and Immunology of the First Affiliated Hospital of Anhui University of Chinese Medicine from January 2009 to June 2021. The propensity score matching method was used to match baseline data. Multivariate analysis was conducted to analyze sex, age, the incidence of hypertension, diabetes, and hyperlipidemia and identify the risk of readmission, Sjogren’s syndrome, surgical treatment, and all-cause death. Users of TCMCP and nonusers of TCMCP were defined as the TCMCP and non-TCMCP groups, respectively. Results. A total of 11,074 patients with RA were included in the study. The median follow-up time was 54.85 months. After propensity score matching, the baseline data of TCMCP users corresponded with those of non-TCMCP users, with 3517 cases in each group. Retrospective analysis revealed that TCMCP significantly reduced clinical, immune, and inflammatory indices in patients with RA, and these indices were highly correlated. Notably, the composite endpoint prognosis for treatment failure in TCMCP users was better than that in non-TCMCP users ( HR = 0.75 (0.71-0.80)). The risk of RA-related complications in TCMCP users with high-exposure intensity ( HR = 0.669 (0.650-0.751)) and medium-exposure intensity ( HR = 0.796 (0.691-0.918)) was significantly lower than those in non-TCMCP users. An increase in exposure intensity was associated with a concomitant decrease in the risk of RA-related complications. Conclusion. The use of TCMCPs, as well as long-term exposure to TCMCPs, may lower RA-related complications, including readmission, Sjogren’s syndrome, surgical treatment, and all-cause death, in patients with RA.

Objective: To explore the effect of Xinfeng Capsule (XFC) on hypercoagulable state in patients with rheumatoid arthritis (RA) using data mining and network pharmacology. Methods: The data were collected of 524 inpatients with RA who were treated with XFC in the Department of Rheumatology and Immunology of the First Affiliated Hospital of Anhui University of traditional Chinese medicine (TCM) before October 2021. The changes of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), complement component 3 (C3), C4, platelet (PLT), fibrinogen (FBG), thrombin time (TT), prothrombin time (PT), and activated partial thromboplastin time (APTT) were observed before and after the treatment. By implementing the Apriori module, the association rules between XFC and immune-inflammation indexes and coagulation indexes were analyzed. XFC and disease targets were obtained through traditional chinese medicine systems pharmacology database and analysis platform, Genecards, OMIM, and other databases. The cross targets and core targets were screened, and the network diagram of TCM—active ingredients—potential targets was constructed using Cytoscape3.7.2 software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed through Database for Annotation, Visualization and Integrated Discovery (DAVID) database. AutoDock Vina software was used for molecular docking between active ingredients and core targets. The docking results were visualized using PyMOL2.3.0 software. Results: (1) Data mining results showed that the inflammation and coagulation indexes of RA patients were significantly improved after XFC treatment, and there was a strong correlation between XFC and the improvement of CRP, ESR, RF, C3, C4, PLT, FBG, TT, PT, and APTT. (2) Network pharmacology results showed that prostaglandin-endoperoxide synthase 2 (PTGS2), CASP3, tumor necrosis factor (TNF), AKT1, and JUN, the main targets of XFC in the treatment of RA, were closely related to apoptosis and were mainly involved in interleukin 17 (IL-17), TNF, and nuclear factor-κB (NF-κb), and other apoptotic and inflammatory signaling pathways. (3) Molecular docking results showed that the active components of XFC, β- sitosterol, and stigmasterol, had good docking with TNF and PTGS2, which might be the key active components of XFC in the treatment of RA-related hypercoagulable state. Conclusion: XFC can improve the hypercoagulable state of patients with RA by promoting cell apoptosis and improving immune inflammatory response.

Background. Ankylosing spondylitis (AS) is a rheumatism that mainly affects the axial bones and joints. Xinfeng capsule (XFC) is a preparation with a remarkable clinical effect that is used in our hospital. And it has definite curative effect and less side effects in the treatment of AS. Objective. Data mining and network pharmacology were used to analyze the efficacy of Chinese medicine Xinfeng capsule on treating the hypercoagulable state of ankylosing spondylitis and the underlying mechanism behind it. Methods. Clinical data were collected and compiled from the Department of Rheumatology and Immunology of the First Affiliated Hospital of Anhui University of Chinese Medicine. Cluster analysis was used to investigate herbs that frequently used to treat AS, Apriori module was used to analyze the association rules between herbs and laboratory indexes, and the random walk model was used to reveal the therapeutic efficacy of XFC against AS. The TCMSP database was used to acquire the active components and targets of XFC, and the GeneCards and OMIM database were used to obtain the targets of AS. Afterward, an active ingredient-target network was established and core targets were screened for; overlapping targets were screened for the protein-protein interaction (PPI) network analysis, the Gene Ontology (GO) enrichment analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Molecular docking was adopted to investigate the interactions between main active components and core targets. Results. Frequently used herbs could be divided into three groups, and according to the analysis of Apriori module, there is a strong correlation between XFC and the improvement of ESR and hs-CRP, and the results of the random walk model demonstrated that the effect of XFC on improving PLT, ESR, and hs-CRP was superior to the use of traditional Chinese medicine alone. In total, 103 active compounds of XFC and 59 overlapping targets were obtained. The PPI relationships were obtained through the STRING database, and 13 core targets were identified. 1786 GO enrichment results and 205 KEGG enrichment results were obtained, including NF-kappa B signaling pathway, TNF signaling pathway, and IL17 signaling pathway. The outcomes of molecular docking revealed a close relationship between the active compounds of XFC and core targets. Conclusion. This study demonstrated that XFC can effectively improve the hypercoagulable state and the inflammatory indices of AS patients through data mining, and it has a strong correlation with the clinical improvement of inflammation. The active compounds of formononetin, triptolide, quercetin, and kaempferol may be the key active components of XFC in regulating AS, possibly through inhibiting the activation of NF-kappa B signaling pathway to improve hypercoagulable state.

Background. Scutellaria baicalensis Georgi (SBG) has significant anti-inflammatory and immune-modulating activities and is widely used in the treatment of inflammatory and autoimmune diseases. However, the mechanism of SBG in the treatment of ankylosing spondylitis (AS) remains to be elucidated. Methods. Differentially expressed genes (DEGs) related to AS were analyzed based on two GEO gene chips. The DEGs were merged with the data derived from OMIM, GeneCards, and PharmGKB databases to ascertain AS-related targets. Active components of SBG and their targets were acquired from the TCMSP database. After overlapping the targets of AS and SBG, the action targets were acquired. Subsequently, protein-protein interaction (PPI) network and core target screening were conducted using the STRING database and Cytoscape software. Moreover, the DAVID platform was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of action targets. Finally, the affinity of major active components and core targets was validated with molecular docking. Results. A total of 36 active components of SBG were acquired from TCMSP database. Among these, the main active components were baicalein, wogonin, and oroxylin A. The PPI network and screening showed TNF, IL-6, CXCL8, PTGS2, and VEGFA as core targets associated SBG against AS. GO and KEGG analyses indicated that SBG participated in various biological processes, via regulating IL-17, TNF, and NF-κB signaling pathways. Molecular docking results confirmed a strong binding activity between the main active components and the core targets. Conclusion. The therapeutic mechanism of SBG associated with AS can be characterized as a multicomponent, multitarget, and multipathway mechanism. SBG may be a promising therapeutic candidate for AS.

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.