[Clinical advantage staging and underlying mechanisms of Wangbi Tablets against knee osteoarthritis based on "disease-formula" interaction network].

The clinical advantage staging and underlying mechanisms of Wangbi Tablets against knee osteoarthritis(KOA) were studied based on the "disease-formula" interaction network. Firstly, the clinical symptoms and related genes corresponding to Wangbi Tablets and KOA in the acute, remission, and recovery phases were collected from clinical guidelines/consensus and SoFDA database, and the putative targets of Wangbi Tablets were obtained from ETCM 2.0. Then, Jaccard similarity and cosine similarity were employed to assess the similarities of clinical symptoms, genes, and enriched pathways between Wangbi Tablets and KOA in different phases. The "disease-formula" interaction network of the drug targets and disease genes was constructed, and the key targets were screened by topological feature calculation. KEGG and Reactome database were used for the functional enrichment of the key targets, on the basis of which the functional characteristics of Wangbi Tablets against KOA in the acute, remission, and recovery phases were predicted. Finally, the SW1353 cells exposed to lipopolysaccharide were used to decipher the mechanism of Wangbi Tablets against KOA. The results showed that 92/3 921, 138/3 708, 139/3 800, and 196/3 946 clinical symptoms and the related genes corresponded to KOA in the acute, remission, and recovery phases and Wangbi Tablets were collected from SoFDA, and 260 putative targets of Wangbi Tablets were obtained from ETCM 2.0. Wangbi Tablets had highest similarity of clinical symptoms, genes, and enriched pathways with KOA in the remission phase and the secondary highest similarity with KOA in the recovery phase. The key targets of Wangbi Tablets mainly participated in the regulation of immunity-inflammation imbalance and exerted pain-relieving and bone-protecting effects to alleviate symptoms such as knee joint pain, joint swelling, soreness, fatigue, and dysfunction. Intriguingly, the key targets of Wangbi Tablets possessed antioxidant effects during KOA in the acute and remission phases, while they maintained material and energy metabolism homeostasis and protected vessels during KOA in the recovery phase. The cell experiment indicated that Wangbi Tablets down-regulated the expression of interleukin(IL)-6, IL-1ß, tumor necrosis factor-α(TNF-α), and Bcl-2-associated X protein(Bax)/B-cell lymphoma 2(Bcl-2) via regulating the phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt) signaling pathway. The findings lay a theoretical foundation for further clarifying the clinical advantage stage and precise clinical application of Wangbi Tablets in treating KOA.

An integrated transcriptomics and network pharmacology approach to explore the mechanism of Wang-Bi tablet against SAPHO syndrome.

BACKGROUND: SAPHO syndrome is recognized as a rare entity with damage to skin and bones due to inflammation. Currently, the treatment for SAPHO syndrome is still a challenge in clinical practice. In this study, an integrated transcriptomics and network pharmacology approach was applied to explore the therapeutic effect and mechanism of Wang-Bi tablet (WBT) on SAPHO syndrome. METHODS: The main components of WBT and their targets, as well as the targets of SAPHO syndrome, were collected from databases. Network visualization was performed using Cytoscape software. The GO and KEGG enrichment analysis was executed by David dataset. Then, the molecular mechanism of WBT improving SAPHO syndrome was validated by transcriptomics of peripheral blood neutrophils in SAPHO syndrome. Finally, the above results were validated by molecular docking. RESULTS: The Network Pharmacology results showed there are 152 core targets for WBT treatment on SAPHO syndrome. RNA-seq data showed 442 differentially expressed genes (DEGs) in peripheral blood neutrophils of SAPHO patients. Intriguingly, NIK/NF-kappaB-, MyD88-dependent toll-like receptor-, and MAPK pathway were included in the enrichment results of network pharmacology and RNA-seq. Moreover, we verified that the core components of WBT have good affinity with the core targets of NIK/NF-kappaB-, MyD88-dependent toll-like receptor-, and MAPK pathway by molecular docking. CONCLUSIONS: This study illustrated that the possible mechanisms of WBT against SAPHO syndrome may be related to NIK/NF-kappaB-, MyD88-dependent toll-like receptor-, and MAPK pathway, and further experiments are needed to prove these predictions.

China rheumatoid arthritis registry of patients with Chinese medicine (CERTAIN): Rationale, design, and baseline characteristics of the first 11,764 enrollees.

BACKGROUND: Chinese medicine (CM) has become a popular interventional treatment for rheumatoid arthritis (RA). However, limited knowledge about general characteristics and long-term clinical outcomes hampers the development of CM for RA. PURPOSE: The main objectives of the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) were to describe the population of RA patients receiving CM treatment in multiple centers in China using different variables and compare these findings with internationally reported data. STUDY DESIGN: The CERTAIN is a prospective, multicenter, observational disease registry. METHODS: Adult RA patients who fulfilled the 2010 American College of Rheumatology/ European League Against Rheumatism classification criteria for RA and received CM treatment were recruited into the CERTAIN by rheumatologists from 145 hospitals across 30 provinces in China. Data on demographics, disease characteristics, comorbidities, treatments, and adverse events, with a 2-year follow-up, were collected and documented using a predefined protocol. RESULTS: In the 2 years since the study began in September 2019, 11,764 patients have been enrolled (enrolment is ongoing), and 13.10% of participants have completed the 6-month follow-up. We present the baseline characteristics of the first 11,764 enrollees. CONCLUSIONS: The CERTAIN is the first nationwide registry to document comprehensive data on CM treatment in patients with RA. The development of the CERTAIN resource is a significant step forward for Chinese RA patients, herbal medicine users, and research communities and will deepen our understanding of CM for RA. REGISTRATION: The study was registered at ClinicalTrials.gov (NCT05219214).