Tanshinone IIA inhibits osteoclastogenesis in rheumatoid arthritis via LDHC-regulated ROS generation.

Rheumatoid arthritis (RA) is characterized by bone destruction in the afflicted joints, and during the process of bone destruction, osteoclasts play a crucial role. Tanshinone IIA (Tan IIA) has shown anti-inflammatory effects in RA. However, the exact molecular mechanisms by which it delays bone destruction remain largely unexplained. Here, we found that Tan IIA decreased the severity of and ameliorated bone loss in an AIA rat model. In vitro, Tan IIA inhibited RANKL-induced osteoclast differentiation. By activity-based protein analysis (ABPP) combined with LC‒MS/MS, we discovered that Tan IIA covalently binds to the lactate dehydrogenase subunit LDHC and inhibits its enzymatic activity. Moreover, we found that Tan IIA inhibits the generation of osteoclast-specific markers by reducing the accumulation of reactive oxygen species (ROS), thus reducing osteoclast differentiation. Finally, our results reveal that Tan IIA suppresses osteoclast differentiation via LDHC-mediated ROS generation in osteoclasts. Tan IIA can thus be regarded as an effective drug for the treatment of bone damage in RA.

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).

Life among Chinese fibromyalgia patients: a cross-sectional study.

OBJECTIVE: This study is to examine the impact of age on the clinical characteristics, fibromyalgia-related symptom severity and quality of life (QOL) among Chinese fibromyalgia patients. METHODS: A packet of questionnaires on demographics, medical history, and severity of six major symptoms of fibromyalgia (i.e., pain, fatigue, sleep quality, depression, stress, and QOL) was completed by 124 Chinese patients. The patients were stratified into three groups by age (32 (25.8%) "young" patients, ≤ 39 years; 73 (58.9%) "middle-age" patients, 40-59 years; and 19 (15.3%) "older" patients, ≥ 60 years). Analysis of covariance was conducted and adjusted for body mass index and symptom fibromyalgia duration. RESULTS: The majority of patients in this study were women (107, 86.3%), and the mean age was 49.4 years (SD 10.8 years). Pairwise comparisons among the three age groups found that the young and middle-aged patients were significantly more troubled than the older patients by their symptoms in several categories: morning tiredness (P ≤ 0.012), depression (P ≤ 0.002), anxiety (P ≤ 0.004), mental health index (P ≤ 0.002), and mental component summary score (P ≤ 0.017). The middle-aged patients reported more trouble than the older patients with regard to social functioning (P = 0.008), emotional roles (P = 0.012), depression (P = 0.012), and sleep quality (P = 0.017). The young patients exhibited the highest levels of current experienced stress (young vs. old, P = 0.013). CONCLUSION: This study has identified that middle-aged Chinese fibromyalgia patients exhibited less compromise of their QOL than did their older peers. This discrepancy begs a logical explanation and deserves further study. Key Points • This is the first clinical study to show the potential effect of age on fibromyalgia patients in China. • Characteristics, symptom severity, and QOL differ in different age groups. • The younger patients are, the worse their quality of life.

Acupuncture for primary fibromyalgia: Study protocol of a randomized controlled trial.

BACKGROUND: Acupuncture is well recognized for its unique therapeutic effect for many diseases as a nonpharmacological therapy in traditional Chinese medicine (TCM). However, whether acupuncture can effectively treat fibromyalgia is currently unclear. Therefore, we aim to design a study protocol of a randomized controlled clinical trial and assess the effectiveness of acupuncture for patients with fibromyalgia, which may lead to alleviation of clinical symptoms and improvement of patients' quality of life. METHODS: The study is designed as a randomized, blinded, placebo-controlled trial of two cohorts conducted at Guang'anmen Hospital of China Academy of Chinese Medical Sciences and Shenzhen Traditional Chinese Medicine Hospital, respectively. A total of 68 patients with primary fibromyalgia, diagnosed with the American College of Rheumatology criteria, are randomly allocated with a 1:1 ratio to acupuncture or sham acupuncture groups. All subjects will receive acupuncture intervention for 8 weeks with follow-up assessments every 4 weeks for 16 weeks. The primary outcome will be evaluated using the visual analogue scale (VAS) and revised fibromyalgia impact questionnaire (FIQR) for pain intensity. The secondary outcome measures will include: Multidimensional Assessment of Fatigue scale (MAF), Short Form-36 (SF-36), Beck Depression Inventory (BDI), Pittsburgh Sleep Quality Index (PSQI), Chinese perceived stress scales (pss-14), changes in the number of 18 tender points, patient satisfaction for the treatment and adverse events. The mentioned outcome measurements will be assessed every 4 weeks for 6 months. DISCUSSION: This clinical trial will use advanced research methods to evaluate the efficacy and safety of acupuncture on fibromyalgia. The results of this trial may provide clinical evidence on the beneficial effects of acupuncture in treating fibromyalgia. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800016826: AMCTR-IOR-18000184. Registered 27 June 2018, http://www.acmctr.org/listbycreater.aspx.