Rheumatoid arthritis belongs to arthralgia in the theory of traditional Chinese medicine, with cold dampness obstruction pattern (CDO) and damp heat obstruction pattern (DHO) as the main pattern types. Fine therapeutic effects have been obtained in clinical practice following the differentiation of CDO and DHO. However, suitable animal models are not available currently. For adapting to the clinical diagnosis, as well as carrying out basic research of integrated Chinese and Western medicine and preclinical study on new Chinese medicine in a better way, the “Guidelines for Establishing Animal Models of Rheumatoid Arthritis with Cold Dampness Obstruction Pattern and Damp Heat Obstruction Pattern” (referred to as “Guidelines”) were compiled by our research group in cooperation with renowned experts in clinical, pharmaceutical, zoological, and methodological research fields. According to the theory of disease and syndrome integration, experts standardized the establishment methods for animal models of rheumatoid arthritis with CDO and DHO. The Guidelines were compiled via the nominal group method according to the principle of evidence coming in main place, consensus as the auxiliary, and experience as the references. Contents such as animal species, arthritis induction methods, external stimulation conditions, and assessment indicators were specified in the Guidelines based on the comprehensive evaluation of pathogenesis homology, behavioral phenotypic consistency, and drug therapy predictability between animal models and human diseases. The Guidelines will be applicable to the research on syndromes in rheumatoid arthritis, elucidation of acting mechanism, and development of new medicine, and provide reference for standardizing other types of animal models with the integration of disease and syndrome, to promote the modernization of Chinese medicine research.

Rheumatoid arthritis belongs to arthralgia syndrome in the theory of traditional Chinese medicine， and cold-dampness obstruction syndrome and dampness-heat obstruction syndrome are core syndromes and main syndrome differentiation types of this disease. Fine therapeutic effects have been obtained in the long-term clinical practice of many famous traditional Chinese medicine practitioners following the syndrome differentiation and treatment based on the guiding principles of cold and heat. To adapt to the clinical diagnosis practice of combining disease differentiation and syndrome differentiation， and to better carry out basic research on integrated Chinese and Western medicine and preclinical study on new traditional Chinese medicines， Guidelines for Establishing Animal Models of Rheumatoid Arthritis with Cold-Dampness Obstruction Syndrome and Dampness-Heat Obstruction Syndrome （hereinafter referred to as the Guidelines） were compiled by our research group， in cooperation with the renowned experts in research fields including traditional Chinese medicine， clinical medicine， zoology and evidence-based medicine， which provide a meaningful reference for scientific research， teaching and clinical applications. The compilation process of the Guidelines was guided by the theory of disease and syndrome integration and the principles of "evidence takes the main place， consensus plays an auxiliary role， and experience serves as the reference". Based on the comprehensive evaluation of pathogenesis homology， behavioral phenotypic consistency， and drug treatment predictability compared between animal models and human diseases， by the nominal group method， "recommendations" were formed for recommendations supported by evidence， and "consensus recommendations" were formed for recommendations not supported by evidence. Guidelines were formed involving content such as animal types， arthritis modeling methods， external stimulation conditions， and modeling assessment indicators during the establishment of the animal models of rheumatoid arthritis with cold-dampness obstruction syndrome and dampness-heat obstruction syndrome. The Guidelines are applicable for the disease and syndrome research on rheumatoid arthritis， investigation of therapeutic mechanisms， and development of new traditional Chinese medicine. The Guidelines also provide a reference for the establishment of guidelines on other types of diseases and syndromes combined with animal models to further promote the modernization of traditional Chinese medicine research and its integration with international academic development.

The Guidelines for Establishing Animal Models of Rheumatoid Arthritis with Cold-dampness Obstruction Syndrome and Dampness-heat Obstruction Syndrome （hereinafter referred to as the Guidelines） （No. T/CACM1567-2024） was published by Chinese Association of Chinese Medicine on January 11， 2024. To assist researchers and medical workers in understanding and applying the Guidelines more accurately， and also to provide reference and assistance for the establishment of guidelines on other types of diseases and syndromes combined with animal models， this paper made a declaration of the workflow， technological links， development references， promotion of its application and after-effect evaluation of the Guidelines that has been made according to the requirements of "Draft Group Standard of the Standardization Office of the Chinese Association of Traditional Chinese Medicine".

Notch signaling pathway regulates cell development,differentiation,proliferation,and apoptosis,one of the most important pathways that determine cell fate.Research has found that the Notch pathway is involved in developing rheumatoid arthritis(RA).In this article,we reviewed the composition,activation pathway,function,and role of the Notch pathway in RA,and analyzed the research progress of the Notch pathway in macrophages,osteoclasts,vascular endothelial cells,lymphocytes,and fibroblast-like synovial cells.Further exploration of the mechanism of the Notch pathway in RA can provide direction for clinical drug development and new targets for treating RA.

Objective: To investigate the clinical characteristics and the effectiveness of surgical treatment of adrenal cysts. Methods: The clinical data of adrenal cysts in Affiliated Zhangye people′s Hospital, Hexi College from May 2005 to July 2018 were retrospectively analyzed, including clinical manifestations, diagnosis, surgical methods, postoperative pathological results and follow-up process. Seventeen patients with adrenal cysts were identified including 10 males and 7 females. The median age was 45.6 ranging from 30 to 75. There were 12 left lesions and 5 right lesions. Only 4 patients (23.5%) had clinical symptoms, including low back pain, abdominal pain and dizziness caused by hypertension. Ultrasound, CT and MRI were the main imaging methods for preoperative diagnosis. Results: All patients underwent surgical treatment. Laparoscopic surgery was adapted in 14 cases. The average operation time was (70.2 ± 18.5) min and the average bleeding was (47.0 ± 12.1) ml. For open surgery in 3 cases, the average operation time was (103.5 ± 25.0) min and the average bleeding was (85.6 ± 20.5) ml. Postoperative pathological results showed endothelial cysts in 11 cases, epithelial cysts in 3 cases and pseudocysts in 3 cases. No recurrence of cysts or hypoadrenalism occurred in 3-75 months′ follow-up. Conclusions Adrenal cysts are relatively rare and generally benign lesions. Imaging examination, especially abdominal enhanced CT is essential for diagnosis. Laparoscopic surgery is a safe and effective method for the treatment of adrenal cysts.

Over one half the patients with rheumatoid arthritis (RA) are being treated with methotrexate (MTX). Although well proven, the efficacy of MTX varies in individual patients. This study examined the metabolic biomarkers that can be used to predict the therapeutic effect of MTX by using metabolomic analysis. Rats were immunized with collagen to rapidly cause collagen-induced arthritis (CIA) and then treated with 0.1 mg/kg MTX for 4 weeks. The clinical signs and the histopathological features of CIA were observed to evaluate the therapeutic effects. Urine samples of CIA rats were collected, and analyzed by using 600 M (1)H-nuclear magnetic resonance ((1)H-NMR) for spectral binning after the therapy. The urine spectra were divided into spectral bins, and 20 endogenous metabolites were assigned by Chenomx Suite. Multivariate analyses were performed to identify the spectral pattern of endogenous metabolites related to MTX therapy. The results showed that the clustering of the spectra of the urine samples from the responsive rats (n=20) was different from that from the non-responsive rats (n=11). Multivariate analysis showed difference in metabolic profiles between the responsive and non-responsive rats by using partial least squares-discrimination analysis (PLS-DA) (R(2)=0.812, Q(2)=0.604). In targeted profiling, 13 endogenous metabolites (uric acid, taurine, histidine, methionine, glycine, etc.) were selected as putative biomarkers for predicting therapeutic response to MTX. It was suggested that (1)H-NMR-based metabolomic analysis can be used to predict the therapeutic effect of MTX, and several metabolites were found to be related to the therapeutic effects of MTX.
Animals ; Antirheumatic Agents ; administration & dosage ; Arthritis ; chemically induced ; drug therapy ; urine ; Biomarkers ; urine ; Collagen Type II ; Dose-Response Relationship, Drug ; Immunosuppressive Agents ; administration & dosage ; Magnetic Resonance Spectroscopy ; methods ; Male ; Metabolome ; Methotrexate ; administration & dosage ; Proteome ; analysis ; Protons ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results ; Sensitivity and Specificity ; Treatment Outcome

ObjectiveTo study the regulatory effect of Tripterygium wilfprdii polyglycoside (TWP) on the expression of EGFR and ErbB-2 induced arthritis rats.The effect of TWP on arthritis was also explored.MethodsAfter the model of CIA rats were established,the expression of EGFR and ErbB-2 in the synovium and articular cartilage were tested by immunohistochemical stain and real time PCR.ANOVA was used for statistical analysis.ResultsThe protein and mRNA expression of EGFR and ErbB-2 in the synovium (EGFR 0.268±0.059,ErbB-2 0.25±0.04,EGFR mRNA:14.2±0.55,ErbB-2 mRNA 23.46±3.64) and articular cartilage (EGFR 0.193±0.018,ErbB-2 0.217±0.033,EGFR mRNA:4.16±0.50,ErbB-2 mRNA 9.23±0.66) of the model group were significantly higher than those of the control group(P＜0.01).After being treated with TWP and MTX,the protein and mRNA expression of the EGFR and ErbB-2 decreased markedly (P＜0.01).Conclusion EGFR and ErbB-2 may play an important role in the pathogenesis of arthritis development.The molecular mechanism that TWP can treat synovitis and bone destruction of RA is related to the inhibition of EGFR and ErbB-2.

Over one half the patients with rheumatoid arthritis (RA) are being treated with methotrexate (MTX). Although well proven, the efficacy of MTX varies in individual patients. This study examined the metabolic biomarkers that can be used to predict the therapeutic effect of MTX by using metabolomic analysis. Rats were immunized with collagen to rapidly cause collagen-induced arthritis (CIA) and then treated with 0.1 mg/kg MTX for 4 weeks. The clinical signs and the histopathological features of CIA were observed to evaluate the therapeutic effects. Urine samples of CIA rats were collected, and analyzed by using 600 M (1)H-nuclear magnetic resonance ((1)H-NMR) for spectral binning after the therapy. The urine spectra were divided into spectral bins, and 20 endogenous metabolites were assigned by Chenomx Suite. Multivariate analyses were performed to identify the spectral pattern of endogenous metabolites related to MTX therapy. The results showed that the clustering of the spectra of the urine samples from the responsive rats (n=20) was different from that from the non-responsive rats (n=11). Multivariate analysis showed difference in metabolic profiles between the responsive and non-responsive rats by using partial least squares-discrimination analysis (PLS-DA) (R(2)=0.812, Q(2)=0.604). In targeted profiling, 13 endogenous metabolites (uric acid, taurine, histidine, methionine, glycine, etc.) were selected as putative biomarkers for predicting therapeutic response to MTX. It was suggested that (1)H-NMR-based metabolomic analysis can be used to predict the therapeutic effect of MTX, and several metabolites were found to be related to the therapeutic effects of MTX.

Objective To observe the effect of osteopontin (OPN) and integrin αtvβ3 in collageninduced arthritis (CIA) and the possible mechanism of Tripterygium wilfordii polyglycoside (TWP) in the treatment of rheumatoid arthritis (RA). Methods CIA rats model were developed and were randomly divided into the experimental group and the TWP group.And tissue samples were obtained 4 weeks later.Then the expressions of OPN and integrin αvβ3 in the synovium,synovium fluid and serum of each group were determined by immunohistochemical stain and ELISA.Variance analysis was used for data analysis.Results The concentrations of OPN of the normal controls,experimental group and the TWP group in the serum were (5.7±2.9), (7.8±6.2), (5.0±1.9) ng/ml respectively and there were significant differences between these 3 groups (F=6.74,P=0.016).The concentration of OPN (measured by mean grey value) in the synovium and cartilage of the three groups were 229±15,81±15,93±13 and 211±17,91±19,100±15 and there were significant differences between the three groups (F=52.48,P＜0.01; F=18.98,P=0.01).The concentrations of protein αvβ3 (measured by mean grey value) in the synovium and cartilage were 235±16,91±16,131±14 and 198±10,99±15,113±14,respectively and there were significant differences between the three groups (F=23.03,P=0.002; F=12.04,P=0.008).The expressions of OPN and integrin αvβ3 in the synovium,synovium fluid and serum of the experimental group were markedly higher than that of the controls.The expressions of OPN and integrin αvβ3 in the synovium,synovium fluid and serum of the treatment group were obviously lower than the experimental group.Conclusion OPN and integrin αtvβ3 are involved in the hyperplasia of the synovium,cartilage and bone destruction in CIA rats.The underlying molecular mechanism that TWP is effective in treating synovitis and bone destruction of RA is possibly related to down-regulation of the expression of OPN protein and integrin αvβ3.

Objective To study the regulatory effect of triptolide(TP)on the angiogenesis of coll-agen-induced arthritis(CIA) rats.The effect of TP on arthritis is also explored.Methods After the model of CIA was established,the articular volume was measured and the synovium was examined with regular HE stainand the inflammation and pathological changes were evaluated.In addition,the vascular endothelial growth factor (VEGF),basic fibroblast growth factor (bFGF)and endostatin protein expressions in synovium and serum were tested.The micro-vessel density (MVD) of synovium was also measured by caulating CD34 level.Results The expressions of VEGF,bFGF and MVD in CIA rats'synovium and serum were evidently higher than the control group(X2=65.3,31.6,q=9.2,P＜O.01,respectively),while the expression of endostatin showed no statistical difference with controls (X2=0.8,P＞0.05).After treated with TP,the expressions of VEGF,bFGFand MVD decreased markedly(X2=19.7,6.0,q=6.5,P＜O.01,respectively),but the pmtein expression of endostatin significantly increased (X2=3.9,P＜O.05).However,only the expression of endostatin increased significantly after treated with MTX (X2=17.9,P＜0.01).Conclusion Imbalance in growth factors prnduction may play an important role in the process of arthritis development.Re-establishing the balance of growth factors maybe one of the mechanisms of TP in the treatment of arthritis.