Extra-cellular signals, including T lymphoc ytes, cytokines,growth factors,interferons and neuropeptides, which could modulate matrix metalloproteinases expression in synoviocytes of rheumatoid arthritis(RA), are often mediated by G-protein-coupled Receptors (GPCR)-initiated signaling and mitogen-activated protein kinase (MAPK) cascades. Drug targets which aim at the extra-cellular signals or intra-cellular cascades is required for ameliorating inflammatory reaction and preventing joint destruction in RA.

The activation of MAPKs signal transduction parthways, is a typical feature of chronic synovitis in rheumatoid arthritis. The phosphorylation of synoviocytes cytoplasm proteins induced transcription factor and nucleus proteins phosphorylation such as c-fos, c-jun, AP-1 and NF-?B via MAPKs signal transduction, which promotes synoviocytes proliferation and activation. These findings may be beneficial for the elucidation of the pathogenesis and the development of new drugs for rheumatoid arthritis.

Aim To investigate the effects and mechanisms of glucosides of chaenomeles speciosa (GCS) in mice with contact hypersensitivity (CHS) response. Methods CHS model in mice induced by 2,4-dinitro-I-dinitroflurobenzene (DNFB) was used in this study. Concanavalin A (Con A)-induced splenocytes proliferation was measured by the MTT colorimetric method and interleukin-2 (IL-2) activity was measured by testing its ability to support ConA-induced mice splenocytes proliferation by MTT method. Interleukin-4 (IL-4) and transforming growth factor -beta 1 (TGF-? 1) levels were determined by ELISA. T lymphocytes subsets were measured by flow cytometry. Results Similar as the control drug 4-acetylaminophenylacetic acid (actarit or Acta) (120 mg?kg -1), GCS (240 mg?kg -1) could inhibit the thymus index and spleen index in CHS mice. GCS( 60,120,240 mg?kg -1) could inhibit the ear swelling of CHS mice and could inhibit the splenocytes proliferation induced by ConA. GCS (240 mg?kg -1)decreased CD4 +CD8 +T lymphocytes subsets ratio and resumed the CD4 +CD8 -subsets ratio in CHS mice;GCS(240,60 mg?kg -1) resumed the CD4 -CD8 -subsets ratio in CHS mice. GCS also decreased the TGF-? 1 and IL-2 levels and increased the IL-4 levels in mice thymus with CHS. Conclusion GCS could inhibit mice CHS reaction and resume the balance of T lymphocytes subsets in mice thymus with CHS, and also could modulate the cytokines production by CD4 + T lymphocytes of CHS mice.

OBJECTIVETo observe the therapeutic effect and mechanism of nux vomica total alkali gel (NVTAG) on adjuvants arthritis (AA) rats.

METHODSD rats were randomly divided into nine groups: the normal group, the AA model group, NVTAG high, middle and low-dose (25, 12.5, 6.25 mg x kg(-1)) groups and the Votalin control (diclofenac diethylamine emulgel, 50 mg x kg(-1)) group. Except for the normal group, the remaining groups were transcutaneously administered with 0.1 mL freund's adjuvant complete (FCA) for inflammation in left rear feet and then evenly treated with medicine and packed with oilpapers. The foot volume method was adopted to determine foot swelling degree, with pain scoring and polyarthritis scoring. HE staining was used to observe arthro-pathologic injury. The content of prostaglandin E2 (PGE2), interleukin-1 (IL-1), IL-6, tumor necrosis factor (TNF-alpha) and vascular epidermal growth factor (VEGF) in synovium homogenates were measured by enzyme-linked immuno-absorbent assay (ELISA) respectively.

RESULTCompared with the model group, NVTAG and control gel can obviously reduce the foot swelling degree, polyarthritis indicators and relieve arthro-pathologic injury in AA rats (17-21 d). The levels of IL-1, PGE2, IL-6, VEGF and TNF-alpha in synovial homogenates of AA rats were also reduced by NVTAG significantly.

CONCLUSIONNVTAG shows an antergic effect on AA progress in rats, which is closely related to inhibition of development of inflammatory mediator.

Alkalies ; Animals ; Arthritis, Experimental ; drug therapy ; immunology ; pathology ; Cytokines ; analysis ; Gels ; Male ; Phytotherapy ; Rats ; Rats, Wistar ; Strychnos nux-vomica

Objective:To evaluate the diagnostic efficacy of brush cytology and transpapillary biopsy sampling under the guidance of endoscopic retrograde cholangiopancreatography (ERCP) in distinguishing between benign and malignant biliary strictures.Methods:A total of 470 patients with unknown biliary strictures who underwent ERCP at Department of Gastroenterology, Beijing Friendship Hospital from January 2013 to January 2022 were enrolled. Brush cytology was performed before biopsy in a single procedure, and with multiple ERCP brush cytologies or biopsy performed for challenging cases. Clinical data, ERCP procedures, pathological results, and follow-up data were collected. With the final diagnosis as the golden standard, the diagnostic efficacy of brush cytology and biopsy sampling were calculated.Results:The final diagnosis showed 251 cases of malignant and 219 cases of benign biliary strictures. All 470 patients received brush cytology, among whom, 37 patients underwent multiple brush cytologies. Additionally, 114 patients were treated with biopsy sampling. The single brush cytology showed a sensitivity of 49.40% (124/251) and a specificity of 99.09% (217/219) for diagnosing malignant biliary strictures. Multiple brush cytologies showed a sensitivity of 68.42% (13/19) and a specificity of 100.00% (18/18). Biopsy sampling showed a sensitivity of 68.18% (45/66) and a specificity of 97.92% (47/48). Among the 114 patients who underwent both brush cytology and biopsy sampling, the results showed that the diagnostic sensitivity of brush cytology combined with biopsy sampling [77.27% (51/66)] and the sensitivity of single biopsy sampling [68.18% (45/66)] were significantly higher than that of single brush cytology [43.94% (29/66), χ 2=13.99, P<0.001; χ 2=6.92, P=0.009]. Conclusion:Combining brush cytology and biopsy forceps during ERCP enhances diagnostic sensitivity in identifying malignant biliary strictures. Biopsy sampling stands out as more sensitive compared with single brush cytology, emphasizing its role in improving diagnostic capabilities.