Objective To establish an UPLC method for determination of Triptolide in serum and explore its pharmacokinetics in patients with rheumatoid arthritis after oral administration of tripterygium glycosides tablet. Methods Three patients with rheumatoid arthritis were enrolled. Using Estazolam as internal standard, serum was extracted with acetic ether, and determination was performed on column of Waters Acquity C18 (2.1 mm×100 mm, 1.7 μm) with mobile phase consisted of acetonitrile-0.1% glacial acetic acid (30∶70) at the flow rate of 0.2 mL/min. The column temperature was 30 ℃, and the detection wavelength was set at 220 nm. The serum concentration of Triptolide was processed by DAS 2.1.1 computer program. Results Triptolide was well-separated from internal standard, and the retention time were about 4.9 min and 8.9 min, respectively. Linear range of Triptolide was 13.13-840.00 ng/mL. RSD of intra-day and inter-day were lower than 15%and the recoveries were 88.25%-99.33%. Pharmacokinetic parameters were as follows:Cmax was (159.97±42.43) ng/mL, Tmax was (1.33±0.58) h, T1/2βwas (7.51±2.26) h, and AUC0-12 h was (1131.12±89.20) mg?h/L, respectively. Conclusion Pharmacokinetics of Triptolide conformed to two compartment model. Triptolide can be quickly absorbed, and exists differences among individuals.

Objective:To observe the effect of Xinfeng Capsule (XFC) on synovial membrane PI3K/AKT/mTOR pathway in adjuvant arthritis (AA) rats.Methods:Rats were randomly divided into normal control group,model control group,methotrexate group,tripterygium glycoside group and XFC group.The expressions of IL-6,IL-10,HIF-1α and VEGF-A were detected by immunohistochemical method,and the expressions of PI3K,AKT1 and p-AKT1 were detected by immunoblotting.Results:Expression of AKT1,mTOR and ES proteins in synovial blood vessels.The expression of IL-6,VEGF,HIF-1α and synovial membrane PI3K,AKT1,p-AKT1,mTOR,ES in the model group were significantly higher than those in the control group The expression of PI3K,p-AKT1,mTOR,ES in synovial membrane decreased,and IL-10 in serum increased in XFC group,and the expression of HIF-1α,IL-6 and VEGF-A were decreased.Conclusion:XFC can improve angiogenesis in AA synovium by regulating PI3K/AKT/mTOR signaling pathway,HIF-1α and ES expression.

Rheumatoid arthritis (RA), as a common systemic inflammatory autoimmune disease, affects approximately 1 in 100 individuals. Effective treatment for RA is not yet available because current research does not have a clear understanding of the etiology and pathogenesis of RA. Xinfeng Capsule, a patent Chinese herbal medicine, has been used in the treatment of RA in recent years. Despite its reported clinical efficacy, there are no large-sample, multicenter, randomized trials that support the use of Xinfeng Capsule for RA. Therefore, we designed a randomized, double-blind, multicenter, placebo-controlled trial to assess the efficacy and safety of Xinfeng Capsule in the treatment of RA.

Long non-coding RNAs(lncRNAs)can be involved in regulating gene expression through multiple interactions with DNA,RNA or proteins.Studies have shown that lncRNAs not only regulate innate immune response,but also regulate immune cell development and adaptive immunity.According to recent reports,a number of lncRNAs play a role in the pathogenesis of immune-mediated inflammatory diseases,including systemic lupus erythematosus(SLE),and may become a diagnostic marker and prognostic reference for diseases.This paper summarizes the research progress of lncRNAs in SLE,with the hope of providing more new ideas and methods for the study of SLE.

OBJECTIVE: To observe the changes of pulmonary function and Notch signaling pathway of lung tissues in adjuvant-induced arthritis rats, and to investigate the mechanism of reduced lung function. METHODS: A total of 30 rats were randomly divided into a normal group and a model group. Rats in the model group were induced to establish the adjuvant arthritis AA model by intradermally injecting 0.1 mL Freund's complete adjuvant into the right paw. After 30 days, we observed the paw edema volume, arthritis index, pulmonary function, histomorphology, and Notch receptor/ligand of the lung tissue. RESULTS: Compared with the normal group, the paw edema volume, arthritis index, average expiratory flow within 0.3 s (FEV0.3/FVC), and the level of Notch3, Notch4 and Jagged2 of the lung tissue in the model group was significantly increased, while maximum expiratory flow at 50% of vital capacity (FEF50), maximum expiratory flow at 75% of vital capacity (FEF75), forced expiratory flow (PEF) and the expression of Notch1 of Jagged1 and Delta1 in the lung were significantly decreased (P<0.05, P<0.01). There were significant positive correlations between FEV0.3/FVC and Notch4. FEV0.3/FVC, FEF25, FEF50 and Notch3, Delta1 were negatively correlated, respectively (P<0.05, P<0.01). CONCLUSION While arthritis occurs in AA rats, pulmonary function declines and significantly correlates with the expression of Notch receptor/ligand. The deposition of immune complex in the lung after the injection of CFA activates the Notch signaling pathway, and results in further decline of pulmonary function by signaling cascades.
Animals ; Arthritis, Experimental ; metabolism ; physiopathology ; Calcium-Binding Proteins ; metabolism ; Freund's Adjuvant ; Intercellular Signaling Peptides and Proteins ; metabolism ; Intracellular Signaling Peptides and Proteins ; metabolism ; Jagged-1 Protein ; Lung ; metabolism ; pathology ; Membrane Proteins ; metabolism ; Rats ; Receptors, Notch ; metabolism ; Respiratory Insufficiency ; metabolism ; physiopathology ; Serrate-Jagged Proteins ; Signal Transduction ; Vital Capacity

Objective To explore the therapeutic mechanism of Jianpi Zishen(JPZS)granules for systemic lupus erythematosus(SLE)in light of podocyte autophagy regulation.Methods TCMSP,GeneCards,OMIM,and TTD databases were used to obtain the targets of JPZS granules,SLE,and podocyte autophagy.The protein-protein interaction network was constructed using Cytoscape,and the key active ingredients and targets were screened for molecular docking.In the clinical study,46 patients with SLE were randomized into two groups to receive baseline treatment with prednisone acetate and mycophenolate mofetil(control group)and additional treatment with JPZS granules(observation group)for 12 weeks,with 10 healthy volunteers as the healthy control group.Urinary levels of nephrin and synaptopodin of the patients were detected with ELISA.Western blotting was performed to determine peripheral blood levels of p-JAK1/JAK1,p-STAT1/STAT1,LC3Ⅱ/LC3I,and p62 proteins of the participants.Results Four key active ingredients and 5 core target genes(STAT1,PIK3CG,MAPK1,PRKCA,and CJA1)were obtained,and enrichment analysis identified the potentially involved signaling pathways including AGE-RAGE,JAK/STAT,EGFR,and PI3K/Akt.Molecular docking analysis showed that STAT1 was the most promising target protein with the highest binding activity,suggesting its role as an important mediator for signal transduction after JPZS granule treatment.In the 43 SLE patients available for analysis,treatment with JPZS granule significantly reduced serum levels of p-JAK1/JAK1,p-STAT1/STAT1,and LC3Ⅱ/LC3I(P<0.05 or 0.01),increased the protein level of P62(P<0.05),and reduced urinary levels of nephrin and synaptopodin(P<0.05).Conclusion The therapeutic effect of JPZS granules on SLE is mediated probably by coordinated actions of quercetin,kaempferol,β-sitosterol,and isorhamnetin on their target gene STAT1 to inhibit the JAK/STAT pathway,thus suppressing autophagy and alleviating podocyte injuries in SLE.

Objective To explore the therapeutic mechanism of Jianpi Zishen(JPZS)granules for systemic lupus erythematosus(SLE)in light of podocyte autophagy regulation.Methods TCMSP,GeneCards,OMIM,and TTD databases were used to obtain the targets of JPZS granules,SLE,and podocyte autophagy.The protein-protein interaction network was constructed using Cytoscape,and the key active ingredients and targets were screened for molecular docking.In the clinical study,46 patients with SLE were randomized into two groups to receive baseline treatment with prednisone acetate and mycophenolate mofetil(control group)and additional treatment with JPZS granules(observation group)for 12 weeks,with 10 healthy volunteers as the healthy control group.Urinary levels of nephrin and synaptopodin of the patients were detected with ELISA.Western blotting was performed to determine peripheral blood levels of p-JAK1/JAK1,p-STAT1/STAT1,LC3Ⅱ/LC3I,and p62 proteins of the participants.Results Four key active ingredients and 5 core target genes(STAT1,PIK3CG,MAPK1,PRKCA,and CJA1)were obtained,and enrichment analysis identified the potentially involved signaling pathways including AGE-RAGE,JAK/STAT,EGFR,and PI3K/Akt.Molecular docking analysis showed that STAT1 was the most promising target protein with the highest binding activity,suggesting its role as an important mediator for signal transduction after JPZS granule treatment.In the 43 SLE patients available for analysis,treatment with JPZS granule significantly reduced serum levels of p-JAK1/JAK1,p-STAT1/STAT1,and LC3Ⅱ/LC3I(P<0.05 or 0.01),increased the protein level of P62(P<0.05),and reduced urinary levels of nephrin and synaptopodin(P<0.05).Conclusion The therapeutic effect of JPZS granules on SLE is mediated probably by coordinated actions of quercetin,kaempferol,β-sitosterol,and isorhamnetin on their target gene STAT1 to inhibit the JAK/STAT pathway,thus suppressing autophagy and alleviating podocyte injuries in SLE.

Rheumatoid arthritis(RA)is a common chronic autoimmune disease with synovitis as its pathological basis and erosive arthritis as its main symptom.Pathogenesis of RA is complex,combination of genetic factors,environmental factors,immune cells,cytokines and autoantibodies causes joint injury,bone destruction and multi-system disease of RA.However,the above mecha-nisms can not fully explain the poor prognosis,high disability rate and poor clinical treatment effect of RA.Therefore,exploring new pathogenesis and therapeutic targets of RA is the focus of RA research.In recent years,with the deepening of RA research,it has been found that there is a new form of cell death in pathological process of RA,namely ferroptosis.Ferroptosis is a type of cell death caused by inhibition of glutathione peroxidase activity and accumulation of lipid reactive oxygen species.Previous studies have con-firmed the close correlation between RA and ferroptosis,this paper mainly explores ferroptosis-related signal pathways that affect the change and development of RA disease from the perspective of regulating the main signal pathways of ferroptosis,so as to find new therapeutic targets for RA and new therapeutic ideas for research.

ObjectiveTo investigate the clinical efficacy and safety of Qihuang Jianpi Zishen granules in the treatment of cardiac involvement in systemic lupus erythematosus （SLE）. MethodA total of 62 SLE patients with cardiac involvement treated in the Department of Rheumatology and Immunology， the First Affiliated Hospital of Anhui University of Chinese Medicine from June 2021 to December 2022 were randomized into control and observation groups （n=31）. The control group was treated with methylprednisolone tablets and hydroxychloroquine sulfate tablets， and the observation group with Qihuang Jianpi Zishen granules on the basis of the therapy in the control group. After 12 weeks of treatment， the two groups were compared in terms of the therapeutic effect， cardiac function indicators ［left atrial end-diastolic diameter （LADd）， left ventricular end-diastolic diameter （LVDd）， left ventricular posterior wall thickness （LVPWTd）， peak blood flow velocity in early diastolic period （peak E）， peak blood flow velocity in late diastolic period （peak A）， E/A ratio， stroke volume （SV）， left ventricular ejection fraction （LVEF）， left ventricular short axis shortening rate （LVFS）， and B-type natriuretic peptide （BNP）］， vascular damage indicators ［nitric oxide （NO）， endothelin-1 （ET-1）， vascular endothelial growth factor （VEGF）， and homocysteine （Hcy）］， inflammation indicators ［erythrocyte sedimentation rate （ESR） and hypersensitive C-reactive protein （Hs-CRP）］， anti-double-stranded DNA （dsDNA） antibodies， disease activity index （SLEDAI） score， mitigation of symptoms and signs， and occurrence of adverse reactions. ResultThe total response rate in the observation group was 87.09%， which was higher than that （67.74%） in the control group （P<0.01）， and the incidence of adverse reactions had no significant difference between the two groups. After treatment， the control group showed lowered LVDd， LVPWTd， BNP， ET-1， VEGF， and Hcy （P<0.05） and increased E peak， E/A ratio， SV， LVEF， and LVFS （P<0.05）. In the observation group， LADd， LVDd， LVPWTd， peak A， BNP， NO， ET-1， VEGF， and Hcy decreased （P<0.05）， while peak E， E/A ratio， SV， LVEF and LVFS increased （P<0.05） after treatment. The treatment in both groups decreased the scores of palpitation， chest tightness， dyspnea， and edema （P<0.05）， reduced ESR， Hs-CRP， ds-DNA， and SLEDAI （P<0.05）. After treatment， the observation group had lower LADd， LVDd， LVPWTd， peak A， BNP， and scores of palpation， chest tightness， dyspnea， and edema （P<0.05） and higher peak E， E/A ratio， SV， LVEF， and LVFS （P<0.05） than the control group. In addition， the observation group had lower NO， ET-1， VEGF， Hcy， ESR， Hs-CRP， ds-DNA， and SLEDAI than the control group （P<0.05）. ConclusionQihuang Jianpi Zishen granules combined with hydroxychloroquine sulfate and methylprednisolone can improve multiple indicators and mitigate the symptoms and signs of SLE patients with cardiac involvement， demonstrating a clinical application value.

ObjectiveTo investigate the effects of retention enema with Huangling Jiedu Xiezhuo granules（HJXG） on Nod-like receptor protein 3（NLRP3）， intestinal flora， and short-term prognosis in patients with gout. MethodsA total of 60 patients with gout admitted to the hospital from January 2021 to December 2023 were selected and divided into a control group and an observation group according to the random number table method， with 30 cases in each group. The control group was treated with febuxostat， and the observation group was treated with retention enema with HJXG on the basis of the control group. After 14 days of continuous treatment， the clinical efficacy， traditional Chinese medicine （TCM） syndrome score， and visual analogue scale （VAS） pain index of the two groups were compared， and serum creatinine（SCr）， blood urea nitrogen（BUN）， uric acid（UA）， cystatin C（CysC）， β₂- microglobulin（β₂-MG）， glomerular filtration rate test（GFR）， creatinine clearance rate （Ccr）， erythrocyte sedimentation rate（ESR）， hypersensitive C-reactive protein，（hs-CRP）， interleukin 6（IL-6）， interleukin-1β（IL-1β）， interleukin-18 （IL-18）， NLRP3 inflammasome levels， and the number of intestinal flora were detected in the two groups. The prognosis of patients was followed up within 12 weeks. COX regression analysis was used to analyze the effect of short-term prognosis. ResultsAfter treatment， TCM syndrome scores and VAS pain index in both groups were reduced （P<0.05）， and TCM syndrome scores in the observation group were significantly lower than those in the control group. After treatment， ESR， hs-CRP， IL-6， NLRP3， IL-18， and IL-1β were significantly decreased in both groups （P<0.01）， and the levels of IL-6， ESR， NLRP3， and IL-18 were significantly improved in the observation group compared with the control group （P<0.05）. BUN， SCr， UA， β₂-MG， GFR indexes in both groups were significantly lower after treatment， Ccr indexes in both groups were significantly higher after treatment， and the levels of SCr， UA， CysC， and Ccr in the observation group were significantly better than those in the control group （P<0.05）. After treatment， the intestinal flora in both groups was improved， and the observation group was significantly improved compared with the control group in terms of Lactobacillus， Proteus， Bacteroides， and Escherichia coli （P<0.05）. COX regression analysis showed that retention enema with HJXG could reduce the risk of poor short-term prognosis in patients with gout compared with Western medicine alone. ConclusionThe retention enema with HJXG can improve the curative effect of patients with gout， improve the TCM syndromes， reduce inflammation， and enhance renal function， intestinal flora， and short-term prognosis.