The main pathogenesis of Sjogren's syndrome was Yin Deficiency, dryness caused by blood stasis,dryness caused by dry poisoning, dryness caused by dampness, Qi deficiency, and incoordination of spleen and stomach,which led to damage of body fluid or transport barrier. Usually such factors were mutually intercross and interact, existing in the whole process of the disease. This is the important factor for a long course and intractable disease.

Objective To study the influence of the Runzaoling on AQP1 and AQP5 in submaxillary gland of mice with Sjogren syndrome.Methods Sjogren syndrome mice models were setup by innducement method and divided into six groups randomly,including A group(blank group),B group(model group),C group (low dose group),D group(moderate dose group),E group(high dosage group)and F group(prednisone group).Immunohistochemical method was used to detect the of expressions of AQP1 and AQP5 of submaxillary gland in model mice.Result AQP1 expression showed:scattered flavescent particles were only found in submaxillary gland of group B and group C;AQP5 expression showed:brown-stained granules can be found in gland alveolous teleblem,lateral membrane,and basal lamina of submaxillary gland,secretory duct,and duct epithelia in B group mice;light brawn-stained granules can be found in group C mice;attenuated or disappear stained granules were found in acinus,secretory tube,and duct in D,E,and F group mice.Conclusion Runzaoling Can raise the expression of AQP5 in submaxillary gland of SS mice and increase the absorption quantity of water.

Objective To observe the effects of Chinese medicine ingredient ginger phenol on expressions of IL-17 and IL-23 in collagen-induced arthritis (CIA) rats;To investigate the role and mechanism of ginger phenol in CIA rats.Methods Forty female Wistar rats were randomly divided into 4 groups:blank group, model control group, ginger phenol treatment group and tripterygium glucosides control group. After CIA was established in rats successfully, ginger phenol treatment group and tripterygium glycosides control group were treated with ginger phenol and tripterygium glycosides by gavage, while the control group and model control group were fed with the same amount of saline. Four weeks after the treatment, the rats were collected serum and sacrificed. The pathological of CIA joint synovial was observed by electron microscope. The expressions of IL-17 and IL-23 in serum were detected by ELISA.Results The hyperplasia of synovial tissue and angiogenesis was reduced in gingerol phenol treatment group. Infiltration of inflammatory cells and edema was improved. IL-17 and IL-23 expressions of in serum of CIA rats were significantly higher than those of the blank group (P<0.01). Ginger phenol and tripterygium glycosides down-regulated the expressions of IL-23 and IL-17 (P<0.05,P<0.01). Ginger phenol group was better than that of tripterygium glycosides control group (P<0.05).Conclusion Chinese medicine ingredient ginger phenol can reduce expressions IL-17 and IL-23 in serum of CIA rats.

Objective To investigate the effect of Miao medicine Jinwu Jiangu decoction containing serum freeze-dried powder on levels of IL-17,ACT1 and TRAF6 in human rheumatoid arthritis fibroblast like synoviocytes (RA-HFLS).Methods Rabbits were randomly divided into blank control group (recieving normal saline of the same volume),Jinwu Jiangu decoction high-dose,medium-dose and low-dose group (intragastrically administrated with Jinwu Jiangu decoction at doses of 14.4,4.8 and 2.4 g·kg-1,respectively),tripterygium glycosides group and prednisone group (treated with human equivalent dosage).RA-HFLS primary cell model was established in the experiment.ELISA method was used to detect effect of lyophilized powder on IL-17 secretion.Expression of ACT1,TRAF6 mRNA was detected by RT-PCR.Results Compared with the blank control gorup,IL-17 in the supernatant of each medication administration group was significantly decreased (all P<0.01),and it was decreased most significantly in Jinwu Jiangu decoction high-dose and medium-dose group.IL-17 was down-regulated more significantly in high-dose group than that in tripterygium glycosides group (P<0.01).Compared with the blank control group,TRAF6 and ACT1 mRNA expression level of each medication administration group were significantly decreased (all P<0.01),and in the high-dose group that were decreased most significantly,but not significantly different as compared with tripterygium glycosides group and prednisone group (P>0.05).Conclusion Freeze-dried powder of Jinwu Jiangu decoction can decrease the secretion of IL-17 and down-regulate expression of ACT1,TRAF6 with RA-HFLS.

Objective To study the influence of serum containing Fuzheng Toudu Qudu Recipe, a Chinese formula with the actions of supporting healthy qi to expel and remove toxicity, on serum levels of interleukin 2 (IL-2) and soluble interleukin 2 receptor (sIL-2R) at different stages of CD34+derived dendritic cells (DC) of patients with minimal residual disease of myelogenous leukemia ( MRD-L) , and to explore the biological mechanism of Fuzheng Toudu Qudu Recipe in promoting CD34+ to transform into DC in MRD-L patients. Methods Bone marrow mononuclear cells ( BMMC) were separated from the bone marrow of acute myeloid leukemia patients at complete remission stage by using Ficoll centrifugation. CD34+ cells were isolated by using immuno-magnetic mircobeads method, and then were cultured with various concentrations of Chinese medicine medicated serum and cytokines in vitro for the induction of DC. The morphologic characteristics of DC were observed with the inverted phase contrast microscope, and the expression levels of DC surface molecules such as CD83, CD80, CD86, CD1a and HLA-DR were detected by using flow cytometry. On culturing day 0, 6 and 9, serum levels of IL-2 and sIL-2R of each group were measured by enzyme-linked immunosorbent assay ( ELISA). Results ( 1) Chinese medicine medicated serum combined with cytokines was effective on promoting CD34+ to differentiate into DC with typical morphology, and inducing DC to have high expression of CD80, CD83, CD86 and HLA-DR, which differed from those in fetal calf serum (FCS) group and blank rabbit serum group (P<0.01). Middle- and low-dose combination groups increased expression of CD1a, which differed from high-dose combination group and cytokines group ( P<0.01). ( 2) Content of IL-2 in combination groups was higher than that in blank rabbit serum group on culturing day 0. In the combination groups, IL-2 was higher on culturing day 6 and 9 than that on culturing day 0. Middle and high-dose combination groups had higher IL-2 content on culturing day 9 than on culturing day 6 ( P<0.05 or P<0.01). At the same time point, combination groups had higher IL-2 content than the blank rabbit serum group (P<0.05 or P<0.01). (3) Content of sIL-2R in the combination groups was lower than that in blank rabbit serum group on culturing day 0. In the combination groups, sIL-2R was lower on culturing day 9 than that on culturing day 0 and 6 ( P<0.01) . High-dose combination group had lower sIL-2R content on culturing day 6 than that on culturing day 0 (P<0.05), and the difference of sIL-2R in other groups was insignicant between on culturing day 6 and on culturing day 0 ( P>0.05) . At the same time point, combination groups had lower IL-2 content than the blank rabbit serum group (P<0.05 or P<0.01). Conclusion Fuzheng Toudu Qudu Recipe is effective on increasing serum content of IL-2 and reducing sIL-2R content, and the changes of cytokine contents are more obvious along with the maturity of DC, which indicates that the recipe plays positive effect in the process of promoting CD34+cells to differentiate into DC.

Objective:To investigate the role of IL-17A in the regulation of inflammatory factors and autophagy genes of PBMCs in pSS patients.Methods:Thirty patients fulfilled the diagnosis of pSS were selected, 20 mL of peripheral blood was drawn, PBMCs were isolated and divided into the PBMCs group, IL-17A stimulant group and IL-17A inhibitor group. After warm incubation 48 h of immunofluorescence was applied to detect microtubule-associated protein l light chain 3 (LC3), and the ELISA method was used to detect the expression of the inflammatory factors IL-4, IFN-γ, IL-13 expression. Real-time fluorescence polymerase chain reaction (qRT-PCR) was used to detect the expression of autophagy-inducing genes Ambra-1, Bif-1 and apoptosis genes Bcl-2 and Bcl-XL mRNA, and immunoprotein blotting was used to detect the expression of Beclin1 and LC3 protein. ANOVA was used to compare the differences between groups, and t-test was used for two-by-two comparisons. Results:The immunofluorescence results showed a significant increase in LC3 autophagic vesicles in the IL-17A inhibited group compared with the IL-17A stimulator group. The ELISA results showed that, compared with the PBMCs group [IL-4: (13.39±0.32) pg/ml, IFN-γ: (14.4±0.4) pg/ml, and IL-13: (854±36) pg/ml], IL-4 secretion in the IL-17A stimulated group (11.54±0.30) was decreased ( t=12.83, P=0.024), IFN-γ and IL-13 secretion [(17.6±0.4), (908±51) pg/ml] were increased ( t=19.35, P=0.033; t=2.55, P=0.020); compared with IL-17A inhibitor group [IL-4: (15.65±0.26) pg/ml, IFN-γ: (13.6±0.3) pg/ml, and IL-13: (792±57) pg/ml]. Compared with the IL-17A stimulator group, IL-4 secretion was decreased ( t=21.31, P=0.006), and IFN-γ and IL-13 expression was increased ( t=17.34, P=0.015; t=5.14, P=0.007). The PCR results showed that, compared with Ambra-1, Bif-1, Bcl-2, and Bcl-XL mRNA expression (5.61±0.33, 5.04±0.60, 1.28±0.09, 1.56±0.03) in the PBMCs group, Ambra-1, Bif-1 mRNA in the IL-17A-stimulated group expression (3.76±0.24, 4.68±0.41) were down-regulated ( t=14.30, P=0.007; t=15.02, P=0.012), and Ambra-1, Bif-1 mRNA expression (7.91±1.17, 9.30±0.25) were increased in the IL-17A inhibition group, ( t=13.59, P=0.025; t=11.54, P=0.031), anti-apoptotic proteins Bcl-2, Bcl-XL mRNA expression (1.75±0.06, 2.43±0.16) was up-regulated in IL-17A stimulated group ( t=19.92, P=0.006; t=21.04, P=0.007) were up-regulated and Bcl-2, Bcl-XL mRNA expression (0.48±0.03, 0.83±0.10) were down-regulated in the IL-17A inhibition group ( t=29.44, P=0.027; t=16.31, P=0.023). The results of protein blotting assay showed that, Beclin-1 and LC3 protein expression (0.51±0.10, 0.559±0.010) were decreased in IL-17A stimulated group compared with Beclin-1, LC3 protein expression (0.72±0.09, 0.635±0.017) in PBMCs group ( t=14.38, P=0.034; t=17.99, P=0.014); BecLin-1 and LC3 protein expression (0.83±0.11, 0.737±0.025) increased in the IL-17A inhibition group ( t=9.72, P=0.027; t=22.35, P=0.007). Conclusion:IL-17A plays a role in pSS by regulating the expression of inflammatory factors IL-4, IFN-γ, IL-13 and autophagy related genes Beclin1 and LC3.

Objective:To retrospectively analyze the correlation between blood lipoprotein levels and the risk of osteoporosis (OP) development in postmenopausal patients with RA and its influencing factors.Methods:Patients hospitalized with a definite diagnosis of RA from July 2017 to May 2020 were retrospectively collected and analyzed by bone mineral density (BMD) in subgroups, using correlation analysis, di-chotomous Logistic regression to quantify independent associations between laboratory test results and out-comes, and restrictive cubic spline (RCS) to fit the relationship of OP risk occurrence.Results:Six hundred and sixty-six eligible RA patients were included according to inclusion criteria, including 253 RA-OP and 413 RA-non-OP patients. After exclusion of relevant influencing factors by comparing demographic characteristics, a significant correlation was found between blood HDL-C ( r=-0.11, P=0.006) LDL-C ( r=0.12, P=0.003) levels and RA-OP( P<0.05), and dichotomous Logistic regression showed that as BMI ( OR(95% CI)=0.81(0.77, 0.86), P<0.001], calcium [ OR(95% CI)=0.24(0.10, 0.63), P<0.001], HDL-C[ OR(95% CI)=0.38(0.22, 0.66), P<0.001] increased, the risk of developing OP in RA patients decreased. In contrast, the risk of developing OP increased with increasing age [ OR(95% CI)=1.10(1.07, 1.21), P<0.001), disease duration [ OR(95% CI)=1.00(1.00, 1.00), P=0.020], and LDL-C[ OR(95% CI)=1.71(1.38, 2.12), P<0.001]. Conclusion:Blood HDL-C and LDL-C levels are significantly correlated with the development of RA-OP, and can be used as predictors of OP development and good indicators for disease monitoring in RA patients.

Objective Given that the PI3K/AKT/mTOR signaling pathway is associated with the progression of knee osteoarthritis(KOA),this study aims to investigate whether the polarization induction of synovial macrophages mediated by the PI3K/AKT/mTOR signaling axis is the cause of KOA progression.Methods The synovial fluid of KOA KL-Ⅱ and KL-Ⅲ patients and normal individuals was collected,and the percentage of M1 macrophages(CD80,CD86)and M2 macrophages(CD163,CD206)in the synovial fluid(M1/M2 ratio)was measured to e-valuate the polarization of macrophage cytokines such as IL-1,IL-6,IL-10,and tumor necrosis factor(TNF)-α,transforming growth factor(TGF)-β Expression in KOA synovial fluid,and detect and analyze of key molecules PI3K/AKT/mTOR signaling axis PI3K,AKT3,mTORC1,and inducible nitric oxide synthase(iONS)in KOA synovial fluid.Results Compared with the synovial fluid of normal individuals,the percentage of M1 macrophages(CD80,CD86)in KOA patients increased(P<0.01),and the M1/M2 ratio increased(P<0.001);The ex-pression of IL-1,IL-6,and TNF-α in the synovial fluid of the KOA group was also higher than that of the control group(P<0.01),while the expression of IL-10 and TGF-β in the KOA group was significantly reduced(P<0.01);The key proteins PI3K,AKT3,mTORC1,and downstream inflammatory factor iONS in the PI3K/AKT/mTOR signaling pathway in the synovial fluid of the KOA group were higher than those in the control group(P<0.01).Conclusion In KOA synovial fluid,M1 macrophage polarization plays a dominant role,and the inflam-matory response mediated by M1 macrophage polarization may be the cause of synovitis.At the same time,the PI3K/AKT/mTOR signaling pathway may mediate the polarization of M1 macrophages involved in KOA inflammato-ry response.

Objective To explore the causal relationship between rheumatoid arthritis(RA)and iron deficiency a-nemia(IDA)in European population by two-sample Mendelian randomization analysis.Methods The single nu-cleotide polymorphisms(SNPs)of RA and IDA were analyzed using public genome-wide association studies(GWAS).The inverse variance weighting method(IVW)was used as the main analysis method to evaluate the causal effect of RA on IDA.MR-Egger method,weighted median method(WM),weighted model method and simple model method were used as regression supplements to evaluate the robustness of sensitivity analysis results.The het-erogeneity function was used to calculate the P-value to test the heterogeneity,and the intercept term intercept was used to test the level pleiotropy.Results In the FINNGEN database at the genome-wide level,strong-related SNPs that removed linkage disequilibrium and met the P＜5.0 × 10-8 by Mendelian randomization analysis were select-ed.After integrating exposure and outcome data,31 SNPs were obtained as the final effective instrumental variables.IVW showed that RA was a risk factor for IDA(the risk of IDA in RA patients was 1.064 times higher than that in non-RA patients,OR=1.064,95％CI:1.028-1.103).The weighted median method and MR-Egger method re-sults supported the positive correlation between RA and IDA.The intercept value was close to 0,indicating that there was no horizontal pleiotropy between exposure and outcome.The heterogeneity function's P＜0.05 indicated that there was heterogeneity between exposure and outcome,but the random effect model test showed P＜0.05,indi-cating that even if there was heterogeneity in causality,the overall trend was stable.Conclusion RA is a risk factor for IDA,and there is a positive correlation between RA and IDA.

Objective To investigate the effect of leflunomide(LEF)on the expression of associated autophagy genes in synoviocytes of rheumatoid arthritis(RA)by regulating HIF-1α signal pathway.Methods Three genera-tions of RA synovial cells were divided into blank control group,LEF group and Tripterygium wilfordii polyglyco-sides group.The blank control group was added with the same volume of DMEM culture medium.The drug group was treated with LEF(concentration 0.2 mg/ml)and Tripterygium wilfordii polyglycosides(concentration 0.03 mg/ml),the proliferation and apoptosis of synovial cells were detected by flow cytometry,the expression of IL-1 β,TNF-α,ANGPTL-4 and VEGF was detected by ELISA,the expression of HIF-1α mRNA was detected by qRT-PCR,and the expression of HIF-1 α,Beclin-1 and BNIP3 protein was detected by Western blot.Results Com-pared with Tripterygium wilfordii polyglycosides group,the expression of IL-1 α,TNF-α,ANGPTL-4 and VEGF in synovial supernatant of LEF group decreased;compared with the blank control group,the expression of HIF-1αmRNA in synovial cells of LEF group and Tripterygium wilfordii polyglycosides group decreased,and the effect of LEF group was the most obvious;compared with the blank control group,the protein expressions of HIF-1α,Bec-lin-1 and BNIP3 in synovial cells of LEF group and Tripterygium wilfordii polyglycosides group decreased,and the effect of LEF group was the most obvious.Conclusion LEF can inhibit the expression of inflammatory factors in RA synovial cells,inhibit HIF-1α signaling pathway,inhibit the expression of autophagy-related genes Beclin-1 and BNIP3,and improve the pathological state of synovitis.