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Objective:To study the expression of receptor activator of nuclear factor-κB ligand (RANKL) induced by interleukin-6 (IL-6) in fibroblast-like synoviocytes of rheumatoid arthritis (RA-FLS) and its signal pathway, to clarify the synergistic mechanism of methotrexate (MTX) combined with cyclophosphamide (CTX) in inhibiting RA bone erosion.Methods:The synovial tissues of 6 patients with active RA were collected, and RA-FLS were cultured in vitro. IL-6/sIL-6R and drug intervention were given successively. All RA-FLS were divided into five groups, including blank control group, IL-6/sIL-6R group, CTX group, MTX group and MTX+CTX group. The expression levels of RANKL and signal pathway protein in RA-FLS were detected by real-time quantitative polymerase chain reaction (qPCR), Western blotting and cell-based enzyme-linked im-munosorbent assay (ELISA). Single factor analysis of variance was used to compare in the comparison of multiple groups, LSD- t test or Dunnett's T3 test was used in the comparison of two groups, and 2×2 factorial analysis of var-iance was used in the interaction of two drugs. Results:① There were statistically significant differences in the mRNA and protein levels of RANKL in each group ( F=26.246, P<0.01; F=4.565, P=0.023). The highest level of RANKL mRNA (2.14±0.40) and protein (2.33±0.39) was found in IL-6/sIL-6R group, and the lowest level of RANKL mRNA (0.10±0.08) and protein (0.75±0.21) in MTX+CTX group. ② The difference of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) level in each group was statistically significant ( F=18.151, P<0.01). The level of p-STAT3 (0.328±0.073) was the highest in IL-6/sIL-6R group and the lowest (0.178±0.022) in MTX+CTX group. There was no significant difference in STAT3 in each group ( F=3.173, P=0.051). ③ MTX combined with CTX had interaction on the expression of RANKL mRNA and protein ( F=33.932, P<0.01; F=16.265, P<0.01), and had interaction on the expression of p-STAT3 ( F=16.477, P=0.01), but had no interaction on the expression of STAT3 ( F=0.471, P=0.500). Conclusion:IL-6 can up-regulate the expression of RANKL in RA-FLS through JAK2/STAT3 signal pathway. MTX combined with CTX can down-regulate the expression of RANKL by inhibiting the phosphorylation of STAT3, and this combination is synergistic.
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Objective@#To analyze the clinical characteristics of oral candidiasis (OC) in in-patients with rheumatism, in order to provide theoretical basis for the prevention and treatment of OC in rheumatism patients.@*Methods@#One thousand eight hundred and eight in-patients were recruited in the Department of Rheumatology, the Second Hospital of Shanxi Medical University from January 2017 to December 2017. The patients included 607 males and 1 201 females. Their average age was (49.5±15.5) years old with a ranging from 14 to 81 years. According to occurrence of OC or not, the patients were divided into OC group and non-OC group. The differences of general data, primary diseases, laboratory examinations, usage of glucocorticoid and immunosuppressant therapy were compared between the two groups, and the risk factors of OC occurrence were analyzed.@*Results@#Two hundred and sixty-nine patients had OC and 1 539 patients had no OC. Age [(54.9±14.7) years], duration of illness [(9.4±4.4) years] and hospital stay [(15.3±5.7) d] in OC group were significantly longer than those in non-OC group. OC incidence in patients with connective tissue disease (CTD) [17.40% (193/1 109)] was higher than that in non-CTD patients [10.87% (75/699)] (P<0.001). OC most likely occurred in patients with such CTD as Sjögren syndrome (SS) and Behcet syndrome. OC incidence in non-CTD patients with osteoarthritis (OA) was highest. The salivary flow rate in OC group [(0.65±0.45) ml/min] was significantly lower than that in non-OC group [(0.78± 0.39) ml/min] (t=2.394, P=0.017). There was no statistical differences in other laboratory examinations between the two groups, including white blood cells (WBC), lymphocyte, platelet count, liver function, renal function, erythrocyte sedimentation rate, C-reactive protein, procalcitonin, immunoglobulin G, immunoglobulin M, immunoglobulin A, C3, C4 and so on. OC incidence in patients using prednisone≥15 mg/d [17.16% (133/775)] was higher than that in patients using prednisone<15 mg/d [12.53% (94/750)] and patients not using prednisone [14.84% (42/283)] (P<0.05). The incidence of OC in patients with immunosuppressant therapy [16.11% (226/1 403)] was statistically higher than that in non-immunosuppressant patients [10.62% (43/405)] (P<0.01). Logistic regression analysis showed that the risk factors of OC occurrence included primary diseases (P<0.001), age (P<0.001), duration of illness (P=0.001) and duration of hospitalization (P=0.002).@*Conclusions@#OC occurred commonly in rheumatism in-patients, especially in elder patients, patients with long duration of illness and hospital stay. OC incidence in CTD patients is significantly higher than that in non-CTD patients. Glucocorticoid and immunosuppressant therapy might significantly reduce the anti-fungal immunity of the patients.
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Objective To observe the effect of paclitaxel long-circulating thermo-sensitive liposome ( PLTL) on inhibiting the growth of transplanting Lewis lung cancer cells in C57BL/ 6 mice. Methods The model of mice carried Lewis lung cancer was established. 40 tumor-bearing mice were divided into five groups randomly: blank control group, model control group, PTX group, PTL group and PLTL group, 8 mice for each group. The blank control group and the model control group were injected with 0. 9% sodium chloride solution. In PTX group, PTL group and PLTL group, the dose of per injection was calculated with the reference of PTX for 20 mg·kg-1 , diluted with 0. 9% sodium chloride solution, and the mice were injected via the tail vein with a volume of 0. 2 mL each time. Except for the blank control group, 5 minutes after administration, the tumors of the other groups were subjected to local hyperthermia at (42±0. 5) ℃ for 30 min. During the treatment period, transplantation tumor growth was observed; pathological morphology changes of tumor tissues and cells were detected by HE stain; apoptosis rate of tumor cells was determined by flow cytometry to investigate the inhibition effect of PLTL combined with local thermal therapy on the tumor. Results The inhibition rate of tumor in model control group, PTX group, PTL group and PLTL group was 21. 81% , 48. 87% , 57. 22% and 78. 87% , respectively. The apoptosis rate of tumor cells was (20. 4 ± 4. 2)% , (42. 7 ± 3. 8)% , (54. 6±2. 9)% and (69. 7±5. 0)% , respectively. Observed by pathology, apoptosis rate and necrosis number of tumor cells in PLTL group were significantly increased. Conclusion Compared with PTX and PTL, PLTL has an evident thermo-sensitive feature and can increase the anticancer effect of paclitaxel remarkably when combined with local hyperthermia.
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Objective To investigate the tumor inhibition effect of paclitaxel long-circulating thermo sensitive liposomes (PLTL) in mice bearing Lewis lung carcinoma cells. Methods A tumor-bearing mouse model was established, and the mice were randomly divided into five groups: control, heating, paclitaxel (PTX), paclitaxel thermo sensitive liposomes (PTL), and PLTL groups. The living status was observed in the mice. The volume and weight of the tumor were measured. The morphological changes in the tumor cells were observed f by HE staining and apoptosis of the tumor cells was determined by flow cytometry. Results The inhibition rate of tumor in PTX, PTL and PLTL groups was 48.87%, 57.22%and 78.87%, respectively. The apoptotic rate of tumor cell in PTX, PTL and PLTL groups was (42.7 ± 3 .8)%, (54.6 ± 2.9)%and (69.7 ± 5.0)%, respectively. Conclusions PLTL, as compared with PTX and PTL, has an evident thermo sensitive feature and increases the anticancer effect of paclitaxel remarkably in combination with local hyperthermia.
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ObjectiveTo examine the clinical features of fractures and related risk factors in patients with rheumatoid arthritis(RA) in China.MethodsSix hundred and eighty-one RA patients were randomly selected from department of rheumatology of 18 hospitals of China.Data were obtained from the questionnaire,including age,sex,disease duration,the involvement of joints,treatment regimen,features of fractures etc.The possible risk factors of fracture in patients with RA were analyzed with a multi-variate Logistic regression analysis.Results① In 681 RA patients of the survey,48 patients had 54 fractures,and the incidence of fractures was about 8％.② Fractures occurred at various sites.Foot/ankle,femur,spine and wrist were the mostfrequent sites.③ The Logistic regression analysis showed that several factors increased the risk of fracture in RA patients,including long disease duration (OR:1.245,95％CI:0.987-1.570,P=0.065),male gender(OR:0.433,95％CI:0.199-0.942,P=0.035),more deformed joints(OR:1.042,95％CI:1.006-1.079,P=0.023),family history of RA (OR:2.201,95％CI:0.984-4.923,P=0.055),and high scores of SF-36(OR:1.017,95％CI:1.002-1.033,P=0.028).④ According to the degree of correlation from strong to weak,the risk factors of fracture were disease duration,SF-36,sex,number of deformed joints and family history of rheumatoid arthritis.ConclusionThe incidence of fracture is high in patients with rheumatoid arthritis.Several factors could increase the risk of fractures in RA patients,including long disease duration,male gender,more deformed joints,and family history of RA.In order to prevent the occurrence of fractures,cautions should be taken to prevent the development of fractures and treat the disease aggressively to suppress the disease activity of RA.
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ObjectiveTo explore the effects and possible mechanisms of VCR combined with low dose cyclophosphamide(CTX) intermittently to treat severe systemic lupus erythematosus(SLE).It is assumed that this might be a new combination therapy for SLE and expected to improve the overall prognosis and outcome of SLE.MethodsMurine chronic graft-versus-host disease(cGVHD) model were developed for study.They were randomly divided into the control group,vincristine (VCR) pulse therapy group,CTX pulse therapy group,CTX every other day(EOD) group,VCR+CTX combination group.One way ANOVA and repeated measure variance analysis were used for statistical analysis.Results① Six weeks after cGVHD models were set up,the average 24-hour urine protein quantification was(5.02±0.88) mg,anti-dsDNA antibody was positive,and Ⅳ LN pathology could be observed histologically in the model murine.So cGVHD models were successfully developed.② Significantly difference in decreasing of 24-hour urine protein quantification was found in the CTX EOD group,VCR+CTX combination group and other groups (P＜0.01).Significant decrease in Cr,ALT,anti-dsDNA,was found in the CTX EOD group,VCR+CTX combination group,CTX pulse therapy group and other groups(P＜0.05).Decrease in urine MCP-1 and TGF-β1 could be detected,and statistical significant difference in these parameters could be found in the CTX EOD group,CTX pulse therapy group,VCR+CTX combination group and other groups (P＜0.01).MCP-1 and TGF-β1'expression in model kidney were reduced in the CTX EOD group,VCR+CTX combination group and had statistical significant difference in the CTX EOD group,VCR+CTX combination group,VCR pulse therapy group,and CTX pulse therapy group.③ VCRand CTX combination treatment was effectivein 24-hour urine protein quantification,blood Cr,ALT,anti-dsDNA and urine MCP-1,as well as urine TGF-β1 (P＜0.05).Conclusion ① The combination of VCR and CTX is synergistic in decreasing 24-hour urine protein quantification,Cr,and the expression of MCP-1,TGF-β1.② The adverse effect of VCR+CTX combination group is similar to VCR pulse therapy group and CTX pulse therapy group.
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Objective To investigate the lipid profiles of patients with primary Sjogren's syndrome (pSS) and to analyze the correlation between abnormal serum lipids and the inflammationsof SS. Methods One hundred and fourteen pSS patients and 20 gendermatehed healthy controls were studied. Serum lipids were measured in both groups. Results There was statistically significant difference between SS and healthy controls, and the serum HDL-c and apoA<,1 concentrations were significantly lower in patients (P<0.05). The incidence of abnormal serum lipids was 39.5% in these patients. Patients with abnormal lipids had longer course of disease, higher ESR level, lower salivary flow rate and more frequent parotid gland enlargement than those without abnormal lipids(P<0.05). Logistic regression analysis revealed statistically significant association between serum lipids levels and occurrence of parotid gland enlargement. Conclusion Findings from this study suggest that patients with SS have altered lipid profiles and the decrease of apoA, and HDL-c levels may be the correlated factors of SS. The inflammation of SS may cause changes in lipids metabolisms.
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Objective To investigate the effect of combination therapy by observing the salivary glands function and related organ pathology after given methotrexate (MTX) and cyclophosphamide (CTX) intermittently in induced mice model of Sjogren's syndrome (SS). To further explore the synergistic effect of combination therapy by detecting the immunological regulatory factor B cell activation factor belonging to the TNF family (BAFF) expression. Methods The ingredients of Lewis rat's exocrine glands homogenate were injected into female C57BL/6 mice to set up the mice model of SS. After established the SS mice model successfully, they were randomly divided into six SS model group, including low-dose MTX treatment group (0.02 mg/w), high-dose MTX treatment group (0.06 mg/w), CTX pause treatment group (1.2 mg/3 w), CTX alternate day treatment group (0.6 mg/2 d), MTX+CTX combination treatment group (MTX 0.02 mg/3 w+ CTX 1.2 mg/3 w). Treatment effects were assessed both clinically and histologically. Results Eighteen weeks after the first treatment, the improvement of the salivary secretion of the CTX alternate day treatment group and MTX+CTX combination treatment group were higher than other groups, which showed statistically significant difference (P<0.01). Compared with the SS model control group, HE staining showed that the lymphocytic infiltration of exoerine glands was decreased in the treatment group. In the CTX alternate day treatment group and MTX+CTX combination treatment group, few amount of inflammatory cell infiltration were found, and the expression intensity of BAFF mRNA and protein were decreased markedly in salivary gland than others by RT-PCR and immunohistochemistry assay (P<0.01). Conclusion MTX and CTX can inhibit lymphocytic infiltration of the salivary glands, inhibit BAFF transcriptional level and production of BAFF protein, leading to an increase of fluid production. It suggests that modulation of signaling via BAFF pathways may be a mechanism of action. MTX and CTX combination therapy is more effective than single-agent therapy. The inhibitory effects of MTX and CTX on BAFF-mediated inflammatory pathways are primarily synergistic.
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Objective To evaluate the value of IgA and IgG antibodies against α-fodrin in both serum antibodies in SS is also assessed.Methods Samples from 39 patients with SS(25 primary and 14 secondary),8 patients with systemic lupus erythematosus(SLE),and 15 patients with rheumatoid arthritis (RA)as well as 10 healthy blood donors were collected.Anti-α-fodrin antibodies were measured using ELISA.Results The titer of serum anti-α-fodrin was higher in SS than in other connective tissue diseases group and healthy group(P<0.01).IgA type anti-α-fodrin antibodies was detected in 60%.44% of serum and saliva in patients with pSS respectively.IgG antibodies were detected in 43% of sera,and 29% of saliva of patients with pSS.The sensitivity and specificity of serum anti-α-fodrin IgA in SS was 54%and 85%.The level of anti-α-fodrin was positively associated with xerostomia and parotid swelling (P<0.05),and was negatively associated with xeroma,renal tubule acidosis,lung interstitial disease and hepatic damages(P>0.05).Conclusion Saliva and serLlm anti-α-fodrin level may be diagnostic for SS.It may be a useful screening marker.