Clinical characteristics of patients with rheumatic diseases and abnormal liver function / 中华内科杂志

Objective:To investigate the clinical characteristics of patients with rheumatic diseases and abnormal liver function, as well as determine the proportion and severity of liver function abnormalities.Methods:Cross-sectional study. Data were collected from patients registered in the Chinese Rheumatism Date Center from 2011 to 2021. The rheumatic diseases analyzed in this study were rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren syndrome (SS), ankylosing spondylitis (AS), and gout. Patient data, including demographic characteristics [ such as age, sex, body mass index,(BMI), and smoking history], liver function test results [including alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase(ALP), and total bilirubin], and use of anti-rheumatic immune drugs and liver-protective drugs, were collected and compared between groups with normal and abnormal liver functions. In addition, the proportions of abnormal liver function were compared between sex and age groups.Results:A total of 116 308 patients were included in this study, including 49 659 with RA, 17 597 with SLE, 9 039 with SS, 11 321 with AS, and 28 692 with gout. The lowest proportion of liver function abnormalities was observed in patients with RA[11.02% (5 470/49 659)], followed by those with SS[17.97% (1 624/9 039)] and AS [18.22% (2 063/11 321) ], whereas patients with SLE [21.14% (3 720/17 597) ] and gout [28.73% (8 242/28 692)] exhibited the highest proportion of these abnormalities. Elevated ALT, mostly classified as grade 1, was the most commonly noted liver function abnormality, whereas elevated ALP was the least common. Some patients who took liver-protective drugs had normal liver function, with the lowest percentage observed in patients with gout [7.45% (36/483) ] and ranging from 21.7% to 30.34% in patients with RA, SLE, SS, and AS. The proportion of liver function abnormalities was higher in males than in females for all disease types [RA: 13.8%(1 368/9 906) vs. 10.3%(4 102/39 753); SLE: 33.6% (479/1 424) vs. 20.0% (3 241/16 173); SS: 25.4%(111/437) vs. 17.6%(1 513/8 602); AS: 20.1%(1 629/8 119) vs. 13.6% (434/3 202); and gout: 29.3% (8 033/27 394) vs. 16.1% (209/1 298)]. In RA, SLE, and AS, the proportions of liver function abnormalities were similar across all age groups. In SS, the proportion of liver function abnormalities increased with age [<40 years: 14.9%(294/1 979); 40-59 years: 18.1%(858/4 741); ≥60 years: 20.4%(472/2 319)], whereas a reversal of this trend was observed in gout [<40 years: 34.9%(4 294/12 320); 40-59 years: 25.5%(2 905/11 398);≥60 years: 21.0%(1 042/4 971)].Conclusions:The proportions of combined liver function abnormalities in patients with rheumatologic diseases were high, and the utilization rates of liver-protective drugs were low. It is necessary to pay more attention to monitoring patients′ liver function, timely administer liver-protective drugs, and optimize liver-protective regimens during the treatment of rheumatic diseases.

Enthesitis in patients with psoriatic arthritis: A nationwide data from the Chinese Registry of Psoriatic Arthritis (CREPAR) / 中华医学杂志(英文版)

BACKGROUND@#The clinical features of enthesitis in patients with psoriatic arthritis (PsA) have been reported in some Western countries, but data in China are very limited. This study aimed to describe the characteristics of enthesitis in Chinese patients with PsA and compared them with those in other cohorts.@*METHODS@#Patients with PsA enrolled in the Chinese Registry of Psoriatic Arthritis (CREPAR) (December 2018 to June 2021) were included. Data including demographics, clinical characteristics, disease activity measures, and treatment were collected at enrollment. Enthesitis was assessed by the Spondyloarthritis Research Consortium of Canada (SPARCC), Maastricht ankylosing spondylitis enthesitis score (MASES), and Leeds enthesitis index (LEI) indices. A multivariable logistic model was used to identify factors related to enthesitis. We also compared our results with those of other cohorts.@*RESULTS@#In total, 1074 PsA patients were included, 308 (28.7%) of whom had enthesitis. The average number of enthesitis was 3.3 ± 2.8 (range: 1.0-18.0). More than half of the patients (165, 53.6%) had one or two tender entheseal sites. Patients with enthesitis had an earlier age of onset for both psoriasis and arthritis, reported a higher proportion of PsA duration over 5 years, and had a higher percentage of axial involvement and greater disease activity. Multivariable logistic regression showed that axial involvement (odds ratio [OR] 2.21, 95% confidence interval [CI], 1.59-3.08; P <0.001), psoriasis area and severity index (PASI) (OR: 1.03, 95% CI: 1.01-1.04; P = 0.002), and disease activity score 28-C reactive protein (DAS28-CRP) (OR: 1.25, 95% CI: 1.01-1.55; P = 0.037) were associated with enthesitis. Compared with the results of other studies, Chinese patients with enthesitis had a younger age, lower body mass index (BMI), a higher rate of positive human leukocyte antigen (HLA)-B27, more frequent dactylitis, and a higher proportion of conventional synthetic disease-modifying antirheumatic drugs' (csDMARDs) use.@*CONCLUSIONS@#Enthesitis is a common condition among Chinese patients with PsA. It is important to evaluate entheses in both peripheral and axial sites.

Progress in signaling pathways related to the fibrosis mechanism in systemic sclerosis / 中华微生物学和免疫学杂志

Systemic sclerosis (SSc) is a complex and chronic autoimmune disease causing fibrosis in multiple tissues and organs. The cause of fibrosis may be related to the production of extracellular matrix (ECM) such as type Ⅰ and Ⅲ collagens, elastin and fibronectin resulting from the transformation of activated fibroblasts (FB) into muscle-forming fibroblasts (MFB). ECM could seriously damage the skin, lung, heart, kidney and other organs. At present, many studies have shown that several signaling pathways including TGF-β, mTOR, JAK/STAT, Wnt/β-Catenin, Hedgehog and Notch are involved in the proliferation of FB and the transformation of FB to MFB, which led to the production and deposition of a great quantity of ECM. Therefore, this article reviewed the relationship between these signaling pathways and fibrosis in SSc, hoping to provided reference for the development of effective treatments for SSc.

Therapeutic effects of IL-6 and BAFF fusion protein eukaryotic expression plasmid on animal model of Sj?gren′s syndrome / 中华微生物学和免疫学杂志

Objective:To investigate the effects of a eukaryotic expression plasmid for IL-6 and B-cell activating factor (BAFF) fusion protein on the histopathological changes in salivary and lacrimal glands of non-obese diabetic (NOD) mice with Sj?gren′s syndrome and to elucidate the possible therapeutic mechanism of IL-6/BAFF fusion protein eukaryotic expression plasmid in NOD mice.Methods:The eukaryotic expression plasmid for IL-6/BAFF fusion protein was constructed. After transfecting CHO cells with the plasmid, the expression of IL-6/BAFF fusion protein was detected by Western blot. BALB/c mice were injected with the plasmid every two weeks for three times and the titers of anti-IL-6 and anti-BAFF antibodies were measured by ELISA. Twenty-one NOD mice were randomly divided into three groups (control group, empty vector group and therapy group) by numerical table method. The mice in the therapy group were injected with the IL-6/BAFF fusion protein eukaryotic expression plasmid once a week for six times and the mice in the empty vector group were injected with empty plasmid. The levels of anti-IL-6 and anti-BAFF antibodies as well as cytokines (IL-6, BAFF, INF-γ, IL-10 and IL-17A) in mouse serum samples were detected by ELISA. The proportions of Th17, Treg, Th1 and Th2 cells in mouse splenocytes were measured by flow cytometry. Focal lymphocyte infiltration and pathological changes in the lacrimal and salivary glands of mice were observed under light microscopy after HE staining.Results:The eukaryotic expression plasmid for IL-6/BAFF fusion protein increased the levels of anti-IL-6 and anti-BAFF antibodies in the serum of BALB/c mice ( P<0.05). The levels of anti-IL-6 and anti-BAFF antibodies in the serum of NOD mice in the therapy group increased ( P<0.01), while the expression of IL-6, BAFF, INF-γ, IL-10 and IL-17A in NOD mice in the therapy group was lower than that in the control group and the empty vector group ( P<0.05). The percentages of Treg and Th2 cells in the splenocytes of NOD mice increased after treatment ( P<0.05). Moreover, the eukaryotic expression plasmid for IL-6/BAFF fusion protein significantly improved the irregular size and morphology of glandular vesicles in the lacrimal and salivary glands, reduced the ductal dilatation and decreased the focal lymphocyte infiltration in NOD mice. Conclusions:The eukaryotic expression plasmid for IL-6/BAFF fusion protein induced the production of anti-IL-6 and anti-BAFF antibodies, decreased the expression of inflammatory cytokines, regulated the balance of Th17/Treg and Th1/Th2 cells, improved the irregular alveolar structure and ductal dilation in the lacrimal and salivary glands and reduced the focal lymphocyte infiltration in NOD mice. This study showed that eukaryotic expression plasmid for IL-6/BAFF fusion protein might serve as a potential target for therapeutic targeting of T and B cells.

Recommendations of diagnosis and treatment of juvenile idiopathic arthritis in China / 中华内科杂志

The common clinical subtypes of juvenile idiopathic arthritis (JIA) include systemic onset juvenile idiopathic arthritis (SOJIA), oligoarthritis/polyarthritis juvenile idiopathic arthritis and juvenile spondyloarthritis. Juvenile idiopathic arthritis has no specific diagnostic index, and needs to be differentiated from infectious diseases and malignant diseases. The onset of SOJIA is rapid, the disease progresses rapidly, and it is easy to be complicated with macrophage activation syndrome (MAS) which is life-threatening. The experience of pediatric rheumatologists in dealing with JIA is still insufficient, and the standardized diagnosis and treatment level of this disease needs to be further improved. Based on the experience and guidelines of diagnosis and treatment in China and abroad, we formulated this diagnosis and treatment standard, aiming at standardizing the diagnosis and treatment of the subtypes of JIA and MAS, so as to reduce the incidence of disability and serious complications and improve the prognosis.

Effect of co-expression of IL-10 and sleeping beauty transposon on balance of Th17/Treg cells in splenocytes of NOD mice / 吉林大学学报(医学版)

Objective:To investigate the effect of co-expression of sleeping beauty(SB)transposon and IL-10 mediated by adenovirus on the balance of Th17/Treg cells in the splenocytes of the non-obese diabetes(NOD)mice, and to illuminate the possible mechanism of IL-10 in the treatment of NOD mice.Methods:The splenocytes were extracted from spleen of the C57BL6 mice and cultured.The splenocytes were divided into control group,empty vector group and therapy group.The cells in control group didn't receive any treatment,the cells in empty vector group were co-infected with the adenovirus vector without IL-10 gene containing transposon sequence and the adenovirus vector without transposase,and the cells in therapy cells were co-infected with the adenovirus vector containing IL-10 gene and transposon sequence and the adenovirus vector with transposase.After 48 h of infection, the expression leves of IL-10 mRNA in the splenocytes of the mice in various groups were assessed by RT-PCR. The cells of above three groups were subcutaneously injected into popliteal space in right hind leg of the NOD mice in control group,empty vector group and therapy group;there were six mice in each group;once a week and six times.The mice were killed 4 weeks after injection,the expression levels of IL-10 in serum of the NOD mice in various groups were assessed by ELISA,and the proportions of CD4+IL-10+,CD4+IFN-γ+,Th17 and Treg cells in the splenocytes were detected by flow cytometry.Results:Compared with control group and empty vector group,the expression level of IL-10 mRNA in splenocytes of the C57BL6 mice in therapy group was increased (F=72.71,P<0.05);the expression level of IL-10 in serum of the NOD mice was increased(F=8.89,P<0.05);the proportions of CD4+IL-10+ cells and Treg cells were significantly increased(F=72.09,P<0.05;F=12.98,P<0.05);the proportion of Th17 cells was decreased(F=6.39,P<0.05).The proportion of CD4+IFN-γ+ cells had no significant differences between various groups(F=2.72,P>0.05).Conclusion:The co-expression of SB transposon and IL-10 can significantly increase the IL-10 level in serum of the NOD mice,increase the proportion of CD4+IL-10+ cells,decrease the proportion of Th17 cells and increase the proportion of Treg cells in the splenocytes,which can regulate the balance of Th1/Th2 and Th17/Treg cells and play a therapeutic effect in the NOD mice.

Significance of anti-nucleosome antibody, anti-C1q antibody and anti-double stranded DNA antibody in diagnosis of lupus nephritis / 吉林大学学报(医学版)

Objective:To investigate the clinical and laboratory characteristics of lupus nephritis(LN) patients by detecting the anti-nucleosome antibodies, anti-C1q antibodies and anti-double stranded antibodies(anti-ds DNA), and to clarify the risk factors of LN in the patients with systemic lupus erythematosus(SLE),and the significance of three kinds of antibodies in diagnosis of LN.Methods:A total of 120 SLE patients were selected and divided into LN group(n=60) and non-LN group(n=60).The ANAS data of 120 patients were retrospectively analyzed,the levels of anti-C1q antibodies were measured.The clinical symptoms and laboratory data of the patients with positive anti-dsDNA,-nucleosome and-C1q antibodies (3-pos group)and negative three kinds of antibodies(non 3-pos group) were analyzed in LN group.Results:The positive rate of anti-C1q antibody of the patients in LN group (40.00%) was higher than that in non-LN group (21.67%) (χ2=4.728, P=0.03).The positive rate of anti-dsDNA antibody in LN group was 66.67%, and it was 46.67% in non-LN group;the positive rates of the patients had significant difference between two groups (χ2=4.887, P=0.027).The positive rate of anti-nucleosome antibody in LN group was 58.33%, and it was 40.00% in non-LN group;the positive rates of the patients had significant difference between two groups (χ2=4.034, P=0.045).The positive rates of U1-snRNP, SmD1 and other antibodies Jo-1, SSA/Ro60kD, SSA/Ro52kD, SSB, ScL-70, CENP-B,and P0 had no significant differences between two groups(P>0.05).The levels of C3 and C4 and hemoglobinin of the patients in 3-pos group were higher than those innon 3-pos group (P0.05).The clinical symptoms were not statistically significant in 3-pos and non 3-pos groups (P>0.05).Conclusion:The anti-nucleosome, anti-C1q and anti-dsDNA antibodies are the risk factors of SLE complicated with LN;the positive antibodies can improve the diagnostic rate of LN.The 3-pos patients have more severe damage in complements and blood system with higher renal disease activities.

Analysis of clinical characteristics in elderly onset rheumatoid arthritis patients combined with interstitial lung disease / 中国综合临床

Objective To analyze the clinical characteristics in elderly onset rheumatoid arthritis(RA) patients combined with interstitial lung disease(ILD).Methods Four hundred and four cases of elderly onset RA patients were summarized.They were divided into two groups according to whether combined with ILD.Its clinical manifestations,laboratory examinations and combined diseases were analyzed.Results (1)Male elderly patients with onset of RA were more likely to occur ILD than female(χ2=6.251,P=0.012).There was no significant difference in duration analysis of two groups(t=1.750,P=0.081).(2)The elderly onset patients in RA with knee pain were more likely to happen ILD(χ2=7.048,P=0.008),the difference was significant.And there was no significantly statistical difference in the shoulder joint pain(χ2=0.028,P=0.866),elbow pain(χ2=0.022,P=0.882),hand joint pain(χ2=2.041,P=0.153),hip pain(χ2=0.129,P=0.720),joint deformities(χ2=0.013,P=0.908),morning stiffness(χ2=0.000,P=0.984) and joints rheumatoid nodules(χ2=0.349,P=0.555) of two groups.(3)The elderly onset RA patients with a high level of serum RF were more likely to happen ILD(t=3.325,P=0.001),the difference was significant.And there was no significantly statistical difference in serum ANA antibodies(χ2=0.004,P=0.948),anti SSA(χ2=0.718,P=0.397),SSB antibody(χ2=0.638,P=0.424),AKA antibody(χ2=0.949,P=0.330),CCP antibody(χ2=0.500,P=0.479) and the level of ESR(t=0.582,P=0.561),CRP(t=0.381,P=0.703) and PLT(t=-1.246,P=0.213).(4)The elderly onset RA patients with ILD were more likely to appear osteoporosis(χ2=7.467,P=0.006),the difference was significant.And there was no significantly statistical difference in the occurrence of high blood pressure(χ2=0.403,P=0.526) and diabetes(χ2=0.180,P=0.671) in the two groups.Conclusion Male patients,the elderly onset RA patients with knee pain and associated with high level of serum RF more often occur with ILD.And the elderly onset RA patients with ILD are more likely to appear osteoporosis.

Effect of CD40 siRNA on inflammatory response of MRL/Lpr mice / 北京大学学报(医学版)

Objective:To observe the effect of CD40 siRNA on expression of IFN-γ,IL-17,IL-4 and anti-dsDNA antibody of systemic lupus erythematosus (SLE)animal model MRL/Lpr mice and to discuss its therapy on MRL/Lpr mice.Methods:In the study,16 female MRL/Lpr mice were randomly divided into control group (n =4),empty vector group (n =4),CD40-siRNA1 group (n =4)and CD40-siR-NA2 group (n =4).The vectors expressing siRNA against CD40 were injected by tail veil into MRL/Lpr mice,while MRL/Lpr mice in control group and empty vector group were injected with the same dose of PBS and pGFP-V-RS vector respectively.The injection was given six times and every one day.The mice were sacrificed 14 d after injection,and the spleen tissue was weighed.The pGFP-V-RS was labeled by green fluorescent protein(GFP)and the tissue sections were observed whether siRNA expressed in the spleen.The expression levels of IFN-γ,IL-17,IL-4 and anti-dsDNA antibody in the sera were detected by ELISA method on the 1st day before the first time and the 2nd,5th,8th,11th,and 14th days after last injection,and the expression levels of CD40 mRNA in spleen tissue of MRL/Lpr mice were detected by RT-PCR and the expression levels of CD40 protein in spleen tissue of MRL/Lpr mice were detected by immunohistochemistry method.Results:The expression vector of CD40-siRNA could express in the spleen of MRL/Lpr.The spleens in CD40-siRNA1 group [(78.85 ±5.61 )mg]and CD40-siRNA2 group [(80.25 ±4.07)mg]were lower than those in control [(141.88 ±7.81)mg]and empty vector group [(153.10 ±7.60)mg].The levels of IL-17,IFN-γand anti-dsDNA antibody were lower and the levels of IL-4 was higher in CD40-siRNA1 group and CD40-siRNA2 group on the 2nd,5th and 8th days after last injection than on the 1st day before the first time (P 0.05). Though the levels of anti-dsDNA antibody in CD40-siRNA1 group and CD40-siRNA2 group on the 11th day was higher than on the 8th day,there was more significance than those in control group and empty vector group (P <0.05).There was no significance between the 4 groups on the 14th day.The levels of CD40 mRNA and protein were lower in CD40-siRNA1 group and CD40-siRNA2 group than in control group and empty vector group on the 14th day after last injection (P <0.05).Conclusion:CD-40 si-RNA can reduce the concentration of IL-17,IFN-γand of anti-dsDNA antibody in serum,and at the same time,it can elevate the concentration of IL-4 and suppress CD40 mRNA and protein of spleen in MRL/Lpr.Meanwhile after suppressing CD40 mRNA and protein,it can reduce inflammatory response of the mice and the disease activity of MRL/Lpr,suggesting that CD-40 siRNA has therapy effect on SLE.

Effect of α-Fodrin siRNA on human salivary gland cells / 重庆医学

Objective To observe the effect of α‐Fodrin siRNA on human salivary gland(HSG)cells and to discuss its thera‐py on sj?gren′s syndrome(SS) .Methods The vectors expressing siRNA againstα‐Fodrin of human were transfected into HSG cells of 10μg α‐fodrin siRNA1 group andα‐Fodrin siRNA2 group ,while pGFP‐V‐RS vector were transfected into the cells of empty vec‐tor group ,there was no handling in HSG cell of control group .The efficiency was observed by fluorescence microscope after trans‐fection of 24 ,48 ,72 and 96 h by lipofectamine 2000 .The expression levels of α‐Fodrin mRNA and protein of HSG were detected by real‐time(RT)‐PCR and immunohistochemistry method respectively .The expression levels of IFN‐γ and IL‐10 in supernatant of cells were detected by ELISA .Results The efficiency was highest on 48 h after transfection .The level of α‐Fodrin mRNA and pro‐tein was lower in α‐fodrin siRNA1 group and α‐fodrin siRNA2 group than control group and empty vector group on 48 h after transfection (P0 .05) .The levels IFN‐γ in α‐fodrin siRNA1 group and α‐fodrin siRNA2 group were lower than of control group and empty vector group on 48 h after transfection ,but there were no significant differences in the four groups (P>0 .05) .Conclusion Theα‐fodrin siRNA1 andα‐fodrin siRNA2 can suppress the levels of α‐fodrin mRNA and protein of HSG cells ,at the same time;they can elevate the expression of IL‐10 and decrease the level of IFN‐γ.Soα‐Fodrin siRNA reduce the levels of inflammatory cyto‐kines and provide experimental basis to therapy of SS .

E ffect of deacetylase inhibitor VPA on polarization of macrophages / 中国免疫学杂志

Objective:By analyzing the effect of deacetylase inhibitors on macrophage polarization process of histone modification,and the influence of the process of macrophage polarization ,analysis deacetylase inhibitors whether have the effect on the activity of the macrophage polarization by altered histone modification of macrophages , in order to provide a new perspective for the treatment of autoimmune diseases .Methods:Using lipopolysaccharide ( LPS) and interferon-γ( IFN-γ) to stimulate J774.1 cells for 24 h,and interleukin-4 ( IL-4 ) to stimulate J774.1 cells for 24 h.And 2 mmol/L valproic acid ( VPA ) was added in the induction process.Collecting J774.1 cells,fluorescent quantitation PCR assay and ELISA assay was used for the detection of specific markers of gene expression in macrophage polarization , flow cytometry and immunofluorescence assay for the detection of histone modifications.Results:J774.1 cells were polarized into M1 macrophages which were stimulated by LPS and IFN-γfor 24 h;and also J774.1 cells were polarized into M2 macrophages which were stimulated by IL-4 for 24 h.The degree of acetylation of H 3K9 for M1 phenotype was increased after VPA treatment , the expression of interleukin-6 (IL-6 ) , inducible nitric oxide synthase ( iNOS ) , and chemotactic factor(CCL-2) was decreased,and the expression of CD86 was increased.The degree of acetylation of H3K9 for M1 phenotype was also increased after VPA treatment ,and also the expression of Arginase,Fizz-1,mannose receptor(CD 206) and Ym1 were increased.Conclusion:The polarization state of the macrophages and histone modification had a certain relevance .VPA could induce the transformation of M1 phenotype to M2 phenotype in the induction system of the M1 macrophages,however,the expression of specific genes in M1 phenotype was inhibited in the induction system of the M 2 macrophages.

Effect of CD40 siRNA on lupus nephritis of MRL/Lpr mice / 中国免疫学杂志

Objective:To observe the effect of CD40 siRNA on the changes in kidney,urinary protein and complement C3 of MRL/Lpr mice and explore its therapy on lupus nephritis.Methods: 16 female MRL/Lpr mice were randomly divided into control group,empty vector group,CD40-siRNA1 group and CD40-siRNA2 group.The vectors expressing siRNA against CD40 were injected by tail veil into MRL/Lpr mice,while MRL/Lpr mice in control group and empty vector group were injected with the same dose of PBS and pGFP-V-RS vector respectively.There were six times injection and every one day.The 24 hours urine output was gathered 24 hours before mice were killed.Fourteen days following administration,these mice were killed,tissue sections of kidney were observed if the signal of siRNA were expressed in kidney.The expression levels of CD40 mRNA and protein in kidney tissue of MRL/Lpr mice were detected by RT-PCR and immunohistochemistry methods respectively.At the same time,the pathological changes of the kidney were observed by haematoxylin-eosin ( HE) staining method.The 24 h urinary protein content was detected using the method of coomassie brilliant blue and the expression levels of complement C3 in serum were detected by Immunoturbidimetric assays.Results:The vector of CD40-siRNA was expressed in kidney of MRL/Lpr.The expression levels of CD40 mRNA and protein in kidney were lower in CD40-siRNA1 group and CD40-siRNA2 group than control group and empty vector group on the 14th day after last injection ( P<0.05).The inflammatory cells infiltration of kidney and some glomerular volume were significantly reduced in CD40-siRNA1 group and CD40-siRNA2 group than control group and empty vector group.The renal tubular swelling was alleviated in CD40-siRNA1 group and CD40-siRNA2 group than control group and empty vector group.The levels of 24 hours urinary protein were lower and the levels of complement C3 were higher in CD40-siRNA1 group and CD40-siRNA2 group than control group and empty vector group ( P<0.05). Conclusion:CD-40 siRNA can suppress the expression levels of CD40 mRNA and protein and decrease inflammatory cells infiltration in kidney of MRL/Lpr.Meanwhile after suppressing expression of CD40 mRNA and protein, it can reduce the content of 24 hours urinary protein and elevate the level of complement C3 in serum,which CD-40 siRNA can delay progress of the disease and protect kidney,so that it has therapy effect on lupus nephritis.

The features of patients with cyclic citrullinated peptide antibodies in primary Sj(o)gren's syndrome / 中国医师杂志

Objective To investigate the features of patients with cyclic citrullinated peptide (CCP) antibodies in primary Sj(o)gren's syndrome (pSS) with the retrospective method.Methods Seventy eight pSS patients were studied.Enzyme-linked immunosorbent assay (ELISA) indirect immunofluorescence was used to measure anti-CCP antibodies.The patients with and without anti-CCP antibodies were correspondingly classified as autoantibody-positive and negative pSS groups.Clinical and laboratory features were compared between autoantibody-negative and positive group.Results (1) Seven (9.0％) of pSS patients had positive anti-CCP antibody.No significant difference was found in sex,ages,and disease course between autoantibody-nagative and positive pSS patients.(2) The anti-CCP-positive pSS was associated with the rates of decayed tooth,fatigue,dry mouth,dry eyes,and tender of joint (P ＜ 0.05).Whereas,the antiCCP-negative pSS was not significantly related to fever and mumps (P ＞ 0.05).(3)From serologic characteristics aspects,the anti-CCP-positive patients showed higher level of tender of joint than the anti-CCP-negative patients.No significant difference was found in white blood cell (WBC),hemoglobin (HGB),platelet (PLT),erythrocyte sedimentation rate (ESR),C-reactive protein (CRP),immunoglobulin A (IgA),IgG,IgM,and rheumatoid factor (RF) between two groups (P ＞ 0.05).Conclusions The anti-CCP-positive patients were 9％ ofpSS patients,and were more likely to occur tender of joint with higher level of tender of joint.

Clinical value of anti-cyclic citrullinated peptides antibody in diagnosis, treatment and prognosis of rheumatoid arthritis / 中国免疫学杂志

Objective:To investigate the diagnostic values of anti-cyclic citrullinated peptides antibody ( anti-CCP ) and rheumatoid factor( RF) in rheumatoid arthritis( RA) ,and analyse the clinical relevance of prognosis,drug reaction and bone destruction between anti-CCP and RA.Methods: Serum anti-CCP was detected by enzyme-linked immunosorbent assay ( ELISA ) , and RF was detected by immune rate nephelometry.Results:The sensitivity and specificity of anti-CCP in RA were 83.0%and 96.7%,while the sensitivity and specificity of RF in RA were 76.0%and 70.0%.When joint detect anti-CCP and RF,with anti-CCP or RF positive as a positive determination,with anti-CCP and RF negative as a negative judgment,the combined sensitivity was 87.0%,higher than that of detection alone.The combined specificity was 98.3%, higher than that of single detection.There were big different concentrations of anti-CCP among RA patients before treatment, three months after treatment and six months after treatment.There were significant differences between bone erosion and non-bone erosion in RA patients.And the more serious joint damage,the higher the concentrations of anti-CCP.As for treatment,anti-CCP concentrations declined.Conclusion:Combined detection of anti-CCP and RF can significantly improve the diagnosis and differential diagnosis of RA.The concentration of anti-CCP can change with effective treatment,then dynamic monitoring can be used as study drug efficacy.At the same time,the level of anti-CCP in patients with RA can reflect the degree of bone erosion,and serious bone destruction who was poor treatment effect.

Immunoregulation role of adipose mesenchymal stem cells in J774.1 cells / 中国组织工程研究

BACKGROUND:Recent studies have found that adipose mesenchymal stem cells can inhibit immune responses of T cells, B cells and dendritic cells. But it is unclear whether adipose mesenchymal stem cells are able to regulate the immune responses of macrophages. OBJECTIVE:To observe the expression of interleukin-6 and tumor necrosis factorαin J774.1 cells co-cultured with adipose mesenchymal stem cells co-cultured. METHODS:Adipose mesenchymal stem cells at a density of 2×107 per wel were inoculated into the upper chamber of the transwel and 24-wel plates. Then, J774.1 cells were suspended with cellculture medium containing 1 mg/L lipopolysaccharide and planted into the lower chamber of the transwel and 24-wel plates containing adipose mesenchymal stem cells as co-culture group. Meanwhile, inactive J774.1 cells to lipopolysaccharide-activat J774.1 cells served as negative and positive control groups, respectively. After 48 hours, the J774.1 cells were col ected to extract the RNA samples. Then, mRNA expressions of interleukin-6 and tumor necrosis factorαwere measured by real-time quantitative PCR. RESULTS AND CONCLUSION:Compared with the positive control group, direct-contact co-culture of adipose mesenchymal stem cells and J774.1 cells significantly reduced expressions of interleukin-6 and tumor necrosis factorαin J774.1 cells, but non-contact co-culture only reduced interleukin-6 expression. These findings indicate that adipose mesenchymal stem cells can inhibit the immune response of J774.1 cells activated by lipopolysaccharide.

Prevalence and significance of immunoglobulin G-anti-cyclic citrullinated peptide an-tibodies in primary Sj?gren’ s syndrome patients / 北京大学学报(医学版)

Objective:To investigate the prevalence and significance of IgG-anti-cyclic citrullinated pep-tides (CCP) antibody in PSS patients .Methods:A total of 120 patients diagnosed with PSS were investi-gated in the first affiliated hospital of Baotou Medical College from March 2006 to December 2009.IgG-anti-CCP antibody was assayed by enzyme-linked immunosorbent assay (ELISA), also anti-Sj?gren’s syn-drome type A ( SSA) and Sj?gren’ s syndrome type B ( SSB) antibody were assayed by immunoblotting . Erythrocyte sedimentation rate ( ESR ) was assayed by westergren in serum , and C reactive protein (CRP), IgA, IgM, IgG and IgM-RF were detected by immune turbidimetric .At the same time, clinical symptoms and involvement of important organs were observed .Following up the patients above 3 years, the primary Sj?gren’ s syndrome ( PSS) patients who had progressed to rheumatoid arthritis ( RA) were evaluated .Results:The positive rate of anti-CCP antibody in the PSS patients was 19 .17%; After 3 years, more patients who were positive for anti-CCP antibody had progressed to RA (χ2 =5.015,P=0.022) than the patients in negative group;The patients in anti-CCP antibody positive group were more prone to joint involvement (χ2 =8.058,P0.05); The positive rate of anti-SSA and SSB antibody in anti-CCP antibody positive group and negative group had no significant difference (χ2 =0.008 and 0.56,P>0.05);Multiple linear regression showed that the level of anti-CCP antibody was positively correlated with IgM-RF levels in the PSS patients (B=0.61, 95%CI =0.36 -0.86, P0.05).There were no significant differences in the level of ESR, CRP, IgA, IgM and IgG between anti-CCP antibody positive group and negative group ( P >0.05), but the level of IgM-RF in anti-CCP antibody positive group was significantly higher than that in the negative group (U=623.50, P<0.05).Conclusion:Positive rate of IgG-anti-CCP antibody in PSS is 19 .17%, also it is associated with joint involvement and more prone to progressing to RA .

Analysis of dyslipidemia and the correlated disease factors in systemic lupus erythematosus patients / 中华风湿病学杂志

Objective To explore the clinical significance of dyslipidemia in patients with systemic lupus erythematosus (SLE).Methods By independent-samples t test,serum lipid level was compared between 326 SLE patients and 300 healthy controls.The total cholesterol (TC),triglyceride (TG),lowdensity lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels were partially compared in subgroups of SLE patients.The correlation of serum TC,TG,LDL-C and HDL-C with clinical manifestations and laboratory findings in SLE was analyzed by Pearson or Spearman correlation analysis.Results ①The serum levels of TC [(3.8±1.5) mmol/L],TG [(2.1±1.6) mmol/L] and LDL-C [(2.1±0.9) mmol/L] were significantly higher in SLE group than those of the control group [(3.4±0.6),(0.8±0.4),(1.9± 0.5) mmol/L],and the serum level of HDL-C [(1.2±0.9) mmol/L] was significantly lower in SLE group than that of the control group [(2.0±0.5) mmolFL] (t=4.953,P=0.000; t=14.569,P=0.000; t=3.204,P=0.001; t=-14.335,P=0.000].② The serum levels of TC [(4.0± 1.7) mmol/L],TG [(2.5± 1.7) mmol/L] and LDL-C [(2.2±1.0) mmol/L] were significantly higher in LN group than those of the non-LN group [(3.6±1.0),(1.6± 1.0),(1.9±0.7) mmol/L; t=2.646,P=0.009; t=6.292,P=0.000; t=3.261,P=0.001].③ The serum level of TG [(2.2±1.6) vs (1.8±1.4) mmol/L] was significantly higher in SLE patients with hypocomplementemia than that of the normal ones (t =2.098,P=0.038).The serum level of HDL-C [(1.1 ±0.4) vs (1.6± 1.7) mmol/L] was significantly lower in SLE patients with hypocomplementemia than that of the normal ones (t=-2.375,P=0.020).④ The serum level of TG [(2.3±1.7) vs (2.0±1.4) mmol/L] was significantly higher in anti-dsDNA antibody positive patients than that of negative ones (t=1.989,P=0.048).The serum level of HDL-C [(1.5± 0.4) vs (1.4±1.2) mmol/L] was significantly lower in anti-dsDNA antibody positive patients than that of negative ones (t=-2.979,P=0.003).⑤ The lipid level was correlated with the clinical manifestations and laboratory findings in SLE patients.Conclusion Dyslipidemia exists in patients with SLE and has close correlation with LN,hypocomplementemia and positive anti-dsDNA antibody.

Prevalence and significance of anti-SSA60 antibodies and anti-SSB antibodies in systemic lupus erythematosus patients / 中华风湿病学杂志

Objective To investigate the detection rate of anti-SSA60 and SSB antibodies in sera of patients with systemic lupus erythematosus (SLE).The correlation of anti-SSA and SSB antibodies with SLE clinical outcome was also investigated.Methods This study included 251 cases of SLE diagnosed in our hospital between 2007 and 2010.ELISA and double immunodiffusion method was used to detect the sera antiSSA60 and SSB antibodies.The patients were closely monitored for three years in terms of clinical and laboratory parameters and the presence of associated Sj(o)gren' s syndrome (SS).Statistical analysis were performed using student t test or x2 test.Results ① The detection rate of anti-SSA60 antibody in serum of patients with SLE was 65.3％.The detection rate of anti-SSB antibody in serum of patients with SLE was 28.3％; ② During the three-year follow up,patients with anti-SSA60 (29.3％,48 cases) or SSB antibodies (35.2％,25 cases) were more likely to have dry mouth and eyes and later developed SS (P＜0.05); ③ Patients with anti-SSA60 antibody were more likely to develop serositis (20.7％ vs 8.0％),neuropsychiatric lupus erythematosus (NPLE)(18.9％ vs 8.0％),and hematuria (35.4％ vs 21.8％)(P＜0.05).Patients with negative anti-SSB antibody were more likely to have fever (43.7％ vs 57.8％,x2=4.082,P＜0.05); ④ Patients positive for anti-SSB antibody were also positive for anti-Sm antibody (50.7％ vs 32.8％,x2=6.956,P＜0.05);⑤ Younger patients were more likely to have anti-SSA60 and SSB antibodies in their sera (P＜0.05); ⑥Patients positive for anti-SSA60 antibody had higher SLE disease activity index (SLEDAI) than patients with negative anti-SSA60 antibody [(17±9) vs (15±7),t=2.389,P＜0.05].Patients positive for anti-SSB antibody had higher level of IgG [(18±7) vs (16±6) g/L,t=2.304,P=0.023],and lower level of CRP than patients negative for anti-SSB antibody [(14±20) vs (21±33) mg/L,t=-2.173,P=0.031].Conclusion Patients positive for anti-SSA60 antibody have higher SLEDAI and more severe clinical outcomes.Patients with antiSSA or anti-SSB antibody are more likely to develop dry mouth and eyes which eventually leads to SS.

Diagnostic value of anti-mutated citrullinated vimentin antibodies for rheumatoid arthritis / 中国免疫学杂志

Objective: Combined detection of anti-mutated citrullinated vimentin ( anti-MCV ) antibodies, anti-cyclic citrullinated peptide ( anti-CCP) antibodies and rheumatoid factor ( RF-IgM) levels to investigate the diagnostic value of anti-mutated citrullinated vimentin (anti-MCV) antibodies for rheumatoid arthritis(RA).Methods: A total of 359 patients with RA,128 patients with other rheumatic diseases and 90 healthy controls were involved.Enzyme linked immunosorbent assay ( ELISA) was used to detect anti-MCV and anti-CCP, and dynamic immune nephelometry was applied to detect RF-IgM .The sensitivity and specificity were obtained from the experimental data.Results:The sensitivities of anti-MCV,anti-CCP and RF-IgM were 85.1%,76.7% and 82.7%in RA respectively.The specificities were 93.2%,95.1%and 80.1%respectively.Combined detection of anti-MCV and anti-CCP,the sensitivity decreased to 70.2%; but the specificity increased to 98.7%.The sensitivity reached to 89.5% with specificity 97.6%when the union of anti-MCV and anti-CCP positivity was used as criterion.Conclusion:Anti-MCV and anti-CCP are novel makers for RA diagnosis with high sensitivity and high specificity.Combination of anti-MCV and anti-CCP is more helpful for RA diagnosis.

Construction of TNF-αsiRNA Expression Vector and its Therapeutic Effect on TNF-αand IL-1 in TypeⅡCollagen Induced Arthritis Rat / 天津医药

Objective To investigate the therapeutic effect of tumor necrosis factor (TNF)-αsiRNA on typeⅡcolla-gen induced arthritis (CIA) in rats. Methods The expression vectors of siRNA against TNF-αgene were constructed suc-cessfully and were injected by tail veil into CIA rats. Twenty-four CIA rats were randomly divided into 4 groups including model group, empty vector group, TNF-α-siRNA1 group and TNF-α-siRNA2 group. CIA rats were injected with the same dose of phosphate buffered sodium (PBS) and pGFP-V-RS vector respectively in model group and empty vector group, while TNF-α-siRNA1 group and TNF-α-siRNA2 group were injected with TNF-α-siRNA1 eukaryotic expression vector and TNF-α-siRNA2 eukaryotic expression vector respectively. Another 6 rats, which were not established CIA model, were in-jected with PBS (blank control group). The serum expression levels of IL-1 were detected by ELISA on day 1, 5, 9 and 13 af-ter injection. The expression level of TNF-αmRNA was detected by reverse transcriptase polymerase chain reaction (RT-PCR) on day 13. Results The expression level of IL-1 was significantly higher on day 1, 5, 9 and 13 in model group than that of blank group (P＜0.05). The expression levels of IL-1 were significantly lower on day 1, 5 and 9 in TNF-α-siRNA1 group and TNF-α-siRNA2 group than that of model group and blank group (P ＜ 0.05). The expression level of TNF-αmRNA was significantly higher on day 13 in model group than that of blank group (P＜0.05). The expression levels of TNF-αmRNA were significantly lower in TNF-α-siRNA1 group and TNF-α-siRNA2 group than those of model group and emp-ty vector group (P＜0.05). Conclusion TNF-αspecific siRNA can suppress the levels of TNF-αmRNA and IL-1, which provides experimental basis for gene therapy of rheumatoid arthritis.