Objective:Anti-cyclic citrullinated peptide (CCP) antibody is an important biomarker as-sociated with the diagnosis and prognosis of rheumatoid arthritis (RA). Different studies showed inconsistency in the relationship between anti-CCP antibody titers and RA disease activity. Therefore, we investigated the association between anti-CCP antibody with the possibility of achieving treatment target and flare.Methods:The enrolled RA patients must be anti-CCP antibody positive at baseline, and had at least one test result of anti-CCP antibody during follow-up at least one year after the baseline. The patients were divided into declined group and non-declined group according to the decrease of anti-CCP antibody titer over 10% or not during follow-up from the baseline. Single factor comparison, Pearson correlation, Spearman correlation and Kendall correlation analysis were used.Results:A total of 124 patients were included in this study. Sixty-five and 59 patients were in anti-CCP antibody declined and non-declined groups, respectively. At the end of the follow-up, the proportion of patients who achieved clinical remission or low disease activity were 78%(51/65) and 68% (40/59)in the declined and the non-declined groups, respectively ( P=0.181). The changes of Disease Activity Score with 28 joint (DAS28)-C-reaction protein (CRP), DAS28-erythrocyte sedimentation rate (ESR), tender joint count (TJC) and CRP in the declined group were significantly greater than those of the non-declined group ( P values <0.05). There was no positive correlation between anti-CCP antibody titer and several disease activity indicators at baseline ( r values <0.3, P values >0.05). The changes of anti-CCP antibody titers during the follow-up were also not correlated with changes in disease activity (but r values <0.3, P values <0.05). Meanwhile, both the baseline anti-CCP antibody titers and the changes of the anti-CCP antibody titers during follow-up were neither correlated with whether the patient achieved clinical remission or low disease activity at the end of the follow-up nor whether relapse happened. Conclusion:There is no significant correlation between anti-CCP antibody levels at baseline and disease activity, achievement of treatment target, or recurrence after treatment. The value of anti-CCP antibody in assessing disease activity, predicting treatment response, and predicting relapse needs to be confirmed in further large-scale prospective studies.

Objective To examine the effects of IL-10 on cardiac fibroblasts ( CFBs) proliferation and phenotype transformation to myofibroblasts (MyoFbs) induced by transforming growth factor-β1 (TGF-β1);and to investigate the regulating pathways .Methods Cardiac fibroblasts were isolated from cardiac ventricles of neonatal SD rats . The passage 2~4 were used and divided into the following groups for treatment:1) control group, 2) IL-10 reac-tion group, 3) TGF-β1 reaction group, and 4) IL-10 plus TGF-β1 reaction group (TGF-β1 treatment followed with IL-10 pretreatment ) .Cells proliferation was assessed by MTT assay and immunocytochemistry staining for prolifera-ting cell nuclear antigen (PCNA);the phenotype transformation into MyoFbs was assessed by immunocytochemistry of α-smooth muscle actin (α-SMA);extracellular signal related kinase ( ERK1/2) and P38 kinase pathways were assessed by western-blot.Results TGF-β1 (10 μg/L) treatment boosted the proliferation and the expression ofα-SMA significantly (P<0.01), while IL-10 (10, 50 or 100 μg/L) plus TGF-β1 co-treatment induced lower cell proliferation and expression of α-SMA than treating with TGF-β1 alone ( P<0.05 ) , with the inhibitory effect of IL-10 being concentration dependent .TGF-β1 could significantly stimulate the ERK 1/2 and P38 kinase phospho-rylation ( P<0.01 ) , however IL-10 (100 μg/L) plus TGF-β1 co-treatment failed to down-regulated the phospho-rylation of ERK1/2 and P38 kinase compared with TGF-β1 alone ( ERK1/2:P<0.05;P38:P<0.01 ) .Conclu-sions IL-10 can attenuate TGF-β1-induced CFBs proliferation and phenotype transformation to MyoFbs .The in-hibitory effects may explained by a mechanism of inhibiting the activation of ERK 1/2 and P38 kinase .

SUMMARY A 36-year-old woman had an 8-year history of systemic lupus erythematosus (SLE) and was being treated with 10 mg/d of prednisone.She presented with a 6-month history of intermittent fever and multiple painful multi skin erythematous macules in her button, hips and extremities that had slowly en-larged to 8 cm ×4 cm in diameter.The lesions started as painful erythematous macules, which eventually ulcerated and scared.Laboratory tests showed leukopenia, protenuria, positive anti-double strand DNA and hypocomplementemia.Cultures of the bottom ulcer were E.Coli, fugus and Tuberculous mycobacteria were both negative.Biopsy was performed and revealed necrosis of epidermis, thrombus and cellulose de-generation in epidermis with neutrophils karyorrhexis and vasculitis.Her SLE was active, so she was pre-scribed antibiotics for 2 weeks and prednisone was added to 60 mg/d for a month.However her skin ul-cers did not relieve.When prednisone was added to 120 mg/d with combination therapy of cyclophospha-mide and hydroxychloroquine, her skin ulcer cicatrized gradually.

Objective To assess the clinical features and risk factors of coronary heart disease(CHD)in patients with systemic lupus erythematosus (SLE).Methods The clinical data of 32 lupus patients with CHD and 64 age and sex-matched lupus patients without CHD from a total of 1792 in-patients with lupus from January 1994 to December 2008 were collected and retrospectively analyzed.The traditional risk factors of atherosclemsis as well as their association with the characteristics of lupus were evaluated and compared between the two group of patients.Results The average age of CHD group was(51±12)years with an average disease duration of((8±6) years、.The most common coronary events were acute myocardial infaretio(53%)and non-stable,angina[34%).Among the 12 patients who accepted coronary angiography or computed tomography scan of coronary artery,11 patients had significant atheroselerosis lesions and 1 had thrombosis in coronary arteries.Their atheroselerosis lesions were severe,which manifested as diffuse stenosis and severe calcification.Compared to the control group,the CHD group patients had more traditional risk factors[(3.9±1.8)vs(2.0±1.6),P<0.01 j as well as higher prevalence of hypertension,hyperlipidemia,postmenopausal and smoking(P<0.05).Meanwhile,the CHD group patients had longer SLE duration[12.0(6.3~19.8)vs 2.0[O.8～9.0)years,P<0.01)J,higher C3 level[(750±364)vs(598±267)mg/L,P<0.05]and higher totalprednisone dose[28.8(0~49.8)vs 24.0(0~24.6)g,P<0.05]compared to patients without CHD.No significant differences were found in auto-antibodies,SLE disease activity,organ damage,average Drednisone dose and cyclophosI,hamide usage between the two groups of patients.Multi-variate analysls showed more traditional risk factors(OR:1.62)and longer SLE duration(OR=1.09)Were independent predictors of CHD.Condusion Atherosclerosis is a common pathological change of coronary in lupus patients with CHD.Traditional risk flactors of atherosclerosis and lupus duration are identified to be the independent risk factors of CHD in SLE patients.Early interventions for traditional risk factors and appropriate control of lupus arerecommended.

Objective To evaluate the correlation between pathological findings and clinical characteristics of patients with Sj(o)gren's syndrome (SS). Methods Eighty-four patients diagnosed with SS from 119 suspected ones at Peking University First Hospital were recruited. According to the pathological changes of lip biopsy, 64 patients were focus score (FS)( + ) and 20 patients were FS (-). In the FS( + ) group, 20 patients had germinal center (GC)( + ) and 44 patients had no GC. x2 test and t test were used for statistical analysis. Results The duration of symptoms of dry eyes or dry mouth in the FS (+) group was longer than that in the FS (-) group (P＜0.05). In the FS ( + ) patients, those with GC (+) had significantly longer duration of xerothalmia or xerostomia, higher serum IgG levels, greater FS score, and higher incidence of system involvement than those without GC patients (P＜0.05). In the FS (-) group, lip biopsies showed degenerative changes in 6 (30%) patients. Those with degenerative changes had longer duration of dry eyes and dry mouth and higher incidence of system involvement. Conclusion GC (+) in FS (+) patients and degenerative changes in FS (-) patients from lip biopsy are associated with severer clinical manifestations in patients with SS, suggesting that more clinical attention should be paid to this subgroup of patients.

Objective To investigate the effect of berberine on the radiosensitivity of cervical cancer cells.Methods 5,10,15,20 μmol/L of berberine were used to treat cervical cancer cell lines of Siha,HeLa,Caski.DMSO was applied as control of drug treatment.Cell proliferation was detected by the CCK-8 method,and then the half inhibitory concentration of berberine was calculated.Cell apoptosis and cell cycle distribution were detected by flow cytometry.Protein expressions of Cleaved Caspase-3,Cyclin B1,CDK1,STAT3 and p-STAT3 were detected by Western blot.Cervical cancer cells of Siha were treated by berberine with a half inhibitory concentration for 24 h and then irradiated with 0,2,4,6,8 Gy of X-rays.Cell clone assay was used to detect cell survival.Results Berberine could inhibit the growth of cervical cancer cells with a half inhibition concentration of(16.84 ± 3.52),(23.54 ± 8.67),(21.86 ± 6.35)μmol/L for Siha,Caski,and HeLa cells,respectively.The berberine at 17 μmol/L could induce apoptosis (t =56.847,P ＜ 0.01) and G2/M phase arrest (t =47.251,P ＜ 0.01) in Siha cells,which also inhibited the expressions of Cyclin B1,CDK1 and p-STAT3 and promoted the expression of cleaved Caspase-3,but did not influence the expression of STAT3 in cervical cancer cells.Treatment of cells with 17 μmol/L berberine increased the radiosensitivity of cervical cancer cells with a sensitivity enhancement ratio of 1.55.Conclusions Berberine can inhibit cell proliferation,promote apoptosis,block cell cycle,and increase radiosensitivity of cervical cancer cells.

Objective To evaluate the prevalence of subclinical atherosclerosis in rheumatoid arthritis (RA) and the related risk factors.Methods Fifty RA patients without overt atherosclerotic disease and 121 control subjects matched for age and sex were recruited.Duplex carotid sonography was used to measure intima-media thickness (IMT) and plaque formation assessment.Differences between RA and the control group were compared, and the risk factors were explored.RA patients then were divided into two subgroups according to IMT and the comparison between the two subgroups were completed.T test, Mann-Whitney U test, chi-square test, Pearson's correlation and Logistic regression analysis were used for statistical analysis.Results Although RA patients had lower level of serum lipids and body mass index than the control group, the mean IMT value was significantly higher in the RA group than that in the control group [(0.78±0.18) mm vs (0.62±0.14) mm, t=5.853, P=0.000], and plaque formation was more prevalent [56.0％(28/50) vs 36.4％ (44/121),x2=5.596, P=0.018].The difference was especially significant in the younger groups (＜50 years old group and 50-60 years old group).Logistic regression showed that the presence of RA [OR=7.34, 95％CI (2.53, 21.25)], male [OR=2.0, 95％CI (91.25, 3.17)] and old age [OR=1.1, 95％CI (1.04, 21.15)] were the independent risk factors for abnormal IMT (thickened or the presence of carotid plaques).The RA patients were divided into two subgroups according to IMT.Compared with patients with normal IMT, patients with abnormal IMT were older and more common in postmenopausal, and had longer RA duration and higher cholesterol level.In treatment, less patients with abnormal IMT had been taking methotrexate (MTX) for more than 3 months compared with patients with normal IMT.Among these parameters, old age [OR=1.13, 95％CI (1.03, 1.23)] was shown to be the independent risk factor for abnormal IMT in RA patients, and more than 3 months of MTX treatment [OR=0.12, 95％CI (0.02, 0.71)] was the protective factor.Conclusion Atherosclerosis occurs frequently and prematurely in patients with RA and the presence of RA is an independent risk factor for atherosclerosis.Early primary prevention for atherosclerosis should be recommended.MTX probably has a positive effect on preventing atherosclerosis for RA patients, which needs to be confirmed by further study.

Objective:To verify the fracture risk assessment tool ( FRAX) to estimate the probability of osteoporotic fracture in patients with rheumatoid arthritis ( RA ) with or without bone mineral density (BMD), and identify associated risk factors of osteoporosis .Methods: In the study, 200 patients with rheumatoid arthritis aged more than 40 years in Peking University First Hospital from Dec .2009 to Dec. 2012 were recruited.Clinical information was obtained from a questionnaire of their case history and medical records.FRAX tool was administered.Their lumber spine and left femoral BMD were determined by dual energy X ray absorptiometry.The gender, age, disease duration, menopause status, body mass index ( BMI) and accumulative dose of glucocorticoid were obtained in retrospect .Correlation analysis was conducted between the BMD and clinical information .Results:The study population ( female, 77.5%) had a mean age of 59.4 years, in which 10 (13%) patients showed a normal BMD, 67 (87%) were osteopenia or osteoporosis , while 32 patients (16%) had fragile fracture.Compared with the patients with normal BMD, the subjects with low BMD had significantly older age , longer period for corticoids usage , higher day dose and accumulated dose of corticoids .The 10-year fracture risk of sustai-ning major osteoporotic fractures and hip fracture was higher .No significant difference was observed be-tween the 10-year fracture risks calculated with BMD and without BMD .The values of the different area under the receiver operating characteristic ( ROC) curve ( AUC) for major and hip fractures calculated in three ways:without BMD, with the femoral neck BMD, and with T-score.The best result was for FRAX tool for hip fracture with the T-score ( AUC 0 .899 ) .A stepwise multivariate linear regression model was constructed to explore the relationship between the different clinical factors studied and a low BMD . Three statistically significant variables for lumber BMD were pain on visual assessment scale ( VAS ) (P=0.02), fracture history (P=0.003) and a higher steroid accumulated dose (P=0.008).Three statistically significant variables for left hip BMD were age (P<0.001), fracture history (P=0.05) and lower BMI ( P=0.03) .Conclusion:Low BMD is a common complication in RA patients .Risk factors for major fracture and hip fracture are increased .There is a positive correlation between FRAX calculated with and without BMD or T score .FRAX with the femoral neck T score or BMD presents a discriminatory capacity better than FRAX without BMD , according to the AUC ROC .

Objective To investigate the outcomes of patients with rheumatoid arthritis (RA) treated by different combination of synthetic disease modifying antirheumatic drugs (DMARDs) under the guidance of treat-to-target strategy.Methods Forty-two RA patients with high disease activity were enrolled into this randomized,open-label and prospective study.It was comprised of a maximal 36-week induction phase and then followed by a maintenance phase up to 84 weeks.Combination of synthetic DMARDs was initiated in the induction phase,with or without low dose glucocorticoids (GCs) during the first 12 weeks.Patients who achieved low disease activity (LDA) were randomized into two maintenance groups.An increase of DAS28 by 0.6 was defined as relapse.The patients achieved LDA in the induction phase,relapsed during maintenance phase and possible relevant risk factors were analyzed.Results Twenty-seven (64％) patients achieved LDA during the induction phase.More non-smoking patients achieved LDA than those smoked [85％ (11/13) vs 55％(16/29),P＜0.05].During the maintenance phase,14 (61％) out of 27 patients relapsed.Patients taking GCs during the first 12 weeks had a significantly higher relapse rate compared to those without GC (83％ vs 36％,P=0.021).Patients who entered maintenance phase at week 12 had a significantly higher tendency to relapse compared to those who entered the maintenance phase at week 24 [75％(9/12) vs 33％(3/9),P=0.026].Conclusion Smoking seems to be a risk factor for RA patients who fail to reach LDA.Low dose GCs as a bridge therapy may require a longer duration.High relapse rates in both the maintenance groups indicat that a longer tight induction phase may be appropriate before downstairs therapy.

Objective To explore the characteristics and survival of connective tissue disease (CTD) patients with both of pulmonary arterial hypertension (PAH) arnd interstitial lung disease (ILD),and to compare with CTD patients with isolated PAH.Methods All adult CTD patients who visited one of the three referral centers in China with a diagnosis of PAH confirmed by right heart catheterization from July 2006 to May 2011 were enrolled.They were then divided into two groups (ILD with and without-ILD group) based on chest CT and then the comparison of baseline characteristics and survival at the endpoint of follow up were made between the two groups.T test,Mann-Whitney U test,x2 test,Kaplan-Meier survival analysis and Cox regression analysis were used for statistical analyses.Results One hundred and twenty-six patients were recruited into the study.Patients with ILD (n=27) were older than those without ILD (n=99).Lung function results including FVC [(75±18)％ vs (83±13)％,t=2.212,P=0.037] and DLCO [(54±22)％ vs (68±20)％,t=2.392,P=0.019] in ILD group were significantly wose than those without-ILD group.Although some important hemodynamic parameters such as mean pulmonary arterial pressure and pulmonary vascular resistance were better in the ILD group than the without-ILD group,Kaplan-Meier analysis showed that the short term survival of ILD group was significantly worse than that of the without-ILD group (72.7％ versus 94.7％ at 1 year and 63.6％ versus 81.1％ at 3 year,P=0.047).In ILD group,Cox regression analysis showed that SvO2 was the only independent factor for the short term survival [HR=0.19,95％CI (0.04,0.83),P=0.027],and Kaplan-Meier analysis showed patients with SvO2＜60％ had significantly lower short term survival than patients with SvO2 ≥60％ (1 and 2 year survival were 60.0％ and 40.0％ versus 92.9％ and 77.4％ respectively,P=0.002).Conclusion Patients with both PAH and ILD is a special subtype in CTD.Although with the superiority of hemodynamics,these patients have significantly worse survival than CTD patients with isolated PAH.Low SvO2 is the independent risk factor for the short term mortality in patients of CTD complicated by both PAH and ILD.More attention should be paid to these patients and the management strategy should be investigated further.