[Clinical effect of tocilizumab on patients with severe active rheumatoid arthritis].

OBJECTIVE: To evaluate therapeutic effects and adverse reactions of tocilizumab on patients with severe active rheumatoid arthritis (RA).
 Methods: Twelve patients with severe refractory RA were treated with tocilizumab. The clinical and laboratory indices and the side effects were recorded after treatment.
 Results: The clinical and laboratory indices and the disease activity score 28 (DAS28) were observed in all patients, which were significantly improved after TCZ therapy (P<0.05), and no obvious adverse reactions were found.
 Conclusion: Tocilizumab can effectively relieve the symptoms and improve the conditions of severe active RA.

Association of TNFRSF1B +676 gene polymorphism with the risk of rheumatoid arthritis in Han Chinese population in Hunan.

OBJECTIVE: To study the association of TNFRSF1B +676 gene (rs1061622) polymorphism with the risk of rheumatoid arthritis (RA ) in Han Chinese population of Hunan. METHODS: A total of 112 patients with RA from Han Chinese population in Hunan were recruited, along with 129 healthy controls. TNFRSF1B +676 (rs1061622) gene polymorphisms were examined by PCR-RFLP. Serum levels of soluble TNFR II were analyzed by ELISA. RESULTS: RA patients displayed a similar TNFRSF1B +676 genotype to controls (GG/TG/TT: 5/62/45 vs 9/56/64, P=0.167), but signifi cant diff erence was found between female RA patients and female controls (GG/TG/TT: 3/49/24 vs 8/28/48, P<0.001). No significant difference was found in the frequency of TNFRSF1B +676 T or G allele between RA patients and controls (P>0.05). RA patients showed a signifi cantly higher level of serum soluble tumor necrosis factor receptor II (sTNFR II) than controls [(7.83±2.61) ng/mL vs (4.32±1.67) ng/mL, P<0.001], but there was no diff erence among the three genotypes (P>0.05). No association was found between TNFRSF1B+676 gene polymorphism and RA clinical characteristics. CONCLUSION: In Han Chinese population of Hunan province, TNFRSF1B+676 gene polymorphisms are not associated with the genetic risk of RA .

[Changes of six serum biomarkers of rabbits with experimental osteoarthritis].

OBJECTIVE: To investigate the value and significance of six serum biomarkers to the early diagnosis of osteoarthritis by means of quantitative detection of interleukin-1 beta (IL-1ß), matrix metalloproteinase 13 (MMP-13), IL-6, C-terminal telopeptide of collagen type II (CTX2), cyclooxygenase 2 (COX2) and prostaglandin E2 (PGE2) levels with time going on. METHODS: 40 New Zealand white rabbits were divided into experimental group (n=20) and control group (n=20). Injection of collagenase into articular cavity was performed in the experimental group for modeling. No treatment was done in the control group. Pathological observation, X-ray examination and HE staining of knee joints were conducted to verify the establishment of modeling. IL-1, MMP-13, IL-6, CTX2, COX2 and PGE2 levels were detected every two weeks after modeling in the experimental group, and these biomarkers were also detected in the control group at the same time points. RESULTS: Levels of the six serum biomarkers in the experimental group were significantly higher than those in the control group at each time point after modeling and were the most distinguishing at the 4th week. CONCLUSION: Combined detection of IL-1ß, IL-6, CTX2, COX2 and PGE2 in serum is helpful for early diagnosis of osteoarthritis.

Association of TNF-α gene polymorphisms with the risk of rheumatoid arthritis in Han Chinese population from Hunan.

OBJECTIVE: To investigate the association of TNF-α-308 gene polymorphism with the risk of RA in Hunan's Han Chinese population.
 METHODS: A total of 112 patients with RA from Han Chinese population in Hunan were recruited, along with 129 healthy controls. TNF-α-308 (rs1800629) gene polymorphisms were analyzed by PCR-RFLP. Serum levels of TNF-α were detected by ELISA.
 RESULTS: TNF-α-308 A allele carrier was 3.6% in RA patients and 10.5% in controls (P=0.004); male RA patients displayed noticeably lower rates of TNF-α-308 A allele than that in the male controls (2.8% vs 15.6%, OR=0.179, P=0.007). Patients containing both HLA-DRB1*04 and TNF-α-308 GG genotype showed a significant increase in risk for RA (OR=6.107), no matter they were male (OR=7.273) or female (OR=5.029). Female RA patients with both HLA-DRB1*04 and TNF-α-308 GG showed earlier disease onset and higher TNF-α level.
 CONCLUSION: In Han Chinese population from Hunan, susceptibility of RA was increased in patients with TNF-α-308 G allele, especially in the female carrier of genotypes; TNF-α-308 A allele may play a positive role in reduction of RA risk in males.

Pharmacokinetics and tissue distribution study of tanshinone IIA after oral administration of Bushen Huoxue Qubi granules to rats with blood stasis syndrome.

BACKGROUND: Bushen Huoxue Qubi (BHQ) granules, a traditional Chinese medicine preparation, has been clinically used for the treatment of the blood stasis syndrome. OBJECTIVE: The main objective is to investigate whether the diseased condition would alter the pharmacokinetics and tissue distribution of tanshinone IIA in BHQ, which was given orally to the acute blood stasis rats. MATERIALS AND METHODS: The main bioactive constituent in BHQ, tanshinone IIA, was measured in the plasma and tissues of animals by the high performance liquid chromatography with ultraviolet detection. The analysis was successfully performed on an Agilent TC-C18 column (250 × 4.6 mm I.D., 5 µm) protected with a  Octadecylsilane (ODS) guard column (10 × 4.6 mm I.D., 5 µm). The mobile phase was aqueous solution (A) (containing 0.40% aqueous acetic acid) and acetonitrile (B). The conditions of the solvent gradient elution were 35-40% (B) in 0-15 min, 40-42% (B) in 15-18 min and 42-70% (B) in 18-30 min at a flow rate of 1.0 mL/min. Detection was conducted with wavelength of 270 nm at 30°C. RESULTS: Good linearity relationships were found (r (2)> 0.9955) over the investigated concentration range for bio-samples. Blood stasis was associated with significantly higher area under the concentration-time curve (AUC), the maximum plasma concentration (Cmax) and biological half-life (t1/2), lower total body clearance (CL) and apparent volume of distribution (Vd) of tanshinone IIA in plasma and higher AUC0-t of tanshinone IIA in the analyzed tissues of rats treated with BHQ. CONCLUSION: Blood stasis could alter pharmacokinetics and tissue distribution of tanshinone IIA in BHQ.

Value of ultrasonography for diagnosis of synovitis associated with rheumatoid arthritis.

AIM: To investigate the value of ultrasonography (US) for diagnosing synovitis associated with rheumatoid arthritis (RA). METHOD: Bilateral metacarpophalangeal (MCP), proximal interphalangeal (PIP) II-V and wrist joints of 46 RA patients and 35 healthy controls were evaluated by quantitative and semiquantitative US. Wrists on more severely affected sides of 20 of the 46 patients also underwent magnetic resonance imaging (MRI). The MRI and US results were compared. The US cutoff to distinguish pathology was calculated. The two US methods were compared and the correlation between quantitative methods and clinical serologic markers was analyzed. RESULTS: The imaging techniques (US and MRI) for detecting synovitis produced consistent results (γ = 0.70-0.77, P < 0.001). When the cutoffs for the MCP and PIP joints were 2.5 and 2.6 mm, respectively; the sensitivities/specificities were 82.8%/85.8% and 98.2%/84.8%, respectively. When the cutoff for the wrist was 5.2 mm, the sensitivity/specificity was 93.4%/93.4%. The average synovial membrane thickness was positively related to biochemical markers erythrocyte sedimentation rate, C-reactive protein, anticyclic citrullinated peptide antibody, and Disease Activity Index of 28 joints (γ = 0.307-0.614; P = 0.020, 0.038, 0.01, < 0.001, respectively) but was poorly related to rheumatoid factor immunoglobulin A (RF-IgA), RF-IgM, and RF-IgG (γ = 0.06-0.115; P = 0.45, 0.45, 0.62, respectively). CONCLUSIONS: US is a valid method for diagnosing early-stage synovitis, with high-accuracy cutoffs for MCP, PIP and wrist joints set at 2.5, 2.6 and 5.2 mm. The mean synovial thicknesses of the bilateral wrist, MCP II-IV and PIP II-IV joints can be used to assess disease activity.

[Meta analysis of infection risks of anti-TNF-α treatment in rheumatoid arthritis].

OBJECTIVE: To systematically evaluate the risks of anti-TNF-α treatment-associated infection, severe infection and tuberculosis in rheumatoid arthritis (RA) patients, and to reduce the infection incidences associated with anti-TNF-α therapy. METHODS: We used Meta analysis to systematically review randomized controlled trials on anti- TNF-α treatment associated risks of infection, severe infection and tuberculosis in RA patients. RESULTS: Although no statistically significant differences were detected in TB risk between anit- TNF-α treatment and the control group (0.5% vs 0.07%; P=0.27, OR=1.85, 95% CI: 0.62-5.52), there still existed a clinically obvious elevation of TB risk in monoclonal anti-TNF-α treatment, which was illustrated by the results that no TB case was reported in the etanercept group, but 11 TBs in 2050 infliximab-treated cases, and 3 TBs in 722 adalimumab-treated cases. The total infection and severe infection risks were also significantly higher in patients receiving anti-TNF-α treatment (P<0.05). Subanalysis revealed that etanercept showed no significantly higher infection or severe infection risk than control group (P>0.05), while both kinds of monoclonal antibodies of TNF-α blockers showed a significantly elevated infection or severe infection risks (P<0.05). High doses of anti-TNF-α treatment were associated with statistically increased risks of severe infection (6.0% vs 2.8%, P=0.04, OR=1.68, 95% CI: 1.02-2.78). CONCLUSION: The TB risk of anti-TNF-α treatment deserves close attention, especially in places with high rate of BCG vaccination and MTb infection. Monoclonal anti-TNF-α treatment brings higher risks of infection and severe infection than soluble TNF-α receptor.

Resveratrol inhibits TNF-α-induced IL-1ß, MMP-3 production in human rheumatoid arthritis fibroblast-like synoviocytes via modulation of PI3kinase/Akt pathway.

Resveratrol (trans-3,4'-trihydroxystilbene), a natural phytoalexin, possesses anti-inflammatory, anti-proliferative, and immunomodulatory properties and has the potential for treating inflammatory disorders. The present study was designed to investigate the effects of resveratrol on TNF-α-induced inflammatory cytokines production of IL-1ß and MMP3 in Rheumatoid arthritis (RA) Fibroblast-like synoviocytes (FLS) and further to explore the role of PI3K/Akt signaling pathway by which resveratrol modulates those cytokines production. The levels of IL-1ß, MMP-3 in cultural supernatants among groups were measured by enzyme-linked immunosorbent assay. Messenger RNA expression of IL-1ß and MMP-3 in RA FLS was analyzed using a reverse transcription-polymerase chain reaction. Western blot analysis was used to detect proteins expression in RA FLS intervened by resveratrol. Resveratrol inhibited both mRNA and proteins expressions of IL-1ß and MMP-3 on RA FLS in a dose-dependent manner. Resveratrol also decreased significantly the expression of phosphorylated Akt dose dependently. Activation of PI3K/Akt signaling pathway exists in TNF-α-induced production of IL-1ß and MMP3 on RA FLS, which is hampered by PI3K inhibitor LY294002. Immunofluorescence staining showed that TNF-α alone increased the production of P-Akt, whereas LY294002 and 50 µM resveratrol suppressed the TNF-α-stimulated expression of P-Akt. Resveratrol attenuates TNF-α-induced production of IL-1ß and MMP-3 via inhibition of PI3K-Akt signaling pathway in RA FLS, suggesting that resveratrol plays an anti-inflammatory role and might have beneficial effects in preventing and treating RA.

[Grey scale and power Doppler ultrasonographic assessment of bone erosion and disease activity in early rheumatoid arthritis].

OBJECTIVE: To evaluate the sensitivity and predictive value of grey scale and power Doppler ultrasound assessment of bone erosionin disease activity in patients with early rheumatoid arthritis (RA). METHODS: Fifty-six patients with early RA underwent blinded sequential clinical, laboratory and ultrasound assessments, and at the same time 20 of these patients underwent X-ray and enhanced MRI. For each patient, 28-joint disease activity score (DAS28), erythrocyte sedimentation rate (ESR), C reactive protein (CRP) and health assessment questionnaire (HAQ) were recorded. The presence of bone erosion and synovitis was investigated in 28 joints by gray-scale and power Doppler ultrasonography. The ultrasound joint count and index for active synovitis with power Doppler signal were calculated. RESULTS: The number of bone erosions detected by ultrasonography was 5.7 times that of X-ray, while both MRI and ultrasonography were consistent (91.5%). The number of synovitis detected by ultrasonography was 1.6 times as much as by physical examination, and consistent MRI (95.7%). PDUS parameters demonstrated a highly significant correlation with DAS28, ESR and CRP, while a negative correlation with HAQ. CONCLUSION: Grey scale and power Doppler ultrasonography is a sensitive and reliable method to assess bone erosion and inflammatory activity in early RA. PDUS findings may have a predictive value in disease activity.

Effects of trimethoxystilbene on proliferation and apoptosis of pulmonary artery smooth muscle cells.

Proliferation of pulmonary artery smooth muscle cells (PASMC) is an important contributor to the progress of pulmonary arterial hypertension (PAH). Anti-inflammatory therapies may have therapeutic applicability for PAH. Resveratrol (RES) has prominent anti-inflammatory effects in vitro, but in vivo its beneficial effects are limited by short systemic half life and poor lipotrophy. A derivative of RES, trimethoxystilbene (TMS), has higher lipotropy and extended half life compared with RES, and can potentially overcome the limitations of RES. In the present study, we studied the effects of TMS and RES on proliferation and apoptosis of PASMC stimulated with Tumor Necrosis Factor-α. The effects on PASMC proliferation were quantified by MTT, while apoptosis was assessed by flow cytometry (Annexin V/propidium iodide assay). We observed strong inhibitory effects of TMS on the growth of PASMC, and these effects were 20 times more potent than those of RES. We further documented induction of apoptosis in PASMC treated with TMS, again, to a higher degree than with RES. In conclusion, TMS is more potent than RES in the inhibition of proliferation and induction of apoptosis of PASMC, demonstrating its potentially beneficial role for treating PAH.

[Clinical efficacy of bushen huoxue qubi decoction on treatment of knee-osteoarthritis and its effect on hemarheology, anti-inflammation and antioxidation].

OBJECTIVE: To prove the clinical effect and mechanism of Bushen Huoxue Qubi Decoction on treatment of knee-osteoarthritis. METHOD: Ninty-six knee-osteoarthritic patients accompanied with symptoms of liver and kidney deficiency and blocked main and collateral channels were divided into two groups randomly. Patients in the treatment group (n = 48) were administrated by Bushen Huoxue Qubi Decoction one bag/day for four weeks; and those in the control group (n = 48) were given diacerein (50 mg Bid, Po) and celecoxib (0.2 Qd, Po) for four weeks. The changes of VAS score, Womac score, relative viscosity, aggregation index and IL-1beta, NO, iNOS, LPO, SOD in serum were observed. Adverse effects were determined during follow-up visit and detection for blood routine and hepatic and renal functions. RESULT: Its clinical control rates as per Western medicine and TCM standards for treatment of knee-osteoarthritis and effective rate were 33.3%, 37.5% and 97.9% respectively, which was remarkably higher than those in the control group (18.8%, 20.8% and 95.5%). Their difference showed statistical significance, P<0.05 or 0.01. Bushen Huoxue Qubi Decoction had an effect in obviously improving hemarheological index in 42 days and inhibiting IL-1beta, NO, iNOS and LPO better than the control group, by the contrast of 58.6% vs 47.3%, 50.1% vs 36%, 55.1% vs 41.9% and 46.7% vs 20.6% (P<0.05 or P<0.01). The treatment group also displayed a higher SOD capability the control group (2 514.71 +/- 812.65) vs (2 013.41 +/- 781.3), (P<0.01). Both groups reported no adverse effect. CONCLUSION: Bushen Huoxue Qubi Decoction has a better efficacy on knee-OA than traditional treatment methods (diacereinand + celecoxib) and showed no adverse effect.

[Trimethoxystilbene and its effects on the proliferation and apoptosis of PASMCs].

OBJECTIVE: To synthesize 3, 5, 4' -trimethoxystilbene (TMS) by methylation of resveratrol (Res), a natural compound extracted from polygonum cuspidatum, to identify the chemical structure of TMS, to test its pharmacokinetics, and to determine the effects of TMS on the growth inhibition and apoptosis in pulmonary artery smooth muscle cells (PASMCs). METHODS: The chemical structure of TMS was analyzed by UV- and IR- absorption spectrometry, (1)H-NMR and (13)C-NMR spectroscopy and mass spectrometry. We measured the bioavailability, the characteristics of intestinal absorption, and the distribution of TMS in body and excretions of SD rats after oral administration of TMS. The acute toxicity of TMS in mice was tested. PASMCs were prepared from pulmonary artery of SD rats. The PASMCs were divided into 8 groups. Group of A (control) was cultured without TNF-α, TMS, or Res. Group of B (TNF-α) was cultured with 100 pg/mL TNF-α. Groups of C-E (low-high concentrations of TMS) were cultured with 100 pg/mL TNF-α and 5, 10, 20 µmol/L TMS, respectively. Groups of F-H (low-high concentrations of Res) were cultured with 100 pg/mL TNF-α and 50, 100, 200 µmol/L Res, respectively. The proliferation of PASMCs after treatment was determined by MTT assay. The apoptosis of PASMCs after treatment was determined by flow cytometry. RESULTS: The UV absorption map of TMS showed λmax(MeOH) at 318, 306.2, and 217.8 nm. Analysis of infrared spectrum of TMS showed IRvKBr max /cm at 2999, 2935, 2836, 1591, 1511 and 1456/cm. The (1)H-NMR map showed that the synthetic product contained three hydroxy groups, while (13)C-NMR map showed 17 carbon signals and some symmetrical structural fragments. Electospray ionization mass spectrometry of the productshowed m/z peaks corresponded to 271[M+H](+), 256[M+H-CH(3)](+) and 241[256-CH(3)](+); the implied relative molecular weight is 270 and the implied molecular formula is C17H18O3. These data confirm the product is 3,5,4' - trimethoxystilbene. The absolute bioavailability of TMS was 45.4%. TMS was well absorped in the upper small intestine; it was excreted in stool and bile and distributed into several tissues. The maximal tolerance dose (MTD) of TMS was 5.85 g/kg. MTT assay showed TMS inhibited the proliferation of PASMCs in a dose-dependent manner. The extent of growth inhibition in A-H groups were (4.07±2.12)%, (6.54±4.78)%, (9.35±4.26)%, (16.75±5.34)%, (23.74±7.07)%, (6.78±5.58) %, (8.81±5.16) %, and (17.81±6.03) %, respectively. Flow cytometry showed the extent of apoptosis in PASMCs (after being treated with TMS for 24 h) was significantly higher than that in PASMCs treated only with TNF-α. The apoptosis rates of A-H groups were (2.63±0.74)%, (3.54±0.81)%, (5.77±4.62)%, (11.68±5.35)%, (18.79±4.15)%, (4.11±3.59)%, (6.33±4.8) %, and (12.47±5.06)%, respectively. CONCLUSION: We have confirmed our synthetic product as 3,5,4'-trimethoxystilbene (TMS), with the molecular formula of C17H18O3 and appropriate molecular weight and absorbption and NMR spectra. The bioavailability of TMS was to 45%. It strongly inhibits the proliferation of PASMCs in a dose-dependent manner and induces apoptosis of PASMCs.

Effect of resveratrol on cartilage protection and apoptosis inhibition in experimental osteoarthritis of rabbit.

To observe the effect of resveratol on cartilage, chondrocyte apoptosis, and nitric oxide in experimental osteoarthritis (OA) of rabbit and to study the mechanism of resveratol in the treatment of osteoarthritis. Thirty New Zealand rabbits were randomly divided into 5 groups: group A (normal control group), group B (model control group), group C (resveratrol intervention high-dosage group), group D (resveratrol intervention middle dosage group), and group E (resveratrol intervention low-dosage group). The model of OA of the knee was established using Hulth technique in groups B, C, D, and E. After 4 weeks, group A and group B rabbits were administered daily a knees injection of dimethylsulfoxide (DMSO), whereas groups C, D, and E were administered daily a knees injection of resveratrol in DMSO in different dosages for 2 weeks. Daily dosage for rabbits of groups C, D, and E was fixed at 50, 20, and 10 µmol/kg, respectively. Then, the rabbits were killed, and the lateral cartilage sections of right femoral medial condyle were evaluated using a histological scoring system (H&E and safranin-O staining) and analyzed by TUNEL for apoptosis. Nitric oxide (NO) in synovial fluid was measured by nitrate reduction method. Histological evaluation of cartilage tissue revealed a significantly reduced cartilage destruction; the evaluation also revealed the loss of matrix proteoglycan content in cartilage in resveratrol intervention groups compared to the model control. Resveratrol reduced the apoptosis rate of chondrocyte and level of NO in the synovial fluid. In the above experiments of OA rabbits, the protective effects of resveratrol were enhanced with increased resveratrol dosage. Resveratrol controls the progression of experimental OA. One of the mechanism(s) responsible for this effect would include lowering of the apoptosis rate of chondrocyte and reducing the production of NO in experimental OA.

A T-cell-based enzyme-linked immunospot assay for tuberculosis screening in Chinese patients with rheumatic diseases receiving infliximab therapy.

Anti-tumour necrosis factor-α (TNF-α) therapy brought new hopes for treating rheumatic diseases but also increased the risk of infection, including mycobacterium tuberculosis (MTb). Conventional screening tools, such as tuberculin skin test (TST), lack sensitivity or specificity. Recently, T-SPOT.TB has been introduced to detect tuberculosis infection. Reports have proved its superior performance in detecting tuberculosis infection in various patient populations than the TST. To compare the value of a T-cell-based enzyme-linked immunospot assay (ELISPOT) T-SPOT.TB and conventional (TST) in screening and monitoring tuberculosis in patients with rheumatic diseases during infliximab therapy in China. Fifty-eight patients with various rheumatic diseases who received infliximab therapy were enrolled in the trial. Freshly isolated peripheral blood mononuclear cells were stimulated with MTb-specific antigens (ESAT-6 and CFP10), and IFN-γ-producing cells were counted. TST was performed with 1 TU PPD injected intradermally into the volar aspect of forearm. A cutaneous induration with diameter ≥5 mm was considered as positive TST, and an increment ≥5 mm of cutaneous induration was considered as TST conversion. TST and T-SPOT.TB test were carried out at baseline and repeated 12 months after infliximab therapy (if no active TB occurs) or at times when TB occurred. Moreover, all patients were initially evaluated for latent tuberculosis infection (LTBI) with clinical examination and chest radiograph. The McNemar test was used for TST and T-SPOT.TB concordance analysis. Cohen's kappa coefficient was used to assess strength of the agreement. Among the 58 patients evaluated, 25 (43.1%) had ankylosing spondylitis, 24 (41.4%) had rheumatoid arthritis, 4 (6.9%) had undifferentiated spondyloarthropathy, 3 (5.2%) had psoriatic arthritis and 2 (3.4%) had reactive arthritis. A total of 52 patients (89.7%) had previously received vaccination with Bacille Calmette-Guerin. All of the patients received either single or combination of disease modifying anti-rheumatic drug (DMARDs) therapy, and 16 (27.4%) had previously or presently received glucocorticoid therapy. Before infliximab therapy, 12 patients (20.7%) had positive and 46 (79.3%) had negative TST results, and only 1 (1.7%) had positive T-SPOT.TB. Among 51 patients completing the repeated TST and T-SPOT.TB assay, 7 patients (13.7%) had TST conversion and 4 (7.8%) had positive T-SPOT.TB results. Of 7 patients with TST conversion, 2 patients (28.6%) developed active TB and also had positive T-SPOT.TB results; of 44 patients with no TST conversion, 2 patients (4.5%) had positive T-SPOT.TB and 1 (2.3%) had active TB. If 5 mm was used as the cut-off value of TST, TST and T-SPOT.TB, had an agreement value of 68.6% with a kappa value of 0.166. If 10 mm was used as the cut-off value, the agreement between TST and T-SPOT.TB was 88.2% with a kappa value of 0.338. T-SPOT.TB was more specific than TST in detecting tuberculosis during infliximab therapy in China with high BCG vaccination and high prevalence of TB. It can be used as a reliable tool for TB monitoring during infliximab therapy in Chinese patients with rheumatic diseases. Finally, it is recommended to repeat the TST and T-SPOT.TB periodically during biological treatment.

Multicenter validation of the value of BASFI and BASDAI in Chinese ankylosing spondylitis and undifferentiated spondyloarthropathy patients.

The objectives of this study were to evaluate the reliability of Bath ankylosing spondylitis functional index (BASFI) and Bath ankylosing spondylitis disease activity index (BASDAI) in Chinese ankylosing spondylitis (AS) and undifferentiated spondyloarthropathy (USpA) patients. 664 AS patients by the revised New York criteria for AS and 252 USpA patients by the European Spondyloarthropathy Study Group criteria were enrolled. BASDAI and BASFI questionnaires were translated into Chinese. Participants were required to fill in BASFI and BASDAI questionnaires again after 24 h. Moreover, BASDAI and BASFI were compared in AS patients receiving Enbrel or infliximab before and after treatment. For AS group, BASDAI ICC: 0.9502 (95% CI: 0.9330-0.9502, α=0.9702), BASFI ICC: 0.9587 (95% CI: 0.9521-0.9645, α=0.9789). For USpA group, BASDAI ICC: 0.9530 (95% CI: 0.9402-0.9632, α=0.9760), BASFI ICC: 0.9900 (95% CI: 0.9871-0.9922, α=0.9950). In the AS group, disease duration, occipital wall distance, modified Schober test, chest expansion, ESR, and CRP showed significant correlation with BASDAI and BASFI (all P<0.01). In the USpA group, onset age, ESR, and CRP were significantly correlated with BASDAI (all P<0.05), while modified Schober test, ESR, and CRP were significantly associated with BASFI (all P<0.05). The change in BASDAI and BASFI via Enbrel or infliximab treatment showed a significant positive correlation (P<0.01). The two instruments have good reliability and reference value regarding the evaluation of patient's condition and anti-TNF-α treatment response.

[Effects of resveratrol on proliferation and apoptosis of TNF-alpha induced rheumatoid arthritis fibroblast-like synoviocytes].

OBJECTIVE: To observe the effect of resveratrol (Res) on in vitro proliferation and apoptosis of TNF-alpha induced rheumatoid arthritis fibroblast-like synoviocytes (RA FLS), and further to investigate the PI3 K/Akt/BAD signal mechanism. METHOD: The inhibition rate of RA FLS was examined by MTT assay. Cell cycle and the amount of apoptotic cells was measured by flow cytometry. PI3K/Akt/BAD signal transduction proteins expression was measured by western blot. RESULT: The living cells measured by MTT dose and time-dependently reduced in Res groups. In Res groups, the fraction of living cells in the S-phase and G2/M-phase decreased respectively, while that in G1-phase increased, the difference was statistically significant compared with the TNF-alpha group (P < 0.05). Flow cytometry demonstrated that the apoptosis rate increased with increased Res concentration. Res inhibited TNF-alpha induced phosphorylation of Akt and BAD in RA FLS. CONCLUSION: Res can inhibit RA FLS proliferation and induce apoptosis through inhibition of PI3K/Akt/BAD signalling pathway. Res may provide a new therapeutic approach in treatment of RA.

Case report: Infliximab treatment in two Chinese patients with psoriatic arthritis.

Psoriatic arthritis (PsA) is a rheumatoid factor (RF)-seronegative systemic inflammatory disorder associated with psoriasis. Current treatment for PsA in China is still focused on disease modifying anti-rheumatic drugs (DMARDs). In this paper, we report two Chinese patients with active longstanding PsA treated with infliximab, a human-mouse chimeric monoclonal antibody against tumor necrosis factor alpha (TNF-α). The results show that infliximab acted quickly and effectively in relieving peripheral and axial symptoms and refractory skin lesions, even in recombinant human TNF-α receptor (rhTNFR)-resistant case. The take-home message from our cases is that infliximab is a useful therapeutic option for refractory PsA, especially when a patient has a combination of psoriasis and psoriatic arthritis. Further local evidence and experience must be accumulated in order to make anti-TNF-α therapy more accessible to PsA patients in China.

[Inhibitory effect of resveratrol on the proliferation of synoviocytes in rheumatoid arthritis and its mechanism in vitro].

OBJECTIVE: To investigate the effect of resveratrol on the proliferation and apoptosis of synoviocytes in patients with rheumatoid arthritis (RA) in vitro and explore its mechanism. METHODS: The levels of cell proliferation of synoviocytes in RA after 24 h treated with different concentrations of resveratrol were measured by monotetrazolium colourmetric assay method. The percentages of synoviocytes apoptosis in RA after 24 h treated with different concentrations of resveratrol were tested by TUNEL and flow cytometry. The relative activities of caspase-3 were determined by colorimetric assay after 4, 8, 12, 18, and 24 h treated with resveratrol (200 micromol/L) and 12 h treated with different concentrations of resveratrol. The cleavages of pro-caspase-3 were analyzed by Western blot after 24 h treated with different concentrations of resveratrol. RESULTS: The levels of cell proliferation of synoviocytes with RA after 24 h treated with different concentrations of resveratrol were significantly decreased compared with the control group (P<0.01). The percentages of the apoptotic cells were increased of resveratrol-treated after 24 h, the apoptosis rates between the treated groups and the control group were significantly different (P<0.01). When the synoviocytes in RA were treated with 200 micromol/L resveratrol for different time respectively, the caspase-3 activity began to rise significantly at 4h, reaching the peak at 12 h, and was still much higher than that of the control group at 24 h (P<0.01). After the cells were treated with different concentrations of resveratrol for 12 h, caspase-3 activity increased in a concentration-dependent manner. After synoviocytes in RA were treated with different concentrations of resveratrol for 24 h, the expressions of pro-caspase-3 decreased as the concentration increased, the caspase-3 active fragment P11 (11 kD) appeared at 100 micromol/L and was increased at 400 micromol/L. CONCLUSION: Resveratrol inhibits the proliferation of synoviocytes and induces cell apoptosis in rheumatoid arthritis in vitro, which may relate to the activation of caspase-3.

Effect of Yangqixue Qufengshi Recipe on rheumatoid arthritis model mice under different genetic backgrounds.

OBJECTIVE: To study the effect of Yangqixue Qufengshi Recipe (YQXQFS) on rheumatoid arthritis (RA) model mice under different genetic backgrounds. METHODS: Collagen Induced Arthritis (CIA) were established on HLA-DR4 transgenic (TG) mice and non-transgenic (NTG) mice, which partly were raised with YQXQFS, and the onset day of CIA, the level of type II collagen (CII)-reactive antibodies and the pathological scores of CIA were assessed. RESULTS: Under HLA-DR4 TG background (compared with NTG mice), the earlier onset day of CIA (11.22 +/- 3.35 days vs 16.56 +/- 4.75 days, P < 0.05) and higher level of CII-reactive antibodies (0.2274 +/- 0.1390 microg/ml vs 0.1101 +/- 0.0560 microg/ml, P < 0.05) were observed, but the pathological scores of CIA remained unchanged. YQXQFS could not influence the onset day of CIA and the level of CII-reactive antibodies, but had a certain effect on the total pathological scores (6.56 +/- 3.43 scores vs 11.11 +/- 5.64 scores) and bone erosion (0.22 +/- 0.44 scores vs 1.67 +/- 1.50 scores) of CIA on NTG mice (P < 0.05), NTG YQXQFS group compared with NTG experimental group. CONCLUSION: YQXQFS had a certain effect on RA model, but had no significant effect on HLA-DR4 related CIA.