Background Eicosapentaenoic acid(EPA)function as the critical lipid mediators involved in several biological events in human body and play important role in suppressing the genesis of vascular endothelial growth factor (VEGF),migration and proliferation of vascular endothelial cells.Many ocular diseases were proved to be associated with neovascularization.Objecfive The purpose of this study was to investigate the inhibitory effect of EPA on the proliferation of human umbilical vein endothelial cells (HUVEC) indueed by VEGF. Methods HUVEC strain was cultured and passaged,and difierent concentrations of EPA were added to the medium with and without VEGF.The cultured cells were identified by antiofactor Ⅷ polyclonal antibody.The suppressing role of different concentrations of EPA on the proliferation of VEGF-induced or-uninduced HUVEC was assessed by MTT method.The influence of difierent concentrations of EPA on the cellular cycle of VEGF-induced HUVEC was assayed using flow eytometry.The expression of Flk-1,a receptor of VEGF,in the HUVEC Was detected by immunohistochemistry. Results Cultured HUVEC showed the ftlsiform in shape and presented with the cobblestone-like arrangement with the positive response for Ⅷ factor-related antigen.Various concentrations of EPA showed obviously inhibitory effect on VEGF-induced or-unindueed HUVEC at a dose-dependent manner (F=23.072.P=0.000).The inhibitory ability of EPA on VEGF-induced HUVEC was stronger than VEGF-uninduced HUVEC(F=41.417,P=0.000).In 24,48 and 72 hours,the action of EPA on the proliferation of HUVEC was gradually enhanced with the prolong of time(F=1.495,P=0.236).Cell cycle analysis indicated that EPA arrested VEGF-induced HUVEC in G0/G1 phase.The ratio of HUVEC in G0/G1 phase in EPA group was(75.83±1.56)%,and that in control groups was(68.62±1.44)%,showing a significant difference between them(t=-5.88,P=0.00),and no apoptosis of HUVEC was found in both groups.Flk-1 was strongly expressed in the cellular nucleus and cytoplasm in control group.However,the positive expressing intensity of Flk-1 in the HUVEC weakened,and the positive cell number was evidently less in EPA group. Conclusion EPA can inhibit the proliferation of VEGF induced HUVEC through arresting the synthesis of DNA of HUVEC and downregulate the expression of Flk-1 in HUVEC.These results suggest that EPA might exert an antiangiogenic effect.

Objective To observe the effect of resveratrol on the apoptosis and expressions of bal-2 and bax protein in articular chondrecytes of rabbits experimental osteoarthritis (OA) model,and further explore the mechanisms of resveratrol in the treatment of OA.Methods Thirty Newzealand 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),group E (resveratrel intervention low dosage group).The model of OA was established with Hulth's modeling method in group B,C,D,E.Four weeks later,groups A and B received intragastric administration of distilled water containing 0.1% DMSO daily and group C,D,E received intragastric administration of resveratrol solution daily (concentration was 60 mg/ml) in different dosages for 6 weeks.Daily dosages of group C,D,E were 120,60,30 mg·kg-1·d-1,respectively.Then the rabbits were sacrificed and the cartilage sections of right femoral medial condyle were analyzed by immunohistochemistry for bcl-2 and bax,TUNEL for apoptosis.Results ① The apoptosis rates of chondrocytes in group B,C,D,E were significantly higher than those in group A (P＜0.01).The apoptosis rates of chandrocytes in group C,D,E were decreased compared with those in group B (P＜0.05).②The positive rates of bcl-2 and bax expression in chondrocytes in group B were significantly higher than those in group A (P＜0.01),but the ratio of the positive rate of bcl-2 expression to that of bax in group B was lower than that in group A (P＜0.01).The positive rates of bcl-2 expression in chondrocytes in group C,D,E were much higher compared with those in group B (P＜0.01).The positive rotes of bax expression in chondrocytes in group C,D,E were lower compared with those in group B (P＜0.01).The ratio of the positive rate of bcl-2 expression to that of bax was increased in group C,D,E compared with group B (P＜0.01).Conclusion Resveratrol can suppress the excessive apoptosis of chondrocytes in experimental OA by up-regulating the expression of bcl-2 while down-regulating the expression of bax and improving the ratio of bcl-2 to bax .Suppressing the excessive apoptosis of chondrocytes in experimental OA may be one of the mechanisms for resveratroi's effect in the treatment of osteoarthritis.

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.

Objective To investigate the anti-inflammatory effect of Resveratrol on type Ⅱ collagen induced arthritis.Methods Collagen induced arthritis (CIA) animal model was established by subcutaneous injection of type Ⅱ collagen emulsified with incomplete and complete Freud's adjuvant to Wistar rats.Fortytwo rats were successfully induced and randomly divided into 7 groups:the experimental group (A),the leflunomide treatment group (B),the TGP treatment group (C),the methotrexate group (D),the low dose Resveratrol group (E),the medium dose Resveratral group (F) and high dose Resveratrol group (G) and the normal control group (H).Symptoms of arthritis were recorded and selalm levels of the anti-C Ⅱ antibody were detected by ELISA.Results For arthritis index.there was no significant difference between groups E and A,neither between groups C and F.The arthritis index was lower in group G than group C,but both of them were higher than groups B and D.② For serum anti-C Ⅱ antibody level,that of group A was higher than groups B,C,D,F and G.There was no difference between groups A and E,and groups C and F.That of Group G was lower than groups C and E.Conclusion High and medium dose of Resveratrol can relieve foot joints swelling in the CIA rats,but low dose does not have similar effect.The effect of medium dose of Resveratrol iS similar to TGP,but weaker than that of leflunomide.Resveratrol may conduct its anti-inflammatory effect via lowering the concentration of the anti-C Ⅱ antibody in the serum.

Objective To investigate the relationship between plasma homocysteine (Hey) level and ankylosing spondylitis (AS).To analyze the association between the NS,N10 methylenetetrahydrofolate reductase (MTFHR) gene polymorphism and AS.Methods One hundred patients with AS and 60 healthy controls were included in the study.The plasma Hey level was examined by enzyme-linked immunoadsorbent assay and MTHFR gene polymorphism was analyzed by the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP).Results Compared with heahhy controls,the plasma Hey level in AS patients was significantly higher than that of the controls (P＜0.01).There was no significant difference in the frequen-cies of MTHFR genotype and alleles between AS and the controls (P＞0.05),But the ratio of T/T genotype mutation was different between AS and the controls (P＜0.05).The plasma Hey level of T/T genotype was significantly higher than that of C/T or C/C genotype in AS and the controls (P＜0.01).Logisticalregression analysis indicated that Hey was an independent risk factor for AS (P＜0.01,0R=4.582,95%CI=1.984～10.585).Conclusion The plasma homocysteine level is significantly increased in AS patients.Hyperhomo-cysteinemia is an independent risk factor for AS.MTHFR T/T genotype mutation is an important mechanism of hyperhomocysteinemia and may be related with AS.

Objective To explore the efficacy and safety of intravenous immunoglobulin and glucocorticoid treatment in elderly dermatomyositis patients. Methods Sixty elderly patients with dermatomyositis were randomly divided into two groups: prednisone alone (n= 30, PA) (first 1 mg per kilogram of body weight daily,then decrease the dose according to disease activity), and the combined treatment (n=30,CT,first 1 mg per kilogram of body weight daily, then decrease the dose according to disease activity, and intravenous immunoglobulin 0. 4 g per kilogram of body weight per month for three months). The improvement of clinical symptoms and the occurrence of side effects were observed at the end of month 3. Results The time of muscle strength recovery, remittences of myasthenia and myalgia visual analogue scale(VAS), the decreasing rates of creatine phospho kinase (CPK) level and the dose of prednisone at the end of month 3 were superior in CT group versus PA group (P<0. 05), while no significant differences in the improvement of rash, muscle strength,erythrocyte sedimentation rate(ESR),C-reactive protein (CRP) and side effects between two groups.Conclusions Combination with intravenous immunoglobulin and oral glucocorticoid is a safe and effective treatment for elderly patients with dermatomyositis, it can alleviate symptoms quickly,decrease CPK level and prednisone dose significantly.

Objective To study the clinical significance and diagnostic value of anti-proliferating cell nuclear antigen (PCNA) antibodies.Methods A retrospective analysis was conducted for the diagnoses and clinical features of 102 patients with anti-PCNA antibodies.Line immunoassay was used to detect anti-PCNA antibody of 536 systemic lupus erythematosus (SLE) patients.Possible relationship between anti-PCNA anti-body and clinical features and other antibodies in SLE were analyzed.Comparisons between groups were performed by t-test or x2 test.Results In the 102 patients with anti-PCNA antibodies,49 had SLE (48.0％).Other disorders associated with anti-PCNA antibodies included primary Sj(o)gren's syndrome(24.5％),systemic sclerosis (12.7％),primary biliary cirrhosis (3.9％),auto-immune thyroiditis (6.9％),polymyositis/dermatomyositis (2.0％) and hepatitis C virus infection (1.0％).9.1％ of SLE patients showed positive anti-PCNA antibody.Compared with those SLE patients with negative anti-PCNA antibody,the occurrences of rash,neuropsychiatric SLE,renal involvement was significantly higher in the anti-PCNA positive patients.In addition,the SLEDAI score was significantly higher in the latter.The positive rates of anti-Rib-P,anti-dsDNA,anti-Ro52,anti-RNP/Sm were higher in patients of SLE with positive anti-PCNA antibody.Conclusion Sera anti-PCNA antibody is not specific for SLE and it is associated with the occurrences of rash,Raynaud's phenomenon,neuropsychiatric SLE,renal involvement and positive rates of anti-Rib-P,anti-dsDNA,antiRo52,anti-RNP/Sm.In addition,anti-PCNA antibody is associa-ted with the disease activity of SLE.

Objective:To systematically evaluate the risks of anti-TNF-αtreatment-associated infection, severe infection and tuberculosis in rheumatoid arthritis (RA) patients, and to reduce the infection incidences associated with anti-TNF-αtherapy. Methods:We used Meta analysis to systematically review randomized controlled trials on anti-TNF-αtreatment associated risks of infecion, severe infection and tuberculosis in AR patients.Results:Although no statistically significant differences were detected in TB risk between anit-TNF-αtreatment 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-αtreatment, 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 signiifcantly higher in patients receiving anti-TNF-αtreatment (P<0.05). Subanalysis revealed that etanercept showed no signiifcantly higher infection or severe infection risk than control group (P>0.05), while both kinds of monoclonal antibodies of TNF-αblockers showed a signiifcantly elevated infection or severe infection risks (P<0.05). High doses of anti-TNF-αtreatment 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-αtreatment deserves close attention, especially in places with high rate of BCG vaccination and MTb infection. Monoclonal anti-TNF-αtreatment brings higher risks of infection and severe infection than soluble TNF-αreceptor.

OBJECTIVETo 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.

METHODThe 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.

RESULTThe 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.

CONCLUSIONRes 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.

Aged ; Apoptosis ; drug effects ; Arthritis, Rheumatoid ; drug therapy ; immunology ; physiopathology ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Female ; Fibroblasts ; cytology ; drug effects ; Humans ; Male ; Middle Aged ; Stilbenes ; pharmacology ; Synovial Membrane ; cytology ; drug effects ; immunology ; Tumor Necrosis Factor-alpha ; immunology

Quercetin has a variety of biological activities and pharmacological effects, but its clinical application is limited due to its low water solubility, low bioavailability and poor chemical stability. In order to overcome the above shortcomings of quercetin and achieve better clinical efficacy, many new drug delivery systems have been studied and developed in recent years, of which nano drug delivery system has become a research hotspot. Nano drug delivery system includes nanoparticles, nanocapsules, nanoliposomes, nanomicelles, nanosuspensions and nanoemulsions, with the advantages of reducing particle size, enlarging surface area, increasing drug permeability, improving intracorporeal circulation and distribution of the drug, enhancing drug targeting and so on. This article reviewed the latest progress at home and abroad about the studies and application of quercetin in nano drug delivery system, such as increasing solubility and dissolution, elevating bioavailability, raising drug stability, delaying drug release, enhancing skin permeability, promoting antioxidant capacity and improving therapeutic effect, in the hope of providing references for further research of quercetin preparations.