Association of TNFRSF1B +676 gene polymorphism with the risk of rheumatoid arthritis in Han Chinese population in Hunan / 中南大学学报(医学版)

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, P0.05). 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, P0.05). 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 .

Association of TNF-α gene polymorphisms with the risk of rheumatoid arthritis in Han Chinese population from Hunan / 中南大学学报(医学版)

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.

Grey scale and power Doppler ultrasonographic assessment of bone erosion and disease activity in early rheumatoid arthritis / 中南大学学报(医学版)

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.

Meta analysis of infection risks of anti-TNF-αtreatment in rheumatoid arthritis / 中南大学学报(医学版)

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 (P0.05), 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.

Trimethoxystilbene and its effects on the proliferation and apoptosis of PASMCs / 中南大学学报(医学版)

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.

Clinical significance of antibody to proliferating cell nuclear antigen in patients with systemic lupus erythematosus / 中华风湿病学杂志

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.

Clinical efficacy of bushen huoxue qubi decoction on treatment of knee-osteoarthritis and its effect on hemarheology, anti-inflammation and antioxidation / 中国中药杂志

<p><b>OBJECTIVE</b>To prove the clinical effect and mechanism of Bushen Huoxue Qubi Decoction on treatment of knee-osteoarthritis.</p><p><b>METHOD</b>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.</p><p><b>RESULT</b>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.</p><p><b>CONCLUSION</b>Bushen Huoxue Qubi Decoction has a better efficacy on knee-OA than traditional treatment methods (diacereinand + celecoxib) and showed no adverse effect.</p>

Tapering of recombinant human tumor necrosis factor receptor-Fc fusion protein dosage combined with DMARDs in the treatment of peripheral joints involvement of ankylosing spondylitis / 中华风湿病学杂志

Objective To evaluate the clinical efficacy and safety of tapering the dosage of recom-binant human tumor necrosis factor receptor-Fc fusion protein (rhTNFR-Fc) combined with DMARDs in the treatment of peripheral joints involvement of ankylosing spondylitis. Methods Sixty patients who met the classification criteria of ankyloding spondylitis were enrolled. Meanwhile, all patients had one or more of the following joint involvement: hip, knee, ankle, and shoulder. Their BASDAI was higher than 4, joint pain VAS≥4, ESR ≥30 mm/1 h and CRP≥8 mg/L. Tuberculosis, hepatitis B, hepatitis C infection or other microorgan-isms infections were excluded. All enrolled patients had no serious heart,liver,kidney, or other internal organ involvement. During the first stage (The first eight weeks patients were matched by age and, disease activity, then randomly divided into the rhTNFR-Fc (the control group) treatment group in which patients were treated with 25 mg rhTNFR-Fc subcutaneous injection twice per week for 4 months) and rhTNFR-Fc dosage tapering group in which 25 mg rhTNFR-Fc were subcutaneously injected once per week for 4 weeks and then followed by 12.5 mg per week for 4 weeks, then once every 10 days for 6 times. Then the dosage of rhTNFR-Fc dosage of the dosage tapering group (the experimental group) was changed to 12.5 mg subcutaneous injection once every 15 days for another 4 times combined with methotrexate 7.5 mg per week and Salfasalazine 2 g daily and thalidomide 100 mg per night. The second stage started from week 9 to 24. In addition to the 30 cases at the first stage, 42 cases were included based on the same inclusion criteria for stage one. Patients' clinical and laboratory parameters were evaluated at week 0, 4, 8, 16 and 24. Results During the first four weeks, all patients of both control group and experimental group reached ASAS20, 97% (29/30) patients reached ASAS50 in the control group, 83% (25/30) patients reached ASAS50 in the experimental group. At week 8, patients in both groups maintained at 100% ASAS20 improvement, 100% (13/13) patients in the control group reached ASAS50, and that of the experimental group was 97% (29/30), the differences between the two groups were not statistically significant (P>0.05). In the second stage, 72 cases (100%) could achieve ASAS20, 63 cases (88%) achieved ASASSO at week 16. At week 24, 72 cases (100%) remained to achieve ASAS20, 71 cases (99%) achieved ASAS50. The safety and compliance of the two groups were good. Two cases developed infection, one patient had mild elevation of serum transaminase. Conclusion Tapering the dosage combined with DMARDs is an effective and safe approach in the treatment of peripheral joints involvement of ankylosing spondylitis. The compliance of this strategy is good and only few patients have serum transaminase elevation. But attention should be paid to the increased rate of infection.

Effects of resveratrol on proliferation and apoptosis of TNF-alpha induced rheumatoid arthritis fibroblast-like synoviocytes / 中国中药杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHOD</b>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.</p><p><b>RESULT</b>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.</p><p><b>CONCLUSION</b>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.</p>

Effect of resveratrol on apoptosis and expression of bal-2 and bax protein in articular chondrocytes of experimental osteoarthritis model / 中华风湿病学杂志

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.

The anti-inflammatory effect of Resveratrol on collagen-induced arthritis rats / 中华风湿病学杂志

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.

Efficacy and safety of the combined treatment with intravenous immunoglobulin and oral glucocorticoid in the elderly with dermatomyositis / 中华老年医学杂志

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.

The association analysis of plasma Hcy level and MTHFR gene polymorphism with ankylosing spondylitis / 中华风湿病学杂志

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.