A mangiferin aglycon derivative J99745 has been identified as a potent xanthine oxidase (XOD) inhibitor by previous study. This study aimed to evaluate the hypouricemic effects of J99745 in experimental hyperuricemia mice, and explore the underlying mechanisms. Mice were orally administered 600 mg/kg xanthine once daily for 7 days and intraperitoneally injected 250 mg/kg oxonic acid on the 7th day to induce hyperuricemia. Meanwhile, J99745 (3, 10, and 30 mg/kg), allopurinol (20 mg/kg) or benzbromarone (20 mg/kg) were orally administered to mice for 7 days. On the 7th day, uric acid and creatinine in serum and urine, blood urea nitrogen (BUN), malondialdehyde (MDA) content and XOD activities in serum and liver were determined. Morphological changes in kidney were observed using hematoxylin and eosin (H&E) staining. Hepatic XOD, renal urate transporter 1 (URAT1), glucose transporter type 9 (GLUT9), organic anion transporter 1 (OAT1) and ATP-binding cassette transporter G2 (ABCG2) were detected by Western blot and real time polymerase chain reaction (PCR). The results showed that J99745 at doses of 10 and 30 mg/kg significantly reduced serum urate, and enhanced fractional excretion of uric acid (FEUA). H&E staining confirmed that J99745 provided greater nephroprotective effects than allopurinol and benzbromarone. Moreover, serum and hepatic XOD activities and renal URAT1 expression declined in J99745-treated hyperuricemia mice. In consistence with the ability to inhibit XOD, J99745 lowered serum MDA content in hyperuricemia mice. Our results suggest that J99745 exerts urate-lowering effect by inhibiting XOD activity and URAT1 expression, thus representing a promising candidate as an anti-hyperuricemia agent.

Objective To investigate the prevalence of balance deficiency and falls in patients with rheumatoid arthritis (RA),and to explore the effect of above factors on osteoporotic fracture (OPF).Methods A total of 386 patients with RA and 158 age,gender-matched normal subjects from Jan 2013 to Oct.2015 were recruited.Antero-posterior and lateral X-rays scanning of vertebral column (T5-L5) were conducted for each individual,and semi-quantity method was used as the standard for determining vertebral OPF.Falls in 296 RA were recorded in details.The balance ability of 263 cases were measured by Berg balance scale.Statistical analysis was performed with ttest and Chi-square text and logistic regression analysis.Results ① The prevalence of vertebral OPF in RA was 17.4％(67/386),which was 4.5 times the prevalence of the control group (6/158,3.8％) (x2=17.743,P＜0.01).The occurrence rate of falls in RA was 20.3％ during the last year (60/296).② Compared to RA without OPF,patients with OPF had lower Berg balance score (43±14 vs 33±15,t=4.150,P＜0.01).Patients with falls also had lower Berg balance scale scorethan that in RA without falls (31± 16 vs 41±14,t=4.373,P＜0.01).③ The prevalence of falls during the last year in RA with vertebral OPF was 39.2％ (20/51),which was higher than that in RA without OPF (15.7％,22/140) (x2=12.036,P=0.01).The prevalence of falls during the last year in RA with Berg balance scale score ＜40 was 32.5％,which was higher than that in patients with Berg balance scale score≥40 (P＜0.01).Incidence of Berg balance scale score ＜40 in patients with OPF (68.8％,33/48) was higher than that in group without OPF (29.7％,35/118) (x2=21.558,P＜0.01).④ Logistic regression analysis found that age [OR=1.064,P=0.001,95％CI (1.025,1.103)] and falls [OR=2.735,P=0.021,95％CI(1.168,6.407)] were risk factors for OPF in RA patients,while Berg balance scale score [OR=0.957,P=0.016,95％CI (0.924,0.992)] was negatively correlated with spinal OPF in RA patients.Conclusion Falls and decreased balance capacity in RA are closely correlated with OPF in RA.

Objective To investigate the value of serum levels of peroxisome proliferater-activated receptor (PPAR)γin patients with rheumatoid arthritis (RA) and to explore the associations between serum PPARγwith disease activity of RA and RA-associated osteoporosis (OP).Methods One hundred and one cases of hospitalized patients with RA were enrolled.A total of 88 normal subjects during the same period were recruited as the control group.Levels of serum PPARγwere detected by enzyme linked immunosorbent assay (ELISA).Bone mineral density (BMD) was measured by dual energy X-ray absortiometry.All the clinical and laboratory indexes of RA patients were recorded in detail.T-test (or t'-test) was used for comparison of measurement data between the two groups,non-parametric test was applied for skewed distribution data.Comparison of incidence was analyzed with x2 test,correlation analysis was represented ascorrelation coefficient (r).Results Binary logistic regression analysis was used for multivariate regression analysis.Serum levels of PPARγ(3.38/4.00 ng/ml) in RA patients were higher than thosein normal subjects (2.63/1.76) ng/ml (Z=3.204,P=0.001).The positive rate of serum levels of PPARγin RA was 35.6％ (36/101),while the positive rate in the controls was (2.3％,2/88,x2=32.602,P＜0.01).The incidence of OP in RA was 34.7％(35/101;while the levels of serum PPARγ in RA without OP at femur area (femoral neck,total hip) and lumbar spine (L1,L1-4) were higher than that in RA with OP (P＜0.05).Serum levels of PPARγ between groups with different disease activity had no significant difference (P＞0.05).Serum levels of PPARγ in RA with negative RF or negative anti-CCP were higher than thosetin the RA group with positive RF or positive anti-CCP(P＜0.05).Serum levels of PPARγ in RA were negatively correlated with serum RF,anti-CCP,hemoglobin (P ＜0.05-0.001),and positively correlated with erythrocyte sedimentation rate,platelet,BMD at sites of femur neck andWard (P＜0.05-0.001).Results of binary logistic regression analysis showed that levels of serum PPARγwere protective factors in RA for OP at femurneck [OR=0.577,P=0.005,95％CI (0.394-0.846)],and total hip [OR=0.754,P=0.033,95％CI (0.581-0.978)].Condusion Serum levels of PPARγ in patients with RA are significantly increased,and negatively correlate with autoantibodies.Serum levels of PPARγare protective factors for OP in RA.

Objective To investigate the effect of sarcopenia and vitamin D deficiency on osteoporosis (OP) in patients with rheumatoid arthritis (RA).Methods Six hundred and forty-eight patients with RA were enrolled into the study,while 158 normal subjects were recruited as the control group.Bone mineral density (BMD) at total hip and lumbar vertebra 2-4 were measured by dual energy X-ray absorptiometry (DEXA),limbs skeletal muscle mass was determined in 267 patients with RA and 156 normal subjects by bioelectrical impedance method.Serum 25-hydroxy vitamin D [25(OH)D] levels were determined by electrochemiluminescence in 234 RA patients and 68 normal subjects.Clinical and laboratory features,daily dosage and duration of glucocorticoid (GC) were recorded.Numerical data and categorical data comparisons were analyzed using t test,x2 test,linear correlation analysis,single factor analysis of variance test and Logistic regression analysis test.Results ① Incidence of OP in RA (37.8％,245/648) was significantly higher than that in the controls (13.9％,22/158)(x2=32.712,P＜0.01).Incidence of sarcopenia was evidently higher in RA,compared with normal subjects [55.8％(149/267),9.0％(14/156),x2=91.176,P＜0.01].Percentage of sarcopenia was higher in RA with OP compared with RA without OP group [76.6％(49/64),39.3％(35/89),x2=20.848,P＜0.01].②Compared to control group,serum 25 (OH)D levels were significantly lower in RA group [(13.4±9.7) ng/ml,(22.4±6.3) ng/ml,t=9.063,P＜0.01].Rate of vitamin D deficiency iu RA was also higher than that in controls [80.8％(189/234),36.8％(25/68),x2=49.412,P＜0.01].③The differences of serum 25 (OH)D levels among different bone metabolic state groups at lumbar vertebra in RA (normal bone mass,osteopenia,OP) were statistically significant (F=6.263,P=0.003),whichrepresented a clearly decreasing trend along with the decreasing of serum 25 (OH)D levels (P=0.001).④Linear correlation analysis found that skeletal muscle mass indexes at limbs in RA were positively correlated with BMD and serum 25 (OH)D levels (P＜0.05).⑥Logistic Regression analysis revealed that sarcopenia (OR=4.373,P=0.002),age (OR=1.083,P=0.001) and duration of disease (OR=1.074,P=0.029) were the risk factors for occurrence of OP in patients with RA.Conclusion Sarcopenia generally exists in patients with RA,which is correlated with decreasing of serum 25 (OH)D levels,and also is the risk factor for the occurring of OP in RA.

Objective To analyze and compare the clinical and laboratory features between patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (nr-axSpA).Methods One hundred and forty-one patients with AS and 73 cases with nr-axSpA were recruited.Clinical and laboratory indexes of individuals were recorded in detail,Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) crp were calculated.Spondyloarthritis research consortium of Canada (SPARCC) score standard was used to evaluate the degree of bone marrow edema in sacr-oiliac joint under magnetic resonance imaging scanning.T test,rank test and x2 test were used for statistical analysis.Results The average age of patients with AS was obviously higher than that of patients with nr-axSpA (t=4.962,P＜0.01).Patients with AS were more often male,and those with nr-axSpA were more often female (82.0％ of the AS patients were men and 49.3％ of the nr-axSpA patients were men (x2=24.079,P＜0.01).Disease duration of AS was significantly longer than that of the nr-axSpA (Z=6.396,P＜0.01).The incidence of human leukocyte antigen (HLA)-B27 positive in AS was 89.4％,which was similar to that in patients with nr-axSpA (84.9％) (x2=0.884,P＞0.05).21.6％ (21 cases) of patients with AS had peripheral swollen joints,which was higher than that in nr-axSpA (2.2％,x2=8.861,P=0.003).Forty cases in AS had tender joints (41.2％),only 6 patients in nr-axSpA had tender joints (13.3％,x2=11.458,P＜0.01).Serum erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) levels in patients with AS were clearly higher than those in nr-axSpA (P＜0.01) patients.In AS,the patient global assessment (PGA),BASDAI and ASDAScrp value was significantly higher than that in nr-axSpA (P＜0.01).There were no differences in SPARCC score or incidence of bone marrow edema in sacroiliac joint in magnetic resonance imaging scanning between AS and nr-axSpA (P＞0.05).Percentage of patients with occipit-to-wall distance higher than 0 cm in AS was higher than that in nr-axSpA,and the mean distance of fingers to ground in AS was also higher than that in nr-axSpA (x2=19.844,P＜0.01;Z=5.724,P＜0.01).Chest expansion degree and Schboer's test in AS was much lower than that in nr-axSpA,respectively (Z=3.083,P=0.002;Z=5.103,P＜0.01).BASFI in AS was higher than that in nr-axSpA (Z=5.840,P＜0.01).The ratio of joint function in AS was obviously worse than that in nr-axSpA (x2=1 1.369,P=0.01).Conclusion Compared to patients with nr-axSpA,AS patients are male predominant,and have severer inflammation in clinical and laboratory findings and are worse in functional status.

Objective To investigate the prevalence of balance capacity declining and sarcopenia in patients with rheumatoid arthritis (RA),and to explore the effect of balance capacity declining and sarcopenia on spinal osteoporotic fracture (OPF)in RA. Methods A total of 963 hospitalized patients with RA and 158 age, gender-matched normal subjects from Jan. 2013 to Oct. 2015 were recruited from department of Rheumatology and Immunology, the first affiliated hospital of Anhui Medical University. Anteroposterior and lateral X-ray scanning of vertebral column(T5-L5)was conducted for every individual and semi-quantity method were used as the standard for determining vertebral OPF. Two hundred and sixty-seven RA patients and 156 control individuals were measured by bioelectrical impedance method for detecting skeletal muscle mass. Berg balance scale method was used to determine the balance capacity in RA patients. Statistical analyses were performed using statistical product and service solutions (SPSS) software (Version 17.0). Comparison of frequency among different groups was used by x2test. Ranksum test was used to compare the median of measurement data in different groups when the data were skewed in distribution. Linear correlation between two indicators was represented with correlation coefficient. Multivariate regression was analyzed by binary logistic Regression(Backward LR). Results ①The prevalence of vertebral OPF in RA was 15.1%(141/936), which was higher than that in the control group (6/158, 3.8%) ( x2=18.658, P<0.01). The incidence of sarcopenia in RA patients was 55.8%(149/267), which was significantly higher than that in control group (9.0%, 14/156) ( x2=91.176, P<0.01).②Compared to RA without spinal OPF, skeletal muscle mass of general body and every part of extremities were apparently decreased in RA with spinal OPF (P<0.05). Berg balance scale score in RA with spinal OPF (33±15) was lower than that in RA without spinal OPF (43 ±14) (t=4.150, P<0.01). ③Berg balance scale score in RA patients with sarcopenia was lower than that in RA without sarcopenia (37±14 vs 43±13, t=3.524, P=0.001) and the proportion of Berg balance scale score ≤40 in RA with sarcopenia was higher than that in RA without sarcopenia (50.8%,65/128 vs 29.9%,32/107, x2=10.477, P=0.001).Skeletal muscle mass of general body(18±4 vs 20±5,t=3.563,P<0.01)and every part of extremities in RA patients with Berg balance scale score ≤40 also were significantly reduced than that in RA group with Berg balance scale score >40(P<0.05). ④ Linear correlation analysis found that Berg balance scale score was positively correlated with skeletal muscle index (SMI)(r=0.299, P<0.01), skeletal muscle mass of general body (r=0.251, P<0.01), muscle mass of right upper limb (r=0.225, P<0.01), muscle mass of left upper limb (r=0.221,P<0.01).muscle mass of trunk(r=0.230,P<0.01),muscle mass of right lower limb(r=0.228, P<0.01), muscle mass of left lower limb (r=0.245, P<0.01) in RA. ⑤Logistic regression analysis (LR Backward) discovered that age (OR=1.075, P=0.002, 95%CI (1.028,1.124)] was the risk factor for spinal OPF in RA patients, while skeletal muscle mass index (SMI) [OR=0.649, P=0.020, 95% CI (0.451, 0.933)] and Berg balance scale score [OR=0.957, P=0.016, 95%CI (0.924, 0.992)] were protective factors for the occurrence of spinal OPF in RA. Conclusion Sarcopeniaand balance capacity declining are probably correlated with spinal OPF in RA.

OBJECTIVE:To elucidate the efficacy and mechanism of Hugan tablets in hepatoprotective effects from perspective of metabolic pathways. METHODS:36 male rats were randomly divided into normal group (0.5%sodium carboxymethyl cellu-lose),model group(0.5%sodium carboxymethyl cellulose)and Hugan tablets group(1.7 g/kg),12 in each group,intragastrically administrated once a day,for 9 d. After 1 h of last administration,rats in model group and Hugan tablets group were intraperitone-ally injected 50%CCl4 peanut oil solution 1 mL/kg to induce liver injury. After 24 h of modeling,malondialdehyde(MDA),super-oxide dismutase(SOD),glutathione peroxidase(GSH-Px)levels in liver tissue of rats were detected. Nuclear magnetic resonance spectroscopy(1H-NMR)metabolomics technique was adopted to establish the serum and liver metabolite profiles of rats,and the ef-fects of Hugan tablets on changes of metabolic profile and potential biomarkers in serum and liver of rats with CCl4-induced acute liver injury were analyzed. RESULTS:Compared with normal group,MDA level in liver tissue of rats in model group was signifi-cantly increased(P<0.05),SOD and GSH-Px levels were significantly reduced(P<0.05). Both body physiology and material me-tabolism of rats were obviously changed,and levels of 11 metabolic potential biomarkers in serum and 14 metabolic potential bio-markers in liver were significantly increased/decreased (P<0.05). Compared with model group,MDA level in liver tissue in Hugan tablets group was significantly reduced(P<0.05),SOD and GSH-Px levels were significantly increased(P<0.05). Serum and liver metabolism tended to be normal,6 metabolic potential biomarkers(isoleucine,leucine,3-hydroxybutyrate,acetone,ace-toacetate,choline) in serum and 8 metabolic potential biomarkers (3-hydroxybutyrate,alanine,glutamate,pyruvate,succinate, choline,lactate,glucose)in liver got significant callback(P<0.05). CONCLUSIONS:The hepatoprotective mechanism of Hugan tablets may be associated with antioxidative stress and regula-tion of lipid metabolism,glucose metabolism and amino acid metabolism.

Objective To explore the value of patient global assessment (PGA) on evaluating disease activity in patients with axial spondyloarthritis (SpA),Methods A total of 222 patients with axial SpA were recruited.Scores of PGA,disease activity index [Bath ankylosing spondylitis disease activity index (BASDAI),ankylosing spondylitis disease activity score (ASDAS)crp] and spondyloarthritis research consortium of Canada (SPARCC) were calculated.Differences of PGA scores between different disease activity groups in axial SpA were compared and correlations between different disease activity index with PGA scores were analyzed.Statistical analyses were performed using Statistical Product and Service Solutions (SPSS) software (version 17.0).Comparison of frequency among different groups was performed by x2 test.Rank-sum test was used to compare the median of measurement data in different groups when the data were skewed in distribution.Cut-off value of PGA for assessing disease activity in axial SpA was calculated by ROC curve.Results Medians of PGA score in groups with BASDAI remission[3(1,4) vs 5(4,7)] and ASDAScrp remission [1(1,2) vs 4(2,5)] were lower than that in disease activity group (P＜0.01).BASDAI scores [1.80(1.20,2.90) vs 3.40(2.28,4.63) vs 5.15 (4.08,5.88)] and ASDAScrp scores [2.19(1.34,2.76) vs 2.86(2.08,3.54) vs 4.08(2.96,4.41)] were significant different among PGA groups (≤3,4-6 and ≥7) (P＜0.01).Differences of SPARCC scores [6.00(0,18.00) vs 7.50(3.75,18.00) vs 18.50(6.75,24.50)] were statistically significant among PGA groups (Z=7.427,P=0.037).Erythrocyte sedimentation rate (ESR) [12.00(5.00,23.00) mm/1 h vs 19.50(7.00,44.50) mm/1 h vs 18.00(7.75,54.75) mm/1 h],C-reactive protein (CRP) [7.85(2.37,22.49) mg/L vs 10.07(3.02,28.51) mg/L vs 21.28(7.14,37.74) mg/L] and Bath ankylosing spondylitis functional index (BASFI) [0.70(0.10,1.30) vs 2.25(0.60,3.30) vs 2.85(0.83,6.53)] were also different among PGA groups (P＜0.01,separately).Proportion of axial SpA patients in BASDAI disease activity group or ASDAScrp higher disease activity group were different among PGA groups (P＜0.01,separately),while represented as positive correlations (P＜0.01,separately).Correlation analyses revealed that PGA was positively correlated with ASDAScrp (r=0.694),BASDAI(r=0.616),SPARCC (r=0.271),ESR (r=0.288),CRP(r=0.215),occipital wall distance (r=0.196),finger-floor distance (r=0.385) and negatively correlated with Sschober's test (r=-0.195) (P＜0.05).Receiver operator characteristic (ROC) curve analysis found that PGA-BASDAI AUC was 0.813,the cut off value of PGA was 3.5 and PGA-ASDAScrp AUC was 0.860,the cut off value of PGA was 2.5.Conclusion PGA has good correlations with the disease activity indexes in axial SpA patients.It can also reflect the degree of inflammation in iconography.PGA may reflect disease activity especially when the value of PGA is around 3.

Objective To investigate the clinical value of serum 14-3-3η protein levels in patients with rheumatoid arthritis (RA) and secondary osteoporosis (OP). Methods 259 RA patients and 80 healthy controls were recruited. Serum 14-3-3η levels were determined by ELISA and bone mineral density (BMD) were detected by the DEXA. Results Firstly, the levels and the positive rate of serum 14-3-3η protein were significantly high-er in RA patients than healthy controls (P < 0.000 1). Secondly, ROC curve revealed that the sensitivity of 14-3-3η protein for diagnosis of early RA was 91.7% and its specificity was 99.6% when the cut-off point was 0.879 ng/mL (AUC = 0.917, P < 0.000 1). Finally, 14-3-3η protein concentrations revealed significant differ-ence among the groups of bone mass normal, osteopenia and osteoporosis in early RA (χ2=7.974, P = 0.019). Conclusion Serum 14-3-3η protein levels increase significantly in RA , especially in early RA , which is relat-ed to clinical symptoms and osteoporosis.

The relationship between peripheral blood platelet-to-lymphocyte ratio (PLR) and the type 2 diabetic nephropathy was investigated.PLR was positivly related with microalbuminuria(P＜0.01).The multifactor logistic regression analysis showed that PLR was a risk factor of type 2 diabetic nephropathy (OR =2.012,95％ CI 1.000-5.023,P＜0.05).