Recommendations for the diagnosis and treatment of connective tissue disease-associated interstitial lung disease in China / 中华内科杂志

Interstitial lung disease (ILD) is a frequent complication of patients with connective tissue disease (CTD) and significantly affects morbidity and mortality. Disease course may vary from stable or mildly progressive to more severe, with rapid loss of lung function. At present, there are great challenges and poor prognosis in the diagnosis and treatment of CTD-ILD. Based on the evidence and guidelines from China and other countries, experts from the Chinese Rheumatology Association developed standardization of diagnosis and treatment of CTD-ILD. The aim is to strengthen the early identification of, standardize the diagnosis and treatment of CTD-ILD, and delay the progress of the disease.

Recommendations of diagnosis and treatment of gout in China / 中华内科杂志

Gout is a crystal associated arthritis caused by monosodium urate (MSU) accumulating in joint, and it belongs to metabolic rheumatic disease. In China, gout is common but it is insufficient for education of standardized diagnosis and treatment for gout. Based on the evidence and guidelines from China and other countries, Chinese gout Collaborative Research Group developed standardization of diagnosis and treatment of gout in China. The purpose is to standardize the methods for diagnosis of gout, treatment opportunity and strategies in order to reduce misdiagnosis, missed diagnosis and irreversible damage.

Expression and significance of miR-21 in primary gout patients / 中华风湿病学杂志

Objective To explore the expression and significance of miR-21 in patients with primary gout. Methods The patients were divided into 4 groups: 35 acute gout patients (AG), 50 intermittent gout patients (IG), 25 chronic gout patients (CG) and 39 healthy patients. Their peripheral blood were collected and laboratory indexes were recorded. The expression of miR-21 and Nod-like receptor pyrin domain-containing protein 3 (NLRP3) mRNA in the peripheral blood mononuclear cells (PBMCs) was detected by real-time quantitative polymerase chain reaction (RT-qPCR). The blood and clinical data of another 5 healthy volunteers were collected, their peripheral blood was stimulated with 100 μg/ml monosodium urate (MSU) for 1 hour, pho-sphate buffer (PBS) was used as controls, then the expression of microRNA (miR)-21, NLRP3, interleukin (IL)-1β mRNA was detected by RT-qPCR. Rank sum test and spearman correlation analysis were used for data analysis. Results In primary gout patients, the expression of miR-21 in AG [12 ×10-4 (8.0 ×10-4)], IG [9.4 ×10-4 (6.9 ×10-4)], CG [7.3 ×10-4 (5.6 ×10-4)] was significantly higher than that in healthy control group [1.0×10-4(2.0×10-4)] (Z=9.83, P=0.02], while the expression of NLRP3 in AG[0.0444(0.0233)], IG[0.0581(0.0326)], CG[0.0314(0.0198)] was significantly lower than that in healthy control group [0.0886(0.0359)] (Z=13.82, P<0.01). In the primary gout of IG group, the expression of miR-21 was positively correlated with NLRP3 mRNA (r=0.449, P=0.016). After stimulated by 100 μg/ml MSU, the expression of miR-21 of the stimulated group [8.78×10-4(14×10-4)] was higher than that in the control group [6.25×10-4(6×10-4)](Z=-2.203, P<0.05), and the expression of IL-1βin stimulated group [3.06(2.00)] was higher than that in the control group [2.64 (1.22] (Z=-2.203, P<0.05). The level of miR-21 in patients with primary gout was positively correlated with the level of uric acid (UA), glutamic oxaloacetic transaminase (AST) and glutamic pyruvic transaminase (ALT) (r=0.473, 0.639, 0.487, P<0.05). Conclusion The increase of miR-21 in patients with primary gout may be involved in the inflammatory reaction of gout.

Expression and clinical significance of long noncoding RNA-AK001903 in patients with gouty arthritis / 中华风湿病学杂志

Objective To investigate the role of long noncoding RNA-AK001903 in the pathogenesis of primary gout arthritis (GA).Methods The subjects were divided into four groups:30 acute gout patients (AGA),24 non-acute gout patients (NAGA),24 healthy controls and 24 hyperuricemia (HUA).Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to examine the expression of AK001903 in peripheral blood mononuclear cells (PBMCs) from four groups.100 μg/ml monosodium (MSU) was used to stimulate the peripheral blood of NAGA and healthy control patients.Then the expression of AK001903 was detected by RT-qPCR.Kruskal-Wallis test,Mann-Whitney test,Spearman correlations were used for statistical analysis.Results The expression level of AK001903 in the AGA group (0.079±0.022) and the NAGA group (0.071±0.021) were higher than the healthy control group (0.014±0.004).There was no significant difference between the NAGA group and the NAGA group (Z=-0.655,P＞0.05).Those of the GA group (0.078±0.018) and the HUA group(0.047±0.016) was higher than the healthy control group (0.014±0.004) (Z=-2.887,Z=-4.157;P＜0.05).Compared with the control group,the expression of AK001903 in NAGA and the healthy control group which were stimulated by MSU was significantly increased.The Spearman correlation analysis found that the AK001903 expression levels in the GA groups were correlated with TG (r=0.938,P＜0.05),VLDL (r=0.873,P＜0.05),GLU9 (r=0.671,P＜0.05) and were negatively correlated with apoA1 (r=-0.661,P＜0.05).Conclusion Altered expression of AK001903 may be involved in the process of imbalance between lipid metabolism and hyperuricemia,and takes part in the pathogenesis of GA.

Changes of estrogen and its receptor ERα, ERβ and GPR30 in asymptomatic hyperuricemia / 中华风湿病学杂志

Objective To investigate the changes aad possible role of estrogen and its receptor ERα、ERβ、GPR30 in the pathogenesis of asymptomatic hyperuricemia.Methods The peripheral blood of 62 asymptomatic hyperuricemia patients (AH) and 68 healthy controls (HC) were collected.The expression of estradial (E2) in serum was detected by the chemilluminescent microparticle immunoassay (CMIA).The expression of ERα,ERβ,GPR30 mRNA in peripheral blood mononuclear cells (PBMCs) was measured using Real time quantitative polymerase chain reaction (RT-qPCR).Statistical Package form Soci-science (SPSS) 17.0 statistical software was used for data analysis.The measurement data were compared by t test,rank sum test or one factor analysis of variance test.The correlation between variables was used by Spearman correlation analysis.Results ① The expression of E2 in serum of the HC group was higher than that in the AH group [(38.7±10.2) pg/ml vs (33.7±8.6) pg/ml,Z=-0.356,P＜0.05].② The expression of ERα,GPR30 mRNA in PBMCs of HC group was increased,compared with that in the AH group (0.000 17±0.000 23 vs 0.000 12± 0.000 12,0.002 0±0.002 1 vs 0.001 5±0.000 8,Z=-2.112,-2.147,P＜0.05,respectively).No significant difference in PBMCs ERβ mRNA levels was found between HC group and AH group,while a slight but not significant increase was observed in HC group.③ The Spearman correlation analysis found that the expression of ERα and ERβ mRNA,E2 and GR,ERβ and GLU in the AH group were positively related (r=0.259,0.251,0.260,P＜0.05,respectively).Conclusion The expression of E2,ERα,ERβ,GPR30 mRNA in the peripheral blood of patients with AH is decreased,suggesting that the estrogen and its receptor may be involved in the patho-genesis of hyperuricemia.

The clinical characteristics, diagnosis and treatment of patients with gout in China / 中华内科杂志

Objective To investigate the demographic characteristics, clinical features, diagnosis and treatment of patients with gout in China.Methods Clinical data of 6 814 patients with gout from 100 hospitals in 27 provinces, municipalities or autonomous regions in China were collected and analyzed. Results (1)The ratio of male to female in patients with gout was 14.7:1.The mean age of onset was(48.8 ± 15.1)years old.Mean serum urate level was(526.7 ± 132.3)μmol/L.Patients'education background was of U-shaped distribution; (2) Hypertension was the most common comorbidity [15.8%(1 079/6 814)], then overweight or obesity[51.9%(3 536/6 814)];(3)Alcohol and high-purine food intake were dominant triggering factors in men. The diagnosis of gout was made after onset in majority of patients with cardinal symptom arthralgia.Most patients had the disease less than 5 years,and the longer the course,the more flares in the previous year of entry;(4)Febuxostat was the mostly used urate-lowering medication.20.7%(1 412/6 814), 10.8%(739/6 814) and 3.9%(265/6 814) of patients were followed up in 4 weeks, 12 weeks and 24 weeks after registration,and 18.9%(267/1 412),29.1%(215/739)and 38.1%(101/265)of them reached the control target of serum urate levels,respectively.After treatment,patients'liver function was not affected,but serum creatinine levels decreased significantly. Conclusions The proportion of gout patients who reach target serum urate level is very low.Further steps including education and survey need to be carried on.

Study on the expression and significance of Th1/Th2 cells in the blood of patients with primary gouty arthritis / 中华风湿病学杂志

Objective This study is aimed to investigate the possible role of Th1/Th2 cell in the pathogenesis of primary gout arthritis. Methods The peripheral blood of 21 acute gout patients (AG), 20 intermittent gout patients (IG) and 20 healthy controls (HC) were collected. The clinical data and laboratory indicators of them were enrolled. The percentages of Th1 and Th2 cells were detected by flow cytometry (FCM). The expression of GATA-3, T-bet, IL-4 and interferon (IFN)-γ mRNA in Peripheral blood mononuclear cells (PBMCs) were measured using Real time quantitative polymerase chain reaction (PCR). The protein expression levels of IL-4 and IFN-γ in serum were detected by enzyme-linked immuno sorbent assay (ELISA). The measurement data were compared by one factor analysis of variance test. The correlation between variables was used by Spearman correlation analysis. Results The percentage of Th1 cells in peripheral blood of the AG group was [(23.2 ±8.3)％], and the IG group was [(20.5 ±9.3)％], which were significantly higher (F=6.520, P<0.05) than the percentage of HC group [(14.8±3.8)％]. There was no significant difference between AG group and IG group. The percentage of Th2 cells in peripheral blood of AG group were [(1.9 ±0.7)％], which was significantly lower (F=8.267, P<0.05) than and the percentage of HC group [(3.4±1.8)％] and IG group [(3.3± 1.2)％]. There was no significant difference between the IG group and the HC group. And the proportion of TH1/Th2 cells in the AG group was higher than that of the IG group and the HC group (F=10.406, P<0.01). The expression of T-bet mRNA and IFN-γ mRNA in the AG group and IG group were higher than that in the HC group (F=4.942, P=0.010)、(F=4.458, P=0.016). However, there was no significant difference between IG group and AG group. The expression of GATA-3 mRNA and IL-4 mRNA was significantly lower (F=3.564, P=0.035) (F=5.385, P=0.007) in the AG group and IG group when compared to the HC group. And there was no significant difference between the AG and the IG group. The IFN-γ level increased in the AG and IG group compared to the HC group (F=7.659, P=0.001). The IL-4 levels in the AG group was lower (F=7.099, P=0.002) than those of the IG and HC group. Conclusion Th1 cells in the peripheral blood of patients with GA are increased and accompanied with the decrease of Th2 cells. The results of this study suggest that the imbalance of Th1/Th2 cells in the inflammatory and immune response plays a critical role in the pathogenesis of GA.

LncRNAs expression profile of ankylosing sporidylitis revealed by microarray / 中国医师杂志

Objective To investigate the expression profile variation of long non-coding RNAs (lncRNAs) in ankylosing sporidylitis (AS) and explore the role of lncRNAs in the pathogenesis of AS.Methods The peripheral blood mononuclear cells of AS patients and health controls (HC) were used to detect for differently expressed lncRNAs by microarray.The roles of lncRNAs were predicted with GO and pathway analysis.The results were verified by real time-polymerase chain reaction (PCR).Results A total of 148 lncRNAs and 134 mRNAs were detected,which had more than 2-fold differentially expressed in AS patients.Bioinformatics analysis found that GO term enrichment included protein binding,regulation of transcription,metabolism,signal transduction,et al.and might involve in toll-like receptor pathway,protein kinase,complement pathway,notch signaling pathway and so on.The expressions of three lncRNAs were estimated by real time-PCR which found that consistent with that of microarrays.Among these,D90064 was the most aberrantly expressed lncRNAs.Conclusions Several lncRNAs expression was changed significantly in AS patients in comparison with HC,which implies that those different lncRNAs may have an important role in the development and progression of AS.

Altered expression of miR-223 might be involved in regulation of inflammation in primary gout patients / 中华风湿病学杂志

Objective To investigate the role of miR-223 in the pathogenesis of acute gouty inflammation.Methods The subjects were divided into 3 groups:65 acute gout patients (AG),50 inter-critical gout patients (IG),and 45 healthy controls (HC).The peripheral blood mononuclear cells (PBMCs) and the clinical laboratory parameters were all collected.The expression of miR-223 in the PBMCs was detected using realtime fluorescent quantitative polymerase chain reaction (RT-qPCR) (TaqMan probe).The PBMCs of 5 healthy people were stimulated with monosodium urate (MSU) (100 μg/ml) for 12 h,and then,miR-223,NLRP3 mRNA and IL-1β production were all measured using RT-qPCR and ELISA respectively.All data were analyzed by SPSS 17.0 statistical software,Wilcoxon rank sum test,t test and Spearman's correlations analysis were used for statistical analysis.Results ① The expression of miR-223 in AG and IG groups was both significantly decreased than that in the HC group (8±17 vs 26±76,P＜0.05;9±17 vs 26±76,P＜0.05;respectively),AG group was significantly decreased than that in the IG group [8(17) vs 9(17),Z=11.387,P＜0.01].② After stimulated with MSU in healthy controls,IL-1β production and NLRP3 mRNA were both significantly increased [(86±5) pg/ml vs (13±6) pg/ml,t=21.042,P＜0.01;5.2±0.4 vs 1.2±0.4,t=14.640,P＜0.01;respectively],while the expression of miR-223 was significantly decreased (0.34±0.20 vs 1.05±0.24,t=-5.164,P＜0.01).Conclusion The data suggests that miR-223 might be involved in the patho-genesis of spontaneous regulation,but further study is needed to discover the exact mechanism.

The mechanism of lipoxin A4 intervention on the oxidative stress induced by uric acid in human umbilical vein endothelial cells / 中华风湿病学杂志

Objective To investigate the effect and mechanism of lipoxin A4 (LXA4) on uric acid (UA) induced oxidative stress of human umbilical vein endothelial cells (HUVECs).Methods The HUVECs was treated with uric acid to constructing the model of oxidative stress,and intervene the model with LXA4 and xylene based iodine (DPI),rotenone.Reactive oxygen species (ROS) of HUVEC were detected by a fluorescence probe 2',7'-dichlorofluorescin diacetate (DCFH-DA).The activity of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and p47phox protein was measured by Lucigenin enhanced chemiluminescence and Western blotting among control,uric acid (UA),LXA4 and UA +LXA4 groups,respectively.All the results were described by the relative expression of the control group,repeated measure variance analysis and least significant difference test (LSD) were used for statistical analysis.Results UA could stimulate HUVEC to generate ROS with different concentrations and times (F=7.286,F=4.532,P＜0.05).Compared with the control group(100±l 1),the ROS production of group with 80 mg/L UA (177±18),120 mg/L (226±29) and 160 mg/L (225±16) increased significantly (t=4.127,t=7.591,t=7.236,P＜0.05).Compare with baseline(100±8),the ROS production increased significantly (t=3.688,t=3.513,t=4.526,t=8.269,t=3.829,P＜ 0.05) at 3 h(143±16),6 h(140±17),12 h(183±20),24 h(240±29) and 48 h(160±22).LXA4 could inhibit ROS generation at different concentrations and times (F=4.008,F =4.497,P ＜0.05).Compared with LXA4 concentration of 0 nmol/L,the LXA4 concentrations of 10 nmol/L (162±16) and 100 nmol/L (132±15) could significantly inhibit ROS generation(t=3.712,t=4.083,P＜0.05).Compared with pretreatment (269±39),the ROS generation decreased significantly (t=6.373,t=6.426,t=7.125,t=6.981,P＜0.05).with LXA4 pretreated for 15 min (160±16),30 rain(158±21),1 h (136±13) and 2 h(140±13).Compared with the UA group(252±31),LXA4 and DPI could significantly inhibited ROS generation (145±29,154±27;t=6.356,t=5.853,P＜0.05),but Rot was not significantly intervented (241±32;t=1.027,P＞0.05).The NADPH oxidase activity in the UA group was significantly higher than that in the control group (144±16,100±13;t=3.659,P＜0.05),but the group of LXA4+ UA was significantly lower than that of the UA group (119±14;t=3.124,P＜0.05).The cytoplasmic expression of NADPH oxidase subunit p47phox of UA group was significantly lower than that in the control group (47±6,100±8;t=7.562,P＜0.05),but the LXA4+UA group was significantly increased compare with the UA group (83±6,t=5.386,P＜0.05).The cytomembrane expression of p47phox of UA group was significantly higher than that in the control group (328±36,100±4,t=12.817,P＜0.05),but the LXA4+UA group was significantly decreased compared with the UA group (183±30,t=5.129,P＜0.05).Conclusion LXA4 inhibits UA induced ROS production in HUVECs.This mechanism might be through inhibiting p47phox trafficing from cytoplasm to cytomembrane,results in inhibiting the activation of NADPH oxidase.

Expression and clinical significance of long noncodi ng RNA AJ227913 in patients with gouty arthritis / 中华风湿病学杂志

Objective To investigate the role of long noncoding RNA-AJ227913 in the pathogenesis of primary gout arthritis (GA). Methods The subjects were divided into three groups:30 acute gout patients (AGA), 30 non-acute gout patients (NAGA), 30 healthy controlsand 30 hyperuricemia patients (HUA). Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to examine the expression of AJ227913 in peripheral blood mononuclear cells(PBMCs) from four groups. 100 μg/ml monosodium urate (MSU) was used to stimulate the peripheral blood of NAGA and healthy controls patients. Then the expression ofAJ227913 was detected by RT-qPCR. Kruskal-Wallis test, Mann-Whitney test, Spearman correlations were used for statistical analysis. Results The expression level of AJ227913 in the AGA group (0.0557 ±0.0156) was higher than that in the NAGA group (0.0223±0.018) and healthy controls group (0.0038±0.0013). There was significant difference between the NAGA group and healthy controls group (P>0.05). Compared with the control group, the expression of AJ227913 in NAGA group which were stimulated by MSU was significantly increased. The Spearman correlation analysis found that the AJ227913 expression levels in GA groups were correlated with UREA (r=0.608, P<0.01), CREA (r=0.337, P<0.05), CYSC (r=0.422, P<0.01). Conclusion Altered expression of AJ227913 may be involved in the inflammatory process of GA and the balance of uricacid.

Change and clinical significance of high mobility group protein B1 and its advanced glycation end product receptor in patients with systemic lupus erythematosus / 重庆医学

Objective To investigate the possible role of high mobility group box 1 protein (HMGB1) and its advanced gly‐cation end products receptor (RAGE) in the pathogenesis of systemic lupus erythematosus (SLE) .Methods The enzyme‐linked immunosorbent assay (ELISA) was used to determine the level of plasma HMGB1 in 52 cases of SLE (SLE group) and 40 healthy females undergoing physical examination (HC group) ,at the same time real time quantitative polymerase chain reaction (RT‐qPCR) was employed to detect the expression of HMGB1 and RAGE mRNA in peripheral blood mononuclear cells (PBMCs) .The correlation between plasma HMGB1 ,PBMCs HMGB1 and RAGE mRNA levels with clinical indicators was analyzed .Results The levels of plasma HMGB1 ,PBMCs HMGB1 mRNA in the SLE group were significantly higher than those in the HC group ,the differences were statistically significant (P0 .05);the Spearman correlation analysis showed that the level of plasma HMGB1 was positively correlated with antinuclear anti‐bodies titers and SLEDAI score in the SLE patients (P0 .05);the HMGB1 mRNA expression level was positively correlated with the RAGE mRNA expression level and SLEDAI scores(P0 .05) . Conclusion The abnormal expression of plasma HMGB1 and PBMCs HMGB1 mRNA in SLE patients prompts that which might be involved in the occurrence and development of SLE ,might participate in the immune and inflammatory regulation of SLE .

The changes and significance of sCD14 in gouty arthritis patients’inflammatory reaction / 西安交通大学学报(医学版)

Objective To study the changes and significance of sCD14 in inflammatory response of patients with gouty arthritis.Methods CD14 mRNA was measured using quantitative real-time PCR in peripheral blood mononuclear cells (PBMCs).The expression of CD14 mRNA in PBMCs was compared between patients with acute gouty arthritis (AGA)(n =31)and non-acute gouty arthritis (NAGA)(n =23)and healthy controls (HC)(n =20).β-actin was selected as the internal control.The protein expressions of sCD14,IL-1βand TNF-αwere measured using enzyme linked immunosorbent assay (ELISA) in patients’ plasma.The protein expression of CRP was measured using immunoturbidimetry in patients’ plasma. Routine blood and blood biochemistry indexes were measured by routine blood analyzer and blood biochemistry analyzer of patients with AGA,NAGA and HC.We analyzed the correlation between CD14 mRNA,sCD14 protein expression and each clinical indicator.Results When compared with that in AGA group,the mRNA expression of CD14 increased significantly in PBMCs of HC patients (P < 0.05 ).When compared with that in HC and NAGA patients,the protein expression of sCD14 increased significantly in the plasma of AGA patients (P <0.01).The protein expression of sCD14 was significantly lower in the plasma of NAGA than in HC (P <0.05).The protein expression of sCD14 increased significantly in the plasma of AGA compared with HC and NAGA (P < 0.01 ).When compared with those in HC,the protein expressions of IL-1β and TNF-α increased significantly in the plasma of AGA and NAGA (P < 0.01 ).When compared with that in NAGA,the protein expression of IL-1βincreased significantly in plasma of AGA (P <0.01). The indexes of WBC increased significantly in AGA compared with HC (P <0.01),and WBC increased significantly in NAGA compared with HC (P <0.05).The indexes of GR and MO increased significantly in AGA compared with HC (P <0.05),and MO increased significantly in AGA compared with NAGA (P < 0.05 ).The indexes of UA increased significantly in AGA and NAGA compared with HC (P <0.01).There was a positive correlation between CD14 mRNA expression and IL-1β in PBMCs in AGA group (r s =0.362,P =0.045).A positive correlation was found between GR and the protein expression of sCD14 in NAGA patients’plasma (r s = 0.397,P = 0.030 ). Conclusion The dysregulated expressions of CD14 mRNA in PBMCs and sCD14 protein in GA show that sCD14 may play a significantly regulatory role in inflammatory reaction.

The ABCG2 gene rs2231142 polymorphism contributes to the increased risk for gout:a meta-analysis / 中华风湿病学杂志

Objective This study is aimed to evaluate the association between the ABCG2 gene rs2231142 variant and gout using meta-analysis. Methods Related studies were identified by searching extensively in Chinese and foreign language databases such as Pubmed, EMBASE, Cochrane Library, CBMdisc databases and so on. The quality of included studies was assessed by using the Newcastle-Ottawa Scale (NOS). The odds ratio (OR) was calculated using a random-effects or fixed-effects model. A Q statistic was used to evaluate the heterogeneity, and Eggerˊs test and funnel plot were used to assess publication bias. Sub-group analyses on ethnicities and sex were also performed. Results A total of 10 studies, including 3 478 gout patients and 10,089 controls from 6 countries or regions, were included and identified for the current metaan-alysis. It was found that the A allele or AA genotype of the ABCG2 rs2231142 polymorphism had an increased risk for gout in the general population [A allele: OR=2.03, 95%CI (1.77, 2.34), P<0.01 and AA genotype: OR=3.01, 95%CI (2.34, 3.88), P<0.01, respectively]. Similar results were found in sub-group analyses of different gender and races. Conclusion Existing evidence indicate that rs2231142 polymorphism (the A allele and AA genotype) is associated with increased risk of gout.

Altered expression of IL-1 β in peripheral blood from gout patients and its association with gouty arthritis / 中华全科医师杂志

Objective To explore the role of interleukin (IL)-1β in the pathogenesis of gout.Methods Real-time quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay(ELISA) were used to measure the expression of IL-1β mRNA in peripheral blood mononuclear cells (PBMCs) and IL-1β in plasma samples from 120 acute gouty (AG) arthritis,70 chronic gouty (CG) arthritis,80 intercritical gouty (IG) arthritis patients and 96 healthy control subjects respectively.Results The expression of PBMCs IL-1β mRNA and plasma concentration of IL-1β were both much higher in gout patients than those in controls (P ＜ 0.01,respectively).And the plasma levels of IL-1β mRNA and IL-1β significantly increased in the AG group compared with CG and IG groups (P ＜ 0.01,respectively) and much higher in the CG group than those in the IG group.Positive correlations existed between plasma concentration of IL-1β and the levels of white blood cell,neutrophil,monocyte,erythrocyte sedimentation rate,blood uric acid,globulin and PBMCs IL-1β mRNA (P ＜ 0.01,respectively) while negative correlation between plasma IL-1β and plasma level of apolipoprotein in gout patients (P ＜ 0.05).Conclusion Elevated plasma level of IL-1β may be involved in the pathogenesis of acute and chronic gouty arthritis.

Effects of lipoxin A4 on the inflammatory reaction induced by uric acid in human umbilical vein endothelial cells / 中华内分泌代谢杂志

Objective To investigate the effects of lipoxin A4 ( LXA4 ) on inflammatory related factors induced by uric acid( UA) in human umbilical vein endothelial cells( HUVECs) . Methods HUVECs were treated with 5, 25, and 50 ng/ml LXA4 prior to exposure to 12 mg/dl UA. Tumor necrosis factor-alpha(TNF-α), interleukin ( IL)-1β, and IL-6 were analyzed with ELISA and realtime PCR. The phosphorylation levels of p38 mitogen-activated protein kinases( MAPK) and NF-κB/p65 were observed with Western blot. Results Stimulation of HUVECs with 12 mg/dl UA markedly increased TNF-α, IL-1β, and IL-6 production(P<0. 01). Pretreatment with LXA4 significantly inhibited UA-induced production of TNF-α, IL-1β, and IL-6 in a concentration dependent manner(P<0. 01). The mRNA expressions of TNF-α, IL-1β, and IL-6 in response to UA were also decreased by LXA4(P<0. 05). Western blot analysis showed that the phosphorylation levels of p38 MAPK and NF-κB/p65 were significantly raised by 12 mg/dl UA in HUVECs(P<0. 05), but attenuated significantly in the presence of 50 ng/ml LXA4. Conclusion LXA4 may inhibit the expressions of inflammatory related factors induced by UA via reducing p38 MAPK and NF-κB/p65 phosphorylation and play a role in anti-inflammation.

Expression of high mobility group box 1 protein and the receptor for advanced glycation end products in patients with primary gouty arthritis / 中华风湿病学杂志

Objective To investigate the role of high mobility group box 1 protein(HMGB1) and the receptor for advanced glycation end products (RAGE) in the pathogenesis of primary gouty arthritis (GA).Methods Enzyme-linked immunosorbent assay(ELISA) was used to determine the level of plasma HMGB1 in 68 acute gout (AG),48 quiescent gout (QG) and 45 healthy control(HC).Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to measure the expression of HMGB1 and RAGE mRNA in the peripheral blood mononuclear cells (PBMCs) in 68 AG,48 QG and 94 HC.One way ANOVA or Wilcoxon test and Spearman's correlations were used for statistical analysis.Results The level of plasma HMGB1,PBMCs HMGB1 and RAGE mRNA were significantly higher in GA than that in HC [(24±34) ng/ml,0.019±0.029,0.000 5±0.000 3] (P＜0.05),while the level of plasma HMGB1 and PBMCs HMGB1 mRNA were significantly higher in AG [(222±178) ng/ml,0.235±0.954,0.001 5±0.003 5] than that in QG [(107±176) ng/ml,0.044±0.117,0.001 3±0.000 9] (P＜0.05),and the level of PBMCs RAGE mRNA was higher in AG than that in QG (P＞0.05).In the GA patients,the level of plasma HMGB1 was positively correlated with white blood cell count,neutrophile granulocytes count,mononuclear cells and erythrocyte sedimentation rate (r=0.34,0.44,0.39,0.33; P＜0.05),while negatively correlated with apolipoprotein A1 (r=-0.28,P＜0.05); the level of PBMCs HMGB1 mRNA was positively correlated with RAGE mRNA,white blood cell counts,neutrophil counts,lymphocyte counts,serum total cholesterol level,low density lipoprotein level and apolipoprotein B100 level (r=0.29,0.36,0.26,0.28,0.29; P＜0.05),while negatively correlated with high density lipoprotein (r=-0.30,P＜0.01); the level of PBMCs RAGE mRNA was positively correlated with lymphocyte counts,total cholesterol and apolipoprotein B100 (r=0.35,0.35,0.44; P＜0.05).Conclusion HMGB1 and its signaling pathway may play important role in the pathogenesis of gouty arthritis,which may also be involved in the regulation of the lipid metabolism of gout.

The comparative study of left ventricular diastolic function and disease activity in rheumatoid arthritis / 中华风湿病学杂志

Objective To evaluate the change of left ventricular diastolic function and investigate the relation between left ventricular diastolic function and disease activity in rheumatoid arthritis (RA) without clinical manifestations of heart diseases. Methods Seventy consecutive active RA in-patients without clinical manifestations of heart disease were enrolled, while the control group was recruited from outpatient health physical check-up center and consisted of 60 age- and sex-matched healthy subjects. Cardiac related parame-ters were determined by echocardiography and the correlation between left ventricular diastolic function and the disease activity indexes were evaluated. Chi-square test, t test, Pearson or Spearman′s correlation test and Stepwise backward linear regression analysis were used for statistical analysis. Results RA patients had lower mitral inflow E/A ratio (1.2±0.4, 1.5±0.4, P<0.01), higher E/Em ratio (9.6±3.7, 7.8±2.0, P<0.01), longer isovolumetric relaxation time(IVRT)[(64±16) ms,(58±16) ms, P<0.05] than control group. Whilst, RA patients had higher pulmonary venous inflow A wave velocity-time integral (ArVTI) and A wave duration (DAr)[3.2±0.7,(2.8±0.6) cm; 117±11,(102±9) ms, P<0.05]. Moreover, the E/Em was positively corre-lated with C-reactive protein(CRP)(r=0.581, P<0.01), DAS28(r=0.456, P<0.01). Anti-CCP level was also associated with Em and early diastolic pulmonary venous inflow peak velocity(PVD)(r=-0.359, P<0.05;r=-0.305, P<0.05). In addition, multivariate analysis also revealed that there was linear regression relation-ship between E/Em and CRP, DAS28(t=3.266, P=0.002; t=2.949, P=0.005). Conclusion The study has revealed that left ventricular diastolic function is impaired in RA patients and the left ventricular diastolic function parameters is associated with the disease activity indexes. These results suggest that the decline of left ventricular diastolic function is associated with the inflammation activity in RA patients without clinical manifestations of heart disease.

Association of the rs3733591(C>T) polymorphism of SLC2A9 gene with primary gout in Chinese Han population / 中华风湿病学杂志

Objective To investigate the single nucleotide polymorphisms(SNPs) rs3733591(C>T) of SLC2A9 gene in Chinese Han population, and to explore the association of this gene polymorphisms with gout susceptibility, tophi, serum uric acid levels, other clinical and laboratory data and the levels of SLC2A9 mRNA of peripheral blood mononuclear cells(PBMCs). Methods ① A total of 297 primary gout arthritis patients(GA) and 211 normal controls(NC) were enrolled into this study. The clinical and laboratory data of patients were collected. The genotypes and alleles frequencies were measured by using TaqMan ?SNP Geno-typing Assays and the possible association between gene polymorphism of SLC2A9 and gout was investigated by Chi-square test. The odds ratios(OR) and 95% confidence intervals(95%CI) were calculated. ② The lev-els of SLC2A9 mRNA on PBMCs of 86 gout patients(46 patients in remission) and controls were measured by real-time quantitative polymerase chain reaction (RT-qPCR). The nonparametric test was used to analyze the expression in different groups. Results The frequencies of genotypes and alleles of rs3733591(C>T) in gout patients were different from controls(P0.05). However, there was no significant difference in the distribution of genotypes and alleles between 30 tophaceous gout patients and 190 non-tophaceous gout patients(P>0.05). Conclusion Results of present study suggest the rs3733591(C>T) polymorphism of the SLC2A9 gene might be associated with gout development, but not with tophaceous gout. The C allele predisposes to gout, and TT genotype and T allele might protect Chinese Han population from developing gout. The rs3733591(C>T) polymorphism probably affects the susceptibility to gout by influencing the f expression of SLC2A9 mRNA susceptibility.

Expression of androgen and its receptor in patients with primary gouty arthritis / 中华风湿病学杂志

Objective To measure the level of androgen receptor (AR) mRNA in peripheral blood monocytes (PBMCs) and serum testosterone level of patients with gouty arthritis (GA) and healthy controls (HC),and to explore the role of testosterone and AR in the pathogenesis of GA.Methods Chemilluminescence was used to detect the level of serum testosterone in GA [including 119 acute GA (AGA) and 60 nonacute GA (NAGA) patients] and 47 HC group.Real-time quantitative polymerase chain reaction (RT-qPCR)was used to measure AR mRNA in PBMCs from 41 GA and 35 HC.Western blotting was used to measure PBMCs AR in GA and HC for each 6 cases.One-way ANOVA,t test and Spearman's correlation were adopted for statistical analysis.Results Serum testosterone was significantly reduced in AGA and NAGA group compared to that in HC group [(6.1±1.5) ng/ml,P＜0.01,respectively],and the expression was lower in the AGA [(3.7±1.4) ng/ml] group [(4.9±2.0) ng/ml] than that in the NAGA group (P＜0.01).The level of AR mRNA and protein was much lower in the GA group than that in the HC group (P＜0.01,respectively).Negative correlations was detected between AR mRNA and uric acid in GA patients.There was negative correlation between serum testosterone and VLDL,GLU; meanwhile,positive correlation was found between serum testosterone and HDL (P＜0.05,respectively) in NAGA patients.There were no correlations between testosterone and other laboratory data.There was no correlation between AR and other laboratory data in GA patients and healthy controls (P＞0.05,respectively).Conclusion Altered expression of testosterone and its receptor may be involved in the pathogenesis of gouty inflammation.Further study will be needed to shed light on the exact role of androgen and AR in gout.