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(P<0.05). The frequency of TT genotype was significantly lower than that in controls (P<0.05) and the relative risk of this genotype to develop gout was 0.647 (95%CI: 0.452-0.925). Moreover, the frequency of T allele in cases was much lower than in controls (60.9% vs 69.2%, χ2=7.324, P=0.007, OR=0.695), but the frequency of C allele was much higher(39.1% vs 30.8%, χ2=1.440, P=0.007, OR=1.440). Interestingly, the levels of SLC2A9 mRNA on PBMCs in gout patients who carried TC genotype of rs3733591 was higher than those who carried TT genotype(P<0.05). There was no difference in the expression of SLC2A9 mRNA on PBMCs among different genotype carriers of rs3733591 in controls (P>0.05). 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.

Objective To investigate the role of adiponectin (ADP) and its receptors (ADR) in pati ents with primary gouty arthritis (GA).Methods Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of plasma ADP in 88 GA and 80 healthy controls (NC).Real time quantitative polymerase chain reaction (RT-qPCR) was employed to study the expression of ADR1 and ADR2 mRNA in peripheral blood mononuclear cells (PBMCs).The biochemical indicator of TG,HDL,LDL,VLDL,apoA1,apoB100 and uric acid (UA) were detected at the same time.T test,Spearman's correlations and regression analysis were used for statistical analysis.Results The concentration of plasma ADP was significantly lower in GA than that in NC [(6±7) μg/ml,(8±6) μg/ml,t=-3.71,P＜0.01 ],the expression of ADR1 and ADR2 mRNA in GA (ADR1:0.09±0.08,ADR2:0.0122±0.0164) was significantly increased when compared to the NC (ADR1:0.05±0.03,ADR2:0.0054±0.0024) (t=2.71,2.35,P＜0.05).In the GA patients,the level of ADP was negatively correlated with the lymphocytes count (LY) and UA (r=-0.32,-0.36,P＜0.05),and it was positively correlated with ESR and LDL level (r=0.31,0.39,P＜0.05).The expression of ADR1 mRNAwas negatively correlated with TG (r=-0.43,P＜0.05 ),but positivdy correlated with ESR and CRP level (r=0.45,0.57,P＜0.05).The expression of ADR2 mRNA was negatively correlated with glucose and UA(r=-0.50,-0.59,P＜0.05).Conclusion Altered expression of ADP and its receptors may be involved in thepathogenesis of gouty inflammation.

Objective To study the expression level of NLRP3 (NLR family, pyrin domain containing3) inflammasome (NLRP3, ASC, caspase-1 ) mRNA in peripheral blood monocytes (PBMCs) from patients with gout arthritis (GA) and to explore the pathogenesis of GA. Methods NLRP3 inflammasome mRNA was measured using quantitative real-time PCR in PBMCs. The expression of NLRP3 inflammasome mRNA in PBMCs was compared between patients with GA (n=24) and healthy controls (n=24). β-actin was selected as the internal control. Students' t-test was used in two independent samples and Spearman's correlation was used to evaluate the relationship between mRNA level and inflammatory parameters. Results The expression of ASC mRNA in GA increased significantly when compared to healthy controls [(0.029±0.021 ) vs (0.009±0.007 ), P＜0.01 ], and the expression of NLRP3 and caspase-1 mRNA was significantly lower in patients with GA compared to healthy controls [(0.062±0.084) vs (0.133±0.106), P＜0.05; (0.025±0.014) vs (0.117±0.156), P＜0.01]. Moreover, the expression of ASC mRNA was found to correlate significantly with globulin (r=-0.547, P＜0.05) and very low density lipoprotein cholesterol (r=-0.540, P＜0.05) in GA patients,and caspase-1 was correlated to globulin(r= -0.773. P＜0.01) and very low density lipoprotein cholesterol (r=-0.465. P＜0.05). Furthermore, the ASC mRNA in GA patients was associated significantly with NLRP3 mRNA(r=-0.450, P＜0.05) and caspase-1 (r=0.604, P＜0.01 ). Conclusion Dysregulated expression of the NLRP3inflammasome is involved in the inflammatory response and plays a key role in the pathogenesis of GA.

:In order to improve the compliance of patients with Alzheimer′s disease and maintain the continuity of treatment by reducing administration frequency of memantine hydrochloride, a series of memantine long-acting nanosuspension-based injectable formulations were prepared using a hydrophobic salt formation method. Four hydrophobic salt forms of memantine were prepared, including memantine oleate(Mem-Ole), memantine stearate(Mem-Ste), memantine palmitate(Mem-Pal)and memantine pamoate(Mem-Pam). The salt forms of memantine were characterized using fourier transform infrared(FTIR)spectroscopy, proton nuclear magnetic resonance(1H NMR)spectroscopy and powder X-ray diffraction(PXRD)analysis. The equilibrium solubilities of different salt forms of memantine and the in vitro drug release of long-acting injectable formulations were investigated. In comparison with memantine alone, the equilibrium solubilities of Mem-Ole, Mem-Ste, Mem-Pal and Mem-Pam in simulated body fluid were decreased by 95. 1%、96. 2%、96. 7% and 99. 6%, respectively. Meanwhile, the equilibrium solubilities of Mem-Pam in simulated body fluid with pH ranging from 5 to 8 were all lower than 0. 07 mg/mL. The order of the in vitro drug release rate of the four long-acting injectable formulations with nanosuspensions of memantine was Mem-Ste> Mem-Pal≈Mem-Ole> Mem-Pam> Memantine. The Mem-Pam nanosuspensions could sustain drug release for seven days and exhibited a zero-order drug release profile(y=0. 549 9x+7. 594 2, r=0. 988 3). In conclusion, injectable Mem-Pam nanosuspensions showed desired drug release behavior and might potentially be applied in vivo for a week with a steady plasma drug concentration-time profile.

Objective: To quantitatively study the morphological structure and parameter of right atrial appendage (RAA) by 256-slice spiral CT to provide RAA imaging reference for interventional or surgical therapy in clinical practice. Methods: A total of 200 patients with negative CTA results examined in our hospital were studied including 96 male and 104 female; by age division, Age≤40 years group,n=29, Age (40-60) years group,n=114 and Age>60 years group,n=57. The original scanning data was reconstructed for RAA establishment, indexes of volume, radial lines were measured and compared between different gender and age groups to obtain 95% normal imaging references of RAA. Results:①The volume, height, basilar part circumference, anteroposterior spread of RAA in male were greater than female, allP<0.05; with surface area standardization, the long and short diameter of basilar part, area, circumference in female were greater than male, allP<0.05.②Anteroposterior angle and spread of RAA in Age<40 years group were higher than both Age (40-60) years group and Age>60 years group,P<0.05, the above parameters were similar between Age (40-60) years group and Age>60 years group,P>0.05.③95% normal reference ranges of RAA were as following: volume (4.83-19.97) ml, height (21.46-41.80) mm; basilar part longest diameter (25.89-41.65) mm, short diameter (19.34-36.24) mm, area (459.30-1093.28) mm2, circumference (86.16-147.04) mm; anteroposterior angle (1.67-31.23) °, spread (8.07-34.37) mm. Conclusion: 256-slice CT may quantitatively study the morphological structure and parameter of RAA and establish its 95% normal imaging references for clinical practice.

Objective To investigate the mRNA and protein expression levels of telomeric-repeat binding factor-1 (TRF1) and TRF2 in the peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE),and the relations between these gene expression levels and clinical data of SLE patients were explored.Methods According to disease activity,these SLE patients were divided into the active group (40 cases) and the stable group (67 cases).These patients were also grouped as renal damage group (46 cases) and renal damage-free group (61 cases) based on their renal conditions.Healthy individuals (41 cases) were also included as control.Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to study the mRNA expression of TRF1 and TRF2.The protein levels of TRF1 and TRF2 were measured by Western Blot (WB).Independent-Samples t test or one-way analysis of variance (ANOVA) in conjunction with the Least-Significant Difference method (LSD method) wasperformed if the data were in normal distributions;otherwise,the Kruskal-Wallis test was applied.Spearman's correlation analysis was also used for statistical analysis.Results The mRNA and protein expression levels of TRF1 and TRF2 in the PBMCs of the active group (TRF1:0.003 1±0.003 3;TRF2:0.010 5±0.064 8) and renal damage group (TRF1:0.002 3 ±0.002 6;TRF2:0.004 3 ±0.003 3) were significantly increased compared to the stable group (TRF1:0.001 2±0.001 1;TRF2:0.004 2±0.008 6),the renal damage-free group (TRF1:0.001 3±0.001 8;TRF2:0.003 4±0.007 2) and healthy (TRF1:0.001 2±0.003 0;TRF2:0.003 4±0.002 7) individuals respectively (P＜0.05).In SLE patients,the expression levels of TRF1 mRNA were correlated with erythrocyte sedimentation rate (r=0.365,P＜0.05);the expression levels of TRF2 mRNA were correlated with SLEDAI score (r=0.270,P＜0.05),erythrocyte sedimentation rate (r=0.304,P＜0.05),creatinine (r=0.258,P＜0.05) and 24-hour urinary protein (r=0.344,P＜0.05).Conclusion Altered expression of TRF1 and TRF2 might be involved in the pathogenesis of Systemic lupus erythematosus.The positive correlation between TRF2 and SLEDAI score,24-hour urinary protein suggest that TRF2 might be usedas a biomarker for disease activity or renal damage in

Objective To detect the distribution of SLC2A9 rs10489070 polymorphism genotypes in Chinese Han population,and to explore the association of this gene polymorphism with gout susceptibility,tophi,serum uric acid levels and other clinical and laboratory data.Methods A total of 151 primary gout patients and 176.healthy controls were enrolled into this study.The genotypes and alleles frequencies were calculated by using TaqMan(R) SNP Genotyping Assays and the possible association between gene polymorphism of SLC2A9 and gout was investigated.T test,Chi-square and Fisher exact probabilities were used for statistcal analysis.Results Genotypes distribution were in Hardy-Weinberg equilibrium in gout patients and controls (P＞0.05).The frequency of CC genotype in gout patients was significantly higher than that in the controls (78.8％ vs 68.5％,P＜0.05),aand the frequency of CG genotype in gout patients was significantly lower (19.9％ vs 30.1％,P＜0.05).However,there were no statistical differences in the alleles frequencies of C and G between gout patients and controls (P＞0.05).Interestingly,there was significant difference in the distribution of genotypes between tophaceous gout patients and non-tophaceous gout patients (P＜0.05),and the frequency of CG genolype was much lower in tophaceous gout patients (0 vs 22.7％,P＜0.05).Conclusion Results of present study suggest that rs10489070 polymorphism of the SLC2A9 gene might be associated with gout development.CC genotype predisposes to gout,and CG genotype might protect Chinese Han population from gout and tophi development.

objective The roles of TLRs and their signal pathway in gouty arthritis(GA)were explored.Methods TLR2 and TLR4 mRNA was measured using real-time quantitative polymerase chain reaction(RT-PCR)in PBMCs,IL-1β level was detected using ELISA in plasma,and NF-κB p65 protein level in PBMCs was measured using Western blot.Level of TLR2 mRNA,ILR4 mRNA,IL-1β,NF-κB p65protein was compared among acute GA,non-acute GA and healthy controls.Correlation between TLR2mRNA,TLR4 mRNA and serum uric acid,IL-1β level in GA patients was analyzed.One-way ANOVA was used to analyze data between multiple groups and q-test was used for two-two comparison.Spearman's analysis was applied for correlation analysis.Resuits The expression of TLR4 mRNA,NF-KB p65 protein,IL-1β arid serum uric acid level in patients with acute GA [(5.0±1.2), (7.11±0.18), (283±83)pg/ml,[585±123)μmol/L] was significantly increased compared to non-acute GA[(2.3±0.4),(0.63±0.06),(134±29)pg/ml,(493±107)μmol/Lj and healthy controls(1.1±0.6),(0.52±0.12),(97±17)pg/ml,(326±65)μmol/L](P<0.01,respectively).Significant diffefence was also observed between non-acute GA patients and healthy controls(P<0.05,respectively).The level of TLRR4 mRNA was positively correlated with uric acid and IL-1β level in GA patients(rs=0.876,0.779;P<0.05,respectively).Conclusion Innate immunity are activated by membrane-type pattern recognition receptors in primary GA.TLR4-NFκB p65-IL-1β signat transduction may participate in the inflammatory mechanisms of gout.Urate crystals in patients with gout may:be involved in the activation of TLR4 and its signal pathway.

Objective To investigate the expression levels of telomeric protein TPP1 and POT1mRNA in the peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE), and the relations between these gene expression levels and disease activity are explored. Methods TPP1 and POT1 genes were measured using real-time polymerase chain reaction (RT-PCR) in PBMCs. The expression levels of TPP1 and POT1 genes in PBMCs were compared between 48 SLE patients and 30 healthy indivi-duals. Results The expression levels of TPP1 and POT1 in the PBMCs of SLE patients significantly decreased compared to healthy individuals (P<0.01). The expression levels of TPP1 and POT1 were much lower in SLE patients with lupus nephritis than those in patients without lupus nephritis (P<0.01), and in LN patients, the levels of TPP1 and POT1 were negatively correlated with proteinuria. The expression levels of POT1 in active SLE patients was lower than that in inactive SLE patients (P<0.05). The expression levels of POT1 was negatively correlated with serum IgG and SLEDAI scores, but positively correlated with complement C3, but no correlation between ESR, CRP, C4,ANA and the expression levels of TPP1, POT1, SLEDAI scores. Conclusion TPP1 and POT1 genes play a key role in the etiology of SLE, and they are involved in the pathogenesis of lupus nephritis. POT1 is helpful in evaluating SLE disease activity and severity.

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.