BACKGROUND:Activated charcoal (AC), a known adsorbent in the gastrointestinal tract, has been reported to reduce serum urate (SU) levels. This study aimed to assess the efficacy and safety of AC in managing primary gout. METHODS:This double-blind, double-dummy, randomized controlled trial involved 348 patients, who were randomly assigned to one of four groups: febuxostat 40 mg, febuxostat 20 mg + AC 4.5 g, febuxostat 20 mg + AC 7.2 g, and febuxostat 20 mg. Patients were followed-up every 4 weeks until week 24. The primary endpoint was the proportion of patients achieving SU level < 360 μmol/L. RESULTS:All 348 enrolled patients were included in analysis. The febuxostat-AC combination regimen didn't demonstrate superior efficacy in controlling SU levels. However, the combination regimen significantly reduced flare rates compared to the febuxostat 20 mg group (≥ 1 and ≥ 3 flares, P < 0.05) and the febuxostat 40 mg group (≥ 1 flare, P < 0.05; ≥ 3 flares, P < 0.01), and it also significantly prolonged the time to first flare. Additionally, the combination regimen resulted in significantly lower low-density lipoprotein cholesterol (LDL-C) levels at week 24. The incidence of adverse events was similar across the groups. CONCLUSIONS:The febuxostat-AC combination regimen didn't enhance urate-lowering effects but significantly reduced gout flare frequency, delayed the onset of first flare, and improved LDL-C levels. These findings underscore the role of AC in comprehensive gout management. TRIAL REGISTRATION:ChiCTR, http://www.chictr.org.cn, ChiCTR2000034138.

People with gout and combined-type hyperuricemia, defined as renal urate overload and renal urate under-excretion, have diminished responsiveness to urate-lowering therapy. Emerging observational data suggest that urine alkalization might improve responsiveness to febuxostat. Hence, this prospective study evaluated the urate-lowering efficacy of citrate mixture added to febuxostat in people with gout and combined-type hyperuricemia. Patients with combined-type hyperuricemia and low urine pH (< 6.2) were prospectively enrolled from a gout clinic. All were treated with febuxostat (initially 20 mg daily, escalated to 40 mg daily if serum urate (SU) ≥360µmol/L). Citrate mixture (3.5 g twice daily, open label) was added according to shared decision of both physician and patient (alkalization vs. non-alkalization). Participants were followed for 12 weeks, with primary endpoint being achievement of SU < 360 µmol/L at final assessment. We enrolled 234 eligible patients, with 194 completing 12 weeks follow-up (98 non-alkalization and 96 with alkalization). At week 12, more patients in the alkalization group achieved SU < 360µmol/L (57.3

Objectives Obesity affects 53% of gout patients, while its effect on urate-lowering therapy (ULT) is unclear. This study aimed to compare the response to febuxostat among different BMI catalogs of male gout patients. Methods A prospective study recruited 633 men with gout, classified by BMI into normal-weight, overweight and obese groups. Baseline age, disease duration and serum urate (SU) levels were matched simultaneously. All participants received febuxostat for 12 weeks, increasing the dosage from 20 to 40 mg daily. We compared the efficacy of ULT and the incidence of gout flares in three groups. Cox regression analysis was used to identify risk factors for achieving target SU levels before and after matching. Restricted cubic spline (RCS) curves were used to illustrate the relationship between BMI and hazard ratio (HR) for SU achievement. Results The proportion of participants achieving SU < 6.0 mg/dl in the obese group was 38.9%, significantly lower than the overweight (54.2%) and normal-weight groups (63.8%) (P < 0.05), with no significant difference between the overweight and normal-weight groups at week 12. High BMI (HR = 0.92, 95% CI 0.89-0.96, P < 0.001) independently prevented achieving the SU target, with a similar effect after matching. Obese and overweight individuals had a higher cumulative incidence of gout flares compared with the normal-weight group (P < 0.05). The linear relationship between BMI and HR for achieving the SU target was suggested by RCS (nonlinear P > 0.05). Conclusion Obesity significantly reduces the efficacy of febuxostat-based ULT in male gout patients rather than being overweight. Trial registration China Clinical Trial Registry, #ChiCTR2300078804.

OBJECTIVES:Stage ≥3 chronic kidney disease (CKD) affects ∼25% of people with gout. The effects of urate-lowering therapy (ULT) on CKD incidence and progression have remained inconclusive. Here, we assessed the impact of a gout ULT clinic intervention using artificial intelligence (AI) on CKD incidence and achievement of serum urate (SU) target. METHODS:An observational study compared propensity score (PS)-matched gout cohorts from an AI-based Gout Intelligent Management System (GIMS) and a standard Electronic Medical Records system (EMRS) clinic database. The GIMS included a mobile application, data fusion interface and modules for expert consultation and laboratory results management. All patients had gout and a starting estimated glomerular filtration rate >60 ml/min. Using a 1:2 PS-matched cohort study design, we assessed the impact of the AI-based system on CKD outcomes and ULT effectiveness over 4 years of follow-up. RESULTS:Compared with EMRS, GIMS was associated with reduced incidence of CKD stage ≥3. Specifically, 169/4117 new-onset CKD stage ≥3 (incidence 4.1 per 100 person-years) with GIMS compared with 164/2128 with EMRS (incidence 7.7 per 100 person-years) during follow-up. More participants achieved SU <6.0 mg/dl with GIMS versus EMRS during follow-up (49.8% vs 25.9%, P < 0.001). CONCLUSION:Application of the artificial intelligence-based Gout Intelligent Management System was associated with lower incidence of chronic kidney disease stage ≥3 and superior target serum urate achievement in people with gout. The Gout Intelligent Management System represents a novel approach to improve real-world renal outcomes and urate-lowering therapy success in gout.

OBJECTIVES:Gout patients frequently have decreased urine pH, related to metabolic syndrome (MetS) and chronic kidney disease. Here, we aimed to investigate whether the addition of urine alkalization to urate-lowering therapy (ULT) is associated with improvements in albuminuria, gout flares or MetS outcomes in men with gout and low urinary pH (pH < 6.2). METHODS:A prospective cohort study enrolled 385 participants starting ULT with febuxostat (initially 20 mg daily, escalated to 40 mg daily if serum urate ≥360 µmol/l), with or without alkalization based on patient preference using a 3.5 g bid citrate mixture. Participants were followed every 4 weeks to week 12. The primary outcome was urine albumin-to-creatinine ratio (UACR) at week 12. RESULTS:In total, 343 participants completed the week 12 visit (137 alkalization, 206 controls). At week 12, compared with controls, participants receiving alkalization required a significantly lower febuxostat dose (by ∼20%) but had no significant difference in serum urate at target <360 µmol/l. Urine pH increased significantly in the alkalization group from week 4 (P < 0.001). At week 12, the alkalization group had a significantly lower UACR compared with control (P < 0.001), without significantly different eGFR. Participants in the alkalization group experienced fewer gout flares and had lower pain visual analogue scale scores (P < 0.001). There were lower serum triglyceride levels (P < 0.01) and higher HDL-C levels (P < 0.001) in the alkalization group. No other differences in metabolic outcomes were observed. CONCLUSION:Urine alkalization was associated with lower UACR, fewer gout flares, and improved serum lipid profile in febuxostat-treated men with gout and low urine pH. TRIAL REGISTRATION:ChiCTR, http://www.chictr.org.cn, ChiCTR2100043573.

In the dogfish (Scyliorhinus canicula L.) the testicular germinative zone (GZ), composed of large isolated spermatogonia surrounded by elongating pre-Sertoli cells, is located between the albuginea and the ventrolateral intratesticular vessel. During the spermatogenic wave, cysts radiate in maturational order forming distinct testicular zones. In this study, soluble proteins of the GZ and of the zone containing cysts with spermatocytes were separated by two-dimensional electrophoresis. Gel images were matched and then evaluated for GZ-specific proteins. From the1400 protein spots identified, 680 were found to be apparently specific to this zone. Using MALDI-TOF/TOF mass spectrometry, de novo sequences were obtained for 33 proteins out of the 169 selected for identification by mass spectrometry, but only 16 of these 169 proteins were identified. One of them, proteasome subunit alpha-6, was analyzed further by immunohistochemistry. This study demonstrates the utility of the dogfish as a model for proteome analysis of the spermatogonial stem cell niche, even if it remains restricted by the lack of genomic data available on Elasmobranchs.

Summary Background Gout is a polygenetic inflammatory disease. Although hundreds of genetic variants associated with gout and serum urate levels have been identified in studies of adults, the pathogenesis of adolescent-onset gout remains unclear. To better characterize the genetic landscape of adolescent-onset gout, a whole genome sequencing study was done in a large Chinese adolescent-onset gout cohort. Methods We conducted whole genome sequencing in a discovery adolescent-onset gout cohort of 905 individuals (gout onset 12-19 years) to discover common SNVs, uncommon SNVs, and indels associated with gout. Candidate common SNVs were replicated in an early-onset gout cohort of 2834 individuals (gout onset ≤ 30 years old). Loci associated with early-onset gout ( P < 5.0 × 10 −8 ) were identified after meta-analysis with the discovery and replication cohorts. Transcriptome and epigenomic analyses, RT-qPCR and RNA-seq in human peripheral blood leukocytes, and knock-down experiments in human THP-1 macrophage cells investigated regulation and functions of candidate gene RCOR1 . Findings In addition to ABCG2 , a urate transporter previously linked to pediatric-onset and early-onset gout, we identified four novel loci: VPRBP (rs868933181, P meta = 6.27 × 10 −9 ; OR meta = 1.66), NKILA-MIR4532 (rs72626599, P meta = 6.48 × 10 −9 ; OR meta = 1.58), RCOR1 (rs12887440, P meta = 3.37 × 10 −8 ; OR meta = 1.48), and FSTL5 - MIR4454 (rs35213808, P meta = 4.02 × 10 −8 ; OR meta = 1.49). Additionally, we found association at ABCG2 and SLC22A12 that was driven by low frequency SNVs. Furthermore, eight uncommon SNVs and three indels in the exome were predicted to be harmful. SNVs in RCOR1 were linked to heightened blood leukocyte mRNA levels. THP-1 macrophage culture studies revealed the potential of decreased RCOR1 to suppress gouty inflammation. Interpretation Performing the first comprehensive characterization of adolescent-onset gout genomes identified risk loci of early-onset gout. Loci mediate inflammatory responsiveness to crystals that could mediate gouty arthritis. This study will contribute to risk prediction and therapeutic interventions to prevent adolescent-onset gout. Funding The National Natural Science Foundation of China and the National Key R&D Program of China. Research in context Evidence before this study Gout is a polygenic disease and can present in adolescents and young adults. We searched PubMed for studies published as of Dec 31, 2021, without starting date or language restrictions and with the terms “adolescent-onset gout”, “early-onset gout”, “whole genome sequencing”, and “GWAS”, and no reports were found. Although GWAS have identified hundreds of genetic variants associated with gout and serum urate levels, they are all identified in adults (mean age 37.6-76.4 years old). The mechanism of early-onset gout is still unclear. The variants previously associated with early-onset gout are only in ABCG2 . Due to the lack of large-scale genetic studies of the adolescent gout population, the mechanism of the early-onset gout is unknown. Added value of this study To the best of our knowledge, this is the first report of the comprehensive characterization of adolescent gout genomes. We identified common and uncommon risk loci of early-onset gout, most of which implicated in inflammation response, including RCOR1 . SNVs in candidate risk gene RCOR1 displayed expression regulation function. Knockdown of RCOR1 decreased IL-1β levels in THP-1 cells after MSU treatment. These immune-related genetic variants leading to heightened inflammatory responses to monosodium urate (MSU) crystals may contribute to early onset of gout in adolescents. Implications of all the available evidence This is the first report of the genetic landscape of adolescent-onset gout and increases our knowledge of the biological mechanisms underlying early-onset gout. The immune-related loci associated with early-onset gout discovered in this study are potential drug targets. Reducing inflammatory MSU crystal inflammatory responses to MSU crystals is a central objective in the prevention and treatment of adolescent-onset gout.

Low urine pH, which may be mediated by metabolic syndrome (MetS), is common in gout. Tart cherries are shown to improve MetS symptoms and possess anti-inflammatory properties. However, the efficacy of tart cherry supplements on urine pH has yet to be studied. This study aimed to investigate the efficacy and safety of tart cherry supplementary citrate (TaCCi) mixture on urine pH, serum urate (sUA), C-reactive protein (CRP), and gout flares in gout patients initiating urate-lowering therapy (ULT), in comparison to citrate mixture and sodium bicarbonate. A prospective, randomized (1:1:1), open-label, parallel-controlled trial was conducted among 282 men with gout and fasting urine pH ≤ 6, who were initiating ULT with febuxostat (initially 20 mg daily, escalating to 40 mg daily if serum urate ≥ 360 μmol/L). Participants were randomized to groups taking either sodium bicarbonate, citrate mixture, or TaCCi mixture. All participants were followed every 4 weeks until week 12. Urine pH and sUA were co-primary outcomes, with various biochemical and clinical secondary endpoints. Urine pH increased to a similar extent in all three groups. SUA levels declined in all three groups as well, with no significant differences observed between the groups. At week 12, the TaCCi mixture group exhibited a greater reduction in the urine albumin/creatinine ratio (UACR) compared to the other two groups (p < 0.05). Participants taking TaCCi mixture or citrate mixture experienced fewer gout flares than those in the sodium bicarbonate group over the study period (p < 0.05). Additionally, the TaCCi mixture group had a lower CRP level at week 12 relative to the other two groups (p < 0.01). Adverse events were similar across all three groups. The TaCCi mixture had similar efficacy and safety on urine alkalization and sUA-lowering as the citrate mixture and sodium bicarbonate in patients with gout. However, the TaCCi mixture resulted in greater improvements in UACR and CRP, which suggests that tart cherry supplements may provide additional benefits for renal protection and reduce inflammation in gout, particularly when starting ULT. This project was registered in ChiCTR ( www.chictr.org.cn ), with the registration number: ChiCTR2100050749.

Objective: Extrachromosomal circular DNA elements (eccDNAs) are known for their broad existence in cells and plasma, which may potentially play important roles in many biological processes. Our aim was to identify potentially functional or marked eccDNAs in gout patients.Methods: The Circle-Seq approach was applied for eccDNA detection from plasma in acute gout patients and healthy controls. Further analysis was performed on the distribution of genomic elements and eccDNA gene annotations in two groups.Results: We detected 57,216 and 109,683 eccDNAs from the acute gout and healthy control plasma, respectively. EccDNAs were mapped to the reference genome to identify diverse classes of genomic elements and there was no significant difference of eccDNAs on genomic element annotation between gout and control group. A total of 256 eccDNA-associated genes were detected as gout unique eccDNA genes, including COL1A1 and EPB42, which potentially contribute to hyperuricemia and gout, and a couple of genes involved in inflammation or immune response. Enrichment analysis showed that these eccDNA genes were highly correlated with defense response, stress response, and immune and inflammatory responses, including T cell receptor signaling pathway, Fc epsilon RI signaling pathway, and JAK-STAT signaling pathway.Conclusion: Our discovery reveals the novel potential biological roles of plasma eccDNAs in gouty arthritis.

Background: Gout is most common inflammatory arthritis characterized by deposition of monosodium urate crystals in joints. Several genome-wide association studies (GWAS) have reported associations between common genetic variants and gout status. This study aimed to further elucidate the genetic architecture of gout for better understanding of pathogenesis. Methods: We conducted a large clinically defined gout GWAS in Chinese male descent (n case=3,669, n control=8,838) by using genome-wide genotyping arrays. Additional comprehensive analyses, including eQTL, pathway enrichment and connectivity enrichment analyses, were performed to further prioritize relevant genes, pathways and cell types that contributed to pathogenesis. The cell type intervention experiments were further performed in a MSU induced air-pouch mouse model of acute gouty arthritis to identify the role of different cell types in the gout pathogenesis. Findings: In addition to five previously reported urate- and gout-related loci, we detected four novel genome-wide significant (GWS, p<5.0×10-8) risk loci (1p35.2, 5q35.1, 7p13 and 22q12.3). For the GWS variants and their proxy (r 2 >0.8), 11 missense variants in 7 genes were identified, and eQTL analysis suggested involvement of MAPK signaling pathway. Genome-wide gene and gene-set analyses revealed novel gene and pathway associations (eg. T cell lineage commitment) with gout and also highlighted urate-related findings by single-SNP analysis. We also confirmed that CD4 T cell blockade can effectively alleviate the pathological process of gout. Interpretation: Our largest genome-wide data of clinically defined gout identified non urate-related associations at the variant, gene, pathway and cell type levels, and provided a better understanding of the pathogenesis of gout. Fundings: This work was supported by research project grants from National Natural Science Foundation of China, Shandong Province Key Research and Development Program, Taishan Scholar Program of Shandong Province, Shandong Province Natural Science Foundation, Shandong Provincial Science Foundation for Outstanding Youth Scholars, National Key R&D Program of China.Declaration of Interest: None declared.Ethical Approval: The study procedure complied with the Declaration of Helsinki and obtained ethical approval from the ethics committee of the Affiliated Hospital of Qingdao University.

Objective: Urate-lowering therapy (ULT) nonadherence is common and problematic in gout. Since, sociocultural factors affect adherence, we analyzed a Chinese cohort. Methods: We studied 903 Chinese gout patients aged 46.4 +/- 14.7 years (mean +/- SD), uniquely extending to assay of 2-year medication possession ratio (MPR) >= 80% defined as high adherence. Multivariable logistic regression analyses evaluated factors linked with adherence and ULT target attainment. Results: Characterization of ULT outcomes in this cohort revealed that after 2 years ULT, MPR >= 80% patients had better target serum urate (SU) achievement (from 23.3% to 71.0%, P < 0.001), lower flare frequency and palpable tophi compared to MPR < 80%. However, only 44.7% of cohort subjects had MPR >= 80%. Male sex (OR 3.68), gout onset age >60 years (OR 3.51), disease duration >5 years (OR 1.70), more comorbidities (OR 1.74), baseline palpable tophi (OR 1.53), SU < 6 mg/dL (360 mu mol/L) (OR 1.92) and more frequent follow-up visits (OR 1.98) were significantly associated with high adherence. Nevertheless, significant independent risk factors for failed SU target achievement included male sex (OR 0.36) and more comorbidities (OR 0.85). Conclusion: Despite adherence to ULT linked to better outcomes for flares and tophi, the more adherent Chinese male patients and those with more comorbidities had decreased target SU attainment. Differences in adherence of Chinese gout patients compared to several primarily Western studies emphasize the importance of not stereotyping gout patients for projected nonadherence. Results underline the dual importance of identifying gout patients more likely to be ULT-adherent and leveraging adherence to drive treatment to SU target. (c) 2022 Societe franc, aise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.

Objective. To investigate the incidence and potential risk factors for development of fenofibrate-associated nephrotoxicity in gout patients. Methods. A total of 983 gout patients on fenofibrate treatment who visited the dedicated Gout Clinic at the Affiliated Hospital of Qingdao University between September 2016 and June 2020 were retrospectively enrolled from the electronic records system. Fenofibrate-associated nephrotoxicity was defined as an increase in serum creatinine (SCr) >= 0.3 mg/dl within 6 months of fenofibrate initiation. The change trend of SCr and uric acid levels during the treatment period were assessed by a generalised additive mixed model (GAMM). Multivariate analysis was performed for risk factors affecting elevated SCr. Results. A total of 100 (10.2%) patients experienced an increase in SCr >= 0.3 mg/dl within 6 months after fenofibrate initiation. The median change of SCr in the whole cohort was 0.11 mg/dl [interquartile range (IQR) 0.03-0.20], whereas it was 0.36 (0.33-0.45) in the fenofibrate-associated nephrotoxicity group. In a multivariable regression model, chronic kidney disease (CKD) [odds ratio (OR) 2.39 (95% CI 1.48, 3.86)] and tophus [OR 2.29 (95% CI 1.39, 3.78)] were identified to be risk predictors, independent of measured covariates, of fenofibrate-associated nephrotoxicity. During the treatment period, although SCr temporarily increased, serum urate and triglyceride concentrations decreased using the interaction analysis of GAMM. Of those with fenofibrate withdrawal records, the SCr increase in 65% of patients was reversed after an average of 49 days off the drug. Conclusions. This observational study implied that fenofibrate-associated nephrotoxicity occurs frequently in gout patients, especially in patients with tophi or CKD. The potential renal risks of fenofibrate usage in gout needs additional research.

Abstract Objectives To compare the efficacy and safety of citrate mixture and sodium bicarbonate on urine alkalization in gout patients under benzbromarone treatment. Methods A prospective, randomized, parallel controlled trial was conducted among 200 gout patients in the dedicated gout clinic of the Affiliated Hospital of Qingdao University. The participants were randomly divided into two groups (1:1), sodium bicarbonate group (3 g/day) and citrate mixture group (7 g/day). All patients were prescribed with 25 mg/day benzbromarone at initiation and maintained at a dose of 50 mg/day. Clinical and biochemical data were collected at each follow-up time point (baseline, weeks 2, 4, 8 and 12). Results A total of 182 patients completed the 12-week urine alkalization study. The urine pH value of both groups increased significantly from the baseline to the final follow-up time point (sodium bicarbonate group, 5.50–6.00, P < 0.05; citrate mixture group, 5.53–5.93, P < 0.05). While the comparisons regarding urine pH between treatment groups showed no significant differences for each time point. The estimated glomerular filtration rate (eGFR) dropped significantly after 12 weeks’ trial in the sodium bicarbonate group (P < 0.01), while it was comparable between baseline and the last follow-up (P > 0.05) in the citrate mixture group. Results of urine analysis showed that the incident rate of occult blood in the sodium bicarbonate group was higher than that in the citrate mixture group (38 vs 24%, P < 0.05), accompanied by a similar occurrence of kidney stones. After 12-week follow-up, the frequency of twice gout flare in the citrate mixture group was significantly lower than that in sodium bicarbonate group (4 vs 12%, P = 0.037). No treatment-emergent adverse events occurred. Conclusion The efficacy of citrate mixture on urine alkalization is comparable to sodium bicarbonate under benzbromarone treatment without significant adverse events. Citrate mixture is superior to sodium bicarbonate in lowering the incidence of urine occult blood and the frequency of gout attacks. Trial registration Registered with ChiCTR (http://www.chictr.org.cn), No. ChiCTR1800018518.

Fenofibrate is a marketed fibric acid derivative for lipid-lowering in patients with lipid disorders. Numerous studies have proven fenofibrate had a certain effect on serum uric acid, here we conducted this study to quantitatively assess the effect of fenofibrate intervention in modulating serum uric acid concentration and the influence on serum creatinine. The PubMed, Embase and Cochrane were systematically searched for randomized controlled trials update to January, 2020. Primary endpoints focused on serum uric acid concentration and serum creatinine concentration. The pooled effects were calculated as weighted mean difference (WMD) by a random-effects model. Finally, 9 studies representing 487 patients were included in the meta-analysis. The meta-analysis demonstrated that fenofibrate significantly reduced serum uric acid levels (WMD -1.32 mg/dL, 95%CI -1.61 to -1.03, p < 0.001) and an elevated level in serum creatinine (WMD 0.09 mg/dL, 95%CI 0.02 to 0.15, p < 0.001) following fenofibrate therapy compared with placebo. The present study provided strong evidence that fenofibrate intervention exerted a significant reduction on serum uric acid and a mild increase on serum creatinine. Meta-analysis suggested that there were no significant association between the serum uric acid lowering effect with either dose or treatment duration. Overall, our meta-analysis ascertained that fenofibrate have potential therapeutic effects in patients with lipid metabolic abnormalities but with mid nephrotoxicity. There is strong evidence to provide future direction of practical application and clinical researches of fenofibrate.

Background The prevalence of hyperuricemia is increasing in adults, while the prevalence among adolescents is seldom reported. Methods A cross-sectional survey by multistage, stratified sampling method was carried out in Shandong Province during 2017–2018. A total of 9371 adolescents aged from 13 to 19 years were randomly sampled and analyzed in this survey. Results The overall mean serum uric acid (sUA) concentration was 6.08 ± 1.57 mg/dL and overall hyperuricemia prevalence was 25.4% and 60.5% (when hyperuricemia was defined as sUA ≥ 7 mg/dL or ≥ 5.5 mg/dL). Prevalence were 42.3% (male) and 8.0% (female) when limit was 7 mg/dL and prevalence were 82.1% (male) and 38.4% (female) when limit was 5.5 mg/dL. Male gender, increased body mass index, increased waist circumstance, increased triglycerides, increased fasting blood glucose, increased systolic blood pressure, decreased estimated glomerular filtration rate, and positive family gout history were associated with the enhanced risk of hyperuricemia according to univariate and/or multivariate logistic regression analysis. Food intake frequency of carbonate beverage, mutton, and other kinds varied between hyperuricemia adolescents and normal sUA ones. Conclusions The studied adolescent population showed sUA level and hyperuricemia prevalence which are even higher than those of adults in China. The epidemic of youth hyperuricemia may pose a future threat of gout attacks and other hyperuricemia-related diseases, which alarms the public, health professionals and health policy makers to prepare the future health challenges.

Objective:This study aimed to evaluate the accuracy of a portable REF-XT01 uric acid meter in measuring blood uric acid concentration, and to determine whether the results of the uric acid meter could be used to guide the adjustment of uric acid-lowering drugs.Methods:1 551 subjects were enrolled from the Gout Clinical Medical Center of the Affiliated Hospital of Qingdao University. The fasting venous blood was collected and the serum uric acid was measured by an automatic biochemical analyzer. Meanwhile, the capillary blood uric acid was measured by fingertip puncture using the REF-XT01 uric acid meter. Linear regression, intra-group correlation coefficient(ICC), and Bland-Altman plots were used to analyze the uric acid concentration correlation between the biochemical analyzer(sUA BA)and the uric acid meter(sUA UM). The receiver operating characteristic curve(ROC curve)was conducted to evaluate whether sUA UM can be used as a reference for the gout patients to take uric acid-lowering drugs. Results:The regression analysis showed correlation between sUA BA and sUA UM, with the regression formula Y=0.875X+ 39.525( r=0.84, P<0.01)and the ICC was 0.829(95% CI 0.814-0.844, P<0.01). The Bland-Altman diagram showed a good consistence(the absolute deviation was-143.4-114.5 μmol/L, mean deviation was -14.4 μmol/L)between sUA BA and sUA UM. The sensitivity was 96.61%, specificity was 48.81%, and the area under the ROC curve(AUC)was 0.926( P<0.01)when 300 μmol/L was defined as the detection threshold of the uric acid meter, the sensitivity was 90.98%, specificity was 66.78%, and the area under the ROC curve(AUC)was 0.914( P<0.01)when 360 μmol/L was defined as the detection threshold of the uric acid meter. Conclusion:REF-XT01 uric acid meter is applicable for the adjustment of uric acid-lowering drugs for the gout patients, because of its high accuracy for the detection of uric acid.

Hyperuricemia (HU) is a cause of gout. Clinical studies show a link between HU and cardiovascular disease. However, the role of soluble serum urate (SU) on atherosclerosis development remains elusive. We aimed to use a new HU mouse model [Uricase/Uox knockout (KO)] to further investigate the relationship between HU and atherosclerosis. A mouse model by perivascular collar placement of induced carotid atherosclerosis was established in male Uox-KO mice. The Uox-KO mice had elevated SU levels and enhanced levels of atherosclerosis inflammatory response proteins. In contrast, Uox-KO mice with carotid atherosclerosis showed severe neointimal changes in histology staining consistent with increases in intimal area and increases in proliferating cell nuclear antigen (PCNA)- and F4/80-positive cells. Allopurinol reduced neointimal areas induced by the perivascular collar in hyperuricemic mice, accompanied by decreased expression of PCNA- and F4/80-positive cells. Urate-lowering treatment alleviated atherosclerosis inflammatory response factors and reactive oxygen species (ROS) intensities in both collar placement Uox-KO mice and urate-stimulated human umbilical vein endothelial cells (HUVECs). In vitro results using HUVECs showed ROS was induced by urate and ROS induction was abrogated using antioxidants. These data demonstrate that urate per se does not trigger atherosclerosis intima lesions in male mice. Urate worsens carotid neointimal lesions induced by the perivascular collar and urate-lowering therapy partially abrogates the effects. The current study warrants clinical studies on the possible benefits of urate-lowering therapy in atherosclerosis patients with HU.

Hyperuricemia (HU) is a cause of gout. Clinical studies show a link between HU and cardiovascular disease. However, the role of soluble serum urate on atherosclerosis development remains elusive. We aimed to use a new HU mouse model ( Uricase/Uox knockout (KO)) to further investigate the relationship between HU and atherosclerosis. Mouse model of induced carotid atherosclerosis was established in the novel spontaneous HU Uox- KO mouse and their wild type littermates (C57BL/6J background). Mice were implanted with a perivascular collar placement around the right carotid artery in combination with a western-type diet. To investigate urate-lowering treatment (ULT) effects on intima, the mice were gavaged daily from the age of 6 weeks with allopurinol. Human umbilical vein endothelial cells (HUVECs) were co-incubated with soluble urate, with and without probenecid, to study the mechanism of urate-related atherosclerosis. The Uox- KO mice had significantly elevated serum urate levels combined with higher blood urea nitrogen and serum creatinine. Western blot analysis showed enhanced levels of atherosclerosis inflammatory response proteins. However, there were no other risk indicators for the pathogenesis of atherosclerosis, including increased fasting glucose, altered lipid and atherosclerosis characterized cardiovascular and histological manifestations. In contrast, collar placement Uox- KO mice showed severe neointimal changes in histology staining consistent with increases in intimal area and increases in proliferating cell nuclear antigen (PCNA) - and F4/80-positive cells. Allopurinol reduced neointimal areas induced by the perivascular collar in hyperuricemic mice accompanied by decreased expression of PCNA- and F4/80-positive cells ( P < 0.05). ULT alleviated atherosclerosis inflammatory response factors and reactive oxygen species intensities in both collar placement Uox- KO mice and urate-stimulated HUVECs . In vitro results using HUVECs showed ROS was induced by urate and ROS induction was abrogated using antioxidants. These data demonstrate that urate per se does not trigger atherosclerosis intima lesions in mice. Urate worsens carotid neointimal lesions induced by the perivascular collar and urate-lowering therapy partially abrogates the effects. The current study warrants the further human based study on the possible benefits of urate-lowering therapy in atherosclerosis patients with HU.Summary statement We generated a carotid collar placement atherosclerosis model in the novel spontaneous HU Uox-KO mouse and demonstrate that urate plays a contributing rather than a causal role in the carotid neointimal lesions, while urate-lowering treatment may bring additional benefits in this HU mouse model.