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The predominant mechanism driving hyperuricemia in gout is renal uric acid underexcretion; however, the standard urate-lowering therapy (ULT) recommendation is first-line xanthine oxidase inhibitor (XOI), irrespective of the cause of hyperuricemia. This comparative effectiveness clinical trial was undertaken to compare first-line nontitrated low-dose benzbromarone (LDBen) uricosuric therapy to XOI ULT with low-dose febuxostat (LDFeb) in gout patients with renal uric acid underexcretion.We conducted a prospective, randomized, single-center, open-label trial in men with gout and renal uric acid underexcretion (defined as fractional excretion of urate5.5% and uric acid excretion ≤600 mg/day/1.73 mMore participants in the LDBen group achieved the serum urate target than those in the LDFeb group (61% compared to 32%, P 0.001). Rates of adverse events, including gout flares and urolithiasis, did not differ between groups, with the exception of greater transaminase elevation in the LDFeb group (4% for LDBen compared to 15% for LDFeb, P = 0.008).Compared to LDFeb, LDBen has superior urate-lowering efficacy and similar safety in treating relatively young and healthy patients with renal uric acid underexcretion-type gout.

SummaryBackgroundGout 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.MethodsWe 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 geneRCOR1.FindingsIn addition toABCG2, a urate transporter previously linked to pediatric-onset and early-onset gout, we identified four novel loci:VPRBP(rs868933181,Pmeta= 6.27 × 10−9; ORmeta= 1.66),NKILA-MIR4532(rs72626599,Pmeta= 6.48 × 10−9; ORmeta= 1.58),RCOR1(rs12887440,Pmeta= 3.37 × 10−8; ORmeta= 1.48), andFSTL5-MIR4454(rs35213808,Pmeta= 4.02 × 10−8; ORmeta= 1.49). Additionally, we found association atABCG2andSLC22A12that was driven by low frequency SNVs. Furthermore, eight uncommon SNVs and three indels in the exome were predicted to be harmful. SNVs inRCOR1were linked to heightened blood leukocyte mRNA levels. THP-1 macrophage culture studies revealed the potential of decreased RCOR1 to suppress gouty inflammation.InterpretationPerforming 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.FundingThe National Natural Science Foundation of China and the National Key R&D Program of China.Research in contextEvidence before this studyGout 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 inABCG2. 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 studyTo 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, includingRCOR1. SNVs in candidate risk geneRCOR1displayed 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 evidenceThis 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.

ObjectivesCOVID-19 vaccination often triggers a constellation of transitory inflammatory symptoms. Gout is associated with several comorbidities linked to poor outcomes in COVID-19, and gout flares can be triggered by some vaccinations. We analysed the risk of gout flares in the first 3 months after COVID-19 vaccination with inactivated virus, and whether colchicine can prevent gout flares following post-COVID-19 vaccination.MethodsA clinical delivery population-based cross-sectional study was conducted in the Gout Clinic at the Affiliated Hospital of Qingdao University between February and October 2021. Study participants were selected using a systematic random sampling technique among follow-up patients with gout. We collected data, including vaccinations and potential risk factors, using a combination of interviews, health QR codes and medical records. Logistic regression was used to adjust for covariates.ResultsWe enrolled 549 gout participants (median age 39 years, 84.2% vaccinated). For the 462 patients who received COVID-19 vaccine, 203 (43.9%) developed at least one gout flare in the 3 months after vaccination. Most of these flares were experienced within 1 month after the first (99/119 (83.2%)) or second (70/115 (60.9%)) dose of vaccine. Compared with unvaccinated participants, COVID-19 vaccination was associated with higher odds of gout flare within 3 months (adjusted OR 6.02; 95% CI 3.00 to 12.08). Colchicine use was associated with 47% less likelihood of postvaccine gout flare.ConclusionCOVID-19 vaccination was associated with increased odds of gout flare, which developed mainly in month 1 after each vaccine dose, and was negatively associated with colchicine prophylaxis.

Objective Gout flares during urate-lowering therapy (ULT) initiation are common, but predictors of these flares are poorly understood. The aim of this study was to determine whether serum CA72-4 is an independent predictor for gout flares during ULT initiation. Methods A prospective cohort study was conducted between March 2021 and January 2022. Men with gout, at least one gout flare in the past year, and at least three serum CA72-4 measurements in the previous six months were enrolled. Participants were grouped according to their highest recorded serum CA72-4 levels (above or within the normal range). All participants took oral febuxostat 20 mg daily without flare prophylaxis therapy, and attended face-to-face visits every four weeks until 24 weeks. The incidence of gout flare was compared between the two groups. Backward stepwise logistic regression analyses were used to identify risk factors associated with flares. Receiver operating characteristic curve analysis was used to evaluate prediction efficacy. Results A total of 193 completed the study (79 with high CA72-4; 114 with normal CA72-4). The cumulative incidence of at least one gout flare was 48.1% (62.1% in the high CA72-4 group, 38.4% in the normal CA72-4 group, P = 0.001), and recurrent (≥2) flares was 33.0% (47.1% in the high CA72-4 group, 23.2% in the normal CA72-4, P Conclusion High serum CA72-4 predicts the risk of gout flares during ULT initiation. Trial registration ChiCTR; https://www.chictr.org.cn/; ChiCTR2100043573.

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) 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 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.

In the recent technological era, we can note a tremendous development in the information technology sector, which has made all other sectors work to face a revolution and profit. In comparison with other organizations, educational departments have shown the best utilization of technology in their teaching and learning process. Teaching and learning (TaL) music and musical instruments are very challenging for teachers and students of remote areas. In this research work, TaL of piano playing is considered for the study by taking the MIDI and Audio Edited for Synchronous TRacks and Organization (MAESTRO) dataset. This dataset has virtual recorded piano performances with a label for notes and audio waveforms. The multiple signal classification (MSC) algorithm with the artificial intelligence (AI) is implemented on the dataset to train the students with artificial intelligence’s support. This MSC algorithm is executed on wireless networks (WN) to classify the signal data after recording and updating the dataset. With the help of the MSC algorithm with WN, the selection of teachers becomes easier for the student. This proposed work shows effective results for the TaL performance.

Background Low doses of febuxostat or benzbromarone are widely used in Asian countries, but lacking studies to compare the efficacy and safety of the two urate-lowering drugs. Methods To compare the efficacy and safety of low-dose febuxostat with low-dose benzbromarone in patients with primary gout, a randomized controlled, open-label trial was performed among male patients with primary gout for urate-lowering therapy (ULT) in a dedicated gout clinic in China. Randomization was carried out by a third-party institution according to random number table. Patients were randomly assigned 1:1 to febuxostat group (Feb group) (20 mg daily) or benzbromarone group (Ben group) (25 mg daily) and treated for 12 weeks. General information and biochemical data were collected at baseline and at every visit monthly. Clinical characteristics before and after the ULT were analyzed in the two groups by SPSS and EmpowerStats software. Results Two hundred forty patients were enrolled and randomized in the two groups, with 214 patients completing 12 weeks’ ULT (105 in the Feb group and 109 in the Ben group). After 12 weeks, substantial percentages of patients in both Feb and Ben group achieved the target serum uric acid (sUA) (

In this paper, the dispersive long wave equation is studied by Lie symmetry group theory. Firstly, the Lie symmetries of this system are calculated. Secondly, one dimensional optimal systems of Lie algebra and all the symmetry reductions are obtained. Finally, based on the power series method and the extended Tanh function method, some new explicit solutions of this system are constructed.

The relationship between Sn substitution for Ti and microwave dielectric properties of Mg(Ti1-xSnx)O3 ceramics was investigated. Sn4+ could substitute for Ti4+ in MgTiO3 and increase the crystal volume. All samples exhibited the MgTiO3-type phase with ilmenite structure as main phase. At the x range from 0 to 0.05, the secondary phase of Mg2TiO5 was observed. Upon further increasing Sn content up to 0.15, the SnO2 phase appeared. When the x value increased from 0 to 0.05, the dielectric constant decreased slightly and the quality factor increased sharply, whereas the dielectric constant increased and the quality factor decreased as the x value varied from 0.05 to 0.15. The temperature coefficient of resonant frequency moved toward positive value with Sn substitution. In particular, at the x range from 0.05 to 0.07, the ceramic sintered at 1360°C for 4 h exhibited excellent microwave dielectric properties of er = 16.8–17.1, Qf = 298,000–312,000 and τf = −53~−50 ppm/°C.

The phase composition and microwave dielectric properties of Mg-excess MgTiO3 (Mg/Ti = 1, 1.02, 1.04, 1.05, 1.07) ceramics prepared via the conventional solid-state reaction route were investigated. A slight deviation from stoichiometry does not practically affect the relative permittivity and temperature coefficient of resonant frequency of the specimen. However, the Q f value is very sensitive to the composition and it shows a non-linear variation corresponding to a relative amount of Mg. A very high Q f can be achieved for specimen with single MgTiO3 phase, which can be obtained within the suitable composition. As the increasing of Mg content, the MgTi2O5 phase which was derived from Mg/Ti = 1 was disappeared, and when it exceeded 1.02, the phase of Mg2TiO4 emerged. Along with the augmentation of Mg/Ti, the bulk density and Q f showed an initial increase, followed by a decrease, but er had been declining. The specimen with single MgTiO3 phase was obtained at the level of Mg/Ti = 1.02. A high Q f of 357,400 GHz (at 10 GHz) together with an er = 17 and τ f = −51 ppm/°C for MgTiO3 ceramics (Mg/Ti = 1.02) were obtained at 1,390 °C sintered for 4 h.