OBJECTIVE:The objective of this study was to examine changes of age of onset and disease characteristics of gout between 2003 and 2022 in multiple centres in mainland China. METHODS:A cross-sectional cohort study was conducted among people with gout from two geographically separate centres in China. Baseline gout clinic data were collected through a electronic medical records review. The onset age trends and disease characteristics of patients who developed gout between 2003 and 2012 (first decade) and between 2013 and 2022 (second decade) were compared. RESULTS:A total of 10 658 patients were included. The age of gout onset declined over the two decades (Ptrend < 0.001), with the average onset age decreasing from 42.0 in 2003 to 38.9 years in 2022. The proportion of patients with an onset age of ≤19 and of 20-29 years increased annually by 5.8% and 9.6%, respectively (Ptrend < 0.05). Compared with age-, sex- and disease duration-matched patients in the first decade, patients who developed gout in the second decade were more likely to have a history of smoking and alcohol consumption, and less likely to engage in regular exercise (P < 0.001). Additionally, those with onset of gout in the second decade had higher rates of s.c. tophi, frequent gout flares, nephrolithiasis, hypertension and diabetes, though lower rates of dyslipidaemia (P < 0.05). CONCLUSION:Over the past two decades in mainland China, there has been a noticeable trend towards younger onset of gout, alongside an increase in disease severity and metabolic comorbidities.

To explore the molecular mechanisms underlying the effects of a specific small cluster mineral water (C-cell mineral water) on ethanol metabolism, we conducted a series of assessments comprising anti-acute alcohol toxicity experiments including behavioral hangover responses, serum ethanol levels, liver activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), along with metabolomic and transcriptomic analyses within 24h, and anti-chronic alcohol toxicity experiments including analysis of liver catalase (CAT) activity, along with metabolomic and transcriptomic profiling after 21d intervention of ethanol accompany with C-cell mineral water. The results suggested that the C-cell mineral water significantly delayed the latency of drunken and decreased the duration of drunken in mice, simultaneously reduced serum ethanol level at 3h and 4h. It also enhanced liver ADH and ALDH activities at 2h and activated CAT activity at 21d, compared to purified water. Transcriptomic analysis revealed that some genes related to ethanol metabolism including CYP450s, ALDH3B3, and SULT5A1 were up-regulated. Additionally, the metabolomic analysis identified that the most significantly altered pathways included primary bile acid biosynthesis, various drug metabolism pathways, and CYP450-mediated drug metabolism. Subnetworks with maximum changes featured interactions between pathways of oxidative phosphorylation, arginine biosynthesis, and primary bile acid biosynthesis, etc. The results showed that the effect of C-cell mineral water was better than that of purified water on relieving drunken, which could accelerate the conversion of acetaldehyde to acetate, and ultimately metabolize into CO2 and H2O through TCA cycle. These findings will provide innovative strategies for preventing acute alcoholism and relieving chronic alcohol toxicity.

Tart cherries are recognized as a valuable resource for the agro-processing industry due to their distinctive tart flavor, limited direct freshness and excellent nutritional value. Studies have demonstrated that tart cherries are rich in anthocyanins, a type of flavonoid compound known for its anti-inflammatory and antioxidant properties. However, the function of tart cherries in alleviating inflammation associated with gout remains unclear. In this study, active components were extracted from tart cherries by ethanol sonication (TCU) and thermal reflux (TCH), and then orally administered to mice to investigate their effects on monosodium urate (MSU) crystals induced acute gouty arthritis. Changes in joint thickness and mechanical pain thresholds were monitored over time. The results showed that TCH supplementation significantly reduced joint erythema and increased the mechanical pain threshold in mice. In MSU crystals induced air pouch model, TCH significantly reduced neutrophil recruitment, decreased the levels of inflammatory cytokines IL-1(3 and TNF-alpha, and down-regulated the expression of NF-kappa B signaling pathway TRIF, and inhibited the activation of NLRP3 inflammatome by increasing superoxide dismutase (SOD). This study provides preliminary evidence that TCH has potential as an anti-gout inflammation modifier, thereby offering a theoretical basis for the valuable utilization of tart cherries.

OBJECTIVE:Mechanisms underlying the adolescent-onset and early-onset gout are unclear. This study aimed to discover variants associated with early-onset gout. METHODS:We conducted whole-genome sequencing in a discovery adolescent-onset gout cohort of 905 individuals (gout onset 12 to 19 years) to discover common and low-frequency single-nucleotide variants (SNVs) associated with gout. Candidate common SNVs were genotyped in an early-onset gout cohort of 2,834 individuals (gout onset ≤30 years old), and meta-analysis was performed with the discovery and replication cohorts to identify loci associated with early-onset gout. Transcriptome and epigenomic analyses, quantitative real-time polymerase chain reaction and RNA sequencing in human peripheral blood leukocytes, and knock-down experiments in human THP-1 macrophage cells investigated the regulation and function of candidate gene RCOR1. RESULTS:In addition to ABCG2, a urate transporter previously linked to pediatric-onset and early-onset gout, we identified two novel loci (Pmeta < 5.0 × 10-8): rs12887440 (RCOR1) and rs35213808 (FSTL5-MIR4454). Additionally, we found associations at ABCG2 and SLC22A12 that were driven by low-frequency SNVs. SNVs in RCOR1 were linked to elevated blood leukocyte messenger RNA levels. THP-1 macrophage culture studies revealed the potential of decreased RCOR1 to suppress gouty inflammation. CONCLUSION:This is the first comprehensive genetic characterization of adolescent-onset gout. The identified risk loci of early-onset gout 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.

Purpose:Previous studies have linked high-density lipoprotein cholesterol (HDL-C) to gout, but little is known about the dose-effect relationship between serum HDL-C levels and gout flares. This study aimed to quantify the association between the two during urate-lowering therapy initiation and develop a regression equation to predict gout flares. Patients and Methods:We conducted a prospective, observational, single-center cohort study of men with gout. Patients were identified and grouped according to the level of serum HDL-C (1.16 mmol/L) at baseline and followed-up every four weeks until 12 weeks. Results:A total of 394 participants completed the study (203 in the low HDL-C group; 191 in the high HDL-C group). The proportion of participants with gout flares in the low HDL-C group was significantly higher than in the high HDL-C group after 12 weeks follow-up (52.2% versus 35.6%, P=0.001). Patients with lower serum HDL-C level had higher risk of gout flares analyzed by restricted cubic spline and when serum HDL-C level = 1.15mmol/L, flareHR = 1. When combined with well-known risk factors, serum HDL-C predicted gout flares with an area under curve (AUC) of 0.75 (95% CI=0.70-0.80). Based on the logistic regression coefficients, we derived the following regression equation: Logit (P)= -2.282+0.05× [disease duration]+1.015× [recurrent flares in the last year]+0.698× [palpable tophus]+0.345× [serum urate]-1.349×[serum HDL-C]. Conclusion:Patients with gout presented a negative linear relationship between serum HDL-C and gout flares. Together with common clinical indicators, the AUC for gout flare prediction increased to 0.75. For patients with gout, remaining serum HDL-C level above 1.15 mmol/L may reduce the risk of gout flares.

Objective There is an unmet need for simpler urate‐lowering therapy (ULT) regimens that achieve the serum urate target and improve the overall quality of gout care. We report a comparative effectiveness trial of febuxostat monotherapy versus benzbromarone add‐on to low‐dose febuxostat in gout specifically with combined renal urate underexcretion and overload. Methods A prospective randomized trial was conducted on patients with combined‐type hyperuricemia and estimated glomerular filtration rate >60 mL/min/1.73 m 2 1:1 randomly assigned to febuxostat and benzbromarone combination therapy (initially febuxostat at 20 mg/day, with benzbromarone at 25 mg/day added onto 20 mg/day of febuxostat if not at target) or febuxostat monotherapy (initially 20 mg/day, escalating to 40 mg/day if not at target). The primary end point at 12 weeks was the proportion achieving a serum urate (SU) level <360 μmol/L. Other outcomes included altered liver and kidney function, new‐onset urolithiasis, and gout flares. Results There were 250 participants randomized; 219 completed 12‐week treatment. More patients in the febuxostat and benzbromarone combination group achieved the SU target compared to patients in the febuxostat monotherapy group (75.5% vs 47.7%; odds ratio 3.37 [95% confidence interval 1.90–5.98]). Safety profiles were comparable between the two groups. Conclusion Simply adding on low‐dose benzbromarone (25 mg/day) to low‐dose (20 mg/day) febuxostat showed superior urate lowering compared to febuxostat monotherapy in gout with a combined‐type hyperuricemia. For selected patients, expedited achievement of the SU target in more than 75% of patients using one titration step and low xanthine oxidase inhibitor and uricosuric doses is a potential alternative to standard ULT regimens.

Objectives: To evaluate whether ultrasound findings of monosodium urate (MSU) crystal deposition predict frequent gout flares in index joints over 12 months. Methods: This single-center study enrolled people with at least one gout flare involving the MTP1, ankle or knee joint. The most painful or most frequently joint was identified as index joint for analysis. All participants were started on urate-lowering therapy and had an ultrasound scan of the index joints at the baseline visit. OMERACT scores (for tophus, double contour sign and aggregates) were used to analyze whether ultrasound scores predicted frequent (>= 2) gout flares in the index joint over 12 months. Results: Frequent flares were significantly higher in those with ultrasound findings in all index joints (MTP1: tophus: 85.0% vs 46.0%, P < 0.001, aggregates: 78.8% vs 59.0%, P < 0.01; ankle: tophus: 54.6% vs 20.8%, P < 0.001; aggregates: 60.0% vs 35.9%, P < 0.05; knee: tophus: 68.4% vs 28.6%, P < 0.05). For the MTP1, for each 1-point increase in tophus score, the odds of frequent gout flares increased by 5.19 [(95%CI: 1.26-21.41), 7.91 [(95%CI: 2.23-28.14), and 13.79 [(95%CI: 3.79-50.20)] fold respectively. For the ankle, a tophus score of 3 markedly improved the prediction of the frequent flares [OR= 9.24 (95%CI=2.85-29.91)]. Semi-quantitative sum scores were associated with frequent flares with an OR (95%CI) of 13.66 (3.44-54.18), P < 0.001 at the MTP1, 7.05 (1.98-25.12), P < 0.001 at the ankle. Conclusion: Ultrasound features of MSU crystal deposition at the MTP1 and knee predict subsequent risk of frequent gout flares in the same joints following initiation of urate-lowering therapy, with the highest risk in those with high tophus scores.

Access to clean and safe drinking water is essential. This study aimed to evaluate the effect of a kind of small molecular natural mineral water, C-cell mineral water on hyperuricemia male mice metabolism condition. A 13-week drinking water intervention study was conducted in Uox-knockout mice (KO). The hepatic metabolite profiling and related genes expression were detected by UPLC-TOF-MS and transcriptomic, and the gut microbiota of KO mice was determined by metagenomics sequencing. Results showed that the body weight of mice fed with C-cell water was remarkably lower than that of control mice on D 77 and D 91. Hepatic metabolite profiling revealed a shift in the pathway of glycine, serine and threonine metabolism, pantothenate and CoA biosynthesis, and biosynthesis of cofactors in KO mice fed with C-cell mineral water. Increased energy metabolism levels were related to increased hepatic expression of genes responsible for coenzyme metabolism and lipid metabolism. Gut microbiota was characterized by increasing activity of beneficial bacteria Blautia, and reducing activity of pathobiont bacteria Parasutterella. These genera have been reported to be associated with obesity. Small molecular mineral-rich natural water ingestion regulates metabolism and gut microbiota, protecting against obesity induced by hyperuricemia through mediating a microbiota-liver axis.

Purpose: Higher baseline serum urate or higher initial urate-lowering medication dose increased risk of gout flares during uratelowering therapy (ULT) initiation. The decrease in serum urate may play a crucial role in this process. Therefore, we aim to explore the relationship between decrease in serum urate and the risk of gout flares during ULT initiation.Patients and Methods: A 12-week prospective cohort study of Chinese male gout patients was conducted at Shandong Provincial Clinical Research Center for Immune Diseases and Gout in China. Patients were grouped by baseline serum urate (7-7.9 mg/dL, 8- 8.9 mg/dL and =9 mg/dL). All patients received febuxostat 20 mg daily during weeks 0-4, then escalated to 40mg during weeks 4-12 if serum urate >6mg/dL. The main outcomes were the number of gout flares and the decrease in serum urate. Poisson regression was performed.Results: A total of 282 participants were enrolled, of whom 260 completed (84, 87 and 89 in each group) from March 2021 to December 2021. A 44.2% of all participants experienced at least one gout flare. In the multivariate Poisson regression 1, ? serum urate 0-12 weeks (IRR 1.184, 95% CI, 1.062-1.320; P=0.002), the number of gout flares before treatment 1 year (1.017, 1.010-1.024; P<0.001) and tophus (1.580, 1.023-2.440; P=0.039) were independently associated with the number of gout flares. While in the multivariate Poisson regression 2, baseline serum urate (1.256, 1.050-1.503; P=0.013) and the number of gout flares before treatment 1 year (1.014, 1.007-1.022; P<0.001) were independently associated with the number of gout flares, ? serum urate 0-12 weeks (1.055, 0.923-1.207; P=0.433) was no longer a risk factor.Conclusion: ULT-induced gout flares depend on the degree of decrease in serum urate, which is affected by baseline serum urate. Higher baseline serum urate and greater decrease in serum urate lead to higher risk of gout flares.

The deposition of monosodium urate (MSU) crystals within synovial joints and tissues is the initiating factor for gout arthritis. Thus, MSU crystals are a vital tool for studying gout's molecular mechanism in animal and cellular models. This study mainly compared the excellence and worseness of MSU crystals prepared by different processes and the degree of inflammation induced by MSU crystals.MSU crystals were prepared using neutralization, alkali titration, and acid titration methods. The crystals' shape, length, quality, and uniformity were observed by polarized light microscopy and calculated by the software Image J. The foot pad and air pouch models were used to assess the different degrees of inflammation induced by the MSU crystals prepared by the three different methods at different time points. Paw swelling was evaluated by caliper. In air pouch lavage fluid, inflammatory cell recruitment was measured by hemocytometer, and the level of IL-1β, TNF-α, and IL-18 by ELISA. Inflammatory cell infiltration was assayed by immunohistochemistry of air pouch synovial slices.For the preparation of MSU crystals with the same uric acid, the quantity acquired by the alkalization method was highest, followed by neutralization, with the acid titration method being the lowest. The crystals prepared by neutralization were the longest. The swelling index of the foot pad induced by MSU crystals prepared by acid titration was significantly lower than that of the other methods at 24 h. The inflammatory cell recruitment and level of IL-1β, TNF-α, and IL-18 in air pouch lavage fluid were lowest in animals with crystals prepared by acid titration. IL-1β secretion induced by MSU crystals prepared by acid titration was significantly lower than that of the other two groups, but there was no significant difference in IL-18 secretion between the three groups in THP-1 macrophages and BMDMs.All three methods can successfully prepare MSU crystals, but the levels of inflammation induced by the crystals prepared by the three methods were not identical. The degree of inflammation induced by MSU crystals prepared by neutralization and alkalization is greater than by acid titration, but the quantity of MSU crystals obtained by the alkalization method is higher and less time-consuming. Apparently, the window of inflammation triggered by acid titration preparation is shorter compared to other forms of crystal preparation. Overall, MSU crystals prepared by the alkaline method should be recommended for studying the molecular mechanisms of gout in animal and cellular models.

Cadmium (Cd) exposure has been associated with the development of enterohepatic circulation disorders and hyperuricemia, but the possible contribution of chronic low-dose Cd exposure to disease progression is still need to be explored. A mouse model of wild-type mice (WT) and Uox-knockout mice (Uox-KO) to find out the toxic effects of chronic low-dose Cd exposure on liver purine metabolism by liquid chromatography-mass spectrometry (LC-MS) platform and associated intestinal flora. High throughput omics analysis including metabolomics and transcriptomics showed that Cd exposure can cause disruption of purine metabolism and energy metabolism. Cd changes several metabolites associated with purine metabolism (xanthine, hypoxanthine, adenosine, uridine, inosine) and related genes, which are associated with elevated urate levels. Microbiome analysis showed that Cd exposure altered the disturbance of homeostasis in the gut. Uox-KO mice were more susceptible to Cd than WT mice. Our findings extend the understanding of potential toxicological interactions between liver and gut microbiota and shed light on the progression of metabolic diseases caused by Cd exposure.

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.

Hyperuricemia (HUA) is closely associated with kidney damage and kidney diseases in humans; however, the underlying mechanisms of HUA-induced kidney diseases remain unknown. In the present study, we examined the kidney and plasma metabolic profiles in a HUA mouse model constructed by knocking out (Ko) the urate oxidase (Uox) gene. The Uox-Ko mice were characterized by an increase in uric acid, glycine, 3'-adenosine monophosphate, citrate, N-acetyl-l-glutamate, l-kynurenine, 5-hydroxyindoleacetate, xanthurenic acid, cortisol, and (-)-prostaglandin e2 together with a decrease of inosine in the kidneys. These altered metabolites confirmed disturbances of purine metabolism, amino acid biosynthesis, tryptophan metabolism, and neuroactive ligand-receptor interaction in Uox-Ko mice. Betaine and biotin were related to kidney function and identified as the potential plasma metabolic biomarker for predicting urate nephropathy (UN). Taken together, these results revealed the underlying pathogenic mechanisms of UN. Investigating these pathways might provide novel targets for the therapeutic intervention of UN and can potentially lead to new treatment strategies.

Cadmium (Cd) and lead (Pb) are toxic heavy metals with endocrine-disrupting properties. We investigated the associations of low-level environmental exposure to Cd/Pb and gout status (intercritical gout, gout flare and combined gout) in a cohort study. We measured by ICP-MS the levels of Cd and Pb in blood (Cd-B and Pb-B) and urine (Cd-U and Pb-U) from 408 participants with blood and 346 participants with urine samples recruited from a hospital gout clinic. The median levels of Cd-B and Pb-B (in mu g/L) in the gout flare group were 0.87 (range 0.41-2.49) and 31.54 (25.38-41.46), respectively, and the median levels of Cd-U and Pb-U in the gout flare group were 1.05 (0.69-1.91) and 3.86 (3.49-4.44), respectively. These medians were significantly higher than those in the control or intercritical groups (P < 0.05). For Cd-B in tertile 2 (T2) and Cd-U in tertile 3, Cd levels were significantly associated with gout flare status compared to the reference tertile 1 (OR = 4.3, P = 0.041 and OR = 25.1, P = 0.002, respectively) after adjustment under Model 3. For Pb-U, the risk of gout flare status was significantly higher in T2 (OR = 51.0, P = 0.002) compared to the T1 under Model 3. Our results show that median levels of Cd-B, Pb-B, Cd-U and Pb-U in the gout flare group were significantly higher than participants without gout or with gout but in the intercritical period. We provide evidence that the risk of gout flare status is associated with increased Cd levels, and that blood and urine levels of Cd are a risk factor for gout flare status. (C) 2021 Elsevier Ltd. All rights reserved.

Objective:To explore the role of transgelin(TAGLN) in the occurrence and development of papillary thyroid carcinoma (PTC) and its possible signal pathway.Methods:One hundred cases of PTC tissues and corresponding paracancerous normal thyroid tissues were collected. Realtime quantitative PCR (RT-qPCR), Western blotting, and immunohistochemistry were used to analyze the expression of TAGLN in PTC tissues and corresponding paracancerous normal thyroid tissues. PTC cells were transfected with plasmid and shRNA lentivirus vector respectively to up-regulate or down-regulate the expression of TAGLN in order to detect the effects of them on the proliferation, invasion, and migration by cell proliferation assay(cell counting kit-8, CCK-8)and cell invasion and migration assays (Transwell). The effects of TAGLN on mitogen-activated protein kinase (MAPK)/extracellular-signal regulating kinase (ERK) signal pathway was detected with Western blotting.Results:RT-qPCR showed that there was no difference in the expression of TAGLN mRNA between PTC and corresponding paracancerous normal thyroid tissues ( P>0.05); Western blotting demonstrated that the expression of TAGLN protein in PTC tissues was significantly lower than that in corresponding paracancerous normal thyroid tissues ( P<0.01). Immunohistochemical results revealed that the expression of TAGLN in PTC tissues was significantly lower than that in corresponding paracancerous normal thyroid tissues. Overexpression of TAGLN inhibited the proliferation, invasion, and migration of PTC cells ( P<0.01), but knockdown of TAGLN promoted the proliferation, invasion, and migration of PTC cells ( P<0.01). Overexpression of TAGLN decreased the expression of phosphorylated ERK ( P<0.05), whereas silencing TAGLN increased phosphorylated ERK level in PTC cells( P<0.01). Conclusion:The expression of TAGLN in PTC is significantly decreased. It is related to the occurrence and development of PTC, and its mechanism may be related to MAPK/ERK signal pathway.

Background The Reporting Items for Practice Guidelines in Healthcare (RIGHT) checklist was used to assess the reporting quality of 2009–2019 clinical practice guidelines (CPGs) regarding gout and hyperuricemia, aimed to improve the reporting quality of future guidelines. Methods We searched PubMed, the Chinese Biomedical Literature database, the Wanfang Database, and the China National Knowledge Infrastructure from January 2009 to June 2019 for guidelines regarding gout and hyperuricemia. We also searched the websites of guideline development organizations (the Guidelines International Network, the National Institute for Health and Clinical Excellence, the American College of Rheumatology, and the European League Against Rheumatism (EULAR)). Furthermore, supplementary guidelines reported in included articles were systematically searched, as well as Google Scholar. Results Seventeen guidelines were included, of which one was in Chinese and 16 were in English. The mean reporting rate of the 35 items specified was 14.9 (42.5%); only five CPGs (29.4%) had a reporting rate >50%. Of the 35 items, three were very frequently reported. The reporting proportion of the seven domains (basic information, background, evidence, recommendations, review and quality assurance, funding and declaration and management of interests, and other information) were 64.7%, 36.8%, 50.6%, 42.9%, 8.82%, 33.8%, and 31.4%, respectively. Conclusion The reporting quality of the present guidelines for gout and hyperuricemia is relatively poor. We suggest that the RIGHT reporting checklist should be used by CPG developers to ensure higher reporting quality of future guidelines.

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.

BACKGROUND: Peripheral nerve injury can lead to extensive changes in central nervous system, and exercise training can promote the recovery of locomotor function following central nervous system injury. OBJECTIVE: To observe the changes of locomotor function and the expression levels of vesicular glutamate transporter VGLUT1 in the spinal cord in a rat model of dorsal root ganglion resection after treadmill exercise and to explore the effect of treadmill training on the locomotor function after peripheral nerve injury. METHODS: Thirty-nine 10-week-old male Wistar rats were randomized into experimental (n=15), control (n=15) and sham operation (n=9) groups. The rats in the experimental and control groups received the dorsal root ganglion resection at L3and L4segments to establish the model of peripheral nerve injury under local anesthesia, while the rats in the sham operation group were only subjected to dorsal root ganglion exposure. The rats in the experimental group underwent 15 m/minute treadmill training at postoperative 7 days, while rats in the other two groups were in free movement. Gait analysis was performed at preoperative 3 days, postoperative 7, 14, 21, and 28 days, respectively, and the behavioral changes of rats were observed. The tissue sections were obtained from L3segment at postoperative 7, 14, and 28 days to detect the expression levels of VGLUT1 in the spinal cord by immunohistochemistry. RESULTS AND CONCLUSION: The peroneal nerve function index in the experimental and control groups was lower than that before surgery and that in the sham operation group at postoperative different time points (all P ＜ 0.05). The index in the experimental and control groups was the lowest on day 7 postoperatively (P ＜ 0.05), then the index gradually increased, but was still lower than the preoperative level (P ＜ 0.05). The index in the experimental group was significantly higher than that in the control group at postoperative 21 and 28 days (P ＜ 0.05). The expression levels of VGLUT1 in the lamina IX in the experimental and control groups were significantly lower than those in the sham operation group at different time points after surgery (P ＜ 0.01). The levels in the experimental group were significantly higher than those in the control group at postoperative 14 and 28 days (P ＜ 0.05). The levels in both groups on a decline after surgery, especially the control group (P ＜ 0.05). These results suggest that treadmill can promote the recovery of locomotor function post peripheral nerve injury.

周围神经损伤在临床上较为常见,严重影响病人的生活质量.周围神经损伤后,不仅会在其直接损伤部位产生炎症反应、神经纤维脱髓鞘变性等病理过程,也会对受累脊髓节段造成不同程度影响.越来越多研究表明,周围神经损伤后脊髓受损程度与感觉运动功能损害关系密切.本文就周围神经损伤后脊髓内部神经元死亡、神经营养因子变化、胶质反应以及康复训练的作用等几个方面进行综述.