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1.
Rheumatology (Oxford) ; 62(5): 1972-1979, 2023 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-36111871

RESUMO

OBJECTIVE: Oxylipins modulate inflammation via complex pathways. The oxylipin profile in gout remains unexplored. In this study, we systemically profiled oxylipins in young men and identified new oxylipin biomarkers for clinical use in differentiating gout from hyperuricaemia. MATERIAL AND METHODS: Oxylipin profiling was performed in 90 men (30 very early onset gout, 30 asymptomatic hyperuricaemia [HU] and 30 normouricaemia [NU], all aged <20 years) divided into discovery and validation sample sets. The dataset was analysed based on orthogonal projection to latent structure-discriminant analysis. Correlation network and pathway enrichment were conducted to reveal potential oxylipin-involved pathways of gout. Candidate oxylipins were further evaluated and optimized in the validation cohort, and differential oxylipin biomarkers combined with or without serum urate were applied to construct diagnostic models. RESULTS: In discovery stage, 21 differential oxylipins in the gout vs HU comparisons and 14 differential oxylipins in the gout vs NU comparisons were discovered. Correlation network analysis was performed and 14(S)-HDHA (14S-hydroxy-4Z,7Z,10Z,12E,16Z,19Z-docosahexaenoic acid) was identified as a hub metabolite in both comparisons. Seven down-regulated oxylipins in the gout vs HU group and five down-regulated oxylipins in the gout vs NU group were validated. Diagnostic models were constructed with the above oxylipins, with 14(S)-HDHA alone having an area under the curve of 1 (95% CI, 1, 1) in both comparisons. CONCLUSIONS: Young men with very early onset gout have distinct oxylipin spectrums, especially those derived from arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid. Differential oxylipins could serve as candidate serum biomarkers in differentiating gout from hyperuricaemia.


Assuntos
Gota , Hiperuricemia , Masculino , Humanos , Adolescente , Oxilipinas , Ácidos Docosa-Hexaenoicos , Biomarcadores
2.
Rheumatology (Oxford) ; 62(7): 2435-2443, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-36409036

RESUMO

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 < 0.001). High CA72-4, disease duration, intra-articular tophus size, glucose, high-density lipoprotein-cholesterol and ESR were independent risk factors for gout flares. Serum CA72-4 alone predicted recurrent flares with an area under the curve of 0.63 (95% CI = 0.54, 0.71), and 0.78 (95% CI = 0.71, 0.85) when combined with other independent variables. CONCLUSION: High serum CA72-4 predicts the risk of gout flares during ULT initiation. TRIAL REGISTRATION: ChiCTR; https://www.chictr.org.cn/; ChiCTR2100043573.


Assuntos
Gota , Masculino , Humanos , Ácido Úrico , Supressores da Gota/uso terapêutico , Estudos Prospectivos , Exacerbação dos Sintomas
3.
Phys Chem Chem Phys ; 26(1): 342-351, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38063083

RESUMO

According to Hückel's rule, cyclic species are aromatic if they have 4n + 2 (n = 0, 1, 2, etc.) π electrons. However, large aromatic rings (atom number > 4) with minimum 2π electrons (i.e., n = 0) are rather rare because of the structural instability stemming from the deficient π electrons compared to the ring size. To date, the largest 2π-aromatic ring is a five-membered Ga5 core reported in a recent experiment. Herein, density functional theory calculations predicted seven inverse-sandwich Na2(MH)5 and half-sandwich Ca(MH)5 or Ca(MH)6 (M = Al, Ga or In) structures. They all have planar central five- or six-membered Al/Ga/In rings, rather negative binding energies and large HOMO-LUMO gaps. Their dianionic metal rings exhibit obvious aromatic characters and appreciable diatropic ring currents due to the good delocalization of 2π electrons donated by the Na/Ca metals. Interestingly, they also have novel collective bonding with the Na/Ca atoms interacting with both the metal ring and surrounding H atoms. These metalloaromatic rings not only greatly enrich the precious family of 2π aromatics, but also increase the maximum ring atom number from five to six, thus paving the way for Hückel-type 2π-aromatic large rings.

4.
Ecotoxicol Environ Saf ; 266: 115587, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37837700

RESUMO

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.


Assuntos
Cádmio , Microbioma Gastrointestinal , Animais , Camundongos , Cádmio/metabolismo , Fígado , Metabolômica , Homeostase , Modelos Animais de Doenças
5.
Sensors (Basel) ; 23(12)2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37420819

RESUMO

Intelligent devices, which significantly improve the quality of life and work efficiency, are now widely integrated into people's daily lives and work. A precise understanding and analysis of human motion is essential for achieving harmonious coexistence and efficient interaction between intelligent devices and humans. However, existing human motion prediction methods often fail to fully exploit the dynamic spatial correlations and temporal dependencies inherent in motion sequence data, which leads to unsatisfactory prediction results. To address this issue, we proposed a novel human motion prediction method that utilizes dual-attention and multi-granularity temporal convolutional networks (DA-MgTCNs). Firstly, we designed a unique dual-attention (DA) model that combines joint attention and channel attention to extract spatial features from both joint and 3D coordinate dimensions. Next, we designed a multi-granularity temporal convolutional networks (MgTCNs) model with varying receptive fields to flexibly capture complex temporal dependencies. Finally, the experimental results from two benchmark datasets, Human3.6M and CMU-Mocap, demonstrated that our proposed method significantly outperformed other methods in both short-term and long-term prediction, thereby verifying the effectiveness of our algorithm.


Assuntos
Algoritmos , Qualidade de Vida , Humanos , Benchmarking , Inteligência , Movimento (Física)
6.
Ann Rheum Dis ; 81(8): 1189-1193, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35277390

RESUMO

OBJECTIVES: COVID-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. METHODS: A 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. RESULTS: We 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. CONCLUSION: COVID-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.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Colchicina , Supressores da Gota , Gota , Exacerbação dos Sintomas , Adulto , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Colchicina/uso terapêutico , Estudos Transversais , Gota/tratamento farmacológico , Supressores da Gota/uso terapêutico , Humanos , Vacinação , Vacinas/uso terapêutico
7.
Rheumatology (Oxford) ; 60(11): 5020-5027, 2021 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33704429

RESUMO

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.


Assuntos
Creatinina/sangue , Fenofibrato , Gota , Nefropatias , Triglicerídeos/sangue , Ácido Úrico/sangue , Monitoramento de Medicamentos/métodos , Monitoramento de Medicamentos/estatística & dados numéricos , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Fenofibrato/administração & dosagem , Fenofibrato/efeitos adversos , Gota/sangue , Gota/diagnóstico , Gota/terapia , Humanos , Hipolipemiantes/administração & dosagem , Hipolipemiantes/efeitos adversos , Nefropatias/induzido quimicamente , Nefropatias/diagnóstico , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Medição de Risco/métodos , Fatores de Risco
8.
Rheumatology (Oxford) ; 60(6): 2661-2671, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-33211886

RESUMO

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.


Assuntos
Benzobromarona/uso terapêutico , Citratos/uso terapêutico , Gota/tratamento farmacológico , Bicarbonato de Sódio/uso terapêutico , Uricosúricos/uso terapêutico , Adulto , Benzobromarona/administração & dosagem , China , Citratos/efeitos adversos , Esquema de Medicação , Taxa de Filtração Glomerular/efeitos dos fármacos , Gota/urina , Humanos , Concentração de Íons de Hidrogênio , Incidência , Cálculos Renais/induzido quimicamente , Cálculos Renais/epidemiologia , Sangue Oculto , Estudos Prospectivos , Bicarbonato de Sódio/efeitos adversos , Uricosúricos/administração & dosagem
9.
Sensors (Basel) ; 21(16)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34450964

RESUMO

Currently, simultaneous localization and mapping (SLAM) is one of the main research topics in the robotics field. Visual-inertia SLAM, which consists of a camera and an inertial measurement unit (IMU), can significantly improve robustness and enable scale weak-visibility, whereas monocular visual SLAM is scale-invisible. For ground mobile robots, the introduction of a wheel speed sensor can solve the scale weak-visibility problem and improve robustness under abnormal conditions. In this paper, a multi-sensor fusion SLAM algorithm using monocular vision, inertia, and wheel speed measurements is proposed. The sensor measurements are combined in a tightly coupled manner, and a nonlinear optimization method is used to maximize the posterior probability to solve the optimal state estimation. Loop detection and back-end optimization are added to help reduce or even eliminate the cumulative error of the estimated poses, thus ensuring global consistency of the trajectory and map. The outstanding contribution of this paper is that the wheel odometer pre-integration algorithm, which combines the chassis speed and IMU angular speed, can avoid the repeated integration caused by linearization point changes during iterative optimization; state initialization based on the wheel odometer and IMU enables a quick and reliable calculation of the initial state values required by the state estimator in both stationary and moving states. Comparative experiments were conducted in room-scale scenes, building scale scenes, and visual loss scenarios. The results showed that the proposed algorithm is highly accurate-2.2 m of cumulative error after moving 812 m (0.28%, loopback optimization disabled)-robust, and has an effective localization capability even in the event of sensor loss, including visual loss. The accuracy and robustness of the proposed method are superior to those of monocular visual inertia SLAM and traditional wheel odometers.

10.
Rheumatology (Oxford) ; 59(10): 2872-2880, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32087013

RESUMO

OBJECTIVES: Serum CA72-4 levels are elevated in some gout patients but this has not been comprehensively described. The present study profiled serum CA72-4 expression in gout patients and verified the hypothesis that CA72-4 is a predictor of future flares in a prospective gout cohort. METHODS: To profile CA72-4 expression, a cross-sectional study was conducted in subjects with gouty arthritis, asymptomatic hyperuricaemia, four major arthritis types (OA, RA, SpA, septic arthritis) and healthy controls. A prospective gout cohort study was initiated to test the value of CA72-4 for predicting gout flares. During a 6-month follow-up, gout flares, CA72-4 levels and other gout-related clinical variables were observed at 1, 3 and 6 months. RESULTS: CA72-4 was highly expressed in patients with gouty arthritis [median (interquartile range) 4.55 (1.56, 32.64) U/ml] compared with hyperuricaemia patients [1.47 (0.87, 3.29) U/ml], healthy subjects [1.59 (0.99, 3.39) U/ml] and other arthritis patients [septic arthritis, 1.38 (0.99, 2.66) U/ml; RA, 1.58 (0.95, 3.37) U/ml; SpA, 1.56 (0.98, 2.85) U/ml; OA, 1.54 (0.94, 3.34) U/ml; P < 0.001, respectively]. Gout patients with frequent flares (twice or more in the last year) had higher CA72-4 levels than patients with fewer flares (fewer than twice in the last year). High CA72-4 level (>6.9 U/ml) was the strongest predictor of gout flares (hazard ratio = 3.889). Prophylactic colchicine was effective, especially for patients with high CA72-4 levels (P = 0.014). CONCLUSION: CA72-4 levels were upregulated in gout patients who experienced frequent flares and CA72-4 was a useful biomarker to predict future flares.


Assuntos
Antígenos Glicosídicos Associados a Tumores/sangue , Artrite Gotosa/sangue , Exacerbação dos Sintomas , Artrite Infecciosa/sangue , Artrite Reumatoide/sangue , Biomarcadores/sangue , Estudos Transversais , Feminino , Gota/sangue , Humanos , Hiperuricemia/sangue , Masculino , Pessoa de Meia-Idade , Osteoartrite/sangue , Estudos Prospectivos , Espondilartrite/sangue , Fatores de Tempo
11.
Pediatr Nephrol ; 35(3): 441-446, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31811538

RESUMO

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.


Assuntos
Hiperuricemia/epidemiologia , Ácido Úrico/sangue , Adolescente , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Hiperuricemia/sangue , Hiperuricemia/diagnóstico , Masculino , Prevalência , Valores de Referência , Fatores de Risco , Fatores Sexuais , Adulto Jovem
12.
Hereditas ; 156: 4, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30679935

RESUMO

BACKGROUND: Serum uric acid (SUA), hyperuricemia (HUA) and gout are complex traits with relatively high heritability. This study aims to identify whether a candidate gene, SLC28A2, exerts susceptibility for SUA fluctuation and incidence of HUA and gout in the Han Chinese population. RESULTS: Three sample sets of 1376 gout patients, 1290 long-term HUA subjects (no gout attack) and 1349 normouricemic controls were recruited for this study. Eight polymorphisms in the SLC28A2 gene were genotyped using the ligase detection reaction-polymerase chain reaction (LDR-PCR) technology. Rs16941238 showed the most significant associations with SUA level (minor allele "A", BETA = - 13.84 µmol/L, P = 0.0041, Pperm = 0.0042) and HUA (OR = 0.7734, P = 0.0033, Pperm = 0.0020), but not with gout (OR = 0.8801, P = 0.1315, Pperm = 0.1491). Rs2271437 was significantly associated with gout (minor allele "G", OR = 1.387, P = 0.0277, Pperm = 0.0288), and was further confirmed in the meta-analysis with the previously published gout GWAS dataset (OR = 1.3221, P = 0.0089). Each variant basically conferred consistent OR direction on gout and HUA, compared with the normouricemic control. CONCLUSIONS: Our findings support the associations of the SLC28A2 gene with the SUA level, the HUA phenotype and gout in Han Chinese.


Assuntos
Gota/genética , Hiperuricemia/genética , Proteínas de Membrana Transportadoras/genética , Ácido Úrico/sangue , Adulto , Idoso , Povo Asiático , Estudos de Casos e Controles , China , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
13.
Sensors (Basel) ; 19(7)2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30939747

RESUMO

The use of renewable energy has increased dramatically over the past couple of decades. Wind farms, consisting of wind turbines, play a vital role in the generation of renewable energy. For monitoring and maintenance purposes, a wind turbine has a variety of sensors to measure the state of the turbine. Sensor measurements are transmitted to a control center, which is located away from the wind farm, for monitoring and maintenance purposes. It is therefore desirable to ensure reliable wireless communication between the wind turbines and the control center while integrating the observations from different sensors. In this paper, we propose an IoT based communication framework for the purpose of reliable communication between wind turbines and control center. The communication framework is based on repeat-accumulate coded communication to enhance reliability. A fusion algorithm is proposed to exploit the observations from multiple sensors while taking into consideration the unpredictable nature of the wireless channel. The numerical results show that the proposed scheme can closely predict the state of a wind turbine. We also show that the proposed scheme significantly outperforms traditional estimation schemes.

14.
Kidney Int ; 93(1): 69-80, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28729031

RESUMO

The urate oxidase (Uox) gene encodes uricase that in the rodent liver degrades uric acid into allantoin, forming an obstacle for establishing stable mouse models of hyperuricemia. The loss of uricase in humans during primate evolution causes their vulnerability to hyperuricemia. Thus, we generated a Uox-knockout mouse model on a pure C57BL/6J background using the transcription activator-like effector nuclease (TALEN) technique. These Uox-knockout mice spontaneously developed hyperuricemia (over 420 µmol/l) with about 40% survival up to 62 weeks. Renal dysfunction (elevated serum creatinine and blood urea nitrogen) and glomerular/tubular lesions were observed in these Uox-knockout mice. Male Uox-knockout mice developed glycol-metabolic disorders associated with compromised insulin secretion and elevated vulnerability to streptozotocin-induced diabetes, whereas female mice developed hypertension accompanied by aberrant lipo-metabolism. Urate-lowering drugs reduced serum uric acid and improved hyperuricemia-induced disorders. Thus, uricase knockout provides a suitable mouse model to investigate hyperuricemia and associated disorders mimicking the human condition, suggesting that hyperuricemia has a causal role in the development of metabolic disorders and hypertension.


Assuntos
Hiperuricemia/enzimologia , Rim/metabolismo , Fígado/enzimologia , Urato Oxidase/deficiência , Ácido Úrico/sangue , Animais , Biomarcadores/sangue , Glicemia/metabolismo , Pressão Sanguínea , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/enzimologia , Diabetes Mellitus Experimental/genética , Modelos Animais de Doenças , Progressão da Doença , Dislipidemias/sangue , Dislipidemias/enzimologia , Dislipidemias/genética , Feminino , Predisposição Genética para Doença , Supressores da Gota/farmacologia , Hipertensão/enzimologia , Hipertensão/genética , Hipertensão/fisiopatologia , Hiperuricemia/sangue , Hiperuricemia/tratamento farmacológico , Hiperuricemia/genética , Insulina/sangue , Rim/patologia , Rim/fisiopatologia , Lipídeos/sangue , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fenótipo , Fatores de Tempo , Urato Oxidase/genética
15.
Intern Med J ; 47(10): 1147-1153, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28696562

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is associated with the risk of coronary heart diseases; however, the relationship between NAFLD and peripheral artery disease (PAD) in patients with type 2 diabetes has not been investigated. AIM: To investigate the association between NAFLD and PAD in patients with type 2 diabetes. METHODS: We carried out a cross-sectional study on 2646 type 2 diabetes patients ≥ 40 years. All patients provided fasting blood samples and underwent a liver ultrasonography and ankle-brachial index (ABI) test. PAD was defined as an ABI <0.9. Multiple logistic regression analyses were performed to investigate the odds ratio (OR) for PAD associated with NAFLD. RESULTS: Our analyses showed that patients with NAFLD had a significantly higher prevalence of PAD compared with those without NAFLD (12.8% vs 7.8%). NAFLD was associated with a 75% (OR 1.75, 95% confidence interval (CI) 1.35-2.28) increased risk of PAD after adjustment for demographic factors. Addition of various metabolic risk factors as confounders attenuated the association (OR 1.49, 95% CI 1.12-2.00). Further adjustment for C-reactive protein led the association to be marginally significant (OR 1.33, 95% CI 0.99-1.80). Analyses stratified by gender suggested the association was much stronger among women than among men. CONCLUSION: Type 2 diabetes patients with NAFLD had a higher prevalence of PAD, and this association was partly, but not entirely, explained by metabolic risk factors and inflammation.


Assuntos
Diabetes Mellitus Tipo 2/diagnóstico por imagem , Diabetes Mellitus Tipo 2/epidemiologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/epidemiologia , Idoso , Índice Tornozelo-Braço/métodos , Glicemia/metabolismo , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Doença Arterial Periférica/sangue , Fatores de Risco , Inquéritos e Questionários
16.
Sensors (Basel) ; 17(5)2017 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-28448454

RESUMO

This paper presents a chirp based ultrasonic positioning system (UPS) using orthogonal chirp waveforms. In the proposed method, multiple transmitters can simultaneously transmit chirp signals, as a result, it can efficiently utilize the entire available frequency spectrum. The fundamental idea behind the proposed multiple access scheme is to utilize the oversampling methodology of orthogonal frequency-division multiplexing (OFDM) modulation and orthogonality of the discrete frequency components of a chirp waveform. In addition, the proposed orthogonal chirp waveforms also have all the advantages of a classical chirp waveform. Firstly, the performance of the waveforms is investigated through correlation analysis and then, in an indoor environment, evaluated through simulations and experiments for ultrasonic (US) positioning. For an operational range of approximately 1000 mm, the positioning root-mean-square-errors (RMSEs) &90% error were 4.54 mm and 6.68 mm respectively.

17.
Rheumatol Int ; 35(6): 963-71, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25377645

RESUMO

Previous studies have showed that patients with gout showed lower serum 25(OH)D levels. As the specific receptor of vitamin D, VDR plays an important role in regulating immune system by combining with vitamin D. In this study, we investigated whether the functional VDR polymorphisms were associated with susceptibility to gout in Chinese Han male population. A total of 504 patients with gout and 523 gout-free controls were recruited from the Affiliated Hospital of the Medical College, Qingdao University. Genotyping of VDR rs11568820, rs2228570 and rs1544410 was performed by TaqMan allele discrimination assays. An association analysis was carried out using the χ(2) test. A genotype-phenotype analysis was also conducted. Our results showed that polymorphisms of rs11568820 and rs1544410 in VDR were associated with gout in Chinese Han male population. The A allele of both rs11568820 and rs1544410 was associated with the risk of gout [P = 0.012 OR 1.251, 95% CI (1.051-1.490); P = 0.006, OR 1.574, 95% CI (1.139-2.175)]. However, there was no statistic significance between rs2228570 and gout (P = 0.186). Our study suggested that the polymorphisms of VDR may be relevant host susceptibility factors for the development of gout in Chinese Han male population. However, further study should be done in a larger size sample and other ethic to test and verify our result.


Assuntos
Povo Asiático/genética , Gota/genética , Polimorfismo Genético , Receptores de Calcitriol/genética , Adulto , Idoso , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , China , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Gota/diagnóstico , Gota/etnologia , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Fatores de Risco , Fatores Sexuais
18.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 32(4): 538-42, 2015 Aug.
Artigo em Zh | MEDLINE | ID: mdl-26252103

RESUMO

OBJECTIVE: To assess the association of cytochrome P450 gene single nucleotide polymorphisms (SNPs) with susceptibility to gout in ethnic Han males from coastal regions of Shandong province. METHODS: Four hundred and eighty male patients with gout and 480 healthy male controls were included. Genotyping was carried out with a custom Illumina GoldenGate Genotyping assay to detect SNP rs2275620 of CYP2C8 gene, SNP rs2070676 of CYP2E1 gene, SNP rs837395 of CYP4B1 gene, and SNP rs194150 of TBXAS1 gene. The association was assessed with chi-square test. RESULTS: No significant difference has been found between the two groups in regard to the genotypic and allelic frequencies of the TT, AT, AA genotypes and A, T alleles of the SNP rs2275620 of the CYP2C8 gene (P=0.88; P=0.97), the CC, CG, GG genotypes and C,G alleles of SNP rs2070676 of the CYP2E1 gene (P=0.24; P=0.09), the TT, AT, AA genotypes and A, T alleles of SNP rs837395 of the CYP4B1 (P=0.88; P=0.97), and TT, AT, AA genotypes and the A,T alleles of SNP rs194150 of TBXAS1 gene (P=0.15; P=0.06). CONCLUSION: This study has identified no association of SNP loci rs2275620(A/T) of CYP2C8, rs2070676(C/G) of CYP2E1, rs837395(A/T) of CYP4B1 and rs194150(A/T) of TBXAS1 with gout in ethnic Han males from coastal regions in Shandong province. However, our result needs to be replicated in larger sets of patients collected from other regions and populations.


Assuntos
Hidrocarboneto de Aril Hidroxilases/genética , Citocromo P-450 CYP2C8/genética , Citocromo P-450 CYP2E1/genética , Gota/enzimologia , Gota/genética , Polimorfismo de Nucleotídeo Único , Tromboxano-A Sintase/genética , Adulto , Povo Asiático/etnologia , Povo Asiático/genética , China/etnologia , Suscetibilidade a Doenças , Feminino , Gota/etnologia , Humanos , Masculino , Pessoa de Meia-Idade
19.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 32(5): 711-4, 2015 Oct.
Artigo em Zh | MEDLINE | ID: mdl-26418998

RESUMO

OBJECTIVE To assess the association of single nucleotide polymorphisms (SNPs) of susceptibility genes of type 2 diabetes mellitus (T2DM) with liability to gout among ethnic Han Chinese males from coastal region of Shandong province. METHODS Seven SNPs within the susceptibility genes of T2DM, including rs10773971(G/C) and rs4766398(G/C) of WNT5B gene, rs10225163(G/C) of JAZF1 gene, rs2069590(T/A) of BDKRB2 gene, rs5745709(G/A) of HGF gene, rs1991914(C/A) of OTOP1 gene and rs2236479(G/A) of COL18A1 gene, were typed with a custom-made Illumina GoldenGate Genotyping assay in 480 male patients with gout and 480 male controls. Potential association was assessed with the chi-square test. RESULTS No significant difference was detected for the 7 selected SNPs in terms of genotypic and allelic frequencies (P > 0.05). When age and body mass index (BMI) were adjusted, the 7 genetic variants still showed no significant association with gout. CONCLUSION The genotypes of the 7 selected SNPs are not associated with gout in ethnic Han Chinese male patients from the coastal region of Shandong province. However, the results need to be replicated in larger sets of patients collected from other regions and populations.


Assuntos
Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Gota/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , China/etnologia , Etnicidade , Humanos , Masculino , Pessoa de Meia-Idade
20.
Arthritis Care Res (Hoboken) ; 76(1): 131-139, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37553607

RESUMO

OBJECTIVE: To assess post-COVID-19 vaccination gout flare risk with differing baseline flare burden. METHODS: We prospectively studied gout patients with infrequent or frequent flares, defined as ≤1 flare/year or ≥2 flares/year, respectively. COVID-19 vaccine-naive patients managed with urate-lowering therapy between February and June 2021 were included and voluntarily decided on vaccination. Participants were followed for 12 weeks after enrollment or first vaccine dose. Gout flares and risk factors were compared between groups. RESULTS: Of 530 participants, 308 (58.1%) had infrequent flares and 222 (41.9%) had frequent flares at baseline, with 248 (142 infrequent and 106 frequent) receiving two-dose COVID-19 vaccination. Vaccination increased cumulative flare incidence at 12 weeks in the infrequent but not the frequent flare group (26.1% vs 10.8%, P = 0.001, compared with 60.4% vs 65.5%, P = 0.428). Flare incidence in the final 4 weeks of observation decreased significantly only in the vaccinated infrequent flare group (4.3% vs 12.0%, P = 0.017). Multivariable analyses showed that vaccination (odds ratio [OR] 2.82, 95% confidence interval [95% CI] 1.50-5.30, P = 0.001), flare in the preceding year (OR 1.95, 95% CI 1.03-3.71, P = 0.04), and body mass index (OR 1.09, 95% CI 1.01-1.19, P = 0.03) were independently associated with increased flare risk in the infrequent flare group. Baseline serum urate (mg/dl) was an independent risk factor in the frequent flare group (OR 1.23, 95% CI 1.05-1.45, P = 0.012). CONCLUSION: COVID-19 vaccination was associated with increased early gout flares only in patients with previously infrequent flares.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Gota , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Gota/tratamento farmacológico , Gota/epidemiologia , Supressores da Gota/uso terapêutico , Estudos Prospectivos , Exacerbação dos Sintomas , Ácido Úrico , Vacinação/efeitos adversos
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