摘要
Objective To compare the difference of peripheral blood adiponectin and CD4+T cell subsets between patients with a-cute gouty arthritis and healthy controls,to explore the correlation between adiponectin and serum uric acid,disease activity,CT4+T cell subsets and some cytokines in patients with gout.Methods The clinical data(including general data,neutrophils,erythrocyte sedimen-tation rate,C-reactive protein,blood uric acid,CT4+T cell subsets and some cytokines)of acute gout group(n=90)and healthy con-trol group(n=72)were collected.The level of adiponectin in peripheral blood of two groups were detected,and the differences of adi-ponectin and CD4+T cell subsets between the two groups were compared;the correlation between adiponectin and clinical data was ana-lyzed.Results The levels of serum adiponectin in the acute gout group were significantly lower than those in the healthy control group(P＜0.001),and the levels of Th2,Thl7,Th17/Treg were significantly higher than those in the healthy control group(P＜0.05),while the levels of Treg and Th1/Th2 were significantly lower than those in the healthy control group(P＜0.05).In the acute gout group,adiponectin was negatively correlated with neutrophil,erythrocyte sedimentation rate and C-reactive proten(r=-0.244,P＜0.05;r=-0.311,P＜0.05;r=-0.506,P＜0.001),there was no correlation with serum uric acid.In acute gout group,adiponectin was posi-tively correlated with Th1 and Th1/Th2(r=0.252,P＜0.05;r=0.218,P＜0.05).In acute gout group,adiponectin in peripheral blood was positively correlated with interleukin-2(IL-2),interleukin-4(IL-4)and interleukin-10(IL-10)(r=0.323,P＜0.05;r=0.377,P＜0.05;r=0.359,P＜0.05).There was a negative correlation between interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)(r=-0.265,P＜0.05;r=-0.299,P＜0.05).Multiple linear regression analysis showed that adiponectin in the acute gout group was negatively correlated with erythrocyte sedimentation rate,C-reactive protein,IL-6 and TNF-α(BESR=-12.541,P=0.003;BCRP=-8.256,P=0.024;BIL-6=-15.907,P=0.037;BTNF-α=-79.770,P=0.040),but positively correlated with Th1(BTh1=2.959,P=0.006).Conclusion The levels of adiponectin in the peripheral blood of patients with acute gouty arthritis were decreased,the levels of Th2 and Th17 were increased,and the levels of Treg were decreased.The decrease of adi-ponectin was related to the immunological disorder and inflammation in the patients with acute gouty arthritis.
摘要
Objective:To explore expression of each member of miR17-92 cluster in peripheral blood mononuclear cells(PBMCs)of patients with gout,to predict their possible targets and pathways of action,and to evaluate their possible mechanism and clinical significance in gout.Methods:A total 67 gouty arthritis(GA)patients were selected,including 22 patients with acute gout arthritis(AG)and 45 patients with intermittent gout(IG),and 35 normal health control(HC)were selected in Affiliated Hospital of North Sichuan Medical College.RT-qPCR measured expressions of miR17-92 cluster,IFN-γ,IL-10 and some members of JAK-STAT pathway,and relevant laboratory indicators were collected to analyze correlation between each other.Results:Relative expressions of miR17,miR18a,miR19a,miR20a and miR19b were significantly changed in AG,IG and HC(H=8.753,P<0.05;H=6.338,P<0.05;H=6.523,P<0.05;H=9.061,P<0.05;H=9.729,P<0.01).JAK3 and STAT2 expressions were statistically different in AG,IG and HC groups(H=10.349,P<0.01;H=14.801,P<0.01).Expression of IFN-γ was statistically different among AG,IG and HC groups(H=8.734,P<0.05).In AG patients,miR18a expression was inversely correlated with IBIL,Crea,MO and HGB.miR19a ex-pression was negatively associated and TC,UA and HGB.miR20a expression was negatively associated with Crea.miR19b expression was negatively associated with UA and HGB.In IG patients,miR17 expression was negatively associated with IBIL,WBC,LY and MO.miR18a expression was positively associated with ALP,miR19a expression was negatively associated with TC and UA,and miR20a expression was negatively associated with ADA and UA.Conclusion:miR17-92 cluster may regulate development and partici-pate in clinical pathology of gout by targeting JAK-STAT pathway.
摘要
Objective:To study the differential gene expression and immune cell infiltration of gout patients,to find the key genes and immune cells of gout pathogenesis,and to explore the relationship between immune cells and gout.Methods:The gout chip GSE160170 was downloaded from the GEO database,and the differential gene expression analysis was carried out with the help of R language.Then,the STRING database was used to analyze the differential gene,and the Cytoscape software was used to screen the key genes,and then carry out enrichment analysis.At the same time,the infiltration of immune cells were analyzed.Results:The study found that IL-6,IL-1β,TNF,CCL3,CXCL8 and CXCL1 were key genes in the pathogenesis of gout,which were mainly exerted by IL-17,Toll-like receptor,NOD-like receptor,NF-κB and other signaling pathways.Processes such as cellular responses to lipo-polysaccharides,bacteria-derived molecules,and biological stimuli lead to disease;immune infiltration results indicate that memory B cells,activated NK cells,activated dendritic cells,activated mast cells and eosinophils were involved in the disease.It was signifi-cantly expressed in gout patients;the correlation analysis between immune cells showed that the expression of follicular helper T cells were positively correlated with the expression of activated mast cells,and the expression of unactivated NK cells and monocyte were negatively correlated.Conclusion:Key genes and differentially expressed immune cells are closely related to the pathogenesis of gout,providing new ideas for the study of the molecular mechanism of gout.
摘要
[Objective]To explore the medication rule of TCM compound patent in the treatment of gout,and analyze the mechanism of action of the core herbs based on the national patent database.[Methods]The Chinese herbal compound patent database for gout treatment was retrieved and entered into the Website of China Patent Announcement of The State Intellectual Property Office.The characteristics of medications were analyzed by frequency statistics,Apriori algorithm,factor analysis and systematic clustering method.The Chinese herbs targets of the core herbs combinations were obtained through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the gout disease targets were obtained from Human Gene database(GeneCards)and Online Mendelian Inheritance in Man(OMIM)database.The intersection of the two targets was imported into Cytoscape 3.9.1 software,and the Cluego plug-in was used to complete the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of the herb combinations.The intersection targets were imported into STRING database to obtain protein-protein interaction(PPI)network,and some key targets were selected for molecular docking with corresponding active compounds of Chinese herbs.[Results]A total of 508 Chinese herbal compound patents were included in the treatment of gout,involving 401 Chinese herbs,and the frequency of herbs was 6 082 times.Chinese herbs for diuresis-inducing and dampness-draining were mainly used,followed by herbs for tonifying deficiency,clearing heat,promoting blood circulation and removing blood stasis.The analysis of association rules obtained 3 binomial association rules and 5 trinomial association rules.Eight common factors were extracted by factor analysis.Three groups of herbs combinations were obtained by systematic clustering analysis,and 56 common biological pathways of herbs combination enrichment were found.Molecular docking results showed that the combination of Quercetin and tumor necrosis factor(TNF)was the best,followed by Baicalein and interleukin-6(IL-6),and the combination of Quercetin and adenosine triphosphate binding cassette super family G member 2(ABCG2)was good.[Conclusion]The national patent prescriptions for gout treatment based on the core pathogenesis of"turbid dampness and blood stasis"are mainly from three aspects of dampness,blood stasis and deficiency.The core herbs combinations are often supplemented or subtracted based on Simiao Powder,Fuling Zexie Decoction and Siwu Decoction.Chinese herbs mainly exert their effects through multiple signaling pathways such as TNF,hypoxia inducible factor-1(HIF-1),Toll-like receptors(TLRs)and IL-17 and promote excretion of uric acid.
摘要
@#Objective To investigate the mechanism of anti-IL-17A monoclonal antibody(secukinumab) regulating autophagy and inflammation in gout.Methods The peripheral venous blood samples from 57 patients with acute gout(AG),57patients with intermittent gout(IG) and 82 healthy volunteers were collected and measured for the mRNA transcription levels of autophagy-related genes(ATGs) ATG4B,ATG7, A TG16L1,Beclin-1 and LC3B by RT-qPCR.The model of AG inflammation was established by adding monosodium urate(MSU) crystals into the peripheral venous blood samples of healthy volunteers,and the transcription and protein expression of IL-1β were detected by RT-qPCR and ELISA at 0,1,2,4,6 and8 h and different concentrations(0,100,200 and 400 μmol/L) of secukinumab.The peripheral blood samples of healthy volunteers were divided into control(without MSU treatment),MSU(100 μg/mL),MSU+colchicine(100 μg/mL+30 μg/mL) and MSU+secukinumab(100 μg/mL+400 μmol/L) groups,which were detected for the mRNA transcription and protein expression of IL-1 β and ATGs by RT-qPCR and Western blot,and for the expression of IL-1β,IL-12 and IL-35 by ELISA.Results The mRNA expression levels of ATG4B, Beclin-1 and LC3B in AG,IG and healthy control groups were significantly different(F=3.896,11.78 and 3.856,respectively,each P <0.05),among which the mRNA levels in AG were lower than those in IG and HC groups(t=2.692,3.234,2.231 and 2.085,4.795,2.748,respectively,each P <0.05);the expression levels of ATG16L1 mRNA were significantly different in the three groups(F=7.949,P <0.001),and was significantly lower in AG group than HC group(t=3.860,P <0.001).In AG inflammation model,the mRNA and protein expression of IL-1 β reached their peak in 2—4 h,and the anti-inflammation effect of secukinumab was the strongest at the concentration of 400 μmol/L.Compared with MSU group,the mRNA levels of ATG16L1 and LC3B(t=2.343 and 2.916,respectively,each P <0.05) as well as the expression levels of ATG4B,ATG7,Beclin-1,ATG16L1 and LC3B-Ⅱ proteins(t=28.84,11.6,8.402,4.124 and 2.458,respectively,each P <0.05) in MSU+secukinumab group decreased significantly.The expression levels of IL-12 and IL-35 in the control,MSU,MSU+colchicine and MSU+secukinumab groups showed significant difference(F=7.009 and 6.518,respectively,each P <0.01).Compared with MSU group,the expression level of IL-12 significantly decreased(t=2.604,P <0.05)in MSU+secukinumab group,and the expression level of IL-35 also decreased,while with no significant difference(t=1.928,P> 0.05).Conclusion Secukinumab can regulate the mRNA and protein expression of ATGs,reduce the levels of pro-inflammatory cytokines,and inhibit gout inflammation,which provides a reference for the treatment of gout.
摘要
@#Abstract: Hyperuricemia is a metabolic disease caused by elevated uric acid in the body, and is closely related to the increased risk of cardiovascular disease, metabolic disorders, and renal complications. In the development process of uric acid-lowering drugs, activity evaluation is a crucial step. At present, the activity screening methods of uric acid-lowering drugs can be roughly divided into two categories: in vitro and in vivo. In vitro screening is mainly for such targets as xanthine oxidase, urate transporters, and purine nucleoside phosphorylase, etc.; while in vivo screening is achieved by rodent, poultry and organoid models. In this article, the activity evaluation methods for uric acid-lowering compounds are comprehensively summarized both in vitro and in vivo, aiming to provide some insight for the development of uric acid-lowering drugs.
摘要
Gout is a metabolic disease closely associated with hyperuricemia and urate deposition. Because of the complex pathogenesis， high morbidity， multiple complications， and increasingly young patients， gout has received worldwide attention. Currently， western medicine mainly treats gout by lowering the uric acid level and reducing inflammation， which， however， causes serious adverse reactions and has contraindications. Phellodendri Chinensis Cortex （PCC） is the dried bark of Phellodendron chinense， with the effects of clearing heat， drying dampness， purging fire， detoxifying， and treating sores. Studies have shown that PCC and its active components have anti-inflammatory， pain-relieving， uric acid-lowering， and anti-gout activities， with extensive sources and high safety. PCC and its active components could prevent and treat gout through multi-targets and multi-pathways， whereas the systematic review remains to be carried out. Therefore， this paper summarized the pharmacological activities and mechanisms of PCC and its active components in the treatment of gout. The available studies have shown that PCC and its active components exert the anti-gout effect by lowering the uric acid level， reducing inflammation， alleviating oxidative stress， and regulationg intestinal flora， and protecting the kidneys. Particularly， the active components represented by alkaloids contribute obviously to the therapeutic effect of of PCC. Herein， we analyzed the problems and future development of the research on PCC， aiming to provide theoretical support and a scientific basis for the research and development of new drugs against gout.
摘要
@#Objective To investigate the mechanism of anti-IL-17A monoclonal antibody(secukinumab) regulating autophagy and inflammation in gout.Methods The peripheral venous blood samples from 57 patients with acute gout(AG),57patients with intermittent gout(IG) and 82 healthy volunteers were collected and measured for the mRNA transcription levels of autophagy-related genes(ATGs) ATG4B,ATG7, A TG16L1,Beclin-1 and LC3B by RT-qPCR.The model of AG inflammation was established by adding monosodium urate(MSU) crystals into the peripheral venous blood samples of healthy volunteers,and the transcription and protein expression of IL-1β were detected by RT-qPCR and ELISA at 0,1,2,4,6 and8 h and different concentrations(0,100,200 and 400 μmol/L) of secukinumab.The peripheral blood samples of healthy volunteers were divided into control(without MSU treatment),MSU(100 μg/mL),MSU+colchicine(100 μg/mL+30 μg/mL) and MSU+secukinumab(100 μg/mL+400 μmol/L) groups,which were detected for the mRNA transcription and protein expression of IL-1 β and ATGs by RT-qPCR and Western blot,and for the expression of IL-1β,IL-12 and IL-35 by ELISA.Results The mRNA expression levels of ATG4B, Beclin-1 and LC3B in AG,IG and healthy control groups were significantly different(F=3.896,11.78 and 3.856,respectively,each P <0.05),among which the mRNA levels in AG were lower than those in IG and HC groups(t=2.692,3.234,2.231 and 2.085,4.795,2.748,respectively,each P <0.05);the expression levels of ATG16L1 mRNA were significantly different in the three groups(F=7.949,P <0.001),and was significantly lower in AG group than HC group(t=3.860,P <0.001).In AG inflammation model,the mRNA and protein expression of IL-1 β reached their peak in 2—4 h,and the anti-inflammation effect of secukinumab was the strongest at the concentration of 400 μmol/L.Compared with MSU group,the mRNA levels of ATG16L1 and LC3B(t=2.343 and 2.916,respectively,each P <0.05) as well as the expression levels of ATG4B,ATG7,Beclin-1,ATG16L1 and LC3B-Ⅱ proteins(t=28.84,11.6,8.402,4.124 and 2.458,respectively,each P <0.05) in MSU+secukinumab group decreased significantly.The expression levels of IL-12 and IL-35 in the control,MSU,MSU+colchicine and MSU+secukinumab groups showed significant difference(F=7.009 and 6.518,respectively,each P <0.01).Compared with MSU group,the expression level of IL-12 significantly decreased(t=2.604,P <0.05)in MSU+secukinumab group,and the expression level of IL-35 also decreased,while with no significant difference(t=1.928,P> 0.05).Conclusion Secukinumab can regulate the mRNA and protein expression of ATGs,reduce the levels of pro-inflammatory cytokines,and inhibit gout inflammation,which provides a reference for the treatment of gout.
摘要
Currently, clinically used drugs for the treatment of gout inflammation, such as colchicine, nonsteroidal anti-inflammatory drugs, and glucocorticoids, can only relieve the pain of joint inflammation and have severe hepatorenal toxicity and multiple organ adverse reactions. The NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome is a key complex that induces the onset of gout inflammation and has become a crucial target in the development of anti-gout drugs. This article reviews the research progress of anti-gout small molecules targeting the NLRP3 inflammasome and their bioactivity evaluation methods in the past five years, in order to provide information for the development of specific drugs for the treatment of gout inflammation.
摘要
BACKGROUND:In chronic gout patients,sodium urate is deposited in bone joints and around synovial membranes,eroding and destroying bone,leading to serious complications such as gouty arthritis and deformity.Research on the mechanisms by which sodium urate crystals erode and destroy bone can help early clinical intervention in gouty diseases and prevent and delay the complications caused by bone destruction. OBJECTIVE:To explore the destructive effects of gout crystals on bone through clinical imaging studies and experimental basic research,review the current progress and development prospects of research on the phenomenon and mechanism of bone destruction caused by gout,guide the clinical early intervention of gouty bone destruction,and guide the direction of research on the role of bone destruction. METHODS:The Chinese search terms were"gout,bone destruction,bone erosion"and the English search terms were"tophi,gout,RANKL,bone destruction,bone erosion,"which were used in the computer search of WanFang and PubMed databases.Finally,64 articles were selected for review according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:The specific manifestations of clinical studies(imaging,histopathology)to some extent elaborate the osteolytic process of gout,and in basic studies,the mechanism of gout-causing bone destruction can be divided into the five aspects:(1)Sodium acid crystals have an important role in bone destruction,directly affecting osteocytes,chondrocytes,osteoblasts and proresorptive factors that promote bone destruction;(2)Receptor activator of nuclear factor-κB ligand and other proresorptive factors are involved in bone destruction;(3)T cell-mediated cellular immunity functions as a bridge in bone destruction,and activated T cells induce osteoclast differentiation;(4)Monocytes/macrophages are not only precursors of osteoclast-like cells,but also induce the expression of proresorptive factors such as Receptor activator of nuclear factor-κB ligand;(5)Neutrophils affect the morphology of osteoclast arrangement,and neutrophil extracellular trap networks promote osteolysis by promoting osteoclast differentiation.
摘要
BACKGROUND:Excessive accumulation of uric acid in the body can lead to diseases such as hyperuricemia and gout,which is a risk factor for cardiovascular and renal dysfunction.Many sports medicine organizations at home and abroad advocate the formulation of exercise prescription to prevent and treat chronic diseases,but this method has not been effectively carried out in the prevention and treatment of hyperuricemia. OBJECTIVE:Based on an overview of the formation of hyperuricemia and the regulation of uric acid by exercise and its related mechanisms,to condense a program suitable for popular exercise to prevent and assist in the treatment of hyperuricemia,and to propose precautions to be taken when exercising for patients with different stages of hyperuricemia. METHODS:PubMed and CNKI were searched for relevant literature published before October 2023 using the keywords of"uric acid,gout,aerobic exercise,strength training,high-intensity interval training,obesity"in English and Chinese,respectively.Initial screening was done by reading the titles and abstracts to exclude repetitive studies and literature with irrelevant content,and finally 64 papers were included for review. RESULTS AND CONCLUSION:The formation of hyperuricemia is caused by excessive synthesis of uric acid by the liver,insufficient excretion by the kidneys,or both.Exercise can improve the uric acid level in the body by regulating the activity of antioxidant enzymes,the expression of uric acid excretion protein and lipid metabolism.Aerobic exercise,strength training,high-intensity intermittent exercise can effectively regulate uric acid levels,reduce inflammation,promote the expression of uric acid excretion protein and lipid metabolism,and achieve good results in the prevention and treatment of hyperuricemia.Currently,there is a lack of research on the mechanisms underlying direct regulation of uric acid levels by exercise,and future studies need to explore in greater depth the possible mechanisms of regulation of uric acid levels by exercise and refine the effects of different exercise modalities on patients with different characteristics of hyperuricemia.
摘要
Resumen Antecedentes: Los trastornos musculoesqueléticos (TME) afectan a 1710 millones de personas en todo el mundo y es la principal causa de discapacidad. Objetivo: Analizar los años vividos con discapacidad (AVD) por TME en México entre 1990 y 2021. Material y métodos: Con las estimaciones del estudio de la Carga Global de la Enfermedad 2021 se analizaron los AVD por TME y sus seis categorías: osteoartritis, artritis reumatoide, gota, dolor cervical, lumbalgia y otros TME. Se evaluaron patrones y tendencias del número, tasa cruda y tasa estandarizada por edad de los AVD a nivel nacional, estatal, por grupos de edad y sexo. Resultados: Los TME constituyeron la principal causa de AVD en México entre 1990 y 2021, con un incremento de 57.3 %; pasaron de 1458.4 a 2293.7 por 100 000 habitantes. La lumbalgia (840.6 AVD) destacó con la mayor tasa en 2021 y la osteoartritis, con el mayor incremento. Los TME se incrementaron con la edad y, con excepción de la gota, afectaron más a las mujeres. Conclusiones: De 1990 a 2021, los TME constituyeron la principal causa de AVD en México, con mayor impacto en adultos y mujeres. Los TME se evidencian desde edades tempranas, de ahí la necesidad de intervenciones continuas para preservar la calidad de vida.
Abstract Background: Musculoskeletal disorders (MSD) affect 1.71 billion people worldwide and are the leading cause of disability. Objective: To analyze the years lived with disability (YLD) attributed to MSD in Mexico between 1990 and 2021. Material and methods: With estimates from the Global Burden of Disease 2021 study, the YLDs due to MSD and their six categories were analyzed, including osteoarthritis, rheumatoid arthritis, gout, neck pain, low back pain, as well as other MSDs. Patterns and trends in the number, crude rate, and YLD age-standardized rate were evaluated at the national and state levels, as well as by age group and gender. Results: MSDs were the main cause of YLDs in Mexico between 1990 and 2021, with an increase of 57.3%, going from 1,458.4 to 2,293.7 per 100,000 population. Low back pain (840.6 YLD) showed the highest rate in 2021, while osteoarthritis had the largest increase. MSDs increased with age and, and except for gout, affected women more often. Conclusions: From 1990 to 2021, MSDs were the main cause of YLDs in Mexico, with a higher impact on adults and women. MSDs can appear early in life, hence the need for continuous interventions in order to preserve quality of life.
摘要
ABSTRACT Background: Colorectal cancer is the third most common type of cancer in both men and women and ranks second as the most common cause of cancer death in the United States. Classic risk factors include tobacco smoking, high alcohol consumption, physical inactivity and excess body weight. A prospective study found that an elevated serum uric acid was associated with higher rates of cancer-associated polyps. Interestingly, other studies found an association between elevated levels of serum uric acid and other types of cancer including colorectal cancer. Objective: Our study aimed to evaluate whether patients with chronic tophaceous gout had an increased risk of developing colorectal cancer. Methods: A validated multicenter and research platform database of more than 360 hospitals from 26 different healthcare systems across the United States was utilized to construct this study. Patients aged 18 years and above were included. Individuals who have had a history of familial adenomatous polyposis, a family history of colon cancer, and those diagnosed with inflammatory bowel disease were excluded from the analysis. The risk of developing colon cancer was calculated using a multivariate regression analysis to account for potential confounders. Results: 80,927,194 individuals were screened in the database and 70,177,200 were selected in the final analysis after accounting for inclusion and exclusion criteria. Type 2 diabetics (28.57%), smokers (10.98%), obese individuals (18.71%), alcoholics (3.13%), and patients who have had a diagnosis of chronic tophaceous gout were more common in the colon cancer group compared to those without the malignancy. Using multivariate regression analysis, risk of colon cancer was calculated for male gender (OR: 1.02; 95%CI: 1.01-1.03), smokers (OR: 1.54; 95%CI: 1.52-1.56), alcoholics (OR: 1.40; 95%CI: 1.37-1.43), obese patients (OR: 1.52; 95%CI: 1.50-1.54), type 2 diabetic individuals (OR: 3.53; 95%CI: 3.50-3.57), and those who have had a diagnosis of chronic tophaceous gout (OR: 1.40; 95%CI: 2.48-3.23). Conclusion: As expected, patients with colon cancer were found to have a higher prevalence in males, obese, tobacco and alcohol users. We also demonstrated that patients with gout have a significantly higher prevalence of CRC than those who do not before and after adjusting for metabolic risk factors. In fact, uric acid was found to induce production of reactive oxygen species, thus potentially promoting tumorigenesis. It would be interesting to assess the prevalence of colon cancer in patients with gout who have a serum uric acid that is less than 7 mg/dL. This might promote a tighter control of serum uric acid levels in this population in order to decrease the risk of colon cancer.
RESUMO Contexto: O câncer colorretal é o terceiro tipo mais comum de câncer em homens e mulheres e ocupa o segundo lugar como a causa mais comum de morte por câncer nos EUA. Os fatores de risco clássicos incluem tabagismo, alto consumo de álcool, inatividade física e excesso de peso corporal. Um estudo prospectivo descobriu que um ácido úrico sérico elevado estava associado a taxas mais altas de pólipos associados ao câncer. Curiosamente, outros estudos encontraram uma associação entre níveis elevados de ácido úrico sérico e outros tipos de câncer, incluindo o câncer colorretal. Objetivo: Nosso estudo teve como objetivo avaliar se os pacientes com gota tofácea crônica tinham um risco aumentado de desenvolver câncer colorretal. Métodos: Utilizou-se um banco de dados validado multicêntrico e de plataforma de pesquisa de mais de 360 hospitais de 26 diferentes sistemas de saúde nos Estados Unidos para a construção deste estudo. Foram incluídos pacientes com 18 anos ou mais. Indivíduos com histórico de polipose adenomatosa familiar, histórico familiar de câncer de cólon e aqueles diagnosticados com doença inflamatória intestinal foram excluídos da análise. O risco de desenvolver câncer de cólon foi calculado usando uma análise de regressão multivariada para contabilizar possíveis confusões. Resultados: 80.927.194 indivíduos foram rastreados no banco de dados e 70.177.200 foram selecionados na análise final após considerar critérios de inclusão e exclusão. Diabéticos tipo 2 (28,57%), fumantes (10,98%), indivíduos obesos (18,71%), alcoólatras (3,13%) e pacientes que tiveram diagnóstico de gota tofácea crônica foram mais comuns no grupo de câncer de cólon em comparação com aqueles sem a malignidade. Usando a análise de regressão multivariada, o risco de câncer de cólon foi calculado para o sexo masculino (OR: 1,02; IC95%: 1,01-1,03), fumantes (OR: 1,54; IC95%: 1,52-1,56), alcoólatras (OR: 1,40; IC95%: 1,37-1,43), pacientes obesos (OR: 1,52; IC95%: 1,50-1,54), indivíduos diabéticos tipo 2 (OR: 3,53; IC95%: 3,50-3,57), e aqueles que tiveram diagnóstico de gota tofácea crônica (OR: 1,40; IC95%: 2,48-3,23). Conclusão: Como esperado, os pacientes com câncer de cólon foram encontrados com maior prevalência em homens, obesos, usuários de tabaco e álcool. Demonstramos também que os pacientes com gota têm uma prevalência significativamente maior de câncer colorretal do que aqueles que não a têm, antes e após o ajuste para fatores de risco metabólicos. De fato, descobriu-se que o ácido úrico induz a produção de espécies reativas de oxigênio, promovendo assim potencialmente a tumorigênese. Seria interessante avaliar a prevalência de câncer de cólon em pacientes com gota que têm um ácido úrico sérico inferior a 7 mg/dL. Isso poderia promover um controle mais rígido dos níveis de ácido úrico sérico nesta população para diminuir o risco de câncer de cólon.
摘要
Periprosthetic gout flare is a rare arthritic condition after total knee arthroplasty, but the symptoms of gout may have often been mistaken as acute periprosthetic infection given their similarity. Misdiagnosis as periprosthetic infection can lead to unnecessary surgery, long-term dependence on anti-biotics, and even malfunction of the involved knee joint. Here, we report a case study of a patient with immunodeficiency condition of long-term oral glucocorticoid and diabetes mellitus, who had undergone a knee replacement 8 weeks before. The initial symptoms of fever and joint pain together with the dysfunction of her right knee with elevated inflammatory markers, such as increased serum leukocytes, erythrocyte sedimentation rate, C-reactive protein, and synovial cell counts led to a diagnosis of acute periprosthetic infection. Arthrocentesis and bacterial culture were performed preoperatively. According to the current Musculoskeletal Infection Society (MSIS) criteria for diagnosis of periprosthetic infection, the case was classified as periprosthetic infection and a prosthesis retained debridement surgery was performed. However we got negative culture results in all the pre-operative and intro-operative samples. The symptoms as well as the laboratory inflammatory markers improved shortly after the debridement surgery until the 11th day when all the similar systemic and local symptoms recurred. With a remedial crystal analysis of synovial fluid from the patient, gouty flare was found to be the cause of acute arthritis finally. Accor-dingly, after anti-gout medications were administrated, the symptoms associated with acute arthritis gra- dually subsided, and there was no recurrence during a 24-month follow-up. This article described the cli-nical manifestation, diagnosis and differential diagnosis, treatment of a case of periprosthetic gout. Although relatively rare, gout should be considered as a differential diagnosis in suspected periprosthetic infection. Current criteria for periprosthetic infection can not exclude the diagnosis of periprosthetic gout flare, it is therefore imperative that the analysis of joint aspirate for crystals be conducted to determine the correct course of treatment, or unnecessary surgical procedure may be performed in periprosthetic gout case.
Subject(s)
Humans , Female , Arthroplasty, Replacement, Knee/methods , Gout/complications , Prosthesis-Related Infections/surgery , Symptom Flare Up , C-Reactive Protein/analysis , Biomarkers/analysis摘要
A 24-year-old male was admitted due to recurrent redness, swelling, fever and pain in the ankle, frequently accompanied by hungry feeling. Dual energy CT scans showed multiple small gouty stones in the posterior edge of the bilateral calcaneus and in the space between the bilateral metatarsophalangeal joints. The laboratory examination results indicated hyperlipidemia, high lactate lipids, and low fasting blood glucose. Histopathology of liver biopsy showed significant glycogen accumulation. The results of gene sequencing revealed the compound heterozygous mutations of the G6PC gene c.248G>A (p.Arg83His) and c.238T>A (p.Phe80Ile) in the proband. The c.248G>A mutation was from mother and the c.238T>A mutation was from father. The diagnosis of glycogen storage disease type Ⅰa was confirmed. After giving a high starch diet and limiting monosaccharide intake, as well as receiving uric acid and blood lipids lowering therapy, the condition of the patient was gradually stabilized. After a one-year follow-up, there were no acute episodes of gout and a significant improvement in hungry feeling in the patient.
Subject(s)
Male , Humans , Young Adult , Adult , Glycogen Storage Disease Type I/genetics , Gout/genetics , Mutation , Lipids摘要
Objective:To explore the therapeutic characteristics of population with gout achieving treat-to-target (T2T) indicators through real-world research and evaluate their safety.Methods:A total of 3 287 patients diagnosed with gout by rheumatologists in 21 first-class tertiary hospitals in 10 provinces, municipalities, and autonomous regions in China from January 2015 to December 2021 were included in this polycentric cross-sectional study. The database included patients′ general information, disease characteristics, and clinical application of traditional Chinese and Western medicine treatment measures. SPSS and Excel software were used for data analysis. Frequency analysis, cluster analysis, and factor analysis were used to summarize the characteristics and rules of treatment measures for patients with gout who achieved the target after treatment. The occurrence of adverse events (AE) was recorded during treatment.Results:After treatment, 691 visits (7%) achieved the serum urate (SUA) target, and the most frequent use of urate-lowering therapy (ULT) was febuxostat, followed by benzbromarone. The most common treatment options were following: GroupⅠ: traditional Chinese medicine (TCM) decoction-TCM external treatment-physical exercise-proprietary Chinese medicine; GroupⅡ: ferulic acid-nonsteroidal anti-inflammatory drugs (NSAIDs); Group Ⅲ: allopurinol-sodium bicarbonate-benzbromarone; Group Ⅳ: glucocorticoid-colchicine; Group Ⅴ: febuxostat. A total of 5 898 visits (60%) chieved manifestations of joint pain VAS scores target, and the most frequently used drug to control joint symptoms was NSAIDs. The frequency of use of drugs to control joint symptoms were 2 118 times (usage rate reached 35.9%), while the frequency of ULT were 2 504 times (usage rate reached 42.5%), which was higher than the joint symptom control drug. The most common treatment options were following: Group Ⅰ: proprietary Chinese medicine-TCM decoction-TCM external treatment-physical exercise; Group Ⅱ: NSAIDs-colchicine hormones; Group Ⅲ: allopurinol, Group Ⅳ: benzbromarone; Group Ⅴ: febuxostat. A total of 59 adverse events occurred during treatment.Conclusion:The proportions of gout patients who reach target serum urate level & good control of joint symptoms are both very low, and ULT and anti-inflammatory prescription patterns are very different from international guidelines, so it is necessary to strengthen the standardized management of gout patients. At the same time, life intervention measures account for a certain proportion of the treatment plans for the T2T population, and further exploration is needed.
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Objective:To analyze the clinical characteristics of elderly-onset gouty arthritis and risk factors of tophi.Methods:A total of 1 239 gout patients were retrospective selected in the outpatient department of the Gout Clinical Medical Center of the Affiliated Hospital of Qingdao University from 2016 to 2022. According to age of onset, they were divided into the young and middle-aged group(aged<60) consisted of 826 cases, and the elderly group(aged≥60) consisted of 413 cases. Compare the clinical characteristics of elderly with Young and Middle-aged patients.Results:The systolic blood pressure, fasting blood glucose, creatinine, regular exercise, comorbidities, and tophi in the elderly group was higher than that in the middle-aged and young group. The proportion of diastolic blood pressure, serum triglycerides, eGFR, serum uric acid, alcohol consumption rate, and family history of gout was lower than that of young and middle-aged group( P<0.05); In the elderly-onset group, the initial site of arthritis was commonly observed in the first metatarsophalangeal joint. The proportion of the first attack with the upper limb joint was higher in old age group than in young and middle age group( P<0.05). Renal underexcretion type was the main subtype in the elderly group, and the proportion of overproduction type was higher than that of the young and middle-aged group( P<0.05). The logistic regression analysis showed that age, urea nitrogen, disease duration≥10 years and family history of gout were risk factors for tophi in elderly patients( P<0.05). Conclusion:The elderly-onset gout has unique clinical characteristics, characterized by a higher prevalence of tophi, a higher rate of complications. An initial site of arthritis commonly observed in the first metatarsophalangeal joint and the predominant type of uric acid excretion is renal excretion impairment. Early diagnosis and treatment, control of blood uric acid levels, smoking cessation and alcohol, regular exercise should be applied to prevent or delay the formation of tophi.
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Objective:To investigate the clinical characteristics and risk factors of multiple tophi among gout patients.Methods:Gout patients treated at Affiliated Hospital of Qingdao University from September 2017 to September 2021 were included retrospectively. According to the number of tophi, the patients were divided into the multiple tophi group, the single tophi group and the non-tophi group. Clinical data were collected, biochemical indices and urine pH value were determined. One- way ANOVA or Chi-square test was used to compare groups, and multivariate logistic regression was used to analyze the risk factors. Results:The age, disease course, blood pressure, serum uric acid, urea nitrogen, and the rate of family history, smoking, drinking, gout attacks≥2 twice per year, hypertension, cardio-cerebrovascular diseases, kidney stones in the multiple tophi group were significantly higher than those in the single tophi group and the non-tophi group. The glomerular filtration rate, urine pH value and the rate of regular exercise were significantly lower than those of single tophi group and non-tophi group. In the multiple tophi group, 245 cases(44.46%) were involved in the interphalangeal joint or metacarpophalangeal joint, 212 cases(38.47%) were involved in other joints of the upper limb, which was second only to the first metatarsophalangeal joint(349 cases, 63.33%). Logistic regression analysis showed that the course of disease, urea nitrogen, serum uric acid, positive family history, drinking, gout attacks ≥twice per year and hypertension were the risk factors for multiple tophi in gout patients. Conclusion:Patients with a long disease course, elevated uric acid, high urea nitrogen, positive family history, alcohol consumption, frequent gout flare and hypertension are more likely to develop multiple tophi.
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[Objective]To evaluate the anti-inflammatory effect of cepharanthin in vitro and in vivo,and to explore its mechanism of action in the treatment of gouty arthritis.[Methods]3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay was used to evaluate the effect of cepharanthin on cell viability in RAW264.7 cells.Enzyme linked immunosorbent assay(ELISA)and Western blot methods were used to detect the effects of cepharanthin on secretion and protein expression of inflammatory factors tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),toll-like receptor 4(TLR4),myeloid differentiation factor 88(MYD88)and NOD-like receptor protein 3(NLRP3)/apoptosis-associated speck-like protein containing a CARD(ASC)/caspase-1 inflammasome in vitro and in vivo.Gouty arthritis model was established by monosodium urate(MSU)stimulation in SD rats.The anti-inflammatory related indexes of cepharanthin were detected.The anti-inflammatory effect of cepharanthin was evaluated by detecting the expression of TNF-α,IL-1β,IL-6 and TLR4-NLRP3 related protein.[Results]The half maximal inhibitory concentration(IC50)of cepharanthin to cell viability in RAW264.7 cells was(62.51±5.36)μmol·L-1,weaker than that of colchicine(26.89±5.14)μmol·L-1.In RAW264.7 cells,1～10 μmol·L-1 cepharanthin significantly inhibited the secretion and mRNA expression of MSU-induced inflammatory factors TNF-α,IL-1β and IL-6,as also protein expression of TLR4-NLRP3 inflammasome.In rats arthritis model,1～10 mg·kg-1 cepharanthin dose-dependently improved toe swelling,and reduced the secretion of inflammatory factors TNF-α,IL-1β and IL-6,and protein expression of TLR4-NLRP3 inflammasome.[Conclusion]Cepharanthin exerts anti-arthritis effects by inhibiting the expression of inflammatory factors TNF-α,IL-1βand IL-6,and the expression of TLR4-NLRP3 inflammasome induced by MSU.
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OBJECTIVE@#To observe the diurnal difference of acute gout attacks in men, and provide reference for accurate clinical prevention and treatment.@*METHODS@#Using a single-center, cross-sectional study design, the patients diagnosed with gout in the outpatient department of Rheumatology and Immuno-logy of PLA Joint Logistic Support Force No.980 Hospital from October 2021 to April 2022 were selected. The information about the patient's current/last acute gout attacks (less than 2 weeks from visit), date and time of attacks, joint symptoms and signs, medication use, and relevant biochemical tests on the day of visit was recorded. The diurnal time difference of acute gout attacks in male patients was analyzed, and univariate comparison and multivariate Logistic regression analyses were conducted to compare the diurnal difference of acute gout attacks with clinical characteristics and biochemical indicators.@*RESULTS@#A total of 100 male gout patients were included, and 100 acute attacks were recorded. Diurnal distribution of acute gout attacks: morning (6:00~11:59, 18, 18%), afternoon (12:00~17:59, 11, 11%), the first half of the night (18:00~23:59, 22, 22%), the second half of the night (0:00~05:59, 49, 49%); During the day (included morning and afternoon, 29, 29%) and at night (included the first half of the night and the second half of the night, 71, 71%). The rate of acute gout attack was significantly higher at night than in the day (about 2.5 ∶1). No matter the first or recurrent gout, no matter the duration of the disease, the number of acute gout attacks had the difference of less in the day and more in the night. Serum urate (SU) level was higher in the patients with nocturnal attack than in those with daytime attack (P=0.044). Comorbidities were significantly different in the day-night ratio of the number of acute gout attack (P=0.028). Multiple Logistic regression analysis showed that SU level (OR=1.005, 95%CI: 1.001-1.009) and comorbidities (OR=3.812, 95%CI: 1.443-10.144) were the correlative factors of nocturnal acute gout attacks.@*CONCLUSION@#No matter the first or recurrent gout, no matter the duration of the disease, it has a diurnal variation characterized by multiple attacks at night, increased SU level and comorbidities are correlative factors for nocturnal acute attack of gout.