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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.
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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.
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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.
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@#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.
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@#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.
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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.
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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.
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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.
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[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.
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@#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.
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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.
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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.
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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.
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Objective:To investigate the risk factors of gout and establish a columnar graph model to predict the risk of gout development.Methods:A total of 1 032 Han Chinese men attending the Affiliated Hospital of Traditional Chinese Medicine of Xinjiang Medical University, People′s Hospital of Xinjiang Uygur Autonomous Region, and the First Affiliated Hospital of Xinjiang Medical University from 2018 to 2020 were selected as study subjects and divided into training set(722 cases)and validation set(310 cases)by simple random sampling method in the ratio of 7∶3. General information and biochemical indices of the subjects were collected. The collected information was used to assess the risk of gout prevalence. LASSO regression analysis of R Studio software was used to screen the best predictors, and was introduced to construct a column line graph model for predicting gout risk using receiver operating characteristic(ROC)curves, and the Hosmer-Lemeshow test was used to assess the discrimination and calibration of the column line graph model. Finally, decision curve analysis(DCA)was performed using the rmda program package to assess the clinical utility of the model in validation data.Results:Age, uric acid, body mass index, total cholesterol, and waist-to-hip ratio were risk factors for gout( P<0.05). The column line graph prediction model based on the above five independent risk factors had good discrimination(AUC value: 0.923 for training set validation and 0.922 for validation set validation)and accuracy(Hosmer-Lemeshow test: P>0.05 for validation set validation); decision curve analysis showed that the prediction model curve had clinical practical value. Conclusion:The nomogram model established by combining age, uric acid, body mass index, total cholesterol, and waist-to-hip ratio indicators can predict the risk of gout more accurately.
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Objective:To explore the effect of triglyceride glucose(TyG) index, single nucleotide polymorphism of Toll-like receptor 4(TLR4) and NOD-like receptor thermal protein domain associated protein 3(NLRP3) genes, and its interaction on the risk of gout.Methods:A total of 315 male patients with gout and 499 men for health checkup at the same period were selected. General data were collected through questionnaires, and peripheral venous blood was collected for biochemical test. Three single nucleotide polymorphisms(SNPs) of NLRP3 and TLR4 were detected with multiplex ligase assay reaction, and logistic regression analysis was applied to compare the correlation between NLRP3 and TLR4 alleles and gout risk. The interaction of SNP and TyG index with gout was analyzed by generalized multi-factor dimensionality reduction(GMDR) model and logistic regression.Results:After adjusting for smoking, drinking, and other factors, the risk of gout increased by 61.1% for each standard deviation increase in TyG index. CC genotypes of rs10754558, rs10759932, and rs7525979 were high risk genotypes of gout in Han ethnicity. GMDR results showed significant differences in the interaction models of rs10754558-TyG index, rs7525979-TyG index, and rs10759932-TyG index between control group and gout group( P<0.05), suggesting an interaction between the three genotypes of SNPs selected and TyG index. Stratified analysis of the three selected SNPs and TyG index showed that after adjusting for age, smoking, and other factors, the high TyG index patients carrying C/C or C/G genotype at rs10754558 displayed an increased risk of gout compared with those carrying GG genotype and low TyG index( OR=2.127, P<0.05). Conclusion:The CC genotypes of rs10754558, rs10759932, and rs7525979 are high risk genotypes for gout in Han ethnicity. The interaction between rs10754558 and TyG index may increase the risk of gout development.
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Gout is a metabolic disease resulting from the accumulation of monosodium urate (MSU) in joints, leading to crystal-induced arthritis. In China, gout is common, but there is insufficient knowledge regarding standardized criteria for the diagnosis and treatment of this condition. Based on evidence and guidelines from China and other countries, the Chinese Rheumatology Association developed standardized criteria for the diagnosis and treatment of gout in China. The purpose was to standardize gout diagnosis methods as well as treatment opportunities and strategies in order to reduce misdiagnosis, missed diagnosis, and irreversible damage.
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Objective:To investigate the clinical characteristics of patients with rheumatic diseases and abnormal liver function, as well as determine the proportion and severity of liver function abnormalities.Methods:Cross-sectional study. Data were collected from patients registered in the Chinese Rheumatism Date Center from 2011 to 2021. The rheumatic diseases analyzed in this study were rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren syndrome (SS), ankylosing spondylitis (AS), and gout. Patient data, including demographic characteristics [ such as age, sex, body mass index,(BMI), and smoking history], liver function test results [including alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase(ALP), and total bilirubin], and use of anti-rheumatic immune drugs and liver-protective drugs, were collected and compared between groups with normal and abnormal liver functions. In addition, the proportions of abnormal liver function were compared between sex and age groups.Results:A total of 116 308 patients were included in this study, including 49 659 with RA, 17 597 with SLE, 9 039 with SS, 11 321 with AS, and 28 692 with gout. The lowest proportion of liver function abnormalities was observed in patients with RA[11.02% (5 470/49 659)], followed by those with SS[17.97% (1 624/9 039)] and AS [18.22% (2 063/11 321) ], whereas patients with SLE [21.14% (3 720/17 597) ] and gout [28.73% (8 242/28 692)] exhibited the highest proportion of these abnormalities. Elevated ALT, mostly classified as grade 1, was the most commonly noted liver function abnormality, whereas elevated ALP was the least common. Some patients who took liver-protective drugs had normal liver function, with the lowest percentage observed in patients with gout [7.45% (36/483) ] and ranging from 21.7% to 30.34% in patients with RA, SLE, SS, and AS. The proportion of liver function abnormalities was higher in males than in females for all disease types [RA: 13.8%(1 368/9 906) vs. 10.3%(4 102/39 753); SLE: 33.6% (479/1 424) vs. 20.0% (3 241/16 173); SS: 25.4%(111/437) vs. 17.6%(1 513/8 602); AS: 20.1%(1 629/8 119) vs. 13.6% (434/3 202); and gout: 29.3% (8 033/27 394) vs. 16.1% (209/1 298)]. In RA, SLE, and AS, the proportions of liver function abnormalities were similar across all age groups. In SS, the proportion of liver function abnormalities increased with age [<40 years: 14.9%(294/1 979); 40-59 years: 18.1%(858/4 741); ≥60 years: 20.4%(472/2 319)], whereas a reversal of this trend was observed in gout [<40 years: 34.9%(4 294/12 320); 40-59 years: 25.5%(2 905/11 398);≥60 years: 21.0%(1 042/4 971)].Conclusions:The proportions of combined liver function abnormalities in patients with rheumatologic diseases were high, and the utilization rates of liver-protective drugs were low. It is necessary to pay more attention to monitoring patients′ liver function, timely administer liver-protective drugs, and optimize liver-protective regimens during the treatment of rheumatic diseases.
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Gout is a metabolic disorder characterized by elevated uric acid levels， often caused by purine metabolism disturbances or abnormalities in uric acid （UA） excretion. Currently， western medicine is the primary treatment approach for gout， but it often comes with significant side effects. Traditional Chinese medicine （TCM） has gained significant development in the field of gout treatment due to its safety and effectiveness. This article aimed to explore TCM strategies in the management of gout， providing insights for the development and application of TCM in the field of gout treatment. Relevant literature retrieved from PubMed， Web of Science， China National Knowledge Infrastructure （CNKI）， Wanfang Data， and VIP databases was systematically analyzed with such keywords as "Chinese herbal medicine"， "traditional Chinese medicine"， "TCM"， and "gout". The findings suggest that TCM can treat gout through a syndrome differentiation approach that encompasses four pathological mechanisms： phlegm， blood stasis， dampness， and deficiency， simultaneously addressing both excess and deficiency syndromes in gout. Based on the pathological characteristics of four syndromes， namely dampness-heat retention， blood stasis-heat obstruction， phlegm-turbidity obstruction， and liver and kidney Yin deficiency， TCM adopts specific treatment approaches including clearing heat and promoting diuresis， activating blood and resolving stasis， resolving phlegm and reducing turbidity， and nourishing the liver and kidneys. These targeted approaches have proven to be effective in gout management. The main mechanisms of TCM in gout management include inflammation resistance ［regulating inflammatory pathways such as tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， interleukin-8 （IL-8）， and other chemokines， as well as inflammatory signaling pathways like nuclear factor-kappa B （NF-κB） and NOD-like receptor protein 3 （NLRP3）］， uric acid reduction （modulating uric acid transporters and inhibiting xanthine oxidase （XOD） activation）， antioxidant stress mitigation （suppressing reactive oxygen species and regulating nitric oxide， malondialdehyde， and other oxidative markers）， and immune system regulation.
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ObjectiveTo explore the anti-gout effect and mechanism of Derris eriocarpa extract by network pharmacological analysis combined with in vivo and in vitro experimental verification. MethodThe chemical components and candidate targets of D. eriocarpa were obtained from the database. The key targets and potential active components of D. eriocarpa in the treatment of gout were screened by the protein-protein interaction analysis， and then the Gene Ontology （GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment were performed for the key targets. A mouse model of hyperuricemia was established by intraperitoneal injection of hypoxanthine to observe the effect of D. eriocarpa alcohol extract on hyperuricemia. A rat model of gouty inflammation induced by the injection of microcrystalline sodium urate crystals into the foot and plantar was used to observe the effect of D. eriocarpa alcohol extract on gouty inflammation. A xylene-induced acute inflammation model was established to observe the anti-inflammatory effect of D. eriocarpa alcohol extract. The hot plate test and twisting test were performed to observe the pain-relieving effect of D. eriocarpa. The lipopolysaccharide （LPS）-induced RAW264.7 cells were used to study the anti-gout effect and mechanism of D. eriocarpa alcohol extract. ResultA total of 12 key targets and 15 potential active components were obtained from the D. eriocarpa-component-gout target network. The emodin， betulinic acid， and medicarpin endowed D. eriocarpa with anti-hyperuricemia， anti-inflammatory， and pain-relieving effects by acting on Toll-like receptor 4 （TLR4）， NOD-like reception protein 3 （NLRP3）， and nuclear factor （NF）-κB. Compared with the control group， the model groups showed elevated serum uric acid level in mice （P<0.01）， increased swelling degree of rats （P<0.05， P<0.01）， alleviated the auricular swelling of mice （P<0.05）， reduced the twisting times of mice （P<0.05， P<0.01）， and increased the hot plate pain threshold （P<0.05）. Moreover， the model group showed up-regulated mRNA level of TLR4 and protein levels of TLR4， NF-κB， and NLRP3 in cells （P<0.01）， and elevated levels of TLR4 and NF-κB in the cell supernatant （P<0.05， P<0.01）. Compared with the model group， the alcoholic extracts （20， 10， 5 g·kg-1） of D. eriocarpa lowered the serum uric acid level in hyperuricemic mice （P<0.01）， inhibited foot and plantar swelling in rats （P<0.05， P<0.01）， down-regulated the mRNA level of TLR4 and the protein levels of TLR4， NF-κB， NLRP3 in cells， and lowered the levels of TLR4， TNF-α， NF-κB， and IL-6 in cell supernatants （P<0.05， P<0.01）. ConclusionD. eriocarpa alcohol extract may exert the anti-gout， anti-inflammatory， and pain-relieving effects by regulating the TLR4/NF-κB/NLRP3 signaling pathway.
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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.