Biomimetic Integrated Nanozyme for Flare and Recurrence of Gouty Arthritis

Flare and multiple recurrences pose significant challenges in gouty arthritis.Traditional treatments provide temporary relief from inflammation but fail to promptly alleviate patient pain or effectively prevent subsequent recurrences.It should also be noted that both anti-inflammation and metabolism of uric acid are necessary for gouty arthritis,calling for therapeutic systems to achieve these two goals simultaneously.In this study,we propose a biomimetic integrated nanozyme,HMPB-Pt@MM,comprising platinum nanozyme and hollow Prussian blue.It demonstrates anti-inflammatory properties by eliminating reactive oxygen species and reducing infiltration of inflammatory macrophages.Additionally,it rapidly targets inflamed ankles through the camouflage of macrophage membranes.Furthermore,HMPB-Pt@MM exhibits urate oxidase-like capabilities,continuously metabolizing locally elevated uric acid concentrations,ultimately inhibiting multiple recurrences of gouty arthritis.In summary,HMPB-Pt@MM integrates ROS clearance with uric acid metabolism,offering a promising platform for the treatment of gouty arthritis.

Efficacy and safety of Jiawei Simiao powder combined with celecoxib for acute gouty arthritis:A meta-analysis

Objective:To evaluate the efficacy and safety of Jiawei Simiao powder(JWSMP)combined with celecoxib for the treatment of acute gouty arthritis by conducting a meta-analysis of randomized controlled trials(RCTs).Methods: The Chinese National Knowledge Infrastructure Databases,Chinese Scientific Journal Database,Wanfang,Cochrane Library,EMBASE,PubMed,and Web of Science databases were searched from inception until December 2023.Continuous variables were analyzed using the mean difference(MD)for analysis,and dichotomous variables were used as risk ratios.Data with similar characteristics were pooled for meta-analysis,and heterogeneity was assessed using I2.The Cochrane Handbook was used to assess the risk of bias and quality.RevMan 5.3 software was used to perform the meta-analysis.Results: Thirteen RCTs involving 1007 patients were included in the study.The quality of the included studies was low(unclear randomization processes and insufficient blinding reporting).The group receiving JWSMP combined with celecoxib showed significantly lower levels of serum uric acid(SUA,MD=−66.32,95%confidence interval(CI):−80.97 to−51.67,P<.001),erythrocyte sedimentation rate(ESR,MD=−6.05,95%CI:−8.29 to−3.82,P<.001),C-reactive protein(CRP,MD=−7.39,95%CI:−11.15,−3.63,P<.001),and joint pain score(VAS score,MD=−2.14,95%CI:−2.4 to−1.88,P<.001)compared to celecoxib alone.Additionally,the JWSMP combined group had a higher total effective rate(risk ratio=1.22,95%CI:1.14 to 1.29,P<.001)and fewer adverse compared to celecoxib alone.Conclusions: JWSMP combined with celecoxib is more effective than celecoxib alone in improving the total efficacy rate,alleviating joint pain,and improving SUA,ESR,and CRP levels.JWSMP also reduced the occurrence of adverse events caused by celecoxib.However,the quality of the included studies was low,highlighting the need for further high-quality research with larger sample sizes and robust methodologies,such as double-blind randomization,to confirm these findings.

Arthroscopic synovectomy for synovial hyperplasia in chronic knee gouty arthritis:A case report

BACKGROUND Chronic synovitis due to chronic knee gouty arthritis(KGA)resulting in synovial hyperplasia has not been documented in the current literature,and thus the optimal management for this condition remains unclear.This case report discusses a 34-year-old man with a history of chronic KGA who presented with recurrent knee effusion resulting from synovial hyperplasia.CASE SUMMARY A 34-year-old man presented to our outpatient clinic with a 5-year recurrent knee effusion and a history of chronic KGA.Symptoms persisted despite serial aspiration and urate-lowering medication(febuxostat 80 mg once daily)for 2 months.Diagnostic arthroscopy was performed due to the recalcitrant symptoms.Intraoperatively,tophi deposition and excessive thickening of the synovial membrane were observed.Synovial biopsy and partial synovectomy were performed,revealing chronic synovitis with synovial hyperplasia that was consistent with chronic KGA.At follow-up after 6 months,the patient reported no further episode of knee effusion.CONCLUSION Arthroscopic synovectomy for synovial hyperplasia in chronic KGA sufficiently eradicates the symptoms of recurrent knee effusion.

Mechanism of Sanshi decoction inhibits macrophage pyroptosis by inhibiting BRD4/NF-κB/NLRP3 pathway in the treatment of gouty arthritis

Objective:To observe the effect of Sanshi decoction on BRD4/NF-κB/NLRP3 pathwaymediated macrophage pyroptosis,so as to elucidate the molecular mechanism of Sanshi decoction in the treatment of gouty arthritis.Methods:THP-1 was induced into macrophages with foboside and the divided into the control group,model group,low-dose,medium-dose,high-dose group of Sanshi decoction,and BRD4 inhibitor group.Except for the control group,the remaining groups were induced with monosodium urate crystals to construct a gouty arthritis cell model.The activity of macrophages was detected by CCK8,the level of macrophage pyroptosis was detected by flow cytometry,the activity of LDH,the content of IL-1β and IL-18 were detected by enzyme-linked immunosorbent assay,and the expression of related proteins in the BRD4/NF-κB/NLRP3 pathway was detected by Western blot.Results:Compared with the control group,macrophage activity was decreased in the model group,and the level of pyroptosis,LDH activity,contents of IL-1β and IL-18,expression levels of BRD4,p-NF-kB p65,NLRP3,Caspase-1 p20,and IL-1β protein were significantly up-regulated,the differences were statistically significant(P<0.05 and P<0.01).Compared with the model group,macrophage activity was up-regulated in the Sanshi Decoction,and the level of pyroptosis,LDH activity,IL-1β and IL-18 contents,expression levels of BRD4,p-NF-kB p65,NLRP3,Caspase-1 p20,and IL-1β protein were significantly decreased with statistically significant differences(P<0.05 and P<0.01).Conclusion:Sanshi decoction inhibits macrophage pyroptosis by inhibiting BRD4/NF-κB/NLRP3 pathway activation,thus improving the inflammation level of gouty arthritis.

Mechanism of Sanshi decoction in the treatment of gouty arthritis by NLRP3 inflammasome

Objective:To observe the effect of Sanshi decoction on P2X7R/PKR pathway-mediated activation of macrophage NLRP3 inflammasome to elucidate the molecular mechanism of Sanshi decoction in the treatment of gouty arthritis.Methods:THP-1 macrophages were divided into control group,model group,low dose group,medium dose group,high dose group of Sanshi decoction and inhibitor group.The remaining groups were induced with monosodium urate crystals to establish a gouty arthritis cell model except the control group.Flow cytometry was used to detect macrophage ROS levels in each group,ELISA to detect MDA levels and SOD and GSH-PX activities in each group,and Western blot to detect P2X7R/PKR pathway and NLRP3 inflammasome-associated protein expression.We also used CCK-8 and flow cytometry to measure MH7A activity and apoptotic levels.Results:Compared with the control group,the ROS level,the content of MDA,the activities of SOD and GSH-PX were significantly increased,and the expression levels of NLRP3,full-length IL-1β,pro-IL-1β,full-length IL-18,pro-IL-18,full-length caspase-1,GSDMD-NT,P2X7R and p-PKR protein expression levels were significantly upregulated,and GSDMD-FL protein expression was significantly downregulated in the model group,and that the differences between them were statistically significant(P<0.05 and P<0.01).Compared with the model group,Sanshi decoction could reduce macrophage ROS levels,MDA content,SOD and GSHPX activities,and downregulate macrophage NLRP3,mature IL-1β,pro IL-1β,mature IL-18,pro IL-18,mature caspase-1,GSDMD-NT,P2X7R and p-PKR protein expression,and upregulate GSDMD-FL protein expression,with statistically significant differences(P<0.05 and P<0.01).In addition,MH7A activity was downregulated,and apoptosis level was upregulated in the model group in comparison with the control group,and differences were all significantly different(P<0.05).As compared to the model group,Sanshi decoction could significantly increase the activity of MH7A and inhibit the level of apoptosis,and that the differences between them were statistically significant(P<0.05 and P<0.01).Conclusion:Sanshi decoction can achieve the therapeutic effect of gouty arthritis by inhibiting P2X7R/PKR pathway activation,thus reducing the activation level of NLRP3.

FORTY-EIGHT CASES OF ACUTE GOUTY ARTHRITIS TREATED COMPREHENSIVELY WITH ELECTROACUPUNCTURE AND WARMING MOXIBUSTION

Objective To probe into the effects on acute gouty arthritis treated comprehensively with electroacupuncture (EA) and warming moxibustion. Methods 70 cases were randomized into treatment group (48 cases), in which the EA+warming moxibustion was applied; and controlled group (22 cases), in which, colchicine was prescribed for oral administration. Results The statistical outcomes after 1 course treatment in treatment group: 28 cases were cured (58.33%), 18 cases improved (37.50%) and the total effective rate was 95.83%. In controlled group: 12 cases (54.55%) were cured, 8 cases improved (36.36%) and the total effective rate was 90.91%. The therapeutic effects of two groups were basically consistent, without significant different (P>0.05). But, concerning to side effect, there was no any toxic side effects in the group treated with EA+warming moxibustion, and the occurrence rate in the group treated with colchicine was 40.91%. Conclusion Electroacupuncture+warming moxibustion achieves good therapeutic effects without any side effects.

Determination of gouty arthritis' biomarkers in human urine using reversed-phase high-performance liquid chromatography

Creatinine, uric acid, hypoxanthine and xanthine are important diagnostic biomarkers in human urine for gouty arthritis or renal disease diacrisis. A simple method for simultaneous determination of these biomarkers in urine based on reversed-phase high-performance liquid chromatography （RP-HPLC） with ultraviolet （UV） detector was proposed. After pretreatment by dilution, centrifugation and filtration, the biomarkers in urine samples were separated by ODS-BP column by elution with methanol/50 mM NaH2PO4 buffer solution at pH 5.26 （5：95）. Good linearity between peak areas and concentrations of standards was obtained for the biomarkers with correlation coefficients in the range of 0.9957-0.9993. The proposed analytical method has satisfactory repeatability （the recovery of data in a range of creatinine, uric acid, hypoxanthine and xanthine was 93.49-97.90%, 95.38-96.45%, 112.46-115.78%and 90.82-97.13%with standard deviation of o5%, respectively） and the limits of detection （LODs, S/N Z 3） for creatinine, uric acid, hypoxanthine, and xanthine were 0.010, 0.025, 0.050 and 0.025 mg/L, respectively. The established method was proved to be simple, accurate, sensitive and reliable for the quantitation of gouty arthritis＇ biomarkers in human urine samples. The ratio of creatinine to uric acid was found to be a possible factor for assessment of gouty arthritis.

Treatment of 60 Cases of Gouty Arthritis with Modified Simiao Tang

Objective:To observe the clinical effect of a modified Simiao Tang (加味四妙汤 Modified Decoction of Four Wonderful Drugs) for gouty arthritis and its influence on uric acid in blood. Methods: 120 cases of gouty arthritis were randomly divided into the treatment group and control group with 60 cases in each group. Modified Simiao Tang (MST) was orally administered to the patients in the treatment group and allopurinol tablet was orally administered to the patients in the control group. The clinical effects of two groups were evaluated after one-week treatment and uric acid (UA) and C-reactive protein (CRP) levels in blood were determined after 1-month treatment. Results: The total effective rate in the treatment group was significantly higher than in the control group, 86.7% vs. 68.3% (P< 0.01). And the treatment group was also significantly better than the control group in decreasing UA and CRP (P<0.05 or P<0.01). Conclusions: MST can significantly improve the symptoms and signs of gouty arthritis and decrease the levels of UA and CRP. It is good for gouty arthritis.

Effects of Rebixiao Granules (热痹消颗粒剂) on Blood Uric Acid in Patients with Repeatedly Attacking Acute Gouty Arthritis

Objective: To observe the clinical effect of Rebixiao granule (热痹消颗粒剂, RBXG) in treating repeatedly attacking acute gouty arthritis and through experimental study on blood uric acid to explore RBXG's therapeutic mechanism. Methods: Ninety repeatedly attacking acute gouty arthritis patients were divided into the treated group ( n =60) and control group ( n =30). The treated group was treated with RBXG, and the control group was treated with Futalin tablets (diclofenac sodium). The baseline treatment including good rest, low purine diet, sufficient water drinking and urine alkalization, etc. was then given to both groups. Hypoxanthine 600 mg/kg and niacin 100 mg/kg was applied to hyperuricemic mice by gastrogavage to establish the animal models. Results: The clinical effective rate of the treated group was 95.0% and that of the control 90.0%. Good therapeutic effects were won, insignificant difference ( P >0.05)was shown between the two groups. However, the cure rate of the treated group was 26.7% while that of the control group was 10.0%, with significant difference ( P <0.01) shown between them. The treated group had its blood uric acid lowered, which was significantly different ( P <0.05) from that of the control group. The animal experiment indicated that all the three groups treated with different dosages of RBXG, as well as the Ash bark and Smilax glabra rhizome groups had their blood uric acid content reduced in the hyperuricemic mice. Conclusion: RBXG has a quicker initiation and better treatment effects than sole anti-inflammatory and analgesic agents on the treatment of repeatedly attacking acute gouty arthritis, showing no obvious toxic or adverse reactions and therefore good for long-term administration and likely to be a safe TCM preparation to control the symptoms and reduce the onsets of repeatedly attacking of acute gouty arthritis. The animal experiment shows that both the compound preparation and part of the single ingredients in the recipe have the function of reducing blood uric acid. However, the compound recipe has better therapeutic effects, proving to be superior to single drugs.

Meta-analysis of the clinical efficacy of Chinese herbal decoction combined with arthroscopy in the treatment of gouty arthritis

Objective:To systematically evaluate the efficacy of traditional Chinese medicine decoction combined with arthroscopy in the treatment of gouty arthritis.Methods:A systematic search of CNKI,CBM,WanFang,VIP,PubMed,Cochrane Library,and EMBASE databases,and the receipt of the database until February 2021.Randomized controlled trials(RCTs)of traditional Chinese medicine(TCM)decoction combined with arthroscopy in the treatment of gouty arthritis.Two researchers independently read the title and abstract to screen and them read the full text to clarify whether it should be included.The method of Cochrane systematic review was used to evaluate the quality of the literature,and the RevMan 5.3 software was used to conduct meta-analysis of the data.Results:Nineteen RCTs were finally included.A total of 1383 patients,697 cases in the treatment group were treated with traditional Chinese medicine decoction combined with arthroscopy,and 686 cases in the control group were treated with arthroscopy alone or combined with western medicine.Meta-analysis results showed that the total clinical effective rate(P<0.00001)of the treatment group was better than that of the control group.Visual analogue scoring(VAS)score(P=0.0005,P<0.00001,P=0.03)and erythrocyte sedimentation rate(ESR)level(P<0.00001,P<0.00001,P<0.00001)reduction in each subgroup was better than that of the control group.The Lysholm score of the treatment group increased(P<0.00001,P<0.00001,P=0.19),while for blood uric acid(UA)level(P<0.00001,P=0.18,P<0.0001)and C-reactive protein(CRP)levels(P<0.0001,P<0.00001,P=0.23)two subgroups were better than the control group,but there was no significant difference in one subgroup.Conclusion:Traditional Chinese medicine decoction combined with arthroscopy is effective in treating gouty arthritis,which can relieve pain,improve joint function,and reduce body inflammation and uric acid levels.However,in the future,clinical studies with larger sample sizes,more reasonable designs,and higher quality are still needed to demonstrate this conclusion.

Study on effect of imbalance of TRAF-6, IRAK-1 and NALP3 inflammatory factors in patients with gouty arthritis

Objective:To explore the effect of imbalance of tumor necrosis factor receptor related factor-6(TRAF-6),interleukin 1 receptor associated kinase-1(IRAK-1)and neutrophil alkaline phosphatase-3(NALP3)in patients with gouty arthritis.Methods:The retrospective experiment was conducted on 105 patients with gouty arthritis admitted to our hospital(47 patients with acute onset and 58 patients with remission,namely group A and group B);meanwhile,another 61 healthy volunteers were selected for control,namely group C.The enrolling of the three groups was dated from May 2017 to May 2018,and TRAF-6,IRAK-1 and NALP3 of all subjects were tested through real-time fluorescence quantification(RT-PCR),and the correlation between the three inflammatory factors and gouty arthritis was compared.Results:1)Through treatment,ESR,BUA and total addiment in group A and B were higher than those in group C,among which the three indicators in group A were higher than those in group B(P<0.05),while CRP was lower than that of group C,and the two indicators in group A were lower than those in group B(P<0.05).2)There was no significant difference in the relative expression of TRAF-6 mRNA between group A and group B before treatment(P>0.05),significantly lower than group C(P<0.05);the above indicators of group A and group B were improved to some extent after treatment,but group A was still lower than group B(P<0.05),and the degree of improvement of group A was also lower than that of group C(P<0.05),while the degree of improvement of group B was not significantly different from that of group C(P>0.05).3)The relative expression level of IRAK-1mRNA in group A and group B before treatment showed no significant difference(P>0.05),but was also lower than that in group C(P<0.05).The relative expression level of IRAK-1mRNA in group A and group B increased to some extent after treatment,with group A significantly lower than group C(P<0.05),and group B showed no significant difference compared with group C(P>0.05).4)The relative expression level of NALP-3 mRNA in group A and group B showed no significant difference(P>0.05)before treatment,significantly higher than that in group C(P<0.05);the relative expression of NALP-3 mRNA in group A was not significantly decreased(P>0.05)after treatment,while that in group B was significantly decreased after treatment(P<0.05),indicating significant different compared with group A and group C.5)There was no correlation between)TRAF-6,ESR,CRP and total addiment(P>0.05);IRAK-1 was negatively correlated with CRP,BUA and total addiment(P<0.05);NALP-3 was negatively correlated with ESR and CRP(P<0.05).Conclusion:TRAF-6,IRAK-1 and NALP-3 are all under abnormal expression in the developing of new gouty arthritis,acting as important participants in promoting the occurrence,development and outcome of illness states,so the intervening measures should be taken.

A network pharmacology approach to explore action mechanisms of Bi xie and Tu fuling for treating gouty arthritis

Objective:The mechanism of Chinese herbal medicine"Bi xie and Tu fuling"on the treatment of gouty arthritis was explored through network pharmacological methods.Methods:First,the TCMSP Chinese medicine system pharmacology database and analysis platform were used to define the bioavailability(OB)30%and drug-likeness(DL)0.18.Database to mine genetic targets related to gouty arthritis disease.Finally,the two genes are intersected to construct a Chinese medicine regulatory network of Chinese medicine-components-target genes-disease.The genes in the network are used to construct a protein interaction network to find core genes for analysis of GO and KEGG.Results:There were a total of 84 active ingredients in Chinese medicine Poria and Poria cocos,and 17 effective ingredients and 180 genetic targets were obtained after screening.600 disease targets for gouty arthritis were identified,and 58 were common target genes for both.PPI network analysis revealed that IL1β,VEGFA,MAPK1,IL10,and PTGS2 may be drugs for treating gouty arthritis.Key targets.GO enrichment analysis identified 1,399 entries(P<0.05),of which biological processes mainly include biological stimulation,biological regulation,cell metabolism,etc;KEGG pathway enrichment analysis identified 152 signal pathways,of which signal pathways involved inflammation,metabolism,In terms of aging,mainly including the IL-4,IL-10,IL-13,IL-17signal pathway,etc.Conclusion:"Bi xie and Tu fuling"drugs have anti-inflammatory and immunological effects on gouty arthritis through multiple targets and multiple pathways.The mechanism of lowering uric acid and protecting liver and kidney is not clear.It needs molecular biology research to improve it.The mechanism of the action of the"Bi xie and Tu fuling"medicine pair provides new ideas for the clinical prescriptions.

Effect of Simiao Liangxue Granule on Acute Gouty Arthritis in Rats

[Objectives]To study the anti-inflammatory effect of Simiao Liangxue granule on the rats with acute gouty arthritis(AGA).[Methods]A total of 60 male SD rats were randomly divided into 6 groups with 10 rats in each group.The rats in the colchicine group were intragastrically administered with 0.65 mg/kg colchicine,and the rats in low,medium and high dose groups of Simiao Liangxue granule were intragastrically administered with Simiao Liangxue granule with mass concentration of 0.4,0.8 and 1.6 g/kg,respectively.The rats in the normal control group and the model group were given the same amount of normal saline for 7 d,and the acute gouty arthritis model was prepared 1 h after administration on the 5th d.At the end of the experiment,the degree of joint swelling and joint inflammation index,the content of interleukin-1β,tumor necrosis factor-a and cyclooxygenase-2 in articular cartilage,and the content of interleukin-8,NO and UA in serum of rats were measured,and the histomorphological observation was performed.[Results]Compared with the normal control group,the joints of rats were swollen to different degrees,the inflammation score was significantly increased,and the content of IL-1β,TNF-αand COX-2 in the soft tissue of the joints was significantly increased in each group(P<0.05);compared with the model group,the joint swelling degree and inflammation score of rats in the colchicine group and Simiao Liangxue granule group were significantly decreased,the content of IL-1β,TNF-αand COX-2 in the joint soft tissue was also significantly decreased(P<0.05),and the indexes of each dose group of Simiao Liangxue granule were similar to those of the colchicine group;compared with the normal control group,the content of IL-8,NO and UA in the joint soft tissue of rats was significantly increased in each group(P<0.05);compared with the model group,the content of all indexes in joint soft tissue of rats in normal control group,colchicine group and Simiao Liangxue granule group were significantly decreased(P<0.05);the content of various indexes in the joint soft tissue of rats in the low and medium dose groups of Simiao Liangxue granule was higher than that in the colchicine group,and decreased significantly with the increase of the dose of Simiao Liangxue granule(P<0.05);the inflammatory index decreased significantly with the increase of the dose of Simiao Liangxue granule(P<0.05);the inflammation and degeneration in each dose group of Simiao Liangxue granule were milder than those in the model group,and the symptoms were relieved to some extent with the increase of dose(P<0.05).[Conclusions]Simiao Liangxue granule has the effect of anti-inflammation and detumescence,and its mechanism may be related to the content of factors that reduce inflammation including IL-1β,TNF-α,C0X-2,IL-8,NO and UA.

A network pharmacology approach to explore action mechanisms of Si Miao decoction for treating acute gouty arthritis

Objective:To Find the core targets and drug action mechanism of Si Miao decoction for the treatment of acute gouty arthritis.Methods:Through the TCMSP database,the chemical composition of all the drugs in Si Miao decoction was obtained.The Perl script was compiled and the UniProt database was searched to determine the corresponding target of the chemical composition.Then,the disease databases such as OMIM,DisGeNET,and GeneCards were searched in order to determine acute gouty arthritis Related targets.Finally,screen common targets for drugs and diseases,use the STRING database and Cytoscape software to build a network control map of drugs-chemical components-targets-disease.Use R language software to screen common targets and find the four best The core targets of San for the treatment of acute gouty arthritis.The GO and KEGG analysis of the core targets were performed to clarify the core targets and mechanism of Si Miao decoction for the treatment of gout.Results:There are 64 effective chemical components in Si Miao decoction,197 genetic targets,600 disease targets,and 58 common targets.It is predicted that IL6,VEGFA,IL1B,JUN,PTGS2,and CCL2 may be treated by Si Miao decoction for gout The core target of arthritis.GO enrichment analysis identified 85 entries,of which biological processes mainly included the regulation of cytokine activity,protease activation,nucleic acid expression,etc.;KEGG pathway enrichment analysis identified 135 signaling pathways,of which signaling pathways involved the IL-17 signaling pathway,TNF signaling pathway,Th17 cell differentiation and other pathways.Conclusion:Si Miao decoction acts on acute gouty arthritis by regulating the occurrence of inflammation,and has significant anti-inflammatory and immune effects.The formula is rigorous and scientific,and it is worthy of clinical application.

Study on anti-inflammatory mechanism and effects of Flemingia Roxb.exAit extract intervene acute gouty arthritis in rats

Objective:To investigate the effect and anti-inflammatory mechanism the effect of Flemingia Roxb.exAit extract on acute gouty arthritis.Methods:Sixty SD rats were randomly divided into 6 groups by weight,control and model group,(100、150、200 mg/kg)of Flemingia Roxb.exAit extract group and colchicine group.The rats of each group were given by intragastric for 7 days of continuous administration,meanwhile,there were given 0.9%NaCl solution instead as control and model group.The acute gouty arthritis model was constructed through right ankle joint cavity injection of sodium urate crystal solutionon day 5 after 1 h,but rats in the negative control group were injected with 0.9%NaCl solution into the articular cavity of the right foot.The general condition of rats and the degree of joint swelling,and the gait was observed after constructed model.To detected the joint fluid IL-1β、TNF-α、IL-6 indicators,and the expression of NLRP3,Caspase-1 protein in ankle joint tissue for 2 hours after the last administration.Results:Groups of Flemingia Roxb.exAit extract could markedly reduce the joint swelling on acute gouty arthritis rat model,improve gait in a dose-dependent manner,high dose group of Flemingia Roxb.exAit extract did particularly well(Pjoint swelling<0.01;Pgait<0.05),close to the therapeutic effect colchicine group.Further mechanism studies show that the joint fluid IL-1β、TNF-α、IL-6 level was reduced by Flemingia Roxb.exAit extract group,the expressions of NLRP3、Caspase-1 protein of Flemingia Roxb.exAit extract group was decreased observbly than model group,but the most obvious is that high dose group as well as colchicine group(PNALP3<0.01;PCaspase-1<0.01).Conclusion:Flemingia Roxb.exAit extract has the effect of treating acute gouty arthritis and its mechanism may be related toinhibiting NLRP3 inflammasome activation and inhibiting inflammatory response.

OBSERVATION ON THE THERAPEUTIC EFFECT OF ACUPOINT INJECTION FOR TREATMENT OF GOUTY ARTHRITIS

In the present paper, 60 cases of gouty arthritis patients were randomly divided into acupuncture group (n=30) and acupoint injection group (n=30). In these two groups, the tender point was used as the main acupoint, combined with Taichong (LR 3), Yinbai (SP 1), Sanyinjiao (SP 6), Juegu (GB 39), Xuehai (SP 10), etc. 10% Chishao (Radix Paeoniae Rubra) Injection and dexamethasone were used for acupoint injection. Results indicated that in acupoint injection and acupuncture groups, 15 (50.0%) and 9 (30.0%) cases had marked improvement, 12 (40.0%) and 10 (33.3%) were effective, and 3 (10.0%) and 11(36.7%) failed in treatment, with the total effective rats being 90.0% and 63.3% respectively. Statistical analysis shows that acupoint injection is significantly superior to simple acupuncture in the therapeutic effect (P<0.05).

Nuclear receptor coactivator 6 is a critical regulator of NLRP3 inflammasome activation and gouty arthritis

Transcriptional coactivators regulate the rate of gene expression in the nucleus.Nuclear receptor coactivator 6(NCOA6),a coactivator,has been implicated in embryonic development,metabolism,and cancer pathogenesis,but its role in innate immunity and inflammatory diseases remains unclear.Here,we demonstrated that NCOA6 was expressed in monocytes and macrophages and that its level was increased under proinflammatory conditions.Unexpectedly,nuclear NCOA6 was found to translocate to the cytoplasm in activated monocytes and then become incorporated into the inflammasome with NLRP3 and ASC,forming cytoplasmic specks.Mechanistically,NCOA6 associated with the ATP hydrolysis motifs in the NACHT domain of NLRP3,promoting the oligomerization of NLRP3 and ASC and thereby instigating the production of IL-1βand active caspase-1.Of note,Ncoa6 deficiency markedly inhibited NLRP3 hyperactivation caused by the Nlrp3^(R258W) gain-of-function mutation in macrophages.Genetic ablation of Ncoa6 substantially attenuated the severity of two NLRP3-dependent diseases,folic-induced acute tubular necrosis and crystal-induced arthritis,in mice.Consistent with these findings,NCOA6 was highly expressed in macrophages derived from gout patients,and NCOA6-positive macrophages were significantly enriched in gout macrophages according to the transcriptome profiling results.Conclusively,NCOA6 is a critical regulator of NLRP3 inflammasome activation and is therefore a promising target for NLRP3-dependent diseases,including gout.

Efficacy and safety of Huzhang Granule,a compound Chinese herbal medicine,for acute gouty arthritis:A double-blind,randomized controlled trial

Background:Acute gouty arthritis(AGA)is an inflammatory joint disease with a high prevalence.Typical medical interventions,including nonsteroidal anti-inflammatory drugs,colchicine and glucocorticoids,can have serious adverse reactions.Huzhang Granule(HZG),a compound Chinese herbal medicine,has been used to treat AGA for more than 30 years with satisfactory effects and no significant adverse reactions.However,the efficacy and safety of HZG in AGA patients remains unknown.Objective:The present investigation was designed to examine the efficacy and safety profile of HZG in managing AGA patients.Design,setting,participants and interventions:The current study was conducted as a noninferiority,randomized controlled clinical trial on 180 eligible enrolled participants.Participants were randomly assigned into the HZG and etoricoxib groups.Treatments were administered for 5 d,during which the HZG group received HZG and placebo etoricoxib,while the etoricoxib group received etoricoxib and placebo HZG in the same ratio(1:1).Main outcome measures:The primary outcome was pain experienced by the patient in the gout-afflicted joint from days 2 to 5 of the treatment window.The pain level was measured via a visual analogue scale,ranging from 0 mm to 100 mm.The secondary outcomes comprised joint tenderness and swelling,reduction of inflammatory biomarkers,and the patient’s and investigator’s global evaluations of therapeutic response.Results:The mean reduction in pain was-51.22 mm(95%confidence interval[CI],[-53.42,-49.03]mm)for the HZG and-52.00 mm(95%CI,[-54.06,-49.94]mm)for the etoricoxib groups.The mean difference between the two groups was 0.78 mm(95%CI,[-2.25,3.81]mm).All additional efficacy endpoints,covering decreased inflammation and pain relief,yielded compelling proof of noninferiority.Patients in the HZG group exhibited a comparatively lower rate of adverse events compared to those in the etoricoxib group(4.44%vs 13.33%;P≤0.05).Conclusion:HZG and etoricoxib groups demonstrated similar levels of analgesic effectiveness.The safety and efficacy of HZG indicates that it can be used as a potential therapeutic option for treating AGA.

Fire needling and bloodletting at cleft points in treatment of 35 patients with acute gouty arthritis

Objective To observe the clinical efficacy of fire needling and bloodletting at cleft points for acute gouty arthritis, and to explore its functional mechanism. Methods Thirty-five patients with acute gouty arthritis were enrolled into this study, and fire needling and bloodletting with 10 mL/ time were applied at cleft points of corresponding meridians and collaterals at the affected side. The treatment was conducted for once every other day, and treatment for three consecutive times was needed. Serum uric acid （UA） and pain score were tested in patients before treatment and on the 6th day after treatment, follow-up visit for 3 months was performed in patients who stopped treatment, and recurrence rate was calculated. Results Budzyuski 6-point behavioral rating scale was applied to score pain. T-test was conducted on mean and standard deviation of pain score before treatment （4.09 ＋ 0.82） and after treatment （1.14 ＋ 1.33）, showing that the difference was significant （P〈0.05）; t-test was also conducted on mean and standard deviation of serum UA before treatment [（555.34 ＋ 53.09） pmol/L] and after treatment [（414.23 ＋ 67.04） pmol/L], showing that the difference was significant （P〈0.05）; among the 35 patients with acute gouty arthritis, 14 patients were cured （40.0%）, improvement was found in 19 patients （54.3%）, and effectiveness was found in 33 patients （94.3%）. Based on follow-up visit for 3 months in 33 patients with efficacy, recurrence was found in 3 patients （9.1%）. Conclusion Fire needling and bloodletting at cleft points is an effective method in treatment of acute gouty arthritis with significant analgesic effect, efficacy of reducing serum UA, high cure rate and low recurrence rate, which is worth of being generalized clinically.

Anti-inflammatory activity of curcumin-loaded tetrahedral framework nucleic acids on acute gouty arthritis

Gouty arthritis is a very familiar inflammatory arthritis.Controlling inflammation is the key to preventing gouty arthritis.However,colchicine,the most highly represented drug used in clinical practice,has strict contraindications owing to some severe side effects.Curcumin(Cur),a natural anti-inflammatory drug,has demonstrated good safety and efficacy.However,the rapid degradation,poor aqueous solubility,and low bioavailability of Cur limit its therapeutic effect.To strengthen the effectiveness and bioavailability of Cur.Cur loaded tetrahedral framework nucleic acids(Cur-TFNAs)were synthesized to deliver Cur.Compared with free Cur,Cur-TFNAs exhibit a preferable drug stability,good biocompatibility(CCK-8 assay),ease of uptake(immunofluorescence),and higher tissue utilization(in vivo biodistribution).Most importantly,Cur-TFNAs present better anti-inflammatory effect than free Cur both in vivo and in vitro experiments through the determination of inflammation-related cytokines expression.Therefore,we believe that Cur-TFNAs have great prospects for the prevention of gout and similar inflammatory diseases.