[Objectives]To investigate the anti-inflammatory effect of Embelia parviflora Wall.polysaccharide on rheumatoid arthritis(RA)in rats.[Methods]RA rat model was induced by type II collagen.After successful modeling,the ...[Objectives]To investigate the anti-inflammatory effect of Embelia parviflora Wall.polysaccharide on rheumatoid arthritis(RA)in rats.[Methods]RA rat model was induced by type II collagen.After successful modeling,the rats were divided into model group,positive group,low,medium and high dose of E.parviflora Wall.polysaccharide groups,and normal control group.Body mass,toe volume and arthritis index were measured,and thymus index and spleen index were calculated.The levels of interleukin-1β,interleukin-6 and tumor necrosis factor-αin serum and synovial tissue of ankle joint were detected by ELISA.[Results]Compared with the normal control group,the pathological changes such as synovial hyperplasia and unclear layer were observed in the model group,the body mass was decreased(P<0.05),the toe volume,arthritis index,thymus and spleen index were increased(P<0.05),and the levels of IL-1β,IL-6 and TNF-αin serum and ankle synovial tissue were increased(P<0.05).Compared with the model group,the histopathological changes in synovium of ankle joint in the positive group and the medium and high dose groups of E.parviflora Wall.polysaccharide were significantly improved,and the body mass was increased(P<0.05).The toe volume,arthritis index,thymus index and spleen index were decreased(P<0.05).The levels of IL-Iβ,IL-6 and TNF-αin serum and synovial tissue of ankle joint were increased(P<0.05),while there was no significant difference between the low dose group of E.parviflora Wall.polysaccharide and the model group(P>0.05).[Conclusions]E.parviflora Wall.polysaccharide can reduce the body's inflammatory response and improve RA,which may be related to the inhibition of the activation of inflammatory cytokines IL-1β,IL-6 and TNF-α.展开更多
The aim of this study was to design a compound transdermal patch containing diclofenac(DA)and teriflunomide(TEF)for the treatment of rheumatoid arthritis(RA).The various organic amines salts of DA were prepared and th...The aim of this study was to design a compound transdermal patch containing diclofenac(DA)and teriflunomide(TEF)for the treatment of rheumatoid arthritis(RA).The various organic amines salts of DA were prepared and their forming was confirmed using DSC and FTIR.The percutaneous permeation of organic amines salt of DA was investigated in vitro using a two-chamber diffusion cell with excised rabbit skin as transdermal barrier.The formulation of the patch was optimized in terms of the concentration of percutaneous permeation enhancer and the loading dose of drugs.The pharmacokinetic behavior of the optimal formulation was studies in rabbits and the anti-inflammatory and analgesic effects of the optimal patch were evaluated with the adjuvant arthritis model in rats and the pain model in mice,respectively.The result showed that skin penetration of diclofenactriethylamine(DA-TEtA)salt was better than other organic amine salts.Based on previous study of our laboratory,teriflunomide-triethylamine(TEF-TEtA)significantly enhanced the skin permeation of TEF.10%of azone(AZ)was the best enhancer for the two drugs.The optimal patch formulation was composed of 2%of TEF-TEtA,6%of DA-TEtA and 10%of AZ.The cumulative permeated amount of DA-TEtA in vitro was comparable with that of the commercial diclofenac-diethylamine(DA-DEtA)patch.The absolute bioavailability of TEFTEtA was 42%,which could achieve the therapeutic drug levels.In animal study,the optimized compound patch containing DA-TEtA and TEF-TEtA displayed significant antiinflammatory and analgesic effect,which indicated the potential of the compound patch.展开更多
Objective: To investigate whether glucose-6-phosphate isomerase (G6PI) antigen and anti-G6PI antibodies could be applied for the clinical diagnostic markers of rheumatoid arthritis (RA) and its associations with RA ac...Objective: To investigate whether glucose-6-phosphate isomerase (G6PI) antigen and anti-G6PI antibodies could be applied for the clinical diagnostic markers of rheumatoid arthritis (RA) and its associations with RA activity states. Methods: The levels of G6PI antigens and anti-G6PI Abs in sera from 176 RA patients in different states, 35 non-RA patients and 100 healthy donors and in synovia fluids from 33 patients and 11 non-RA patients were measured by ELISA. Results: The sensitivity and specificity of G6PI antigens in the RA patients were 75.0% and 93.3%, respectively. The levels of serum G6PI antigens in 176 RA patients were significantly higher than non-RA patients and the health controls. Especially, there was a significant difference between the active phase and the inactive phase in G6PI antigens levels. The levels of G6PI antigens in synovia fluid were also significantly higher in RA groups than in non-RA patients. With the values of the anti-G6PI Abs in sera, there were no marked differences among RA, non-RA patients and health controls. Also, there was no significant difference between the active phase and the inactive phase in RA patients. However, there were no significant differences of G6PI and anti-G6PI between RA patients and health controls in synovial fluid. Conclusions: G6PI is highly correlated with the activity states of RA, and could be applied for a clinical biomarker with high sensitivity and specificity for the diagnosis of RA.展开更多
[Objectives]To explore the anti-rheumatoid arthritis effect of Lignum Xanthocerais Sorbifoliae by network pharmacology method.[Methods]The chemical constituents and action targets of Lignum Xanthocerais Sorbifoliae we...[Objectives]To explore the anti-rheumatoid arthritis effect of Lignum Xanthocerais Sorbifoliae by network pharmacology method.[Methods]The chemical constituents and action targets of Lignum Xanthocerais Sorbifoliae were collected by Traditional Chinese Medicine Systems Pharmacology(TCMSP).Target genes of rheumatoid arthritis(RA)were obtained from TTD database.ClusterProfiler was used for gene ontology(GO)enrichment,and Cytoscape 3.7.2 software was used for Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment and screening of active component-target core network.[Results]There were 24 intersecting targets between active components and diseases.The analysis of GO enrichment and KEGG pathway enrichment indicated that the therapeutic effect of Lignum Xanthocerais Sorbifoliae on rheumatoid arthritis might be related to AGE-RAGE signaling pathway,IL-17 signaling pathway,rheumatoid arthritis pathway,C-type signaling pathway and Toll-like receptor signaling pathway.13 drug active components[flavanes,dihydroflavonoids,stigmasterol,oleanolic acid,kaempferol,ellagic acid,Terchebulin B,Copaene,(Z)-β-Caryophyllene,Aromadendrene,β-Elemene,emodin]and 12 core targets(TNF,IL6,ALOX5,MAPK14,PPARA,AKR1B1,CCR5,PLA2G1B,ADAM17,MMP1,PTGS1,SYK)constituted a core network.[Conclusions]This study could provide a theoretical basis for the treatment of RA with Lignum Xanthocerais Sorbifoliae preparation.展开更多
Background:Rheumatoid arthritis(RA)is a worldwide public health problem.Intervention and prevention before the onset of rheumatic diseases is a new direction in current research.Objective:The aim of this study was to ...Background:Rheumatoid arthritis(RA)is a worldwide public health problem.Intervention and prevention before the onset of rheumatic diseases is a new direction in current research.Objective:The aim of this study was to evaluate the potential and feasibility of traditional Chinese medicine(TCM)in the prevention of RA.Methods:This was a single-armed prospective clinical trial.All participants were recruited from a single center in Guangdong,China.Adults who were tested positive for anti-cyclic citrullinated peptide antibody(anti-CCP)and/or rheumatoid factor(RF),had no synovitis and never been treated with disease-modifying anti-rheumatic drugs(DMARDs),were enrolled to take the Huayu-Qiangshen-Tongbi(HQT)decoction orally twice daily,200 mL each time for 24 weeks.Primary outcome was the proportion of patients who met 2010 ACR(American College of Rheumatology)/EULAR(European League Against Rheumatism)classification criteria of RA during observation.Secondary outcomes included levels of anti-CCP,RF,erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),assessment of signs and symptoms,and radiographic progression by magnetic resonance imaging(MRI).Results:19 individuals were enrolled in the study,4 of which withdrew because of the epidemic of COVID-19.During the observation period,3 individuals(20%)developed RA and they had longer morning stiffness(P=0.009)and more obvious synovial enhancement in MRI(P=0.041)at baseline when compared with those who did not develop RA.After 24 weeks of intervention,there were improvements in 28-swollen joint count(SJC28)(P=0.046),Visual Analog Scale(VAS)(P=0.019),Patient’s Global Assessment(PtGA)(P=0.019)and Physician’s Global Assessment(PGA)(P=0.031),but no statistical significance was observed in the levels of anti-CCP,RF,ESR,CRP,morning stiffness,28-tender joint count(TJC28),Health Assessment Questionnaire(HAQ)and magnetic resonance imaging(MRI)analysis(P>0.05).Conclusion:The HQT formula is safe and could improve joint symptoms and signs in these at-risk individuals,but it remains to be investigated in futher study to see if it might potentially reduce the risk of developing RA.Besides,for individuals at high risk to develop RA,morning stiffness and synovial enhancement in MRI might be predictive factors and warning signs.展开更多
Aim of Work: Initial observations implied IgG rheumatoid factor (RF) to be common among Malaysian rheumatoid arthritis (RA) patients. We tested this hypothesis and used a multiethnic RA cohort (Malays, Chinese and Ind...Aim of Work: Initial observations implied IgG rheumatoid factor (RF) to be common among Malaysian rheumatoid arthritis (RA) patients. We tested this hypothesis and used a multiethnic RA cohort (Malays, Chinese and Indians) to investigate whether the IgG RF predominance might be genetically or environmentally determined. Patients and Methods: 556 serum samples comprising 171 patients classified as RA according to the 1987 ACR criteria, 60 patients with other rheumatic diseases and 325 non-rheumatic controls were tested for IgG RF, IgM RF and anti-CCP by ELISA. The findings were then tested in a larger RA case-control cohort (n = 1844). Results: IgG RF predominated over IgM RF in all the investigated ethnic groups. The sensitivity, specificity, and diagnostic accuracy of IgG RF (55.6%, 91.2% and 80.2%, respectively) were superior compared to IgM RF, but comparable to anti-CCP. IgG RF was however, also increased in the Malaysian controls, but the IgG RF superiority over IgM RF was still apparent after cutoff adjustment according to the 1987 ACR criteria. Autoantibody levels did not differ between the three ethnic groups. The Receiver Operating Characteristics (ROC) curves showed larger areas under the curves for IgG RF (0.826) and for anti-CCP (0.867) than for IgM RF (0.737). Review of the literature showed consistently higher sensitivity for IgG RF in studies of Asian RA patients as compared to Caucasian and African-American studies. Conclusion: Increased frequency of IgG RF-positive in RA populations with different genetic background living in Malaysia argues for an environmental factor selectively amplifying the IgG RF response.展开更多
Aim of Work: To investigate the value of the detection of antibodies against modified citrullinated vimentin antibodies (anti-MCV) in comparison with anti-CCP2-for the diagnosis of rheumatoid arthritis (RA). Patients ...Aim of Work: To investigate the value of the detection of antibodies against modified citrullinated vimentin antibodies (anti-MCV) in comparison with anti-CCP2-for the diagnosis of rheumatoid arthritis (RA). Patients and Methods: The study Included Forty patients with Rheumatoid arthritis (RA). They under went assessment by the disease activity score (DAS-28), visual analogue scale (VAS) and health assessment questionnaire (HAQ). Thirty healthy subjects matched for age and sex served as a control group. Blood samples were obtained from patients and controls for erythrocyte sedimentation rate (ESR), C reactive protein (CRP), rheumatoid factor (RF). Anti-CCP2 and anti-MCV were determined using ELISA technique. Results: Estimated serum levels of anti-CCP2 and anti-MCV were significantly higher in patients compared to controls (p 0.001). There were no significant correlations between anti-MCV levels and age, dis- ease duration, duration of morning stiffness, number of swollen and tender joints, HAQ or ESR in patients with RA, while serum levels correlates significantly with DAS28, VAS and CRP (p 0.05). Anti-CCP2 correlates significantly with DAS28, VAS and CRP and ANA (p 0.05). Serum anti-MCV and anti-CCP2 were significantly correlated with each other (r = 0.483;p The receiver operating characteristic (ROC) curve was drawn and it showed that anti-MCV had diagnostic specificity, sensitivity of 93.3%, 75.5%, respectively, while anti-CCP2 specificity, sensitivity of 98.1%, 85%, respectively. Conclusion: Serum anti-MCV as well as the anti-CCP-2 assay perform comparably well in the diagnosis of RA. In the high-specificity range, however, the anti-CCP2 assay appears to be superior to the anti-MCV test.展开更多
Objective: To assess the efficacy and safety of modified Guizhi Shaoyao Zhimu Tang (GSZT) with the Western medicines in treating rheumatoid arthritis. Methods: All the relevant studies were collected by searching the ...Objective: To assess the efficacy and safety of modified Guizhi Shaoyao Zhimu Tang (GSZT) with the Western medicines in treating rheumatoid arthritis. Methods: All the relevant studies were collected by searching the Pubmed, Web of science, Embase, Cochrane Library, SpringerLink, China National Knowledge Infrastructure (CNKI), VIP Journals database, and Wanfang database from their inception to October 2017. After the assessment, the eligible ones were subject to Jadad score. The meta-analysis was conducted by RevMan 5.3 software. Results: Totally 10 randomized controlled trials (RCTs) involving 962 patients were enrolled. The clinical efficacy of analysis showed that modified GSZT with the Western medicines can significantly improve the clinical total effective rate [OR = 4.64, 95%CI (3.03, 7.12), P −14.58, 95%CI (−16.49, −12.68), P −12.62 95%CI (−18.69, −6.54), P −49.88, 95%CI (−77.6, −22.09), P −5.34, 95%CI (−5.86, −4.82), P < 0.001]. The adverse events had been seen in both of the two groups, however, the clinical symptoms of the group on modified GSZT with the Western medicines were obviously reduced than the other one [OR = 0.25, 95%CI (0.10, 0.61), Z = 3.06, P < 0.01]. This system review shows that the modified GSZT with the Western medicines improved the clinical efficacy, symptoms and the blood biochemical indicators were improved significantly than that of Western medicines alone on rheumatoid arthritis. At the same time, it can reduce adverse effects and enhance safety.展开更多
Objective: To observe the effect and adverse reaction of tripterygium polyglycosides (TP) combined with small dose of methotrexate (MTX) in treating senile rheumatoid arthritis (RA). Methods: Sixty old patients with R...Objective: To observe the effect and adverse reaction of tripterygium polyglycosides (TP) combined with small dose of methotrexate (MTX) in treating senile rheumatoid arthritis (RA). Methods: Sixty old patients with RA were equally divided into two groups, the treated group was treated with oral intake of TP (10 mg three times per day) plus MTX (7.5 mg, once per week), and the control group was treated with MTX (15 mg per week) respectively for 3 months. The changes from before to after treatment in resting pain, morning rigidity, bilateral grip strength, local tenderness index, arthroncus index, patient's evaluation, doctor's evaluation, erythrocyte sedimentation rate (ESR), C-reaction protein (CRP) and rheumatoid factor(RF) titre were observed and the clinical therapeutic effect assessed. Results: The total effective rate in the treated group was 86.67% and that in the control group 83.33% , showing insignificant difference between them (P>0.05). But the improvement in local tenderness index, arthroncus index, morning rigidity and ESR in the treated group was significantly better than those in the control group (P<0.01 or P<0.05). The occurrence rate of adverse reaction in the treated group was 26. 67% , which was lower than that in the control group (43.33%), showing significant difference (P<0.01). Conclusion: TP combined with small dose of MTX is a favorable therapeutic method for treating senile RA.展开更多
The disruption and reconstruction of the TREM2^(+) tissue resident macrophage(TRM)barrier on the surface of synovial lining play a key role in the activation and"remission"of rheumatoid arthritis(RA),which e...The disruption and reconstruction of the TREM2^(+) tissue resident macrophage(TRM)barrier on the surface of synovial lining play a key role in the activation and"remission"of rheumatoid arthritis(RA),which engender the prediction of this immunologic barrier as a potential driver for the achievement of"cure"in RA.However,strategies to promote the reconstruction of this barrier have not been reported,and the effect of patching this barrier remains unidentified.On the other hand,appropriate piezoelectric stimulation can reprogram macrophages,which has never been exerted on this barrier TRM yet.Herein,we design piezoelectric tetragonal BaTiO_(3)(BTO)ultrasound-driven nanorobots(USNRs)by the solvothermal synthesis method,which demonstrates satisfactory electro-mechanical conversion effects,paving the way to generate controllable electrical stimulation under ultrasound to reprogram the barrier TRM by minimally invasive injection into joint cavity.It is demonstrated that the immunologic barrier could be patched by this USNR effectively,thereby eliminating the hyperplasia of vessels and nerves(HVN)and synovitis.Additionally,TREM2 deficiency serum-transfected arthritis(STA)mice models are applied and proved the indispensable role of TREM2 in RA curing mediated by USNR.In all,our work is an interesting and important exploration to expand the classical tetragonal BTO nanoparticles in the treatment of autoimmune diseases,providing a new idea and direction for the biomedical application of piezoelectric ceramics.展开更多
Objective:To elucidate the effects of Huangqin Qingre Chubi capsule(HQC)on bone metabolism and serum TLR4 and NF-kB in rats with rheumatoid arthritis(RA),and to provide experimental bases for the treatment of RA with ...Objective:To elucidate the effects of Huangqin Qingre Chubi capsule(HQC)on bone metabolism and serum TLR4 and NF-kB in rats with rheumatoid arthritis(RA),and to provide experimental bases for the treatment of RA with HQC.Methods:A total of 40 SD rats were randomly divided into the normal group,model group,western medicine treatment group,and HQC group,with 10 rats in each group,and the RA model was induced by complete adjuvant in all groups except the normal group.After successful modeling,they were treated for 4 weeks to compare the degree of joint swelling;meanwhile,micro-CT was used to evaluate bone microstructural parameters,and changes in serum TLR4 and NF-kB expression levels were detected by ELISA.Results:There was no statistical significance in comparing the degree of joint swelling among the model group,western medicine treatment group and HQC group(P>0.05);Micro-CT results showed that bone microstructural parameters deteriorated in the osteoporosis model group compared with the normal group.Both western medicine and traditional Chinese medicine HQC could improve the bone microjunction of RA rats,and the HQC group was better than the western medicine treatment in improving the number of bone trabeculae(2.58±0.19)·mm^(-1);the serum results showed that RA was accompanied by the up-regulation of the expression of TLR4 and NF-kB.Both western drugs and HQC down-regulated the high expression of serum TLR4 and NF-kB in osteoporotic rats,and the down-regulation of serum TLR4(9.90±0.55)ng·ml^(-1)and NF-kB(350.29±3.14)ng·L^(-1)by HQC was more obvious.Conclusion:Chinese herbal medicine HQC can significantly improve the bone microstructure of RA rats,and its effect is better than that of western medicine in some aspects.The mechanism of action of HQC is related to the inhibition of the activation of the TLR4/NF-kB pathway,and this study provides an experimental basis for the further development and utilization of HQC.展开更多
基金Supported by State Administration of Traditional Chinese Medicine High-level Key Discipline Construction Project of Traditional Chinese Medicine-Ethnic Minority Pharmacy (Zhuang Pharmacy) (zyyzdxk-2023165)Young Talent Cultivation Program of Guangxi International Zhuang Medicine Hospital (2022001)+4 种基金Key R&D Project of Guangxi Science and Technology Department (Guike AB21196057)Guangxi Traditional Chinese Medicine Interdisciplinary Innovation Team Project (GZKJ2309)Funding Project of High-level Talent Cultivation and Innovation Team of Guangxi University of Chinese Medicine (2022A008)The Third Batch of"Qihuang Project"High-Level Talent Team Training Project of Guangxi University of Chinese Medicine (202414)Three-year Action Plan for the Construction of High-level Talents Team of Guangxi International Zhuang Medicine Hospital in 2023 (GZCX20231203).
文摘[Objectives]To investigate the anti-inflammatory effect of Embelia parviflora Wall.polysaccharide on rheumatoid arthritis(RA)in rats.[Methods]RA rat model was induced by type II collagen.After successful modeling,the rats were divided into model group,positive group,low,medium and high dose of E.parviflora Wall.polysaccharide groups,and normal control group.Body mass,toe volume and arthritis index were measured,and thymus index and spleen index were calculated.The levels of interleukin-1β,interleukin-6 and tumor necrosis factor-αin serum and synovial tissue of ankle joint were detected by ELISA.[Results]Compared with the normal control group,the pathological changes such as synovial hyperplasia and unclear layer were observed in the model group,the body mass was decreased(P<0.05),the toe volume,arthritis index,thymus and spleen index were increased(P<0.05),and the levels of IL-1β,IL-6 and TNF-αin serum and ankle synovial tissue were increased(P<0.05).Compared with the model group,the histopathological changes in synovium of ankle joint in the positive group and the medium and high dose groups of E.parviflora Wall.polysaccharide were significantly improved,and the body mass was increased(P<0.05).The toe volume,arthritis index,thymus index and spleen index were decreased(P<0.05).The levels of IL-Iβ,IL-6 and TNF-αin serum and synovial tissue of ankle joint were increased(P<0.05),while there was no significant difference between the low dose group of E.parviflora Wall.polysaccharide and the model group(P>0.05).[Conclusions]E.parviflora Wall.polysaccharide can reduce the body's inflammatory response and improve RA,which may be related to the inhibition of the activation of inflammatory cytokines IL-1β,IL-6 and TNF-α.
文摘The aim of this study was to design a compound transdermal patch containing diclofenac(DA)and teriflunomide(TEF)for the treatment of rheumatoid arthritis(RA).The various organic amines salts of DA were prepared and their forming was confirmed using DSC and FTIR.The percutaneous permeation of organic amines salt of DA was investigated in vitro using a two-chamber diffusion cell with excised rabbit skin as transdermal barrier.The formulation of the patch was optimized in terms of the concentration of percutaneous permeation enhancer and the loading dose of drugs.The pharmacokinetic behavior of the optimal formulation was studies in rabbits and the anti-inflammatory and analgesic effects of the optimal patch were evaluated with the adjuvant arthritis model in rats and the pain model in mice,respectively.The result showed that skin penetration of diclofenactriethylamine(DA-TEtA)salt was better than other organic amine salts.Based on previous study of our laboratory,teriflunomide-triethylamine(TEF-TEtA)significantly enhanced the skin permeation of TEF.10%of azone(AZ)was the best enhancer for the two drugs.The optimal patch formulation was composed of 2%of TEF-TEtA,6%of DA-TEtA and 10%of AZ.The cumulative permeated amount of DA-TEtA in vitro was comparable with that of the commercial diclofenac-diethylamine(DA-DEtA)patch.The absolute bioavailability of TEFTEtA was 42%,which could achieve the therapeutic drug levels.In animal study,the optimized compound patch containing DA-TEtA and TEF-TEtA displayed significant antiinflammatory and analgesic effect,which indicated the potential of the compound patch.
文摘Objective: To investigate whether glucose-6-phosphate isomerase (G6PI) antigen and anti-G6PI antibodies could be applied for the clinical diagnostic markers of rheumatoid arthritis (RA) and its associations with RA activity states. Methods: The levels of G6PI antigens and anti-G6PI Abs in sera from 176 RA patients in different states, 35 non-RA patients and 100 healthy donors and in synovia fluids from 33 patients and 11 non-RA patients were measured by ELISA. Results: The sensitivity and specificity of G6PI antigens in the RA patients were 75.0% and 93.3%, respectively. The levels of serum G6PI antigens in 176 RA patients were significantly higher than non-RA patients and the health controls. Especially, there was a significant difference between the active phase and the inactive phase in G6PI antigens levels. The levels of G6PI antigens in synovia fluid were also significantly higher in RA groups than in non-RA patients. With the values of the anti-G6PI Abs in sera, there were no marked differences among RA, non-RA patients and health controls. Also, there was no significant difference between the active phase and the inactive phase in RA patients. However, there were no significant differences of G6PI and anti-G6PI between RA patients and health controls in synovial fluid. Conclusions: G6PI is highly correlated with the activity states of RA, and could be applied for a clinical biomarker with high sensitivity and specificity for the diagnosis of RA.
基金National Natural Science Foundation of China(81560702)Joint Research Project of Inner Mongolia Minzu University and Mongolian Academy of Sciences(NMDGJ0014)Graduate Research and Innovation Project in Inner Mongolia Autonomous Region(S20210280Z)。
文摘[Objectives]To explore the anti-rheumatoid arthritis effect of Lignum Xanthocerais Sorbifoliae by network pharmacology method.[Methods]The chemical constituents and action targets of Lignum Xanthocerais Sorbifoliae were collected by Traditional Chinese Medicine Systems Pharmacology(TCMSP).Target genes of rheumatoid arthritis(RA)were obtained from TTD database.ClusterProfiler was used for gene ontology(GO)enrichment,and Cytoscape 3.7.2 software was used for Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment and screening of active component-target core network.[Results]There were 24 intersecting targets between active components and diseases.The analysis of GO enrichment and KEGG pathway enrichment indicated that the therapeutic effect of Lignum Xanthocerais Sorbifoliae on rheumatoid arthritis might be related to AGE-RAGE signaling pathway,IL-17 signaling pathway,rheumatoid arthritis pathway,C-type signaling pathway and Toll-like receptor signaling pathway.13 drug active components[flavanes,dihydroflavonoids,stigmasterol,oleanolic acid,kaempferol,ellagic acid,Terchebulin B,Copaene,(Z)-β-Caryophyllene,Aromadendrene,β-Elemene,emodin]and 12 core targets(TNF,IL6,ALOX5,MAPK14,PPARA,AKR1B1,CCR5,PLA2G1B,ADAM17,MMP1,PTGS1,SYK)constituted a core network.[Conclusions]This study could provide a theoretical basis for the treatment of RA with Lignum Xanthocerais Sorbifoliae preparation.
基金This study was supported by the National Natural Science Foun-dation of China(81804041)the special project of State Key Laboratory of Dampness Syndrome of Chinese Medicine(SZ2020ZZ17)+5 种基金the 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund(The Guangdong-Hong Kong-Macao Joint Lab)(2020B1212030006)Natural Science Foundation of Guang-dong Province(2021A1515011477,2021A1515011593)grant from Guangzhou Basic Research Program(202102010256)the Key Research Project of Guangzhou University of Chinese Medicine(XK2019021)opening project of Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases(2018)(2018B030322012,MB2020KF03),Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-C-202204)as well as grants from Guangdong Provincial Hospital of Chinese Medicine(MB2019ZZ07,YN10101906,YN2018ML08,YN2018ZD06)。
文摘Background:Rheumatoid arthritis(RA)is a worldwide public health problem.Intervention and prevention before the onset of rheumatic diseases is a new direction in current research.Objective:The aim of this study was to evaluate the potential and feasibility of traditional Chinese medicine(TCM)in the prevention of RA.Methods:This was a single-armed prospective clinical trial.All participants were recruited from a single center in Guangdong,China.Adults who were tested positive for anti-cyclic citrullinated peptide antibody(anti-CCP)and/or rheumatoid factor(RF),had no synovitis and never been treated with disease-modifying anti-rheumatic drugs(DMARDs),were enrolled to take the Huayu-Qiangshen-Tongbi(HQT)decoction orally twice daily,200 mL each time for 24 weeks.Primary outcome was the proportion of patients who met 2010 ACR(American College of Rheumatology)/EULAR(European League Against Rheumatism)classification criteria of RA during observation.Secondary outcomes included levels of anti-CCP,RF,erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),assessment of signs and symptoms,and radiographic progression by magnetic resonance imaging(MRI).Results:19 individuals were enrolled in the study,4 of which withdrew because of the epidemic of COVID-19.During the observation period,3 individuals(20%)developed RA and they had longer morning stiffness(P=0.009)and more obvious synovial enhancement in MRI(P=0.041)at baseline when compared with those who did not develop RA.After 24 weeks of intervention,there were improvements in 28-swollen joint count(SJC28)(P=0.046),Visual Analog Scale(VAS)(P=0.019),Patient’s Global Assessment(PtGA)(P=0.019)and Physician’s Global Assessment(PGA)(P=0.031),but no statistical significance was observed in the levels of anti-CCP,RF,ESR,CRP,morning stiffness,28-tender joint count(TJC28),Health Assessment Questionnaire(HAQ)and magnetic resonance imaging(MRI)analysis(P>0.05).Conclusion:The HQT formula is safe and could improve joint symptoms and signs in these at-risk individuals,but it remains to be investigated in futher study to see if it might potentially reduce the risk of developing RA.Besides,for individuals at high risk to develop RA,morning stiffness and synovial enhancement in MRI might be predictive factors and warning signs.
基金This study was supported by the Ministry of Health(MoH),Malaysia:MRG 7/2005,IMR/PK/05/061 and JPP-IMR 08-012.
文摘Aim of Work: Initial observations implied IgG rheumatoid factor (RF) to be common among Malaysian rheumatoid arthritis (RA) patients. We tested this hypothesis and used a multiethnic RA cohort (Malays, Chinese and Indians) to investigate whether the IgG RF predominance might be genetically or environmentally determined. Patients and Methods: 556 serum samples comprising 171 patients classified as RA according to the 1987 ACR criteria, 60 patients with other rheumatic diseases and 325 non-rheumatic controls were tested for IgG RF, IgM RF and anti-CCP by ELISA. The findings were then tested in a larger RA case-control cohort (n = 1844). Results: IgG RF predominated over IgM RF in all the investigated ethnic groups. The sensitivity, specificity, and diagnostic accuracy of IgG RF (55.6%, 91.2% and 80.2%, respectively) were superior compared to IgM RF, but comparable to anti-CCP. IgG RF was however, also increased in the Malaysian controls, but the IgG RF superiority over IgM RF was still apparent after cutoff adjustment according to the 1987 ACR criteria. Autoantibody levels did not differ between the three ethnic groups. The Receiver Operating Characteristics (ROC) curves showed larger areas under the curves for IgG RF (0.826) and for anti-CCP (0.867) than for IgM RF (0.737). Review of the literature showed consistently higher sensitivity for IgG RF in studies of Asian RA patients as compared to Caucasian and African-American studies. Conclusion: Increased frequency of IgG RF-positive in RA populations with different genetic background living in Malaysia argues for an environmental factor selectively amplifying the IgG RF response.
文摘Aim of Work: To investigate the value of the detection of antibodies against modified citrullinated vimentin antibodies (anti-MCV) in comparison with anti-CCP2-for the diagnosis of rheumatoid arthritis (RA). Patients and Methods: The study Included Forty patients with Rheumatoid arthritis (RA). They under went assessment by the disease activity score (DAS-28), visual analogue scale (VAS) and health assessment questionnaire (HAQ). Thirty healthy subjects matched for age and sex served as a control group. Blood samples were obtained from patients and controls for erythrocyte sedimentation rate (ESR), C reactive protein (CRP), rheumatoid factor (RF). Anti-CCP2 and anti-MCV were determined using ELISA technique. Results: Estimated serum levels of anti-CCP2 and anti-MCV were significantly higher in patients compared to controls (p 0.001). There were no significant correlations between anti-MCV levels and age, dis- ease duration, duration of morning stiffness, number of swollen and tender joints, HAQ or ESR in patients with RA, while serum levels correlates significantly with DAS28, VAS and CRP (p 0.05). Anti-CCP2 correlates significantly with DAS28, VAS and CRP and ANA (p 0.05). Serum anti-MCV and anti-CCP2 were significantly correlated with each other (r = 0.483;p The receiver operating characteristic (ROC) curve was drawn and it showed that anti-MCV had diagnostic specificity, sensitivity of 93.3%, 75.5%, respectively, while anti-CCP2 specificity, sensitivity of 98.1%, 85%, respectively. Conclusion: Serum anti-MCV as well as the anti-CCP-2 assay perform comparably well in the diagnosis of RA. In the high-specificity range, however, the anti-CCP2 assay appears to be superior to the anti-MCV test.
文摘Objective: To assess the efficacy and safety of modified Guizhi Shaoyao Zhimu Tang (GSZT) with the Western medicines in treating rheumatoid arthritis. Methods: All the relevant studies were collected by searching the Pubmed, Web of science, Embase, Cochrane Library, SpringerLink, China National Knowledge Infrastructure (CNKI), VIP Journals database, and Wanfang database from their inception to October 2017. After the assessment, the eligible ones were subject to Jadad score. The meta-analysis was conducted by RevMan 5.3 software. Results: Totally 10 randomized controlled trials (RCTs) involving 962 patients were enrolled. The clinical efficacy of analysis showed that modified GSZT with the Western medicines can significantly improve the clinical total effective rate [OR = 4.64, 95%CI (3.03, 7.12), P −14.58, 95%CI (−16.49, −12.68), P −12.62 95%CI (−18.69, −6.54), P −49.88, 95%CI (−77.6, −22.09), P −5.34, 95%CI (−5.86, −4.82), P < 0.001]. The adverse events had been seen in both of the two groups, however, the clinical symptoms of the group on modified GSZT with the Western medicines were obviously reduced than the other one [OR = 0.25, 95%CI (0.10, 0.61), Z = 3.06, P < 0.01]. This system review shows that the modified GSZT with the Western medicines improved the clinical efficacy, symptoms and the blood biochemical indicators were improved significantly than that of Western medicines alone on rheumatoid arthritis. At the same time, it can reduce adverse effects and enhance safety.
文摘Objective: To observe the effect and adverse reaction of tripterygium polyglycosides (TP) combined with small dose of methotrexate (MTX) in treating senile rheumatoid arthritis (RA). Methods: Sixty old patients with RA were equally divided into two groups, the treated group was treated with oral intake of TP (10 mg three times per day) plus MTX (7.5 mg, once per week), and the control group was treated with MTX (15 mg per week) respectively for 3 months. The changes from before to after treatment in resting pain, morning rigidity, bilateral grip strength, local tenderness index, arthroncus index, patient's evaluation, doctor's evaluation, erythrocyte sedimentation rate (ESR), C-reaction protein (CRP) and rheumatoid factor(RF) titre were observed and the clinical therapeutic effect assessed. Results: The total effective rate in the treated group was 86.67% and that in the control group 83.33% , showing insignificant difference between them (P>0.05). But the improvement in local tenderness index, arthroncus index, morning rigidity and ESR in the treated group was significantly better than those in the control group (P<0.01 or P<0.05). The occurrence rate of adverse reaction in the treated group was 26. 67% , which was lower than that in the control group (43.33%), showing significant difference (P<0.01). Conclusion: TP combined with small dose of MTX is a favorable therapeutic method for treating senile RA.
基金This work was supported by the National Natural Science Foundation of China(Grant Nos.52072210 and 52111530230)Key R&D Projects of Social Development of Hainan Provincial Department of Science and Technology(Grant No.ZDYF2020137)Tsinghua University Beijing Union Medical CollegeeHospital Cooperation Project(Grant No.20191080871).
文摘The disruption and reconstruction of the TREM2^(+) tissue resident macrophage(TRM)barrier on the surface of synovial lining play a key role in the activation and"remission"of rheumatoid arthritis(RA),which engender the prediction of this immunologic barrier as a potential driver for the achievement of"cure"in RA.However,strategies to promote the reconstruction of this barrier have not been reported,and the effect of patching this barrier remains unidentified.On the other hand,appropriate piezoelectric stimulation can reprogram macrophages,which has never been exerted on this barrier TRM yet.Herein,we design piezoelectric tetragonal BaTiO_(3)(BTO)ultrasound-driven nanorobots(USNRs)by the solvothermal synthesis method,which demonstrates satisfactory electro-mechanical conversion effects,paving the way to generate controllable electrical stimulation under ultrasound to reprogram the barrier TRM by minimally invasive injection into joint cavity.It is demonstrated that the immunologic barrier could be patched by this USNR effectively,thereby eliminating the hyperplasia of vessels and nerves(HVN)and synovitis.Additionally,TREM2 deficiency serum-transfected arthritis(STA)mice models are applied and proved the indispensable role of TREM2 in RA curing mediated by USNR.In all,our work is an interesting and important exploration to expand the classical tetragonal BTO nanoparticles in the treatment of autoimmune diseases,providing a new idea and direction for the biomedical application of piezoelectric ceramics.
文摘Objective:To elucidate the effects of Huangqin Qingre Chubi capsule(HQC)on bone metabolism and serum TLR4 and NF-kB in rats with rheumatoid arthritis(RA),and to provide experimental bases for the treatment of RA with HQC.Methods:A total of 40 SD rats were randomly divided into the normal group,model group,western medicine treatment group,and HQC group,with 10 rats in each group,and the RA model was induced by complete adjuvant in all groups except the normal group.After successful modeling,they were treated for 4 weeks to compare the degree of joint swelling;meanwhile,micro-CT was used to evaluate bone microstructural parameters,and changes in serum TLR4 and NF-kB expression levels were detected by ELISA.Results:There was no statistical significance in comparing the degree of joint swelling among the model group,western medicine treatment group and HQC group(P>0.05);Micro-CT results showed that bone microstructural parameters deteriorated in the osteoporosis model group compared with the normal group.Both western medicine and traditional Chinese medicine HQC could improve the bone microjunction of RA rats,and the HQC group was better than the western medicine treatment in improving the number of bone trabeculae(2.58±0.19)·mm^(-1);the serum results showed that RA was accompanied by the up-regulation of the expression of TLR4 and NF-kB.Both western drugs and HQC down-regulated the high expression of serum TLR4 and NF-kB in osteoporotic rats,and the down-regulation of serum TLR4(9.90±0.55)ng·ml^(-1)and NF-kB(350.29±3.14)ng·L^(-1)by HQC was more obvious.Conclusion:Chinese herbal medicine HQC can significantly improve the bone microstructure of RA rats,and its effect is better than that of western medicine in some aspects.The mechanism of action of HQC is related to the inhibition of the activation of the TLR4/NF-kB pathway,and this study provides an experimental basis for the further development and utilization of HQC.