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Enhancing convolutional neural network scheme for rheumatoid arthritis grading with limited clinical data

Chinese Physics B 2019年第3期28卷 391-398页

作者： Jian Tang Zhibin Jin Xue Zhou Weijing Zhang Min Wu Qinghong Shen Qian Cheng Xueding Wang Jie Yuan School of Electronic Science and Engineering Nanjing University Nanjing Drum Tower Hospital Institution of Acoustics Tongji University

The gray-scale ultrasound(US) imaging method is usually used to assess synovitis in rheumatoid arthritis(RA) in clinical practice. This four-grade scoring system depends highly on the sonographer's experience and has relatively lower validity compared with quantitative indexes. However, the training of a qualified sonographer is expensive and timeconsuming while few studies focused on automatic RA grading methods. The purpose of this study is to propose an automatic RA grading method using deep convolutional neural networks(DCNN) to assist clinical assessment. Gray-scale ultrasound images of finger joints are taken as inputs while the output is the corresponding RA grading results. Firstly,we performed the auto-localization of synovium in the RA image and obtained a high precision in localization. In order to make up for the lack of a large annotated training dataset, we performed data augmentation to increase the number of training samples. Motivated by the approach of transfer learning, we pre-trained the GoogLeNet on ImageNet as a feature extractor and then fine-tuned it on our own dataset. The detection results showed an average precision exceeding 90%. In the experiment of grading RA severity, the four-grade classification accuracy exceeded 90% while the binary classification accuracies exceeded 95%. The results demonstrate that our proposed method achieves performances comparable to RA experts in multi-class classification. The promising results of our proposed DCNN-based RA grading method can have the ability to provide an objective and accurate reference to assist RA diagnosis and the training of sonographers.

关键词： rheumatoid arthritis convolutional neural network medical ultrasound images

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Current Immunotherapy Strategies for rheumatoid Arthritis:The Immunoengineering and Delivery Systems

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Research 2024年第3期2023卷 169-189页

作者： Chenyu Zhang Peixiang Ma An Qin Liao Wang Kerong Dai Yuanyuan Liu Jie Zhao Zuyan Lu School of Medicine Shanghai UniversityShanghaiChina Clinical and Translational Research Center for 3D Printing Technology Shanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Shanghai Key Laboratory of Orthopedic Implants Department of Orthopedic SurgeryShanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Shanghai Frontiers Science Center of Degeneration and Regeneration in Skeletal System ShanghaiChina.

rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease accompanied by persistent multiarticular synovitis and cartilage degradation. The present clinical treatments are limited to disease-modifying anti-rheumatic drugs (DMARDs) and aims to relieve pain and control the inflammation of RA. Despite considerable advances in the research of RA, the employment of current clinical procedure is enormous, hindered by systemic side effect, frequent administration, tolerance from long-lasting administration, and high costs. Emerging immunoengineering-based strategies, such as multiple immune-active nanotechnologies via mechanism-based immunology approaches, have been developed to improve specific targeting and to reduce adverse reactions for RA treatments. Here, we review recent studies in immunoengineering for the treatment of RA. The prospect of future immunoengineering treatment for RA has also been discussed.

关键词： drugs rheumatoid treatment

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ROS-Responsive Berberine Polymeric Micelles Effectively Suppressed the Inflammation of rheumatoid Arthritis by Targeting Mitochondria

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Nano-Micro Letters 2020年第6期12卷 138-151页

作者： Xing-xing Fan Meng-ze Xu Elaine Lai-Han Leung Cai Jun Zhen Yuan Liang Liu State Key Laboratory of Quality Research in Chinese Medicine Macao Institute For Applied Research in Medicine and HealthMacao University of Science and TechnologyAvenida Wai LongTaipaMacao SARChina Faculty of Health Sciences University of MacaoTaipaMacao SARChina

rheumatoid arthritis(RA)is an autoimmune disease,which attacks human joint system and causes lifelong inflammatory *** date,no cure is available for RA and even the ratio of achieving remission is very ***,to enhance the efficacy of RA treatment,it is essential to develop novel approaches specifically targeting pathological *** this study,we discovered that RA synovial fibroblasts exhibited higher reactive oxygen species(ROS)and mitochondrial superoxide level,which were adopted to develop ROS-responsive nano-medicines in inflammatory microenvironment for enhanced RA treatment.A selenocystamine-based polymer was synthesized as a ROS-responsive carrier nanoplatform,and berberine serves as a tool *** assembling,ROS-responsive berberine polymeric micelles were fabricated,which remarkably increased the uptake of berberine in RA fibroblast and improved in vitro and in vivo efficacy ten times ***,the anti-RA effect of micelles was blocked by the co-treatment of AMPK inhibitor or palmitic acid,indicating that the mechanism of micelles was carried out through targeting mitochondrial,suppressing lipogenesis and finally inhibiting cellular *** together,our ROS-responsive nano-medicines represent an effective way of preferentially releasing prodrug at the inflammatory microenvironment and improving RA therapeutic efficacy.

关键词： rheumatoid arthritis Reactive oxygen species Nanoparticles Berberine Oxygen consumption rate

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Optimized in vivo performance of acid-liable micelles for the treatment of rheumatoid arthritis by one single injection

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Nano Research 2019年第2期12卷 421-428页

作者： Qin Wang Yan Li Xiaoyan Chen Hao Jiang Zhirong Zhang Xun Sun Key Laboratory of Drug Targeting and Drug Delivery Systems Ministry of Education West China School of Pharmacy Sichuan University Chengdu 610041 China

Current therapeutic limitations existed in effective treatment of rheumatoid arthritis (RA) have motivated numerous researches on finding new *** to the non-targeted distribution and uncontrollable in vivo performance which hinder the effective treatment for RA,we designed an acid-responsive polymeric micelle formulation by attaching the dexamethasone (Dex) to the side chains of a wheat-like polyethylene glycol (PEG) derivate via a hydrazone *** self-assembly micelles with the diameter around 50 nm could passively migrate to inflamed *** presence of hydrazone linkers avoided the drug leakage in circulation and ensured the preferential release in acidic arthritic ***,we evaluated how the polymer-drug micelles with different density of drug payloads influenced the release pattem,pharmacokinetics and biodistribution,as well as the most importantly,the duration of the therapeutic *** exploration would offer the chemical and structural basis for designing and optimizing the nanocarriers for enhanced therapeutic efficacy.

关键词： rheumatoid arthritis pH-responsive micelles dexamethasone

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Genetic and clinical markers for predicting treatment responsiveness in rheumatoid arthritis

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Frontiers of Medicine 2019年第4期13卷 411-419页

作者： Xin Wu Xiaobao Sheng Rong Sheng Hongjuan Lu Huji Xu Department of Rheumatology and Immunology Shanghai Changzheng Hospital the Second Military Medical University Shanghai 200003 China School ofEconomics and Management Tongji University Shanghai 200092 China The Third Research Institute of the Ministry of Public Security Shanghai 200031 China Beijing Tsinghua Changgung Hospital School of Clinical Medicine Tsinghua University Beijing 100084 China Peking-Tsingh ua Center for Life Sciences Tsinghua University Beijing 100084 China

Although many drugs and therapeutic strategies have been developed for rheumatoid arthritis (RA) treatment, numerous patients with RA fail to respond to currently available agents. In this review, we provide an overview of the complexity of this autoimmune disease by showing the rapidly increasing number of genes associated with RA. We then systematically review various factors that have a predictive value (predictors) for the response to different drugs in RA treatment, especially recent advances. These predictors include but are certainly not limited to genetic variations, clinical factors, and demographic factors. However, no clinical application is currently available. This review also describes the challenges in treating patients with RA and the need for personalized medicine. At the end of this review, we discuss possible strategies to enhance the prediction of drug responsiveness in patients with RA.

关键词： rheumatoid arthritis gene clinical markers therapy

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Moxibustion enables protective effects on rheumatoid arthritis-induced myocardial injury via transforming growth factor beta1 signaling and metabolic reprogramming

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Journal of Traditional Chinese Medicine 2023年第6期43卷 1190-1199页

作者： WANG Miao ZHU Yan ZHAO Hui ZHAO Hongfang the Geriatrics Anhui University of Traditional Chinese MedicineHefei 230031China the Geriatrics the Second Hospital Affiliated of Anhui University of Traditional Chinese MedicineHefei 230061China

OBJECTIVE:To examine the effects of moxibustion on myocardial injury and myocardial metabolomics in rats with rheumatoid arthritis(RA)based on the transforming growth factor beta1(TGF-β1)/Smads signaling ***:One hundred rats were treated with saline[normal control(NC)group]or complete Freund’s adjuvant(CFA)by right plantar injection for the RA model group,and the latter were randomly divided into 4 *** wilfordii polyglycoside tablets(雷公藤多苷片,TPT)have anti-inflammatory and are widely used in the clinical treatment of RA,therefore serving as a positive control *** days post injection rats were given TPT tablet(TPT group),acupuncture therapy(APT group),and moxibustion treatment(MOX group)for 15 consecutive days,while NC group and model group were equally grasped and fixed and received normal *** joint swelling scores and arthritis index(AI)were evaluated in each group before the CFA challenge,therapy and after receiving *** ultrastructure was observed by electron ***-linked immunosorbent assay was used to detect cardiac troponin I(cTnI)levels in rat myocardial *** reverse transcription polymerase chain reaction and Western blotting analysis were used to measure the mRNA and protein levels of TGF-βsignaling molecules including TGF-β1,Smad2,Smad3,Smad4,and *** metabolomics was analyzed using gas chromatography-mass ***:Compared with model group,RA model rats receiving TPT,acupuncture,or moxibustion therapy all showed reduced joint swelling scores and AI(all P<0.01)and improved myocardial damage,whereas rats treated with moxibustion were found to be more ***,the expressions of cTnI,TGF-β1,Smad2,Smad3,and Smad4 were found to be elevated in model rat group in contrast to NC rats and were significantly downregulated in TPT,APT and MOX group when compared with model group,while the levels of Smad7 showed the opposite result(all P<0.01).Moreover,

关键词： moxibustion arthritis rheumatoid transforming growth factor beta1 smad proteins signal transduction myocardial injury metabolomics

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Effects of Xinfeng capsule on the Fas/FasL-mediated apoptotic pathway in patients with rheumatoid arthritis

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Journal of Traditional Chinese Medicine 2018年第4期38卷 601-609页

作者： Sun Yue Liu Jian Cao Yonghe Department of Rheumatism Immunity The First Affiliated HospitalAnhui University of Chinese Medicine Department of Traditional Chinese Medicine The First Affiliated HospitalXinxiang Medical University

OBJECTIVE:To observe the effects of Xinfeng capsule on the apoptosis of peripheral blood CD4+ T lymphocytes and changes in the Fas/Fas L-mediated apoptotic pathway in patients with rheumatoid arthritis(RA).METHODS:A total of 28 RA patients were included in the study;they were randomly divided into the Xinfeng capsule(XFC) group(3 capsules,3 per day)and the leflunomide(LEF) group(1 pellet,once per night).The treatment course in each groups was 12 *** normal control(NC) group consisted of10 healthy *** apoptotic rate was examined using flow ***,Fas L,caspase 8,caspase 3,bcl-2,and bax m RNA were examined using q *** proteins Fas,Fas L,caspase8,and caspase 3 were examined using western ***:After treatment,patients in the two groups all showed some trend of *** activity indexes,joint morning stiffness time,joint swelling/tenderness number,health assessment questionnaire(HAQ) score,RA quality of life(RAQOL) questionnaire,and self-rating anxiety scale(SAS),as well as all apoptotic related indicators were reduced in both groups after treatment with no significant difference between *** the improvement in terms of the self-rating depression scale(SDS) in the XFC group was better than in the LEF *** patients showed lower apoptotic rates in CD4+ T cells,lower bax,Fas,caspase 8,and caspase 3 m RNA,and less protein expression of Fas,caspase 8,and caspase3 than in the NC *** indicators increased after ***,the level of Bcl-2 m RNA was higher in the XFC group than in the NC group before treatment,and it subsequently *** XFC group expressed lower Bcl-2 m RNA than the LEF *** correlations were found between ESR and the apoptotic rate in CD4 + T cells,Fas,and caspase 3;CRP and Fas;and,swollen joint count and Bax,while positive correlations were found between ESR and ***:XFC can regulate the Fas/Fas L system and promote CD4+ T cell apoptosis and thus redu

关键词： Arthritis rheumatoid Fas ligand protein CD4 lymphocyte count Apoptosis Xinfengcapsule

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Effect of Sanhuangyilong decoction plus methotrexate on tumor necrosis factor alpha and interferon gamma in serum and synovial fluid in rheumatoid arthritis patients with symptom pattern of damp heat obstruction

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Journal of Traditional Chinese Medicine 2016年第5期36卷 625-633页

作者： Liu Defang Yan Jiao Yun Mingdong Yang Ming Luo Yong Zhang Jun Guo Mingyang Yang Mei Yuan Weili Zou Wei Li Hua Hu Yonghe Postgraduate Department of Second Military Medical University General Hospital of Chengdu Military Region Shanghai 200433 China Department of Integrative Medicine on rheumatoid General Hospital of Chengdu Military Region Chengdu 610083 China Department of Oncology of General Hospital of Chengdu Military Region Chengdu 610083 China

OBJECTIVE: To investigate the effect of Sanhuangyilong decoction plus methotrexate(MTX) on Interferon gamma(IFN-γ) and tumor necrosis factor alpha(TNF-α) in the serum and synovial fluid of rheumatoid arthritis(RA) patients with damp-heat-obstruction symptom pattern, Sanhuangyilong decoction and the role of TNF-α and IFN-γ in the development of ***: RA inpatients with damp-heat-obstruction symptom pattern(partly with knee joint effusion) were selected as the research subjects. Before the treatment, healthy subjects and osteoarthritis(OA) patients with knee joint effusion were assigned to the serum control group and the synovial fluid control group, respectively; during the treatment, RA patients with damp-heat-obstruction symptom pattern were divided into two groups:one is combined group that was administered Sanhuangyilong decoction plus MTX; the other group was MTX group that received MTX only. The expression levels of TNF-α and IFN-γ in the serum and synovial fluid were measured with enzyme-linked immunosorbent assay(ELISA) before and after the treatment, and the peripheral blood levels of erythrocyte sedimentation rate(ESR), C-reactive protein(CRP) and disease activity score in 28 joints(DAS28)were ***: Before treatment, the serum levels of TNF-α and IFN-γ in the RA patients with dampheat-obstruction symptom pattern were higher than those in healthy control group(P 0.05). After 2 weeks of treatment, the expression level of TNF-α and IFN-γ in the combined group ha

关键词： Arthritis rheumatoid Dampness-heat Cytokines Blood sedimentation C-reactive protein Methotrexate Sanhuangyilong decoction

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Effect of moxibustion on autophagy and the inflammatory response of synovial cells in rheumatoid arthritis model rats

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Journal of Traditional Chinese Medicine 2022年第1期42卷 73-82页

作者： HAO Feng WANG Qiang LIU Lei WU Libin CAI Ronglin SANG Jiajia HU Jun WANG Jie YU Qing HE Lu SHEN Yingchao MIAO Yiming HU Ling WU Zijian College of Acupuncture-moxibustion and Tuina Nanjing University of Chinese MedicineNanjing 210023China Translational Medicine Research Center of Nanjing University of Chinese Medicine Nanjing 210023China Changshu Hospital Affiliated to Nanjing University of Chinese Medicine Changshu 215500China College of Acupuncture-moxibustion and Tuina Anhui University of Chinese MedicineHefei 230012China Institute of Acupuncture and Meridian Anhui Academy of Chinese MedicineHefei 230038China Affiliate Hospital of Nanjing University of Chinese Medicine/Jiangsu Province of Chinese Medicine Nanjing 210029China the first clinical medical college of Nanjing University of Chinese Medicine Nanjing 210029China

OBJECTIVE:To investigate the effect of moxibustion on synovitis and the autophagy of synoviocytes in rheumatoid arthritis(RA).METHODS:Forty Sprague-Dawley rats were randomly divided into a normal group,model group,moxibustion group,cigarette moxibustion group,and medicine group,with eight rats included in each *** RA model was established by subcutaneous injection of complete Freund's adjuvant into the left posterior *** in the model group were not interfered *** the moxibustion group,rats were treated by moxibustion,where a 1-cm diameter moxa stick was applied at the left Zusanli(ST 36)*** distance of the moxa stick to the skin was 2 cm and moxibustion was completed for 20 min daily for 15 d *** the cigarette moxibustion group,the moxa stick was replaced by a common *** the medicine group,rats were treated with a tripterygium glycoside suspension(8 mg/kg)once a day for 15 d *** each group,the left hind limb toe volume was measured with a toe volume meter;the synovial cells were observed by hematoxylin and eosin staining;the interleukin(IL)-4,IL-6,IL-10,IL-1β,IL-23,IL-17,and tumor necrosis factor(TNF)-αlevels in serum were measured by enzyme-linked immunosorbent assay;the erythrocyte sedimentation rate(ESR)were detected by Westergren sedimentation rate testing;the C-reactive protein(CRP)and rheumatoid factor(RF)levels in serum were detected by rate nephelometry;the expression levels of ULK1,autophagy-associated protein(Atg)3,Atg5,and Atg12 messenger RNA(m RNA)in synovium were detected by real time-quantitative polymerase chain reaction(RT-q PCR);and the protein expression levels of phosphatidylinositol-3-kinase(PI3K),protein kinase B(Akt),mammalian target of rapamycin(mTOR),LC3-Ⅱ,beclin-1,phosphorylated-PI3K(p-PI3K),p-Akt,p-mTOR in synovium were detected by Western ***:Among the RA model rats,joint swelling,an inflammatory reaction,and the proliferation of synovial tissue were obvious and the signal of the PI3K/Ak

关键词： moxibustion arthritis rheumatoid synovitis autophagy

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Madecassoside impedes invasion of rheumatoid fibroblast-like synoviocyte from adjuvant arthritis rats via inhibition of NF-κB-mediated matrix metalloproteinase-13 expression

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Chinese Journal of Natural Medicines 2018年第5期16卷 330-338页

作者： YU Wei-Guang SHEN Yong WU Jian-Zhong GAO Yan-Bing ZHANG Li-Xing Department of Orthopedics Lesion 2 Shijiazhuang No. 1 Hospital Shijiazhuang 050000 China Department of Orthopedics Lesion Spine Third Hospital of Hebei Medical University Shjiazhuang 050000 China

Fibroblast-like synoviocytes(FLS) play a pivotal role in rheumatoid arthritis(RA) pathogenesis through aggressive migration and invasion. Madecassoside(Madec), a triterpenoid saponin present in Centella asiatica herbs, has a potent anti-inflammatory effect. In the present study, Madec exerted an obvious therapeutic effect in reversing the histological lesions in adjuvant-induced arthritis(AIA) rats. To recognize the anti-rheumatoid potentials of Madec, we further investigated whether Madec interfered with FLS invasion and metalloproteinase(MMP) expression. In cultures of primary FLS isolated from the AIA rats, Madec(10 and 30 μmol·L–1) was proven to considerably inhibit migration and invasion of FLS induced by interleukin 1β(IL-1β), but exhibiting no obvious effect on cell proliferation. Madec repressed IL-1β-triggered FLS invasion by prohibiting the expression of MMP-13. Additionally, Madec suppressed MMP-13 transcription via inhibiting the MMP-13 promoter-binding activity of NF-κB. Our results further showed that Madec down-regulated the translocation and phosphorylation of NF-κB as demonstrated by Western blotting and immunofluorescence assays. In conclusion, our results suggest that Madec exerts anti-RA activity via inhibiting the NF-κB/MMP-13 pathway.

关键词： rheumatoid arthritis Fibroblast-like synoviocytes Madecassoside Adjuvant-induced arthritis Matrix metalloproteinase-13 Invasion

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