The therapeutic effects in treating the intermediate and late rheumatoid arthritis by supplementing the kidney and invigorating blood circulation were observed. In the 43 cases of the treatment group, No. 2 Qu Feng Sh...The therapeutic effects in treating the intermediate and late rheumatoid arthritis by supplementing the kidney and invigorating blood circulation were observed. In the 43 cases of the treatment group, No. 2 Qu Feng Shi Ling capsules (祛风湿灵胶囊2号) and Fenbid (芬必得) were prescribed, while in the 39 cases of the control group Lei Gong Teng Tablets (雷公藤总甙片) and Fenbid were given. The results showed that the total effective rate in the treatment group was more satisfactory than that in the control (P<0.05 or P<0.01). With less toxic effects, the former could better improve the local swelling and lower the blood viscosity.展开更多
Background: Transcranial direct current stimulation (tDCS) has emerged as an adjuvant noninvasive neuromodulation tool to control fatigue and pain. To date, no studies have assessed the safety and efficiency of tDCS i...Background: Transcranial direct current stimulation (tDCS) has emerged as an adjuvant noninvasive neuromodulation tool to control fatigue and pain. To date, no studies have assessed the safety and efficiency of tDCS in patients with rheumatoid arthritis and with fatigue, poor quality of life, and refractory radicular pain associated with spinal stenosis. Case Presentation: An 85-year-old woman patient presented with rheumatoid arthritis in remission, refractory radicular pain-associated spinal stenosis, fatigue, and impaired quality of life. The patient underwent 16 daily sessions of tDCS intervention (2 mA, 20 min, positively and negatively charged electrodes were positioned at C1 and Fp2, respectively), in addition to simultaneous peripheral neuromuscular electrical stimulation (frequency of 100 Hz and amplitude of 500 μs). After the intervention, neither disease relapse nor clinical intercurrence occurred. Moreover, there was a significant and sustained improvement in her health-related quality of life, with a reduction in the level of pain and chronic fatigue. Conclusion: The present case report shows that tDCS is safe and may be an adjuvant tool for the treatment of pain and fatigue in patients with systemic autoimmune disease, as well as for improving quality of life. Further studies are required to corroborate this case report.展开更多
Inflammatory rheumatological diseases like rheumatoid arthritis (RA) and ankylosing spondylitis/Spondyloarthritis (AS/SpA), have been treated with NSAIDs (non steroidal anti-inflammatory drugs), corticosteroids, and D...Inflammatory rheumatological diseases like rheumatoid arthritis (RA) and ankylosing spondylitis/Spondyloarthritis (AS/SpA), have been treated with NSAIDs (non steroidal anti-inflammatory drugs), corticosteroids, and DMARDs (disease modifying anti-rheumatic drugs).These have been only partially effective for the management of symptoms, since they are rarely associated with the complete control of disease and rarely slow down radiological damage. Several cytokines have been implicated in the pathogenesis of the inflammation and tumor necrosis factor (TNF) is the most important. The last decade and a half has seen advances in the form of “anti-TNF” therapies for RA and AS/SpA patients which target and neutralize the TNF cytokines, and thus reduce the disease activity. Two anti-TNF therapies have been used in India for treating DMARD resistant RA and AS/SpA for the last 13 years;Infliximab and Etanercept respectively. This paper is a description of the clinical outcomes and unmet needs/toxicities associated with the treatment of RA and AS/SpA with anti-TNF therapies (Infliximab, Etanercept), at a single rheumatology center (tertiary care, super-specialty hospital, Indraprastha Apollo Hospitals, New Delhi) in north India.展开更多
Biologics have greatly improved the management of rheumatoid arthritis (RA), demonstrating efficacy and safety in alleviating symptoms, inhibiting bone erosion, and preventing loss of function. Unmet therapeutic needs...Biologics have greatly improved the management of rheumatoid arthritis (RA), demonstrating efficacy and safety in alleviating symptoms, inhibiting bone erosion, and preventing loss of function. Unmet therapeutic needs in RA remain;however, further advances require an understanding of issues left unaddressed under the current treatment paradigm. Most biologic-na?ve and biologic-pretreated patients who initiate a biologic therapy, for example, do not reach American College of Rheumatology 50% (ACR50) response, and few achieve remission. Responses are often not durable, prompting frequent treatment switching. Predictive markers are unavailable to guide therapy selection, and clinical trial data are lacking on whether a tumor necrosis factor inhibitor (TNFi) is the best first-line biologic and on the optimal sequence of use for the different biologics. Risk of serious infection is the major safety concern. Translating preclinical and clinical findings into new therapeutics may help address unmet needs. An increasing body of evidence indicates that the cytokine interleukin (IL)-17A represents an important therapeutic target;ongoing trials with IL-17A inhibitors will determine whether these agents can address some of the unmet needs associated with current biologics.展开更多
Objective:Sleep apnea hypopnea syndrome (SAHS) is a common sleep disorder, which is manifested as a reduction in tidal volume or apnea during sleep, which results in intermittent hypoxia and tissue hypoxia and induces...Objective:Sleep apnea hypopnea syndrome (SAHS) is a common sleep disorder, which is manifested as a reduction in tidal volume or apnea during sleep, which results in intermittent hypoxia and tissue hypoxia and induces oxidative stress and inflammatory responses. Rheumatoid arthritis (RA) is a systemic disease contributing to hyperplasia of synovial membrane, cartilage erosion and joint damage. Fibroblast like synoviocytes (FLS), which make up the lining of the synovial membrane, are believed to play a role in the pathogenesis of RA. RA is a series of inflammation-like responses that induce joint damage and dysfunction and impair patients' life quality. This article first introduced the basic features of RA and analyzes the pathogenesis of RA with SAHS. Then the relationship between RA and SAHS was investigated. Finally, the progress in the treatment for RA with SAHS was reviewed emphatically.展开更多
Inflammatory diseases such as rheumatoid arthritis (RA) can lead to chronic pain and joint deformity. First line treatment includes disease-modifying antirheumatic drugs (DMARDs) to slow disease progression, but RA pa...Inflammatory diseases such as rheumatoid arthritis (RA) can lead to chronic pain and joint deformity. First line treatment includes disease-modifying antirheumatic drugs (DMARDs) to slow disease progression, but RA patients are often left with debilitating symptoms. This article explores alternative topical and naturally based options to treat RA symptoms, with supporting evidence for their use. Considered options include Aloe vera, Perillyl Alcohol (POH), Aleurites moluccana, Calendula officinalis extract (quercetin), Achyranthes species, Guizhi Shaoyao Zhimu, Curcumin (turmeric), Wutou, Radix paeoniae extract (Paeoniflorin), Tripterygium wilfordii Hook F (TWHF), Capsaicin, Cannabinoids (CBD), and Berberine. Many of these products show promising data for supplemental treatment of RA through various mechanisms, with CBD and TWHF having the most robust evidence supporting their use.展开更多
Rheumatoid Arthritis (RA) is an inflammatory disease associated with high morbidity and increased cardiovascular disease, and Metabolic Syndrome (MS) is understood as a set of metabolic disorders that correlates with ...Rheumatoid Arthritis (RA) is an inflammatory disease associated with high morbidity and increased cardiovascular disease, and Metabolic Syndrome (MS) is understood as a set of metabolic disorders that correlates with obesity and sedentary lifestyle. The aim of this study is to evaluate the prevalence of MS in a cohort of patients with RA and its correlation to specific factors of the disease. A retrospective cohort study was conducted with 283 patients with RA, followed at the Rheumatology Outpatient Clinic of the Hospital de Clínicas de Porto Alegre (HCPA) between 2008 and 2016;187 continued to be followed and agreed to be reevaluated between January and November 2016. MS was defined according to the National Cholesterol Education Program and disease activity was assessed using the Disease Activity Score (DAS28). Clinical, biochemical, and anthropometric evaluations were conducted. The prevalence of MS in the first evaluation was 43.9% and, after 8 years, 59.4%. Increased waist circumference and blood pressures, elevated triglycerides and low High-Density Lipoprotein were the most frequent features of MS. The DAS28 was significantly lower in the reevaluation (p = 0.006). The prevalence of MS was higher at the end of 8 years;disease activity, as well as blood pressure, decreased during this period. Steroid use had also decreased at the end of follow-up. There was an increase of 15% of cases with MS in an 8-year follow-up cohort of patients, which was in agreement with the current literature and showed how the inflammatory process in RA is correlated to MS. The parameters of MS that varied the most were blood pressure, cholesterol and triglycerides. Ultimately, these parameters and disease activity must be observed closely in order to improve the prognosis of patients with RA.展开更多
AIM: To evaluate the role of fluorine-18-labeled fluorodeoxyglucose positron emission tomography (18F-FDG PET) in various rheumatic diseases and its potential in the early assessment of treatment response in a limited...AIM: To evaluate the role of fluorine-18-labeled fluorodeoxyglucose positron emission tomography (18F-FDG PET) in various rheumatic diseases and its potential in the early assessment of treatment response in a limited number of patients. METHODS: This study involved 28 newly diagnosed patients, of these 17 had rheumatoid arthritis (RA) and 11 had seronegative spondyloarthropathy (SSA). In the SSA group, 7 patients had ankylosing spondylitis, 3 had psoriatic arthritis, and one had non-specific SSA. Patients with RA were selected as per the American College of Rheumatology criteria. One hour after FDG injection, a whole body PET scan was performed from the skull vertex to below the knee joints using a GE Advance dedicated PET scanner. Separate scans were acquired for both upper and lower limbs. Post-treatment scans were performed in 9 patients in the RA group (at 6-9 wk from baseline) and in 1 patient with psoriatic arthropathy. The pattern of FDG uptake was analysed visually and quantified as maximum standardized uptake value (SUVmax) in a standard region of interest. Metabolic response on the scan was assessed qualitatively and quantitatively and was correlated with clinical assessment. RESULTS: The qualitative FDG uptake was in agreement with the clinically involved joints, erythrocyte sedimentation rate, C-reactive protein values and the clinical assessment by the rheumatologist. All 17 patients in the RA group showed the highest FDG avidity in painful/swollen/tender joints. The uptake pattern was homogeneous, intense and poly-articular in distribution. Hypermetabolism in the regional nodes (axillary nodes in the case of upper limb joint involvement and inguinal nodes in lower limb joints) was a constant feature in patients with RA. Multiple other extra-articular lesions were also observed including thyroid glands (in associated thyroiditis) and in the subcutaneous nodules. Treatment response was better appreciated using SUVmax values than visual interpretation, when compared with clinical evaluation. Four patients showed a favourable response, while 3 had stable disease and 2 showed disease progression. The resolution of regional nodal uptake (axillary or inguinal nodes based on site of joint involvement) in RA following disease modifying anti-rheumatoid drugs was noteworthy, which could be regarded as an additional parameter for identifying responding patients. In the SSA group, uptake in the affected joint was heterogeneous, low grade and nonsymmetrical. In particular, there was intense tendon and muscular uptake corresponding to symptomatic joints. The patients with psoriatic arthritis showed intense FDG uptake in the joints and soft tissue. CONCLUSION: 18F-FDG PET accurately delineates the ongoing inflammatory activity in various rheumatic diseases (both at articular and extra-articular sites) and relates well to clinical symptoms. Different metabolic patterns on FDG-PET scanning in RA and SSA can have important implications for their diagnosis and management in the future with the support of larger studies. FDG-PET molecular imaging is also a sensitive tool in the early assessment of treatment response, especially when using quantitative information. With these benefits, FDG-PET could play a pivotal clinical role in the management of inflammatory joint disorders in the future.展开更多
In rheumatoid arthritis the small joints of the feet and hands are the first targets of the autoimmune process. In about one half of the patient the wrist is involved in the first stages of the disease(two years) incr...In rheumatoid arthritis the small joints of the feet and hands are the first targets of the autoimmune process. In about one half of the patient the wrist is involved in the first stages of the disease(two years) increasing up to nearly 90 percent after a decade often including both sides. Osteoarthritis of the wrist is one of the most common conditions encountered by hand surgeons. One aim of all treatment options is to achieve the best possible hand function without pain. If conservative treatment fails, operative treatment is necessary. Choice of surgical treatment depends on the soft tissue and bone situation. Techniques can be differentiated by joint preservation or joint replacement. The first include radio-synoviorthesis, synovectomy and tendon repair, the latter resection-arthroplasty, total joint arthroplasty and arthrodesis. In this paper arthrodesis of the wrist as one treatment option is reviewed.展开更多
Superficial thrombophlebitis is known as a frequent complication of Beh?et’s disease. Infliximab may promote healing of superficial thrombophlebitis in patients with Beh?et’s disease. However, thrombophlebitis as a ...Superficial thrombophlebitis is known as a frequent complication of Beh?et’s disease. Infliximab may promote healing of superficial thrombophlebitis in patients with Beh?et’s disease. However, thrombophlebitis as a complication of rheumatoid arthritis (RA) is rare and treatments have not been reported. We describe the case of a 47-year-old man with RA with complications of superficial thrombophlebitis who was treated using methotrexate and infliximab. Erythema nodosum and cord-like induration with pain in the extremities completely disappeared following a single infusion of infliximab and oral acetylsalicylic acid was not needed. This case suggests that infliximab might offer effective treatment for patients showing superficial thrombophlebitis with RA.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
Background:Despite the recent advances in treatments for rheumatoid arthritis (RA), there are still unmet needs in disease outcomes. This study aimed to analyze the satisfaction with drug therapies for RA according to...Background:Despite the recent advances in treatments for rheumatoid arthritis (RA), there are still unmet needs in disease outcomes. This study aimed to analyze the satisfaction with drug therapies for RA according to the levels of disease severity (patientassessed) and proportions of treatment cost to household income.Methods:This was a subgroup study of a cross-sectional study in patients with RA and their physicians. The patients were subdivided into different subgroups based on their self-assessed severity of RA and on the proportions of treatment cost to household income (<10%, 10-30%, 31-50%, and >50%). The Treatment Satisfaction Questionnaire for Medication version II was used to assess patients’ treatment satisfaction.Results:When considering all medications, effectiveness, convenience, and global satisfaction scores were lower in the severe and moderate RA subgroups than those in the mild and extremely mild RA subgroups (all P < 0.001). Effectiveness, side effects, and convenience scores were higher in the <10% subgroup compared to those in the >50% subgroup (all P < 0.05). Global satisfaction score was higher in the <10% subgroup than that in the 31% to 50% subgroup ( F = 13.183, P = 0.004). For biological diseasemodifying anti-rheumatic drugs, effectiveness and convenience scores were lower in the severe RA subgroup than those in the extremely mild RA subgroup (both P < 0.05). Convenience score was higher in the <10% subgroup compared to that in the 31% to 50% and >50% subgroups ( F = 12.646, P = 0.005). Global satisfaction score was higher in the <10% subgroup than that in the 31% to 50% subgroup ( F = 8.794, P = 0.032). Conclusion:Higher disease severity and higher financial burden were associated with lower patient satisfaction.展开更多
Objective: To identify the commonalities between rheumatoid arthritis (RA) and diabetes mellitus (DM) to understand the mechanisms of Chinese medicine (CM) in different diseases with the same treatment. Methods...Objective: To identify the commonalities between rheumatoid arthritis (RA) and diabetes mellitus (DM) to understand the mechanisms of Chinese medicine (CM) in different diseases with the same treatment. Methods: A text mining approach was adopted to analyze the commonalities between RA and DM according to CM and biological elements. The major commonalities were subsequently verified in RA and DM rat models, in which herbal formula for the treatment of both RA and DM identified via text mining was used as the intervention. Results: Similarities were identified between RA and DM regarding the CM approach used for diagnosis and treatment, as well as the networks of biological activities affected by each disease, including the involvement of adhesion molecules, oxidative stress, cytokines, T-lymphocytes, apoptosis, and inflammation. The Ramulus Cinnamomi-Radix Paeoniae Alba-Rhizoma Anemarrhenae is an herbal combination used to treat RA and DM. This formula demonstrated similar effects on oxidative stress and inflammation in rats with collagen-induced arthritis, which supports the text mining results regarding the commonalities between RA and DM. Conclusion: Commonalities between the biological activities involved in RA and DM were identified through text mining, and both RA and DM might be responsive to the same intervention at a specific stage.展开更多
Background:Rheumatoid arthritis (RA), a systemic autoimmune disease characterized by synovial inflammation, can cause cartilage and bone damage as well as disability. The aim of this study was to explore whether serum...Background:Rheumatoid arthritis (RA), a systemic autoimmune disease characterized by synovial inflammation, can cause cartilage and bone damage as well as disability. The aim of this study was to explore whether serum glucose-6-phosphate isomerase (GPI) is correlated with disease activity and the value of GPI in the evaluation of infliximab treatment in patients with RA.Methods:Sixty-two patients with RA who had an inadequate response to methotrexate (MTX) were enrolled in Peking University People’s Hospital from July 1, 2016 to July 31, 2018. Infliximab (3 mg/kg, intravenous at weeks 0, 2, and 6 and then every 8 weeks) was administered to patients with stable background MTX therapy. Serum samples were obtained at baseline and week 18. Serum GPI levels were determined using enzyme-linked immunosorbent assay. The associations between serum GPI levels and clinical features were analyzed.Results:Serum GPI was positively correlated with Disease Activity Score in 28 joints (DAS28), swollen joint count, tender joint count and C-reactive protein level ( P < 0.001, P < 0.001, P < 0.001, and P = 0.033, respectively). The change of DAS28 in GPI-positive patients was greater than that in GPI-negative patients ( P < 0.001). Compared with those for patients receiving MTX monotherapy at baseline, the GPI levels were significantly declined when MTX was combined with infliximab ( P < 0.001). Conclusion:Serum GPI is related to disease activity and clinical response to infliximab treatment.展开更多
Rheumatoid arthritis (RA) etiology and amelioration remains a challenge in modern therapeutics. Herein, we explored the synergistic effect of allogenic bone marrow stem cell (BMSC) translation and photodynamic tre...Rheumatoid arthritis (RA) etiology and amelioration remains a challenge in modern therapeutics. Herein, we explored the synergistic effect of allogenic bone marrow stem cell (BMSC) translation and photodynamic treatment of RA with tetra sulfonatophenyl porphyrin (TSPP) and TiO2 nanocomposites as a new strategy for RA theranostics. The translation of BMSCs with miRNAs into infected joints in long bones post-photodynamic therapy is helpful for treating and understanding RA pathophysiology. We observed that allogenic BMSC translation combined with TSPP-TiO2 nanocomposites can significantly (p 〈 0.01) lower the concentrations of serum biomarkers (tumor necrosis factor-α and interleukin-17) in a collagen induced arthritis (CIA) murine model, both in vitro and in vivo, as well as improve other parameters such as arthritis score, BMSC count, complete blood count, and numbers of platelets, red blood cells, and white blood cells. Moreover, a fluorescent TSPP in the feet or long bones and X-ray bioimaging of RA joints revealed the clinical efficacy of BMSCs combined with TSPP-TiO2 nanocomposites. Microarray data analysis illustrated that rnomir-375-3p and rno-mir-196b-3p were up-regulated by approximately 100-fold in the BMSCs of ameliorated RA post-photodynamic therapy with TSPP-TiO2 nanocomposites. Our study not only suggests a new approach for RA theranostics, but also helps in understanding RA pathophysiology.展开更多
Introduction Rheumatoid arthritis (RA) is a chronic systemic disease in which immunologically mediated inflammation of synovia-lined joints can result in marked disruption of joint structure and function. With adva...Introduction Rheumatoid arthritis (RA) is a chronic systemic disease in which immunologically mediated inflammation of synovia-lined joints can result in marked disruption of joint structure and function. With advances in our understanding of the pathogenesis of RA over the past two decades,展开更多
Rheumatoid arthritis(RA)is a chronic inflammatory disease characterized by synovitis and destruction of cartilage,promoted by sustained inflammation.However,current treatments remain unsatisfactory due to lacking of s...Rheumatoid arthritis(RA)is a chronic inflammatory disease characterized by synovitis and destruction of cartilage,promoted by sustained inflammation.However,current treatments remain unsatisfactory due to lacking of selective and effective strategies for alleviating inflammatory environments in RA joint.Inspired by neutrophil chemotaxis for inflammatory region,we therefore developed neutrophil-derived exosomes functionalized with sub-5 nm ultrasmall Prussian blue nanoparticles(uPB-Exo)via click chemistry,inheriting neutrophil-targeted biological molecules and owning excellent anti-inflammatory properties.uPB-Exo can selectively accumulate in activated fibroblast-like synoviocytes,subsequently neutralizing pro-inflammatory factors,scavenging reactive oxygen species,and alleviating inflammatory stress.In addition,uPB-Exo effectively targeted to inflammatory synovitis,penetrated deeply into the cartilage and real-time visualized inflamed joint through MRI system,leading to precise diagnosis of RA in vivo with high sensitivity and specificity.Particularly,uPB-Exo induced a cascade of anti-inflammatory events via Th17/Treg cell balance regulation,thereby significantly ameliorating joint damage.Therefore,nanoenzyme functionalized exosomes hold the great potential for enhanced treatment of RA in clinic.展开更多
Background: The impact of sex on the clinical manifestations of rheumatoid arthritis (RA) were diversely reported in the literature. The Chinese Registry of rhEumatoiD arthrITis provides a platform for the investigati...Background: The impact of sex on the clinical manifestations of rheumatoid arthritis (RA) were diversely reported in the literature. The Chinese Registry of rhEumatoiD arthrITis provides a platform for the investigation of this issue in Chinese patients.Methods: Demographic and clinical parameters were collected from all enrolled patients with RA and from patients with early RA (disease duration ≤6 months). The differences in data regarding disease activity, comorbidities, and medications for RA were compared between men and women. The proportions of patients who achieved remission and low disease activity were compared at enrollment and during 3-, 6-, and 12-month follow-up visits.Results: A total of 11,564 patients were enrolled, 83.6% of whom were female. In all the enrolled patients and patients with early RA, C-reactive protein (CRP, 12.0vs. 6.7 mg/L), pain visual analogue scale (4.8vs. 4.5), patient’s and physician’s global assessment (4.9vs. 4.5 and 4.9vs. 4.5), 28-joint disease activity score using DAS28-CRP (4.3vs. 4.0) simplified disease activity index (21.9vs. 19.9), and clinical disease activity index (19.3vs. 18.0) were significantly higher in men than in women. Additionally, the swollen joint count/tender joint count and DAS28 using erythrocyte sedimentation rate were higher in male patients than in female patients with early RA. More female patients with early RA reached the treatment target at baseline than male patients (23.4%vs. 18.2%, assessed by CDAI). At 3 months, 6 months, and 12 months, the proportion of remission and treatment target achievement was similar in both sexes. Coronary artery disease (CAD) and stroke were more frequent in men than in women.Conclusions: In Chinese patients with RA, men were found to have more active disease, as well as more cases of CAD and stroke. Therefore, sex should be carefully considered during the personalization of RA treatment.展开更多
The biological properties of therapeutic peptides,such as their pharmacokinetics and pharmacodynamics,are correlated with their structure and aggregation properties.Herein,we studied the aggregation properties of a th...The biological properties of therapeutic peptides,such as their pharmacokinetics and pharmacodynamics,are correlated with their structure and aggregation properties.Herein,we studied the aggregation properties of a therapeutic peptide(CIGB-814),currently in phase 2 clinical trial,for the treatment of rheumatoid arthritis over a wide range of concentrations(μM-mM).We applied spectroscopic techniques(fluorescence,circular dichro-ism,resonance,and dynamic light scattering),atomic force microscopy,and molecular dynamics simulations to determine the aggregation mechanism of CIGB-814.We found that the hierarchical aggregation of CIGB-814 at micromolar concentrations was initiated by the formation of peptide oligomers.Subsequently,the peptide oligomers trigger the nucleation and growth of peptide nanostructures(cac=123μM),ultimately leading to the fibrillization of CIGB-814(cac’=508μM).These results pave the way for a deeper understanding of the CIGB-814 therapeutic activity and may give important insights on its pharmacokinetics.展开更多
OBJECTIVE:To evaluate the efficacy and safety of Xinfeng capsule in patients suffering rheumatoid arthritis(RA).METHODS:A multi-center parallel-group designed,double-blind,randomized,controlled trial was conducted.Tot...OBJECTIVE:To evaluate the efficacy and safety of Xinfeng capsule in patients suffering rheumatoid arthritis(RA).METHODS:A multi-center parallel-group designed,double-blind,randomized,controlled trial was conducted.Totally 304 RA patients were assigned to two groups:one group was administered Xinfeng capsule(XFC) plus the placebo of leflunomide and the other given leflunomide(LEF) plus the placebo of XFC for twelve weeks.The clinical and laboratory parameters were compared at baseline and fourth,eighth,and twelfth weeks.RESULTS:After twelve-week treatment,patients in two groups all showed some trend of effectiveness when compared in terms of American Rheumatism Association(ACR) recommended 20%,50%,70%improvement criteria,but it was insignificant.The validity in ameliorate modified disease activity score(DAS28) and laboratory indexes as erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),rheumatoid factor(RF) were also found no difference.The score of health assessment questionnaire(HAQ),self-rating anxiety scale(SAS),self-rating depression scale(SDS) and quality of life questionnaire with rheumatoid arthritis(RAQOL)both lower than the first week and the changes showed no difference.However,the score of SDS dropped more in XFC group than in the other.A total of 147 adverse reaction cases were reported,which shows no difference between the two groups.The most common adverse reactions were hepatic impairment,anemia,leukocytopenia,epigastric discomfort and phalacrosis.CONCLUSION:XFC demonstrated better improvement in the scores of SDS and compared with those of LEF group.展开更多
文摘The therapeutic effects in treating the intermediate and late rheumatoid arthritis by supplementing the kidney and invigorating blood circulation were observed. In the 43 cases of the treatment group, No. 2 Qu Feng Shi Ling capsules (祛风湿灵胶囊2号) and Fenbid (芬必得) were prescribed, while in the 39 cases of the control group Lei Gong Teng Tablets (雷公藤总甙片) and Fenbid were given. The results showed that the total effective rate in the treatment group was more satisfactory than that in the control (P<0.05 or P<0.01). With less toxic effects, the former could better improve the local swelling and lower the blood viscosity.
文摘Background: Transcranial direct current stimulation (tDCS) has emerged as an adjuvant noninvasive neuromodulation tool to control fatigue and pain. To date, no studies have assessed the safety and efficiency of tDCS in patients with rheumatoid arthritis and with fatigue, poor quality of life, and refractory radicular pain associated with spinal stenosis. Case Presentation: An 85-year-old woman patient presented with rheumatoid arthritis in remission, refractory radicular pain-associated spinal stenosis, fatigue, and impaired quality of life. The patient underwent 16 daily sessions of tDCS intervention (2 mA, 20 min, positively and negatively charged electrodes were positioned at C1 and Fp2, respectively), in addition to simultaneous peripheral neuromuscular electrical stimulation (frequency of 100 Hz and amplitude of 500 μs). After the intervention, neither disease relapse nor clinical intercurrence occurred. Moreover, there was a significant and sustained improvement in her health-related quality of life, with a reduction in the level of pain and chronic fatigue. Conclusion: The present case report shows that tDCS is safe and may be an adjuvant tool for the treatment of pain and fatigue in patients with systemic autoimmune disease, as well as for improving quality of life. Further studies are required to corroborate this case report.
文摘Inflammatory rheumatological diseases like rheumatoid arthritis (RA) and ankylosing spondylitis/Spondyloarthritis (AS/SpA), have been treated with NSAIDs (non steroidal anti-inflammatory drugs), corticosteroids, and DMARDs (disease modifying anti-rheumatic drugs).These have been only partially effective for the management of symptoms, since they are rarely associated with the complete control of disease and rarely slow down radiological damage. Several cytokines have been implicated in the pathogenesis of the inflammation and tumor necrosis factor (TNF) is the most important. The last decade and a half has seen advances in the form of “anti-TNF” therapies for RA and AS/SpA patients which target and neutralize the TNF cytokines, and thus reduce the disease activity. Two anti-TNF therapies have been used in India for treating DMARD resistant RA and AS/SpA for the last 13 years;Infliximab and Etanercept respectively. This paper is a description of the clinical outcomes and unmet needs/toxicities associated with the treatment of RA and AS/SpA with anti-TNF therapies (Infliximab, Etanercept), at a single rheumatology center (tertiary care, super-specialty hospital, Indraprastha Apollo Hospitals, New Delhi) in north India.
文摘Biologics have greatly improved the management of rheumatoid arthritis (RA), demonstrating efficacy and safety in alleviating symptoms, inhibiting bone erosion, and preventing loss of function. Unmet therapeutic needs in RA remain;however, further advances require an understanding of issues left unaddressed under the current treatment paradigm. Most biologic-na?ve and biologic-pretreated patients who initiate a biologic therapy, for example, do not reach American College of Rheumatology 50% (ACR50) response, and few achieve remission. Responses are often not durable, prompting frequent treatment switching. Predictive markers are unavailable to guide therapy selection, and clinical trial data are lacking on whether a tumor necrosis factor inhibitor (TNFi) is the best first-line biologic and on the optimal sequence of use for the different biologics. Risk of serious infection is the major safety concern. Translating preclinical and clinical findings into new therapeutics may help address unmet needs. An increasing body of evidence indicates that the cytokine interleukin (IL)-17A represents an important therapeutic target;ongoing trials with IL-17A inhibitors will determine whether these agents can address some of the unmet needs associated with current biologics.
文摘Objective:Sleep apnea hypopnea syndrome (SAHS) is a common sleep disorder, which is manifested as a reduction in tidal volume or apnea during sleep, which results in intermittent hypoxia and tissue hypoxia and induces oxidative stress and inflammatory responses. Rheumatoid arthritis (RA) is a systemic disease contributing to hyperplasia of synovial membrane, cartilage erosion and joint damage. Fibroblast like synoviocytes (FLS), which make up the lining of the synovial membrane, are believed to play a role in the pathogenesis of RA. RA is a series of inflammation-like responses that induce joint damage and dysfunction and impair patients' life quality. This article first introduced the basic features of RA and analyzes the pathogenesis of RA with SAHS. Then the relationship between RA and SAHS was investigated. Finally, the progress in the treatment for RA with SAHS was reviewed emphatically.
文摘Inflammatory diseases such as rheumatoid arthritis (RA) can lead to chronic pain and joint deformity. First line treatment includes disease-modifying antirheumatic drugs (DMARDs) to slow disease progression, but RA patients are often left with debilitating symptoms. This article explores alternative topical and naturally based options to treat RA symptoms, with supporting evidence for their use. Considered options include Aloe vera, Perillyl Alcohol (POH), Aleurites moluccana, Calendula officinalis extract (quercetin), Achyranthes species, Guizhi Shaoyao Zhimu, Curcumin (turmeric), Wutou, Radix paeoniae extract (Paeoniflorin), Tripterygium wilfordii Hook F (TWHF), Capsaicin, Cannabinoids (CBD), and Berberine. Many of these products show promising data for supplemental treatment of RA through various mechanisms, with CBD and TWHF having the most robust evidence supporting their use.
文摘Rheumatoid Arthritis (RA) is an inflammatory disease associated with high morbidity and increased cardiovascular disease, and Metabolic Syndrome (MS) is understood as a set of metabolic disorders that correlates with obesity and sedentary lifestyle. The aim of this study is to evaluate the prevalence of MS in a cohort of patients with RA and its correlation to specific factors of the disease. A retrospective cohort study was conducted with 283 patients with RA, followed at the Rheumatology Outpatient Clinic of the Hospital de Clínicas de Porto Alegre (HCPA) between 2008 and 2016;187 continued to be followed and agreed to be reevaluated between January and November 2016. MS was defined according to the National Cholesterol Education Program and disease activity was assessed using the Disease Activity Score (DAS28). Clinical, biochemical, and anthropometric evaluations were conducted. The prevalence of MS in the first evaluation was 43.9% and, after 8 years, 59.4%. Increased waist circumference and blood pressures, elevated triglycerides and low High-Density Lipoprotein were the most frequent features of MS. The DAS28 was significantly lower in the reevaluation (p = 0.006). The prevalence of MS was higher at the end of 8 years;disease activity, as well as blood pressure, decreased during this period. Steroid use had also decreased at the end of follow-up. There was an increase of 15% of cases with MS in an 8-year follow-up cohort of patients, which was in agreement with the current literature and showed how the inflammatory process in RA is correlated to MS. The parameters of MS that varied the most were blood pressure, cholesterol and triglycerides. Ultimately, these parameters and disease activity must be observed closely in order to improve the prognosis of patients with RA.
文摘AIM: To evaluate the role of fluorine-18-labeled fluorodeoxyglucose positron emission tomography (18F-FDG PET) in various rheumatic diseases and its potential in the early assessment of treatment response in a limited number of patients. METHODS: This study involved 28 newly diagnosed patients, of these 17 had rheumatoid arthritis (RA) and 11 had seronegative spondyloarthropathy (SSA). In the SSA group, 7 patients had ankylosing spondylitis, 3 had psoriatic arthritis, and one had non-specific SSA. Patients with RA were selected as per the American College of Rheumatology criteria. One hour after FDG injection, a whole body PET scan was performed from the skull vertex to below the knee joints using a GE Advance dedicated PET scanner. Separate scans were acquired for both upper and lower limbs. Post-treatment scans were performed in 9 patients in the RA group (at 6-9 wk from baseline) and in 1 patient with psoriatic arthropathy. The pattern of FDG uptake was analysed visually and quantified as maximum standardized uptake value (SUVmax) in a standard region of interest. Metabolic response on the scan was assessed qualitatively and quantitatively and was correlated with clinical assessment. RESULTS: The qualitative FDG uptake was in agreement with the clinically involved joints, erythrocyte sedimentation rate, C-reactive protein values and the clinical assessment by the rheumatologist. All 17 patients in the RA group showed the highest FDG avidity in painful/swollen/tender joints. The uptake pattern was homogeneous, intense and poly-articular in distribution. Hypermetabolism in the regional nodes (axillary nodes in the case of upper limb joint involvement and inguinal nodes in lower limb joints) was a constant feature in patients with RA. Multiple other extra-articular lesions were also observed including thyroid glands (in associated thyroiditis) and in the subcutaneous nodules. Treatment response was better appreciated using SUVmax values than visual interpretation, when compared with clinical evaluation. Four patients showed a favourable response, while 3 had stable disease and 2 showed disease progression. The resolution of regional nodal uptake (axillary or inguinal nodes based on site of joint involvement) in RA following disease modifying anti-rheumatoid drugs was noteworthy, which could be regarded as an additional parameter for identifying responding patients. In the SSA group, uptake in the affected joint was heterogeneous, low grade and nonsymmetrical. In particular, there was intense tendon and muscular uptake corresponding to symptomatic joints. The patients with psoriatic arthritis showed intense FDG uptake in the joints and soft tissue. CONCLUSION: 18F-FDG PET accurately delineates the ongoing inflammatory activity in various rheumatic diseases (both at articular and extra-articular sites) and relates well to clinical symptoms. Different metabolic patterns on FDG-PET scanning in RA and SSA can have important implications for their diagnosis and management in the future with the support of larger studies. FDG-PET molecular imaging is also a sensitive tool in the early assessment of treatment response, especially when using quantitative information. With these benefits, FDG-PET could play a pivotal clinical role in the management of inflammatory joint disorders in the future.
文摘In rheumatoid arthritis the small joints of the feet and hands are the first targets of the autoimmune process. In about one half of the patient the wrist is involved in the first stages of the disease(two years) increasing up to nearly 90 percent after a decade often including both sides. Osteoarthritis of the wrist is one of the most common conditions encountered by hand surgeons. One aim of all treatment options is to achieve the best possible hand function without pain. If conservative treatment fails, operative treatment is necessary. Choice of surgical treatment depends on the soft tissue and bone situation. Techniques can be differentiated by joint preservation or joint replacement. The first include radio-synoviorthesis, synovectomy and tendon repair, the latter resection-arthroplasty, total joint arthroplasty and arthrodesis. In this paper arthrodesis of the wrist as one treatment option is reviewed.
文摘Superficial thrombophlebitis is known as a frequent complication of Beh?et’s disease. Infliximab may promote healing of superficial thrombophlebitis in patients with Beh?et’s disease. However, thrombophlebitis as a complication of rheumatoid arthritis (RA) is rare and treatments have not been reported. We describe the case of a 47-year-old man with RA with complications of superficial thrombophlebitis who was treated using methotrexate and infliximab. Erythema nodosum and cord-like induration with pain in the extremities completely disappeared following a single infusion of infliximab and oral acetylsalicylic acid was not needed. This case suggests that infliximab might offer effective treatment for patients showing superficial thrombophlebitis with RA.
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 work was supported by grants from the Chinese National Key Research R&D Program(Nos.2017YFC0907601,2017YFC0907604)。
文摘Background:Despite the recent advances in treatments for rheumatoid arthritis (RA), there are still unmet needs in disease outcomes. This study aimed to analyze the satisfaction with drug therapies for RA according to the levels of disease severity (patientassessed) and proportions of treatment cost to household income.Methods:This was a subgroup study of a cross-sectional study in patients with RA and their physicians. The patients were subdivided into different subgroups based on their self-assessed severity of RA and on the proportions of treatment cost to household income (<10%, 10-30%, 31-50%, and >50%). The Treatment Satisfaction Questionnaire for Medication version II was used to assess patients’ treatment satisfaction.Results:When considering all medications, effectiveness, convenience, and global satisfaction scores were lower in the severe and moderate RA subgroups than those in the mild and extremely mild RA subgroups (all P < 0.001). Effectiveness, side effects, and convenience scores were higher in the <10% subgroup compared to those in the >50% subgroup (all P < 0.05). Global satisfaction score was higher in the <10% subgroup than that in the 31% to 50% subgroup ( F = 13.183, P = 0.004). For biological diseasemodifying anti-rheumatic drugs, effectiveness and convenience scores were lower in the severe RA subgroup than those in the extremely mild RA subgroup (both P < 0.05). Convenience score was higher in the <10% subgroup compared to that in the 31% to 50% and >50% subgroups ( F = 12.646, P = 0.005). Global satisfaction score was higher in the <10% subgroup than that in the 31% to 50% subgroup ( F = 8.794, P = 0.032). Conclusion:Higher disease severity and higher financial burden were associated with lower patient satisfaction.
基金Supported by the National Natural Science Foundation of China(No.81573845,81473367,81403209,30825047)China Academy of Chinese Medical Sciences Project(No.Z0412)Beijing Nova Program(No.xx2014B073)
文摘Objective: To identify the commonalities between rheumatoid arthritis (RA) and diabetes mellitus (DM) to understand the mechanisms of Chinese medicine (CM) in different diseases with the same treatment. Methods: A text mining approach was adopted to analyze the commonalities between RA and DM according to CM and biological elements. The major commonalities were subsequently verified in RA and DM rat models, in which herbal formula for the treatment of both RA and DM identified via text mining was used as the intervention. Results: Similarities were identified between RA and DM regarding the CM approach used for diagnosis and treatment, as well as the networks of biological activities affected by each disease, including the involvement of adhesion molecules, oxidative stress, cytokines, T-lymphocytes, apoptosis, and inflammation. The Ramulus Cinnamomi-Radix Paeoniae Alba-Rhizoma Anemarrhenae is an herbal combination used to treat RA and DM. This formula demonstrated similar effects on oxidative stress and inflammation in rats with collagen-induced arthritis, which supports the text mining results regarding the commonalities between RA and DM. Conclusion: Commonalities between the biological activities involved in RA and DM were identified through text mining, and both RA and DM might be responsive to the same intervention at a specific stage.
基金This study was supported by grants from the National Natural Science and Foundation of China(Nos.81701598 and 31240023)Beijing Municipal Science and Technology Project(No.Z171100000417007)。
文摘Background:Rheumatoid arthritis (RA), a systemic autoimmune disease characterized by synovial inflammation, can cause cartilage and bone damage as well as disability. The aim of this study was to explore whether serum glucose-6-phosphate isomerase (GPI) is correlated with disease activity and the value of GPI in the evaluation of infliximab treatment in patients with RA.Methods:Sixty-two patients with RA who had an inadequate response to methotrexate (MTX) were enrolled in Peking University People’s Hospital from July 1, 2016 to July 31, 2018. Infliximab (3 mg/kg, intravenous at weeks 0, 2, and 6 and then every 8 weeks) was administered to patients with stable background MTX therapy. Serum samples were obtained at baseline and week 18. Serum GPI levels were determined using enzyme-linked immunosorbent assay. The associations between serum GPI levels and clinical features were analyzed.Results:Serum GPI was positively correlated with Disease Activity Score in 28 joints (DAS28), swollen joint count, tender joint count and C-reactive protein level ( P < 0.001, P < 0.001, P < 0.001, and P = 0.033, respectively). The change of DAS28 in GPI-positive patients was greater than that in GPI-negative patients ( P < 0.001). Compared with those for patients receiving MTX monotherapy at baseline, the GPI levels were significantly declined when MTX was combined with infliximab ( P < 0.001). Conclusion:Serum GPI is related to disease activity and clinical response to infliximab treatment.
基金This work is supported by National High-tech R&D Program of China (No. 2015AA020502) and the National Natural Science Foundation of China (Nos. 81325011, 21327902 and 21175020). M. S. acknowledges support from the NSF-PREM program (NSF Award DRM- 1523588). H. J. acknowledges support from the Fundamental Research Funds for the Central Universities (No. 2242016K41023), China.
文摘Rheumatoid arthritis (RA) etiology and amelioration remains a challenge in modern therapeutics. Herein, we explored the synergistic effect of allogenic bone marrow stem cell (BMSC) translation and photodynamic treatment of RA with tetra sulfonatophenyl porphyrin (TSPP) and TiO2 nanocomposites as a new strategy for RA theranostics. The translation of BMSCs with miRNAs into infected joints in long bones post-photodynamic therapy is helpful for treating and understanding RA pathophysiology. We observed that allogenic BMSC translation combined with TSPP-TiO2 nanocomposites can significantly (p 〈 0.01) lower the concentrations of serum biomarkers (tumor necrosis factor-α and interleukin-17) in a collagen induced arthritis (CIA) murine model, both in vitro and in vivo, as well as improve other parameters such as arthritis score, BMSC count, complete blood count, and numbers of platelets, red blood cells, and white blood cells. Moreover, a fluorescent TSPP in the feet or long bones and X-ray bioimaging of RA joints revealed the clinical efficacy of BMSCs combined with TSPP-TiO2 nanocomposites. Microarray data analysis illustrated that rnomir-375-3p and rno-mir-196b-3p were up-regulated by approximately 100-fold in the BMSCs of ameliorated RA post-photodynamic therapy with TSPP-TiO2 nanocomposites. Our study not only suggests a new approach for RA theranostics, but also helps in understanding RA pathophysiology.
基金Supported by the Administration of Traditional Chinese Medicine of Jiangsu Province(No.JD11040)
文摘Introduction Rheumatoid arthritis (RA) is a chronic systemic disease in which immunologically mediated inflammation of synovia-lined joints can result in marked disruption of joint structure and function. With advances in our understanding of the pathogenesis of RA over the past two decades,
基金Key Program of NSFC(81730067)Major Project of NSFC(81991514)+5 种基金Fundamental Research Funds for the Central Universities(14380493,14380494)National Science Foundation of China(Grant No 82002370,31800806,82000069)China Postdoctoral Science Foundation(Grant No 2019M661806)Natural science foundation of Jiangsu province(Grant No BK20200117,BK20200314),Jiangsu postdoctoral research support project(Grant No 2021K059A)Nanjing University Innovation Program for PhD candidates(CXYJ21-62)Jiangsu Provincial Key Medical Center Foundation,Jiangsu Provincial Medical Outstanding Talent Foundation,Jiangsu Provincial Medical Youth Talent Foundation,Jiangsu Provincial Key Medical Talent Foundation,Program of Innovation and Entrepreneurship of Jiangsu Province.
文摘Rheumatoid arthritis(RA)is a chronic inflammatory disease characterized by synovitis and destruction of cartilage,promoted by sustained inflammation.However,current treatments remain unsatisfactory due to lacking of selective and effective strategies for alleviating inflammatory environments in RA joint.Inspired by neutrophil chemotaxis for inflammatory region,we therefore developed neutrophil-derived exosomes functionalized with sub-5 nm ultrasmall Prussian blue nanoparticles(uPB-Exo)via click chemistry,inheriting neutrophil-targeted biological molecules and owning excellent anti-inflammatory properties.uPB-Exo can selectively accumulate in activated fibroblast-like synoviocytes,subsequently neutralizing pro-inflammatory factors,scavenging reactive oxygen species,and alleviating inflammatory stress.In addition,uPB-Exo effectively targeted to inflammatory synovitis,penetrated deeply into the cartilage and real-time visualized inflamed joint through MRI system,leading to precise diagnosis of RA in vivo with high sensitivity and specificity.Particularly,uPB-Exo induced a cascade of anti-inflammatory events via Th17/Treg cell balance regulation,thereby significantly ameliorating joint damage.Therefore,nanoenzyme functionalized exosomes hold the great potential for enhanced treatment of RA in clinic.
基金supported by grants from the Chinese National Key Technology R&D Program,Ministry of Science and Technology(Nos.2017YFC0907601,2017YFC0907602,and 2017YFC0907603)the Beijing Municipal Science and Technology Commission(Nos.Z201100005520022,23,and 25–27)the CAMS Innovation Fund for Medical Sciences(CIFMS)(No.2021-I2M-1-005).
文摘Background: The impact of sex on the clinical manifestations of rheumatoid arthritis (RA) were diversely reported in the literature. The Chinese Registry of rhEumatoiD arthrITis provides a platform for the investigation of this issue in Chinese patients.Methods: Demographic and clinical parameters were collected from all enrolled patients with RA and from patients with early RA (disease duration ≤6 months). The differences in data regarding disease activity, comorbidities, and medications for RA were compared between men and women. The proportions of patients who achieved remission and low disease activity were compared at enrollment and during 3-, 6-, and 12-month follow-up visits.Results: A total of 11,564 patients were enrolled, 83.6% of whom were female. In all the enrolled patients and patients with early RA, C-reactive protein (CRP, 12.0vs. 6.7 mg/L), pain visual analogue scale (4.8vs. 4.5), patient’s and physician’s global assessment (4.9vs. 4.5 and 4.9vs. 4.5), 28-joint disease activity score using DAS28-CRP (4.3vs. 4.0) simplified disease activity index (21.9vs. 19.9), and clinical disease activity index (19.3vs. 18.0) were significantly higher in men than in women. Additionally, the swollen joint count/tender joint count and DAS28 using erythrocyte sedimentation rate were higher in male patients than in female patients with early RA. More female patients with early RA reached the treatment target at baseline than male patients (23.4%vs. 18.2%, assessed by CDAI). At 3 months, 6 months, and 12 months, the proportion of remission and treatment target achievement was similar in both sexes. Coronary artery disease (CAD) and stroke were more frequent in men than in women.Conclusions: In Chinese patients with RA, men were found to have more active disease, as well as more cases of CAD and stroke. Therefore, sex should be carefully considered during the personalization of RA treatment.
基金This project received funding from the European Union Horizon 2020 Research and Innovation Program under the Marie Skłodowska-Curie grant agreement no.872233(“PEPSA-MATE”).GB acknowledges CINECA and the EU-PRACE program for the CPU time.FC acknowledges the funding received as an award of an RMIT senior vice chancellor fel-lowship.
文摘The biological properties of therapeutic peptides,such as their pharmacokinetics and pharmacodynamics,are correlated with their structure and aggregation properties.Herein,we studied the aggregation properties of a therapeutic peptide(CIGB-814),currently in phase 2 clinical trial,for the treatment of rheumatoid arthritis over a wide range of concentrations(μM-mM).We applied spectroscopic techniques(fluorescence,circular dichro-ism,resonance,and dynamic light scattering),atomic force microscopy,and molecular dynamics simulations to determine the aggregation mechanism of CIGB-814.We found that the hierarchical aggregation of CIGB-814 at micromolar concentrations was initiated by the formation of peptide oligomers.Subsequently,the peptide oligomers trigger the nucleation and growth of peptide nanostructures(cac=123μM),ultimately leading to the fibrillization of CIGB-814(cac’=508μM).These results pave the way for a deeper understanding of the CIGB-814 therapeutic activity and may give important insights on its pharmacokinetics.
基金Supported by the Key Projects in the National Science&Technology Pillar Program in the Twelfth Five-Year Plan Period:Clinical Research on Xin'an Medicine Prevention and Treatment of Difficult Diseases of Chinese Medicine(No.2012BA126B02).ClinicalTrials.gov Identifier:NCT01774877
文摘OBJECTIVE:To evaluate the efficacy and safety of Xinfeng capsule in patients suffering rheumatoid arthritis(RA).METHODS:A multi-center parallel-group designed,double-blind,randomized,controlled trial was conducted.Totally 304 RA patients were assigned to two groups:one group was administered Xinfeng capsule(XFC) plus the placebo of leflunomide and the other given leflunomide(LEF) plus the placebo of XFC for twelve weeks.The clinical and laboratory parameters were compared at baseline and fourth,eighth,and twelfth weeks.RESULTS:After twelve-week treatment,patients in two groups all showed some trend of effectiveness when compared in terms of American Rheumatism Association(ACR) recommended 20%,50%,70%improvement criteria,but it was insignificant.The validity in ameliorate modified disease activity score(DAS28) and laboratory indexes as erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),rheumatoid factor(RF) were also found no difference.The score of health assessment questionnaire(HAQ),self-rating anxiety scale(SAS),self-rating depression scale(SDS) and quality of life questionnaire with rheumatoid arthritis(RAQOL)both lower than the first week and the changes showed no difference.However,the score of SDS dropped more in XFC group than in the other.A total of 147 adverse reaction cases were reported,which shows no difference between the two groups.The most common adverse reactions were hepatic impairment,anemia,leukocytopenia,epigastric discomfort and phalacrosis.CONCLUSION:XFC demonstrated better improvement in the scores of SDS and compared with those of LEF group.