The aim of this study is to identify osteoarthritis (OA)-associated differentially methylated genes in human articular chondrocytes from patients with OA. DNA methylation profiling of articular ...chondrocytes from OA patients, rheumatoid arthritis (RA) patients, and controls was performed, and candidate genes were chosen for validation of gene demethylation status. The mRNA expression levels of candidate genes in chondrocytes were detected by real-time quantitative PCR. Chondrocytes from OA and RA group were treated with 5-Aza-2-deoxycytidine (5-Aza), and then the mRNA expression levels were detected. Forty-five genes with significant methylation differences between OA and control group were identified. Tumor necrosis factor receptor-associated factor 1 (TRAF1), connective tissue growth factor (CTGF), and chemokine (C-X3-C motif) ligand 1(CX3CL1) genes were hypomethylated in chondrocytes of OA and RA patients, which verified by bisulfite sequencing analysis. The mRNA expression level of TRAF1 and CTGF was significantly increased in OA and RA group (
p
< 0.05), while the expression level of CX3CL1 was only increased in OA group (
p
< 0.05). For the chondrocytes from OA and RA treated with 5-Aza, the mRNA expression level of TRAF1 and CTGF was highly increased (
p
< 0.05). It is the first time to show that TRAF1, CTGF, and CX3CL1 genes were hypomethylated in OA chondrocytes and have a consistent correlation with mRNA expression, which suggests that epigenetic changes in the methylation status of TRAF1, CTGF, and CX3CL1 contribute to the pathology of OA.
The aim of this study is to characterize the serum metabolic profiles of patients with systemic lupus erythematosus (SLE) using metabolomics.
Serum samples were collected from patients with SLE (n = ...80) and gender- and age-matched healthy controls (n = 57). Metabolite profiles were performed with gas chromatography-mass spectrometry in conjunction with multivariate statistical analysis, and possible biomarker metabolites were identified.
SLE and disease severity-related metabolic phenotypes were identified in sera. Parameters of the metabolomic model were correlated with SLEDAI (SLE disease activity index) scores in SLE. The metabolic signature of SLE patients comprised metabolite changes associated with amino acid turnover or protein biosynthesis, saccharometabolism, lipid metabolism, and gut microbial metabolism. Disease activity-related alterations included glutamate, 2-hydroxyisobutyrate, citrate, glycerol, linoleic acid, and propylparaben metabolites. Parts of endogenous metabolites related to SLE had the relationship with serum immunological parameters and organ manifestations. Moreover, receiver operating characteristic curve analysis revealed a higher diagnosis accuracy of endogenous metabolites.
Our study distinguished serum metabotypes associated with SLE and disease activities. The implementation of this metabolomic strategy may help to develop biochemical insight into the metabolic alterations in SLE.
Since the COVID-19 pandemic, several therapeutic agents have been used in COVID-19 management. However, the results were controversial. Here, we aimed to evaluate the efficacy and safety of ...hydroxychloroquine (HCQ)/chloroquine (CQ) in COVID-19.
We retrospectively reviewed the medical charts of patients with COVID-19 admitted to an inpatient ward in Wuhan from 2020/Feb/08 to 2020/Mar/05. Patients with HCQ/CQ and age, gender, disease severity matched ones without HCQ/CQ were selected at a 1:2 ratio. The clinical, laboratory and imaging findings were compared between these two groups. The multivariate linear regression analysis was performed to identify the factors that might influence patients' virus shedding periods (VSPs).
A total of 14 patients with HCQ/CQ and 21 matched ones were analyzed. The HCQ/CQ treatment lasted for an average of 10.36 ± 3.12 days. The mean VSPs were longer in the HCQ/CQ treatment group (26.57 ± 10.35 days vs. 19.10 ± 7.80 days, P = 0.020). There were 3 patients deceased during inpatient period, two patients were with HCQ/CQ treatment (P = 0.551). In the multivariate linear regression analysis, disease durations at admission (t = 3.643, P = 0.001) and HCQ/CQ treatment (t = 2.637, P = 0.013) were independent parameters for patients' VSPs. One patient with CQ had recurrent first-degree atrioventricular block (AVB) and obvious QTc elongation, another one complained about dizziness and blurred vision which disappeared after CQ discontinuation. One patient with HCQ had transient AVB.
In summary, we identify that the HCQ/CQ administration is not related to less mortality cases at later phase of COVID-19. More studies are needed to explore whether HCQ/CQ treatment would lead to SARS-Cov-2 RNA clearance delay or not.
Aim
The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) algorithm for the management of knee osteoarthritis (OA) is available ...worldwide from 2014, but in 2019 an update was published. Based on this algorithm, a Working Group (WG), including ESCEO members and Chinese experts, wished to see how the new ESCEO algorithm was perceived by Chinese experts in knee OA and how it was integrated into their clinical practice.
Methods
A WG was held between members of the international ESCEO task force and a group of Chinese experts.
Results
Non-pharmacological approach should be combined with pharmacological interventions. In step 1, symptomatic slow-acting drugs for osteoarthritis (SYSADOA) are the most important background drugs. Evidence, supported by high-quality research, is available only for crystalline glucosamine sulfate (pCGS) and chondroitin sulfate. Topical NSAIDs could be used as an additional option. In step 2, oral NSAIDs could be useful, but cardiovascular/renal/gastrointestinal profiles of the patients should be considered. Intra-articular hyaluronic acid and corticosteroids are alternative to oral NSAIDs, but the evidence is still limited. If steps 1 and 2 are not sufficient, weak opioids could be used
.
Overall, the conclusions of the ESCEO algorithm are accepted in China for products available in this country. The WG suggests the importance of economic studies, specifically made in China.
Conclusion
This work provides evidence-based advice to establish a treatment algorithm in knee OA, for practical implementation in clinical practice in China.
Behcet's disease (BD) is a chronic, multisystem-involved vasculitis and its pathogenesis remains elusive. No specific serological markers for BD diagnosis have been established. Identification of ...novel diagnostic biomarkers will be helpful in timely diagnostic and treatment for Behcet's disease.
To screen novel autoantigens or autoantibodies with potential diagnostic value in circulating immune complexes (CICs) from BD patients.
A proteomic strategy for immune complexome analysis was developed, in which CICs were separated from serum sample of 10 BD patients and 10 healthy controls and then subjected to Orbitrap mass spectrometry for autoantigen profiling. Anti-tubulin-α-1c antibody levels were further determined by enzyme-linked immunosorbent assay (ELISA) in sera of patients with BD, systemic lupus erythematosus (SLE), recurrent aphthous ulcers (RAU), ANCA associated systemic vasculitis (AASV), Takayasu's arteritis (TA) and 59 healthy controls.
A total of 17 potential antigens were identified in CICs from BD patients, but not in HC. The autoantibody to one of the identified antigens, tubulin-α-1c, was significantly increased in BD patients compared with that in healthy and disease controls. The sensitivity and specificity of tubulin-α-1c antibody in the diagnosis of BD in this study were 61.36% and 88.4%, respectively. Further analysis demonstrated that anti-tubulin-α-1c was associated with complications of deep venous thrombosis and erythema nodosum in BD. The levels of anti-tubulin-α-1c were also significantly correlated with the BD inflammation and disease activity markers ESR, CRP and BVAS.
Anti-tubulin-α-1c antibody is a promising biomarker in diagnosis and severity evaluation of BD and in indicating the risk of deep venous thrombosis and erythema nodosum. The immune complexome analysis by proteomic CIC autoantigen screening is a feasible way of identifying novel biomarkers in BD.
Although the original purpose of the systemic lupus erythematosus (SLE) classification criteria was to distinguish SLE from other mimic diseases, and to facilitate sample selection in scientific ...research, they have become widely used as diagnostic criteria in clinical situations. It is not known yet if regarding classification criteria as diagnostic criteria, what problems might be encountered? This is the first study comparing the three sets of classification criteria for SLE, the 1997 American College of Rheumatology (ACR’97), 2012 Systemic Lupus International Collaborating Clinics (SLICC’12) and 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR’19), for their ability to distinguish patients with SLE from patients with pure mucocutaneous manifestations (isolated cutaneous lupus erythematosus without internal disease, i-CLE) in the lupus disease spectrum. 1,865 patients with SLE and 232 patients with i-CLE were recruited from a multicenter study. We found that, due to low specificity, none of the three criteria are adept at distinguishing patients with SLE from patients with i-CLE. SLICC’12 performed best among the original three criteria, but if a positive ANA was removed as an entry criterion, EULAR/ACR’19 would performed better. A review of previous studies that compared the three sets of criteria was presented in this work.
Objective
The equivalence of the biosimilar HS016 to adalimumab (Humira) for the treatment of active ankylosing spondylitis (AS) patients has been previously validated. The aim was to compare the ...efficacy of HS016 and adalimumab in stratified subgroups at different time points using Health Assessment Questionnaire for Spondyloarthropathies (HAQ-S) and short form 36 (SF-36) questionnaires.
Methods
We carried out a multicenter, randomized, double-blind, parallel, positive control, phase 3 trial of patients with active AS. They were selected randomly to be subcutaneously administered 40 mg HS016 or adalimumab every 2 weeks for a total treatment period of 24 weeks in a 2:1 ratio. A health surveys were used to assess mental and physical improvements of patients as well as other factors.
Results
HAQ-S revealed that changes in scores from baseline in both groups were time dependent until 14 weeks and that during the first 4 weeks of treatment the changes declined rapidly. The SF-36 health survey revealed that both HS016 and adalimumab produced rapid beneficial effects against AS during the first 2 weeks of therapy, which gradually declined between 2 and 12 weeks and flattened out after 12 weeks until 24 weeks.
Conclusion
This trial demonstrated that both HS016 and adalimumab produced rapid improvements in symptoms during the first 2 weeks of treatment. These findings suggest that HS016 is an alternative economical treatment for Chinese AS patients producing a rapid amelioration of symptoms, aiding them to recover their lifestyle satisfaction.
Trial registration
http://www.chictr.org.cn/enindex.aspx
, ChiCTR1900022520, retrospectively registered.
Key points
• HS016 and adalimumab produced rapid AS symptom improvements during the first 2 weeks followed by a slowdown of improvements until week 4 with afterwards few improvements evaluated by HAQ-S
• The improvements according to the short form of the 36 (SF-36) questionnaires revealed similar trends as for HAQ-S
• There was no significant difference in HAQ-S and SF-36 scores between HS016 and adalimumab
Clinical case
We report a case of rheumatoid arthritis‐associated peripheral ulcerative keratitis (PUK) successfully treated with tocilizumab. Despite being treated with systemic corticosteroids and ...several disease‐modifying antirheumatic drugs, evern though received corneal transplantation, the patient was still going to lose her sight. Tocilizumab resulted in a good response with control of her systemic illness and preventing the progress of corneal lesions.
Discussion
Tocilizumab may be an additional tool for the patients with rheumatoid arthritis associated PUK that is refractory to other drugs.
(A) An invasive ulcer presented in nasal limbus with perforation and iris prolapse at 9 o'clock in the right eye of a 64‐year‐old female with rheumatoid arthritis. (B) Seven months after the treatment with tocilizumab. Corneal pannus completely covers the ulcer surface. The central depth of the anterior chamber was 4ct, anterior synechia, normal fundus.
Key points
Peripheral ulcerative keratitis is a rare complication in patients with rheumatoid arthritis and it may cause a marked decrease of visual acuity or the loss of an eye.
Tocilizumab may be an additional tool for patients with rheumatoid arthritis‐associated peripheral ulcerative keratitis that is refractory to other drugs.
Abstract
Background
Osteoarthritis (OA) is a common chronic disease in older adults. Currently, there are no effective therapies to reduce disease severity and progression of knee OA (KOA), ...particularly in mid- to late-stages. This study aims to examine the effect of methotrexate (MTX) on knee effusion-synovitis and pain in symptomatic patients with mid- to late-stage KOA.
Methods/design
This protocol describes a multicentre randomised placebo-controlled clinical trial aiming to recruit 200 participants with mid- to late-stage symptomatic KOA and with effusion-synovitis grade of ≥ 2. Participants will be randomly allocated to the MTX group (start from 5 mg per week for the first 2 weeks and increase to 10 mg per week for the second 2 weeks and 15 mg per week for the remaining period if tolerated) or the placebo group. Primary outcomes are effusion-synovitis size measured by magnetic resonance imaging (MRI) and knee pain assessed by visual analogue scale (VAS). Secondary outcomes are signal intensity alteration within infrapatellar fat pad (IPFP) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score and subscores, and the Outcome Measures in Rheumatology Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) responders. Both intention-to-treat and per-protocol analyses will be performed.
Discussion
If MTX intervention can relieve symptoms and reduce inflammation in patients with mid- to late-stage KOA, it has the potential for significant clinical and public health impact as this low-cost and commonly used intervention would delay the time to knee replacement, leading to substantial cost savings and improve quality of life.
Trial registration
ClinicalTrials.gov
NCT03815448
. Registered on 21 January 2019.
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