Safety and efficacy of peficitinib in Asian patients with rheumatoid arthritis who had an inadequate response or intolerance to methotrexate: results of a multicenter, randomized, double-blind, placebo-controlled phase 3 study.

Background: The efficacy and safety of the oral Janus kinase inhibitor peficitinib were investigated in Asian patients with rheumatoid arthritis (RA). Methods: In this double-blind, phase 3 study, patients from mainland China, Korea, and Taiwan with RA and an inadequate response/intolerance to methotrexate were randomized (1:1:1) to once-daily placebo (N = 128), peficitinib 100 mg (N = 129), or 150 mg (N = 128) in combination with non-biologic DMARDs. At Week 24, patients receiving placebo switched to peficitinib 100 mg or 150 mg. American College of Rheumatology (ACR) 20 response at Week 24/early termination (ET) was the primary endpoint. Adverse events (AEs) were assessed. The study was registered at ClinicalTrials (NCT03660059). Findings: 385 patients were included in the analysis. ACR20 responses were statistically significantly higher in both peficitinib 100 mg (56.6%) and 150 mg (56.3%) groups versus placebo (24.2%); Odds Ratio (95% confidence interval, CI) 4.14 (2.42, 7.08) and 4.07 (2.38, 6.96), respectively (both P < 0.001) at Week 24/ET. The incidence rate of herpes zoster related disease (herpes zoster and varicella) was higher in patients who received peficitinib versus placebo, but no dose dependency was observed (incidence rate/100 patient-years (95% CI): peficitinib 6.7 (4.32, 10.37); placebo 3.7 (0.93, 14.88). Interpretation: In Asian patients with RA and an inadequate response/intolerance to methotrexate, peficitinib 100 mg and 150 mg demonstrated superiority to placebo in the reduction of RA symptoms and was well tolerated. No additional benefit was observed with use of the higher peficitinib dose in this study population of predominantly Chinese patients. Funding: Astellas Pharma.

Ixekizumab for Active Radiographic Axial Spondyloarthritis in Chinese Patients: 16- and 52-Week Results from a Phase III, Randomized, Double-Blind, Placebo-Controlled Study.

INTRODUCTION: Ixekizumab, an interleukin-17A inhibitor, was efficacious and well tolerated for the treatment of active radiographic axial spondyloarthritis (r-axSpA) in international clinical studies. This phase III study aimed to determine the efficacy and safety of ixekizumab for treating Chinese patients with active r-axSpA. METHODS: Adults with active r-axSpA naïve to biologic disease-modifying antirheumatic drugs (bDMARDs), or with an inadequate response/intolerance to one tumor necrosis factor inhibitor, were randomized (1:1), double-blind, to receive ixekizumab 80 mg every 4 weeks (IXEQ4W; starting dose 160 mg), or placebo, for 16 weeks. Patients receiving placebo were then switched to IXEQ4W, and those receiving IXEQ4W continued, until week 52. The primary endpoint was the proportion of bDMARD-naïve patients achieving an Assessment of SpondyloArthritis International Society 40 (ASAS40) response at week 16. RESULTS: In total, 147 patients were randomized to receive placebo (n = 73) or IXEQ4W (n = 74). At week 16, more bDMARD-naive patients achieved ASAS40 in the IXEQ4W group (n = 66; 40.9%) than the placebo group (n = 64, 7.8%; p < 0.001). In the overall study population, ASAS40 was also achieved by more patients in the IXEQ4W group (37.8%) than the placebo group (8.2%; p < 0.001) at week 16, with a significant difference observed as early as week 1. There were significant improvements in all key secondary endpoints at week 16 with IXEQ4W versus placebo. Efficacy was sustained at week 52 in patients who continued IXEQ4W and there were also clinical improvements from weeks 16 to 52 in patients switched to IXEQ4W. The safety profile of ixekizumab was consistent with that described previously. Infections and injection-site reactions were the most frequently reported events of special interest. CONCLUSIONS: IXEQ4W was associated with rapid and significant improvements in the signs and symptoms of active r-axSpA in Chinese patients at week 16 that were sustained at week 52, with no new safety signals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT04285229.

Effect of runx2b deficiency in intermuscular bones on the regulatory network of lncRNA-miRNA-mRNA.

Intermuscular bones (IBs) are mineralized spicules that negatively impact the quality and value of fish products. Runx2b is a crucial modulator in promoting bone formation through regulating osteoblast differentiation. Previous studies suggested that loss of runx2b gene completely inhibited IBs formation in zebrafish. However, how the whole transcriptome, including mRNA and non-coding RNA (ncRNA), affects the IBs development in runx2b-/- zebrafish are not known. The aim of this study was to identify the regulatory networks of differentially expressed (DE) lncRNAs, miRNAs, and mRNAs in zebrafish with and without IBs (runx2b+/+ fish and runx2b-/- fish) utilizing high-throughput sequencing techniques. All together there are 1051 mRNAs, 456 lncRNAs, and 18 miRNAs differentially expressed were found between these two strains. The analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) has highlighted significant pathways linked to the development of IBs, specifically the TGF-beta and Wnt signaling pathways, and a number of genes concentrated on these two signaling pathways related to the formation of IBs. Further, 1989 competing endogenous RNA (ceRNA) networks were created according to the correlation among mRNAs, miRNAs and lncRNAs. The ceRNA networks results revealed 52 ceRNA pairs related to the IBs formation, consisting of 52 mRNAs, 37 lncRNAs, and 6 miRNAs. Of these, we found that dre-miR-2189 was the key element of ceRNA pairs, interacting with 19 mRNAs and 11 lncRNAs, and MSTRG.13175.1 could regulate sp7 expression by interacting with dre-miR-2189 to function in osteogenic differentiation. Subsequent experiments at the cellular level also revealed the interaction mechanism. The outcomes indicated a crucial role of miRNAs and lncRNAs in the development of fish IBs, which offer new views into the functions of ncRNAs involved in IBs formation.

Comparison of clinical characteristics between adult-onset and juvenile-onset non-radiographic axial spondyloarthritis in Chinese patients: results from the COCAS cohort.

BACKGROUND: Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease predominantly affecting the axial skeleton. We aimed to describe the clinical characteristics of patients with non-radiographic axSpA (nr-axSpA) in China and compare the differences between adult- and juvenile-onset cases. METHODS: A cross-sectional study was conducted using data from 776 patients with nr-axSpA in the Clinical Characteristic and Outcome in Chinese Axial Spondyloarthritis (COCAS) study cohort. Patients were divided into two groups including the adult-onset group (n = 662) and the juvenile-onset group (n = 114) according to age at disease onset. Baseline demographics and clinical characteristics were compared between patients with adult-onset and juvenile-onset nr-axSpA. RESULTS: Overall, the male-to-female ratio was 1.26:1, the prevalence of HLA-B27 positivity was 72.2%, and the median age at disease onset of nr-axSpA was 22 years. Nearly 75% of nr-axSpA patients had peripheral arthritis in the disease course, and the prevalence of extra-articular manifestations was 10.4%. The juvenile-onset group contained a higher proportion of men (66.7% vs. 53.9%, P = 0.011) and a longer baseline disease duration (4.0 [4.0] vs. 1.6 [3.5], P < 0.001) than the adult-onset group. A family history of spondyloarthritis was more frequent in the juvenile-onset group than in the adult-onset group (23.7% vs. 15.4%, P = 0.028), but no significant difference in the prevalence of HLA-B27 positivity was observed between the two groups (P = 0.537). Regarding initial symptoms, peripheral arthritis occurred more often in patients with juvenile-onset nr-axSpA, whereas patients with adult-onset nr-axSpA presented more frequently with axial involvement. The prevalence of inflammatory back pain (IBP) was higher in the adult-onset group than in the juvenile-onset group (85.0% vs. 75.4%, P = 0.010), whereas the juvenile-onset group showed a higher prevalence of peripheral arthritis and enthesitis than the adult-onset group (67.5% vs. 48.5%, P < 0.001; 35.1% vs. 23.3%, P = 0.007, respectively). CONCLUSIONS: Compared with adult-onset nr-axSpA, juvenile-onset nr-axSpA was more common in men and those with a family history of spondyloarthritis. Juvenile-onset nr-axSpA presents with a "peripheral predominant" mode at disease onset and a higher frequency of peripheral arthritis and enthesitis during the disease course.

Strain-Driven Bidirectional Spin Orientation Control in Epitaxial High Entropy Oxide Films.

High entropy oxides (HEOs), based on the incorporation of multiple-principal cations into the crystal lattice, offer the possibility to explore previously inaccessible oxide compositions and unconventional properties. Here it is demonstrated that despite the chemical complexity of HEOs external stimuli, such as epitaxial strain, can selectively stabilize certain magneto-electronic states. Epitaxial (Co0.2 Cr0.2 Fe0.2 Mn0.2 Ni0.2 )3 O4 -HEO thin films are grown in three different strain states: tensile, compressive, and relaxed. A unique coexistence of rocksalt and spinel-HEO phases, which are fully coherent with no detectable chemical segregation, is revealed by transmission electron microscopy. This dual-phase coexistence appears as a universal phenomenon in (Co0.2 Cr0.2 Fe0.2 Mn0.2 Ni0.2 )3 O4 epitaxial films. Prominent changes in the magnetic anisotropy and domain structure highlight the strain-induced bidirectional control of magnetic properties in HEOs. When the films are relaxed, their magnetization behavior is isotropic, similar to that of bulk materials. However, under tensile strain, the hardness of the out-of-plane (OOP) axis increases significantly. On the other hand, compressive straining results in an easy OOP magnetization and a maze-like magnetic domain structure, indicating the perpendicular magnetic anisotropy. Generally, this study emphasizes the adaptability of the high entropy design strategy, which, when combined with coherent strain engineering, opens additional prospects for fine-tuning properties in oxides.

A novel target state detection method for accurate cardiopulmonary signal extraction based on FMCW radar signals.

Frequency-modulated continuous wave radar is capable of constant, real-time detection of human presence and monitoring of cardiopulmonary signals such as respiration and heartbeat. In highly cluttered environments or when the human body moves randomly, noise signals may be relatively large in some range bins, making it crucial to accurately select the range bin containing the target cardiopulmonary signal. In this paper, we propose a target range bin selection algorithm based on a mixed-modal information threshold. We introduce a confidence value in the frequency domain to determine the state of the human target and employ the range bin variance in the time domain to determine the range bin change status of the target. The proposed method accurately detects the state of the target and effectively selects the range bin containing the cardiopulmonary signal with a high signal-to-noise ratio. Experimental results demonstrate that the proposed method achieves better accuracy in cardiopulmonary signal rate estimation. Moreover, the proposed algorithm is lightweight in data processing and has good real-time performance.

Risk factors for progression of juvenile-onset non-radiographic axial spondyloarthritis to juvenile-onset ankylosing spondylitis: a nested case-control study.

OBJECTIVE: To evaluate the clinical characteristics of juvenile-onset non-radiographic axial spondyloarthritis (nr-axSpA) and to investigate risk factors associated with progression to juvenile-onset ankylosing spondylitis (JoAS). METHODS: A nested case-control study was conducted using the retrospectively collected data of 106 patients with juvenile-onset nr-axSpA (age at disease onset, <16 years) in the Clinical characteristic and Outcome in Chinese Axial Spondyloarthritis study cohort. Baseline demographic and clinical characteristics and prognosis were reviewed. Logistic regression analyses were performed to investigate risk factors associated with progression to JoAS. RESULTS: Overall, 58.5% of patients with juvenile-onset nr-axSpA presented with peripheral symptoms at disease onset. In 82.1% of these patients, axial with peripheral involvement occurred during the disease course. The rate of disease onset at >12 years and disease duration of ≤10 years were significantly higher in those with progression to JoAS than in those without progression to JoAS (83.0% vs 52.8%, p=0.001; 92.5% vs 56.6%, p<0.001, respectively). Multivariable logistic regression analysis revealed that inflammatory back pain (IBP) (OR 13.359 (95% CI 2.549 to 70.013)), buttock pain (OR 10.171 (95% CI 2.197 to 47.085)), enthesitis (OR 7.113 (95% CI 1.670 to 30.305)), elevated baseline C reactive protein (CRP) levels (OR 7.295 (95% CI 1.984 to 26.820)) and sacroiliac joint-MRI (SIJ-MRI) positivity (OR 53.821 (95% CI 9.705 to 298.475)) were significantly associated with progression to JoAS. CONCLUSION: Peripheral involvement was prevalent in juvenile-onset nr-axSpA. IBP, buttock pain, enthesitis, elevated baseline CRP levels and SIJ-MRI positivity in patients with the disease are associated with higher risk of progression to JoAS.

Rapid Onset of Efficacy of Baricitinib in Chinese Patients with Moderate to Severe Rheumatoid Arthritis: Results from Study RA-BALANCE.

INTRODUCTION: Baricitinib is an oral, selective inhibitor of Janus kinase which demonstrates clinical efficacy in patients with rheumatoid arthritis (RA). This report aims to analyze the onset time of baricitinib in Chinese patients with moderately to severely active RA who had an inadequate response to methotrexate. METHODS: This post hoc analysis evaluated clinical improvements of Chinese patients treated with baricitinib 4 mg once daily compared with placebo, based on data from a phase 3 study RA-BALANCE. Efficacy measures including American College of Rheumatology 20% (ACR20) response, ACR core set values, Disease Activity Score modified to include the 28 diarthrodial joint count (DAS28) using high-sensitivity C-reactive protein (hsCRP), DAS28-erythrocyte sedimentation rate, Simplified Disease Activity Index, Clinical Disease Activity Index, DAS28-hsCRP ≤ 3.2 response (low disease activity), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were evaluated at weeks 1, 2, 4, 8, 12, 14, 16, 20, and 24 (except for FACIT-F evaluated every 4 weeks). A logistic regression model and an analysis of covariance model were used to analyze treatment comparisons of categorical and continuous measures, respectively. RESULTS: Statistically significant (p ≤ 0.05) improvements were observed as early as week 1 or 2 for the baricitinib group compared to placebo in almost all main efficacy measures. For other outcomes including 66 swollen joint count, 68 tender joint count, FACIT-F, and DAS28-hsCRP ≤ 3.2 response rate, differences were evident (p ≤ 0.05) by week 4 in the baricitinib group compared with placebo. Significant improvements in all efficacy measures were sustained through 24 weeks. CONCLUSIONS: Baricitinib demonstrated a rapid onset of efficacy on ACR20 response, ACR core set values, disease activity, and patient-reported outcome improvements in Chinese patients from RA-BALANCE. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02265705.

Quantum chemical calculation to elucidate the biodegradation pathway of methylphenanthrene by green microalgae.

Alkylated polycyclic aromatic hydrocarbons (APAHs) are the main components of polycyclic aromatic hydrocarbons (PAHs) in petroleum-contaminated waters. In our study, three kinds of green microalgae (Pseudokirchneriella subcapitata, Chlorella vulgaris and Scenedesmus obliquus) were shown to degrade six kinds of methylphenanthrenes (1-methylphenanthren, 2-methylphenanthrenem, 3-nmmethylphenanthrene, 4-methylphenanthren, 9-methylphenanthrene and 3,6-dimethylphenanthrene) with different degrading abilities. Among the six methylphenanthrenes, 99.8% of 1-methylphenanthrene (1-MP) was removed and 75.6% of 3,6-dimethylphenanthrene (3,6-DMP) was removed by P. subcapitata after 7 days of incubation. The metabolites of 1-MP and 3,6-DMP were identified by gas chromatograph-mass spectrometer (GC-MS). Six metabolites of 1-MP and one metabolite of 3,6-DMP were found, they were all monohydroxylated methylphenanthrenes. The -OH group was added to either methyl-group or benzene ring through the monooxygenase system, and the methyl-group attack was the main pathway. This research increases our knowledge of the degrading ability of APAHs by green microalgae and offers information for the bioremediation of APAHs. Quantum chemical calculation was conducted to elucidate the biodegradation metabolites of methylphenanthrene by green microalgae, which is a helpful tool in the bioremediation of environmental pollution.

The influence of an ultra-high resistivity Ta underlayer on perpendicular magnetic anisotropy in Ta/Pt/Co/Pt heterostructures.

Thin films with perpendicular magnetic anisotropy (PMA) play an essential role in the development of technologies due to their excellent thermal stability and potential application in devices with high density, high stability, and low energy consumption. Many studies have focused on the relationship between the resistivity of heavy metals and the PMA of the neighbouring magnetic metals in magnetic multi-layered films. However, reports on the effects of heavy metals non-adjacent to the magnetic metals on the PMA are rare. Herein, we demonstrate the influence of the heavy metal Ta underlayer non-adjacent to the magnetic Co layer on the PMA and thermal stability in the Ta/Pt/Co/Pt heterostructures. A type of amorphous Ta film having an ultra-high resistivity (ρ max = 3.9 × 105 µΩ cm) was optimized by DC sputtering at a high sputtering Ar pressure, low sputtering power, and large target-to-substrate distance. The value of resistivity is three orders of magnitude higher than that of the ß-Ta underlayer. We found that this special Ta underlayer can effectively improve the PMA and thermal stability of the magnetic Co layer based on the anomalous Hall and planar Hall effect measurements. The maximum magnetic anisotropic field reaches 1.1 T at a low temperature. It is very likely that the ultra-high resistivity leads to the increase in the additional electron scattering in the Ta/Pt interface, while the latter results in the enhancement of the PMA and thermal stability in the structure. These results reveal the inherent relationship between the resistivity of the heavy metal underlayer and PMA, and provide a novel approach to improve the PMA and thermal stability of heavy metal/magnetic metal multi-layered films.

IBI303, a biosimilar to adalimumab, for the treatment of patients with ankylosing spondylitis in China: a randomised, double-blind, phase 3 equivalence trial.

BACKGROUND: China approved adalimumab for the treatment of ankylosing spondylitis in 2013. However, the cost of the standard dose regimen exceeds ¥15 000 (around US$2250) per month, which is well beyond affordability for most Chinese patients. No biosimilars of adalimumab are available in China; IBI303 is a monoclonal antibody against TNFα that is currently in development. This study aimed to assess the clinical equivalence of IBI303 to adalimumab in patients with ankylosing spondylitis. METHODS: This phase 3, multicenter, double-blind, parallel, randomised controlled equivalence trial was done in 20 centers across China. Patients were randomly assigned in a 1:1 ratio to receive either 40 mg of IBI303 or 40 mg of adalimumab as a subcutaneous injection every 2 weeks until week 22. Patients were eligible for inclusion if they were between 18 and 65 years old, fulfilled the 1984 Modified New York Criteria for ankylosing spondylitis, were non-responders, inadequate responders, or intolerant to treatment with NSAIDs for 4 or more weeks, and had active ankylosing spondylitis defined by two or more indicators of disease severity. The investigators, site staff, patients, sponsors, and the contract research organisation were masked to treatment allocation. The primary outcome was the proportion of patients who met the Assessment of SpondyloArthritis international Society (ASAS) Response Criteria for a 20% improvement (ASAS20) at week 24 after treatment. Equivalence was established if the 95% CI of the difference in responses between groups was between -15% and 15%. Efficacy analyses were done in the full analysis population and in the per-protocol population. Safety analyses were done in all randomly assigned patients who received at least one drug dose. This trial is registered with ClinicalTrials.gov, number NCT02893254. FINDINGS: Between Sept 22, 2016, and May 11, 2018, 438 patients were randomly allocated either to the biosimilar IBI303 group (n=220) or the adalimumab group (n=218). In the full analysis population, 165 (75%) of 220 patients in the IBI303 group (95% CI 68·7-80·6) and 158 (72%) of 218 patients in the adalimumab group (66·0-78·3) reached the primary outcome of ASAS20 at week 24. The difference between the two groups was 2·3% with a 95% CI of -5·9 to 10·6, which fell within the pre-specified equivalence boundaries at week 24 (-15 to 15). In the per-protocol population, 163 (80%) of 203 patients in the IBI303 group reached ASAS20 at week 24 (95% CI 74·1-85·5), compared with 150 (80%) of 188 patients in the adalimumab group (73·3-85·3%). The difference between the groups was 0·6% with a 95% CI of -7·4 to 8·6%, which also fell within the pre-specified equivalence boundaries at week 24. Safety and tolerability profiles were similar between the two groups; 174 (79%) of 220 patients in the IBI303 group and 178 (82%) of 218 patients in the adalimumab group had treatment-emergent adverse events. INTERPRETATION: This trial showed therapeutic equivalence of IBI303 and adalimumab in the treatment of ankylosing spondylitis. The efficacy, safety, and immunogenicity of both drugs are highly similar. IBI303 could be an alternative treatment option for patients with ankylosing spondylitis in China. FUNDING: Innovent Biologics, National Major Scientific and Technological Special Project for "Significant New Drugs Development".

Natural Porphyrins Accelerating the Phototransformation of Benzo[a]pyrene in Water.

Phototransformation is one of the most important transformation pathways of organic contaminants in the water environment. However, how active compounds enable and accelerate the phototransformation of organic pollutants remains to be elucidated. In this study, the phototransformation of benzo[a]pyrene (BaP, the first class "human carcinogens") by various natural porphyrins under solar irradiation was investigated, including chlorophyll a, sodium copper chlorophyllin, hematin, cobalamin, and pheophorbide a. Transformation efficiency of BaP varied considerably with chemical stabilities of the porphyrins. Porphyrins with a lower stability displayed higher BaP transformation efficiencies. BaP transformation had a significant positive correlation with the production of singlet oxygen. Identical phototransformation products of BaP were observed for all investigated porphyrins, and the main products were identified as BaP-quinones, including BaP-1,6-dione, BaP-3,6-dione, and BaP-6,12-dione. The mechanism of natural porphyrins accelerating the BaP phototransformation in water was proposed to proceed via the photocatalytic generation of singlet oxygen resulting in the transformation of BaP to quinones.

Bone edema on magnetic resonance imaging is highly associated with low bone mineral density in patients with ankylosing spondylitis.

OBJECTIVE: This study aimed to assess the relationship between bone marrow edema (BME) on magnetic resonance imaging (MRI) and bone mineral density (BMD) in patients with ankylosing spondylitis (AS). METHODS: The study included 333 patients with AS who underwent BMD measurements and axial MRI. Additionally, 106 normal controls were included. The modified New York criteria were used as the classification criteria of AS. Clinical, laboratory, and imaging data were collected and analyzed. Lumbar spine and proximal femur BMD were assessed using dual-energy X-ray absorptiometry. Low BMD was defined by a Z-score ≤-2. The Spondyloarthritis Research Consortium of Canada (SPARCC) MRI index was used to assess inflammation at the sacroiliac joint (SIJ) and spine. RESULTS: Among the 333 patients, the male:female ratio was 4.6:1, mean patient age was 28.5±10.6 years, and mean disease duration was 7.3±6.8 years. The prevalences of low BMD, osteopenia, and osteoporosis were significantly higher among AS patients than among controls (19.8%, 62.8%, and 5.7% vs. 4.7%, 33.0%, and 0%, respectively, P = 0.000). The BMD values were significantly lower and prevalences of low BMD at both the spine and femur were significantly higher among patients with BME on MRI than among those without BME. Multivariate logistic regression analysis showed that male sex (OR 3.87, 95% CI 1.21-7.36, P = 0.023), high ASDAS-CRP score (OR 2.83, 95% CI 1.36-4.76, P = 0.015), the presence of BME on sacroiliac MRI (OR 2.83, 95% CI 1.77-6.23, P = 0.000) and spinal MRI (OR 4.06, 95% CI 1.96-8.46, P = 0.000), and high grade of sacroiliitis (OR 2.93, 95% CI 1.82-4.45, P = 0.002) were risk factors for low BMD (any site). The SPARCC scores of the SIJ were negatively correlated with femoral BMD (r = -0.22, 95% CI -0.33 to -0.10, P = 0.000). Additionally, the SPARCC scores of the spine were negatively correlated with BMD values (r = -0.23, 95% CI -0.36 to -0.09, P = 0.003) and Z-scores (r = -0.24, 95% CI -0.36 to -0.12, P = 0.001) at the spine. CONCLUSION: Low BMD is common in AS patients. BME on MRI is highly associated with low BMD at both the spine and femur.

Immunohistological analysis of active sacroiliitis in patients with axial spondyloarthritis.

The sacroiliac joints (SIJs) are one of the most common sites involved in axial spondyloarthritis (axSpA), and there are few studies on the histopathology of the SIJ in this group of patients.Mononuclear cell infiltrates in the bone marrow and fibrous tissue resembling a pannus formation were the pathological features of early sacroiliitis in our previous study. We undertook a further immunohistological evaluation of these features in patients with axSpA.Biopsy specimens from the SIJ of 6 patients with established ankylosing spondylitis (AS) and 13 patients with nonradiographic axial spondyloarthritis (nr-axSpA) were analyzed. An immunohistological method was performed to examine the macrophages (CD163), T cells (CD3), and B cells (CD20).Mononuclear cell infiltrates in the bone marrow were observed in only 6 patients with nr-axSpA. Fibrous tissue was observed in all patients with established AS and 9 patients with nr-axSpA. Macrophage, T cell, and B cell infiltrates could be detected in both the bone marrow and fibrous tissue. All bone marrow specimens from 6 nr-axSpA patients exhibited CD163+ macrophage infiltrates; of these, 5 exhibited CD20+ B cell infiltrates and 3 exhibited CD3+ T cell infiltrates. Among the fibrous tissue specimens, all exhibited macrophage infiltrates, 9 exhibited B cell infiltrates, and 4 exhibited T cell infiltrates.In addition to macrophages and T cells, B cells are also involved in active sacroiliitis in patients with axSpA.

Bone Mineral Density in Patients With Rheumatoid Arthritis and 4-Year Follow-up Results.

BACKGROUND: Osteoporosis is a common complication in patients with rheumatoid arthritis (RA). The change of bone mineral density (BMD) in patients with RA is slow, and little data are known about the long-term change of BMD. OBJECTIVES: This study aimed to determine the frequency of osteoporosis and the long-term change on BMD in a cohort of Chinese patients with RA routinely receiving calcium and vitamin D supplementation. METHODS: A total of 304 consecutive patients with RA were recruited. Bone mineral density measurements of the forearm, lumbar spine, and total hip were performed by dual-energy x-ray absorptiometry and compared with 200 age- and sex-matched healthy controls. Risk factors were analyzed by logistic regression models. RESULTS: The prevalence of osteoporosis at all measured sites in patients with RA was statistically significantly higher than in healthy controls. A total of 107 patients of the cohort had a mean of 4 years of follow-up. More patients with BMD decrease were found without calcium and vitamin D use compared with those who continuously took calcium and vitamin D (64.3% vs 19.8% at the forearm and 28.6% vs 16.1% at the total hip, respectively). Only the use of calcium and vitamin D supplementation was associated with a decreased risk of BMD decrease both at the forearm and at the total hip. CONCLUSIONS: Osteoporosis is common in Chinese patients with RA. Routine use of calcium and vitamin D supplementation decreased the risk of BMD decrease and should be recommended for all patients with RA.

A long-term, observational cohort study on the safety of low-dose glucocorticoids in ankylosing spondylitis: adverse events and effects on bone mineral density, blood lipid and glucose levels and body mass index.

OBJECTIVES: This study aimed to investigate the risk of adverse events and effects on bone mineral density (BMD), blood lipid and glucose levels and body mass index (BMI) of low-dose glucocorticoid (GC) treatment in ankylosing spondylitis. DESIGN: We performed a retrospective, observational cohort study. Adverse effects were compared between GC users and non-GC users, and we analysed differences in the duration of GC exposure (no GC exposure, <6 months, 6 months to 2 years and >2 years). SETTING: Outpatient clinic in a tertiary general hospital in China, rheumatology follow-up visits over the past 30 years. PARTICIPANTS: We included 830 patients with ankylosing spondylitis who were followed up for at least 6 months without a previous history or current complications of active gastrointestinal problems, hypertension, psychiatric or mental problems, diabetes mellitus, tuberculosis and hepatitis. The median follow-up time was 1.6 years (range 0.5-15 years, a total of 1801 patient-years). RESULTS: A total of 555 (66.9%) patients were treated with low-dose GCs, and the median cumulative duration of GC therapy was 1.3 years (range 0.1-8.5 years). Dermatological incidents, including acne, bruisability and cutaneous infections, were the most common adverse events, with a cumulative incidence rate of 5.4% (22.2 events per 1000 patient-years), followed by a puffy and rounded face (1.6%), symptoms of weight gain (1.1%) and serious infections (1.0%). The rates of all other types of adverse events were less than 1%. The GC groups (GC users and non-GC users) and the duration of GC therapy were not associated with the frequency of low BMD, dyslipidaemia, hyperglycaemia or obesity (p<0.05). CONCLUSIONS: Adverse events during long-term treatment of low-dose GCs are limited. Low-dose GCs do not have an adverse effect on BMD, blood lipid and glucose levels and BMI.

Prevalence and risk factors of osteoporosis in patients with ankylosing spondylitis: a 5-year follow-up study of 504 cases.

OBJECTIVES: The objective of this study was to assess the prevalence and risk factors of osteoporosis (OP) in patients with ankylosing spondylitis (AS). METHODS: Demographic and clinical data of 504 AS patients were collected. Bone mineral density (BMD) measurements of the lumbar spine, proximal femur and forearm were performed by dual-energy x-ray absorptiometry at baseline and follow-up. 106 cases of sex- and age-matched healthy volunteers were enrolled as normal controls. RESULTS: In contrast to normal controls, AS patients displayed a higher prevalence of both OP (9.7% vs. 0%) and osteopenia (57.5% vs. 34.9%). The prevalence of OP was significantly higher and the BMD were significantly lower in patients with elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) than patients with normal ESR and CRP. Juvenile onset, morning stiffness lasting over 0.5 hours and elevated ESR levels were risk factors for bone loss at the lumbar spine; Male gender, older age, hip involvement and lack of regular treatment were risk factors for bone loss at the femur. 173 cases were followed up for 1 to 5 years, BMD changes per year at the lumbar spine, femur and forearm were 4.8%, 2.7%, and 2.6% respectively. There was no significant difference in annual BMD change between patients treated with or without low dose glucocorticoids (GCs). Hip involvement and persistent elevated ESR levels, but not GCs treatment, were associated with decreased BMD at both the lumbar spine and the femur during follow-up in longitudinal regression analysis. CONCLUSIONS: High disease activity and hip involvement are risk factors of bone loss in patients with AS. Low-dose GCs treatment in AS does not increase the risk of OP.

Arylamine N-acetyltransferase polymorphisms in Han Chinese patients with ankylosing spondylitis and their correlation to the adverse drug reactions to sulfasalazine.

BACKGROUND: Polymorphisms of Arylamine N-acetyltransferase (NAT) that contribute to diverse susceptibilities of some autoimmune diseases are also linked to the metabolism of several drugs including sulfasalazine (SSZ). The aim of this study was to investigate the distribution of NAT polymorphisms in Han Chinese patients with ankylosing spondylitis (AS) and their correlation to sulfasalazine-induced adverse drug reactions (ADRs). METHODS: Arylamine N-acetyltransferase 1 (NAT1) and arylamine N-acetyltransferase 2 (NAT2) genotypes were determined in 266 AS patients who received SSZ treatment and 280 healthy controls. The correlation between NAT polymorphisms and SSZ-induced ADRs was analyzed. RESULTS: The co-occurrence frequency of NAT2 fast acetylator genotype and NAT1*10/NAT1*10 genotype was lower in AS patients than in controls. No positive correlations were detected between NAT polymorphisms and AS clinical features. The prevalence of SSZ-induced ADRs and drug withdrawal was 9.4% and 7.1%, respectively. The frequencies of overall ADRs, dose-related ADRs, and termination of drug treatment because of intolerance were higher in the NAT2 slow acetylator genotype carriers than in the fast-type carriers and in those with co-existence of NAT1 and NAT2 slow acetylator genotypes. Furthermore, the ADRs emerged earlier in the AS cases carrying both NAT1 and NAT2 slow acetylator genotypes. CONCLUSIONS: The prevalence of co-occurring NAT2 fast acetylator genotype and NAT1*10/NAT1*10 genotype was lower in AS patients than in controls. The NAT2 slow acetylator genotype and co-existing NAT1 and NAT2 slow acetylator genotypes appear to be associated with higher risks of SSZ-induced ADRs.

Design of the high-resolution soft X-ray imaging system on the Joint Texas Experimental Tokamak.

A new soft X-ray diagnostic system has been designed on the Joint Texas Experimental Tokamak (J-TEXT) aiming to observe and survey the magnetohydrodynamic (MHD) activities. The system consists of five cameras located at the same toroidal position. Each camera has 16 photodiode elements. Three imaging cameras view the internal plasma region (r/a < 0.7) with a spatial resolution about 2 cm. By tomographic method, heat transport outside from the 1/1 mode X-point during the sawtooth collapse is found. The other two cameras with a higher spatial resolution 1 cm are designed for monitoring local MHD activities respectively in plasma core and boundary.

Ten years' experience with needle biopsy in the early diagnosis of sacroiliitis.

OBJECTIVE: To evaluate the usefulness of needle biopsy in the diagnosis of early sacroiliitis to improve the diagnostic level and outcome of ankylosing spondylitis (AS). METHODS: One hundred nine patients in whom early AS was highly suspected, but in whom only sacroiliitis of grade I or lower on radiography/computed tomography (CT) was seen, were recruited for study. CT-guided needle biopsy of the sacroiliac joints was performed, and the patients were followed up for 5-10 years. RESULTS: Of the 109 patients, magnetic resonance imaging (MRI) was used to confirm the presence or absence of sacroiliitis in 77 patients. Of these, 23 patients were determined to have sacroiliitis on MRI, and 54 had no sacroiliitis on MRI. Needle biopsy was performed on all 109 patients. Features of inflammation were found in 85 patients, which included all 23 patients with MRI evidence of sacroiliitis and 38 of the 54 patients without MRI evidence of sacroiliitis. No features of inflammation were found on needle biopsy in 24 of the patients, including the remaining 16 patients who did not have sacroiliitis on MRI. The sensitivity and specificity of MRI for the early diagnosis of sacroiliitis in these patients were 37.7% and 100%, respectively. Thirty-four patients with pathologic evidence of sacroiliitis were followed up for 5-10 years. At the study end point, 16 of these 34 patients continued to show grade I or lower changes on CT, and 18 had changes of grade II or higher. These 18 patients included 7 of the 8 patients with evidence of sacroiliitis on MRI and 6 of the 20 patients confirmed not to have MRI evidence of sacroiliitis at baseline. CONCLUSION: MRI, though of low sensitivity, is specific for the diagnosis of early sacroiliitis. Sacroiliitis can be detected earlier by needle biopsy than by MRI.