Publications by authors named "Xiao Ming Shu"

23 Publications

  • Page 1 of 1

Clinical characteristics of anti-isoleucyl-tRNA synthetase antibody associated syndrome and comparison with different patient cohorts.

Clin Exp Rheumatol 2021 Jun 8. Epub 2021 Jun 8.

Department of Rheumatology, China-Japan Friendship Hospital, Beijing, China.

Objectives: This study aimed to analyse the clinical features of anti-isoleucyl-tRNA synthetase (OJ) antibodies in Chinese patients and to compare with previously published cohorts. We reviewed the clinical data of anti-OJ antibody positive patients, including their long-term follow-up.

Results: Anti-OJ antibodies were present in 10 of 1269 (0.8%) patients with idiopathic inflammatory myopathies (IIMs), and 10/320 (3.1%) patients with anti-synthetase syndrome (ASS). Of the anti-OJ antibody-positive patients, 90% had interstitial lung disease (ILD), of whom three (30%) developed rapidly progressive ILD (RP-ILD). Half (50%) of the patients were febrile and developed myocardial involvement; 40% of patients experienced myositis, mechanic's hands and arthritis. Compared to the anti-Jo-1 group, the levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in the anti-OJ antibody-positive group were higher (p<0.05). From a review of the literature regarding the clinical features of anti-OJ, fever was more common in the eastern cohort (41.7% vs. 8.3%, p=0.002), whereas patients in western countries were more likely to develop arthritis (20.9% vs. 58.1%, p=0.001). With complete follow-up of the present cohort, 80% improved with treatment, including one patient who underwent lung transplant.

Conclusions: The anti-OJ antibody occurred infrequently in Chinese patients, ILD was the major clinical feature, but myocardial injury was also a prominent associated complication. Anti-OJ positive patients were responsive to treatment.
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June 2021

Identification of a novel autoantibody against heat shock factor 1 in idiopathic inflammatory myopathy.

Clin Exp Rheumatol 2020 Nov-Dec;38(6):1191-1200. Epub 2020 Mar 5.

Department of Rheumatology, Beijing Key Lab for Immune-Mediated Inflammatory Diseases, China-Japan Friendship Hospital, Beijing, China.

Objectives: Myositis autoantibodies show great utility in the diagnosis and clinico-serological phenotyping of idiopathic inflammatory myopathy (IIM). We identified a novel autoantibody against heat shock factor 1 (HSF1) and further evaluated its disease specificity and clinical significance in IIM patients.

Methods: A human protein microarray was used to identify autoantibodies in myositis sera. ELISA, immunoblot and dot blot assays were applied to examine anti-HSF1 autoantibodies in IIM patients and controls. Immunofluorescence was used to detect HSF1 expression in muscle tissues.

Results: Anti-HSF1 was identified as a novel autoantibody by protein microarray and the seroreactivity was confirmed by immunoprecipitation, ELISA, immunoblot and dot blot assays. Anti-HSF1 autoantibodies were present in 64/581 (11.0%) IIM, 4/37 (10.8%) rheumatoid arthritis, 5/40 (12.5%) primary Sjögren's syndrome, 2/40 (5%) systemic lupus erythematosus, while largely negative in healthy controls. Anti-HSF1 autoantibodies were significantly associated with pruritus, hypergammaglobulinaemia, and elevated erythrocyte sedimentation rate in IIM patients. Anti-HSF1 autoantibodies were more prevalent in cancer-associated myositis (CAM) compared to non-CAM patients (17.2% vs. 7.5%, p=0.009), nevertheless were undetectable in cancer controls. Meanwhile, cross-sectional and longitudinal analyses revealed positive correlations between anti-HSF1 levels and disease activity in IIM patients without cancer. Additionally, increased expression of HSF1 was found in regenerating muscle cells of myositis muscle tissues.

Conclusions: These data reveal anti-HSF1 as a new autoantibody associated with CAM in IIM. The autoimmunity against HSF1 may be involved in the immunopathogenesis of myositis.
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December 2020

[Removal and Influence of Ciprofloxacin in a Membrane Bioreactor].

Huan Jing Ke Xue 2018 Jan;39(1):212-218

Zhejiang Provincial Key Laboratory of Water Science and Technology, Department of Ecological Environment, Yangtze Delta Region Institute of Tsinghua University, Jiaxing 314006, China.

A membrane bioreactor (MBR) was used to treat ciprofloxacin (CIP)-contaminated artificial wastewater. The pollutant removal performance and the microbial community structure of the MBR were studied at three different CIP dosages (0 mg·L, 5 mg·L, and 10 mg·L). The results showed that the sludge concentration in the reactor decreased and then levelled off as the dosage of CIP was increased from 0 mg·L to 5 mg·L and further to 10 mg·L. The mean removal of TOC and COD decreased from 98.40% and 97.80% to 84.20% and 94.10%, respectively, indicating that the CIP negatively influenced the organic removal but the effect was minor. In contrast, the ammonium removal was greatly influenced by the dosage of CIP. When the CIP dosage increased from 0 mg·L to 5 mg·L and further to 10 mg·L, the ammonium removal efficiency decreased from 96.91% to 84.14% and then to 77.80%, and the activity of , , , and were greatly inhibited. The CIP removal initially increased and then decreased. The mass balance revealed that the removal of CIP in the MBR was principally attributed to biodegradation and sludge adsorption, which accounted for 30.13% and 0.25%, respectively, at a CIP dosage of 5 mg·L and 7.55% and 1.81% at a CIP dosage of 10 mg·L.
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http://dx.doi.org/10.13227/j.hjkx.201704059DOI Listing
January 2018

[Influence of Ciprofloxacin on the Microbial Community and Antibiotics Resistance Genes in a Membrane Bioreactor].

Huan Jing Ke Xue 2018 Mar;39(3):1333-1341

Zhejiang Provincial Key Laboratory of Water Science and Technology, Department of Environment in Yangtze Delta Region Institute of Tsinghua University, Zhejiang, Jiaxing 314006, China.

A membrane bioreactor (MBR) was used to treat ciprofloxacin (CIP)-contaminated artificial wastewater. The microbial community structure and the abundance of antibiotic resistant genes (ARGs) in the MBR were studied at four CIP dosages (0, 5 mg·L, 10 mg·L, and 15 mg·L). The results showed that Proteobacteria and Bacteroidetes remained the dominant phylum, with relative abundances of 57.5% and 12.7%, respectively, as the dosage of CIP was increased from 0 mg·L to 15 mg·L. Rhodocyclaceae, Chitinophagaceae, and Comamonadaceae became the dominant family with abundances of 29.96%, 5.44%, and 6.60%, respectively. , and became the dominant genus, with relative abundances of 21.70%, 7.56%, 5.24%, and 4.15%, respectively. The decrease of Chao1, ACE, and Shannon and the increase of Simpson indicated a decrease in microbial abundance and diversity. The relative abundances of , and decreased, which caused a decrease in the NH-N removal rate. A CIP-ARGs analysis revealed that the relative abundances of , and were increased, beginning after the sludge was dosed with 5 mg·Lof CIP for 33 days, which augmented the risk for microbial drug-resistance.
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http://dx.doi.org/10.13227/j.hjkx.201706179DOI Listing
March 2018

The prevalence and clinical significance of anti-PUF60 antibodies in patients with idiopathic inflammatory myopathy.

Clin Rheumatol 2018 Jun 15;37(6):1573-1580. Epub 2018 Mar 15.

Department of Rheumatology, Beijing Key Lab for Immune-Mediated Inflammatory Diseases, China-Japan Friendship Hospital, Yinghua East Road, Chaoyang District, Beijing, 100029, China.

Autoantibodies against poly-U-binding factor 60 kDa protein (PUF60) have been reported in Caucasian dermatomyositis (DM) patients. However, their clinical significance in idiopathic inflammatory myopathy (IIM) remains to be fully clarified. Our objective was to analyze the prevalence and clinical significance of anti-PUF60 antibodies in a large cohort of Chinese IIM patients. In our study, 388 IIM patients, 301 disease controls, and 167 healthy controls (HCs) were involved. An enzyme-linked immunosorbent assay (ELISA) was developed to detect serum anti-PUF60 levels and was validated using immunoblotting methods. Unpaired Mann-Whitney U test and Spearman correlation analysis were used when appropriate. Anti-PUF60 antibodies were observed in IIM patients at a frequency of 10.6% (41/388). Subgrouping analysis revealed that the prevalence of anti-PUF60 antibodies was 10% in DM, 5.5% in polymyositis (PM), 10% in immune-mediated necrotizing myositis (IMNM), and 26.5% in myositis-overlap syndrome. Anti-PUF60 antibodies were also observed in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren's syndrome (SS) patients at a positive rate of 17.3, 14.5, and 10.1% respectively. Intriguingly, anti-PUF60 antibodies were frequently observed in clinically amyopathic dermatomyositis (CADM) patients and DM patients without currently known myositis autoantibodies. Furthermore, DM patients with anti-PUF60 antibodies had higher prevalence of skin ulcerations. Moreover, longitudinal investigation in eight DM patients with anti-PUF60 antibodies revealed that the antibodies levels decreased with disease remission. Anti-PUF60 antibodies were nonspecific for myositis, since they could be detected in other rheumatic diseases. Further investigation of anti-PUF60 antibodies may reveal shared pathogenic pathways in systemic autoimmune disorders.
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http://dx.doi.org/10.1007/s10067-018-4031-4DOI Listing
June 2018

A simple method for removing low-density granulocytes to purify T lymphocytes from peripheral blood mononuclear cells.

J Zhejiang Univ Sci B 2017 Jul;18(7):605-614

Department of Rheumatology, China-Japan Friendship Hospital, Beijing 100029, China.

Objective: Low-density granulocytes (LDGs) can form neutrophil extracellular traps (NETs) spontaneously and excessively. When peripheral blood mononuclear cells (PBMCs) are used for studying T lymphocytes, LDGs contained in the PBMCs may decrease the threshold of activating T lymphocytes by forming NETs. This study focused on the profiles of LDGs in common autoimmune diseases and methods for removing LDGs from PBMCs.

Methods: The percentages of LDGs in PBMCs from 55 patients with dermatomyositis (DM), 15 with polymyositis (PM), 42 with rheumatoid arthritis (RA), 25 with systemic lupus erythematosus (SLE), and 19 healthy controls were determined by flow cytometry. Three methods of removing LDGs were explored and compared. After removal, PBMCs from six patients with positive T-SPOT.TB were tested again to find out if LDGs contained in the PBMCs could influence T lymphocyte reactions.

Results: Significantly higher LDG percentages were found in PBMCs from patients with DM ((8.41±10.87)%, P<0.0001), PM ((8.41±10.39)%, P<0.0001), RA ((4.05±6.97)%, P=0.0249), and SLE ((7.53±11.52)%, P=0.0006), compared with the controls ((1.28±0.73)%). The T-SPOT.TB values significantly decreased after LDGs were removed. Increasing relative centrifugal force (RCF) within a limited range can decrease the LDG percentage from an initial high level, but not markedly increase the LDG clearance rate. Compared with the whole blood sediment method, the PBMC adherence method can significantly remove LDGs yet scarcely influence the T lymphocyte percentage in PBMCs.

Conclusions: The LDG percentage in PBMCs is significantly increased in patients with SLE, DM, PM, and RA. The influence of LDGs on T lymphocytes cannot be ignored in PBMC cultures. The adherence method is a simple and easy-to-use method for removing LDGs and purifying T lymphocytes from PBMCs.
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http://dx.doi.org/10.1631/jzus.B1600064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498841PMC
July 2017

Transcriptomic profiling of long non-coding RNAs in dermatomyositis by microarray analysis.

Sci Rep 2016 09 8;6:32818. Epub 2016 Sep 8.

Department of Rheumatology, China-Japan Friendship Hospital, Beijing, China.

Long non-coding RNAs (lncRNAs) are prevalently transcribed in the genome and have been found to be of functional importance. However, the potential roles of lncRNAs in dermatomyositis (DM) remain unknown. In this study, a lncRNA + mRNA microarray analysis was performed to profile lncRNAs and mRNAs from 15 treatment-naive DM patients and 5 healthy controls. We revealed a total of 1198 lncRNAs (322 up-regulated and 876 down-regulated) and 1213 mRNAs (665 up-regulated and 548 down-regulated) were significantly differentially expressed in DM patients compared with the healthy controls (fold change>2, P < 0.05). Subgrouping DM patients according to the presence of interstitial lung disease and anti-Jo-1 antibody revealed different expression patterns of the lncRNAs. Pathway and gene ontology analysis for the differentially expressed mRNAs confirmed that type 1 interferon signaling was the most significantly dysregulated pathway in all DM subgroups. In addition, distinct pathways that uniquely associated with DM subgroup were also identified. Bioinformatics prediction suggested that linc-DGCR6-1 may be a lncRNA that regulates type 1 interferon-inducible gene USP18, which was found highly expressed in the perifascicular areas of the muscle fibers of DM patients. Our findings provide an overview of aberrantly expressed lncRNAs in DM muscle and further broaden the understanding of DM pathogenesis.
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http://dx.doi.org/10.1038/srep32818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015085PMC
September 2016

[Removal of AOX, Chroma and TOC in Chemical Dyestuff Wastewater with Iron Scraps-Fenton-Coagulation Combined Process].

Huan Jing Ke Xue 2016 Jul;37(7):2618-2624

Zhejiang Provincial Key Laboratory of Water Science and Technology, Department of Ecological Environment, Yangtze Delta Region Institute of Tsinghua University, Jiaxing 314006, China.

Iron scraps-Fenton-coagulation process was applied to chemical dyestuff wastewater. The removal performance of absorbable organic halogens(AOX), chroma and total organic carbon (TOC) was investigated at different molar ratios of Fe to HO (1:3-1:15), iron scraps reaction time (2-5 h) and Fenton reaction time (20-80 min). The results showed that the removal ratios of AOX, chroma and TOC firstly increased and then decreased with the decrease of the molar ratio of Fe to HO, while continuously increased with the increase of iron scraps and Fenton reaction time. The optimal condition was determined as Fe:HO ratio of 1:8, iron scraps reaction time of 4 h and Fenton reaction time of 60 min, under which 94.2% of AOX, 93.7% of chroma and 27.2% of TOC were removed. A comparison study revealed that the iron scraps-Fenton-coagulation combined process could achieve much better removal of AOX, chroma and TOC than any other single or combined processes of iron treatment, Fenton oxidation and coagulation. GC-MS analysis revealed that halogenated compounds and anilines were efficiently removed, as well as nitrobenzenes, phenols, benzaldehydes, ethers, nitriles and heterocyclic compounds.·OH was found to devote much in the Fenton reaction according to the tert-butyl alcohol trapping hydroxyl radicals test.
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http://dx.doi.org/10.13227/j.hjkx.2016.07.026DOI Listing
July 2016

[Removal of AOX and Chroma in Biologically Treated Effluent of Chemical Dyestuff Wastewater with Nanoscale Ni/Fe].

Huan Jing Ke Xue 2016 Feb;37(2):655-61

Nanoscale Ni/Fe was applied to biologically treated effluent of chemical dyestuff wastewater. The removal rates of absorbable organic halogens (AOX) and chroma were investigated at different Ni loadings (0-5%), initial wastewater pH (4.1-10.0), Ni/Fe dosage (1-5 g x L(-1)) and reaction time (0.5-96 h). The results showed that the removal rates of AOX and chroma firstly increased and then decreased with the increase of the Ni loading, while continuously increased with the decrease of the initial wastewater pH and the increase of Ni/Fe dosage. The optimal condition was Ni loading of 1%, initial wastewater pH of 4.1 and Ni/Fe dosage of 3 g x L(-1), under which 29.2% of AOX and 79.6% of chroma were removed after 24 h reaction, and 50.6% of AOX and 80.7% of chroma were removed after 96 h reaction. GC-MS analysis revealed that toxicants such as chlorinated anilines, p-nitroaniline, 4-methoxy-2-nitroaniline and halogenated hydrocarbons were efficiently removed.
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February 2016

[AOX Pollution in Wastewater Treatment Process of Dyeing and Dyestuff Chemical Industries].

Huan Jing Ke Xue 2015 Sep;36(9):3304-10

Selecting six large-scale dyeing factories and four large-scale dyestuff chemical factories in the well-developed Yangtze River Delta region, this study aimed to investigate the AOX pollution status in the raw wastewater as well as in the activated sludge treatment system. The components of AOX were characterized by GC-MS. Results showed that AOX concentration was low in wastewater from the six dyeing enterprises, ranging 0. 15-1. 62 mg.L-1 in the raw wastewater and 0. 06-1. 30 mg.L-1 in the biologically treated effluent. All the biologically treated effluent met the emission limits of 8 mg.L-1 in the Discharge Standard of Water Pollutants for Dyeing and Finishing of Textile Industry. Sludge in five factories with AOX was below 621 mg.kg-1, only one factory was with high AOX concentration of 3 280 mg.kg-1. By comparison, AOX concentration greatly varied between the wastewater from dyestuff chemical factories, was 1. 70 mg.L-1 to 78. 72 mg.L-1 in the raw wastewater and was 1. 88 mg.L-1 to 33. 11 mg.L-1 in the biologically treated effluent. AOX concentration in the activated sludge was as high as 960-2,297 mg.kg-1. Chlorobenzenes, chloronitrobenzenes, chloroanilines, chlorine nitroanilines and halophenols were typical TOX components detectable in the dyestuff chemical wastewater. Halophenols and chlorine nitroanilines could be efficiently removed. Single chloroanilines and single chloronitrobenzenes seemed to be easier removable than polychlorinated anilines and polychlorinated nitrobenzenes. Polychlorinated benzenes were also easily removal but the products chlorobenzene was hard to remove.
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September 2015

Ginsenoside Rg1 relieves tert-Butyl hydroperoxide-induced cell impairment in mouse microglial BV2 cells.

J Asian Nat Prod Res 2015 14;17(9):930-45. Epub 2015 May 14.

a Key Laboratory of State Administration of Traditional Chinese Medicine of China, Department of Pathophysiology , School of Medicine, Institute of Brain Research, Jinan University , Guangzhou 510632 , China.

Microglial activation plays an important role in neurodegenerative diseases associated with oxidative stress. tert-Butyl hydroperoxide (t-BHP), an analog of hydroperoxide, mimics the oxidative damage to microglial cells. It has been reported that ginsenoside Rg1 (G-Rg1), an active ingredient of Panax ginseng, has anti-stress and anti-inflammatory properties. The present study aims to investigate the ability of G-Rg1 to decrease the t-BHP-mediated cell damage of BV2 microglial cells. We performed flow cytometry assays to facilitate the detection of reactive oxygen species as well as Western blotting analyses and immunofluorescence assays using specific antibodies, such as antibodies against phospho-mitogen-activated protein kinases (p-MAPKs), phospho-nuclear factor-κB (p-NF-κB), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X (Bax), Caspase-3, autophagy marker light chain 3 (LC3), and Becline-1. We found that treatment with 50 μM G-Rg1 protected microglial cells against oxidative damage induced by 10 μM t-BHP.
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http://dx.doi.org/10.1080/10286020.2015.1031117DOI Listing
December 2015

Elevated Serum Levels of Soluble CD163 in Polymyositis and Dermatomyositis: Associated with Macrophage Infiltration in Muscle Tissue.

J Rheumatol 2015 Jun 15;42(6):979-87. Epub 2015 Apr 15.

From the Department of Rheumatology, China-Japan Friendship Hospital, Beijing, China.Q.L. Peng, MS; Y.L. Zhang, MD; X.M. Shu, MD; H.B. Yang, MS; L. Zhang, MD; F. Chen, MD; X. Lu, MD; G.C. Wang, MD, Department of Rheumatology, China-Japan Friendship Hospital.

Objective: To investigate serum levels of soluble CD163 (sCD163) in patients with polymyositis (PM) and dermatomyositis (DM), and to correlate these to clinical manifestations and laboratory data.

Methods: Serum levels of sCD163 were detected in 24 patients with PM, 84 patients with DM, and 46 healthy controls by using the ELISA method. Immunohistochemistry staining of macrophage infiltration in muscle tissue using anti-CD163 monoclonal antibody was conducted on muscle biopsy specimens from 13 patients with PM and 17 with DM.

Results: Serum levels of sCD163 were significantly increased in patients compared with healthy controls (p < 0.001). Patients with interstitial lung disease (ILD) had statistically higher sCD163 levels than patients without ILD (p < 0.001). High serum sCD163 levels were associated with increased incidence of antinuclear antibody (p < 0.05), higher serum levels of immunoglobulin G (p < 0.01) and immunoglobulin A (p < 0.05), and increased erythrocyte sedimentation rates (p < 0.01). Serum sCD163 levels were inversely correlated with CD3+ T cell counts in peripheral blood of patients (r = -0.306, p < 0.01). Cross-sectional assessment and longitudinal study revealed a significant correlation between serum sCD163 levels and disease activity. Patients with high serum sCD163 levels showed a higher incidence of CD163+ macrophage infiltration in muscle tissue than patients with normal sCD163 levels (chi-square value = 10.804, p < 0.01).

Conclusion: Serum levels of sCD163 were significantly elevated and correlated with disease severity in patients with PM/DM, suggesting serum sCD163 as a promising biomarker in the disease evaluation of PM/DM. Our finding of elevated serum sCD163 levels associated with muscle macrophage infiltration highlights the role activated macrophage plays in the pathogenesis of PM/DM.
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http://dx.doi.org/10.3899/jrheum.141307DOI Listing
June 2015

B-cell activating factor as a serological biomarker for polymyositis and dermatomyositis.

Biomark Med 2014 ;8(3):395-403

Department of Rheumatology, China-Japan Friendship Hospital, Ying Hua East Road, Chao Yang District, Beijing 100029, China.

Aim: To investigate serum levels of B-cell activating factor (BAFF) in the patients with polymyositis (PM) and dermatomyositis (DM), and to systematically examine the association between serum BAFF levels and disease activity in PM/DM patients.

Patients & Methods: A cross-sectional analysis included 92 PM/DM patients and 25 healthy control subjects. A longitudinal study followed 24 patients. Serum BAFF concentrations were detected by the ELISA method.

Results: Serum BAFF levels in PM/DM patients were significantly higher than those in healthy controls. A cross-sectional assessment revealed a modest correlation between serum BAFF levels and global disease activity and a mild correlation between serum BAFF levels and muscle disease activity. The longitudinal study showed that serum BAFF levels modestly correlated with global disease activity and muscle disease activity.

Conclusion: Resulting data showed high serum BAFF levels in PM/DM patients and suggested BAFF as a serological biomarker for PM/DM disease activity.
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http://dx.doi.org/10.2217/bmm.13.124DOI Listing
November 2014

Expression of tumor necrosis factor-like weak inducer of apoptosis and fibroblast growth factor-inducible 14 in patients with polymyositis and dermatomyositis.

Arthritis Res Ther 2014 Jan 27;16(1):R26. Epub 2014 Jan 27.

Introduction: The aim of this study was to investigate the expression of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) in patients with polymyositis (PM) and dermatomyositis (DM), and their relation to clinical manifestations.

Methods: Serum levels of TWEAK were detected in 98 PM/DM patients and 37 healthy controls by using the ELISA method. Total RNA isolated from fresh-frozen muscle tissue samples of 36 PM/DM patients and 10 healthy controls were used for analyzing the mRNA levels of TWEAK and Fn14 by quantitative reverse transcription polymerase chain reaction (RT-PCR). Immunofluorescence staining of TWEAK and Fn14 was conducted on muscle biopsy specimens from 23 PM/DM patients and seven healthy controls.

Results: Serum levels of TWEAK were significantly decreased in the PM/DM patients compared to those in the healthy controls (P < 0.001), and serum TWEAK levels negatively correlated with serum CD163 levels in PM/DM patients (r = -0.49, P < 0.001). The expression of Fn14 mRNA was significantly increased in the muscle tissue of PM/DM patients than in the muscle tissue of healthy controls (P < 0.01), whereas the expression of TWEAK mRNA in PM/DM patients was not statistically different from that of the healthy controls (P > 0.05). Fn14 mRNA levels in muscle tissue positively correlated with muscle disease activity (r = 0.512, P < 0.01). Patients with oropharyngeal dysphagia had significantly higher Fn14 mRNA levels than patients without oropharyngeal dysphagia (P < 0.05). The results of immunofluorescence staining showed that 19 out of 23 PM/DM patients were TWEAK-positive, and 20 out of 23 PM/DM patients were Fn14-positive. No detectable expressions of TWEAK or Fn14 were observed in the healthy controls.

Conclusions: TWEAK-Fn14 axis may be involved in the pathogenesis of PM/DM. Further understanding of TWEAK-Fn14 function in PM/DM may help to define therapeutic targets for PM/DM.
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http://dx.doi.org/10.1186/ar4454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3978894PMC
January 2014

Left ventricular diastolic dysfunction -- early cardiac impairment in patients with polymyositis/dermatomyositis: a tissue Doppler imaging study.

J Rheumatol 2013 Sep 1;40(9):1572-7. Epub 2013 Aug 1.

Department of Rheumatology, China-Japan Friendship Hospital, Beijing, China.

Objective: To investigate early cardiac involvement in patients with polymyositis/dermatomyositis (PM/DM), and to evaluate the risk factors for early cardiac impairment.

Methods: The study population included 46 patients with PM/DM who did not have overt cardiovascular manifestations and 21 age- and sex-matched healthy controls. Traditional echocardiography and tissue Doppler imaging (TDI) were used to evaluate cardiac function in both groups. Clinical characteristics were recorded. Multivariate logistics regression analysis was applied to investigate risk factors for early cardiac impairment in patients with PM/DM.

Results: No significant difference was found between patients and controls by traditional echocardiography. However, compared to controls, PM/DM patients had a significantly lower ratio of early diastolic mitral annulus velocity to late diastolic mitral annulus velocity (Em/Am; 1.23 ± 0.52, 1.79 ± 0.37, respectively; t = -4.485, p < 0.001) and a higher ratio of peak early diastolic transmitral flow velocity to Em (E/Em; 8.26 ± 2.57, 6.76 ± 1.17; t = 3.287, p < 0.05) as found by TDI measurements. There was no significant difference between the TDI variables of patients with PM and DM. The multivariate regression analysis showed that female sex (OR 11.044, 95% CI 1.066-114.357, p = 0.044), late onset (OR 1.157, 95% CI 1.047-1.278, p = 0.004), and duration of disease (OR 1.060, 95% CI 1.008-1.115, p = 0.023) were risk factors for abnormal left ventricular filling pressures.

Conclusion: TDI is useful for detecting early cardiac impairment in patients with PM/DM. Left ventricular diastolic dysfunction is an early feature of cardiac involvement. Female sex, late onset, and long course of disease are 3 independent risk factors for predicting left ventricular diastolic dysfunction in patients with PM/DM.
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http://dx.doi.org/10.3899/jrheum.130044DOI Listing
September 2013

[Surfactant proteins-A and D as important serum markers for interstitial lung disease in patients with polymyositis or dermatomyositis].

Zhonghua Yi Xue Za Zhi 2012 Aug;92(31):2182-5

Graduate School, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.

Objective: To explore the possible diagnostic values of serum surfactant protein-A (SP-A) and surfactant protein-D (SP-D) for interstitial lung diseases (ILD) in patients with polymyositis or dermatomyositis (PM/DM).

Methods: Serum MCP-1 concentrations were measured by enzyme-linked immunosorbent assay (ELISA) in 100 adult PM/DM patients, 20 patients with pulmonary infection and 42 healthy controls. And the association with their clinical features and serum levels of SP-A and SP-D was analyzed.

Results: The serum levels of SP-A and SP-D in the PM/DM patients with ILD were both significantly higher than those without ILD and healthy controls (all P < 0.01) while there were no significance differences with those with infectious lung diseases (P > 0.05). The sensitivity of serum abnormal levels of SP-A, SP-D and combination of SP-A and SP-D for ILD in PM/DM patients were 66.1%, 64.3% and 80.0% and the specificity 72.7%, 72.7% and 70.2% respectively. The serum levels of SP-A were positively correlated with serum ferritin and C-reactive protein (CRP) and negatively with percent carbon monoxide diffusing capacity (DLCO%) (r = -0.474, P < 0.05), VC% (r = -0.404, P < 0.05) while the serum levels of SP-D were negatively correlated with circulating CD3+T cells (r = -0.244, P < 0.05) and CD4+T cells (r = -0.277, P < 0.05) in PM/DM patients. Furthermore, SP-A was an independent risk factor for death of ILD in PM/DM (OR 1.032, 95%CI 1.006 - 1.059, P < 0.05).

Conclusion: SP-A and SP-D may be potential useful serum markers for the diagnosis of ILD in PM/DM patients. And the combined detection of SP-A and SP-D offers a higher sensitivity than either marker alone. As a risk factor, serum SP-A can predict the prognosis of PM/DM patients with ILD.
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August 2012

Clinical significance of peripheral blood lymphocyte subsets in patients with polymyositis and dermatomyositis.

Clin Rheumatol 2012 Dec 30;31(12):1691-7. Epub 2012 Aug 30.

Department of rheumatology, China-Japan Friendship hospital, Yinghua East road, Chaoyang district, Beijing, China.

Peripheral blood lymphocyte subsets were determined by flow cytometry in 89 Chinese patients with polymyositis (PM) and dermatomyositis (DM). We aimed to investigate the clinical significance of peripheral blood lymphocyte subsets in PM/DM. Patients with active DM showed significant decreases in numbers of CD3(+) cells, CD3(+)CD4(+) cells, and CD3(+)CD8(+) cells, as compared to patients with inactive DM and healthy controls (P < 0.05). CD3(+) and CD3(+)CD4(+) cell counts were significantly lower in DM before treatment, compared with after treatment (t = -5.714 and -3.665, P < 0.05). Counts of CD3(+) cells, CD3(+)CD4(+) cells, CD3(+)CD8(+) cells, and CD19(+)CD5(-) cells were all correlated with the total disease activity score as determined by the Myositis Disease Activity Assessment Visual Analogue Scale (P < 0.05). The decreased number of CD3(+) cells and the decreased percentage of CD3(+)CD4(+) cells were additionally correlated with the presence of interstitial lung disease in PM/DM (P < 0.05). The presence of levels of CD3(+)CD8(+) cells was risk factor for death (b = -0.011, OR = 0.989, P < 0.05). The identification of peripheral blood T lymphocyte subsets in PM/DM appears to be useful as a reference marker in the evaluation of clinical disease activity, and be useful in the comprehensive assessment of clinical lung involvement. A decrease in CD8(+) T cells may predict a poor outcome in patients with PM/DM.
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http://dx.doi.org/10.1007/s10067-012-2075-4DOI Listing
December 2012

[The levels and clinical significance of serum B cell activating factor in Chinese patients with polymyositis or dermatomyositis].

Zhonghua Nei Ke Za Zhi 2012 Mar;51(3):210-3

Department of Rheumatology and Immunology, China-Japan Friendship Hospital, Beijing 100029, China.

Objectives: To investigate serum levels of B cell activating factor (BAFF) in Chinese patients with polymyositis (PM) or dermatomyositis (DM), and analyze the correlation of BAFF with autoantibodies and clinical phenotypes.

Methods: Serum BAFF levels of 28 PM patients and 30 DM patients (study group), and 25 matched healthy controls (control group) were measured by ELISA. Serum anti-Jo-1 antibody levels were also measured by ELISA in all the subjects. The results of the two groups were compared by unpaired t test and the relevance was analyzed by Pearson's correlation analysis.

Results: Serum levels of BAFF in PM/DM patients were significantly higher compared to healthy controls (P = 0.000), but there was no statistically significant difference between the PM and DM patients (P > 0.05). Patients with interstitial lung disease (ILD) had significantly higher serum BAFF level than the patients without ILD (P = 0.000) or the controls (P = 0.000). Serum BAFF levels of patients with positive anti-nuclear antibody (ANA) were significantly higher than those with negative ANA (P = 0.003). For patients with anti-Jo-1 antibodies, the serum BAFF levels were correlated with the serum concentration of anti-Jo-1 antibodies (r = 0.799, P = 0.006).

Conclusions: Serum levels of BAFF are increased in Chinese PM/DM patients. These findings indicate that BAFF may be possibly enrolled in the pathogenesis of PM/DM. Detecting serum BAFF levels could have some implication for the diagnosis and treatment of PM/DM.
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March 2012

[Measurement and clinical significance of serum monocyte chemoattractant protein-1 in patients with polymyosits/dermatomyosits].

Beijing Da Xue Xue Bao Yi Xue Ban 2012 Apr;44(2):204-8

Department of Rheumatology, China-Japan Friendship Hospital, Beijing 100029, China.

Objective: To analyze the correlated clinical significance by testing the serum monocyte chemoattractant protein-1 (MCP-1) levels of patients with polymyositis/dermatomyositis (PM/DM).

Methods: The sera from 100 adult PM/DM patients, 20 patients with pulmonary infection and 42 healthy controls were selected. The serum MCP-1 concentrations were detected by enzyme-linked immunosorbent assay (ELISA). The correlations between serum MCP-1 levels and clinical features or laboratory examinations of PM/DM patients were investigated.

Results: The serum levels of MCP-1 were (1 869 ±1 590) ng/L, (1 349±1 303) ng/L, (493±255) ng/L and (256±144) ng/L in PM/DM patients with interstitial lung disease (ILD) and without ILD, patients with infectious lung disease and healthy controls, respectively. Serum MCP-1 levels in the PM/DM patients with ILD were significantly higher than those of the PM/DM patients without ILD, patients with infectious lung disease and healthy controls (all P values<0.01). Significant correlations were found between the elevated levels of serum MCP-1 and the presence of ILD in the patients with PM/DM (χ2=9.6, P<0.01). The sensitivity and specificity of serum abnormal MCP-1 levels for ILD in the patients with PM/DM were 60.7% and 68.2%, respectively. The incidence of fever, arthritis, decreased %DL(CO) , erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and serum ferritin were significantly higher in the MCP-1 raised group than in the MCP-1 normal group (all P values<0.005). Additionally, Spearman rank correlation analysis showed that serum MCP-1 levels were positively correlated with serum ferritin in peripheral blood in the patients with PM/DM.

Conclusion: The levels of serum MCP-1 are significantly elevated in PM/DM and it is significantly associated with ILD complication, and may contribute to the early differentiation of ILD from lung infectious disease.
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April 2012

Intravenous immunoglobulin therapy in adult patients with polymyositis/dermatomyositis: a systematic literature review.

Clin Rheumatol 2012 May 26;31(5):801-6. Epub 2012 Jan 26.

Department of Rheumatology, China-Japan Friendship Hospital, Yinghua East Road, Chaoyang District, Beijing 100029, China.

The objectives of this study are to review and summarize published information on the use, effectiveness, and adverse effects of intravenous immunoglobulin (IVIG) in patients with polymyositis (PM) or dermatomyositis (DM) and to search MEDLINE and CNKI (Chinese) databases from 1985 to 2011 to retrieve clinical research articles concerning IVIG in adult patients with PM/DM. Of the 14 articles selected, two were randomized controlled trials, nine prospective open studies, and three retrospective studies with a total of 308 adult patients. IVIG has been used successfully in the treatment of PM/DM. The standard dose is 2 g/kg, given in two to five individual daily doses. The course of IVIG treatment is usually 3~6 months. IVIG therapy seemed rarely employed as first-line therapy in PM/DM. In a double-blind study conducted in patients with refractory DM, IVIG combined with corticosteroid significantly improved muscle strength and decreased serum creatine kinase level, compared with placebo. The beneficial effect of IVIG in refractory, flare-up, rapidly progressive, or severe PM/DM has been documented in many open-label trials. IVIG was shown to be effective in most of PM/DM patients with lung involvement and esophageal involvement. In some patients, IVIG can lower the corticosteroid dose required for maintenance, demonstrating the most effective steroid-sparing effect. Adverse effects were generally tolerable. IVIG is effective in the treatment of adult patients with PM/DM and appears to be relatively well tolerated and safe. IVIG may be a good choice especially in patients with refractory, flare-up, rapidly progressive, or severe PM/DM, and can be tried in patients with a contraindication for corticosteroid.
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http://dx.doi.org/10.1007/s10067-012-1940-5DOI Listing
May 2012

Clinical characteristics and favorable long-term outcomes for patients with idiopathic inflammatory myopathies: a retrospective single center study in China.

BMC Neurol 2011 Nov 9;11:143. Epub 2011 Nov 9.

Department of Rheumatology, China-Japan Friendship Hospital, the Ministry of Health, Chao Yang District, 100029, Beijing, China.

Background: Little is known about the clinical features and true survival risk factors in Chinese Han population. We conducted the current study to investigate the clinical features, long-term outcome and true potential indicators associated with mortality of idiopathic inflammatory myopathies (IIM) in China.

Methods: We restrospectvely investigated 188 patients diagnosed with IIM at our hospital from January 1986 to April 2009. The primary outcome was determined with mortality. The secondary outcomes for survival patients were organ damage and disease activity, health status, and disability, which were assessed with Myositis Damage Index, Myositis Disease Activity Assessment Visual Analogue Scales, Health Assessment Questionnaire Disability Index, and the Modified Rankin Scale, respectively. Potential prognostic factors for mortality were analyzed with the multivariate Cox regression model.

Results: Mean age at disease onset was 43.8 ± 15.8 years and male to female ratio was 1:2.1 in this cohort. The 1-, 5-, 10-, 15- and 20-year survival rates were 93.6%, 88.7%, 81%, 73.6% and 65.6%. The independent predicators for mortality were age at disease onset [hazard ratio (HR):1.05, 95% CI 1.02 - 1.08], presence of cancer (HR:3.68, 95%CI 1.39 - 9.74), and elevated IgA level at diagnosis (HR:2.80, 95% CI 1.16-6.74). At the end of the follow-up, 29 patients manifested drug withdrawal within an average 4.1 years (range 0.5-15.2 year), most patients (85.9%) had no disease activity and 130 patients (83.4%) had no disability.

Conclusions: The long-term outcomes of IIM patients in our cohort have improved dramatically. Those patients most likely to survive had a high chance of reaching stable disease status, and obtained long-term or possibly permanent remission to a large extent.
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http://dx.doi.org/10.1186/1471-2377-11-143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3226631PMC
November 2011

[Myositis disease activity tool in Chinese patients with polymyositis/dermatomyositis].

Zhonghua Yi Xue Za Zhi 2011 May;91(19):1328-30

Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.

Objective: To test the reliability, discriminating validity and clinical value of myositis disease activity tool in Chinese patients with polymyositis/dermatomyositis (PM/DM).

Methods: Fifty-four PM/DM patients (PM, n = 18; DM, n = 36) at our hospital between January 2009 and June 2010 were enrolled into this prospective study. The disease activity was assessed by the MDAAT (myositis disease activity assessment tool). The reliability and discriminating validity were assessed with test-retest reliability, interrater reliability and t-test analysis.

Results: The reliability analysis of MDAAT indicated 8 items (constitutional, cutaneous, skeletal, gastrointestinal, pulmonary, cardiovascular, muscular & global) had excellent reliability, the ICC (intraclass correlation coefficient) was 0.72 (95%CI: 0.57, 0.83), 0.88 (95%CI: 0.79, 0.93), 0.83 (95%CI: 0.72, 0.90), 0.62 (95%CI: 0.42, 0.76), 0.81 (95%CI: 0.70, 0.89), 0.59 (95%CI: 0.38, 0.74), 0.85 (95%CI: 0.75, 0.91) and 0.84 (95%CI: 0.73, 0.90) respectively. MDAAT had excellent discrimination validity in all items except for cardiovascular ones.

Conclusion: With excellent reliability and discriminating validity, MDAAT may be used to assess the disease activity and therapeutic effects of Chinese PM/DM patients.
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May 2011

Autophagy inhibition enhances etoposide-induced cell death in human hepatoma G2 cells.

Int J Mol Med 2011 Apr 27;27(4):599-606. Epub 2011 Jan 27.

Graduate School, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, P.R. China.

Induction of autophagy usually acts as a survival mechanism of cancer cells in response to chemotherapy. However, the function and molecular mechanism of autophagy in human hepatoma cells under drug treatment is still not clear. To address this issue, we established an experimental model in which HepG2 cells were treated with etoposide, a widely used anticancer agent. We demonstrate the etoposide-induced accumulation of GFP-LC3 dots by fluorescent microscopy, the up-regulation of LC3-II protein expression by Western blotting and the increased number of autophagic vacuoles by electron microscopy, confirming the activation of autophagy by etoposide in HepG2 cells. Inhibition of autophagy by either 3-methyladenine (3MA) or beclin-1 small interfering RNA enhanced etoposide-induced cell death. Furthermore, activation of p53 and AMPK was detected in etoposide-treated cells and inhibition of AMPK triggered apoptosis through suppression of autophagy. On the other hand, inactivation of p53 promoted cell survival through augmentation of autophagy. Collectively, these findings indicate that etoposide-induced autophagy promotes hepatoma cell adaptation and survival, and that autophagy inhibition improves the chemotherapeutic effect of etoposide. Moreover, AMPK activation is clearly associated with etoposide-induced autophagy. We conclude that manipulation of AMPK may be a promising approach of adjuvant chemotherapy for hepatocellular carcinoma.
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http://dx.doi.org/10.3892/ijmm.2011.607DOI Listing
April 2011
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