المؤلفون: Ma, Xinlei, Yang, Fan, Wu, Jinzhi, Xu, Bei, Jiang, Mengdi, Sun, Yiduo, Sun, Chuanying, Yu, Ye, Xu, Danyi, Xiao, Lanlan, Ren, Chunyun, Chen, Chunyan, Ye, Zi, Liang, Junyu, Lin, Jin, Chen, Weiqian

المساهمون: Natural Science Foundation of China, Key Technologies Research and Development Program

المصدر: PLOS Medicine ; volume 20, issue 6, page e1004249 ; ISSN 1549-1676

الوصف: Background Polymyalgia rheumatica (PMR) is a common inflammatory disease in elderly persons whose mechanism of pathogenesis has not been elucidated. Glucocorticoids are the main first-line treatments but result in numerous side effects. Therefore, there is a need to explore pathogenetic factors and identify possible glucocorticoid-sparing agents. We aimed to study the pathogenetic features of the disease and assess the efficacy and safety of Janus tyrosine kinase (JAK)-inhibitor tofacitinib in patients with PMR. Methods and findings We recruited treatment-naïve PMR patients from the First Affiliated Hospital, Zhejiang University School of Medicine, between September 2020 and September 2022. In the first cohort, we found that the gene expression patterns of peripheral blood mononuclear cells (PBMCs) in 11 patients (10 female, 1 male, age 68.0 ± 8.3) with newly diagnosed PMR were significantly different from 20 healthy controls (17 female, 3 male, age 63.7 ± 9.8) by RNA sequencing. Inflammatory response and cytokine–cytokine receptor interaction were the most notable pathways affected. We observed marked increases in expression of IL6R, IL1B, IL1R1, JAK2, TLR2, TLR4, TLR8, CCR1, CR1, S100A8, S100A12, and IL17RA, which could trigger JAK signaling. Furthermore, tofacitinib suppressed the IL-6R and JAK2 expression of CD4 + T cells from patients with PMR in vitro . In the second cohort, patients with PMR were randomized and treated with tofacitinib or glucocorticoids (1/1) for 24 weeks. All PMR patients underwent clinical and laboratory examinations at 0, 4, 8, 12, 16, 20, and 24 weeks, and PMR activity disease scores (PMR-AS) were calculated. The primary endpoint was the proportion of patients with PMR-AS ≤10 at weeks 12 and 24. Secondary endpoints: PMR-AS score, c-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) at weeks 12 and 24. Thirty-nine patients with newly diagnosed PMR received tofacitinib, and 37 patients received glucocorticoid. Thirty-five patients (29 female, 6 male, age 64.4 ± 8.4) and ...

الإتاحة: https://doi.org/10.1371/journal.pmed.1004249Test

المؤلفون: Liang, Junyu, Wan, Liyan, Yao, Yake, Cui, Xiao, He, Ye, Li, Shuangshuang, Jiang, Mengdi, Sun, Yiduo, Cao, Heng, Lin, Jin

المصدر: Clinical Rheumatology; Jun2024, Vol. 43 Issue 6, p1959-1969, 11p

مصطلحات موضوعية: NOMOGRAPHY (Mathematics), LACTATE dehydrogenase, ADULTS, MYOSITIS, LOGISTIC regression analysis, IDIOPATHIC diseases

مصطلحات جغرافية: CHINA

مستخلص: Objectives: This study aimed at identifying clinical and laboratory risk factors for myocardial involvement (MI) in idiopathic inflammatory myopathies (IIMs) patients as well as constructing a risk-predicted nomogram for prediction and early identification of MI. Methods: An IIMs cohort in southeastern China was constructed, including 504 adult IIMs patients who met the inclusion and exclusion criteria, and were hospitalized at four divisions of the First Affiliated Hospital, Zhejiang University School of Medicine from January 1st 2018 to April 30st 2022. After dividing patients into the training cohort and the validation cohort, risk factors for MI were identified through least absolute shrinkage and selection operator regression and multivariate logistic regression. A risk-predicted nomogram was established and validated internally and externally for discrimination, calibration and practicability. Results: In this cohort, 17.7% of patients developed MI and the survival was significantly inferior to that of IIMs patients without MI (P < 0.001). In the training cohort, age > 55 years old (P < 0.001), disease activity > 10 points (P < 0.001), interleukin-17A (IL-17A) > 7.5 pg/ml (P < 0.001), lactic dehydrogenase (LDH) > 425 U/L (P < 0.001), anti-mitochondrial antibodies (AMAs, P = 0.017), and anti-MDA5 antibody (P = 0.037) were significantly correlated with development of MI. A nomogram was established by including the above values to predict MI and was found efficient in discrimination, calibration, and practicability through internal and external validation. Conclusion: This study developed and validated a nomogram model to predict the risk of MI in adult IIMs patients, which can benefit the prediction and early identification of MI as well as timely intervention in these patients. [ABSTRACT FROM AUTHOR]

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المؤلفون: Liang, Junyu, Cao, Heng, Liu, Yinuo, Ye, Bingjue, Sun, Yiduo, Ke, Yini, He, Ye, Xu, Bei, Lin, Jin

المساهمون: National Natural Science Foundation of China

المصدر: Arthritis Research & Therapy ; volume 23, issue 1 ; ISSN 1478-6362

الوصف: Background Interstitial lung disease (ILD) and its rapid progression (RP) are the main contributors to unfavourable outcomes of patients with idiopathic inflammatory myopathy (IIM). This study aimed to identify the clinical value of PET/CT scans in IIM-ILD patients and to construct a predictive model for RP-ILD. Methods Adult IIM-ILD patients who were hospitalized at four divisions of the First Affiliated Hospital, Zhejiang University School of Medicine (FAHZJU), from 1 January 2017 to 31 December 2020 were reviewed. PET/CT scans and other characteristics of patients who met the inclusion and exclusion criteria were collected and analysed. Results A total of 61 IIM-ILD patients were enrolled in this study. Twenty-one patients (34.4%) developed RP-ILD, and 24 patients (39.3%) died during follow-up. After false discovery rate (FDR) correction, the percent-predicted diffusing capacity of the lung for carbon monoxide (DLCO%, P = 0.014), bilateral lung mean standard uptake value (SUVmean, P = 0.014) and abnormal mediastinal lymph node ( P = 0.045) were significantly different between the RP-ILD and non-RP-ILD groups. The subsequent univariate and multivariate logistic regression analyses verified our findings. A “DLM” model was established by including the above three values to predict RP-ILD with a cut-off value of ≥ 2 and an area under the curve (AUC) of 0.905. Higher bilateral lung SUVmean ( P = 0.019) and spleen SUVmean ( P = 0.011) were observed in IIM-ILD patients who died within 3 months, and a moderate correlation was recognized between the two values. Conclusions Elevated bilateral lung SUVmean, abnormal mediastinal lymph nodes and decreased DLCO% were significantly associated with RP-ILD in IIM-ILD patients. The “DLM” model was valuable in predicting RP-ILD and requires further validation.

الإتاحة: https://doi.org/10.1186/s13075-021-02578-9Test

المؤلفون: Cao, Heng, Liang, Junyu, Xu, Danyi, Liu, Yinuo, Yao, Yinan, Sun, Yiduo, He, Ye, Lin, Jin

المساهمون: National Natural Science Foundation of China

المصدر: Frontiers in Medicine ; volume 8 ; ISSN 2296-858X

الوصف: Objective: To elucidate the 18 F-fluorodeoxyglucose (FDG) PET/CT characteristics and its prognostic value in the patients with anti-melanoma differentiation associated protein 5 antibody positive (anti-MDA5+) dermatomyositis (DM). Methods: This retrospective cross-sectional study included 26 patients with anti-MDA5+ DM and 43 patients with anti-MDA5 negative (anti-MDA5–) idiopathic inflammatory myopathy (IIM) who were examined by 18 F-FDG PET/CT from January 1, 2017 to December 31, 2020. The maximum standardized uptake value (SUVmax) of multiple organs and other clinical characteristics of the patients were measured and analyzed. Results: Compared with the anti-MDA5– group, the patients in the anti-MDA5+ group showed higher bilateral lung SUVmax ( p = 0.029), higher SUVmax of spleen ( p = 0.011), and bone marrow ( p = 0.048). Significant correlations between the spleen SUVmax and serum ferritin levels ( r = 0.398, p < 0.001), erythrocyte sedimentation rate (ESR) ( r = 0.274, p = 0.023), platelet count ( r = −0.265, p = 0.028), myositis disease activity assessment score ( r = 0.332, p = 0.005), bone marrow SUVmax ( r = 0.564, p < 0.001), and bilateral lung SUVmax ( r = 0.393, p < 0.001) were observed. Conclusion: 18 F-FDG PET/CT was found valuable in quantifying the pulmonary focal inflammation and potentially unveil the distinctive characteristics and pathophysiological mechanisms in the patients with anti-MDA5+ DM.

الإتاحة: https://doi.org/10.3389/fmed.2021.779272Test

المؤلفون: Cao, Heng, Liang, Junyu, Liu, Jing, He, Ye, Ke, Yini, Sun, Yiduo, Jiang, Song, Lin, Jin

المصدر: Frontiers in Immunology ; volume 12 ; ISSN 1664-3224

الوصف: Objectives Combination therapy with mycophenolate mofetil, tacrolimus and steroids are effective in achieving complete remission in lupus nephritis (LN). Combination therapy uniquely downregulated caspase-1 compared with monotherapies, which can cleave gasdermin D (GSDMD) and was recently identified as the pyroptosis executioner. We therefore investigated whether combination therapy enabled the suppression of caspase-1/GSDMD-mediated pyroptosis in LN. Methods Expression and activation of GSDMD were detected in kidney specimens of the human and mouse with LN using immunohistochemical staining and immunoblotting. Primary podocytes isolated from MRL/lpr mice were incubated with LPS+ATP, and pretreated with monotherapy or combination therapy. Inhibition of caspase-1/GSDMD-induced pyroptosis by combination therapy were assessed in MRL/lpr mice and human specimens. Pyroptosis was examined using a FAM caspase-1 kit and flow cytometry. The correlation between pyroptosis in peripheral blood and the systemic lupus erythematosus disease activity index (SLEDAI) was analyzed. Results Kidney tissue specimens from LN patients and mice exhibited greatly increased expression levels and cleavage of GSDMD. In cultured podocytes, combination treatment significantly suppressed the activation of NLRP3 and caspase-1 and reduced GSDMD N-terminal levels. Combination therapy repressed disease progression through inhibition of caspase-1/GSDMD-mediated pyroptosis in both humans and MRL/lpr mice. Caspase-1/PI positive cell numbers in peripheral blood were positively correlated with SLE-DAI. LN patients with complete remission and partial remission had remarkably reduced caspase-1/PI positive cell numbers compared to baseline. Ac-FLTD-CMK, a GSDMD-derived inhibitor, prevented the development of LN. Conclusion Combination therapy suppressed caspase-1/GSDMD-mediated pyroptosis in vitro and in vivo and reduced disease progression.

الإتاحة: https://doi.org/10.3389/fimmu.2021.720877Test

المؤلفون: Liang, Junyu, Cao, Heng, Wu, Bowen, Liu, Yinuo, He, Ye, Xu, Bei, Sun, Yiduo, Ye, Bingjue, Lin, Jin

المصدر: Frontiers in Immunology ; volume 12 ; ISSN 1664-3224

مصطلحات موضوعية: Immunology, Immunology and Allergy

الوصف: Background Secondary hemophagocytic lymphohistiocytosis (sHLH) is a rare but fatal complication in idiopathic inflammatory myopathy (IIM) patients. The clinical value of radiological manifestations and serum cytokines remain unknown in this systemic crisis. This study aims to investigate the clinical value of PET/CT scan and cytokine profiles in predicting and understanding sHLH in IIM patients. Methods Adult IIM patients who were admitted to the four divisions of the First Affiliated Hospital, Zhejiang University School of Medicine (FAHZJU) from January 1, 2017 to December 31, 2020 were reviewed. PET/CT scan, cytokine profiles, and other factors of patients who met the inclusion and exclusion criteria were collected and analyzed. Results Sixty-nine out of 352 IIM patients were finally enrolled into the study. Ten patients developed sHLH and 70.0% of them died within 6 months. After false discovery rate (FDR) correction and multivariate logistic regression analysis, increased serum interferon (IFN)-γ level ( p = 0.017), higher spleen mean standard uptake value (SUVmean, p = 0.035), and positivity of anti-MDA5 antibody ( p = 0.049) were found to be significantly correlated with development of sHLH in IIM patients. The combination of serum IFN-γ, spleen SUVmean, and anti-MDA5 antibody found a balanced and satisfying predictor with a cutoff value of 0.047 and AUC of 0.946. A moderate correlation was identified between ferritin and spleen SUVmean ( p = 0.001, r = 0.380) as well as serum IFN-γ( p = 0.001, r = 0.398). Before FDR correction, higher bilateral lung SUVmean ( p = 0.034) and higher colon/rectum SUVmean ( p = 0.013) were also observed in IIM patients who developed sHLH. By narrowing down to IIM patients with sHLH, anti-MDA5-antibody-positive DM patients tended to suffer from unfavorable outcome ( p = 0.004) in Kaplan–Meier survival analysis. Conclusion Increased serum level of IFN-γ, elevated splenic FDG uptake, and positivity of anti-MDA5 antibody were significantly correlated with development of sHLH in ...

الإتاحة: https://doi.org/10.3389/fimmu.2021.745211Test

المؤلفون: Peng, Liying, Wu, Chanyuan, Hong, Ruping, Sun, Yiduo, Qian, Junyan, Zhao, Jiuliang, Wang, Qian, Tian, Xinping, Wang, Yanhong, Li, Mengtao, Zeng, Xiaofeng

المساهمون: national key research and development program of china stem cell and translational research, Chinese National Key Research and Development Program, Chinese National High Technology Research and Development Program

المصدر: Therapeutic Advances in Musculoskeletal Disease ; volume 12, page 1759720X2095333 ; ISSN 1759-720X 1759-7218

الوصف: Objective: To provide real-world data and summarize current clinical evidence on the efficacy and safety of sirolimus in active systemic lupus erythematosus (SLE) patients. Methods: This was a prospective real-world clinical study. Included SLE patients should have Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) ⩾ 2. They were treated with sirolimus and followed up regularly. The SLEDAI-2K, Physician Global Assessment (PGA), serological activity indices, and remission of organ manifestations were evaluated. We also performed a meta-analysis to integrate current evidence of sirolimus in SLE. Results: A total of 49 patients were included in the final analysis. After treatment, the SLEDAI-2K (6.2 ± 3.1 versus 4.0 ± 3.4, p = 0.001) decreased significantly, and the prednisone dosage was tapered successfully (9.9 ± 8.8 mg/day versus 5.9 ± 4.0 mg/day, p = 0.002). Serological activity indices also improved [complement 3 (C3): 0.690 ± 0.209 g/l versus 0.884 ± 0.219 g/l, p < 0.001; complement 4: 0.105 ± 0.059 g/l versus 0.141 ± 0.069 g/l, p < 0.001; anti-dsDNA antibody, 200 ± 178 IU/ml versus 156 ± 163 IU/ml, p = 0.022]. The remission proportions of arthritis, skin rash, and thrombocytopenia were 100%, 88.8%, and 46.2%, respectively. A total of 41.2% of lupus nephritis (LN) patients achieved renal remission, but the average 24-h urine protein level was not significantly changed. Meta-analysis enrolled five studies with 149 patients included, and revealed similar results regarding the changes of SLEDAI-2K [−3.5 (−5.0, −2.1)], C3 [0.224 (0.136, 0.311) g/l] and daily dosage of prednisone [−12.7 (−19.9, −5.6) mg/day]. Conclusion: Sirolimus might be effective and tolerated in SLE. The role of sirolimus in LN requires further study.

الإتاحة: https://doi.org/10.1177/1759720x20953336Test

المؤلفون: Zhang, Chao, Sun, Yiduo, Hu, Ruifa, Huang, Jikun, Huang, Xusheng, Li, Yifan, Yin, Yanhong, Chen, Zhaohui

المصدر: Scientific Reports ; volume 8, issue 1 ; ISSN 2045-2322

مصطلحات موضوعية: Multidisciplinary

الوصف: Evidence on the adverse effects of agricultural pesticide use by farmers under the actual field conditions on their peripheral nerve conduction in China is limited. This study was to investigate the association of agricultural pesticide use with the abnormalities of farmers’ peripheral nerve conduction based on two rounds of conventional nerve conduction studies. The level of pesticide exposure was assessed by measuring total amount of pesticides used by farmers in 2012. The logistic and negative binomial regression analyses were performed on a cohort study of 218 farmers. Results show that agricultural use of neither glyphosate nor non-glyphosate herbicides was not found to induce the abnormalities of farmers’ peripheral nerve conduction. However, agricultural use of organophosphorus compounds was significantly associated with increased risk of demylination disease of peripheral nerve conduction described by the reduced velocity. Moreover, the use of organonitrogen compounds by farmers would not only increase risk of demylination disease but axonal damages described by the reduced amplitude. By contrast, agricultural uses of organosulfur and pyrethroid compounds would not induce the abnormalities of farmers’ peripheral nerve conduction. The findings demonstrated the importance of developing health-friendly pesticides to replace organophosphorus and organonitrogen insecticides and fungicides in China.

الإتاحة: https://doi.org/10.1038/s41598-018-27713-6Test
https://www.nature.com/articles/s41598-018-27713-6.pdfTest
https://www.nature.com/articles/s41598-018-27713-6Test

المؤلفون: Ma, Yiyangzi, Guo, Ruru, Sun, Yiduo, Li, Xin, He, Lun, Li, Zhao, Silverman, Gregg J., Chen, Guobing, Gao, Feng, Yuan, Jiali, Wei, Qiang, Li, Mengtao, Lu, Liangjing, Niu, Haitao

المصدر: Clinical Immunology ; volume 233, page 108892 ; ISSN 1521-6616

مصطلحات موضوعية: Immunology, Immunology and Allergy

الإتاحة: https://doi.org/10.1016/j.clim.2021.108892Test
https://api.elsevier.com/content/article/PII:S1521661621002291?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S1521661621002291?httpAccept=text/plainTest

المؤلفون: Zhang, Chao, Sun, Yiduo, Hu, Ruifa, Yang, Fan, Shen, Xin

المساهمون: Ministry of Science and Technology of China, National Natural Science Foundation of China

المصدر: Journal of Cleaner Production ; volume 280, page 124429 ; ISSN 0959-6526

مصطلحات موضوعية: Industrial and Manufacturing Engineering, Strategy and Management, General Environmental Science, Renewable Energy, Sustainability and the Environment

الإتاحة: https://doi.org/10.1016/j.jclepro.2020.124429Test
https://api.elsevier.com/content/article/PII:S0959652620344735?httpAccept=text/xmlTest
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