1.Expression of glucocorticoids receptor isoforms and their correlations with disease activities in pa-tients with systemic lupus erythematosus or rheumatoid arthritis
Yanchun GUAN ; Dandan YU ; Xiangnan SUN ; Liangliang MA ; Meiyun FANG
Chinese Journal of Microbiology and Immunology 2014;(11):868-873
Objective To analyze the differences with the expression of glucocorticoids receptor isoforms ( GRα, GRβ, GRγand GR-P ) and cytokines [ IL-6, macrophage migration inhibitory factor (MIF), IFN-γand IL-10] between patients with systemic lupus erythematosus (SLE) and rheumatoid ar-thritis ( RA) , and to further understand their correlations with disease activities.Methods Fifty-five pa-tients with SLE, forty-nine patients with RA and thirty-eight healthy subjects were recruited in this study. All patients were steroid-naive.The expression of GRα, GRβ, GRγ, and GR-P in peripheral blood mononu-clear cells at transcript levels were determined by real-time PCR.Enzyme-linked immunosorbent assay was used to detect the expression of IL-6, MIF, IFN-γand IL-10 in serum samples.Results The percentages of GRαin all subjects were the highest among four isoforms of GR, followed by GR-P, GRγand GRβ.Com-pared with healthy subjects, patients with SLE or RA showed significantly decreased expression of GRα( P<0.05), but increased expression of GR-P (P<0.05).The percentages of GR-P in patients with RA were higher than those in patients with SLE (P<0.05).The expression of GRαwas negatively correlated with SLE disease activity index (SLEDAI) and disease activity score 28 (DAS28).SLE or RA patients with high disease activity showed lower expression of GRαthan those with low disease activity.The levels of IL-6, IFN-γand MIF in patients with SLE or RA were significantly higher than those in healthy subjects ( P<0.05).A negative correlation was observed between the expression of IL-6 and GRαin patients with SLE (P<0.05).The expression of IFN-γwas negatively correlated with GRαin patients with RA (P<0.05). Conclusion There were significant differences with the expression of GR isoforms among patients with SLE, patients with RA and healthy subjects, indicating the change of internal environment in patients might be in-volved in GR alternative splicing.GRαwas the predominant isoform and was negatively correlated with dis-ease activities.Oversecretion of cytokines resulted in a decreased expression of GRα.This study would be useful for the diagnosis of the disease status and for monitoring clinical treatment.
2.The relationship between mRNA level of glucocorticoid receptor α, heat shock protein 90, protein level of macrophage migration inhibitory factor and glucocorticoid resistance in systemic lupus erythematosus
Yanchun GUAN ; Yanmin ZHANG ; Meiyun FANG ; Jingfan GUAN ; Xiangnan SUN ; Jiewen ZHANG
Chinese Journal of Internal Medicine 2015;54(11):922-926
Objective To investigate the mRNA level of glucocorticoid receptor α (GRα) and heat shock protein 90 (HSP90) in peripheral blood mononuclear cells (PBMCs) and the plasma protein level of macrophage migration inhibitory factor (MIF) in patients with systemic lupus erythematosus (SLE) and to analyze their association with glucocorticoid (GC) resistance.Methods One hundred and six patients with SLE and thirty-eight healthy controls were enrolled in this study.Transcription levels of GRα and HSP90 were determined by real-time polymerase chain reaction.Enzyme-linked immunosorbent assay was used to detect the protein level of plasma MIF.The association between these parameters and GC resistance was analyzed by Spearman correlation analysis.The multivariate logistic regression model was used to analyze the risk factors for GC resistance.Results The mRNA level of GRα and HSP90 in GC resistance group was significantly lower than that in GC sensitive group [10.18(3.12,17.20) vs 16.83(12.01,24.18), P =0.001;18.46(14.77,26.45) vs 25.84 (17.97,35.90), P =0.005].MIF protein level in GC resistance group was significantly higher than that in GC sensitive group [(23.21 ±7.98) μg/L vs (18.34 ±6.29)μg/L;P =0.013].The mRNA level of HSP90 in the high MIF group was significantly lower than that in the low MIF group [23.67 (13.84,28.32) vs 26.64 (23.61,47.16);P =0.001], as well as HSP90/GRαratio(P =0.008).Additionally, the plasma protein level of MIF was negatively correlated with HSP90 (r =-0.275, P =0.004) and HSP90/GRα ratio(r =-0.341, P < 0.001).SLE activity index score in GC resistance group was significantly higher than that in GC sensitive group [(12.23 ±2.86) μg./L vs (9.63 ± 3.48) μg/L;P =0.003].Logistic regression model indicated that disease activity was an independent risk factor for GC resistance (OR =17.481, 95% CI 1.747-174.903, P =0.015).Conclusions Our preliminary findings suggest that low mRNA level of GRα and HSP90 and high protein level of MIF are associated with GC resistance.Elevated MIF level in SLE patients may play an important role in the development of GC resistance through down-regulating HSP90 and destabilizing the balance of HSP90/ Grα.Disease activity is the risk factor for GC resistance, which might be the viable evidence of therapy response.
3.Effect of Electromyography Feedback Functional Electrical Stimulation on Plantar Pressure under Walking in Stroke Patients
Xiangnan YUAN ; Xiaoting LI ; Hanting LI ; Yu LIU ; Shi SUN ; Yucen WAN ; Zhiqiang ZHANG
Chinese Journal of Rehabilitation Theory and Practice 2015;21(10):1191-1196
Objective To evaluate the therapeutic effects of electromyography feedback functional electrical stimulation (FES) on plantar pressure of stroke patients. Methods 18 subjects were included in this study, who were with drop foot resulting from stroke, but could partly dorsiflex the paretic limb's ankle (Manual Muscle Test >2). They were tested on the RS-footscan plate before and after stimulation. The plantar pressure data of paretic foot and walking velocity before and after stimulation were compared. Results The initial touchdown points of most paretic foot were changed from Meta (metatarsal) 5 to heel; the time of initial touchdown of heel medial and heel lateral significantly improved, while that of Meta 3, Meta 4 and Meta 5 significantly delayed; the peak force, impulse and contact area of the heel significantly improved after stimulation (P<0.05). At the same time, the time of initial touchdown of heel medial and heel lateral of nonparetic foot significantly improved (P<0.05). Conclusion Electromyography feedback functional electrical stimulation can improve the gait pattern and the stability of patients with stroke.
5.Role of LncRNA TCONS_00003757 in papillary thyroid carcinoma
Xinyu NAN ; Qi SUN ; Hui FANG ; Qian ZHENG ; Ying YANG ; Xiangnan WANG ; Lijing SUN
Chinese Journal of Endocrinology and Metabolism 2019;35(4):282-288
Objective To investigate the expression of LncRNA TCONS_00003757 in papillary thyroid carcinoma ( PTC) , and to explore the effect of LncRNA TCONS_00003757 on the proliferation, migration, and invasion in TPC-1 cells. Methods Sixty cases of papillary thyroid carcinoma specimens and paired normal tissues were collected after surgery from October 2017 to March 2018 in the Tangshan Workers Hospital. Real-time PCR analysis was used to examine the expression level of LncRNA TCONS_00003757 in PTC tissues, and the association of LncRNA TCONS_00003757 expression levels with the clinicopathological data of patients was analyzed. The effects of LncRNA TCONS_00003757 and ST3GAL5 silencing on the proliferation, migration, and invasion in TPC-1 cells were assessed by MTT, scratch test, and transwell assay. Protein expression of ST3GAL5 was detected by Western blot after LncRNA TCONS_00003757 silencing. Results LncRNA TCONS_00003757 expression was increased in PTC tissues compared with that in normal tissues ( P<0. 05 ) , which was correlated with capsule invasion and lymph node metastasis( P<0.05) . LncRNA TCONS_00003757 expression in TPC-1 cells was higher than that in normal thyroid follicular epithelial Nthy-ori 3-1 cells(P<0.05). LncRNA TCONS_00003757 and ST3GAL5 silencing inhibited the proliferation, migration, and invasion of thyroid cancer TPC-1 cells, and ST3GAL5 expression was decreased after LncRNA TCONS_00003757 silencing (P<0.05). Conclusion LncRNA TCONS_00003757 expression in PTC is significantly increased and correlated with its occurrence and development. Silencing LncRNA TCONS_00003757 may inhibit the proliferation, migration, and invasion of thyroid papillary cancer cells via decreasing ST3GAL5 expression.
6.Electrophysiologic Characteristics of Post-cardiac-surgical Atrial Tachycardia under Ultra-high Density and High-resolution Mapping
Jie LI ; Feng-jiao YAN ; Na TANG ; Chen SU ; Jing-zhou JIANG ; Meng-hui LIU ; Jian-gui HE ; Li-chun WANG
Journal of Sun Yat-sen University(Medical Sciences) 2021;42(1):95-101
ObjectiveTo explore the electrophysiologic characteristics of post-cardiac-surgical atrial tachycardia (AT) under ultra-high density and high-resolution mapping. MethodsConsecutive cases with post-cardiac-surgical AT and taking mapping using Orion basketball mini-electrode and Rhythmia mapping system were collected and analyzed in the first affiliated hospital of Sun Yat-sen University from march 2016 to december 2019. ResultsTotally 26 ATs were recorded in the 21 patients with a mean mapping time (19.1±7.1)min. Among them, 20 (76.9%) ATs located in right atrium, 5 (19.2%) in left atrium, and one was a bi-atrial macro-reentrant AT. According the difference of tachycardia mechanism, 24 (92.3%) were macro-reentrant ATs, one was micro-reentrant, and the other was local activation. In the macro-reentrant ATs, 7 cases showed a dual-loop reentrant circuit configurated “figure-of-eight”, one was a bi-atrial macro-reentry with a transmural conduction from left side to right side of atrial septum. During ablation, 4 patients in the 7 cases with “figure-of-eight” dual-loop reentries turned into a single-loop reentry. During follow-up with an average of 16 (4, 36) months, 2 cases recurred, and one was because of no prophylactic ablation on the tricuspid isthmus. ConclusionsPost-cardiac-surgical atrial tachycardia mainly manifests as complicated macro-reentrant AT. Some show a dual-loop reentry and sometimes a bi-atrial macro-reentry. During ablation, some prophylactic ablation according to the substrate is necessary.
7.5-Hydroxymethylome in Circulating Cell-free DNA as A Potential Biomarker for Non-small-cell Lung Cancer.
Ji ZHANG ; Xiao HAN ; Chunchun GAO ; Yurong XING ; Zheng QI ; Ruijuan LIU ; Yueqin WANG ; Xiaojian ZHANG ; Yun-Gui YANG ; Xiangnan LI ; Baofa SUN ; Xin TIAN
Genomics, Proteomics & Bioinformatics 2018;16(3):187-199
Non-small-cell lung cancer (NSCLC), the most common type of lung cancer accounting for 85% of the cases, is often diagnosed at advanced stages owing to the lack of efficient early diagnostic tools. 5-Hydroxymethylcytosine (5hmC) signatures in circulating cell-free DNA (cfDNA) that carries the cancer-specific epigenetic patterns may represent the valuable biomarkers for discriminating tumor and healthy individuals, and thus could be potentially useful for NSCLC diagnosis. Here, we employed a sensitive and reliable method to map genome-wide 5hmC in the cfDNA of Chinese NSCLC patients and detected a significant 5hmC gain in both the gene bodies and promoter regions in the blood samples from tumor patients compared with healthy controls. Specifically, we identified six potential biomarkers from 66 patients and 67 healthy controls (mean decrease accuracy >3.2, P < 3.68E-19) using machine-learning-based tumor classifiers with high accuracy. Thus, the unique signature of 5hmC in tumor patient's cfDNA identified in our study may provide valuable information in facilitating the development of new diagnostic and therapeutic modalities for NSCLC.
5-Methylcytosine
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analogs & derivatives
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blood
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Biomarkers, Tumor
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blood
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genetics
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Carcinoma, Non-Small-Cell Lung
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blood
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diagnosis
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genetics
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Case-Control Studies
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Circulating Tumor DNA
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blood
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DNA Methylation
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Epigenomics
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Female
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Humans
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Lung Neoplasms
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blood
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diagnosis
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genetics
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Male
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Middle Aged
8.Construction of the Chinese Veteran Clinical Research (CVCR) platform for the assessment of non-communicable diseases.
Jiping TAN ; Nan LI ; Jing GAO ; Yuhe GUO ; Wei HU ; Jinsheng YANG ; Baocheng YU ; Jianmin YU ; Wei DU ; Wenjun ZHANG ; Lianqi CUI ; Qingsong WANG ; Xiangnan XIA ; Jianjun LI ; Peiyi ZHOU ; Baohe ZHANG ; Zhiying LIU ; Shaogang ZHANG ; Lanying SUN ; Nan LIU ; Ruixiang DENG ; Wenguang DAI ; Fang YI ; Wenjun CHEN ; Yongqing ZHANG ; Shenwu XUE ; Bo CUI ; Yiming ZHAO ; Luning WANG
Chinese Medical Journal 2014;127(3):448-456
BACKGROUNDBased on the excellent medical care and management system for Chinese veterans, as well as the detailed medical documentation available, we aim to construct a Chinese Veteran Clinical Research (CVCR) platform on non-communicable diseases (NCDs) and carry out studies of the primary disabling NCDs.
METHODSThe Geriatric Neurology Department of Chinese People's Liberation Army General Hospital and veterans' hospitals serve as the leading and participating units in the platform construction. The fundamental constituents of the platform are veteran communities. Stratified typical cluster sampling is adopted to recruit veteran communities. A cross-sectional study of mental, neurological, and substance use (MNS) disorders are performed in two stages using screening scale such as the Mini-Mental State Examination and Montreal cognitive assessment, followed by systematic neuropsychological assessments to make clinical diagnoses, evaluated disease awareness and care situation.
RESULTSA total of 9 676 among 277 veteran communities from 18 cities are recruited into this platform, yielding a response rate of 83.86%. 8 812 subjects complete the MNS subproject screening and total response rate is 91.70%. The average participant age is (82.01±4.61) years, 69.47% of veterans are 80 years or older. Most participants are male (94.01%), 83.36% of subjects have at least a junior high school degree. The overall health status of veterans is good and stable. The most common NCD are cardiovascular disorders (86.44%), urinary and genital diseases (73.14%), eye and ear problems (66.25%), endocrine (56.56%) and neuro-psychiatric disturbances (50.78%).
CONCLUSIONWe first construct a veterans' comprehensive clinical research platform for the study of NCDs that is primarily composed of highly educated Chinese males of advanced age and utilize this platform to complete a cross-sectional national investigation of MNS disorders among veterans. The good and stable health condition of the veterans could facilitate the long-term follow-up studies of NCDs and provide prospective data to the prevention and management of NCDs.
Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; Cross-Sectional Studies ; Disease ; Female ; Health Status ; Humans ; Male ; Veterans ; statistics & numerical data