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Moxibustion of Zusanli(ST36)and Shenshu(BL23)alleviates the inflammation of rheumatoid arthritis in rats through regulating macrophage migration inhibitory factor/Glucocorticoids signaling

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Journal of Traditional Chinese Medicine 2024年第2期44卷 353-361页

作者： ZHANG Linlin ZHONG Yumei LU Wenting SHANG Yanan GUO Yanding LUO Xiaochao CHEN Yang LUO Kun HU Danhui YU Huiling ZHOU Haiyan Acupuncture and Moxibustion College Chengdu University of Traditional Chinese MedicineChengdu 610075China Department of Painology First People's Hospital of ChengduChengdu 610095China Chinese Evidence-Based Medicine Centre West China HospitalSichuan UniversityChengdu 610044China Traditional Chinese Medicine College Chongqing Medical UniversityChongqing 400016China External treatment center First People's Hospital of ChengduChengdu 610095China

OBJECTIVE:To test the hypothesis that moxibustion may inhibit rheumatoid arthritis(RA)synovial inflammation by regulating the expression of macrophage migration inhibitory factor(MIF)/Glucocorticoids(GCs).METHODS:Fifty male Sprague-Dawley rats were randomly divided into five groups(n=10 each):blank Control(CON)group,RA Model(RA)group,Moxibustion(MOX)group,MIF inhibitor(S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester(ISO-1)group,and Moxibustion+MIF inhibitor ISO-1(MOX+ISO-1)group.Rats in the ISO-1 group and ISO-1+MOX group were intraperitoneally injected with the inhibitor ISO-1.The rats in the RA group,ISO-1 group,MOX group,and ISO-1+MOX group were injected with Freund's complete adjuvant(FCA)in the right hind footpad to establish an experimental RA rat model.In the MOX group and MOX+ISO-1 group,rats were treated with Moxa.The thickness of the footpads of the rats in each group was measured at three-time points before,after modeling and after moxibustion treatment.The contents of serum MIF,corticosterone(CORT),tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)were detected by enzyme-linked immunosorbent assay;and the contents of synovial MIF were detected by Western blot.Hematoxylin-eosin(HE)staining method was used to observe the pathological changes of synovial tissue under a section light microscope,and pathological scoring was performed according to the grading standard of the degree of synovial tissue disease.RESULTS:Moxibustion was found to reduce the level of MIF and alleviate inflammation in RA rats in this study.In addition,after inhibiting the expression of MIF,the level of CORT increased,and the level of TNF-α decreased.Treating RA rats with inhibited MIF by moxibustion,the level of CORT was almost unchanged,but the level of TNF-α further decreased.The correlation analysis data suggested that MIF was positively related to the expression of TNF-α and negatively correlated with the expression of CORT.CONCLUSION:Reducing MIF to increase CORT and decrease TNF-α by moxibustion

关键词： rheumatoid arthritis macrophage migration inhibitory factor moxibustion corticosterone Glucocorticoids

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Efficacy of Glucocorticoids,chloroquine and vitamin A on cytokine release syndrome:a network pharmacology study

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Journal of Traditional Chinese Medicine 2022年第1期42卷 116-121页

作者： ZHANG Jing ZHU Jingjing HE Siqi WANG Jianxun School of Life Sciences Beijing University of Chinese MedicineBeijingChina

OBJECTIVE:To verify the efficacy of Glucocorticoids,chloroquine and vitamin A in the treatment of cytokine release syndrome(CRS),and to investigate the underlying mechanisms,based on network pharmacology.METHODS:We used network pharmacology analysis and found 20 co-targeted genes of Glucocorticoids,chloroquine,vitamin A and CRS.The pharmacological functions and therapeutic pathways of the genes were analyzed by gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment.The candidate naturally bioactive compounds against the key genes were predicted by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.The anti-inflammatory activity of luteolin was assessed by real-time polymerase chain reaction.RESULTS:Among the 20 co-targeted genes of Glucocorticoids,chloroquine and vitamin A,interleukin 10(IL-10),interleukin 2(IL-2),interleukin 4(IL-4)and tumor necrosis factor-α(TNF-α)were the key cytokines against CRS.The key pathway involved in the pharmacological mechanism could be cytokine-cytokine receptor interaction pathway,T cell receptor signaling pathway,Janus Kinase-signal transducer and activator of transcription signaling pathway and phosphatidylinositol 3-kinase-protein kinase B signaling pathway.Luteolin targeted by IL-10,IL-4,IL-2 and TNF-αcould be one candidate drug for the treatment of CRS.CONCLUSION:This study comprehensively elucidates the pharmacological mechanism for the treatment of CRS and provides a new method for the discovery of drugs for this disease.

关键词： Glucocorticoids chloroquine vitamin A cytokine release syndrome inflammation luteolin network pharmacology

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Association of Serum Glucocorticoids with Various Blood Pressure Indices in Patients with Dysglycemia and Hypertension:the Henan Rural Cohort Study

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Biomedical and Environmental Sciences 2021年第12期34卷 952-962页

作者： XUE Yuan MAO Zhen Xing LIU Xue WEI Dan Dan LIU Chang PANG Shan Bin YU Song Cheng GAO Jiao Jiao LIN Ji Song ZHANG Dong Dong WANG Chong Jian LI Wen Jie LI Xing Department of Nutrition and Food Hygiene School of Public HealthZhengzhou UniversityZhengzhou 450001HenanChina Department of Epidemiology School of Public HealthZhengzhou UniversityZhengzhou 450001HenanChina Department of Clinincal Nutrition The Fifth Affiliated Hospital of Zhengzhou UniversityZhengzhou 450000HenanChina

Objective To our knowledge, no definitive conclusion has been reached regarding the relationship between Glucocorticoids and hypertension. Here, we aimed to explore the characteristics of Glucocorticoids in participants with dysglycemia and hypertension, and to analyze their association with blood pressure indicators.Methods The participants of this study were from the Henan Rural Cohort study. A total of 1,688 patients 18–79 years of age were included in the matched case control study after application of the inclusion and exclusion criteria. Statistical methods were used to analyze the association between Glucocorticoids and various indices of blood pressure, through approaches such as logistic regression analysis, trend tests, linear regression, and restricted cubic regression.Results The study population consisted of 552 patients with dysglycemia and hypertension(32.7%).The patients with co-morbidities had higher levels of serum cortisol(P = 0.009) and deoxycortisol(P Glucocorticoids(deoxycortisol and cortisol) increase the risk of hypertension in people with dysglycemia, particularly in those with T2 DM.

关键词： Glucocorticoids Dysglycemia with hypertension Blood pressure Chinese rural

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Regulation of natural killer cell activity by Glucocorticoids,serotonin,dopamine,and epinephrine

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Cellular & Molecular Immunology 2020年第7期17卷 705-711页

作者： Silvia Capellino Maren Claus Carsten Watzl Department for Immunology Leibniz Research Centre for Working Environment and Human Factors(IfADo)at TU DortmundDortmundGermany

The immune system and the nervous system are highly complex organs composed of various different cells that must interact with each other for proper function of the system.This communication can be mediated by soluble factors.The factors released by the nervous system(neurotransmitters)differ from those released by the immune system(cytokines).Nevertheless,the nervous and immune systems can influence each other’s activity because immune cells express neurotransmitter receptors,and neurons express cytokine receptors.Moreover,immune cells can synthesize and release neurotransmitters themselves,thus using neurotransmittermediated pathways via autocrine and paracrine mechanisms.Natural killer(NK)cells are innate lymphocytes that are important for early and effective immune reactions against infections and cancer.Many studies have shown the strong influence of stress and the nervous system on NK cell activity.This phenomenon may be one reason why chronic stress leads to a higher incidence of infections and cancer.Here,we review the effects of neuroendocrine factors on the different activities of NK cells.Understanding the effects of neuroendocrine factors on NK cell activities during physiological and pathophysiological conditions may result in novel therapeutic strategies to enhance NK cell functions against tumors.

关键词： Natural Killer Cells Catecholamines Glucocorticoids Neurotransmitters

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Effects of rhubarb on the expression of Glucocorticoids receptor and regulation of cellular immunity in burn-induced septic rats

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Chinese Medical Journal 2019年第10期132卷 1188-1193页

作者： Jiao Liu Guang Li Yi-Zhu Chen Li-Di Zhang Tao Wang Zhen-Liang Wen Lu Wang De-Chang Chen Department of Critical Care Medicine Shanghai Jiaotong University School of Medicine Ruijin Hospital North Shanghai 201801 China Department of Critical Care Medicine Renmin Hospital of Wuhan University Wuhan Hubei 430060 China

Background: It is important to modulate the expression of Glucocorticoids receptor (GR) in tress and maintain the immunity homeostasis in sepsis process. Rhubarb have been shown to have potential effects on anti-inflammatory and immune modulation. The present study was designed to investigate the effects of rhubarb on the expression of GR and cellular immunity in burn-induced septic rats. Methods: Sixty-six healthy male Sprague Dawley (SD) rats were randomized into sepsis group (n = 24), rhubarb group (n = 24), and control group (n = 18);each group were further randomized into 12, 24, and 72 h subgroups according to different time points. During onset of the sepsis model, the rats in the rhubarb group were infused with 50 mg/kg rhubarb powder dissolved into 1 mL saline through gastric tube, while sepsis and control groups were treated with saline. The binding activity of GR in liver cytosol and binding capacity of GR in peripheral blood leucocyte were analyzed by radiation ligands binding assay. The percentages of CD4^+, CD8^+,CD4^+CD25^+T cells, CD19^+B cells as well as natural killer (NK) cells in the lymphocytes in peripheral blood were detected by flow cytometer. For assessing the differences among groups, one-way analysis of variance (ANOVA) with Scheffe multi-comparison techniques were employed. Comparisons between time-based measurements within each group were performed with ANOVA repeated measurement. Results: The binding activity of GR in liver cytosol and binding capacity of GR in peripheral blood leucocyte were significantly decreased in a time-dependent manner in sepsis group (t = 23.045, P < 0.01;t = 24.395, P < 0.05, respectively), which were increased in a time-dependent manner after rhubarb administration (t = 19.965, P < 0.05;t = 17.140, P < 0.05, respectively). Twelve hours after sepsis, the percentages of CD4^+ T cells, CD47CD25^+ T cell ratio, and CD19^+ B cells in the peripheral blood were significantly increased in the sepsis group (t =—3.395, P < 0.01;t = 2.568, P < 0.05;t = 2.993, P < 0.05

关键词： Rhubarb Sepsis Cellular immunity Glucocorticoids receptor

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Intravenous Glucocorticoids therapy in the treatment of Graves’ ophthalmopathy: a systematic review and Meta-analysis

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International Journal of Ophthalmology(English edition) 2019年第7期12卷 1177-1186页

作者： Li-Quan Zhao Dan-Yang Yu Jin-Wei Cheng Department of Ophthalmology Shanghai Pudong New Area People's Hospital Shanghai 201200China Department of Ophthalmology 920th Hospital of Jiont Logistics Support Force Kunming 6500032Yunnan Province China Department of Ophthalmology Shanghai General Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200080China

AIM: To evaluate the benefit and harms of high-dose intravenous Glucocorticoids(IVGC) as first-line treatment for Graves’ ophthalmopathy(GO).METHODS: A systematic review and Meta-analysis of randomized clinical trials(RCTs) comparing IVGC for the treatment of GO, with placebo or other treatments, were conducted. Electronic databases were searched, and standard methodological guidance of Cochrane Handbook for Systematic Reviews of Interventions was used. The primary outcome was overall response, and secondary outcomes included the improvement and change in clinical activity score(CAS), and adverse events.RESULTS: Ten RCTs were included in the Meta-analysis. Low quality evidence(one trial) showed that participants receiving IVGC achieved significantly higher response compared to participants receiving placebo [risk ratio(RR) 7.50, 95% confidence interval(CI) 1.14 to 49.26]. Moderate quality evidence(four trials) support appreciable benefit of IVGC in response compared with oral Glucocorticoids(OGC), with of RR being 1.51(95%CI 1.25 to 1.83). There was low quality evidence(one trial) compatible with appreciable benefit for IVGC plus orbital radiotherapy in response(RR 1.38, 95%CI 1.07 to 1.79), compared with OGC plus orbital radiotherapy. One IVGC versus rituximab trial provided moderate quality evidence suggesting that participants using IVGC achieved significantly lowerresponse compared to participants using rituximab(RR 0.70, 95%CI 0.50 to 0.98). One IVGC versus mycophenolate mofetil(MMF) trial provided moderate quality evidence suggesting that participants using IVGC achieved significantly lower response compared to participants using MMF(RR 0.74, 95%CI 0.63 to 0.88). Very low quality evidence(one trial) showed that participants with dysthyroid optic neuropathy(DON) receiving IVGC were more likely to achieve response compared to participants receiving orbital decompression(RR 3.33, 95%CI 0.51 to 21.89).CONCLUSION: The current evidence is moderate quality, which is sufficient to support IVGC to be as the first-li

关键词： Glucocorticoids Graves' ophthalmopathy Meta-analysis

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The effect of intravenous high-dose Glucocorticoids and orbital decompression surgery on sight-threatening thyroid-associated ophthalmopathy

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International Journal of Ophthalmology(English edition) 2019年第11期12卷 1737-1745页

作者： Yun Wen Jian-Hua Yan The State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat-sen University

AIM: To report the effects of intravenous high-dose Glucocorticoids(iv GC) and orbital decompression(OD) surgery for treatment of sight-threatening thyroid-associated ophthalmopathy(TAO).METHODS: A retrospective review of medical records from patients with sight-threatening TAO [definite or highly suspected dysthyroid optic neuropathy(DON)] treated with iv GC(60 cases) and OD(25 cases) was conducted at the Zhongshan Ophthalmic Center between January 2001 and January 2009. Patients were initially treated with iv GC(iv GC group). If no significant improvement in visual function was obtained, they then received OD surgery(OD group). The pre-versus post-treatment efficacies of either iv GC or OD in these patients were assessed using several indices, including visual acuity, intraocular pressure, ocular alignment, ocular motility, and exophthalmos. RESULTS: Nighty-one eyes had definite DON while 79 were considered to have highly suspected DON. In the iv GC group, 51 individuals(85.0%) eventually demonstrated normal vision, while 10 patients(16.7%) demonstrated a reduction in deviation(P<0.01), and 35 cases(58.3%) showed slight improvements in ocular motility(P<0.01). In OD group, visual acuity improved in 24 cases(96.0%, P<0.01) and all patients showed varying reductions of exophthalmos(mean: 4.35±1.13 mm, P<0.01). Eight cases(32.0%) experienced an 8-15 PD reduction of deviation and ocular motility improved in 12 cases(48.0%), while 3 patients(12.0%) developed new-onset strabismus with diplopia post-surgically(P<0.01). Patients were followed up at an average of 1.55±1.07 y. CONCLUSION: Both iv GC and OD show good therapeutic efficacy in the treatment of sight-threatening TAO. Thepresence of extremely poor eyesight(≥0.5 log MAR) was corrected in some patients with iv GC alone, thus sparing these patients from subsequent OD surgery. In patients who were refractory to steroids, subsequent OD surgery often provided satisfactory outcomes, however, new-onset strabismus with diplopia was observed in 12.0% of these cases.

关键词： thyroid-associated ophthalmopathy dysthyroid optic neuropathy Glucocorticoids orbital decompression orbital surgery

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A Historical Cohort Study on the Efficacy of Glucocorticoids and Riboflavin Among Patients with Late-onset Multiple AcyI-CoA Dehydrogenase Deficiency

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Chinese Medical Journal 2016年第2期129卷 142-146页

作者： Xin-Yi Liu Zhi-Qiang Wang Dan-Ni Wang Min-Ting Lin Ning Wang Department of Neurology and Institute of Neurology First Affiliated Hospital Fujian Medical University Fuzhou Fujian 350005 China Fujian Key Laboratory of Molecular Neurology Fuzhou Fujian 350005 China

Background： Late-onset multiple acyl-CoA dehydrogenase deficiency （MADD） is the most common type of lipid storage myopathies in China. Most patients with late-onset MADD are well responsive to riboflavin. Up to now, these patients are often treated with Glucocorticoids as the first-line drug because they are misdiagnosed as polymyositis without muscle biopsy or gene analysis. Although Glucocorticoids seem to improve the fatty acid metabolism of late-onset MADD, the objective evaluation of their rationalization on this disorder and comparison with riboflavin treatment are unknown. Methods： We performed a historical cohort study on the efficacy of the two drugs among 45 patients with late-onset MADD, who were divided into Glucocorticoids group and riboflavin group. Detailed clinical information of baseline and 1-month follow-up were collected. Results： After 1-month treatment, a dramatic improvement of muscle strength was found in riboflavin group （P 〈 0.05）. There was no significant difference in muscle enzymes between the two groups. Significantly, the number of patients with full recovery in Glucocorticoids group was less than the number in riboflavin group （P 〈 0.05）. On the other hand, almost half of the patients in riboflavin group still presented high-level muscle enzymes and weak muscle strength after 1-month riboflavin treatment, meaning that l-month treatment duration maybe insufficient and patients should keep on riboflavin supplement for a longer time. Conclusions： Our results provide credible evidences that the overall efficacy of riboflavin is superior to Glucocorticoids, and a longer duration of riboflavin treatment is necessary for patients with late-onset MADD.

关键词： Glucocorticoids Historical Cohort Study Late-onset Multiple Acyl-CoA Dehydrogenase Deficiency Lipid StorageMyopathy Riboflavin

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Luteotropic Roles of Glucocorticoids in Rat Granulosa Cells

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Reproductive and Developmental Medicine 2020年第4期4卷 195-203页

作者： Huang Xin-Yan Xu Yin-Yan Xie Juan Wang Li Department of Pharmacy Women’s Hospital of Nanjing Medical UniversityNanjing Maternity and Child Health Care HospitalNanjing 210004JiangsuChina

Objective:The study objective was to investigate whether endogenous Glucocorticoids directly impact the functions and proliferation/apoptosis of ovarian granulosa cells.Methods:Primary rat ovarian granulosa cells were cultured and treated with graded concentrations of corticosterone either alone or in the presence of the indicated drugs.After 48 h of treatment,the cells and growth media were collected to measure intracellular and extracellular progesterone/estradiol concentrations,and steroid secretion ratios were obtained by parameter calculation.The number of granulosa cells was determined by Cell Counting Kit-8.To determine the impact on cell numbers,granulosa cell proliferation was detected using the BrdU incorporation method and cell apoptosis was detected by flow cytometry.Results:First,high corticosterone concentrations significantly stimulated progesterone synthesis/secretion and inhibited estradiol synthesis in cultured granulosa cells.Second,accompanied by follicle-stimulating hormone,high corticosterone concentrations promoted progesterone synthesis/release and estradiol release.Last,high corticosterone concentrations increased the cell number and suppressed apoptosis but did not induce cell proliferation.Conclusions:These indicate that high glucocorticoid concentrations may play luteotropic roles in the functions and number of corpora lutea.

关键词： Apoptosis Glucocorticoids Granulosa Cells Ovary Steroid

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Central serous chorioretinopathy:from Glucocorticoids to light intensity

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International Journal of Ophthalmology(English edition) 2016年第2期9卷 312-314页

作者： Amir Norouzpour Majid Abrishami Eye Research Center Khatam-A1-Anbia Eye HospitalMashhad University of Medical Sciences Mashhad 91959-65919 Iran Retina Research Center Khatam-A1-Anbia Eye HospitalMashhad University of Medical Sciences Mashhad 91959-65919 Iran

Central serous chorioretinopathy （CSC） is characterized by a localized accumulation of subretinal fluid and an idiopathic focal leakage from choroidal vessels. The exact pathogenesis of CSC, however, still remains obscure. In this paper, we hypothesized that CSC may result from a response of choroidal vessels to an acute increase in the environmental light intensity leading to a focal leakage from the choroidal vessels. High levels of Glucocorticoids, in our proposed model, may cause persistence rather than initiation of the focal leakage, probably by suppressing the synthesis of collagen and extracellular matrix components and inhibiting fibroblastic activity.

关键词： central serous chorioretinopathy Glucocorticoids light intensity temperature choroidal vessels

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