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Glucocorticoid receptor signaling in the brain and its involvement in cognitive function
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作者 Chonglin Su Taiqi Huang +3 位作者 Meiyu Zhang Yanyu Zhang Yan Zeng Xingxing Chen 《Neural Regeneration Research》 SCIE CAS 2025年第9期2520-2537,共18页
The hypothalamic-pituitary-adrenal axis regulates the secretion of glucoco rticoids in response to environmental challenges.In the brain,a nuclear receptor transcription fa ctor,the glucocorticoid recepto r,is an impo... The hypothalamic-pituitary-adrenal axis regulates the secretion of glucoco rticoids in response to environmental challenges.In the brain,a nuclear receptor transcription fa ctor,the glucocorticoid recepto r,is an important component of the hypothalamicpituitary-a d renal axis's negative feedback loop and plays a key role in regulating cognitive equilibrium and neuroplasticity.The glucoco rticoid receptor influences cognitive processes,including glutamate neurotransmission,calcium signaling,and the activation of brain-derived neurotrophic factor-mediated pathways,through a combination of genomic and non-genomic mechanisms.Protein interactions within the central nervous system can alter the expression and activity of the glucocorticoid receptor,there by affecting the hypothalamic-pituitary-a d renal axis and stress-related cognitive functions.An appropriate level of glucocorticoid receptor expression can improve cognitive function,while excessive glucocorticoid receptors or long-term exposure to glucoco rticoids may lead to cognitive impairment.Patients with cognitive impairment-associated diseases,such as Alzheimer's disease,aging,depression,Parkinson's disease,Huntington's disease,stroke,and addiction,often present with dysregulation of the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor expression.This review provides a comprehensive overview of the functions of the glucoco rticoid receptor in the hypothalamic-pituitary-a d renal axis and cognitive activities.It emphasizes that appropriate glucocorticoid receptor signaling fa cilitates learning and memory,while its dysregulation can lead to cognitive impairment.This provides clues about how glucocorticoid receptor signaling can be targeted to ove rcome cognitive disability-related disorders. 展开更多
关键词 brain-derived neurotrophic factor calcium signaling glucocorticoid receptor glucocorticoid glutamate transmission hypothalamic-pituitary-adrenal axis long-term potentiation neurocognitive disorders NEUROPLASTICITY stress
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Study of the Effects of Glucocorticoid on Growth and Adult Final Height in Children with Primary Nephrotic Syndrome
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作者 Fazhan Zhong Miao Zhang Yan Gao 《Open Journal of Nephrology》 2024年第1期1-9,共9页
Objective: To analyze the epidemiological characteristics of growth, as well as factors associated with growth retardation in children with primary nephrotic syndrome (PNS), and to investigate the effect of glucocorti... Objective: To analyze the epidemiological characteristics of growth, as well as factors associated with growth retardation in children with primary nephrotic syndrome (PNS), and to investigate the effect of glucocorticoid (GC) use duration on growth retardation in these children. Methods: Clinical and laboratory data of 353 PNS children treated at our hospital from July 2014 to June 2015 were collected through the medical record management system. Height, weight, and GC usage were recorded. Follow-up assessments were conducted in August 2022 for the original group, recording height, weight, and GC usage. Height and weight were evaluated using standard deviation scores (SDS). Categorical data were analyzed using chi-square test while continuous measurement data were analyzed using t-test or rank-sum test. Linear regression was used to assess the association between two single independent variables, and logistic regression analysis was used to screen for risk factors related to growth retardation in children with PNS. Results: Among the 353 PNS children enrolled in this study, male-to-female ratio of 2.64:1 (256 males vs 97 females). A total of 119 children exhibited growth retardation, incidence rate of 33.71%. The duration of GC usage among those with growth retardation was significantly longer compared to those without it (762.81 ± 934.50 days vs 263.77 ± 420.49 days;p Conclusion: PNS children treated with GC have a high incidence of growth retardation, and a high proportion of short stature in adulthood, especially in children with growth retardation in childhood, most of them have short stature after grown up. Time of GC usage is a risk factor for growth retardation in children with PNS. 展开更多
关键词 Primary Nephrotic Syndrome glucocorticoid CHILDREN Growth Retardation Adult Height
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Progress in the Use of Glucocorticoids and Biological Agents in Non-Infectious Uveitis
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作者 Yuxuan Liu Xunyu Zou +1 位作者 Shizhou Cheng Zuhai Zhang 《Journal of Biosciences and Medicines》 2024年第2期138-155,共18页
One of the main immune-mediated diseases that lead to avoidable blindness is non-infectious uveitis. Glucocorticoids are the first-line therapy choice for noninfectious uveitis;however, biologics are also showing prom... One of the main immune-mediated diseases that lead to avoidable blindness is non-infectious uveitis. Glucocorticoids are the first-line therapy choice for noninfectious uveitis;however, biologics are also showing promise in the management of this condition. The description of glucocorticoid and biologic usage in non-infectious uveitis is the main topic of this paper. 展开更多
关键词 Non-Infectious Uveitis glucocorticoidS Biological Agents
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Shenqi Fuzheng injection alleviates chemotherapy-induced cachexia by restoring glucocorticoid signaling in hypothalamus
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作者 Entezar Berik Zijia Zhang +16 位作者 Wei Li Yawen Liu Sihan Chen Wenyong Wu Zhaojun Wang Xinqin Kong Wenqiang Pei Huiqing Dong Huali Long Min Lei Jennifer Yiyang Wang Liangfeng Liu Jinjun Hou Jing Feng Zhaoxia Li Wanying Wu De-an Guo 《Journal of Pharmaceutical Analysis》 SCIE CAS CSCD 2024年第3期431-434,共4页
Chemotherapy-induced cachexia(CIC)is a debilitating condition characterized by weight loss,muscle atrophy,and anorexia[1].While peripheral mechanisms of cachexia have been extensively studied,the involvement of the ce... Chemotherapy-induced cachexia(CIC)is a debilitating condition characterized by weight loss,muscle atrophy,and anorexia[1].While peripheral mechanisms of cachexia have been extensively studied,the involvement of the central nervous system(CNS)in CIC is often overlooked.Chemotherapeutic drugs cause stress responses and inflammation,which may impact the hypothalamus and disrupt systemic energy and neuroendocrine functions.Understanding hypothalamic roles in regulating these processes can provide insights into CIC's mechanisms and aid in developing novel therapies. 展开更多
关键词 injection DRUGS glucocorticoid CHEMOTHERAPY
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Comparison of inebilizumab or rituximab in addition to glucocorticoid therapy for neuromyelitis optica spectrum disorders
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作者 Chu-Yuan Lou Yong Wang +4 位作者 Jia-Yuan Xing Teng Ma Lei Tao Xiao-Tang Wang Run-Sheng Wang 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2024年第6期1073-1078,共6页
AIM:To investigate the short-term efficacy and safety of inebilizumab for neuromyelitis optica spectrum disorders(NMOSD).METHODS:A total of 33 patients with NMOSD treated with inebilizumab(Group INB,n=15)or rituximab(... AIM:To investigate the short-term efficacy and safety of inebilizumab for neuromyelitis optica spectrum disorders(NMOSD).METHODS:A total of 33 patients with NMOSD treated with inebilizumab(Group INB,n=15)or rituximab(Group RTX,n=18)in addition to high-dose glucocorticoids were included.Both groups underwent hormone shock therapy during the acute phase.Subsequently,Group INB received inebilizumab injections during the remission phase,while Group RTX received rituximab injections.A comparison of aquaporins 4(AQP4)titer values,peripheral blood B lymphocyte counts,and visual function recovery was conducted before and 8wk after treatment.Additionally,adverse reactions and patient tolerability were analyzed after using inebilizumab treatment regimes.RESULTS:Following inebilizumab treatment,there was a significantly improvement in the visual acuity of NMOSD patients(P<0.05),accompanied by a notable decrease in AQP4 titer values and B lymphocyte ratio(P<0.05).Moreover,inebilizumab treatment showed a partial effect in preventing optic nerve atrophy(P<0.05).However,there were no significant differences in other therapeutic effects compared to rituximab,which has previously demonstrated substantial therapeutic efficacy(P>0.05).Furthermore,inebilizumab exhibited higher safety levels than that of rituximab injections.CONCLUSION:The combination of inebilizumab and high-dose glucocorticoids proves to be effective.In comparison to rituximab injections,inebilizumab displays better tolerance and safety.Moreover,it demonstrates a partial effect in preventing optic nerve atrophy.Thus,it stands as an effective method to reduce the disability rates and improve the daily living ability of patients with NMOSD. 展开更多
关键词 neuromyelitis optica spectrum disorders inebilizumab RITUXIMAB glucocorticoidS
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Glucocorticoids-based prodrug design:Current strategies and research progress
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作者 Hongbing Liu Muse Ji +5 位作者 Peifu Xiao Jingxin Gou Tian Yin Haibing He Xing Tang Yu Zhang 《Asian Journal of Pharmaceutical Sciences》 SCIE CAS 2024年第3期41-78,共38页
Attributing to their broad pharmacological effects encompassing anti-inflammation,antitoxin,and immunosuppression,glucocorticoids(GCs)are extensively utilized in the clinic for the treatment of diverse diseases such a... Attributing to their broad pharmacological effects encompassing anti-inflammation,antitoxin,and immunosuppression,glucocorticoids(GCs)are extensively utilized in the clinic for the treatment of diverse diseases such as lupus erythematosus,nephritis,arthritis,ulcerative colitis,asthma,keratitis,macular edema,and leukemia.However,longterm use often causes undesirable side effects,including metabolic disorders-induced Cushing's syndrome(buffalo back,full moon face,hyperglycemia,etc.),osteoporosis,aggravated infection,psychosis,glaucoma,and cataract.These notorious side effects seriously compromise patients'quality of life,especially in patients with chronic diseases.Therefore,glucocorticoid-based advanced drug delivery systems for reducing adverse effects have received extensive attention.Among them,prodrugs have the advantages of low investment,low risk,and high success rate,making them a promising strategy.In this review,we propose the strategies for the design and summarize current research progress of glucocorticoid-based prodrugs in recent decades,including polymer-based prodrugs,dendrimer-based prodrugs,antibody-drug conjugates,peptide-drug conjugates,carbohydrate-based prodrugs,aliphatic acid-based prodrugs and so on.Besides,we also raise issues that need to be focused on during the development of glucocorticoid-based prodrugs.This review is expected to be helpful for the research and development of novel GCs and prodrugs. 展开更多
关键词 glucocorticoidS Prodrug design Targeted drug delivery Research progress
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Combination treatment with telitacicept,mycophenolate mofetil and glucocorticoids for immunoglobulin A nephropathy:A case report
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作者 Yan Shen Jin Yuan +4 位作者 Shuang Chen Yong-Feng Zhang Ling Yin Qin Hong Yan Zha 《World Journal of Clinical Cases》 SCIE 2024年第29期6307-6313,共7页
BACKGROUND Telitacicept reduces B cell activation and abnormal immunoglobulin A(IgA)antibody production by inhibiting the activity of B lymphocyte stimulator(BLyS)and a proliferation-inducing ligand(APRIL),thereby dec... BACKGROUND Telitacicept reduces B cell activation and abnormal immunoglobulin A(IgA)antibody production by inhibiting the activity of B lymphocyte stimulator(BLyS)and a proliferation-inducing ligand(APRIL),thereby decreasing IgA deposition in the glomeruli and local inflammatory response.This ultimately protects the kidneys from damage.This mechanism suggests that Telitacicept has potential efficacy in the treatment of IgA nephropathy.CASE SUMMARY We present the case of a 24-year-old female who was diagnosed with IgA nephropathy due to significant proteinuria and mild renal impairment.Pathologically,she exhibited focal proliferative glomerulonephritis.Treatment with angiotensin II receptor blocker,hormones,and mycophenolate mofetil did not lead to a significant improvement in her condition.However,upon the addition of telitacicept,the patient’s renal function recovered and her proteinuria rapidly reduced.Hormones were swiftly tapered and discontinued,with no occurrence of severe infections or related complications.CONCLUSION Telitacicept combined with hormones and mycophenolate mofetil may be a safe and effective induction therapy for IgA nephropathy. 展开更多
关键词 IgA nephropathy Telitacicept Mycophenolate mofetil glucocorticoidS Case report
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Glucocorticoid therapy in pancreatic portal hypertension associated with autoimmune pancreatitis:A case report
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作者 Yi Zhang Zhao-Dong Li +3 位作者 Yuan-Jing He Wei Peng Yu-Jun Luo Xiao-An Li 《World Journal of Clinical Cases》 SCIE 2024年第22期5184-5188,共5页
BACKGROUND Autoimmune pancreatitis(AIP)is a chronic form of pancreatitis characterized by diffused enlargement of the pancreas and irregular stenosis of the main pancreatic duct.Some studies have reported that AIP can... BACKGROUND Autoimmune pancreatitis(AIP)is a chronic form of pancreatitis characterized by diffused enlargement of the pancreas and irregular stenosis of the main pancreatic duct.Some studies have reported that AIP can cause hemorrhage of gastric varices(GV)related to portal hypertension(PH).However,such cases are rare.In addition,the association of PH with AIP is unclear.At the same time,the efficacy and duration of glucocorticoid therapy is also controversial.CASE SUMMARY In this case,we reported a case of GV in pancreatic PH associated with AIP.Enhanced abdominal computed tomography(CT)suggested splenic vein(SV)and superior mesenteric vein(SMV)thromboses.The patient received a long-term glucocorticoid therapy,that the initial dose of 40 mg is reduced weekly by 5 mg,and then reduced to 5 mg for long-term maintenance.CT and gastroscopic examination after 8 mo of treatment indicated that SV and SMV were recanalized,pancreatic stiffness and swelling were ameliorated,and the GV almost completely disappeared.CONCLUSION Long-term glucocorticoid therapy can alleviate the development of GV in patients with AIP and has potential reversibility. 展开更多
关键词 Autoimmune pancreatitis Pancreatic portal hypertension Gastric varices glucocorticoid therapy Case report
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Home-Nebulized Inhaled Glucocorticoid Therapy in Pediatric Respiratory Diseases
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作者 Jiuwei Dong Lili Zhang Xiaohua Jiang 《Journal of Clinical and Nursing Research》 2024年第5期188-193,共6页
Objective:To evaluate the therapeutic effect of home-nebulized inhaled glucocorticoid therapy in pediatric respiratory diseases.Methods:60 cases of children with respiratory diseases admitted between October 2022 and ... Objective:To evaluate the therapeutic effect of home-nebulized inhaled glucocorticoid therapy in pediatric respiratory diseases.Methods:60 cases of children with respiratory diseases admitted between October 2022 and October 2023 were selected as study subjects and randomly divided into the control group and the observation group,30 cases each.The control group was provided with conventional treatment only,while the observation group was provided with home-nebulized inhalation glucocorticosteroid treatment,and the treatment effects,clinical symptom relief time,disease recurrence rate,and treatment satisfaction of the children’s families were recorded and compared between the two groups.Results:A comparison of the two groups in terms of gender and age showed that the differences were not statistically significant(P>0.05).In terms of clinical efficacy,the total effective rate of the observation group was 90.00%,which was significantly higher than that of the control group of 66.67%(P<0.05).Compared with the control group,the disappearance time of the clinical symptoms of the observed group was significantly shortened(P<0.05).In addition,the satisfaction scores of the families of the children in the observation group were significantly higher than those of the control group(P<0.05).Conclusion:Home-nebulized inhalation glucocorticoid therapy shows significant clinical efficacy in pediatric respiratory diseases,significantly reduces the time of disappearance of clinical symptoms,and improves the satisfaction of patients’families,which provides an effective treatment option for children. 展开更多
关键词 Home-nebulized inhalation glucocorticoidS Pediatric respiratory diseases
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中药调控成骨细胞铁死亡治疗激素性股骨头坏死
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作者 张绵钰 韩杰 +2 位作者 曾浩 陈相汕 高振罡 《中国组织工程研究》 CAS 北大核心 2025年第1期185-192,共8页
背景:有研究发现成骨细胞铁死亡可作为重要的发病机制诱导激素性股骨头坏死的发生与发展。随着祖国医学的发展,有学者发现某些中药单体、中药复方及中成药等可通过多种通路机制调控成骨细胞铁死亡,最终起到治疗激素性股骨头坏死的作用... 背景:有研究发现成骨细胞铁死亡可作为重要的发病机制诱导激素性股骨头坏死的发生与发展。随着祖国医学的发展,有学者发现某些中药单体、中药复方及中成药等可通过多种通路机制调控成骨细胞铁死亡,最终起到治疗激素性股骨头坏死的作用。目的:探讨成骨细胞铁死亡与激素性股骨头坏死的关系及中草药调控成骨细胞铁死亡治疗激素性股骨头坏死的作用机制,为激素性股骨头坏死的诊治提供新的思路。方法:以“铁死亡,激素性股骨头坏死,成骨细胞,中草药,糖皮质激素,铁代谢,活性氧,谷胱甘肽过氧化物酶”为中文检索词,以“ferroptosis,Hormonal necrosis of the femoral head,osteoblast,Chinese herbal medicine,glucocorticoid,iron metabolism,ROS,GPX4”为英文检索词,检索中国知网、Pub Med、万方及维普数据库,筛选各数据库建库至2023年成骨细胞铁死亡与激素性股骨头坏死及中草药干预调控研究相关的文章,最终纳入74篇文献进行综述分析。结果与结论:(1)成骨细胞铁死亡在激素性股骨头坏死发病中起重要作用。(2)成骨细胞铁死亡的发生受到多种机制通路调控,如细胞内铁超载引起铁死亡;细胞发生脂质过氧化损伤细胞膜引起铁死亡;细胞膜上胱氨酸/谷氨酸逆向转运蛋白通过影响谷胱甘肽水平和谷胱甘肽过氧化物酶4活性,从而诱导铁死亡;细胞内发生芬顿反应产生大量活性氧引起铁死亡等。(3)中药单体淫羊藿苷等、中药复方青娥丸等及中成药补肾活血颗粒等均可通过调控成骨细胞铁死亡的发生,有助于防治激素性股骨头坏死。(4)目前关于成骨细胞铁死亡相关机制尚不明确,继续深入探明两者的作用机制,有望为临床治疗激素性股骨头坏死提供新选择。 展开更多
关键词 股骨头坏死 铁死亡 中医药 成骨细胞 糖皮质激素 铁代谢 活性氧 谷胱甘肽 谷胱甘肽过氧化物酶 脂质过氧化
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Morphological and behavioral consequences of recurrent seizures in neo-natal rats are associated with glucocorticoid levels 被引量:1
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作者 石秀玉 王纪文 +1 位作者 雷格非 孙若鹏 《Neuroscience Bulletin》 SCIE CAS CSCD 2007年第2期83-91,共9页
Objective It is well documented that epilepsy can increase neurogenesis in certain brain regions and cause behavioral alternations in patients and different epileptic animal models. A series of experimental studies ha... Objective It is well documented that epilepsy can increase neurogenesis in certain brain regions and cause behavioral alternations in patients and different epileptic animal models. A series of experimental studies have demonstrated that neurogenesis is regulated by various factors including glucocorticoid (CORT), which can reduce neurogenesis. Most of studies in animal have been focused on adulthood stage, while the effect of recurrent seizures to immature brain in neonatal period has not been well established. This study was designed to investigate how the recurrent seizures occurred in the neonatal period affected the immature brain and how CORT regulated neurogenesis in immature animals. Methods Neonatal rats were subjected to 3 pilocarpine-induced seizures from postnatal day 1 to day 7. Then neurogenesis at different postnatal ages (i.e. P8, P12, P22, P50) was observed. Behavioral performance was tested when the rats were mature (P40), and plasma CORT levels following recurrent seizures were simultaneously monitored. Results Rats with neonatal seizures had a significant reduction in the number of Bromodeoxyuridine (BrdU) labeled cells in the dentate gyrus compared with the control groups when the animals were euthanized on P8 or P12 (P 〈 0.05); whereas there was no difference between the two groups on P22. Until P50, rats with neonatal seizures had increased number of BrdU-labeled cells compared with the control group (P 〈 0.05). In Morris water maze task, pilocarpine-treated rats were significantly slower than the control rats at the first and second day, and there were no differences at other days. In probe trial, there was no significant difference in time spent in the goal quadrant between the two groups. Endocrine studies showed a correla- tion between the number of BrdU positive cells and the CORT level. Sustained increase in circulating CORT levels was observed following neonatal seizures on P8 and P12. Conclusion Neonatal recurrent seizures can biphasely modulate neurogenesis over different time windows with a down-regulation at early time and up-regulation afterwards, cause persistent deficits in cognitive functions of adults, and increase the circulating CORT levels. CORT levels are related with the morphological and behavioral consequences of recurrent seizures. 展开更多
关键词 EPILEPSY development cell proliferation learning memory glucocorticoid
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下肢关节置换前糖皮质激素静脉注射对疗效及安全性影响的Meta分析
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作者 王建磊 何培亮 孙永建 《中国组织工程研究》 CAS 北大核心 2025年第3期599-607,共9页
目的:术前静脉用糖皮质激素对下肢关节置换患者的临床疗效及安全性仍存在争议。因此进行了一项基于随机对照试验的荟萃分析,以评估术前静脉注射糖皮质激素对临床下肢关节置换治疗的有效性和安全性。方法:系统检索了中外数据库截至2023年... 目的:术前静脉用糖皮质激素对下肢关节置换患者的临床疗效及安全性仍存在争议。因此进行了一项基于随机对照试验的荟萃分析,以评估术前静脉注射糖皮质激素对临床下肢关节置换治疗的有效性和安全性。方法:系统检索了中外数据库截至2023年6月关于术前静脉注射糖皮质激素对下肢关节置换疗效及安全性影响的随机对照试验,包括PubMed、Embase、Web of Science、Cochrane图书馆、中国万方数据库和中国知网。试验组术前静脉注射糖皮质激素以控制疼痛;对照组使用安慰剂或静脉生理盐水;观察指标包括术后静息疼痛评分、术后C-反应蛋白、术后5 m步行试验疼痛评分、住院天数、手术时间、术后追加吗啡阿片类药物量、术后发生恶心呕吐反应及术后假体周围感染并发症。结果:①共纳入9项随机对照试验,包括613例患者(糖皮质激素311例,对照组302例);②与对照组相比,术前静脉注射糖皮质激素可显著降低下肢关节置换患者术后6,12 h的静息疼痛评分及术后第1天下地活动5 m的疼痛评分;此外,糖皮质激素组在术后追加吗啡阿片类药物需要量减少、术后恶心呕吐发生率降低,术后3 d内炎症C-反应蛋白水平较对照组降低,住院天数缩短,差异均有显著性意义(P<0.05);③但是两组患者关节置换术后感染发生率、手术时长及24,48 h的疼痛评分则无明显差异。结论:作为一种有效的围术期多模式镇痛方案,术前静脉注射糖皮质激素是改善下肢关节置换患者术后超急性疼痛和关节活动有效和安全的方法;但需要更多的研究来确定糖皮质激素的最佳剂量和类型,以最大限度地控制疼痛。 展开更多
关键词 关节置换 糖皮质激素 术后疼痛 安全性 META分析
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High-dose dexamethasone regulates microglial polarization via the GR/JAK1/STAT3 signaling pathway after traumatic brain injury
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作者 Mengshi Yang Miao Bai +10 位作者 Yuan Zhuang Shenghua Lu Qianqian Ge Hao Li Yu Deng Hongbin Wu Xiaojian Xu Fei Niu Xinlong Dong Bin Zhang Baiyun Liu 《Neural Regeneration Research》 SCIE CAS 2025年第9期2611-2623,共13页
Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently understood.As potent anti-i... Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently understood.As potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet known.In the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of action.In vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial polarization.Lipopolysaccharide,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were administered.RNA-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of dexamethasone.The Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our hypothesis.High-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain injury.Thus dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in vivo.Glucocorticoid receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain injury.Additionally,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is the GR/JAK1/STAT3 pathway.Overactivation of glucocorticoid receptor by high-dose dexamethasone reduced the expression of M2 microglia,which plays an antiinflammatory role.In contrast,inhibiting the activation of glucocorticoid receptor reduced the number of apoptotic glia and neurons and decreased the loss of dendritic spines after traumatic brain injury.Dexamethasone may exe rt its neurotoxic effects by inhibiting M2 microglia through the GR/JAK1/STAT3 signaling pathway. 展开更多
关键词 apoptosis BV2 microglia DEXAMETHASONE glucocorticoid receptor glucocorticoidS innate immune system microglial polarization neuroinflammation primary microglia traumatic brain injury
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The effect of intravenous high-dose glucocorticoids and orbital decompression surgery on sight-threatening thyroid-associated ophthalmopathy 被引量:8
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作者 Yun Wen Jian-Hua Yan 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2019年第11期1737-1745,共9页
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 revie... 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. 展开更多
关键词 thyroid-associated OPHTHALMOPATHY dysthyroid optic NEUROPATHY glucocorticoidS ORBITAL DECOMPRESSION ORBITAL surgery
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Rapamycin Sensitizes Glucocorticoid Resistant Acute Lymphoblastic Leukemia CEM-C1 Cells to Dexamethasone Induced Apoptosis through both mTOR Suppression and Up-Regulation and Activation of Glucocorticoid Receptor 被引量:4
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作者 GUO Xia ZHOU Chen Yan +4 位作者 LI Qiang GAO Ju ZHU Yi Ping GU Ling MA Zhi Gui 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2013年第5期371-381,共11页
Objective To explore the role of glucocorticoid (GC) receptor (GR) in rapamycin's reversion of GC resistance in humanGC-resistant T-acute lymphoblastic leukemia (ALL) CEM-C1 cells. Methods CEM-C1 cells were cul... Objective To explore the role of glucocorticoid (GC) receptor (GR) in rapamycin's reversion of GC resistance in humanGC-resistant T-acute lymphoblastic leukemia (ALL) CEM-C1 cells. Methods CEM-C1 cells were cultured in vitro and treated with rapamycin at different concentrations with or without 1 μmol/L dexamethasone (Dex). 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) test was performed to assess cell proliferation. The cell cycle and cell apoptosis were analyzed by flow cytometry. The expression of GRα mRNA was determined by real-time quantitative RT-PCR. The expression of GR, p-70S6K, Mcl-1, and Bim proteins was detected by Western blot. Results When incubated with rapamycin at different concentrations, CEM-C1 cells showed significant growth inhibition in a time- and concentration-dependent manner. The growth inhibition was synergistically increased when CEM-C1 cells were treated with rapamycin plus 1 μmol/L Dex. CEM-C1 cells treated with rapamycin alone showed no apparent apoptosis, and were arrested at G0/G1 phase. After the treatment with Dex plus rapamycin, CEM-C1 cells demonstrated apparent apoptosis and increased the cell cycle arrested at G0/G1 phase. Rapamycin combined with Dex up-regulated GRα, phosphorylated GR(p-GR), and pro-apoptotic protein Bim-EL in CEM-C1 cells, but inhibited the expression of p-p70S6K, a downstream target protein ofmTOR (mammalian target of rapamycin). Conclusion After the treatment with rapamycin plus Dex, Dex resistant CEM-C1 cells induce growth inhibition and apoptosis. The underlying mechanism may involve inhibition of the mTOR signaling pathway and also be associated with up-regulation of GR expression and activation of GC-GR signaling pathway. 展开更多
关键词 Acute lymphoblastic leukemia MTOR glucocorticoid resistance RAPAMYCIN glucocorticoid receptor
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MicroRNAs as tools to predict glucocorticoid response in inflammatory bowel diseases 被引量:4
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作者 Sara De Iudicibus Marianna Lucafò +3 位作者 Stefano Martelossi Chiara Pierobon Alessandro Ventura Giuliana Decorti 《World Journal of Gastroenterology》 SCIE CAS 2013年第44期7947-7954,共8页
In spite of the introduction in therapy of highly effective biological agents,glucocorticoids(GCs)are still employed to induce remission in moderate to severe inflammatory bowel diseases(IBD),but considerable inter-in... In spite of the introduction in therapy of highly effective biological agents,glucocorticoids(GCs)are still employed to induce remission in moderate to severe inflammatory bowel diseases(IBD),but considerable inter-individual differences in their efficacy and side effects have been reported.The effectiveness of these drugs is indeed very variable and side effects,particularly severe in pediatric patients,are common and often unpredictable:the understanding of the complex gene regulation mediated by GCs could shed light on the causes of this variability.In this context,microRNAs(miRNAs)represent a new and promising field of research.miRNAs are small non-coding RNA molecules that suppress gene expression at post-transcriptional level,and are fine-tuning regulators of diverse biological processes,including the development and function of the immune system,apoptosis,metabolism and inflammation.Emerging data have implicated the deregulated expression of certain miRNA networks in the pathogenesis of autoimmune and inflammatory diseases,such as IBD.There is a great interest in the identification of the role of miRNAs in the modulation of pharmacological response;however,the association between miRNA and GC response in patients with IBD has not yet been evaluated in a prospective clinical study.The identification of miRNAs differently expressed as a consequence of GC treatment in comparison to diagnosis,represents an important innovative approach that could be translated into clinical practice.In this review we highlight the altered regulation of proteins involved in GC molecular mechanism by miRNAs,and their potential role as molecular markers useful for predicting in advance GC response. 展开更多
关键词 glucocorticoidS INFLAMMATORY BOWEL diseases MicroRNA Molecular MARKERS PHARMACOGENOMICS
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Intravenous glucocorticoids therapy in the treatment of Graves’ ophthalmopathy: a systematic review and Meta-analysis 被引量:6
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作者 Li-Quan Zhao Dan-Yang Yu Jin-Wei Cheng 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2019年第7期1177-1186,共10页
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 trial... 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-line treatment for moderate-to-severe GO, and the use of rituximab or MMF to be the second-line treatment instead of IVGC. However, the evidence is very low quality, which is insufficient to support the use of IVGC or orbital decompression as the first-line treatment of DON. 展开更多
关键词 glucocorticoidS Graves' OPHTHALMOPATHY META-ANALYSIS
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Impact of glucocorticoid on neurogenesis 被引量:5
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作者 Haruki Odaka Naoki Adachi Tadahiro Numakawa 《Neural Regeneration Research》 SCIE CAS CSCD 2017年第7期1028-1035,共8页
Neurogenesis is currently an area of great interest in neuroscience.It is closely linked to brain diseases,including mental disorders and neurodevelopmental disease.Both embryonic and adult neurogeneses are influenced... Neurogenesis is currently an area of great interest in neuroscience.It is closely linked to brain diseases,including mental disorders and neurodevelopmental disease.Both embryonic and adult neurogeneses are influenced by glucocorticoids secreted from the adrenal glands in response to a variety of stressors.Moreover,proliferation/differentiation of the neural stem/progenitor cells(NSPCs)is affected by glucocorticoids through intracellular signaling pathways such as phosphoinositide 3-kinase(PI3K)/Akt,hedgehog,and Wnt.Our review presents recent evidence of the impact of glucocorticoids on NSPC behaviors and the underlying molecular mechanisms;this provides important information for understanding the pathological role of glucocorticoids on neurogenesis-associated brain diseases. 展开更多
关键词 neural progenitor cells glucocorticoidS NEUROGENESIS in tracellular signaling pathways
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Central serous chorioretinopathy:from glucocorticoids to light intensity 被引量:4
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作者 Amir Norouzpour Majid Abrishami 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2016年第2期312-314,共3页
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 o... 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. 展开更多
关键词 central serous chorioretinopathy glucocorticoidS light intensity TEMPERATURE choroidal vessels
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Glucocorticoids and prostate cancer treatment: friend or foe? 被引量:2
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作者 Bruce Montgomery Heather H Cheng +1 位作者 James Drechsler Elahe A Mostaghel 《Asian Journal of Andrology》 SCIE CAS CSCD 2014年第3期354-358,共5页
Glucocorticoids have been used in the treatment of prostate cancer to slow disease progression, improve pain control and offset side effects of chemo- and hormonal therapy. However, they may also have the potential to... Glucocorticoids have been used in the treatment of prostate cancer to slow disease progression, improve pain control and offset side effects of chemo- and hormonal therapy. However, they may also have the potential to drive prostate cancer growth via mutated androgen receptors or glucocorticoid receptors (GRs). In this review we examine historical and contemporary use of glucocorticoids in the treatment of prostate cancer, review potential mechanisms by which they may inhibit or drive prostate cancer growth, and describe potential means of defining their contribution to the biology of prostate cancer. 展开更多
关键词 androgen receptor DIHYDROTESTOSTERONE glucocorticoid receptor glucocorticoidS prostate cancer STEROIDS TESTOSTERONE
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