BACKGROUND Thymic epithelial neoplasms are rare malignant neoplasms originating in the thymus gland.There have been case reports of patients with advanced thymomas treated with a methylprednisolone pulse or with gluco...BACKGROUND Thymic epithelial neoplasms are rare malignant neoplasms originating in the thymus gland.There have been case reports of patients with advanced thymomas treated with a methylprednisolone pulse or with glucocorticoid(GCs)shock be-fore surgery,followed by surgical treatment,all of whom achieved good results.The effect of GCs on thymomas is related mainly to the action on GC receptors in thymic lymphocytes and epithelial cells.GC receptor expression has been asso-ciated with a better prognosis in patients with thymomas,including those with surgically removed thymomas.CASE SUMMARY We report a case of a patient with thymoma who had a significant response to preoperative low-dose GC therapy.A mediastinal tumor was detected in the patient via computerized tomography upon admission.The tumor was initially suspected to be a thymic tumor,but lymphoma could not be ruled out.The tumor shrank significantly after low-dose(5 mg/day)GC therapy.Thoracoscopic thy-moma resection was performed after puncture pathology was confirmed.The patient recovered well after the operation and is currently performing well with no recurrence of the tumor.CONCLUSION This case highlights that low-dose GCs are effective in the treatment of thymomas,and we believe that GCs should be applied more frequently and studied more thoroughly in the treatment of thymomas.展开更多
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
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:Fift...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 treatment in RA.MIF may be a factor for moxibustion to regulate the expression of CORT,but the expression of TNF-α is due to the incomplete regulation of the MIF.This study added to the body of evidence pointing to moxibustion's antiinflammatory mechanism in the treatment of RA.展开更多
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
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
Objective:To analyze changes in liver and kidney function and lipid metabolism in patients with refractory nephrotic syndrome(RNS)after receiving different treatments.Methods:A total of 64 patients treated in the Wuwe...Objective:To analyze changes in liver and kidney function and lipid metabolism in patients with refractory nephrotic syndrome(RNS)after receiving different treatments.Methods:A total of 64 patients treated in the Wuwei Hospital of Traditional Chinese Medicine from January 2018 to January 2021 were included in this study.All subjects were diagnosed with RNS and randomly assigned to groups:a control group(32 cases)and an observation group(32 cases).The control group received cyclophosphamide+glucocorticoids,while the observation group received tacrolimus+glucocorticoids,both for six months.The various indicators of the two groups were compared.Results:After six months of treatment,the overall clinical efficacy rate of the observation group was significantly higher than that of the control group.Six months post-treatment,levels of serum ALT,AST,BUN,SCr,24 h UTP,TG,and TC were reduced in both groups compared to baseline levels,with reductions more pronounced in the observation group.Serum ALB levels increased in both groups,with a more significant increase in the observation group.Statistical analysis showed these differences were significant(P<0.05).There were no significant changes in FBG levels in either group(P>0.05).Conclusion:For RNS patients,treatment with tacrolimus combined with glucocorticoids significantly reduces liver function damage,improves kidney function and lipid metabolism,and enhances clinical efficacy.展开更多
There is an interaction between tacrolimus(TAC) and glucocorticoids where glucocorticoids is a known CYP3A4 and P-gp inducer.However, the dose of glucocorticoids reported is low but not pulse therapy.We retrospectivel...There is an interaction between tacrolimus(TAC) and glucocorticoids where glucocorticoids is a known CYP3A4 and P-gp inducer.However, the dose of glucocorticoids reported is low but not pulse therapy.We retrospectively studied 63 renal transplant recipients receiving TAC after transplantation.All the patients were classified as 500 mg(POD 1–3), 30 mg(POD 4–10), 25 mg(POD 11–17), 20 mg(POD 18–24), 15 mg(POD 25–31), 10 mg(POD 32–60) and 10 mg(POD 61–90).We recorded daily data for each patient from the day of transplantation until POD 90.There was no difference in TAC blood levels within the 3 months after transplantation in the glucocorticoids groups.However, the average daily dose of TAC was significantly lower by weekly reductions of 5 mg dose.The TAC daily dose was not changed from POD 1–4, but the blood concentrations of TAC were significantly lower after the glucocorticoid dose was changed from 500 mg to 30 mg.We demonstrated the induction effect of low-dose glucocorticoids on TAC in renal transplant recipients, and found that the high-dose of glucocorticoids might play a role in substrate competition.We proposed that monitoring of the blood concentrations of TAC was needed when the glucocorticoid dose was changed in the patient undergoing renal transplantation.展开更多
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
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
AIM： To determine how glucocorticoids （GCs） may affect the growth and chemosensitivity of common carcinoma cells. METHODS： The effect of dexamethasone （DEX） on growth and chemosensitivity was assessed in 14 carc...AIM： To determine how glucocorticoids （GCs） may affect the growth and chemosensitivity of common carcinoma cells. METHODS： The effect of dexamethasone （DEX） on growth and chemosensitivity was assessed in 14 carcinoma cell lines. The function of GC receptors （GR） was assessed by MMTV reporter assay. Overexpression of GR was done by in vitro transfection and expression of a GR-expressing vector. Immunohistochemical stain of tissues and ceils were done by PA1-511A, an anti-GR monodonal antibody. RESULTS： DEX inhibited cell growth of four （MCF-7, MCF- 7/MXR1, MCF-7/TPT300, and HeLa）, increased cisplatin cytoxicity of one （SiHa）, and decreased dsplatin cytotoxicity of two （H460 and Hep3B） cell lines. The GR content of the seven cell lines affected by DEX was significantly higher than those of the seven cell lines unaffected by DEX （5.2±2.5×10^4 sites/cell vs1.3±1.4×10^4 sites/cell, P= 0.005）. Only two DEX-unresponsive cell lines {NPC-TW01 and NPC- TW04） oontained high GR amounts in the range （1.9-8.1×10^4 sites/cell） of the seven DEX-responsive cell lines. The GR function of NPC-TW01 and NPC-TW04, however, was foundto be impaired. The importance of high cellular amount of GR in mediating DEX susceptibility of the cells was further exemplified by GR dose-dependent drug resistance to cisplatin of AGS, a cell line with low GR content and was unaffected by DEX before transfection of GR-expressing vector. Immunohistochemical studies of human cancer tissues showed that 5 of the 45 （11.1%） breast cancer and 43 of the 85 （50.6%） non-small cell lung cancer had high GR contents at the ranges of the GC-responsive carcinoma cell lines. CONCLUSION： The growth and chemosensitivity of human carcinomas with high GR contents may be affected by GC. However, in light of the heterogeneous and even contradictive effects of GC on these cells, routine examination of GR contents of human carcinoma tissues may not be clinically useful until other markers that help predict the ultimate effect of GC on individual patients are identified.展开更多
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
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
While the adverse effects of glucocorticoids on bone are well described, positive effects of glucocorticoids on the differentiation of osteoblasts are also observed. These paradoxical effects of glucocorticoids are do...While the adverse effects of glucocorticoids on bone are well described, positive effects of glucocorticoids on the differentiation of osteoblasts are also observed. These paradoxical effects of glucocorticoids are dose dependent. At both physiologicaland supraphysiological levels of glucocorticoids, osteoblasts and osteocytes are the major glucocorticoid target cells. However, the response of the osteoblasts to each of these is quite distinct. At physiology levels, glucocorticoids direct mesenchymal progenitor cells to differentiate towards osteoblasts and thus increase bone formation in a positive way. In contrast with ageing, the excess production of glucocorticoids, at both systemic and intracellular levels, appear to impact on osteoblast and osteocytes in a negative way in a similar fashion to that seen with therapeutic glucocorticoids. This review will focus on therole of glucocorticoids in normal bone physiology, with particular emphasis on the mechanism by which endogenous glucocorticoids impact on bone and its constituent cells.展开更多
BACKGROUND: Community-acquired pneumonia(CAP) is pneumonia acquired infectiously from normal social contact as opposed to being acquired during hospitalization. CAP is a leading cause of illness and death. This review...BACKGROUND: Community-acquired pneumonia(CAP) is pneumonia acquired infectiously from normal social contact as opposed to being acquired during hospitalization. CAP is a leading cause of illness and death. This review aims to determine the efficacy and safety of glucocorticoids in the treatment of community-acquired pneumonia(CAP).DATA SOURCES: We searched randomized controlled trials(RCTs) from Pubmed, EMBASE, Cochrane Library, Chinese Journal Full-text Database, and Chinese Biomedical Literature Database to obtain the information by using steroids, glucocorticoids, cortisol, corticosteroids, community-acquired pneumonia and CAP as key words. The quality of RCTs was evaluated. A Meta-analysis was made using Rev Man 5.0 provided by the Cochrance Collaboration.RESULTS: Seven RCTs involving 944 patients were included in the meta-analysis. The mean length of hospital stay in glucocorticoids treatment group was significantly shorter than that in standard treatment group(WMD=–1.70, 95%CI 2.01–1.39, Z=10.81, P<0.00001). No statistically significant differences were found in the mortality rate(RR=0.77,95%CI 0.46–1.27, Z=1.03, P=0.30), the mean length of hospital stay in ICU(WMD=1.17, 95%CI 1.68–4.02, Z=0.81, P=0.42), the incidence of super infection(RR=1.32, 95%CI 0.66–2.63, Z=0.79, P=0.43), the incidence of hyperglycemia(RR=1.84, 95%CI 0.76–4.41, Z=1.36, P=0.17), the incidence of upper gastrointestinal bleeding(RR=1.98, 95%CI 0.37–10.59, Z=0.80, P=0.42) between the standard treatment group and the glucocorticoids treatment group.CONCLUSIONS: The use of glucocorticoids in patients with community-acquired pneumonia can significantly shorten the duration of illness and have a favorable safety profile. However, it could not reduce the overall mortality.展开更多
Background: Henoch Schonlein Purpura (HSP) is a common immune-related allergic disease in children. It is very important to understand the clinical features of this disease for doctors. Objective: To explore the clini...Background: Henoch Schonlein Purpura (HSP) is a common immune-related allergic disease in children. It is very important to understand the clinical features of this disease for doctors. Objective: To explore the clinical efficacy of glucocorticoids in the treatment of HSP in Tibetan children at high altitude, and to analyze the possible causes of HSP in children at high altitude. The risk factors of the disease provide a reference for the treatment of HSP in children in high altitude areas. Methods: Selecting January 2015 to November 2020, 88 children diagnosed with Henoch-Schonlein Purpura in the outpatient and inpatient departments of the People’s Hospital of Bomi County, Tibet Autonomous Region were the subjects of the study. Its gender, age of onset, season of onset, predisposing factors, allergy history, first symptoms, clinical manifestations, laboratory examinations, etc., perform retrospective analysis. Results: Among 88 children with allergic purpura, 55 were boys, accounting for 62.5%, and 33 were girls, accounting for 37.5%. Men have more cases than women. All have clinical manifestations of purpura of the skin, among which 35 cases have obvious triggers, of which the above there were 26 cases of respiratory infections, 6 cases of dietary factors, and 3 cases of contact with allergic substances. Simple skin type: 18 cases, accounting for 20.45%;Abdominal type: 6 cases, accounting for 6.82%;2 male cases, accounting for 33.33%;4 female cases, accounting for 66.67%;Articular type: 8 cases, accounting for 33.33%;Renal type: 2 cases, accounting for 2.27%;54 cases of mixed type, accounting for 61.36%. After glucocorticoids, the rashes disappeared, no any adverse reactions. Conclusion: Allergic purpura in children is more common in school-age children, and upper respiratory tract infection is the main predisposing factor. Skin purpura is the main clinical manifestation, often associated with lower extremity joint swelling and pain. There is no significant difference in the efficacy and course of the disease between intravenous and oral treatment. Therefore, clinicians should strictly grasp the indications of glucocorticoids to reduce the occurrence of complications.展开更多
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 us...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.展开更多
Glucocorticoid and glucocorticoid receptor（GC/GR） interactions alter numerous aspects of neuronal function. These consequences（e.g., anti-inflammatory vs. pro-inflammatory） can vary depending on the duration of GC...Glucocorticoid and glucocorticoid receptor（GC/GR） interactions alter numerous aspects of neuronal function. These consequences（e.g., anti-inflammatory vs. pro-inflammatory） can vary depending on the duration of GC exposure or central nervous system（CNS） injury model. In this review we discuss how GC/GR interactions impact neuronal recovery after a central or peripheral nerve injury and discuss how GC exposure duration can produce divergent CNS neuronal growth responses. Finally we consider how new findings on gender specific immune cell responses after a nerve injury could intersect with GC/GR interactions to impact pain processing.展开更多
Liquid chromatography tandem mass chromatography （LC-MS/MS） is an important hyphenated technique for quantitative analysis of drugs in biological fluids. Because of high sensitivity and selectivity, LC-MS/MS has bee...Liquid chromatography tandem mass chromatography （LC-MS/MS） is an important hyphenated technique for quantitative analysis of drugs in biological fluids. Because of high sensitivity and selectivity, LC-MS/MS has been used for pharmacokinetic studies, metabolites identification in the plasma and urine. This manuscript gives comprehensive analytical review, focusing on chromatographic separation approaches （column packing materials, column length and mobile phase） as well as different acquisition modes （SIM, MRM） for quantitative analysis of glucocorticoids and stimulants. This review is not meant to be exhaustive but rather to provide a general overview for detection and confirmation of target drugs using LC-MS/MS and thus useful in the doping analysis, toxicological studies as well as in pharmaceutical analysis.展开更多
OBJECTIVE To investigate the anti-rheumatoid arthritis(RA)effect of Escin combined with low dose of GCs(dexameth⁃asone,Dex)and its underlying mechanism.METHODS Adjuvant-induced rheumatoid arthritis rats and LPS-injure...OBJECTIVE To investigate the anti-rheumatoid arthritis(RA)effect of Escin combined with low dose of GCs(dexameth⁃asone,Dex)and its underlying mechanism.METHODS Adjuvant-induced rheumatoid arthritis rats and LPS-injured RAW 264.7 were used to investigate the anti-RA effects of Escin combined with low dose Dex in vivo and in vitro.In vivo experiment:rats were randomly divided into model group(AIA),dexamethasone high dose(Dex,0.2 mg·kg^-1)group,dexamethasone low dose(Dex,0.05 mg·kg^-1)group,Escin 10 mg·kg^-1 group,Dex 0.05+Escin group,10 rats in each group,another 10 were used as normal control group.The vehicle and the corresponding drug were administered intragastrically(ig)daily for 14 d.In vitro experiment:LPS was used to stimulate RAW 264.7 macrophages for inflammatory models,which were divided into control group,LPS group,Dex with high dose(50 nmol·L^-1)group,and Dex with low dose(12.5 nmol·L^-1)group.In the Escin 10μmol·L^-1 group and the Dex+Escin(12.5 nmol·L^-1+10μmol·L^-1)group,the corresponding drugs were added to each well.After 2 h,LPS was added to induce inflammation.RESULTS Escin combined with low dose Dex significantly decreased arthritic index,serum IL-6 and TNF-α,improved paw swelling,and ameliorated the joint pathology immune organ pathology significantly.Gene chip results revealed that Nr3c1(GR)altered significantly.And that GR activation by Escin and low dose Dex was confirmed both in vivo and in vitro.Furthermore,Escin combined with low dose Dex also significant increase GR mRNA expression.However,when suppression of GR by its specific inhibitor,the anti-RA effect of Escin combined with low dose Dex was abolished.CONCLUSION Escin combined with Dex reduces the dose of Dex,and exerts significant anti-RA effects,which could also reduce the adverse effects of Dex.This combination might be attributed to GR activation.This study might provide a new combination drugs for the treatment of RA.展开更多
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 participan...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 <0.001). The adjusted odds ratios(and 95% confidence intervals) for dysglycemia with hypertension were1.55(1.18, 2.04) for the highest tertile of Ln-cortisol compared with the lowest tertile. Additionally, the highest Ln-deoxycortisol levels were associated with increased prevalence of dysglycemia with hypertension by 159%(95% confidence interval: 122%, 207%).Conclusions Serum deoxycortisol was positively correlated with systolic blood pressure, pulse pressure, mean arterial pressure, mean blood pressure, and mean proportional arterial pressure.Glucocorticoids(deoxycortisol and cortisol) increase the risk of hypertension in people with dysglycemia, particularly in those with T2 DM.展开更多
文摘BACKGROUND Thymic epithelial neoplasms are rare malignant neoplasms originating in the thymus gland.There have been case reports of patients with advanced thymomas treated with a methylprednisolone pulse or with glucocorticoid(GCs)shock be-fore surgery,followed by surgical treatment,all of whom achieved good results.The effect of GCs on thymomas is related mainly to the action on GC receptors in thymic lymphocytes and epithelial cells.GC receptor expression has been asso-ciated with a better prognosis in patients with thymomas,including those with surgically removed thymomas.CASE SUMMARY We report a case of a patient with thymoma who had a significant response to preoperative low-dose GC therapy.A mediastinal tumor was detected in the patient via computerized tomography upon admission.The tumor was initially suspected to be a thymic tumor,but lymphoma could not be ruled out.The tumor shrank significantly after low-dose(5 mg/day)GC therapy.Thoracoscopic thy-moma resection was performed after puncture pathology was confirmed.The patient recovered well after the operation and is currently performing well with no recurrence of the tumor.CONCLUSION This case highlights that low-dose GCs are effective in the treatment of thymomas,and we believe that GCs should be applied more frequently and studied more thoroughly in the treatment of thymomas.
基金supported by the National Natural Science Foundation of China[82172086]National Key R&D Program of China[2020YFE0201700]+2 种基金Shenyang Science and Technology Talent Support Program[RC210447]Career Development Program for Young and Middle-aged Teachers of Shenyang Pharmaceutical University[ZQN2019004]“Dual Service”Program of University in Shenyang。
文摘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.
基金National Key R&D Program of China:Research on the Functional Characteristics of"Special Effects"and"Common Effects"of Acupoints(No.2019YFC1709001)the National Natural Science Foundation of China:Study on the Immune Mechanisms of Macrophage M1/M2 Polarization in the Treatment of Rheumatoid Arthritis by Moxibustion"Strengthening Body Resistance and Eliminating Evil"(No.81973959)+3 种基金Research on"ImmuneInflammation"Molecular Signal Regulation of NLRP3 Inflammasomes in RA with Moxibustion Treatment(No.81774435)Foundation of Sichuan Provincial Administration of Traditional Chinese Medicine:Research on the Mechanism of MIF-GC Rhythm in the Anti-inflammatory Effect of Moxibustion in Treating Rheumatoid Arthritis(No.2018JC007)Science and Technology Innovation Seedling Project of Sichuan Province,China:based on Macrophage M1 Polarization Signaling Pathway TLR4-MyD88-NF-κB and Its Regulatory Molecule TIM-3 Exploring the Effect Mechanism of Moxibustion on Experimental RA Model(No.2022037)Chengdu University of Traditional Chinese Medicine Foundation:Study on the Mechanism of"MIF-target Protein-GC-inflammation"in the AntiInflammatory Effect of Moxibustion in the Treatment of RA(No.QNXZ2018034)。
文摘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 treatment in RA.MIF may be a factor for moxibustion to regulate the expression of CORT,but the expression of TNF-α is due to the incomplete regulation of the MIF.This study added to the body of evidence pointing to moxibustion's antiinflammatory mechanism in the treatment of RA.
文摘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.
文摘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.
基金Wuwei City Science and Technology Plan Project“Efficacy Analysis of Tacrolimus Combined with Glucocorticoids in the Treatment of Refractory Nephrotic Syndrome”(Project No.WW2101161)。
文摘Objective:To analyze changes in liver and kidney function and lipid metabolism in patients with refractory nephrotic syndrome(RNS)after receiving different treatments.Methods:A total of 64 patients treated in the Wuwei Hospital of Traditional Chinese Medicine from January 2018 to January 2021 were included in this study.All subjects were diagnosed with RNS and randomly assigned to groups:a control group(32 cases)and an observation group(32 cases).The control group received cyclophosphamide+glucocorticoids,while the observation group received tacrolimus+glucocorticoids,both for six months.The various indicators of the two groups were compared.Results:After six months of treatment,the overall clinical efficacy rate of the observation group was significantly higher than that of the control group.Six months post-treatment,levels of serum ALT,AST,BUN,SCr,24 h UTP,TG,and TC were reduced in both groups compared to baseline levels,with reductions more pronounced in the observation group.Serum ALB levels increased in both groups,with a more significant increase in the observation group.Statistical analysis showed these differences were significant(P<0.05).There were no significant changes in FBG levels in either group(P>0.05).Conclusion:For RNS patients,treatment with tacrolimus combined with glucocorticoids significantly reduces liver function damage,improves kidney function and lipid metabolism,and enhances clinical efficacy.
文摘There is an interaction between tacrolimus(TAC) and glucocorticoids where glucocorticoids is a known CYP3A4 and P-gp inducer.However, the dose of glucocorticoids reported is low but not pulse therapy.We retrospectively studied 63 renal transplant recipients receiving TAC after transplantation.All the patients were classified as 500 mg(POD 1–3), 30 mg(POD 4–10), 25 mg(POD 11–17), 20 mg(POD 18–24), 15 mg(POD 25–31), 10 mg(POD 32–60) and 10 mg(POD 61–90).We recorded daily data for each patient from the day of transplantation until POD 90.There was no difference in TAC blood levels within the 3 months after transplantation in the glucocorticoids groups.However, the average daily dose of TAC was significantly lower by weekly reductions of 5 mg dose.The TAC daily dose was not changed from POD 1–4, but the blood concentrations of TAC were significantly lower after the glucocorticoid dose was changed from 500 mg to 30 mg.We demonstrated the induction effect of low-dose glucocorticoids on TAC in renal transplant recipients, and found that the high-dose of glucocorticoids might play a role in substrate competition.We proposed that monitoring of the blood concentrations of TAC was needed when the glucocorticoid dose was changed in the patient undergoing renal transplantation.
基金Supported by the National Natural Science Foundation of China (No.81670885)the Science and Technology Program of Guangdong Province, China (No.2013B020400003)the Science and Technology Program of Guangzhou, China (No.15570001)
文摘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.
基金Supported by National Natural Science Foundation of China(No.81170874)
文摘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.
基金Supported by grants from the National Science Council No.NSC 93-2314-B-002-006, Taiwan, and grants from National Taiwan University Hospital 91-N006
文摘AIM： To determine how glucocorticoids （GCs） may affect the growth and chemosensitivity of common carcinoma cells. METHODS： The effect of dexamethasone （DEX） on growth and chemosensitivity was assessed in 14 carcinoma cell lines. The function of GC receptors （GR） was assessed by MMTV reporter assay. Overexpression of GR was done by in vitro transfection and expression of a GR-expressing vector. Immunohistochemical stain of tissues and ceils were done by PA1-511A, an anti-GR monodonal antibody. RESULTS： DEX inhibited cell growth of four （MCF-7, MCF- 7/MXR1, MCF-7/TPT300, and HeLa）, increased cisplatin cytoxicity of one （SiHa）, and decreased dsplatin cytotoxicity of two （H460 and Hep3B） cell lines. The GR content of the seven cell lines affected by DEX was significantly higher than those of the seven cell lines unaffected by DEX （5.2±2.5×10^4 sites/cell vs1.3±1.4×10^4 sites/cell, P= 0.005）. Only two DEX-unresponsive cell lines {NPC-TW01 and NPC- TW04） oontained high GR amounts in the range （1.9-8.1×10^4 sites/cell） of the seven DEX-responsive cell lines. The GR function of NPC-TW01 and NPC-TW04, however, was foundto be impaired. The importance of high cellular amount of GR in mediating DEX susceptibility of the cells was further exemplified by GR dose-dependent drug resistance to cisplatin of AGS, a cell line with low GR content and was unaffected by DEX before transfection of GR-expressing vector. Immunohistochemical studies of human cancer tissues showed that 5 of the 45 （11.1%） breast cancer and 43 of the 85 （50.6%） non-small cell lung cancer had high GR contents at the ranges of the GC-responsive carcinoma cell lines. CONCLUSION： The growth and chemosensitivity of human carcinomas with high GR contents may be affected by GC. However, in light of the heterogeneous and even contradictive effects of GC on these cells, routine examination of GR contents of human carcinoma tissues may not be clinically useful until other markers that help predict the ultimate effect of GC on individual patients are identified.
文摘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.
文摘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.
基金supported by the National Health & Medical Research Council,Australia,Project Grants 402462,570946 and 632819 to HZ and MJSProject Grant 632818 to HZ,MSC and MJS
文摘While the adverse effects of glucocorticoids on bone are well described, positive effects of glucocorticoids on the differentiation of osteoblasts are also observed. These paradoxical effects of glucocorticoids are dose dependent. At both physiologicaland supraphysiological levels of glucocorticoids, osteoblasts and osteocytes are the major glucocorticoid target cells. However, the response of the osteoblasts to each of these is quite distinct. At physiology levels, glucocorticoids direct mesenchymal progenitor cells to differentiate towards osteoblasts and thus increase bone formation in a positive way. In contrast with ageing, the excess production of glucocorticoids, at both systemic and intracellular levels, appear to impact on osteoblast and osteocytes in a negative way in a similar fashion to that seen with therapeutic glucocorticoids. This review will focus on therole of glucocorticoids in normal bone physiology, with particular emphasis on the mechanism by which endogenous glucocorticoids impact on bone and its constituent cells.
文摘BACKGROUND: Community-acquired pneumonia(CAP) is pneumonia acquired infectiously from normal social contact as opposed to being acquired during hospitalization. CAP is a leading cause of illness and death. This review aims to determine the efficacy and safety of glucocorticoids in the treatment of community-acquired pneumonia(CAP).DATA SOURCES: We searched randomized controlled trials(RCTs) from Pubmed, EMBASE, Cochrane Library, Chinese Journal Full-text Database, and Chinese Biomedical Literature Database to obtain the information by using steroids, glucocorticoids, cortisol, corticosteroids, community-acquired pneumonia and CAP as key words. The quality of RCTs was evaluated. A Meta-analysis was made using Rev Man 5.0 provided by the Cochrance Collaboration.RESULTS: Seven RCTs involving 944 patients were included in the meta-analysis. The mean length of hospital stay in glucocorticoids treatment group was significantly shorter than that in standard treatment group(WMD=–1.70, 95%CI 2.01–1.39, Z=10.81, P<0.00001). No statistically significant differences were found in the mortality rate(RR=0.77,95%CI 0.46–1.27, Z=1.03, P=0.30), the mean length of hospital stay in ICU(WMD=1.17, 95%CI 1.68–4.02, Z=0.81, P=0.42), the incidence of super infection(RR=1.32, 95%CI 0.66–2.63, Z=0.79, P=0.43), the incidence of hyperglycemia(RR=1.84, 95%CI 0.76–4.41, Z=1.36, P=0.17), the incidence of upper gastrointestinal bleeding(RR=1.98, 95%CI 0.37–10.59, Z=0.80, P=0.42) between the standard treatment group and the glucocorticoids treatment group.CONCLUSIONS: The use of glucocorticoids in patients with community-acquired pneumonia can significantly shorten the duration of illness and have a favorable safety profile. However, it could not reduce the overall mortality.
文摘Background: Henoch Schonlein Purpura (HSP) is a common immune-related allergic disease in children. It is very important to understand the clinical features of this disease for doctors. Objective: To explore the clinical efficacy of glucocorticoids in the treatment of HSP in Tibetan children at high altitude, and to analyze the possible causes of HSP in children at high altitude. The risk factors of the disease provide a reference for the treatment of HSP in children in high altitude areas. Methods: Selecting January 2015 to November 2020, 88 children diagnosed with Henoch-Schonlein Purpura in the outpatient and inpatient departments of the People’s Hospital of Bomi County, Tibet Autonomous Region were the subjects of the study. Its gender, age of onset, season of onset, predisposing factors, allergy history, first symptoms, clinical manifestations, laboratory examinations, etc., perform retrospective analysis. Results: Among 88 children with allergic purpura, 55 were boys, accounting for 62.5%, and 33 were girls, accounting for 37.5%. Men have more cases than women. All have clinical manifestations of purpura of the skin, among which 35 cases have obvious triggers, of which the above there were 26 cases of respiratory infections, 6 cases of dietary factors, and 3 cases of contact with allergic substances. Simple skin type: 18 cases, accounting for 20.45%;Abdominal type: 6 cases, accounting for 6.82%;2 male cases, accounting for 33.33%;4 female cases, accounting for 66.67%;Articular type: 8 cases, accounting for 33.33%;Renal type: 2 cases, accounting for 2.27%;54 cases of mixed type, accounting for 61.36%. After glucocorticoids, the rashes disappeared, no any adverse reactions. Conclusion: Allergic purpura in children is more common in school-age children, and upper respiratory tract infection is the main predisposing factor. Skin purpura is the main clinical manifestation, often associated with lower extremity joint swelling and pain. There is no significant difference in the efficacy and course of the disease between intravenous and oral treatment. Therefore, clinicians should strictly grasp the indications of glucocorticoids to reduce the occurrence of complications.
基金Supported by the“Double-First Class”project of Beijing(No.1000041510155)。
文摘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.
文摘Glucocorticoid and glucocorticoid receptor（GC/GR） interactions alter numerous aspects of neuronal function. These consequences（e.g., anti-inflammatory vs. pro-inflammatory） can vary depending on the duration of GC exposure or central nervous system（CNS） injury model. In this review we discuss how GC/GR interactions impact neuronal recovery after a central or peripheral nerve injury and discuss how GC exposure duration can produce divergent CNS neuronal growth responses. Finally we consider how new findings on gender specific immune cell responses after a nerve injury could intersect with GC/GR interactions to impact pain processing.
文摘Liquid chromatography tandem mass chromatography （LC-MS/MS） is an important hyphenated technique for quantitative analysis of drugs in biological fluids. Because of high sensitivity and selectivity, LC-MS/MS has been used for pharmacokinetic studies, metabolites identification in the plasma and urine. This manuscript gives comprehensive analytical review, focusing on chromatographic separation approaches （column packing materials, column length and mobile phase） as well as different acquisition modes （SIM, MRM） for quantitative analysis of glucocorticoids and stimulants. This review is not meant to be exhaustive but rather to provide a general overview for detection and confirmation of target drugs using LC-MS/MS and thus useful in the doping analysis, toxicological studies as well as in pharmaceutical analysis.
基金National Natural Science Foundation of China(8187303981973547)Natural Science Foundation of Shandong Province(ZR2017MH068)
文摘OBJECTIVE To investigate the anti-rheumatoid arthritis(RA)effect of Escin combined with low dose of GCs(dexameth⁃asone,Dex)and its underlying mechanism.METHODS Adjuvant-induced rheumatoid arthritis rats and LPS-injured RAW 264.7 were used to investigate the anti-RA effects of Escin combined with low dose Dex in vivo and in vitro.In vivo experiment:rats were randomly divided into model group(AIA),dexamethasone high dose(Dex,0.2 mg·kg^-1)group,dexamethasone low dose(Dex,0.05 mg·kg^-1)group,Escin 10 mg·kg^-1 group,Dex 0.05+Escin group,10 rats in each group,another 10 were used as normal control group.The vehicle and the corresponding drug were administered intragastrically(ig)daily for 14 d.In vitro experiment:LPS was used to stimulate RAW 264.7 macrophages for inflammatory models,which were divided into control group,LPS group,Dex with high dose(50 nmol·L^-1)group,and Dex with low dose(12.5 nmol·L^-1)group.In the Escin 10μmol·L^-1 group and the Dex+Escin(12.5 nmol·L^-1+10μmol·L^-1)group,the corresponding drugs were added to each well.After 2 h,LPS was added to induce inflammation.RESULTS Escin combined with low dose Dex significantly decreased arthritic index,serum IL-6 and TNF-α,improved paw swelling,and ameliorated the joint pathology immune organ pathology significantly.Gene chip results revealed that Nr3c1(GR)altered significantly.And that GR activation by Escin and low dose Dex was confirmed both in vivo and in vitro.Furthermore,Escin combined with low dose Dex also significant increase GR mRNA expression.However,when suppression of GR by its specific inhibitor,the anti-RA effect of Escin combined with low dose Dex was abolished.CONCLUSION Escin combined with Dex reduces the dose of Dex,and exerts significant anti-RA effects,which could also reduce the adverse effects of Dex.This combination might be attributed to GR activation.This study might provide a new combination drugs for the treatment of RA.
基金supported by the National Key Research and Development Program Precision Medicine Initiative of China[grant number:2016YFC0900803]National Natural Science Foundation of China[grant number:81872626,82003454]+2 种基金Chinese Nutrition Society-Bright Moon Seaweed Group Nutrition and Health Research Fund[grant number:CNS-BMSG2020A63]Chinese Nutrition Society-Zhendong National Physical Fitness and Health Research Fund[grant number:CNS-ZD2019066]Key R&D and promotion projects in Henan Province[grant number:212102310219]。
文摘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 <0.001). The adjusted odds ratios(and 95% confidence intervals) for dysglycemia with hypertension were1.55(1.18, 2.04) for the highest tertile of Ln-cortisol compared with the lowest tertile. Additionally, the highest Ln-deoxycortisol levels were associated with increased prevalence of dysglycemia with hypertension by 159%(95% confidence interval: 122%, 207%).Conclusions Serum deoxycortisol was positively correlated with systolic blood pressure, pulse pressure, mean arterial pressure, mean blood pressure, and mean proportional arterial pressure.Glucocorticoids(deoxycortisol and cortisol) increase the risk of hypertension in people with dysglycemia, particularly in those with T2 DM.
