The aim of this study is to investigate the apoptotic inhibition and its molecular mechanism of dexamethasone (DEX) acting on cisplatin (CDDP)-induced apoptosis of human lung adenocarcinoma cell SPC-A1. SPC-A1 cells were pre-cultured in vitro for 24 hours with DEX in different concentrations and then CDDP was added in different concentrations for culturing for further 48 hours. The survival rates of the cells were determined by MTT. The expression of serum/glucocorticoid-induced kinase (SGK-1) and mitogen-activated protein kinase phosphatase-1 (MKP-1) in SPC-A1 cells after being cultured by 1 μmol/L DEX at different time was detected by semi-quantitative RT-PCR technology. The expression of glucocorticoid receptor (GR) in SPC-A1 cells was measured by immunohistochemistry (IHC) with biotin-labeled anti-GR. The results of MTT showed that SPC-A1 cells had resistance to CDDP-induced apoptosis with pre-cultured DEX and the resistance intensity presented DEX concentration-dependent. The expressing quantity of SGK-1 in SPC-A1 cells stimulated by DEX could be elevated and increased with intention of time, but the express of MKP-1 was not detected. Up-regulated expression of GR in SPC-A1 cells stimulated by DEX was detected by IHC. The number of cells expressing GR in SPC-A1 cells was significantly higher than that in the control group. The results showed that DEX inhibited apoptosis of SPC-A1 cells induced by CDDP. The possible molecular mechanism is that elevated expression of GR induced by DEX up-regulates the expression of SGK-1 which locates at the downstream of anti-apoptosis pathway. The apoptosis resistance of SPC-A1 cells may account for all above the factors.
Objective To investigate the potential effect of glucocorticoids (referred to as 'hormones' here) on decreasing case fatality rate in patients with human immunodeficiency virus (HIV) negative Pneumocystis jirovecii pneumonia (PJP). Methods The clinical data of a cohort of 93 patients that were diagnosed with HIV-negative PJP at Jiangxi Provincial People's Hospital between April 2019 and April 2022 were retrospectively analyzed. These patients were classified into two groups based on the partial pressure of oxygen in arterial blood (PaO2), specifically PaO2 ≥70 mm Hg and PaO2 <70 mm Hg. The association between case fatality rate and various factors such as underlying diseases, hormone use, mechanical ventilation, and others was examined. Results Over a period of three years, 93 cases of HIV-negative PJP were identified. The most prevalent underlying diseases were solid organ transplantation (n=34, 36.6%), rheumatic system diseases (n=26, 28.0%), and malignant tumors (n=15, 16.1%). 51 cases had arterial PaO2 levels ≥70 mm Hg, while 42 cases had levels <70 mm Hg. Moreover, 19 patients required invasive ventilation, 39 patients were treated with non-invasive ventilation, while 50 patients received oxygenation using a nasal cannula. Out of the 93 patients, 31 died from the disease, resulting in an overall case fatality rate of 33.3%. Meanwhile, 62 patients survived. In patients with arterial PaO2 levels ≥70 mm Hg, the administration of hormones did not significantly affect the case fatality rate (P > 0.05); In patients with arterial PaO2 level <70 mm Hg, the administration of hormones did not significantly affect the case fatality rate (P > 0.05). Conclusion Hormone use did not contribute to improved survival rates in HIV-negative PJP patients, regardless of arterial PaO2 level.
ObjectiveTo investigate the perioperative safety of patients with myasthenia gravis who take high doses of oral corticosteroids. MethodsA retrospective analysis was conducted on the clinical data of patients with myasthenia gravis who received oral corticosteroids and underwent thoracoscopic thymectomy at the Department of Thoracic Surgery, the University of Hong Kong-Shenzhen Hospital from April 2013 to October 2019. Patients were divided into a high-dose steroid group and a medium-to-low dose steroid group based on the dosage of oral steroids, and the clinical data of the two groups were compared. ResultsA total of 102 patients were included, including 19 (18.62%) males and 83 (81.37%) females, with an average age of (32.25±9.83) years. All patients in both groups successfully completed the surgery without major intraoperative bleeding, conversion to open chest surgery, delayed extubation, severe infection, or perioperative death. The daily oral steroid dose for the high-dose steroid group was (35.81±4.29) mg, and for the medium-to-low dose steroid group it was (15.29±2.17) mg. There was no statistical difference in the operation time [(124.69±23.51) min vs. (117.89±21.46) min, P=0.172] and intraoperative blood loss [(21.19±3.48) mL vs. (20.56±3.41) mL, P=0.419] between the two groups. Postoperatively, 12 (11.76%) patients developed complications: one patient of myasthenic crisis (medium-to-low dose steroid group), which was improved after short-term respiratory support and intravenous immunoglobulin treatment; 11 patients of respiratory/swallowing difficulties (9 in the low-dose steroid group and 2 in the high-dose steroid group), which were improved after anticholinergic treatment to reduce oral secretions and sputum suction, and the patients were discharged smoothly. There was no statistical difference in the incidence of postoperative complications between the two groups (P=0.637). ConclusionOn the basis of good perioperative management, it is safe and feasible for patients with myasthenia gravis who take high dose of oral steroids to undergo thymectomy, and they have the same perioperative safety as patients with medium-to-low dose steroids.
Delayed encephalopathy due to acute carbon monoxide poisoning (DEACMP) is a serious complication of acute carbon monoxide poisoning. Patients with DEACMP often present with cognitive impairment, abnormal mental behavior, extrapyramidal system symptoms, pyramidal system symptoms, and may also have focal cortical dysfunction, which is closely related to the poor prognosis of the patients. Current research shows that the occurrence of DEACMP is related to multiple factors such as immune disorders, and glucocorticoids can exert certain therapeutic effects by suppressing the immune system. This article reviews the risk factors of DEACMP, the clinical research progress and possible mechanisms of glucocorticoid treatment for DEACMP, providing more references for the clinical treatment of DEACMP.
Objective To study the effect of glucocorticoid-containing triple therapy on the acute exacerbation frequency of patients with moderate to severe chronic obstructive pulmonary disease (COPD) with different blood eosinophil percentage (EOS%). Methods One hundred and twenty-four patients who were admitted to the hospital with moderate to severe COPD from January 2020 to March 2020 in the Department of Respiratory and Critical Care Medicine in this hospital were selected as the research subjects, and the patients were divided into group A according to EOS% (EOS%<2%) and B group (EOS%≥2%). Then the A and B groups were randomly divided into four subgroups A1, A2 and B1, B2, and the patients in groups A1 and B1 were treated with dual long-acting bronchodilation. The medication for the patients in groups A2 and B2 was a triple preparation containing glucocorticoids. Namely A1 group (EOS%<2%, dual therapy), A2 group (EOS%<2%, triple therapy), B1 group (EOS%≥2%, dual therapy), B2 group (EOS%≥2%, triple therapy). The patients were instructed to take medication regularly as in hospital after discharge. After discharge, patients were followed up by telephone every two weeks for a period of one year. The number of acute exacerbations, the change of forced expiratory volume in the first second as a percentage of the expected value (FEV1%pred) and the incidence of pneumonia were compared between group A and group B during the follow-up period of one year. Results In the patients with EOS%≥2%, triple therapy reduced the number of acute attacks by 40% during treatment compared with dual therapy patients (average 0.875 vs. 1.471 times per patient per year, P=0.0278). While in the patients with EOS%<2%, it was reduced by 4% (1.080 vs. 1.125 times, P=0.3527). In the same use of glucocorticoid-containing triple preparations, the number of acute exacerbations in the patients with EOS%≥2% during medication was 19% less than that of the patients with EOS%<2% (an average of 0.875 to 1.080 times per patient per year, P=0.0462). Regardless of EOS%≥2% or <2%, there was no significant difference in the changes of FEV1%pred between triple therapy and double therapy patients before and after treatment (P>0.05). Regardless of EOS%≥2% or <2%, there was no statistically significant difference in the incidence of pneumonia between patients with triple therapy and double therapy during medication (P>0.05). Conclusion Inhaled glucocorticoid triple therapy is suitable for moderate to severe COPD patients with high percentages of blood eosinophils.
Chronic central serous chorioretinopathy (CSC) usually demonstrates frequent recurrence, diffuse leakage and persistent subretinal fluid, which cannot be absorbed, thus lead to photoreceptor damage and poor visual acuity. As glucocorticoids have been implicated in the pathogenesis of chronic CSC, various anti-glucocorticoids oral drugs were used in the clinic to promote retinal fluid absorption and reduce the central retinal thickness of the macula and improve the vision outcomes. In addition, the 5α-reductase-specific inhibitor finasteride, the P450-3A4 inducer rifampicin, circadian rhythmic regulator melatonin, and systemic anti-inflammatory drug methotrexate have also been put into clinical trials for chronic CSC, and achieved certain effects. However, most of the clinical studies on these oral drugs were case reports, but not multi-center randomized clinical trials. The long-term effects of these oral drugs need to be observed and studied further.
Objective To systematically evaluate the effectiveness of N-acetylcysteine (NAC) combined with low-dose glucocorticoid for patients with idiopathic pulmonary fibrosis (IPF). Methods Such databases as The Cochrane Library (Issue 12, 2012), EMbase (January 1974 to July 2012), PubMed (January 1966 to July 2012), CHEST (January 1995 to July 2012), CNKI (January 1994 to July 2012), CBM (January 1978 to July 2012), VIP (January 1989 to July 2012) and WanFang Data (January 1995 to July 2012) were searched to collect the randomized controlled trials (RCTs) about NAC combined with low-dose glucocorticoid versus glucocorticoid alone for IPF patients. Two reviewers independently screened the literature according to the inclusion and exclusion criteria, extracted the data, and assessed the quality, and then the meta-analysis was performed using RevMan 5.1 software. Results A total of seven RCTs including 264 IPF patients were included. The results of meta-analysis demonstrated that, compared with the glucocorticoid used alone, a) NAC combined with low-dose glucocorticoid could significantly improve PaO2 (SMD=0.82 mmHg, 95%CI 0.30 to 1.35, P=0.002) and DLco (SMD=0.59 mmHg, 95%CI 0.16 to 1.03, P=0.008) with a significant difference. b) NAC combined with low-dose glucocorticoid could significantly improve all clinical symptoms (RR=1.56, 95%CI 1.26 to 1.92, Plt;0.000 1). Conclusion NAC combined with low-dose glucocorticoid for IPF patients can significantly improve PaO2, DLco, and the clinical symptoms such as cough, difficulty breathing after activities, cyanosis, and Velcro rales. Due to the quantity and quality limitation of included studies, this conclusion still needs to be further proved by more high quality and double blind RCTs.
ObjectiveTo explore the effect of preoperative glucocorticoid on systemic inflammatory indexes and pulmonary inflammation after radical esophagectomy.MethodsA total of 44 patients with esophageal cancer treated in the First Affiliated Hospital of Xiamen University from July 2019 to September 2020 were selected and randomly divided into an intervention group and an observation group by random number table. There were 22 patients in the intervention group, including 20 males and 2 females with an average age of 62.86±5.22 years and 22 patients in the observation group, including 19 males and 3 females with an average age of 63.00±6.19 years. Two groups were given thoracoscope-assisted incision via right chest, upper abdomen and left neck. The intervention group was given an intravenous infusion of methylprednisolone 500 mg before induction of anesthesia, and the observation group was given the same dose of normal saline. The second generation cephalosporins were routinely used to prevent infection in the two groups. The levels of interleukin-6 (IL-6) and C-reactive protein (CRP), lymphocyte and neutrophil count before operation and 1 day, 3 days and 5 days after operation were recorded and compared between the two groups. Utrecht Pneumonia Scoring System (UPSS) score 1 day after operation, the healing of the surgical incision and the anastomotic leakage within 2 weeks after the operation were evaluated.ResultsThe level of IL-6 in the intervention group was significantly lower than that in the observation group at 1 hour and 1 day after operation (both P<0.05). CRP showed significant difference between the two groups 2 days after operation (P=0.044). The white blood cell count in the intervention group was significantly less than that in the observation group 1 day and 3 days after operation (both P<0.05). There was no significant difference in lymphocyte or neutrophil count between the two groups 1 day after operation. There was no significant difference in the rate of non-grade A wound healing or the incidence of anastomotic leakage between the two groups within 2 weeks after operation. The pneumonia score of UPSS in the intervention group was lower than that in the observation group 1 day after operation (P=0.027).ConclusionThe use of glucocorticoid before radical esophagectomy can reduce the systemic inflammatory reaction and improve the short-term postoperative pulmonary inflammation. At the same time, no adverse effect on the healing of surgical incision and anastomotic stoma is found, which has certain safety.
ObjectiveTo evaluate the effects of icariin on autophagy induced by low-concentration of glucocorticoid and exosome production in bone microvascular endothelial cells (BMECs).MethodsBMECs were isolated from femoral heads resected in total hip arthroplasty and then intervened with hydrocortisone of low concentration (0, 0.03, 0.06, 0.10 mg/mL), which were set as groups A, B, C, and D, respectively. On the basis of hydrocortisone intervention, 5×10−5 mol/L of icariin was added to each group (set as groups A1, B1, C1 and D1, respectively). Western blot was used to detect the expressions of microtubule-associated protein 1 light chain 3B (LC3B) and dead bone slice 1 (p62) after 24 hours. Exosomes were extracted from BMECs treated with icariin (intervention group) and without icariin (non-intervention group), and the diameter and concentration of exosomes were evaluated by nanoparticle tracking analysis technique. The total protein content of exosomes was detected by BCA method, and the expressions of proteins carried by exosomes including CD9, CD81, transforming growth factor β1 (TGF-β1), and vascular endothelial growth factor A (VEGFA) were assessed by Western blot. The BMECs were further divided into three groups: BMECs in the experimental group and the control group were co-cultured with exosomes secreted by BMECs treated with or without icariin, respectively; the blank control group was BMECs without exosome intervention. The three groups were treated with hydrocortisone and Western blot was used to detect the expressions of LC3B and p62. The scratching assay was used to detect cell migration ability; angiogenic ability of BMECs was also assessed.ResultsWith the increase of hydrocortisone concentration, the protein expression of LC3B-Ⅱ increased gradually, and the protein expression of p62 decreased gradually (P<0.01). Compared with group with same concentration of hydrocortisone, the protein expression of LC3B-Ⅱ decreased and the protein expression of p62 increased after the administration of icariin (P<0.01). The concentration of exosomes in the intervention group was significantly higher than that in the non-intervention group (t=−10.191, P=0.001); and there was no significant difference in exosome diameter and total protein content between the two groups (P>0.05). CD9 and CD81 proteins were highly expressed in the non-intervention group and the intervention group, and the relative expression ratios of VEGFA/CD9 and TGF-β1/CD9 proteins in the intervention group were significantly higher than those in the non-intervention group (P<0.01). After co-culture of exosomes, the protein expression of p62 increased in blank control group, control group, and experimental group, while the protein expression of LC3B-Ⅱ decreased. There were significant differences among groups (P<0.05). When treated with hydrocortisone for 12 and 24 hours, the scratch closure rate of the control group and experimental group was significantly higher than that of the blank control group (P<0.05), and the scratch closure rate of the experimental group was significantly higher than that of the control group (P<0.05). When treated with hydrocortisone for 4 and 8 hours, the number of lumens, number of sprouting vessels, and length of tubule branches in the experimental group and the control group were significantly greater than those in the blank control group (P<0.05); the length of tubule branches and the number of lumens in the experimental group were significantly greater than those in the control group (P<0.05).ConclusionIcariin and BMECs-derived exosomes can improve the autophagy of BMECs induced by low concentration of glucocorticoid.
Objective To evaluate the clinical short-term efficacy and safety of application of glucocorticoids (GCs) before major abdominal surgery. Methods The randomized controlled trials (RCTs) on application of GCs before major elective abdominal surgery were systematically and comprehensively searched in Medline (1966–2022), Embase (1947–2022), Web of Science, and PubMed databases, and systematic review and meta-analysis of the included studies were performed to explore the effects of application of GCs before major abdominal surgery on postoperative complication, hospital stay, and serum interleukin-6 level. Results Nineteen moderate quality RCTs with 1 535 patients were finally included in the analysis. Preoperative application of GCs reduced postoperative IL-6 level [MD=–51.00, 95%CI (–62.36, –39.63), P<0.001], reduced postoperative complications [OR=0.53, 95%CI (0.35, 0.81), P=0.003], shorten hospital stay [MD=–0.64, 95%CI (–1.04, –0.24), P=0.002], and reduced the occurrence of infectious complications [OR=0.50, 95%CI (0.36, 0.70), P<0.01]. However, there were no statistically significant difference in incidence of anastomotic leakage [OR=1.15, 95%CI (0.43, 3.04), P=0.780] and bile leakage [OR=1.95, 95%CI (0.76, 5.00), P=0.170]. Conclusion Preoperative application of GCs can reduce the level of IL-6, reduce complications after major abdominal surgery and shorten postoperative hospital stay.