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.
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.
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.
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.
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.
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.
ObjectiveTo systematically review the association between inhaled corticosteroids (ICS) and the risk of lung cancer in patients with chronic obstructive pulmonary disease (COPD). MethodsPubMed, EMbase, Web of Science, Cochrane Library, CNKI, WanFang Data and VIP databases were electronically searched to collect cohort studies on the risk of lung cancer in COPD patients using ICS from inception to August 15, 2022. Two reviewers independently screened the literature, extracted data, and evaluated the risk of bias of the included studies. Meta-analysis was then performed by using RevMan 5.4 software. ResultsA total of 8 cohort studies involving 1 184 238 patients were included. The results of meta-analysis showed that ICS use decreased risk of lung cancer in COPD patients (HR=0.68, 95%CI 0.62 to 0.75, P<0.01). The dose of ICS was an influencing factor for the risk of lung cancer in COPD patients and a large dose of ICS could significantly reduce the risk. ConclusionCurrent evidence shows that the use of ICS can reduce the risk of lung cancer in patients with COPD, especially in high-dose patients. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.
Objective To describe the disease characteristics of osteonecrosis of the femoral head (ONFH) in patients with systemic lupus erythematosus (SLE) who experiencing prolonged glucocorticoid (GC) exposure. Methods Between January 2016 and June 2019, 449 SLE patients meeting the criteria were recruited from multiple centers. Hip MRI examinations were performed during screening and regular follow-up to determine the occurrence of ONFH. The cohort was divided into ONFH and non-ONFH groups, and the differences in demographic baseline characteristics, general clinical characteristics, GC medication information, combined medication, and hip clinical features were compared and comprehensively described. ResultsThe age at SLE diagnosis was 29.8 (23.2, 40.9) years, with 93.1% (418 cases) being female. The duration of GC exposure was 5.3 (2.0, 10.5) years, and the cumulative incidence of SLE-ONFH was 9.1%. Significant differences (P<0.05) between ONFH and non-ONFH groups were observed in the following clinical characteristics: ① Demographic baseline characteristics: ONFH group had a higher proportion of patients with body mass index (BMI)<20 kg/m2 compared to non-ONFH group. ② General clinical characteristics: ONFH group showed a higher proportion of patients with cutaneous and renal manifestations, positive antiphospholipid antibodies (aPLs) and anticardiolipin antibodies, severe SLE patients [baseline SLE Disease Activity Index 2000 (SLEDAI-2K) score ≥15], and secondary hypertension. Fasting blood glucose in ONFH group was also higher. ③ GC medication information: ONFH group had higher initial intravenous GC exposure rates, duration, cumulative doses, higher cumulative GC doses in the first month and the first 3 months, higher average daily doses in the first 3 months, and higher proportions of average daily doses ≥15.0 mg/d and ≥30.0 mg/d, as well as higher full-course average daily doses and proportion of full-course daily doses ≥30.0 mg/d compared to non-ONFH group. ④ Combined medications: ONFH group had a significantly higher rate of antiplatelet drug use than non-ONFH group. ⑤ Hip clinical features: ONFH group had a higher proportion of hip discomfort or pain and a higher incidence of hip joint effusion before MRI screening than non-ONFH group. Conclusion The incidence of ONFH after GC exposure in China’s SLE population remains high (9.1%), with short-term (first 3 months), medium-to-high dose (average daily dose ≥15 mg/d) GC being closely associated with ONFH. Severe SLE, low BMI, certain clinical phenotypes, positive aPLs, and secondary hypertension may also be related to ONFH.
ObjectiveTo analyze the prognostic factors of vision of myelin oligodendrocyte glycoprotein (MOG) antibody positive associated optic neuritis (ON) after methylprednisolone pulse therapy. MethodsA clinical observational study. A total of 32 patients (47 eyes) with MOG antibody positive ON were observed and followed up in the ophthalmology department of Beijing Tongren Hospital Affiliated to Capital Medical University and Beijing Puren Hospital from March 2019 to January 2022. Clinical data including the best corrected visual acuity (BCVA) and orbital magnetic resonance imaging were recorded. The BCVA was examined by Snellen visual acuity chart, which was finally converted into the logarithm of the minimal angle of resolution (logMAR) for statistical analysis. There were 22 case (38 eyes) with complete image data. All patients were treated with intravenous methylprednisolone pulse (IVMP) for 3-5 days. According to the intervention time (from onset to glucocorticoid treatment), the patients were divided into three groups: ＜7 d group, 7-14 d and ＞14 d group, with 16, 13, 11 eyes, respectively. The median follow-up time was 28 months. After 1 week, 1, 3 and 6 months treatment, the same equipment and methods were used for relevant examinations to observe the changes of visual acuity and the factors influencing the prognosis of visual acuity after IVMP treatment. Logistic regression and linear regression were used to analyze the prognostic correlation factors. Receiver operating characteristic (ROC) curve was used to determine the critical cut-off point of intervention timing. ResultsAmong the patients, 16 were male and 16 were female. The median onset age was 26 years. The onset duration time was 5-60 days. There were 18 cases (56.3%, 18/32) with abnormal serum immune indexes. The initial symptom was decreased vision with unilateral or bilateral ON. Seventeen (53.1%, 17/32) cases had unilateral ON and 15 (46.9%, 15/32) cases with bilateral ON. Thirty-six eyes (76.6%, 36/47) got optic disc edema, 37 eyes (78.7%, 37/47) accompanied by pain of ocular movement. The nadir logMAR BCVA was mean 1.69±0.13. Long T2WI signals with segmental thickening in the orbital segment of the optic nerve were obtained in 27 eyes (71.1%, 27/38) and in 24 eyes (63.2%, 24/38) with optic nerve and sheath enhancement. During the follow-up period, there were 10 cases of relapse (31.3%, 10/32). The logMAR BCVA of attacked eyes were 0.52±0.09, 0.22±0.06, 0.12±0.06, 0.10±0.06 at 1 week and 1, 3 and 6 months after IVMP treatment, respectively. The rate of BCVA improvement was the fastest at 1 week after treatment, and BCVA returned to stability at 3 months. Logistic regression analysis showed that the timing of intervention was significantly correlated with the prognosis of vision in primary onset patients (odds ratio=12.17, P=0.006), with a negative linear regression relationship (r=－0.48, 95% confidence interval －0.71-－0.17, P=0.008). Comparing the logMAR BCVA between the intervention time ＞14 group with the ＜7 group and the 7-14 group, there were statistically significant difference (P=0.017, 0.037), respectively. The cut-off point of ROC curve to predict the optimal intervention time was 13.5 days. Other factors such as: gender, age, predisposing factor, pain of eye motion, edema of optic disc, bilateral ON, imaging changes, abnormal autoimmune indicators were not associated with the prognosis of visual acuity. ConclusionThe timing of hormone intervention in primary onset patients is an important factor affecting the prognosis of vision and the optimal intervention time window of IVMP is two weeks.
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.