ObjectiveTo evaluate the efficacy and safety of bisphosphonates in preventing and treating glucocorticoid induced osteoporosis. MethodsDatabases including PubMed, EMbase, The Cochrane Library (Issue 1, 2016), CNKI, WanFang Data and VIP were searched to collect randomized controlled trials (RCTs) related bisphosphonates for the prevention and treatment of glucocorticoid induced osteoporosis from inception to January 2016. Two reviewers independently screened literature, extracted data, and evaluated the risk of bias of included studies. Meta-analysis was performed using RevMan 5.3 software. ResultsA total of 20 RCTs were included, which involved 2 330 patients. The results of meta-analysis showed that, compared with the placebo group, the bisphosphonates group could significantly increase the bone mineral density (BMD) at lumbar and femoral neck (MD=3.70, 95%CI 2.65 to 4.75, P<0.000 01; MD=2.18, 95%CI 1.30 to 3.06, P<0.000 01), but the bisphosphonates group could not decrease the incidence rates of vertebral fracture or non-vertebral fracture (OR=0.66, 95%CI 0.38 to 1.16, P=0.15; OR=0.73, 95%CI 0.42 to 1.28, P=0.28). There were no significant differences in the incidence rates of total adverse reactions and total severe adverse reactions between the two groups (OR=0.89, 95%CI 0.62 to 1.28, P=0.53; OR=0.93, 95%CI 0.62 to 1.39, P=0.72). ConclusionCurrent evidence shows that, compared with placebo, bisphosphonates canld effectively prevent and treat the decrease of bone mineral density of glucocorticoid induced osteoporosis, not decrease the incidence of fracture, but not increase the incidence of adverse reactions.
ObjectiveTo analyze the phasic changes of bone mass, bone turnover markers, and estrogen levels at different time points after glucocorticoid (GC) intervention in rat and their correlation. MethodsThirty-four female 3-month-old Sprague Dawley rats were randomly divided into the following 3 groups:baseline group (n=6), dexamethasone (DXM) group (n=14), and control group (n=14). Rats were injected with DXM at the dose of 0.75 mg/kg, twice a week for 12 weeks in DXM group, with salt solution lavage in control group, and no treatment was given in baseline group. The body mass, adrenal weight, and uterus weight were measured. Bone mineral density (BMD), bone mineral content (BMC), and bone area (BA) of lumbar vertebral and femurs were detected by dual energy X-ray absorptiometry. Meanwhile, the serum levels of N-terminal propeptide of type I procollagen (PINP), C-terminal cross-linking telopeptide of type I collagen (β-CTX), and estrogen levels were determined by ELISA before experiment in baseline group and at 4, 8, and 12 weeks after experiment in control and DXM groups. At last, the correlation was analyzed among body weight, BMD, PINP, β-CTX, estrogen levels, and GC intervention duration of DXM group. ResultsThe body mass, adrenal weight, and uterus weight in DXM group were significantly lower than those in baseline group and control group at all the time points (P<0.05). The levels of PINP and β-CTX elevated slowly in DXM group, significant difference was found at 12 weeks (P<0.05), but no significant difference at the 4 and 8 weeks (P>0.05) when compared with those in baseline group and control group. The estrogen level in DXM group was significantly lower than that in baseline group and control group at all the time points (P<0.05). BMD, BMC, and BA of lumbar vertebral and femurs in DXM group were significantly lower than those in control group at all the time points after GC intervention (P<0.05). Loss of bone mass of L2 and femoral trochanteric region in DXM group was the lowest of all ranges of interest (ROIs). BMC and BA of lumbar vertebrae and BA of femoral shaft in DXM group at 4 weeks were significantly lower than those in baseline group (P<0.05). But there was no significant difference in BMD, BMC, and BA of other lumbar vertebrae and femurs' ROIs between DXM group and baseline group at all the time points (P>0.05). After GC intervention, BMD of lumbar vertebrae and femurs had negative correlation with PINP and β-CTX (P<0.05) and positive correlation with estrogen level (P<0.05). ConclusionThe bone mass decreases rapidly at the early stage after GC intervention and then maintains a low level with time, the levels of bone turnover markers show a progressive increase, and the estrogen levels show a decrease trend. In addition, body weight, the levels of bone turnover markers and estrogen are associated with the change of bone mass.
Objective Glucocorticoid is the main cause of non-traumatic avascular necrosis of femoral head. To explore the changes of reactive oxygen species (ROS) in the bone microvascular endothel ial cells treated with glucocorticoid so as to investigate the pathogenesis of steroid-induced avascular necrosis of femoral head. Methods The cancellous bone of femoral head was harvested from voluntary donators undergoing total hip arthroplasty, and then the bone microvascular endothel ial cells were isolated by enzyme digestion. The cells at passage 3 were cocultured with different concentrations of hydrocortisone (0, 0.03, 0.10, 0.30, and 1.00 mg/mL) for 24 hours. MTT assay was used for the inhibitory rate of cell prol iferation, flow cytometry for apoptosis rate, and fluorescence probe for the production of ROS and xanthine oxidase (XOD). Results At 2-3 days primary culture, the cells were spindle and arranged l ike cobbles and they reached confluence after 1 week. The inhibitory rates of cell prol iferation in 0.03, 0.10, 0.30, and 1.00 mg/mL groups were 20.22% ± 2.97%, 22.94% ± 4.52%, 43.98% ± 3.35%, and 78.29% ± 3.85%, respectively; and 2 high-concentration groups (0.30 and 1.00 mg/mL groups) were significantly higher (P lt; 0.05) than 2 low-concentration groups (0.03 and 0.10 mg/mL groups). The apoptosis rates in 0, 0.03, 0.10, 0.30, and 1.00 mg/mL groups were 0.10% ± 0.01%, 0.23% ± 0.02%, 1.83% ± 0.04%, 6.34% ± 0.11%, and 15.33% ± 0.53%, respectively; 2 high-concentration groups (0.30 and 1.00 mg/mL groups) were significantly higher (P lt; 0.05) than 0 mg/mL group. In 0, 0.30, and 1.00 mg/ mL groups, the ROS levels were 57.35 ± 7.11, 120.47 ± 15.68, and 166.15 ± 11.57, respectively, and the XOD levels were 0.017 9 ± 0.000 9, 0.028 3 ± 0.001 7, and 0.067 7 ± 0.004 1, respectively; there were significant differences in the levels of ROS and XOD among 3 groups (P lt; 0.05). Conclusion Increasing of ROS production in bone microvascular endothel ial cells can be induced by high concentration glucocorticoid, and it can result in cell injury
糖皮质激素在甲型H1N1流感中的应用探讨
The mineralocorticoid receptor (MR) belongs to the nuclear receptor superfamily and is expressed in the retina and choroid. MR antagonist (MRA) has a long history of application in non-ophthalmic clinical practice. Various cellular and animal models indicated that inappropriate activation of MR participated in pathological angiogenesis, oxidative stress, inflammation, disturbance of ion/water homeostasis and neurodegenerative changes, while the application of MRA can reduce or reverse these pathological processes. After using MRA in central serous chorioretinopathy (CSC) patients, improved visual function, less subretinal fluid and reduced sub-foveal choroidal thickness were observed. Single nucleotide polymorphisms in MR and plasma aldosterone levels were significantly different between chronic CSC patients and CSC patients with spontaneous remission. Novel formulation for sustained-release MRA and the mechanisms involving inflammation may become the new focus of MR study. This review summarizes the research status of MR and MRA in order to provide a reference for future basic research and clinical treatment.
ObjectiveTo systematically review the efficacy of preoperative corticosteroids use as an adjunctive treatment for rhegmatogenous retinal detachment associated with choroidal detachment (RRDCD). MethodsA evidence-based medicine study. The National Library of Medicine's PubMed, Web of Science, CNKI, and WanFang database were searched. Clinical controlled studies were selected the study object was RRDCD patients and the interventions were preoperative corticosteroids used as an adjunctive treatment. The search was conducted from January 2000 to January 2022. Duplicated, incomplete, or irrelevant articles were excluded. The conventional meta-analysis was used to evaluate the efficacy of corticosteroids used before surgery. The network meta-analysis was used to directly or indirectly compare the efficacy of oral corticosteroids or intravenous dexamethasone, peribulbar injection of glucocorticoids, prednisolone acetate eye-drops, intravitreal injection of triamcinolone acetonide (TA) and posterior sub-tenon injection of triamcinolone acetonide. Publication bias was evaluated by funnel plot. ResultsAccording to the search strategy, 43 articles were initially retrieved, and 929 eyes of 13 articles were finally included for analysis; 6 and 10 articles were included in the traditional meta-analysis and the network meta-analysis. Among the 6 studies included in the conventional meta-analysis, 5 studies were retrospective and 1 study was a randomized controlled trial, involving a total of 575 eyes. The analysis results showed that there was no significant difference in the primary retinal reattachment rate between the corticosteroids group and the control group [odds ratio (OR)= 1.53, 95% confidence interval (CI) 0.67-3.53, P=0.314]. Among the 10 studies included in the network meta-analysis, 7 studies were retrospective trials, 2 studies were randomized controlled trials, and 1 study was prospective trial, involving a total of 575 eyes. The analysis results showed that there were significant differences in the primary retinal reattachment rate between the triamcinolone acetonide intravitreal injection group and the no corticosteroid treatment group (OR=4.09, 95%CI 1.06-15.79). Sub-tenon injection triamcinolone acetonide had a higher incidence rate of ocular hypertension than oral glucocorticoid or intravenous dexamethasone (OR= 4.47, 95%CI 1.42-14.13). ConclusionsTriamcinolone acetonide intravitreal injection before surgery can improve the primary retinal reattachment rate in RRDCD patients. Patients with the posterior sub-tenon injection of triamcinolone acetonide should be alert to elevated intraocular pressure.
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.
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 expression levels of osteoprotegerin (OPG) and receptor activator of NF-κB l igand (RANKL) mRNAs in bone tissues of the femoral head of the patients suffering glucocorticoid-induced osteonecrosisof the femoral head (ONFH), and to discuss the relationship between OPG/RANKL and ONFH. Methods Between March2007 and March 2008, bone tissues of the femoral head were collected as the experimental material from 35 patients suffering ONFH (experimental group) and from 21 patients suffering fracture of femoral neck (control group). The ratio of men to women in both groups was 4 ∶ 3, whose age was 41-70 years old (55.34 on average in the experimental group and 55.33 on average in the control group). The experimental group received over 3 weeks’ glucocorticoid treatment or more than 1 week’ s high-dose glucocorticoid treatment in recent 2 years, while the control group never received more than 1 week’s hormone treatment. In the two groups, the microstructure of bone tissues of the femoral head was detected by HE staining and the bone tissue total RNA was extracted, and then the expression levels of OPG mRNA and RANKL mRNA were examined by realtime quantitative PCR (RTQ-PCR) for each sample. Results HE staining: bone trabeculae and bone units were replaced by interrupted bone fragments, which were surrounded by many inflammatory granulation tissues and few osteocytes were seen in bone lacunae in the experimental group. In the control group, bone trabeculae and bone units were made by complete lamellar bones which surrounded blood vessels and osteocytes were seen in lacunae. RTQ-PCR testing: in the experimental group, OPG mRNA and RANKL mRNA were 1.35 ± 0.42 and 4.36 ± 1.35, respectively, while in the control group they were 1.78 ± 0.63 and 3.49 ± 1.02, respectively. The expression level of OPG mRNA in the experimental group was significantly lower than that in the control group, and the expression level of RANKL mRNA of the former was significantly higher than the latter. The OPG mRNA/ RANKL mRNA ratio in the xperiment group (0.34 ± 0.16) was significantly lower than that in the control group (0.54 ± 0.20), and there was significant difference (P lt; 0.05). Conclusion The glucocorticoid-induced ONFH may be related to the expression levels of OPG mRNA/RANKL mRNA in bone tissues.