Objective To investigate the effect of glucocorticoid on the expression levels of osteoprotegerin (OPG)/receptor activator of nuclear factor kappa B ligand (RANKL)-matrix metalloproteinases (MMP)/tissue inhibitor of matrix metalloproteinase (TIMP) system in bone tissues of femoral head of rats, and to discuss its interrelated action mechanism in glucocorticoid-induced avascular necrosis of femoral head (ANFH). Methods Forty adult Sprague Dawley rats, weighing 250-300 g, half males and half females, were randomly divided into 4 groups: high dose glucocorticoid group (HD, n=10), medium dose glucocorticoid group (MD, n=10), low dose glucocorticoid group (LD, n=10), and control group (n=10). The rats in HD group, MD group, and LD group were intramuscularly injected with 25.0, 12.5, and 7.0 mg/kg of prednisolone respectively, and the rats in the control group were injected with physiological saline. After 4 weeks intervention, the osteonecrosis of left femoral heads was observed by HE staining, total RNA was extracted from the right femoral head bone tissue and the mRNA expression levels of OPG, RANKL, MMP-2, MMP-9, TIMP-1, and TIMP-2 were detected by RT-PCR. Results After injection of prednisolone, 4 rats of HD group and 1 rat of MD group died of systemic failure caused by the decreased food and weight culminating in cachexia. HE staining showed that the integrity of bone trabecula and osteon was destroyed at different levels, discontinuous bone chips formed, and osteocytes were replaced by granulation tissue in some lacunae in HD, MD, and LD groups; the integrated osteon was observed, the lamellar structure formed concentric circles around the blood vessel and osteocytes were seen in the lacunae in the control group. The necrosis rates of femoral head were 83.3% (5/6), 66.7% (6/9), 30.0% (3/10), and 0 (0/10) in HD, MD, LD, and control groups. The results of RT-PCR showed: the mRNA expression levels of the OPG, TIMP-1, TIMP-2 in HD, MD, and LD groups were lower than those in the control group, showing significant differences (P lt; 0.05) and there was negative correlation with the hormone dosage. The difference in OPG expression was significant between the hormone groups (P lt; 0.05); the differences in the TIMP-1 and TIMP-2 expressions were not significant between the LD group and MD group (P gt; 0.05), but there were significant differences when compared with HD group (P lt; 0.05). The RANKL, MMP-2, and MMP-9 mRNA expression levels in HD, MD, and LD groups were higher than those in the control group and there was a positive correlation with the hormone dosage, showing significant differences when compared MD and HD groups with control group (P lt; 0.05); there was no significant difference in RANKL expression between HD group and MD group (P gt; 0.05), but there was significant difference when compared HD and MD groups with LD group (P gt; 0.05); no significant difference was observed in the MMP-2 and MMP-9 expression between MD group and LD group (P gt; 0.05), but the differences were significant when compared with HD group (P lt; 0.05). Conclusion Glucocorticoid-induced ANFH may be related to the expression levels of OPG/RANKL-MMP/TIMP mRNA regulated by glucocorticoid.
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
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 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 investigate drug usage and costs of inpatients with asthma in Karamay Central Hospital in 2014 and to provide baseline for evidence-based pharmacy study of single disease in respiratory system. Methods The information of drug use and expenditure of asthma inpatients were collected from the hospital information system (HIS). We analyzed the data including frequency, proportion and cumulative proportion by Excel 2007 software. Results A total of 150 asthma inpatients were included, the average age was 56.25±18.83 years old. Three kinds of the most commonly used drugs were corticosteroids, antibiotics and antiasthmatic drugs. Budesonide suspension for inhalation, moxifloxacin needle, doxofylline needle accounted for 32.84%, 31.11% and 45.31% in these three categories of drugs, respectively. Conclusion The mainly drugs for treatment of asthma inpatients in Karamay Central Hospital in 2014 are corticosteroids, antibiotics and antiasthmatic drugs. The frequency of systemic corticosteroids is too high, and the frequency of antimicrobial use is irrational, which needs further specification.
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.
【摘要】 目的 探讨影响糖皮质激素治疗特发性血小板减少性紫癜疗效的主要因素。 方法 回顾分析2008年1月-2010年7月173例特发性血小板减少性紫癜患者的临床资料，采用χ2检验及Logistic回归分析影响糖皮质激素疗效的相关临床因素。 结果 单因素χ2检验分析显示性别、骨髓巨核细胞计数水平、骨髓产板巨核细胞比例、乙型肝炎表面抗原（HBsAg）、血清免疫球蛋白水平对糖皮质激素疗效的影响有统计学意义（Plt;0.05）。脾脏长大、抗核抗体（ANA）阳性、补体C3水平降低与糖皮质激素疗效无关。多因素Logistic回归分析显示性别、HBsAg是影响糖皮质激素疗效的相关因素。 结论 男性、骨髓巨核细胞计数增多、产板巨比例降低者对糖皮质激素治疗反应较好。女性、血清免疫球蛋白水平异常、骨髓巨核细胞不增多者及HBsAg阳性的患者对糖皮质激素治疗反应相对较差。性别、HBsAg是影响糖皮质激素疗效的主要因素。【Abstract】 Objective To discuss the influencing factors associated with the efficacy of glucocorticoid for idiopathic thrombocytopenic purpura. Methods We retrospectively analyzed the clinical data of 173 patients with idiopathic thrombocytopenic purpura who accepted their first treatment in West China Hospital between January 2008 and July 2010. The affecting factors on the efficacy of the treatment were analyzed by means of Chi-square test and binary logistic regression analysis. Results The results of Chi-square test showed that gender, bone marrow megakaryocyte count, the percentage of platelet-producing megakaryocytes, HBsAg, and the level of serum immunoglobulin could have a significant influence on the outcome of glucocorticoid treatment (Plt;0.05), while splenomegaly, positive ANA and decreasing of the level of complement C3 were not correlated with the outcome of glucocorticoid treatment. The results of multivariate logistic regression analysis showed that gender and HBsAg were correlated with the glucocorticoid treatment for patients with idiopathic thrombocytopenic purpura. Conclusion Male patients, patients with increasing bone marrow megakaryocytes and patients with decreasing percentage of platelet-producing megakaryocytes have better responses to glucocorticoid, while female patients, patients with abnormal serum immunoglobulin level and patients with non-increasing number of bone marrow megakaryocytes have poor responses toward glucocorticoid treatment. Gender and HBsAg are the main influencing factors for the response to glucocorticoid.
Objective To describe the underlying conditions of chronic pulmonary aspergillosis (CPA). Methods A retrospective study was performed. Details of the clinical, imaging features, and the underlying conditions of CPA patients admitted to a tertiary university teaching hospital from January 2009 to December 2016 were extracted from clinical records. The classification distribution of CPA, and underlying conditions were analyzed. Results Among the 108 CPA patients, 87 cases had underlying conditions, 21 cases had no underlying conditions. Seventy two (66.7%) patients were engaged in agriculture, the proportion of which was significantly higher in the cases without underlying conditions (85.7% vs. 62.1%). Chronic necrotizing pulmonary aspergillosis (CNPA) was the most common type of these CPA cases. The cases without underlying conditions had significantly more proportion of CNPA than the cases with underlying conditions (85.7% vs. 62.1%). The cases with systemic underlying conditions had significantly more proportion of CNPA than the cases only with pulmonary underlying conditions (82.8% vs. 51.7%). Chronic cavity pulmonary aspergillosis (24/108, 22.2%) only existed in the cases with pulmonary underlying conditions. Underlying conditions were identified in 87 cases of CPA, with 85.1% (74/87) pulmonary and 33.3% (29/87) systemic underlying diseases. Previous tuberculosis mycobacterial infection, bronchiectasis and chronic obstructive pulmonary disease were the most common pulmonary underlying conditions (40.2%, 39.1% and 35.6%, respectively). Diabetes (16.1%) and glucocorticoid using (13.8%) were the most two common systemic underlying conditions. Conclusions CPA can occur in patients with and without underlying diseases. CNPA is the most common type of these CPA, the proportion of which is higher in cases without underlying conditions and cases with systemic underlying conditions. Farming maybe the risk factors of CPA. Chronic pulmonary primary diseases are the most common underlying conditions. The most common systemic factors are diabetes and glucocorticoid using.