Exploring the intervention mechanism of Ginkgo biloba for steroid-induced necrosis of the femoral head based on network pharmacology / 中国临床药理学与治疗学

AIM: To explore the mechanism of Ginkgo biloba in the treatment of steroid-induced osteonecrosis of the femoral head based on network pharmacology. METHODS: The active ingredients and targets of Ginkgo biloba were predicted by the TCMSP, ADME, and PharmMapper databases. The disease targets related to steroid-induced osteonecrosis of the femoral head were searched by the GeneCards and OMIM databases. Cytoscape 3.6.1 was used to construct a protein-protein interaction network. The core target analysis, modular analysis, GO enrichment analysis, and KEGG pathway analysis of the targets of Ginkgo biloba in the intervention of steroid-induced osteonecrosis of the femoral head were performed by the STRING database. RESULTS: In this study, a total of 16 active ingredients of Ginkgo biloba and 547 targets were screened, of which 133 targets were related to steroid-induced femoral head necrosis. By PPI network topology analysis, TP53, AKT1, IL6, VEGFA, MAPK1, JUN, MAPK8, EGFR, EGF, and MYC were identified as the core targets. GO modularization analysis showed that these core targets were mainly related to apoptosis and angiogenesis. GO enrichment analysis was used to analyze the biological processes, cellular localization, and molecular functions of the core targets. KEGG enrichment analysis showed that the targets were mainly involved in molecular signaling pathways, among which the PI3K/AKT signaling pathway was the most relevant. CONCLUSION: Ginkgo biloba can inhibit steroid-induced osteonecrosis of the femoral head through multiple components, targets, and pathways, which provides the theoretical basis and reference for subsequent cell and animal experiments.

Traditional Chinese Medicine Regulates Wnt/β-catenin Signaling Pathway to Treat Steroid-induced Femoral Head Necrosis： A Review / 中国实验方剂学杂志

Steroid-induced necrosis of the femoral head （SNOFH） is a common orthopedic disease，which is difficult to cure and has poor clinical prognosis. The number of SNOFH patients in China is still increasing year by year，which seriously threatens human health. Long-term non-standard or short-term extensive use of hormone （GC） is an important reason for the occurrence of this disease. At present，SNOFH is mostly treated by surgical methods such as hip replacement，which has limitations of great harm to patients and high cost. In recent years，with the continuous deepening and innovation of traditional Chinese medicine（TCM） research，the use of TCM to treat SNOFH has been widely used in clinical practice. The main TCM pathogenesis of SNOFH is kidney deficiency and blood stasis. Therefore，TCM monomer and compound compound of tonifying kidney and promoting blood circulation are used to treat SNOFH. And TCM has obvious therapeutic effect，small side effects，less cost and other advantages. Glycoprotein/beta chain protein secretion （Wnt/beta- catenin） signaling pathway as a classic signaling pathway is closely related to the bone，between its by promoting bone marrow mesenchymal stem cell update，enhance the activity of osteoblast and suppress the apoptosis，which adjust the metabolic balance of bone tissue，increase bone density，will play an important role in the process of bone formation. In recent years，the use of TCM monomers and compounds to regulate Wnt/β-catenin signaling pathway to accelerate bone marrow mesenchymal stem cells，promote their transformation into osteoblasts，and maintain bone metabolic balance mechanism to treat SNOFH has become a new research hotspot. This article reviews the research progress of TCM in the prevention and treatment of SNOFH by regulating Wnt/β-catenin signaling pathway，in order to provide reference for the application of TCM in the treatment of SNOFH.

Characteristic changes of blood stasis syndrome in rat model of steroid-induced femoral head necrosis based on the combination of disease, syndrome, and symptom / 中国中药杂志

The approach combining disease, syndrome, and symptom was employed to investigate the characteristic changes of blood stasis syndrome in a rat model of steroid-induced osteonecrosis of the femoral head(SONFH) during disease onset and progression. Seventy-two male SD rats were randomized into a healthy control group and a model group. The rat model of SONFH was established by injection of lipopolysaccharide(LPS) in the tail vein at a dose of 20 μg·kg~(-1)·d~(-1) on days 1 and 2 and gluteal intramuscular injection of methylprednisolone sodium succinate(MPS) at a dose of 40 mg·kg~(-1)·d~(-1) on days 3-5, while the healthy control group received an equal volume of saline. The mechanical pain test, tongue color RGB technique, gait detection, open field test, and inclined plane test were employed to assess hip pain, tongue color, limping, joint activity, and lower limb strength, respectively, at different time points within 21 weeks of modeling. At weeks 2, 4, 8, 12, 16, and 21 after modeling, histopathological changes of the femoral head were observed by hematoxylin-eosin(HE) staining and micro-CT scanning; four coagulation items were measured by rotational thromboelastometry; and enzyme-linked immunosorbent assay(ELISA) was employed to determine the levels of six blood lipids, vascular endothelial growth factor(VEGF), endothelin-1(ET-1), nitric oxide(NO), tissue-type plasminogen activator(t-PA), plasminogen activator inhibitor factor-1(PAI-1), bone gla protein(BGP), alkaline phosphatase(ALP), receptor activator of nuclear factor-κB(RANKL), osteoprotegerin(OPG), and tartrate-resistant acid phosphatase 5b(TRAP5b) in the serum, as well as the levels of 6-keto-prostaglandin 1α(6-keto-PGF1α) and thromboxane B2(TXB2) in the plasma. The results demonstrated that the pathological alterations in the SONFH rats were severer over time. The bone trabecular area ratio, adipocyte number, empty lacuna rate, bone mineral density(BMD), bone volume/tissue volume(BV/TV), trabecular thickness(Tb.Th), trabecular number(Tb.N), bone surface area/bone volume(BS/BV), and trabecular separation(Tb.Sp) all significantly increased or decreased over the modeling time after week 4. Compared with the healthy control group, the mechanical pain threshold, gait swing speed, stride, standing time, and walking cycle of SONFH rats changed significantly within 21 weeks after modeling, with the greatest difference observed 12 weeks after modeling. The time spent in the central zone, rearing score, and maximum tilt angle in the open field test of SONFH rats also changed significantly over the modeling time. Compared with the healthy control group, the R, G, and B values of the tongue color of the model rats decreased significantly, with the greatest difference observed 11 weeks after modeling. The levels of total cholesterol(TC), total triglycerides(TG), low-density lipoprotein-cholesterol(LDL-C), and apoprotein B(ApoB) in the SONFH rats changed significantly 4 and 8 weeks after modeling. The levels of VEGF, ET-1, NO, t-PA, PAI-1, 6-keto-PGF1α, TXB2, four coagulation items, and TXB2/6-keto-PGF1α ratio in the serum of SONFH rats changed significantly 4-16 weeks after modeling, with the greatest differences observed 12 weeks after modeling. The levels of BGP, TRAP5b, RANKL, OPG, and RANKL/OPG ratio in the serum of SONFH rats changed significantly 8-21 weeks after modeling. During the entire onset and progression of SONFH in rats, the blood stasis syndrome characteristics such as hyperalgesia, tongue color darkening, gait abnormalities, platelet, vascular, and coagulation dysfunctions were observed, which gradually worsened and then gradually alleviated in the disease course(2-21 weeks), with the most notable differences occurred around 12 weeks after modeling.

Active Components in Chinese Medicinal Herbs Regulate Osteogenic Signaling Pathway in Treatment of Steroid-induced Osteonecrosis of Femoral Head： A Review / 中国实验方剂学杂志

As a threat to human health， steroid-induced osteonecrosis of femur head is a common refractory orthopedic disease mainly caused by glucocorticoids， with poor prognosis and unclear pathogenesis. Osteogenesis-associated signaling pathways play an important role in bone formation. Glucocorticoid-induced abnormal activation and transport of these signaling pathways lead to abnormal differentiation of bone marrow mesenchymal stem cells， dysfunction of bone metabolism， and osteogenesis disorders， which may be the main reasons for the occurrence and development of steroid-induced osteonecrosis of femur head. Bone formation and remodeling need the participation of bone marrow mesenchymal stem cells， which are stem cells characterized by continuous self-renewal and differentiation. The key to strengthening bone remodeling is to improve the osteogenic differentiation capacity， which is the key point to inhibit bone resorption and prevent bone marrow mesenchymal stem cells from differentiating into osteoclasts. Traditional Chinese medicine （TCM） has been used in the treatment of osteonecrosis in ancient times. It is recorded in the Treasury of Words on Materia Medica （《本草汇编》） that "The deficiency in the lower energizer cannot be tonified without Eucommiae Cortexz.The soreness in lower legs cannot be alleviated without Eucommiae Cortex...The pain in the waist and knee cannot be relieved without Eucommiae Cortex...Tonifying liver and invigorating kidney， Eucommiae Cortex is an essential medicine." This indicates that ancient physicians have already begun to use the liver-tonifying， kidney-invigorating， and sinew-bone-strengthening effects of Eucommiae Cortex for the treatment of osteonecrosis. As the national support for the development of TCM strengthens， increasing studies have been conducted on the TCM prevention and treatment of steroid-induced osteonecrosis of femur head. Studies have suggested that Chinese medicinal herbs can exert a positive effect on the differentiation of bone marrow mesenchymal stem cells by affecting targeted signaling molecules， and promote osteogenesis and bone defect repair， thus combating the occurrence and development of steroid-induced osteonecrosis of femur head. The regulation of osteogenic signaling pathway by Chinese medicines to prevent steroid-induced osteonecrosis of femoral head has become a hot research topic. This article reviews the studies about the prevention and treatment of steroid-induced osteonecrosis of femur head with the active components in Chinese medicinal herbs by regulating osteogenic signaling pathways. We then explore the mechanism of the active components in promoting the differentiation of bone marrow mesenchymal stem cells into osteoblasts and inhibiting their differentiation into osteoclasts to facilitate bone formation， aiming to provide a reference for the further study of treating steroid-induced osteonecrosis of femoral head with Chinese medicinal herbs.

A comparative analysis of surgical outcome in uveitic and non-uveitic steroid–induced glaucoma in children

Purpose: To compare outcomes of surgical management of uveitic glaucoma (UG) and steroid?induced glaucoma (SIG) in children in terms of intraocular pressure (IOP) control, visual acuity, and associations for failure. Methods: This was a retrospective case–control study of consecutive UG (cases) and non?uveitic SIG (controls) in children <18 years of age who underwent surgery between January 2005 and December 2017. Results: Primary trabeculectomy with mitomycin C (MMC) was performed in 12 cases (mean age: 9.2 ± 4.3 years) and 40 controls (mean age: 10.4 ± 3.7 years) (P = 0.33). Primary phaco?trabeculectomy with MMC was performed in 11 cases (mean age: 11.4 ± 4.7 years) and 16 controls (mean age: 10.4 ± 3.4 years) (P = 0.57). IOP control (P = 0.26), visual acuity (P = 0.97), number of glaucoma medications (P = 0.06), and survival rates (49% cases vs. 68% controls at 5 years; P = 0.22) were similar between the two groups following trabeculectomy. Survival rates in the phaco?trabeculectomy group at 5 years were 68% cases vs. 69% controls (P = 0.71). IOP was higher (P = 0.008) and visual acuity was worse (P = 0.02) in cases at the last visit. Associations for failure (univariate analysis) were younger age (OR: 6.29, 95% CL: 1.43, 27.67; P = 0.03) and male gender (OR: 4.79, 95% CL: 1.09, 20.97; P = 0.04). On multivariate analysis, younger age (OR: 11.985, 95% CL: 1.071, 134.153; P = 0.04) remained significant. Preoperative number of uveitic attacks was protective on univariate (OR: 0.75, 95% CL: 0.48, 1.15; P = 0.1) and multivariate analyses (OR: 0.49, 95% CL: 0.24, 0.09; P = 0.04). Conclusion: Outcomes of trabeculectomy between cases and controls were similar in our series. However, phaco?trabeculectomy in pediatric uveitic eye group fared worse than eyes with SIG.

Long-term outcomes and risk factors for failure of glaucoma filtering surgery in eyes with vernal keratoconjunctivitis and steroid-induced glaucoma

Purpose: To report outcomes and assess the risk factors for failure of trabeculectomy (trab), trabeculectomy with mitomycin?C (trabMMC), and combined trabeculectomy with cataract extraction (CT) in vernal keratoconjunctivitis (VKC) eyes with steroid?induced glaucoma (SIG). Methods: Trab was performed in 45 eyes of 30 subjects, trabMMC in 36 eyes of 25 subjects, and CT in 34 eyes of 27 subjects. Success was complete when intraocular pressure (IOP) was between 6 and 21 mm Hg without anti?glaucoma medications (AGM) and qualified with AGM. Results: Median age (14 vs. 16.3 and 17.4 years) was significantly less in the trab cohort (P = 0.007). Majority (88%–93%) were male (P = 0.78). Preoperatively, median duration of steroid usage was >2 years (P = 0.52), mean IOP (32, 29.4, and 28.4; P = 0.26) and median cup:disc ratio (CDR) (0.9; P = 0.27) were similar in the three groups. Complete success (76%, 71%, and 66% at 5 years; P = 0.91), and qualified success (88%, 97%, and 94% at 5 years; P = 1.0) with trab, trabMMC, and CT, respectively, were similar. Preoperative factors significantly associated with qualified failure (multiple logistic regression) were older children, longer duration of VKC, longer duration and mixed type of steroid use (all P < 0.001) and larger CDR (P < 0.02). At the last follow?up, 38% in trab, 33% in trabMMC, and 50% eyes in CT were blind (visual acuity ?20/400 and/or visual field ?10°) due to glaucoma (P = 0.33). Conclusion: The surgical success for all three types of surgery was similar at 5?years. Chronic VKC and long?term steroid use were associated with surgical failure. The majority had advanced disease and a significant proportion were blind due to glaucoma.

Effect of Jianpi Huogu Formula on function damage of vascular endothelial cells induced by glucocorticoid / 中国中药杂志

This study aimed to observe the intervention effect of Jianpi Huogu Formula(JPHGF) on the functional damage of vascular endothelial cells caused by glucocorticoid, and explore its action mechanism from the PI3 K/Akt and mitogen activated protein kinase(MAPK) signaling pathways. The extracted thoracic aorta ring of normal SD rats were intervened first with vascularendothelial growth factor(VEGF, 20 μg·L-1) and/or sodium succinate(MPS, 0. 04 g·L-1) in vitro and then with JPHGF(8, 16, and 32 μg·L-1) for five mcontinuous ethylpdays, rednisolofollowed nebythe statistics of the number, length, and area of microvessels budding fromvascular rings. In addition, the human umbilical vein endothelial cells(HUVECs) induced by VEGF(20 μg·L-1) were added with MPS(0. 04 g·L-1) and then with JPHGF(8, 16, and 32 μg·L-1) for observing the migration, invasion, and luminal formation abilities of HUVECs in the migration, invasion and luminal formation experiments. The protein expression levels of PI3 K, p-Akt, p-JN K, and p-ERK in HUVECs were assayed by Western blot. The results showed that JPHGF dose-dependently improved the num-ber,length, and area of microvessels in MPS-induced rat thoracic aortic ring, reversed the migration, invasion and lumen formation abiliti es of HUVECs reduced by MPS, and up-regulated the protein expression levels of PI3 K, p-Akt, and p-JNK in HUVECs. All thesehave suggested that JPHGF exerts the protective effect against hormone-induced damage to the angiogenesis of vascular endothelial cells by activating the PI3 K/Akt and MAPK signaling pathways, which has provided reference for exploring the mechanism of JPHGF in treating s teroid-induced avascular necrosis of femoral head(SANFH) and also the experimental evidence for enriching the scientific connotationof spleen-invigorating and blood-activating therapy.

Research progress on the relationship between steroid-induced avascular necrosis of the femoral head and microRNA / 中国医师杂志

Steroid-induced avascular necrosis of the femoral head (SANFH) is the death of the femoral head caused by long-term use of glucocorticoid (GC). Its pathological manifestations are mainly trabecular bone collapse and increased empty bone lacunas, osteocyte apoptosis rate and autophagy rate. Its pathogenesis is complicated, and the exact pathogenesis is still unclear. MicroRNAs (miRNAs) are a group of endogenous, non-coding small RNAs with an average length of 23 nucleotides. They are responsible for negatively regulating gene expression after transcription by inhibiting target messenger RNAs (mRNAs). MiRNAs play an important role in physiological processes, including cell development, proliferation, differentiation, metabolism, migration and apoptosis. According to bioinformatics analysis, MiRNAs play an important role in regulating gene expression, and it is estimated that more than one-third of human genes are regulated by them. In the past few years, more and more miRNAs have been found to be related to osteonecrosis, such as regulating the proliferation and differentiation of mesenchymal stem cells and osteoblasts. This article aims to review the relationship between steroid-induced femoral head necrosis and miRNAs.

Research progress in osteogenic differentiation of bone marrow mesenchymal stem cells in steroid-induced osteonecrosis of the femoral head / 解放军医学杂志

Steroid-induced osteonecrosis of the femoral head (SONFH) is a kind of disease caused by hip joint dysfunction. Long-term or high-dose application of hormone drugs leads to impaired blood supply to the femoral head and the death of a variety of bone stromal cells, resulting in the structural change of trabecular bone in the load-bearing area of the femoral head and irreversible collapse of the femoral head. Early manifestations were hip pain and discomfort, and tenderness in the inguinal region, in the middle stage, pain affects activity; in the later stage, the hip joint space become narrowed, the motion of the hip joint is reduced, and the motion is limited. SONFH has greatly affected the quality of life of patients, so modern medicine is dedicated to improve the symptoms of patients through early intervention, enabling SONFH to get effective treatment and reducing the pressure of life and economic burden of patients. Bone marrow mesenchymal stem cells (BMSCs) have become a focus in the early treatment of SONFH due to its osteogenic differentiation. BMSCs are stem cells with multi-directional differentiation potential, with self-proliferation and differentiation characteristics, which can differentiate into bone, provide mechanical support for the necrotic area and secrete a variety of growth factors to support hematopoiesis, slow down the progress of disease, and extend the service life of their own joints. The unreasonable use of hormones mainly inhibits the osteogenic activity of BMSCs, resulting in the occurrence of SONFH. This paper reviews the research on BMSC osteogenic differentiation in recent years, hoping to improve the therapeutic effect of SONFH.

MicroRNA-141 is regulated by serum of velvet antler to promote the proliferation of bone marrow mesenchymal stem cells in dexamethasone-induced cell model / 中国组织工程研究

BACKGROUND: The proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) can delay the procession of steroid-induced femoral head necrosis. Besides, microRNA-141 (miR-141) is one of the important regulatory factors to promote cell proliferation. In addition, velvet antler is a traditional Chinese medicine which has significant roles in repairing bone and tissue and improving health. OBJECTIVE: To investigate whether velvet antler serum can regulate the expression of miR-141 to promote the proliferation of BMSCs, and further delay or reverse the progression of steroid-induced femoral head necrosis. METHODS: BMSCs were isolated and cultured from Sprague-Dawley rats. The passage 3 BMSCs were transfected with miR-141 mimic or miR-141 inhibitors, and then real-time PCR and methyl thiazolyl tetrazolium (MTT) assay were performed for detecting miR-141 expression and cell proliferation, respectively. The passage 3 BMSCs were divided into three groups: control group (α-MEM), dexamethasone group (α-MEM+1 μmol/L dexamethasone), and velvet antler serum group (α-MEM+1 μmol/L dexamethasone+15% velvet antler serum). Expression of miR-141 mRNA was detected by real-time PCR at 24 hours after intervention. The proliferation ability of BMSCs was evaluated by MTT assay at 24, 48, and 72 hours after intervention. RESULTS AND CONCLUSION: After transfection with miR-141 mimic, the expression of miR-141 mRNA was upregulated, while the cell proliferation was reduced. After transfection with miR-141 inhibitor, the expression of miR-141 mRNA was downregulated, while the cell proliferation was increased. The expression of miR-141 mRNA was significantly higher in the dexamethasone group than the control group (P < 0.01), while the treatment with velvet antler serum could significantly downregulate the expression of miR-141 mRNA (P < 0.01). The absorbance of BMSCs in the dexamethasone group was significantly lower than that in the control group (P < 0.01), and the absorbance value in the velvet antler serum group was significantly higher than that in the dexamethasone group (P < 0.01). In conclusion, the serum containing velvet antler can downregulate the expression of miR-141 which is upregulated by dexamethasone and then do help to promote the proliferation of BMSCs.

Study on the distribution of necrotic tissue in steroid-induced osteonecrosis of femoral head patients based on three-dimensional reconstruction of CT / 中国修复重建外科杂志

Objective: To observe the volume and distribution of necrotic tissue of femoral head in steroid-induced osteonecrosis of femoral head (SONFH) patients by three-dimensional reconstruction of CT. Methods: A clinical data of 25 patients with SONFH between September 2016 and December 2018 was analyzed. There were 22 males and 3 females, with an average age of 38.8 years (range, 20-63 years). The necrosis of the femoral head was in stage Ⅱ of Association Research Circulation Osseous (ARCO). The disease duration ranged from 3 to 18 months, with an average of 9.2 months. A three-dimensional reconstruction with CT data of SONFH patients were performed by Mimics Research 21.0 software and the femoral head was segmented into eight regions by 3-matic Research 13.0 software. The volume of necrotic tissue of the femoral head and the volume rate of necrotic tissue to femoral head were calculated and the distribution was also analyzed. Results: The three-dimensional digital model of the femoral head showed that the necrotic tissue of the femoral head was located above the anterior superior medial, and the area of the necrotic tissue was in a dome-like shape. The results showed that the necrotic tissue in the femoral head was mainly concentrated on the anterior superior internal area, the anterior superior outer area, and the posterior superior internal area. The volume of femoral head was (48 399.52±9 408.90) mm 3, and the volume of necrotic tissue was (20 917.08±6 566.94) mm 3, and the volume ratio of necrotic tissue to femoral head was 44.75%±15.72%. The proportion of necrotic volume in different regions was different, and the necrotic tissues were mainly distributed in the anterior superior internal area, the anterior superior outer area, and the posterior superior internal area. Conclusion: The volume and distribution of necrotic tissue in femoral head can be evaluated quickly and intuitively by three-dimensional reconstruction of CT in Mimics software.

Effect of icariin on early steroid-induced osteonecrosis of the femoral head in rabbits / 中国修复重建外科杂志

Objective: To explore the effect of icariin on early steroid-induced osteonecrosis of the femoral head in rabbits. Methods: Fifty mature New Zealand rabbits (weighing, 2.5-3.0 kg) were randomly divided into control group ( n=10), model group ( n=20), and experimental group ( n=20). The rabbits of model and experimental groups were injected with lipopolysaccharide and methylprednisolone to establish the animal model of early steroid-induced osteonecrosis of the femoral head. The rabbits of experimental group were feeded with icariin solution once a day for 6 weeks since the first injection of methylprednisolone, whereas the rabbits of control and model groups were given normal saline at the same time points. The left femoral heads were removed after 6 weeks and gross morphological features were evaluated. Micro-CT scan was performed to analyze the trabecular microstructure with the following parameters: trabecular bone volume to total volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Tn), and trabecular separation (Tb.Sp). The Micro-CT scan was also converted to three-dimensional reconstruction images for observation. HE staining was applied to observe the trabecular structure and morphological changes of osteocytes and marrow adipocytes. It was also used to determine whether the samples of femoral heads occurred osteonecrosis based on the criteria for pathological diagnosis, and calculate the rate of empty lacunae. Results: Seven rabbits died during the study, and 9, 16, and 18 rabbits in the control, model, and experimental groups, respectively, enrolled the final analysis. Compared with control group, the femoral head collapse and trabecular breaks were more obvious, and the trabeculae were sparse with irregular arrangement in the model group according to the results of gross observation, Micro-CT scan, and three-dimensional reconstruction images. But in the experimental group, the surface of femoral head was slight shrinking without obvious collapse, and the degeneration of trabecular structure was mild. According to bone microstructures analysis, the Tb.N, Tb.Tn, and BV/TV of femoral head in model and experimental groups were lower than those in control group, while the Tb.Sp in the model and experimental groups were significantly higher. The Tb.N, Tb.Tn, and BV/TV of femoral head in experimental group were higher than those in model group, while the Tb.Sp in the experimental group was significantly lower. The differences between groups were all significant ( P<0.05). In the model group, HE staining showed that the number of osteocytes reduced, the number of empty lacunae increased, and the marrow adipocytes piled up in the space between femoral trabeculae, some even mashed together like a cyst. In the experimental group, the trabecular structure was still relatively complete compared with model group, no obvious apoptosis of osteocytes was observed, the size and number of adipocytes were basically normal. None of the animals in control group occurred osteonecrosis of the femoral head based on the criteria for pathological diagnosis, and the incidence of osteonecrosis were 81.3% (13/16) in the model group and 66.7% (12/18) in the experimental group, and the difference was not significant ( P=0.448). The rate of empty lacunae of osteonecrotic femoral heads in the model group was 33.1%±1.4%, which was higher than that in experimental group (18.9%±0.8%) and in control group (12.7%±1.5%), and the differences between groups were significant ( P<0.05). Conclusion: The icariin has a protective effect on the early steroid-induced osteonecrosis of the femoral head in rabbits, which can decrease osteocytes apoptosis, improve the bone microstructure, and delay such disease processes.

Pattern of steroid misuse in vernal keratoconjunctivitis resulting in steroid induced glaucoma and visual disability in Indian rural population: An important public health problem in pediatric age group

Purpose: To know the pattern of presentations and management outcome of steroid induced glaucoma in vernal keratoconjunctivitis (VKC). Methods: Children of VKC using steroid with two of the following criteria were enrolled: Intraocular pressure (IOP) >21 mm Hg, glaucomatous optic disc and visual field defects. Misused topical steroids were classified in 4 groups; A- Highly potent drugs (dexamethasone, betamethasone), B- Moderate (prednisolone), C- Weak (loteprednol, fluorometholone), D- Unknown drugs. Active/conservative interventions were done to control IOP. Corrected distance visual acuity (CDVA), IOP, anterior segment and fundus examinations were noted. One-way ANOVA test and post hoc Tukey HSD test were used to compare the groups. Results: Out of 1423 VKC patients, 240 were using topical steroid without prescriptions. 92 eyes of 47 patients had steroid induced glaucoma. Hence prevalence of this complication was 3.30% in this study population. Mean age was 14.1 ± 3.8 years. Mean IOP was 38 ± 12 mm of Hg and mean vertical cup disc ratio was 0.67 ± 0.25. IOP was controlled by withdrawal of steroids (9 eyes), with antiglaucoma medications (27), trabeculectomy (57) and glaucoma drainage device (1). Mean CDVA at presentation was better in group C (0.23 log MAR). Mean IOP was highest in group A (43.1 mm Hg) followed by group D (40.5 mm Hg). At presentation 17 were blind (CDVA <3/60). Post treatment marginal improvement in CDVA was found (P = 0.46). However, statistically significantly improvement was noticed in IOP (P < 0.00001). Conclusion: Injudicious use of steroids leads to vision threatening complications like ocular hypertension and glaucoma in children of VKC. Weak steroids like loteprednol or fluorometholone should be used instead of higher potency drugs. Vision and IOP should be monitored fortnightly in children using topical steroids to detect steroid responders at the earliest.

Steroid Induced Myopathy in Dermatomyositis Patients

Symmetrical proximal weakness and characteristic dermatologic manifestations are important in the diagnosis of dermatomyositis. We report a case of atypical presentation of dermatomyositis due to previous steroid use and also report steroid-induced myopathy which may occur from steroid administration during the course of treatment. A 77-year-old man, previous steroid user, showed rapidly progressing weakness after abruptly stopped medication. He has presented erythematous papule on face and anterior chest but no heliotrope rash and Gottron's papules were observed. Muscle enzyme (creatine kinase) concentration is increased, and needle electromyography shows increased spontaneous activity on proximal limb muscle. The muscle biopsy confirmed dermatomyositis. During the course of treatment, he revealed persistent weakness despite the continuous steroid use and stable creatine kinase level. Electrodiagnostic study suggests steroid-induced myopathy and after tapering steroid, proximal muscle strength improved. This case reports the effect of steroid use on dermatomyositis patients and a process of diagnosing coexisting steroid induced myopathy during treatment.

Mailuoning Compound for Treatment of Early Steroid-induced Osteonecrosis of Femoral Head in Rats by Obturator Nerve Block / 中国实验方剂学杂志

Objective: To investigate the effect and mechanism of Mailuoning Compound for treatment of early steroid-induced osteonecrosis of femoral head (SONFH) in rats by obturator nerve block. Method: 24 rats were injected with endotoxin 10 μg·kg-1 through tail vein. After 24 hours, prednisolone acetate 20 mg·kg-1 was given by intraperitoneal injection, once every 24 hours for 3 consecutive days. After successful modeling, the rats were randomly divided into the model group (n=12), the treatment group (n=12) and the normal control group (n=6). In the treatment group, 2 mL·kg-1 of Mailuoning compound was injected into the obturator nerve from the 4th day, 3 times a week for 8 weeks. The arterial blood was collected from rats on the first day of the 9th week after model building to detect the content of blood lipid; the femoral head was taken to prepare the paraffin section, and the pathological changes of femoral head was observed and the changes of empty bone lacuna rate, bone trabecular area and bone lacuna area were quantitatively analyzed; The changes of bone morphogenetic proteins(BMPs),transforming growth factor-β1(TGF-β1),vascular endothelial cell growth factor(VEGF),and Ⅷ factor related antigen(Ⅷ-R Ag) were quantitatively analyzed by immunohistochemical method. Result: In the model group, the bone trabeculae were sparse, thin, disorganized and broken; some of the bone cells were necrotic and the number of empty bone lacunae was increased. In the treatment group, the number of trabeculae was increased; the structure was clear, most of which was normal bone cells, with a few necrotic bone cells, and the number of empty bone lacunae was decreased obviously. The rate of empty bone lacuna and the area of bone lacuna in the treatment group were significantly lower than those in the model group (Pβ1 and the microvessel density of Ⅷ-R Ag in the treatment group were significantly higher than those in the model group (PPConclusion: Mailuoning compound can improve the microcirculation state of femoral head, promote the formation of new bone and blood vessel in femoral head by regulating the expression of VEGF, BMPs, TGF-β1, Ⅷ-R Ag and down-regulating blood lipid content, thus effectively controlling the development of early SONFH. This can provide a theoretical basis for the treatment of early SONFH.

Efficacy of Wenyangbushen Formula on mRNA Expression of Osteoprotegerin, Receptor Activator of Nuclear Factor-kappa B and Its Ligand in Rabbits with Steroid-induced Avascular Necrosis of Femoral Head / 中国康复理论与实践

Objective:To observe the effect of Wenyangbushen formula on mRNA expression of osteoprotegerin (OPG), receptor activator of nuclear factor- kappa B (RANK) and receptor activator of nuclear factor- kappa B ligand (RANKL) in rabbits with steroid-induced avascular necrosis of femoral head (SANFH). Methods:A total of 46 healthy conventional New Zealand white rabbits were randomly divided into normal group (n = 10) and model building group (n = 36). The modified method of horse serum plus methylprednisolone was used to establish the SANFH model. Two rabbits from the normal group and four from the model building group were used for HE staining. Then the other models were randomly divided into model group, and low-dose, medium-dose and high-dose treatment groups, with eight rabbits in each group. The normal group was given normal saline 10 ml/d, and the treatment groups were given Wenyangbushen formula 6.44 g/(kg·d), 9.66 g/(kg·d) and 12.88 g/(kg·d), respectively, for eight weeks. The mRNA expression of OPG, RANK and RANKL was detected by reverse transcription- polymerase chain reaction. Results:The empty lacuna rate was significantly higher in the model group than in the normal group (t = 17.085, P < 0.001). Compared with the model group, the mRNA expression of OPG increased (P < 0.01), and the mRNA expression of RANK and RANKL decreased (P < 0.01), in the treatment groups. Compared with the low-dose treatment group, the mRNA expression of OPG increased (P < 0.01), and the mRNA expression of RANK and RANKL decreased (P < 0.01), in the medium-dose and high-dose treatment groups. There was no significant difference in the mRNA expression of OPG, RANK and RANKL between the low-dose treatment group and the high-dose treatment group (P > 0.05). Conclusion:Wenyangbushen formula could increase the mRNA expression of OPG and inhibit the mRNA expression of RANK and RANKL in the femoral head tissue of the rabbits with SANFH.

Effect and mechanisms of vitamin E on early steroid-induced avascular necrosis of femoral head in rats / 中国修复重建外科杂志

Objective: To investigate the possibility of mitochondria-dependent apoptosis as a mechanism of early steroid-induced avascular necrosis of femoral head (SANFH) in rats and vitamin E as a possible prevention strategy. Methods: Seventy-two male Sprague Dawley rats were randomly divided into control group, model group, and intervention group, with 24 rats in each group. The rats in control group were not treated as normal control. The rats in model group and intervention group were established early SANFH models by lipopolysaccharide combined with methylprednisolone injection. At the same time, the rats in intervention group were injected with vitamin E (40 mg/kg) every day for 7 days. At 2, 4, and 8 weeks after the final injection, the bilateral femoral heads were harvested and observed by HE staining, TUNEL assay, immunohistochemical staining, and Western blot. The rate of empty lacunae, apoptotic index, and the expressions of Caspase-9, Caspase-3, and cytochrome-c (Cyt-c) proteins were calculated. Results: According to histological staining, there were significant differences in the rate of empty lacunae between intervention group and control group at 8 weeks ( P<0.05) and between intervention group and model group at 4 and 8 weeks ( P<0.05). The apoptotic index of intervention group was significantly lower than that of model group at each time point ( P<0.05). And there was significant difference between the intervention group and the control group at 8 weeks ( P<0.05). According to immunohistochemistry staining and Western blot, the expressions of Cyt-c, Caspase-9, and Caspase-3 all significantly decreased in intervention group than those in model group at each time point ( P<0.05); and the differences were significant between intervention group and control group at 8 weeks ( P<0.05). Conclusion: Vitamin E can delay the progression of early SANFH by reducing mitochondrial dependent osteocyte apoptosis.

Effect of platelet rich plasma combined with core decompression on the repair of steroid-induced avascular necrosis of the femoral head and the MMP/TIMP in rabbits / 中国比较医学杂志

Objective To observe the effect of platelet rich plasma(PRP)combined with core decompression on the steroid-induced avascular necrosis of the femoral head(SANFH)and on MMP/TIM in rabbits.Methods A total of 42 New Zealand white rabbits were used in this study,and were randomly divided into 3 groups(decompression,combination and control groups,each n=14). The rabbit model of SANFH was established by i.m. injecting prednisolone acetate in the decompression group and combination group. The improved Landesberg method was used to make the platelet rich plasma. The decompression group received core decompression treatment while the combination group received PRP combined with core decompression for bone repair. X-ray photography of the hip joint of the two groups were taken at 2,6 and 10 weeks after the surgery,and the Lane-Sandhu X-ray scores and new bone area ratio were compared. Venous blood samples of the 3 groups were collected and the bilateral femoral heads were taken for further examination. The left femoral heads were used for histopathological observation and the right ones were used to determine the expression of the mRNA of MMP-2,MMP-9, TIMP-1, and TIMP-2. Results The levels of MMP-2 and MMP-9 in the decompression group were higher than that in the combination group and control group after surgery. The levels of TIMP-1 and TIMP-2 in the decompression group were significantly lower than the combination group and control group(P < 0.05). The IL-6 level and the rate of empty bone lacunae in the decompression group were significantly higher than the combination group and control group(P < 0.05), and that of the combination group was higher than the control group(P < 0.05). The combination group had a better joint imaging and histopathological evaluation than the decompression group after surgery. Conclusions Our findings demonstrate that PRP combined with core decompression can exert a positive effect on the MMP/TIMP and bone tissue repair in the treatment of steroid-induced avascular necrosis of the femoral head in rabbits.

Research Progress in Relationship Between Treating Steroid-induced Osteonecrosis of Femoral Head by Deficiency and OPG/RANK/RANKL / 中国中医药信息杂志

Recent studies have shown that TCM treatment for bone metabolic diseases, such as steroid-induced avascular necrosis of the femoral head, has definite efficacy and has received extensive attention. However, due to lack of molecular biological basis of pharmacodynamics mechanism, it has not yet reached the standard of scientific treatment. The discovery of OPG/RANK/RANKL system has become a new breakthrough point in the prevention and treatment of bone metabolic diseases. The pathogenesis of deficiency of spleen and kidney - blood stasis - caused by phlegm arthralgia caused by blood stasis is closely related to the system. The effect of the final control of the system from the deficiency theory can be expressed through the axial micro-information. This article discussed the TCM syndrome differentiation of steroid-induced osteonecrosis of the femoral head and the relation of regulation of bone metabolism combined with the OPG/RANK/RANKL system, and provided the basis for prevention and treatment of this disease.

Influence factors and clinical treatment of high intraocular pressure after LASEK / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To analyze the influence factors of high intraocular pressure after laser epithelial keratomileusis(LASEK), and to discuss the clinical treatment and prognosis of the high intraocular pressure patients. <p>METHODS: A retrospective study was used. From August 2013 to February 2016, 160 LASEK patients(160 eyes)in our hospital were selected. Visual acuity after operation was recorded. The incidence and influence factors of high intraocular pressure were investigated. The treatment method and prognosis of high intraocular pressure were recorded. <p>RESULTS: In the 160 patients, all patients had complete epithelial flap and different degree of photophobia. There were 19 patients with postoperative photophobia, conjunctival hyperemia and foreign body sensation significantly. At postoperative 3mo, average intraocular pressure were 18.40±4.98mmHg, which was higher than that of preoperative, 16.27±2.24mmHg(<i>P</i><0.05), and at postoperative 3mo, visual acuity was significantly higher than preoperative(<i>P</i><0.05). There were 9 patients with postoperative steroid induced ocular hypertension, the incidence rate was 5.6%; Multiple linear regression analysis showed that the cutting depth(<i>OR</i>=3.209), maximum diameter of curvature(<i>OR</i>=3.071)and fundus C/D(<i>OR</i>=9.224)value were the main risk factors leading to postoperative steroid induced ocular hypertension(<i>P</i><0.05). <p>CONCLUSION: The postoperative steroid induced ocular hypertension in LASEK is common, but has no obvious effect on visual acuity. The cutting depth, maximum diameter, curvature fundus C/D value were the main influencing factors, so we should careful use the hormone drugs in treatment and prevention. Periodic review and detection for change of intraocular pressure are needed.