Objective To investigate the effect of steroid receptor coactivator family in initiation, development, treatment and prognosis of breast cancer. Methods The literatures in recent years which have related to the effect of steroid receptor coactivators in breast cancer are reviewed. Results Steroid receptor coactivators are essential for several kinds of steroid hormones binding to steroid receptors, so they are important accessory factors that induce the initiation, development and recurrence of breast cancer, and predictive factors that estimate the prognosis of breast cancer. Conclusion Inhibition of the expression and signaling pathway of steroid receptor coactivators may be effective for breast cancer prevention and treatment.
Objective To explore the significance of osteocyte apoptosis in steroidinduced osteonecrosis of the femoral head. Methods SixtyNew Zealand rabbits were divided into experimental group and control group(n=30). The experimental group was given 10 ml/kg of horse serum intravenously 2 times at 2 weeks intervals and an intraperitoneal injection of 45 ml/kg·d of methylprednisolone acetate for 3 days；the control group was given equal isotonic Na chloride. Osteocyteapoptosis was observe by means of TUNEL. Results The number of apoptosis in the experimental group(112.33‰±26.12‰) was significantly higher than that in the control(47.01‰±22.95‰) (Plt;0.01)in the 4th week. With time, osteocytes apoptosis progressively increased. In the 6thand 8th weeks, the percentage of empty osteocyte lacunae in the experimental group (17.23%±3.44%, 28.56%±3.45%) was significantly higher than that in the control group (11.29%±2.89%,11.26%±2.75%，Ｐlt;0.05). The transmission electron microscope showed that the characteristics of osteocyte apoptosisincluded intact nuclear membrane,comdensed chromatin and increased electron dense. Conclusion Osteocytes apoptosis may play a key role in the process of steroidinduced early osteonecrosis of the femoral head.
Objective To investigate the significance of sensory neuropeptides [calcitonin gene related peptide (CGRP) and substance P (SP)] in steroid-induced avascular necrosis of the femoral head (ANFH) by using a rabbit model. Methods Fifty-five adult female Japanese White rabbits (weighing 3 kg and aging 24 months) were randomly divided into experimental group (n=45) and control group (n=10). The rabbits in experimental group received a single intramuscularinjection of methylprednisolone at a dose of 4 mg/kg and then were sacrificed after 3 days (n=15), 1 week (n=15), and 2 weeks (n=15) of injection. The rabbits in control group were fed without any treatment. The necrosis of the femoral head was observed. And the expressions of the monoclonal antibodies CGRP and SP were observed with immunohistochemical staining. Also, the integrated absorbance (IA) value of the positive area was calculated. Results All rabbits survived to the end of the experiment. There was no necrosis of the bone or bone marrow in experimental group at 3 days; whereas ANFH was observed in 5 rabbits at 1 week (33%) and in 8 rabbits at 2 weeks (53%). There were significant differences in the rate of ANFH between 1 week, 2 weeks and 3 days (P lt; 0.05); but there was no significant difference between 1 week and 2 weeks (P gt; 0.05). The intensity of CGRP immunoreactivity increased and reached the peak at 1 week, and then decreased at 2 weeks in experimental group. The IA value of CGRP in experimental group at 1 week was significantly higher than that of control group and that of experimental group at 3 days (P lt; 0.05). The IA value of CGRP in experimental group at 2 weeks was significantly lower than those at 3 days and 1 week (P lt; 0.05). The intensity of SP immunoreactivity decreased and reached the lowest at 1 week, and then increased. The IA value of SP in experimental group at 1 week was significantly lower than that of control group and that of experimental group at 2 weeks (P lt; 0.05). Conclusion The sensory neuropeptides may be affected by the steroid, which may play a key role in the process of steroid-induced ANFH by imbalance of bone metabol ism, disturbance of the microcirculation of bone, and disorder of the protective pain-transmission.
【Abstract】 Objective To investigate both incidence and mechanism attributing to steroid-associated osteonecrosisof femoral head(ONFH) using an experimental protocol with a single low-dose l i popolysaccharide (LPS) injection andsubsequently three injections of high-dose methylprednisolone (MPS). Methods Twenty-five New Zealand white rabbits with body weight of (3.0 ± 0.3) kg were divided randomly into 2 groups. In treatment group, 19 rabbits received one intravenous injection of LPS (10 μg/kg); 24 hours later, three injections of 20 mg/kg of MPS were given intramuscularly at an interval of 24 hours. Additional 6 rabbits which received normal sal ine injection at the same time point were used as controls(control group). The blood samples were collected for hematological examinations before and after LPS injection, MRI was performed on bilateral hip six weeks after last MPS injection, meanwhile, bone marrow was aspirated from femoral head region to evaluate stem cell’s activity. Bilateral femoral heads were harvested to make histopathology examination. Results All animals survived throughout the experiment period except one death on the second day after LPS injection. In the histopathological examinationfor the femoral head, ONFH+ was observed in 16 rabbits (88.9%), and the lesions were mainly in the metaphysis. In ONFH+ rabbits, micro vessels fibrous thrombosis and extravascular marrow fat cell size increasing were found around necrotic bone; The femoral heads of control group had no changes. MRI accurate ratio was 93.8% (15/16). Compared to basel ine, a significant decrease in ratio of tissue plasminogen activator/plasminogen activator inhibitor 1 and activated partial thromboplatin time, and a significant increase in ratio of low-density l ipoprotein/high-density l ipoprotein were only found in ONFH+ rabbits (P lt; 0.05). Meanwhile there was a significant decrease in the number of CFU-F (8.50 ± 9.63) compared with the control (70.17 ± 7.78, P lt; 0.05). Conclusion A single low-dose LPS injection and subsequent three injections of high-dose MPS is effective on building steroid-associated ONFH model, coagulation and l ipometabol ism abnormal ity, activity degeneration of stem cell may be the key factors of ONFH.
【Abstract】 Objective To approach the possibil ity of combination of simvastatin and BMSCs transplantation forsteroid-associated osteonecrosis of femoral head. Methods The BMSCs harvested from 24 rabbits were prepared for cell suspension at a concentration of 1 × 107/mL, and combined with gelatin sponge. Seventy New Zealand white rabbits received one intravenous injection of l ipopolysaccharide (10 μg/ kg). After 24 hours, three injections of 20 mg/kg of methylprednisolone were given intramuscularly at a time interval of 24 hours. Forty-eight rabbits diagnosed as having femoral head necrosis by MRI were divided into 4 groups randomly, group A: no treatment; group B: only decompression; group C: decompression and BMSCs transplantation; and group D: simvastatin drench (10 mg/kg.d) decompression and BMSCs transplantation. The general information of animals were recorded; after 4 and 8 weeks of operation, 6 rabbits of each group were chosen randomly to do MRI scan, and femoral heads were harvested to do histopathology and scanning electron microscope examination. Results After 8 weeks, rabbits became more active than before treatment, and walking way became normal gradually in groups C and D. Fourweeks after operation, the MRI low signal region of all groups had no obvious changes, but 8 weeks later, the necrosis signal region of group A magnified while it reduced obviously in group D. Histopathological observation: 4 weeks after operation, diffuse presence of empty lacunae and pyknotic nuclei of osteocytes were found in the trabeculae, and few newborn micrangium could been seen in group A; lots of empty lacunae and a small quantity of newborn micrangium could been found in group B; and large amounts of osteoblats and newborn micrangium were found around the necrosis regions in groups C and D. The positive ratio of empty lacunae and microvessel density in group D were 19.30 ± 1.52 and 7.08 ± 1.09, showing significant difference compared with other groups (P lt; 0.05). After 8 weeks of treatment, the bone trabecula collapsed in many regions in group A; there was fibra callus formation along the decompression channel in group B; few empty lacunae was in the bone trabecular, but the shape of marrow cavity was not normal in group C; and it showed almost normal appearance in group D. The positive ratio of empty lacunae and microvessel density in group D were 11.31 ± 1.28 and 12.37 ± 1.32, showing significant differences compared with other groups (P lt; 0.05), meanwhile, showing significant difference compared with that of 4 weeks after operation(P lt; 0.05). Scanning electron microscope: 8 weeks after operation, the bone trabecula collapsed in many regions, and few osteoblasts could be found on the surface, a great quantity of fat cells cumulated in the bone marrow in group A; cracked bone trabecula could be found occasionally in group B; the density of bone trabecula was lower than the normal in group C; and the shape of the marrow avity and thedensity of bone trabecula were similar to the normal in group D. Conclusion Simvastatin can promote the differentiation of osteocyte and vascular endothel ial cell from MSCs, the combination of simvastatin and marrow stem cells transplantation for the treatment of steroid-associated osteonecrosis of femoral head have good appl ication prospects.
ObjectiveTo establish an rabbit model of early steroid-induced avascular necrosis of the femoral head (SANFH) and evaluate its validity with MRI and pathological examination. MethodsTwenty 6-month-old rabbits (weighing, 2-3 kg) were randomly divided into 2 groups (control group and model group), 10 rabbits in each group. Dexamethasone sodium phosphate solution (10 mg/kg) was injected into bilateral gluteus in model group, and the same amount of saline was injected in control group, every 3 days for 14 times. General observation was done after modelling. Osteonecrosis was verified by pathological observation and MRI findings at 6 weeks. ResultsAfter 6 weeks, rabbits did not show obvious changes in control group; increased hair removal, decreased food intake, and slight limp were observed in model group. The MRI results showed normal shape of the bilateral femoral head and no abnormal signals in control group; irregular shape of the bilateral femoral head and a slice of irregular abnormal signals were observed, and necrosis and cystolization of the subchondral bone and sparse changes of trabecular bone were shown in model group. General observation from coronal section of femoral head showed smooth red cartilage surface in control group; on the contrary, the cartilage surface of the femoral head became dull, thin even visible hemorrhage under articular cartilage and necrosis of the femoral head were observed. The histopathological examination indicated that trabecular bone of the femoral head in control group was massive, thick, and close, and osteocytes in the bone lacunae had normal shapes. The osseous trabecular became thinner and broken; karyopyknosis of osteocytes and bone empty lacunae could be obviously seen in model group. The rates of empty lacunae were 8.0%±0.5% in control group and 49.0%±0.3% in model group, showing significant difference (t=21.940, P=0.000). ConclusionEstablishing a model of early SANFH through injecting shortterm, shock, and high dose of dexamethasone, and it can been evaluated effectively with MRI and pathological examination.
In order to evaluate the long-term effect of total hip replacement (THR) in patients with steroid-induced femoral head necrosis, 40 cases of 50 hips received THR patients were followed up for an average of 8.5 years after operation. Evaluation was carried act according to Harris score system. In these cases, average score was seventy-five points. Revision rate among them was 2% after four years and 18% after five to eight and a half years, with as overall rate of 20%. It was found that the main reason for revision was looseness of the prosthesis. In this follow-up, it showed that besides foreigen body reaction, abnormal osseous remodelling was the main factor in long-term failure of this arthroplasty. It was also proved that it was a good selection to perform cemented total hip replacement in younger patients, which could improve living quality.
Objective To investigate the postoperative biochemical changes and the strategy of steroid treatment for autoimmune pancreatitis （AIP）. Methods Six patients with AIP from January 2007 to October 2011 in this hospital were included in this study. Four patients received pancreaticoduodenectomy or distal pancreatectomy for being preoperatively misdiagnosed as malignant tumors. Two patients avoided the unnecessary resection and received the internal drainage for obstructive jaundice and postoperative steroid medication because of a confirmation of AIP by intraoperative frozen biopsy. All the patients underwent routine examinations， including liver function， CA19-9 level， and imaging data. Measurement of serum IgG or IgG4 was performed for fewer patients after operation. Results CA19-9 levels were normal or slightly elevated in six AIP patients. For five patients with AIP in the head of pancreas， preoperative serum γ-GT levels were elevated. For these patients， whether pancreaticoduodenectomy or the internal drainage were performed， TB/DB levels were transiently elevated on day 1 or 4 after operation but dropped to below preoperative levelsor normal levels on day 7 after operation， and serum γ-GT levels among them presented a downward. Serum γ-globulin levels exhibited a downward trend among four AIP patients after resection， while a upward trend was found in another two AIP patients receiving internal drainage. From the limited data， elevated serum level of IgG in the AIP patients were found. As to IgG4， the only case was tested on month 7 after operation， the serum IgG4 level was elevated. CT showed that the swollen status of pancreas obviously reduced on month 3 after operation as compared with before operation.Conclusions Postoperative steroid therapy of AIP should be based on the serum γ-globulin level and operation method. CT or MRI imaging is used to evaluate the response to steroid treatment for the AIP patients.
Objective To evaluate the effects and the molecular mechanism of Liuwei dihuang pills in preventing steroid-induced osteonecrosis of the femoral head (ONFH) so as to provide an expremental basis for preventing ONFH cl inically. Methods Thirty-six adult Kunming mice (weighing 40-50 g, 46 g on average) were randomly divided into three groups (n=12): group A (control group), group B (model group) and group C (prevention group). In groups B and C, ONFHmice models were produced by intraperitoneal injection of horse serum at first (10 mL/kg) and a second injection of horse serum intraperitoneally (5 mL/kg) and prednisolone intramuscularly [45 mL/(kg•day), for 5 days] 2 weeks later. At the same time, the mice in group C were given Liuwei dihuang pills intragastrically [2 g/(kg•day)] and were given normal sal ine [10 mL/(kg•day)] in group B. In group A, mice were given normal sal ine intramuscularly and intragastrically as controls. The animals were sacrificed 2, 4, and 8 weeks after first treatment with prednisone, and femoral heads and l ivers were harvested to do histopathology analysis and apoptosis assay. Results Other mice survived throughout the experiment period except two death at 7 and 11 days after second injection of horse serum intraperitoneally in group B and one death at 24 hours after second injection of horse serum intraperitoneally in group C. The appearance and shape of the femoral head and the surface of cartilages were all normal. The histological observation showed: normal structures of l iver and femoral head were seen in group A at each time point; swell ing l iver cells with small fat vacuole, unclear structure of hepatic cords and narrower sinus hepaticus were seen, the bone trabeculae of femoral head was thin, sparse and collapsed in some regions and the changes became more obvious with time in group B; group C had similar results to group A. The percentage of empty osteocyte lacunae was significantly higher in group B than in groups A and C (P lt; 0.01). The osteoprotegrin expression significantly decreased and the osteoprotegrin l igand expressionsignificantly increased in group B when compared with groups A and C (P lt; 0.01). Apoptosis analysis showed that the apoptosis index in group B was significantly higher than that in groups A and C (P lt; 0.01). Conclusion Liuwei dihuang pills can prevent steroid-induced ONFH by improving l ipid metabol ism, releiving bone lesion, and protecting against cell death.
【Abstract】 Objective The present study employed both static and dynamic imaging modal ities to study bothintra- and extravascular events attributing to steroid-associated osteonecrosis (ON) using an experimental protocol with a single low-dose l i ppolysaccharide (LPS) injection and subsequently three injections of high-dose methylprednisolone (MPS). Methods Fourteen 28-week-old male New Zealand white rabbits received one intravenous injection of LPS (10 μg/ kg). After 24 hours, three injections of 20 mg/kg of MPS were given intramuscularly at a time interval of 24 hours. Additional 6 rabbits were used as controls. Dynamic MRI was performed on bilateral femora for local intraosseous perfusion before and after LPS injection. Blood samples were collected for haematological examinations before and after LPS injection. Bilateral femora were dissected and decalcified for microCT-based microangiography. ON lesion, intravascular thrombus and extravascular marrow fat cell size were examined histopathologically. Results Intravascular thrombus was observed in all ON rabbits. Extravascular marrow fat cell size was significantly increased in ON rabbits than that of the controls (P lt; 0.05). Compared to basel ine, a significant decrease in ratio of tissue-type-plasminogen-activator/plasminogen-activator inhibitor 1,activated-partial- thromboplatin-time, and a significant increase in ratio of low-density-l ipoprotein/high-density-l ipoprotein were only found in ON rabbits (P lt; 0.05). Dynamic MRI showed a significant decrease in the perfusion index ‘maximum enhancement’ in the ON rabbits (P lt; 0.05) and microCT-based microangiography showed blocked stem vessels in ON samples.Overall, 93% of the rabbits (13/14) developed ON and no rabbits died throughout the experiment period. Conclusion Bothintra- and extravascular events were found attributing to the steroid- associated ON based on our experimental protocol with a single low-dose LPS injection and subsequent three injections of high-dose MPS. Both high ON incidence and no mortal ity in rabbits treated with this inductive protocol suggested its effectiveness for future studies on evaluation of therapeutic efficacy of interventions developed for prevention of steroid-associated ON.