Wenwei Qian

Glucocorticoid Receptor and Sequential P53 Activation by Dexamethasone Mediates Apoptosis and Cell Cycle Arrest of Osteoblastic MC3T3-E1 Cells

Glucocorticoids play a pivotal role in the proliferation of osteoblasts, but the underlying mechanism has not been successfully elucidated. In this report, we have investigated the molecular mechanism which elucidates the inhibitory effects of dexamethasone on murine osteoblastic MC3T3-E1 cells. It was found that the inhibitory effects were largely attributed to apoptosis and G1 phase arrest. Both the cell cycle arrest and apoptosis were dependent on glucocorticoid receptor (GR), as they were abolished by GR blocker RU486 pre-treatment and GR interference. G1 phase arrest and apoptosis were accompanied with a p53-dependent up-regulation of p21 and pro-apoptotic genes NOXA and PUMA. We also proved that dexamethasone can’t induce apoptosis and cell cycle arrest when p53 was inhibited by p53 RNA interference. These data demonstrate that proliferation of MC3T3-E1 cell was significantly and directly inhibited by dexamethasone treatment via aberrant GR activation and subsequently P53 activation.

Pathogenesis of glucocorticoid-induced avascular necrosis: A microarray analysis of gene expression in vitro

Avascular necrosis of the femoral head (ANFH) occurs following exposure to corticosteroids, and the proliferative capacity of the mesenchymal stem cells (MSCs) belonging to ANFH was reduced. The previous studies indicate that microRNA (miRNA) has an important regulatory role during proliferation and osteogenic differentiation of MSCs. Therefore, MSCs were obtained from healthy adults, and were cultured and osteogenically-induced by different dexamethasone concentrations. The proliferation and osteogenic differentiation capacities were examined through observing cellular morphology, alkaline phosphatase and alizarin red; miRNA expression was investigated using an miRNA gene chip and miRNA of differential expressions were retrieved through a database to analyze its regulatory effect. Dexamethasone at a concentration of 10−7 mol/l induced the proliferation and osteogenic differentiation of MSCs and resulted in evident miRNA expression profile changes. In total, 11 miRNAs were upregulated at 10−7 mol/l while 6 were downregulated, and partial miRNA was identified to participate in the regulation of cell proliferation and cell apoptosis, MSC osteogenic differentiation, lipid metabolism and other processes.

Preliminary screening of differentially expressed circulating microRNAs in patients with steroid‑induced osteonecrosis of the femoral head

microRNAs have been shown to be stable and detectable in circulating blood, and circulating microRNAs are specifically expressed in numerous diseases. However, to date, the association between microRNAs and osteonecrosis of the femoral head (ONFH) has remained elusive. It was hypothesized that specific microRNAs in the serum of ONFH patients may participate in the pathogenesis of ONFH. In the present study, therefore, the ONFH‑specific serum microRNAs were screened using deep sequencing technology. Peripheral blood serum was collected from three steroid‑induced ONFH patients with systemic lupus erythematosus (SLE), three SLE controls and three healthy controls, respectively. Total RNA was extracted from the serum and a microRNA cDNA library was built. High‑throughput sequencing was then used to sequence the serum microRNAs of the samples and screen differentially expressed serum microRNAs in patients with steroid‑induced ONFH. 27 differentially expressed microRNAs from ONFH serum were selected; of these, 15 microRNAs were over‑expressed and 12 were under‑expressed compared with SLE controls and healthy controls. The present study showed that abnormally expressed microRNAs existed in the serum of ONFH patients and therefore have the potential to be diagnostic markers.

Outcome of total knee arthroplasty combined patelloplasty for end-stage type A hemophilic arthropathy

The aim of this study was to retrospectively evaluate the outcome of total knee arthroplasty for end-stage hemophilic arthropathy, based on effectiveness of operation, the specificity of surgical technique, the complications of TKA operation and the strategy of handling of patella. Nineteen patients (25 knees) with type A hemophilic arthropathy were treated with TKA from June 2003 to February 2010. Average patella thickness was 16.3±0.4mm and all patellas were treated by patelloplasty. The patient followed up data was recorded, which included the information of hospital for special surgery knee score(HSS), range of motion(ROM), post-operative complication, and anterior knee pain. The patients were followed for an average post-operative period of 41months (10 to 78months). The mean preoperative HSS score was 51 (31 to 64). Post-operative HSS score was 91 (75 to 110) when followed-up. ROM was modified to 82 degree (60 to 105), compared with 55 degree (5 to 110) preoperatively. Thirteen patients with flexion contracture were corrected from 19 degree (0 to 45) to 2.7 degree (0 to 10). Four patients complained mild but endurable anterior knee pain. The study concludes that TKA is an effective treatment for end-stage hemophilic arthropathy of knee joint, providing good clinical outcome and improving quality of life. Patella of hemophiliac is relatively thin and osteoporotic. Patelloplasty is useful technique for handling of patella during TKA procedure for hemophiliac, with improved knee function, low and acceptable anterior knee pain rate, low reoperation rate.

Perioperative Period of a Hemophilia‐related Osteoarthropathy Therapeutic Regimen and Analysis of Complications

To investigate the effectiveness of our departments therapeutic regimen and treatment of complications during the perioperative period of hemophilia‐related osteoarthropathy.

Thirty-day Postoperative Complications following Primary Total Knee Arthroplasty: A Retrospective Study of Incidence and Risk Factors at a Single Center in China

Background: Total knee arthroplasty (TKA) may be associated with serious complications that adversely affect outcomes and increase the likelihood of disability. However, few studies with sufficient sample size have reported postoperative complications following TKA among Chinese patients. This study aimed to evaluate complications of TKA within 30 postoperative days and to identify the related risk factors. Methods: A retrospective complication-based analysis of TKA using the arthroplasty registry between 2008 and 2013 was performed by summarizing complications of TKA within 30 postoperative days. Multivariate logistic regression was used to identify the predicting factors for complications 30 days after operation. Results: A total of 1542 patients underwent 2254 primary TKA between January 2008 and December 2013. A total of 137 complications occurred within 30 days after operation with an incidence rate of 6.1%. The incidence rate of major systemic complications within postoperative 30 days was 2.3%, with cardiovascular and respiratory complications as the most common complications. The incidence rates of deep venous thrombosis (DVT) and local complications were 2.4% and 1.0%, respectively. The 30-day postoperative mortality rate was 0.1% (3/2254). Multivariate logistic regression analyses identified body mass index (BMI) of ≥30.0 kg/m2 (odds ratio [OR]: 1.47) and age ≥80 years (OR: 1.87) as significant risk factors for postoperative systemic complications. A BMI of ≥30.0 kg/m2 was a significant risk factor for DVT (OR: 2.86) and other complications (OR: 2.11). The comorbidity of diabetes was a risk factor for postoperative mortality (OR: 19.20). Conclusions: This study highlighted complications with cardiac and respiratory origins as the most common complications within 30 postoperative days following primary TKA. The BMI of ≥30.0 kg/m2 and age ≥80 years were significant risk factors for 30-day postoperative complications.

Efficacy of a modified coagulation factor substitution for total hip arthroplasty in patients with end-stage haemophilic arthropathy.

Total hip arthroplasty (THA) is an effective treatment for end-stage haemophilic arthropathy, and substitution therapy plays a key role in the success of THA. The aim of this study was to evaluate the efficacy of a modified coagulation factor substitution regime in THA. Nineteen haemophiliac patients (20 hips) who received primary cementless THA were enrolled. Based on World Federation of Haemophilia (WFH) guideline, a modified coagulation factor substitution regime was adopted. Blood loss, implant survival rates and complications were reviewed, retrospectively. The mean age at surgery was 29.7 years (15–49 years) and the mean follow-up period was 91 months (43–151 months). Mean total blood loss, external blood loss and hidden blood loss were 3543 (1494–7576), 1435 (600–3440), and 2110 ml (534–4402), respectively. Mean intraoperative blood loss and postoperative drainage were 715 (300–2000) and 713 ml (200–2950), respectively. Mean red blood cell transfusion used was 5 U (0–14). All prostheses were found to have bony ingrowth. One patient had hematoma formation in the thigh and one with a lower limb deep vein thrombosis, postoperatively. Other complications included one skin ulcer, one femur splitting fracture, and one transient neuropraxia. Intraoperative blood loss and wound drainage, in our study, were similar to that in haemophiliac patients and nonhaemophilic patients in literature. This supports the efficacy of the modified coagulation factor substitution strategy in our study.

The Effect of Previous Coronary Artery Revascularization on the Adverse Cardiac Events Ninety days After Total Joint Arthroplasty

BACKGROUND Although coronary artery revascularization therapies are effective for treating coronary artery disease (CAD), these patients may be more susceptible to adverse cardiac events during later non-cardiac surgeries. The purpose of this study is to evaluate post-operative 90-day complications of total joint arthroplasty (TJA) in CAD patients with a history of CAD and to study the risk factors for cardiac complications. METHODS We performed a retrospective analysis of TJA patients between 2005 and 2015 at our institute by summarizing the history of CAD, cardiac revascularization, and cardiac complications within 90 days after the operation. Multivariate logistic regression was performed to identify the factors that predicted cardiac complications within 90 days after the operation. RESULTS A total of 4414 patients were included; of these, 64 underwent cardiac revascularization and 201 CAD patients underwent medical therapy other than revascularization. All the revascularization had history of myocardial infarction (MI). The rate of cardiac complications within 90 days for the CAD with revascularization was 18.7%, 18.4% for the CAD without revascularization, and 2.0% for the non-CAD group. A history of CAD and revascularization, bilateral TJA, general anesthesia, body mass index ≥30 kg/m2, and history of MI were associated with a higher risk of cardiac complications. Patients who underwent TJA within 2 years after cardiac revascularization had a significantly higher cardiac complication rate, and the risk decreased with time. CONCLUSION There is an increased risk of cardiac complications within 90 days after the operation among TJA patients with a history of CAD. Revascularization cannot significantly reduce the risk of cardiac complications after TJA for CAD patients. However, the risk decreased as the interval between revascularization and TJA increased.