Biomimetic composite hydrogel promotes new bone formation in rat bone defects through regulation of miR-19b-3p/WWP1 axis by loaded extracellular vesicles.

OBJECTIVE: This study aims to investigate the mechanism by which biomimetic composite hydrogels loaded with bone marrow mesenchymal stem cells (BMSCs) derived microRNA-19b-3p/WWP1 axis through extracellular vesicles (EVs) affect the new bone formation in rat bone defects. METHODS: First, synthesize the bionic composite hydrogel Gel-OCS/MBGN. Characterize it through field-emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), and FTIR. Then, conduct performance tests such as rheology, dynamic mechanical analysis, in vitro mineralization, and degradation. Rat BMSCs were selected for in vitro cell experiments, and EVs derived from BMSCs were obtained by differential centrifugation. The EVs were loaded onto Gel-OCS/MBGN to obtain Gel-OCS/MBGN@EVs hydrogel. Cell viability and proliferation were detected by live/dead cell staining and CCK-8 assay, respectively. ALP and ARS staining was used to evaluate the osteogenic differentiation of BMSCs. Differential gene expression analysis of osteogenic differentiation was performed using high-throughput sequencing. TargetScan database predicted the binding site between miR-19b-3p and WWP1, and a dual-luciferase reporter assay was performed to confirm the targeting binding site. A rat bone defect model was established, and new bone formation was evaluated by Micro-CT, H&E staining, and Masson's trichrome staining. Immunofluorescence staining and immunohistochemistry were used to detect the expression levels of osteogenic-related factors in rat BMSCs. RT-qPCR and Western blot were used to detect the expression levels of genes and proteins in tissues and cells. RESULT: Gel-OCS/MBGN was successfully constructed and loaded with EVs, resulting in Gel-OCS/MBGN@EVs. The in vitro drug release experiment results show that Gel-OCS/MBGN could sustainably release EVs. Further experiments have shown that Gel-OCS/MBGN@EVs could significantly promote the differentiation of BMSCs into osteoblasts. Experiments have shown that WWP1 is a key factor in osteogenic differentiation and is regulated by miR-19b-3p. EVs promote osteogenic differentiation by suppressing WWP1 expression through the transmission of miR-19b-3p. In vivo animal experiments have demonstrated that Gel-OCS/MBGN@EVs significantly promote bone repair in rats with bone defects by regulating the miR-19b-3p/WWP1 signaling axis. CONCLUSION: Functional Gel-OCS/MBGN@EVs were obtained by constructing Gel-OCS/MBGN and loading EVs onto it. EVs could deliver miR-19b-3p to BMSCs, inhibit the expression of WWP1, and promote the osteogenic differentiation of BMSCs, ultimately promoting bone regeneration in rats with bone defects.

Relationship between knee osteophytes and calcitonin gene-related peptide concentrations of serum and synovial fluid in knee of osteoarthritis.

To explore the relationship between knee osteophytes of osteoarthritic knee and calcitonin gene-related peptide (CGRP) concentrations of serum and synovial fluid (SF). 65 patients with knee medial compartment osteoarthritis (OA) were recruited and examined with weight-bearing radiographs of the entire lower limb. The concentrations of CGRP in serum/SF were also detected in surgery. The relationship between the concentrations of CGRP in serum/SF and osteophyte scores were detected with Spearman rank correlation coefficient. CGRP concentrations in serum and SF were significantly correlated with osteophyte score of overall knee respectively (R = 0.462, P < .001; R = 0.435, P < .001). In addition, a correlation tended to be observed about the relationship between CGRP concentrations in serum and SF and osteophyte scores of medial compartment (R = 0.426, P < .001; R = 0.363, P = .003), and osteophyte scores of lateral compartment (R = 0.429, P < .001; R = 0.444, P < .001). In this study, the relationship between CGRP in serum/SF and knee osteophyte scores in different subregions were explored, which showed significant positive correlations, that possibly reflecting the contribution of CGRP influencing osteophyte formation. Positive correlations between osteophyte scores and CGRP suggest that CGRP promote the growth of osteophyte formation. It has the potential to be selected as a biomarker for the assessment of severity in knee OA patients and predict the progression of knee OA. It also provides a potential therapeutic target to delay the progression and relieve the symptom of OA.

Mechanism and influencing factors of proximal fibular osteotomy for treatment of medial compartment knee osteoarthritis: A prospective study.

Objectives This study was performed to explore the mechanism of proximal fibular osteotomy (PFO) for treatment of medial compartment knee osteoarthritis (OA) and evaluate the relevant factors influencing the treatment outcome. Methods Fifty-two patients with medial compartment knee OA with varus deformities were prospectively selected. Radiographs were obtained preoperatively and postoperatively. Knee function and OA severity were evaluated using the Hospital for Special Surgery (HSS) knee score and the Kellgren-Lawrence (KL) score. Multivariable linear regression models were used to examine associations between increases in the HSS score and selected factors influencing knee OA. Results Sixty-seven knee joints of 45 patients undergoing PFO were included. The HSS scores were significantly better at the final follow-up than preoperatively. Regression analysis identified five factors influencing changes in the HSS score: the change in the vertical distance between the fibular head and tibial plateau, the KL score for tibiofibular joint arthritis, the body mass index, the inclination of the tibiofibular joint, and the preoperative HSS score. Conclusions PFO is a simple and effective procedure for medial compartment knee OA. Greater distal displacement of the fibular head suggests greater range of motion of the tibiofibular joint and more evident improvement of postoperative OA symptoms.

Proximal fibular osteotomy to treat medial compartment knee osteoarthritis: Preoperational factors for short-term prognosis.

OBJECTIVE: The purpose of this study was to determine the association between preoperational factors and patients' short-term outcome after proximal fibular osteotomy (PFO) and to provide a basis for detailed surgical indication and patient selection. METHODS: This was a retrospective study of patients undergoing PFO between January 2015 and December 2015. Preoperational clinical data including gender, age, duration of disease, visual analogue score (VAS) and American Knee Society (KSS) score were collected. The radiological factors including hip-knee-ankle angle (HKA angle), condyle-plateau angle (CP angle), Kellgren and Lawrence grade (KL grade), joint space width of both compartments and settlement value were also considered. Patients were followed for at 12 months postoperatively. Both clinical and functional KSS scores were obtained. The outcome of interest was divided into clinical outcome and functional outcome. For each, two criteria were defined: satisfaction and significant improvement. Satisfaction is characterized by a KSS clinical or functional score over 70 points (excellent and good results); significant improvement refers to an increase in KSS scores of more than 15 points. Bivariate logistic regression for the association between preoperational factors and outcomes of interest was performed. Multivariable logistic regression analyses were used to detect the independent factors affecting the outcomes. RESULTS: A total of 84 patients and 111 knees were followed-up. Of these, 17 knees were from males and 94 were from females. The average age was 59.45±8.82 years. The average preoperational VAS score, KSS clinical and functional score were 7.08±1.41 points, 49.14±10.95 points and 44.97±17.71 points, respectively. According to KL grading, there were 17 knees of grade 2, 47 knees of grade 3, and 47 knees of grade 4. In clinical outcomes, there were 51 knees in the satisfaction group and 77 knees in the significant improvement group. In functional outcomes, 43 knees were in the satisfaction group and 76 knees in the significant improvement group. KSS clinical score (OR = 1.134, 95%CI = 1.067-1.205, P = 0.000) was the independent factor associated with clinical satisfaction. Age (OR = 1.072, 95%CI = 1.000-1.150, P = 0.048), VAS score (OR = 1.679, 95%CI = 1.041-2.706, P = 0.033), KSS clinical (OR = 1.072, 95%CI = 1.005-1.144, P = 0.034) and functional (OR = 1.100, 95%CI = 1.044-1.159, P = 0.000) score, HKA angle (OR = 1.345, 95%CI = 1.119-1.617, P = 0.002) and settlement value (OR = 7.540, 95%CI = 1.307-43.484, P = 0.024) were the independent factors associated with functional satisfaction. KSS clinical (OR = 0.905, 95%CI = 0.850-0.963, P = 0.002) score, CP angle (OR = 0.760, 95%CI = 0.593-0.973, P = 0.030) and medial joint space width (OR = 0.001, 95%CI = 0.000-0.107, P = 0.003) were the independent factors associated with significant clinical improvement; VAS score (OR = 1.582, 95%CI = 1.042-2.402, P = 0.031), KSS functional (OR = 0.888, 95%CI = 0.838-0.942, P = 0.000) score, HKA angle (OR = 1.292, 95%CI = 1.101-1.518, P = 0.002) and settlement value (OR = 9.990, 95%CI = 1.485-67.197, P = 0.018) were the independent factors associated with significant functional improvement. CONCLUSIONS: The independent factors affecting postoperative clinical outcome after PFO were KSS clinical score, CP angle and medial joint space width. In addition, the independent factors that influenced functional outcome included age, VAS score, KSS score, HKA angle and settlement value. As objective radiological evidence, HKA angle and settlement value could be used as an important basis for patient selection for PFO.

Incidence and risk factors for surgical site infection following open reduction and internal fixation of adult tibial plateau fractures.

PURPOSE: The aim of this study was to identify independent risk factors for surgical site infection (SSI) and quantify the incidence of SSI in tibial plateau fractures after open reduction and internal fixation (ORIF). METHODS: This retrospective study was performed at a level 1 trauma centre from January 2015 to June 2016. Data of adult patients with tibial plateau fractures treated by ORIF were extracted from the electronic medical records. A total of 370 patients were collected. We reviewed the patients' demographics, characteristics of fracture, treatment-related variables, and indexes of laboratory examination. Multivariate logistic analysis models were performed respectively to determine independent predictors of SSI. RESULTS: Twenty-one patients developed SSI in this study. The overall incidence of SSI after ORIF of tibial fracture was 5.7%, with six (1.6%) for deep infection and 15 (4.1%) for superficial SSI. Independent predictors of SSI identified by multivariate analysis were open fracture (odds ratio=4.53; 95% CI=1.64-15.26; p=0.000), intra-operative duration (odds ratio=2.72; 95% CI=1.17-6.29; p=0.020), and smoking (odds ratio=4.79; 95% CI=1.46-15.73; p=0.010). CONCLUSIONS: The SSI incidence was high (5.7%) after surgical tibial plateau fractures by ORIF and open fracture, operative time, and smoking were identified as independent related risk factors. Therefore, we recommend that a smoking cessation program is introduced immediately at the time of admission to hospital. More reasonable management strategies on open injury should be utilized to reduce the SSI rate.

Local application of an ibandronate/collagen sponge improves femoral fracture healing in ovariectomized rats.

Non-union is a major clinical problem in the healing of fractures, especially in patients with osteoporosis. The systemic administration of drugs is time consuming and large doses are demanding and act slowly, whereas local release acts rapidly, increases the quality and quantity of the bone tissue. We hypothesize that local delivery demonstrates better therapeutic effects on an osteoporotic fracture. The aim of this paper is to investigate the effect of the local application of ibandronate loaded with a collagen sponge on regulating bone formation and remodeling in an osteoporotic rat model of fracture healing. We found that the local delivery of ibandronate exhibited excellent effects on improving the bone microarchitecture and suppressed effects on bone remodeling. At 4 weeks, more callus formation and improvement of mechanical character and microstructure were observed in a local delivery via µCT, mechanical test, histological research and serum analysis. The suppression of bone remodeling was compared with a systemic treatment at 12 weeks, and the structural mechanical properties and microarchitecture were also improved with local delivery. This research identifies an earlier, safer and integrated approach for local delivery of ibandronate with collagen and provides a better strategy for the treatment of osteoporotic fracture in rats.

Levodopa attenuates cellular apoptosis in steroid-associated necrosis of the femoral head.

The present study aimed to investigate the effects of levodopa (LEV) on cellular apoptosis in a rabbit model of steroid-associated necrosis of the femoral head (SANFH). A total of 44 healthy adult Chinese rabbits were randomly divided into three groups: Group A (n=15), administered a combination of lipopolysaccharide and hormone to establish the SANFH animal model; group B (n=15), SANFH animal model as in group A orally administered LEV (0.4 g/kg/day) on the day of injection; and group C (n=14), the control group. On the 6th and 8th week of modeling, seven rabbits from each group were sacrificed to harvest bilateral femoral head specimens for hematoxylin and eosin staining and apoptosis detection by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay analysis, as well as for observing pathological changes and analyzing cellular apoptosis. Eight weeks after modeling, the serum insulin-like growth factor (IGF)-1 levels of the three groups were measured. The empty lacunae rate and apoptosis index of bone cells in the treatment group were significantly lower than that of the model group (P<0.01). Eight weeks after treatment, the serum levels of IGF-1 were significantly higher than that of the model group (P<0.01). These findings suggested that LEV was able to reduce steroid-induced bone cellular apoptosis, reduce the occurrence of necrosis of the femoral head and, through in vivo metabolism, it may promote the synthesis and release of IGF-1, which could be one of its biological pathways to prevent and treat SANFH.

Meta-analysis of two surgical approaches for calcaneal fractures: sinus tarsi versus extensile lateral approach.

BACKGROUND: There remains a controversy between extensile lateral approach and sinus tarsi approach (STA) to treat calcaneal fractures. The aim of this study is to evaluate the medium- and long-term outcomes of the STA versus extensile lateral approach in terms of intraoperative variables, quality of alignment on a lateral radiograph incidence of wound healing complication, visual analogue scale and American Orthopaedic Foot and Ankle Society for the treatment of calcaneal fractures. METHODS: Relevant original studies were searched in PubMed, Medline and Embase and Chinese National Knowledge Infrastructure (January 1990 and November 2015). Studies included in this meta-analysis had to compare the effectiveness or complications and provide sufficient data of interest. The patients treated by both methods were similar statistically in age, gender or injury mechanism. The Stata 11.0 was used to analyse all data. RESULTS: Eight studies involving 564 participants were included. STA was associated with decreased incidence of overall complications (odds ratio: 0.14; 95% confidence interval (CI): 0.05-0.38) and wound healing complications (odds ratio: 0.16; 95% CI: 0.06-0.41) and lower visual analogue scale score (standardized mean difference: -1.28; 95% CI: -2.27 to -0.29). However, there were no significant differences in other adverse events including the quality of anatomical reduction and the excellent and good rate according to the American Orthopaedic Foot and Ankle Society. CONCLUSION: The existing evidence supports STA to be a better approach for treating calcaneal fractures, and this might aid in the management of this injury.

Risk factors for postoperative delirium following hip fracture repair in elderly patients: a systematic review and meta-analysis.

BACKGROUND: No formal systematic review or meta-analysis was performed up to now to summarize the risk factors of delirium after hip surgery. AIMS: The present study aimed to quantitatively and comprehensively conclude the risk factors of delirium after hip surgery in elderly patients. METHODS: A search was applied to CNKI, Embase, Medline, and Cochrane central database (all up to August 2015). All studies assessing the risk factors of delirium after hip surgery in elderly patients without language restriction were reviewed, and qualities of included studies were assessed using the Newcastle-Ottawa Scale. Data were pooled and a meta-analysis was completed. RESULTS: A total of 24 studies were selected, which altogether included 5364 patients with hip fracture. One thousand and ninety of them were cases of delirium occurred after surgery, suggesting the accumulated incidence of 24.0 %. Results of meta-analyses showed that elderly patients with preoperative cognitive impairment [odds ratio (OR) 3.21, 95 % confidence interval (CI) 2.26-4.56), advanced age (standardized mean difference 0.50, 95 % CI 0.33-0.67), living in an institution (OR 2.94; 95 % CI 1.65-5.23), heart failure (OR 2.46; 95 % CI 1.72-3.53), total hip arthroplasty (OR 2.21; 95 % CI 1.16-4.22), multiple comorbidities (OR 1.37; 95 % CI 1.12-1.68) and morphine usage (OR 3.01; 95 % CI 1.30-6.94) were more likely to sustain delirium after hip surgery. Females were less likely to develop delirium after hip surgery (OR 0.83; 95 % CI 0.70-0.98). CONCLUSIONS: Related prophylaxis strategies should be implemented in elderly patients involved with above-mentioned risk factors to prevent delirium after hip surgery.

Radiographic measures of settlement phenomenon in patients with medial compartment knee osteoarthritis.

In this study, we proposed for the first time the theory of "settlement phenomenon" in tibial plateau and carefully explored the role of settlement of tibial plateau in the occurrence and progression of medial compartment knee osteoarthritis (OA) through investigating the relationship between the degree of settlement and the radiographic severity of OA. One hundred twenty-seven patients with knee medial compartment OA were recruited and examined with weight-bearing radiographs of the entire lower limb. The radiographic severity of OA was evaluated using the Kellgren and Lawrence (KL) grading methods. The settlement value, hip-knee-ankle angle, minimum medial joint space width, and condylar plateau angle were measured at the same time. The settlement value increases with the upgrading of KL grades (r = 0.352, P < 0.001) and is significantly correlated with the changes of hip-knee-ankle angle, minimum medial joint space width, and condylar plateau angle (r = -0.527, -0.271, and 0.415, P < 0.001, respectively). These results suggest that the settlement of tibial plateau could be an evaluable indicator of medial compartment knee OA and be used in the early diagnosis and progression of OA.

[Clinical features and proportion analysis of adult hip fractures at 11 hospitals in Southwest China from 2010 to 2011].

OBJECTIVE: To analyze the clinical feature and constituent ratio of adult hip fractures in Southwest China. METHODS: The data of adult inpatients and outpatients with hip fractures treated between January 2010 and December 2011 in 11 hospitals of the Southwest China were collected and analyzed. The data includes gender, age, age distribution and fracture pattern according to AO classification. RESULTS: There were a total of 2,833 adult hip fractures, including 1,340 (47.30%) males and 1,493 (52.70%) females, with a male-to-female incidence ratio of 1: 1.11 and a mean age of (66±18) years. The highest frequency of hip fractures was seen in the 71 to 85 years age group (42.18%, 1,195/2,833). There were 844 fractures (29.79%) in the young and middle-aged group (16-<60 years) and 1 898 fractures (70.21%) in the geriatric group (≥60 years). Men had a higher rate than women (men: 577 fractures, 68.4%) in the young and middle-aged group, while women had a higher rate than men (women: 1,226 fractures, 61.64%) in the geriatric group, with a significant difference in the sex distribution between the two groups (χ2=214.001, P<0.01). The proportion of intertrochanteric fracture (type 31-A), femoral neck (type 31-B) and femoral head fracture (type 31-C) was 46.59%, 49.74% and 3.67% respectively. The highest frequency of the sub-type in each fracture type was type 31-A2, type 31-B2 and type 31-C2. CONCLUSIONS: Women have a higher rate than men in Southwest China. Geriatric patients are more than the young and middle-aged patients. The femoral neck fractures, intertrochanteric fractures and femoral head fractures are in descending orders according to the proportion of the three different hip fractures.

Spondin 1 promotes metastatic progression through Fak and Src dependent pathway in human osteosarcoma.

Spondin 1 (SPON1) is cell adhesion protein that involved in attachment of sensory neuron cells and outgrowth of neurites. Its cellular functions and related mechanisms in cancers, however, remain largely unexplored. In this study, we first identified that SPON1 acts a critical factor in the metastatic progression of osteosarcoma through analysis of a GEO dataset. Then we demonstrated that SPON1 was significantly up-regulated in 72 osteosarcoma specimens compared with benign osteochondroma samples and elevated SPON1 was positively correlated with MMP9 expression. Knockdown of SPON1 expression in two metastatic osteosarcoma cell lines, HKOS and KRIB, dramatically suppressed cell migration and invasion. Treatment with recombinant SPON1 protein in two non-metastatic osteosarcoma cell lines, HOS and U2OS, significantly promoted cell migration and invasion in vitro. Meanwhile, suppression of SPON1 in KHOS cells resulted in decreased pulmonary metastasis in vivo. Mechanistically, we determined that the effects of SPON1 on osteosarcoma cell motility were primarily mediated through Fak and Src dependent pathway. Taken together, our study provides evidence of the contributions of SPON1 and the Fak and Src signaling to the progression of osteosarcoma and suggests that this axis may represent a potential therapeutic target for osteosarcoma.

Calcitonin gene-related peptide can be selected as a predictive biomarker on progression and prognosis of knee osteoarthritis.

PURPOSE: The purpose of this study was to examine calcitonin gene-related peptide (CGRP) concentrations in serum and synovial fluid of patients with primary knee osteoarthritis (OA) and healthy controls and to explore their relationship with clinical and radiographic severity of OA. METHODS: Sixty-five patients with primary knee OA and 21 healthy controls were recruited. CGRP concentrations in the serum and synovial fluid were measured using enzyme-linked immunosorbent assays. The radiographic severity of OA was evaluated using the Kellgren and Lawrence (KL) classification. The Western Ontario and McMaster University Osteoarthritis Index (WOMAC) was used to assess pain, stiffness and physical function. RESULTS: Serum and synovial fluid CGRP concentrations tended to be higher with the increase in KL grades (r = 0.565 and r = 0.441, P < 0.001, respectively), and were significantly positively correlated with KL grades, total WOMAC score and each subscale (pain, stiffness and physical function). CONCLUSIONS: The result demonstrated that CGRP in serum and synovial fluid was related to progressive joint damage in knee OA. CGRP can be selected as a biomarker for monitoring disease severity and could be a predictive role on prognosis and progression of knee OA.

Management of the mid-shaft clavicle fractures using plate fixation versus intramedullary fixation: an updated meta-analysis.

PURPOSE: This meta-analysis of randomised controlled trials (RCTs) aimed to investigate the comparative outcomes between plate fixation and intramedullary fixation for management of mid-shaft clavicle fractures. METHODS: Relevant original studies were searched in electronic databases of PubMed, Medline, Embase and CNKI (all through October 2014). RCTs that investigated the effectiveness or complications between both groups and provided sufficient data of interest were included in this meta-analysis. RESULTS: Five RCTs fulfilled inclusion and exclusion criteria and were included in this meta-analysis, with 128 participants in a plate fixation (PF) group and 157 in an intramedullary fixation (IF) group. Patients were followed up for at least one year in all the studies. Compared to PFs, IF is a better alternative for treatment of MSCFs than PF, with a reduced surgery time, a shorter incision, rapid union time, better shoulder function at one year and fewer complications such as infection, symptomatic hardware and hypertrophic scar. In other aspects such as complications of implant failure, refracture and nonunion, both techniques were comparable. CONCLUSIONS: If the surgery is indicated, intramedullary fixation has more advantages than plate fixation for treatment of mid-shaft clavicular fracture. This definitive conclusion could aid surgeons in making evidence-based decisions when selecting an optimal fixation pattern.

One-stage partial vertebrectomy, titanium mesh implantation and pedicle screw fixation in the treatment of thoracolumbar burst fractures through a posterior approach.

OBJECTIVE: To analyze the clinical results of a partial vertebrectomy with titanium mesh implantation and pedicle screw fixation using a posterior approach to reconstruct the spine in the treatment of thoracolumbar burst fractures. METHOD: From January 2006 to August 2008, 20 patients with severe thoracolumbar fractures were treated.For vertebral bodies associated with one injured intervertebral disk, subtotal vertebrectomy surgery and single-segment fusion were performed. For vertebral bodies with two injured adjacent intervertebral disks, partial vertebrectomy surgery and two-segment fusion were performed. RESULTS: All 20 patients were followed up for 12 to 24 months (average of 18 months). There were no complications such as wound infections, hemopneumothorax or abdominal infections in any of the patients. The neurological status of all of the patients was improved by at least one American Spinal Injury Association grade by the last follow-up. The anterior vertebral body height was an average of 50.77% before surgery, 88.51% after surgery and 87.86% at the last follow up; the sagittal Cobb angle was improved, on average, from 26.15° to 5.39° and was 5.90° at the last follow up. The percentage of spinal stenosis was improved, on average, from 26.07% to 4.93%° and was 6.15% at the last follow up. There were significant differences in the anterior vertebral body height pre- and post-surgery and in the sagittal Cobb angle and the percentage of spinal stenosis (p<0) in all patients. CONCLUSIONS: This surgical procedure is simple and can accomplish decompression, reduction, fixation and fusion of the spine in one stage. This approach could be widely used in orthopedics.

One-stage partial vertebrectomy, titanium mesh implantation and pedicle screw fixation in the treatment of thoracolumbar burst fractures through a posterior approach

OBJECTIVE: To analyze the clinical results of a partial vertebrectomy with titanium mesh implantation and pedicle screw fixation using a posterior approach to reconstruct the spine in the treatment of thoracolumbar burst fractures. METHOD: From January 2006 to August 2008, 20 patients with severe thoracolumbar fractures were treated.For vertebral bodies associated with one injured intervertebral disk, subtotal vertebrectomy surgery and single-segment fusion were performed. For vertebral bodies with two injured adjacent intervertebral disks, partial vertebrectomy surgery and two-segment fusion were performed. RESULTS: All 20 patients were followed up for 12 to 24 months (average of 18 months). There were no complications such as wound infections, hemopneumothorax or abdominal infections in any of the patients. The neurological status of all of the patients was improved by at least one American Spinal Injury Association grade by the last follow-up. The anterior vertebral body height was an average of 50.77% before surgery, 88.51% after surgery and 87.86% at the last follow up; the sagittal Cobb angle was improved, on average, from 26.15° to 5.39° and was 5.90° at the last follow up. The percentage of spinal stenosis was improved, on average, from 26.07% to 4.93%° and was 6.15% at the last follow up. There were significant differences ...

Follistatin-like protein 1: a serum biochemical marker reflecting the severity of joint damage in patients with osteoarthritis.

INTRODUCTION: Follistatin-like protein 1 (FSTL1) is a secreted glycoprotein that has been implicated in arthritis pathogenesis in a mouse model. The aim of this study is to detect FSTL1 expression and to further assess its potential utility as a biomarker of joint damage in osteoarthritis (OA) patients. METHODS: FSTL1 expression was detected by real-time PCR, western blot and immunohistochemistry (IHC) in the synovial tissues (STs) and by IHC in the articular cartilage from OA patients and control trauma patients. The serum and synovial fluid (SF) FSTL1 concentrations were measured by ELISA in OA patients and control individuals. Linear regression analyses were used to assess correlations between the serum FSTL1 levels and the clinical characteristics in OA patients. RESULTS: The FSTL1 mRNA and protein levels were substantially elevated in the STs from OA patients compared with those from control trauma patients. The FSTL1 expression was strong in the cytoplasm of the synovial and capillary endothelial cells of the STs, but weak in the chondrocytes of the articular cartilage from OA patients. Furthermore, the serum and SF FSTL1 concentrations were significantly higher in OA patients than in respective control subjects. Interestingly, the serum and SF FSTL1 levels were markedly higher in female OA patients than in males. Importantly, bivariate regression analysis revealed that the serum FSTL1 levels in female OA patients had significant correlations with Kellgren and Lawrence (KL) grade, joint space narrowing (JSN) and the Western Ontario McMaster and Universities Osteoarthritis (WOMAC) stiffness subscale, an inverse correlation with height, and marginal correlations with the total WOMAC score and the WOMAC function subscale. Multivariate regression analysis revealed that the serum FSTL1 levels correlated independently with KL grade in female OA patients. Bivariate analysis also revealed that the serum FSTL1 levels correlated significantly with age and disease duration, and they correlated marginally with high sensitivity C-reactive protein (hs-CRP) and KL grade in male OA patients. CONCLUSIONS: Increased FSTL1 expression may be a characteristic of OA patients. FSTL1 is a potential serum biomarker that may reflect the severity of joint damage, and further studies are required to evaluate its potential application for monitoring the course of the disease and the efficacy of therapies in OA patients.

MDM4 overexpression contributes to synoviocyte proliferation in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease with features of inflammatory cell infiltration, synovial cell invasive proliferation, and ultimately, irreversible joint destruction. It has been reported that the p53 pathway is involved in RA pathogenesis. MDM4/MDMX is a major negative regulator of p53. To determine whether MDM4 contributes to RA pathogenesis, MDM4 mRNA and protein expression were assessed in fibroblast-like synoviocytes (FLS) by real-time PCR, western blotting, and in synovial tissues by immunohistochemistry. Furthermore, MDM4 was knocked down and overexpressed by lentivirus-mediated expression, and the proliferative capacity of FLS was determined by MTS assay. We found that cultured FLS from RA and osteoarthritis (OA) patients exhibited higher levels of MDM4 mRNA and protein expression than those from trauma controls. MDM4 protein was highly expressed in the synovial lining and sublining cells from both types of arthritis. Finally, MDM4 knockdown inhibited the proliferation of RA FLS by enhancing functional p53 levels while MDM4 overexpression promoted the growth of RA FLS by inhibiting p53 effects. Taken together, our results suggest that the abundant expression of MDM4 in FLS may contribute to the hyperplasia phenotype of RA synovial tissues.

[Total hip surface replacement arthroplasty: report of 31 cases].

OBJECTIVE: To introduce the technique of total hip surface replacement, evaluate the early results and review the factors which affect the results. METHODS: From October 2000 to January 2005, 31 patients (37 hips) with osteonecrosis, osteoarthritis, hip dysplasia, ankylosing spondylitis were treated with the total hip surface replacement. Among them, 15 were male, and 16 were female, with an average age of 42 years (range from 23 - 65 years). All the 31 patients had the indications for hip surface replacement. Standard operation technique which was brought forth by Amstutz and Nelson was employed, and all patients were followed up after operation. RESULTS: Patients were followed up for an average period of 42 months (3 - 51 months). There were no femoral neck fracture, no dislocation, no infection in all patients. Radiolucent line existed around acetabular prosthesis in 1 hip and another hip had been revised because the prosthesis of femoral head was in incorrect situation. The average Harris hip score improved significantly from 30 to 90, and the score was 93 in the latest follow-up. Based on Harris system, 35 hips were excellent, 1 hip good, and 1 hip fail. CONCLUSIONS: The total hip surface replacement is an effective solution for the problem of the patients with osteonecrosis of the femoral head, osteoarthritis, hip dysplasia and ankylosing spondylitis. The short-term results are satisfied.

[Resurfacing arthroplasty for treatment of avascular necrosis of femoral head in young and middle-aged patients].

OBJECTIVE: To investigate the early clinical effect of resurfacing arthroplasty on the treatment of avascular necrosis of the femoral head in the young and middle-aged patients. METHODS: Eleven patients with avascular necrosis of the femoral head in Ficat Stages III -IV (14 hips) were treated by femoral head resurfacing operations. Of 11 cases, there were 7 males and 4 females. With an age range of 35 to 49 years. While 13 patients with avascular necrosis of the femoral head in Ficat Stages III - IV (16 hips) were treated by total hip resurfacing arthroplasty of 13 cases there were 8 males and 5 females. With an age range of 23 to 48 years. The prostheses were improved in light of the anatomic features of the Chinese. RESULTS: These patients treated by femoral head resurfacing operations were followed up for 1 to 5 years. The average Harris hip score was increased from 39 points preoperatively to 91 points postoperatively. These patients treated by total hip resurfacing operations were followed up for 6 to 40 months. The average Harris hip score was increased from 30 points preoperatively to 93 points postoperatively. CONCLUSION: Hip resurfacing operations may be the most effective treatment for avascular necrosis of the femoral head in the young and middle aged patients.