Xisheng Weng

MicroRNA-10b promotes nucleus pulposus cell proliferation through RhoC-Akt pathway by targeting HOXD10 in intervetebral disc degeneration.

Aberrant proliferation of nucleus pulposus cell is implicated in the pathogenesis of intervertebral disc degeneration. Recent findings revealed that microRNAs, a class of small noncoding RNAs, could regulate cell proliferation in many pathological conditions. Here, we showed that miR-10b was dramatically upregulated in degenerative nucleus pulposus tissues when compared with nucleus pulposus tissues isolated from patients with idiopathic scoliosis. Moreover, miR-10b levels were associated with disc degeneration grade and downregulation of HOXD10. In cultured nucleus pulposus cells, miR-10b overexpression stimulated cell proliferation with concomitant translational inhibition of HOXD10 whereas restored expression of HOXD10 reversed the mitogenic effect of miR-10b. MiR-10b-mediated downregulation of HOXD10 led to increased RhoC expression and Akt phosphorylation. Either knockdown of RhoC or inhibition of Akt abolished the effect of miR-10b on nucleus pulposus cell proliferation. Taken together, aberrant miR-10b upregulation in intervertebral disc degeneration could contribute to abnormal nucleus pulposus cell proliferation through derepressing the RhoC-Akt pathway by targeting HOXD10. Our study also underscores the potential of miR-10b and the RhoC-Akt pathway as novel therapeutic targets in intervertebral disc degeneration.

A new operative classification of idiopathic scoliosis: a peking union medical college method.

Study Design. A retrospective radiographic study on the type of surgically treated idiopathic scoliosis, with a prospective study on the reliability of the type-related fusion guide. Objectives. To identify and classify surgically treated idiopathic scoliosis, and define its related fusion levels by a new classification system. Summary of Background Data. Some classification methods for idiopathic scoliosis have been suggested. However, poor intraobserver reproducibility and interobserver reliability were experienced in these studies, and were not appropriate for guiding surgical planning. Methods. A total of 427 surgically treated idiopathic scoliosis cases were reviewed. Preoperative and postoperative standing anteroposterior, lateral, and preoperative supine side-bending radiograph were analyzed using the Scoliosis Research Society definition of scoliosis and curve apex. The resulting classification was tested for intraobserver reliability and interobserver reliability, and by 6 surgeons. Apical frequencies were determined for each type, and prospective surgical testing of the new type and its related fusion guide was performed. Results. Three major types and 13 subtypes were identified, of which the Peking Union Medical College type I accounted for 56.62%, type II 42.16%, and type III 1.22%. The interobserver reliability testing was 85% (kappa coefficient 0.832), while intraobserver reproducibility was 91% (kappa coefficient 0.898). Each type had its corresponding fusion levels. A prospective study of 152 cases was performed according to the classification. All of these cases were followed over 18 months, and no postoperative decompensation was noted. Conclusion. The Peking Union Medical College classification of idiopathic scoliosis is one system to combine each type with its corresponding fusion level, and it had much higher interobserver reliability and intraobserver reproducibility than the King system. Further prospectivestudies would help to clarify and expand this system.

The role of preoperative pulmonary function tests in the surgical treatment of scoliosis.

Study Design. A retrospective study on the correlation between preoperative pulmonary function tests, preoperative pulmonary symptoms, and postoperative pulmonary complications. Objective. To evaluate the incidence of immediate postoperative pulmonary complications and their correlation to pulmonary function tests, preoperative pulmonary symptoms, and surgical approaches. Summary of Background Data. The pulmonary function of patients with scoliosis is likely to be abnormal, whereas surgical procedures may lead to further deterioration and postoperative pulmonary complications. Evaluation of the pulmonary symptoms and pulmonary function before surgery is helpful to predict and avoid postoperative pulmonary complications by selecting the appropriate surgical approach. Methods. This study reviewed 298 scoliosis patients (107 male, 191 female) who underwent anterior and/or posterior operation. The mean age of the patients was 16.4 years (range 6–62 years). The average coronal Cobb angle was 73.26° (range 45–141°). Preoperative pulmonary function tests of 115 cases were normal, whereas the other 183 cases were abnormal. Seventeen cases had preoperative pulmonary symptoms and 3 of them had normal preoperative pulmonary function tests. Seventy-nine cases received transthoracic surgery, and 19 cases had postoperative pulmonary complications, including postoperative ventilation support in 6 cases, atelectasis in 4 cases, hydrothorax in 2 cases, pneumothorax in 3 cases, pneumonia in 3 cases, and hypoxemia in 1 case. Of these 19 patients, 12 patients received anterior transthoracic procedure. When the patients with abnormal pulmonary function tests were divided into 3 groups: 1) 60% ≤ forced vital capacity ratio < 80%; 2) 40% ≤ forced vital capacity ratio < 60%; and 3) forced vital capacity ratio < 40%, the incidence of postoperative pulmonary complications were 2.72% (3 out of 110), 7.40% (4 out of 54) and 31.60% (6 out of 19), respectively. Results. There was significant correlation between abnormal preoperative pulmonary function tests and preoperative pulmonary symptoms (P = 0.0086). No significant correlation was found between preoperative pulmonary symptoms and postoperative pulmonary complications (P = 0.5164). There was a trend that the postoperative complications increased with the deterioration of pulmonary function. The correlation between postoperative pulmonary complications and the surgical approach was statistically significant (P = 0.0000); the incidence of postoperative pulmonary complication of transthoracic procedure was 18 times as that of posterior approach. No significant difference was noted regarding ages, preoperative coronal Cobb angles, and preoperative pulmonary function between these 2 groups. There was no significant correlation between preoperative pulmonary symptoms and postoperative complications. Conclusions. The incidence of postoperative pulmonary complications increased with the deterioration of pulmonary function tests. The posterior procedure had a very low incidence of postoperative pulmonary complications, but a transthoracic procedure increased the complications significantly. Preoperative pulmonary symptoms usually predicted abnormal results of pulmonary function tests but had no correlation with postoperative pulmonary complication.

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.

Cemented versus uncemented hemiarthroplasty for femoral neck fractures in elderly patients: a meta-analysis.

Objective Controversy still exists regarding using cemented or uncemented hemiarthroplasty for femoral neck fractures in elderly patients. The aim of this study is to compare the effectiveness and safety of the two surgical techniques in femoral neck fracture patients over 70 years old. Methods We searched PUBMED, EMBASE, Cochrane Library, CNKI and VIP Database from inception to December 2012 for relevant randomized controlled trials (RCTs). Outcomes of interest include postoperative hip function, residue pain, complication rates, mortality, reoperation rate, operation time and intraoperative blood loss. Odds ratios (OR) and weighted mean differences (WMD) from each trial were pooled using random-effects model or fixed-effects model given on the heterogeneity of the included studies. Results 7 RCTs involving 1,125 patients (1,125 hips) were eligible for meta-analysis. Our results demonstrate that cemented hemiarthroplasty is associated with better postoperative hip function (OR = 0.48, 95% CI, 0.31–0.76; P = 0.002), lower residual pain (OR = 0.43, 95%CI, 0.29–0.64; P<0.0001), less implant-related complications (OR = 0.15, 95%CI, 0.09–0.26; P<0.00001) and longer operation time (WMD = 7.43 min, 95% CI, 5.37–9.49 min; P<0.00001). No significant difference was observed between the two groups in mortality, cardiovascular and cerebrovascular complications, local complications, general complications, reoperation rate and intraoperative blood loss. Conclusions Compared with uncemented hemiarthroplasty, the existing evidence indicates that cemented hemiarthroplasty can achieve better hip function, lower residual pain and less implant-related complications with no increased risk of mortality, cardiovascular and cerebrovascular complications, general complications, local complications and reoperation rate in treating elderly patients with femoral neck fractures.

Dual Growing Rods Technique for Congenital Scoliosis: More Than 2 Years Outcomes

Study Design. Retrospective study. Objective. To evaluate clinical outcomes of dual growing rod (GR) technique in treating children with congenital scoliosis (CS). Summary of Background Data. Published reports on the dual GR technique results of early-onset scoliosis demonstrate it to be safe and effective. However, the use of GR in congenital spinal deformities is controversial, and there have been no reports on the results and complications of dual GR technique for CS with large series of patients. Methods. During 2004 to 2009, a total of 30 patients with CS underwent dual GR procedures. Of the 159 total procedures conducted within the treatment period, 125 were lengthenings with an average of 4.2 lengthenings per patient. Five patients with severe rigid deformity or kyphosis had an osteotomy at apex vertebra with short segmental fusion. The analysis included age at initial surgery and final fusion (if applicable), number and frequency of lengthenings, and complications. Radiographical evaluation was conducted. Results. The mean scoliosis improved from 72.3° to 34.9° after initial surgery and was 35.2° at the last follow-up or after final fusion. T1–S1 length increased from 25.42 to 29.03 cm after initial surgery and to 33.32 cm at last follow-up or after final fusion with an average T1–S1 length increase of 1.49 cm per year. The space available for lung ratio in patients with thoracic curves improved from 0.84 to 0.96 at the latest follow-up. Three patients reached final fusion. Complications occurred in 7 of the 30 patients, and they had a total of 13 complications. Conclusion. The dual GR technique is safe and effective in the treatment of selected cases of long, complex CS. It maintains correction achieved at initial surgery while allowing spinal growth to continue. And it has an acceptable rate of complications. The osteotomy at the apex vertebra with short segmental fusion of the severe rigid scoliosis or the patients with kyphosis could help to improve the correction and decrease the implant failures, with little influence on the length of the spine.

MicroRNA Expression Profile of Dexamethasone‐Induced Human Bone Marrow‐Derived Mesenchymal Stem Cells During Osteogenic Differentiation

MiRNAs have been identified in various plants and animals where they function in post‐transcriptional regulation. Although studies revealed that dexamethasone play a pivotal role in the osteogenic differentiation of human bone marrow‐derived mesenchymal stem cells (hBMSCs), the identification of specific miRNAs and their regulatory roles in this process remain poorly defined. In this study, microarrays were used to analyze the miRNA expression profile of dexamethasone‐induced hBMSCs derived from three donors, and RT‐PCRs were used to confirm the microarray results. Nine upregulated miRNAs and seven downregulated miRNAs were identified. The putative target genes of these miRNAs were predicted using bioinformatics analysis. Subsequently, we focused our attention on the functional analysis of an upregulated miRNA, miR‐23a. Overexpression of miR‐23a inhibited osteogenic differentiation of hBMSCs at the cellular, mRNA, and protein levels. The results of our study provide an experimental basis for further research on miRNAs functions during osteogenic differentiation of dexamethasone‐induced hBMSCs. J. Cell. Biochem. 115: 1683–1691, 2014.

How to make the best use of intraoperative motor evoked potential monitoring? Experience in 1162 consecutive spinal deformity surgical procedures.

Study Design. A retrospective study of 1162 consecutive patients who underwent spinal deformity surgical procedures at our spine center from January 2010 to December 2013. Objective. To develop and evaluate a protocol of intraoperative motor evoked potential (MEP) monitoring with the warning criteria we had established on the basis of our clinical experiences and the review of previous literature. Summary of Background Data. Though MEPs monitoring have become widely used in spinal deformity surgery, different alarm criteria and response protocol used in different studies compromised their comparability; Furthermore, high false-positive rate of MEP reported by previous studies has become an increasingly prominent problem that will limit its clinical use and development. Methods. The intraoperative monitoring data of 1162 consecutive patients who underwent spinal deformity surgical procedures at our spine center were retrospectively analyzed. Age, sex, diagnosis, preoperative neurological status, intraspinal anomalies, baseline MEP, and MEP change were collected. The protocol with the warning criteria we had established was used. The false-positive rate, false-negative rate, and positive predictive value were calculated. Results. Significant intraoperative changes were seen in the MEP data in 52 (4.4%) of all the cases. In 25 cases among which, significant MEP changes were synchronously and logically associated with high-risk surgical maneuver (pedicle screw insertion, osteotomy, correction, etc.). The false-positive rate of MEP monitoring was 0.26% (3/1140), whereas the sensitivity and specificity of MEP for detection of clinically significant intraoperative cord injury were 100% and 99.7%, respectively. The positive predictive value of a MEP alert in terms of a new postoperative neurological deficit was 83.3%. Conclusion. Our study indicates that the appropriate use of MEP monitoring based on our protocol is able to obtain satisfying sensitivity and specificity and thus provide important information for intraoperative decision making. Level of Evidence: 4

The limited use of a tourniquet during total knee arthroplasty: A randomized controlled trial

BACKGROUND Total knee arthroplasty (TKA) is commonly performed using a tourniquet. However, some studies have reported that several complications were associated with the use of a tourniquet in TKA. In this study we investigate whether the limited use of a tourniquet in TKA would reduce complications and facilitate postoperative recovery. METHODS Sixty patients were randomly divided into two groups (30 cases/group): group A using the tourniquet throughout the surgical procedure, and group B using the tourniquet starting from the cementation to the completion of the procedure. Operation time, total measured blood loss, and incidence of complications were all recorded. RESULTS There was no significant difference in operation time, total measured blood loss, and hemoglobin concentration between the two groups. Incidence of postoperative complications in group B was significantly decreased in comparison to that in group A. The limb circumference at 10 cm above the superior patellar pole or below the inferior patellar pole and the pain score in group B were significantly decreased compared with that in group A at any time point. Range of motion in group B was significantly increased at three and 5 days postoperatively in comparison to that in group A. CONCLUSIONS The limited use of a tourniquet in TKA provides the benefit of decreased limb swelling and knee joint pain while not compromising the operation time or blood loss and recovery. LEVEL OF EVIDENCE Level I (Therapeutic). TRIAL REGISTRATION NUMBER NCT02102581.

Long-term follow-up of cemented fixed-bearing total knee arthroplasty in a Chinese population: a survival analysis of more than 10 years.

The aims of this study were to evaluate the long term clinical outcomes and survival rate of total knee arthroplasty (TKA) in Chinese population and the risk factors for failure. Between 1985 to 2001, 297 patients underwent primary TKAs with cemented fixed bearing platform in our center. Survival rate was 92.7% at 10 years, with reoperation of the implant as the endpoint, and 90.4% at 15 years. Main reasons for failure were infection and aseptic loosening. Clinical evaluation of 96 knees with HSS knee score showed the mean scores increased from 56.58 ± 11.05 preoperatively to 92.29 ± 10.95 postoperatively. RA patients had lower long-term survivorship compared with OA patients. Younger patients had better HSS scores. Patella strategy and posterior-cruciate-ligament (PCL) strategy had no effect on implant survivorship and clinical outcome. In conclusion, this was one of first studies showing valid long-term outcomes of primary TKA in Chinese.