There is considerable discordance in the curve progression of adolescent idiopathic scoliosis (AIS) patients between monozygotic (MZ) twins, indicating that nongenetic factors must be involved in the curve progression of AIS patients. Epigenetic processes may constitute one of these factors and have not yet been investigated in relation to curve progression in AIS patients. The genome and methylome of peripheral monocytes were compared between MZ twins discordant for curve progression. Sets of differentially methylated sites were validated using the MassARRAY platform of Sequenome on additional samples. In the discovery study, we found evidence suggesting a lack of differences at the genome sequence level and the presence of epigenetic differences related to the curve progression of AIS patients. The top 4 differentially methylated CpG sites associated with curve severity were tested, and only site cg01374129 (CpG site located at chr8:122583383, Hg19) was confirmed in two replication cohorts. The methylation levels of site cg01374129 were significantly lower in the progression group than in the nonprogression group. Cox regression analysis demonstrated that hypo-methylation of site cg01374129 was an independent prognostic factor for curve severity. Site cg01374129 methylation as a marker achieved a sensitivity of 76.4% and a specificity of 85.6% in differentiating between samples from patients with and without curve progression (AUC = 0.827; 95% CI: 0.780 to 0.876). Increased curvature is associated with decreased methylation at site cg01374129. Our results indicate that methylation of site cg01374129 may therefore serve as a promising biomarker in differing between patients with and without curve progression.
Targeted transfection of siRNA to preosteoclasts features the potential of anti-osteoporosis, yet challenge arises from the development of satisfied delivery vehicles. Here, we design a rational core-shell nanoparticle (NP) composed of cationic and responsive core for controlled load and release of small interfering RNA (siRNA) and compatible polyethylene glycol shell modified with alendronate for enhanced circulation and bone-targeted delivery of siRNA. The designed NPs perform well on transfection of an active siRNA (siDcstamp) that interferes Dcstamp mRNA expression, leading to impeded preosteoclast fusion and bone resorption, as well as promoted osteogenesis. In vivo results corroborate the abundant siDcstamp accumulation on bone surfaces and the enhanced trabecular bone mass volume and microstructure in treating osteoporotic OVX mice by rebalancing bone resorption, formation, and vascularization. Our study validates the hypothesis that satisfied transfection of siRNA enables preserved preosteoclasts that regulate bone resorption and formation simultaneously as potential anabolic treatment for osteoporosis.
Postoperative analgesia remains a challenge for orthopedic surgeons. The aim of this meta-analysis is to compare the efficacy of epidural analgesia (EA) and intravenous patient-controlled analgesia (IV-PCA) following major spine surgery. We searched electronic databases, including the PubMed, EMBASE, Ovid and Cochrane databases, for randomized controlled trials (RCTs) published before June 2016. The quality of the included trials was assessed using the Cochrane risk-of-bias tool. Random effects models were used to estimate the standardized mean differences (SMDs) and relative risks (RRs), with the corresponding 95% confidence intervals (CI). Subgroup analyses stratified by the type of epidural-infused medication and epidural delivery were also performed. A total of 17 trials matched the inclusion criteria and were chosen for the following meta-analysis. Overall, EA provided significantly superior analgesia, higher patient satisfaction and decreased overall opioid consumption compared with IV-PCA following major spine surgery. Additionally, no differences were found in the side effects associated with these two methods of analgesia. Egger’s and Begg’s tests showed no significant publication bias. We suggest that EA is superior to IV-PCA for pain management after major spine surgery. More large-scale, high-quality trials are needed to verify these findings.
OBJECTIVE: Surgical management of scoliosis curves between 70° and 100° remains controversial. The authors designed this randomized controlled trial to validate the efficacy of intraoperative halo-femoral traction (IOHFT) in patients with adolescent idiopathic scoliosis (AIS), Cobb angles between 70° and 100°, and flexibility < 35%. METHODS: The authors prospectively recruited and randomized 29 patients with severe AIS scheduled for posterior surgery into a traction group or control (nontraction) group. The primary outcome measures were operative time, blood loss, and length of hospital stay. Secondary outcomes included degree of spine deformity correction, traction-related complications, and health-related quality of life. RESULTS: In the traction group, the average preoperative Cobb angle was 83.2°, with an average 20.6% flexibility. The average postoperative Cobb angle was 16.1° and the major curve was 18.3° at the final follow-up. In the control group, the average preoperative major curve was 80.3° with 22.8% flexibility. The average postoperative Cobb angle was 16.1° and the major curve was 18.1° at the final follow-up. The operative duration was 325.7 minutes for the traction group and 385.4 minutes for the control group (p = 0.018). Compared with the control group, the traction group had a 29.5% reduction in intraoperative blood loss and a significantly lower rate of blood transfusion (13.3% vs 50.0%, p = 0.033). There were no neurological complications in either group. One patient in the traction group had a superficial infection at the traction site. CONCLUSIONS: Use of IOHFT contributed to significant reductions in operative time and blood transfusion requirements, with no added morbidity. It is an effective and safe method to assist correction of AIS curves between 70° and 100° and flexibility < 35%.