Unraveling IGFBP3-mediated m6A modification in fracture healing.

BACKGROUND: This study investigates the role of IGFBP3-mediated m6A modification in regulating the miR-23a-3p/SMAD5 axis and its impact on fracture healing, aiming to provide insights into potential therapeutic targets. METHODS: Utilizing fracture-related datasets, we identified m6A modification-related mRNA and predicted miR-23a-3p as a regulator of SMAD5. We established a mouse fracture healing model and conducted experiments, including Micro-CT, RT-qPCR, Alizarin Red staining, and Alkaline phosphatase (ALP) staining, to assess gene expression and osteogenic differentiation. RESULTS: IGFBP3 emerged as a crucial player in fracture healing, stabilizing miR-23a-3p through m6A modification, leading to SMAD5 downregulation. This, in turn, inhibited osteogenic differentiation and delayed fracture healing. Inhibition of IGFBP3 partially reversed through SMAD5 inhibition, restoring osteogenic differentiation and fracture healing in vivo. CONCLUSION: The IGFBP3/miR-23a-3p/SMAD5 axis plays a pivotal role in fracture healing, highlighting the relevance of m6A modification. IGFBP3's role in stabilizing miR-23a-3p expression through m6A modification offers a potential therapeutic target for enhancing fracture healing outcomes.

Intraoperative halo-femoral traction during posterior spinal arthrodesis for adolescent idiopathic scoliosis curves between 70° and 100°: a randomized controlled trial.

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%.

MiR-149-3p can improve the osteogenic differentiation of human adipose-derived stem cells via targeting AKT1.

The study aims to investigate the role of microRNA-149-3p (miR-149-3p) in regulating osteogenic differentiation of human adipose-derived stem cells (hADSCs) by targeting v-akt murine thymoma viral oncogene homolog 1 (AKT1). Bioinformatics websites and a dual luciferase reporter assay were used to predict and verify the targeting relationship between miR-149-3p and AKT1. The hADSCs were divided into the blank, negative control (NC), mimic, control siRNA, AKT1 siRNA, and miR-149-3p inhibitors + AKT1 siRNA groups and then subjected to Alizarin Red staining, Alkaline phosphatase (ALP) staining, ALP activity detections, MTT assay, and EdU cell proliferation assay. Gene or protein expression was quantified using quantitative real-time PCR (qRT-PCR) or Western blotting, respectively. The miR-149-3p expression increased gradually and AKT1 expression decreased gradually during osteogenic differentiation of hADSCs. The prediction of bioinformatics websites miRTarBase and TargetScan and the dual luciferase reporter assay indicated that miR-149-3p can directly target AKT1. After hADSCs were transfected with miR-149-3p mimic, AKT1 expression was significantly downregulated. However, transfection with AKT1 siRNA did not have an impact on miR-149-3p in hADSCs. In comparison with the AKT1 siRNA group, the miR-149-3p inhibitors + AKT1 siRNA group showed decreased miR-149-3p expression but increased AKT1 expression. In addition, AKT1 siRNA enhanced the cell viability and proliferation of hADSCs and increased mineral calcium deposition and ALP activity, resulting in higher expression of osteogenic differentiation-related genes, which was reversed by miR-149-3p inhibition. The miR-149-3p can increase the expression of osteogenic differentiation-related genes by targeting AKT1 and thereby enhance the osteogenic differentiation of hADSCs.

Influence of Insurance Status on Curve Magnitude in Adolescent Idiopathic Scoliosis in Mainland China.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To determine whether there is an association between insurance status and curve magnitude in idiopathic scoliosis pediatric patients in mainland China. METHODS: Medical records of patients with adolescent idiopathic scoliosis in 4 tertiary spine centers across China from January 2013 to December 2017 were analyzed. Data was extracted on insurance status, curve magnitude, recommended treatment at presentation, source of referral, and treatment initiated. Additional information was collected for patients requiring corrective surgery, including time from recommendation for surgery to surgery and clinically relevant parameters such as, postoperative complications, and pre-/postoperative Scoliosis Research Society-22 scores were also collected for patients requiring corrective surgery. RESULTS: Of the 1785 patients included, 1032 were Urban Resident Basic Medical Insurance Scheme (URBMS) insured and 753 were New Rural Cooperative Medical Scheme (NRCMS) insured. NRCMS patients presented with a larger major curve than URBMS patients (32.9° ± 15.1° vs 29.3° ± 12.6°, P = .028). For patients having surgery recommended, NRCMS patients presented with a larger mean Cobb angle at the first presentation (57.7° vs 50.9°, P < .0001) and at time of surgery (61.3° vs 52.2°, P < .0001), and experienced a significantly longer time from surgery recommendation to decision for surgery. Complication rates were comparable between the 2 groups, except for pulmonary complications (NRCMS 7.3% vs URBMS 2.8%, P = .04). Postoperatively, patients covered by NRCMS insurance experienced greater overall improvement in health-related quality of life and were less satisfied with the treatments. CONCLUSIONS: This study shows that health insurance may influence the severity of scoliosis on presentation, with implications on early diagnosis and surgery time.

[Bridging system for severe comminuted femoral fracture].

OBJECTIVE: To explore the clinical effect of bridging system in the treatment of severe comminuted femoral fracture. METHODS: From March 2016 to October 2018, 50 patients with severe comminuted femoral fracture including 35 males and 15 females, aged 48 to 72(54.6±8.7) years, were admitted. All cases were comminuted fractures of the femoral shaft, 16 with proximal femur fractures and 7 with distal femur fractures. All cases were all unilateral fractures, 23 on the left and 27 on the right. The time from injury to operation was 5 to 60 (26.7±13.3) hours. The cause of injury was traffic accident, 12 cases with high fall, 35 cases fell and 3 cases fell accidentally. The patients were treated with bridge combined internal fixation system, and the operative effect and fracture healing were analyzed. RESULTS: The operation was successful in all patients. There was no change to other fixed operation. The operation time was (75.8±12.3) min, the amount of bleeding was(356.4±64.8) ml, and there was no serious postoperative complications such as infection, internal fixation displacement, re fracture and nonunion. After 6 to 36 months follow-up, the fracture healing was evaluated by Warden's score. With the extension of observation time, Warden's score gradually increased, and the time of bone healing was(5.5±0.9) months. Harris score and HSS score were used to evaluate the function of hip and knee joint respectively. With the extension of time, Harris score and HSS score increased gradually. Six months after operation, Harris score was 83.5±11.2, HSS score was 79.7±10.5. During the follow-up period, there were no serious complications such as internal fixation displacement, re-fracture, nonunion of fracture and deep vein thrombosis of lower extremity. CONCLUSION: The bridge combined internalfixation system has better safety and effectiveness in the treatment of severe comminuted femoral fracture. As long as the requirements of local anatomy and biomechanics are strictly mastered and the operation risks are fully evaluated in combination with imaging, the better fixation effect can be achieved. The operation has less trauma, fewer complications and simple operation, which is believed to have a wider application potential. Due to the limited sample size and follow-up time, no clinical control was set up, the results of the study still need to be further verified by prospective trials.