Background How to obtain a small interfering RNA (siRNA) vector has become a moot point in recent years. Exosomes (Exo) show advantages of long survival time in vivo, high transmission efficiency, and easy penetration across the blood-spinal cord barrier, renowned as excellent carriers of bioactive substances. Methods We applied mesenchymal stem cell (MSC)-derived exosomes as the delivery of synthesized siRNA, which were extracted from rat bone marrow. We constructed exosomes-siRNA (Exo-siRNA) that could specifically silence CTGF gene in the injury sites by electroporation. During the administration, we injected Exo-siRNA into the tail vein of SCI rats, Results In vivo and in vitro experiments showed that Exo-siRNA not only effectively inhibited the expressions of CTGF gene, but quenched inflammation, and thwarted neuronal apoptosis and reactive astrocytes and glial scar formation. Besides, it significantly upregulated several neurotrophic factors and anti-inflammatory factors, acting as a facilitator of locomotor recovery of rats with spinal cord injury (SCI). Conclusions In conclusion, this study has combined the thoroughness of gene therapy and the excellent drug-loading characteristics of Exo for the precise treatment of SCI, which will shed new light on the drug-loading field of Exo.

Objective: To compare the von Mises stresses of the pedicle screw system and the displacement of injured vertebrae using 3-D finite element analysis, and to evaluate the curative effect of the pedicle screw system. Methods:Finite element methods were used for biomechanical comparison of four posterior short segment pedicle screw fixation techniques. The different pedicle screw models are traditional trajectory (TT), Universal Spine System (USS), cortical bone trajectory (CBT), and CBT at the cranial level and pedicle screw (PS) at the caudal level (UP-CBT). The stress distribution of the screws and connecting rods under different working conditions and the displacement of the injured vertebrae were compared and analyzed.Results: After the pedicle screw system was fixed, the stress under vertical compression was mainly concentrated at the proximal end of the screw, while the stress was mainly concentrated on the connecting rod during flexion, extension, lateral flexion, and rotation. The TT group had the greatest stress during the flexion, extension, and left and right rotation. The UP-CBT group was most stressed when the left and right sides were flexed; the stress of the USS screw system was less than that of the other three models during flexion, lateral flexion, and rotation. The maximum von Mises stress values of pedicle screws in all exercise states were 556.2, 340.7, 458.1, and 533.4 MPa, respectively. In the USS group, the displacement of the injured vertebra was small in the flexion, and the left and right lateral flexion and the right rotation were higher than in the TT group and the CBT group. The maximum displacements of the injured vertebrae in all motion states were 1.679, 1.604, 1.752, and 1.777 mm, respectively.Conclusion: Universal Spine System pedicle screws are relatively less stressed under different working conditions, the risk of breakage is small, and the model is relatively stable; CBT screws do not exhibit better mechanical properties than conventional pedicle screws and USS pedicle screws.

Study Design. A systematic review and meta-analysis. Objective. This study was performed to evaluate the effects of different rehabilitation interventions in spinal cord injury. Summary of Background Data. Several activity-based interventions have been widely applied in spinal cord injury in the past, but the effects of these rehabilitation exercises are controversial. Methods. Publications were searched from databases (PubMed, Embase, Cochrane, the database of the U.S. National Institutes of Health and World Health Organization International Clinical Trials Registry Platform) using the searching terms like spinal cord injury, transcranial magnetic stimulation, functional electrical stimulation, activity-based therapy, and robotic-assisted locomotor training. Randomized controlled trials and controlled trials were included. The primary outcomes included functional upper/lower extremity independence, walking capacity, spasticity, and life quality of individuals with spinal cord injury. Meta-analysis was performed using Revman 5.0 software. Results. Thirty-one articles were included. Meta-analysis showed that transcranial magnetic stimulation improved walking speed (95% confidence interval [CI] 0.01, 0.16) and lower extremity function (95% CI 1.55, 7.27); functional electrical stimulation significantly increased upper extremity independence (95% CI 0.37, 5.48). Robotic-assisted treadmill training improved lower extremity function (95% CI 3.44, 6.56) compared with related controls. Conclusion. Activity-based intervention like transcranial magnetic stimulation, functional electrical stimulation, and robotic-assisted treadmill training are effective in improving function in individuals with spinal cord injury. Level of Evidence: 1

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Background Insulin‐like growth factor‐1 (IGF‐1) promotes osteoblast differentiation and mineralization. The objective of this study was to investigate the effects of IGF‐1 on proliferation, mineralization, alkaline phosphatase (ALP) synthesis, and gene expression of osteoblast differentiation in MC3T3‐E1 osteoblasts cells, and to explore gene expression profiling differential genes. Methods MC3T3‐E1 osteoblasts cells were cultured in medium with or without IGF‐1. The ALP assay was employed to determine the osteoblast mineralization, and Alizarin red S to stain for calcium deposits, which were the indicators of mature osteocytes. The living cell number was assessed by the Cell Counting Kit‐8 method. RNA‐seq analysis was applied to identify genes that were differentially expressed in with or without IGF‐1 as well as genes that varied between these two groups. The expression of osteogenic marker genes was determined by quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blot analysis. Result The cell number of osteoblasts exposed to IGF‐1 at 200 μg/L significantly increased compared with the control group. The ALP activity in IGF‐1‐treated cells was higher than that in the control group. IGF‐1 can increase ALP synthesis in osteoblasts in vitro. RNA‐seq analysis showed that 677 triggered differentially expressed genes by IGF, of which 383 genes were downregulated and 294 genes were upregulated. Gene ontology (GO) analysis showed that IGF‐1 caused a significant change in gene expression patterns. Conclusions This result suggested that IGF‐1 could probably promote the synthesis of organic matrix and mineralize action of bone. Osteogenic‐related genes (DMP1, PHEX, SOST, BMP2, RUNX2, OPN, and OCN) were significantly upregulated both in GO analysis and in pathway analysis to perform qRT‐PCR. Western blot analysis demonstrated that the Notch pathway was highly upregulated in MC3T3‐E1 cells.

As RNA interference (RNAi) received solicitous attention by many for its promising performance in gene therapy recently, and how to obtain a choice small interfering RNA (siRNA) vector has become a moot point at this moment. Exosomes (Exo) show advantages of long survival time in vivo, high transmission efficiency and easy penetration across the blood-brain/spinal cord barrier, renowned as excellent carriers of bioactive substances. Previous studies have confirmed the detrimental effect of connective tissue growth factor (CTGF) on axonal regeneration after spinal cord injury (SCI) via stimulating the unrestricted growth of glial scars. In this study, we applied mesenchymal stem cells (MSCs)-derived Exo as the delivery of synthesized siRNA, which were extracted from rat bone marrow. We constructed exosome-siRNA (Exo-siRNA) that could specifically silence Ctgf gene in the injury sites by electroporation.During the administration, we injected Exo-siRNAs into the tail vein of SCI rats, and their distribution and accumulation in the spinal cord were visualized by in vivo fluorescence imaging. Relevant in vivo and in vitro experiments in this study showed that Exo-siRNA not only effectively inhibited the expressions of Ctgf gene and glial scar formation related proteins, such as GFAP, vimentin fibronectin and laminin, in the injured spinal cord segments, but quenched inflammation, and thwarted neuronal apoptosis and reactive astrocytes and glial scar formation. Besides, it significantly up-regulated several neurotrophic factors and anti-inflammatory factors (e.g., TGF-β1), acting as a facilitator of axon regeneration of nerve-injured motor neurons. Thus, the motor function of SCI rats were remarkably promoted.In conclusion, this study has combined the thoroughness of gene therapy and the excellent drug-loading characteristics of Exo for the precise treatment of SCI, which will shed new light on the drug-loading field of Exo.

Rationale: Angiosarcoma is a rare malignant tumors. The objective of this study is to report a patient who suffered from a progressive low back pain and left lower extremities radiation pain for about 8 months, After diagnoses, this was identified as an extremely rare case of primary multiple angiosarcoma of vertebra. Patient concerns: A 54-year-old man with a history of 2-year hypertension and 8-year diabetes, both of which were well controlled by drug management. Lately, he suffered from a progressive low back pain and left lower extremities radiation pain for about 8 months. Diagnoses: Magnetic resonance imaging of lumbar showed a clear pathological fracture and primary multiple angiosarcoma of all vertebra. Postoperative pathology and High-throughput sequencing confirmed the diagnosis of primary multiple angiosarcoma of vertebra. Interventions: The patient underwent minimally invasive pedicle screw fixation combined with bone cement augmentation for the purpose of stabilizing the damaged vertebrae. Following operation, he received both radiotherapy and chemotherapy for a period of time. Outcomes: The operation has achieved positive results in relieving pain and stabilizing the spine. No wound problem or operative complications occurred after operation. The patient reported an obvious remission of low back pain and was only capable to perform restricted physiological activities. A long-term palliative radiotherapy and chemotherapy were performed after operation. Unfortunately, the patient died 18 months later. Conclusion: This article emphasizes primary multiple angiosarcoma of vertebra. Despite being rare, it should be part of the differential when the patient manifested back pain and radiculopathy. We recommended the minimally invasive pedicle screw fixation for angiosarcoma of vertebra. Osteoplasty by bone cement augmentation was also an ideal choice for surgical treatment. It also advocates the use of specific targeted radiotherapy drugs based on gene analysis of tumors.