Background: Spinal cord injury (SCI) is an inflammatory condition, and excessive adenosine triphosphate (ATP) is released into the extracellular space, which can be catabolized into adenosine by CD73. Extracellular vesicles have been designed as nano drug carriers in many diseases. However, their impacts on delivery of CD73 after SCI are not yet known. We aimed to construct CD73 modified extracellular vesicles and explore the anti-inflammatory effects after SCI. Methods: CD73 engineered extracellular vesicles (CD73+ hucMSC-EVs) were firstly established, which were derived from human umbilical cord mesenchymal stem cells (hucMSCs) transduced by lentiviral vectors to upregulate the expression of CD73. Effects of CD73+ hucMSC-EVs on hydrolyzing ATP into adenosine were detected. The polarization of M2/M1 was verified by immunofluorescence. Furthermore, A2aR and A_2bR inhibitors and A2bR knockdown cells were used to investigate the activated adenosine receptor. Biomarkers of microglia and levels of cAMP/PKA were also detected. Repetitively in vivo study, morphology staining, flow cytometry, cytokine analysis, and ELISA assay, were also applied for verifications. Results: CD73+ hucMSC-EVs reduced concentration of ATP and promoted the level of adenosine. In vitro experiments, CD73+ hucMSC-EVs increased macrophages/microglia M2:M1 polarization, activated adenosine 2b receptor (A2bR), and then promoted cAMP/PKA signaling pathway. In mice using model of thoracic spinal cord contusion injury, CD73+ hucMSC-EVs improved the functional recovery after SCI through decreasing the content of ATP in cerebrospinal fluid and improving the polarization from M1 to M2 phenotype. Thus, the cascaded pro-inflammatory cytokines were downregulated, such as TNF-α, IL-1β, and IL-6, while the anti-inflammatory cytokines were upregulated, such as IL-10 and IL-4. Conclusions: CD73+ hucMSC-EVs ameliorated inflammation after spinal cord injury by reducing extracellular ATP, promoting A2bR/cAMP/PKA pathway and M2/M1 polarization. CD73+ hucMSC-EVs might be promising nano drugs for clinical application in SCI therapy. Graphical

Spinal fusion is considered the gold standard procedure for treating spinal degeneration, tumors, and trauma. An inflammatory response is an important part of bone repair. We investigated the polarization change of inflammatory macrophages (M1) and resident macrophages (M2) during low-intensity pulsed ultrasound (LIPUS) treatment. Thirty male Sprague Dawley rats (age: 12 weeks; weight: 300 g) were used in the study. A rat spinal fusion model was established by surgical procedures. LIPUS treatment (20 min. d, 5 d/wk) was begun 3 days after surgery. The rats were randomly divided into a control group (5 subgroups, 3 rats in each subgroup) and LIPUS group (5 subgroups, 3 rats in each subgroup), and sacrificed on day 3, 5, 7, 10, and 14 after spinal fusion surgery for further evaluation. Bone volume was measured by micro-CT, fusion region was examined by histological analyses, types of macrophages in the fusion area were examined by immunohistochemical staining. Raw264.7 cells and bone marrow-derived macrophages (BMDM) were used in cell experiments. Cells were divided into a control group and LIPUS group. Flow cytometry was used to examine the rate of resident macrophages, and real-time PCR was used to examine the mRNA expression of anti-inflammation genes. LIPUS promoted spinal fusion and stimulated the transition of F4-80+/Mac-2+ (M1) to F4-80+/Mac-2- (M2), leading to the early appearance of resident macrophages. Cell experiments showed CD206+ macrophages (M2) were significantly increased after LIPUS treatment. M2-related genes and anti-inflammation factors (Arg-1, PPAR-γ, and IL-4) were increased after LIPUS treatment. The earlier transition from inflammatory to resident macrophage might be one reason for the positive effect of LIPUS on spinal fusion.

Background. Osteoarthritis (OA) is a common degeneration disease characterized with joint pain. The aim of the present study was to systemically review the effects of LIPUS on pain relief and functional recovery in patients with knee osteoarthritis (OA). Methods. PubMed, Embase, and Cochrane Library were searched manually for researches on LIPUS treatment in patients with knee OA from 1945 to July 2017. Two investigators independently selected the studies according to the inclusion and exclusion criteria, extracted the concerned data, and assessed the included studies. Meta-analysis was performed to evaluate VAS, WOMAC, and ambulation speed between control and LIPUS groups. Results. Five studies were selected in this study. Compared with control group, LIPUS group received a decrease of pain intensity with moderate heterogeneity (-0.79, 95% CI, -1.57 to 0.00; I² = 65%, P = 0.04) by VAS and improvement in knee function by WOMAC (-5.30, 95% CI, -2.88 to -7.71; I² = 44%, P = 0.17). No significant improvement was found in ambulation speed (0.08 m/s, 95% CI, -0.02 to 0.18 m/s; I² = 68%, P = 0.03). Conclusion. The present study includes 5 high quality randomized controlled trials. The result indicated that LIPUS, used to treat knee OA without any adverse effect, had a beneficial effect on pain relief and knee functional recovery. More evidence is needed to prove whether LIPUS is effective in improving walking ability.

Selective fusion of the thoracolumbar/lumbar (TL/L) curve is an effective method for the treatment of Lenke type 5C curves. Several studies have demonstrated that spontaneous correction of the thoracic curve does indeed occur. However, how this correction occurs after isolated posterior segmental instrumentation of the structural lumbar curve has not been well described. The aim of this study was to evaluate the response of the thoracic curve to selective TL/L curve fusion in patients with Lenke type 5C adolescent idiopathic scoliosis (AIS) and assess the correlative clinical outcomes. Thirty-four consecutive patients with Lenke type 5C AIS were included in this study. All patients underwent selective TL/L curve instrumentation and fusion via the posterior approach. Coronal and sagittal radiographs were analyzed before surgery, at 1 week after surgery and at least 2 years after surgery. The preoperative coronal Cobb angle of the major TL/L curve was 45.4° ± 7.0°, and that of the minor thoracic curve was 25.4° ± 8.8°. The major TL/L and minor thoracic curves were corrected to postoperative angles of 9.5° ± 5.0° and 11.2° ± 5.2°, respectively, and measured 10.5° ± 6.0° and 13.4° ± 7.5° at the follow-up, respectively. The supine side-bending average Cobb angle of the thoracic curve was 9.9°. These results demonstrate satisfactory improvements because of coronal and sagittal restoration. Significant correlations were found between the preoperative and early postoperative conditions and the Cobb angle changes of the minor thoracic curve and the major TL/L curves (r = 0.42, P = 0.01). Significant correlations were also observed between the early and final follow-up postoperative conditions and the Cobb angle changes of the minor thoracic curve and the major TL/L curves (r = 0.57, P < 0.001). Significant correlations were observed between increased thoracic kyphosis (TK) and increased lumbar lordosis (LL) in the preoperative and early postoperative conditions (r = 0.36, P = 0.035) and between increased TK and increased LL in the preoperative and final follow-up postoperative conditions (r = 0.51, P = 0.002). Spontaneous correction of the thoracic curve is a reflection of the TL/L curve correction in Lenke 5C AIS patients. Supine side-bending radiographs are an effective method of predicting the spontaneous correction of thoracic curves. The correction of LL is important for maintaining spinal sagittal alignment.

Background: In recent years, there has been increased interest in the use of ultrasound technology in the evaluation of spinal and paraspinal regions. Objective: This study aimed to investigate trends in spinal ultrasound research from 1994 to 2015 and compare the contributions of such research from different countries and authors. Study design: Bibliometric analysis. Setting: Publications related to spinal ultrasound from 1994 to 2015 were retrieved from the Web of Science database. Methods: Excel 2013, GraphPad Prism 5, and VOSviewer were used to summarise bibliometric features, including the number of publications, citation frequency, H-index, and country contributions and hotspots (keywords of popular scientific fields). Results: A total of 3859 papers were included. The global inflection point (the point in time when the publication growth rate moved from positive to negative) came in 2010. The United States contributed the largest percentage of articles (1041; 26.9%), with the most citations (19 848) and the highest H-index (61). The journals Osteoporosis International and Spine had the highest publication number. The University of Toronto and the University of California, San Francisco were the most contributive institutions. Studies could be divided into three clusters: surgery, osteoporosis, and others. The keywords ‘adolescent idiopathic scoliosis’ and ‘anaesthesia’ were the latest hotspots, appearing around 2012. Conclusion: Spinal ultrasound literature has grown continuously over the last 22 years, with the rate slowing down after 2010. The United States was the largest contributor in this field. Recent studies on topics related to ‘adolescent idiopathic scoliosis’ and ‘anaesthesia’ were relatively new and should be closely followed in spinal ultrasound research.