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

Study Design. A retrospective radiographic study. Objective. To investigate which preoperative radiographic parameters best correlate with the angulation and translation of the lowest instrumented vertebra (LIV) and global coronal balance after posterior spinal pedicle screw fixation for thoracolumbar/lumbar (TL/L) adolescent idiopathic scoliosis. Summary of Background Data. Lenke 5C patients with a single, structural TL/L curve can be treated by either an anterior or posterior approach. One of the operative goals when treating Lenke 5C patients is to level and center the LIV, thereby achieving a better global coronal balance. To our knowledge, no study has investigated which specific radiographic parameters correlate with these surgical outcomes after posterior pedicle screw fixation. Methods. Twenty-seven patients with TL/L adolescent idiopathic scoliosis were identified in this study, and they underwent posterior fixation and fusion by pedicle screws with a minimum 2-year follow-up. Preoperative and postoperative radiographs were reviewed measuring various radiographic parameters as well as specific measurements related to the LIV. Correlation of these parameters to LIV translation and global and regional coronal balance (C7-central sacral vertical line [CSVL], LIV-CSVL distance) were then evaluated. Results. Four patients demonstrated global coronal imbalance postoperatively by radiographic and clinical evaluation. Regression analysis identified three radiographic parameters that correlated significantly with the postoperative global coronal balance (C7-CSVL): preoperative C7-CSVL (r = 0.44, P = 0.023), preoperative LIV tilt (r = 0.60, P = 0.001), and postoperative LIV tilt (r = 0.65, P = 0.0002). The radiographic parameters that correlated with postoperative LIV-CSVL were: preoperative LIV-CSVL (r = 0.57, P = 0.017), preoperative LIV tilt (r = 0.40, P = 0.04), and postoperative LIV tilt (r = 0.46, P = 0.015). The radiographic parameters correlating to LIV translation were preoperative LIV-CSVL (r = 0.88, P < 0.001) and preoperative C7-CSVL (r = 0.44, P = 0.02). Conclusion. LIV tilt is a very important radiographic parameter that strongly correlates to postoperative global and regional coronal balance. In patients with Lenke 5C curves undergoing posterior spinal fixation using pedicle screw constructs, preoperative LIV tilt equal to or exceeding 25° and failure of postoperative LIV tilt to reduce below 8° correlate with a high risk of developing postoperative global coronal imbalance.

Validation study to define validity and reliability of an adapted and translated questionnaire. This study attempted to validate the traditional Chinese (Hong Kong) version of the modified Scoliosis Research Society (SRS) Outcomes Instrument, SRS-22, into simplified Chinese for use in mainland China. Although a traditional Chinese (Hong Kong) adaptation of the SRS-22 has been previously validated, no culturally adapted, validated SRS-22 exists for use in mainland China. Adhering to International Quality of Life Assessment Project guidelines, the adapted traditional Chinese SRS-22 was translated into simplified Chinese while referencing the original English questionnaire. To examine the psychometric properties and clinical application of the adapted simplified Chinese SRS-22, a survey was conducted in a group of randomly selected 87 patients previously surgically treated at an outpatient clinic. Reliability assessment of the simplified Chinese version of the SRS-22 was determined by calculating Cronbach's alpha and intraclass coefficient (ICC) values. Concurrent validity was evaluated by comparing SRS-22 domains with relevant domains of the simplified Short-Form-36 questionnaire; correlation was made using Pearson correlation coefficients. Cronbach's alpha, applied to each of the 22 questions of the adapted SRS-22, revealed very satisfactory internal consistency (Cronbach's alpha = 0.80-0.89) for function/activity and pain, and good consistency (Cronbach's alpha = 0.50-0.79) for the remaining domains. The test/retest reproducibility was found to be good (ICC > or =0.40-0.75) in the function/activity domain, and excellent (ICC > or =0.75) in the remaining domains. In terms of concurrent validity, 3 domains had excellent correlation, while 10 had good correlation, and 21 had moderate correlation. The authors report the validation of a simplified Chinese SRS-22 for use in mainland China, which is culturally relevant, reliable, repeatable, psychometrically sound, and suitable for immediate clinical use.

Spinal tuberculosis is the most common form of skeletal tuberculosis. However, there were limited data to evaluate the trend of spinal tuberculosis research. This study aims to investigate the trend of spinal tuberculosis research and compare the contribution of research from different countries and authors. Spinal tuberculosis-related publications from 1994 to 2015 were retrieved from the Web of Science database. Excel 2013, GraphPad Prism 5, and VOSviewer software were used to analyze the search results for number of publications, cited frequency, H-index, and country contributions. A total of 1558 papers were identified and were cited 16,152 times as of January 25, 2016. The United States accounted for 15.1% of the articles, 22.3% of the citations, and the highest H-index (33). China ranked third in total number of articles, fifth in citation frequency (815), and ranked seventh in H-index (13). The journal Spine (IF 2.297) had the highest number of publications. The author Jain A.K. has published the most papers in this field (20). The article titled “Tuberculosis of the spine: Controversies and a new challenge” was the most popular article and cited a total of 1138 times. The keyword “disease” was mentioned the most for 118 times and the word “bone fusion” was the latest hotspot by 2015. Literature growth in spinal tuberculosis is slowly expanding. Although publications from China are increasing, the quality of the articles still requires improvements. Meanwhile, the United States continues to be the largest contributor in the field of spinal tuberculosis. According to our bibliometric study, bone fusion may be an emerging topic within spinal tuberculosis research and is something that should be closely observed.