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Background: Play is an indispensable and meaningful activity in children's daily life. Research has shown that autistic children often exhibit differences in play development. The core traits of autism, such as distinct patterns in social interaction and communication, focused interests, and repetitive behaviors, frequently manifest in their play. Therefore, play may serve as an insightful measure of these differences. Unlike previous studies focusing on play behaviors only, we explored other behaviors associated with autism during free play, and constructed a clinical prediction model for effectively screening autistic children., Methods: Participants, including 123 autistic children and 123 neurotypical children aged 1-6 years, engaged in a 1.5-min free play with fixed toys, which was videotaped. A novel behavior-coding scheme was used to code these videos for 19 autistic behaviors, including play. The coding details of the 19 behaviors were then converted and expanded to 81 digital behavior indicators, including counts, duration, and proportion., Results: The autistic children showed less functional play and imaginative play and reduced social communication and interactions, such as eye contact, facial expressions, and vocalizations, compared to the neurotypical children during free play. Furthermore, 5 behavioral indicators were selected for the prediction model through stepwise logistic regression, including 1 on socially oriented vocalizations and 4 on count and duration of functional play. The receiver operating characteristic (ROC) curve revealed a good prediction performance with an area under the curve (AUC) of 0.826, a sensitivity of 85.4%, and a specificity of 68.3%., Conclusion: Our findings highlight differences in play performance and social communication and interactions during free play among autistic children. Based on these findings, we constructed a good clinical prediction model, which might be a potential digital tool used by clinicians to effectively screen autistic children., Competing Interests: Declarations Ethics approval and consent to participate All methods were carried out in accordance with the guidelines and recommendations specified within the Helsinki declaration. The procedure was approved by the Ethics Committee of Peking University Sixth Hospital (approval no. 2021-71), and written informed consent was obtained from the parents/legal guardians of all participants before enrolling in this study. Consent for publication Not applicable. Competing interests The authors (Z.M., Y.J., JH.C., Y.G., X.L., and J.L.) declare that there were two patent applications related to this research (No. 202310300588.1 and No. 202310315701.3). Q.L., R.H., X.S., JL.C., and T.Y. have no conflicts of interest with regard to the content of this manuscript., (© 2024. The Author(s).)

Study Design: Retrospective clinical study., Objective: The purpose of this study was to establish a novel classification of migrated lumbar disk herniation (LDH) based on magnetic resonance imaging and provide appropriate treatment strategies for each type through algorithms., Summary of Background Data: Full-endoscopic lumbar discectomy is a surgical technique that has been developed rapidly in recent years. For migrated LDH, few surgeons currently classify it with multiplanar positioning, and there is no consensus on the choice of treatment strategy. Therefore, we established a new multiplanar classification criteria that can localize the lesions more accurately than previous studies., Methods: A total of 263 eligible patients from March 2017 to March 2022 were included. Protrusions for each patient were located based on our classification and the surgical approach was selected according to our algorithms. The clinical symptoms of all patients before surgery, and at 1 day, 1 month, 3 months, 6 months, and 12 months after surgery were collected. Evaluations were performed using visual analogue scale (VAS), Oswestry Disability Index (ODI) and modified MacNab criteria. We used the chi-squared test, one-way analysis of variance (ANOVA), and t-test to compare perioperative results and postoperative 3-month, 6-month, and 12-month follow-up results., Results: VAS (low back pain) scores were reduced from 5.33 ± 2.67 to 0.73 ± 0.77 (p < 0.001), and VAS (leg pain) scores were reduced from 7.44 ± 2.21 to 0.37 ± 0.51 (p < 0.001). ODI scores improved from 58.46 ± 8.04 to 12.57 ± 2.51 (p < 0.001). According to the modified MacNab criteria, the excellent and good rate reached 92.78% at the 12-month follow-up. Twenty-six patients developed complications, all of which improved after treatment. Recurrence occurred in 13 patients, and four of them underwent secondary surgery., Conclusions: This is an innovative classification method using multi-plane positioning, and the algorithm used with it can help surgeons make appropriate choices when using endoscopic technology to treat migrated LDH. Statistical analysis of follow-up data confirmed that this is a safe and effective strategy., (© 2024 The Author(s). Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Palladium hydride (PdH x ) is one of the well-known electrocatalytic materials, yet its synthesis is still a challenge through an energy-efficient and straightforward method. Herein, we propose a new and facile cyanogel-assisted synthesis strategy for the preparation of PdH 0.649 at a mild environment with NaBH 4 as the hydrogen source. Unlike traditional inorganic Pd precursors, the unique Pd-CN-Pd bridge in Pd x [Pd(CN) 4 ] y  ⋅ aH 2 O cyanogel offers more favourable spatial sites for insertion of H atoms. The characteristic three-dimensional backbone of cyanogel also acts as a support scaffold resulting in the interconnected network structure of PdH 0.649 . Due to the incorporation of H atoms and interconnected network structure, the PdH 0.649 achieves a high half-wave potential of 0.932 V, a high onset potential of 1.062 V, and a low activation energy, as well as a long-term lifetime for oxygen reduction reaction. Theoretical calculation demonstrates a downshift of the d-band centre of Pd in PdH 0.649 owing to the dominant Pd-H incorporation that weakens the binding energies of the *OH intermediate species. Zn-air batteries (ZAB) based on PdH 0.649 exhibits high power density, competitive open circuit voltage, and good stability, exceeding that of commercial Pt black. This work not only opens up a new avenue for the development of high-efficiency Pt-free catalysts but also provides an original approach and insight into the synthesis of PdH x ., (© 2024 Wiley-VCH GmbH.)

Objective: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by increasing prevalence, diverse impairments, and unclear origins and mechanisms. To gain a better grasp of the origins of ASD, it is essential to identify the most distinctive structural brain abnormalities in individuals with ASD., Methods: A Multi-Stage Progressive Feature Refinement Approach was employed to identify the most pivotal structural magnetic resonance imaging (MRI) features that distinguish individuals with ASD from typically developing (TD) individuals. The study included 175 individuals with ASD and 69 TD individuals, all aged between 7 and 18 years, matched in terms of age and gender. Both cortical and subcortical features were integrated, with a particular focus on hippocampal subfields., Results: Out of 317 features, 9 had the most significant impact on distinguishing ASD from TD individuals. These structural features, which include a specific hippocampal subfield, are closely related to the brain areas associated with the reward system., Conclusion: Structural irregularities in the reward system may play a crucial role in the pathophysiology of ASD, and specific hippocampal subfields may also contribute uniquely, warranting further investigation., Competing Interests: Author AS was employed by the company Yizhun Medical AI Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sun, Xu, Kat, Sun, Yin, Zhao, Su, Chen, Wang, Gong, Liu, Han, Peng, Li and Liu.)

Spinal cord injury (SCI) compromises the blood-spinal cord barrier (BSCB) and induces neuroinflammation, potentially exacerbating neuronal damage. This underscores the importance of maintaining BSCB integrity and mitigating neuroinflammation in SCI treatment. Our study explores an innovative approach to treating SCI by utilizing platelet-rich plasma-derived exosomes (PRP-Exos) to stabilize BSCB function and alleviate neuroinflammation. We successfully isolated exosomes from platelet-rich plasma and conducted both in vivo and in vitro experiments to assess the therapeutic effects of PRP-Exos and explore their potential mechanisms in stabilizing the BSCB, reducing neuroinflammation, and promoting neural functional recovery.In vitro results demonstrate that PRP-Exos significantly reduce the permeability of bEnd.3 cells under hypoxic-hypoglycemic conditions, thereby restoring the integrity of tight junctions. Additionally, our study elucidates the critical role of the NF-κB signaling pathway in the amelioration of neuroinflammation by PRP-Exos. In the SCI model, local injection of hydrogel-encapsulated PRP-Exos reduced Evans blue dye leakage, enhanced the expression of tight junction proteins, alleviated the inflammatory environment in the damaged area, and improved neural functional recovery. In conclusion, PRP-Exos presents a promising and effective treatment option for SCI., (© 2024. The Author(s).)

Study Design: A systematic review and Bayesian network meta-analysis (NMA)., Objective: To compare the effectiveness and safety of different posterior decompression techniques for LSS. Lumbar spinal stenosis (LSS) is one of the most common degenerative spinal diseases that result in claudication, back and leg pain, and disability. Currently, posterior decompression techniques are widely used as an effective treatment for LSS., Methods: An electronic literature search was performed using the EMBASE, Web of Science, PubMed, and Cochrane Library databases. Two authors independently performed data extraction and quality assessment. A Bayesian random effects model was constructed to incorporate the estimates of direct and indirect treatment comparisons and rank the interventions in order., Results: In all, 14 eligible studies comprising 1,260 patients with LSS were included. Five interventions were identified, namely, spinal processes osteotomy (SPO), conventional laminotomy/laminectomy (CL), unilateral laminotomy/laminectomy (UL), bilateral laminotomy/ laminectomy (BL), and spinous process-splitting laminotomy/laminectomy (SPSL). Among these, SPO was the most promising surgical option for decreasing back and leg pain and for lowering the Oswestry Disability Index (ODI). SSPL had the shortest operation time, while SPSL was associated with maximum blood loss. SPO and UL were superior to other posterior decompression techniques concerning lesser blood loss and shorter length of hospital stay, respectively. Patients who underwent BL had the lowest postoperative complication rates., Conclusion: Overall, SPO was found to be a good surgical choice for patients with LSS., (© 2024. The Author(s).)

Individuals with autism spectrum disorder have deficits in facial emotion recognition and white matter microstructural alterations. Nonetheless, most previous studies were confounded by different variables, such as psychiatric comorbidities and psychotropic medications used by ASD participants. Also, it remains unclear how exactly FER deficits are related to white matter microstructural alterations in ASD. Accordingly, we aimed to investigate the FER functions, white matter microstructure, and their relationship in drug-naive and comorbidity-free ASD individuals. 59 ASD individuals and 59 typically developed individuals were included, where 46 ASD and 50 TD individuals completed FER tasks. Covariance analysis showed scores were lower in both basic and complex FER tasks in the ASD group. Tract-Based Spatial Statistics showed FA values in widespread white matter fibers were lower in the ASD group than in the TD group, including forceps major and forceps minor of the corpus callosum, anterior thalamic radiation, corticospinal tract, cingulum, inferior frontal-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus. Moreover, in the TD group but not the ASD group, the performance in the complex FER task was negatively correlated with the FA value in some white matter fibers, including forceps major of the corpus callosum, ATR, CT, cingulum, IFOF, ILF, SLF. Our study suggests children with ASD may experience deficits in facial emotion recognition and exhibit alterations in white matter microstructure. More importantly, our study indicates that white matter microstructural alterations may be involved in FER deficits in children with ASD., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease with a high mortality rate and limited treatment efficacy. Nintedanib, a tyrosine kinase inhibitor, is clinically used to treat pulmonary fibrosis. At present, only nintedanib is on the market for the treatment of pulmonary fibrosis. Pazopanib is a drug for the treatment of renal cell carcinoma and advanced soft tissue sarcoma., Methods: In this study, we explored whether pazopanib can attenuate bleomycin (BLM)-induced pulmonary fibrosis and explored its antifibrotic mechanism. In vivo and in vitro investigations were carried out to investigate the efficacy and mechanism of action of pazopanib in pulmonary fibrosis., Results: In vivo experiments showed that pazopanib can alleviate pulmonary fibrosis caused by BLM, reduce the degree of collagen deposition and improve lung function. In vitro experiments showed that pazopanib suppressed transforming growth factor-β1 (TGF-β1)-induced myofibroblast activation and promoted apoptosis and autophagy in myofibroblasts. Further mechanistic studies demonstrated that pazopanib inhibited the TGF-β1/Smad and non-Smad signaling pathways during fibroblast activation., Conclusions: In conclusion, pazopanib attenuated BLM-induced pulmonary fibrosis by suppressing the TGF-β1 signaling pathway. Pazopanib inhibits myofibroblast activation, migration, autophagy, apoptosis, and extracellular matrix (ECM) buildup by downregulating the TGF-β1/Smad signal route and the TGF-β1/non-Smad signal pathway. It has the same target as nintedanib and is a tyrosine kinase inhibitor., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1349/coif). H.R., C.G., Z.W., L.T., S.G., H.Z., and H.Y. are employees of China Resources Biopharmaceutical Co., Ltd. The other authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Neurotrauma, encompassing traumatic brain injuries (TBI) and spinal cord injuries (SCI) impacts a significant portion of the global population. While spontaneous recovery post-TBI or SCI is possible, recent advancements in cell-based therapies aim to bolster these natural reparative mechanisms. Emerging research indicates that the beneficial outcomes of such therapies might be largely mediated by exosomes secreted from the administered cells. While stem cells have garnered much attention, exosomes derived from non-stem cells, including neurons, Schwann cells, microglia, and vascular endothelial cells, have shown notable therapeutic potential. These exosomes contribute to angiogenesis, neurogenesis, and axon remodeling, and display anti-inflammatory properties, marking them as promising agents for neurorestorative treatments. This review provides an in-depth exploration of the current methodologies, challenges, and future directions regarding the therapeutic role of non-stem cell-derived exosomes in neurotrauma., (© 2024. The Author(s).)

Objective: The study involved 17 children with Autism Spectrum Disorder (ASD), 21 with ADHD, 30 with both (ASD + ADHD), and 28 typically developing children (TD)., Methods: The amplitude of low-frequency fluctuations (ALFF) was measured as a regional brain function index. Intrinsic functional connectivity (iFC) was also analyzed using the region of interest (ROI) identified in ALFF analysis. Statistical analysis was done via one-way ANCOVA, Gaussian random field (GRF) theory, and post-hoc pair-wise comparisons., Results: The ASD + ADHD group showed increased ALFF in the left middle frontal gyrus (MFG.L) compared to the TD group. In terms of global brain function, the ASD group displayed underconnectivity in specific regions compared to the ASD + ADHD and TD groups., Conclusion: The findings contribute to understanding the neural mechanisms underlying ASD + ADHD., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Many human tissues exhibit a highly oriented architecture that confers them with distinct mechanical properties, enabling adaptation to diverse and challenging environments. Hydrogels, with their water-rich "soft and wet" structure, have emerged as promising biomimetic materials in tissue engineering for repairing and replacing damaged tissues and organs. Highly oriented hydrogels can especially emulate the structural orientation found in human tissue, exhibiting unique physiological functions and properties absent in traditional homogeneous isotropic hydrogels. The design and preparation of highly oriented hydrogels involve strategies like including hydrogels with highly oriented nanofillers, polymer-chain networks, void channels, and microfabricated structures. Understanding the specific mechanism of action of how these highly oriented hydrogels affect cell behavior and their biological applications for repairing highly oriented tissues such as the cornea, skin, skeletal muscle, tendon, ligament, cartilage, bone, blood vessels, heart, etc., requires further exploration and generalization. Therefore, this review aims to fill that gap by focusing on the design strategy of highly oriented hydrogels and their application in the field of tissue engineering. Furthermore, we provide a detailed discussion on the application of highly oriented hydrogels in various tissues and organs and the mechanisms through which highly oriented structures influence cell behavior., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

In recent years, owing to the ongoing advancements in polymer materials, hydrogels have found increasing applications in the biomedical domain, notably in the realm of stimuli-responsive "smart" hydrogels. Nonetheless, conventional single-network stimuli-responsive "smart" hydrogels frequently exhibit deficiencies, including low mechanical strength, limited biocompatibility, and extended response times. In response, researchers have addressed these challenges by introducing a second network to create stimuli-responsive "smart" Interpenetrating Polymer Network (IPN) hydrogels. The mechanical strength of the material can be significantly improved due to the topological entanglement and physical interactions within the interpenetrating structure. Simultaneously, combining different network structures enhances the biocompatibility and stimulus responsiveness of the gel, endowing it with unique properties such as cell adhesion, conductivity, hemostasis/antioxidation, and color-changing capabilities. This article primarily aims to elucidate the stimulus-inducing factors in stimuli-responsive "smart" IPN hydrogels, the impact of the gels on cell behaviors and their biomedical application range. Additionally, we also offer an in-depth exposition of their categorization, mechanisms, performance characteristics, and related aspects. This review furnishes a comprehensive assessment and outlook for the advancement of stimuli-responsive "smart" IPN hydrogels within the biomedical arena. We believe that, as the biomedical field increasingly demands novel materials featuring improved mechanical properties, robust biocompatibility, and heightened stimulus responsiveness, stimuli-responsive "smart" IPN hydrogels will hold substantial promise for wide-ranging applications in this domain., Competing Interests: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled “Biomedical applications of stimuli-responsive “smart” Interpenetrating Polymer Network hydrogels”., (© 2024 The Authors. Published by Elsevier Ltd.)

Background/motivation: This article presents a systematic review aimed at examining the utilization of learning analytics (LA) to enhance teachers' professional capital., Aim: The study focuses on three primary research questions: (1) exploring the characteristics and approaches of LA in professional capital, (2) investigating suggestions from LA for assessing and improving professional capital, and (3) examining variables studied in enhancing the most intricate dimension of professional capital using LA., Methodology: To address the research objectives, a systematic review was conducted focusing on the key concepts "learning analytics" and "professional capital." Following the procedures outlined encompassed in four stages: identification, screening, inclusion, and adequacy. The PRISMA 2009 protocol guided the systematic review process., Principal Findings: The findings of the study underscore the efficacy of LA as a catalyst for improving professional capital, particularly through collaborative learning and the utilization of tools like forums and online learning platforms. Social capital emerges as a pivotal component in integrating diverse types of professional capital, fostering opportunities for knowledge creation and social networking., Conclusion/significance: In conclusion, the study highlights the paramount significance of addressing teachers' professional capital development through collaborative approaches and leveraging technology, particularly in primary education. The article concludes by emphasizing the imperative for more research and knowledge dissemination in this field, aiming to ensure equity in learning and address the challenges posed by the COVID-19 pandemic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 de La Hoz-Ruiz, Khalil, Domingo Segovia and Liu.)

Polyetheretherketone (PEEK) material has become a potential bone replacement material due to its elastic modulus, which is close to that of human bone, and stable chemical properties. However, its biological inertness has hindered its clinical application. To improve the biological inertia of PEEK material, a hyaluronic acid (HA) hydrogel coating loaded with platelet-rich plasma (PRP) and nerve growth factor (NGF) was constructed on the surface of PEEK material in this study. After the hybrid hydrogel coating was constructed, scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), Fourier transform infrared spectroscopy (FT-IR), degradation tests, and enzyme-linked immunosorbent assays (ELISAs) were used to evaluate its characteristics and biological properties. The osteogenic and angiogenic potentials were also investigated in vitro and in vivo. Our results showed that the HA hydrogel loaded with RPP and NGF on the PEEK surface degraded slowly and could sustainably release various growth factors, including NGF. The results of in vitro tests showed that the hybrid hydrogel on the surface of PEEK effectively promoted osteogenesis and angiogenesis. The in vivo experiment also confirmed that the PEEK surface hydrogel could promote osseointegration of the implant and the integration of new bone and neovascularization. Our results suggest that the cross-linked hyaluronic acid hydrogel loaded with PRP and NGF can significantly improve the biological inertia of PEEK material, endowing PEEK material with good osteogenic and angiogenic ability., Competing Interests: Conflicts of interest: none. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Ltd.)

There is a pressing need for studies of large sample sizes and variable age ranges to delineate the mechanism underlying reduced visual attention to biological motion in autism. Here we focused on the basic movement of the eyes or mouth in guiding attention. The stimuli face blinked continuously or moved the mouth silently. In a large sample (145 autistic and 132 non-autistic participants) ranging from 3 to 17 years old, we assessed whether autistic participants showed reduced visual attention to basic movement of the eyes or mouth using a free-viewing eye-tracking task. We found that, like non-autistic participants, autistic participants increased their eye-looking time when viewing the blinking face and increased mouth-looking time when viewing the mouth-moving face. Furthermore, these effects were stable across ages, suggesting the presence of a developmentally stable attentional capture by basic face movements in both groups. We also found that autistic participants looked less at basic face movement than non-autistic participants. Our results suggest that autistic children and adolescents could modulate their visual attention to the basic face movements, but their modulation effect is weaker than non-autistic participants. These results further our understanding of the mechanism underlying visual attention-to-face movement in autistic people.

Background: There is a limited understanding of the risk factors for lumbar disc herniation (LDH) in younger people, even though the evidence suggests that LDH is more prevalent in this population. This study aimed to comprehensively analyze the risk factors for LDH in adolescents and young adults., Methods: The medical records of all patients were retrospectively reviewed with inclusion criteria of being younger than 25 years. Magnetic resonance imaging (MRI) was used to confirm LDH from September 2016 to September 2021. Furthermore, 104 healthy people in the same age range were enrolled as the control group from physical examination centers. Gender, BMI, smoking, drinking, genetic history, sitting posture, daily sitting time, traumatic history of the lower back, scoliosis, and daily exercise time were examined for all enrolled people. These factors were statistically analyzed to determine the high-risk factors., Results: A total of 208 young individuals were enrolled in the present study. The mean age of the study group and the control group was 21.06 ± 3.27 years (range: 11-25 years) and 21.26 ± 2.23 years (range: 15-25 years), respectively. The result of the chi-squared test demonstrated that there was a significant difference in BMI of more than 30 ( p  < 0.001), genetic history ( p  = 0.004), sitting posture ( p  < 0.001), daily sitting time of more than 6 h ( p  < 0.001), and the history of low back trauma ( p  = 0.002). Additionally, multivariate logistic regression showed that these were high-risk factors for LDH, particularly the duration of daily sitting time (more than 6 h)., Conclusions: BMI of more than 30, genetic history, sitting posture, daily sitting time of more than 6 h, and a history of low back trauma are the high-risk factors for adolescents and young adults with LDH. Therefore, providing them with the proper guidance and education, particularly about the protection of the lower back and the reduction of spinal load, could play a key role in preventing and reducing LDH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Qi, Luo, Meng, Zhang, Yu, Nie and Liu.)

This study aimed to develop a predictive system for prognostic evaluation of osteosarcoma patients. We obtained osteosarcoma sample data from 1998 to 2016 using SEER*Stat software version 8.3.8, and established a multivariable Cox regression model using R-4.0.3 software. Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The diagnosis of the model was completed through influential cases, proportionality, and multicollinearity. The predictive ability of the model was tested using area under the curve (AUC), calibration curves, and Brier scores. Finally, the bootstrap method was used to internally verify the model. In total, data from 3566 patients with osteosarcoma were included in this study. The multivariate Cox regression model was used to determine the independent prognostic variables. A nomogram and Kaplan-Meier survival curve were established. The AUC and Brier scores indicated that the model had a good predictive calibration. In addition, we found that the radiotherapy appears to be a risk factor of patients with osteosarcoma and made a discussion. We developed a prognostic evaluation system for patients with osteosarcoma for 1-, 3-, and 5-year overall survival with good predictive ability using sample data extracted from the SEER database. This has important clinical significance for the early identification and treatment of high-risk groups of osteosarcoma patients., (© 2023. The Author(s).)

Background: Lumbar disc herniation (LDH) is the main cause of low back pain and/or radiculopathy. Currently, epidural intervention is a widely used and effective conservative treatment method for managing low back and radicular pain caused by LDH., Objectives: To explore the effectiveness of different epidural injection approaches in adult patients with lumbosacral radicular pain., Study Design: Systematic review and network meta-analysis (NMA)., Methods: An electronic literature search was performed in the Pubmed, Embase, Cochrane Library, and Web of Science databases. Two authors independently performed data extraction and quality assessment. A Bayesian random effects model was conducted to incorporate the estimates of direct and indirect treatment comparisons and rank the interventions in order. Effect estimates from Bayesian NMA were presented as mean difference (MD) with 95% credible intervals (CrI)., Results: This NMA assessed caudal (C), interlaminar (IL), transforaminal (TF) and parasagittal interlaminar (PIL) epidural injection approaches for lumbosacral radicular pain from 7 trials. A statistically significant treatment difference for pain relief was reported for midline interlaminar (MIL) vs PIL (MD, 1.16; 95%CrI, 0.31-2.06), MIL vs TF (MD, 1.12; 95%CrI, 0.51-1.85), C vs TF (MD, 1.07; 95%CrI, 0.01-2.18) in short-term follow-up and MIL vs TF (MD, 1.8; 95% CrI, 0.3-3.48) in intermediate-term follow-up. For functional improvement, a statistically significant difference was observed with MIL vs PIL (MD, 9.9; 95% CrI, 0.64-19.94) and MIL vs TF (MD, 1.08; 95% CrI, 1.08-17.08) in short-term follow-up. Moreover, the PIL approach and TF appeoach were ranked in the top 2 for pain relief and functional improvement, both in short-term and intermediate-term follow-up., Limitations: 1) The number of studies included was small; 2) some treatments lacked direct comparisons; 3) only scores from the visual analog scale for pain and the Oswestry Disability Index were included in the result; 4) important outcomes, such as complications, were not included., Conclusion: In short-term and intermediate-term follow-up, the PIL approach has the highest probability for pain relief and functional improvement.

Spinal cord injury (SCI) is a devastating disorder of the central nervous system (CNS). It is mainly caused by trauma and reduces the quality of life of the affected individual. Ginsenosides are safe and effective traditional Chinese medicines (TCMs), and their efficacy against SCI is being increasingly researched in many countries, especially in China and Korea. This systematic review evaluated the neuroprotective effects of ginsenosides in SCI and elucidated their properties., Methods: All experimental information and summaries used in this review were acquired from peer-reviewed articles in the relevant fields. The PubMed, Web of Science, Google Scholar, and China National Knowledge Infrastructure databases were searched for relevant articles. Information on the manual classification and selection of ginsenosides that protect against SCI is included in this review., Results: A literature survey yielded studies reporting several properties of ginsenosides, including anti-inflammation, anti-apoptosis, anti-oxidative stress, and inhibition of glial scar formation., Conclusion: In this review, we discuss the mechanisms of action of different ginsenosides that exert neuroprotective effects in SCI. These results suggest that after further verification in the future, ginsenosides may be used as adjunctive therapy to promote neurological recovery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Qi, Zhang, Wang, An, Xue, Liu and Zhang.)

Background: Facet joint pain is a common cause of chronic low back pain (CLBP). Radiofrequency (RF) denervation is an effective treatment option., Purpose: A systematic review and network meta-analysis (NMA) was performed to evaluate and compare the efficacy and effectiveness of different RF denervation treatments in managing facet joint-derived CLBP., Methods: The Cochrane Library, Embase, PubMed, and China Biology Medicine were searched to identify eligible randomized controlled trials (RCTs) from January 1966 through December 2021. Interventions included conventional radiofrequency denervation (CRF), pulsed radiofrequency denervation (PRF), pulsed radiofrequency treatment of the dorsal root ganglia (PRF-DRG), radiofrequency facet capsule denervation (RF-FC), and radiofrequency ablation under endoscopic guidance (ERFA). The outcome was the mean change in visual analog scale (VAS) score from baseline. A random-effects NMA was used to compare the pain relief effects of the interventions over the short term (≤6 months) and long term (12 months). The rank of effect estimation for each intervention was computed using the surface under the cumulative ranking curve., Results: A total of 10 RCTs with 715 patients met the inclusion criteria. Moderate evidence indicated that CRF denervation had a greater effect on pain relief than sham control in the short term (standardized mean difference (SMD) -1.58, 95% confidence intervals (CI) -2.98 to -0.18) and the long term (SMD -4.90, 95% CI, -5.86 to -3.94). Fair evidence indicated that PRF denervation was more effective than sham control for pain over the long term (SMD -1.30, 95% CI, -2.17 to -0.43). Fair evidence showed that ERFA denervation was more effective for pain relief than sham control in the short term (SMD -3.07, 95% CI, -5.81 to -0.32) and the long term (SMD -4.00, 95% CI, -4.95 to -3.05). Fair evidence showed that RF-FC denervation was more effective for pain relief than sham control in the long term (SMD -1.11, 95% CI, -2.07 to -0.15). A fair level of evidence indicated that PRF-DRG denervation was more effective for pain relief than sham control in the short term (SMD -5.34, 95% CI, -8.30 to -2.39)., Conclusion: RF is an effective option for patients diagnosed with facet joint-derived CLBP. Systematic Review Registration: Identifier: CRD42022298238., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Li, An, Zhang, Kong, Yun, Yu, Nie and Liu.)

Introduction: This study aimed to demonstrate the safety and effectiveness of modified percutaneous endoscopic transforaminal discectomy (PETD) in the surgical management of single-segment lumbar disc herniation (LDH) gluteal pain and to determine whether it provides a better clinical outcome than open lumbar discectomy (OD)., Methods: A retrospective analysis of patients treated with modified PETD and OD for gluteal pain in LDH from January 2015 to December 2020 was conducted. Sample size was determined using a priori power analysis. Demographic information, surgical outcomes including procedure time (minutes), intraoperative blood loss (mL), hospital days, costs (RMB), fluoroscopy shots, recurrence and complications, etc., were recorded and analyzed. Prognostic outcomes were assessed using the visual analog scale (VAS), the Oswestry Disability Index (ODI), the Japanese Orthopedic Association Score (JOA) and modified MacNab criteria. The preoperative and postoperative VAS, ODI and JOA scores were recorded by two assistants. When the results were inconsistent, the scores were recorded again by the lead professor until all scores were consistently recorded in the data. MRI was used to assess radiological improvement and all patients received follow-ups for at least one year., Results: The sample size required for the study was calculated by a priori analysis, and a total of 72 participants were required for the study to achieve 95% statistical test power. A total of 93 patients were included, 47 of whom underwent modified PETD, and 46 of whom underwent OD. In the modified PETD intragroup comparison, VAS scores ranged from 7.14 ± 0.89 preoperatively to 2.00 ± 0.58, 2.68 ± 0.70, 2.55 ± 0.69, 2.23 ± 0.81, and 1.85 ± 0.72 at 7 days, 1 month, 3 months, 6 months, and 12 months postoperatively. Patients showed significant pain relief postoperatively ( P  < 0.01). According to the modified MacNab score, the excellent rate in the PETD group was 89.36%. There was no significant difference compared to the OD group (89.13%, P  > 0.05). Complication rates were lower ( P  > 0.05) but recurrence rates were higher ( P  > 0.05) in the modified PETD group than in the OD group. The modified PETD group had a faster operative time ( P  < 0.01), shorter hospital stay ( P  < 0.01), less intraoperative bleeding ( P  < 0.01), and less financial burden to the patient ( P  < 0.01) than the OD group. At 7 days postoperatively, the VAS score for low back pain was higher in the OD group than in the modified PETD group ( P  < 0.01). The VAS and JOA scores at 1, 3, 6, and 12 months postoperatively were not significantly different between the modified PETD and OD groups ( P  > 0.05), and the ODI was significantly different at 3 months postoperatively ( P  < 0.05)., Conclusion: Modified PETD treatment is safe and effective for gluteal pain due to L4/5 disc herniation and has the advantages of a lower complication rate, faster postoperative recovery, shorter length of stay, fewer anesthesia risks and lower cost of the procedure compared with OD. However, modified PETD has a higher recurrence rate., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 An, Zhang, Yu, Wu, Nie, He, Yun, Liu, Xue, Qi, Li and Liu.)

This study investigates how the COVID-19 pandemic has affected teachers' job-specific stresses and their enthusiasm for the teaching occupation. We use unique data from China that cover the periods before and after the start of the pandemic and apply various estimation methods. We find that, among rural young teachers, the pandemic has caused higher teaching stress and career development stress and has reduced passion toward the teaching occupation. We investigate the working channels of the pandemic, including changes in job-related activities and social network. After controlling for possible working channels, the COVID-19 pandemic still shows a strong direct impact on job sentiments., (© 2022 Elsevier Inc. All rights reserved.)

Minimally invasive surgeries, including posterior endoscopic cervical foraminotomy (PECF), microsurgical anterior cervical foraminotomy (MACF), anterior transdiscal approach of endoscopic cervical discectomy (ATd-ECD), and anterior transcorporeal approach of endoscopic cervical discectomy (ATc-ECD), have obtained positive results for cervical spondylotic radiculopathy. Nonetheless, there is a lack of comparison among them regarding their biomechanical performance. The purpose of this study is to investigate the biomechanical changes of operated and adjacent segments after minimally invasive surgeries compared to a normal cervical spine. A three-dimensional model of normal cervical vertebrae C3-C7 was established using finite element analysis. Afterwards, four surgical models (PECF, MACF, ATd-ECD, and ATc-ECD) were constructed on the basis of the normal model. Identical load conditions were applied to simulate flexion, extension, lateral bending, and axial rotation of the cervical spine. We calculated the range of motion (ROM), intradiscal pressure (IDP), annulus fibrosus pressure (AFP), uncovertebral joints contact pressure (CPRESS), and facet joints CPRESS under different motions. For all circumstances, ATc-ECD was close to the normal cervical spine model, whereas ATd-ECD significantly increased ROM and joints CPRESS and decreased IDP in the operated segment. PECF increased more the operated segment ROM than did the MACF, but the MACF obtained maximum IDP and AFP. Except for ATc-ECD, the other models increased joints CPRESS of the operated segment. For adjacent segments, ROM, IDP, and joints CPRESS showed a downward trend in all models. All models showed good biomechanical stability. With their combination biomechanics, safety, and conditions of application, PECF and ATc-ECD could be appropriate choices for cervical spondylotic radiculopathy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 He, Zhang, Yu, Wu, Yuan, Liu, Yun, Du, Qi, An, Xue, Nie and Liu.)

Platelet-rich plasma (PRP), due to its promising therapeutic properties, has been used in regenerative medicine for more than 30 years and numerous encouraging outcomes have been obtained. Currently, by benefiting from new insights into PRP mechanisms and the excellent performance of extracellular vesicles (EVs) in the field of tissue repair and regeneration, studies have found that a large number of EVs released from activated platelets also participate in the regulation of tissue repair. A growing number of preclinical studies are exploring the functions of PRP-derived EVs (PRP-EVs), especially in tissue regeneration. Here, we summarize the latest progress in PRP-EVs as a superior alternative cell-free therapeutic strategy in regenerative medicine, clarify their underlying molecular mechanisms, and discuss the advantages and limitations of the upcoming clinical applications. This review highlights the potential of PRP-EVs to replace the application of PRP or even become a superior alternative in regenerative medicine., (© 2021 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.)

We explored the social synchronization of gaze-shift behaviors when responding to joint attention in children with autism spectrum disorder (ASD). Forty-one children aged 5 to 8 with ASD and 43 typically developing (TD) children watched a video to complete the response to joint attention (RJA) tasks, during which their gaze data were collected. The synchronization of gaze-shift behaviors between children and the female model in the video was measured with the cross-recurrence quantification analysis (CRQA). Ultimately, we discovered that children with ASD had the ability to synchronize their gaze shifts with the female model in the video during RJA tasks. Compared to the TD children, they displayed lower levels of synchronization and longer latency in this synchronized behavior. These findings provide a new avenue to deepen our understanding of the impairments of social interaction in children with ASD. Notably, the analytic method can be further applied to explore the social synchronization of numerous other social interactive behaviors in ASD. LAY SUMMARY: This study explored how autistic children synchronized their gazed shifts with others' gaze cues during joint attention. We found that compared to typical children, autistic children synchronized their gazed shifts less and needed more time to follow others' gaze. These findings provide a new avenue to deepen our understanding of the impairments of social interaction in children with ASD., (© 2021 International Society for Autism Research and Wiley Periodicals LLC.)

Polymethyl methacrylate (PMMA) bone cement is a commonly used filling material in orthopedic surgery. Its good and stable performances make it the most widely used in all kinds of bone cement. With the advancement of the application and research of PMMA bone cement by surgeons, its disadvantages such as non-degradation and non-bioactivity are gradually exposed. In recent years, the biological functions of lactoferrin (LF) have been gradually explored, especially its role in promoting osteogenesis. In this study, LF was modified on the surface of solidified PMMA bone cement (LF/PMMA bone cement) by physical/chemical mixed modification and verified by cytological experiments in vitro. In vitro studies have implicated that PMMA bone cement modified with LF can improve the attachment, expansion, proliferation, extracellular matrix secretion and osteogenic differentiation of mouse preosteoblasts (MC3T3-E1) cells, indicating biocompatibility. This experiment provides a novel insight for improving the biological activity of PMMA bone cement and lays a foundation for broadening the clinical application of PMMA bone cement., (Copyright © 2021 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

Background: Health-related risky behaviors (HRB) generally refer to behaviors that have a negative influence on health and quality of life. HRB in adolescents with autism have not been well understood so far. We aim to explore health-related risky behaviors and their risk factors with autistic adolescents., Methods: In this study, 150 adolescents with autism and 150 neurotypical adolescents were enrolled. Participants in both groups completed the Adolescent Health-Related Risky Behavior Inventory (AHRBI). Autism Spectrum Screening Questionnaire (ASSQ), Wechsler Intelligence Scale, Theory of Mind (ToM) Test, Zung Self-rating Anxiety Scale (SAS), Zung Self-rating Depression Scale (SDS), and Self-Esteem Scale (SES) were also assessed in the autism group to explore risk factors., Results: The results showed that the total score of AHRBI and scores of "aggression and violence (AV)", "suicide or self-injury (SS)", "health-compromising behavior (HCB)", and "unprotected sex (US)" subscales in the autism group were significantly higher than those in the control group (Z value = - 4.58 ~ - 2.26, all P < 0.05). Anxiety, depression, low self-esteem, low IQ score, low ToM test score, increasing age, and communication disorder were found as risk factors for health-related risky behaviors in autistic adolescents., Conclusions: Adolescents with autism have more health-related risky behaviors than neurotypical adolescents. We should pay attention to the emotional state, self-esteem, cognitive function, and verbal communication levels of autistic adolescent with health-related risky behaviors., (© 2021. The Author(s).)

Idiopathic pulmonary fibrosis (IPF) is a fatal and age-related pulmonary disease. Nintedanib is a receptor tyrosine kinase inhibitor, and one of the only two listed drugs against IPF. Regorafenib is a novel, orally active, multi-kinase inhibitor that has similar targets to nintedanib and is applied to treat colorectal cancer and gastrointestinal stromal tumors in patients. In this study, we first identified that regorafenib could alleviate bleomycin-induced pulmonary fibrosis in mice. The in vivo experiments indicated that regorafenib suppresses collagen accumulation and myofibroblast activation. Further in vitro mechanism studies showed that regorafenib inhibits the activation and migration of myofibroblasts and extracellular matrix production, mainly through suppressing the transforming growth factor (TGF)-β1/Smad and non-Smad signaling pathways. In vitro studies have also indicated that regorafenib could augment autophagy in myofibroblasts by suppressing TGF-β1/mTOR (mechanistic target of rapamycin) signaling, and could promote apoptosis in myofibroblasts. In conclusion, regorafenib attenuates bleomycin-induced pulmonary fibrosis by suppressing the TGF-β1 signaling pathway.

Fabricating a desired porous structure on the surface of biomedical polyetheretherketone (PEEK) implants for enhancing biological functions is crucial and difficult due to its inherent chemical inertness. In this study, a porous surface of PEEK implants was fabricated by controllable sulfonation using gaseous sulfur trioxide (SO 3 ) for different time (5, 15, 30, 60 and 90 min). Micro-topological structure was generated on the surface of sulfonated PEEK implants preserving original mechanical properties. The protein absorption capacity and apatite forming ability was thus improved by the morphological and elemental change with higher degree of sulfonation. In combination of the appropriate micromorphology and bioactive sulfonate components, the cell adhesion, migration, proliferation and extracellular matrix secretion were obviously enhanced by the SPEEK-15 samples which were sulfonated for 15 min. Finding from this study revealed that controllable sulfonation by gaseous SO 3 would be an extraordinarily strategy for improving osseointegration of PEEK implants by adjusting the microstructure and chemical composition while maintaining excellent mechanical properties., Competing Interests: The authors declare that they have no competing interests., (© 2020 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

Introduction: Basilar invagination (BI) is a common deformity in the occipitocervical region. The traditional surgical method of BI is direct transoral decompression followed by posterior decompression and fixation. Posterior-only decompression and fixation have achieved good efficacy in the treatment of BI in recent years, but complications are common due to the operation in the upper cervical vertebra and the medulla oblongata region. Moreover, posterior-only occipitocervical fusion combined with an intraoperative 3-dimensional (3D) navigation system is relatively rare, and reports of this procedure combined with 3D printing technology have not been published. We present a case of BI treated with posterior-only occipitocervical fusion combined with 3D printing technology and 3D navigation system to reduce the risk of surgical complications., Patient Concerns: A 55-year-old patient with a history of neck pain and numbness of the extremities for 6 years developed a walking disorder for 1 year., Diagnoses: Atlantoaxial dislocation with BI., Interventions: The patient underwent posterior-only occipitocervical fusion combined with intraoperative 3D navigation system and 3D printing technology., Outcomes: The patient's walking disorder was resolved and he was able to walk approximately 100 m by himself when he was allowed to get up and move around with the help of a neck brace. At 6 months postoperatively, the patient reported that the numbness of the limbs was reduced, and he could walk >500 m by himself., Conclusion: Occipitocervical fusion is one of the established techniques for the treatment of BI. The biggest advantage of the 2 technologies was that it ensured precise implant placement. The advantages of intraoperative 3D navigation systems are as follows: real-time intraoperative monitoring of the angle and depth of implant placement; the best nailing point can be determined at the time of implantation, rather than according to the operator's previous experience; and the extent of screw insertion is visible to the naked eye, rather than being dependent on the "hand feel" of the surgeon. At the same time, the 3D printing technology can be applied to clarify the relationship between blood vessels and bone around the implant to minimize injury to important structures during implantation.

Spinal cord injury (SCI) can lead to permanent and severe functional impairment below the lesion level and is still one of the most challenging clinical problems. The treatment of SCI has progressed with the development of tissue engineering techniques. Insulin-like growth factor 1 (IGF-1) and brain-derived neurotrophic factor (BDNF) are growth factors closely related to nerve regeneration. In this study, IGF-1 and BDNF were successfully immobilized on biodegradable graphene oxide (GO)-incorporated PLGA (PLGA/GO) electrospun nanofibres. The effect of PLGA/GO nanofibres with immobilized IGF-1 and BDNF on neurogenesis was investigated in vitro and in vivo utilizing MTT assays, immunofluorescence, motor function detection and histology observations. We demonstrated that PLGA/GO nanofibres loaded with IGF-1 and BDNF not only protected NSCs from oxidative stress induced by H 2 O 2 but also enhanced NSC proliferation and neuronal differentiation in vitro. The in vivo study of an SCI animal model demonstrated that local delivery of IGF-1 and BDNF immobilized to PLGA/GO nanofibres significantly improved functional locomotor recovery, reduced cavity formation and increased the number of neurons at the injury site. Our study indicated that PLGA/GO is an effective carrier for IGF-1 and BDNF delivery and that immobilization of IGF-1 and BDNF onto PLGA/GO nanofibres has a great potential as a nerve implant for spinal cord injury applications.

Background: In China, despite the decrease in average road traffic fatalities per capita, the fatality rate and injury rate have been increasing until 2015., Purpose: This study aims to analyze the road traffic accident severity in China from a macro viewpoint and various aspects and illuminate several key causal factors. From these analyses, we propose possible countermeasures to reduce accident severity., Method: The severity of traffic accidents is measured by human damage (HD) and case fatality rate (CFR). Different categorizations of national road traffic census data are analyzed to evaluate the severity of different types of accidents and further to demonstrate the key factors that contribute to the increase in accident severity. Regional data from selected major municipalities and provinces are also compared with national traffic census data to verify data consistency., Results: From 2000 to 2016, the overall CFR and HD of road accidents in China have increased by 19.0% and 63.7%, respectively. In 2016, CFR of freight vehicles is 33.5% higher than average; late-night accidents are more fatal than those that occur at other periods. The speeding issue is severely becoming worse. In 2000, its CFR is only 5.3% higher than average, while in 2016, the number is 42.0%. Conclusion and practical implementation: A growing trend of accident severity was found to be contrasting to the decline of road traffic accidents. From the analysis of casual factors, it was confirmed that the release way of the impact energy and the protection worn by the victims are key variables contributing to the severity of road traffic accidents., (Copyright © 2019 Elsevier Ltd and National Safety Council. All rights reserved.)

Rationale: Cauda equina syndrome (CES) refers to a group of symptoms that occur when the nerves in the cauda equina become compressed or damaged. The most common etiology of CES is lumbar intervertebral disc herniation, but CES following lumbar spinal surgery is rare, especially without motor dysfunction. Herein, we illustrate a case of CES that developed as a complication of spinal surgery and to deduce its possible underlying cause., Patient Concerns: A 46-year-old man experienced lumbago, bilateral shank pain, and numbness with neurogenic claudication for 3 years due to degenerative lumbar disc herniation and spinal cord stenosis. After a thorough examination to diagnose lumbar spinal stenosis, the patient underwent bilateral decompression and pedicle screw system internal fixation with bone graft. Postoperatively, the patient showed regained strength in his bilateral shanks, and he did not complain of lumbago and shank pain, but CES occurred, which manifested as underpants-type numbness in the perineum without bladder, anal, and motor dysfunction., Diagnoses: CES as a postoperative complication of lumbar stenosis., Interventions: The patient underwent bilateral laminectomies, partial facetectomies, and pedicle screw system internal fixation and fusion with bone graft. Postoperatively, the patient performed adequate rehabilitation exercises and was expected to recover spontaneously., Outcomes: The symptoms of pain and claudication resolved after 3 weeks in the hospital, but an underpants-type hypoesthesia in the perineum without motor dysfunction developed. The patient experienced full recovery from CES 6 months after surgery., Lessons: CES as a complication of lumbar spinal surgery is very rare. Excessive sensitivity to the traction of the dural sac was, in our opinion, the most possible cause of postoperative CES in this case. When the nerve root is pulled intraoperatively, it is best not to cross the central line of the spinous process. The plane of the nerve retractor needs to be parallel to the dural sac at the pulling point to reduce the formation of shear force. Most importantly, gentle maneuver is required because sensitivity to the traction of the dural sac varies individually.

The mammalian central nervous system has a limited ability for self-repair under injury conditions. The treatment of nerve injuries has been revolutionised with the development of tissue engineering techniques. However, the lack of bioactivity has severely restricted the application of biodegradable implants for neurogenesis. Therefore, surface modification of biomaterials is crucial to improve their bioactivity and promote endogenous repair mechanisms for nerve regeneration. Insulin-like growth factor 1 (IGF-1) is a growth factor for neuroprotection and neurogenesis. In this study, IGF-1 was successfully immobilised on graphene oxide (GO)-incorporated poly(lactic- co -glycolic acid) (PLGA) biodegradable electrospun nanofibres. For the in vitro investigation, neural stem cells (NSCs) were cultured on different nanofibres to observe various cellular activities. GO enhanced NSC survival under H 2 O 2 pre-treatment and neuronal differentiation to some extent. More importantly, the immobilisation of IGF-1 onto the PLGA/GO nanofibres resulted in significantly increased NSC survival, proliferation, and differentiation. Findings from this study revealed that using PLGA/GO electrospun nanofibres to immobilise IGF-1 has excellent potential for the enhancement of the neuroprotective and neurogenic effects of nerve implants., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Objective: The present paper aimed to investigate the therapeutic effect of quercetin in a rat model of bone cancer pain, and to further explore the molecular mechanism of quercetin in the treatment of bone cancer pain., Methods: The activation status of the osteoblasts in each group of rats was detected by anti-tartaric acid phosphatase (TRAP) immunohistochemistry, while the activation status of the osteoclasts was detected by alkaline phosphatase (BAP) immunohistochemistry. An ELISA assay was used to detect the levels of serum type I collagen carboxy-terminal pro-peptide (CDC), tartrate-resistant acid phosphatase (TRAP5b), and osteocalcin in each group, as well as the expressions of the main inflammatory mediator membrane protease (trypsin), TNF-α, and IL-1β in the PAR2/TRPV1 pathway in serum. Taking CD68 as a marker, immunohistochemistry was used to detect the positive proportion of macrophages in the left tibia of each group. Western blot was applied to analyze the expressions of the RANKL, OPG, RANK, PTHrP and IGF-1 proteins in rat bone tissue, the inflammatory mediators IL-8, M-CSF and TNF-α, and the PAR2/TRPV1 pathway-related molecules PAR2, TRPV1, PKC-Y and PKA in rat DRG neurons, as well as the neurotransmitters c-Fos, GFAP, PKR, and CGRP in the spinal cord., Results: Quercetin significantly reduces serum CTX, TRAP and osteocalcin expressions in a rat model of bone cancer pain and also significantly reduces the proportion of TRAP-positive cells. The drug can significantly reduce the positive proportion of local bone tissue macrophages in rats with bone cancer pain. It can significantly decrease the expressions of RANKL, RANK, PTHrP and IGF-1 proteins and the inflammatory mediators such as IL-8, M-CSF and TNF-α, significantly increase the expressions of OPG and further significantly inhibit the expressions of the PAR2/TRPV1 pathway-related molecules PAR2, TRPV1, PKC-γ and PKA in DRG neurons, as well as significantly reduce the levels of major inflammatory mediators (trypsin), TNF-α, and IL-1β in the PAR2/TRPV1 pathway., Conclusion: Quercetin can inhibit osteoclast activation and reduce bone destruction in the bone cancer pain model by regulating the RANKL/RANK/OPG signaling pathway and the inflammatory response. It can inhibit peripheral sensitization and central sensitization in bone cancer pain by regulating the PAR2/TRPV1 signaling pathway., Competing Interests: None., (IJCEP Copyright © 2018.)

One of the goals of bone tissue engineering is to create scaffolds with excellent biocompatibility, osteoinductive ability and mechanical properties. The application of bioactive proteins, such as bone morphogenetic protein (BMP)-2 and basic fibroblast growth factor (bFGF), has been showed to be an effective way to improve the osteoinductivity and biocompatibility of bone scaffold materials. Therefore, the development of novel materials capable of delivering multiple growth factors is urgent and essential for bone defect repair. In this study, a composite nanofibre scaffold composed of poly(l-lactic- co -glycolic acid) (PLGA), hydroxyapatite (HA), and graphene oxide (GO) has been fabricated to deliver basic fibroblast growth factor (bFGF) and bone morphogenetic protein-2 (BMP-2) simultaneously. The data show that the incorporation of GO and HA into PLGA nanofibres significantly improved the mechanical properties and hydrophilicity of the nanofibre scaffolds. More importantly, compared to PLGA and PLGA/HA nanofibre scaffolds, the PLGA/HA/GO nanofibre scaffolds could more efficiently immobilize bFGF and BMP-2. Moreover, biological assays indicated that the loaded bFGF and BMP-2 loaded in the composite nanofibre scaffolds have a synergistic differentiation effect on the cell adhesion, proliferation, and osteogenesis differentiation of MC3T3-E1 cells. In contrast to the PLGA/HA/GO/bFGF and PLGA/HA/GO/BMP-2 nanofibre scaffolds, the PLGA/HA/GO/bFGF/BMP-2 scaffolds have shown higher ALP activity and higher expression levels of osteogenesis-related genes. In summary, our findings indicated that the incorporation of GO into nanofibre scaffolds is an effective method to immobilize growth factors onto biomaterial surfaces, and the synergistic effects of a combination of BMP-2 and bFGF may have potential use in bone regenerative therapeutics., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

Polyetheretherketone (PEEK) is a high-performance semicrystalline thermoplastic polymer that is widely used in the orthopedics treatment. However, due to its biological inertness, the surface modification of PEEK using different methods to improve the biocompatibility remains a significant challenge. Herein, we attempted to use the covalently coating of phosphorylated gelatin loaded with bone morphogenetic protein 2 (BMP-2) on hydroxylated micro-porous PEEK films for enhancing the biological activity. Environmental scanning electron microscope (ESEM), fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS) and water contact angle measurements were applied to characterize the surface of modified or untreated PEEK films. The influence on cell adhesion, proliferation and differentiation was evaluated by culturing of mouse pre-osteoblasts (MC3T3-E1) on different modified PEEK substrates in vitro. Surface characterization showed that the modification was successfully performed on PEEK films. The biological results indicated that surface modification of micro-porous PEEK using phosphorylated gelatin significantly promoted cell adhesion and proliferation. And the osteogenic differentiation was effectively improved while loading with different amounts of BMP-2. Findings from this study indicated that this novel biological modification on PEEK films might be helpful for altering its biological inertness and further expand its medical applications as a kind of orthopedic implants., (Copyright © 2018. Published by Elsevier B.V.)

Objectives: To compare the effectiveness and safety between autologous platelet-rich plasma (PRP) and Local Anesthetic (LA)/corticosteroid in intra-articular injection for the treatment of lumbar facet joint syndrome., Methods: Forty-six eligible patients with lumbar facet joint syndrome were randomized into group A (intra-articular injection with PRP) and group B (intra-articular injection with LA/corticosteroid). The following contents were evaluated: pain visual analog scale (VAS) at rest and during flexion, and the Roland-Morris Disability Questionnaire (RMQ), Oswestry Disability Index (ODI), and modified MacNab criteria for pain relief and applications of post-treatment drugs. All outcome assessments were performed immediately after and at 1 week, 1, 2, 3, and 6 months after treatment., Results: No significant difference between groups was observed at baseline. Compared with pretreatment, both group A and group B demonstrated statistical improvements in the pain VAS score at rest or during flexion, the RMQ, and the ODI (P < 0.01). And there were significant differences between the 2 groups on the above-mentioned items (P < 0.05). For group B, subjective satisfaction based on the modified MacNab criteria and objective success rate were highest (80% and 85%) after 1 month, but only 50% and 20% after 6 months. However, for group A, they increased over time. In addition, there were no treatment-related complications in either group during follow-up., Conclusions: Both autologous PRP and LA/corticosteroid for intra-articular injection are effective, easy, and safe enough in the treatment of lumbar facet joint syndrome. However, autologous PRP is a superior treatment option for longer duration efficacy., (© 2016 World Institute of Pain.)

Background and Objectives: Lumbar facet joint syndrome is currently suggested to be a main source of axial low back pain, and a large portion of axial low back pain is caused by disorders in lumbar facet joints. Intra-articular injection is one of the most common treatment methods in the early clinical application. Therefore, we attempt to seek a new injectable material, autologous platelet rich plasma (PRP), to treat lumbar facet syndrome, as well as to assess its therapeutic effectiveness and safety., Study Design: A prospective clinic evaluation., Setting: The outpatient clinic of a single academic medical center., Methods: Total 19 patients with lumbar facet joint syndrome (8 men, 11 women; mean ages: 52.53 ± 6.79 years, range: 38 - 62 years) were enrolled to receive lumbar facet joint injection with autologous PRP under x-ray fluoroscopic control. Patients were followed up immediately, at one week, one month, 2 months, and 3 months following treatment, and the elements of this analysis included low back pain visual analogue scale (VAS) at rest and during flexion, Roland-Morris Disability Questionnaire (RMQ), Oswestry Disability Index (ODI), and modified MacNab criteria for the pain relief., Results: All the 19 patients completed the intra-articular injections with autologous PRP successfully. At one week after treatment, low back pain reduced significantly compared with prior to treatment both at rest and during flexion. The outcomes were assessed as "good" or "excellent" for 9 patients (47.37%) immediately after treatment, 14 patients (73.68%) at one week, 15 patients (78.95%) at one month, 15 patients (78.95%) at 2 months, and 15 patients (78.95%) at 3 months. Statistically significant differences were observed based on RMQ and a more than 10% improvement in lumbar functional capacity was observed based on ODI between pre-treatment and post-treatment. In addition, there were no severe relevant complications during the whole process of injection and follow-up period., Limitations: A control group and the curative effect observations with longer follow-up may lead to a more convincing result for our study., Conclusions: In the short-term period of 3 months, the new technique of lumbar facet joint injection with autologous PRP is effective and safe for patients with lumbar facet joint syndrome. Key words: Low back pain, lumbar facet joint syndrome, autologous platelet rich plasma, intra-articular injection.

The role of insulin signaling on the mechanism underlying fluoride induced osteopathology was studied. We analyzed the expression of genes related with bone turnover and insulin signaling in rats treated by varying dose of fluoride with or without streptozotocin (STZ) in vivo. Furthermore, insulin receptor (InR) expression in MC3T3-E1 cells (pre-osteoblast cell line) was interfered with small interfering RNA (siRNA), and genes related with osteoblastic and osteoclastic differentiation were investigated in cells exposed to fluoride in vitro for 2 days. The in vivo study indicated the possible role of insulin in bone lesion induced by excessive amount of fluoride. Fluoride activated the InR and Insulin-like growth factor 1 (IGF1) signaling, which were involved in the mechanism underlying fluoride induced bone turnover. The TGFβ1 and Wnt10/β-catenin pathway took part in the mechanism of bone lesion induced by fluoride, and insulin probably modulated the TGFβ1 and β-catenin to exert action on bone turnover during the development of bone lesion. The in vitro study showed the concomitant decrease of OPG, osterix and OCN with inhibition of InR expression in osteoblast, and three genes still was low in cells co-treated with fluoride and InR siRNA, which suggested that fluoride probably stimulated the expression of OPG, osterix and OCN through InR signaling. In conclusion, insulin played the important role in bone lesion induced by excessive amount of fluoride through mediating InR receptor signaling, and IGF1 signaling probably exerted action on bone turnover caused by overdose of fluoride.

Aims: The aim of the present study was to investigate the prognostic value of B-cell associated protein 31 (BAP31) in human primary hepatocellular carcinoma (HCC)., Methods and Results: BAP31 levels were evaluated by immunohistochemistry on tissue microarrays. The integral optical density, representing the expression level of BAP31 in each tissue sample, was calculated with image-pro plus. Immunohistochemical analysis of BAP31 levels in 74 paired HCC tissues and peritumoral non-cancerous tissues showed that BAP31 expression was significantly higher in HCC tumour tissues (P = 0.025). The prognostic value of BAP31 in HCC was evaluated in 234 cases in a training cohort and in 63 cases in a validation cohort. The expression level of BAP31 was significantly correlated with overall survival (OS) in both the training cohort and the validation cohort. The lower the level of BAP31 expression in HCC tissue, the poorer the prognosis. Univariate and multivariate analyses showed that the expression level of BAP31 in HCC was an independent prognostic factor for OS in both the training cohort and the validation cohort., Conclusions: BAP31 expression is an independent prognostic factor for OS of patients with postoperative HCC, and low expression levels of BAP31 in HCC may indicate poor outcomes of HCC patient after surgical resection., (© 2015 John Wiley & Sons Ltd.)

Aims: Sorafenib, which has been used extensively for the treatment of renal cell cancer and advanced hepatocellular carcinoma (HCC), has also been shown to have antifibrotic effects in liver fibrosis. However, the effects of sorafenib on renal fibrosis are unknown. Therefore, we investigated whether sorafenib inhibited renal fibrosis in a mouse model of unilateral ureteral obstruction (UUO) and further explored the potential mechanism., Methods: Mice underwent UUO followed by vehicle or sorafenib treatment. The expression of CD68, a macrophage marker, and the pro-inflammatory cytokines, MCP1 and CXCR3, were immunohistochemically analyzed. The involvement of macrophages in the formation of renal fibrosis was studied using confocal microscopy., Results: Renal histopathology improved in the UUO-sorafenib mice. Sorafenib notably suppressed TGF-β1-mediated renal fibrogenic effects. The mRNA and protein expressions of CD68, MCP1, and CXCR3 in the obstructed kidney were significantly decreased by sorafenib. Immunohistochemistry showed that CD68 and CXCR3 had a similar distribution, whereas MCP1 was observed predominantly in the tubular epithelial cells. Double immunofluorescence demonstrated that CD68-positive macrophages could co-localize with CXCR3. It also revealed that CXCR3 interacted with CXCL11 in the UUO mouse kidneys. Widespread adhesion of macrophages to myofibroblasts was markedly inhibited in UUO-sorafenib mouse kidneys., Conclusions: Taken together, the results indicated that sorafenib had protective effects against renal fibrosis; its mechanism of action was associated with inhibition of macrophage infiltration via the CXCR3/CXCL11 pathway. These data suggest the clinical potential of sorafenib for treatment of renal fibrosis and illustrate the immunological mechanisms underlying the protective effects of sorafenib., (© 2016 The Author(s) Published by S. Karger AG, Basel.)

The purpose of this work is to study the action of fluoride on osteoblastic function through knocking down double-stranded RNA-activated protein kinase (PKR)-like ER kinase (PERK) mRNA in OS732 cells (human osteoblast-like cell line). The previous researches had demonstrated that fluoride induced endoplasmic reticulum (ER) stresses in other cells or tissues. PERK as one branch of UPR to combat ER stress played a role in mediating the proliferation and differentiation of osteoblast. The mechanism of skeletal fluorosis by which fluoride regulated osteoblast was not fully defined. We used the real-time PCR and small interfering RNA techniques to determine the expression PERK signaling and osteoblastic and osteoclastic differentiation-related factors and investigated the role of PERK signaling in fluoride-stimulated osteoblastic function. Cells transfected with 50 nM small interfering RNA (siRNA)-PERK showed effectively decreased protein and gene expression of PERK and reduced protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2). Meantime, cells transfected with siRNA significantly decreased the protein level of alkaline phosphatase (ALP) and nuclear factor kappa B ligand (RANKL) in cells under fluoride exposure. It suggested that knockdown of PERK expression hardly stimulated osteoblastic and osteoclastic early differentiation induced by fluoride. Conversely, there were littler effect of siRNA PERK on expression of Runt-related transcription factor 2 (RUNX2) and osteoprotegerin (OPG) in cells, but fluoride exposure markedly stimulated their expression. This study proved that the mechanism underlying fluoride induced osteoblastic and osteoclastic differentiation possible was due to activation of ALP and RANKL mediated by PERK in OS732 cells.

Schwann cells (SCs) are the major cells constituting the peripheral nerve structure and function, and also secret a variety of neurotrophic factors. Schwann cell (SC) transplantation has recently emerged as a promising therapeutic strategy for spinal cord injury (SCI). In the present study, the ability of genetically modified SCs producing high levels of glial cell line‑derived neurotrophic factor (GDNF) to promote spinal cord repair was assessed. The GDNF gene was transduced into SCs. The engineered SCs were characterized by their ability to express and secrete biologically active GDNF, which was shown to inhibit apoptosis of primary rat neurons induced by radiation, and upregulate the expression of B‑cell lymphoma 2 (Bcl‑2) and downregulate the expression of Bcl‑2 associated X protein (Bax) in vitro. Following SC implantation into the spinal cord of adult rats with SCI induced by weight‑drop impact, the survival of rats with transplanted SCs, histology of the spinal cord and expression levels of Bcl‑2 and Bax were examined. Transplantation of unmodified and genetically modified SCs producing GDNF attenuated SCI by inhibiting apoptosis via the Bcl‑2/Bax pathways. The genetically modified SCs demonstrated markedly improved recovery of SCI as compared with unmodified SCs. The present study combined the outgrowth‑promoting property of SCs with the neuroprotective effects of overexpressed GDNF and identified this as a potential novel therapeutic strategy for SCI.

P15, a synthetic 15 amino acid peptide, mimics the cell-binding domain within the alpha-1 chain of human collagen is being tested in clinical trials to determine if it enhances bone formation in spinal fusions. We hypothesize that covalent attachment of P15 to titanium implants may also serve to promote osseointegration. To test this hypothesis, we measured osteoblast and mesenchymal cell adhesion, proliferation, and maturation on P15 tethered to a titanium (Ti-P15) surface. P15 peptide was covalently bonded to titanium alloy surfaces and incubated with osteoblast like cells. Cell toxicity, adhesion, spreading, and differentiation was then evaluated. Real-time quantitative PCR, Western blot analysis, and fluorescent immunohistochemistry was performed to measure osteoblast gene expression and differentiation. There was no evidence of toxicity. Significant increases in early cell attachment, spreading, and proliferation were observed on the Ti-P15 surface. Increased filapodial attachments, α(2) integrin expression, and phosphorylated focal adhesion kinase immunostaining indicated activation of integrin signaling pathways. qRT-PCR analysis indicated there was significant increase in osteogenic differentiation markers in cells grown on Ti-P15 compared to control-Ti. Western blotting confirmed these findings. Surface modification of titanium with P15 significantly increased cell attachment, spreading, osteogenic gene expression, and differentiation. Results of this study suggest that Ti-P15 has the potential to safely enhance bone formation and promote osseointegration of titanium implants., (Copyright © 2012 Orthopaedic Research Society.)

Study Design: Two-year prospective multicenter clinical trial., Objective: To determine the safety and efficacy of the anterior I/F Cage in the primary treatment of single-level degenerative disc disease., Summary of Background Data: A carbon fiber-reinforced polymer cage was designed to replace the traditional allograft/autograft structural graft used in an anterior lumbar interbody fusion (ALIF). Although the outcomes of various types of ALIF cages have previously been reported, the safety and efficacy of the I/F cage are unknown., Methods: Between June 2000 and June 2004, 112 patients were prospectively enrolled at 12 study sites for the current study. Efficacy was evaluated clinically and radiographically. "Patient success" was declared only when the following 4 criteria were present at final follow-up: (1) "clinical success": improvement of 15 points on Oswestry Disability Index, (2) absence of a new neurologic abnormality, (3) successful radiographic fusion, and (4) no subsequent secondary surgical intervention at 24-month follow-up. Safety was inferred by way of an objective summary of complications and adverse events, as reported at regular intervals throughout the course of the study., Results: A total of 112 patients (mean age: 41.7 years) underwent a single-level ALIF procedure (L5-S1: 95 patients, L4-L5: 17 patients). The mean surgical time was 126 minutes, the mean estimated blood loss was 134 mL, and the mean duration of hospitalization was 3.3 days. There were 80 patients available for 24-month follow-up. Overall patient success was 25% (20/80). Clinical success was present in 46.3% (37/80), fusion success was 57.5% (46/80), and 87.5% of patients (70/80) avoided a subsequent secondary surgical intervention. Disc space height had significantly increased after surgery, and this increase was maintained at 2 years follow-up period. Complications and adverse events included the following: 8 infections (7.1%) (7 superficial, 1 deep), 2 vascular injuries (1.8%) (left common iliac vein), and 12 secondary surgical interventions (15%)., Conclusion: This safety and efficacy study suggests that the anterior I/F Cage is a safe surgical option in the treatment of single-level lumbar degenerative disc disease. As a stand-alone construct, the I/F Cage yields suboptimal radiographic and clinical outcomes. Additional benefit may be gained from adjunctive posterior stabilization.

Objective: To investigate the surgical method and perioperative treatment for senile lumbar disease accompanied by internal disease., Methods: From June 2000 to December 2003, the complete neurological and physical examinations were performed on the patients before operation, as treatment of internal diseases could improve the patients' conditions. Lumbar operations were performed on 125 patients, among whom 23 had simple lumbar disc herniation, 13 had lumbar spine stenosis, 81 had lumbar disc herniation with lumbar spine stenosis, and 8 had spondylolisthesis. The JOA score was 11.6 +/- 2.5. There were 3 patients undergoing fenestration + discectomy, 16 undergoing semi-laminectomy + discectomy, 82 undergoing total-laminectomy + discectomy, 5 undergoing total-laminectomy+discectomy+pedicle fixation, 11 undergoing lamina decompression+nerve-root pathway decompression, and 8 undergoing pedicle screw fixation+bone graft and fusion in spondylolisthesis., Results: With an effective medical treatment, the internal disease produced little effect on the operation. Improved functions and bone fusions were observed after operation. According to the JOA standards, the average alleviation rate was 87.9%., Conclusion: Early neurological examination and proper treatment of internal diseases are the keys to the successful operation on the senile patients with lumbar disease. Radiological data are important in avoidance of mistaken diagnosis.