Salidroside promotes the repair of spinal cord injury by inhibiting astrocyte polarization, promoting neural stem cell proliferation and neuronal differentiation.

Spinal cord injury (SCI) remains a formidable challenge, lacking effective treatments. Following SCI, neural stem cells (NSCs) migrate to SCI sites, offering a potential avenue for nerve regeneration, but the effectiveness of this intrinsic repair mechanism remains suboptimal. Salidroside has demonstrated pro-repair attributes in various pathological conditions, including arthritis and cerebral ischemia, and the ability to curtail early-stage inflammation following SCI. However, the specific role of salidroside in the late-stage repair processes of SCI remains less defined. In this investigation, we observed that continuous salidroside treatment in SCI mice improved motor function recovery. Immunofluorescence-staining corroborated salidroside's capacity to stimulate nerve regeneration and remyelination, suppress glial scar hyperplasia, reduce the activation of neurotoxic A1 astrocytes, and facilitate NSCs migration towards the injured region. Mechanistically, in vitro experiments elucidated salidroside's significant role in restraining astrocyte proliferation and A1 polarization. It was further established that A1 astrocytes hinder NSCs proliferation while inducing their differentiation into astrocytes. Salidroside effectively ameliorated this inhibition of NSCs proliferation through diminishing c-Jun N-terminal kinase (JNK) pathway phosphorylation and restored their differentiation into neurons by suppressing the signal transducer and activator of transcription 3 (STAT3) pathway. In summary, our findings suggest that salidroside holds promise as a therapeutic agent for traumatic SCI treatment.

Co-overexpression of OPN, IGF-1 and CNTF augment the therapeutic effect of DPSC on spinal cord injury.

Background aims: Spinal cord injury (SCI) is one of the most complex and destructive diseases of the nervous system, which can lead to permanent loss of tactile perception. But existing treatment methods have limited effects. To establish a novel method that may be therapeutic in repairing the injured spinal cord, gene-modified dental pulp stem cells (DPSCs) were injected in situ. Methods: Adenovirus carrying osteopontin (OPN), Insulin-like growth factor 1 (IGF-1) and cailiary-derived neurotrophic factor (CNTF) (Ad-OIC) was constructed. After modified with Ad-OIC, supernatant of DPSC were co-cultured with HT-22 cells and the effect of DPSC-OIC on the HT-22 cells were evaluated via Cell Counting Kit-8 (CCK-8) assay, Real-Time polymerase chain reaction (PCR) analysis, laser confocal microscopy and fluorescence activating cell sorter (FACS). DPSC-OIC were injected in the lesion area of injured spinal cord and the survival time of transplanted cells were measured by bioluminescence imaging system. The recovery of the injured spinal cord was evaluated by behavioral score, radiological evaluation and immunopathological analysis. Results: DPSC-OIC could enhance the proliferation and axon growth of HT-22 cells, and protect HT-22 cells from H2O2 induced apoptosis. The transplanted DPSC-Null or DPSC-OIC could survive for more than two weeks in local injection site. DPSC-OIC treatment could increase Basso-Mouse Scale (BMS) scores, improve Magnetic Resonance Imaging (MRI) manifestation and promote bladder function recovery. Less apoptotic neurons and more proliferative cells were found in the lesion area of DPSC-OIC treated spinal cord. Nestin+ cells and neural stem cell marker (Sox2) were both up-regulated after DPSC-OIC treatment. Additionally, inhibitory extracellular matrix proteoglycan Neural/Glial Antigen 2 (NG2) was down-regulated and axon growth promotive factor fibronectin was up-regulated after both DPSC-Null (DPSCs infected with Ad-Null) and DPSC-OIC treatments. Conclusions: DPSC-OIC could be a novel effective method for treating SCI.

Periostin-targeted SDSSD peptide decorated calcium phosphate nanocomposites incorporation with simvastatin for osteoporosis treatment.

The limited options of anabolic drugs restrict their application potential in osteoporosis treatment, despite their theoretical superiority in therapeutic efficacy over antiresorptive drugs. As a prevailing strategy, nano-delivery systems could offer a wider choice of anabolic drugs. In this study, calcium phosphate nanocomposites incorporated with simvastatin (Sim) with periostin-targeting ability were designed and prepared for osteoporosis treatment. Carboxymethyl dextran (CMD) as an anionic and hydrophilic dextran derivative was used to stabilize CaP. In addition, periosteum-targeted peptide (SDSSD) was further grafted on CMD to achieve the bone targeting function. In a one-step coordination assembly strategy, hydrophobic anabolic agent Sim and SDSSD-CMD graft (SDSSD-CMD) were incorporated into the CaP nanoparticles forming SDSSD@CaP/Sim nanocomposites. The resulting SDSSD@CaP/Sim possesses uniform size, great short-term stability and excellent biocompatibility. Moreover, SDSSD@CaP/Sim exhibited a reduced release rate of Sim and showed slow-release behaviour. As anticipated, the nanocomposites exhibited bone bonding capacity in both cellular and animal studies. Besides, SDSSD@CaP/Sim achieved obviously enhanced osteoporosis treatment effect compared to direct injection of Simin vivo. Therefore, our findings highlight the potential of SDSSD-incorporated and CaP-based nanocomposites as a viable strategy to enhance the therapeutic efficacy of anabolic drugs for osteoporosis treatment.

Preparation and Characterization of Body-Temperature-Responsive Thermoset Shape Memory Polyurethane for Medical Applications.

Shape memory polymers (SMPs) are currently one of the most attractive smart materials expected to replace traditional shape memory alloys and ceramics (SMAs and SMCs, respectively) in some fields because of their unique properties of high deformability, low density, easy processing, and low cost. As one of the most popular SMPs, shape memory polyurethane (SMPU) has received extensive attention in the fields of biomedicine and smart textiles due to its biocompatibility and adjustable thermal transition temperature. However, its laborious synthesis, limitation to thermal response, poor conductivity, and low modulus limit its wider application. In this work, biocompatible poly(ε-caprolactone) diol (PCL-2OH) is used as the soft segment, isophorone diisocyanate (IPDI) is used as the hard segment, and glycerol (GL) is used as the crosslinking agent to prepare thermoset SMPU with a thermal transition temperature close to body temperature for convenient medical applications. The effects of different soft-chain molecular weights and crosslinking densities on the SMPU's properties are studied. It is determined that the SMPU has the best comprehensive performance when the molar ratio of IPDI:PCL-2OH:GL is 2:1.5:0.33, which can trigger shape memory recovery at body temperature and maintain 450% recoverable strain. Such materials are excellent candidates for medical devices and can make great contributions to human health.

Mid-term low back pain improvement after total hip arthroplasty in 306 patients with developmental dysplasia of the hip.

BACKGROUND: Low back pain (LBP) from hip and spinal disorders has been one of the main reasons for visiting physicians in patients with developmental dysplasia of the hip (DDH). It is essential to identify the LBP improvement among all grades of DDH patients treated with total hip arthroplasty (THA) at 5-year follow-up. METHODS: The study included 407 hips of 306 patients (38 males, 268 females) who underwent THA between July 2007 and December 2016. There were 65 hips in Crowe I, 61 hips in Crowe II, 69 hips in Crowe III, and 212 hips in Crowe IV. One hundred and fourteen hips received subtrochanteric shortening. Patients included 101 bilateral THA (BTHA) and 205 unilateral THA (UTHA). The evaluation was performed through Back Pain Function Scale (BPFS), Harris hip score, Visual Analogue Scale (VAS), operative data and radiographic examinations. RESULTS: The BPFS in patients of unilateral Crowe III and IV relieved significantly more (p < 0.05). However, the BPFS in patients with bilateral symmetry DDH hips relieved significantly less than other groups of DDH hips (p < 0.05). Harris in hips of Crowe II improved significantly more (p < 0.05). The VAS in hips of Crowe II and III improved significantly more (p < 0.05). The unilateral THA surgical time, blood loss, blood transfusion, and osteotomy number and length in Crowe IV were significantly more (p < 0.05). CONCLUSION: THA is reliable to relieve LBP in DDH patients of unilateral Crowe III and IV; however, in patients with unilateral Crowe I, Crowe II, and bilateral DDH hips, the LBP improvements were limited. This should assist shared decision-making between orthopedic surgeons and patients. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

A biomimetic gradient porous cage with a micro-structure for enhancing mechanical properties and accelerating osseointegration in spinal fusion.

Objectives: Spinal fusion is a widely employed treatment of patients with degenerative disc disease, in which a cage is used to replace the disc for spinal fusion. But it often fails for insufficient mechanical strength and poor osseointegration. Here, we designed a polyether-ether-ketone (PEEK)/tantalum (Ta) composite cage with a biomimetic gradient porous micro-structure, simultaneously enhancing mechanical properties and accelerating osseointegration in spinal fusion. Materials and methods: In the study, based on the mechanical performances of PEEK and osteogenic potential of Ta, and the three-dimensional (3D) structures of cuttlebone and vertebra, the cages were respectively 3D printed by pure PEEK, PEEK with 5 wt% Ta (PEEK/Ta-5), PEEK with 10 wt% Ta (PEEK/Ta-10) and PEEK with 15 wt% Ta (PEEK/Ta-15), then verified in vitro and in sheep cervical fusion model systematically. Results: Vertebral Gyroid structure PEEK/Ta-15 cage exhibited superior mechanical properties than Cuttlebone-like structure PEEK/Ta-15 cage, closer to the cervical vertebra. Furthermore, PEEK/Ta-15 cage with higher Ta microparticles in PEEK provided a biomimetic gradient porous micro-structure with higher surface energy, guiding cell biological behavior, promoting new bone penetration, and accelerating osseointegration in vivo. Conclusion: In conclusion, the study designed a biomimetic gradient porous cage with a micro-structure for enhancing mechanical properties, accelerating osseointegration and forming an anatomical lock in the fusion segment through composites, mechanical efficiency, surface extension, and pores.

Titanium surface polyethylene glycol hydrogel and gentamicin-loaded cross-linked starch microspheres release system for anti-infective drugs.

OBJECTIVE: To design and construct a hydrogel drug-controlled release system loaded with gentamicin on a titanium surface, and to evaluate the in vitro drug release behaviour and antibacterial properties and biocompatibility of the controlled release system. METHODS: Titanium (Ti) surface was coated with poly dopamine (PDA) substrate, and then polyethylene glycol (PEG) was attached to PDA. The composite drug microsphere controlled release layer formed by gentamicin (GEN) and cross-linked starch (CSt) were subsequently covered with poly lactic⁃co⁃glycolic acid (PLGA) as a barrier to construct a Ti-GEN-Cst-PLGA anti-infective drug controlled release system. RESULTS: The hydrogel drug release system was successfully constructed. The results of in vitro anti-staphylococcus aureus (SAU) assay, anti-staphylococcus epidermidis (SEP) assay and anti-Escherichia coli (ECO) assay showed that Ti-GEN-Cst-PLGA could effectively inhibit the growth of three bacteria. Assay in the New Zealand rabbit found that Ti-GEN-Cst-PLGA could promote wound healing at the 3rd week after implantation, and the pathology assay found that the Ti-GEN-Cst-PLGA group had less inflammatory reactions and significant tissue proliferation at the endophyte contact surface. CONCLUSION: Ti-GEN-Cst-PLGA can effectively inhibit the inflammatory response and promote wound healing, or may be a potential treatment for orthopaedic endophytes.

Cross-cultural adaptation and validation of the simplified Chinese version of the Exercise-Induced Leg Pain Questionnaire (EILP).

PURPOSE: This study cross-culturally adapted and psychometrically validated a simplified Chinese version of the Exercise-Induced Leg Pain Questionnaire (SC-EILP) for evaluating the severity of symptoms and sports ability among individuals with exercise-induced leg pain. MATERIALS AND METHODS: One hundred and fourteen participants with exercise-induced leg pain were included. To assess reliability, we calculated Cronbach's α and intra-class correlation coefficient (ICC). Construct validity was analysed by assessing the correlations between SC-EILP and visual analogue scale (VAS), University of California Los Angeles activity score (UCLA), and short form (36) health survey (SF-36). Factorial validity was used to establish the factor structure of the questionnaire. RESULTS: The EILP was cross-culturally well-adapted and translated into simplified Chinese. Each item was appropriately correlated with the total items. SC-EILP had nearly good reliability [Cronbach's α = 0.798, ICC = 0.897, 95% confidence interval 0.851-0.929]. The elimination of any one item in all did not result in a value of Cronbach's α of <0.80. SC-EILP had a very good correlation with VAS (-0.607, p < 0.01) and a moderate correlation with UCLA (0.581, p < 0.01) and physical domains of SF-36 (0.499-0.528, p < 0.01). Exploratory factor analysis revealed the 3-factor loading explained 74.736% of the total variance [Kaiser-Mayer-Olkin (KMO) = 0.672, C2 = 665.34, p < 0.001]. CONCLUSIONS: SC-EILP showed excellent acceptability, internal consistency, reliability, and construct validity, and could be recommended for individuals in Mainland China.

This study translated and cross-culturally adapted Exercise-Induced Leg Pain Questionnaire into a Simplified Chinese version, and evaluated its reliability and validity in individuals with exercise-induced leg pain.Moderate to substantial correlations between the Simplified Chinese version of the Exercise-Induced Leg Pain Questionnaire and VAS, UCLA, as well as physical subscales of SF-36 were observed.Exploratory factor analysis revealed that the 3-factor loading explained 74.736% of the total variance [Kaiser­Mayer­Olkin (KMO) = 0.672, C² = 665.34, p < 0.001].Simplified Chinese version of the Exercise-Induced Leg Pain Questionnaire was demonstrated to have acceptable simplicity, good reliability, and validity in individuals with exercise-induced leg pain, which could be recommended for patients in Chinese mainland.

Hydroxytyrosol Ameliorates Intervertebral Disc Degeneration and Neuropathic Pain by Reducing Oxidative Stress and Inflammation.

Low back pain (LBP) seriously affects human quality of life. Intervertebral disc degeneration (IVDD) is the main pathological factor that leads to LBP, but the pathological mechanism underlying IVDD has not been fully elucidated. Neuropathic pain caused by IVDD is an important pathological factor affecting people's daily lives. Therefore, it is very important to identify therapeutic drugs to ameliorate IVDD and secondary neuropathic pain. Hydroxytyrosol (HT) is a natural compound derived from olive leaves and oil and has anti-inflammatory, antioxidant, and antitumor activities and other properties. In this study, TNF-α-stimulated human nucleus pulposus cells (HNPCs) were used to simulate the local inflammatory microenvironment observed in IVDD in vitro to explore the role of HT in alleviating various pathological processes associated with IVDD. A rat needle puncture model was used to further explore the role of HT in alleviating IVDD. Lipopolysaccharide (LPS) was used to stimulate microglia in vitro to comprehensively explore the role of HT in alleviating neuropathic pain, and a rat model involving chronic compression of the dorsal root ganglion (CCD) was established to simulate the neuropathic pain caused by IVDD. This study suggests that HT reduces the expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4) and matrix metalloproteinase-13 (MMP-13); inhibits the production of mitochondrial reactive oxygen species (ROS); and maintains mitochondrial homeostasis. Thus, HT appears to reduce the rate of apoptosis and mitigate the loss of major intervertebral disc components by inhibiting the nuclear factor kappa-B (NF-κB) signaling pathway. Moreover, HT inhibited the secretion of COX-2, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1ß, and iNOS and activation of the NLRP3 inflammasome in microglia by inhibiting the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and extracellular regulated protein kinase (ERK) signaling pathways. In conclusion, HT plays a protective role against IVDD and secondary neuropathic pain by inhibiting the NF-κB, PI3K/AKT, and ERK signaling pathways.

DPSCs Protect Architectural Integrity and Alleviate Intervertebral Disc Degeneration by Regulating Nucleus Pulposus Immune Status.

Intervertebral disc (IVD) degeneration is the primary cause for low back pain that has a high prevalence in modern society and poses enormous economic burden on patients. Few effective therapeutic strategies are available for IVD degeneration treatment. To understand the biological effects of dental pulp stem cells (DPSCs) on nucleus pulposus (NP) cells, we carried out RNA sequencing, bioinformatic analysis which unveiled gene expression differences, and pathway variation in primarily isolated patients' NP cells after treatment with DPSCs supernatant. Western blot and immunofluorescence were used to verify these molecular alterations. Besides, to evaluate the therapeutic effect of DPSCs in IVD degeneration treatment, DPSCs were injected into a degeneration rat model in situ, with treatment outcome measured by micro-CT and histological analysis. RNA sequencing and in vitro experiments demonstrated that DPSCs supernatant could downregulate NP cells' inflammation-related NF-κB and JAK-STAT pathways, reduce IL-6 production, increase collagen II expression, and mitigate apoptosis. In vivo results showed that DPSCs treatment protected the integrity of the disc structure, alleviated extracellular matrix degradation, and increased collagen fiber expression. In this study, we verified the therapeutic effect of DPSCs in an IVD degeneration rat model and elucidated the underlying molecular mechanism of DPSCs treatment, which provides a foundation for the application of DPSCs in IVD degeneration treatment.

Are Both Preoperative Full-Spine 3Dimensional Computed Tomography Scans and X-Ray Films Necessary for Patients with Ankylosing Spondylitis Kyphosis?

OBJECTIVE: This study is aimed to investigate whether both pre-operative full-spine 3Dimensional computed tomography scan (3D CT) and X-ray film were necessary for patients with severe ankylosing spondylitis (AS) kyphosis deformity. METHODS: The research objects were selected from the inpatients with AS in our hospital from 2017 to 2019. A total of 42 patients were included in the study. On both the synthesized 2Dimensional (2D) lateral radiograph and X-ray film, the globe kyphosis (GK), the lumber lordosis (LL), the thoracolumbar kyphosis (TLK) and the thoracic kyphosis (TK) were measured. And the angle seventh thoracic vertebra (T7), the angle twelfth thoracic vertebra (T12) and the angle third lumber vertebra (L3) were also measured. Two researchers with professional medical education were randomly selected to perform the measurement method and record the measurement data. Two researchers independently completed, recorded, and evaluated the accuracy and consistency of the measurement data. This study used intraclass correlation coefficient (ICC) to analyze the synthesized 2D lateral radiograph and general X-ray film of 42 subjects by two researchers, in order to evaluate the consistency of data measurement results between the examiners. Through the comparison of the above parameters that the GK, LL, TLK, TK, angle T7, angle T12 and angle L3, the evaluation was made both pre-operative full-spine 3D CT and X-ray film were necessary for patients with severe AS kyphosis deformity. RESULTS: There was no significant difference between the GK, LL, TLK, TK, angle T7, angle T12, angle L3 on the synthesized 2D lateral radiograph and that on X-ray film (P = 0.240, 0.324, 0.199, 0.095, 0.421, 0.087, 0.478). Agreement two researchers was excellent with ICC of the GK, LL, TLK, TK, angle T7, angle T12, angle L3 (0.977, 0.969, 0.986, 0.945, 0.947, 0.915, 0.857) on the synthesized 2D lateral radiograph. The Bland-Altman plot results that the measurement results of examiners are reliable and stable. CONCLUSION: By estimating the degree of spinal sagittal imbalance and measuring the Cobb angle, we can see that full-length spine radiographs of the patients are unnecessary for patients with severe AS kyphosis deformity who will or have undergone preoperative spine 3D CT.

Clinical Results of Utilizing the Satellite Rod Technique in Treating Ankylosing Spondylitis Kyphosis.

OBJECTIVE: According to the literature, there are no clinical reports documenting the use of the satellite rod technique in the treatment of ankylosing spondylitis kyphosis. The purpose of this retrospective study was to compare the clinical outcome of patients with ankylosing spondylitis kyphosis who adopted satellite rods versus those who did not. METHODS: Patients with ankylosing spondylitis kyphosis who underwent one or two-level pedicle subtraction osteotomy (PSO) were reviewed, and total of 119 patients (112 males and seven females, average age 39.89 ± 6.61 years) were eligible and included in this present study. Anterior-posterior and lateral full-length spine X-ray films were performed preoperatively and at the two-year follow-up visit. Global kyphosis (GK), lumbar lordosis (LL), thoracolumbar kyphosis (TLK), thoracic kyphosis (TK), and osteotomy angle (OA) were measured. The complications of every group of patients were collected. Pre- and postoperative health-related quality of life instruments, including the Bath Ankylosing Spondylitis Functional Index (Basfi) and Scoliosis Research Society outcomes instrument-22 (SRS-22), were recorded. The patients were divided into three groups based on features of their osteotomy including PSO levels and whether the satellite rod technique was applied. Patients who underwent one-level PSO without the satellite rod technique were categorized in the one-level group. Patients who underwent one-level PSO with the satellite rod technique were classified in the satellite rod group. Patients who underwent two-level PSO without the satellite rod technique were included in the two-level group. The paired sample t test was used to compare pre- and postoperative parameters. One-way ANOVA was performed for multiple group comparisons. RESULTS: The average follow-up time is 29.31 ± 3.66 months. The patients' GK were significantly improved from 46.84 ± 20.37 degree to 3.31 ± 15.09 degree. OS achieved through each osteotomy segment of one-level group (39.78 ± 12.29 degree) and satellite rods group (42.23 ± 9.82 degree), was larger than that of two-level group (34.73 ± 7.54 and 28.85 ± 7.26 degree). There was no significant difference between the one-level group and the satellite rod group in achieving the OS. Thirteen patients experienced different complications (10.92%). Three patients experienced rod fracture in the one-level group. There was no rod fracture or screw failure in the satellite rod group or the two-level group. CONCLUSION: The satellite rod technique is also recommended for patients who undergo PSO osteotomy to correct ankylosing spondylitis kyphosis deformities.

A Comparison Between Retaining and Resecting the Posterior Longitudinal Ligament in Percutaneous Endoscopic Transforaminal Discectomy for Disc Herniation: A Retrospective Cohort Study.

OBJECTIVE: To compare the efficacy and safety of retaining the posterior longitudinal ligament (PLL) with resecting the PLL in inside-out percutaneous endoscopic transforaminal discectomy (PETD) surgery for lumbar disc herniation (LDH). METHOD: A total of 135 patients with symptomatic LDH who were treated by inside-out PETD surgery from January 2015 to January 2017were included in this retrospective analysis. There were 38 males and 30 females in the PLL resection group (mean age = 52.40 ± 8.73 years) and 35 males and 32 females in the PLL retention group (mean age = 53.50 ± 9.24 years). The visual analogue scale (VAS) score, Oswestry disability index (ODI), and modified MacNab criteria were used to evaluate clinical outcomes. Operation time, blood loss, recurrence of LDH, and complications were recorded. Three months after surgery, magnetic resonance imaging was performed to confirm that nerve root compression was relieved. RESULTS: The VAS and ODI scores improved significantly immediately after surgery, at 1 month after surgery, at 3 months after surgery, and at last follow-up compared with those before surgery (P < 0.01). The scores also improved significantly between immediately after surgery and 1 month after surgery in the two groups (P < 0.001). Multivariate analysis indicated that age ≥ 50 years (odds ratio (OR) = 6.33, 95% confidence interval (CI): 1.64-21.98, P = 0.014), pain duration ≥6 months (OR = 4.68, 95% CI: 1.29-6.51, P = 0.025), pre-ODI score ≥ 40% (OR = 5.97, 95% CI: 2.41-14.86, P = 0.003) were all associated with poor functional outcomes. There was no significant difference in the excellent/good ratio between the two groups and the mean operation time of the retention group was 71.5% of that of the resection group (82.7 ± 18.5 min vs 115.6 ± 24.6 min, P < 0.01). In the patients, no serious complications, such as dural tear, wound infection, or persistent nerve root injury, were observed during the follow-up period. There was no significant difference in the complication rate between the two groups (6/68 vs 6/67, P = 0.979). Although the recurrence rate was higher in retention group, there was no significant difference between the two groups (1/68 vs 2/67, P = 0.551). CONCLUSION: The PLL is recommended to be retained for inside-out PETD surgery.

Dental pulp stem cell-derived exosomes suppress M1 macrophage polarization through the ROS-MAPK-NFκB P65 signaling pathway after spinal cord injury.

Stem cell-derived exosomes have recently been regarded as potential drugs for treating spinal cord injury (SCI) by reducing reactive oxygen species (ROS) and suppressing M1 macrophage polarization. However, the roles of ROS and exosomes in the process of M1 macrophage polarization are not known. Herein, we demonstrated that ROS can induce M1 macrophage polarization and have a concentration-dependent effect. ROS can induce M1 macrophage polarization through the MAPK-NFκB P65 signaling pathway. Dental pulp stem cell (DPSC)-derived exosomes can reduce macrophage M1 polarization through the ROS-MAPK-NFκB P65 signaling pathway in treating SCI. This study suggested that DPSC-derived exosomes might be a potential drug for treating SCI. Disruption of the cycle between ROS and M1 macrophage polarization might also be a potential effective treatment by reducing secondary damage.

Cross-cultural adaptation and validation of the simplified chinese version of the fremantle back awareness questionnaire in patients with low back Pain.

PURPOSE: The Fremantle back awareness questionnaire (FreBAQ) was recently developed as simple and quick tool to assess back-specific body perception in Low back pain (LBP) patients. The aim of the present study was to translate and cross-culturally adapt the Fremantle back awareness questionnaire (FreBAQ) into a Simplified Chinese version (FreBAQ-C), and evaluate the reliability and validity of the FreBAQ-C in patients with non-specific Chronic Low back pain (CLBP). METHODS: The FreBAQ was translated into Chinese according to established methods. Internal consistency was assessed according to Cronbach's alpha. Test-retest reliability was estimated by Intraclass correlation coefficient (ICC). Construct validity was evaluated by correlations between the FreBAQ-C and Visual analogue scale (VAS), Roland-Morris disability questionnaire (RDQ), Pain catastrophizing scale (PCS), Tampa scale for kinesiophobia (TSK) as well as Hospital anxiety and depression scale (HADS). RESULTS: A total of 105 participants (38 males and 67 females) were included in this study with the mean age of 54.1 ± 15.6 years, mean duration of LBP of 6.8 ± 4.6 years. The FreBAQ-C total scores were well distributed, with no floor or ceiling effects. Internal consistency was excellent (Cronbach's alpha = 0.833). ICC of test-retest reliability was good (0.897, 95% confidence interval: 0.852-0.929). The limits of agreement (LOA) ranged from - 5.8 to 6.3. The Standard error of measurement (SEM) and Minimum detectable change (MDC) were 2.16 and 5.99. Construct validity was confirmed by significant correlation of The FreBAQ-C and VAS during motion (r = 0.274, p = 0.005) and rest (r = 0.243, p = 0.012), RDQ (r = 0.377, p < 0.001), PCS (r = 0.439, p < 0.001), and TSK(r = 0.311, p = 0.001). CONCLUSIONS: The FreBAQ-C was demonstrated to have acceptable reliability and validity for patients with non-specific CLBP in Chinese mainland. It will allow evaluating body preception of the back in the Chinese population with CLBP.

Simplified Chinese Version of the Back Pain Function Scale (BPFS) for Patients with Low Back Pain: Cross-Cultural Adaptation and Validation.

STUDY DESIGN: A cross-sectional study. OBJECTIVE: To translate and cross-culturally adapt back pain function scale (BPFS) into a simplified Chinese version (SC-BPFS), and evaluate the reliability and validity of SC-BPFS in patients with low back pain. SUMMARY OF BACKGROUND DATA: The BPFS is a reliable and valid evaluation instrument for low back pain. However, simplified Chinese version of BPFS has not been validated. METHODS: Cross-cultural adaptation was performed according to the internationally recognized guidelines of the American Academy of Orthopaedic Surgeons Outcome Committee. One-hundred and sixty-two participants with low back pain (LBP) were included in this study. Reliability was tested based on test-retest reliability and internal consistency. We calculated Cronbach alpha and intra-class correlation coefficient (ICC). Construct validity was analyzed by evaluating the correlations between SC-BPFS and the Oswestry disability index (ODI), the visual analogue scale (VAS), and the short form (36) health survey (SF-36). RESULTS: The original version of the BPFS was cross-culturally well adapted and translated into simplified Chinese. Each item of the SC-BPFS was properly responded and correlated with the total items. SC-BPFS had good reliability (Cronbach alpha = 0.847, intra-class correlation coefficient [ICC] = 0.891, 95% confidence interval [CI] 0.864-0.914). Elimination of any one item in all did not result in a value of Cronbach alpha of <0.80. SC-BPFS had a high correlation with ODI (0.712, P < 0.01) and a moderate correlation with VAS (0.484, P < 0.01). And it was also fairly to very well correlated with physical domains of SF-36 (0.334-0.632, P < 0.01), and not correlated with mental domains of SF-36 (0.022-0.119, P > 0.05). CONCLUSION: SC-BPFS demonstrated outstanding acceptability, internal consistency, reliability, and construct validity, and could be recommended for patients with LBP in Mainland China.Level of Evidence: 3.

Anterior Pelvic Plane: A Potentially Useful Pelvic Anatomical Reference Plane in Assessing the Patients' Ideal Pelvic Parameters Without the Influence of Spinal Sagittal Deformity.

STUDY DESIGN: Observational study. OBJECTIVE: This study was aimed at investigating the reliability of anterior pelvic plane (APP) as an anatomical reference plane for assessing the patients' pelvic incidence in patients with ankylosing spondylitis kyphosis deformity. METHODS: The globe kyphosis (GK), lumber lordosis (LL), thoracolumbar kyphosis (TLK), thoracic kyphosis (TK), anatomical cervical 7 sacrum angle (aC7SA), and cervical 7 sacrum angle (C7SA) were measured on full-length spine radiography imagines. The pelvic incidence (PI), anatomical pelvic tilt (aPT), and anatomical sacral slope (aSS) were measured on the pelvic synthesized 2D lateral radiography imagines. Because the angle between APP and vertical line was about 4°, Angle1 and tPT were calculated using the following formulas: Angle1 = aC7SA - 4; PT = aPT + 4. According to the study conducted by Vialle, traditional PT (tPT) was calculated using the following widely accepted formula: tPT = PI * 0.37 - 7. Measured PT (mPT) was also measured on the full-length spine radiography imagines. RESULTS: The data analysis showed that PI, mPT, aSS, aPT, and APPA were 50.83 ± 13.44°, 32.52 ± 4.64°, 41.36 ± 9.46°, 8.56 ± 6.80°, and 23.95 ± 5.17°, respectively. There was no significant difference between the PT and tPT (12.56 ± 6.80, 11.49 ± 4.73; P = .152). So, the results demonstrated that the PT could play the equivalent effect as tPT did for making surgical plans in patients with kyphosis deformity. CONCLUSION: The pelvic anatomical reference plane had potential to be used in assessing the patients' ideal pelvic incident without the influence of spinal sagittal deformity. The aPT+4 may represent patients' postoperative ideal PT.

Hematopoietic cell kinase enhances osteosarcoma development via the MEK/ERK pathway.

Osteosarcoma (OS) is a sarcoma with high rates of pulmonary metastases and mortality. The mechanisms underlying tumour generation and development in OS are not well-understood. Haematopoietic cell kinase (HCK), a vital member of the Src family of kinase proteins, plays crucial roles in cancer progression and may act as an anticancer target; however, the mechanism by which HCK enhances OS development remains unexplored. Therefore, we investigated the role of HCK in OS development in vitro and in vivo. Downregulation of HCK attenuated OS cell proliferation, migration and invasion and increased OS cell apoptosis, whereas overexpression of HCK enhanced these processes. Mechanistically, HCK expression enhanced OS tumorigenesis via the mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway; HCK upregulation increased the phosphorylation of MEK and ERK and promoted epithelial-mesenchymal transition, with a reduction in E-cadherin in vitro. Furthermore, HCK downregulation decreased the tumour volume and weight in mice transplanted with OS cells. In conclusion, HCK plays a crucial role in OS tumorigenesis, progression and metastasis via the MEK/ERK pathway, suggesting that HCK is a potential target for developing treatments for OS.

Isobavachalcone prevents osteoporosis by suppressing activation of ERK and NF-κB pathways and M1 polarization of macrophages.

Estrogen receptors alpha (ERα), a member of the nuclear receptor protein family, was found to play an important role in maintaining bone mass. Its downstream signaling proteins such as ERK and NF-κB were reported to be involved in development of osteoporosis, which meant that targeting ERα might be an effective strategy for searching for new drugs to prevent bone loss. In this study, we demonstrate that isobavachalcone (ISO), as one of bioactive compounds isolated from Psoralea corylifoliaLinn, has high affinity with ERα. The effects of ISO are investigated on receptor activator of NF-κB ligand (RANKL)-induced osteocalstogenesis. It is reported that ISO inhibits the RANKL-mediated increase of osteoclast-related genes MMP9, cathepsink and TRAR in RAW264.7 cells. Moreover, in vitro experiment shows that ISO exhibits an inhibitory effect on ERK and NF-κB signaling pathway, and suppresses RANKL-induced expression of osteoclast-related transcription factors NFATc1 and c-Fos. However, the impact of ISO in these molecules is eliminated by the application of ERα antagonist AZD9496.We further verified pharmacological effects of ISO in ovariectomized osteoporotic mice, and ISO significantly prevented bone loss and decreased M1 polarization of macrophages from marrow and spleen. Collectively, our data suggest that ISO prevents osteoporosis via suppressing activation of ERK and NF-κB signaling pathways as well as M1 polarization of macrophages.

Cross-cultural Adaptation and Validation of the Simplified Chinese Version of the Copenhagen Neck Function Disability Scale.

STUDY DESIGN: A cross-sectional study. OBJECTIVE: Th aim of this study was to translate and cross-culturally adapt Copenhagen Neck Function Disability Scale into a Simplified Chinese version (CNFDS-C), and evaluate the reliability and validity of CNFDS-C in patients with nonspecific chronic neck pain. SUMMARY OF BACKGROUND DATA: The CNFDS is a reliable and valid evaluation instrument for chronic neck pain. However, Simplified Chinese version of CNFDS hasn't been validated. METHODS: A total of 150 participants were included in this study. Internal consistency was estimated according to Cronbach alpha. Test-retest reliability was assessed by intra-class correlation coefficient (ICC). Construct validity was analyzed by correlations between CNFDS-C and the Neck Disability Index (NDI), Visual Analogue Scale (VAS) as well as the short form (36) health survey (SF-36). RESULTS: The original version of the CNFDS was cross-culturally adapted and translated into Simplified Chinese. CNFDS-C was indicated to have excellent reliability (Cronbach alpha = 0.810, ICC = 0.927). Moderate to substantial correlations between CNFDS-C and NDI (r = 0.642, P < 0.001), VAS (r = 0.581, P < 0.001), as well as Physical Function (r = -0.583, P < .001), Role Physical (r = -0.478, P < 0.001), Bodily Pain (r = -0.610, P < 0.001), and General Health (r = -0.439, P < 0.001) subscales of SF-36 were observed. CONCLUSION: CNFDS-C was demonstrated to have acceptable reliability and validity in patients with nonspecific chronic neck pain, which could be recommended for patients in Chinese mainland.Level of Evidence: 3.