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Bupivacaine (BUP) may cause neurotoxic effects after spinal anesthesia. Resveratrol (RSV), a natural agonist of Silent information regulator 1 (SIRT1), protects various tissues and organs from damage by regulating endoplasmic reticulum (ER) stress. The aim of this study is to explore whether RSV could alleviate the neurotoxicity induced by bupivacaine via regulating ER stress. We established a model of bupivacaine-induced spinal neurotoxicity in rats using intrathecal injection of 5% bupivacaine. The protective effect of RSV was evaluated by injecting intrathecally with 30 μg/μL RSV in total of 10 μL per day for 4 consecutive days. On day 3 after bupivacaine administration, tail-flick latency (TFL) tests and the Basso, Beattie, and Bresnahan (BBB) locomotor scores were assessed to neurological function, and the lumbar enlargement of the spinal cord was obtained. H&E and Nissl staining were used to evaluate the histomorphological changes and the number of survival neurons. TUNEL staining was conducted to determine apoptotic cells. The expression of proteins was detected by IHC, immunofluorescence, and western blot. The mRNA level of SIRT1 was determined by RT-PCR. Bupivacaine caused spinal cord neurotoxicity by inducing cell apoptosis and triggering ER stress. RSV treatment promoted the recovery of neurological dysfunction after bupivacaine administration by suppressing neuronal apoptosis and ER stress. Furthermore, RSV upregulated SIRT1 expression and inhibited PERK signaling pathway activation. In summary, resveratrol suppresses bupivacaine-induced spinal neurotoxicity in rats by inhibiting endoplasmic reticulum stress via SIRT1 modulation. [ABSTRACT FROM AUTHOR]

Purpose. This study aims at constructing a clinical predictive model that predicted the risk factors for leg numbness after spinal endoscopic surgery. Methods. We collected the clinical data of patients, including general information, imaging parameters, and clinical score, from our hospital's electronic database. Based on the postoperative leg numbness visual analog scale (LN-VAS), the clinical data were divided into the leg numbness group (≥25) and the improvement group (<25). All parameters were included in the least absolute shrinkage and selection operator (LASSO) regression analysis, while the parameters with the area under the curve (AUC) greater than 0.7 were selected to construct nomograms. Furthermore, the accuracy and validity of the model were evaluated using the C-index, decision curve analysis (DCA), calibration curve, and receiver operating characteristic curve (ROC). Results. A total of 73 patients' clinical data were included in the training set, where 51 patients were assigned to the improvement group and 22 to the leg numbness group. The nomogram was constructed using four selected parameters, including symptom duration, lumbar spinal stenosis (LSS), pelvic incidence (PI), and preoperative low back pain visual analog scale (LBP-VAS). The nomogram predictions were found to range between 0.01 and 0.99. The values of the C-index, AUC, and internally validated C-index were 0.96, 0.96, and 0.94, respectively. Our result showed that the clinical net benefit of the nomogram ranged between 0.01 and 0.99. Conclusion. Our clinical prediction model demonstrated high predictive ability and clinical validity. Moreover, we found that symptom duration, LSS, PI, and preoperative LBP-VAS were the predictive risk factors for leg numbness after spinal endoscopic surgery. [ABSTRACT FROM AUTHOR]

Purpose. Lumbar fusion combined with lateral lumbar interbody fusion (LLIF) and percutaneous pedicle screws (PPS) is a widely used, minimally invasive surgical treatment, but studies on incidence and risk factors for subsequent adjacent segment degeneration (ASD) are limited. This study was aimed at investigating midterm incidence and reoperation rate of ASD after indirect decompression (IDD) with LLIF and PPS and at clarifying the impact of preexisting adjacent facet osteoarthritis on development of ASD after IDD. Methods. Forty-one patients who underwent short-segment (1- or 2-level) lumbar fusion with LLIF and PPS with a minimum 5-year follow-up were analyzed. Cephalad adjacent facet osteoarthritis was classified as 1 (normal) to 4 (severe) by an established classification system on preoperative CT. ASD was diagnosed with plain radiographs taken preoperatively and up to 5 years postoperatively, and preoperative degree of facet osteoarthritis was compared between the ASD+ group and ASD- group (control). We also divided patients into two groups according to severity of facet degeneration, mild (grades 1-2) group and severe (grades 3-4) group, and investigated ASD-free survival of the groups by the Kaplan-Meier method. Results. The incidence of ASD at 5 years postoperatively was 34.1%, and the reoperation rate for ASD was 4.9%. The degree of preexisting facet joint osteoarthritis was significantly different between the ASD+ and ASD- groups (grade 1/2/3/4: 0/29/64/7% and 29/62/29/10%, P = 0.008). Kaplan-Meier analysis showed the severe group to have significantly lower ASD-free survival than the mild group (P = 0.017) at 5 years postoperatively. Conclusion. Comparative analysis of the ASD+ versus ASD- group showed preexisting facet joint osteoarthritis to be a risk factor for ASD progression after IDD. Additional longitudinal studies with long-term follow-up are needed to understand the causal relationship between facet joint degeneration and progression of adjacent segment deterioration following IDD. [ABSTRACT FROM AUTHOR]

Objectives. To study the resorption of the herniated lumbar disc (RHLD) and its mechanism in the SD rats of lumbar intervertebral disc herniation treated with Hui medicine moxibustion (HMM). Methods. Forty SD rats were randomly divided into four groups, normal group, lumbar disc herniation (LDH) group, HMM group, and antagonist (HMM+Met12) group, with 10 rats in each group. The rat model of LDH was prepared with the method of lumbar epidural emplacement of the caudal intervertebral disc. In the HMM group and HMM+Met12 groups, 4 weeks after modeling, HMM therapy was performed in the lumbar spine for 3 months with 1 time per day and 20 min each time, the samples were collected 8 weeks after the treatment. The histological degeneration was observed through HE staining, and the neovascularization of intervertebral disc tissues was detected by the expression of CD34 and vascular endothelial growth factor (VEGF). The apoptosis of nucleus pulpous cells was detected by TUNEL assay, and the activity of caspase-3, -8, and -9 and extracellular matrix enzymes was detected by western blotting. Results. HMM treatment significantly improved the behavioral ability of rats with LDH surgery. The morphological structure was obviously destroyed in the LDH group, but disc structure was significantly repaired in the HMM group, and mild structure alterations were observed in the HMM+Met12 group. Higher levels of CD34 and VEGF were detected in the HMM group indicating that neovascularization is formed. The expression level of FasL was significantly increased in the HMM group. The protein expression levels of cleaved-caspase-3, cleaved-caspase-8, and cleaved-caspase-9 in nucleus pulposus (NP) tissues were also elevated when treated with HMM, and the TUNEL staining showed the same results. The protein expression levels of matrix metalloproteinases- (MMP-) 1, MMP-2, MMP-3, MMP-13, and ADAMTS-4 were markedly promoted in the HMM group. Met12, a small peptide antagonist of FasL, significantly reduced the effects of HMM. Conclusion. HMM can promote the formation of neovascularization of lumbar intervertebral disc, support the apoptosis of NP cells through Fas/FasL signaling, and regulate the degradation of extracellular matrix enzyme, which then accelerates the absorption of lumbar intervertebral disc herniation and the recovery of motor function in rats. [ABSTRACT FROM AUTHOR]

Intervertebral disc degeneration (IDD) is a chronic progressive condition mainly caused by excessive inflammatory cytokines. Berberine (BBR) exerts anti-inflammatory effect on diseases and protective effect against IDD. However, the mechanism is not uncertain. This study is aimed at investigating the molecular mechanism of BBR on IDD. Nucleus pulposus (NP) cells were treated with BBR at different concentrations. The IDD rat model was established by acupuncture. The effect of BBR on interleukin- (IL-) 1β-induced cell proliferation was measured by CCK-8 assay and BrdU staining. The role of BBR in IL-1β-induced apoptosis, autophagy repression, and extracellular matrix (ECM) degradation was measured by Annexin/PI staining, immunofluorescence, and immunoblot. The effect of BBR on IDD was investigated in rat. Our findings showed that BBR restored cell growth and attenuated apoptosis in IL-1β-induced NP cells. BBR also prevented the IL-1β-induced ECM degradation through regulating ECM-related enzymes and factors. Additionally, BBR significantly activated autophagy repressed by IL-1β. Autophagy stimulated by BBR was diminished by the inhibition of the AMPK/mTOR/Ulk1 signaling pathway. In vivo study also showed BBR attenuated intervertebral disc degeneration. BBR could attenuate NP cells apoptosis and ECM degradation induced by IL-1β through autophagy by the AMPK/mTOR/Ulk1 pathway. This study suggests BBR might function as an AMPK activator to alleviate IDD progression. [ABSTRACT FROM AUTHOR]

Background. Low back pain (LBP) has the characteristics of chronic and persistence, which is a heavy social burden. Intervertebral disc degeneration (IVDD) is a major cause of LBP. The typical features of IVDD are extracellular matrix (ECM) degradation and nucleus pulposus cell (NP) apoptosis. Bushen Huoxue Formula (BSHXF) has good clinical effects on LBP. However, the mechanism of BSHXF affecting ECM and NP cells is still unclear. Aim of the Study. In this study, the impact of BSHXF on autophagy and apoptosis of NP cells was studied through the AMPK/SIRT1 pathway. Material and Methods. NP cells were extracted through the digestion of collagenase and trypsin, and the components of BSHXF were identified. Cell Counting Kit-8 was applied to detect the impact of BSHXF on NP cells. Mitochondrial function was detected using MitoTracker assay, ATP kit, and SOD kit. Autophagy and apoptosis were detected by RT-qPCR, western blotting, and flow cytometry. Results. BSHXF promoted NP cell survival in a concentration-dependent manner, and the elimination of rat serum did not increase cell proliferation; TNF-α accelerated ECM degradation, ROS accumulation, and NP cell apoptosis and decreased autophagic flux. BSHXF restored mitochondrial function and autophagic flux. In addition, AMPK/SIRT1 pathway activation was associated with IVDD. Conclusions. BSHXF regulates autophagy and enhances autophagic flux to suppress excessive ROS production and restore mitochondrial function in an AMPK/SIRT1-dependent manner. However, the protection of BSHXF on TNF-α-treated cells was eliminated by 3-MA. Furthermore, the protective impact of BSHXF on ECM degradation and apoptosis induced by TNF-α was restrained by an AMPK inhibitor. Therefore, maintaining the proper autophagy illustrates treatment strategy for IVDD. [ABSTRACT FROM AUTHOR]

Background. Rheumatoid arthritis (RA) can cause deformity in particularly the craniocervical but also in the lower cervical region. Objectives. The aim of this study is to give an overview of current literature on the association of disease activity score (DAS) and the prevalence and progression of rheumatoid arthritis-associated cervical spine deformities. Methods. A literature search was done in PubMed, Embase, and Web of Science using a sensitive search string combination (Supplemental File). Studies describing the association between DAS and the incidence and progression of atlantoaxial subluxation, vertical subluxation, and subaxial subluxation were selected by predefined selection criteria, and risk of bias was assessed using a Cochrane checklist adjusted for this purpose. Results. Twelve articles were retrieved, and risk of bias on study level was low to moderate. In the eight longitudinal studies, patients demonstrated high DAS at baseline, which decreased upon treatment with medication: cervical deformity at the end of follow-up was associated with higher DAS values. The four cross-sectional studies did not demonstrate a straightforward correlation between DAS and cervical deformity. Deformity progression was evaluated in three studies, but no convincing association with DAS was established. Conclusion. A positive association between prevalence of cervical spine deformities and high disease activity was demonstrated, but quality of evidence was low. Progression of cervical deformity in association with DAS control over time is only scarcely studied, and future investigations should focus on halting of deformity progression. [ABSTRACT FROM AUTHOR]

Objective. The purpose of this study was to investigate the feasibility and clinical efficacy of the percutaneous bilateral endoscopy technique (microendoscopic trans-Kambin's triangle lumbar interbody fusion + percutaneous endoscopic transforaminal decompression of the lumbar spinal canal, ME-TKT-LIF+ PETD) in the treatment of lumbar degenerative diseases. Methods. From May 2016 to September 2018, 29 patients (16 males and 13 females) who suffered from neurologic symptoms due to degenerative lumbar spine disease and underwent percutaneous bilateral endoscopy technique were enrolled. A microendoscope was used for fusion, and a percutaneous endoscope was used for spinal canal decompression. These patients' perioperative and clinical outcome-related parameters were collected and analyzed. Results. The mean intraoperative blood loss was 72.8 ± 40.6 ml, the operation time was 87.1 ± 10.1 min, the postoperative ambulatory time was 1.69 ± 1.0 days, the hospital stay was 2.6 ± 1.3 days, and the follow-up period was 22.34 ± 4.2 months. The visual analog scale (VAS) and the Oswestry disability index (ODI) were significantly improved at the early postoperative and last follow-up, respectively. According to the modified MacNab criteria, 11 (11/29) cases were rated as excellent, 15 (15/29) as good, and 3 (3/29) as fair, and the excellent and good rate was 89.7%. Twenty-eight (28/29) cases demonstrated solid fusion, and the fusion rate was 96.6%. Conclusion. The percutaneous bilateral endoscopy technique is safe and feasible in the treatment of lumbar degenerative diseases, with the advantage that more normal anatomical structures are preserved. It is an optional method of lumbar interbody fusion. [ABSTRACT FROM AUTHOR]

Endoscopic techniques in spine surgery are rapidly evolving, with operations becoming progressively safer and less invasive. Lumbar interbody fusion (LIF) procedures comprise many spine procedures that have benefited from endoscopic assistance and minimally invasive approaches. Though considerable variation exists within endoscopic LIF, similar principles and techniques are common to all types. Nonetheless, innovations continually emerge, requiring trainees and experienced surgeons to maintain familiarity with the domain and its possibilities. We present two illustrative cases of endoscopic transforaminal lumbar interbody fusion with a comprehensive literature review of the different approaches to endoscopic LIF procedures. [ABSTRACT FROM AUTHOR]

Adolescent idiopathic scoliosis (AIS) is characterized by uneven shoulders, spinal curvature, and uneven hips, and asymmetry in paraspinal muscle activities is common in AIS. This pilot study was aimed at examining the use of a surface electromyography (sEMG) biofeedback posture training program in adolescents with mild scoliosis (Cob b ' s angle < 30 ° ) to attenuate asymmetry in paraspinal muscle activities and control the curve progression. Seven female adolescents (age, 12–14 years) with mild scoliosis (Cob b ' s angle < 30 ° ) were recruited. The participants received 30 tailor-made sessions of sEMG biofeedback posture training at a rate of one to two sessions per week for approximately 6 months. The activities of the paraspinal muscles (the trapezius, latissimus dorsi, thoracic erector spinae, and lumbar erector spinae) measured by sEMG during habitual sitting postures and spinal deformity evaluated by 3D ultrasound imaging were compared before and after training. The mean values of the root-mean-square sEMG ratio, an index of symmetry in paraspinal muscle activities of the muscle pairs between the concave and convex sides of the spinal curve, revealed significant asymmetry over the trapezius and lumbar erector spinae before the training (p <0.05). After the training, all seven adolescents achieved relatively more symmetrical paraspinal muscle activities over these two muscle pairs (p < 0.05). In two adolescents, the spinal curvature decreased by 5.7° and 5.6°, respectively, whereas the remaining adolescents showed a minimal curve progression with changes in the spinal curvature controlled under 5°. To conclude, sEMG biofeedback posture training can reduce asymmetry in paraspinal muscle activities and control curve progression in adolescents with mild scoliosis and can potentially be considered an alternative early intervention for muscle reeducation in this cohort. [ABSTRACT FROM AUTHOR]

Background. Intervertebral disc degeneration (IVDD) is the most significant cause of low back pain, the sixth-largest disease burden globally, and the leading cause of disability. This study is aimed at investigating the molecular biological mechanism of Danggui-Sini formula (DSF) mediated IVDD treatment. Methods. A potential gene set for DSF treatment of IVDD was identified through TCMSP, UniProt, and five disease gene databases. A protein interaction network of common targets between DSF and IVDD was established by using the STRING database. GO and KEGG enrichment analyses were performed using the R platform to discover the potential mechanism. Moreover, AutoDock Vina was used to verify molecular docking and calculate the binding energy. Results. A total of 119 active ingredients and 136 common genes were identified, including 10 core genes (AKT1, IL6, ALB, TNF, VEGFA, TP53, MAPK3, CASP3, JUN, and EGF). Enrichment analysis results showed that the therapeutic targets of DSF for diseases mainly focused on the AGE-RAGE signaling pathway involved in diabetic complications, IL-17 signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway, apoptosis, cellular senescence, PI3K-Akt signaling pathway, and FoxO signaling pathway. These biological processes are induced mainly in response to oxidative stress and reactive oxygen species and the regulation of apoptotic signaling pathways. Molecular docking showed that there was a stable affinity between the core genes and the key components. Conclusions. The combination of network pharmacology and molecular docking provides a practical way to analyze the molecular biological mechanism of DSF-mediated IVDD treatment, which confirms the "multicomponent, multitarget and multipathway" characteristics of DSF and provides an essential theoretical basis for clinical practice. [ABSTRACT FROM AUTHOR]

Background. The extracorporeal shock wave therapy (ESWT) has been fully utilized in orthopedics, but there are few studies in the treatment of lower limb spasm and pain caused by lumbar degenerative disorders (LDD). This study assesses the influence of ESWT in patients with LDD. Methods. From October 2017 to June 2019, 126 patients with LDD were enrolled. All patients received shock wave therapy, once every two days for four weeks in total. Each treatment consisted of 2,000 shocks with a frequency of 8-10 shocks per second. To analyze the therapeutic progress, the following tests were performed (before and after therapy; 1- and 3-month follow-up) to assess pain and functional efficiency: (1) Visual Analog Scale (VAS), (2) the frequency and duration of muscle cramps, and (3) Fugl-Meyer (LL). Results. Mean BMI of the participants was 26.1 ± 3.0 kg/m2. There was no statistically significant difference in terms of age or BMI between the groups (p > 0.05). Although all scoring parameters improved in both groups, the improvement in the ESWT group was more pronounced in pain (p < 0.001 and p < 0.001 , respectively). A review of the LMA scores of our patients demonstrated moderate functional limitations before treatment and increased functional status after treatment in all patients, while overall functional status was fully improved in patients of the ESWT group (p < 0.001). Conclusion. The ESWT is particularly effective effect for patients with LDD. The use of ESWT has a significant long-term influence on the reduction of pain, leg cramps, and the improvement of the general functional state in relation to the conventional motor improvement program. [ABSTRACT FROM AUTHOR]

Diabetes mellitus- (DM-) associated hyperglycemia promotes apoptosis of disc nucleus pulposus (NP) cells, which is a contributor to intervertebral disc degeneration (IDD). Melatonin is able to protect against cell apoptosis. However, its effects on apoptosis of NP cell in a high-glucose culture remain unclear. The purpose of the present study was to investigate the effects and molecular mechanism of melatonin on NP cell apoptosis in a high-glucose culture. NP cells were cultured in the baseline medium supplemented with a high-glucose concentration (0.2 M) for 3 days. The control cells were only cultured in the baseline medium. Additionally, the pharmaceutical inhibitor LY294002 was added along with the culture medium to investigate the possible role of the PI3K/Akt pathway. Apoptosis, autophagy, and activity of the PI3K/Akt pathway of NP cells among these groups were evaluated. Compared with the control NP cells, high glucose significantly increased cell apoptosis ratio and caspase-3/caspase-9 activity and decreased mRNA expression of Bcl-2, whereas it increased mRNA or protein expression of Bax, caspase-3, cleaved caspase-3, cleaved PARP, and autophagy-related molecules (Atg3, Atg5, Beclin-1, and LC3-II) and decreased protein expression of p-Akt compared with the control cells. Additionally, melatonin partly inhibited the effects of high glucose on those parameters of cell apoptosis, autophagy, and activation of PI3K/Akt. In conclusion, melatonin attenuates apoptosis of NP cells through inhibiting the excessive autophagy via the PI3K/Akt pathway in a high-glucose culture. This study provides new theoretical basis of the protective effects of melatonin against disc degeneration in a DM patient. [ABSTRACT FROM AUTHOR]

Purpose. Oblique lumbar interbody fusion (OLIF) approach has been increasingly frequently performed in recent years. However, neither studies of OLIF approach nor the researches of the application of enhanced recovery after surgery (ERAS) in spinal surgery are relatively rare. Here, our study is aimed at investigating the therapeutic effects of the application of OLIF compared with transforaminal lumbar interbody fusion (TLIF) approach combined with ERAS in dealing with this disorder at short-term follow-up. Material and Methods. Thirty-eight patients who undergone OLIF and forty patients who undergone TLIF with pedicle screws were included in our study. The concept of ERAS was applied in the perioperative period of the patients. Preoperative and postoperative laboratory test indexes of blood were examined and evaluated in all individuals. Visual analogue scale (VAS), Oswestry disability index (ODI), and Clinical Symptom Score of the Japanese Orthopaedic Association (JOA) were used in preoperative evaluation and postoperative follow-up. Satisfaction survey was also performed after surgery. Result. The postoperative results of red blood count, C-reaction protein, D-dimer, and albumin were still within the reference ranges in most of the patients. It was shown that objective evaluations including VAS score, ODI index, and JOA score were significantly improved after OLIF and TLIF surgery. The follow-up of 6 months after surgery showed that VAS, ODI, and JOA were improved more in the OLIF group than that in the TLIF group. The overall satisfaction (satisfied and very satisfied) was 95% and 97.4% in the TLIF group and the OLIF group, respectively, and there was no difference between the two groups. Conclusion. This study indicated that OLIF and TLIF approach were both rather effective therapies for patients with lumbar degenerative diseases. The effect of OLIF procedure could be better than TLIF procedure in the early stage after surgery. [ABSTRACT FROM AUTHOR]

Objective. To identify significant pathways and genes in intervertebral disc degeneration (IDD) based on bioinformatics analysis. Design. The GEO database was used to download the GSE124272 dataset. Differentially expressed genes (DEGs) were analyzed using Limma package in R language. Then, gene ontologies (GO), Kyoto encyclopedia of genes and genomes (KEGG), and protein-protein interaction (PPI) networks were used to further identify hub genes. The mRNA expression levels of top six hub genes were verified. Results. We found 563 DEGs, of which 214 were upregulated and 349 were downregulated. The top 5 GO terms and pathways were shown including immune response, cell cycle, and p53 pathway. Based on the PPI analysis, we verified the mRNA expression levels of 6 hub genes. The mRNA levels of CHEK1, CDCA2, SKA3, and KIF20A were upregulated in degenerative NP tissue than in healthy NP tissue. However, the mRNA level of BUB1 and SPC25 was downregulated. Conclusions. This study may provide new biomarkers for the IDD and treatments to repair IDD related to CHEK1, CDCA2, SKA3, BUB1, KIF20A, and SPC25. [ABSTRACT FROM AUTHOR]

Background. The competing endogenous RNA- (ceRNA-) mediated regulatory mechanisms are known to play a pivotal role in intervertebral disc degeneration (IDD). Our research intended to establish a ceRNA regulatory network related to IDD through bioinformatics analyses. Methods. The expression profiles of circRNA, miRNA, and mRNA were obtained from the public Gene Expression Omnibus (GEO) datasets. Then, we use sequence-based bioinformatics methods to select differentially expressed mRNAs (DEmRNAs), microRNAs (DEmiRNAs), or circRNAs (DEcircRNAs) related to IDD. We used ChEA3 to verify the targets of transcription factors (TFs). Then, we used DAVID to annotate the DEmRNAs. Finally, we constructed a potentially circRNA-miRNA-mRNA network related to IDD by predicting in the database (ENCORI, TargetScan, miRecords, miRmap, and circBank). Results. We identified 31 common DEmRNAs by Venn analysis, of which MMP2 was regarded as the key hub genes. Simultaneously, miR-423-5p and miR-185-5p were predicted as the upstream molecules of MMP2. Furthermore, a total of six DEcircRNAs were predicted as the upstream circRNAs of miR-423-5p and miR-185-5p. Then, a potential circRNA-miRNA-mRNA network related to IDD was constructed by bioinformatics analysis. Conclusion. A comprehensive ceRNA regulatory network was constructed, which was found to be significant in IDD progression. [ABSTRACT FROM AUTHOR]

Background. Diagnosis of intervertebral disc degeneration (IVDD) is challenging at the early stage. The cartilage oligomeric matrix protein (COMP) and extracellular matrix degradation products of C-telopeptide of type II collagen (CTX-II) serve as markers for the serological diagnosis of IVDD. Oxidative stress might cause IVDD and matrix degeneration. Methods. A total of 128 male adult Sprague–Dawley (SD) rats were randomly and equally assigned to the experimental and control groups. The experimental group was used to construct IVDD models by acupuncture, while the control group underwent sham operation. The animals were executed every week for 8 weeks after intervertebral disc acupuncture, and serum samples were collected for the estimation of CTX-II and COMP concentrations by enzyme-linked immunosorbent assay (ELISA). Also, the histological changes and caudal magnetic resonance imaging (MRI) changes were examined in the intervertebral disc. Results. IVDD in rats worsened with prolonged follow-up after acupuncture. At all the time points, the experimental group showed altered histological and caudal vertebra MRI signals, and serum CTX-II and COMP concentrations were significantly greater than those of the control group. These levels increase with the process of IVDD. Conclusion. Serum CTX-II and COMP estimation is a reliable method to diagnose IVDD, and their concentrations show a positive correlation with the process of IVDD. [ABSTRACT FROM AUTHOR]

Age is a key factor in intervertebral disc (IVD) degeneration; however, the changes that occur in IVDs with age are not fully understood. Tissue-resident macrophages are critical for tissue homeostasis and are regulated by transforming growth factor- (TGF-) β. We examined changes in the proportion of resident macrophages in young versus aged mice and the role of TGF-β in regulating resident macrophages in IVDs. IVDs were harvested from 4-month (young) and 18-month-old (aged) C57BL/6J mice. The proportion of macrophages in IVDs was determined using flow cytometry (n = 5 for each time point) and the expression of Cd11b, Cd206, and Tgfb genes, which encode CD11b, CD206, and TGF-β protein, respectively, using real-time PCR. To study the role of TGF-β in the polarization of resident macrophages, resident macrophages isolated from IVDs from young and aged mice were treated with recombinant TGF-β with and without a TGF-β inhibitor (SB431542). Additionally, SB431542 was intraperitoneally injected into young and aged mice, and Cd206 expression was examined using real-time PCR (n = 10 for each time point). The proportion of CD11b+ and CD11b+ CD206+ cells was significantly reduced in aged versus young mice, as was Cd11b, Cd206, and Tgfb expression. TGF-β/IL10 stimulation significantly increased the expression of Cd206, an M2 macrophage marker, in disc macrophages from both young and aged mice. Meanwhile, administration of a TGF-β inhibitor significantly reduced Cd206 expression compared to vehicle control in both groups. Conclusion. Resident macrophages decrease with age in IVDs, which may be associated with the concomitant decrease in TGF-β. Our findings provide new insight into the mechanisms of age-related IVD pathology. [ABSTRACT FROM AUTHOR]

The intervertebral disc degeneration (IDD) is considered to be an initiator of a series of spinal diseases, among which changes in the nucleus pulposus (NP) are the most significant. NP cells reside in a microenvironment with a lack of blood vessels, hypoxia, and low glucose within the intervertebral disc. Due to the strong activity of HIF-1α, glycolysis is the main pathway for energy metabolism in NP cells. Our previous study found that higher SIRT1 expression is beneficial to delay the degeneration of NP cells. In order to find the downstream genes by which SIRT1 acts on NP cells, we used iTRAQ sequencing to detect the differences between degenerated NP cells overexpressing SIRT1 and a control group (human NP cells were derived from surgery) and found that the expression of LDHA changed in the same direction with SIRT1. This suggests that SIRT1 may delay the degeneration of NP cells by regulating glycolysis. We then used a Seahorse XFe24 analyzer to measure the bioenergetic parameters of NP cells and obtained three findings: (a) glycolysis is the main energy metabolism pathway in NP cells, (b) there is a large difference in ATP production between senescent cells and young cells, and (c) SIRT1 can regulate the production of ATP from glycolysis by regulating LDHA. We also found that SIRT1 in NP cells has a positive regulatory effect on c-Myc which is an upstream gene of LDHA. Through observing IDD-related indicators such as apoptosis, proliferation, senescence, and extracellular matrix, we found that SIRT1 can delay degeneration, and interference with c-Myc and LDHA, respectively, weakens the protective effect of SIRT1. Interfering with LDHA alone can also inhibit glycolysis and accelerate degeneration. Overall, we found that the inhibition of glycolysis in Np cells significantly affects their normal physiological functions and determined that LDHA is a potential therapeutic target for the treatment of IDD. [ABSTRACT FROM AUTHOR]

Low back pain which resulted from intervertebral disc degeneration (IDD) is a common health problem that afflicts people all over the world. Due to the lack of an overall understanding of the molecular interactions involved in IDD, we hope to better understand the pathogenetic mechanisms that drive the degenerative process. The purpose of this study is to obtain mRNAs, miRNAs, lncRNAs, and circRNAs associated with IDD gained from public databases and to establish an interaction network. According to the results of microarray analysis and bioinformatics analysis from the contrast of IDD and normal nucleus pulposus tissues, a total of 49 mRNAs, 10 miRNAs, 30 lncRNAs, and 4 circRNAs were obtained and a lncRNA/circRNA–miRNA–mRNA interaction network was constructed. NEAT1–miR-5100–COL10A1 and miR663AHG/HEIH/hsa-circ-0003600–miR-4741–HAS2/HYAL1/LYVE1 might be potential interaction axes of the molecular mechanism in IDD. The increased expression of NEAT1 might inhibit miR-5100 and subsequently upregulate the expression of COL10A1, which leads to IDD, while the increased expression of miR663AHG/HEIH/hsa-circ-0003600 might inhibit miR-4741 and indirectly upregulate HAS2/HYAL1/LYVE1, and leads to the protection from IDD. More interaction axes are to be exploited to provide theoretical bases for further study on IDD. [ABSTRACT FROM AUTHOR]

Background. Intervertebral disc degeneration (IDD) disease is a global challenge because of its predominant pathogenic factor in triggering low back pain, whereas cartilaginous endplate degeneration (CEPD) is the main cause of IDD. Accumulating evidence have indicated that the differentially expressed microRNAs (DEMs) and differentially expressed genes (DEGs) have been determined to be involved in multiple biological processes to mediate CEPD progression. However, the differentially expressed circular RNAs (DECs) and their potential biofunctions in CEPD have not been identified. Methods. GSE153761 dataset was analyzed using R software to predict DECs, DEMs, and DEGs. Pathway enrichment analysis of DEGs and host genes of DECs and protein-protein interaction network of DEGs were conducted to explore their potential biofunctions. Furthermore, we explore the potential relationship between DEGs and DECs. Results. There were 74 DECs, 17 DEMs, and 68 DEGs upregulated whereas 50 DECs, 16 DEMs, and 67 DEGs downregulated in CEPD group. Pathway analysis unveiled that these RNAs might regulate CEPD via mediating inflammatory response, ECM metabolism, chondrocytes apoptosis, and chondrocytes growth. A total of 17 overlapping genes were predicted between the host genes of DEGs and DECs, such as SDC1 and MAOA. Moreover, 6 upregulated DECs, of which hsa_circ_0052830 was the most upregulated circRNA in CEPD, were derived from the host genes SDC1, whereas 8 downregulated DECs were derived from the host genes MAOA. Conclusion. This will provide novel clues for future experimental studies to elucidate the pathomechanism of CEPD and therapeutic targets for CEPD-related diseases. [ABSTRACT FROM AUTHOR]

Objectives. To establish a novel animal model of intervertebral disc degeneration (IVDD) in rats and to investigate the effect of 17β-estradiol (E2) intervention in this model. Methods. This study was divided into two parts: animal model (four groups: Sham, ovariectomy (OVX), Puncture, and OVX+Puncture; three-time points: 4, 8, and 12 weeks; three female rats/group/time point) and drug intervention (Sham, OVX+Puncture+corn oil, and OVX+Puncture+E2; three female rats/group). The rats were analyzed by micromagnetic resonance imaging (MRI), hematoxylin and eosin (HE) staining, and safranin-O staining. Results. MRI and histological scores significantly differed among the four groups at the three-time points (all P < 0.05). IVDD progressed with time in the OVX, Puncture, and OVX+Puncture groups (all P < 0.05). The changes were the most obvious in the OVX+Puncture group. In the E2 intervention part, the Veh group had the worst MRI signals and histological scores (P < 0.05). The MRI scores in the E2 group were less obvious compared to the Sham group (P > 0.05). Also, the histological scores were significantly different between the Sham and E2 groups (P < 0.05). Conclusions. The combination of ovariectomy and needle puncture can synergically induce IVDD in rat coccygeal discs. Estrogen treatment can effectively ameliorate IVDD progression in the newly established IVDD models. [ABSTRACT FROM AUTHOR]

Intervertebral disc degeneration (IVDD) is a degenerative and chronic spinal disorder often associated with the older population. Oxidative stress is a major pathogenic factor of aging that results in the apoptosis of nucleus pulposus cells (NPCs) and extracellular matrix (ECM) degradation. Quercetin (QUE), a naturally occurring flavonoid with antioxidant and anti-inflammatory properties, has been studied in research on degenerative diseases. However, the potential effects and mechanisms of action of QUE on IVDD remain unclear. In this study, the effects of QUE on antiapoptosis and ECM metabolism were firstly investigated in TBHP-treated NPCs. Meanwhile, the autophagy inhibitor, 3-MA, and p38 MAPK inhibitor, SB203580, were used in subsequent TBHP-induced NPC experiments to determine whether QUE exerted its protective effects through autophagy and the p38 MAPK/mTOR signaling pathway. Finally, the therapeutic effects of QUE were confirmed in vivo using a rat tail needle puncture-induced model of IVDD. We found that QUE treatment significantly alleviated oxidative stress-decreased cell viability and intracellular ROS levels in NPCs treated with TBHP. Furthermore, treatment with QUE led to a decrease in apoptosis as measured by decreased Bax and increased Bcl-2 expression and PE/7-AAD flow cytometry analysis. QUE also promoted ECM stability as measured by increased collagen II and aggrecan and decreased MMP13 levels. Our results also showed that QUE promoted the expression of autophagy markers beclin-1, LC3-II/I, and decreased p62. Inhibition of autophagy by inhibitor 3-MA may partially reverse the protective effect of QUE on apoptosis and ECM degeneration, indicating that autophagy was involved in the protective effect of QUE in NPCs. Further study confirmed that QUE partially inhibited the p38 MAPK signaling pathway and inhibition of p38 MAPK by SB203580 activated autophagy, indicating that QUE protected NPCs against apoptosis and prevented ECM degeneration via the p38 MAPK-autophagy pathway. Finally, using a rat tail puncture-induced model of IVDD, we confirmed that QUE had a protective effect against IVDD. Our results suggest that QUE could prevent IVDD by modulating p38 MAPK-mediated autophagy and, therefore, is a potential therapeutic strategy in the treatment of IVDD. [ABSTRACT FROM AUTHOR]

Background. The application of biomolecular interventions in the early stage of intervertebral disc degeneration (IVDD) is considered an ideal method for the treatment of IVDD. However, the precise definition of the "early stage" of IVDD is unclear. Silent information regulation 2 homologue-1 (SIRT1) can protect human degenerative nucleus pulposus (NP) cells from apoptosis by activating autophagy. However, the mechanism of this effect is still unclear. This study tried to confirm the "early stage" of IVDD and the role of NP cell autophagy during IVDD as well as to determine the mechanism by which SIRT1 protects NP cells. Methods. The characteristics of the NP in various stages of degeneration were assessed to confirm the "early stage" of IVDD. Then, autophagy and apoptosis were detected in NP cells after SIRT1 upregulation/downregulation. Finally, LY294002 and PD98059 were used to inhibit the AKT/ERK pathway to determine the mechanism by which SIRT1 regulates autophagy in NP cells. Results. Our data showed that mildly degenerative (Pfirrmann grade III with normal height of intervertebral disc) NP cells may be the key target for biomolecular interventions in IVDD and that SIRT1 protects human mildly degenerative NP cells from apoptosis by activating autophagy via the ERK signalling pathway. Conclusion. Our data showed that SIRT1 inhibits apoptosis by promoting the autophagic flux in NP cells via the ERK signalling pathway during the key stage of degeneration. These findings will assist in the development of novel therapeutic approaches for IVDD treatment. [ABSTRACT FROM AUTHOR]

As a newly discovered mechanosensitive ion channel protein, the piezo1 protein participates in the transmission of mechanical signals on the cell membrane and plays a vital role in mammalian biomechanics. Piezo1 has attracted widespread attention since it was discovered in 2010. In recent years, studies on piezo1 have gradually increased and deepened. In addition to the discovery that piezo1 is expressed in the respiratory, cardiovascular, gastrointestinal, and urinary systems, it is also stably expressed in cells such as mesenchymal stem cells (MSCs), osteoblasts, osteoclasts, chondrocytes, and nucleus pulposus cells that constitute vertebral bodies and intervertebral discs. They can all receive external mechanical stimulation through the piezo1 protein channel to affect cell proliferation, differentiation, migration, and apoptosis to promote the occurrence and development of lumbar degenerative diseases. Through reviewing the relevant literature of piezo1 in the abovementioned cells, this paper discusses the effect of piezo1 protein expression under mechanical stress stimuli on spinal degenerative disease, providing the molecular basis for the pathological mechanism of spinal degenerative disease and also a new basis, ideas, and methods for the prevention and treatment of this degenerative disease. [ABSTRACT FROM AUTHOR]

Interbody fusion is a common surgical technique for diseases of the lumbar spine. Biportal endoscopic-assisted lumbar interbody fusion (BE-LIF) is a novel minimally invasive technique that has a long learning curve, which can be a barrier for surgeons. Therefore, we analyzed the learning curve in terms of operative time and evaluated the outcomes of BE-LIF. A retrospective study of fifty-seven consecutive patients who underwent BE-LIF for degenerative lumbar disease by a single surgeon from January 2017 to December 2018 was performed. Fifty patients underwent a single-level procedure, and 7 underwent surgery at two levels. The mean follow-up period was 24 months (range, 14–38). Total operative time, postoperative drainage volume, time to ambulation, and complications were analyzed. Clinical outcome was measured using the Oswestry Disability Index (ODI), Visual Analog Scale (VAS) score for back and leg pain, and modified Macnab criteria. The learning curve was evaluated by a nonparametric regression locally weighted scatterplot smoothing curve. Cases before the stable point on the curve were designated as group A, and those after the stable point were designated group B. Operative time decreased as the number of cases increased. A stable point was noticed on the 400th day and the 34th case after the first BE-LIF was performed. All cases showed improved ODI and VAS scores at the final follow-up. Overall mean operative time was 171.74 ± 35.1 min. Mean operative time was significantly lower in group B (139.7 ± 11.6 min) compared to group A (193.4 ± 28.3 min). Time to ambulation was significantly lower in group B compared to group A. VAS and ODI scores did not differ between the two groups. BE-LIF is an effective minimally invasive technique for lumbar degenerative disease. In our case series, this technique required approximately 34 cases to reach an adequate performance level. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the efficacy and safety of different dose regimens of intravenous (IV) tranexamic acid (TXA) in adolescent spinal deformity surgery. Methods. Two researchers independently searched multiple databases, including PubMed, Embase, Cochrane Library, and Web of Science to find studies that met the inclusion criteria. A meta-analysis was performed based on the guidelines of the Cochrane Reviewer's Handbook. Results. Six randomized controlled trials (RCTs) and eleven non-RCTs were identified, including 1148 patients. According to different dose regimens of IV TXA, the included studies were divided into the high-dose group and the low-dose group. Compared with placebo, both groups had less total blood loss (TBL) (high dose: WMD = − 1737.55 , 95% CI: (-2247.16, -1227.94), P < 0.001 , I 2 = 0 % ; low dose: WMD = − 528.67 , 95% CI: (-666.06, -391.28), P < 0.001 , I 2 = 0 %), intraoperative blood loss (IBL) (high dose: WMD = − 301.48 , 95% CI: (-524.3, -78.66), P = 0.008 , I 2 = 60.3 % ; low dose: WMD = − 751.14 , 95% CI: (-967.21, -535.08), P < 0.001 , I 2 = 0 %), and blood transfusion rates (high dose: RR = 0.19 , 95% CI: (0.1, 0.37), P < 0.001 , I 2 = 0 % ; low dose: RR = 0.4 , 95% CI: (0.18, 0.91), P = 0.029 , I 2 = 57 %). High-dose IV TXA use was associated with more vertebral fusion segments (WMD = 0.53 , 95% CI: (0.23, 0.82), P < 0.001 , I 2 = 31.2 %). Low-dose IV TXA use was associated with shorter operative time (WMD = − 18.43 , 95% CI: (-26.68, -10.17), P < 0.001 , I 2 = 0 %). Conclusion. High-dose and low-dose IV TXA were effective in reducing TBL, IBL, and blood transfusion rates without increasing complications in adolescent patients undergoing spinal deformity surgery. Low-dose IV TXA was effective in reducing the operative time. Both the high-dose and low-dose groups had similar preoperative and postoperative Hb levels compared to the control group. [ABSTRACT FROM AUTHOR]

Purpose. A hybrid pedicle screw system for minimally invasive spinal fixation was developed based on the uniplanar pedicle screw construct and a new intermediate screw. Its biomechanical performance was evaluated using finite element (FE) analysis. Methods. A T12-L2 FE model was established to simulate the L1 vertebral compression fracture with Magerl classification A1.2. Six fixation models were developed to simulate the posterior pedicle screw fracture fixation, which were divided into two subgroups with different construct configurations: (1) six-monoaxial/uniplanar/polyaxial pedicle screw constructs and (2) four-monoaxial/uniplanar/polyaxial pedicle screw constructs with the new intermediate screw. After model validation, flexion, extension, lateral bending, and axial rotation with 7.5 Nm moments and preloading of 500 N vertical compression were applied to the FE models to compare the biomechanical performances of the six fixation models with maximum von Mises stress, range of motion, and maximum displacement of the vertebra. Results. Under four loading scenarios, the maximum von Mises stresses were found to be at the roots of the upper or lower pedicle screws. In the cases of flexion, lateral bending, and axial rotation, the maximum von Mises stress of the uniplanar screw construct lay in between the monoaxial and polyaxial screw constructs in each subgroup. Considering lateral bending, the uniplanar screw construct enabled to lower the maximum von Mises stress than monoaxial and polyaxial pedicle screw constructs in each subgroup. Two subgroups showed comparable results of the maximum von Mises stress on the endplates, range of motion of T12-L1, and maximum displacement of T12 between the corresponding constructs with the new intermediate screw or not. Conclusions. The observations shown in this study verified that the hybrid uniplanar pedicle screw system exhibited comparable biomechanical performance as compared with other posterior short-segment constructs. The potential advantage of this new fixation system may provide researchers and clinical practitioners an alternative for minimally invasive spinal fixation with vertebral augmentation. [ABSTRACT FROM AUTHOR]

Purpose. The aim of this study was to describe the characteristics of each locomotive syndrome (LS) risk stage, including global spine sagittal alignment, spinal degenerative changes evident on plain radiographs, low back pain (LBP), muscle strength, and physical ability in middle-aged and elderly people in a health checkup. Methods. This study included 211 healthy Japanese volunteers (89 men and 122 women; mean age, 64.0 years) who underwent assessment with both radiographs and Spinal Mouse. Spinal sagittal parameters included thoracic kyphosis angle (TKA), lumbar lordosis angle (LLA), sagittal vertical axis, and spinal inclination angle (SIA). Lumbar disc height (LDH) and lumbar osteophyte formation (LOF) at each level were evaluated as the spinal degenerative changes. The LS assessment comprised three tests: stand-up test, two-step test, and 25-question Geriatric Locomotive Function Scale (GLFS-25). The subjects were divided into three groups (no risk, stage 1 LS, or stage 2 LS) according to LS risk test criteria. The prevalence of LBP was investigated with a visual analogue scale (VAS), and physical performances were also compared among the groups. Results. Of the participants, 122 had no risk of LS, 56 had stage 1 LS risk, and 29 had stage 2 LS risk. With increasing LS risk stage, the prevalence of and VAS score for LBP increased significantly, and back muscle strength and physical abilities decreased significantly. The TKA did not differ among the three groups. The LLA decreased gradually with LS risk stage (P = 0.0001). At each level except L1–L2 and L5–S1, LDH decreased gradually with LS risk stage. The prevalence of LOF increased significantly with increasing LS risk stage. The SIA increased significantly with LS risk stage (P = 0.0167). Conclusions. Participants with LS had higher prevalence of spinal degeneration, small LLA, and global spinal imbalance by anterior spinal inclination. [ABSTRACT FROM AUTHOR]

Background. Intervertebral disc degeneration is related to tissue fibrosis. ADAMTS can degrade the important components of the ECM during the process of intervertebral disc degeneration, ultimately resulting in the loss of intervertebral disc function. sIL-13Rα2-Fc can inhibit fibrosis and slow down the degeneration process, but the mechanism involved remains unclear. Objective. To determine the mechanism by which sIL-13Rα2-Fc inhibits ECM degradation and reduces intervertebral disc tissue fibrosis using a transcriptomics analysis. Methods. A rat model of caudal intervertebral disc degeneration was established, and Sirius red staining was used to observe the pathological changes in the caudal intervertebral disc. Transcriptome sequencing was employed to assess the gene expression profiles of the intervertebral disc tissues in the model group and the sIL-13Rα2-Fc-treated group. Differentially expressed genes were identified and analyzed using GO annotation and KEGG pathway analyses. Real-time fluorescence quantitative PCR was used to verify the expression levels of candidate genes. The levels of GAG and HA were quantitatively assessed by ELISA, and the levels of collagen I and collagen II were analyzed by western blotting. Results. Sirius red staining showed that in the model group, the annulus fibrosus was disordered, the number of breaks increased, and the type I collagen protein levels increased, whereas in the sIL-13Rα2-Fc group, the annulus fibrosus was ordered, the number of breaks decreased, and the type II collagen protein levels increased. In comparison with the model group, we identified 58 differentially expressed genes in the sIL-13Rα2-Fc group, and these were involved in 35 signaling pathways. Compared with those in the model group, the mRNA expression levels of Rnux1, Sod2, and Tnfaip6 in the IL-13Rα2-Fc group were upregulated, and the mRNA expression levels of Aldh3a1, Galnt3, Fgf1, Celsr1, and Adamts8 were downregulated; these results were verified by real-time fluorescence quantitative PCR. TIMP-1 (an ADAMTS inhibitor) and TIMP-1 combined with the sIL-13Rα2-Fc intervention increased the levels of GAG and HA, inhibited the expression of type I collagen, and promoted the expression of type II collagen. Conclusion. Adamts8 may participate in the degradation of ECM components such as GAG and HA and lead to an imbalance in the ECM of the intervertebral disc, resulting in intervertebral disc degeneration. sIL-13Rα2-Fc promoted anabolism of the ECM and increased the levels of ECM components by inhibiting the expression of Adamts8, thus maintaining the dynamic equilibrium of the ECM and ultimately delaying intervertebral disc degeneration. [ABSTRACT FROM AUTHOR]

Background. Spinal manipulation (SM) has been widely recognized and used with success in health care fields for spinal joint dysfunction and pain. SM is a procedure that involves small amplitude manipulative thrusts performed with speed. These forces are complex three-dimensional (3-D) forces delivered to create forces and moments at the joint of interest to cause joint movements. The aim of this study was to conduct a 3-dimensional analysis of the magnitude and direction of the forces transmitted in 2 techniques of thoracic spinal manipulation (TSM). Materials/Methods. Thirty-two healthy participants were recruited from the university community. The physical therapist performed TSM using anterior (A) to posterior (P) and P to A techniques once at each of T3, T7, and T12 spinal levels. The magnitude and direction of the forces transmitted during TSM were sensed by the force plates, and the camera system monitored vertebral motion by tracking motion markers. Results. There were no significant differences on the x -axis while there were significant differences on the y -axis between the measured spinal levels in the P to A technique. There were significant differences found at preload force maximum, preload force minimum, and peak force between T3 and T12 and between T7 and T12 and at peak base force between T7 and T12 on the z -axis. In the A to P technique, there were significant differences in the change of force in measured spinal levels at different axes. Conclusion. These study findings can help therapists better understand the mechanism of TSM and enhance the clinical usefulness of TSM. [ABSTRACT FROM AUTHOR]

To align multimodal images is important for information fusion, clinical diagnosis, treatment planning, and delivery, while few methods have been dedicated to matching computerized tomography (CT) and magnetic resonance (MR) images of lumbar spine. This study proposes a coarse-to-fine registration framework to address this issue. Firstly, a pair of CT-MR images are rigidly aligned for global positioning. Then, a bending energy term is penalized into the normalized mutual information for the local deformation of soft tissues. In the end, the framework is validated on 40 pairs of CT-MR images from our in-house collection and 15 image pairs from the SpineWeb database. Experimental results show high overlapping ratio (in-house collection, vertebrae 0.97 ± 0.02 , blood vessel 0.88 ± 0.07 ; SpineWeb, vertebrae 0.95 ± 0.03 , blood vessel 0.93 ± 0.10) and low target registration error (in-house collection, ≤ 2.00 ± 0.62 mm ; SpineWeb, ≤ 2.37 ± 0.76 mm) are achieved. The proposed framework concerns both the incompressibility of bone structures and the nonrigid deformation of soft tissues. It enables accurate CT-MR registration of lumbar spine images and facilitates image fusion, spine disease diagnosis, and interventional treatment delivery. [ABSTRACT FROM AUTHOR]

Background. TSC1-related signaling plays a pivotal role in intramembranous and endochondral ossification processes during skeletogenesis. This study was aimed at determining the significance of the TSC1 gene at different stages of spinal development. Materials and Methods. TSC1-floxed mice (TSC1flox/flox) were crossed with Prrx1-Cre or BGLAP-Cre transgenic mice or mesenchymal stem cell- and osteoblast-specific TSC1-deficient mice, respectively. Somatic and vertebral differences between WT and Prrx1-TSC1 null mice were examined at 4 weeks after birth. Results. No apparent body size abnormalities were apparent in newborn and 4-week- to 2-month-old mice with BGLAP-Cre driver-depleted TSC1. Vertebral and intervertebral discs displayed strong dysplasia in Prrx1-TSC1 null mice. In contrast, vertebrae were only slightly affected, and intervertebral discs from skeletal preparations displayed no apparent changes in BGLAP-TSC1 null mice. Conclusion. Our data suggest that the TSC1 gene is crucial for endochondral ossification during postnatal spine development but plays discriminative roles at different stages. Mesenchymal stem cell-specific ablation of TSC1 led to severe spinal dysplasia at early stages of endochondral ossification while osteoblast-specific deletion of TSC1 affected vertebrae slightly and had no detectable effects on intervertebral discs. [ABSTRACT FROM AUTHOR]

Objective. Tranexamic acid (TXA), an antifibrinolytic agent, interferes with fibrinolysis and has been used for many years to reduce blood loss during spine surgery. The purpose of our meta-analysis was to compare the effect of intravenous versus topical administration of TXA in patients undergoing nondeformity spine surgery. Methods. We searched multiple databases, including PubMed, Embase, the Cochrane library, CNKI, WanFang database, and VIP to find studies that met the inclusion criteria. A meta-analysis was performed according to the guidelines of the Cochrane Reviewer's Handbook. Results. Eight randomized controlled trials (RCTs) were identified, including 660 patients. The surgical methods used in the included studies were nondeformity spine surgery. No significant differences were found in the two groups regarding total blood loss, intraoperative blood loss, hidden blood loss, hematocrit, hemoglobin, fibrinogen, postoperative prothrombin time (PT), postoperative activated partial thromboplastin time (APTT), drainage volume, and blood transfusion rate. There were statistically significant differences in the two groups in terms of preoperative PT (MD = −0.39, 95% CI: [−0.63, −0.15], P = 0.002) and preoperative APTT (MD = 1.12, 95% CI: [0.57, 1.68], P < 0.0001). Conclusion. During nondeformity spine surgery, intravenous administration of TXA did not have a significant effect on the decrease of blood loss and blood transfusion rate compared with the topical group. According to the pooled analysis of PT and APTT, intravenous and topical application of TXA may have different effects on the coagulation pathway. More high-quality RCTs are needed to explore the optimal dosage, method, timing in the future in order to recommend TXA widespread use in spine surgery. [ABSTRACT FROM AUTHOR]

Background. Apelin alleviates oxidative stress which contributes to the development of aging. IVDD is a disease closely correlated to aging and oxidative stress which is known to be harmful to NP cells' matrix synthesis. The purpose of the present study was to investigate the role and underlying mechanism of Apelin in NP cells' matrix degradation under oxidative stress. Methods. First, the mRNA and protein expressions of Apelin were checked by RT-PCR and Western blot in NP from normal and degenerative IVD to explore the relationship between Apelin and IVDD preliminarily. Then, H2O2 was used to mimic oxidative stress of NP cells. After treated with Apelin 13 and CQ, the GAG content was assessed by DMMB and the mRNA/protein expressions of NP matrix macromolecules (Collagen II and Aggrecan) and autophagy-related markers (LC3 and p62) were assessed by RT-PCR/Western blot. Finally, TFEB was knocked down by esiRNA-TFEB transfection and the nucleoprotein expression of TFEB and autophagy-related markers (LC3 and p62) were assessed by Western blot to discuss whether TFEB is involved in Apelin regulating autophagy flux in NP cells under oxidative stress. Results. Our data first confirmed that the mRNA and protein expressions of Apelin were decreased with IVDD. Furthermore, Apelin increased GAG content of NP cells and mRNA/protein expressions of NP matrix macromolecules (Collagen II and Aggrecan) and promoted autophagic flux (LC3II/I increased and p62 decreased) under oxidative stress. Finally, after transfected with esiRNA-TFEB, Apelin cannot promote autophagic flux any more in human degenerative NP cells. Conclusion. Our data indicated that Apelin promotes ECM synthesis by enhancing autophagy flux via TFEB in human degenerative NP cells under oxidative stress. This viewpoint may provide a new therapeutic idea for IVDD. [ABSTRACT FROM AUTHOR]

Purpose. The endplate defects (EDs), Modic changes (MCs), disc degeneration (DD), facet orientation (FO), and facet tropism (FT) were demonstrated to be related to the low back pain (LBP). The aim of this study was to investigate possible correlations between them. Methods. 75 patients were reviewed to evaluate the degenerative change in vertebral bodies (EDs and MCs), intervertebral discs (DD), and facet joint degeneration (FO and FT). All patients were categorized into four groups based on the grade of EDs. Clinical outcomes were evaluated with the visual analog scale (VAS) and Oswestry disability index (ODI) before and after surgery. Results. There was no difference between the four groups in baseline characteristics except for gender and weight. FT is positively correlated with FO. The same rule exists between EDs, the size of MCs II, FO (left) and FO (right), and VAS and ODI. The grade of EDs is positively correlated with the grade of DD. L4-L5 can bear more load than other levels; thus, the grade of EDs is higher than that of other lumbar levels. The preoperative LBP was relieved in all groups in varying degrees. The change of pain and dysfunction is inversely proportional to the grade of EDs in the general trend. Conclusion. The relationship between weight, gender, and disc degeneration provided a mechanism by which increasing weight can predispose to DD. Different grades of EDs had different effects on patients with LBP. There was a significant correlation between EDs, MCs II, DD, FT, and FO. [ABSTRACT FROM AUTHOR]

Low back pain is a major cause of disability worldwide. Although numerous potential biomarkers for the early diagnosis or treatment of intervertebral disc degeneration (IDD) have been identified subsequent to the development of molecular biology technologies, the mechanisms of IDD remain unknown. Published studies found the unbalance of anabolism and catabolism of annulus fibrosus (AF) played an important role in it. The present study was aimed to identify the potential targets and signaling pathways of IDD, through the combined analysis of differential expression and based on the Gene Expression Omnibus (GEO) dataset from NCBI. PPI Networks Analysis indicated that MMP2 and AGE-RAGE signaling pathway and estrogen signaling pathway may play important roles in initiation and development of IDD. This study forecasted the pathogenesis molecular mechanism of IDD and the potential prognostic and diagnostic biomarkers, but we need to make further molecular biological experiments to confirm our assumptions. [ABSTRACT FROM AUTHOR]

Objective. There is a steep learning curve with traditional percutaneous endoscopic lumbar discectomy (PELD). The aim of this study is to assess the safety and efficacy of PELD assisted by O-arm-based navigation for treating lumbar disc herniation (LDH). Methods. From September of 2017 to January of 2018, 118 patients with symptomatic LDH were enrolled in the prospective cohort study. The patients undergoing PELD with O-arm-based navigation technique were defined as group A (58 cases), and those undergoing traditional X-ray fluoroscopy method were defined as group B (60 cases). We recorded the operation time, cannula placement time, radiation exposure time, visual analog scale (VAS), Oswestry Disability Index (ODI), and Macnab criteria score of the 2 groups. Results. The average operation time (95.21 ± 19.05 mins) and the cannula placement time (36.38 ± 14.67 mins) in group A were significantly reduced compared with group B (operation time, 113.83 ± 22.01 mins, P<0.001; cannula placement time, 52.63 ± 17.94 mins, P<0.001). The learning curve of PELD in group A was steeper than that in group B and was lower in the relatively flat region of the end. There were significant differences of the clinical parameters at different time points (VAS of low back, P < 0.001; VAS of leg, P < 0.001; and ODI, P < 0.001). The VAS scores for low back pain and leg pain improved significantly in both groups after surgery and gradually improved as time went by. No serious complication was observed in any patients in either group. Conclusion. The study indicated that PELD assisted by O-arm navigation is safe, accurate, and efficient for the treatment of lumbar intervertebral disc herniation. It reshaped the learning curve of PELD, reduced the difficulty of surgery, and minimized radiation exposure to surgeons. This study was registered at Chinese Clinical Trail Registry (Registration Number: ChiCTR1800019586). [ABSTRACT FROM AUTHOR]

Introduction. The multifocal lumbar pathology including disc herniation and stenosis in the spinal canal or foramen has been considered the most difficult to approach surgically. It often requires mandatory dual approaches and/or fusion techniques. Traditional percutaneous endoscopic lumbar transforaminal and interlaminar approach has been focused on unifocal disc herniation. However, the development of endoscopic spinal instruments and surgical technique has broadened surgical indication and therapeutic boundary in endoscopic spine surgery. Cases Presentation. The authors present outcomes of four patients with multilumbar pathology including highly inferior migrated disc combined with lateral recess stenosis, multifocal disc herniation, bilateral disc herniations in spinal canal and foraminal disc herniation combined with central canal stenosis. They were successfully treated by percutaneous uniportal full endoscopic approach with single incision. Conclusion. Percutaneous endoscopic spine surgery is a safe and effective tool to figure out multilumbar pathology in a minimal invasive way. [ABSTRACT FROM AUTHOR]

Objective. Endoscopic surgeries have been attempted in the field of lumbar decompression and fusion surgery in the past decade. Percutaneous endoscopic lumbar interbody fusion (PELIF) is a new-emerging technique taking advantages of an anatomical (Kambin’s triangle) to achieve simultaneous decompression and fusion under endoscopic visualization. The purpose of this study is to evaluate the feasibility and safety of PELIF technique with general anesthesia and neuromonitoring. Methods. The authors present the details of PELIF technique with general anesthesia and neuromonitoring. The first 7 consecutive patients treated with minimum of 2 year’s follow-up were included. Clinical outcomes were assessed by visual analog scale (VAS) for back and leg pain, Oswestry Disability Index (ODI) scores, and the Short Form-36 health survey questionnaire (SF-36) in the immediate preoperative period and during the follow-up period. Results. All patients underwent single-level PELIF surgery successfully and without conversion to open surgery. The average age was 56.0±13.0 years. All patients had Grade I degenerative/isthmic spondylolisthesis and 4 patients coexisted with disc herniation. The mean operative time was 167.5±30.9 minutes, and intraoperative blood loss was 70.0±24.5 ml. Postoperative drainage volume was 24.5±18.3 ml. The differences in the VAS scores for low back pain and leg pain between preoperative and follow-up were significant (P<0.05). The SF-36 Physical Component Summary (PCS) improved from 38.83±4.17 to 55.67±2.58 (P<0.001). The SF-36 Mental Component Summary (MCS) improved from 43.83±3.13 to 57.50±5.36 (P=0.001). The ODI score improvement rate was 33.7±3.7 %. All cases demonstrated radiopaque graft in the intervertebral disc space consistent with solid arthrodesis. Conclusions. PELIF technique seems to be a promising surgical technique for selected appropriate patients, with the minimal invasive advantages in decreased blood, shortage of ambulation time, and hospital stay, compared with MIS-TLIF. Because of limited Kambin’s triangle space and the exiting nerve root nearby, PELIF is still a challenging technique. Future advancement and development in instrument and cage design are vital for application and popularization of this technique. Prospective, randomized, controlled studies with large sample size on PELIF technique are still needed to prove its safety, efficacy, and minimal invasive advantages. [ABSTRACT FROM AUTHOR]

The aim of this study was to reveal whether demographic aspect, vertebral morphometry, and spine degeneration are associated with lumbar Schmorl’s nodes (SNs). A retrospective cross-sectional study was performed using data from the Department of Radiology (Carmel, Medical Center, Israel) for 180 individuals: age range between 40 and 99 years; 90 males and 90 females. All participants had undergone high-resolution CT scans for abdominal diagnostic purposes in the same supine position prior to our study, which enabled the processing of the scans in all planes and allowed a 3D reconstruction of the lower lumbar region. Eighty individuals (44.4%) had at least one SN along the lumbar spine, particularly at L3-4 level (30%). Vertebral body length (L1 to L3) and width (L1 and L4) were significantly greater in the SNs group compared to non-SNs group. On contrast, disc height (L3-4 and L4-5) was significantly lesser in SNs group than non-SNs group. SNs was significantly associated with smoking (X2= 4.436, P=0.02) and degenerative lumbar spinal stenosis (X2= 5.197, P=0.038). Moreover, the prevalence of SN was significantly greater in individuals with vacuum phenomenon and osteophytes formation (L1-2 to L4-5 levels). This study indicates that vacuum phenomenon on L3-4 (OR: 4.7, P=0.034), smoking habit (OR: 3.2, P=0.003), disc height loss of L4-5 (OR: 0.798, P=0.008), vertebral body length of L1 (OR: 1.37, P<0.001), and age (OR: 1.05, P=0.002) increase the probability of developing lumbar SNs. [ABSTRACT FROM AUTHOR]

Study Design. A retrospective cross-sectional study of type II Modic changes (MCs). Objective. To evaluate the CT values of type II MCs and determine their relationship with disc degeneration. Methods. 124 type II MCs from 66 patients’ MRI and CT were included and analyzed. Disc degeneration adjacent to MCs was evaluated based on Pfirrmann classification. CT values of bone marrow area and endplate from MC regions, adjacent non-MC regions, and L1 vertebra were measured. CT value changes (ΔCT value) were defined as MCs’ CT value minus non-MCs’. According to the types of variables, paired t-test, signed-rank test, two-way ANOVA, and Friedman test were used. Results. The CT value of MCs was significantly higher than that of non-MCs at both bone marrow area and endplate (P<0.0001, resp.). Good consistency was found between non-MCs and L1 vertebra in the CT value of bone marrow area and endplate (P=0.2129, P=0.2272, resp.), suggesting the control group was valid. Adjacent to type II MCs, there were 8 (6.4%) discs with grade III degeneration, 58 (46.8%) with grade IV, and 58 (46.8%) with grade V. The ΔCT value of grade V disc degeneration was larger than that of grade IV at the endplate (P=0.0150). Conclusions. Osteosclerosis may exist in type II MCs. The more severe the degeneration of the adjacent disc, the greater the degree of osteosclerosis. [ABSTRACT FROM AUTHOR]

Background. Facet joint violation (FV) was reported as variable iatrogenic damage that can be a crucial risk factor leading to the adjacent segment degeneration (ASD). “Blind” screw placement technique in minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) contributes to the increasing incidence of FV that can be influenced by several potential factors. Many controversies about these factors and clinical outcomes of different types of FV patients exist, yet they have not been analyzed. Methods. 99 cases undergoing single-segment MIS-TLIF from July 2013 to December 2015 were retrospectively analyzed. Computed tomography (CT) was applied to determine the incidence of FV, and then the correlation between FV and relevant factors, including gender, age, body mass index (BMI), top-screw level, and decompression, was analyzed. A total of 53 cases were followed up after one year, 31 cases in noninjury (A group) and 22 patients in FV injury (B group). Results. The incidence of FV was 39. 39% (39/99) in the patients and 23.23% (46/198) in the screws. Logistic regression analysis showed that screw at L5 in patients with BMI > 30 kg/m2 was vulnerable to FV (P<0.05). Moreover, postoperative average intervertebral disc height (AIDH) of fusion segment, visual analog scale (VAS), and Oswestry disability index (ODI) scores improved significantly in group A and B when compared with preoperative data (P<0.05). Adjacent superior average intervertebral disc height (ASAIDH) presented decrease, but adjacent superior intervertebral disc Cobb angle (ASIDCA) appeared to increase in the two groups at the final follow-up compared with postoperative 3 days (P<0.05). Low back VAS and ODI scores in group A (31 cases) were lower than those in group B (22 cases) in the final follow-up (P<0.05). Conclusion. MIS-TLIF is an effective treatment for lumbar degenerative disease, but FV occurred at a higher incidence. Facet joints should be protected in MIS-TLIF to avoid FV. [ABSTRACT FROM AUTHOR]

Introduction. A prospective comparative study between classical posterior interbody fusion with peduncular screws and the new technique with divergent cortical screws was conducted. Material and Methods. Only patients with monosegmental degenerative disease were recruited into this study. We analyzed a cohort of 40 patients treated from January 2015 to March 2016 divided into 2 groups (20 patients went to traditional open surgery and 20 patients under mini-invasive strategy). Primary endpoints of this study are fusion rate and muscular damage; secondary endpoints analyzed were three different clinical scores (ODI, VAS, and EQ) and the morbidity rate of both techniques. Results. There was no significant difference in fusion rate between the two techniques. In addition, a significant difference in muscular damage was found according to the MRI evaluation. Clinical outcomes, based on pain intensity, Oswestry Disability Index status, and Euroquality-5D score, were found to be also statistically different, even one year after surgery. This study also demonstrated a correlation between patients’ muscular damage and their clinical outcome. Conclusions. Cortical bone trajectory screws would provide similar outcomes compared to pedicle screws in posterior lumbar interbody fusion at one year after surgery, and this technique represents a reasonable alternative to pedicle screws. [ABSTRACT FROM AUTHOR]

Magnetic resonance neurography is a high-resolution imaging technique that allows evaluating different neurological pathologies in correlation to clinical and the electrophysiological data. The aim of this article is to present a review on the anatomy of the lumbosacral plexus nerves, along with imaging protocols, interpretation pitfalls, and most common pathologies that should be recognized by the radiologist: traumatic, iatrogenic, entrapment, tumoral, infectious, and inflammatory conditions. An extensive series of clinical and imaging cases is presented to illustrate key-points throughout the article. [ABSTRACT FROM AUTHOR]

Objectives. Several animal studies have demonstrated the positive effects of platelet-rich plasma (PRP) on disc degeneration retardation. The present meta-analysis was to verify the efficacy of PRP in retarding disc degeneration in animal. Methods. Relevant studies were identified and evaluated according to our inclusion and exclusion criteria. The standardized mean difference (SMD) and related 95% confidence interval (95% CI) were estimated to assess PRP efficiency. Results. In total, eleven studies were included in this meta-analysis. Significant differences were found in the PRP treatment group, which showed increased disc height (SMD = 2.66, 95% CI: 1.86, 3.47, p=0.000), increased MRI T2 signal intensity (SMD = −3.29, 95% CI: −4.44, −2.13, p=0.000), and decreased histological degeneration grade (SMD = −4.28, 95% CI: −5.26, −3.30, p=0.000). However, no significant increase in collagen II expression was found (SMD = 25389.74, 95% CI: −27585.72, 78365.21, p=0.348). Apart from the subgroup analysis of the disc height based on animal species (pig) and disc degeneration model (chymopapain induction), other subgroup analysis based on animal species (rabbit and rat), study design, disc degeneration model, and follow-up period demonstrated that PRP treatment can significantly restore disc height and increase MRI T2 signal intensity. Conclusions. PRP treatment is potentially effective in restoring disc height of rodent rabbit and rat, reducing histological degeneration grade, and increasing MRI T2 image signal. PRP injection may be promising therapy for retarding disc degeneration. [ABSTRACT FROM AUTHOR]

Congenital spinal deformity is the most severe clinical orthopedic issue worldwide. Among all the pathological processes of congenital spinal deformity, the imbalance of endochondral ossification is considered to be the most important developmental cause of spinal dysplasia. We established chondrocyte-specific TSC-1 knockout (KO) mice to overactivate the energy metabolic component, mammalian target of rapamycin complex 1 (mTORC1), and measured the spinal development by general, imaging, histological, and Western-blot assessments. In addition to skeletal dysplasia, the KO mice displayed severe congenital spinal deformity and significant intervertebral disc changes. This study suggests that, in the process of endochondral ossification, excessive activation of mTORC1 signaling in chondrocytes induces obvious spinal deformity, and the chondrocytes may be the cell type responsible for congenital spinal deformity. [ABSTRACT FROM AUTHOR]

The “topping-off” technique is a new concept applying dynamic or less rigid fixation such as hybrid stabilization device (HSD) or interspinous process device (IPD) for the purpose of avoiding adjacent segment disease (ASD) proximal to the fusion construct. A systematic review of the literature was performed on the effect of topping-off techniques to prevent or decrease the occurrence of ASD after lumbar fusion surgery. We searched through major online databases, PubMed and MEDLINE, using key words related to “topping-off” technique. We reviewed the surgical results of “topping-off” techniques with either HSD or IPD, including the incidence of ASD at two proximal adjacent levels (index and supra-adjacent level) as compared to the fusion alone group. The results showed that the fusion alone group had statistically higher incidence of radiographic (52.6%) and symptomatic (11.6%) ASD at the index level as well as higher incidence (8.1%) of revision surgery. Besides, the HSD (10.5%) and fusion groups (24.7%) had statistically higher incidences of radiographic ASD at supra-adjacent level than the IPD (1%). The findings suggest that the “topping-off” technique may potentially decrease the occurrence of ASD at the proximal motion segments. However, higher quality prospective randomized trials are required prior to wide clinical application. [ABSTRACT FROM AUTHOR]