Phillyrin reduces ROS production to alleviate the progression of intervertebral disc degeneration by inhibiting NF-κB pathway.

BACKGROUND: Intervertebral disc degeneration (IDD) is an increasingly important cause of low back pain (LBP) that results in substantial health and economic burdens. Inflammatory pathway activation and the production of reactive oxygen species (ROS) play vital roles in the progression of IDD. Several studies have suggested that phillyrin has a protective role and inhibits inflammation and the production of ROS. However, the role of phillyrin in IDD has not been confirmed. PURPOSE: The purpose of this study was to investigate the role of phillyrin in IDD and its mechanisms. STUDY DESIGN: To establish IDD models in vivo, ex-vivo, and in vitro to verify the function of phillyrin in IDD. METHOD: The effects of phillyrin on extracellular matrix (ECM) degeneration, inflammation, and oxidation in nucleus pulposus (NP) cells were assessed using immunoblotting and immunofluorescence analysis. Additionally, the impact of phillyrin administration on acupuncture-mediated intervertebral disc degeneration (IDD) in rats was evaluated using various techniques such as MRI, HE staining, S-O staining, and immunohistochemistry (IHC). RESULT: Pretreatment with phillyrin significantly inhibited the IL-1ß-mediated reduction in the degeneration of ECM and apoptosis by alleviating activation of the NF-κB inflammatory pathway and the generation of ROS. In addition, in vivo and ex-vivo experiments verified the protective effect of phillyrin against IDD. CONCLUSION: Phillyrin can attenuate the progression of IDD by reducing ROS production and activating inflammatory pathways.

Opportunistic prediction of osteoporosis in patients with degenerative lumbar diseases: a simplified T12 vertebral bone quality approach.

BACKGROUND: Osteoporosis is one of the risk factors for screw loosening after lumbar fusion. However, the probability of preoperative osteoporosis screening in patients with lumbar degenerative disease is low. Therefore, the aim of this study was to investigate whether a simplified vertebral bone quality (VBQ) score based on T12 T1-MRI could opportunistically predict osteoporosis in patients with degenerative lumbar spine diseases. METHODS: We retrospectively analyzed cases treated for lumbar degenerative diseases at a single institution between August 2021 and June 2022. The patients were divided into three groups by the lowest T-score: osteoporosis group, osteopenia group, and normal bone mineral density (BMD) group. The signal intensity based on the T12 vertebral body divided by the signal intensity of the cerebrospinal fluid was calculated to obtain the simplified VBQ score, as well as the CT-based T12HU value and the traditional L1-4VBQ score. Various statistical analyses were used to compare VBQ, HU and DEXA, and the optimal T12VBQ threshold for predicting osteoporosis was obtained by plotting the receiver operating curve (ROC) analysis. RESULTS: Total of 166 patients were included in this study. There was a statistically significant difference in T12VBQ scores between the three groups (p < 0.001). Pearson correlation showed that there was a moderate correlation between T12VBQ and T-score (r=-0.406, p < 0.001). The AUC value of T12VBQ, which distinguishes between normal and low BMD, was 0.756, and the optimal diagnostic threshold was 2.94. The AUC value of T12VBQ, which distinguishes osteoporosis from non-osteoporosis, was 0.634, and the optimal diagnostic threshold was 3.18. CONCLUSION: T12VBQ can be used as an effective opportunistic screening method for osteoporosis in patients with lumbar degenerative diseases. It can be used as a supplement to the evaluation of DEXA and preoperative evaluation. TRIAL REGISTRATION: retrospectively registered number:1502-009-644; retrospectively registered number date:27 oct 2022.

Evaluating lumbar disc degeneration by MRI quantitative metabolic indicators: the perspective of factor analysis.

PURPOSE: This study aimed to investigate an early diagnostic method for lumbar disc degeneration (LDD) and improve its diagnostic accuracy. METHODS: Quantitative biomarkers of the lumbar body (LB) and lumbar discs (LDs) were obtained using nuclear magnetic resonance (NMR) detection technology. The diagnostic weights of each biological metabolism indicator were screened using the factor analysis method. RESULTS: Through factor analysis, common factors such as the LB fat fraction, fat content, and T2* value of LDs were identified as covariates for the diagnostic model for the evaluation of LDD. This model can optimize the accuracy and reliability of LDD diagnosis. CONCLUSION: The application of biomarker quantification methods based on NMR detection technology combined with factor analysis provides an effective means for the early diagnosis of LDD, thereby improving diagnostic accuracy and reliability.

Identification of key eRNAs for intervertebral disc degeneration by integrated multinomial bioinformatics analysis.

BACKGROUND: Intervertebral disc degeneration (IVDD) is a common degenerative condition leading to abnormal stress distribution under load, causing intervertebral stenosis, facet joint degeneration, and foraminal stenosis. Very little is known about the molecular mechanism of eRNAs in IVDD. METHODS: Gene expression profiles of 38 annulus disc samples composed of 27 less degenerated discs (LDs) and 11 more degenerated discs (MDs) were retrieved from the GEO database. Then, differentially expressed enhancer RNAs (DEeRNAs), differentially expressed target genes (DETGs), and differentially expressed transcription factors (DETFs), hallmark of cancer signalling pathways according to GSVA; the types and quantity of immune cells according to CIBERSORT; and immune gene sets according to ssGSEA were analysed to construct an IVDD-related eRNA network. Then, multidimensional validation was performed to explore the interactions among DEeRNAs, DETFs and DEGs in space. RESULTS: A total of 53 components, 14 DETGs, 15 DEeRNAs, 3 DETFs, 5 immune cells, 9 hallmarks, and 7 immune gene sets, were selected to construct the regulatory network. After validation by online multidimensional databases, 21 interactive DEeRNA-DEG-DETF axes related to IVDD exacerbation were identified, among which the C1S-CTNNB1-CHD4 axis was the most significant. CONCLUSION: Based upon the results of our study, we theorize that the C1S-CTNNB1-CHD4 axis plays a vital role in IVDD exacerbation. Specifically, C1S recruits CTNNB1 and upregulates the expression of CHD4 in IVDD, and subsequently, CHD4 suppresses glycolysis and activates oxidative phosphorylation, thus generating insoluble collagen fibre deposits and leading to the progression of IVDD. Overall, these DEeRNAs could comprise promising therapeutic targets for IVDD due to their high tissue specificity.

Comparison of the Outcomes of Anterior Cervical Discectomy and Fusion and Cervical Disc Replacement for Cervical Disc Disease.

OBJECTIVE: To compare the radiological outcome and development of heterotopic ossification (HO) following single-segment anterior cervical discectomy and fusion (ACDF) and cervical disc replacement (CDR) for cervical disc herniation and evaluate their impact on surgical success. STUDY DESIGN: Descriptive comparative study. Place and Duration of the Study: Neurosurgery Department at Bozyaka Education and Research Hospital, Izmir, Turkiye, between January 2020 and June 2022. METHODOLOGY: Patients aged 18-70 years with radicular neck pain unresponsive to conventional medical treatment and an MRI-confirmed diagnosis were included. Patients with osteoporosis (OP) were excluded. Patients were randomised into two treatment groups (ACDF and CDR) and stratified by age and symptom severity. Radiographic assessments and HO classification according to McAfee were performed. RESULTS: Among the included patients, 56 underwent ACDF and 45 underwent CDR. The mean patient age was 48.29 ± 9.530 and 41.84 ± 7.239 years in the ACDF and CDR groups, respectively (p <0.001). The postoperative disc height increased in both groups. The T1 slope was significantly higher preoperatively and in the early postoperative period in the CDR group than in the ACDF group (p = 0.001). HO was graded as 1, 2, 3, and 4 in 28 (27.7%), 6 (5.9%), 7 (6.9%), and 4 (3%) patients, respectively. CONCLUSION: ACDF and CDR provided similar improvements in radiological measurements and pain relief. Although both procedures significantly enhanced the patient's quality of life and disability scores, HO was more prevalent following CDR during long-term follow-up. KEY WORDS: Cervical disc replacement, Anterior cervical discectomy and fusion, Spinal surgery techniques, Heterotopic ossification.

Long-term efficacy of Waveflex semi-rigid-dynamic-internal-fixation system in delaying intervertebral disc degeneration at adjacent segments and improving spinal sagittal imbalance.

The Waveflex semi-rigid-dynamic-internal-fixation system shows good short-term effects in the treatment of lumbar degenerative diseases, but there are few long-term follow-up studies, especially for recovery of sagittal balance. Fifty patients with lumbar degenerative diseases treated from January 2016 to October 2017 were retrospectively analysed: 25 patients treated with Waveflex semi-rigid-dynamic-internal-fixation system (Waveflex group) and 25 patients treated with double-segment PLIF (PLIF group). Clinical efficacy was evaluated by Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI). Imaging data before surgery and at 3 months, 1 year, and 5 years postoperatively was used for imaging indicator assessment. Local disc degeneration of the cephalic adjacent segment (including disc height index (DHI), intervertebral foramen height (IFH), and range of motion (ROM)) and overall spinal motor function (including lumbar lordosis (LL), pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), and |PI-LL|) were analysed. Regarding clinical efficacy, comparison of VAS and ODI scores between the Waveflex and PLIF groups showed no significant preoperative or postoperative differences. The comparison of the objective imaging indicators showed no significant differences in the DHI, IFH, LL, |PI-LL|, and SS values between the Waveflex and PLIF groups preoperatively and 3 months postoperatively (P > 0.05). These values were significantly different at 1 and 5 years postoperatively (P < 0.05), and the Waveflex group showed better ROM values than those of the PLIF group (P < 0.05). PI values were not significantly different between the groups, but PT showed a significant improvement in the Waveflex group 5 years postoperatively (P < 0.05). The Waveflex semi-rigid dynamic fixation system can effectively reduce the probability of intervertebral disc degeneration in upper adjacent segments. Simultaneously, patients in the Waveflex group showed postoperative improvements in LL, spinal sagittal imbalance, and quality of life.

Proposal for a classification system of radiographic bone changes after cervical disc replacement.

BACKGROUND: The goal of this study is to propose a classification system with a common nomenclature for radiographic observations of periprosthetic bone changes following cTDR. METHODS: Aided by serial plain radiographs from recent cTDR cases (34 patients; 44 devices), a panel of experts assembled for the purpose of creating a classification system to aid in reproducibly and accurately identifying bony changes and assessing cTDR radiographic appearance. Subdividing the superior and inferior vertebral bodies into 3 equal sections, observed bone loss such as endplate rounding, cystic erosion adjacent to the endplate, and cystic erosion not adjacent to the endplate, is recorded. Determining if bone loss is progressive, based on serial radiographs, and estimating severity of bone loss (measured by the percentage of end plate involved) is recorded. Additional relevant bony changes and device observations include radiolucent lines, heterotopic ossification, vertebral body olisthesis, loss of core implant height, and presence of device migration, and subsidence. RESULTS: Serial radiographs from 19 patients (25 devices) implanted with a variety of cTDR designs were assessed by 6 investigators including clinicians and scientists experienced in cTDR or appendicular skeleton joint replacement. The overall agreement of assessments ranged from 49.9% (95% bootstrap confidence interval 45.1-73.1%) to 94.7% (95% CI 86.9-100.0%). There was reasonable agreement on the presence or absence of bone loss or radiolucencies (range: 58.4% (95% CI 51.5-82.7%) to 94.7% (95% CI 86.9-100.0%), as well as in the progression of radiolucent lines (82.9% (95% CI 74.4-96.5%)). CONCLUSIONS: The novel classification system proposed demonstrated good concordance among experienced investigators in this field and represents a useful advancement for improving reporting in cTDR studies.

The Emerging Roles of Nanocarrier Drug Delivery System in Treatment of Intervertebral Disc Degeneration-Current Knowledge, Hot Spots, Challenges and Future Perspectives.

Low back pain (LBP) is a common condition that has substantial consequences on individuals and society, both socially and economically. The primary contributor to LBP is often identified as intervertebral disc degeneration (IVDD), which worsens and leads to significant spinal problems. The conventional treatment approach for IVDD involves physiotherapy, drug therapy for pain management, and, in severe cases, surgery. However, none of these treatments address the underlying cause of the condition, meaning that they cannot fundamentally reverse IVDD or restore the mechanical function of the spine. Nanotechnology and regenerative medicine have made significant advancements in the field of healthcare, particularly in the area of nanodrug delivery systems (NDDSs). These approaches have demonstrated significant potential in enhancing the efficacy of IVDD treatments by providing benefits such as high biocompatibility, biodegradability, precise drug delivery to targeted areas, prolonged drug release, and improved therapeutic results. The advancements in different NDDSs designed for delivering various genes, cells, proteins and therapeutic drugs have opened up new opportunities for effectively addressing IVDD. This comprehensive review provides a consolidated overview of the recent advancements in the use of NDDSs for the treatment of IVDD. It emphasizes the potential of these systems in overcoming the challenges associated with this condition. Meanwhile, the insights and ideas presented in this review aim to contribute to the advancement of precise IVDD treatment using NDDSs.

Effects of miR-129-5p on inflammation and nucleus pulposus cell apoptosis in rats with intervertebral disc degeneration through JNK signaling pathway.

This study aimed to explore the effects of miR-129-5p on inflammation and nucleus pulposus (NP) cell apoptosis in rats with intervertebral disc degeneration (IVDD) through the c-Jun N-terminal kinase (JNK) signaling pathway. A total of 20 rats were randomly divided into control group (n=10) or IVDD group (n=10). The mRNA expressions of miR-129-5p and apoptosis index Fas in IVDD tissues were determined using RT-PCR. NP cell apoptosis rate was detected via TUNEL assay. NP cells were extracted from IVDD tissues for primary culture. Subsequently, the cells were transfected with miR-129-5p inhibitor or mimic to inhibit or overexpress miR-129-5p, respectively. Furthermore, the changes in the JNK pathway indexes and apoptosis indexes were detected using Western blotting. In IVDD group, the expression of miR-129-5p was significantly down-regulated, while the transcriptional level of Fas was up-regulated compared with those in control group. Pearson correlation analysis revealed a negative correlation between the expressions of miR-129-5p and Fas mRNA (r=-0.75, P<0.05). IVDD group exhibited significantly higher levels of serum TNF-α, IL-6 and IL-1 than control group. Subsequent TUNEL assay indicated that the apoptosis rate was evidently higher in IVDD group (60.6%) than control group (2.5%). The results of Western blotting showed that the protein expressions of JNK1, JNK2 and Fas remarkably rose in IVDD group compared with those in control group. However, they declined remarkably in miR-129-5p mimic group compared with those in control group. Furthermore, such trends were significantly reversed in miR-129-5p inhibitor group. MiR-129-5p was significantly down-regulated in IVDD, whose overexpression has anti-inflammatory and anti-apoptotic effects.

Engineered extracellular vesicle-based gene therapy for the treatment of discogenic back pain.

Painful musculoskeletal disorders such as intervertebral disc (IVD) degeneration associated with chronic low back pain (termed "Discogenic back pain", DBP), are a significant socio-economic burden worldwide and contribute to the growing opioid crisis. Yet there are very few if any successful interventions that can restore the tissue's structure and function while also addressing the symptomatic pain. Here we have developed a novel non-viral gene therapy, using engineered extracellular vesicles (eEVs) to deliver the developmental transcription factor FOXF1 to the degenerated IVD in an in vivo model. Injured IVDs treated with eEVs loaded with FOXF1 demonstrated robust sex-specific reductions in pain behaviors compared to control groups. Furthermore, significant restoration of IVD structure and function in animals treated with FOXF1 eEVs were observed, with significant increases in disc height, tissue hydration, proteoglycan content, and mechanical properties. This is the first study to successfully restore tissue function while modulating pain behaviors in an animal model of DBP using eEV-based non-viral delivery of transcription factor genes. Such a strategy can be readily translated to other painful musculoskeletal disorders.

Ephrin B2 (EFNB2) potentially protects against intervertebral disc degeneration through inhibiting nucleus pulposus cell apoptosis.

Nucleus pulposus (NP) cell apoptosis is a significant indication of accelerated intervertebral disc degeneration; however, the precise mechanism is unelucidated as of yet. Ephrin B2 (EFNB2), the only gene down-regulated in the three degraded intervertebral disc tissue microarray groups (GSE70362, GSE147383 and GSE56081), was screened for examination in this study. Subsequently, EFNB2 was verified to be down-regulated in degraded NP tissue samples. Interleukin-1 (IL-1ß) treatment of NP cells to simulate the IDD environment indicated that IL-1ß treatment decreased EFNB2 expression. In degenerative NP cells stimulated by IL-1ß, EFNB2 knockdown significantly increased the rate of apoptosis as well as the apoptosis-related molecules cleaved-caspase-3 and the Bax to Bcl-2 ratio. EFNB2 was found to promote AKT, PI3K, and mTOR phosphorylation; the PI3K/AKT signaling role was investigated using the PI3K inhibitor LY294002. EFNB2 overexpression significantly increased PI3K/AKT pathway activity in IL-1ß-stimulated NP cells than the normal control. Moreover, EFNB2 partially alleviated NP cell apoptosis induced by IL-1ß, reduced the cleaved-cas3 level, and decreased the Bax/Bcl-2 ratio after the addition of the inhibitor LY294002. Additionally, EFNB2 overexpression inhibited the ERK1/2 phosphorylation; the effects of EFNB2 overexpression on ERK1/2 phosphorylation, degenerative NP cell viability, and cell apoptosis were partially reversed by ERK signaling activator Ceramide C6. EFNB2 comprehensively inhibited the apoptosis of NP cells by activating the PI3K/AKT signaling and inhibiting the ERK signaling, obviating the exacerbation of IDD. EFNB2 could be a potential target to protect against degenerative disc changes.

Genkwanin alleviates intervertebral disc degeneration via regulating ITGA2/PI3K/AKT pathway and inhibiting apoptosis and senescence.

Intervertebral disc degeneration (IVDD) is a progressive degenerative disease influenced by various factors. Genkwanin, a known anti-inflammatory flavonoid, has not been explored for its potential in IVDD management. This study aims to investigate the effects and mechanisms of genkwanin on IVDD. In vitro, cell experiments revealed that genkwanin dose-dependently inhibited Interleukin-1ß-induced expression levels of inflammatory factors (Interleukin-6, inducible nitric oxide synthase, cyclooxygenase-2) and degradation metabolic protein (matrix metalloproteinase-13). Concurrently, genkwanin upregulated the expression of synthetic metabolism genes (type II collagen, aggrecan). Moreover, genkwanin effectively reduced the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin, mitogen-activated protein kinase (MAPK), and nuclear factor-κB (NF-κB) pathways. Transcriptome sequencing analysis identified integrin α2 (ITGA2) as a potential target of genkwanin, and silencing ITGA2 reversed the activation of PI3K/AKT pathway induced by Interleukin-1ß. Furthermore, genkwanin alleviated Interleukin-1ß-induced senescence and apoptosis in nucleus pulposus cells. In vivo animal experiments demonstrated that genkwanin mitigated the progression of IVDD in the rat model through imaging and histological examinations. In conclusion, This study suggest that genkwanin inhibits inflammation in nucleus pulposus cells, promotes extracellular matrix remodeling, suppresses cellular senescence and apoptosis, through the ITGA2/PI3K/AKT, NF-κB and MAPK signaling pathways. These findings indicate that genkwanin may be a promising therapeutic candidate for IVDD.

Risk factors for early-onset adjacent segment degeneration after one-segment posterior lumbar interbody fusion.

Adjacent segment degeneration (ASD) is a major postoperative complication associated with posterior lumbar interbody fusion (PLIF). Early-onset ASD may differ pathologically from late-onset ASD. The aim of this study was to identify risk factors for early-onset ASD at the cranial segment occurring within 2 years after surgery. A retrospective study was performed for 170 patients with L4 degenerative spondylolisthesis who underwent one-segment PLIF. Of these patients, 20.6% had early-onset ASD at L3-4. In multivariate logistic regression analysis, preoperative larger % slip, vertebral bone marrow edema at the cranial segment on preoperative MRI (odds ratio 16.8), and surgical disc space distraction (cut-off 4.0 mm) were significant independent risk factors for early-onset ASD. Patients with preoperative imaging findings of bone marrow edema at the cranial segment had a 57.1% rate of early-onset ASD. A vacuum phenomenon and/or concomitant decompression at the cranial segment, the degree of surgical reduction of slippage, and lumbosacral spinal alignment were not risk factors for early-onset ASD. The need for fusion surgery requires careful consideration if vertebral bone marrow edema at the cranial segment adjacent to the fusion segment is detected on preoperative MRI, due to the negative impact of this edema on the incidence of early-onset ASD.

[Comparison of Clinical Effects of Cortical Bone Trajectory Screws and Traditional Pedicle Screws in Posterior Lumbar Fusion]. / è °æ¤ŽåŽè·¯èžåˆæœ¯ä¸­çš®è´¨éª¨è½¨è¿¹èžºé’‰å’Œä¼ ç»Ÿæ¤Žå¼“æ ¹èžºé’‰çš„ä¸´åºŠæ•ˆæžœæ¯”è¾ƒ.

Objective: To compare the clinical effects of cortical bone trajectory screws and traditional pedicle screws in posterior lumbar fusion. Methods: A retrospective study was conducted to analyze lumbar degeneration patients who underwent surgical treatment at our hospital between January 2016 and January 2019. A total of 123 patients who met the inclusion criteria were enrolled. The subjects were divided into two groups according to their surgical procedures and the members of the two groups were matched by age, sex, and the number of fusion segments. There were 63 patients in the traditional pedicle screws (PS) group and 60 in the cortical bone trajectory screws (CBTS) group. The outcomes of the two groups were compared. The primary outcome measures were perioperative conditions, including operation duration, estimated intraoperative blood loss (EBL), and length-of-stay (LOS), visual analog scale (VAS) score, Oswestry Disability Index (ODI) score, and interbody fusion rate. The secondary outcome measures were the time to postoperative ambulation and the incidence of complications. VAS scores and ODI scores were assessed before operation, 1 week, 1 month, 3 months, and 12 months after operation, and at the final follow-up. The interbody fusion rate was assessed in 1 year and 2 years after the operation and at the final follow-up. Results: The CBTS group showed a reduction in operation duration ([142.8±13.1] min vs. [174.7±15.4] min, P<0.001), LOS ([9.5±1.5] d vs. [12.0±2.0] d, P<0.001), and EBL ([194.2±38.3] mL vs. [377.5±33.1] mL, P<0.001) in comparison with the PS group. The VAS score for back pain in the CBTS group was lower than that in the PS group at 1 week and 1 month after operation and the ODI score in the CBTS group was lower than that in the PS group at 1 month after operation, with the differences being statistically significant (P<0.05). At each postoperative time point, the VAS score for leg pain and the interbody fusion rate did not show significant difference between the two groups. The VAS score for back and leg pain and the ODI score at each time point after operation in both the CBTS group and the PS group were significantly lower than those before operation (P<0.05). No significant difference was found in the time to postoperative ambulation or the overall complication incidence between the two groups. Conclusion: The CBTS technique could significantly shorten the operation duration and LOS, reduce EBL, and achieve the same effect as the PS technique does in terms of intervertebral fusion rate, pain relief, functional improvement, and complication incidence in patients undergoing posterior lumbar fusion.

Practice variation in surgical treatment for lumbar degenerative disc disease: exploring regional and hospital factors influencing surgical rates.

The presence of significant, unwarranted variation in treatment suggests that clinical decision making also depends on where patients live instead of what they need and prefer. Historically, high practice variation in surgical treatment for lumbar degenerative disc disease (LDDD) has been documented. This study aimed to investigate current regional variation in surgical treatment for sciatica resulting from LDDD. We conducted a retrospective, cross-sectional analysis of all Dutch adults (>18 years) between 2016 and 2019. Demographic data from Statistics Netherlands were merged with a nationwide claims database, covering over 99% of the population. Inclusion criteria comprised LDDD diagnosis codes and relevant surgical codes. Practice variation was assessed at the level of postal code areas and hospital service areas (HSAs). Multivariable logistic regression analysis was employed to identify variables associated with surgical treatment. Among the 119,148 hospital visitors with LDDD, 14,840 underwent surgical treatment. Practice variation for laminectomies and discectomies showed less than two-fold variation in both postal code and HSAs. However, instrumented fusion surgery demonstrated a five-fold variation in postal code areas and three-fold variation in HSAs. Predictors of receiving surgical treatment included opioid prescription and patient referral status. Gender differences were observed, with males more likely to undergo laminectomy or discectomy, and females more likely to receive instrumented fusion surgery. Our study revealed low variation rates for discectomies and laminectomies, while indicating a high variation rate for instrumented fusion surgery in LDDD patients. High-quality research is needed on the extent of guideline implementation and its influence on practice variation.

Full endoscopic laminotomy decompression versus anterior cervical discectomy and fusion for the treatment of single-segment cervical spinal stenosis: a retrospective, propensity score-matched study.

OBJECTIVE: Anterior cervical discectomy and fusion (ACDF) is the standard procedure for the treatment of cervical spinal stenosis (CSS), but complications such as adjacent segment degeneration can seriously affect the long-term efficacy. Currently, posterior endoscopic surgery has been increasingly used in the clinical treatment of CSS. The aim of this study was to compare the clinical outcomes of single-segment CSS patients who underwent full endoscopic laminotomy decompression or ACDF. METHODS: 138 CSS patients who met the inclusion criteria from June 2018 to August 2020 were retrospectively analyzed and divided into endoscopic and ACDF groups. The propensity score matching (PSM) method was used to adjust the imbalanced confounding variables between the groups. Then, perioperative data were recorded and clinical outcomes were compared, including functional scores and imaging data. Functional scores included Visual Analog Scale of Arms (A-VAS) and Neck pain (N-VAS), Japanese Orthopedic Association score (JOA), Neck Disability Index (NDI), and imaging data included Disc Height Index (DHI), Cervical range of motion (ROM), and Ratio of grey scale (RVG). RESULTS: After PSM, 84 patients were included in the study and followed for 24-30 months. The endoscopic group was significantly superior to the ACDF group in terms of operative time, intraoperative blood loss, incision length, and hospital stay (P < 0.001). Postoperative N-VAS, A-VAS, JOA, and NDI were significantly improved in both groups compared with the preoperative period (P < 0.001), and the endoscopic group showed better improvement at 7 days postoperatively (P < 0.05). The ROM changes of adjacent segments were significantly larger in the ACDF group at 12 months postoperatively and at the last follow-up (P < 0.05). The RVG of adjacent segments showed a decreasing trend, and the decrease was more marked in the ACDF group at last follow-up (P < 0.05). According to the modified MacNab criteria, the excellent and good rates in the endoscopic group and ACDF group were 90.48% and 88.10%, respectively, with no statistically significant difference (P > 0.05). CONCLUSION: Full endoscopic laminotomy decompression is demonstrated to be an efficacious alternative technique to traditional ACDF for the treatment of single-segment CSS, with the advantages of less trauma, faster recovery, and less impact on cervical spine kinematics and adjacent segmental degeneration.

Progress in the study of molecular mechanisms of intervertebral disc degeneration.

Degenerative intervertebral disc disease (IVDD) is one of the main spinal surgery, conditions, which markedly increases the incidence of low back pain and deteriorates the patient's quality of life, and it imposes significant social and economic burdens. The molecular pathology of IVDD is highly complex and multilateral however still not ompletely understood. New findings indicate that IVDD is closely associated with inflammation, oxidative stress, cell injury and extracellular matrix metabolismdysregulation. Symptomatic management is the main therapeutic approach adopted for IVDD, but it fails to address the basic pathological changes and the causes of the disease. However, research is still focusing on molecular aspects in terms of gene expression, growth factors and cell signaling pathways in an attempt to identify specific molecular targets for IVDD treatment. The paper summarizes the most recent achievements in molecularunderstanding of the pathogenesis of IVDD and gives evidence-based recommendations for clinical practice.

Selenomethionine preconditioned mesenchymal stem cells derived extracellular vesicles exert enhanced therapeutic efficacy in intervertebral disc degeneration.

Extracellular vesicles (EVs) derived from Mesenchymal Stromal Cells (MSCs) have shown promising therapeutic potential for multiple diseases, including intervertebral disc degeneration (IDD). Nevertheless, the limited production and unstable quality of EVs hindered the clinical application of EVs in IDD. Selenomethionine (Se-Met), the major form of organic selenium present in the cereal diet, showed various beneficial effects, including antioxidant, immunomodulatory and anti-apoptotic effects. In the current study, Se-Met was employed to treat MSCs to investigate whether Se-Met can facilitate the secretion of EVs by MSCs and optimize their therapeutic effects on IDD. On the one hand, Se-Met promoted the production of EVs by enhancing the autophagy activity of MSCs. On the other hand, Se-Met pretreated MSC-derived EVs (Se-EVs) exhibited an enhanced protective effects on alleviating nucleus pulposus cells (NPCs) senescence and attenuating IDD compared with EVs isolated from control MSCs (C-EVs) in vitro and in vivo. Moreover, we performed a miRNA microarray sequencing analysis on EVs to explore the potential mechanism of the protective effects of EVs. The result indicated that miR-125a-5p is markedly enriched in Se-EVs compared to C-EVs. Further in vitro and in vivo experiments revealed that knockdown of miR-125a-5p in Se-EVs (miRKD-Se-EVs) impeded the protective effects of Se-EVs, while overexpression of miR-125a-5p (miROE-Se-EVs) boosted the protective effects. In conclusion, Se-Met facilitated the MSC-derived EVs production and increased miR-125a-5p delivery in Se-EVs, thereby improving the protective effects of MSC-derived EVs on alleviating NPCs senescence and attenuating IDD.

Half of the adolescent idiopathic scoliosis patients may have lumbar adjacent segment degeneration following spinal fusion: A systemic review and meta-analysis.

OBJECTIVE: This study aims to assess the impact of surgical approaches and other factors on the incidence of Adjacent Segment Degeneration (ASD) following Spinal Fusion for Adolescent Idiopathic Scoliosis (AIS). METHODS: We conducted a comprehensive search of four electronic databases from their inception until March 30, 2023. Two independent reviewers screened titles, abstracts, and full texts and evaluated the methodological quality of the studies. A random-effects model was used to calculate the incidence of ASD. RESULTS: Our analysis included 14 studies involving 651 individuals. The overall incidence of ASD was 47% (95%CI: 0.37, 0.56). Subgroup analyses revealed that the prevalence of ASD increased with postoperative time (53% (95%CI: 0.31, 0.75) versus 48% (95%CI: 0.36, 0.60) versus 39% (95%CI: 0.22, 0.56)). For the number of fused segments, a group with more than 10 segments had a higher prevalence (49% (95%CI: 0.38, 0.60) versus 44% (95%CI: 0.21, 0.69)). In terms of regions, East Asia had the highest prevalence, followed by Occident and West Asia (52% (95%CI: 0.41, 0.62) versus 43% (95%CI: 0.20, 0.68) versus 37% (95%CI: 0.17, 0.59)). However, the surgical approach, male ratio, and the position of the lowest instrumented vertebra (LIV) did not show significant differences between groups. Funnel plots and Egger's test did not reveal any significant publication bias (Egger's test: t = 1.62, p-value = .1274). CONCLUSION: This meta-analysis found that nearly half of AIS patients following spinal fusion surgery experienced ASD. Long-term follow-up, regular screening, and timely interventions are essential to reduce the prevalence of ASD.

Role of Galectin-3 in intervertebral disc degeneration: an experimental study.

BACKGROUND: This study investigated the role of Galectin-3 in the degeneration of intervertebral disc cartilage. METHODS: The patients who underwent lumbar spine surgery due to degenerative disc disease were recruited and divided into Modic I, Modic II, and Modic III; groups. HE staining was used to detect the pathological changes in endplates. The changes of Galectin-3, MMP3, Aggrecan, CCL3, and Col II were detected by immunohistochemistry, RT-PCR, and Western blot. MTT and flow cytometry were used to detect cartilage endplate cell proliferation, cell cycle, and apoptosis. RESULTS: With the progression of degeneration (from Modic I to III), the chondrocytes and density of the cartilage endplate of the intervertebral disc decreased, and the collagen arrangement of the cartilage endplate of the intervertebral disc was broken and calcified. Meanwhile, the expressions of Aggrecan, Col II, Galectin-3, Aggrecan, and CCL3 gradually decreased. After treatment with Galectin-3 inhibitor GB1107, the proliferation of rat cartilage end plate cells was significantly reduced (P < 0.05). GB1107 (25 µmol/L) also significantly promoted the apoptosis of cartilage endplate cells (P < 0.05). Moreover, the percentage of cartilage endplate cells in the G1 phase was significantly higher, while that in the G2 and S phases was significantly lower (P < 0.05). Additionally, the mRNA and protein expression levels of MMP3, CCL3, and Aggrecan in rat cartilage end plate cells were lower than those in the control group. CONCLUSIONS: Galectin-3 decreases with the progression of the cartilage endplate degeneration of the intervertebral disc. Galectin-3 may affect intervertebral disc degeneration by regulating the degradation of the extracellular matrix.