miR-29b-3p Affects the Hypertrophy of Ligamentum Flavum in Lumbar Spinal Stenosis and its Mechanism.

To explore the effect of miR-29b-3p on fibrosis and hypertrophy of ligamentum flavum (LF) in lumbar spinal stenosis (LSS) and its underlying mechanism. Patients with LSS and lumbar disc herniation (LDH) (control) undergoing posterior lumbar laminectomy were included in this study. Human LF samples were obtained for LF cell isolation, RNA, and protein extraction. Histomorphological analysis of LF was performed using hematoxylin-eosin (HE) staining. After isolation, culture, and transfection of primary LF cells, different transfection groups were constructed: NC-mimic, miR-29b-3p-mimic, NC-inhibitor, and miR-29b-3p-inhibitor. Quantitative real time polymerase chain reaction (qRT-PCR) was performed to detect the expression of miR-29b-3p in LF and LF cells. Western blot analysis detected the protein expressions of P16 and CyclinD1. ELISA detected the protein expressions of TGF-ß1, Smad2, Smad3, TLR4, Type I collagen, and Type III collagen. Finally, LF cell viability was detected using the Cell Counting Kit-8 (CCK8) assay. The thickness of LF was significantly thicker in the LSS group compared to the LDH group (p < 0.05), accompanied by a higher calcification degree, more fibroblasts, and a larger area of collagen fiber proliferation. miR-29b-3p expression was significantly lower in LSS-derived LF tissues and cells than in LDH-derived tissues and cells (both p < 0.05). Compared to the NC-mimic group, the miR-29b-3p-mimic group exhibited significantly higher miR-29b-3p expression, decreased protein expressions of Type I collagen, Type III collagen, TGF-ß1, Smad2, Smad3, TLR4, P16, and CyclinD1, and inhibited LF cell proliferation (all p < 0.05). As expected, the miR-29b-3p-inhibitor group displayed contrasting expression patterns (all p < 0.05). Compared to the phosphate buffer saline (PBS) group, the Trimethylamine-N-Oxide (TMAO) group showed significantly increased expressions of TGF-ß1, Smad2, Smad3, TLR4, Type I collagen, Type III collagen, P16, and CyclinD1, as well as enhanced LF cell proliferation (all p < 0.05). However, there was no significant difference between the TMAO group and the Ang II group (all p > 0.05). Upregulation of miR-29b-3p expression may play a role in improving LF fibrosis and hypertrophy in LSS by inhibiting P16 expression and suppressing the activation of the TGF-ß/Smad signaling pathway. This finding offers new insights into future gene modification therapy for this patient population.

Characteristics of paraspinal muscle degeneration in patients with adult degenerative scoliosis.

INTRODUCTION: Adult degenerative scoliosis (ADS) is a 3D deformity that greatly affects the quality of life of patients and is closely related to the quality of paraspinal muscles (PSMs), but the specific degenerative characteristics have not been described. METHODS: This study included ADS patients who were first diagnosed in our hospital from 2018 to 2022. Muscle volume (MV) and fat infiltration (FI) of PSM were measured by 3D reconstruction, and spinal parameters were assessed by X-ray. The values of convex side (CV) and concave side (CC) were compared. RESULTS: Fifty patients were enrolled with a mean age of 64.1 ± 5.8 years old. There were significant differences in MV, FI, and Cobb angle between male and female groups. The MV of MF and PS on the CC was significantly larger than that on the CV. In the apex and the segments above the apex, the FI of the MF on the CC is greater than the CV, and in the CV of the segment below the apex, the FI of the MF is greater than the CC. Besides, there was a significant positive correlation between the FI and Cobb angle in the MF of the CC-CV. CONCLUSION: There were significant differences in the MV and FI of PSM on both sides of the spine in ADS patients. It was determined that the PSM of ADS showed different degrees of degeneration in different levels of the lumbar spine and were positively correlated with Cobb angle.

Alternating current stimulation promotes neurite outgrowth and plasticity in neurons through activation of the PI3K/AKT signaling pathway.

As a commonly used physical intervention, electrical stimulation (ES) has been demonstrated to be effective in the treatment of central nervous system disorders. Currently, researchers are studying the effects of electrical stimulation on individual neurons and neural networks, which are dependent on factors such as stimulation intensity, duration, location, and neuronal properties. However, the exact mechanism of action of electrical stimulation remains unclear. In some cases, repeated or prolonged electrical stimulation can lead to changes in the morphology or function of the neuron. In this study, immunofluorescence staining and Sholl analysis are used to assess changes in the neurite number and axon length to determine the optimal pattern and stimulation parameters of ES for neurons. Neuronal death and plasticity are detected by TUNEL staining and microelectrode array assays, respectively. mRNA sequencing and bioinformatics analysis are applied to predict the key targets of the action of ES on neurons, and the identified targets are validated by western blot analysis and qRT-PCR. The effects of alternating current stimulation (ACS) on neurons are more significant than those of direct current stimulation (DCS), and the optimal parameters are 3 µA and 20 min. ACS stimulation significantly increases the number of neurites, the length of axons and the spontaneous electrical activity of neurons, significantly elevates the expression of growth-associated protein-43 (GAP-43) without significant changes in the expression of neurotrophic factors. Furthermore, application of PI3K/AKT-specific inhibitors significantly abolishes the beneficial effects of ACS on neurons, confirming that the PI3K/AKT pathway is an important potential signaling pathway in the action of ACS.

Low-intensity pulsed ultrasound regulates proliferation and differentiation of neural stem cells through notch signaling pathway.

Low-intensity pulsed ultrasound (LIPUS) is widely used to regulate stem cell proliferation and differentiation. However, the effect of LIPUS stimulation on neural stem cells (NSCs) is not well documented. In this study, we have identified the optimal parameters, and investigated the cellular mechanisms of LIPUS to regulate the proliferation and differentiation of NSCs in vitro. NSCs were obtained and identified by nestin immunostaining. The proliferation of NSCs were measured by using Cell Counting Kit-8 (CCK-8). The expressions of nutritional factors (NTFs) were detected with immunoassay (ELISA). NSCs differentiation were detected by immunofluorescence and immunoblotting analysis. The expression level of proteins involved in the Notch signaling pathway was also measured by immunoblotting assay. Our results showed the intensity of 69.3 mW/cm2 (1 MHz, 8 V) was applicable for LIPUS stimulation. ELISA analysis demonstrated that LIPUS treatment promoted the expression of nutritional factors of NSCs in vitro. Immunofluorescence and immunoblotting analyses suggested that the LIPUS not only reduced the astrocyte differentiation, but also stimulated the differentiation to neurons. Additionally, LIPUS stimulation significantly upregulated expression level of Notch1 and Hes1. Results from our study suggest that LIPUS triggers NSCs proliferation and differentiation by modulating the Notch signaling pathway. This study implies LIPUS as a potential and promising therapeutic platform for the optimization of stem cells and enable noninvasive neuromodulation for central nervous system diseases.

The correlation between imaging expression of P16 and S100 in hypertrophic ligamentum flavum.

BACKGROUND: Lumbar spinal stenosis (LSS) is a common degenerative disease, which can lead to neurological dysfunction and requires surgical treatment. In the previous study, we used H&E staining and immunohistochemistry to qualitatively analyze the expression of S100 and P16 in the pathological process of ligamentum flavum (LF) hypertrophy in patients with LSS. To further explore the relationship between P16, S100 and LF hypertrophy in patients with LSS, we quantitatively detected S100 and P16 and their expressed products based on molecular biology techniques, and analyzed their imaging correlation. METHODS: Before posterior lumbar surgery, LF thickness was measured by Magnetic Resonance Imaging (MRI). Through the operation, we obtained the specimens of LF from 120 patients, all of whom were L4/5 LF. They were designated: simple lumbar disc herniation (LDH), single-segment spinal stenosis (SLSS), and double-segment LSS (DLSS). The detection of each side of LF was assessed. S100 and P16 and their expression products were detected by western blot and quantitative polymerase chain reaction (qPCR). RESULTS: The dorsal mRNA expression of P16 in DLSS group was significantly higher than that in SLSS group. On the dorsal and dural side of LF, the expression of P16 mRNA and proteins in the LDH group was significantly lower than that in SLSS and DLSS groups. We found a correlation between the thickness of LF and the expression of P16. However, there was no significant difference in the expression of S100 mRNA and S100 protein on both sides of the ligament and among the three groups, and no significant correlation between the expression of S100 and the thickness of LF. CONCLUSIONS: P16 is involved in the process of LF hypertrophy in patients with LSS, and the imaging thickness of LF is related to the expression of P16. No obvious evidence proves that S100 may be related to the hypertrophy of LF in patients with LSS.

The expression of P16 and S100 associated with elastin degradation and fibrosis of the Ligamentum Flavum hypertrophy.

BACKGROUND: One of the characteristics of lumbar spinal stenosis (LSS) is elastin degradation and fibrosis in the ligamentum flavum (LF). However, the biochemical factors that cause these histologic changes is unclear. P16 and S100 participate in scar formation and collagen development in wound healing and fibrosis diseases. In this study, we investigate the association between P16 and S100 expression and the fibrosis of the hypertrophic LF in LSS. METHODS: The LF specimens were surgically obtained from 30 patients with single-segment LSS (SLSS), 30 patients with double-segment LSS (DLSS) and 30 patients with L4/5 lumbar disc herniation (LDH). The LF thickness was measured by axial T1-weighted MRI. The extent of LF elastin degradation and fibrosis were graded based on hematoxylin-eosin (HE) and Verhoff's Van Gieson's (VVG) stain, respectively. The localization of P16 and S100 was determined by immunohistochemistry. RESULTS: The Absolute and relative LF thickness were greater in the DLSS group compared with the SLSS and LDH groups (p <  0.05). The elastic tissue from the dorsal aspect to the dural aspect in SLSS and DLSS groups was significantly increased. The amount of collagen deposition and elastic tissue is significantly higher in the DLSS group compared with the SLSS and LDH groups (p <  0.05). The specimens in the DLSS group showed positive staining of P16, especially in the dorsal layer. Almost all samples in the SLSS group were partially positive for P16. The LDH group showed negative staining of P16 in both the dural and dorsal layers. All the three groups were stained with S100 in the dorsal layer of the LF. On the contrary, S100 staining was absent in the dural layer of the LF in the three groups. CONCLUSIONS: Elastin degradation and fibrosis of the LF in the DLSS patients is more severe compared with the SLSS and LDH patients. Increased expression of P16 associated with LF fibrosis and thickness, suggested that the expression of P16 may related to LF hypertrophy in the patients who suffer with LSS. LF hypertrophy process may not be associated with high expression of S100.

The Prognostic Value of Serum Neuron Specific Enolase (NSE) and S100B Level in Patients of Acute Spinal Cord Injury.

BACKGROUND The correlation between serum concentration of neuron specific enolase (NSE), S100B, and the prognosis of patients with acute spinal cord injury (ASCI) remains controversial. MATERIAL AND METHODS Sixty patients with confirmed diagnosis of ASCI were recruited for this study from February 2015 to January 2017. The serum level of NSE and S100B were dynamically measured: on the day of injury and for 2 weeks. The 60 cases were divided into Group A (1 or more than 1 ASIA grade improved at 6 months after the injury) and Group B (ASIA grades changed <1 at 6 months after the injury). The serum level of the 2 groups were compared at different time points. And the prognostic value of serum NSE and S100B as biomarkers in patients with ASCI were calculated by Bayes theorem. RESULTS The serum levels of NSE in Groups A and B on the 2nd day of injury reached a peak at 66.80±13.76 g/L and 98.87±20.12 µg/L, respectively, and then declined gradually. On the 14th day of injury, the serum levels of NSE in both groups were 21.23±8.45 and 39.32±16.31 µg/L, respectively, which were much lower than those on the 2nd day (P<0.05). The serum levels of S100B in Groups A and B rose after the injury and reached a peak on the 4th day of injury. Then, the levels declined gradually to 1.14±0.64 and 1.97±0.98 µg/L, respectively, 2 weeks after the injury. Serum levels of NSE and S100B were good biomarkers for predicting the prognosis of ASCI patients with the sensitivity of 74.35% and 71.79%, the specificity of 71.43% and 66.67%. The cutoff value for serum NSE and S100B were 29.07 µg/L and 1.67 µg/L respectively. The AUCs were 0.78 (95% CI: 0.66-0.89) and 0.76 (95% CI: 0.63-0.89) respectively for serum NSE and S100B. CONCLUSIONS Serum levels of NSE and S100B protein can reflect the degree of spinal cord injury and could be potential biomarkers for the prognosis of acute spinal cord injury.

Human glioma cells-conditioned medium promotes proliferation and migration of human bone marrow mesenchymal stromal cells in vitro.

PURPOSE: To investigate changes in cell proliferation and migration of human bone marrow-derived mesenchymal stromal cells (hMSCs) in glioma environment, in order to assess the tumorigenic risk of hMSCs in the clinical application to treat human gliomas. METHODS: hMSCs were obtained from normal adult persons and identified by their morphological characteristics and test of their stemness. The U251 glioma cell-conditioned medium (U251-CM) was obtained to simulate the human glioma environment in vitro. hMSCs were cultured in the U251-CM or the control medium in the same conditionzs and changes in cell proliferation and migration were detected by MTT assay and wound healing assay. RESULTS: The results of MTT assay showed that, compared with the control group, the proliferation of hMSCs cultured in U251-CM increased significantly, and the results of wound healing assay showed that the migration of hMSCs cultured in U251-CM also increased significantly. CONCLUSIONS: Human glioma cell-conditioned medium may promote the proliferation and migration of hMSCs, and we are concerned about the tumorigenic risk of hMSCs in glioma environment before their clinical application.

Effect of Paravertebral Muscle Degeneration on Lumbar and Pelvic Sagittal Alignment in Patients With Degenerative Scoliosis.

STUDY DESIGN: Retrospective study. OBJECTIVES: To explore the relationship between lumbar spine muscle mass and lumbar pelvic sagittal parameters in patients with degenerative scoliosis. METHODS: This study included ADS patients who were treated in our hospital from 2019 to 2023. The spinal parameters were evaluated through X-rays, and the relative muscle volume (RMV) and fat infiltration (FI) were measured through three-dimensional reconstruction. Patients were categorized into 3 groups based on SRS-Schwab sagittal balance correction (0, +, ++), and into 3 groups based on GAP score (proportioned, moderately dis-proportioned, severely dis-proportioned). Finally, patients were classified into low-quality and high-quality groups based on the FI of Paraspinal muscles (PSM). RESULTS: The study included a total of 63 patients. Significant statistical differences were observed in the FI and RMV of MF, ES and PS among patients classified by SRS-Schwab PT classification. Additionally, significant statistical differences were found in the RMV of MF and PS among patients classified by SRS-Schwab PI-LL classification and GAP score. Furthermore, a significant correlation was found between the FI and RMV of PSM and lumbopelvic sagittal parameters. The ordinal regression model analysis revealed that FI of ES significantly impacted PT imbalance, while RMV of MF significantly impacted PI-LL imbalance. Moreover, significant differences were noted in PT and PI between the low-quality and high-quality multifidus groups. CONCLUSIONS: As sagittal imbalance worsens, PSM degeneration also intensifies, primarily characterized by an increase in FI and a decrease in RMV. Notably, PT and PI-LL are positively correlated with RMV and negatively correlated with FI.

Coordination function index: A novel indicator for assessing hindlimb locomotor recovery in spinal cord injury rats based on catwalk gait parameters.

In preclinical studies of spinal cord injury (SCI), behavioral assessments are crucial for evaluating treatment effectiveness. Commonly used methods include Basso, Beattie, Bresnahan (BBB) score and the Louisville swim scale (LSS), relying on subjective observations. The CatWalk automated gait analysis system is also widely used in SCI studies, providing extensive gait parameters from footprints. However, these parameters are often used independently or combined simply without utilizing the vast amount of data provided by CatWalk. Therefore, it is necessary to develop a novel approach encompassing multiple CatWalk parameters for a comprehensive and objective assessment of locomotor function. In this work, we screened 208 CatWalk XT gait parameters and identified 38 suitable for assessing hindlimb motor function recovery in a rat thoracic contusion SCI model. Exploratory factor analysis was used to reveal structural relationships among these parameters. Weighted scores for Coordination effectively differentiated hindlimb motor function levels, termed as the Coordinated Function Index (CFI). CFI showed high reliability, exhibiting high correlations with BBB scores, LSS, and T2WI lesion area. Finally, we simplified CFI based on factor loadings and correlation analysis, obtaining a streamlined version with reliable assessment efficacy. In conclusion, we developed a systematic assessment indicator utilizing multiple CatWalk parameters to objectively evaluate hindlimb motor function recovery in rats after thoracic contusion SCI.

UAMC-3203 inhibits ferroptosis and promotes functional recovery in rats with spinal cord injury.

Spinal cord injury (SCI) results in irreversible neurological impairment. After SCI, Ferritinophagy-induced free iron released from ferritin can lead to extensive lipid peroxidation and aggravate neurological damage. NRF2/HO-1 pathway is to endow cells with a protective effect against oxidative stress, and it plays an important role in the transcriptional activation of a series of antioxidant and detoxification genes. UAMC-3203 is a ferrostatin-1(Fer-1) analogue with better solubility and stability, which can more effectively inhibit ferroptosis after SCI. A rat SCI model was constructed, and the recovery of motor function was observed after treatment with UAMC-3203. ELISA was employed to assess the impact of UAMC-3203 on inflammation-related factors, while immunofluorescence was utilized to investigate the influence of UAMC-3203 on neuronal count as well as the activation of astrocytes and microglia/macrophages. Malondialdehyde (MDA) were detected to reflect the level of oxidation products. Western blot analysis was used to measure the level of ferroptosis markers and the expression of NRF2/HO-1. Our findings demonstrate that UAMC-3203 inhibits the production of reactive oxygen species (ROS) and lipid peroxides, preventing ferroptosis and reducing neuronal degeneration. Additionally, UAMC-3203 suppresses astrocyte proliferation and microglia/macrophage activation, as well as the release of ferroptosis-related inflammatory factors. These combined effects contribute to the preservation of spinal cord tissue and the facilitation of motor function recovery. UAMC-3203 maybe inhibit ferroptosis after SCI to promote functional recovery.

Epidemiological and clinical features, treatment status, and economic burden of traumatic spinal cord injury in China: a hospital-based retrospective study.

Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death. China has the largest population of patients with traumatic spinal cord injury. Previous studies of traumatic spinal cord injury in China have mostly been regional in scope; national-level studies have been rare. To the best of our knowledge, no national-level study of treatment status and economic burden has been performed. This retrospective study aimed to examine the epidemiological and clinical features, treatment status, and economic burden of traumatic spinal cord injury in China at the national level. We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China. Patient epidemiological and clinical features, treatment status, and total and daily costs were recorded. Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program. The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall (annual percentage change, -0.5% and 2.1%, respectively). A total of 10,053 (74.7%) patients underwent surgery. Only 2.8% of patients who underwent surgery did so within 24 hours of injury. A total of 2005 (14.9%) patients were treated with high-dose (≥ 500 mg) methylprednisolone sodium succinate/methylprednisolone (MPSS/MP); 615 (4.6%) received it within 8 hours. The total cost for acute traumatic spinal cord injury decreased over the study period (-4.7%), while daily cost did not significantly change (1.0% increase). Our findings indicate that public health initiatives should aim at improving hospitals' ability to complete early surgery within 24 hours, which is associated with improved sensorimotor recovery, increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.

Resveratrol improves the prognosis of rats after spinal cord injury by inhibiting mitogen-activated protein kinases signaling pathway.

Spinal cord injury (SCI) is a serious condition that results in irreparable nerve damage and severe loss of motor or sensory function. Resveratrol (3,4',5-trihy- droxystilbene) is a naturally occurring plant-based polyphenol that has demonstrated powerful antioxidative, anti-inflammatory, and anti-carcinogenic pharmaceutical properties in previous studies. In the central nervous system, it promotes neuronal recovery and protects residual function. However, the role of resveratrol in SCI recovery remains elusive. In this study, the potential mechanisms by which resveratrol affect SCI in rats were assessed by constructing a contusion model of SCI. Resveratrol was intraperitoneally administered to rats. Behavioral scores and electrophysiological examinations were performed to assess functional recovery. After magnetic resonance imaging and staining with hematoxylin and eosin (HE) and Luxor Fast Blue (LFB), tissue recovery was analyzed. Immunofluorescence with NeuN and glial fibrillary acidic protein (GFAP) was employed to evaluate neuronal survival and glial changes. TdT-mediated dUTP nick end labeling (TUNEL) assay was performed to examine apoptotic rates. Moreover, network pharmacology was performed to identify relevant pathways of resveratrol for the treatment of SCI. Lastly, ELISA was performed to detect the expression levels of interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and IL-6. Our findings revealed that resveratrol dramatically improved the hindlimb locomotor function and their electrophysiological outcomes. Notably, lesion size was significantly reduced on magnetic resonance imaging. HE and LFB staining exposed increased sparseness of tissue and myelin. GFAP and NeuN immunofluorescence assays at the lesion site determined that resveratrol boosted neuronal survival and attenuated glial cell overgrowth. In addition, resveratrol reduced the density and number of TUNEL-positive cells in rats after injury. Additionally, gene ontology analysis revealed that the enriched differentially expressed protein was associated with the JNK/p38MAPK (c-jun N-terminal kinase/p38 mitogen-activated protein kinase) signaling pathway. Following resveratrol treatment, the expression levels of IL-1ß, TNF-α, and IL-6 were decreased. In summary, the administration of resveratrol protects motor function and neuronal survival in rats after SCI. Furthermore, resveratrol exerts an anti-inflammatory effect by blocking the JNK/p38MAPK signaling pathway.

Effects of low-intensity ultrasound opening the blood-brain barrier on Alzheimer's disease-a mini review.

Due to the complex pathological mechanisms of Alzheimer's disease (AD), its treatment remains a challenge. One of the major difficulties in treating AD is the difficulty for drugs to cross the blood-brain barrier (BBB). Low-intensity ultrasound (LIUS) is a novel type of ultrasound with neuromodulation function. It has been widely reported that LIUS combined with intravenous injection of microbubbles (MB) can effectively, safely, and reversibly open the BBB to achieve non-invasive targeted drug delivery. However, many studies have reported that LIUS combined with MB-mediated BBB opening (LIUS + MB-BBBO) can improve pathological deposition and cognitive impairment in AD patients and mice without delivering additional drugs. This article reviews the relevant research studies on LIUS + MB-BBBO in the treatment of AD, analyzes its potential mechanisms, and summarizes relevant ultrasound parameters.

Corrigendum: Network pharmacology integrated with experimental validation to explore the therapeutic role and potential mechanism of Epimedium for spinal cord injury.

[This corrects the article DOI: 10.3389/fnmol.2023.1074703.].

Network pharmacology integrated with experimental validation to explore the therapeutic role and potential mechanism of Epimedium for spinal cord injury.

Objective: Epimedium (EPI) is a common Chinese herb with neuroprotective effects against a variety of central nervous system disorders, especially spinal cord injury (SCI). In this study, we performed network pharmacology and molecular docking analyses to reveal the mechanism underlying EPI treatment of SCI, then validated its efficacy using animal models. Methods: The active ingredients and targets of EPI were screened by Traditional Chinese Medicine Systems Pharmacology (TCMSP) and their targets annotated on the UniProt platform. SCI-related targets were searched from OMIM, TTD, and GeneCards databases. We employed the STRING platform to construct a protein-protein interaction (PPI) network then visualized the results using Cytoscape (3.8.2) software. We also subjected key EPI targets to ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, then docked the main active ingredients with the key targets. Finally, we established an SCI rat model to evaluate efficacy of EPI in treating SCI and validate the effects of different biofunctional modules predicted by network pharmacology. Results: A total of 133 EPI targets were associated with SCI. GO terms and KEGG pathway enrichment results showed that EPI's effect in treating SCI was significantly associated with inflammatory response, oxidative stress and the PI3K/AKT signaling pathway. Molecular docking results indicated that EPI's active ingredients have a high affinity for the key targets. Results from animal experiments revealed that EPI not only markedly improved Basso, Beattie, and Bresnahan scores in SCI rats, but also significantly improved p-PI3K/PI3K and p-AKT/AKT ratio. Moreover, EPI treatment not only mediated a significant decrease in malondialdehyde (MDA) but also increased both superoxide dismutase (SOD), and glutathione (GSH). However, this phenomenon was successfully reversed by LY294002, a PI3K inhibitor. Conclusion: EPI improves behavioral performance in SCI rats through anti-oxidative stress, which may be mediated by activation of the PI3K/AKT signaling pathway.

Correlation between C7-T1 Intervertebral Foramen Area and Sagittal Parameters in Patients with Cervical Spondylotic Myelopathy.

OBJECTIVE: Cervical spondylotic myelopathy (CSM) is an incomplete spinal cord injury characterized with pain and stiffness in the neck and motor and sensory dysfunction. This study aims to determine whether C7-T1 intervertebral foramen area could be used as a parameter to evaluate the sagittal curvature of cervical spine. METHODS: Patients with clinical manifestations of spinal cord compression were hospitalized in our hospital from September 2018 to August 2019. All patients were diagnosed with CSM by nuclear magnetic imaging and other imaging methods. C2-C7 Cobb angle and T1 slop (T1S) were measured on the sagittal, T2-weighted magnetic resonance image of cervical spine, and C7-T1 intervertebral foramen area were measured using oblique cervical spine X-rays. Patients were divided into two groups according to the value of C2-C7 Cobb angle, including lordosis group (C2-C7 Cobb angle >10°, n = 45) and straight group (C2-7 Cobb angle ≤10°, n = 55). The reliability of the data was evaluated by intraclass correlation coefficient (ICC), and the correlation of the imaging parameters was analyzed by Pearson correlation. RESULTS: A total of 100 patients diagnosed with CSM hospitalized in our department were included. The ICC of the cervical parameters was 0.73. C7-T1 intervertebral foramen area was 40.69 ± 11.44 and 39.95 ± 10.94 mm2 in lordosis and straight group, respectively. The results showed that C7-T1 intervertebral foramen area was positively correlated with both C2-C7 Cobb angle (r = 0.23, p = 0.02) and T1S (r = 0.21, p = 0.03). In lordosis group, there was a positive correlation between C7 and T1 intervertebral foramen area and C2-C7 Cobb angle (r = 0.69, p < 0.01) and T1S (r = 0.34, p = 0.02). However, in straight group, C7-T1 intervertebral foramen area was not correlated with either C2-C7 Cobb angle or T1S. CONCLUSION: C7-T1 intervertebral foramen area measured by oblique X-ray could be an effective method to evaluate the sagittal balance of cervical vertebrae for CSM patients with cervical lordosis.

Mitochondrial regulatory mechanisms in spinal cord injury: A narrative review.

Spinal cord injury is a severe central nervous system injury that results in the permanent loss of motor, sensory, and autonomic functions below the level of injury with limited recovery. The pathological process of spinal cord injury includes primary and secondary injuries, characterized by a progressive cascade. Secondary injury impairs the ability of the mitochondria to maintain homeostasis and leads to calcium overload, excitotoxicity, and oxidative stress, further exacerbating the injury. The defective mitochondrial function observed in these pathologies accelerates neuronal cell death and inhibits regeneration. Treatment of spinal cord injury by preserving mitochondrial biological function is a promising, although still underexplored, therapeutic strategy. This review aimed to explore mitochondrial-based therapeutic advances after spinal cord injury. Specifically, it briefly describes the characteristics of spinal cord injury. It then broadly discusses the drugs used to protect the mitochondria (e.g., cyclosporine A, acetyl-L-carnitine, and alpha-tocopherol), phenomena associated with mitochondrial damage processes (e.g., mitophagy, ferroptosis, and cuproptosis), mitochondrial transplantation for nerve cell regeneration, and innovative mitochondrial combined protection therapy.

Secondary tuberculosis of adjacent segments after anterior cervical discectomy and fusion: A case report.

Introduction: Anterior cervical discectomy and fusion (ACDF) is a common operation for spinal surgery to treat a variety of cervical diseases. The postoperative infection rate of this procedure is extremely low, and adjacent segments are rarely involved. Tuberculosis (TB) is a common infectious disease that affects the spine in less than 1% of cases and is more common in the thoracolumbar and rarely cervical spine. Herein, for the first time, we report tuberculosis infection in adjacent segments after ACDF. Case presentation: We report a 50-year-old patient with cervical spondylotic myelopathy (CSM) who was discharged from the hospital after receiving ACDF at the C3/4 level. Two months later, he was admitted to the hospital with neck pain and found to be infected with tuberculosis in C4/5. After 4 months of anti-tuberculosis treatment, the vertebral body was fused. Conclusion: After ACDF, the adjacent cervical vertebrae were infected with TB but the infection was limited. We believe that the special vertebral blood supply and postoperative secondary blood-borne infection may lead to the occurrence of extrapulmonary tuberculosis.

[Management of postoperative pain after total knee arthroplasty].

OBJECTIVE: To evaluate causes and clinical management of postoperative pain after total knee arthroplasty (TKA). METHODS: From January 2004 to June 2009, 41 patients (44 knees) with knee pain post TKA were treated. There were 9 male and 32 female patients aging from 51 to 84 years with a mean of 63.5 years. The diagnosis followed to Brown diagnostic system. One case of extraarticular pain was complex regional pain syndrome type 1 (CRPS-1) and underwent conservative treatment, the remaining 5 cases were treated by surgery. Three cases of joint instability, 1 case of patellar baja, 2 cases of soft tissue impingement caused by overhang of the prosthesis, 1 case of popliteal tendon impact underwent conservative treatment, the other 27 cases underwent surgical intervention. The patients were followed up and the Knee Society Score (KSS) knee score, pain visual analog scale (VAS) score were recorded. RESULTS: Forty-one cases were followed up for 1 to 6 years. At the last time of follow-up, the 5 cases received surgical treatment to extra-articular pain showed VAS score as 2.5 ± 0.2, KSS clinical and functional score as 92.8 ± 2.6 and 89.0 ± 3.4. There was significantly difference compared with preoperative (P < 0.05). One case of CRPS-1 performed conservative treatment, the therapy was effective. In the infected 12 cases of intra-articular pain, 1 case received amputation, 3 cases received antibiotic bone cement insert, 8 cases received two stage revision. All infections were cured, and VAS score was 3.8 ± 0.2, KSS clinical score was 88.3 ± 4.6, function score was 85.0 ± 4.6 postoperatively, with significantly difference compared with preoperative (P < 0.05). In the 8 cases received conservative treatment in non-infected group, at the last time of follow-up, VAS score was 4.5 ± 0.4, KSS clinical and functional score was 85.4 ± 4.2 and 84.2 ± 2.3, with significantly difference compared with preoperative (P < 0.05). Fifteen cases underwent surgical treatment, at the last time of follow-up, VAS score was 3.4 ± 0.1, KSS clinical and functional score was 86.6 ± 5.4 and 87.1 ± 2.4, with significantly difference compared with preoperative (P < 0.05). CONCLUSIONS: Patients with knee pain post TKA need systematic assessment to identify the causes. Appropriate treatment due to the positive diagnosis generally lead to satisfactory results, surgical intervention with indefinite causes is strictly prohibited.