Identification of Autophagy-Related Genes Involved in Intervertebral Disc Degeneration by Microarray Data Analysis.

BACKGROUND: Nucleus pulposus cells survive in a hypoxic, acidic, nutrient-poor, and hypotonic microenvironment. Consequently, they maintain low proliferation and undergo autophagy to protect themselves from cellular stress. Therefore, we aimed to identify autophagy-related biomarkers involved in intervertebral disc degeneration pathogenesis. METHODS: Autophagy-related differentially expressed genes were derived from the intersection between the public GSE147383 microarray data set to identify differentially expressed genes and online databases to identify autophagy-related genes. Furthermore, we assessed their biological functions with gene annotation and enrichment analysis in the Metscape portal. Then, the STRING database and Cytoscape software allowed inferring a protein-protein interaction (PPI) network and identifying hub genes. In addition, to predict transcription factors that may regulate the hub genes, we used the GeneMANIA website. Finally, the competing endogenous RNA prediction tools and Cytoscape were also used to construct an mRNA-miRNA-lncRNA network. RESULTS: A total of 123 autophagy-related differentially expressed genes were identified, they were mainly involved in phosphoinositide 3-kinase-Akt signaling, autophagy animal, and apoptosis pathways. Nine were identified as hub genes (PTEN, MYC, CTNNB1, JUN, BECN1, ERBB2, FOXO3, ATM, and FN1) and 36 transcription factors were associated with them. Finally, an autophagy-associated competing endogenous RNA network was constructed based on the 9 hub genes. CONCLUSIONS: Nine hub genes were identified and a network of competing endogenous RNA associated with autophagy was established. They can be used as autophagy-related biomarkers of intervertebral disc degeneration and for further exploration.

Bradykinin protects nucleus pulposus cells from tert-butyl hydroperoxide-induced damage and delays intervertebral disc degeneration.

Intervertebral disc degeneration (IVDD) is a leading cause of degenerative spinal disorders, involving complex biological processes. This study investigates the role of the kallikrein-kinin system (KKS) in IVDD, focusing on the protective effects of bradykinin (BK) on nucleus pulposus cells (NPCs) under oxidative stress. Clinical specimens were collected, and experiments were conducted using human and rat primary NPCs to elucidate BK's impact on tert-butyl hydroperoxide (TBHP)-induced oxidative stress and damage. The results demonstrate that BK significantly inhibits TBHP-induced NPC apoptosis and restores mitochondrial function. Further analysis reveals that this protective effect is mediated through the BK receptor 2 (B2R) and its downstream PI3K/AKT pathway. Additionally, BK/PLGA sustained-release microspheres were developed and validated in a rat model, highlighting their potential therapeutic efficacy for IVDD. Overall, this study sheds light on the crucial role of the KKS in IVDD pathogenesis and suggests targeting the B2R as a promising therapeutic strategy to delay IVDD progression and promote disc regeneration.

Risk factors associated with low-grade virulent infection in intervertebral disc degeneration: a systematic review and meta-analysis.

BACKGROUND: An increasing number of research indicates an association between low-grade bacterial infections, particularly those caused by Propionibacterium acnes (P. acnes), and the development of intervertebral disc degeneration (IDD). However, no previous meta-analysis has systematically assessed the risk factors for low-grade bacterial infections that cause IDD. PURPOSE: This study reviewed the literature to evaluate the risk factors associated with low-grade bacterial infection in patients with IDD. STUDY DESIGN: Systematic review and meta-analysis. METHODS: The systematic literature review was conducted using the PubMed, Web of Science, Embase, and Cochrane Library databases. Eligible articles explicitly identified the risk factors for low-grade bacterial infections in IDD patients. Patient demographics and total bacterial infection rates were extracted from each study. Meta-analysis was performed using random- or fixed-effects models, with statistical analyses conducted using Review Manager (RevMan) 5.4 software.aut. RESULTS: Thirty-three studies involving 4,109 patients were included in the meta-analysis. The overall pooled low-grade bacterial infection rate was 30% (range, 24%-37%), with P. acnes accounting for 25% (range, 19%-31%). P. acnes constituted 66.7% of bacteria-positive discs. Fourteen risk factors were identified, of which 8 were quantitatively explored. Strong evidence supported male sex (odds ratio [OR] = 2.15; 95% confidence interval [CI]=1.65-2.79; p<.00001) and Modic changes (MCs) (OR=3.59; 95% CI=1.68-7.76; p=.0009); moderate evidence of sciatica (OR=2.31; 95% CI=1.33-4.00; p=.003) and younger age (OR=-3.47; 95% CI=-6.42 to -0.53; p=.02). No evidence supported previous disc surgery, MC type, Pfirrmann grade, smoking, or diabetes being risk factors for low-grade bacterial infections in patients with IDD. CONCLUSIONS: Current evidence highlights a significant association between IDD and low-grade bacterial infections, predominantly P. acnes being the most common causative agent. Risk factors associated with low-grade bacterial infections in IDD include male sex, MCs, sciatica, and younger age.

S100A6: molecular function and biomarker role.

S100A6 (also called calcyclin) is a Ca2+-binding protein that belongs to the S100 protein family. S100A6 has many functions related to the cytoskeleton, cell stress, proliferation, and differentiation. S100A6 also has many interacting proteins that are distributed in the cytoplasm, nucleus, cell membrane, and outside the cell. Almost all these proteins interact with S100A6 in a Ca2+-dependent manner, and some also have specific motifs responsible for binding to S100A6. The expression of S100A6 is regulated by several transcription factors (such as c-Myc, P53, NF-κB, USF, Nrf2, etc.). The expression level depends on the specific cell type and the transcription factors activated in specific physical and chemical environments, and is also related to histone acetylation, DNA methylation, and other epigenetic modifications. The differential expression of S100A6 in various diseases, and at different stages of those diseases, makes it a good biomarker for differential diagnosis and prognosis evaluation, as well as a potential therapeutic target. In this review, we mainly focus on the S100A6 ligand and its transcriptional regulation, molecular function (cytoskeleton, cell stress, cell differentiation), and role as a biomarker in human disease and stem cells.

TMT-Based Proteomics Analysis of Senescent Nucleus Pulposus from Patients with Intervertebral Disc Degeneration.

Lower back pain, a leading cause of disability worldwide, is associated with intervertebral disc degeneration (IDD) in approximately 40% of cases. Although nucleus pulposus (NP) cell senescence is a major contributor to IDD, the underlying mechanisms remain unclear. We collected NP samples from IDD patients who had undergone spinal surgery. Healthy and senescent NP tissues (n = 3) were screened using the Pfirrmann grading system combined with immunohistochemistry, as well as hematoxylin and eosin, Safranin O, Alcian blue, and Masson staining. Differentially expressed proteins (DEPs) were identified using quantitative TMT-based proteomics technology. Bioinformatics analyses included gene ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and protein-protein interaction (PPI) analyses. In addition, immunofluorescence was used to verify protein expression. In total, 301 DEPs were identified in senescent NP tissues, including 92 upregulated and 209 downregulated proteins. In GO, DEPs were primarily associated with NF-kappaB transcription factor, extracellular regions, cellular protein metabolic processes, and post-translational protein modification. The enriched KEGG pathways included TGF-ß, Wnt, RAP1, interleukin-17, extracellular matrix-receptor adhesion, and PI3K/Akt signaling pathways. PPI analysis demonstrated interactions between multiple proteins. Finally, immunofluorescence verified the expressions of MMP3, LUM, TIMP1, and CDC42 in senescent NP cells. Our study provides valuable insights into the mechanisms underlying senescent NP tissues in IDD patients. DEPs provide a basis for further investigation of the effects of senescent factors on IDD.

The Role of S100A6 in Human Diseases: Molecular Mechanisms and Therapeutic Potential.

S100A6, also known as calcyclin, is a low-molecular-weight Ca2+-binding protein from the S100 family that contains two EF-hands. S100A6 is expressed in a variety of mammalian cells and tissues. It is also expressed in lung, colorectal, pancreatic, and liver cancers, as well as other cancers such as melanoma. S100A6 has many molecular functions related to cell proliferation, the cell cycle, cell differentiation, and the cytoskeleton. It is not only involved in tumor invasion, proliferation, and migration, but also the pathogenesis of other non-neoplastic diseases. In this review, we focus on the molecular mechanisms and potential therapeutic targets of S100A6 in tumors, nervous system diseases, leukemia, endometriosis, cardiovascular disease, osteoarthritis, and other related diseases.

Silencing circular RNA hsa_circABCC1 inhibits osteosarcoma progression through down-regulating HDAC4 via sponging miR-591.

BACKGROUND: Circular RNA (circRNA) has been shown to play an important regulatory role in the development of various cancers, including osteosarcoma (OS). However, the role of circRNA ABCC1 (circABCC1) in OS was still poorly understood. The aim of our study was to investigate the role of circABCC1 in OS progression and its potential molecular mechanisms. METHODS: The expression of circABCC1, microRNA-591 (miR-591) and histone deacetylase 4 (HDAC4) in OS tissues or cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot (WB) analyses. In vitro experiments, the viability, proliferation, apoptosis, migration, invasion and autophagy of U2OS and HOS cells were assessed in vitro using cell counting kit-8 (CCK-8) assay, 5-ethynyl-29-deoxyuridine (EdU) assay, flow cytometry (FCM) assay, transwell migration and invasion assays (transwell) and WB assay, respectively. Interactions between circABCC1 and miR-591, miR-591 and HDAC4 were confirmed using a dual luciferase reporter gene assay system. The oncogenic role of circABCC1 in OS in vivo was examined by establishing a tumor xenograft model. RESULTS: CircABCC1 was significantly elevated in OS tissues (about 3.1-folds) and cells (U2OS (about 2.1-folds) and HOS (about 2.8-folds)) compared with the control (p < .05). Silencing of circABCC1 significantly reduced the viability and proliferation, promoted apoptosis, impaired migration and invasion, and increased autophagy of U2OS and HOS cells (p < .05). In addition, miR-591 was confirmed to be a target of circABCC1, exerting an opposite effect to circABCC1 (p < .05). MiR-591 attenuation in U2OS and HOS cells was able to reply to the inhibition of cell proliferation, migration and invasion as well as promotion of cell apoptosis and autophagy mediated by silencing circABCC1 (p < .05). HDAC4 was verified to be the target gene of miR-591 in U2OS and HOS cells and was regulated by the circABCC1/miR-591 axis (p < .05), and restoration of HDAC4 levels in U2OS and HOS cells was able to restore the altered cellular function caused by silencing circABCC1 (p < .05). In addition, knockdown of circABCC1 attenuated tumor growth in vivo (p < .05). CONCLUSION: Silencing of circABCC1 inhibits osteosarcoma progression by attenuating HDAC4 expression through sponging miR-591.

Effects of spinal deformities on lung development in children: a review.

Scoliosis before the age of 5 years is referred to as early-onset scoliosis (EOS). While causes may vary, EOS can potentially affect respiratory function and lung development as children grow. Moreover, scoliosis can lead to thoracic insufficiency syndrome when aggravated or left untreated. Therefore, spinal thoracic deformities often require intervention in early childhood, and solving these problems requires new methods that include the means for both deformity correction and growth maintenance. Therapeutic strategies for preserving the growing spine and thorax include growth rods, vertically expandable titanium artificial ribs, MAGEC rods, braces and casts. The goals of any growth-promoting surgical strategy are to alter the natural history of cardiorespiratory development, limit the progression of underlying spondylarthrosis deformities and minimize negative changes in spondylothorax biomechanics due to the instrumental action of the implant. This review further elucidates EOS in terms of its aetiology, pathogenesis, pathology and treatment.

Grape Seed Proanthocyanidins Exert a Neuroprotective Effect by Regulating Microglial M1/M2 Polarisation in Rats with Spinal Cord Injury.

Spinal cord injury (SCI) is a highly disabling disorder for which few effective treatments are available. Grape seed proanthocyanidins (GSPs) are polyphenolic compounds with various biological activities. In our preliminary experiment, GSP promoted functional recovery in rats with SCI, but the mechanism remains unclear. Therefore, we explored the protective effects of GSP on SCI and its possible underlying mechanisms. We found that GSP promoted locomotor recovery, reduced neuronal apoptosis, increased neuronal preservation, and regulated microglial polarisation in vivo. We also performed in vitro studies to verify the effects of GSP on neuronal protection and microglial polarisation and their potential mechanisms. We found that GSP regulated microglial polarisation and inhibited apoptosis in PC12 cells induced by M1-BV2 cells through the Toll-like receptor 4- (TLR4-) mediated nuclear factor kappa B (NF-κB) and phosphatidylinositol 3-kinase/serine threonine kinase (PI3K/AKT) signaling pathways. This suggests that GSP regulates microglial polarisation and prevents neuronal apoptosis, possibly by the TLR4-mediated NF-κB and PI3K/AKT signaling pathways.

Role of Caspase Family in Intervertebral Disc Degeneration and Its Therapeutic Prospects.

Intervertebral disc degeneration (IVDD) is a common musculoskeletal degenerative disease worldwide, of which the main clinical manifestation is low back pain (LBP); approximately, 80% of people suffer from it in their lifetime. Currently, the pathogenesis of IVDD is unclear, and modern treatments can only alleviate its symptoms but cannot inhibit or reverse its progression. However, in recent years, targeted therapy has led to new therapeutic strategies. Cysteine-containing aspartate proteolytic enzymes (caspases) are a family of proteases present in the cytoplasm. They are evolutionarily conserved and are involved in cell growth, differentiation, and apoptotic death of eukaryotic cells. In recent years, it has been confirmed to be involved in the pathogenesis of various diseases, mainly by regulating cell apoptosis and inflammatory response. With continuous research on the pathogenesis and pathological process of IVDD, an increasing number of studies have shown that caspases are closely related to the IVDD process, especially in the intervertebral disc (IVD) cell apoptosis and inflammatory response. Therefore, herein we study the role of caspases in IVDD with respect to the structure of caspases and the related signaling pathways involved. This would help explore the strategy of regulating the activity of the caspases involved and develop caspase inhibitors to prevent and treat IVDD. The aim of this review was to identify the caspases involved in IVDD which could be potential targets for the treatment of IVDD.

The PI3K/AKT signalling pathway in inflammation, cell death and glial scar formation after traumatic spinal cord injury: Mechanisms and therapeutic opportunities.

OBJECTS: Traumatic spinal cord injury (TSCI) causes neurological dysfunction below the injured segment of the spinal cord, which significantly impacts the quality of life in affected patients. The phosphoinositide 3kinase/serine-threonine kinase (PI3K/AKT) signaling pathway offers a potential therapeutic target for the inhibition of secondary TSCI. This review summarizes updates concerning the role of the PI3K/AKT pathway in TSCI. MATERIALS AND METHODS: By searching articles related to the TSCI field and the PI3K/AKT signaling pathway, we summarized the mechanisms of secondary TSCI and the PI3K/AKT signaling pathway; we also discuss current and potential future treatment methods for TSCI based on the PI3K/AKT signaling pathway. RESULTS: Early apoptosis and autophagy after TSCI protect the body against injury; a prolonged inflammatory response leads to the accumulation of pro-inflammatory factors and excessive apoptosis, as well as excessive autophagy in the surrounding normal nerve cells, thus aggravating TSCI in the subacute stage of secondary injury. Initial glial scar formation in the subacute phase is a protective mechanism for TSCI, which limits the spread of damage and inflammation. However, mature scar tissue in the chronic phase hinders axon regeneration and prevents the recovery of nerve function. Activation of PI3K/AKT signaling pathway can inhibit the inflammatory response and apoptosis in the subacute phase after secondary TSCI; inhibiting this pathway in the chronic phase can reduce the formation of glial scar. CONCLUSION: The PI3K/AKT signaling pathway has an important role in the recovery of spinal cord function after secondary injury. Inducing the activation of PI3K/AKT signaling pathway in the subacute phase of secondary injury and inhibiting this pathway in the chronic phase may be one of the potential strategies for the treatment of TSCI.

N-acetylserotonin protects PC12 cells from hydrogen peroxide induced damage through ROS mediated PI3K / AKT pathway.

N-acetylserotonin (NAS) exerts neuroprotective, antioxidant, and anti-apoptotic effects. Oxidative stress and apoptosis are the primary causes of spinal cord injury (SCI). Herein, we explored potential protective effects and mechanisms of NAS in a neuron oxidative damage model in vitro. We established an oxidative damage model in PC12 cells induced by hydrogen peroxide (H2O2) and treated these cells with NAS. NAS enhanced the activity of superoxide dismutase and halted the increase in reactive oxygen species (ROS) and the expression of inducible nitric oxide synthase. Additionally, NAS promoted protein expression of Bcl-2, but inhibited protein expressions of Fas, FADD, cytochrome c, Bax, cleaved caspase-9, and cleaved caspase-3, namely, decreasing protein expression of the Fas and mitochondrial pathways. Furthermore, it reduced the rate of apoptosis and necroptosis-related protein expressions of MLKL and p-MLKL. Moreover, NAS promoted the protein expression of p-PI3K and p-AKT, and the addition of the PI3K inhibitor LY294002 partially attenuated the antioxidant stress and anti-apoptotic effects of NAS in H2O2 stimulated PC12 cells. In conclusion, NAS protected PC12 cells from apoptosis and oxidative stress induced by H2O2 by inhibiting ROS activity and activating the PI3K/AKT signaling pathway.

Proanthocyanidins inhibit the apoptosis and aging of nucleus pulposus cells through the PI3K/Akt pathway delaying intervertebral disc degeneration.

BACKGROUND: Low back pain is a common symptom of intervertebral disc degeneration (IDD), which seriously affects the quality of life of patients. The abnormal apoptosis and senescence of nucleus pulposus (NP) cells play important roles in the pathogenesis of IDD. Proanthocyanidins (PACs) are polyphenolic compounds with anti-apoptosis and anti-aging effects. However, their functions in NP cells are not yet clear. Therefore, this study was performed to explore the effects of PACs on NP cell apoptosis and aging and the underlying mechanisms of action. METHODS: Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. The apoptosis rate was determined TUNEL assays. Levels of apoptosis-associated molecules (Bcl-2, Bax, C-caspase-3 and Caspase-9) were evaluated via western blot. The senescence was observed through SA-ß-gal staining and western blotting analysis was performed to observe the expression of senescence-related molecules (p-P53, P53, P21 and P16). RESULTS: Pretreatment with PACs exhibited protective effects against IL-1ß-induced NP cell apoptosis including apoptosis rate, expressions of proapoptosis and antiapoptosis related genes and protein. PACs could also alleviate the increase of p-p53, P21, and P16 in IL-1ß-treated NP cells. SA-ß-gal staining showed that IL-1ß-induced senescence of NP cells was prevented by PACs pertreatment. In addition, PACs activated PI3K/Akt pathway in IL-1ß-stimulated NP cells. However, these protected effects were inhibited after LY294002 treatment. CONCLUSION: The results of the present study showed that PACs inhibit IL-1ß-induced apoptosis and aging of NP cells by activating the PI3K/Akt pathway, and suggested that PACs have therapeutic potential for IDD.

Periostin: an emerging activator of multiple signaling pathways.

Matricellular proteins are responsible for regulating the microenvironment, the behaviors of surrounding cells, and the homeostasis of tissues. Periostin (POSTN), a non-structural matricellular protein, can bind to many extracellular matrix proteins through its different domains. POSTN usually presents at low levels in most adult tissues but is highly expressed in pathological sites such as in tumors and inflamed organs. POSTN can bind to diverse integrins to interact with multiple signaling pathways within cells, which is one of its core biological functions. Increasing evidence shows that POSTN can activate the TGF-ß, the PI3K/Akt, the Wnt, the RhoA/ROCK, the NF-κB, the MAPK and the JAK pathways to promote the occurrence and development of many diseases, especially cancer and inflammatory diseases. Furthermore, POSTN can interact with some pathways in an upstream and downstream relationship, forming complicated crosstalk. This article focuses on the interactions between POSTN and different signaling pathways in diverse diseases, attempting to explain the mechanisms of interaction and provide novel guidelines for the development of targeted therapies.

Experimental study of ß-TCP scaffold loaded with VAN/PLGA microspheres in the treatment of infectious bone defects.

Antibiotic bone cement filling technology has been widely used in the treatment of infectious bone defects for decades. However, the current treatment requires multiple complicated procedures, which would lead to pain and financial burden for patients. Repairing bone defects and control infection at the same time is the pain spot of orthopaedic area. In this study, we develop a composite scaffold that aiming at effectively repair infectious bone defects simultaneously. Vancomycin hydrochloride(Van) /Poly(lactic-co-glycolic) acid(PLGA) microspheres prepared by double emulsion method were successfully loaded into ß-tricalcium phosphate scaffold through electrostatic and physical crosslinking. Full characterization, including mechanical properties, biocompatibility, in vitro release profile and antibacterial properties of the composite scaffolds(CPSFs) were performed. The rabbit osteomyelitis model based on big hole and small hole methods was established. Pharmacodynamics study, including the local bacteriostatic and osteogenic ability were evaluated by X-ray, Micro-CT and histopathology at 4 months after surgery. These findings indicate that a reliable rabbit model of local bone defect infection successfully established by big hole approach. The CPSFs with significant histocompatibility and biocompatibility could sustained release vancomycin for extended duration. It exhibited great application potential in clinical aim at the indication of local infectious bone defects.

Postoperative changes in rib cage deviation in adolescent idiopathic scoliosis.

BACKGROUND: Scoliosis causes changes in the thorax, but it is unclear what type of changes occur in the thoracic profile after scoliosis surgery. OBJECTIVE: To investigate changes in rib cage deviation in the postoperative period after adolescent idiopathic scoliosis (AIS) surgery. METHODS: Forty-four patients with AIS with a main right thoracic curvature underwent posterior surgical fusion (PSF), and radiological parameters of the spine and thorax were evaluated. RESULTS: The correction rates of main thoracic curve (MT)-Cobb angle at immediate after surgery and postoperative follow-up (2 years) were 64% and 66%, respectively. At these two postoperative time points, the correction rates of height of thoracic vertebrae 1 to 12 (T1T12) were 10% and 12%; the correction rates of Rib-vertebra angle difference (RVAD) were 59% and 52%; the correction rates of Apical rib hump prominence (RH) were 58% and 76%; while the correction rates of Apical vertebral body-rib ratio (AVB-R) were 23% and 25%, respectively. Statistical analysis showed that all these radiological parameters at the two postoperative time points were significantly different from the preoperative values (p< 0.001). There were significant correlations between MT-Cobb angle and T1-T12 height (p< 0.001), RVAD (p< 0.001), RH (p< 0.001), and AVB-R (p< 0.001). CONCLUSIONS: Posterior spinal fusion appears to be effective at correcting scoliosis, and the correction of rib cage deviation also plays an important role.

Intervertebral Disc Degeneration Models for Pathophysiology and Regenerative Therapy -Benefits and Limitations.

Aim: This review summarized the recent intervertebral disc degeneration (IDD) models and described their advantages and potential disadvantages, aiming to provide an overview for the current condition of IDD model establishment and new ideas for new strategies development of the treatment and prevention of IDD. Methods: The database of PubMed was searched up to May 2021 with the following search terms: nucleus pulposus, annulus fibrosus, cartilage endplate, intervertebral disc(IVD), intervertebral disc degeneration, animal model, organ culture, bioreactor, inflammatory reaction, mechanical stress, pathophysiology, epidemiology. Any IDD model-related articles were collected and summarized.Results: The best IDD model should have the features of repeatability, measurability and controllability. There are a lot of aspects to be considered in the selection of animals. Mice, rats and rabbits are low-cost and easy to access. However, their IVD size and shape are more different from human anatomy than pigs, cattle, sheep and goats. Organ culture models and animal models are two options in model establishment for IDD. The IVD organ culture model can put the studying variables into the controllable system for transitional research. Unlike the animal model, the organ culture model can only be used to evaluate the short-term effects and it is not applicable in simulating the complex process of IDD. Similarly, the animal models induced by different methods also have their advantages and disadvantages. For studying the mechanism of IDD and the corresponding treatment and prevention strategies, the selection of model should be individualized based on the purpose of each study.Conclusions: Various models have different characteristics and scope of application due to their different rationales and methods of construction. Currently, there is no experimental model that can perfectly mimic the degenerative process of human IVD. Personalized selection of appropriate model based on study purpose and experimental designing can enhance the possibility to obtain reliable and real results.

Treatment of Severe Congenital Scoliosis with Type ІI Respiratory Failure.

We report a case of a 14-year girl with severe congenital scoliosis (CS) and type ІІ respiratory failure (RF), who underwent preoperative halo-gravity traction in combination with intraoperative orthopaedic surgery on the spine based on the results of physical examination, pulmonary function tests (PFTs), computed tomography (CT), and blood gas analysis. The patient's coronal and sagittal Cobb's angles changed from 100° to 45° and 40°, respectively, and RF changed from type ІІ to type І after treatment. Scoliosis was corrected well, and RF was improved. During follow-up for nearly 3 years, no loss of deformity correction and no serious complications occurred, and the patient showed a good clinical outcome and balanced spine. Key Words: Congenital scoliosis, Halo-gravity traction, Respiratory failure.

Different Types of Double-Level Degenerative Lumber Spondylolisthesis: What Is Different in the Sagittal Plane?

BACKGROUND: Degenerative lumber spondylolisthesis (DLS) is a common orthopedic condition, described as a condition that compared with the lower vertebra, the superior vertebra slides forward or backward in the sagittal plane without accompanying isthmic spondylolisthesis. Information pertaining to different types of double-level DLS is scarce. This study aims to analyze parameters of patients with different types of double-level DLS to provide a reference for guiding surgical treatment and restoring sagittal balance of patients with DLS. METHODS: From January 2014 to January 2020, records of patients with double-level DLS were retrospectively reviewed. Patients with double-level DLS were divided into 3 types: anterior, posterior, and combined; the anterior and combined types were studied. The sagittal spinopelvic parameters included C7 tilt, maximal thoracic kyphosis, maximal lumbar lordosis (LLmax), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS). After descriptive analysis, demographic and radiographic data were compared. RESULTS: Forty and 18 patients were included in the anterior and combined type groups, respectively. Both groups had different levels of chronic low back pain, but the incidence of radiating leg pain and neurogenic claudication was significantly higher in the anterior type. Oswestry Disability Index and visual analog scale low back scores were also higher in the anterior type. In the anterior type, C7 tilt (7.14 ± 2.15 vs. 5.41 ± 2.28, P = 0.007), LLmax (50.02 ± 14.76 vs. 36.96 ± 14.56, P = 0.003), PI (68.28 ± 9.16 vs. 55.53 ± 14.19, P < 0.001), PT (28.68 ± 7.31 vs. 19.38 ± 4.70, P < 0.001), and PT/PI (42.45 ± 11.22 vs. 36.04 ± 9.87, P = 0.041) were significantly higher. In the anterior type, PI correlated positively with LLmax (r = 0.59) and SS (r = 0.71). LLmax and SS (r = 0.65) had a positive correlation. PT/PI and SS (r = -0.77) had a negative correlation. In the combined type, PI correlated positively with LLmax (r = 0.61) and SS (r = 0.88), and PT/PI correlated negatively with SS (r = -0.81). CONCLUSIONS: In patients with double-level DLS, the sagittal spinopelvic parameters differed between the anterior and combined types. Overall, spinal surgeons should focus on correcting sagittal deformities, relieving postoperative clinical symptoms, and improving quality of life during fusion surgery.

Grape seed proanthocyanidins protect PC12 cells from hydrogen peroxide-induced damage via the PI3K/AKT signaling pathway.

Grape seed proanthocyanidins (GSP) are natural flavonoids with strong antioxidant and anti-apoptotic effects. Oxidative stress and neuronal apoptosis are major contributors to spinal cord injury (SCI). In this study, we assessed the potential protective effects of GSP on hydrogen peroxide (H2O2)-damaged pheochromocytoma-12 (PC12) cells in an in vitro model of SCI as well as the putative mechanism of action. We established a model using PC12 cells with oxidative damage induced by H2O2. Cells were treated with various concentrations of GSP (control group, 200 µmol/L H2O2 group, 5 µM GSP + H2O2 group, 10 µM GSP + H2O2 group, and 25 µM GSP + H2O2 group). The CCK-8 assay was used to determine cell activity. Dichloro-dihydro-fluorescein diacetate was used to detect intracellular reactive oxygen species (ROS), and flow cytometry was used to determine apoptosis rate. Western blot analysis was used to detect the expression of caspase-3, Bax, Bcl-2, and PI3K/AKT proteins. The results showed that GSP reduced H2O2-induced intracellular ROS and inhibited apoptosis. Furthermore, GSP inhibited the expression of caspase-3 and Bax, while promoting the expression of Bcl-2. In addition, GSP promoted the phosphorylation of PI3K and AKT. Moreover, a PI3K inhibitor (LY294002) weakened the protective effects of GSP on H2O2-induced PC12 cells. In conclusion, GSP pretreatment can protect PC12 cells from oxidative damage induced by H2O2 via the PI3K/AKT signaling pathway.