Effect of Myelin Debris on the Phenotypic Transformation of Astrocytes after Spinal Cord Injury in Rats.

After spinal cord injury (SCI), the accumulation of myelin debris can serve as proinflammatory agents, hindering axon regrowth and exacerbating damage. While astrocytes have been implicated in the phagocytosis of myelin debris, the impact of this process on the phenotypic transformation of astrocytes and their characteristics following SCI in rats is not well understood. Here, we demonstrated that the conditioned medium of myelin debris can trigger apoptosis in rat primary astrocytes in vitro. Using a compressional SCI model in rats, we observed that astrocytes can engulf myelin debris through ATP-binding cassette transporter sub-family A member 1 (ABCA1), and these engulfed cells tend to transform into A1 astrocytes, as indicated by C3 expression. At 4 days post-injury (dpi), astrocytes rapidly transitioned into A1 astrocytes and maintained this phenotype from 4 to 28 dpi, while A2 astrocytes, characterized by S100, were only detected at 14 and 28 dpi. Reactive astrocytes, identified by Nestin, emerged at 4 and 7 dpi, whereas scar-forming astrocytes, marked by N-cadherin, were evident at 14 and 28 dpi. This study illustrates the distribution patterns of astrocyte subtypes and the potential interplay between astrocytes and myelin debris after SCI in rats. We emphasize that myelin debris can induce astrocyte apoptosis in vitro and promote the transformation of astrocytes into A1 astrocytes in vivo. These two classification methods are not mutually exclusive, but rather complementary.

Roles of TRPM channels in glioma.

Gliomas are the most common type of primary brain tumor. Despite advances in treatment, it remains one of the most aggressive and deadly tumor of the central nervous system (CNS). Gliomas are characterized by high malignancy, heterogeneity, invasiveness, and high resistance to radiotherapy and chemotherapy. It is urgent to find potential new molecular targets for glioma. The TRPM channels consist of TRPM1-TPRM8 and play a role in many cellular functions, including proliferation, migration, invasion, angiogenesis, etc. More and more studies have shown that TRPM channels can be used as new therapeutic targets for glioma. In this review, we first introduce the structure, activation patterns, and physiological functions of TRPM channels. Additionally, the pathological mechanism of glioma mediated by TRPM2, 3, 7, and 8 and the related signaling pathways are described. Finally, we discuss the therapeutic potential of targeting TRPM for glioma.

•TRPM channels are widely expressed in the human body and play an important role in gliomas.• Abnormal expression of TRPM2, 3, 7, and 8 channels in gliomas is associated with disease severity and prognosis.•TRPM2, 3, 7, and 8 channels are effective targets in glioma.

Super-enhancer-driven LIF promotes the mesenchymal transition in glioblastoma by activating ITGB2 signaling feedback in microglia.

BACKGROUND: The mesenchymal (MES) subtype of glioblastoma (GBM) is believed to be influenced by both cancer cell-intrinsic alterations and extrinsic cellular interactions, yet the underlying mechanisms remain unexplored. METHODS: Identification of microglial heterogeneity by bioinformatics analysis. Transwell migration, invasion assays, and tumor models were used to determine gene function and the role of small molecule inhibitors. RNA sequencing, chromatin immunoprecipitation, and dual-luciferase reporter assays were performed to explore the underlying regulatory mechanisms. RESULTS: We identified the inflammatory microglial subtype of tumor-associated microglia (TAM) and found that its specific gene ITGB2 was highly expressed in TAM of MES GBM tissues. Mechanistically, the activation of ITGB2 in microglia promoted the interaction between the SH2 domain of STAT3 and the cytoplasmic domain of ITGB2, thereby stimulating the JAK1/STAT3/IL-6 signaling feedback to promote the MES transition of GBM cells. Additionally, microglia communicated with GBM cells through the interaction between the receptor ITGB2 on microglia and the ligand ICAM-1 on GBM cells, while an increased secretion of ICAM-1 was induced by the proinflammatory cytokine LIF. Further studies demonstrated that inhibition of CDK7 substantially reduced the recruitment of SNW1 to the super-enhancer of LIF, resulting in transcriptional inhibition of LIF. We identified notoginsenoside R1 as a novel LIF inhibitor that exhibited synergistic effects in combination with temozolomide. CONCLUSIONS: Our research reveals that the epigenetic-mediated interaction of GBM cells with TAM drives the MES transition of GBM and provides a novel therapeutic avenue for patients with MES GBM.

Unintended dural tears during unilateral biportal endoscopic lumbar surgery: incidence and risk factors.

BACKGROUND: An unintended dural tear (DT) is the most common intraoperative complication of lumbar spine surgery. The unilateral biportal endoscopic technique (UBE) has become increasingly popular for treating various degenerative diseases of the lumbar spine; however, the DT incidence and risk factors specific to UBE remain undetermined. Therefore, this study aimed to evaluate the incidence and risk factors of DTs in UBE. METHOD: Data from all patients who underwent UBE for degenerative lumbar spinal diseases from November 2018 to December 2021 at our institution were used to assess the effects of demographics, diagnosis, and type of surgery on unintended DT risk. RESULTS: Overall, 24/608 patients (3.95%) experienced DTs and were treated with primary suture repair or bed rest. Although several patients experienced mild symptoms of cerebrospinal fluid (CSF) leaks, no serious postoperative sequelae such as nerve root entrapment, meningitis, or intracranial hemorrhage occurred. Additionally, no significant correlations were identified between DT and sex (P = 0.882), body mass index (BMI) (P = 0.758), smoking status (P = 0.506), diabetes (P = 0.672), hypertension (P = 0.187), or surgeon experience (P = 0.442). However, older patients were more likely to experience DT than younger patients (P = 0.034), and patients with lumbar spinal stenosis (LSS) were more likely to experience DT than patients with lumbar disc herniation (LDH) (P = 0.035). Additionally, DT was more common in revision versus primary surgery (P < 0.0001) and in unilateral laminotomy with bilateral decompression (ULBD) versus unilateral decompression (P = 0.031). Univariate logistic regression analysis revealed that age, LSS, ULBD, and revision surgery were significant risk factors for DT. CONCLUSIONS: In this UBE cohort, we found that the incidence of DT was 3.95%. Additionally, older age, LSS, ULBD, and revision surgery significantly increased the risk of DT in UBE surgery.

hBcl2 overexpression in BMSCs enhances resistance to myelin debris-induced apoptosis and facilitates neuroprotection after spinal cord injury in rats.

After spinal cord injury (SCI), the accumulation of myelin debris at the lesion exacerbates cell death and hinders axonal regeneration. Transplanted bone marrow mesenchymal stem cells (BMSCs) have been proven to be beneficial for SCI repair, but they are susceptible to apoptosis. It remains unclear whether this apoptotic process is influenced by myelin debris. Here, we constructed rat BMSCs overexpressing human B-cell lymphoma 2 (hBcl2) alone (hBcl2 group), BMSCs overexpressing hBcl2 with an endoplasmic reticulum-anchored segment (hBcl2-cb) (cb group), and a negative control group (NC group) for transplantation in this study. Immunocytochemistry staining validated the successful expression of hBcl2 in BMSCs within the hBcl2 group and cb group. All BMSCs from each group exhibited the ability to phagocytize myelin debris. Nevertheless, only BMSCs derived from the hBcl2 group exhibited heightened resistance to apoptosis and maintained prolonged viability for up to 5 days when exposed to myelin debris. Notably, overexpression of hBcl2 protein, rather than its endoplasmic reticulum-anchored counterpart, significantly enhanced the resistance of BMSCs against myelin debris-induced apoptosis. This process appeared to be associated with the efficient degradation of myelin debris through the Lamp1+ lysosomal pathway in the hBcl2 group. In vivo, the hBcl2 group exhibited significantly higher numbers of surviving cells and fewer apoptotic BMSCs compared to the cb and NC groups following transplantation. Furthermore, the hBcl2 group displayed reduced GFAP+ glial scarring and greater preservation of NF200+ axons in the lesions of SCI rats. Our results suggest that myelin debris triggers apoptosis in transplanted BMSCs, potentially elucidating the low survival rate of these cells after SCI. Consequently, the survival rate of transplanted BMSCs is improved by hBcl2 overexpression, leading to enhanced preservation of axons within the injured spinal cord.

A Novel Defined Necroptosis-Related Genes Prognostic Signature for Predicting Prognosis and Treatment of Osteosarcoma.

Osteosarcoma (OS) is a frequent primary malignant bone tumor, with a poor prognosis. Necroptosis is strongly correlated with OS and may be an influential target for treating OS. This study's objective was to establish a necroptosis-related gene (NRG) prognostic signature that could predict OS prognosis and guide OS treatment. First, we identified 20 NRGs associated with OS survival based on the TARGET database. We then derived a 7 NRG prognostic signature. Our findings revealed that the 7 NRG prognostic signature performed well in predicting the survival of OS patients. We next analyzed differences in immunological status and immune cell infiltration. In addition, we examined the relationship between chemo/immunotherapeutic response and the 7-NRG prognostic signature. In addition, to probe the mechanisms underlying the NRG prognostic signature, we performed functional enrichment assays including GO and KEGG. Finally, CHMP4C was selected for functional experiments. Silencing CHMP4C prevented OS cells from proliferating, migrating, and invading. This 7-NRG prognostic signature seems to be an excellent predictor that can provide a fresh direction for OS treatment.

Single-Cell RNA Sequencing Pro-angiogenic Macrophage Profiles Reveal Novel Prognostic Biomarkers and Therapeutic Targets for Osteosarcoma.

Osteosarcoma (OS) is a malignant bone tumor that most commonly occurs in children and adolescents. OS patients have a poor prognosis, and 5-year survival rates have rarely improved significantly over the past few decades. OS prognosis may be related to the infiltration of tumor-associated macrophages (TAMs). However, the role of proangiogenic macrophages, a subtype of TAMs, in OS prognosis has not been reported. In this study, seven subtypes of TAMs were identified from single-cell RNA sequencing (scRNA-seq) data that we propose defining as proangiogenic TAMs (Angio-TAMs), interferon-primed TAMs (IFN-TAMs), inflammatory cytokine-enriched TAMs (Inflam-TAMs), immune regulatory TAMs (Reg-TAMs), lipid-associated TAMs (LA-TAMs), and resident-tissue macrophages like TAMs (RTM-TAMs) (containing two subcellular types). In the survival analysis of each macrophage subtype, it was found that patients with Angio-TAMs had the most significant difference in survival. Eight genes associated with Angio-TAMs were obtained by differential expression analysis, and these genes were built into a prognostic model using the LASSO algorithm. Clinical OS case samples were categorized into high-risk and low-risk subgroups using median risk scores. In comparison to the low-risk subgroup, the survival time of the high-risk subgroup was much shorter. Additional studies on immune cell infiltration and immune checkpoint molecule expression in the two risk subgroups were carried out. In immunotherapy response prediction, the Angio-TAM-associated gene risk signature was found to be negatively correlated with immune checkpoint responses. In addition, the associated enriched GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways were mainly involved in the malignant progression of tumors. As suggested by these findings, the Angio-TAM gene risk signature may be an underlying prognostic biomarker and novel therapeutic target for OS patients.Kindly check and confirm whether the ESM file is correctly identifiedWe have checked this file and confirmed that it can be correctly identified.

Unilateral biportal endoscopic technique combined with percutaneous transpedicular screw fixation for thoracolumbar burst fractures with neurological symptoms: technical note and preliminary report.

BACKGROUND: Previous studies on thoracolumbar fractures with neurological symptoms have focused on how to achieve satisfactory fracture reduction, adequate nerve decompression, and stable spinal alignment. With the development of the minimally invasive spine surgery technique, achieving satisfactory treatment results and reducing iatrogenic trauma at the same time has become a new goal of spinal surgery. This research used percutaneous transpedicular screw distraction to partially reduce the fractured vertebrae, followed by completing nerve decompression and reducing residual displacement bone fragments with the assistance of the unilateral biportal endoscopic (UBE) technique to achieve full protection of bone-ligament tissue and obtain good clinical efficacy. METHODS: Guide wires were safely inserted into the fractured vertebra and adjacent upper and lower vertebra under the surveillance of anteroposterior and lateral X-ray fluoroscopy. Transpedicular screws were implanted via guide wires on the side with mild neurological deficits or bone fragment compression (the opposite side of the endoscopic operation). A titanium rod was installed and moderately distracted to reduce the fractured vertebra. Then, under the guidance of the endoscopic view, the laminectomy and ligamentum flavum resection were completed according to the position of the protruding bone fragment into the spinal canal, and the compressed dural sac or nerve root was fully exposed and decompressed. An L-shaped replacer was used to reduce residual bone fragments. The ipsilateral transpedicular screws and rod were installed and adjusted to match the contralateral side. The drainage tube was indwelled, and the incision was closed. The preoperative and postoperative images of the patients were evaluated, and the recovery of neurological symptoms was observed. RESULTS: Surgery was successfully completed on all six patients, and no intraoperative conversion to open surgery was performed. Postoperative images showed good reduction of the protruding bone fragment and good placement of all screws. At the last follow-up, the neurological symptoms of all patients returned to normal. CONCLUSION: The UBE technique combined with percutaneous transpedicular screw fixation in the treatment of thoracolumbar fractures with neurological symptoms can effectively achieve the reduction of displaced bone fragments, improve damaged nerve function, stabilize spinal alignment, and protect the integrity of bone-ligament tissue.

Super-enhancers complexes zoom in transcription in cancer.

Super-enhancers (SEs) consist of multiple typical enhancers enriched at high density with transcription factors, histone-modifying enzymes and cofactors. Oncogenic SEs promote tumorigenesis and malignancy by altering protein-coding gene expression and noncoding regulatory element function. Therefore, they play central roles in the treatment of cancer. Here, we review the structural characteristics, organization, identification, and functions of SEs and the underlying molecular mechanism by which SEs drive oncogenic transcription in tumor cells. We then summarize abnormal SE complexes, SE-driven coding genes, and noncoding RNAs involved in tumor development. In summary, we believe that SEs show great potential as biomarkers and therapeutic targets.

Super-enhancer-driven lncRNA LIMD1-AS1 activated by CDK7 promotes glioma progression.

Long non-coding RNAs (lncRNAs) are tissue-specific expression patterns and dysregulated in cancer. How they are regulated still needs to be determined. We aimed to investigate the functions of glioma-specific lncRNA LIMD1-AS1 activated by super-enhancer (SE) and identify the potential mechanisms. In this paper, we identified a SE-driven lncRNA, LIMD1-AS1, which is expressed at significantly higher levels in glioma than in normal brain tissue. High LIMD1-AS1 levels were significantly associated with a shorter survival time of glioma patients. LIMD1-AS1 overexpression significantly enhanced glioma cells proliferation, colony formation, migration, and invasion, whereas LIMD1-AS1 knockdown inhibited their proliferation, colony formation, migration, and invasion, and the xenograft tumor growth of glioma cells in vivo. Mechanically, inhibition of CDK7 significantly attenuates MED1 recruitment to the super-enhancer of LIMD1-AS1 and then decreases the expression of LIMD1-AS1. Most importantly, LIMD1-AS1 could directly bind to HSPA5, leading to the activation of interferon signaling. Our findings support the idea that CDK7 mediated-epigenetically activation of LIMD1-AS1 plays a crucial role in glioma progression and provides a promising therapeutic approach for patients with glioma.

Identification of a novel MYC target gene set signature for predicting the prognosis of osteosarcoma patients.

Osteosarcoma is a primary malignant tumor found mainly in teenagers and young adults. Patients have very little long-term survival. MYC controls tumor initiation and progression by regulating the expression of its target genes; thus, constructing a risk signature of osteosarcoma MYC target gene set will benefit the evaluation of both treatment and prognosis. In this paper, we used GEO data to download the ChIP-seq data of MYC to obtain the MYC target gene. Then, a risk signature consisting of 10 MYC target genes was developed using Cox regression analysis. The signature indicates that patients in the high-risk group performed poorly. After that, we verified it in the GSE21257 dataset. In addition, the difference in tumor immune function among the low- and high-risk populations was compared by single sample gene enrichment analysis. Immunotherapy and prediction of response to the anticancer drug have shown that the risk signature of the MYC target gene set was positively correlated with immune checkpoint response and drug sensitivity. Functional analysis has demonstrated that these genes are enriched in malignant tumors. Finally, STX10 was selected for functional experimentation. STX10 silence has limited osteosarcoma cell migration, invasion, and proliferation. Therefore, these findings indicated that the MYC target gene set risk signature could be used as a potential therapeutic target and prognostic indicator in patients with osteosarcoma.

PIWI-interacting RNAs: Critical roles and therapeutic targets in cancer.

P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are a novel class of small regulatory RNAs (approximately 24-31 nucleotides in length) that often bind to members of the PIWI protein family. piRNAs regulate transposons in animal germ cells; piRNAs are also specifically expressed in many human tissues and regulate pivotal signaling pathways. Additionally, the abnormal expression of piRNAs and PIWI proteins has been associated with various malignant tumours, and multiple mechanisms of piRNA-mediated target gene dysregulation are involved in tumourigenesis and progression, suggesting that they have the potential to serve as new biomarkers and therapeutic targets for tumours. However, the functions and potential mechanisms of action of piRNAs in cancer have not yet been elucidated. This review summarises the current findings on the biogenesis, function, and mechanisms of piRNAs and PIWI proteins in cancer. We also discuss the clinical significance of piRNAs as diagnostic or prognostic biomarkers and therapeutic tools for cancer. Finally, we present some critical questions regarding piRNA research that need to be addressed to provide insight into the future development of the field.

Tocilizumab promotes repair of spinal cord injury by facilitating the restoration of tight junctions between vascular endothelial cells.

BACKGROUND: Our previous study demonstrated that M1 macrophages could impair tight junctions (TJs) between vascular endothelial cells by secreting interleukin-6 (IL-6) after spinal cord injury (SCI). Tocilizumab, as a humanized IL-6 receptor (IL-6R) monoclonal antibody approved for the clinic, has been applied in the treatment of neurological diseases in recent years, but the treatment effect of Tocilizumab on the TJs restoration of the blood-spinal cord barrier (BSCB) after SCI remains unclear. This study aimed to explore the effect of Tocilizumab on the restoration of TJs between vascular endothelial cells and axon regeneration after SCI. METHODS: In this study, the mouse complete spinal cord crush injury model was used, and Tocilizumab was continuously injected intrathecally until the day of sample collection. A PBS injection in the same location was included as a control. At 14 days postinjury (dpi) and 28 dpi, spinal cord tissue sections were examined via tissue immunofluorescence. The Basso Mouse Scale (BMS) scores and footprint analysis were used to verify the effect of Tocilizumab on the recovery of motor function in mice after SCI. RESULTS: We demonstrated that depletion of macrophages has no effect on axon regeneration and motor functional recovery after SCI, but mice subjected to Tocilizumab showed a significant increase in axon regeneration and a better recovery in motor function during the chronic phase after SCI. Moreover, our study demonstrated that at 14 and 28 dpi, the expression of claudin-5 (CLDN5) and zonula occludens-1 (ZO-1) between vascular endothelial cells was significantly increased and the leakage of BSCB was significantly reduced in the injured core after daily intrathecal injection of Tocilizumab. Notably, the infiltration of CD68+ macrophages/microglia and the formation of fibrotic scar were decreased in the injured core after Tocilizumab treatment. Tocilizumab treatment could effectively reduce the IL-6 expression in macrophages in the injured core. CONCLUSION: The application of Tocilizumab to antagonize IL-6R can effectively reduce the expression of IL-6 in macrophages and facilitate TJs restoration of the BSCB, which is beneficial for axon regeneration and motor functional recovery after SCI. Hence, Tocilizumab treatment is a potential therapeutic strategy for SCI.

Myelin Debris Impairs Tight Junctions and Promotes the Migration of Microvascular Endothelial Cells in the Injured Spinal Cord.

Clearance of myelin debris caused by acute demyelination is an essential process for functional restoration following spinal cord injury (SCI). Microvascular endothelial cells, acting as "amateur" phagocytes, have been confirmed to engulf and degrade myelin debris, promoting the inflammatory response, robust angiogenesis, and persistent fibrosis. However, the effect of myelin debris engulfment on the function of endothelial tight junctions (TJs) remains unclear. Here, we demonstrate that myelin debris uptake impairs TJs and gap junctions of endothelial cells in the lesion core of the injured spinal cord and in vitro, resulting in increased permeability and leakage. We further show that myelin debris acts as an inducer to regulate the endothelial-to-mesenchymal transition in a dose-dependent manner and promotes endothelial cell migration through the PI3K/AKT and ERK signaling pathways. Together, our results indicate that myelin debris engulfment impairs TJs and promotes the migration of endothelial cells. Accelerating myelin debris clearance may help maintain blood-spinal cord barrier integrity, thus facilitating restoration of motor and sensory function following SCI.

Unilateral biportal endoscopic extreme transforaminal lumbar interbody fusion with large cage combined with endoscopic unilateral pedicle screw fixation for lumbar degenerative diseases: a technical note and preliminary effects.

OBJECTIVE: The purpose of the study was to investigate the feasibility and preliminary effects of unilateral biportal endoscopic extreme transforaminal lumbar interbody fusion(UBE-eXTLIF) with large cage combined with endoscopic unilateral pedicle screw fixation for lumbar degenerative diseases. METHODS: Patients with lumbar degenerative diseases who received UBE-eXTLIF with large cage combined with endoscopic unilateral pedicle screw fixation from June 2022 to July 2022 were retrospectively analyzed, including 4 females and 1 males. The clinical symptoms and signs were consistent with the imaging changes. We recorded operation time, length of postoperative hospital stay, and complications. Visual Analogue Scale (VAS), Oswestry Disability Index (ODI), and modified Macnab scale was used to evaluate the clinical efficacy at preoperative, postoperative 1 month, and the last follow-up. RESULTS: The operation was successfully completed in all cases. The operation time was 150-180 min, with an average of 164.60 ± 12.03 min. No serious complications such as dural tears and vascular and nerve injuries occurred during operation. All the patients got out of bed 1-3 days after surgery and were hospitalized 4-5 days after surgery, with an average of 4.20 ± 0.45 days. Preoperative VAS scores of low back pain were 6.20 ± 0.84 and respectively decreased to 2.20 ± 0.45 and 1.40 ± 0.55 at postoperative 1 month and at the last follow-up, and the difference was statistically significant (P < 0.05). Preoperative VAS scores of lower limb pain were 4.60 ± 2.61 and respectively decreased to 1.00 ± 0.71 and 0.60 ± 0.55 at postoperative 1 month and at the last follow-up, and the difference was statistically significant (P < 0.05). Preoperative ODI scores were 62.00 ± 3.16 and respectively decreased to 38.00 ± 1.41 and 32.40 ± 3.29 at postoperative 1 month and at the last follow-up, and the difference was statistically significant (P < 0.05). According to the modified Macnab criteria, the final outcome was excellent in 4 cases and good in 1 case. Five patients could return to normal activities within 3 weeks. CONCLUSIONS: UBE-eXTLIF with large cage combined with endoscopic unilateral pedicle screw fixation can achieve excellent clinical results and may become a new minimally invasive endoscopic fusion method for lumbar degenerative diseases.

Contralateral inclinatory approach for decompression of the lateral recess and same-level foraminal lesions using unilateral biportal endoscopy: A technical report.

Objective: Unilateral biportal endoscopic (UBE)surgery is being increasingly adopted as a minimally invasive technique. The purpose of the current study was to introduce a novel surgical technique for lateral recess and same-level foraminal decompression by the contralateral inclinatory approach with unilateral biportal endoscopy(CIA-UBE) at the lumbar level. Methods: Between January 2020 and February 2022, 10 patients suffering from lateral recess and same-level foraminal stenosis at the lumbar level underwent UBE surgery by contralateral inclinatory approach (CIA-UBE). Magnetic resonance imaging (MRI) scans were examined after surgery to measure the cross-sectional area (CSA) of the spinal canal (CSA-SC), the CSA of the intervertebral foramen (CSA-IVF), and the CSA of the facet joint (CSA-FJ). Postoperative radiologic images using computed tomography (CT) were obtained to investigate the existence of facet joint violation. Clinical outcomes were assessed using Oswestry Disability Index (ODI) scores and visual analogue scale (VAS) scores for buttock and radicular pain. Results: Ten levels were decompressed, and the mean age of the patients was 56.92 ± 13.26 years. The mean follow-up period was 7.60 ± 4.47 months. The average operative time was 85.14 ± 25.65 min. Postoperative CT and MRI revealed ideal neural decompression of the treated segments in all patients. CSA-IVF and CSA-FJ improved significantly, indicating good foraminal and lateral recess decompression with less damage to facet joints. Preoperative VAS and ODI scores improved significantly after surgery. Conclusion: CIA-UBE may be an effective surgical treatment of the lateral recess and same-level foraminal stenosis at the lumbar level, which provides successful surgical decompression for traversing and exiting nerve roots with a better operative view and easier surgical manipulation. This approach may also help to maximize the preservation of the facet joint.

Complete removal of intraspinal extradural mass with unilateral biportal endoscopy.

Introduction: Unilateral biportal endoscopic (UBE) technique can easily decompress the bony spinal canal and accommodate all open surgical instruments under endoscopic guidance. However, indications and reports of this technique have been limited to degenerative and infectious diseases. Methods: We used the UBE technique for the decompression and removal of extradural mass lesions in five patients. Under endoscopic guidance, a unilateral approach was used, and decompression and flavectomy were performed. After decompression, removal of the tumor was performed using various forceps. We evaluated the technical process of the procedure, the patient's pre- and postoperative symptoms, and operative radiology and pathologic results. Results: Postoperative pain and disability improved clinically for all patients. Four patients were confirmed as having an epidural cyst and one patient was diagnosed with hemangioma. During follow-up, no recurrence was observed. Conclusions: We successfully removed five extradural mass lesions using a biportal endoscopic posterior approach without complications. The biportal endoscopic approach may have advantages, such as minimizing trauma to the normal structures, magnified endoscopic view, and early recovery after the surgery. Biportal endoscopy may be used as an alternative surgical treatment for symptomatic intraspinal extradural benign lesions.

Imatinib inhibits pericyte-fibroblast transition and inflammation and promotes axon regeneration by blocking the PDGF-BB/PDGFRß pathway in spinal cord injury.

BACKGROUND: Fibrotic scar formation and inflammation are characteristic pathologies of spinal cord injury (SCI) in the injured core, which has been widely regarded as the main barrier to axonal regeneration resulting in permanent functional recovery failure. Pericytes were shown to be the main source of fibroblasts that form fibrotic scar. However, the mechanism of pericyte-fibroblast transition after SCI remains elusive. METHODS: Fibrotic scarring and microvessels were assessed using immunofluorescence staining after establishing a crush SCI model. To study the process of pericyte-fibroblast transition, we analyzed pericyte marker and fibroblast marker expression using immunofluorescence. The distribution and cellular origin of platelet-derived growth factor (PDGF)-BB were examined with immunofluorescence. Pericyte-fibroblast transition was detected with immunohistochemistry and Western blot assays after PDGF-BB knockdown and blocking PDGF-BB/PDGFRß signaling in vitro. Intrathecal injection of imatinib was used to selectively inhibit PDGF-BB/PDGFRß signaling. The Basso mouse scale score and footprint analysis were performed to assess functional recovery. Subsequently, axonal regeneration, fibrotic scarring, fibroblast population, proliferation and apoptosis of PDGFRß+ cells, microvessel leakage, and the inflammatory response were assessed with immunofluorescence. RESULTS: PDGFRß+ pericytes detached from the blood vessel wall and transitioned into fibroblasts to form fibrotic scar after SCI. PDGF-BB was mainly distributed in the periphery of the injured core, and microvascular endothelial cells were one of the sources of PDGF-BB in the acute phase. Microvascular endothelial cells induced pericyte-fibroblast transition through the PDGF-BB/PDGFRß signaling pathway in vitro. Pharmacologically blocking the PDGF-BB/PDGFRß pathway promoted motor function recovery and axonal regeneration and inhibited fibrotic scar formation. After fibrotic scar formation, blocking the PDGFRß receptor inhibited proliferation and promoted apoptosis of PDGFRß+ cells. Imatinib did not alter pericyte coverage on microvessels, while microvessel leakage and inflammation were significantly decreased after imatinib treatment. CONCLUSIONS: We reveal that the crosstalk between microvascular endothelial cells and pericytes promotes pericyte-fibroblast transition through the PDGF-BB/PDGFRß signaling pathway. Our finding suggests that blocking the PDGF-BB/PDGFRß signaling pathway with imatinib contributes to functional recovery, fibrotic scarring, and inflammatory attenuation after SCI and provides a potential target for the treatment of SCI.

Clinical effects of unilateral biportal endoscopic decompression for lumbar posterior apophyseal ring separation.

Objective: The purpose of the study was to investigate the feasibility and effects of unilateral biportal endoscopic decompression for lumbar posterior apophyseal ring separation (PARS). Methods: Patients with lumbar PARS who received unilateral biportal endoscopic decompression from June 2020 to September 2021 were analyzed, including 11 females and 15 males. The clinical symptoms were consistent with the imaging findings. Operation time, length of postoperative hospital stay and complications were recorded, and the clinical efficacy was evaluated by Visual Analogue Scale (VAS), Oswestry Disability Index (ODI) and modified Macnab scale at preoperative, postoperative 1, 3, 6 months and the last follow-up. Results: Preoperative VAS scores of low back pain were (5.04 ± 1.37) and respectively decreased to (2.81 ± 0.75), (2.35 ± 0.98), (1.65 ± 0.69) and (1.15 ± 0.68) at postoperative 1, 3, 6 months and at the last follow-up, and the difference was statistically significant (F = 127.317, P = 0.000). Preoperative VAS scores of lower limb pain were (6.92 ± 1.38) and respectively decreased to (2.88 ± 1.07), (2.54 ± 1.03), (1.81 ± 0.80) and (1.00 ± 0.69) at postoperative 1, 3, 6 months and at the last follow-up, and the difference was statistically significant (F = 285.289, P = 0.000). Preoperative ODI scores were (60.47 ± 8.89) and respectively decreased to (34.72 ± 4.13), (25.80 ± 3.65), (17.71 ± 3.41) and (5.65 ± 2.22) at postoperative 1, 3, 6 months and at the last follow-up, and the difference was statistically significant (F = 725.255, P = 0.000). According to the modified Macnab criteria, the final outcome was excellent in 22 cases, good in 3 cases, fair in 1 cases. 26 patients could return to work or normal activities within 3 weeks. Conclusions: Unilateral biportal endoscopic decompression has the advantages of clear and wide field of vision, large operating space, relatively simple need of surgical instrument and convenient and flexible operation procedure. It can achieve excellent clinical results with favorable efficacy and safety and may become a new minimally invasive endoscopic treatment for lumbar PARS.

The Learning Curve of Unilateral Biportal Endoscopic (UBE) Spinal Surgery by CUSUM Analysis.

Objective: To assess the learning curve of the unilateral biportal endoscopic (UBE) technique for the treatment of single-level lumbar disc herniation by cumulative summation (CUSUM) method analysis. Methods: A retrospective analysis was conducted to assess 97 patients' general condition, operation time, complications, and curative effect of single segmental UBE surgery performed by a spinal surgeon in his early stage of this technique. The learning curve of operation time was studied using a CUSUM method, and the cut-off point of the learning curve was obtained. Results: The operation time was 30 - 241(97.9 ± 34.7) min. The visual analog scale score of lower limb pain decreased from 5.75 ± 0.81 before the operation to 0.39 ± 0.28 at the last follow-up (P < 0.05). The Oswestry disability index score decreased from 66.48 ± 4.43 before the operation to 14.57 ± 3.99 at the last follow-up (P < 0.05). The CUSUM assessment of operation time revealed the learning curve was the highest in 24 cases. In the learning stage (1-24 cases), the operation time was 120.3 ± 43.8 min. In the skilled stage (25-97 cases), the operation time was 90.5 ± 27.8 min. Conclusions: About 24 cases of single segmental UBE operation are needed to master the UBE technique.