Fascin-1 limits myosin activity in microglia to control mechanical characterization of the injured spinal cord.

BACKGROUND: Mechanical softening of the glial scar region regulates axonal regeneration to impede neurological recovery in central nervous system (CNS) injury. Microglia, a crucial cellular component of the glial scar, facilitate neuronal survival and neurological recovery after spinal cord injury (SCI). However, the critical mechanical characterization of injured spinal cord that harmonizes neuroprotective function of microglia remains poorly understood. METHODS: Spinal cord tissue stiffness was assessed using atomic force microscopy (AFM) in a mouse model of crush injury. Pharmacological depletion of microglia using PLX5622 was used to explore the effect of microglia on mechanical characterization. Conditional knockout of Fascin-1 in microglia (Fascin-1 CKO) alone or in combination with inhibition of myosin activity was performed to delve into relevant mechanisms of microglia regulating mechanical signal. Immunofluorescence staining was performed to evaluate the related protein levels, inflammatory cells, and neuron survival after SCI. The Basso mouse scale score was calculated to assess functional recovery. RESULTS: Spinal cord tissue significantly softens after SCI. Microglia depletion or Fascin-1 knockout in microglia limits tissue softening and alters mechanical characterization, which leads to increased tissue pathology and impaired functional recovery. Mechanistically, Fascin-1 inhibits myosin activation to promote microglial migration and control mechanical characterization after SCI. CONCLUSIONS: We reveal that Fascin-1 limits myosin activity to regulate mechanical characterization after SCI, and this mechanical signal should be considered in future approaches for the treatment of CNS diseases.

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.

Dislocation Does Not Seem To Be an Absolute Factor Effecting the Short- to Medium-Term Poor Prognosis of Patients with Acetabular Posterior Wall Fracture.

Dislocation is a complication of acetabular fractures involving the posterior wall, but whether dislocation is an absolute factor impacting the short- to medium-term prognosis of the hip joint remains controversial. This study aimed to compare the short- to medium-term clinical and radiological results among patients diagnosed with an acetabular fracture involving the posterior wall, with or without dislocation.Seventy-nine patients diagnosed with an acetabular fracture involving the posterior wall were retrospectively divided into posterior dislocation and non-dislocation groups. All fractures were open reduction + internal fixation with a plate screw combination through the single Kocher-Langenbeck approach. The short- to medium-term radiographic outcomes of follow-up were evaluated using the Matta radiologic grading system, while the clinical outcomes were evaluated using the modified Merle d'Aubigné-Postel evaluation system.The mean follow-up duration for all patients was 43.90 (range 24-75) months. Both groups achieved similar short- to medium-term clinical and radiographic results. There seems to be no significant differences between the two groups regarding the short- to medium-term assessment of clinical and radiographic results and the occurrence of postoperative complications (p > 0.05).In patients with acetabular fractures involving the posterior wall, hip dislocation is probably not an absolute determinant of a poor outcome. Even with early reduction, the short- to medium-term prognosis results appear similar to those of patients without dislocation.

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.

Circ_0079471 Regulates the Proliferation, Migration, Invasion and Apoptosis of Osteosarcoma Cells by Mediating miR-485-3p and TRIP6.

BACKGROUND: Circular RNAs (circRNAs) are a special class of non-coding RNA molecules that show a closed circular structure and have been implicated in both tumour formation and oncogenesis. OBJECTIVE: This study aimed to learn more about how circ_0079471 functions in osteosarcomas (OSs). METHOD: Quantitative real-time polymerase chain reaction was used to detect the expression levels of thyroid hormone receptor-interacting protein 6 (TRIP6), miR-485-3p and circ_0079471. Methyl-thiazolyl-tetrazolium and flow cytometry were used to track cell growth and cell-cycle progression, and the research explored wound healing (migration) and invasion using Transwell plates. Western blotting was used to determine the protein expression of TRIP6, proliferating cell nuclear antigen and cyclin D1, and a dual-luciferase assay revealed the target relationship. RESULT: A xenograft experiment evaluated the in vivo effects of circ_0079471 on OS, and the results revealed the high expression of circ_0079471 in OS tissue and cells. The proliferation, cell-cycle migration and invasion of cells were reduced after circ_0079471 knockdown in OS cells; however, the effects of this knockdown were reversed when TRIP6 was overexpressed in the OS cells. The function of circ_0079471 was also achieved by in vivo miR-485-3p sponging. The upregulation of miR-485-3p and the downregulation of TRIP6 partly resulted in circ_0079471 downregulation, which subsequently inhibited OS progression. CONCLUSION: According to these results, circ_0079471 influences the development of OS by regulating miR-485-3p and TRIP6.

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.

Delayed Reconstruction of the Perforator Pedicle Propeller Flap after the Induced Membrane Technique for Gustilo IIIB Open Distal Tibial Fracture.

This study aimed to evaluate the safety and efficacy of delayed reconstruction of the perforator pedicle propeller flap after the induced membrane technique in the treatment of Gustilo IIIB open distal tibial fracture, and to evaluate the clinical outcome and complications of two different perforator pedicle propeller flaps.Thirty-four patients with Gustilo IIIB open distal tibial fractures treated by the induced membrane technique and delayed reconstruction of two different perforator pedicle propeller flaps from May 2017 to March 2022 were retrospectively analyzed. Patients were divided into two groups according to the different kinds of perforator pedicle propeller flaps covered. The operation required two stages. The Radiographic Union Score for Tibial fractures (RUST) was used to evaluate the healing of the tibial bone defect. The American Orthopaedic Foot and Ankle Society (AOFAS) score was used to evaluate ankle function. The complications associated with the technique were recorded.The number of serial debridements, excluding those performed during emergency and final operations, was a mean of 2.28 ± 0.83 in the PAPF group. The PAPF group had a mean bone defect length of 6.76 ± 0.69 cm, the median healing time of 13.11 ± 0.96 months, RUST score 12.68 ± 1.63, and AOFAS score of 84.12 ± 6.38. On the other hand the PTAPF group's mean bone defect length was 6.73 ± 0.95 cm, the median healing time 12.63 ± 1.46 months, RUST score 13.73 ± 1.53 and AOFAS score 82.79 ± 5.49. There were no observed significant differences the two groups in the number of serial debridements, bone defect length, bone union time, RUST score, or AOFAS score (p > 0.05). Flap size ranged from 9 × 6 cm2 to 14 × 7 cm2 in the PAPF group and from 9 × 6 cm2 to 13 × 7 cm2 in the PTAPF group. There were no severe complications such as flap-related complications or amputation. The differences in complications in the two groups were not statistically significant.In cases of severe open tibial fracture, the reconstructive method is important. When delayed reconstruction is inevitable, surgeons should first perform radical debridement, followed by vacuum sealing drainage as a bridging therapy; both PAPF and PTAPF can be considered for definitive soft tissue coverage.

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.

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.

Effect of Schatzker type VI tibial plateau fractures combined with a proximal fibular and/or posterolateral joint facet fracture on early postoperative functional recovery.

PURPOSE: The objective of this study was to investigate the effect of proximal fibular and/or posterolateral joint facet (PJF) fractures on early functional recovery after Schatzker type VI tibial plateau fractures (TPFs). METHODS: Seventy-nine patients with Schatzker type VI TPFs sustained from November 2016 to February 2021 were divided into three groups according to the integrity of the proximal fibula and PJF (groups A, B, and C). Details including demographics, duration of surgery, and complications were recorded. The Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) score, Hospital for Special Surgery (HSS) score, lateral knee pain and lateral hamstring tightness were ascertained at the final follow-up. The HSS and WOMAC scores have high reliability in evaluating knee function and osteoarthritis. RESULTS: There was a significant difference in the HSS score between groups A and C (P < 0.001) and between groups B and C (P = 0.036). The hospital stay was significantly different between groups A and C (P = 0.038) and between groups B and C (P = 0.013). There was a significant difference in lateral knee pain and lateral hamstring tightness between groups A and C (P < 0.001) and between groups B and C (P < 0.001). CONCLUSION: Our study demonstrates that proximal fibular and PJF fractures do not increase the time from injury to surgery, the incidence of complications, or the duration of surgery for Schatzker type VI TPFs. However, fractures of the proximal fibula significantly increase the hospital stay, reduce knee function, and cause lateral knee pain and lateral hamstring tightness. Combined proximal fibular fracture is more decisive than PJF involvement for prognosis.

A Meaningful Attempt: Applying Dielectric Barrier Discharge Plasma to Induce Polarization of Macrophages.

Macrophage polarization plays an important role in many macrophage-related diseases. This study was designed to preliminarily explore the effects of dielectric barrier discharge (DBD) plasma on the polarization direction and cell activity of macrophages with different phenotypes (ie, M0, M1, and M2). The M1 macrophage marker inducible nitric oxide synthase (iNOS) and M2 macrophage marker cluster of differentiation 206 (CD206) were detected by western blot (WB). The effects of DBD plasma on macrophage viability were analyzed by using a cell counting kit-8 detection kit. M0, M1, and M2 macrophages exhibited a decrease in iNOS expression and an increase in CD206 expression after the DBD plasma intervention. Additionally, the decrease in macrophage viability remained non-significant after initiating the intervention. DBD plasma can promote the transformation of M0 and M1 macrophages to M2 macrophages, and can further enhance the expression of the M2 macrophage phenotype marker CD206. Our study not only demonstrates the potential therapeutic value of DBD plasma for macrophage-related diseases, but it also provides a new direction for research to improve the treatment of macrophage-related diseases. © 2023 Bioelectromagnetics Society.

A new type of elastic fixation, using an encircling and binding technique, for tibiofibular syndesmosis stabilization: comparison to traditional cortical screw fixation.

BACKGROUND: The distal tibiofibular syndesmosis (DTS) is a complex fibrous joint that contributes to the stability and weight-bearing function of the ankle. As such, repair of DTS injury is required, providing fixation strength while maintaining ankle range of motion. The aim of this study was to compare a new elastic fixation technique, using an encircling and binding technique, for DTS stabilization, compared to the traditional cortical bone screw fixation. METHODS: This was a retrospective analysis of 67 patients treated for a DTS injury at our hospital, between June 2019 and June 2021. Of them, 33 were treated with encircling and binding (EB group) and 34 using a cortical screw (CS group). The following outcomes were compared between groups: time to inferior tibiofibular fixation; length of hospital stay; time to partial weight bearing; time to complete weight bearing; complications; imaging data; and functional scores. RESULTS: Successful stabilization was achieved in all cases, with a mean follow-up period of 15.78 ± 2.97 months. Time to fixation and time to partial and complete weight bearing were shorter for the EB than that for the CS group. The length of hospital was not different between groups. With regard to complications, a superficial infection developed in one patient in each group, with wound healing achieved after active treatment. Screw fracture occurred in two patients in the CS group. At 3 months post-surgery, the American Foot Surgery Association Ankle-Hindfoot score (AOFAS) was higher and the pain score lower for the EB than that for the CS group, but with no between-group difference at the final follow-up. On imaging, the tibiofibular clear space and tibiofibular overlap were not different between groups. CONCLUSIONS: DTS fixation using encircling and binding yielded better clinical and functional outcomes than did cortical screw fixation at 3 months post-surgery, with no difference at the final follow-up. This novel fixation technique provides firm fixation, combined with earlier return to postoperative exercise and recovery of ankle function.

Fingolimod (FTY720) Hinders Interferon-γ-Mediated Fibrotic Scar Formation and Facilitates Neurological Recovery After Spinal Cord Injury.

Following spinal cord injury (SCI), fibrotic scar inhibits axon regeneration and impairs neurological function recovery. It has been reported that T cell-derived interferon (IFN)-γ plays a pivotal role in promoting fibrotic scarring in neurodegenerative disease. However, the role of IFN-γ in fibrotic scar formation after SCI has not been declared. In this study, a spinal cord crush injury mouse was established. Western blot and immunofluorescence showed that IFN-γ was surrounded by fibroblasts at 3, 7, 14, and 28 days post-injury. Moreover, IFN-γ is mainly secreted by T cells after SCI. Further, in situ injection of IFN-γ into the normal spinal cord resulted in fibrotic scar formation and inflammation response at 7 days post-injection. After SCI, the intraperitoneal injection of fingolimod (FTY720), a sphingosine-1-phosphate receptor 1 (S1PR1) modulator and W146, an S1PR1 antagonist, significantly reduced T cell infiltration, attenuating fibrotic scarring via inhibiting IFN-γ/IFN-γR pathway, while in situ injection of IFN-γ diminished the effect of FTY720 on reducing fibrotic scarring. FTY720 treatment inhibited inflammation, decreased lesion size, and promoted neuroprotection and neurological recovery after SCI. These findings demonstrate that the inhibition of T cell-derived IFN-γ by FTY720 suppressed fibrotic scarring and contributed to neurological recovery after SCI.

Treatment of gorham-stout disease with bisphosphonates and total hip arthroplasty: A case report.

Background: Gorham-Stout disease (GSD) is a rare osteolytic disease with unknown etiology, varied clinical manifestations and unpredictable prognosis. This disease is characterized by progressive massive local osteolysis and resorption caused by intraosseous lymphatic vessel structure and thin-walled vascular proliferation. The diagnosis of GSD has not yet formed a uniform standard, but the combination of clinical manifestations, radiological features and unique histopathological examinations and excluding other diseases contribute to early diagnosis. Although medical therapy, radiotherapy and surgical interventions or combinations have been used for the treatment of GSD, there is currently still no recommended standardized treatment regimen. Case report: This paper presents a case of a previously healthy 70-year-old man presented with a 10-year history of severe right hip pain and progressive walking disorder of the lower limbs. Based on the patient's clear clinical presentation, unique radiological features, and histological findings, a diagnosis of GSD was made with the exclusion of other potential diseases. The patient was treated with bisphosphonates to slow the progression of the disease followed by total hip arthroplasty to help restore walking function. At the 3-year follow-up, the patient returned to normal walking and no recurrence was observed. Conclusion: Bisphosphonates combined with total hip arthroplasty may be an effective method for the treatment of severe GSD in the hip joint.

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.

Inhibition of NUCB2 suppresses the proliferation, migration, and invasion of rheumatoid arthritis synovial fibroblasts from patients with rheumatoid arthritis in vitro.

Rheumatoid arthritis (RA) is an autoimmune polyarthritis in which synovial fibroblasts (SF) play a major role in cartilage and bone destruction through tumorlike proliferation, migration, and invasion. Nesfatin-1, an 82-amino-acid-long peptide discovered by Oh-I in 2006, is derived from the precursor protein nucleobindin-2 (NUCB2). NUCB2/nesfatin-1 promotes cell proliferation, migration, and invasion in various tumors. We have previously shown that increased nesfatin-1 levels in the synovium may be associated with disease severity in patients with RA. However, the effect of NUCB2 on the tumorlike transformation of RASF has not yet been reported. The expression of NUCB2 mRNA in the synovium of RA and non-RA patients was further confirmed using three individual datasets from the NCBI GEO database. Gene set enrichment analysis (GSEA) was employed to explore the association between NUCB2 mRNA and RA-related gene signatures or signaling pathways in the GSE77298 dataset. Cell proliferation, migration, and invasion abilities were determined using Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), wound healing, and transwell assays, respectively. The results showed that the levels of NUCB2 mRNA in the synovium were significantly elevated in patients with RA. Moreover, GSEA showed that high expression of NUCB2 mRNA was related to gene signatures, including those involved in the cell cycle, DNA replication, extracellular matrix-receptor interaction, and focal adhesion. Furthermore, the results of CCK-8 and EdU assays indicated that inhibition of NUCB2 markedly repressed RASF proliferation. Additionally, the results of wound healing and transwell assays demonstrated that inhibition of NUCB2 significantly suppressed the migratory and invasive abilities of RASFs. Our findings are the first to demonstrate that the inhibition of NUCB2 suppresses the proliferation, migration, and invasion of RASFs in vitro.

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.

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.