Schwanns cell (SC) was isolated from sciatic nerve of adult rat with Wallerine degeneration. After culture, SC-serum free culture media (SCSFCM) was obtained. By ultrafiltration with PM-10 Amicon Membrane, electrophoresis with DiscPAGE,and electrical wash-out with Biotrap apparatus, D-band protein was isolated from the SC-SFCM. The D-band protein in the concentration of 25ng/ml could affect the survival of the spinal anterior horn neuron in vitro, prominently and itsactivity was not changed after being frozen. The molecular weight of the protein ranged from 43 to 67 Kd. The D-band protein might be a neurotrophic substancedifferent from the known SCderived neurotrophic factors (NTF). Its concentration with biological activity was high enough to be detected. The advantages of MTT in assessment of NTF activity were also discussed.
Objective To investigate the clinical features, treatment methods, and prognostic influence factors of patients with malignant peripheral nerve sheath tumor (MPNST). MethodsA retrospective analysis was conducted on 96 MPNST patients treated between January 1, 2015 and December 31, 2021. There were 46 males and 50 females, aged between 15 and 87 years (mean, 48.2 years). The tumors were located in the trunk in 50 cases, extremities in 39 cases, and head and neck in 7 cases. The maximum tumor diameter was <5 cm in 49 cases, ≥5 cm in 32 cases, with 15 cases missing data. Tumor depth was deep in 77 cases and superficial in 19 cases. The Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) histological grading was G1 in 9 cases, G2 in 12 cases, and G3 in 34 cases, with 41 cases missing data. There were 37 recurrent MPNST cases, 32 cases with neurofibromatosis type 1 (NF1), and 26 cases in stage Ⅳ. Postoperative adjuvant radiotherapy was administered to 25 patients, perioperative chemotherapy to 45 patients, and anlotinib-targeted therapy to 30 patients. R0 resection was achieved in 73 cases. Patients were divided into groups based on the presence or absence of NF1, and baseline data between the two groups were compared. Kaplan-Meier curves were generated to assess disease-free survival (DFS) and overall survival (OS) based on various factors (age, gender, presence of NF1, recurrent MPNST, stage Ⅳ MPNST, FNCLCC grade, R0 resection, tumor location, tumor size, tumor depth, perioperative chemotherapy, postoperative adjuvant radiotherapy, and anlotinib-targeted therapy), and differences between survival curves were analyzed using the Log-Rank test. Multivariate COX proportional hazards regression was used to identify independent prognostic factors for MPNST. Results Patients with NF1 had a significantly higher proportion of superficial tumors and lower FNCLCC grade compared to those without NF1 (P<0.05); no significant difference was found for other variables (P<0.05). Kaplan-Meier analysis showed that recurrent MPNST, stage Ⅳ MPNST, FNCLCC grade, R0 resection, perioperative chemotherapy, and anlotinib-targeted therapy were factors influencing 1-year DFS (P<0.05), while stage Ⅳ MPNST, FNCLCC grade, and perioperative chemotherapy were factors affecting 3-year OS (P<0.05). Multivariate COX proportional hazards regression analysis revealed that recurrent MPNST and high-grade FNCLCC (G3) were independent prognostic factors for 1-year DFS (P<0.05), while stage Ⅳ MPNST, superficial tumor depth, age over 60 years, postoperative adjuvant radiotherapy, and anlotinib-targeted therapy were independent prognostic factors for 3-year OS (P<0.05). Conclusion MPNST patients with NF1 tend to have more superficial tumors and lower FNCLCC grades. FNCLCC grade, R0 resection, and adjuvant therapies, including radiotherapy and anlotinib-targeted therapy, are closely associated with MPNST prognosis. Complete surgical resection should be prioritized in clinical management, along with adjuvant treatments such as radiotherapy and targeted therapy of anlotinib to improve patient outcomes.
Objective To review the mechanism and effects of cell autophagy in the pathophysiology changes of peripheral nerve injury. Methods The recent literature about cell autophagy in peripheral nerve injury and regeneration was extensively reviewed and summarized. Results The researches through drugs intervention and gene knockout techniques have confirmed that the Schwann cell autophagy influences the myelin degeneration, debris clearance, inflammatory cells infiltration, and axon regeneration through JNK/c-Jun pathway. To adjust autophagy process could slow down the Wallerian degeneration, maintain the integrity of injured nerve, while the effect on axon regeneration is still controversial. Conclusion The Schwann cell autophagy plays a key role in the pathophysiology changes of peripheral nerve injury, the further study of its mechanism could provide new methods for the therapy of peripheral nerve injury.
Objective To explore the clinical features, surgical treatment, and effectiveness of neurofibromas associated with neurofibromatosis type 1 (NF1). Methods A clinical data of 41 patients with NF1 admitted between December 2018 and April 2024 was retrospectively analyzed. There were 15 males and 26 females, with an average age of 27.5 years (range, 5-61 years). Only one type of neurofibroma existed in 3 patients and the rest of the patients had more than two types of neurofibromas. Fourteen patients had total resection of multiple cutaneous neurofibromas (CNF). Eighteen patients of diffuse neurofibromas underwent total, near-total, or subtotal resection. Among the 13 patients of localized nodular neurofibromas, 9 of benign tumors underwent total sub-capsular resection and 4 of malignant peripheral nerve sheath tumor (MPNST) underwent maginal resection, and only 1 underwent postoperative radiotherapy and chemotherapy. Among the 15 patients of plexiform neurofibromas (PNF), 5 patients underwent both superficial and deep PNF resection, 2 underwent the superficial PNF resection, and 8 underwent the large nodular lesions in the deep PNF resection. There were 8 MPNST, of which 7 cases underwent total sub-capsular resection and large tumor capsule resection under neurophysiological monitoring, and 1 case with the tumor located on the top of the head underwent wide resection and skin grafting. One patient underwent proton knife therapy after surgery, 2 patients did not receive radiotherapy, and the remaining patients received conventional radiotherapy. Results All patients were followed up after surgery, and the follow-up time was 3-66 months, with an average of 25.0 months. Patients with CNF recovered satisfactorily after surgery, and there was no recurrence during follow-up. Patients with diffuse neurofibromas relieved preoperative symptoms after surgery. Three patients with diffuse neurofibromas located in the head and face recurred during follow-up. The patients with benign localized nodular neurofibromas recovered well after surgery, and only 1 patient had transient regional neuralgia after surgery. Among the patients with MPNST, 2 patients died of recurrence and lung metastasis, while the remaining 2 patients had no recurrence and metastasis during follow-up. All preoperative symptoms disappeared in patients with benign PNF, and no tumor recurrence was observed during follow-up. Two patients with PNF located in the brachial plexus had difficulty in shoulder abduction after surgery, 1 patient with PNF located in vagus developed hoarseness after surgery. Among the 8 patients with MPNST in PNF, 1 died of lung metastases and 1 died of systemic failure. The remaining 6 patients were in stable condition during follow-up, and no tumor recurrence or metastasis was observed. Conclusion According to the clinical features of neurofibromas in patients with NF1, choosing appropriate surgical approaches can obtain good effectiveness. Because of the difficulty of completely resection, diffuse neurofibromas, especially those located in the head and face, are prone to recurrence after surgery. MPNST has the worst prognosis, high incidence of recurrence/metastasis, and short survival period. Total resection combined with radiotherapy can decrease local recurrence.
Objective To investigate the differences in biomechanical properties between fresh and chemically extracted acellular peri pheral nerve. Methods Thirty-six sciatic nerves were harvested from 18 adult male Wistar rats of 3 months old and randomly assigned into 3 groups (n=12 per group): normal control group (group A), the nerve segments received no treatment; Sondell method group (group B), the nerve segments were chemically extracted with the detergents of Triton X-100 and sodium deoxycholate; and improved method group (group C), chemically extracted acellular treatment of nerve was done with the detergents of Triton X-200, Sulfobetaine-10 (SB-10), and SB-16. After the acellularization, the structural changes of nerves in each group were observed by HE staining and field emission scanning electron microscope,then the biomechanical properties of nerves were tested using mechanical apparatus (Endura TEC ELF 3200). Results HE staining and field emission scanning electron microscope showed that the effect of acellularization of group C was similar to that of group B, but the effects of demyel ination and integrity of nerve fiber tube of group C were better than those of group B; the structure of broken nerves was more chaotic than before biomechanical test. The biomechanical test showed that the ultimate load, ultimate stress, ultimate strain, mechanical work to fracture in group A were the largest, the next was group C, the least was group B; the tenacity and elastic modulus in group C were the largest, the next was group B, the least was group A; but the differences were not significant (P gt; 0.05). Conclusion Compared with Sondell method, the nerve treated by improved method is more appropriate for use in vivo.
ObjectiveTo review the literature on the research status of vascularization of tissue engineered peripheral nerve so as to provide the theoretical basis for the vascularization of tissue engineered peripheral nerve.MethodsThe literature related to the vascularization of peripheral nerve tissue engineering in recent years was reviewed and summarized according to the five aspects of promoting vascularization: local microenvironment and blood supply characteristics of peripheral nerve regeneration, scaffold material modification, seed cells, autologous vascular bundle implantation, and pro-vascular factors.ResultsTissue engineered peripheral nerve has brought a new hope for the repair of peripheral nerve injury, but the repair effect of large nerve defects is not good, which is mainly related to the degree of vascularization of the nerve grafts. So it is particularly important to promote the early vascularization of tissue engineered peripheral nerve. Previous studies have mainly focused on the four aspects of scaffold material modification, seed cells, autologous vascular bundle implantation, and angiogenesis related factors. Recent studies show that the combination of the above two or more factors in the tissue engineered peripheral nerves can better promote the vascularization of tissue engineered peripheral nerves.ConclusionPromoting early vascularization of tissue engineered peripheral nerves can provide timely nutritional support for seed cells on the scaffold, promote axon growth and nerve regeneration, and facilitate the repair of large peripheral nerve defects in clinical practice.
ObjectiveTo explore the preparation method, physical and chemical properties, and biocompatibility of a conductive composite scaffold based on polypyrrole/silk fibroin (PPy/SF) fiber with " shell-core” structure, and to provide a preliminary research basis for the application in the field of tissue engineered neuroscience.Methods The conductive fibers with " shell-core” structure were prepared by three-dimensional printing combined with in-situ polymerization. PPy/SF fiber-based conductive composite scaffolds were formed by electrospinning. In addition, core-free PPy conductive fibers and SF electrospinning fibers were prepared. The stability, biomechanics, electrical conductivity, degradation performance, and biological activity of each material were tested to analyze the comprehensive properties of fiber-based conductive composite scaffolds.ResultsCompared with pure core-free PPy conductive fibers and SF electrospinning fibers, the PPy/SF fiber-based conductive composite scaffolds with " shell-core” structure could better maintain the stability performance, enhance the mechanical stretchability of the composite scaffolds, maintain long-term electrical activity, and improve the anti-degradation performance. At the same time, PPy/SF conductive composite scaffolds were suitable for NIH3T3 cells attachment, conducive to cell proliferation, and had good biological activity.ConclusionPPy/SF fiber-based conductive composite scaffolds meet the needs of conductivity, stability, and biological activity of artificial nerve grafts, and provide a new idea for the development of a new generation of high-performance and multi-functional composite materials.
Objective To explore the role and clinical significance of cell-cycle dependent kinase 1 (CDK1) and its upstream and downstream molecules in the development of malignant peripheral nerve sheath tumor (MPNST) through the analysis of clinical tissue samples. Methods A total of 56 tumor samples from MPNST patients (“Tianjin” dataset) who underwent surgical resection, confirmed by histology and pathology between September 2011 and March 2020, along with 17 normal tissue samples, were selected as the research subjects. MPNST-related hub genes were identified through transcriptome sequencing, bioinformatics analysis, immunohistochemistry staining, and survival analysis, and their expression levels and prognostic associations were analyzed. Results Transcriptome sequencing and bioinformatics analysis revealed that upregulated genes in MPNST were predominantly enriched in cell cycle-related pathways, with CDK1 occupying a central position among all differentially expressed genes. Further differential analysis demonstrated that CDK1 mRNA expression in sarcoma tissues was significantly higher than in normal tissues [based on searching the cancer genome atlas (TCGA) dataset, P<0.05]. In MPNST tissues, CDK1 mRNA expression was not only significantly higher than in normal tissues (based on Tianjin, GSE141438 datasets, P<0.05), but also significantly higher than in neurofibromatosis (NF) and plexiform neurofibromas (PNF) (based on GSE66743 and GSE145064 datasets, P<0.05). Immunohistochemical staining results indicated that the expression rate of CDK1 protein in MPNST tissues was 40.31%. Survival analysis results demonstrated that CDK1 expression was associated with poor prognosis. The survival time of MPNST patients with high CDK1 mRNA expression was significantly lower than that of the low expression group (P<0.05), and the overall survival trend of patients with positive CDK1 protein expression was worse than that of patients with negative CDK1 expression. Additionally, differential analysis of CDK family genes (CDK1-8) revealed that only CDK1 was significantly upregulated in MPNST, NF, and PNF. Conclusion Increased expression of CDK1 is associated with poor prognosis in MPNST patients. Compared to other CDK family members, CDK1 exhibits a unique expression pattern, suggesting its potential as a therapeutic target for MPNST.
Objective To summarize the latest developments in neurosurgical treatments for neurofibromatosis type 1 (NF1) and explore therapeutic strategies to provide comprehensive treatment guidelines for clinicians. Methods The recent domestic and international literature and clinical cases in the field of NF1 were reviewed. The main types of neurological complications associated with NF1 and their treatments were thorough summarized and the future research directions in neurosurgery was analyzed. Results NF1 frequently results in complex and diverse lesions in the central and peripheral nervous systems, particularly low-grade gliomas in the brain and spinal canal and paraspinal neurofibromas. Treatment decisions should be made by a multidisciplinary team. Symptomatic plexiform neurofibromas and tumors with malignant imaging evidence require neurosurgical intervention. The goals of surgery include reducing tumor size, alleviating pain, and improving appearance. Postoperative functional rehabilitation exercises, long-term multidisciplinary follow-up, and psychosocial interventions are crucial for improving the quality of life for patients. Advanced imaging guidance systems and artificial intelligence technologies can help increase tumor resection rates and reduce recurrence. Conclusion Neurosurgical intervention is the primary treatment for symptomatic plexiform neurofibromas and malignant peripheral nerve sheath tumors when medical treatment is ineffective and the lesions progress rapidly. Preoperative multidisciplinary assessment, intraoperative electrophysiological monitoring, and advanced surgical assistance devices significantly enhance surgical efficacy and safety. Future research should continue to explore new surgical techniques and improve postoperative management strategies to achieve more precise and personalized treatment for NF1 patients.
ObjectiveTo investigate the effect of folic acid coated-crosslinked urethane-doped polyester elastomer (fCUPE) nerve conduit in repairing long distance peripheral nerve injury. MethodsThirty-six 3-month-old male Sprague Dawley rats weighing 180-220 g were randomly assigned to 3 groups, each consisting of 12 rats: CUPE nerve conduit transplantation group (group A), fCUPE nerve conduit transplantation group (group B), and autologous nerve transplantation group (group C), the contralateral healthy limb of group C served as the control group (group D). A 20-mm-long sciatic nerve defect model was established in rats, and corresponding materials were used to repair the nerve defect according to the group. The sciatic function index (SFI) of groups A-C was calculated using the Bain formula at 1, 2, and 3 months after operation. The nerve conduction velocity (NCV) of the affected side in groups A-D was assessed using neuroelectrophysiological techniques. At 3 months after operation, the regenerated nerve tissue was collected from groups A-C for S-100 immunohistochemical staining and Schwann cell count in groups A and B to compare the level of nerve repair and regeneration in each group. ResultsAt 3 months after operation, the nerve conduits in all groups partially degraded. There was no significant adhesion between the nerve and the conduit and the surrounding tissues, the conduit was well connected with the distal and proximal nerves, and the nerve-like tissues in the conduit could be observed when the nerve conduit stents were cut off. SFI in group A was significantly higher than that in group C at each time point after operation and was significantly higher than that in group B at 2 and 3 months after operation (P<0.05). There was no significant difference in SFI between groups B and C at each time point after operation (P>0.05). NCV in group A was significantly slower than that in the other 3 groups at each time point after operation (P<0.05). The NCV of groups B and C were slower than that of group D, but the difference was significant only at 1 month after operation (P<0.05). There was no significant difference between groups B and C at each time point after operation (P>0.05). Immunohistochemical staining showed that the nerve tissue of group A had an abnormal cavo-like structure, light tissue staining, and many non-Schwann cells. In group B, a large quantity of normal neural structures was observed, the staining was deeper than that in group A, and the distribution of dedifferentiated Schwann cells was obvious. In group C, the nerve bundles were arranged neatly, and the tissue staining was the deepest. The number of Schwann cells in group B was (727.50±57.60) cells/mm2, which was significantly more than that in group A [(298.33±153.12) cells/mm2] (t=6.139, P<0.001). ConclusionThe fCUPE nerve conduit is effective in repairing long-distance sciatic nerve defects and is comparable to autologous nerve grafts. It has the potential to be used as a substitute material for peripheral nerve defect transplantation.