Objective Benign nerve sheath tumors (BNSTs) present diagnostic challenges due to their heterogeneous nature. This study aimed to determine the significance of NRG1 as a novel diagnostic biomarker in BNST, emphasizing its involvement in the PI3K-Akt pathway and tumor immune regulation. Methods Differential genes related to BNST were identified from the GEO database. Gene co-expression networks, protein-protein interaction networks, and LASSO regression were utilized to pinpoint key genes. The CIBERSORT algorithm assessed immune cell infiltration differences, and functional enrichment analyses explored BNST signaling pathways. Clinical samples helped establish PDX models, and in vitro cell lines to validate NRG1’s role via the PI3K-Akt pathway. Results Nine hundred eighty-two genes were upregulated, and 375 downregulated in BNST samples. WGCNA revealed the brown module with the most significant difference. Top hub genes included NRG1, which was also determined as a pivotal gene in disease characterization. Immune infiltration showed significant variances in neutrophils and M2 macrophages, with NRG1 playing a central role. Functional analyses confirmed NRG1’s involvement in key pathways. Validation experiments using PDX models and cell lines further solidified NRG1’s role in BNST. Conclusion NRG1 emerges as a potential diagnostic biomarker for BNST, influencing the PI3K-Akt pathway, and shaping the tumor immune microenvironment.

Background: Optic nerve sheath diameter (ONSD) is a promising, noninvasive invasive intracranial pressure (ICP) measurement method. This study aims to analyze the differences in ONSD between the left and right eyeballs and the differences in ultrasonic measurement between the transverse and sagittal planes. Methods: Data from a total of 50 eligible patients with various types of brain injury who were admitted to our hospital from May 2019 to June 2021 were analyzed. An ONSD assessment was then performed using Philips B-mode ultrasound, measuring ONSD 3 mm posterior to the eyeballs. The left and right ONSDs in the transverse and sagittal planes were measured. Intraparenchymal fiber optic sensors and catheters were inserted into the ventricles and connected to an external pressure transducer to measure ICP. Results: A total of 164 sonographic measurements of ONSD were performed in 50 patients with brain injury in a prospective observational study. Statistically significant differences were found in ONSD between the transverse and sagittal planes. The difference in the left ONSD between the transverse and sagittal planes was 0.007 ± 0.030 cm (P = 0.003). The Spearman rank correlation test showed that the correlation coefficient between ICP and left/right ONSD in the transverse/sagittal planes was 0.495 vs 0.546 and 0.559 vs 0.605, respectively. The results showed that the areas under the curve of ONSD in the transverse and sagittal planes were 0.843 and 0.805, respectively. Medcalc software was used to compare the areas under the receiver operator characteristic curve, and the results showed that ONSD in the sagittal plane is generally better than in the transverse plane (P = 0.0145). Conclusions: This study found that ONSD in the sagittal plane is superior to the transverse plane regarding the comprehensive efficacy of ICP, and unilateral measurement is sufficient.

This study aims to detect whether the optic nerve sheath diameter (ONSD) can be used to dynamically monitor intracranial pressure (ICP). Adult patients undergoing invasive ICP monitoring on the day of admission are included in this study. For each patient, the ONSD is first measured in the supine position and then in the 30∘ head-up position. Subsequently, a dynamic test is conducted on 16 patients. The ONSD is measured in the supine position once a day for three consecutive days starting on the day of admission. There is a strong correlation between the ONSD and ICP values in the supine position on admission (r = 0.799), and when patients are changed from the supine to the 30∘ head-up position, the ICP and ONSD values decrease correspondingly. However, the change in ICP is not strongly correlated with the change in ONSD (r = 0.358). In the dynamic test, a good agreement between the ICP and ONSD only exists in three patients (18.8%), and three patients have completely different profiles for ICP and ONSD. These results suggest that the changes in the ONSD and ICP values are not closely correlated after dynamic observation. Therefore, measurement of the ONSD may not be a suitable tool to dynamically monitor ICP.

Background This study investigated the clinical effect of laminectomy plus pedicle screw fixation in treating thoracolumbar intradural extramedullary schwannomas. Material/Methods Between October 2011 and May 2017, 57 patients undergoing resection of thoracolumbar schwannomas were retrospectively identified and included in the study. Based on the surgical procedures used, all participants were assigned to either the laminectomy-only group (n=33) or the combination group (laminectomy plus pedicle screw fixation, n=24). All participants were followed up for over 2 years. In the laminectomy, the spinal process, vertebral laminae, and bilateral upper articular processes of the surgical segments were completely resected and the lower articular processes were reserved. For further analysis, we evaluated the pain levels using visual analogue scale (VAS) score. The assessment of neurological function was performed with Japanese Orthopaedic Association (JOA) score and Oswestry disability index (ODI). The comparisons of Cobb angle changes were carried out pre-surgery and post-surgery. Results The demographic data were well matched between the laminectomy-only group and combination group, without significant differences (P>0.05). After surgery, both surgical procedures achieved significant improvement in VAS score, ODI, and JOA score (P<0.001), but no significant differences were found between these 2 surgical procedures (P>0.05). The postoperative change in Cobb angle indicated a significant difference in the laminectomy-only group, but not in the combination group (P<0.05). In addition, postoperative spinal instability/deformity was found in the laminectomy-only group (P<0.05). Conclusions In conclusion, the combination of laminectomy and pedicle screw fixation is a safe and effective surgical procedure when used to treat thoracolumbar schwannoma, and appears to be superior to the laminectomy-only procedure.

Cancer immunotherapy using cytotoxic T cells demonstrates dramatic survival benefits in lymphomas, but its efficacy in solid tumors is limited. Here, we investigated the possibility of using cytotoxic T cells to treat malignant Schwannoma, a rare but aggressive nerve sheath tumor, by examining the native T-cell immunity in the host. We found that compared to CD8(+) T cells from healthy controls or benign Schwannoma patients, the CD8(+) T cells from malignant Schwannoma patients were present at normal frequencies but were substantially enriched with PD-1(-)TIM-3(+) and PD-1(+)TIM-3(+) cells. Compared to the PD-1(-)TIM-3(-) CD8(+) T cells, the PD-1(-)TIM-3(+) and PD-1(+)TIM-3(+) CD8(+) T cells presented significantly lower proliferation capacity, reduced interleukin 2 and interferon gamma expression, and/or dramatically decreased perforin and granzyme B secretion, indicating a whole-spectrum immunosuppression and reduced cytotoxicity. TIM-3 expression alone was associated with lower proliferation and less perforin and granzyme B secretion, whereas PD-1 expression alone was not associated with functional impairments, suggesting that TIM-3 expression was a better marker of exhausted CD8(+) T cells. The expression of galectin 9, a TIM-3 ligand, in CD4(+) Th cells was significantly elevated in malignant, but not benign, Schwannoma patients and were enriched in CD25(+) Treg cells. Both the PD-1(-)TIM-3(+) and PD-1(+)TIM-3(+) CD8(+) T cells responded to Treg-mediated and galectin 9-mediated suppression, whereas the PD-1(+)TIM-3(-) CD8(+) T cells only responded to Treg-mediated suppression. In resected tumors, the malignant Schwannomas had more tumor-infiltrating CD4(+) and CD8(+) T cells than the benign Schwannomas, but a large fraction of these tumor-infiltrating CD4(+) and CD8(+) T cells expressed PD-1 and/or TIM-3, which indicated that their antitumor immunity was compromised. Together, our results suggested that PD-1 and TIM-3 blockade might be necessary in developing effective immunotherapeutic strategies in malignant Schwannoma, in which TIM-3 may play a more important role.

Background: Co-existing of odontoid subluxation syringomyelia and vertebral artery abnormalities is a rare condition occurred in spinal cord, and the therapeutic approach of this disease is also rarely reported. Hence, a case of co-existing of odontoid subluxation syringomyelia and vertebral artery abnormalities was reported in this study. Methods: A male patient, who suffered with limited head and neck functions, was described in the current study. X-ray and MRI examinations for cervical vertebra were performed to examine the conduct physical examination. Meanwhile, the basic personnel characteristics were also collected, including speech, behavior, power, and state of mind. After examinations, patient was received surgery treatment with a prone position, and the outcomes were checked using CT imaging. Results: According to patient’s narration, he had suffered from inability and pain in left lower limb accompanied with limited locomotive for more than 4 months. Further physical examinations showed that patient had a sober mind and powerful shrug, but obvious hoarse voice and blear speech, soft neck, and limited limb activity. Meanwhile, X-ray and MRI results showed obvious occipito-cervical deformity, odontoid subluxation and syringomyelia. During surgery, an obvious insertion and merge of lepospondylous arcus posterior was found in foramen magnum posterior, and no sever events had been observed. The patient recovered gradually after surgery, however long term outcomes of the treatment needed more clinical data of follow-up. Conclusion: Limited neck and limbs activity were the main syndromes of the co-existing of odontoid subluxation syrignomyelia and vertebral artery abnormalities, and bleeding may be an important risk factor and should be significantly considered during surgery treatment.

CD4+Foxp3- type 1 regulatory T (Tr1) cells are potent producers of interleukin 10 (IL-10) and transforming growth factor beta (TGF-β), through which they suppress pathogenic inflammation and autoimmune responses. The role of Tr1 response in glioblastoma multiforme (GBM) is still unclear. Here, we examined the frequency, phenotype, induction mechanism, and function of Tr1 cells in GBM patients. Compared to healthy controls, GBM patients presented significantly higher frequency of Tr1 cells in peripheral blood. The Tr1 frequency was further elevated in the tumor. By surface marker expression, the Tr1 cells were enriched in the antigen-experienced effector/memory cell compartment. A minority of Tr1 cells presented IL-10+TGF-β+ double expression. Interestingly, naive CD4+CD45RA+ T cells could differentiate into IL-10- and TGF-β-expressing cells, if incubated with tumor-associated macrophages (TAMs) or with macrophages conditioned with primary glioma cells, suggesting that tumor cells and TAMs had a role in inducing Tr1 cells in GBM patients. Coculture of Tr1 cells with proinflammatory CD4+ T cells resulted in TGF-β-dependent reduction of interferon gamma (IFN-γ) and IL-10-dependent reduction of tumor necrosis factor alpha (TNF-α), while coculture of Tr1 cells with CD8+ T cells resulted in lower tumor-specific cytotoxicity. Together, these results demonstrated an upregulation of Tr1 cells in GBM with anti-inflammatory functions.

Schwannoma is a common, almost always benign tumor developed from Schwann cells, and can usually be removed by surgery. However, in a minority of patients, schwannoma can reappear at the same location for reasons not completely understood. Furthermore, schwannoma can undergo malignant transformation in a rare subset of patients, which is aggressive, rapidly growing and life threatening. To examine the underlying mechanism in schwannoma regrowth and malignant transformation, we examined the intratumor environment in primary and recurrent schwannomas of both benign and malignant types. We found that compared to the noncancerous, primary tumor, the recurrent schwannoma tumor after the removal of the first expressed significantly higher levels of IL-10. Moreover, the IL-10 level was further upregulated in malignant schwannomas. Malignant tumors also presented an infiltration of macrophages and T cells, which were not observed in benign tumors. Together, we discovered a previously unknown feature of recurrent and malignant schwannomas.