A low prognostic nutritional index is associated with chronic subdural hematoma recurrence.

Chronic subdural hematoma (CSDH) is a common neurosurgical condition. Inflammation has been found to play an essential role in the formation of CSDHs, and the prognostic nutritional index (PNI), a nutritional and inflammatory baseline marker, plays a role in predicting the prognosis of many diseases. We aimed to identify the relationship between PNI and CSDH recurrence. This study retrospectively analyzed 261 CSDH patients who underwent burr hole evacuation in Beijing Tiantan Hospital from August 2013 to March 2018. The PNI was calculated as 5 ∗ lymphocyte count (109/L) + serum albumin concentration (g/L), and these markers were obtained from the peripheral blood test on the day of discharge from the hospital. Recurrence was defined as operated hematoma enlargement accompanied by newly emerging neurological disorders. The comparison of baseline characteristics demonstrated that patients with bilateral hematoma and low levels of albumin, lymphocytes, and PNI were more likely to be recurrent. After adjusting for age, sex, and other important variables, decreased PNI levels were associated with an increased risk of CSDH (OR, 0.803, 95% CI: 0.715-0.902, p = 0.001). The addition of PNI to conventional risk factors significantly improved the risk prediction of CSDH (net reclassification index: 71.12%, p = 0.001; integrated discrimination index: 10.94%, p = 0.006). A low PNI level is associated with an increased risk of CSDH recurrence. As an easily obtainable nutritional and inflammatory marker, PNI may play a significant role in predicting the recurrence of CSDH patients.

Efficacy analysis of neuroendoscopy-assisted burr-hole evacuation for chronic subdural hematoma: a systematic review and meta-analysis.

The purpose of this study was to compare neuroendoscopy-assisted burr-hole evacuation with conventional burr-hole evacuation in the treatment of chronic subdural hematoma (CSDH), and to evaluate the curative effect of neuroendoscopy. This study follows PRISMA guidelines and uses the keywords "chronic subdural hematoma," "neuroendoscopies," "neuroendoscopy," "endoscopy," "endoscopic neurosurgery," and "neuroendoscopic surgery" to conduct an electronic search of online databases, including PubMed, Embase, Web of Science, and Cochrane Library. There were no restrictions on language or publication year. This meta-analysis involved 948 patients in six studies. The results showed that the recurrence rate in the neuroendoscopy group was significantly lower than that in the conventional burr-hole group (3.1% vs. 13.8%, P<0.001). Compared with the control group, the neuroendoscopy group had a longer operation time (P<0.001) and a shorter postoperative drainage time (P<0.001). In addition, there was no significant difference in hospital stay (P=0.14), mortality (P=0.39), postoperative morbidity (P=0.12), or 6-month neurological outcomes (P=0.32) between the two groups. It should be noted that the comparison of neurological outcomes was based on 269 patients (6/106 vs. 14/163). Compared with conventional burr-hole evacuation, neuroendoscopy-assisted burr-hole evacuation reduces the recurrence rate of CSDH and shortens the postoperative drainage time. However, the neuroendoscopy group did not have lower mortality or morbidity or better functional outcomes. In the future, randomized controlled trials are needed to further evaluate the efficacy and safety of neuroendoscopic surgery.

Postoperative pneumocephalus and recurrence and outcome of chronic subdural hematoma: a systematic review and meta-analysis.

We conducted a meta-analysis to analyze the effects of pneumocephalus after chronic subdural hematoma (CSDH) surgery on hematoma recurrence, mortality, and functional outcomes. In this meta-analysis, following PRISMA guidelines, PubMed, Embase, Cochrane Library, and Web of Science online databases were queried using the keywords "pneumocephalus," "pneumoencephalos," "intracranial pneumatocele," "pneumo encephalon," "subdural air," and "chronic subdural hematoma." The results were limited to English-language articles. Through the online database, we identified a total of 276 articles and finally included 14 articles for meta-analysis. The results showed that the recurrence rate in the pneumocephalus group was higher than that in the control group, with a pooled OR of 3.35 (CI: 2.51-4.46, P < 0.001). There was no difference in recurrence rate between the no/few and moderate pneumocephalus groups (OR: 1.27, CI: 0.68-2.37, P = 0.46), but the recurrence rate of the large pneumocephalus group was significantly higher than that of the moderate group, with a pooled OR of 3.29 (CI: 1.71-6.32, P < 0.001). This study failed to show higher mortality and worse outcomes in the pneumocephalus group than in the control. Pneumocephalus after surgical evacuation of CSDH was associated with the recurrence rate of hematoma. Pneumocephalus affecting recurrence was correlated with gas volume, and moderate pneumocephalus may have less impact, while patients with large pneumocephalus are more likely to recur than those with moderate pneumocephalus. More prospective cohort studies are needed for further investigation and verification. This meta-analysis was registered (PROSPERO CRD42022321800).

Identification of genomic alterations in oesophageal squamous cell cancer.

Oesophageal cancer is one of the most aggressive cancers and is the sixth leading cause of cancer death worldwide. Approximately 70% of global oesophageal cancer cases occur in China, with oesophageal squamous cell carcinoma (ESCC) being the histopathological form in the vast majority of cases (>90%). Currently, there are limited clinical approaches for the early diagnosis and treatment of ESCC, resulting in a 10% five-year survival rate for patients. However, the full repertoire of genomic events leading to the pathogenesis of ESCC remains unclear. Here we describe a comprehensive genomic analysis of 158 ESCC cases, as part of the International Cancer Genome Consortium research project. We conducted whole-genome sequencing in 17 ESCC cases and whole-exome sequencing in 71 cases, of which 53 cases, plus an additional 70 ESCC cases not used in the whole-genome and whole-exome sequencing, were subjected to array comparative genomic hybridization analysis. We identified eight significantly mutated genes, of which six are well known tumour-associated genes (TP53, RB1, CDKN2A, PIK3CA, NOTCH1, NFE2L2), and two have not previously been described in ESCC (ADAM29 and FAM135B). Notably, FAM135B is identified as a novel cancer-implicated gene as assayed for its ability to promote malignancy of ESCC cells. Additionally, MIR548K, a microRNA encoded in the amplified 11q13.3-13.4 region, is characterized as a novel oncogene, and functional assays demonstrate that MIR548K enhances malignant phenotypes of ESCC cells. Moreover, we have found that several important histone regulator genes (MLL2 (also called KMT2D), ASH1L, MLL3 (KMT2C), SETD1B, CREBBP and EP300) are frequently altered in ESCC. Pathway assessment reveals that somatic aberrations are mainly involved in the Wnt, cell cycle and Notch pathways. Genomic analyses suggest that ESCC and head and neck squamous cell carcinoma share some common pathogenic mechanisms, and ESCC development is associated with alcohol drinking. This study has explored novel biological markers and tumorigenic pathways that would greatly improve therapeutic strategies for ESCC.

Mutant TP53 G245C and R273H promote cellular malignancy in esophageal squamous cell carcinoma.

BACKGROUND: TP53 gene mutations occur in more than 50% of human cancers and the vast majority of these mutations in human cancers are missense mutations, which broadly occur in DNA binding domain (DBD) (Amino acids 102-292) and mainly reside in six "hotspot" residues. TP53 G245C and R273H point mutations are two of the most frequent mutations in tumors and have been verified in several different cancers. In the previous study of the whole genome sequencing (WGS), we found some mutations of TP53 DBD in esophageal squamous cell carcinoma (ESCC) clinical samples. We focused on two high-frequent mutations TP53 p.G245C and TP53 p.R273H and investigated their oncogenic roles in ESCC cell lines, p53-defective cell lines H1299 and HCT116 p53-/-. RESULTS: MTS and colony formation assays showed that mutant TP53 G245C and R273H increased cell vitality and proliferation. Flow cytometry results revealed inhibition of ultraviolet radiation (UV)- and ionizing radiation (IR)- induced apoptosis and disruption of TP53-mediated cell cycle arrest after UV, IR and Nocodazole treatment. Transwell assays indicated that mutant TP53 G245C and R273H enhanced cell migration and invasion abilities. Moreover, western blot revealed that they were able to suppress the expression of TP53 downstream genes in the process of apoptosis and cell cycle arrest induced by UV, which suggests that these two mutations can influence apoptosis and growth arrest might be due, at least in part, to down-regulate the expression of P21, GADD45α and PARP. CONCLUSIONS: These results indicate that mutant TP53 G245C and R273H can lead to more aggressive phenotypes and enhance cancer cell malignancy, which further uncover TP53 function in carcinogenesis and might be useful in clinical diagnosis and therapy of TP53 mutant cancers.

The chromosome 11q13.3 amplification associated lymph node metastasis is driven by miR-548k through modulating tumor microenvironment.

BACKGROUND: The prognosis for esophageal squamous cell carcinoma (ESCC) patients with lymph node metastasis (LNM) is still dismal. Elucidation of the LNM associated genomic alteration and underlying molecular mechanisms may provide clinical therapeutic strategies for ESCC treatment. METHODS: Joint analysis of ESCC sequencing data were conducted to comprehensively survey SCNAs and identify driver genes which significantly associated with LNM. The roles of miR-548k in lymphangiogensis and lymphatic metastasis were validated both in vitro and in vivo. ESCC tissue and blood samples were analyzed for association between miR-548k expression and patient clinicopathological features and prognosis and diagnosis. RESULTS: In the pooled cohort of 314 ESCC patients, we found 76 significant focused regions including 43 amplifications and 33 deletions. Clinical implication analysis revealed a panel of genes associated with LNM with the most frequently amplified gene being MIR548K harbored in the 11q13.3 amplicon. Overexpression of miR-548k remarkably promotes lymphangiogenesis and lymphatic metastasis in vitro and in vivo. Furthermore, we demonstrated that miR-548k modulating the tumor microenvironment by promoting VEGFC secretion and stimulating lymphangiogenesis through ADAMTS1/VEGFC/VEGFR3 pathways, while promoting metastasis by regulating KLF10/EGFR axis. Importantly, we found that serum miR-548k and VEGFC of early stage ESCC patients were significantly higher than that in healthy donators, suggesting a promising application of miR-548k and VEGFC as biomarkers in early diagnosis of ESCC. CONCLUSIONS: Our study comprehensively characterized SCNAs in ESCC and highlighted the crucial role of miR-548k in promoting lymphatic metastasis, which might be employed as a new diagnostic and prognostic marker for ESCC.

Genomic analyses reveal mutational signatures and frequently altered genes in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide and the fourth most lethal cancer in China. However, although genomic studies have identified some mutations associated with ESCC, we know little of the mutational processes responsible. To identify genome-wide mutational signatures, we performed either whole-genome sequencing (WGS) or whole-exome sequencing (WES) on 104 ESCC individuals and combined our data with those of 88 previously reported samples. An APOBEC-mediated mutational signature in 47% of 192 tumors suggests that APOBEC-catalyzed deamination provides a source of DNA damage in ESCC. Moreover, PIK3CA hotspot mutations (c.1624G>A [p.Glu542Lys] and c.1633G>A [p.Glu545Lys]) were enriched in APOBEC-signature tumors, and no smoking-associated signature was observed in ESCC. In the samples analyzed by WGS, we identified focal (<100 kb) amplifications of CBX4 and CBX8. In our combined cohort, we identified frequent inactivating mutations in AJUBA, ZNF750, and PTCH1 and the chromatin-remodeling genes CREBBP and BAP1, in addition to known mutations. Functional analyses suggest roles for several genes (CBX4, CBX8, AJUBA, and ZNF750) in ESCC. Notably, high activity of hedgehog signaling and the PI3K pathway in approximately 60% of 104 ESCC tumors indicates that therapies targeting these pathways might be particularly promising strategies for ESCC. Collectively, our data provide comprehensive insights into the mutational signatures of ESCC and identify markers for early diagnosis and potential therapeutic targets.

Mig-2 attenuates cisplatin-induced apoptosis of human glioma cells in vitro through AKT/JNK and AKT/p38 signaling pathways.

AIM: Mig-2 (also known as Kindlin-2 and FERMT2) is an important regulator of integrin activation and cell-extracellular matrix adhesion, and involved in carcinogenesis and tumor progression. The aim of this study was to investigate the role of mig-2 in cisplatin-induced apoptosis of human glioma cells in vitro. METHODS: The expression of mig-2 was modulated in human glioma H4, HS 683 and U-87 MG cells by transfection with a plasmid carrying mig-2 or mig-2 siRNA. Cisplatin-induced apoptosis was detected using Annexin V/PI staining and flow cytometry, as well as MTS analyses. The expression of apoptosis-related or signaling proteins was examined using Western blotting analysis. H4 cells were transfected with plasmids carrying mig-2 mutants to determine the functional domain of mig-2. RESULTS: In the 3 glioma cell lines tested, overexpression of mig-2 significantly attenuated cisplatin-induced apoptosis, whereas knock-down of mig-2 potentiated the apoptosis. The mechanisms of action of mig-2 were further addressed in H4 cells: overexpression of mig-2 markedly reduced cleaved caspase-9, caspase-8, caspase-3 and PARP, as well as p-JNK and p-p38, and increased p-AKT in cisplatin-treated H4 cells, whereas mig-2 siRNA reversely changed these apoptosis-related and signaling proteins. Furthermore, pretreatment with JNK inhibitor SP600125 and p38 inhibitor SB203580, or with AKT inhibitor LY294002 abolished the effects of mig-2 on cisplaxtin-induced apoptosis. In H4 cells, GFP-mig-2 F3 plasmid that contained only the F3 subdomain showed the same efficiency in attenuating cisplatin-induced apoptosis, as the mig-2 wild-type vector did, whereas GFP-mig-2 (1-541) plasmid that lacked the F3 subdomain was inactive. CONCLUSION: Mig-2 significantly attenuates the antitumor action of cisplatin against human glioma cells in vitro through AKT/JNK and AKT/p38 signaling pathways. The F3 subdomain of mig-2 is necessary and sufficient for this effect.

Direct resection is a safe and effective strategy to control seizures in patients with hypothalamic hamartoma.

Achieving favorable seizure outcomes is challenging in patients with seizures resulting from hypothalamic hamartoma. Although minimally invasive and non-invasive surgical procedures are used to treat this population, these procedures have limitations. Therefore, we analyzed the outcomes of patients with hypothalamic hamartoma following direct resection. We included 159 patients with hypothalamic hamartoma who underwent direct resection using the transcallosal interforniceal approach between 2011 and 2018. The relationships between clinical parameters and seizure outcomes were analyzed. In total, 55.3% achieved gross total resection and 25.2% underwent near-total resection. Of all patients, 79.2% were overall seizure-free at one year, but this number dropped to 77.0% at more than five years. Moreover, 88.4% (129/146) reached gelastic seizure (GS)-free status at one year and this number increased to 89.0% (97/109) at more than five years. Seventy-one patients took antiseizure medication (ASM) long-term, 68 took it for one year, and 11 took it for one-half year. The duration of ASM consumption (p < 0.001) and extent of hypothalamic hamartoma resection (p = 0.016) were significant independent predictors of long-term overall seizure-free survival, while the duration of ASM consumption (p = 0.011) and extent of hypothalamic hamartoma resection (p = 0.026) were significant independent predictors of long-term GS-free survival. Most patients' behavior, school performance, and intelligence were not affected after surgery. Direct resection is effective and safe strategy for patients with hypothalamic hamartomas. Hypothalamic hamartomas should be removed as completely as possible, and patients should take ASM long-term following surgery to reach long-term overall seizure-free or GS-free status.

LC-MS-based urine metabolomics analysis of chronic subdural hematoma for biomarker discovery.

BACKGROUND: Chronic subdural hematoma (CSDH) is one of the most common neurosurgical diseases with atypical manifestations. The aim of this study was to utilize urine metabolomics to explore potential biomarkers for the diagnosis and prognosis of CSDH. METHODS: Seventy-seven healthy controls and ninety-two patients with CSDH were enrolled in our study. In total, 261 urine samples divided into the discovery group and validation group were analyzed by LC-MS. The statistical analysis and functional annotation were applied to discover potential biomarker panels and altered metabolic pathways. RESULTS: A total of 53 differential metabolites were identified in this study. And the urinary metabolic profiles showed apparent separation between patients and controls. Further functional annotation showed that the differential metabolites were associated with lipid metabolism, fatty acid metabolism, amino acid metabolism, biotin metabolism, steroid hormone biosynthesis, and pentose and glucuronate interconversions. Moreover, one panel of Capryloylglycine, cis-5-Octenoic acid, Ethisterone, and 5,6-DiHETE showed good predictive performance in the diagnosis of CSDH, with an AUC of 0.89 in discovery group and an AUC of 0.822 in validation group. Another five metabolites (Trilobinol, 3'-Hydroxyropivacaine, Ethisterone, Arginyl-Proline, 5-alpha-Dihydrotestosterone glucuronide) showed the levels of them returned to a healthy state after surgery, showing good possibility to monitor the recovery of CSDH patients. CONCLUSION AND CLINICAL RELEVANCE: The findings of the study revealed urine metabolomic differences between CSDH and controls. The potentially diagnostic and prognostic biomarker panels of urine metabolites were established, and functional analysis demonstrated deeper metabolic disorders of CSDH, which might conduce to improve early diagnose of CSDH clinically.

Migfilin protein promotes migration and invasion in human glioma through epidermal growth factor receptor-mediated phospholipase C-γ and STAT3 protein signaling pathways.

Migfilin is critical for cell shape and motile regulation. However, its pathological role in glioma is unknown. Using an immunohistochemical staining assay, we demonstrate that there is a significant correlation between expression of Migfilin and pathological tumor grade in 217 clinical glioma samples. High Migfilin expression is associated with poor prognosis for patients with glioma. Investigation of the molecular mechanism shows that Migfilin promotes migration and invasion in glioma cells. Moreover, Migfilin positively modulates the expression and activity of epidermal growth factor receptor, and Migfilin-mediated migration and invasion depend on epidermal growth factor receptor-induced PLC-γ and STAT3-signaling pathways. Our results may provide significant clinical application, including use of Migfilin as a molecular marker in glioma for early diagnosis and as an indicator of prognosis.

Integrated analysis of multiple methods reveals characteristics of the immune microenvironment in medulloblastoma.

To explore the characteristics of the immune microenvironment (IME) of medulloblastoma (MB) by four methods: flow cytometry (FCM), immunohistochemical (IHC), bulk RNA expression and single cell RNA sequencing (scRNA-seq), we collected the intraoperative specimens of MB, ependymoma (EPN), high-grade glioma (HGG), and low-grade glioma (LGG) to make a cross-cancer comparison. The specimens were subjected to FCM and IHC respectively, and deconvolution from bulk RNA expression data and scRNA-seq analysis were performed in MB from the GEO database. FCM and IHC analysis found that the proportion of lymphocytes (LC) and T cells between MB and other brain tumors were significantly different. The deconvolution of bulk RNA expression data showed that only the proportion of cell types in MCPCOUNTER changed greatly. scRNA-seq found that the proportion of various immune cells in the IME of MB differed between different subtypes. Techniques such as FCM, IHC, bulk RNA expression, and scRNA-seq can sort out different immune cell subsets to a certain extent and quantify their proportions. The four methods have their own strengthens and limitations, but for highly heterogeneous tumor such as MB, integrated analysis of multiple methods is a better choice.

Nutritional and inflammatory peripheral blood markers for risk assessment of chronic subdural hematoma: a case-control study.

BACKGROUND: Some peripheral blood markers have been demonstrated to be correlated with the re-formation of chronic subdural hematoma (CSDH). The aim of this study was to identify the correlation between nutritional/inflammatory peripheral blood markers and CSDH. METHODS: 188 CSDH patients and 188 age-matched healthy controls were included in this research. The clinical characteristics and peripheral blood markers associated with nutritional or inflammatory status were obtained and analyzed. Conditional logistic regression analysis was applied to identify the potential CSDH risk factors. All the participants were divided into 3 groups based on the tertiles of change in risk factors. The Cochran-Armitage test and one way ANOVA were applied to identify the association between baseline characteristics and independent risk factors. Moreover, the net reclassification index (NRI) and integrated discrimination index (IDI) were calculated to evaluate the improvement in model performance after adding the independent risk factors in the conventional model. RESULTS: The logistic regression analysis demonstrated that the increased albumin (OR, 0.615; 95 %CI,0.489-0.773; P < 0.001) and lymphocyte count (OR, 0.141; 95 %CI,0.025-0.796; P = 0.027) were associated with lower risk of CSDH. Moreover, addition of albumin and lymphocyte to conventional risk factors significantly improved the risk prediction of CSDH(NRI: 46.47 %, P < 0.001; IDI: 30.92 %, P < 0.001; NRI: 22.45 %, P = 0.027; IDI: 1.23 %, P = 0.037, respectively) CONCLUSION: The decreased albumin and lymphocyte levels were correlated with a high risk of chronic subdural hematoma. The nutritional and inflammatory serum markers should be put great attention because these markers may play roles in finding the cause of CSDH and predicting its risk.

Poor nutritional status is associated with incomplete functional recovery in elderly patients with mild traumatic brain injury.

Background: The geriatric nutritional risk index (GNRI) is a simple index for evaluating the nutrition status of elderly patients. Many investigations have demonstrated that this index is associated with the prognosis of several diseases. This study aims to identify the relationship between the GNRI and recovery in elderly mild traumatic brain injury (mTBI) patients. Methods: A total of 228 mTBI patients older than 65 years were included in this study. mTBI was defined as an injury to the brain with a loss of consciousness of 30 min or less, a duration of posttraumatic amnesia of <24 h, and an admission Glasgow Coma Scale (GCS) score of 13-15. The Glasgow Outcome Scale Extended (GOSE), an outcome scale assessing functional independence, work, social activities, and personal relationships, was applied to assess the recovery of the patients. The clinical outcome was divided into complete recovery (GOSE = 8) and incomplete recovery (GOSE ≤ 7) at 6 months after the injury. Multivariate logistic regression was applied to evaluate the association between the GNRI and recovery of elderly mTBI patients, with adjustment for age, sex, hypertension, diabetes, and other important factors. Results: The receiver operating curve (ROC) analysis demonstrated that the cutoff value of GNRI was 97.85, and the area under the curve (AUC) was 0.860. Compared to the patients with a high GNRI, the patients with a low GNRI were older, had a higher prevalence of anemia, acute subdural hematoma, and subarachnoid hemorrhage, had a higher age-adjusted Charlson Comorbidity Index value, and had lower levels of albumin, lymphocytes, and hemoglobin. Multivariable analysis showed that high GNRI was associated with a lower risk of 6-month incomplete recovery (OR, 0.770, 95% CI: 0.709-0.837, p < 0.001). Conclusion: The GNRI has utility as part of the objective risk assessment of incomplete 6-month functional recovery in elderly patients with mTBI.

Seizure after chronic subdural hematoma evacuation: associated factors and effect on clinical outcome.

Objective: Chronic subdural hematoma (CSDH) is a common disease in neurosurgery, which usually occurs in the elderly. Seizure is one of the postoperative complications in CSDH patients and can affect patient outcomes. There is currently no consensus on whether antiepileptic drugs should be prescribed prophylactically. The aim of this study was to evaluate independent risk factors for postoperative seizures and unfavorable outcomes in CSDH patients. Methods: We reviewed 1,244 CSDH patients who had undergone burr-hole craniotomy in this study. Patient clinical data, CT scan results, recurrence and outcome data were collected. We divided the patients into two groups based on whether they had a postoperative seizure. Percentages and χ2 tests were applied for categorical variables. Standard deviations and two-sided unpaired t-tests were applied for continuous variables. Stepwise logistic regression analyses were performed to identify the independent factors of postoperative seizures and unfavorable outcomes. Results: The incidence of seizures after CSDH surgery was 4.2% in this study. There was no significant difference in recurrence rate between seizure and non-seizure patients (p = 0.948), and the outcome of seizure patients was significantly poor (p < 0.001). There are more postoperative complications in seizure patients (p < 0.001). Logistic regression analysis showed that the independent risk factors for postoperative seizures included drinking history (p = 0.031), cardiac disease (p = 0.037), brain infarction (p = 0.001) and trabecular hematoma (p < 0.001). The use of urokinase is a protective factor for postoperative seizures (p = 0.028). Hypertension is an independent risk factor for unfavorable outcome in seizure patients (p = 0.038). Conclusion: Seizures after CSDH surgery were associated with postoperative complications, higher mortality and poorer clinical outcomes at follow-up. We believe that alcohol consumption, cardiac disease, brain infarction and trabecular hematoma are independent risk factors for seizures. The use of urokinase is a protective factor against seizures. Patients with postoperative seizures need more stringent management of their blood pressure. A prospective randomized study is necessary to determine which subgroups of CSDH patients would benefit from antiepileptic drugs prophylaxis.

The combined signatures of telomere and immune cell landscape provide a prognostic and therapeutic biomarker in glioma.

Background: Gliomas, the most prevalent primary malignant tumors of the central nervous system in adults, exhibit slow growth in lower-grade gliomas (LGG). However, the majority of LGG cases progress to high-grade gliomas, posing challenges for prognostication. The tumor microenvironment (TME), characterized by telomere-related genes and immune cell infiltration, strongly influences glioma growth and therapeutic response. Therefore, our objective was to develop a Telomere-TME (TM-TME) classifier that integrates telomere-related genes and immune cell landscape to assess prognosis and therapeutic response in glioma. Methods: This study encompassed LGG patients from the TCGA and CCGA databases. TM score and TME score were derived from the expression signatures of telomere-related genes and the presence of immune cells in LGG, respectively. The TM-TME classifier was established by combining TM and TME scores to effectively predict prognosis. Subsequently, we conducted Kaplan-Meier survival estimation, univariate Cox regression analysis, and receiver operating characteristic curves to validate the prognostic prediction capacity of the TM-TME classifier across multiple cohorts. Gene Ontology (GO) analysis, biological processes, and proteomaps were performed to annotate the functional aspects of each subgroup and visualize the cellular signaling pathways. Results: The TM_low+TME_high subgroup exhibited superior prognosis and therapeutic response compared to other subgroups (P<0.001). This finding could be attributed to distinct tumor somatic mutations and cancer cellular signaling pathways. GO analysis indicated that the TM_low+TME_high subgroup is associated with the neuronal system and modulation of chemical synaptic transmission. Conversely, the TM_high+TME_low subgroup showed a strong association with cell cycle and DNA metabolic processes. Furthermore, the classifier significantly differentiated overall survival in the TCGA LGG cohort and served as an independent prognostic factor for LGG patients in both the TCGA cohort (P<0.001) and the CGGA cohort (P<0.001). Conclusion: Overall, our findings underscore the significance of the TM-TME classifier in predicting prognosis and immune therapeutic response in glioma, shedding light on the complex immune landscape within each subgroup. Additionally, our results suggest the potential of integrating risk stratification with precision therapy for LGG.

Exhaustive drainage versus fixed-time drainage for chronic subdural hematoma after one-burr hole craniostomy (ECHO): study protocol for a multicenter randomized controlled trial.

BACKGROUND: Chronic subdural hematomas (CSDHs) are one of the most common neurosurgical conditions. The standard surgical technique includes burr-hole craniostomy, followed by intraoperative irrigation and placement of subdural closed-system drainage. The drainage is generally removed after 48 h, which can be described as fixed-time drainage strategy. According to literature, the recurrence rate is 5-33% with this strategy. In our retrospective study, postoperative hematoma volume was found to significantly increase the risk of recurrence. Based on these results, an exhaustive drainage strategy is conducted to minimize postoperative hematoma volume and achieve a low recurrence rate and good outcomes. METHODS: This is a prospective, multicenter, open-label, blinded endpoint randomized controlled trial designed to include 304 participants over the age of 18-90 years presenting with a symptomatic CSDH verified on cranial computed tomography or magnetic resonance imaging. Participants will be randomly allocated to perform exhaustive drainage (treatment group) or fixed-time drainage (control group) after a one-burr hole craniostomy. The primary endpoint will be recurrence indicating a reoperation within 6 months. DISCUSSION: This study will validate the effect and safety of exhaustive drainage after one-burr hole craniostomy in reducing recurrence rates and provide critical information to improve CSDH surgical management. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04573387. Registered on October 5, 2020.

Migfilin sensitizes cisplatin-induced apoptosis in human glioma cells in vitro.

AIM: Filamin binding LIM protein 1, also known as migfilin, is a skeleton organization protein that binds to mitogen-inducible gene 2 at cell-extracellular matrix adhesions. The aim of this study was to investigate the role of migfilin in cisplatin-induced apoptosis in human glioma cells, to determine the functional domains of migfilin, and to elucidate the molecular mechanisms underlying the regulation of cisplatin-related chemosensitivity. METHODS: The human glioma cell lines Hs683, H4, and U-87 MG were transfected with pEGFP-C2-migfilin to elevate the expression level of migfilin. RNA interference was used to reduce the expression of migfilin. To determine the functional domains of migfilin, U-87 MG cells were transfected with plasmids of migfilin deletion mutants. After treatment with cisplatin (40 µmol/L) for 24 h, the cell viability was assessed using the MTS assay, and the cell apoptotic was examined using the DAPI staining assay and TUNEL analysis. Expression levels of apoptosis-related proteins were detected by Western blot analysis. RESULTS: Overexpression of migfilin significantly enhanced cisplatin-induced apoptosis in Hs683, H4, and U-87 MG cells, whereas downregulation of migfilin expression inhibited the chemosensitivity of these cell lines. The N-terminal region of migfilin alone was able to enhance the cisplatin-induced apoptosis. However, despite the existence of the N-terminal region, mutants of migfilin with any one of three LIM domains deleted led to a function loss. Furthermore, apoptotic proteins (PARP and caspase-3) and the anti-apoptotic protein Bcl-xL were modulated by the expression level of migfilin in combination with cisplatin. CONCLUSION: The LIM1-3 domains of migfilin play a key role in sensitizing glioma cells to cisplatin-induced apoptosis through regulation of apoptosis-related proteins.