Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 19 de 19
Filter
1.
Neurosurg Rev ; 47(1): 118, 2024 Mar 16.
Article in English | MEDLINE | ID: mdl-38491247

ABSTRACT

Meningiomas are the most common tumours that primarily arise in the central nervous system, but their intratumoural heterogeneity has not yet been thoroughly studied. We aimed to investigate the transcriptome characteristics and biological properties of ECM-remodeling meningioma cells. Single-cell RNA sequencing (ScRNA-seq) data from meningioma samples were acquired and used for analyses. We conducted comprehensive bioinformatics analyses, including screening for differentially expressed genes (DEGs), Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway and Gene Ontology (GO) term enrichment analyses, Gene Set Enrichment Analysis (GSEA), protein-protein interaction (PPI) analysis, and copy number variation (CNV) analysis on single-cell sequencing data from meningiomas. Eighteen cell types, including six meningioma subtypes, were identified in the data. ECM-remodeling meningioma cells (MGCs) were mainly distributed in brain-tumour interface tissues. KEGG and GO enrichment analyses revealed that 908 DEGs were mainly related to cell adhesion, extracellular matrix organization, and ECM-receptor interaction. GSEA analysis demonstrated that homophilic cell adhesion via plasma membrane adhesion molecules was significantly enriched (NES = 2.375, P < 0.001). CNV analysis suggested that ECM-remodeling MGCs showed considerably lower average CNV scores. ECM-remodeling MGCs predominantly localized at the brain-tumour interface area and adhere stably to the basement membrane with a lower degree of malignancy. This study provides novel insights into the malignancy of meningiomas.


Subject(s)
Meningeal Neoplasms , Meningioma , Humans , Gene Expression Profiling , Meningioma/genetics , Single-Cell Gene Expression Analysis , DNA Copy Number Variations , Meningeal Neoplasms/genetics
2.
Theranostics ; 14(2): 819-829, 2024.
Article in English | MEDLINE | ID: mdl-38169486

ABSTRACT

Purpose: Lower-grade gliomas (LGGs) are a group of infiltrative growing glial brain tumors characterized by intricate intratumoral heterogeneity and subtle visual appearance differences from non-tumor tissue, which can lead to errors in pathologic tissue sampling. Although 5-ALA fluorescence has been an essential method for visualizing gliomas during surgery, its effectiveness is limited in the case of LGGs due to low sensitivity. Therefore, we developed a novel PET/NIR dual-modality image probe targeting gastrin-releasing peptide receptor (GRPR) in glioma cells to enhance tumor visualization and improve the accuracy of sampling. Methods: A prospective, non-randomized, single-center feasibility clinical trial (NCT03407781) was conducted in the referral center from October 21, 2016, to August 17, 2018. Consecutive enrollment included patients suspected of having LGGs and considered suitable candidates for surgical removal. Group 1 comprised ten patients who underwent preoperative 68Ga-IRDye800CW-BBN PET/MRI assessment followed by intraoperative fluorescence-guided surgery. Group 2 included 42 patients who underwent IRDye800CW-BBN fluorescence-guided surgery. The primary endpoints were the predictive value of preoperative PET imaging for intraoperative fluorescence and the sensitivity and specificity of fluorescence-guided sampling. Results: Thirty-nine patients were included in the in-depth analysis of endpoints, with 25 (64.1%) exhibiting visible fluorescence, while 14 (35.9%) did not. The preoperative positive PET uptake exhibited a greater accuracy in predicting intraoperative fluorescence compared to MRI enhancement (100% [10/10] vs. 87.2% [34/39]). A total of 125 samples were harvested during surgery. Compared with pathology, subjective fluorescence intensity showed a sensitivity of 88.6% and a specificity of 88.2% in identifying WHO grade III samples. For WHO grade II samples, the sensitivity and specificity of fluorescence were 54.7% and 88.2%, respectively. Conclusion: This study has demonstrated the feasibility of the novel dual-modality imaging technique for integrated pre- and intraoperative targeted imaging via the same molecular receptor in surgeries for LGGs. The PET/NIR dual-modality probe exhibits promise for preoperative surgical planning in fluorescence-guided surgery and provides greater accuracy in guiding tumor sampling compared to 5-ALA in patients with LGGs.


Subject(s)
Brain Neoplasms , Glioma , Humans , Receptors, Bombesin , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/surgery , Brain Neoplasms/pathology , Prospective Studies , Glioma/diagnostic imaging , Glioma/surgery , Glioma/pathology , Aminolevulinic Acid , Positron-Emission Tomography/methods
3.
Eur J Med Res ; 28(1): 539, 2023 Nov 24.
Article in English | MEDLINE | ID: mdl-38001553

ABSTRACT

BACKGROUND: The incidence of nonhip femoral fractures is gradually increasing, but few studies have explored the risk factors for in-hospital death in patients with nonhip femoral fractures in the ICU or developed mortality prediction models. Therefore, we chose to study this specific patient group, hoping to help clinicians improve the prognosis of patients. METHODS: This is a retrospective study based on the data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Least absolute shrinkage and selection operator (LASSO) regression was used to screen risk factors. The receiver operating characteristic (ROC) curve was drawn, and the areas under the curve (AUC), net reclassification index (NRI) and integrated discrimination improvement (IDI) were calculated to evaluate the discrimination of the model. The consistency between the actual probability and the predicted probability was assessed by the calibration curve and Hosmer-Lemeshow goodness of fit test (HL test). Decision curve analysis (DCA) was performed, and the nomogram was compared with the scoring system commonly used in clinical practice to evaluate the clinical net benefit. RESULTS: The LASSO regression analysis showed that heart rate, temperature, red blood cell distribution width, blood urea nitrogen, Glasgow Coma Scale (GCS), Simplified Acute Physiology Score II (SAPSII), Charlson comorbidity index and cerebrovascular disease were independent risk factors for in-hospital death in patients with nonhip femoral fractures. The AUC, IDI and NRI of our model in the training set and validation set were better than those of the GCS and SAPSII scoring systems. The calibration curve and HL test results showed that our model prediction results were in good agreement with the actual results (P = 0.833 for the HL test of the training set and P = 0.767 for the HL test of the validation set). DCA showed that our model had a better clinical net benefit than the GCS and SAPSII scoring systems. CONCLUSION: In this study, the independent risk factors for in-hospital death in patients with nonhip femoral fractures were determined, and a prediction model was constructed. The results of this study may help to improve the clinical prognosis of patients with nonhip femoral fractures.


Subject(s)
Femoral Fractures , Nomograms , Humans , Hospital Mortality , Retrospective Studies , Area Under Curve
4.
Neurosurg Rev ; 46(1): 308, 2023 Nov 21.
Article in English | MEDLINE | ID: mdl-37985473

ABSTRACT

The incidence of pneumonia in ICU patients with TBI is very high, seriously affecting the prognosis. This study aims to construct a predictive model for pneumonia in ICU patients with TBI and provide help for the prevention of TBI-related pneumonia.Clinical data of ICU patients with TBI were collected from the Medical Information Mart for Intensive Care (MIMIC)-IV database and hospital data. Variables were screened by lasso and multivariate logistic regression to construct a predictive nomogram model, verified in internal validation cohort and external validation cohort by receiver operator characteristic (ROC) curve, calibration curve and decision curve analysis (DCA).A total of 1850 ICU patients with TBI were enrolled in the study from the MIMIC-IV database, including 1298 in the training cohort and 552 in internal validation cohort. The external validation cohort included 240 ICU patients with TBI from hospital data. Nine variables were selected from the training cohort by lasso regression and multivariate logistic regression, and a pneumonia prediction nomogram was constructed. This nomogram has a high discrimination in training, internal validation and external validation cohorts (AUC = 0.857, 0.877, 0.836). The calibration curve and DCA showed that this nomogram had a high calibration and better clinical decision-making efficiency.The nomogram showed excellent discrimination and clinical utility to predict pneumonia, and could identify pneumonia high-risk patients early, thus providing personalised treatment strategies for ICU patients with TBI.


Subject(s)
Brain Injuries, Traumatic , Pneumonia , Humans , Nomograms , Brain Injuries, Traumatic/complications , Clinical Decision-Making , Intensive Care Units
5.
Mil Med Res ; 10(1): 50, 2023 10 31.
Article in English | MEDLINE | ID: mdl-37899480

ABSTRACT

In the United States (US), the Surveillance, Epidemiology, and End Results (SEER) program is the only comprehensive source of population-based information that includes stage of cancer at the time of diagnosis and patient survival data. This program aims to provide a database about cancer incidence and survival for studies of surveillance and the development of analytical and methodological tools in the cancer field. Currently, the SEER program covers approximately half of the total cancer patients in the US. A growing number of clinical studies have applied the SEER database in various aspects. However, the intrinsic features of the SEER database, such as the huge data volume and complexity of data types, have hindered its application. In this review, we provided a systematic overview of the commonly used methodologies and study designs for retrospective epidemiological research in order to illustrate the application of the SEER database. Therefore, the goal of this review is to assist researchers in the selection of appropriate methods and study designs for enhancing the robustness and reliability of clinical studies by mining the SEER database.


Subject(s)
Neoplasms , Research Design , Humans , United States/epidemiology , Retrospective Studies , Reproducibility of Results , SEER Program
6.
Adv Ther ; 40(6): 2773-2783, 2023 06.
Article in English | MEDLINE | ID: mdl-37084160

ABSTRACT

INTRODUCTION: Research related to the result of patients with mild traumatic brain injury and the role of percutaneous oxygen saturation (SpO2) level is rarely reported. Our study investigated the relationship between SpO2 and the 30- and 90-day mortality among patients with mild TBI. METHODS: A total of 1027 patients with mild TBI [Glasgow Coma Scale (GCS) > 12] were enrolled from the Medical Information Mart for Intensive Care (MIMIC-III) database. The patients were classified into low-SpO2 (< 95%), moderate-SpO2 (95-98%), and high-SpO2 groups (> 98%). With 30- and 90-day mortality rates as the main outcomes, Cox regression and confined cubic spline models were adopted. RESULTS: There was a U-shaped curve in confined cubic splines for the relationship between SpO2 and mortality. Compared with the moderate-SpO2 group, the high-SpO2 group exhibited a much higher risk of mortality after modification, with hazard proportions of 2.108 (95% CI 1.211-3.670, P < 0.05) for the 30-day mortality and 1.760 (95% CI 1.140-2.720, P < 0.05) for the 90-day mortality, and the low-SpO2 group exhibited a much higher risk of mortality after modification, with hazard proportions of 2.215 (95% CI 1.194-4.110, P < 0.05) for the 90-day mortality. CONCLUSION: Among patients with mild TBI, the correlation between SpO2 level and 30- and 90-day mortality followed a U-shaped curve. Both low and high SpO2 level exerted potential harmful effects on the outcomes of patients with mild TBI. The SpO2 range of 95-98% could be the optimal SpO2 level for mild patients with TBI.


Subject(s)
Brain Concussion , Humans , Oxygen Saturation , Hospitalization , Glasgow Coma Scale , Intensive Care Units
7.
Brain Res ; 1811: 148373, 2023 07 15.
Article in English | MEDLINE | ID: mdl-37105375

ABSTRACT

Intracerebral hemorrhage (ICH) refers to the hemorrhage caused by the increase and rupture of vascular brittleness in non traumatic brain parenchyma, which has been demonstrated to be closely related to ferroptosis. This study aimed to examine the effects of methyltransferase like 3 (METTL3) on the ferroptosis in the ICH progression. The PC12 cells was stimulated by hemin to establish a ICH model. The cell viability was tested by CCK8 assay. The Fe2+, reactive oxygen species (ROS), and malondialdehyde (MDA) levels were determined by the corresponding commercial kits. The cell death was analyzed by propidium Iodide (PI) staining. The lactylation levels were detected by western blot. M6A dot blot assay was performed to detected the total m6A levels and MeRIP assay was conducted to determine the m6A levels of transferrin receptor (TFRC). We found that the METTL3 and m6A levels were increased in the hemin treated PC12 cells. METTL3 knockdown increased the cell viability and decreased Fe2+, ROS and MDA levels in the hemin treated PC12 cells. The role of METTL3 knockdown in the hemin treated PC12 cells was reversed after TFRC overexpression. Mechanistically, the METTL3 lactylation was increased in the hemin treated PC12 cells, which further enhanced the protein stability and expression of METTL3. The up-regulated METTL3 increased the m6A levels and mRNA expressions of TFRC, which further induced the ferroptosis of the PC12 cells. In conclusion, the up-regulation of METTL3 lactylation enhanced the METTL3 protein stability and expression levels in hemin treated PC12 cells. METTL3 silenced suppressed the ferroptosis development through regulating the m6A levels of TFRC mRNA.


Subject(s)
Ferroptosis , Rats , Animals , Methyltransferases/genetics , Methyltransferases/metabolism , Reactive Oxygen Species/metabolism , Hemin/pharmacology , Hemin/metabolism , Cerebral Hemorrhage , Receptors, Transferrin/genetics , RNA, Messenger/metabolism
8.
Cancer Med ; 12(9): 10917-10930, 2023 05.
Article in English | MEDLINE | ID: mdl-36924355

ABSTRACT

BACKGROUND: Increasing attention has been paid to the survival of endometrial cancer (EC) patients, but the non-cancer causes of death from EC are rarely reported. This study primarily aimed to investigate the non-cancer causes of death in patients with EC. METHODS: The study collected relevant data, including age, tumour stage and treatment mode, on patients diagnosed with endometrial malignancies from 2000 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) Programme. We analysed the standardised mortality ratio (SMR) to determine the cause of death. RESULTS: The study included 135,831 patients with EC. During the follow-up, 46,604 (34.3%) patients died, of whom 42.9%, 15.6% and 41.5% died of EC, other cancers and non-cancer causes, respectively. As the diagnosis time increased, the number of EC-associated mortalities gradually decreased. The most common non-cancer causes of death were heart disease, cerebrovascular disease and diabetes. Regarding the general population of the United States, patients with EC died of heart disease (SMR: 1.06; 95% confidence interval [CI]: 1.03-1.09), diabetes (SMR: 1.56; 95% CI: 1.47-1.65) and septicaemia (SMR: 1.40; 95% CI: 1.28-1.52), which were statistically significant. CONCLUSIONS: For patients with EC, the number of deaths from non-cancer causes (mainly heart disease, cerebrovascular disease and diabetes mellitus) is equivalent to that of EC. In addition, compared with the general population, EC survivors have a higher risk of death from sepsis and diabetes. These discoveries support how survivors can avoid future-related health risks. By doing this, clinicians can improve the quality of life and chances of the survival of patients with EC.


Subject(s)
Cerebrovascular Disorders , Diabetes Mellitus , Endometrial Neoplasms , Heart Diseases , Female , Humans , United States/epidemiology , Cause of Death , Quality of Life , Endometrial Neoplasms/epidemiology , Survivors , Risk Factors
9.
J Mol Neurosci ; 73(2-3): 185-204, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36705778

ABSTRACT

Cuprotosis is a novel and different cell death mechanism from the existing known ones that can be used to explore new approaches to treating cancer. Just like ferroptosis and pyroptosis, cuprotosis-related genes regulate various types of tumorigenesis, invasion, and metastasis. However, the relationship between cuprotosis-related long non-coding RNA (cuprotosis-related lncRNA) in glioma development and prognosis has not been investigated. We obtained relevant data from the Genotype-Tissue Expression (GTEx), Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and published articles. First, we identified 365 cuprotosis-related lncRNAs based on 10 cuprotosis-related differential genes (|R2|> 0.4, p < 0.001). Then using Lasso and Cox regression analysis methods, 12 prognostic cuprotosis-related lncRNAs were obtained and constructed the CuLncSigi risk score formula. Our next step was to divide the tumor gliomas into two groups (high risk and low risk) based on the median risk score, and we found that patients in the high-risk group had a significantly worse prognosis. We used internal and external validation methods to simultaneously analyze and validate that the risk score model has good predictive power for patients with glioma. Next, we also performed enrichment analyses such as GSEA and aaGSEA and evaluated the relationship between immune-related drugs and tumor treatment. In conclusion, we successfully constructed a formula of cuprotosis-related lncRNAs with a powerful predictive function. More importantly, our study paves the way for exploring cuprotosis mechanisms in glioma occurrence and development and helps to find new relevant biomarkers for glioma early identification and diagnosis and to investigate new therapeutic approaches.


Subject(s)
Apoptosis , Glioma , RNA, Long Noncoding , Humans , Carcinogenesis , Cell Death , Glioma/diagnosis , Glioma/genetics , RNA, Long Noncoding/genetics , Copper
10.
Front Genet ; 13: 961278, 2022.
Article in English | MEDLINE | ID: mdl-36468039

ABSTRACT

Today, numerous international researchers have demonstrated that N7-methylguanosine (m7G) related long non-coding RNAs (m7G-related lncRNAs) are closely linked to the happenings and developments of various human beings' cancers. However, the connection between m7G-related lncRNAs and glioma prognosis has not been investigated. We did this study to look for new potential biomarkers and construct an m7G-related lncRNA prognostic signature for glioma. We identified those lncRNAs associated with DEGs from glioma tissue sequences as m7G-related lncRNAs. First, we used Pearson's correlation analysis to identify 28 DEGs by glioma and normal brain tissue gene sequences and predicated 657 m7G-related lncRNAs. Then, eight lncRNAs associated with prognosis were obtained and used to construct the m7G risk score model by lasso and Cox regression analysis methods. Furthermore, we used Kaplan-Meier analysis, time-dependent ROC, principal component analysis, clinical variables, independent prognostic analysis, nomograms, calibration curves, and expression levels of lncRNAs to determine the model's accuracy. Importantly, we validated the model with external and internal validation methods and found it has strong predictive power. Finally, we performed functional enrichment analysis (GSEA, aaGSEA enrichment analyses) and analyzed immune checkpoints, associated pathways, and drug sensitivity based on predictors. In conclusion, we successfully constructed the formula of m7G-related lncRNAs with powerful predictive functions. Our study provides instructional value for analyzing glioma pathogenesis and offers potential research targets for glioma treatment and scientific research.

11.
Curr Oncol ; 29(11): 8374-8389, 2022 11 02.
Article in English | MEDLINE | ID: mdl-36354720

ABSTRACT

BACKGROUND: Large epidemiological studies describing the trends in incidence rates and mortality of synchronous brain metastases (SBMs) are lacking. The study aimed to provide a comprehensive understanding of the changes in the incidence and mortality of SBMs over the previous ten years. METHODS: Trends in the incidence of solid malignancies outside of the CNS in patients with SBMs and incidence-based mortality rates were assessed using data from the Surveillance, Epidemiology, and End Results database. Joinpoint analyses were used to calculate annual percent changes (APCs) and 95% CIs. RESULTS: Between 2010 and 2019, 66,655 patients, including 34,821 (52.24%) men and 31,834 (47.76%) women, were found to have SBMs, and 57,692 deaths occurred over this period. Lung cancer SBMs, melanoma SBMs, and breast cancer SBMs were ranked in the top three, having the highest age-standardized incidence rates. The incidence of SBMs decreased significantly with an APC of -0.6% from 2010 to 2019, while the APC was 1.2% for lung cancer SBMs, 2.5% for melanoma SBMs, and 0.6% for breast cancer SBMs. The SBM mortality first experienced a rapid increase (APC = 28.6%) from 2010 to 2012 and then showed a significant decline at an APC of -1.8% from 2012 to 2019. Lung cancer SBMs showed similar trends, while melanoma SBM and breast cancer SBM mortality increased continuously. CONCLUSIONS: SBMs incidence (2010-2019) and incidence-based mortality (2012-2019) declined significantly. These findings can advance our understanding of the prevalence of SBMs.


Subject(s)
Brain Neoplasms , Breast Neoplasms , Lung Neoplasms , Melanoma , Male , United States/epidemiology , Humans , Female , Incidence , Brain Neoplasms/epidemiology , Lung Neoplasms/epidemiology , Melanoma/epidemiology
12.
Front Public Health ; 10: 1000415, 2022.
Article in English | MEDLINE | ID: mdl-36211679

ABSTRACT

Background: The extent of the relationship between age and the presence of breast cancer synchronous brain metastases (BCSBMs) and mortality has not yet been well-identified or sufficiently quantified. We aimed to examine the association of age with the presence of BCSBMs and all-cause and cancer-specific mortality outcomes using the SEER database. Methods: Age-associated risk of the presence and survival of BCSBMs were evaluated on a continuous scale (restricted cubic spline, RCS) with logistic or Cox regression models. The main endpoints were the presence of BCSBMs and all-cause mortality or cancer-specific mortality. Cox proportional hazards regression and competing risk models were used in survival analysis. Results: Among 374,132 adult breast cancer patients, 1,441 (0.38%) had BMs. The presence of BCSBMs displayed a U-shaped relationship with age, with the highest point of the curve occurring at the age of 62. In both the younger (age ≤ 61) and older (age ≥ 62) groups, the observed curve showed a nearly linear relationship between age and the presence of BCSBMs. The relationship between age and all-cause mortality (ASM) and cancer-specific mortality (CSM) was linear. Older age at diagnosis was associated with a higher risk of ASM (HR 1.019, 95% CI: 1.013-1.024, p < 0.001) and CSM (HR 1.016, 95% CI: 1.010-1.023, p < 0.001) in multivariable Cox models. Age (sHR 1.007, 95% CI 1-1.013, p = 0.049) was substantially related to a significantly increased risk of CSM in competing risk models. Conclusion: Age had a non-linear U-shaped relationship with the presence of BCSBMs and a linear relationship with BCSBMs mortality.


Subject(s)
Brain Neoplasms , Breast Neoplasms , Adult , Female , Humans , Proportional Hazards Models , SEER Program , Survival Analysis , United States/epidemiology
13.
Cancer Control ; 29: 10732748221135447, 2022.
Article in English | MEDLINE | ID: mdl-36256588

ABSTRACT

BACKGROUND: The rapid increase in the detection rate of thyroid cancer over the past few decades has caused some unexpected economic burdens. However, that of papillary thyroid carcinoma (PTC) seems to have had the opposite trend, which is worthy of further comprehensive exploration. METHODS: The Surveillance, Epidemiology, and End Results 18 database was used to identify patients with PTC diagnosed during 2003-2017. The incidence trends were analyzed using joinpoint analysis and an age-period-cohort model. RESULTS: The overall PTC incidence rate increased from 9.9 to 16.1 per 100 000 between 2003 and 2017. The joinpoint analysis indicated that the incidence growth rate began to slow down in 2009 (annual percentage change [APC] = 3.1%, 95% confidence interval [CI] = 1.9%-4.4%). After reaching its peak in 2015, it began to decrease by 2.8% (95% CI = -4.6% to -1.0%) per year. The stratified analysis indicated that the incidence patterns of different sexes, age groups, races, and tumor stages and sizes had similar downward trends, including for the localized (APC = -4.5%, 95% CI = -7% to -1.9%) and distant (APC = -1.3%, 95% CI = -2.7% to -.1%) stages, and larger tumors (APC = -4%, 95% CI = -12% to 4.7%). The age-period-cohort model indicated a significant period effect on PTC, which gradually weakened after 2008-2012. The cohort effect indicates that the risk of late birth cohorts is gradually stabilizing and lower than that of early birth cohorts. CONCLUSION: The analysis results of the recent downward trend and period effect for the incidence of each subgroup further support the important role of correcting overdiagnosis in reducing the prevalence of PTC. Future research needs to analyze more-recent data to verify these downward trends.


Subject(s)
Thyroid Neoplasms , Humans , United States/epidemiology , Thyroid Cancer, Papillary/epidemiology , Incidence , SEER Program , Thyroid Neoplasms/pathology , Racial Groups
14.
Bioengineered ; 13(6): 14215-14226, 2022 06.
Article in English | MEDLINE | ID: mdl-35758287

ABSTRACT

This study examined the effects of methyltransferase-like 3 (METTL3) on ferroptosis during intracerebral hemorrhage (ICH) progression. The brain microvascular endothelial cells (BMVECs) were stimulated with oxygen and glucose deprivation (OGD) and hemin to establish an ICH model. Cell viability was tested using a CCK8 assay. The levels of Fe2+, glutathione, reactive oxygen species, LPO, and MDA were determined using the corresponding commercial kits. Cell death was analyzed using TUNEL and propidium iodide staining. The correlation between METTL3 and glutathione peroxidase 4 (GPX4) was analyzed using Spearman's correlation test and further confirmed using the CHIP assay. Western blotting and RT-qPCR were performed to measure the relative expression levels. Mice were injected with 0.2 units collagenase IV to establish an ICH model in vivo. We found that the Fe2+, reactive oxygen species, LPO, and MDA levels were enhanced, and glutathione was depleted in OGD/H-treated BMVECs as well as in ICH mice. Additionally, cell viability and SLC7A11 protein levels decreased, and cell death and TFR1 protein levels increased in OGD/H-treated BMVECs. METTL3 silencing relieves OGD/H-induced injury in BMVECs. In addition, METTL3 was significantly negatively related to GPX4, which was further confirmed by the CHIP assay. Silencing of METTL3 decreased the N6-methyladenosine levels of GPX4 and increased its mRNA levels of GPX4. GPX4 knockdown neutralized the role of METTL3 in OGD/H-treated BMVECs. These results implied that ferroptosis occurred in the ODG/H-treated BMVECs and ICH mouse models. METTL3 silencing effectively suppressed ferroptosis by regulating N6-methyladenosine and mRNA levels of GPX4.


Subject(s)
Cerebral Hemorrhage , Ferroptosis , Phospholipid Hydroperoxide Glutathione Peroxidase , Animals , Cerebral Hemorrhage/metabolism , Cerebral Hemorrhage/pathology , Endothelial Cells/metabolism , Glucose/metabolism , Glutathione/metabolism , Methyltransferases/metabolism , Mice , Oxygen/metabolism , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reactive Oxygen Species/metabolism
15.
Cancer Control ; 29: 10732748221095944, 2022.
Article in English | MEDLINE | ID: mdl-35446714

ABSTRACT

BACKGROUND: The correlations of epidemiological characteristics and clinical outcomes with different tumor sites in patients with intracranial typical site germinomas (ICTSGs) have not yet been well established. We analyzed ICTSGs using a multicenter database, focusing on its demographic, management patterns, and long-term survival outcomes. METHODS: Patients diagnosed with ICTSGs were selected from the Surveillance, Epidemiology, and End-Results (SEER) database. Demographic information and management patterns of ICTSGs were extracted for data analysis stratified by different tumor sites. Kaplan-Meier curves were used to evaluate the survival outcome stratified by treatment, tumor site and tumor size. RESULTS: Among the 327 patients enrolled in the study, 16.21% had tumors located in the suprasellar region and 83.79% in the pineal region. The proportion of males was significantly higher among pineal germinomas (94.16 vs 66.04%; P < .001). Smaller tumors (<24 mm) were more common in the suprasellar region (37.74 vs 18.87%; P < .001). A higher percentage of patients with suprasellar germinomas underwent surgery. Radiotherapy (RT) and chemotherapy (CT) was, respectively, administered to 82.97 and 60.61% of patients during the treatment period, with no significant difference between suprasellar and pineal germinomas. CT plus RT was the most common treatment modality for both pituitary (30.19%) and pineal (33.94%) germinomas. Both RT and CT were associated with improved long-term survival. No survival difference was observed between suprasellar and pineal germinomas. CONCLUSIONS: Despite significant differences in epidemiology and management, pineal and suprasellar germinomas had a similar long-term clinical outcome.


Subject(s)
Brain Neoplasms , Germinoma , Pineal Gland , Skull Base Neoplasms , Brain Neoplasms/diagnosis , Brain Neoplasms/epidemiology , Brain Neoplasms/therapy , Germinoma/diagnosis , Germinoma/pathology , Germinoma/therapy , Humans , Male , Pineal Gland/pathology
16.
Neurosurg Rev ; 45(4): 2733-2744, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35441246

ABSTRACT

Spontaneous intracerebral hemorrhage (ICH) is a commonly occurring disease in neurosurgery, yet its surgical treatment is controversial. This paper pertains to the study of the effects of different treatment regimens on the outcome of ICH population. Based on a globally shared third-party MIMIC-III database, the researchers firstly described the dissimilarities in survival probability, mortality, and neurological recovery among mainstream treatments for ICH; secondly, patient classification was determined by important clinical features; and outcome variations among treatment groups were compared. The 28-day, 90-day, and in-hospital mortality in the craniotomy group were significantly lower than minimally invasive surgery (MIS) and non-surgical group patients; and, the medium/long-term mortality in MIS group was significantly lower than the non-surgical group. The craniotomy group positively correlated with short-term GCS recovery compared with the MIS group; no difference existed between the non-surgical and MIS groups. The craniotomy group 90-day survival probability and short-term GCS recovery were superior to the other two treatments in the subgroups of first GCS 3-12; this tendency also presented in the MIS group over non-surgical group. For milder patients (first GCS > 12), the three treatment regimens had a minimal effect on patient survival, but the non-surgical group showed an advantage in short-term GCS recovery. Craniotomy patients have a lower mortality and a better short-term neurological recovery in an ICH population, especially in short-to-medium term mortality and short-term neurological recovery over MIS patients. In addition, surgical treatment is recommendable for patients with a GCS ≤ 12.


Subject(s)
Cerebral Hemorrhage , Data Analysis , Cerebral Hemorrhage/surgery , Craniotomy , Humans , Minimally Invasive Surgical Procedures , Prognosis , Treatment Outcome
17.
Cancer Med ; 11(4): 1202-1216, 2022 02.
Article in English | MEDLINE | ID: mdl-35019232

ABSTRACT

BACKGROUND: Population-based estimates of the impact of gender throughout the whole course of brain metastases (BMs) at the time of diagnosis of systemic malignancies are insufficient. We aimed to discover the influence of gender on the presence of BMs in newly diagnosed malignancies and the survival of those patients on a population-based level. METHODS: Midlife patients (40 years ≤ age ≤60 years) with newly diagnosed malignancies and BMs at the time of diagnosis were abstracted from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute. Clinical variables adjusted patient data. The LASSO regression was performed to exclude the possibility of collinearity. Univariable and multivariable logistic regression analyses were applied to find independent predictors for the presence of BMs, while univariable and multivariable Cox proportional hazard regression analyses were used to determine prognosticators of survival. K-M curves were used to perform the survival analysis. RESULT: 276,327 population-based samples met inclusion criteria between 2014 and 2016, and 5747 (2.08%) patients were diagnosed with BMs at the time of diagnosis of systematic malignancies. Among all midlife patients with cancer, 44.02% (121,634) were male, while 51.68% (2970) were male among patients with BMs at the time of diagnosis. The most frequent tumor type was breast cancer (23.11%), and lung cancer had the highest incidence proportion of BMs among the entire cohort (19.34%). The multivariable logistic regression model suggested that female (vs. male, odds ratio [OR] 1.07, 95% CI: 1.01-1.14, p < 0.001) was associated with a higher risk of the presence of BMs at the time of diagnosis. Moreover, in the multivariable Cox model for all-cause mortality in individuals with BMs at diagnosis, female (vs. male, hazard ratio [HR], 0.86, 95% CI, 0.80-0.92, p < 0.001) was shown to have a lower risk of decreased all-cause mortality. CONCLUSION: The middle-aged females were at increased risk of developing BMs, while the middle-aged males with BMs were at higher risk of having poorer survival.


Subject(s)
Brain Neoplasms , Lung Neoplasms , Brain Neoplasms/secondary , Female , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Prognosis , Proportional Hazards Models , Survival Analysis , United States/epidemiology
18.
World Neurosurg ; 155: e131-e141, 2021 11.
Article in English | MEDLINE | ID: mdl-34403798

ABSTRACT

BACKGROUND: Socioeconomic status (SES) is presented as a complex structure and has not been studied adequately among adult patients with glioma. This study aims to identify the intrinsic linkages of community-level SES multivariables and discover the effects of the various patterns of these indicators on prognosis of adult gliomas. METHODS: Based on data from the SEER (Surveillance Epidemiology and End Results) database, 44,816 adults diagnosed with gliomas from 2007 to 2016 were enrolled for the research. We first used factor analysis and cluster analysis to process SES data. Then, univariable and multivariable Cox proportional hazards models were used to analyze the risk indicators. RESULTS: Four integrated SES factors were identified: factor 1, economic and social disadvantage (economic and education disadvantage); factor 2, immigration-associated characteristics (foreign-born, language isolation, less household room, recent interstate residential stability); factor 3, housing instability; and factor 4, absence of intrastate mobility. Factor 1 was a risk indicator for survival, whereas factor 2 and factor 4 were protective indicators. All patients fell into 7 cluster groups. Compared with cluster 1, clusters 2, 3, 4, and 7 had a better prognosis, whereas cluster 6 had a shorter survival. CONCLUSIONS: The combinatorial patterns of SES indicators and pattern-based groups do influence the outcomes of adult gliomas. Special attention is given to patients living in areas with specialized economic-educational disadvantages, relocation instability, and immigration-related characteristics.


Subject(s)
Brain Neoplasms/mortality , Glioma/mortality , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Proportional Hazards Models , Risk Factors , SEER Program , Social Class , Young Adult
19.
Bioeng Transl Med ; 6(1): e10182, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33532584

ABSTRACT

Supra-maximum surgical tumor resection without neurological damage is highly valuable for treatment and prognosis of patients with glioblastoma multiforme (GBM). We developed a GBM-specific fluorescence probe using IRDye800CW (peak absorption/emission, 778/795 nm) and bombesin (BBN), which (IRDye800-BBN) targets the gastrin-releasing peptide receptor, and evaluated the image-guided resection efficiency, sensitivity, specificity, and survivability. Twenty-nine patients with newly diagnosed GBM were enrolled. Sixteen hours preoperatively, IRDye800-BBN (1 mg in 20 ml sterile water) was intravenously administered. A customized fluorescence surgical navigation system was used intraoperatively. Postoperatively, enhanced magnetic resonance images were used to assess the residual tumor volume, calculate the resection extent, and confirm whether complete resection was achieved. Tumor tissues and nonfluorescent brain tissue in adjacent noneloquent boundary areas were harvested and assessed for diagnostic accuracy. Complete resection was achieved in 82.76% of patients. The median extent of resection was 100% (range, 90.6-100%). Eighty-nine samples were harvested, including 70 fluorescence-positive and 19 fluorescence-negative samples. The sensitivity and specificity of IRDye800-BBN were 94.44% (95% CI, 85.65-98.21%) and 88.24% (95% CI, 62.25-97.94%), respectively. Twenty-five patients were followed up (median, 13.5 [3.1-36.0] months), and 14 had died. The mean preoperative and immediate and 6-month postoperative Karnofsky performance scores were 77.9 ± 11.8, 71.3 ± 19.2, and 82.6 ± 14.7, respectively. The median overall and progression-free survival were 23.1 and 14.1 months, respectively. In conclusion, GBM-specific fluorescent IRDye800-BBN can help neurosurgeons identify the tumor boundary with sensitivity and specificity, and may improve survival outcomes.

SELECTION OF CITATIONS
SEARCH DETAIL
...