The Impact of Time Interval on Prognosis in Patients with Non-Small Cell Lung Cancer Brain Metastases After Metastases Surgery.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a prominent malignancy often linked to the development of brain metastases (BM), which commonly appear at diverse time intervals (TI) following the lung cancer diagnosis. This study endeavors to determine the prognostic significance of the time interval in patients with NSCLC who undergo BM surgery. Through this investigation, we aim to improve our understanding of the factors impacting the prognosis of BM cases originating from NSCLC. METHODS: We analyzed data from 74 patients (2011-2021) who underwent BM surgery at our institution. The relationship between various clinical, radiological, and histopathological factors, as well as TI and overall survival (OS), was examined. RESULTS: The median TI from initial NSCLC diagnosis to BM surgery was 19 months (range: 9-36 months). Notably, a shorter TI of less than 23 months was found to be independently associated with postoperative survival (adjusted odds ratio [aOR] 2.87, 95% confidence interval [CI] 1.03-8.02, P = 0.045). Additionally, a shorter TI was independently correlated with the absence of adjuvant chemotherapy for NSCLC (aOR 0.25, 95% CI 0.07-0.83, P = 0.023) and lack of targeted therapy (aOR 0.02, 95% CI 0.00-0.16, P < 0.001). Late-onset BM (TI ≥ 36 months) was observed in 15 cases (20.3%), in this subgroup, patients aged 60 years or older at the time of lung cancer diagnosis exhibited a significant independent correlation with late-onset BM (aOR 7.24, 95% CI 1.59-32.95, P = 0.011). NSCLC patients who underwent adjuvant chemotherapy displayed a notable correlation with late-onset BM (aOR 6.46, 95% CI 1.52-27.43, P = 0.011), while those who received targeted therapy also exhibited an independent association (aOR 2.27, 95% CI 1.70-3.03, P < 0.001). CONCLUSIONS: Multiple factors contribute to the variability in the onset interval of BM subsequent to NSCLC diagnosis. The occurrence of BM within TI < 23 months following the initial diagnosis of NSCLC was demonstrated as an independent factor associated with an unfavorable prognosis following BM surgery. Furthermore, patients with NSCLC who did not receive adjuvant chemotherapy and lacked targeted therapy were shown to have an elevated likelihood of developing BM after a long progression-free survival.

Hub gene target of glioblastoma: LOX, SERPINH1 and TGFBI.

Glioblastoma (GBM) is a malignant tumor. The long-term prognosis of the patients is poor. Therefore, it is of important clinical value to further explore the pathogenesis and look for molecular markers for early diagnosis and targeted treatment. Two expression profiling datasets [GSE50161 (GPL570 platform), GSE116520 (GPL10558 platform)] were respectively downloaded from the gene expression omnibus database. Volcano diagrams show the Differently expressed genes (DEGs) of GSE50161 and GSE116520. A Venn diagram revealed 467 common DEGs between the 2 datasets. Lysyl oxidase (LOX), serpin family H member 1 (SERPINH1) and transforming growth factor beta induced (TGFBI) were negatively correlated with the overall survival rate in patients with GBM. The hub genes are high in GBM tumor tissues. The relative expression levels of LOX, SERPINH1 and TGFBI were significantly higher in GBM samples, compared with the normal brain tissues groups. Bioinformatics technology could be a useful tool to predict progression of GBM and to explore the mechanism of GBM.LOX, SERPINH1 and TGFBI may be involved in the mechanism of the occurrence and development of GBM, and may be used as molecular targets for early diagnosis and specific treatment. DEGs identified using GEO2R. Functional annotation of DEGs using Kyoto Encyclopedia of Genes and Genomes and gene body pathway enrichment analysis. Construction of a protein-protein interaction network. The pathway and process enrichment analysis of the hub genes were performed by Metascape. Survival analysis was performed in gene expression profiling interactive analysis. Real-time fluorescent quantitative polymerase chain reaction assay was performed to verify. The animal model was established for western blot test analysis.

Hub genes for early diagnosis and therapy of adamantinomatous craniopharyngioma.

BACKGROUND: Adamantinomatous craniopharyngioma (ACP) is a subtype of craniopharyngioma, a neoplastic disease with a benign pathological phenotype but a poor prognosis in the sellar region. The disease has been considered the most common congenital tumor in the skull. Therefore, this article aims to identify hub genes that might serve as genetic markers of diagnosis, treatment, and prognosis of ACP. METHODS: The procedure of this research includes the acquisition of public data, identification and functional annotation of differentially expressed genes (DEGs), construction and analysis of protein-protein interaction network, and the mining and analysis of hub genes by Spearman-rho test, multivariable linear regression, and receiver operator characteristic curve analysis. Quantitative real-time polymerase chain reaction was used to detect the level of mRNA of relative genes. RESULTS: Among 2 datasets, a total of 703 DEGs were identified, mainly enriched in chemical synaptic transmission, cell adhesion, odontogenesis of the dentin-containing tooth, cell junction, extracellular region, extracellular space, structural molecule activity, and structural constituent of cytoskeleton. The protein-protein interaction network was composed of 4379 edges and 589 nodes. Its significant module had 10 hub genes, and SYN1, SYP, and GRIA2 were significantly down-regulated with ACP. CONCLUSION: In a word, we find out the DEGs between ACP patients and standard samples, which are likely to play an essential role in the development of ACP. At the same time, these DEGs are of great value in tumors' diagnosis and targeted therapy and could even be mined as biological molecular targets for diagnosing and treating ACP patients.

Apatinib Induces Ferroptosis of Glioma Cells through Modulation of the VEGFR2/Nrf2 Pathway.

Background: Glioma is a common tumor that originated from the brain, and molecular targeted therapy is one of the important treatment modalities of glioma. Apatinib is a small-molecule tyrosine kinase inhibitor, which is widely used for the treatment of glioma. However, the underlying molecular mechanism has remained elusive. Recently, emerging evidence has proved the remarkable anticancer effects of ferroptosis. In this study, a new ferroptosis-related mechanism of apatinib inhibiting proliferation of glioma cells was investigated, which facilitated further study on inhibitory effects of apatinib on cancer cells. Methods: Human glioma U251 and U87 cell lines and normal astrocytes were treated with apatinib. Ferroptosis, cell cycle, apoptosis, and proliferation were determined. A nude mouse xenograft model was constructed, and tumor growth rate was detected. Tumor tissues were collected to estimate ferroptosis levels and to identify the relevant pathways after treatment with apatinib. Results: Treatment with apatinib could induce loss of cell viability of glioma cells, but not of normal astrocytes, through eliciting ferroptosis in vitro and in vivo. It was also revealed that apatinib triggered ferroptosis of glioma cells via inhibiting the activation of nuclear factor erythroid 2-related factor 2/vascular endothelial growth factor receptor 2 (Nrf2/VEFGR2) pathway. The overexpression of Nrf2 rescued the therapeutic effects of apatinib. Conclusion: Our study proved that treatment with apatinib could restrain proliferation of glioma cells through induction of ferroptosis via inhibiting the activation of VEGFR2/Nrf2/Keap1 pathway. Overexpression of Nrf2 could counteract the induction of ferroptosis by apatinib.

Prognosis of Oligodendroglioma Patients Stratified by Age: A SEER Population-Based Analysis.

PURPOSE: Glioma may affect patients of any age. So far, only a limited number of big data studies have been conducted concerning oligodendroglioma (OG) in diverse age groups. This study evaluated the risk factors for OG in different age groups using the Surveillance, Epidemiology, and End Results (SEER) database built by the National Cancer Institute, which is part of the National Institutes of Health. PATIENTS AND METHODS: A total of 5437 cases within the SEER database were included. These patients were divided into seven age groups. The Kaplan-Meier method was employed for survival analysis. The independent risk factors for the survival of OG patients were identified using the Cox regression model. A nomogram was drawn with R software based on the independent risk factors. The X-tile software was adopted to find the optimal age group at diagnosis. RESULTS: The all-cause mortality and the tumor-specific mortality increased with age. The univariate analysis showed that the patients' age, gender, primary lesion location, side affected by the primary lesion (left or right), surgery for the primary lesion, and tumor size were correlated with survival (P<0.05). Multivariate Cox regression analysis showed that age was an independent risk factor for the survival of OG patients (P<0.05). The optimal cutoff value of age in terms of overall survival (OS) and cause-specific survival (CSS) were identified as 48 and 61 years and 48 and 59 years, respectively. CONCLUSION: The older the age, the worse the survival would be. That's, the mortality increased with age. In the clinic, healthcare professionals should be fully aware of the variability in the prognosis of OG patients in different age groups. Therefore, individualized treatments are recommended to OG patients in different age groups to optimize the prognosis.

Hub biomarkers for the diagnosis and treatment of glioblastoma based on microarray technology.

BACKGROUND: Glioblastoma (GBM) is the most common clinical intracranial malignancy worldwide, and the most common supratentorial tumor in adults. GBM mainly causes damage to the brain tissue, which can be fatal. This research explored potential gene targets for the diagnosis and treatment of GBM using bioinformatic technology. METHODS: Public data from patients with GBM and controls were downloaded from the Gene Expression Omnibus database, and differentially expressed genes (DEGs) were identified by Gene Expression Profiling Interactive Analysis (GEPIA) and Gene Expression Omnibus 2R (GEO2R). Construction of the protein-protein interaction network and the identification of a significant module were performed. Subsequently, hub genes were identified, and their expression was examined and compared by real-time quantitative (RT-q)PCR between patients with GBM and controls. RESULTS: GSE122498 (GPL570 platform), GSE104291 (GPL570 platform), GSE78703_DMSO (GPL15207 platform), and GSE78703_LXR (GPL15207 platform) datasets were obtained from the GEO. A total of 130 DEGs and 10 hub genes were identified by GEPIA and GEO2R between patients with GBM and controls. Of these, strong connections were identified in correlation analysis between CCNB1, CDC6, KIF23, and KIF20A. RT-qPCR showed that all 4 of these genes were expressed at significantly higher levels in patients with GBM compared with controls. CONCLUSIONS: The hub genes CCNB1, CDC6, KIF23, and KIF20A are potential biomarkers for the diagnosis and treatment of GBM.

Identification of Potential Hub Genes of Atherosclerosis Through Bioinformatic Analysis.

Cardiovascular and cerebrovascular diseases, which mainly consist of atherosclerosis (AS), are major causes of death. A great deal of research has been carried out to clarify the molecular mechanisms of AS. However, the etiology of AS remains poorly understood. To screen the potential genes of AS occurrence and development, GSE43292 and GSE57691 were obtained from the Gene Expression Omnibus (GEO) database in this study for bioinformatic analysis. First, GEO2R was used to identify differentially expressed genes (DEGs) and the functional annotation of DEGs was performed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The Search Tool for the Retrieval of Interacting Genes (STRING) tool was used to construct the protein-protein interaction network and the most important modules and core genes were mined. The results show that a total of 211 DEGs are identified. The functional changes of DEGs are mainly associated with the cellular process, catalytic activity, and protein binding. Eighteen genes were identified as core genes. Bioinformatic analysis showed that the core genes are mainly enriched in numerous processes related to actin. In conclusion, the DEGs and hub genes identified in this study may help us understand the potential etiology of the occurrence and development of AS.

HIV-1 genetic diversity and recombinant forms among men who have sex with men at a sentinel surveillance site in Xi'an City, China.

HIV-1 genetic distribution and recombinant patterns are important in understanding the HIV epidemic among men who have sex with men (MSM). In this study, 83 HIV-positive MSM infections were confirmed at a sentinel surveillance site in Xi'an city, China in 2018. HIV-1 genotypes were determined by phylogenetic analyses of HIV-1 gag, pol and env gene fragments, including CRF07_BC (51.8%), CRF01_AE (30.1%), subtype B (3.6%), CRF55_01B (3.6%), CRF104_0107 (1.2%) and unique recombinant forms (URFs) (9.6%). Transmitted drug resistance mutations were detected in 2.4% (2/82) of HIV-infected MSM individuals. The phylogenetic analyses of near full-length genome (NFLG) of HIV-1 URFs were performed. A new circulating recombinant form (CRF), designated as CRF104_0107, was found in three epidemiologically unlinked individuals in Shaanxi province, China. The CRF104_0107 is composed of genomes CRF01_AE and CRF07_BC, with six recombinant breakpoints in the gag, pol, vif and vpr genes. This second-generation CRF has a breakpoint (HXB2 nt 3011) in common with CRF07_BC. The emergence of novel CRF and multiple URFs reflected HIV-1 genetic complexity among the local key populations in Xi'an city, China.

Identification and Functional Enrichment Analysis of Potential Diagnostic and Therapeutic Targets in Adamantinomatous Craniopharyngioma.

Adamantinomatous craniopharyngioma (ACP) is a congenital epithelial tumor in the sellar region with benign histological manifestation but invasive. Currently, surgery is the main treatment for it, but its recurrence rate is high. Therefore, it is of great importance to explore the mechanism of occurrence and development of ACP and to identify new molecules. One gene expression profile, GSE94349, was downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified by the limma package. Gene set enrichment analysis was used to make enrichment analysis using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Then, we performed the construction and analysis of the protein-protein interaction (PPI) network and significant module. The analysis of the GSE94349 dataset identified 109 DEGs, consisting of 80 upregulated genes and 29 downregulated genes in ACP samples compared with normal brain tissues. Functional and pathway enrichment analysis of DEGs provided a comprehensive overview of some major pathophysiological mechanisms in ACP: RNA polymerase II promoter, glutamate receptor binding, and so on. A total of 10 hub genes of DEGs were obtained from the PPI network, which provided potential therapeutic targets for the ACP. In summary, there were DEGs between ACP tissues and normal brain tissues, which may be involved in the mechanisms of occurrence and development of ACP, especially via the regulation of RNA polymerase II promoter and glutamate receptor binding. Key genes in DEGs could serve as new research targets for the diagnosis and treatment of ACP.

Screening and authentication of molecular markers in malignant glioblastoma based on gene expression profiles.

Glioblastoma (GBM) is a malignant tumor of the central nervous system with high mortality rates. Gene expression profiling may determine the chemosensitivity of GBMs. However, the molecular mechanisms underlying GBM remain to be determined. To screen the novel key genes in its occurrence and development, two glioma databases, GSE122498 and GSE104291, were analyzed in the present study. Bioinformatics analyses were performed using the Database for Annotation, Visualization and Integrated Discovery, the Search Tool for the Retrieval of Interacting Genes, Cytoscape, cBioPortal, and Gene Expression Profiling Interactive Analysis softwares. Patients with recurrent GBM showed worse overall survival rate. Overall, 341 differentially expressed genes (DEGs) were authenticated based on two microarray datasets, which were primarily enriched in 'cell division', 'mitotic nuclear division', 'DNA replication', 'nucleoplasm', 'cytosol, nucleus', 'protein binding', 'ATP binding', 'protein C-terminus binding', 'the cell cycle', 'DNA replication', 'oocyte meiosis' and 'valine'. The protein-protein interaction network was composed of 1,799 edges and 237 nodes. Its significant module had 10 hub genes, and CDK1, BUB1B, NDC80, NCAPG, BUB1, CCNB1, TOP2A, DLGAP5, ASPM and MELK were significantly associated with carcinogenesis and the development of GBM. The present study indicated that the DEGs and hub genes, identified based on bioinformatics analyses, had significant diagnostic value for patients with GBM.

Identification of Three HIV-1 Unique (B/C) Recombinant Forms in Shaanxi, China.

HIV-1 intersubtype B/C recombinants were more commonplace reported in high-risk populations in Yunnan province, China. In this study, three unique (B/C) recombinant isolates (2015YL02, 2018YL07, and SN18015) were identified from patients infected with HIV-1 through sexual transmission in Shaanxi province. Phylogenetic and bootscan analyses showed that three recombinants comprised HIV-1 subtype B and subtype C. The recombinant structures revealed that the near full-length sequence of 2015YL02 shared an identical mosaic structure with XC2014EU20, which was isolated from Sichuan province. And two similar breakpoints were observed between 2018YL07 and CRF08_BC in pol gene. The arising B/C recombinant forms enrich evidence of the HIV-1 genetic diversity among sexually transmitted populations and suggest that continuously monitoring HIV-1 molecular epidemiology is needed in Shaanxi province.

Systematic estimation of BMI: A novel insight into predicting overweight/obesity in undergraduates.

The prevalence of overweight-obesity has increased sharply among undergraduates worldwide. In 2016, approximately 52% of adults were overweight-obese. This cross-sectional study aimed to investigate the prevalence of overweight-obesity and explore in depth the connection between eating habits and overweight-obesity among Chinese undergraduates.The study population included 536 undergraduates recruited in Shijiazhuang, China, in 2017. They were administered questionnaires for assessing demographic and daily lifestyle characteristics, including sex, region, eating speed, number of meals per day, and sweetmeat habit. Anthropometric status was assessed by calculating the body mass index (BMI). The determinants of overweight-obesity were investigated by the Pearson χ test, Spearman rho test, multivariable linear regression, univariate/multivariate logistic regression, and receiver operating characteristic curve analysis.The prevalence of undergraduate overweight-obesity was 13.6%. Sex [male vs female, odds ratio (OR): 1.903; 95% confidence interval (95% CI): 1.147-3.156], region (urban vs rural, OR: 1.953; 95% CI: 1.178-3.240), number of meals per day (3 vs 2, OR: 0.290; 95% CI: 0.137-0.612), and sweetmeat habit (every day vs never, OR: 4.167; 95% CI: 1.090-15.933) were significantly associated with overweight-obesity. Eating very fast was positively associated with overweight-obesity and showed the highest OR (vs very slow/slow, OR: 5.486; 95% CI: 1.622-18.553). However, the results of multivariate logistic regression analysis indicated that only higher eating speed is a significant independent risk factor for overweight/obesity (OR: 17.392; 95% CI, 1.614-187.363; P = .019).Scoremeng = 1.402 × scoresex + 1.269 × scoreregion + 19.004 × scoreeatin speed + 2.546 × scorenumber of meals per day + 1.626 × scoresweetmeat habit and BMI = 0.253 × Scoremeng + 18.592. These 2 formulas can help estimate the weight status of undergraduates and predict whether they will be overweight or obese.

Performance of two different constitutive models and microstructural evolution of GH4169 superalloy.

The hot compression tests of GH4169 superalloy were performed in the deformation temperature range of 970 to 1150 ℃ and at the strain rate range of 0.001 to 10 s⁻¹. The flow stress is dependent on temperature and strain rate. The flow stresses were respectively predicted by Arrhenius-type and artificial neural network (ANN) models, and the predicted flow stresses were compared with the experimental data. A processing map can be obtained using the dynamic material models (DMM). A three-dimensional (3D) FEM model was established to simulate the hot compression process of GH4169 superalloy. Investigation of the microstructure of the deformed specimen was carried out using theoretical analysis, experimental research and FEM simulation. And the FEM model of compression tests were verified by experimental data.