Glioblastoma is the most common type of malignant brain tumor. Bioinformatics technology and structure biology were effectively and systematically used to identify specific targets in malignant tumors and screen potential drugs. GBM patients have higher AURKA and KDR mRNA expression compared with normal samples. Then, we identified a small molecular compound, ENMD-2076, could effectively inhibit Aurora kinase A and VEGFR-2 (encoded by KDR) activities. ENMD-2076 is predicted without toxic properties and also has absorption and gratifying brain/blood barrier penetration ability. Further results demonstrated that ENMD-2076 could significantly inhibit GBM cell lines proliferation and vitality, it also suppressed GBM cells migration and invasion. ENMD-2076 induced glioblastoma cell cycle arrest in G2-M phase and apoptosis by inhibiting PI3K/AKT/mTOR signaling pathways. Additionally, ENMD-2076 prolonged the median survival time of tumor-bearing rats and restrained growth rate of tumor volume in vivo. Our findings reveal that ENMD-2076 is a promising drug in dealing with glioblastoma and have a perspective application. We show that AURKA and KDR genes are hub driver genes in glioblastoma with bioinformatics technology including WGCNA analysis, PPI network, GO, KEGG analysis and GSEA analysis. After identifying a compound via virtual screening analysis, further experiments were carried out to examine the anti-glioblastoma activities of the compound in vivo and in vitro.

INTRODUCTION: Visual endoscopic retrograde appendicitis therapy (V-ERAT) involves a single-use video scope, allowing for real-time visualization of the appendiceal lumen during the procedure to treat uncomplicated acute appendicitis (AA). This study aims to compare V-ERAT to antibiotic therapy in treating uncomplicated AA. METHODS: This multicenter, retrospective cohort study was conducted at 9 hospitals in China from August 2021 to July 2023. Propensity score matching was performed to minimize selection bias. A total of 692 uncomplicated AA patients were included, with 188 undergoing V-ERAT and 504 receiving antibiotic therapy. The primary outcome was treatment success rate. The secondary outcomes included recurrent appendicitis rate, the appendectomy rate during the initial hospitalization, length of initial hospitalization, time to disease recurrence, and overall adverse events. RESULTS: The treatment success rate did not differ between the V-ERAT and antibiotic groups (93.6%; 95% confidence interval [CI] 89.1%–96.7% vs 90.5%; 95% CI, 87.6%–92.9%) ( P = 0.225). However, V-ERAT demonstrated a significantly lower risk of appendicitis recurrence compared with antibiotic therapy during the follow-up (log-rank P < 0.001), with a hazard ratio of 0.14 (95% CI, 0.07–0.29, P < 0.001). V-ERAT was associated with a lower appendectomy rate during the initial hospitalization (4.3%; 95% CI, 1.9%–8.2% vs 9.5%; 95% CI, 7.1%–12.4%) ( P = 0.027), a shorter length of initial hospitalization (3 [interquartile range (IQR), 3–4] vs 4 [IQR, 4–6] days, P < 0.001), and a longer time to recurrence (269 [IQR, 210–318] vs 70 [IQR, 21–103] days, P < 0.001). The overall adverse event rates did not differ between the 2 groups (log-rank P = 0.064). DISCUSSION: V-ERAT seems to be a safe and effective alternative to antibiotic therapy in treating uncomplicated AA, significantly reducing the risk of appendicitis recurrence.

Background: Despite progression in its treatment, the clinical outcome of patients with clear cell renal cell carcinoma (ccRCC) remains not ideal. Anoikis is a unique form of programmed apoptosis, owing to insufficient cell-matrix interactions. Anoikis plays a crucial role in tumor migration and invasion, and tumor cells could protect themselves through the capacity of anoikis resistance.Methods: Anoikis-related genes (ARGs) were obtained from Genecards and Harmonizome portals. The ARGs related to ccRCC prognosis were identified through univariate Cox regression analysis, then we utilized these ARGs to construct a novel prognostic model for ccRCC patients. Moreover, we explored the expression profile of ARGs in ccRCC using the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database. We also conducted Real-Time Polymerase Chain Reaction (RT-PCR) to probe ARGs expression of the risk score. Finally, we performed correlation analysis between ARGs and tumor immune microenvironment.Results: We identified 17 ARGs associated with ccRCC survival, from which 7 genes were chosen to construct a prognostic model. The prognostic model was verified as an independent prognostic indicator. The expression of most ARGs was higher in ccRCC samples. These ARGs were closely correlated with immune cell infiltration and immune checkpoint members, and had independent prognostic value respectively. Functional enrichment analysis demonstrated that these ARGs were significantly associated with multiple types of malignances.Conclusion: The prognostic signature was identified to be highly efficient in predicting ccRCC prognosis, and these ARGs were closely related to tumor microenvironment.

Backgrounds: The extended duration of endoplasmic reticulum stress (ERS) can impact the progression of hepatocellular carcinoma (HCC) and the efficacy of immunotherapies by interacting with immune cells that have infiltrated the tumor microenvironment (TME).Methods and results: The study utilized a training cohort of 364 HCC patients with complete information from The Cancer Genome Atlas Program (TCGA) database, and a validation cohort of 231 HCC patients from the International Cancer Genome Consortium (ICGC) database. The genes related to ERS exhibiting a strong correlation with overall survival (OS) were identified using univariate Cox regression analysis. A 13-gene predictive signature was then produced through the least absolute shrinkage and selection operator (LASSO) regression approach. The data revealed that the ERS-associated gene signature effectively stratified patients into high- or low-risk groups regarding OS in both the training and validation cohorts (P < 0.0001 and P = 0.00029, respectively). Using the multivariate method, it is still an independent prognostic factor in both the training and validation cohorts (P < 0.001 and P = 0.008, respectively). Moreover, several metabolic pathways were identified to be enriched among the 13 genes in the predictive signature. When the ERS-associated gene signature was combined with the tumor-node-metastasis (TNM) stage, the ERS nomogram performed better than either the gene signature or the TNM stage alone (C-index values: 0.731, 0.729, and 0.573, respectively). Further analysis revealed that patients in the high-risk group exhibited increased infiltration of immune cells. Additionally, GP6 was downregulated in HCC tissues among these signature genes (P < 0.05), which was related to poor OS.Conclusions: The data suggest that this novel ERS-associated gene signature could contribute to personalized cancer management for HCC. Moreover, targeting GP6 inhibition might be a potential method for HCC therapy.