Epidemiological studies have evaluated the association between ataxia telangiectasia mutated (ATM) gene polymorphisms and breast cancer risk. However, published data are still inconclusive. We performed a meta-analysis for the first time, based on currently available evidence, by searching PubMed, ISI Web of Knowledge, and Embase databases to derive a more precise assessment of the relationship. Following the inclusion and exclusion criteria, nine publications were included in this meta-analysis. Of these studies, one had a deviation from the Hardy-Weinberg equilibrium (HWE) at a statistical significance level of 0.01 in controls, and another two had no available data for HWE. We observed that the ATM 5557G>A polymorphism was significantly correlated with breast cancer risk when all studies were pooled into the meta-analysis (recessive model: odds ratio, OR = 0.67; 95% confidence interval (CI) 0.51-0.89). For the ATM IVS38-8T>C polymorphism, no significant association was found in the allele contrast, heterozygote codominant, and dominant models. There were no available data to perform this meta-analysis in the homozygote codominant and recessive models. For the ATM IVS1+19A>T polymorphism, a significant association with breast cancer risk was found in the allele contrast model (C vs. T: OR = 1.60; 95% CI 1.02-2.52). For the IVS34+60G>A polymorphism, no significant association was found in the allele contrast, codominant, dominant, and recessive models. Egger's test did not suggest any evidence of publication bias (P = 0.47 for the recessive model). In conclusion, there is limited evidence to indicate that ATM polymorphisms are associated with increased risk of breast cancer.

Background Immunotherapy is a novel hotspot for the treatment of pancreatic adenocarcinoma (PAAD). However, potential biomarkers which could identify the inflamed tumor microenvironment (TME) are urgently required. Methods In the present study, we measured the levels of B7-H3, B7-H4, and major tumor-infiltrating immune cells (TIICs) using bioinformatics analyses and immunohistochemistry (IHC) staining on PAAD samples represented in the tissue microarray (TMA) format. Statistical analysis and figures exhibition were performed using R 4.1.0, SPSS 26.0, and GraphPad Prism 6.0. Results B7-H3 and B7-H4 were up-regulated in PAAD compared with para-tumor tissues, and their expression exhibited no tight correlation in PAAD tissues. B7-H3 and B7-H4 were lowly expressed in well-differentiated PAAD tissues and correlated with poorly differentiated grades. Besides, single B7-H3 or B7-H4 expression exhibited limited prognostic value, but co-deficiency of B7-H3 and B7-H4 predicted a better prognosis in PAAD. Moreover, co-deficiency of B7-H3 and B7-H4 indicated immuno-hot tumors with high CD8 + T cell infiltration. Conclusions Overall, combined B7-H3 and B7-H4 expression is a promising stratification strategy to assess prognosis and immunogenicity in PAAD, which could be used as a novel classifier in clinical practice.

Effects of micro ribonucleic acid (miR)-9 on neuronal apoptosis and expression levels of apoptosis genes B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in depression model rats, as well as its regulatory mechanism, were investigated. Thirty Sprague-Dawley rats were randomly divided into control group (n=10), model group (n=10) and miR-9 inhibitor group (n=10). The rat model of depression was established using the chronic stress method. The learning and memory abilities of rats were detected via water maze test, the neuronal morphology of the brain was detected using hematoxylin and eosin (H&E) staining, and the levels of serum Bcl-2 and Bax were determined using the enzyme-linked immunosorbent assay (ELISA) kits. Moreover, the neuronal apoptosis in the brain was determined through terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, and the protein levels of Notch1 and Hes1 in brain tissues were measured via western blot analysis. Compared with the control group, the rats in the model group presented significantly decreased learning and memory abilities, poor neuronal morphology of the brain, significantly higher neuronal apoptosis rate in the brain, decreased level of serum Bcl-2, increased level of serum Bax, and significantly decreased protein levels of Notch1 and Hes1 in brain tissues. Compared with the model group, the rats in miR-9 inhibitor group showed obviously improved learning and memory abilities, improved neuronal morphology of the brain, an obviously lower neuronal apoptosis rate in the brain, increased level of serum Bcl-2, decreased level of serum Bax, and obviously increased protein levels of Notch1 and Hes1 in brain tissues. In conclusion, miR-9 inhibitor can promote the neurological function recovery and inhibit the neuronal apoptosis of depression model rats through activating the Notch signaling pathway, suggesting that miR-9 can be an important therapeutic target for depression.