Co-deficiency of B7-H3 and B7-H4 identifies high CD8 + T cell infiltration and better prognosis in pancreatic 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.

Association between polymorphisms of the ataxia telangiectasia mutated gene and breast cancer risk: evidence from the current studies.

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.

miR-9 inhibition of neuronal apoptosis and expression levels of apoptosis genes Bcl-2 and Bax in depression model rats through Notch pathway.

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.

[An analysis of randomized controlled trials published in the Chinese Journal of Gastrointestinal Surgery between 2003-2009].

OBJECTIVE: To study the academic level of randomized controlled trials (RCT) published in the Chinese Journal of Gastrointestinal Surgery between 2003 and 2009. METHODS: Published RCTs in the 42 issues of the Chinese Journal of Gastrointestinal Surgery was searched for relevant articles published between 2003 and 2009. Data extracted for analysis included the time at manuscript received, publication time, total number of citations, number of citations in Chinese, number of citations in English, author's affiliations, single- or multi- center study, positive conclusions from RCTs, number of patients recruited in RCTs, research funding source, the start time, the finish time and the number of authors in RCTs. RESULTS: During the past seven years, a total of 80 clinical RCTs were published in the Chinese Journal of Gastrointestinal Surgery, accounting for 12% of all the clinical studies published in the journal, and the average number of RCTs in each issue was 1.6. The average delay time before publication was 208 days. The total number of citations and the total number of patients in RCTs were 685 and 9402. The average number of citations, the average number of patients recruited in each RCT, and the average research period in RCTs were 8.6, 118 and 29.2. There were 7 multi-center studies, and the number of single-center study was 73. All the RCT studies had significant conclusions, and 17 (21.3%) RCT studies were funded. Nanjing general hospital of Nanjing military command had the largest number of RCTs (n=6). CONCLUSION: The Chinese Journal of Gastrointestinal Surgery puts emphasis on clinical studies of high evidence level such as RCT, which provide evidence for making the clinical guidelines in the specialty of gastrointestinal surgery.