1.Loss of histone H3K27me3 up-regulates SLC7A11 in diffuse gastric cancer cells
Yuanfeng REN ; Wenkang LIU ; Zhaole CHU ; Biying LIU ; Yongying HOU ; Linyu WU ; Xianfeng LI ; Dongfeng CHEN ; Tao WANG ; Bin WANG ; Min YANG
Journal of Army Medical University 2025;47(1):71-81
Objective To map the genome-wide distribution profile of histone H3K27me3 modification in diffuse gastric cancer tissues,identify target genes regulated by H3K27me3,and primarily explore the potential mechanism of its modification reprogramming in the occurrence and development of the tumor.Methods Normal gastric mucosal tissues and diffuse gastric cancer tissues were harvested from the patients who underwent examinations or treatments in the departments of gastroenterology and gastrointestinal surgery of our medical center between 2021 and 2023.There were 14 patients in the normal group(6 males and 8 females,average age of 46 years)and 14 patients in the gastric cancer group(8 males and 6 females,average age of 63 years).Cleavage under target and tagmentation(CUT&Tag)technology was employed to capture genomic regions modified by H3K27me3,and analyze the reprogramming characteristics of these modifications.RNA sequencing data,data from high-throughput chromosome conformation capture(Hi-C)technology,and publicly available single-cell data were integrated to investigate the target genes regulated by the reprogramming of H3K27me3 modifications in diffuse gastric cancer cells.Results The quality of the CUT&Tag and RNA sequencing data met the standards required for subsequent analysis.Histone H3K27me3 modifications in normal gastric mucosa and diffuse gastric cancer tissues were primarily distributed in distal intergenic regions and intronic regions.In gastric cancer tissues,compared to normal tissues,there was significant reprogramming of H3K27me3 modifications,characterized by a marked reduction in overall H3K27me3 signal intensity.The loss of 2 912 H3K27me3 signal peaks might lead to the up-regulation of 822 tumor-associated genes.Among them,56 genes displayed the most significant up-regulation(fold change in signal intensity≥2,P<0.05),with notable enrichment in the mammalian target of rapamycin complex 1(mTORC1)signaling pathway.Specifically,the methionine transporter SLC7A5 and the cystine transporter SLC7A11 were found to have the highest expression levels in gastric cancer tissues.Single-cell data revealed that the abnormal overexpression of SLC7A11 in diffuse gastric cancer was primarily observed in tumor epithelial cells.Further validation using public data and immunohistochemical experiments confirmed the elevated expression of SLC7A11 in diffuse gastric cancer,which is associated with poor prognosis in gastric cancer patients.Conclusion The reprogramming of histone H3K27me3 modification is an important epigenetic characteristic in diffuse gastric cancer.Loss of H3K27me3 signal peaks may up-regulate the expression of SLC7A11 in diffuse gastric cancer cells,and thereby promote tumor progression.
2.Progress on event-related potentials in children with autism spectrum disorder
Yongying REN ; Jianzhao ZHANG ; Jian YANG
International Journal of Pediatrics 2024;51(10):654-658
Autism spectrum disorder(ASD)is a neurodevelopmental disorder with unknown etiology,and the prevalence of ASD is on the rise worldwide.Studies have found that patients with ASD have abnormal cognitive function,and objective cognitive detection tools can provide an effective method to explore the functional defects of patients with ASD.Event-related potential(ERP),which can reflect the nerve electrophysiological change in the cognitive processing of the brain,have been widely applied in the study of ASD patients in recent years due to its high temporal resolution advantage,showing a great application prospect.This article reviews the clinical application of ERP in children with ASD,in order to reveal the functional defects of ASD children from the perspective of nerve electrophysiology,and provide a reference for the assessment and even early screening of ASD.
3.Comparison of cognitive function in children with different subtypes of attention deficit hyperactivity disorder
Siqi LIU ; Yike ZHU ; Fan ZHANG ; Yongying REN ; Xin WANG ; Lin WANG ; Jian YANG
Chinese Journal of Behavioral Medicine and Brain Science 2021;30(10):910-915
Objective:To explore the heterogeneity of behavioral problems and cognitive function of three subtypes of attention deficit hyperactivity disorder(ADHD), and to analyze the related factors of cognitive function.Methods:The outpatients with ADHD were evaluated by Wechsler children′s intelligence test (C-WISC), SNAP-Ⅳ parental rating scale (SNAP-Ⅳ), Conners parental symptom questionnaire (PSQ) and 12 online cognitive function tests. The differences of behavioral problems and cognitive function of children with different subtypes of ADHD, and the correlation between their intelligence level, PSQ, SNAP-Ⅳ and cognitive function were compared by SPSS 22.0 software.Results:The results of PSQ questionnaire showed that ADHD-C ((1.11±0.59), (1.59±0.58), (1.62±0.50)) had higher behavior problems, impulse-hyperactivity and hyperactivity index than ADHD-I ((0.64±0.27), (1.01±0.54), (1.09±0.32)) and ADHD-HI ((0.75±0.35), (1.22±0.58), (1.05±0.38)) ( F=9.374, F=7.644, F=15.176, P<0.05), while ADHD-C (2.01±0.55) had higher learning problems than ADHD-I (1.66±0.58) and ADHD-HI (1.16±0.43) ( F=11.709, P<0.05). In terms of cognitive function, there were differences in language understanding ability, digital reasoning ability, sequence relationship and short-term memory ability ( χ2=6.734, 7.192, 7.822, 8.646, all P<0.05) among the three groups of ADHD children. ADHD-HI (4.00(4.00, 5.00), 5.00(4.25, 6.00), 5.00(4.00, 7.00)) had better language understanding ability, digital reasoning ability and sequence relationship than ADHD-I (3.00(2.00, 5.00), 3.00(2.50, 6.00), 4.00(3.00, 5.50)). The short-term memory ability of ADHD-HI (5.00(4.00, 6.00)) and ADHD-C (5.00(4.00, 6.00)) were better than that of ADHD-I (4.00(3.00, 5.00)). The intellectual structure of ADHD children was positively correlated with spatial cognitive ability, sequential relationship, Raven reasoning test, short term memory span and Wisconsin card sorting test ( r=0.25-0.57, all P<0.05). Children′s learning problems and psychosomatic problems were negatively correlated with their digital comprehension ability ( r=-0.26, -0.25, both P<0.05). Conclusion:The behavioral problems and cognitive function of children with different subtypes of ADHD are different and have a certain correlation.

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