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.Diagnostic value of endoscopic LCPL sign for high-risk intestinal metaplasia in gastric mucosa
Xipeng ZHENG ; Huilin PAN ; Linyu WU ; Yongying HOU ; Qin LIU ; Qiang MA ; Xiuyuan QIN ; Kaijun LIU ; Bin WANG ; Dongfeng CHEN ; Tao WANG
Journal of Army Medical University 2025;47(5):407-416
Objective To investigate the diagnostic value of endoscopic sign of light blue crest(LBC)capsuling papillary lesion(LCPL)for high-risk intestinal metaplasia(IM).Methods A total of 314 patients(352 biopsy specimens)who underwent endoscopic examination and biopsy in Department of Gastroenterology of Army Medical Center of PLA from January 2021 to June 2023 were recruited,and HE and HID-AB staining(the golden standard of high-risk IM)were apllied to detect the histological types and IM types.The samples were subsequently divided into chronic inflammation group,low-risk IM group,high-risk IM group,well-differentiated intestinal-type gastric cancer group,and poorly-differentiated intestinal-type gastric cancer group.The positive rate of LCPL in each group and its diagnostic efficacy were analyzed based on endoscopic images of the biopsy sites.Logistic regression analysis was used to investigate the relationship between LCPL sign and high-risk IM,as well as the clinical and pathological features associated with LCPL sign.Receiver operating characteristic(ROC)curve was plotted to evaluate the diagnostic efficacy of LCPL for high-risk IM,using indicators such as sensitivity,specificity,Youden index and area under the curve(AUC).Results The positive rate of the LCPL sign in high-risk IM group was 75.70%,significantly higher than that of the other groups(all P<0.001).Logistic regression analysis showed that LCPL sign was significantly correlated with high-risk IM(OR=30.286,95%CI:13.528~67.804,P<0.001).When the sign was employed in diagnosing high-risk IM,the sensitivity was 69.84%,the specificity was 93.75%,the Youden's index was 0.636,and the AUC value was 0.818(95%CI:0.773~0.857).Besides sensitivity,all above parameters of LCPL sign showed significantly better diagnostic efficacy than those of traditional LBC sign,which is used as a sign for diagnosing IM(P<0.001).Moreover,recognition of LCPL sign was not easily affected by age(OR=1.130,95%CI:0.709~1.800,P=0.607),lesion site(Angular incisure:OR=2.360,95%CI:0.732~7.613,P=0.151;Autrum:OR=2.257,95%CI:0.756~6.744,P=0.145),and presence of peptic ulcers(OR=1.085,95%CI:0.208~5.652,P=0.923).Significantly,94.12%of positive and 66.94%of negative LCPL signs could be rapidly recognized within 3 s(OR=4.536,95%CI:1.372~14.997,P=0.013).Conclusion LCPL sign shows high efficacy and potential clinical application value for high-risk IM in gastric mucosa of endoscopic diagnosis.
3.Ameliorating effect of calycosin regulating SIRT3/SOD2 signaling pathway on airway epithelial cell damage in mice
Jia NIE ; Yongying GUO ; Xiangyan YU ; Yuzhen PEI ; Yun LIU ; Zenglu KANG ; Yinghao SU
Tianjin Medical Journal 2024;52(11):1171-1176
Objective To investigate effects of calycosin(CA)on cigarette smoke(CS)induced airway epithelial cell damage in mice and the sirtuin 3/superoxide dismutase 2(SIRT3/SOD2)signaling pathway in mice.Methods A total of 90 mice were randomly separated into the control group,the cigarette smoke(CS)group,the CA low-dose treatment group(CA-L group),the CA high-dose treatment group(CA-H group)and the CA high-dose treatment plus SIRT3 inhibitor 3-TYP group(CA-H+3-TYP group),with 18 mice in each group.Tidal volume(TV)and peak expiratory flow rate(PEF)of lung function were detected by whole body plethysmography system.Serum levels of inflammatory factors[interleukin(IL)-6,tumor necrosis factor(TNF)-α]and oxidative stress indicators[reactive oxygen species(ROS),SOD]were detected by enzyme-linked immunosorbent assay(ELISA).The injury of airway epithelial cells in lung tissue was observed by HE staining.The expression levels of barrier related proteins(OCLN and ZO-1)in airway epithelial cells were detected by immunohistochemistry.Immunoblotting was applied to detect the expression of SIRT3/SOD2 signaling pathway related proteins.Results Compared with the control group,levels of TV,PEF,MAN and SOD and the expression levels of OCLN,ZO-1,SIRT3 and SOD2 were decreased in the CS group,while the levels of MLI,IL-6,TNF-α and ROS were increased(P<0.05).Compared with the control group,the lung tissue structure was significantly damaged,the alveolar enlargement was obvious,the surrounding alveolar was accompanied by inflammatory cell infiltration,and the airway epithelial cells were obviously shed in the CS group.Different doses of CA alleviated lung tissue destruction,improved alveolar structure,reduced inflammatory cell infiltration,reduced airway epithelial cell shedding,increased levels of TV,PEF,MAN,SOD and OCLN,ZO-1,SIRT3 and SOD2,and decreased levels of MLI,IL-6,TNF-α and ROS.The effect of high dose CA was more significant than that of low dose CA(P<0.05).SIRT3/SOD2 signaling pathway inhibitor 3-TYP partially reversed the ameliorative effect of CA on CS induced airway epithelial cell injury in mice.Conclusion CA can ameliorate CS induced airway epithelial cell damage in mice,and its mechanism is related to the activation of the SIRT3/SOD2 signaling pathway.
4.Application of bioinformatics in predicting the risk of hepatocellular carcinoma
Guoxu FANG ; Qinghua ZHANG ; Yongying HUANG ; Jianmin WANG ; Jingfeng LIU
Journal of Clinical Hepatology 2022;38(1):15-19
Bioinformatics is an interdisciplinary science that combines the tools of mathematics, computer science, and biology to clarify and explore the biological implications of large amounts of biological data. With the continuous development of genome sequencing technology, a large number of biological data has been generated, and mining of the biological significance contained in big data has become one of the main tasks that need to be solved urgently. This article summarizes the risk prediction models for hepatocellular carcinoma (HCC) based on feature genes, so as to provide new perspectives for early identification, prognosis, and treatment optimization of HCC.
5.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.
6. Study on the relationship between the 2019 Novel Coronavirus Disease epidemic in China and population migration from Wuhan
Hongtian LI ; Zhihao CHENG ; Yongying HUANG ; Jianmeng LIU
Chinese Journal of Medical Science Research Management 2020;33(0):E007-E007
Objective:
To investigate the relationship between the epidemic of Coronavirus Disease in 2019 (COVID-19) in China and population migration from Wuhan before the city implemented strict migration restrictions.
Methods:
We collected the cumulative number of confirmed cases with COVID-19 up to January 31, 2020 from the official website of the health administrative departments, and information on population migration out of Wuhan during January 10, 2020 and January 24, 2020, approximately half months prior to the implementation of strict migration restrictions by the city, from Baidu population-migration big data platform. Population migration data were provided for the top 100 cities in the form of percentage values, calculated as the number of migrants from Wuhan into these cities divided by the total number of migrants out of Wuhan during the same period multiplied by 100%. The two-independent sample non-parametric Wilcoxon rank-sum test was used to compare the distribution of cumulative number of cases between the top 100 cities and the remaining 205 non-top 100 cities of China. The relationship between the cumulative number of cases and the percentage of migrants from Wuhan into the top 100 cities were further assessed by Pearson correlation and by multiple linear regression with adjustment for population size, population density, and GDP per capita.
Results:
The top 100 cities accounted for 91.6% of total migrants out of Wuhan, and the top 14 cities were all in Hubei province. There were a total of 5,869 cases in the top 100 cities, with a median (interquartile range) of 21.5 (12~55) cases, whereas in the 205 non-top 100 cities there were a total of 1,063 cases, with a median (interquartile range) of 4 (2~7) cases. The median cumulative number of cases differed significantly between the two types of cities (
7.Analysis of adverse reactions induced by combination of statins and other drugs in 78 cases
Shaopeng YANG ; Jian ZHANG ; Yongying LIU
Chinese Journal of Biochemical Pharmaceutics 2017;37(4):404-406
Objective To investigate the adverse reactions induced by statins when combined with other drugs and its influencing factors,so as to provide reference for clinical rational drug use.Methods The clinical data of 78 patients with adverse reactions caused by statins combined with other drugs in our hospital from June 2011 to June 2016 were reviewed and analyzed.Results The adverse reactions of the 78 cases of patients were manifested as muscle toxicity,liver toxicity,digestive discomfort,respiratory discomfort,et al; Inwhich muscle toxicity and liver toxicity were the most common adverse reactions.The incidence rate of rhabdomyolysis was 20.51%,which was significantly higher than that of the other adverse reactions(P<0.05).The incidence rates of adverse reactions induced by simvastatin and atorvastatin were 44.87%and 28.21%,significantly higher than other statins(P<0.05).The incidence of side effects was the highest(30.77%)when the statins combined with antihypertensive drugs and anti myocardial drugs,and the incidence of adverse reactions was 20.51%when combined with lipid-lowering drugs.Conclusion The adverse reaction rate is relatively high when statins,especially simvastatin and atorvastatin combined with antihypertensive,anti-myocardial and lipid-lowering drugs,and the adverse reactions to liver toxicity and muscle toxicity are the main performance.Therefore a standardized and rational medication regimen should be made based on the clinical characteristics of patients and the type of drug in the clinical use of statins,in order to reduce the incidence of adverse reactions to the maximum limit.

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