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.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.
4.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.
5.Hyperbaric Oxygen Pretreatment Improves Cognition and Reduces Hippocampal Damage Via p38 Mitogen-Activated Protein Kinase in a Rat Model.
Baisong ZHAO ; Yongying PAN ; Zixin WANG ; Haiping XU ; Xingrong SONG
Yonsei Medical Journal 2017;58(1):131-138
PURPOSE: To investigate the effects of hyperbaric oxygen (HBO) pretreatment on cognitive decline and neuronal damage in an Alzheimer’s disease (AD) rat model. MATERIALS AND METHODS: Rats were divided into three groups: normal saline (NS), AD, and HBO+AD. In the AD group, amyloid β peptide (Aβ)₁₋₄₀ was injected into the hippocampal CA1 region of the brain. NS rats received NS injection. In the HBO+AD group, rats received 5 days of daily HBO therapy following Aβ₁₋₄₀ injection. Learning and memory capabilities were examined using the Morris water maze task. Neuronal damage and astrocyte activation were evaluated by hematoxylin-eosin staining and immunohistochemistry, respectively. Dendritic spine density was determined by Golgi-Cox staining. Tumor necrosis factor-α, interleukin-1β, and interleukin-10 production was assessed by enzyme-linked immunosorbent assay. Neuron apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling. Protein expression was examined by western blotting. RESULTS: Learning and memory dysfunction was ameliorated in the HBO+AD group, as shown by significantly lower swimming distances and escape latency, compared to the AD group. Lower rates of neuronal damage, astrocyte activation, dendritic spine loss, and hippocampal neuron apoptosis were seen in the HBO+AD than in the AD group. A lower rate of hippocampal p38 mitogen-activated protein kinase (MAPK) phosphorylation was observed in the HBO+AD than in the AD group. CONCLUSION: HBO pretreatment improves cognition and reduces hippocampal damage via p38 MAPK in AD rats.
Alzheimer Disease/*therapy
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Amyloid beta-Peptides/*administration & dosage
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Animals
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Apoptosis
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*Cognition/drug effects
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Disease Models, Animal
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Enzyme-Linked Immunosorbent Assay
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Hippocampus/*enzymology
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*Hyperbaric Oxygenation
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In Situ Nick-End Labeling
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Interleukin-10/biosynthesis
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Interleukin-1beta/biosynthesis
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Learning/drug effects
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Male
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Memory/drug effects
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Neurons
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Peptide Fragments/*administration & dosage
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Rats
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Rats, Sprague-Dawley
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Sodium Chloride/administration & dosage
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Tumor Necrosis Factor-alpha/biosynthesis
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p38 Mitogen-Activated Protein Kinases/*metabolism
6.Obserbation on the effect of the long-term low-dose mifepristone on the treatment of hysteromyoma
Chinese Journal of Biochemical Pharmaceutics 2017;37(7):306-307
Objective To observe the effect of the long-term low-dose mifepristone on the treatment of hysteromyoma.Methods From March 2016 to December 2016 in Haiyan maternal and child health-care center,120 cases with hysteromyoma were selected as the object study and were given long term oral low-dose mifepristone.The uterus size, follicle stimulating hormone, myoma size, luteinizing hormone, estrogen and endometrium were observed Resultsafter treatment, the patients with uterine fibroids situation improved markedly, and appeared amenorrhea.At the same time, in patients with clinical symptoms were improved to a certain extent, six months after a drug follicle-stimulating hormone, luteinizing hormone and estrogen levels significantly decreased, and there is no other significant side effects.In addition, on the analysis of the effectiveness of the treatment,86 cases were markedly improved,28 cases effective,6 cases ineffective, the total effective rate was 95%.Conclusion Long-term low-dose mifepristone has worked well in the treatment of uterine fibroids, can effectively reduce uterine fibroids, high security, in the process of follow-up of patients, no recurrence no satisfaction related data, the result can't reach this Conclusion , the authors modify please.Is the ideal way of conservative treatment of uterine fibroids, and is worth popularizing in the process of clinical application.
7.Relationship between extracellular signal-regulated kinase and ketamine-induced apoptosis in rat hippocampal neurons
Yongying PAN ; Xi CHEN ; Xiaobao BI ; Wenhua ZHANG ; Yingyi XU ; Huaizhen WANG ; Xingrong SONG
Chinese Journal of Anesthesiology 2013;33(9):1073-1075
Objective To evaluate the relationship between extracellular signal-regulated kinase (ERK)and ketamine-induced apoptosis in rat hippocampal neurons.Methods Sprague-Dawley rats at 18 days of gestation were anesthetized.The fetal rats were obtained under the sterile condition and decapitated.The hippocampal neurons were isolated and primarily cultured for 5 days,and were seeded in 6-well plates (2 ml/well) or in 96-well plates (100μl/well) at a density of 5 × 105/ml.The cells were randomly divided into 4 groups (n =18 each):control group (group C),fibroblast growth factor (FGF-2,an ERK agonist) group (group F),ketamine group (group K) and FGF-2 + ketamine group (group FK).The cells were cultured in the plain culture medium in group C.FGF-2 50 ng/ml was added to the culture medium in group F.Ketamine was added to the culture medium in group K.FGF-2 50 ng/ml was added to the culture medium at 20 min before ketamine 100 μmol/L was added in group FK.The phosphorylation of ERK in hippocampal neurons was detected by Western blot at 10 min after treatment.At 24 h after treatment,the neuronal apoptosis was detected by Hoechst33342/PI staining,and the cell survival rate was detected by MTT assay.The apoptosis rate was calculated.Results Compared with group C,the phosphorylation of ERK in hippocampal neurons and the cell survival rate was significantly decreased and the apoptosis rate was increased in K and FK groups (P < 0.05).There was no significant difference in the parameters mentioned above between F and C groups (P > 0.05).The phosphorylation of ERK in hippocampal neurons and the cell survival rat was significantly higher and the apoptosis rate was lower in group FK than in group K (P <0.05).Conclusion Ketamine induces apoptosis in rat hippocampal neurons by inhibiting activation of ERK in hippocampal neurons.
8.Noninvasive assessment of renal allograft status by virtual touch tissue quantification technique
Wanyuan HE ; Chaolun LI ; Zhengbiao JI ; Wenping WANG ; Yongying QIU
Chinese Journal of Ultrasonography 2013;(2):130-132
Objective To evaluate the feasibility of virtual touch tissue quantification (VTQ) for the assessment of renal allograft.Methods A total of 72 kidney recipients were examined with conventional ultrasound and VTQ after transpantation.Biopsies were performed in 34 patients,20 patients were with acute rejection (AR),14 with chronic allograft nephropathy (CAN),38 patients as control group.The peak systolic velocity (PSV) and resistance index(RI) were measured on main,infrarenal and arcuate arteries with conventional ultrasound and shear wave velocity (SWV) of the renal cortex was obtained by VTQ.All the data were compared among three groups.Results There were no significant differences of PSV between two groups.An increased RI was presented in the CAN group(P <0.05).The mean SWV was (2.67 ± 0.27) m/s,(2.90 ± 0.31)m/s and (2.28 ± 0.24)m/s for AR,CAN and normal group,respectively.There were significant differences of SWV among the three groups (P < 0.05).Conclusions VTQ technique could provide a new method for the assessment of transplanted kidney.

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