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.Enhancer remodeling characteristics in diffuse-type gastric cancer and role in upregulating GDF15 expression and promoting cancer cachexia
Yuting TAN ; Linyu WU ; Yuwei PAN ; Shiyin PENG ; Rui XUE ; Xianfeng LI ; Zhaole CHU ; Biying LIU ; Ke LI ; Xuan ZHANG ; Bin WANG
Journal of Army Medical University 2025;47(11):1165-1176
Objective To identify the enhancer landscape marked by histone H3K27ac modifications in diffuse-type gastric cancer(DGC)tissues,and to elucidate the epigenetic remodeling mechanisms by which active enhancers regulate cachexia-related genes.Methods Gastric mucosal tissue samples were collected from Department of Gastroenterology of Army Medical Center of PLA during January 2022 to March 2023,including 10 normal gastric mucosa tissues(Normal group),10 DGC tissues diagnosed with cachexia(DGC group),and 10 organoids derived from DGC tissues(Organoid group).Using H3K27ac chromatin targeting cleavage and tagmentation(CUT&Tag)technology,genomic modification regions were captured to screen specific active enhancers and their potential target genes in DGC tissues.CRISPR-dCas9 gene editing technology was used to intervene with the enhancers,and the expression of target genes was detected with Western blotting and qRT-PCR.Sixteen female SPF-grade BALB/c Nude mice(6~8 weeks old,weighing 18~21 g)were utilized to establish an orthotopic xenograft tumor model using the human diffuse-type gastric cancer cell line MKN45.Cachexia-related phenotypes were evaluated in 3 groups:normal group(n=4),silencing group(n=6),and control group(n=6).Results Significant differential enhancer regions were identified between DGC and normal gastric mucosa tissues.DGC tissues exhibited a marked increase in enhancer abundance(P<0.05)and signal intensity when compared with the normal counterparts.Integrated analysis of transcriptome data revealed that some of these active enhancers up-regulated the expression of GDF15,a cachexia-associated target gene in DGC.Targeted silencing of the active enhancer of GDF15 using CRISPR/dCas9-KRAB plasmid technology resulted in a significant reduction in GDF15 expression at both mRNA levels(P<0.05)and protein.Results from orthotopic transplantation experiments of DGC demonstrated that silencing of active enhancers alleviated the cachexia phenotype in nude mice(P<0.05).Conclusion DGC exhibits enhancer remodeling,which regulates the expression of the cachexia-associated gene GDF15,and thereby contributes to the pathogenesis and progression of cancer cachexia.
3.Treatment of Insomnia by the Method of Unblocking the Bowels and Harmonizing Viscera Based on the Theory of "Viscera-Bowels Extraordinary Connection"
Bin WU ; Zhenyun HAN ; Wenyue HU ; Lei MU ; Biying ZHONG ; Hongpei LI
Journal of Traditional Chinese Medicine 2024;65(17):1769-1774
This paper aimed to explain the clinical thinking of using the method of unblocking the bowels and harmonizing viscera. Based on theory of "viscera-bowels extraordinary connection" of The Gateway to Medicine (《医学入门》), combined with the theoretical research, clinical practice and individual experience of ancient physicians, modern scholars, it is believed that viscera qi disorder caused by bowels qi blocking is the basic mechanism of insomnia. In clinic, it is common that gallbladder phlegm-heat harassing the heart spirit, stagnant blood and qi in stomach blocking the pericardium, turbid heat in large intestine causing fire and affecting liver, dampness insmall intestine trapping the spleen, water retention in the bladder drying up lungs, and the inhibited original qi of sanjiao damaging the kidney, which could be treated with Wendan Decoction (温胆汤), Taohe Chengqi Decoction (桃核承气汤), Chengqi-series Decoction (承气汤类方), Linggui Zhugan Decoction (苓桂术甘汤), Wuling Powder (五苓散), Xiaochaihu Decoction (小柴胡汤), respectively.
4.Study on the correlation of spinal mechanics imbalance and thoraco-dorsal pain in ankylosing spondylitis
Min LI ; Yi LIANG ; Xiaohui WU ; Wenjing YU ; Weien YI ; Quan MA ; Yunlong GENG ; Biying LIU ; Wenqi ZHOU ; Huiwu ZHANG
Chinese Journal of Rheumatology 2019;23(3):170-174
Objective To investigate the correlation of spinal mechanical imbalance and thoraco-dorsal pain of ankylosing spondylitis (AS). Methods The clinical data of 90 patients with AS were collected. Patients were divided into two groups according to the presence of thoracodorsal pain: the AS with thoraco-dorsal pain group (30 cases) and the AS without thoraco-dorsal pain group (60 cases). Clinical symptoms, Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis function index (BASFI), Bath ankylosing spondylitis measurement index (BASMI), ankylosing spondylitis disease activity (ASDAS), and spinal mechanical function and nuclear myocardial force test were compared using t-test, one-way analysis of variance (ANOVA) analysis and Spearman correlation analysis. Results ① There were differences between thoraco-dorsal pain group and patients without thoracodorsal pain group at the time of back muscle strength [(0.82±0.41) min vs (1.33±0.74) min, F=12.372, P=0.001]; ②Thoraco-dorsal pain in the AS group was mainly the middle and lower thoracic vertebrae, such as the inflammation of rib head and rib transverse process, facial arthritis, and spinous ligaments, etc. And the missed diagnosis rate of magnetic resonance imagin (MRI) was high. ③ In healthy control group, the anterior flexion strength of thoracodorsal pain group was signific-antly different from that of patients without thoracodorsal pain [(92.1 ±46.3) Nm vs (126.6±35.7) Nm, F=6.440, P=0.002]. ④ There was significant difference in spinal strength as well as left and right rotation strength between the thoracodorsal pain group and patients without thoracodorsal pain [(1.18 ±0.22) vs (1.05 ±0.17), F=10.044, P<0.01];⑤In the thoraco-dorsal pain group, the right/left index was related to BASDAI (r=-0.522, P=0.004). For spinal mobility, the right/left index was related to cross cutting faces to right ( r=0.435, P=0.021), cross cutting faces to left (r=0.528, P=0.004). In spinal strength, the right/left index was related to left turn (r=0.57, P=0.001); right lateral flexion (r=0.368, P=0.049) and left lateral flexion (r=0.369, P=0.049). Conclusion The thoracodorsal pain of AS is dominated by the middle and lower thoracic vertebrae, and the missed diagnosis rate of MRI is high. The imbalance of the left and right side of the spine is one of the factors of the thoracic back pain in AS.
5.Relationship between different topographic location and neurological deterioration in acute new isolated pontine infarction
Qingchun FENG ; Da HUANG ; Shaomin HU ; Biying WU ; Xingwen WANG ; Fu LIANG ; Xiaoli CHEN ; Meijuan PENG
Journal of Chinese Physician 2017;19(7):995-998
Objective To investigate the relationship between different topographic locations and neurological deteriorations (ND) in patients with acute new isolated pontine infarction.Methods One hundred sixty-eight patients with acute new isolated pontine infarction during arch 2012 to March 2016 were identified by diffusion weighted imaging (DWI) for retrospective review.Patients were divided into two groups according to their clinical symptoms:patients with ND and patients without ND.According to neuroimaging of DWI,the topographic location of pontine infarction was divided into three types:The upper,middle,and lower ones,and the correlations of ND with risk factors,laboratory examination results,clinical manifestations and different topographic locations were explored by statistical tests.Results Of 168 patients,26.8% (45/168) were diagnosed with ND,and 73.2% (123/168) were diagnosed without ND.Univariate analysis showed that there were differences in female ratio [62.2% (28/45) vs 41.5% (51/ 123)],smoking ratio [13.3% (6/45) vs 26.0% (32/123)],mean length of hospital stay [(22.83 ± 7.12)d vs (19.31 ± 7.65)d],ratio of worse short-term clinical outcomes [77.8% (35/45) vs 33.3% (41/123)],and ratio of lower pontine infarction [55.6% (25/45) vs 26.0% (32/123)] between two groups (P < 0.05).Logistic regression analysis showed that lower pontine infarction was the independent risk factor of ND (OR =1.953,95% CI:1.092-3.535,P =0.029).Conclusions Topographic location of lower pons lesions may be reliable predictor of ND in acute new isolated pontine infarction.
6.Correlation analysis between clinical features and renal dysfunction in patients of acute lacunar infarction with progressive cerebral microbleeds
Qingchun FENG ; Da HUANG ; Shaomin HU ; Biying WU ; Xingwen WANG ; Fu LIANG ; Xiaoli CHEN ; Meijuan PENG
Chinese Journal of Postgraduates of Medicine 2017;40(9):817-820
Objective To analyze the correlation between clinical features and renal dysfunction in patients of acute lacunar infarction with progressive cerebral microbleeds (CMBs). Methods Two hundred and sixty-five patients with first-episode acute lacunar infarction were selected. The serum creatinine was measured within 24 h of admission and the estimated glomerular filtration rate (eGFR) was calculated. The brain MRI (including gradient-echo images) was examined within 2 d of admission and after 1 years of follow-up, respectively. The progressive CMBs was assessed with microbleeds anatomical rating scale (MARS), and the patients were divided into progressive CMBs group (progressive group, 42 cases) and non progressive CMBs group (non progressive group, 223 cases). The clinical features of 2 groups were compared and the correlation between progressive CMBs and renal dysfunction was analyzed. Results The age, 24 h pulse pressure, incidences of renal dysfunction and CMBs in progressive group were significantly higher than those in non progressive group: (69.8 ± 5.8) years vs. (61.5 ± 4.9) years, (63.3 ± 3.1) mmHg (1 mmHg=0.133 kPa) vs. (51.8 ± 4.2) mmHg, 69.0%(29/42) vs. 39.9%(89/223) and 57.1%(24/42) vs. 25.1%(56/223), and the platelet was significantly lower than that in non-progression group:(168 ± 35) ×109/L vs. (189 ± 40) ×109/L, and there were statistical differences (P<0.05 or<0.01). The Logistic regression analysis result showed that renal dysfunction and CMBs were Independent risk factors of progressive CMBs (OR = 1.571 and 1.054, 95% CI 1.042 - 2.493 and 1.010 - 1.142, P<0.05). Conclusions The rate of renal dysfunction is higher in patients of acute lacunar infarction with progressive CMBs, and progressive CMBs are associated with renal dysfunction.
7.Epidemiological Trends of Leprosy in Fujian Province
Wenbin WU ; Biying YU ; Dainan ZHENG
Chinese Journal of Dermatology 2000;0(S1):-
Objectives To reveal the epidemiological trends of leprosy and the achievements of leprosy control in Fujian Province. Methods In the light of methods of Basic Statistics in Handbook of Leprosy Control written by Ma Hai De, each statistic index was analyzed. Results① The incidence and detection rate decreased from 0.782/10 000 and 1.231/10 000 in the period of 1955~ 1959 to 0.036/10 000 in the period of 1990~ 1994 and to 0.033/10 000 in the period of 1995~ 1998 respectively;② prevalence dropped from the highest of 0.65‰ in 1959 to 0.007‰ in 1998;③ with the elapse of time, the average age at onset showed a shift to advance age group, and incidence of leprosy in children decreased dramatically;④ the ratio of MB to PB was higher in early period and in late period than that in middle period, and the male ratio of MB to PB was always higher than female ratio;⑤ the average disease duration reduced, and the disability rate of new cases decreased. Conclusion Through the comprehensive measures against leprosy, the endemic of this disease in Fujian Province has been evidently under control.
8.Molecular composition of Enzymolyzed Anchovy Soluble Peptide and its of Nutrition Evaluation
Biying ZHU ; Jinchao WU ; Xigang HU
Chinese Journal of Marine Drugs 1994;0(04):-
The peptides molecular compositions and the amino acids component of the enzymolyzed protein of anchovy soluble peptides hydrolysed by pepsin and trypsin were assayed and determined by gel HPLC and amino acid analytical instrument.The molecular weight of the peptides is less than 7400, of which 1.74 percent is a large peptide chain with composition of 52~58 amino acids and 6600~7400 molecular weight,29.75 percent is a middle large peptide with 20~41 amino acids and 2500~5300 molecular weight , and 50 percent is a oligo-peptide with 2~10 amino acids and less than 1000 molecular weight. The proportion of total nitrogen to rree amino acid nitrogen is 25.9:1 in the hydrolysates. 96 pecent of amino acid exists in form of peptides and 4 percent are free amino acids. The con tent of whole amino acids accounts for 73.98 percent soluble peptides, and the essential amino acid is 32.39 percent or 43.78 percent of the whole amino acids .Comparing whth FAO/WHO , the phenylalanine expresses in the first limited amino acid with the amino acid score of 61. Based on the analysis results, the balance of amino acid composition pf anchovy loluble peptides and the physiological function of loigo-peptide in an animal organism were explored.
9.STUDY ON PHARMACOKINETICS OF TMPH FOR INTRAVENOUS INJECTION IN RAT
Zhili HUANG ; Chen ZHOU ; Biying WU ; Ruiyuan SUN
Chinese Pharmacological Bulletin 1986;0(04):-
Pharmacokinetics of Tetramethylpyrazine Hydrochloride (TMPH) in rat was studied by using Ultraviolet Spectrophotometry. After a bolus iv injection of TMPH 30 mg/kg to rat, the pharmacokinetic characteristics are found to fit a two-compartment open model. The Pharmacokinetic parameters are: t 1/2? = 0 .1441h, t 1/2? = l .6953h, K21=2.1850h-1, K10=0.8605h-1, K12= 2 .0723h-1, AUC = 83 .3660mg?L -1h, CL = 0.3599L?kg-1h-1, Yc =0 .4182L?kg-1 , Vss =0 .7975L.kg-1

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