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.

OBJECT IVE To study the effects of ergosterol peroxide derivatives EP-3P on the proliferation ，migration and invasion of human tripe negative breast cancer cell MDA-MB- 231，and to provide reference for the development of breast cancer related drugs. METHODS MTT assay was adopted to detect the proliferation of MDA-MB- 231 cells after treated with 0（blank control），1.25，2.5，5，10，20，40 μmol/L EP-3P for 24，48 and 72 h. Wound healing assay and Transwell chamber method were adopted to detect the migration and invasion ability of MDA-MB- 231 cells after treated with 0（blank control ），5，10，20 EP-3P for 24 h. The apoptosis and cell cycle distribution were detected by flow cytometry. Western blot assay was used to detect the expressions of B-cell lympho ma-2（Bcl-2），Bcl-2 associated X protein （Bax），caspase-3，cleaved-caspase-3，cytochrome C （Cyt-C），matrix metalloproteinase- 2（MMP-2）and MMP- 9. RESULTS Compared with blank control group ，2.5，5，10，20，40 μmol/L EP-3P could significantly increase the inhibitory rate of cell proliferation （P＜0.05 or P＜0.01）in a dose and time- dependent manner. After 24 h treatment of EP- 3P（10，20 μmol/L），the rate of cell migration and the number of invasive cells were decreased significantly （P＜0.01），and cell was arrested at G 2/M stage （P＜0.05 or P＜0.01）；the apoptotic rate was increased significantly （P＜0.05）；the protein expressions of Bax ，Cyt-C and cleaved-caspase- 3 were upregulated significantly ， while those of Bcl- 2，caspase-3，MMP-2 and MMP- 9 were downregulated significantly （P＜0.01）. CONCLUSIONS EP-3P can inhibit the proliferation ，migration and invasion of human tripe negative breast cancer cells MDA-MB- 231 through mitochondrial mediated endogenous caspase pathway ，and induce the apoptosis of cells .

Objective To explore the Gram-positive bacterial drug resistance in blood culture in 2013 to 2015 from the members of Antimicrobial Resistant Investigation Net of Shaanxi province,and guide the clinicians touse antimicrobial drugs rationally.Methods All the objective bacterial isolates were collected and identified susceptibility date by software WHONET 5.6.Results 8 824 Gran positive bacterial isolates and their antibacterial susceptibilitydata were collected.The top five populations of Gram-positive bacterial isolates were Staphylococcus epidermidis,Staphylococcus hominis,Staphylococcus haemolyticus,Staphylococcus aureus and Enterococcus feacium.The isolating rates of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase negative Staphylococcus(MRCNS) were 33.9 ～ 54.9％ and 72.1 ～88.6 ％ respectively.No vancomycin,Linezolid and teicoplanin resistant Staphylococcus isolates were found.There were 0.9 ～2％ E.faecium vancomycin-resistant isolates.Conclusion The composition of blood culture from 2013 to 2015 was not changed,The rate of MRSA and MRSE showed downward trend.But it was severe that the situation of bacterial drug resistance in blood culture in Shaanxi province.Should fully use bacterial drug resistance surveillance results for supervision and administration,and take effective measures for controlling the spread of resistant isolates.

Objective To establish a mouse model of H.pylori infection, and to evaluate the chronic pathological changes in the gastric mucosa associated with H.pylori infection.Methods 34 male 5~6-week old SPF C57BL/6 mice were used in this study.The mice were intragastrically administrated with a suspension of H.pylori SS1 strain.Two weeks after infection, rapid urease test and PCR were performed to confirm the H.pylori infection.Successfully infected mice were randomly divided into 3 groups including the control group, 6-week and 12-week infected groups.Samples of gastric mucosa were taken for pathological analysis using HE and borax methylene blue staining.The contents of myeloperoxidase (MPO), superoxide dismutase (SOD), malondialdehyde (MDA) and catalase (CAT) in the gastric tissues were detected by biochemistry, and the expression levels of COX-2, iNOS, TNF-α and IL-1β were examined by RT-qPCR.Results Compared with the control group, H.pylori colonization was observed in the gastric mucosa of the 6-week and 12-week infected mice, with chronic inflammatory cell infiltration, glandular atrophy and intestinal metaplasia to varying extents.The contents of CAT and SOD were significantly decreased, while the levels of MPO and malonaldehyde MDA, and the expression levels of COX-2,iNOS,TNF-α and IL-1β were significantly increased (P<0.05 or P<0.01).Conclusions Intragastric administration with H.pylori in C57BL/6 mice can be successfully used to generate the bacterial colonization, leading to chronic inflammatory cell infiltration, enhanced oxidative stress, and up-regulated expression of proinflammatory genes in the gastric glandular tissues at 6 and 12 weeks after inoculation.However, the inflammatory changes are more extensive in the mice at 12 weeks after infection, with glandular atrophy and intestinal metaplasia.

AIM To speculate the hypoglycemic mechanism for rats with type 2 diabetes by exploring the therapeutic effects of leaf aqueous extract from Cyclocarya paliurus on liver insulin receptor (InsR) and insulin receptor substrate 2 (IRS-2).METHODS The diabetic rat model was established through intraperitoneal injection of streptozotocin and fed with high-fat diet.The moleled rats were equally assigned into the control group and leaf aqueous extract from Cyclocarya paliurus group (extract group).After the test extract was orally administrated for four weeks,body weight,urine output,food intake,water intake and fasting blood-glucose (FBG) were measured,and the levels of serum insulin,InsR and IRS-2 mRNA in liver tissue were investigated in rats.RESULTS Compared with the control group,the extract group showed a reduction in urine output,food intake,water intake,FBG and insulin levels.Meanwhile,the rats' body weights in extract group were presented a trend to increase.The gene expressions of InsR and IRS-2 in liver tissue were up-regulated.Moreover,the insulin sensitivity was improved.CONCLUSION The leaf aqueous extract from Cyclocarya paliurus can reduce FBS,improve insulin sensitivity,which may be associated with the increase of InsR and IRS-2 gene expression in liver tissue.

Objective To investigate the changes of the morphology,structure and biological characters of mutated Candida and through its genetic characteristics,research and reveal the mechanism of the variation at the molecular level.Methods Used different nutritional conditions,different growth conditions and different azole antifungal agents to induce mutation of the standard strains of Candida albicans.In clinical study,Candida mutant strains was isolated from vaginal secretions,pleu-ral effusion and gastric juice samples in patients of poor effect with Antifungal therapy,and studied on the morphological characteristics,and the nuclear structure,the biochemical reaction,the drug resistance,the bacterial composition and the ge-netic characteristics of above variants,etc.Results Mycelial?morphology:Candida were prone to mutation like bacteria, mutant bacteria could show G+ Aureus shape,G+ Bacillus,G+ long filamentous,G- Aureus shape,G- Bacillus and G- long filamentous;Nuclear structure:Candida mutant strains changed like prokaryotes under the electron microscope because it lost the original structure of eukaryotic cells.Biochemical reaction:there were 5 different items in 20 biochemical test ob-served.Drug sensitivity test:Candida mutated to antifungal drugs being originally sensitive was completely resistant,sensi-tive and resistant originally was completely sensitive,and the same as ordinary bacteria resistant.The cell component chan-ges:there was significantly different in Candida variant strain and the atavism of variant strain identified by mass spectrome-try.The most conservative fungalgene expression:Candida mutated had conservative gene expression of eukaryotes.It could be demonstrated that oidiomycetes mutant strains like bacterial morphology with prokaryotic cell biological characteristics was derived from Candida with eukaryotic cells.Conclusion Candida was prone to variation like bacterial morphology.The biological characteristics of mutant resembled prokaryote.There was a qualitative change among the standard strains of Can-dida albicans,mutant strains of oidiomycetes like bacterial morphology and the atavism of variant strain with clear genetic re-lationship under the electron microscope in the form of nuclear matter.The study on biological evolution,especially contact in prokaryotic cells and eukaryotic evolution has very important significance.