To map the super-enhancers remodeling of intestinal gastric cancer and reveal the tumor biological functions of the super-enhancers and the downstream target genes that may be activated.

A total of 31 normal gastric mucosal tissues，23 intestinal gastric cancer tissues and 9 intestinal gastric cancer organoids were collected from the Department of Gastroenterology of Army Medical Center of PLA from January to December 2022. Chromatin targeting histone H3K27ac modified chromatin targeting cleavage under targets and tagmentation （CUT&Tag） sequencing was conducted on above tissues. The remodeling profiles of super-enhancers in intestinal gastric cancer were analyzed and the key target genes were identified based on bioinformation tools. CRISPRi technology was used to intervene with the super-enhancers，the expression of target genes was detected with Western blotting，and the proliferation，migration and invasion abilities were detected by CCK-8 assay and Transwell chambers in the control group and the intervention group.

There was a significant difference in the signal of super-enhancers between intestinal gastric cancer tissues and normal gastric mucosal tissues （P<0.05），and the active super-enhancers in cancer tissues may be involved in biological processes such as negative regulation of the immune system and cell adhesion. The expression of up-regulated cell migration-inducing protein （CEMIP） in tumor cells was regulated by the super-enhancers，and intervening the super-enhancers down-regulated the expression of CEMIP （P<0.05），and inhibited the cell proliferation，invasion and migration abilities of tumor cells （P<0.05）.

Super-enhancer remodeling is observed in intestinal gastric cancer，and they can up-regulate the expression of CEMIP gene and promote the growth，migration and invasion of cancer cells.

To investigate the diagnostic value of endoscopic sign of light blue crest (LBC) capsuling papillary lesion (LCPL) for high-risk intestinal metaplasia (IM).

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).

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).

LCPL sign shows high efficacy and potential clinical application value for high-risk IM in gastric mucosa of endoscopic diagnosis.

To draw the genome-wide distribution and remodeling characteristics of H3K27me3 silencers in signet-ring cell carcinoma of the stomach (SRCC) through epigenetic sequencing technology, and to investigate their roles in transcriptional regulation in order to elucidate the regulatory mechanism of SRCC malignant progression.

The study was conducted on 35 gastric samples obtained by gastroendoscopic biopsy (15 normal and 20 SRCC tissues) from Department of Gastroenterology of Army Medical Center of PLA between January 2021 and December 2023. Multi-omics analyses, including assay for transposase-accessible chromatin with high-throughput sequencing （ATAC-seq), cleavage under targets and tagmentation （CUT&Tag) and transcriptome sequencing （RNA-seq), were performed to identify chromatin accessibility, H3K27me3 silencer regions, and transcriptional changes, with aid of Illumina NovaSeq 6000. H3K27me3 related differentially expressed genes (|Log₂FC|>1, FDR<0.05) were screened using DESeq2. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were employed to analyze the enrichment function, and Homer was employed to identify transcription factor motifs. A regulatory network was constructed using Cytoscape, and then validated using immunohistochemistry to explore its regulatory mechanism.

H3K27me3 silencers were primarily located in distal intergenic regions (37.06%) in SRCC. Compared with the normal tissues, SRCC showed a significant reduction in H3K27me3 silencer signals (95%CI:1.34~2.30, P=0.007) with 6 257 lost sites (FDR<0.01). Integrating CUT&Tag and RNA-seq revealed 380 up-regulated immune-related genes, particularly in T cell receptor signaling (OR=4.2, 95%CI: 2.8~6.3, P=0.002). Immunohistochemistry confirmed elevated expression of transcription factor EHF (P<0.05).

There is the remodeling of H3K27me3 silencers in SRCC, and EHF may potentially play a crucial role in the SRCC malignant progression.

To identify the enhancer profile marked by histone H3K27ac modification in high-grade intraepithelial neoplasia (HGIN) in order to reveal the novel regulatory mechanism of HGIN pathogensis.

Gastric tissue samples were collected from Department of Gastroenterology of Army Medical Center of PLA between June 2022 and June 2023, including 14 normal gastric tissues (Nor group), 31 HGIN tissues (HGIN group) and 17 gastric cancer tissues (GC group). Cleavage under targets and tagmentation (CUT&Tag) technique was employed to capture enhancer regions modified by histone H3K27ac. Multi-omics analysis was performed to identify HGIN-specific active enhancers and their potentially regulated genes. Immunohistochemical profiling was performed to assess differential expression of the gene of interest across clinically stratified specimens, combined with CRISPR-dCas9-mediated ablation of active enhancers to monitor the gene of interest transcriptional dynamics and validate enhancer-mediated regulatory mechanisms.

Epigenomic sequencing obtained the data with excellent quality, and indicated that obvious remodeling was observed in H3K27ac enhancers in HGIN and GC groups (P<0.05), though no significant difference in the genome-wide distribution of H3K27ac modification among the 3 groups.Combining transcriptome data revealed that enhancer remodeling may up-regulate the expression of the proliferation-related target gene, CD24, in the HGIN tissue; while, inhibiting enhancer activity can notably reduce CD24 expression level (P<0.05). Immunohistochemical assay displayed a positive correlation between the expression levels of CD24 and Ki-67 (P<0.001).

The remodeling of H3K27ac enhancer represents a significant epigenetic feature of the transformation from normal condition to HGIN. Remodeling of H3K27ac enhancer up-regulates CD24, which may facilitate the abnormal proliferation of gastric epithelial cells.

To investigate the expression of calumenin (CALU) in gastric cancer and its effect on metastasis and invasion of gastric cancer, and analyze its relationship with the prognosis of gastric cancer patients.

The Cancer Genome Atlas (TCGA) database was used to analyze the expression level of CALU in gastric cancer and its impact on patient prognosis. A total of 102 pairs of gastric cancer and paracancerous tissue samples were collected from 189 gastric cancer patients who underwent partial gastrectomy in First Affiliated Hospital of Army Medical University from January 2018 to December 2022. The expression of CALU in gastric cancer and paracancerous tissues was detected by immunohistochemical assay, and the relationship of its expression with clinicopathological parameters was statistically analyzed. After gastric cancer cells with CALU knockdown and overexpression were constructed, and the efficiencies of knockdown and overexpression were evaluated by Western blotting as well as RT-qPCR. Transwell assay was applied to determine the effect of CALU on the migration and invasion abilities of gastric cancer cells.

Bioinformation analysis found that CALU was significantly highly expressed in gastric cancer tissues (P<0.05), and its expression level was negatively correlated with the prognosis of patients (P<0.05). Immunohistochemical results showed that the expression level of CALU was obviously highly in gastric cancer tissues than the paracancerous tissues (P<0.01), and its level was positively correlated with the depth of infiltration (P<0.01), lymph node metastasis (P<0.01), and TNM stage (P<0.05). Statistical analysis revealed that the clinical data of 102 patients showed that CALU expression was positively correlated with the TNM stage (P=0.021) and T stage (P<0.001) and N stage (P=0.028). CALU knockdown significantly inhibited the migration and invasion abilities of gastric cancer cells (P<0.01), while over-expression obtained the opposite results.

CALU is highly expressed in gastric cancer tissues and promotes metastasis and invasion of gastric cancer and thus leads to poor prognosis in patients.

To analyze clinical characteristics of mesenchymal-subtype gastric cancer (Mes-GC) by integrating multi-omics data and explore the characteristics of tumor cells and microenvironment associated with the risk for recurrence.

Gastric tumor tissue samples were collected from the patients who visited Department of Gastroenterology of Army Medical Center of PLA from January 2022 to December 2023. Transcriptome and genome sequencing were applied for these tissue samples, including 19 cases of diffuse-type gastric cancer, 22 cases of intestinal-type gastric cancer, and 23 cases of mixed-type gastric cancer patients. Bioinformatics analysis was employed to investigate the differences in clinical characteristics and tumor microenvironment between Mes-GC and non-mesenchymal-subtype gastric cancer (non-Mes-GC) by integrating data resources including The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and National Genomics Data Center (NGDC).

Compared to non-Mes-GC patients, Mes-GC ones were characterized by later clinical stages, deeper tumor infiltration, and higher rates of lymph node metastasis. Kaplan-Meier survival analysis confirmed that Mes-GC patients were associated with shorter survival time, poor prognosis as well as increased risk of cancer recurrence （P<0.05）. Single-cell RNA sequencing data revealed that tumor cells in Mes-GC showed higher expression levels of the genes related to stemness, metastasis （P<0.05）, and epithelial-mesenchymal transition (EMT). And in the tumor microenvironment, there were significant more myeloid cells, smooth muscle cells, endothelial cells and fibroblasts, with the most pronounced elevation in the proportion of fibroblasts （P<0.05）. Moreover, the patients with larger proportion of fibroblasts were associated with poorer prognosis.

Mes-GC tumor cells exhibit higher stemness and EMT characteristics, and stromal cells such as myeloid cells, endothelial cells, and fibroblasts are enriched in the tumor microenvironment. These features may be key factors contributing to poor prognosis and high recurrence rate of Mes-GC.

To construct an in vitro co-culture model of gastric cancer organoids and cancer-associated fibroblasts (CAFs), and investigate the role of cancer-associated fibroblasts in the proliferation and chemotherapy resistance of gastric cancer organoids.

Tumor tissues from 12 gastric cancer patients undergoing surgical treatment in Department of General Surgery of Second Affiliated Hospital of Army Medical University from February 2023 to March 2024 were collected to construct gastric cancer organoids using 3D culture. HE staining was used to observe the morphology, and immunohistochemical assay was employed to determine the expression of cytokeratin CK7, carcinoembryonic antigen (CEA), and proliferation marker Ki-67. After CAFs derived from the same patient were cultured, observed for their morphology under a light microscope, and detected for the phenotype by flow cytometry, the cells were co-cultured with gastric cancer organoids in a 1:1 ratio. Phase-contrast microscopy was applied to observe the growth of the organoids and analyze the number, average diameter, and total area. Then, organoids cultured alone served as the control group. After the control and co-culture groups were treated with chemotherapy drugs, 5-fluorouracil and oxaliplatin, for 48 h, the viability and apoptosis of organoids were assessed with CellTiter-Glo^® 3D assay and CellEvent™ Caspase 3/7 activity, respectively.

Gastric cancer organoids and CAFs were successfully established from 10 gastric cancer patient-derived samples. The gastric cancer organoids exhibited morphological characteristics consistent with the corresponding primary tumors, and showed positive expression of CK7, CEA, and Ki-67. CAFs displayed typical spindle-shaped morphology and exhibited the phenotypic markers CD326^-, CD45^-, CD31^-, α-SMA⁺, CD73⁺, CD90⁺, and CD105⁺. Compared to the organoids cultured alone, the organoids co-cultured with CAFs showed more formation of organoids, in larger average diameter, and taking larger total area (P<0.05). After the treatment of 5-fluorouracil and oxaliplatin, the half-maximal inhibitory concentration (IC₅₀) was 10.66 and 3.26 μmol/L, respectively in the control group, while was 46.23 and 91.11 μmol/L in the co-culture group. Additionally, the number of CellEvent™ Caspase 3/7 positive apoptotic cells was significantly less in the co-culture group than the control group.

Compared with individually cultured gastric cancer organoids, the co-culture model of gastric cancer organoids and CAFs better simulates the pro-tumor proliferation and drug resistance effects of in vivo tumor microenvironment.

To explore the risk factors of hospitalization within 24 h after birth and respiratory support in late preterm and term neonates.

A case-control study was conducted on 1 468 neonates with gestational ages ≥34 weeks and <42 completed weeks delivered at the University-Town Hospital of Chongqing Medical University from January 2023 to March 2024. Maternal health parameters and neonatal outcomes were systematically obtained through standardized case report forms during the study period. The neonates were stratified into the hospitalization group and the non-hospitalization group based on neonatal ward admission within 24 h. For those hospitalized with infectious diseases, subgroup analysis was conducted with further categorization into respiratory support and the non-respiratory support subgroups according to ventilatory assistance requirements. The perinatal risk factors were compared between groups and subgroups, and the independent risk factors for hospitalization and the need for respiratory support within 24 h in neonates were identified. The indicators with P<0.1 in the univariate analysis were included in the multivariate logistic regression analysis, and the stepwise regression analysis was used to fit the multivariate logistic regression model.

There were 213 cases (14.5%) in the hospitalization group and 1 255 cases (85.5%) in the non-hospitalization group. A total of 150 neonates were hospitalized due to infectious diseases, including 48 cases (32.0%) in the respiratory support subgroup and 102 cases (68.0%) in the non-respiratory support subgroup. The multivariate logistic regression analysis showed that non-regular maternal prenatal examination (OR=2.687, 95%CI: 1.175~6.141, P=0.019), intrauterine growth retardation (OR=2.711, 95%CI: 1.106~6.646, P=0.029), premature rupture of membranes (OR=1.667, 95%CI: 1.139~2.438, P=0.008), chorioamnionitis (OR=4.852, 95%CI: 2.114~11.135, P<0.001), infectious diseases in the first week before delivery (OR=1.531, 95%CI: 1.015~2.310, P=0.042), turbidity of amniotic fluid (OR=3.170, 95%CI: 2.099~4.787, P<0.001), abnormal placenta (OR=2.335, 95%CI: 1.202~4.534, P=0.012), complications during pregnancy (OR=2.367, 95%CI: 1.360~4.118, P=0.002), and the use of glucocorticoids before delivery (OR=2.744, 95%CI: 1.219~5.528, P=0.009) were positively correlated with hospitalization within 24 h postnatally in late preterm and term neonates. Gestational age (OR=0.693, 95%CI: 0.602~0.797, P<0.001), 5-minute Apgar score (OR=0.026, 95%CI: 0.003~0.212, P=0.001), umbilical cord blood pH (OR=0.044, 95%CI: 0.002~0.793, P=0.034), and umbilical cord blood BE (OR=0.885, 95%CI: 0.823~0.823, P=0.001) were negatively correlated with it. Premature rupture of membranes (OR=0.207, 95%CI: 0.070~0.618, P=0.005), infectious diseases in the first week before delivery (OR=0.245, 95%CI: 0.070~0.854, P=0.027), 5-minute Apgar score (OR=0.063, 95%CI: 0.008~0.526, P=0.011), and abnormal C-reactive protein of newborns (OR=0.145, 95%CI: 0.046~0.460, P=0.001) were negatively correlated with the need for respiratory support in neonates hospitalized due to infectious diseases.

Risk factors for neonatal hospitalization within 24 h postnatal late preterm and term are identified as irregular antenatal care, fetal growth restriction and premature rupture of membranes in late preterm and term neonates. premature rupture of membranes, antenatal maternal infections within 1 week prior to delivery and 5-minute Apgar score ≥7 emerge as significant protective factors against respiratory support requirement in neonates hospitalized with infectious diseases.

To explore the efficacy of goal management training (GMT) on core symptoms and mental status in college students with attention deficit hyperactivity disorder (ADHD) inattentive type.

Delphi method was used to construct a GMT program for college students with inattentive ADHD. Then, totally 68 college students with inattentive ADHD were recruited through advertisements published by hospitals and universities (Second Affiliated Hospital of Army Medical University, and 3 universities in Chongqing from March to June 2024. The subjects were randomly divided into an intervention group (n=34) and a control group (n=34). The intervention group received GMT for 2 h, once a week, for 7 weeks, and the control group did not receive training for the time being. The 2 groups were evaluated within 1 week before and in 7 weeks after intervention by using Adult ADHD Self-Report Scale (ASRS), Dysregulation of Emotions Rating Scale (DERS), Generalized Anxiety Disorde-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Self-Compassion Scale (SCS), and Satisfaction with Life Scale (SWLS).

① The expert authority coefficient (Cr) of 2 rounds of expert consultation was 0.83, with a questionnaire recovery rate of 100% and 95%, respectively, the Kendall’s coordination coefficient was 0.081 (P<0.01) and 0.226 (P<0.01), and the coefficient of variation was <0.3, indicating the results of the expert consultation were reliable. The constructed GMT program includes 1 first-level indicator, 7 second-level indicators, and 20 third-level indicators. ② After 7 weeks of GMT intervention, the interaction between the 2 groups and time showed that the experimental group obtained significant improvements than the control group in terms of inattention symptoms (Wald Chi-square=28.35, P<0.001), dysregulation of emotions (Wald Chi-square=23.81, P<0.001), anxiety (Wald Chi-square=22.79, P<0.001), depression (Wald Chi-square=20.52, P<0.001), self-compassion (Wald Chi-square=9.36, P<0.01), and life satisfaction (Wald Chi-square=3.97, P<0.05).

GMT intervention can significantly improve the core symptoms of college students with inattentive ADHD, reduce anxiety and depression levels, enhance their emotion regulation and self-compassion abilities, and improve their life satisfaction.