The impact of sleep quality on emotion regulation difficulties in adolescents: a chained mediation model involving daytime dysfunction, social exclusion, and self-control.

OBJECTIVE: Previous studies have revealed associations between sleep quality and mental health, yet the comprehensive role of sleep quality, daytime dysfunction, social exclusion, and self-control in difficulties with emotion regulation remains unclear. This study aimed to elucidate how sleep quality affects emotion regulation difficulties among middle school students through pathways involving daytime dysfunction, social exclusion, and self-control, thereby providing a more comprehensive theoretical basis for mental health interventions. METHODS: Utilizing the pittsburgh sleep quality index, the adolescent social exclusion scale, the brief self-control scale, and emotion regulation scale-short form, we assessed 1067 students randomly selected from four middle schools from October to November 2023. After the removal of extreme values (those exceeding 3 standard deviations), 806 students were retained for data analysis. RESULTS: Our findings indicate that poor sleep quality significantly contributes to increased daytime dysfunction(ß = 0.86, SE = 0.07, p < .001), which in turn affects social exclusion(ß = 0.60, SE = 0.16, p < 0 0.001), self-control abilities(ß = 1.27, SE = 0.16, p < .001) and emotion regulation difficulties(ß = 1.56, SE = 0.30, p < .001). Social exclusion mediates the relationship between sleep quality and emotion regulation difficulties(Estimate = 0.11, SE = 0.04, 95% CI [0.04, 0.20] ). CONCLUSION: The aim of this study is to provide new insights into the development of effective intervention measures to improve sleep and mental health in adolescents.

Construction of a prognostic risk model based on apoptosis-related genes to assess tumor immune microenvironment and predict prognosis in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a serious malignant disease with high incidence, high mortality and poor prognosis. This study aimed to establish a novel signature based on apoptosis-related genes (ARGs) to predict the prognosis of HCC. METHODS: Expression data of HCC from TCGA database and the list of 160 ARGs from MSigDB were downloaded. The genes included in apoptosis-related signature were selected by univariate Cox regression analysis and lasso Cox regression analysis. Subsequently, a prognostic risk model for scoring patients was developed, and then separates patients into two groups. Kaplan-Meier and receiver operating characteristic analysis were performed to evaluate the prognostic value of the model in TCGA, GEO and ICGC databases. The characteristics of immune cell infiltration between two groups of HCC were investigated. Finally, a nomogram was plotted to visualize the prognosis prediction. RESULTS: Nine genes (CDC25B, DAP3, ETF1, GSR, LGALS3, MGMT, PPP2R5B, SQSTM1 and VDAC2) were included in the prognostic risk model. Survival was lower in the high-risk group. Surprisingly, the high-risk group was significantly more in immune cell infiltration and with higher immunoscore and stromalscore than in the low-risk group. In addition, the risk score was an independent prognostic factor for HCC. CONCLUSIONS: Prognostic signature comprising nine ARGs could be used as a potential prognostic factor for HCC. It also provides an important idea for further understanding the immunotherapy of HCC.

piR-823 contributes to colorectal tumorigenesis by enhancing the transcriptional activity of HSF1.

Piwi-interacting RNAs (piRNAs), a novel class of small non-coding RNAs, were first discovered in germline cells and are thought to silence transposons in spermatogenesis. Recently, piRNAs have also been identified in somatic tissues, and aberrant expression of piRNAs in tumor tissues may be implicated in carcinogenesis. However, the function of piR-823 in colorectal cancer (CRC) remains unclear. Here, we first found that piR-823 was significantly upregulated in CRC tissues compared with its expression in the adjacent tissues. Inhibition of piR-823 suppressed cell proliferation, arrested the cell cycle in the G1 phase and induced cell apoptosis in CRC cell lines HCT116 and DLD-1, whereas overexpression of piR-823 promoted cell proliferation in normal colonic epithelial cell line FHC. Interestingly, Inhibition of piR-823 repressed the expression of heat shock protein (HSP) 27, 60, 70. Furthermore, elevated HSPs expression partially abolished the effect of piR-823 on cell proliferation and apoptosis. In addition, we further demonstrated that piR-823 increased the transcriptional activity of HSF1, the common transcription factor of HSPs, by binding to HSF1 and promoting its phosphorylation at Ser326. Our study reveals that piR-823 plays a tumor-promoting role by upregulating phosphorylation and transcriptional activity of HSF1 and suggests piR-823 as a potential therapeutic target for CRC.

Knockdown of Astrocyte Elevated Gene-1 Inhibits Activation of Hepatic Stellate Cells.

BACKGROUND: Astrocyte elevated gene-1 (AEG-1) is a positive regulator of tumorigenesis and a valuable prognostic marker of a diverse array of cancers, including liver cancer; however, the relationship between AEG-1 and hepatic fibrogenesis is not known. OBJECTIVE: The objective of this study was to explore the expression of AEG-1 during hepatic fibrogenesis and determine how AEG-1 regulates the profibrogenic phenotype of hepatic stellate cells (HSCs). METHODS: The levels of AEG-1 were monitored in the fibrotic livers and transforming growth factor-ß (TGF-ß)- or lipopolysaccharide (LPS)-stimulated HSCs. The expression of AEG-1 was knocked down by lentivirus-mediated short hairpin RNA in HSCs, and collagen expression, proliferation assays, apoptosis induction studies, and migration assays were simultaneously conducted in vitro. RESULTS: AEG-1 expression was increased in the fibrotic livers. At the cellular level, TGF-ß or LPS stimulation, which caused HSC activation, induced AEG-1 expression in HSC-T6 and primary rat HSCs (P < 0.05). Knockdown of AEG-1 inhibited collagen I and α-smooth muscle actin expression (P < 0.05), reduced cell proliferation (P < 0.05) and motility (P < 0.05), and induced cell apoptosis (P < 0.05) in HSCs. This antifibrotic effect caused by lack of AEG-1 was associated with the inactivation of PI3K/Akt and the mitogen-activated protein kinase pathway. CONCLUSIONS: Knockdown of AEG-1 suppressed the activation of HSCs by modulating the phenotype and inducing apoptosis. AEG-1 might be a potential target in treatment of hepatic fibrosis.

[Antibiotic resistance of Helicobacter pylori clinical isolates in Hebei Province].

OBJECTIVE: To evaluate the resistance of Helicobacter pylori (H.pylori) clinical isolates to various antibiotics, in order to guide rational drug use in Hebei Province. METHODS: From January 2014 to July 2015, 260 patients with H. pylori infection who had not received eradication treatment were enrolled in Third Hospital of Hebei Medical University. Gastric mucosa biopsy tissue samples were collected from these patients before treatment for isolation and culture of H. pylori. Kirby-Bauer method was used to detect drug-resistance rate of the H. pylori clinical isolates to metronidazole, clarithromycin, amoxicillin, levofloxacin, and furazolidone. RESULTS: A total of 155 H. pylori strains were isolated from tissue samples of the 260 patients (positive rate, 59.6%). The drug-resistance rate of H. pylori isolated to metronidazole, clarithromycin, amoxicillin, levofloxacin, and furazolidone was 94.2%(146/155), 21.3%(33/155), 2.6%(4/155), 5.8% (9/155), and 1.9%(3/155), respectively. There was no statistically significant difference in positive culture rate and drug-resistance rate between different sex, age, and disease category(all P>0.05). CONCLUSION: In Hebei Province, the resistance rates of H. pylori to metronidazole and clarithromycin appear to be higher than those to amoxicillin, levofloxacin, and furazolidone.

Identification of Immune Infiltrating Cell-Related Biomarkers in Early Gastric Cancer Progression.

OBJECTIVES: Gastric cancer (GC) is one of the most prevalent malignancies worldwide, and early detection is crucial for improving patient survival rates. We aimed to identify immune infiltrating cell-related biomarkers in early gastric cancer (EGC) progression. METHODS: The GSE55696 and GSE130823 datasets with low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and EGC samples were downloaded from the Gene Expression Omnibus database to perform an observational study. Immune infiltration analysis was performed by single sample gene set enrichment analysis and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data. Weighted gene co-expression network analysis was used to explore the co-expression modules and genes, and further enrichment analysis was performed on these genes. A protein-protein interaction (PPI) network of these genes was constructed to identify biomarkers associated with EGC progression. Screened hub genes were validated by the rank sum test and reverse transcription quantitative polymerase chain reaction. RESULTS: Immune scores were significantly elevated in EGC samples compared to LGIN and HGIN samples. The green-yellow module exhibited the strongest correlation with both immune score and disease progression. The 87 genes within this module were associated with the chemokine signaling pathways, the PI3K-Akt signaling pathways, leukocyte transendothelial migration, and Ras signaling pathways. Through PPI network analysis, the hub genes identified were protein tyrosine phosphatase receptor-type C (PTPRC), pleckstrin, CD53, CD48, lymphocyte cytosolic protein 1 (LCP1), hematopoietic cell-specific Lyn substrate 1, IKAROS Family Zinc Finger 1, Bruton tyrosine kinase, and Vav guanine nucleotide exchange factor 1. Notably, CD48, LCP1, and PTPRC showed high expression levels in EGC samples, with the remaining hub genes demonstrating a similar expression trend. CONCLUSION: This study identified 9 immune cell-related biomarkers that may be actively involved in the progression of EGC and serve as potential targets for GC diagnosis and treatment.

Transcription factor Krüppel-like factor 4 upregulated G protein-coupled receptor 30 alleviates intestinal inflammation and apoptosis, and protects intestinal integrity from intestinal ischemia-reperfusion injury.

INTRODUCTION: Intestinal ischemia/reperfusion (I/R) injury is a common clinical event occurring during multiple clinical pathological processes. Here, we designed this paper to discuss the role of G protein-coupled receptor 30 (GPR30) playing in intestinal I/R injury. METHODS: An oxygen-glucose deprivation/reoxygenation (OGD/R) cell model was established to simulate the pathological process of I/R injury. With the application of enzyme-linked immunosorbent assay, TUNEL, and transepithelial electrical resistance (TEER) assays, the levels of inflammatory cytokines, cell apoptosis, and intestinal integrity were estimated. The corresponding proteins were estimated by applying western blot. Immunofluorescence was conducted to examine N-terminal Gasdermin D (GSDMD-N) expression. The interplay between KLF4 and GPR30 was demonstrated by dual-luciferase reporter assay and chromatin immunoprecipitation. RESULTS: The results showed that GPR30 was downregulated in Caco-2 cells exposed to OGD/R. GPR30 overexpression reduced the production of TNF-α, IL-6, IL-1ß, and IL-18, the TUNEL-positive cells, as well as the contents of p-p65, Cox-2, Inos, Bax, and cleaved-PARP, but elevated the expression of Bcl-2 in OGD/R-induced Caco-2 cells. In addition, OGD/R-induced the reduction of TEER value and reduced expression of tight junction proteins in Caco-2 cells, which was partially restored by GPR30 overexpression. Furthermore, GPR30 suppressed nod-like receptor pyrin 3 inflammasome and GSDMD-N expression. It was evidenced that Krüppel-like factor 4 (KLF4) could directly bind to GPR30 promoter and positively regulate GPR30 expression. The regulation of GPR30 overexpression above was weakened by KLF4 knockdown. CONCLUSION: Collectively, our findings suggested that KLF4 could transcriptionally upregulate GPR30, and GPR30 prevented intestine I/R injury by inhibiting inflammation and apoptosis, and maintaining intestinal integrity that provides potential targets for mitigating the I/R injury.

A Single-Center Follow-Up Study of Low-Grade Gastric Intraepithelial Neoplasia and the Screening of Key Genes of Precancerous Lesions.

Objective: The study aimed to summarize the morphological characteristics of low-grade gastric intraepithelial neoplasia (LGIN) and explore its outcomes and risk factors. Additionally, it aimed to screen the core different expression genes (DEGs) of high-grade gastric intraepithelial neoplasia (HGIN) using bioinformatics methods to identify biomarkers for early gastric cancer outcomes. Methods: The clinical and pathological data of 449 patients with LGIN in the endoscopy center of the Second Hospital of Hebei Medical University from June 2013 to September 2018 were collected for retrospective analysis. The GSE130823 and GSE55696 data sets were selected from the Gene Expression Omnibus database, and the GEO2R tool was used to screen DEGs in HGIN and chronic gastritis tissue types. A DEG functional enrichment analysis was conducted using the Database for Annotation, Visualization, and Integrated Discovery. The STRING database was utilized to create a protein-protein interaction network, and the CytoHubba plug-in was used to screen the key genes of HGIN. Results: The incidence of LGIN increased with age, and most of the patients were aged between 45-59 years (P = 0.048). Lesions were found mainly in the cardia, mostly in people aged 60 (P < 0.05). Progression occurred in 42 of 449 patients, with a 9.4% rate of cancer development. Foci larger than 10 mm, ulcerative lesions, and an Helicobacter pylori-positive result were factors affecting the outcome of LGIN (P < 0.05). Seven core genes of HGIN were screened, including MYC, SOX2, CDX2, TBX3, KRT7, CDKN2A, and MUC5AC. Conclusion: The patients with LGIN reflected the potential for developing cancer. A magnifying gastroscope can contribute to the detection of early gastric cancer. Additionally, the MYC, CDX2, and TBX3 genes may act as specific biomarkers of HGIN.

Small RNA sequencing revealed aberrant piRNA expression profiles in colorectal cancer.

Piwi­interacting RNAs (piRNAs), a novel class of non­coding RNAs, are enriched in germ cells and implicated in spermatogenesis. Emerging evidence demonstrated deregulated expression of piRNAs in numerous tumor types. However, changes in piRNA expression profiles in colorectal cancer (CRC) have not yet been investigated. In the present study, small RNA sequencing was used to evaluate the differences in piRNA expression profiles between CRC and adjacent non­tumor tissues, as well as to screen for differentially expressed piRNAs. The present results demonstrated that the percentage of unique piRNA reads had no notable difference between the paired CRC and adjacent non­tumor samples (0.12% vs. 0.13%); however, the counts of total piRNA reads in CRC samples were increased, compared with those in adjacent non­tumor samples (0.15% vs. 0.07%). Differential expression analysis identified 33 upregulated piRNAs and 2 downregulated piRNAs in CRC samples, among which piR­18849, piR­19521 and piR­17724 were the top three upregulated piRNAs. Reverse transcription­quantitative polymerase chain reaction further confirmed that the expression levels of piR­18849, piR­19521 and piR­17724 were increased in 80 CRC tissues, compared with paired adjacent non­tumor tissues. Furthermore, the high expression of piR­18849 and piR­19521 was associated with a poor degree of differentiation. The increased expression of piR­18849 was also associated with high lymph node metastasis. However, no associations were determined between piR­17724 expression and clinicopathological characteristics of patients. In summary, the present study is the first to provide an overview of the changes in piRNA expression patterns in CRC, shedding new light on the regulatory roles of piRNAs in colorectal carcinogenesis. piR­18849 and piR­19521 may be prognostic biomarkers for patients with CRC.

Internal biliary drainage superior to external biliary drainage in improving gut mucosa barrier because of goblet cells and mucin-2 up-regulation.

Backgroud: Obstructive jaundice increases intestinal permeability, but the pathological mechanisms remain obscure, which results in debates about the necessity of performing preoperative biliary drainage in patients with obstructive jaundice. Mucin-2 (MUC2) and goblet cells regulated by bile acids play an important role in maintaining the function of intestinal mucosal barrier. The present study was to investigate the role of goblet cells and MUC2 in obstructive jaundice and evaluate the effect of biliary drainage on intestinal permeability. STUDY DESIGN: We enrolled patients with malignant biliary obstruction and controls. We also did animal studies with four groups of rats: sham operation, obstructive jaundice, internal biliary drainage, and external biliary drainage. Histopathological analysis, biochemical measurement, and electron microscopy examination were done on pertinent samples. RESULTS: Compared with the control group, the small intestinal mucosa was significantly damaged; goblet cells and MUC2 were significantly decreased and serum endotoxin level was significantly increased in patients and rats with obstructive jaundice. Biliary drainage, especially internal biliary drainage, significantly increased goblet cells and MUC2 and attenuated the damage of small intestinal mucosa. CONCLUSIONS: In obstructive jaundice condition, goblet cells and MUC2 were reduced which were involved in the damage of intestinal mucosa barrier; biliary drainage increased goblet cells and MUC2, repaired mucosa layer and restored the intestinal mucosa barrier function.

Bile acid receptor TGR5 overexpression is associated with decreased intestinal mucosal injury and epithelial cell proliferation in obstructive jaundice.

Bile acids stimulate intestinal epithelial proliferation in vitro. We sought to investigate the role of the bile acid receptor TGR5 in the protection of intestinal epithelial proliferation in obstructive jaundice. Intestinal tissues and serum samples were obtained from patients with malignant obstructive jaundice and from bile duct ligation (BDL) rats. Intestinal permeability and morphological changes in the intestinal mucosa were observed. The functions of TGR5 in cell proliferation in intestinal epithelial injury were determined by overexpression or knockdown studies in Caco-2 and FHs 74 Int cells pretreated with lipopolysaccharide (LPS). Internal biliary drainage was superior to external biliary drainage in recovering intestinal permeability and mucosal histology in patients with obstructive jaundice. In BDL rats, feeding of chenodeoxycholic acid (CDCA) decreased intestinal mucosa injury. The levels of PCNA, a marker of proliferation, increased in response to CDCA feeding and were paralleled by elevated TGR5 expression. CDCA upregulated TGR5 expression and promoted proliferation in Caco-2 and FHs 74 Int cells pretreated with LPS. Overexpression of TGR5 resulted in increased PCNA, cell viability, EdU incorporation, and the proportion of cells in S phase, whereas knockdown of TGR5 had the opposite effect. Our data indicate that bile acids promote intestinal epithelial cell proliferation and decrease mucosal injury by upregulating TGR5 expression in obstructive jaundice.

Overexpression of Heparin-Binding Epidermal Growth Factor-Like Growth Factor Mediates Liver Fibrosis in Transgenic Mice.

BACKGROUND: The role of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in liver fibrosis is not clear and is sometimes even contradictory. To clarify this role, a HB-EGF transgenic (Tg) mouse model was, for the first time, used to evaluate the functions of HB-EGF in liver fibrosis. MATERIALS AND METHODS: For the in vivo study, carbon tetrachloride injection and bile duct ligation treatment were used to induce liver fibrosis in HB-EGF Tg mice and wild-type (WT) mice, respectively. Primary hepatic satellite cells (HSCs) were isolated from HB-EGF Tg and WT mice for the in vitro study. RESULTS: Compared with the WT mice, HB-EGF Tg mice were shown to develop more severe liver fibrosis when treated with carbon tetrachloride or bile duct ligation, with increased matrix metalloproteinases 13 activity and enhanced expression of fibrogenic genes including α-smooth muscle actin and collagen I. HB-EGF gene transfer led to an increase in proliferation and a decrease in apoptosis in primary HSCs. The ERK signaling pathway was more highly activated in primary HSCs from HB-EGF Tg mice than in those from WT mice. CONCLUSIONS: Our investigation confirmed the profibrotic effect of HB-EGF on the liver using a Tg mouse model. This result may contribute to the elucidation of HB-EGF as a therapeutic target in liver fibrosis.