Objective To investigate the expression profile, prognostic value, gene co-expression network, and immunomodulatory role of BRF1 in a pan-cancer context, and to explore its biological functions and molecular regulatory mechanisms in esophageal squamous cell carcinoma (ESCC). Methods The pan-cancer dataset from The Cancer Genome Atlas (TCGA) was utilized to analyze the differential expression of BRF1 in tumor versus normal tissues, its association with patient survival, pathway enrichment for co-expressed genes, and immune features (including immune checkpoints, cytokines, and immune cell infiltration). The expression profile of BRF1 in ESCC was validated using the Gene Expression Omnibus (GEO) database. In vitro, BRF1 was knocked down in ESCC cells using siRNA. Cell proliferation and migration were assessed by MTT and Transwell assays, respectively. The expression levels of proliferation- and migration-related proteins were detected by Western blotting. The correlation between BRF1 and ferroptosis was analyzed using TCGA data. Results BRF1 was significantly upregulated in over 20 types of cancer, and its high expression was associated with poor prognosis in patients with adrenocortical carcinoma and prostate adenocarcinoma. BRF1 was found to positively regulate the T-cell-mediated cell death pathway in esophageal adenocarcinoma and was associated with the circadian rhythm regulation pathway in pancreatic adenocarcinoma. The correlation of BRF1 with immune checkpoints, cytokine networks, and immune cell infiltration was found to be cancer type-specific. In vitro experiments demonstrated that knocking down BRF1 significantly inhibited the proliferation of ESCC cells, accompanied by the downregulation of the proliferation marker PCNA. Cell migration was also significantly impaired, with decreased expression of Vimentin and MMPs and increased expression of E-cadherin. Furthermore, the expression of BRF1 was positively correlated with that of ferroptosis-antagonizing genes, such as GPX4, HSPA5, and SLC7A11. Conclusion BRF1 plays complex roles in pan-cancer, participating in the regulation of tumorigenesis, progression, and immune infiltration. BRF1 promotes the proliferation and migration of ESCC cells, a mechanism potentially associated with the regulation of ferroptosis resistance. These findings suggest that BRF1 could be a potential therapeutic target for ESCC.

Hepatic fibrosis is a reversible pathological process in various chronic liver diseases and is closely associated with the development and progression of severe liver diseases such as liver cirrhosis and hepatocellular carcinoma， and it has emerged as a significant global health challenge. In recent years， studies have shown that histone lactylation， a newly discovered epigenetic modification， actively participates in regulating the progression of hepatic fibrosis. This article systematically reviews the core regulatory effect of histone lactylation modification in the interaction between inflammatory microenvironment and hepatic fibrosis， in order to clarify the cascade regulatory mechanism of “inflammation-hepatic fibrosis” and provide new insights for early diagnosis， targeted intervention， and prevention of malignant transformation in hepatic fibrosis.

ObjectiveTo explore the possible mechanism of Tongbian Decoction （通便汤， TD） in treating slow transit constipation （STC）. MethodsTwenty-four SD rats were randomly divided into normal group， model group， TD group， and mosapride group， with 6 rats per group. Except for the normal group， STC models were established by intragastric administration of loperamide hydrochloride combined with normal saline. On the day following successful model establishment， rats in the TD group received 18.63 g·kg⁻¹ of TD by gavage， while those in the mosapride group received 1.605 mg·d⁻¹ of mosapride， and those in the normal group and the model group received 10 ml·kg⁻¹ of normal saline by gavage. All treatments were administered once daily for 7 consecutive days. Twenty-four hours after the last administration， fecal pellet number and fecal water content were measured. After intragastric administration of a 10% activated charcoal suspension， the small intestinal transit rate was calculated 30 minutes later. Serum levels of gastrin （GAS） and motilin （MTL） were measured by ELISA. Colonic histopathology was observed by HE staining， and mucus secretion by Alcian blue-periodic acid-Schiff （AB-PAS） staining. Ultrastructure of colon tissue was examined using transmission electron microscopy. Protein expression levels of C-kit， stem cell factor （SCF）， autophagy-related protein 5 （ATG5）， Beclin1， vesicle-associated membrane protein B （VAPB）， and protein tyrosine phosphatase interacting protein 51 （VAPB-PTPIP51） were measured by Western Blot， and the mRNA levels were detected by real-time PCR. Immunohistochemistry was used to detect SCF， C-kit， Beclin1， and ATG5 expression. The calcium content in colon tissue was determined by ELISA. ResultsCompared to the normal group， rats in the model group showed significantly reduced fecal pellet number， fecal water content， small intestinal transit rate， and serum GAS and MTL levels （P＜0.01）； the number of goblet cells decreased， and the mucosal and muscular layers of the colon became thinner； mRNA and protein expression levels of ATG5 and Beclin1 in colon tissue significantly increased， while calcium content decreased （P＜0.05 or P＜0.01）； and electron microscopy revealed vacuolar degeneration and increased autophagosomes in colonic cells. Compared to the model group， both TD group and mosapride group showed increased fecal pellet number， fecal water content， small intestinal transit rate， serum GAS and MTL levels， and colonic calcium content， along with decreased Beclin1 and ATG5 protein levels （P＜0.05 or P＜0.01）； the mucosal thickness and goblet cell number increased significantly， and autophagosomes decreased； in the TD group， ATG5 and Beclin1 mRNA levels decreased； in the mosapride group， SCF， VAPB， and PTPIP51 mRNA levels increased， while Beclin1 mRNA decreased （P＜0.05 or P＜0.01）. Compared to the mosapride group， the TD group showed higher fecal pellet number， fecal water content， serum GAS levels， colonic calcium content， and C-kit expression， along with lower ATG5 and Beclin1 levels （P＜0.05 or P＜0.01）. ConclusionTD may improve constipation symptoms by upregulating the VAPB-PTPIP51 complex during mitochondria-endoplasmic reticulum interactions， reducing autophagy of interstitial cells of Cajal， and promoting intestinal motility.

ObjectiveTo explore the possible mechanism of Tongbian Decoction （通便汤， TD） in treating slow transit constipation （STC）. MethodsTwenty-four SD rats were randomly divided into normal group， model group， TD group， and mosapride group， with 6 rats per group. Except for the normal group， STC models were established by intragastric administration of loperamide hydrochloride combined with normal saline. On the day following successful model establishment， rats in the TD group received 18.63 g·kg⁻¹ of TD by gavage， while those in the mosapride group received 1.605 mg·d⁻¹ of mosapride， and those in the normal group and the model group received 10 ml·kg⁻¹ of normal saline by gavage. All treatments were administered once daily for 7 consecutive days. Twenty-four hours after the last administration， fecal pellet number and fecal water content were measured. After intragastric administration of a 10% activated charcoal suspension， the small intestinal transit rate was calculated 30 minutes later. Serum levels of gastrin （GAS） and motilin （MTL） were measured by ELISA. Colonic histopathology was observed by HE staining， and mucus secretion by Alcian blue-periodic acid-Schiff （AB-PAS） staining. Ultrastructure of colon tissue was examined using transmission electron microscopy. Protein expression levels of C-kit， stem cell factor （SCF）， autophagy-related protein 5 （ATG5）， Beclin1， vesicle-associated membrane protein B （VAPB）， and protein tyrosine phosphatase interacting protein 51 （VAPB-PTPIP51） were measured by Western Blot， and the mRNA levels were detected by real-time PCR. Immunohistochemistry was used to detect SCF， C-kit， Beclin1， and ATG5 expression. The calcium content in colon tissue was determined by ELISA. ResultsCompared to the normal group， rats in the model group showed significantly reduced fecal pellet number， fecal water content， small intestinal transit rate， and serum GAS and MTL levels （P＜0.01）； the number of goblet cells decreased， and the mucosal and muscular layers of the colon became thinner； mRNA and protein expression levels of ATG5 and Beclin1 in colon tissue significantly increased， while calcium content decreased （P＜0.05 or P＜0.01）； and electron microscopy revealed vacuolar degeneration and increased autophagosomes in colonic cells. Compared to the model group， both TD group and mosapride group showed increased fecal pellet number， fecal water content， small intestinal transit rate， serum GAS and MTL levels， and colonic calcium content， along with decreased Beclin1 and ATG5 protein levels （P＜0.05 or P＜0.01）； the mucosal thickness and goblet cell number increased significantly， and autophagosomes decreased； in the TD group， ATG5 and Beclin1 mRNA levels decreased； in the mosapride group， SCF， VAPB， and PTPIP51 mRNA levels increased， while Beclin1 mRNA decreased （P＜0.05 or P＜0.01）. Compared to the mosapride group， the TD group showed higher fecal pellet number， fecal water content， serum GAS levels， colonic calcium content， and C-kit expression， along with lower ATG5 and Beclin1 levels （P＜0.05 or P＜0.01）. ConclusionTD may improve constipation symptoms by upregulating the VAPB-PTPIP51 complex during mitochondria-endoplasmic reticulum interactions， reducing autophagy of interstitial cells of Cajal， and promoting intestinal motility.

Liver fibrosis is a critical pathological process in the progression of chronic liver diseases and is mainly driven by the activation of hepatic stellate cells， and it is characterized by excessive deposition of extracellular matrix. Programmed cell death is widely observed in liver fibrosis and plays diverse roles in different types of cells. It is not only a mechanism for maintaining cellular homeostasis through metabolism， but it can also regulate the development and progression of diseases. Ferroptosis has recently emerged as a research focus due to its close association with lipid metabolism. This article systematically reviews the related concepts of lipid metabolism， ferroptosis， and liver fibrosis， analyzes the bridging role and dual regulatory function of ferroptosis in lipid metabolism and liver fibrosis， and further highlights the clinical application value of targeting ferroptosis in hepatic stellate cells for the treatment of liver fibrosis， in order to provide new perspectives for the mechanistic studies on liver fibrosis and the optimization of related clinical intervention strategies.

Objective To study the seasonal distribution characteristics of polycyclic aromatic hydrocarbons (PAHs) in PM_2.5 in Lianyungang City, and analyze the sources of PAHs pollution, and to evaluate the health risks of PAHs in different seasons. Methods PM2.5 samples were collected regularly from January 2019 to December 2023, and 16 types of PAHs were determined by HPLC. Kruskal-Wallis H test was used to compare the concentrations of PM2.5 and PAHs in different years and seasons. The source of PAHs was analyzed by characteristic ratio and principal component analysis (PCA). Health risks were assessed using the BaP equivalent method and the incremental lifetime cancer risk (ILCR) model. Results The annual exceedance rates of PM_2.5 and BaP in Lianyungang showed a decreasing trend from 2019 to 2023. PM_2.5, total PAHs and PAHs monomers (except Ace, Flu and Acy) all showed significant seasonal differences, with the highest concentration in winter (P<0.001). The average proportion of 4-ring PAHs was the highest and the average proportion of 2-ring PAHs was the lowest. The proportion of 5-6 ring PAHs was relatively high in winter and spring. PM2.5and PAHs were negatively correlated with temperature, relative humidity and precipitation, and were positively correlated with atmospheric pressure. PM_2.5 was negatively correlated with wind speed, while some PAHs monomers were positively correlated with wind speed. The characteristic ratio and PCA results showed that the main sources of PAHs in Lianyungang City were mixed sources of road dust and vehicle emissions, oil pollution sources and biomass combustion sources. The results of ILCR showed that the highest risk was found in adults, with males slightly higher than females. In Lianyungang, the maximum value of ILCR in winter was more than 10-6 in people over 9 years old. Conclusion The main sources of PAHs in PM_2.5 in Lianyungang City are mixed sources of road dust and vehicle emissions, oil pollution sources, and biomass combustion sources. Under the current exposure level of PAHs in PM_2.5, residents have a certain potential carcinogenic risk.

AIM:This study aims to investigate whether vitamin E succinate(VES)induces autophagy in hu-man gastric cancer cells through the promotion of mitochondria-associated endoplasmic reticulum membranes(MAMs).METHODS:Human gastric cancer cell lines MKN28 and MKN45 were cultured in vitro.Cell viability was assessed us-ing the CCK8 assay,and two cell growth curves were plotted to determine the treatment concentration of VES.Control groups,VES dose groups(MKN28:5,10,20,and 40 mg/L;MKN45:10,20,40,and 80 mg/L),an autophagy-posi-tive control group(rapamycin,RAPA,100 nmol/L),and a MAMs-positive control group(oligomycin A,10 mg/L)were set up.Cells were harvested after 24 h of treatment for subsequent experiments.The formation of autophagosomes and MAMs was observed using transmission electron microscopy.The expression levels of autophagy-related proteins,includ-ing beclin-1,LC3-II/LC3-I,and p62,were detected by Western blot.MAMs labeled with split green fluorescent protein(GFP)were visualized by fluorescence microscopy.The expression of mitofusin 2(MFN2),a key molecule of MAMs,was also detected by Western blot.To inhibit MFN2 specifically,the cells were treated with mitochondrial fusion inhibitor 8(MFI8)and simultaneously transfected with an MFN2 plasmid to achieve MFN2 overexpression(OE-MFN2).The cells were divided into control group,MFI8(20 μmol/L)group,VES groups(20 mg/L for MKN28 cells and 40 mg/L for MKN45 cells),VES+MFI8 group,OE-MFN2+MFI8 group and OE-MFN2+VES+MFI8 group.The MAMs were visualized by fluorescence microscopy,and the expression changes of MFN2,beclin-1 and LC3-II/I were detected by Western blot.RESULTS:The results of the CCK8 assay showed that VES significantly inhibited the viability of both human gastric can-cer cell lines(P<0.05).After VES treatment,the formation of typical autophagosomes and MAMs was observed in both cell lines by transmission electron microscopy.Fluorescence microscopy showed a significant increase in GFP signals of MAMs.Western blot analysis showed that with increasing doses of VES,the expression levels of MFN2,beclin-1,and LC3-II/I were significantly up-regulated,while that of p62 was significantly down-regulated(P<0.05).Compared with VES group,the cells pretreated with MFI8 followed by VES exposure showed markedly reduced GFP signals of MAMs and much lower protein levels of MFN2,beclin-1 and LC3-II/LC3-I(P<0.05).Transfection with an MFN2 overexpression plasmid rescued MFN2 expression.Compared with VES+MFI8 group,the cells in OE-MFN2+VES+MFI8 group had much higher protein expression levels of MFN2,beclin-1 and LC3-II/LC3-I(P<0.05).CONCLUSION:The VES may partici-pates in the regulation of autophagy in human gastric cancer cells by promoting the formation of MAMs.

Objective:To explore the impact of residents′ health literacy on healthcare choices.Methods:This mixed cross-sectional study utilized data from the 2009, 2011, and 2015 waves of the China Health and Nutrition Survey (CHNS), including adults aged≥18 years. Guided by Andersen′s Behavioral Model of Health Services Use and the Knowledge-Attitude-Practice (KAP) framework, variables were collected across three dimensions-predisposing, enabling, and need factors-including gender, marital status, age, education level, employment status, urban/rural residence, health management awareness, income, health insurance coverage, self-rated health, and chronic disease status. A multinomial Logistic regression model was applied to assess the association between health literacy and healthcare choice. Bootstrap analysis was conducted to test the mediating effect of health management awareness.Results:After excluding cases with missing or invalid data, 4 736 valid observations were included. The proportions of choosing township-, county-, and city-level hospitals were 60.60%, 15.08%, and 24.32%, respectively. After adjusting for confounders, health literacy showed a significant effect on healthcare choice ( P<0.05): individuals with higher health literacy were more likely to choose county-level hospitals ( RR=1.035, P<0.05) and city-level hospitals ( RR=1.044, P<0.01). Health management awareness mediated the relationship between health literacy and healthcare choice ( P<0.05). Conclusions:Health literacy significantly influences healthcare choices; individuals with higher health literacy are more inclined to utilize higher-level medical institutions. Furthermore, health literacy affects healthcare choices partly through the mediating role of health management awareness.

An ideal dermal filler should integrate filling, repair, and anti-aging effects, with immediate tissue augmentation, slow degradation, and progressive stimulation of collagen regeneration. However, commonly used hyaluronic acid (HA) hydrogels, while effective for rapid filling, suffer from limited duration of support, weak cell adhesion, and an inability to promote collagen regeneration. Silk fibroin (SF), a natural protein from silkworm cocoons, is known for its excellent cell adhesion and collagen-stimulating abilities. However, its limited gelation capability restricts its potential application as a standalone injectable hydrogel. Based on a complementary strategy, this study combines the rapid gelling properties of HA with the collagen regenerative properties of SF to create a co-crosslinked HA-SF hydrogel. The composite hydrogel merges HA's rapid filling effect with SF's strong tissue adhesion and collagen-stimulating abilities. The formulation, physicochemical properties, degradation, biocompatibility, and filling effects of the HA-SF hydrogel were systematically investigated. HA-SF hydrogel exhibits excellent mechanical properties and ensures long-term support while maintaining injectability. Interestingly, after intradermal injection in the UVB-induced photoaging model, HA-SF hydrogel not only enhances hydrogel-cell interaction but also continues to stimulate collagen regeneration, especially type III collagen. This dual action achieves the biological effects of repair and anti-aging while maintaining the filling effect. Proteomic analysis confirms that repair and anti-aging effects are enhanced by the regulation of skin fibroblasts and modulation of amino acid and lipid metabolism. This composite hydrogel holds strong promise for clinical applications, offering a safer, long-lasting, and more natural injectable filler that combines filling, repair, and anti-aging into one system.

Peritoneal dialysis (PD) is a crucial renal replacement therapy for end-stage renal disease (ESRD), offering significant advantages as high flexibility, hemodynamic stability, and high cost-effectiveness. However, prolonged exposure to intra-abdominal dialysate may predispose to the mechanical complication of abdominal external hernia. Abdominal external hernia may lead to various adverse clinical outcomes. In severe cases, it can progress to incarceration or even rupture, ultimately necessitating discontinuation of the therapy. The authors systematically review PD-associated abdominal external hernias, including their clinical landscape, risk factors, surgical treatment strategies and prognostic determinants. They also assess the effects of hernia repair on residual renal function, aiming to provide references for clinical decision-making.