ETHNOPHARMACOLOGICAL RELEVANCE:The modified Zuojin formula (SQQT) has been clinically prescribed for gastric metaplasia (GM) for several decades in China. The therapeutic efficacy of SQQT and potential mechanisms have been demonstrated in our previous studies. This research will further investigate its mechanism in the immune microenvironment. AIM OF THE STUDY:We aimed to determine the influence of SQQT on the ILC2-mediated JAK-2/STAT5/c-Myc pathway during GM. METHODS:The mechanism of GM in patients was measured through single-cell RNA sequencing. The constituents of SQQT have been examined before. The role of SQQT targets JAK-2/STAT5/c-Myc pathway was verified by network pharmacology and molecular docking. The model of GM was induced by tamoxifen (5 mg/20 g), CD90.2 protein (200 μg) or SQQT (1.69, 3.38, 6.76 g/kg) was given to treat GM mice. The SQQT mechanism was confirmed by both in vitro and in vivo studies. Histological analysis, serum cytokines, and protein levels were assessed. RESULTS:Single-cell RNA sequencing analysis indicated that ILC2 increased in the GM patients, the goblet cells in GM were probably transferred from endocrine cells. Compounds in SQQT are related to cell proliferation and can bind to the JAK-2/STAT5/c-Myc pathway proteins. The main components of SQQT, can spontaneously bind to the JAK-2 protein in 9 sites. Tamoxifen caused body weight decrease, spleen weight increase, stomach injury, ILC2 increase, and cytokines increase in the GM group. After examining the cytokines, IL-5 was the only one significantly increased in the GM group. CD90.2 and SQQT can alleviate histological changes of the stomach corpus, inflammation cytokines, and other GM-related indicators. Moreover, cell proliferation and JAK-2 pathway markers were depressed in GM mice. Besides, SQQT protects GES-1 cells from IL-5 injury related to upregulating JAK-2/STAT5/c-Myc proteins in 24h, 48h and 72h. CONCLUSION:The mechanism of SQQT protected the stomach from metaplasia associated to ILC2 activation and the subsequent cell proliferation through IL-5/JAK-2/STAT5/c-Myc pathway.

BACKGROUND:Non-erosive reflux disease (NERD), the main gastroesophageal reflux subtype, features reflux symptoms without mucosal damage. Anxiety links to visceral hypersensitivity in NERD, yet mechanisms and animal models are unclear. AIM:To establish a translational NERD rat model with anxiety comorbidity via tail clamping and study corticotropin-releasing hormone (CRH)-mediated neuroimmune pathways in visceral hypersensitivity and esophageal injury. METHODS:Sprague-Dawley (SD) and Wistar rats were grouped into sham, model, and modified groups (n = 10 each). The treatments for the modified groups were as follows: SD rats received ovalbumin/aluminum hydroxide suspension + acid perfusion ± tail clamping (40 minutes/day for 7 days), while Wistar rats received fructose water + tail clamping. Esophageal pathology, visceral sensitivity, and behavior were assessed. Serum CRH, calcitonin gene-related peptide (CGRP), 5-hydroxytryptamine (5-HT), and mast cell tryptase (MCT) and central amygdala (CeA) CRH mRNA were measured via ELISA and qRT-PCR. RESULTS:Tail clamping induced anxiety, worsening visceral hypersensitivity (lower abdominal withdrawal reflex thresholds, P < 0.05) and esophageal injury (dilated intercellular spaces and mitochondrial edema). Both models showed raised serum CRH, CGRP, 5-HT, and MCT (P < 0.01) and CeA CRH mRNA expression (P < 0.01). Behavioral tests confirmed anxiety-like phenotypes. NERD-anxiety rats showed clinical-like symptom severity without erosion. CONCLUSION:Tail clamping induces anxiety in NERD models, worsening visceral hypersensitivity via CRH neuroimmune dysregulation, offering a translational model and highlighting CRH as a treatment target.

BackgroundUlcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease. Despite advances in current therapies, safer, more effective drugs are urgently needed. Traditional Chinese herbal formula Gegen Qinlian Decoction (GQD) has been used for gastrointestinal disorders, including UC, though its exact mechanisms require further clarification.ObjectiveThis study aimed to systematically evaluate the therapeutic effects of GQD in UC mice, focusing on serum metabolomics, gut microbiota, and immunomodulatory mechanisms.MethodsA dextran sulfate sodium (DSS)-induced mouse model of UC was established. Serum metabolomics and 16S rRNA sequencing analysis of GQD’s effects on metabolites and gut microbiota. Correlation analysis and network pharmacology identified potential targets and pathways of GQD. Immunofluorescence detected the expression of γδT cells, TNF-α, IFN-γ, and IL-17 proteins in the colonic tissue.ResultsUsing UPLC-QE-Orbitrap-MS, 71 compounds were identified in the GQD quality control analysis. GQD markedly attenuated colonic histopathological damage and suppressed serum pro-inflammatory cytokines IFN-γ, IL-17, and TNF-α. It also modulated key serum metabolites, including succinic acid, glyoxylate, and xanthine, which are primarily involved in amino acid and purine metabolic pathways. GQD further influenced intestinal microbial diversity and composition. Joint analysis revealed GQD modulates gut microbiota, serum amino acid and purine metabolism, and inflammation pathways. Immunohistochemical results demonstrated enhanced infiltration of γδT cells following GQD treatment, accompanied by reduced protein expression levels of TNF-α, IFN-γ, and IL-17.ConclusionGQD exerts therapeutic effects on UC by reshaping gut microbiota composition and metabolic activities, thereby ameliorating intestinal mucosal injury, regulating γδT cell-mediated immune responses, and influencing amino acid and purine metabolic pathways.

Anorexia nervosa is a severe eating disorder with one of the highest mortality rates among psychiatric conditions and disproportionately affects adolescents and young women. However, comprehensive assessments of its long-term global burden and future trajectory remain limited. Methods Data on anorexia nervosa from the Global Burden of Disease (GBD) 2021 study were analyzed from 1990 to 2021. Age-standardized prevalence (ASPR), incidence (ASIR), death rates (ASDR), and disability-adjusted life years (DALYs) were estimated at global, regional, and national levels. Temporal trends were assessed using estimated annual percentage change (EAPC). Analyses were stratified by sex, age group, and Socio-demographic Index (SDI). Future trends from 2022 to 2041 were projected using autoregressive integrated moving average (ARIMA) models. Results Globally, ASPR and ASIR increased modestly from 1990 to 2021, whereas ASDR remained low and showed a slight decline. The burden of anorexia nervosa was substantially higher in high-SDI regions than in low-SDI regions. Females consistently exhibited a markedly higher burden than males, particularly among adolescents and young adults aged 15–24 years. Considerable regional and national heterogeneity was observed. Projections suggest a slight global decline in prevalence over the next two decades; however, the burden among females is expected to remain persistently high. Conclusions Anorexia nervosa continues to pose a significant global health challenge with pronounced disparities by sex, age, and socioeconomic development. These findings underscore the need for disorder-specific prevention strategies and improved surveillance of anorexia nervosa, particularly among adolescent girls and young women.

Background and aimCurrently, the preparation and evaluation of botanical placebos for decoctions lack standardization. This study conducted a multidimensional evaluation of an inert excipient decoction placebo for Chaihu-Shugan-San (CSS) and three low-dose CSS formulations, to determine the optimal CSS formulation for use in the control group of clinical randomized controlled trials. The Four Pillars of Best Practice in Ethnopharmacology guided the analysis.Materials and MethodsCSS was diluted 40-fold, 20-fold, and 10-fold, according to traditional simulated decoction production methods, to obtain 2.5% CSS, 5% CSS, and 10% CSS formulations. These were evaluated together with a pure excipient placebo (pure excipient PBO), consisting solely of excipients and additives. Four CSS decoction formulations were compared for color, odor, and taste using a human scoring method (Likert scale, n = 30). Along with intelligent sensory tools such as a colorimeter, electronic nose, and electronic tongue. Concurrently, the potential pharmacological effects of 4 CSS decoction formulations were examined in animal experiments, including gastric emptying and small intestinal propulsion (n = 80), hot plate analgesia, and the xylene ear swelling test (n = 49).ResultsManual scoring method indicated that the 10% CSS, 5% CSS and 2.5% CSS (difference, 1.57, 1.26 and 0.96 points, respectively, P < 0.01, power = 0.95) scored higher than the pure excipient PBO, with no significant difference in similarity between 5% CSS and 10% CSS (P > 0.05, power = 0.95). The intelligent sensory instrument results revealed that pure excipient PBO displayed the closest color match to the CSS decoction (ΔE = 2.05), while 10% CSS most closely approximated the CSS decoction in odor. Taste differences between the 4 CSS formulations and CSS were significant. Pharmacological studies found no statistically significant differences between the 4 CSS formulation groups and the control group in gastric emptying rate or small intestine propulsive motility (P > 0.05, power = 0.95) nor in ear swelling intensity (H = 8.935, P = 0.177) or pain threshold (P > 0.05, power = 0.004).Conclusion10% CSS and 5% CSS, while most similar in appearance to the CSS decoction, did not show superior in improving gastrointestinal motility, anti-inflammatory properties, or analgesic efficacy. However, their safety profile still requires future validation through animal models and quantitative mass spectrometry analysis.

OBJECTIVE:To explore whether Gegen Qinlian decoction (, GQD) targets ferroptosis pathway to ameliorate experimental colitis in mice. METHODS:A mice model of dextran sulfate sodium (DSS) induced colitis was established and therapeutic effects of GQD were determined by detecting body weight, disease activity index (DAI), colon length and histopathological changes. Then, the expression levels of inflammatory cytokines were detected by enzyme-linked immunosorbent assay, the expression levels of tight junction proteins were detected by immunohistochemistry and the expression levels of ferroptosis-associated proteins were detected by western blotting. RESULTS:GQD treatment attenuated weight loss and DAI score, increased colon length, ameliorated intestinal histopathological damage, inhibited colonic inflammatory cytokine release and enhanced epithelial barrier function in mice with ulcerative colitis (UC). Furthermore, GQD administration obviously improved the expression of ferroptosis-associated proteins (solute carrier family 7 member 11 and acyl-CoA synthetase long chain family member 4). CONCLUSION:GQD could exert a therapeutic effect on colitis by alleviating colon damage and promoting intestinal mucosal barrier repair in DSS-induced colitis mice through the inhibition of ferroptosis, which may provide an effective natural therapy for the treatment of UC.

ETHNOPHARMACOLOGICAL RELEVANCE:Zuojin pill is a well-known traditional Chinese medicine (TCM) for treating gastric disorders. The modified Zuojin pill (SQQT) has been used in the treatment of gastric metaplasia (GM) in China for decades. However, the mechanisms of SQQT treat GM remain unclear. AIM OF THE STUDY:Our goals are to evaluate the effect of SQQT on GM and to investigate its potential mechanisms. METHODS:An animal model of metaplasia was established to study the mechanism of SQQT. RNA-seq was employed to analyze the pathogenesis of GM. Network pharmacological approaches and molecular docking were used to elucidate the mechanisms of SQQT. Common targets of the SQQT and GM mechanism pathways are defined as the key mechanisms of SQQT's treatment in GM. The key mechanisms were validated through in vivo and in vitro experiments. RESULTS:RNA-seq analysis of GM animals and network pharmacology of SQQT indicated that SQQT might treat GM via 20 pathways, including the PPAR pathway. Among the 3 core targets of the PPAR pathway, only PPARG is related to GM progression. Besides, the core components of SQQT have a lower affinity for binding to PPARG. The main mechanism of SQQT ameliorated GM is related to PPARG. In animal experiments, SQQT ameliorated GM through ROS decreasing, mitochondrial damage repairing, and protein marker rectification. In cell experiments, SQQT notably decreased the levels of ferroptosis and metaplasia markers including GPX4, PPARG, MUC6, and ACSL4. CONCLUSION:SQQT ameliorated gastric metaplasia by inhibiting the PPARG/ferroptosis pathway.

The differences in the animal model construction of different subtypes of gastroesophageal reflux disease (GERD) have not been clearly demonstrated at present. We aim to reveal the characteristics and differences between them. The literature related to GERD animal model construction in the past decade was searched and data on animal strains, modeling modes, modeling cycles, and detection indices were extracted, and the results were presented by using descriptive statistical methods of frequency and relative frequency. 88 papers finally met the criteria. Sprague–Dawley (68.25

Background Irritable bowel syndrome with diarrhea (IBS-D) is a common functional gastrointestinal disorder. It is often accompanied by anxiety and depression, and severely impacts patients' quality of life. Visceral hypersensitivity is closely associated with the pathogenesis of IBS-D, potentially involving activation of the AhR-Notch1 signaling pathway in mast cells. Chang'an II recipe is a formulation developed by Prof. Tang Xudong based on the classical formula of Tong-Xie-Yao-Fang, which has documented clinical efficacy in the treatment of IBS-D. However, the mechanism underlying the action of the Chang'an II recipe in treating IBS-D is not fully understood. Objective To investigate the ameliorative efficacy of the Chang'an II recipe on rat models of IBS-D, as well as its underlying mechanism in IBS-D rats and the RBL-2H3 rat basophilic leukemia cell line. Methods The IBS-D model rats received high, medium, and low doses of the Chang'an Ⅱ recipe and the AhR inhibitor Kyn by oral gavage for 14 days. The body weight, food intake, fecal water content (FWC), abdominal withdrawal reflex (AWR), and severity of diarrhea symptoms were assessed. Sera and colonic tissues were collected for histopathological analyses, and relevant indices were measured in tissues and RBL-2H3 cells. Results The Chang'an II recipe effectively alleviated weight loss and increased food intake and intestinal absorption in IBS-D rats. It also alleviated diarrhea, decreased visceral hypersensitivity, and reduced intestinal inflammation. The mechanism underlying the reduction in visceral hypersensitivity was associated with AhR upregulation and Notch1 downregulation, reducing activation of p-p38, p-JNK, and p-ERK1/2. This process suppressed mast cell activation and inhibited the production of biologically active substances such as mast cell tryptase, histamine, IL-4, and TNF-α. Conclusion The Chang’an II recipe alleviates IBS-D symptoms by modulating the AhR/Notch1 signaling pathway, suppressing mast cell activation, and downregulating the PAR2/TRPV1 axis in intestinal afferent nerves. These findings provide novel mechanistic insights into its therapeutic effects, highlighting its potential as a targeted treatment for IBS-D.

BACKGROUND:The interleukin-17 (IL-17) mediated aberrant immune-inflammatory response plays a paramount role in ulcerative colitis (UC). γδT17 cells are one of the critical sources of IL-17, but the role they play in UC remains under debate. AIM:To clarify the role of γδT17 cells in patients with mild-to-moderate UC. METHODS:A single-centre observational pragmatic study was conducted on patients with UC who attended the outpatient and inpatient departments of Xiyuan Hospital of the China Academy of Traditional Chinese Medicine from September 2020 to December 2022. The research population consisted of two groups of adult patients. The first group consisted of healthy volunteers with no significant abnormalities on colonoscopy, and the other group consisted of patients with mild-to-moderate ulcerative colitis. Serum samples from healthy volunteers and patients with UC were collected for the detection of relevant inflammatory factors. Moreover, five colon mucosa samples were randomly selected from each group for testing and analyses. RESULTS:An increased number of γδT17 cells and hyperactivation of the NLR family pyrin domain containing 3/IL-1β signaling pathway were observed in colonic mucosal tissues from patients with UC. CONCLUSION:Hyperactivation of the NLR family pyrin domain containing 3/IL-1β signaling pathway promotes the activation of γδT17 cells in colonic mucosal tissues of patients with UC.

BACKGROUND:The overlap between non-erosive reflux disease (NERD) and epigastric pain syndrome (EPS, a subtype of functional dyspepsia) is common, yet its associated factors remain poorly defined. We aimed to identify factors associated with symptom severity in NERD-EPS overlap, focusing on psychosocial and somatic factors. METHODS:In this multicenter cross-sectional study, 800 patients meeting Rome IV criteria for NERD-EPS overlap were enrolled. Standardized questionnaires assessed gastrointestinal symptoms (GSRS), somatic symptoms (PHQ-15), anxiety/depression (PHQ-4), and sleep quality (SRSS). Multivariable regression models identified factors independently associated with GSRS scores, adjusted for demographics and clinical covariates. Interaction terms were tested to assess whether the association between one factor and GSRS scores varied across different levels of another factor. RESULTS:Of the 800 patients, 67% were female, and the mean age was (44.50 ± 14.43) years. 67% had mild or more sleep problems, and 47% had anxiety or depression. Somatic symptoms (PHQ-15) showed the strongest association with GSRS scores (β = 0.617, P < 0.001), followed by poor sleep quality (SRSS; β = 0.115, P < 0.001) and anxiety/depression (PHQ-4; β = 0.069, P = 0.026). Urban residence (β = 0.071) and mixed labor type (β = -0.066) were also independently associated with symptom burden. CONCLUSION:Somatic symptoms, psychological distress, and sleep disturbances were the factors most strongly associated with symptom severity in NERD-EPS overlap, with additional contributions from younger age, male sex, and urban residence. Our findings advocate for integrated biopsychosocial interventions to alleviate symptom burden in this population.

Background Gastric precancerous lesions (GPL) typically originates from chronic gastritis (CG), and the changes in glycolysis mediated by the HIF-1α pathway during the progression from CG to GPL are unclear. Modified Zuojin pill (SQQT) is a traditional Chinese herbal formula used for treating GPL. However, the underlying mechanism has not been fully elucidated. Purpose To investigate the changes in glycolysis mediated by the HIF-1α pathway during the progression from CG to GPL and whether SQQT can alleviate GPL by attenuating glycolysis through the HIF-1α pathway. Methods A rat model of GPL was established, and the changes of glycolysis mediated by the HIF-1α pathway during the progression from CG to GPL were detected in 12th, 18th, 24th, and 30th weeks. The therapeutic efficacy of SQQT was evaluated through pathological changes. In vitro, the GPL cell model (MC cell) originated from GES-1 cells intervened by MNNG. The effects of SQQT on glycolysis and the HIF-1α pathway were detected in vivo and in vitro. In vitro, HIF-1α overexpression was used to confirmed that SQQT attenuated glycolysis by targeting the HIF-1α pathway. Results Our study revealed that glycolysis mediated by the HIF-1α pathway exhibited dynamic changes in the progression from CG to GPL, characterized by sequential activation, deactivation, and reactivation. SQQT ameliorated gastric mucosal pathology and inflammation in GPL rats. Mechanistic studies revealed that SQQT alleviated glycolysis by targeting the HIF-1α pathway, and improved abnormal cellular proliferation and apoptosis. Importantly, HIF-1α overexpression blocked the effect of SQQT on glycolysis. Conclusion In the progression from CG to GPL, the HIF-1α pathway-mediated glycolysis was characterized by sequential activation, deactivation, and reactivation. SQQT attenuated glycolysis by targeting the HIF-1α pathway and improved abnormal cellular proliferation and apoptosis in the gastric mucosa, thereby exerting therapeutic effects on GPL.

A growing number of systematic reviews and meta-analyses (SRs/MAs) based on randomized clinical trials have been carried out to assess the efficacy of fecal flora transplantation (FMT) in the treatment of ulcerative colitis (UC). An overview of SRs/MAs will be conducted with the aim of systematically compiling, evaluating, and synthesizing the evidence regarding FMT for UC. This is a protocol for an overview of SRs/MAs. We will search eight public electronic databases for the studies of FMT on UC. SRs/MAs of clinical trials evaluating the effect of FMT on UC will be included. Two independent authors will screen titles and abstracts retrieved in the literature search and select reviews meeting the eligibility criteria for full-text review. The methodological quality, reporting quality, and evidence quality of the included studies will be assessed, using, respectively, the AMSTAR-2 tool, PRISMA checklists, and GRADE system. From this study, the methodological quality, reporting quality, and evidence quality of the included SRs/MAs will be evaluated. We will also evaluate the efficacy of FMT in patients with UC. We will ascertain the efficacy of FMT in UC patients to provide evidence to guide the treatment of UC with FMT in the future. As a secondary study based on SRs/MAs, this study does not contain any individual patient information or violate participant rights. It is therefore not necessary to obtain ethics approval. We will report our findings in peer-reviewed journals or disseminate them at relevant conferences. Systematic review registration. PROSPERO CRD42023388682.

Eukaryotic cells contain the endoplasmic reticulum (ER), a prevalent and intricate membranous structural system. During the development of inflammatory bowel disease (IBD), the stress on the ER and the start of the unfolded protein response are very important. Some chemicals, including 4μ8C, small molecule agonists of X-box binding protein 1, and ISRIB, work on the inositol-requiring enzyme 1, turn on transcription factor 6, and activate protein kinase RNA-like ER kinase pathways. This may help ease the symptoms of IBD. Researchers investigating the gut microbiota have discovered a correlation between ER stress and it. This suggests that changing the gut microbiota could help make new medicines for IBD. This study looks at how ER stress works and how it contributes to the emergence of IBD. It also talks about its possible clinical importance as a therapeutic target and looks into new ways to treat this condition.

Background: This study aims to reveal the potential molecular mechanisms of modified Gegen Qinlian decoction (MGQD) in relieving ulcerative colitis (UC).Methods: C57BL/6J mice were used to establish experimental colitis via dextran sodium sulfate (DSS). Body weight, disease activity index (DAI), spleen weight, colon length, and histopathologic features were measured to evaluate the therapeutic effects of MGQD on mice with UC. The ELISA kits were employed to assess the concentrations of interleukin (IL)‐6, IL‐1β, tumor necrosis factor‐α (TNF‐α), glutathione (GSH), reactive oxygen species (ROS), and malondialdehyde (MDA). Western blot analyses were used to assess the levels of IκBα, p65, p‐IκBα, p‐p65, HO‐1, and Nrf2. Moreover, the protein levels of Nrf2 and p‐p65 were assessed by immunofluorescence.Results: Colitis‐related symptoms in mice were significantly alleviated by MGQD. Moreover, MGQD inhibited the levels of TNF‐α, IL‐1β, IL‐6, MDA, and ROS and increased the level of GSH in mice with UC. Mechanistically, MGQD prevented the activation of the NF‐κB pathway and concomitantly promoted the activation of the Nrf2/HO‐1 pathway.Conclusion: MGQD alleviated UC by suppressing inflammation and oxidative stress via the modulation of NF‐κB and Nrf2/HO‐1 pathways, suggesting that MGQD may be a candidate therapy for UC.

Background: Gastric cancer (GC) is the third leading cause of cancer-related death and is associated with high mortality and morbidity. Helicobacter pylori (HP) infection is the most important cause of GC. We aimed to identify the core genes of HP caused GC and further elucidate the underlying mechanisms. Methods: GC and HP associated gastritis (HPAG) gene expression data were sourced from Gene Expression Omnibus. Key genes affecting GC prognosis were identified using Cytoscape software. Patient groups were formed based on key gene expression, and the immune analyses were performed with R. MNU, derived from nitrite by HP, was given to GC mice (240ppm) for histology and fluorescence assays. For in vitro experiments, cells received MNU (20 μM) stimulation for 24 hours. Results: CD14 was the only key gene identified. A total of 412 GC patients were divided into CD14-high and CD14-low groups. The two groups showed significant differences in immune cell populations and immune checkpoints. In particular, there was a notable increase in M2 macrophages in GC patients with high CD14 expression (P <0.001). GC Patients with high CD14 expression exhibited a more pronounced immune response than those with low CD14 expression, and elevated CD14 expression positively correlated with the efficacy of CTLA4 therapy (P <0.05). These results indicated that CD14 expression was strongly correlated with the GC immune response. A noticeable increase in CD14 levels was observed in MNU-induced GC animals, cell models, and GC patients. In addition, the number of M2 macrophages was increased in MNU-induced GC mice. Conclusion: Reducing CD14 expression may increase the survival rate of GC patients through the modulation of immune responses. The complex mechanism of CD14's influence on prognosis deserves further investigation.

Background: Prospective and cross-sectional studies have reported an association between functional gastrointestinal disorders and anxiety and depression. However, the causal relationship remains uncertain. To clarify this, we utilized Mendelian randomization (MR) to assess the causal effects of common gastrointestinal disorders on cortical structures. Methods: Genome-wide association study (GWAS) data was gathered for functional dyspepsia (FD), irritable bowel syndrome (IBS), and gastroesophageal reflux disease (GERD) from European populations numbering 329,262, 16,792, and 602,604, respectively. GWAS cerebral cortical architecture data for cortical thickness (TH) and surface area (SA) were obtained from 51,665 MRI scans. MR was used to analyze the casual relationship between FD, IBS, GERD, and cortical structures. Inverse-variance weighted, weighted median, and MR-Egger tests were performed as assessment indicators. We also evaluated heterogeneity and pleiotropy. Results: FD significantly decreases the TH in the rostral anterior cingulate cortex (nTH =-0.022 mm; 95%CI:-0.035 mm to-0.009 mm2; P TH = 6.89 x 10-4), and IBS significantly decreases the SA of the pars triangularis (nSA =-21.91 mm2; 95%CI:-32.99 mm to-10.83 mm2; P SA = 1.06 x 10-4), precuneus (nSA =-47.53 mm2; 95%CI:-73.57 mm to-21.48 mm2; P SA = 3.48 x 10-4) and superior frontal regions (nSA =-78.70 mm2; 95%CI:-122.61 mm to-34.78 mm2; P SA = 4.4 x 10-4). At the local functional level, GERD significantly increases the SA of the inferior temporal region (nSA =-113.58 mm2, 95%CI:-113.58 mm to-39.01 mm2, P SA = 6.05 x 10-5). Conclusions: FD, IBS and GERD can affect the cerebral cortex architecture through the brain-gut axis, potentially increasing the risks of mental illness and cognitive impairment.

BACKGROUND Esophageal stricture ranks among the most significant complications following endoscopic submucosal dissection (ESD). Excessive fibrotic repair is a typical pathological feature leading to stenosis after ESD. AIM To examine the effectiveness and underlying mechanism of Kangfuxin solution (KFX) in mitigating excessive fibrotic repair of the esophagus post-ESD. METHODS Pigs received KFX at 0.74 mL/kg/d for 21 days after esophageal full circumferential ESD. Endoscopic examinations occurred on days 7 and 21 post-ESD. In vitro , recombinant transforming growth factor (TGF)-β1 (5 ng/mL) induced a fibrotic microenvironment in primary esophageal fibroblasts (pEsF). After 24 hours of KFX treatment (at 1.5%, 1%, and 0.5%), expression of α-smooth muscle actin-2 (ACTA2), fibronectin (FN), and type collagen I was assessed. Profibrotic signaling was analyzed, including TGF-β1, Smad2/3, and phosphor-smad2/3 (p-Smad2/3). RESULTS Compared to the Control group, the groups treated with KFX and prednisolone exhibited reduced esophageal stenosis, lower weight loss rates, and improved food tolerance 21 d after ESD. After treatment, Masson staining revealed thinner and less dense collagen fibers in the submucosal layer. Additionally, the expression of fibrotic effector molecules was notably inhibited. Mechanistically, KFX downregulated the transduction levels of fibrotic functional molecules such as TGF-β1, Smad2/3, and p-Smad2/3. In vitro , pEsF exposed to TGF-β1-induced fibrotic microenvironment displayed increased fibrotic activity, which was reversed by KFX treatment, leading to reduced activation of ACTA2, FN, and collagen I. The 1.5% KFX treatment group showed decreased expression of p-Smad 2/3 in TGF-β1-activated pEsF. CONCLUSION KFX showed promise as a therapeutic option for post-full circumferential esophageal ESD strictures, potentially by suppressing fibroblast fibrotic activity through modulation of the TGF-β1/Smads signaling pathway.