International clinical practice guideline on the use of traditional Chinese medicine for ulcerative colitis by Board of Specialty Committee of Digestive System Disease of World Federation of Chinese Medicine Societies (2023).

Ulcerative colitis (UC), a chronic and nonspecific inflammatory disease of the intestine, has become a prevalent global health concern. This guideline aims to equip clinicians and caregivers with effective strategies for the treatment and management of adult UC patients using traditional Chinese medicine (TCM). The guideline systematically evaluated contemporary evidence through the Grading of Recommendations Assessment, Development, and Evaluation framework. Additionally, it incorporated insights from ancient Chinese medical sources, employing the evidence grading method found in traditional TCM literature. The development process involved collaboration with multidisciplinary experts and included input from patients with UC. The guideline, based on a comprehensive review of available evidence, present 40 recommendations. They offer a condensed overview of TCM's role in understanding the pathogenesis, diagnosis, and treatment of UC, along with an assessment of the efficacy of various TCM-based treatments. TCM exhibits promising outcomes in the treatment of UC. However, to establish its efficacy conclusively, further high-quality clinical studies on TCM for UC are essential.

Clinical guideline on magnetically controlled capsule gastroscopy (2021 edition).

With the development and generalization of endoscopic technology and screening, clinical application of magnetically controlled capsule gastroscopy (MCCG) has been increasing. In recent years, various types of MCCG are used globally. Therefore, establishing relevant guidelines on MCCG is of great significance. The current guidelines containing 23 statements were established based on clinical evidence and expert opinions, mainly focus on aspects including definition and diagnostic accuracy, application population, technical optimization, inspection process, and quality control of MCCG. The level of evidence and strength of recommendations were evaluated. The guidelines are expected to guide the standardized application and scientific innovation of MCCG for the reference of clinicians.

Case report: Coexistence of sigmoid tumor with unusual pathological features and multiple colorectal neuroendocrine tumors with lymph node metastases.

The coexistence of adenocarcinoma and neuroendocrine neoplasm (NEN) in the same tumor is rare. What is rarer is that the neuroendocrine component is a well-differentiated neuroendocrine tumor (NET) Grade (G) 1. Most colorectal NETs are single, but multiple neuroendocrine tumors (M-NETs) are rare. Well-differentiated NETs rarely metastasize. Here, we present a unique case of a synchronous sigmoid tumor and multiple colorectal NETs with lymph node metastases. The sigmoid tumor consisted of adenocarcinoma and NET G1. The metastatic component was NET G1. A 64-year-old man underwent a colonoscopy for persistent changes in bowel habits and positive fecal occult blood for 1 year. An ulcerative lesion, which was diagnosed as colon cancer, was seen in the sigmoid colon. In addition, scattered lesions could be seen in the colon and rectum. Surgical resection was performed. Pathological findings suggested that the ulcerative lesion was composed of 80% adenocarcinoma and 20% neuroendocrine component (NET G1), while the remaining lesions were consistent with NET G1. At the same time, 11 lymph nodes around the resected intestinal segment were invaded by NET G1. The prognosis of the patient was good. After 13 months of follow-up, no recurrence and no metastasis were found. We hope to provide a reference and improve our understanding of the clinicopathological features and biological behavior of these unique tumors. We also aim to emphasize the importance of radical surgery and individualized treatment.

Role of Endoscopy in Esophageal Tuberculosis: A Narrative Review.

Esophageal tuberculosis (ET) is a rare infectious disease of the gastrointestinal tract. Awareness of ET is deficient due to its low incidence. Unexplained dysphagia and upper gastrointestinal bleeding are the most common symptoms of ET. The prognosis is generally good if patients are diagnosed properly and receive anti-tubercular treatment promptly. However, ET is difficult to differentiate from other diseases. Endoscopic techniques such as esophagogastroduodenoscopy (EGD), endoscopic ultrasonography (EUS), contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS), elastography, and endoscopic ultrasound--guided fine-needle aspiration (EUS-FNA) improve the diagnosis of ET. Thus, the characteristics of ET and other difficult-to-detect diseases according to EGD and EUS were summarized. Intriguingly, there is no literature relevant to the application of CH-EUS and elastography in ET. The authors' research center was first in introducing CH-EUS and elastography into the field of ET. The specific manifestation of ET based on CH-EUS was discovered for the first time. Correlative experience and representative cases were shared. The role of endoscopy in acquiring esophageal specimens and treatment for ET was also established. In this review, we aim to introduce a promising technology for the diagnosis and treatment of ET.

Multiple rectal neuroendocrine tumors: An analysis of 15 cases and literature review.

Multiple neuroendocrine tumors (M-NETs) are rare in the rectum and there is no consensus on their characteristics and treatments. Here, we report 15 cases of rectal M-NETs and review the previous literature. We discuss the clinical characteristics, endoscopic features and pathological features of rectal M-NETs, aiming to analyze the treatments and follow-up strategies in combination with these characteristics. We retrospectively reviewed and analyzed the data of 15 patients with rectal M-NETs who were diagnosed and treated at Beijing Friendship Hospital, Capital Medical University. Their clinical data, endoscopic findings, pathological features and treatments were analyzed. Follow-up evaluations and literature review were performed. In all, 14 male (93.3%) and 1 female (6.7%) were recruited. The average age at diagnosis was 55.7 years. The clinical manifestations include asymptomatic in 9 patients (60.0%), defecation habits changes in 2 patients (13.3%), anal distension in 2 patients (13.3%), and abdominal distension in 2 patient (13.3%). The largest tumor diameter ≤10mm was found in 13 patients (86.7%) and >10mm in 2 patients (13.3%). All of the lesions originated from the mucous or submucosa layer. WHO grades were all NET G1. The number of tumors diagnosed by pathology in 13 patients was consistent with that observed by endoscopy, while more lesions were observed by pathology than endoscopy in two patients. Lymph node metastasis occurred in 1 patient (6.7%), and vascular or lymphatic invasion occurred in 9 patients (60.0%). Among the 13 patients with the largest tumor diameter being ≤10mm, lymphovascular invasion occurred in 8 patients (61.5%). And among the 2 patients with the largest tumor diameter of >10mm, lymphovascular invasion occurred in 1 patient (50.0%). 14 patients underwent endoscopic resection and 1 underwent surgical excision. Postoperative follow-up was achieved in 13 patients and no recurrence or metastasis was found. The true number of rectal M-NETs may be more than seen under endoscopy. Rectal M-NETs is associated with a high risk of metastasis; therefore, treatment and surveillance strategies should be more radical than single lesion.

Integrated analysis of 14 lymphoma datasets revealed high expression of CXCL14 promotes cell migration in mantle cell lymphoma.

Lymphoma is accompanied by the impairment of multiple immune functions. Cytokines play an important role in a variety of immune-related functions and affect the tumor microenvironment. However, the exact regulatory mechanisms between them remain unclear. This study aimed to explore the cytokines expression and function in Hodgkin's lymphoma (HL), diffuse large B-cell lymphoma (DLBCL), and mantle cell lymphoma (MCL). We performed a transcriptome integration analysis of 14 lymphoma datasets including 240 Hodgkin's lymphoma, 891 diffuse large B-cell lymphoma, 216 mantle cell lymphoma, and 64 health samples. The results showed that multiple immune functions and signal pathway damage were shared by all three types of lymphoma, and these functions were related to cytokines. Furthermore, through co-expression network and functional interaction network analysis, we identified CXCL14 as a key regulator and it affects cell chemotaxis and migration functions. The functional experiment showed that CXCL14 knockdown inhibited cell migration in MCL cell lines. This study suggested that high expression of CXCL14 may aggravate MCL via promoting cell migration. Our findings provide novel insights into the biology of this disease and would be helpful for the pathogenesis study and drug discovery of lymphomas.

Disposable versus reusable gastroscopes: a prospective randomized noninferiority trial.

BACKGROUND AND AIMS: Disposable gastroscopes have recently been developed to eliminate the risk of infection transmission from contaminated reusable gastroscopes. We compared the performance of disposable and reusable gastroscopes in patients undergoing gastroscopy. METHODS: Patients requiring gastroscopy were randomized to either the disposable or reusable digital gastroscope group. The primary endpoint was the success rate of photographing customary anatomic sites, with a noninferiority margin of -8%. Secondary endpoints were technical performance factors such as gastroscope imaging quality, maneuverability, gastroscopy completion rate, device failure/defect rate, operating time, and safety. Data were analyzed using the Newcombe-Wilson score method and Fisher exact 2-tailed t test. RESULTS: Of 110 patients, 55 were treated using disposable gastroscopes and 55 using reusable gastroscopes. The success rate for capturing images of customary anatomic sites was 100% in both groups. The average imaging quality score was significantly lower (37.02 ± 3.09 vs 39.47 ± 1.92, P < .001) and the operating time significantly longer (P < .001) in the disposable gastroscope group. No significant differences in maneuverability, gastroscopy completion rate, device failure/defect rate, operating time, or safety were found between the 2 groups. CONCLUSIONS: Given the overall safety profile and similar technical performance, disposable gastroscopes represent an alternative to reusable gastroscopes for routine examination, bedside first aid, and some certain circumstances.

Characteristics of endoscopic and pathological findings of amebic colitis.

BACKGROUND: The clinical features of amoebic colitis resemble those of inflammatory bowel disease (IBD), and therefore the risk of misdiagnosis is very high. The aim of this study was to analyse the characteristics of the endoscopic and pathological findings of amebic colitis and the lessons from our patients, which were useful for diagnosing the amebic colitis timely and avoiding the serious complication. METHODS: We retrospectively reviewed data of all amebic colitis admitted to Beijing Friendship Hospital from January 2015 to January 2020. Cases were diagnosed by clinical presentation, laboratory examinations, and colonoscopy with biopsy and histological examination, no ELISA stool antigen or PCR tests were used. RESULTS: 16 patients were diagnosed with amebic colitis by the colonoscopy accompanied by biopsy and microscopic examination. At first time, 12 (75%) patients were misdiagnosed as IBD. Cecum was the most common site of amebic colitis (100%), and the caecum and rectum were also involved in many lesions (68.75%). Multiple lesions of erosion and/or ulcer were recognized in all patients (100%).The endoscopic findings included multiple irregular shaped ulcers and erosions with surrounding erythema, and the ulcers and erosions were covered by the white or yellow exudates. The intervening mucosae between the ulcers or erosions were normal. The features of rectums can be divided to 2 types: in 6 patients (54.5%), the irregular ulcer or erosions covered with white or yellow exudates were observed in rectum and cecum, and the bloody exudates in rectum were more severe than those in cecum; in other 5 patients (45.5%), rectal lesions were much less severe than those in cecum, the small superficial erosion or reddened mucosa were observed in the rectal ampulla. All patients were diagnosed as detection of amebic trophozoites from HE-stained biopsy specimens. The number of trophozoites ranged from 1/HPF to > 50/HPF. Among 16 cases, mild architectural alteration of colon crypt were observed in 10 cases (62.5%), and serious architectural alteration of colon crypt was found which had crypt branch in 1 case (16.7%). Cryptitis was observed in 12 cases (75%) and its severity was mild or moderate. No crypts abscess was observed in all cases. CONCLUSIONS: The colonoscopy with histological examination are very important to diagnose the amebic colitis. Detect the amoebic trophozoites in the exudates by histological examination is the vital. Sometimes a negative biopsy does not rule out amebiasis, repeated biopsies may be needed to make the diagnosis.

Difficult endoscopic resection of a giant esophageal fibrovascular polyp: case report and literature review.

Esophageal fibrovascular polyp is rare in esophageal neoplasms and usually very large. Here, we present a case of giant esophageal fibrovascular polyp. The patient had dysphagia and choking sensation at presentation. She underwent positron emission-computed tomography (PET-CT), endoscopy, endoscopic ultrasonography, and fine needle aspiration. She was clinically diagnosed as having an esophageal benign tumor and underwent endoscopic submucosal dissection. The polyp was successfully resected; however, the process was very difficult, and the lesion was too large to pass through the upper esophagus. Finally, we removed the lesion surgically. Fibrovascular polyps are often large, and if endoscopic resection is chosen, it is necessary to consider the difficulties that may be encountered during resection, before initiating treatment.

Histone H3K9 methylation regulates chronic stress and IL-6-induced colon epithelial permeability and visceral pain.

BACKGROUND: Chronic stress is associated with activation of the HPA axis, elevation in pro-inflammatory cytokines, decrease in intestinal epithelial cell tight junction (TJ) proteins, and enhanced visceral pain. It is unknown whether epigenetic regulatory pathways play a role in chronic stress-induced intestinal barrier dysfunction and visceral hyperalgesia. METHODS: Young adult male rats were subjected to water avoidance stress ± H3K9 methylation inhibitors or siRNAs. Visceral pain response was assessed. Differentiated Caco-2/BBE cells and human colonoids were treated with cortisol or IL-6 ± antagonists. Expression of TJ, IL-6, and H3K9 methylation status at gene promoters was measured. Transepithelial electrical resistance and FITC-dextran permeability were evaluated. KEY RESULTS: Chronic stress induced IL-6 up-regulation prior to a decrease in TJ proteins in the rat colon. The IL-6 level inversely correlated with occludin expression. Treatment with IL-6 decreased occludin and induced visceral hyperalgesia. Chronic stress and IL-6 increased H3K9 methylation and decreased transcriptional GR binding to the occludin gene promoter, leading to down-regulation of protein expression and increase in paracellular permeability. Intrarectal administration of a H3K9 methylation antagonist prevented chronic stress-induced visceral hyperalgesia in the rat. In a human colonoid model, cortisol decreased occludin expression, which was prevented by the GR antagonist RU486, and IL-6 increased H3K9 methylation and decreased TJ protein levels, which were prevented by inhibitors of H3K9 methylation. CONCLUSIONS & INFERENCES: Our findings support a novel role for methylation of the repressive histone H3K9 to regulate chronic stress, pro-inflammatory cytokine-mediated reduction in colon TJ protein levels, and increase in paracellular permeability and visceral hyperalgesia.

Differences between intentional and accidental ingestion of foreign body in China.

BACKGROUNDS: Previous reports of foreign-body ingestion focused primarily on accidental ingestion and very few studies focused on intentional ingestion of foreign body (FB) in China. Our study aimed to compare the prevalence of different age, gender, types, locations and management of FB ingested between intentional ingestion and accidental ingestion of FB in Northern China. METHODS: A retrospective case series studied all patients with suspected FB ingestion in Digestive Endoscopy Center of Beijing Friendship Hospital, between January 2011 and January 2019. The patients were divided into 2 groups. Group A included the patients who intentionally ingested FBs, and Group B included the patients who accidentally ingested FBs. Patients' database (demographics, past medical history, characteristics of FB, endoscopic findings and treatments) were reviewed. Statistical analyses were conducted using SPSS software. RESULTS: Group A consisted of 77 prisoners, 2 suspects and 11 psychologically disabled persons. Group B consisted of 1020 patients with no prisoners, suspects or psychologically disabled persons. In Group A, there were no food-related foreign bodies, and the majority of FBs were metallic objects (54.44%). However in Group B, food-related FBs were the most common (91.37%). In Group A, 58 cases (64.44%) were located in the stomach, while in Group B, 893 cases (87.55%) were located in the esophagus (P < 0.05). 1096 patients successfully underwent endoscopic removal and 14 failed, including 9 cases in Group A and 5 cases in Group B. The duration of FBs impaction was longer in Group A than that in Group B (P < 0.05). CONCLUSIONS: In our study, the patients who intentionally ingested FB were mainly prisoners, FBs were mostly sharp metallic objects, the duration of FBs impaction was longer, and the rate of successful endoscopic treatment was lower than that of the general population. Attention should be focused on these patients.

Model-based process development of continuous chromatography for antibody capture: A case study with twin-column system.

Multi-column periodic counter-current chromatography (PCC) has been developed for continuous antibody capture, but the complexity of continuous processes makes experimental optimization time consuming and costly. In this work, with twin-column continuous system as a typical case, mathematical models were established and used to evaluate the impacts of operating parameters for process development. The model fitted well with the experimental breakthrough curves and process performance under varying protein concentrations and residence times. Three important operating parameters, residence time for interconnected feeding (RTC), breakthrough percentage control for interconnected feeding (s) and disconnected feeding time (tDC), were evaluated systematically. The profiles of productivity and resin capacity utilization showed three phases as a function of RTC, which resulted in different optimization strategies towards s and tDC. Based on the model prediction, a working window of RTC and s can be determined for process development. Finally, a model-based design approach was proposed to determine the optimum operating conditions and to design a suitable continuous process for high productivity and capacity utilization. With the model-based design approach developed, the best performance of 12.8 g/L/h productivity and 91.9% capacity utilization was found for MabSelect SuRe resin under 1 mg/mL feeding IgG concentration at RTC = 2 min, s = 65% and tDC = 26 min.

Hyperactivity of Mek in TNS1 knockouts leads to potential treatments for cystic kidney diseases.

Cystic kidney disease is the progressive development of multiple fluid-filled cysts that may severely compromise kidney functions and lead to renal failure. TNS1 (tensin-1) knockout mice develop cystic kidneys and die from renal failure. Here, we have established TNS1-knockout MDCK cells and applied 3D culture system to investigate the mechanism leading to cyst formation. Unlike wild-type MDCK cells, which form cysts with a single lumen, TNS1-knockout cysts contain multiple lumens and upregulated Mek/Erk activities. The multiple lumen phenotype and Mek/Erk hyperactivities are rescued by re-expression of wild-type TNS1 but not the TNS1 mutant lacking a fragment essential for its cell-cell junction localization. Furthermore, Mek inhibitor treatments restore the multiple lumens back to single lumen cysts. Mek/Erk hyperactivities are also detected in TNS1-knockout mouse kidneys. Treatment with the Mek inhibitor trametinib significantly reduces the levels of interstitial infiltrates, fibrosis and dilated tubules in TNS1-knockout kidneys. These studies establish a critical role of subcellular localization of TNS1 in suppressing Mek/Erk signaling and maintaining lumenogenesis, and provide potential therapeutic strategies by targeting the Mek/Erk pathway for cystic kidney diseases.

EBV-associated lymphoproliferative disorder involving the gastrointestinal tract which mimic IBD in immunocompetent patients: case reports and literature review.

INTRODUCTION: Epstein-Barr virus (EBV)-associated lymphoproliferative diseases (LPD) with digestive tract involvement in immunocompetent patients is rather rare. Since the symptoms of EBV-associated LPD involving the gastrointestinal tract in immunocompetent patients are similar to those of inflammatory bowel disease (IBD), most patients are initially misdiagnosed. CASE PRESENTATION: In this paper, we present two cases of EBV-associated T cell LPD involving the colon in immunocompetent patients and review the relevant literature. CONCLUSION: EBV serological testing may help in detecting this disease, and our findings suggest that histopathological evidence of EBV, such as the Epstein-Barr encoding region, is very important to establish the diagnosis.

Complete excision of esophageal bronchogenic cyst by endoscopic submucosal tunnel dissection: a case presentation.

BACKGROUND: Intramural esophageal bronchogenic cyst is very rare. Surgical removal of the cysts is advised even the patients are asymptomatic, since the cyst can lead to complications, and there is a risk of malignant transformation. Thoracotomy or thoracoscopy is the most commonly used approach for complete excision of the cysts. To our knowledge, this is the first report to excise intramural esophageal bronchogenic cyst completely by endoscopic submucosal tunnel dissection (ESTD). CASE PRESENTATION: A 40-year-old male was referred to our hospital due to the detection of a submucosal tumor at the distal esophagus. The tumor was found during gastroendoscopy in a general health check-up. The patient had no symptoms. A benign esophageal tumor was confirmed by endoscopic ultrasonography (EUS) and computed tomography (CT). On the basis of these results, ESTD was performed. During the procedure, a cystic mass was observed between the mucosa and the muscular layers of the esophagus, and a hybrid knife was used for dissection. Histopathological examination showed the cyst wall was lined by pseudostratified ciliated columnar epithelium, consistent with a bronchogenic cyst. The esophagography using meglumine diatrizoate showed no leakage on the seventh day after ESTD. The patient remained asymptomatic and had a regular diet during the follow-up period. DISCUSSION AND CONCLUSIONS: We successfully utilized ESTD for complete removal of esophageal bronchogenic cysts originating from the muscularis propria. The approach appeared safe, providing a minimally invasive treatment option for patients.

Chronic stress and intestinal permeability: Lubiprostone regulates glucocorticoid receptor-mediated changes in colon epithelial tight junction proteins, barrier function, and visceral pain in the rodent and human.

BACKGROUND: Chronic psychological stress is associated with increased intestinal epithelial permeability and visceral hyperalgesia. Lubiprostone, an agonist for chloride channel-2, promotes secretion and accelerates restoration of injury-induced epithelial barrier dysfunction. The mechanisms underlying how lubiprostone regulates colon epithelial barrier function and visceral hyperalgesia in chronic stress remain unknown. METHODS: Male rats were subjected to water avoidance stress for 10 consecutive days. Lubiprostone was administered daily during the stress phase. Visceromotor response to colorectal distension was measured. Human colon crypts and cell lines were treated with cortisol and lubiprostone. The transepithelial electrical resistance and FITC-dextran permeability were assayed. Chromatin immunoprecipitation was conducted to assess glucocorticoid receptor binding at tight junction gene promoters. KEY RESULTS: Lubiprostone significantly decreased chronic stress-induced visceral hyperalgesia in the rat (P < 0.05; n = 6). WA stress decreased occludin and claudin-1 and increased claudin-2 in rat colon crypts, which was prevented by lubiprostone. Cortisol treatment induced similar alterations of tight junction protein expression in Caco-2/BBE cells (P < 0.05) and significantly changed paracellular permeability in monolayers (P < 0.01). These changes were blocked by lubiprostone. Glucocorticoid receptor and its binding at occludin promoter region were decreased in cortisol-treated cells and human colon crypts, which was largely reversed by lubiprostone. In rat colonic cells, glucocorticoid receptor and its co-chaperone proteins were down-regulated after corticosterone treatment and lubiprostone reversed these changes. CONCLUSIONS & INFERENCES: Lubiprostone preferentially prevents chronic stress-induced alterations of intestinal epithelial tight junctions, barrier function, and visceral hyperalgesia that was associated with modulation of glucocorticoid receptor expression and function.

Transcriptome and methylome profiling in a rat model of irritable bowel syndrome induced by stress.

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is associated with psychological stress. However, the full landscape of IBS­related epigenetic factors remains unveiled and needs to be elucidated. The water­avoidance stress (WAS) method was used to induce a rat IBS model. Each rat was monitored, and its defecation and behavior were recorded. Total colon RNA was isolated and subjected to Affymetrix GeneChip analysis. Reduced Representation Bisulfate Sequencing (RRBS) was applied to determine the genome­wide methylation pattern in both IBS and control rats. Rats with IBS egested a significantly increased amount of dry and loose stools compared with the control animals, without significant changes in body weight. Compared with the control group, 309 genes were upregulated and 224 genes were downregulated in the colon of the IBS rats. Notch signaling and focal adhesion were increased in the differentially expressed genes (DEGs). A total of 541 genes had significant lower methylation level and 626 genes had significantly higher methylation level in their promoter regions. Adherens junction and leukocyte transendothelial migration were enriched in the differentially methylated genes (DMGs). Few genes were identified in common in both DEGs and DMGs, suggesting that gene expression was not altered by promoter methylation. Reverse transcription­quantitative polymerase chain reaction validation revealed that the mRNA levels of SSX2IP, PARD3 and VCL were significantly downregulated in the IBS group, in accordance with hypermethylation of their promoters. In summary, the present study used a WAS­induced IBS rat model to provide transcriptome and methylome profiling. Most DEGs were associated with Notch signaling and focal adhesion, and only a few were altered by promoter methylation. The present results demonstrated that psychological stress could influence the integrity of the intestinal mucosa barrier and regulate inflammatory response.

Chronic stress and intestinal barrier dysfunction: Glucocorticoid receptor and transcription repressor HES1 regulate tight junction protein Claudin-1 promoter.

Chronic stress and elevated glucocorticoid hormone are associated with decreases in the intestinal epithelial tight junction protein claudin-1 (CLDN1). Human/rat CLDN1 promoters contain glucocorticoid response elements (GREs) and adjacent transcription repressor HES1 binding N-boxes. Notch signaling target HES1 expression was high and glucocorticoid receptor (NR3C1) low at the crypt base and the pattern reversed at the crypt apex. Chronic stress reduced overall rat colon HES1 and NR3C1 that was associated with CLDN1 downregulation. Chromatin-immunoprecipitation experiments showed that HES1 and NR3C1 bind to the CLDN1 promoter in rat colon crypts. The binding of NR3C1 but not HES1 to CLDN1 promoter significantly decreased in chronically stressed animals, which was prevented by the NR3C1 antagonist RU486. We employed the 21-day Caco-2/BBe cell model to replicate cell differentiation along the crypt axis. HES1 siRNA treatment early in differentiation increased CLDN1. In contrast, stress levels of cortisol decreased CLDN1 in late differentiation stage but not in the early stage. HES1 was high, whereas NR3C1 and CLDN1 were low in the early stage which reversed in the late stage, e.g. HES1/NR3C1 binding to CLDN1 promoter demonstrates a dynamic and reciprocal pattern. These results suggest that chronic stress impairs colon epithelium homeostasis and barrier function via different mechanisms along the crypt axis.