Ulcerative colitis (UC) is a heterogeneous autoimmune condition. PANoptosis, a new form of programmed cell death, plays a role in inflammatory diseases. This study aimed to identify differentially expressed PANoptosis-related genes (PRGs) involved in immune dysregulation in UC. Three key PRGs-BIRC3, MAGED1, and PSME2 were found using weighted gene co-expression network analysis (WGCNA) and machine learning. Immune infiltration analysis revealed that these key PRGs were associated with neutrophils, CD8+ T cells, activated CD4 T cells, and NK cells. Moreover, these key PRGs were significantly enriched in pathways related to inflammatory bowel disease, the IL-17 signaling pathway, and NOD-like receptor signaling pathway. The expression levels of the key PRGs were validated in various datasets, animal models, and UC intestinal tissue samples. Our findings confirmed the involvement of PANoptosis in UC and predict hub genes and immune characteristics, providing new insights for further investigations into UC pathogenic mechanisms and therapeutic strategies.

Many immune-mediated diseases have the common genetic basis, as an autoimmune disorder, celiac disease (CeD) primarily affects the small intestine, and is caused by the ingestion of gluten in genetically susceptible individuals. As for ulcerative colitis (UC), which most likely involves a complex interplay between some components of the commensal microbiota and other environmental factors in its origin. These two autoimmune diseases share a specific target organ, the bowel. The etiology and immunopathogenesis of both conditions characterized by chronic intestinal inflammation, ulcerative colitis and celiac disease, are not completely understood. Both are complex diseases with genetics and the environmental factors contributing to dysregulation of innate and adaptive immune responses, leading to chronic inflammation and disease. This study is designed to further clarify the relationship between UC and CeD. The GEO database was used to download gene expression profiles for CeD (GSE112102) and UC (GSE75214). The GSEA KEGG pathway analysis revealed that immune-related pathways were significantly associated with both diseases. Further, we screened 187 shared differentially expressed genes (DEGs) of the two diseases. Gene Ontology (GO) and WikiPathways were carried out to perform the biological process and pathway enrichment analysis. Subsequently, based on the DEGs, the least absolute shrinkage and selection operator (LASSO) analysis was performed to screen for the diagnostic biomarkers of the diseases. Moreover, single-cell RNA-sequencing (RNA-seq) data from five colonic propria with UC showed that REG4 expression was present in Goblet cell, Enteroendocrine cell, and Epithelial. Finally, our work identified REG4 is the shared gene of UC and CeD via external data validation, cellular experiments, and immunohistochemistry. In conclusion, our study elucidated that abnormal immune response could be the common pathogenesis of UC and CeD, and REG4 might be a key potential biomarker and therapeutic target for the comorbidity of these two diseases.

Gastrointestinal motility refers to the peristalsis and contractility of gastrointestinal muscles, including the force and frequency of gastrointestinal muscle contraction. Gastrointestinal motility maintains the normal digestive function of the human body and is a critical component of the physiological function of the digestive tract. At present, gastrointestinal motility disorder-related diseases are gradually affecting human production and life. In recent years, it has been consistently reported that the enteric nervous system has a coordinating and controlling role in gastrointestinal motility. Motility disorders are closely related to functional or anatomical changes in the gastrointestinal nervous system. At the same time, some viral infections, such as herpes simplex virus and varicella-zoster virus infections, can cause damage to the gastrointestinal nervous system. Therefore, this paper describes the mechanisms of viral infection in the gastrointestinal nervous system and the associated clinical manifestations. Studies have indicated that the means by which viruses can cause the infection of the enteric nervous system are various, including retrograde transport, hematogenous transmission and centrifugal transmission from the central nervous system. When viruses infect the enteric nervous system, they can cause clinical symptoms, such as abdominal pain, abdominal distension, early satiation, belching, diarrhea, and constipation, by recruiting macrophages, lymphocytes and neutrophils and regulating intestinal microbes. The findings of several case‒control studies suggest that viruses are the cause of some gastrointestinal motility disorders. It is concluded that one of the causes of gastrointestinal motility disorders is viral infection of the enteric nervous system. In such disorders, the relationships between viruses and nerves remain to be studied more deeply. Further studies are necessary to evaluate whether prophylactic antiviral therapy is feasible in gastrointestinal motility disorders.

The aim of the present study was to examine the function of transgelin (TAGLN) and its underlying mechanism in the ferroptosis of esophageal squamous cell carcinoma (ESCC) cells. To meet this aim, the association between TAGLN expression and the prognosis of patients with ESCC was determined using tissue samples and clinical data. Gene Expression Omnibus databank and Gene Set Enrichment Analysis data were used to examine which genes were co-expressed with TAGLN, as well as the influence of TAGLN on ESCC. Subsequently, Transwell chamber, wound healing, Cell Counting Kit-8 viability and colony formation assays were performed to observe the effects of TAGLN on the migration, invasion, viability and proliferation of Eca-109 and KYSE-150 cells. The interaction between TAGLN and p53 in the regulation of ferroptosis was detected using reverse transcription-quantitative PCR, co-immunoprecipitation and fluorescence co-localization assays, and a xenograft tumor model was established to examine the effect of TAGLN on tumor growth. The level of TAGLN expression in patients with ESCC was found to be low, compared with normal esophageal tissue, and a positive association was identified between the prognosis of ESCC and TAGLN expression. The expression of the ferroptosis marker protein, glutathione peroxidase 4, was found to be high, whereas that of acyl-CoA synthetase long-chain family member 4 was lower in patients with ESCC compared with expression levels in healthy patients. The overexpression of TAGLN resulted in a significant decrease in the invasive and proliferative capabilities of Eca-109 and KYSE-150 cells in vitro compared with the control group; in vivo, TAGLN overexpression was found to significantly decrease tumor size, volume and weight after one month of growth. In addition, the proliferation, migration and invasion of Eca-109 cells in vivo was stimulated by the knockdown of TAGLN. The results of the transcriptome analysis further demonstrated that TAGLN was able to induce ferroptosis-associated cell functions and pathways. Finally, TAGLN overexpression was found to promote ferroptosis in ESCC through its interaction with p53. Taken together, the findings of the present study suggested that the malignant development of ESCC may be inhibited by TAGLN through the manifestation of ferroptosis.

Over the last few decades, gut microbiota research has been the focus of intense research and this field has become particularly important. This research aimed to provide a quantitative evaluation of the 100 most-cited articles on gut microbiota and IBS and highlight the most important advances in this field.The database Web of Science Core Collection was used to download the bibliometric information the top 100 most-cited papers. Microsoft Excel 2021, CiteSpace, VOSviewer, R software, and an online analytical platform ( https://bibliometric.com/ ) were was applied to perform bibliometric analysis of these papers.The total citation frequency in the top 100 article ranged from 274 to 2324, with an average citation of 556.57. A total of 24 countries/regions made contributions to the top 100 cited papers, and USA, Ireland, and China were the most top three productive countries. Cryan JF was the most frequently nominated author, and of the top 100 articles, 20 listed his name. Top-cited papers mainly came from the Gastroenterology (n = 13, citations = 6373) and Gut (n = 9, citations = 3903). There was a significant citation path, indicating publications in molecular/biology/immunology primarily cited journals in molecular/biology/genetics fields. Keywords analysis suggested that the main topics on gut microbiota and IBS were mechanisms of microbiome in brain-gut axis." Behavior" was the keyword with the strongest burst strength (2.36), followed by "anxiety like behavior" (2.24), "intestinal microbiota" (2.19), and "chain fatty acid" (1.99), and "maternal separation" (1.95).This study identified and provided the bibliometric information of the top 100 cited publications related to gut microbiota and IBS. The results provided a general overview of this topic and might help researchers to better understand the evolution, Influential findings and hotspots in researching gut microbiota and IBS, thus providing new perspectives and novel research ideas in this specific area.

[This corrects the article DOI: 10.3389/fonc.2021.709486.].

To investigate the therapeutic effects of phellodendrine in ulcerative colitis (UC) through the AMPK/mTOR pathway. Volunteers were recruited to observe the therapeutic effects of Compound Cortex Phellodendri Liquid (Huangbai liniment). The main components of Compound Cortex Phellodendri Liquid were analysed via network pharmacology. The target of phellodendrine was further analysed. Caco-2 cells were cultured, and H2O2 was used to stimulate in vitro cell model. Expression levels of LC3, AMPK, p-AMPK, mTOR and p-mTOR were detected via Western blotting and through immunofluorescence experiments. The therapeutic effects of phellodendrine were analysed via expression spectrum chip sequencing. The sequencing of intestinal flora further elucidated the therapeutic effects of phellodendrine. Compared with the control group, Compound Cortex Phellodendri Liquid could substantially improve the healing of intestinal mucosa. Network pharmacology analysis revealed that phellodendrine is the main component of Compound Cortex Phellodendri Liquid. Moreover, this alkaloid targets the AMPK signalling pathway. Results of animal experiments showed that phellodendrine could reduce the intestinal damage of UC compared with the model group. Findings of cell experiments indicated that phellodendrine treatment could activate the p-AMPK /mTOR signalling pathway, as well as autophagy. Expression spectrum chip sequencing showed that treatment with phellodendrine could promote mucosal healing and reduce inflammatory responses. Results of intestinal flora detection demonstrated that treatment with phellodendrine could increase the abundance of flora and the content of beneficial bacteria. Phellodendrine may promote autophagy by regulating the AMPK-mTOR signalling pathway, thereby reducing intestinal injury due to UC.

Objective:To evaluate the short-term efficacy and safety of peroral endoscopic myotomy (POEM) combined with full thickness V-shaped resection of partial lower esophageal muscle in treatment of achalasia and to develop a method for obtaining full-thickness smooth muscle samples of lower esophageal sphincter.Methods:Achalasia patients who underwent endoscopic surgery at Tianjin Medical University General Hospital from February 2018 to February 2019 were randomly divided into a group of POEM combined with full thickness V-shaped resection of partial lower esophageal muscle (group A) and POEM group (group B) according to the ratio of 1∶3 by using random number table. Operation duration, intraoperative blood loss, and other complications were compared between the two groups. Eckardt score, reflux score, high-resolution esophageal manometry and esophageal emptying parameters were compared 1 and 3 months after treatment in both groups. Additionally, the size, weight and microstructure of smooth muscle samples obtained during the operations were also compared.Results:A total of 57 patients were included in the study, 16 in group A, and 41 in group B, and all underwent operations successfully. No significant differences were found in operation duration or intraoperative bleeding between the two groups [87.81±13.03 min VS 82.20±18.10 min, t=1.302, P=0.201; 6.75±1.44 mL VS 7.00 (2.00) mL, U=-0.903, P=0.348]. No serious complications occurred during or after operation. Follow-ups were performed at 1 and 3 months after operation. Eckardt score [0.00 (1.00) VS 0.00 (1.00), U=-0.156, P=0.876; 0.00 (1.00) VS 0.00 (1.00), U=-0.337, P=0.736], reflux score [0.00 (0.00) VS 0.00 (0.00), U=-0.207, P=0.836; 0.00 (0.00) VS 0.00 (0.00), U=-0.207, P=0.836], lower esophageal sphincter pressure [16.00±7.00 mmHg VS 13.76±6.21 mmHg, t=1.183, P=0.242; 15.06±4.14 mmHg VS 11.00 (7.00) mmHg, U=-1.852, P=0.064](1 mmHg=0.133 kPa), 4 s integrated relaxation pressure (6.57±2.69 mmHg VS 6.82±2.22 mmHg, t=-0.364, P=0.717; 5.96±1.84 mmHg VS 6.46±1.43 mmHg, t=-1.095, P=0.278) and the height of barium in 5 min in esophageal emptying test (2.16±0.91 cm VS 2.13±0.87 cm, t=0.127, P=0.899; 2.22±0.51 cm VS 2.10±0.87 cm, t=0.657, P=0.514) were similar between the two groups, which were lower than those before treatment (all P<0.05). In addition, no differences were found in either group in the above indicators between the two postoperative follow-ups (all P>0.05). One patient in group A and 2 in group B reported reflux symptoms during the short-term follow-up but no drug intervention was required. The size of specimens obtained from group A was bigger [(1.32±0.55) cm × (0.58±0.17) cm × (0.18±0.02) cm VS (0.28±0.05) cm × (0.13±0.03) cm × (0.10±0.03) cm, t=5.244, P<0.001)] and their weight was heavier (0.22±0.09 g VS 0.03±0.01 g, t=7.192, P<0.001) than those of group B. Complete circular muscle, intermuscular plexus and longitudinal muscle could be observed under microscopy in group A, while only circular muscle could be observed in group B. Conclusion:The safety and short-term efficacy of POEM combined with full thickness V-shaped resection of partial lower esophageal muscle in the treatment of achalasia are comparable to those of POEM, which provides ideal histopathological specimens for achalasia pathology.

the GCWB104 and control groups ( P = 0.0452 and P = 0.0486, respectively).Thirteen of 15 individual symptoms of the GSRS improved in the GCWB104 group, while 6 symptoms improved in the control group.In addition, statistically significant changes in rumbling, loose stool, and stool urgency were observed in the GCWB104 group.Blood 8-hydroxy-2'deoxyguanosine (8-OHdG) levels, known as antioxidants, showed significant reductions before and after 8 weeks of administration of GCWB104 (Table ).There were no adverse events related to GCWB104.Conclusions: GCWB104 contributed to lessening mild to moderate FD and IBS symptoms safely.Its antioxidant effects were also suggested Mo1541

Background: To restore esophageal peristalsis of achalasia patients by sequenced electric stimulation, an appropriate method must be established to implant the electrodes and pacemaker safely and effectively. We combined POEM (per-oral endoscopic myotomy) and abdominal wall puncture in pigs in order to explore a feasible procedure for the implantation. Material/Methods: Five healthy male pigs were used in the present study with the permission of the Ethics Committee of Tianjin Medical University General Hospital. The electrodes were implanted in esophageal submucosal tunnel by POEM with the end of the electrode deposited in the abdominal cavity using NOTES technique. A pacemaker was then positioned under the skin of the abdomen. Finally, the electrodes were connected with the pacemaker with the help of endoscopy in the abdominal cavity. Esophageal peristalsis of these pigs after implantation was monitored for esophageal intraluminal pressure changes using electronic gastroscopy and a high-resolution manometry (HRM). The observation lasted for 6 h. Results: The procedure was effective to implant the electrode and the pacemaker using POEM and NOTES techniques. The connection of the 2 devices was also successful. Esophageal intraluminal pressure changes after electrical stimulation were recorded using HRM. Vital signs of the pigs were stable during the 6-h follow-up. Conclusions: From this small-sample, short follow-up animal study, it was found that the implantation of esophageal electrodes and pacemaker based on POEM and NOTES is feasible, safe, and effective. Nevertheless, there is urgent need for long-term follow-up to confirm or disprove the safety of the procedure.

Background and aims POEM is a rescue endoscopic therapy for patients who had previously failed surgical or endoscopic treatment. However, data regarding its effectiveness after failed pneumatic dilation (PD) and its long-term effects are limited. We aimed to retrospectively investigate the long-term outcomes in patients who had undergone POEM after failed PD. Methods Data from 66 achalasia patients with a 2-year follow-up period were analyzed. Intraprocedural events were compared between the first POEM group (patients without prior-endoscopic intervention) and prior PD group (patients who had pre-POEM PD). Symptom evaluation, HRM and 24 h-pH DeMeester scores between the two groups were performed at 2 years after the POEM procedure. Muscularis externa samples were obtained from the lower esophagus using POEM to assess the muscle fibrosis with Azan-Mallory staining. Results POEM was successfully performed for all achalasia patients. During the 2-year follow-up period, the success rate of POEM was 96.15% (25/26) for patients with prior PD and 95% (38/40) with primary POEM. For patients with type II achalasia and who underwent prior PD, the post-procedure DeMeester score was higher compared to patients who underwent POEM only (P < 0.05). A larger number of patients who underwent primary POEM (27.50%, 11/40) complained of mild heartburn compared to patients who underwent POEM after PD (7.69%, 2/26) (P < 0.05). With regards to fibrosis, the majority of patients who underwent POEM only were classified as F-1 (45.00%, 18/40), while the majority of patients who underwent prior PD were classified as F-2 (42.3%, 11/26). The degree of fibrosis was significantly different between the two groups (P < 0.05). Both surgical time and prior PD were correlated with the degree of fibrosis (P < 0.05). Conclusions Despite the technical challenges, pre-POEM endoscopic treatment does not impact the safety and efficacy of POEM in achalasia patients. Longer follow-up studies using larger cohorts are needed to determine long-term outcomes and complications of POEM.

Background: Abdominal bloating/distension are among the most difficult symptoms to evaluate in the clinic, and there is no translation for bloating in some languages such as Spanish.Abdominal inflammation is the mos frequently use expression by patients.Recently we showed that pictograms detected bloating/distension in 48.9% of patients that did not report them by verbal descriptors, and they were more sensitive and specific. 1However, pictograms performance in IBS -the most common FGID-and one with very high prevalence of bloating/distension, 2 is unknown.Aims: To evaluate the use of validated pictograms for bloating/distension and compared them with verbal descriptors in IBS patients in Mexico.Methods: IBS was diagnosed by Rome III Questionnaire and physicians evaluation.They answered a questionnaire with verbal descriptors for bloating/distension, the pictograms, and then were consulted by 2 GI fellows trained to diagnose bloating, distension or both (Physicians Diagnosis: PD)-gold standard.Also, they were asked if they understood the expression abdominal distension and its meaning as well as abdominal inflammation.Based on our previous study, 1 a sample of 144 patients was determined.Variables are expressed in mean±SD and percentages and compared by ANOVA and X 2 , respectively. .Correlations were conducted with Pearson r.A p≤0.05 was considered significant.Results: Patients were 37±10 years-old, F: 112 (77.8%).IBS subtypes were IBS-C: 70(48.6%);IBS-M: 32(22.2%),IBS-D: 31(21.5%),IBS-U: 11(7.6%).Distension was not understood by 59%, while 22.9% reported having it, and 18.1% did not.In contrast, inflammation was reported by 96.5%.Physicians diagnosed boating/distension in 97.9%.Pictograms showed a strong correlation with PD: r=0.8, p<0.000 while verbal descriptors had a negative correlation with PD: r=-0.1, p=0.2.The area under the ROC showed a superiority of pictograms: 0.993 (IC95%: 0.980-1.00),p=0.004 vs. verbal descriptors: 0.323 (0.103-0.542), p=0.294; when contrasted with the PD.Further, in 29 patients that didnt report bloating/distension with verbal descriptors, the pictograms detected 26(89.6%) with any form of bloating/distension.Conclusions: Pictograms are more effective than verbal descriptors to detect any form of bloating/ distension in Rome III-IBS patients.The data supports our previous findings in patients in general, and the usefulness of pictograms for bloating/distension in the clinic and clinical and epidemiology trials.

the remainder of esophageal spasm patients.Results: We identified 8 patients with premature (DL = 5 + 1.5s) esophageal spasm (4F, 66 + 9 years) and 14 patients with delayed (DL = 7.4 + 1.8s) esophageal spasm (13F, 61 + 15 years).Endoscopic evaluation did not show stricture or eosinophilic mucosal infiltration in any of the patients.DS patients were predominantly female (P < 0.05).Age and BMI were similar in both groups, and prevalence of dysphagia, regurgitation, heartburn, chest pain, heartburn and weight loss was not different across the two groups.CFV was similar in the PS and DS groups (8.5 + 0.8 vs 8.3 + 1.2 cm/s, P > 0.5).Both groups displayed a high prevalence of abnormal CCK response with 5 PS patients (63%) and 9 DS patients (64%) showing paradoxical LES contraction (Figure-1).Both groups also showed esophageal body hyperactivity with repetitive non-peristaltic contractions after CCK administration that unveiled abundant contractile reserve (14541 + 15413 mmHg.cm.s) in majority (18/22) of patients (Figure -2).CONCLUSIONS: A significant number of patients with spastic esophageal contractions display abnormal responses to CCK, suggesting impaired inhibitory neurotransmission.Similar to previous findings, the DL did not predict symptom pattern.We further find that DL is not a good predictor of impaired inhibitory neurotransmission.CCK motor response may be a better criterion for identifying those patients with true esophageal spasm than the DL value.

Background: The Rome criteria for functional gastrointestinal diseases (FGIDs) have been updated from Rome III to Rome IV. This study aimed to investigate the impact of the update on patients with irritable bowel syndrome (IBS) in China.Methods: A previous database including consecutive patients with FGIDs (according to Rome III criteria) from gastrointestinal department of a tertiary hospital in China was re-analyzed. Demographic information, clinical symptoms, psychological status (Zung self-rating scale), and sleep quality (Pittsburgh sleep quality index) were compared between patients with Rome III and Rome IV IBS.Results: Of the 946 patients with FGIDs, only 58 (6.1%) were diagnosed with Rome IV IBS [less than 292 (30.9%) under Rome III criteria] with a surge of the number of unspecified functional bowel disorders (U-FBD). All patients with IBS were divided into three groups: group A [meeting both Rome III and IV criteria, accounting for 43 (4.6%) of patients with FGIDs], group B [meeting only Rome III criteria, 249 (26.3%)], and group C [meeting only Rome IV criteria,15 (1.6%)]. Significant differences in frequency and severity of symptoms, subtypes, and sleep quality among groups (all p < .05) were found. Patients with Rome III IBS having sleep disorder tended to be more serious than those without. On the contrary, it was not the case under Rome IV criteria.Conclusions: Number of IBS patients was greatly reduced accompanied by a surge in U-FBD. Besides, the updated criteria also had great impacts on clinical parameters, sleep quality and psychological state of IBS patients.HighlightsRome IV criteria removed the description of abdominal discomfort for IBS.The updated Rome criteria had great impacts on IBS patients in our database.Our study analyzed the characteristics of IBS patients who fulfilled both criteria.Alterations in the Rome criteria also led to changes in the disease spectrum of FBD.

the remainder of esophageal spasm patients.Results: We identified 8 patients with premature (DL = 5 + 1.5s) esophageal spasm (4F, 66 + 9 years) and 14 patients with delayed (DL = 7.4 + 1.8s) esophageal spasm (13F, 61 + 15 years).Endoscopic evaluation did not show stricture or eosinophilic mucosal infiltration in any of the patients.DS patients were predominantly female (P < 0.05).Age and BMI were similar in both groups, and prevalence of dysphagia, regurgitation, heartburn, chest pain, heartburn and weight loss was not different across the two groups.CFV was similar in the PS and DS groups (8.5 + 0.8 vs 8.3 + 1.2 cm/s, P > 0.5).Both groups displayed a high prevalence of abnormal CCK response with 5 PS patients (63%) and 9 DS patients (64%) showing paradoxical LES contraction (Figure-1).Both groups also showed esophageal body hyperactivity with repetitive non-peristaltic contractions after CCK administration that unveiled abundant contractile reserve (14541 + 15413 mmHg.cm.s) in majority (18/22) of patients (Figure -2).CONCLUSIONS: A significant number of patients with spastic esophageal contractions display abnormal responses to CCK, suggesting impaired inhibitory neurotransmission.Similar to previous findings, the DL did not predict symptom pattern.We further find that DL is not a good predictor of impaired inhibitory neurotransmission.CCK motor response may be a better criterion for identifying those patients with true esophageal spasm than the DL value.

Colonoscopy is essential for the diagnosis of many diseases, such as colorectal cancer, colorectal polyps and ulcerative colitis. Nevertheless, for the severe pain caused by colonoscopy, this examination is poorly tolerated. For people who have a very limit tolerance to anesthesia, it is important to find a method to ease their pain. Previous research found that music can reduce anxiety and pain during colonoscopy. The present study aimed to clarify the mechanism.