DHX9 maintains epithelial homeostasis by restraining R-loop-mediated genomic instability in intestinal stem cells.

Epithelial barrier dysfunction and crypt destruction are hallmarks of inflammatory bowel disease (IBD). Intestinal stem cells (ISCs) residing in the crypts play a crucial role in the continuous self-renewal and rapid recovery of intestinal epithelial cells (IECs). However, how ISCs are dysregulated in IBD remains poorly understood. Here, we observe reduced DHX9 protein levels in IBD patients, and mice with conditional DHX9 depletion in the intestinal epithelium (Dhx9ΔIEC) exhibit an increased susceptibility to experimental colitis. Notably, Dhx9ΔIEC mice display a significant reduction in the numbers of ISCs and Paneth cells. Further investigation using ISC-specific or Paneth cell-specific Dhx9-deficient mice demonstrates the involvement of ISC-expressed DHX9 in maintaining epithelial homeostasis. Mechanistically, DHX9 deficiency leads to abnormal R-loop accumulation, resulting in genomic instability and the cGAS-STING-mediated inflammatory response, which together impair ISC function and contribute to the pathogenesis of IBD. Collectively, our findings highlight R-loop-mediated genomic instability in ISCs as a risk factor in IBD.

Transpancreatic Sphincterotomy After Double Guidewire Technique Was Noninferior to Primary Transpancreatic Sphincterotomy in Difficult Biliary Cannulation.

BACKGROUND: When unintentional pancreatic duct access occurs during difficult biliary cannulation, the double guidewire (DGW) or transpancreatic sphincterotomy (TPS) may be utilized. DGW can be easily switched to TPS due to the existing guidewire in the pancreatic duct. However, the efficacy of TPS after DGW, named sequential DGW-TPS technique, versus primary TPS has not been assessed. AIMS: Our aim was to compare the benefits and adverse events of sequential DGW-TPS technique and primary TPS. METHODS: We performed a comparative retrospective cohort study that enrolled a total of 117 patients with native papillae. The patients were divided into one of 2 groups according to the primary bile duct access technique (sequential DGW-TPS or primary TPS), both with pancreatic stenting. RESULTS: Between November 2017 and May 2023, a total of 84 patients were grouped into sequential DGW-TPS and 33 into primary TPS. The overall post-ERCP pancreatitis (PEP) rate was 4.3% in the entire cohort, with no statistical differences were observed between the groups in terms of PEP rates (P = 0.927), PEP severity (P = 1.000), first biliary cannulation success (P = 0.621), overall cannulation success (P = 1.000), hyperamylasemia incidence (P = 0.241), elevated amylase levels (P = 0.881), and postoperative hospital stay (P = 0.185). Furthermore, these results remained consistent in multivariable regression analysis. CONCLUSIONS: The sequential DGW-TPS technique showed a comparable safety and biliary cannulation success rate to primary TPS in difficult biliary cannulation. Given the potential long-term complications associated with TPS, DGW should be first if inadvertent pancreatic access occurs, with TPS serving as second only if DGW fails.

Sporadic gastrinoma with refractory benign esophageal stricture: A case report.

BACKGROUND: Gastrinoma is characterized by an excessive release of gastrin, leading to hypersecretion of gastric acid, subsequently resulting in recurrent peptic ulcers, chronic diarrhea, and even esophageal strictures. This case report aims to improve awareness and facilitate early diagnosis and treatment of gastrinoma by presenting a rare case of gastrinoma with refractory benign esophageal stricture (RBES). Additionally, it highlights the persistent challenges that gastroenterologists encounter in managing RBES. CASE SUMMARY: This case demonstrates a patient with gastrinoma who developed RBES and complete esophageal obstruction despite management with maximal acid suppressive therapy, multiple endoscopic bougie dilations and endoscopic incisional therapy (EIT). CONCLUSION: It is essential to diagnose gastrinoma as early as possible, as inadequately controlled acid secretion over an extended period increases the risk of developing severe esophageal strictures. In patients with esophageal strictures causing complete luminal obstruction, blind reopening EIT presents challenges and carries a high risk of perforation.

Microbiome and its relevance to indigenous inflammatory bowel diseases in China.

BACKGROUND: Inflammatory Bowel Disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract with an unknown etiology. Although dysbiosis is implicated in its pathogenesis, deep sequencing and oral microbiota study in Chinese IBD patients is absent. AIM: To explore the role of oral / intestinal microbiota in patients with IBD and the potential associations therein. METHODS: Clinical data, fecal and saliva samples were harvested from 80 patients with IBD (Crohn's disease, CD, n = 69; Ulcerative colitis, UC, n = 11) and 24 normal controls. Microbiomics (16S rRNA sequencing and 16S rRNA full-length sequencing) were used to detect and analyze the difference between IBD patients and normal control. RESULTS: Compared with normal controls, a higher abundance of the intestinal Shigella spp. (Shigella flexneri and Shigella sonnei, which were positively relate to the severity of IBD), lower abundance of intestinal probiotics (Prevotella, Faecalibacterium and Roseburia), and higher abundance of oral Neisseria were present in IBD patients with microbiome. The higher inflammation-related markers, impaired hepatic and renal function, and dyslipidaemia were present in patients with IBD. A higher intake of red meat and increased abundance of Clostridium in the gut were found in CD patients, while the elevated abundance of Ruminococcus in the gut was showed in UC ones. The bacterial composition of saliva and fecal samples was completely different, yet there was some correlation in the distribution of dominant probiotics. CONCLUSION: Enteric dysbacteriosis and the infections of pathogenic bacteria (Shigella) may associate with the occurrence or development of IBD.

Use of double-balloon endoscopy and an endoscopic scoring system to assess endoscopic remission in isolated small bowel Crohn's disease after treatment with infliximab.

Background: It is unclear how clinical and endoscopic factors affect the attainment of endoscopic remission (ER) in patients with small bowel Crohn's disease (SB-CD) who are infliximab-naïve. Objectives: We aimed to identify the effect of different factors on attaining ER using double-balloon endoscopy (DBE) evaluation. Design: A single-center retrospective observational study was conducted from 1 January 2018 to 30 November 2022. Among 262 patients who were screened for isolated SB-CD by baseline DBE, 108 patients were assessed for effectiveness during maintenance infliximab therapy by a second DBE evaluation. Methods: DBE findings before and after infliximab therapy were compared. ER was defined as a simple endoscopic score for CD (SES-CD) below 3, and segmental ER as SES-CD activity of 0. Multivariate regression with calculations of odds ratios (OR) was used to determine the impact of different factors on attaining ER. Results: In all, 41 patients (38.0%) achieved ER. An elevated C-reactive protein at week 6 was independently associated with a decreased probability of ER [OR: 0.86, 95% confidence interval (CI) = 0.75-0.98, p = 0.03]. Segmental ER of the terminal ileum, rather than the proximal ileum, was associated with a higher rate of ER (60.9% versus 38.2%, p = 0.01). High baseline SES-CD (⩾16) was unrelated to overall ER. For patients with disease in the terminal ileum, those with moderate/severe disease were less likely to attain segmental ER than those with mild disease [adjusted odds ratios (aOR): 0.27, 95% CI: 0.09-0.83, p = 0.02]. A large ulcer in the terminal ileum was associated with a lower rate of segmental ER (aOR: 0.18, 95% CI: 0.06-0.56, p = 0.01). Conclusion: For infliximab-naïve patients with SB-CD, the overall severity of the endoscopic score was unrelated to attainment of ER. Patients were less likely to attain segmental ER if they had greater endoscopic inflammation or larger ulcers in the terminal ileum.

Deep learning based lesions detection and severity grading of small bowel Crohn's disease ulcers on double-balloon endoscopy images.

BACKGROUND AND AIMS: Double-balloon endoscopy (DBE) is widely used in diagnosing small bowel Crohn's disease (CD). However, CD misdiagnosis frequently occurs if inexperienced endoscopists cannot accurately detect the lesions. The CD evaluation may also be inaccurate and less objective due to the subjectivity of endoscopists. Our study aims to utilize artificial intelligence (AI) to accurately detect and objectively assess small bowel CD for more refined disease management. METHODS: We collected 28155 small bowel DBE images from 628 patients between January 2018 and December 2022. Four expert gastroenterologists labeled the images, and at least two endoscopists made the final decision with an agreement. A state-of-the-art deep learning model EfficientNet-b5 was trained to detect CD lesions and evaluate CD ulcers. The detection included lesions of ulcer, non-inflammatory stenosis, and inflammatory stenosis. Ulcer grading had ulcerated surface, ulcer size, and ulcer depth. A comparison of AI model performance with endoscopists was performed. RESULTS: The EfficientNet-b5 achieved high accuracies of 96.3% (95% CI, 95.7%-96.7%), 95.7% (95% CI, 95.1%-96.2%), and 96.7% (95% CI, 96.2%-97.2%) for the detection of ulcers, non-inflammatory stenosis, and inflammatory stenosis, respectively. In ulcer grading, the EfficientNet-b5 exhibited average accuracies of 87.3% (95% CI, 84.6%-89.6%) for grading the ulcerated surface, 87.8% (95% CI, 85.0%-90.2%) for grading the size of ulcers, and 85.2% (95% CI, 83.2%-87.0%) for the ulcer depth assessment. CONCLUSIONS: The EfficientNet-b5 achieved high accuracy in detecting CD lesions and grading CD ulcers. The AI model can provide expert-level accuracy and objective evaluation of small bowel CD to optimize the clinical treatment plans.

Natural Course of Common Bile Duct Microlithiasis.

BACKGROUND: Common bile duct microlithiasis (CBDM) with a diameter of ≤ 3 mm can pass spontaneously without causing any symptoms, but in some cases, it can also cause severe cholangitis and pancreatitis. The optimal strategy for managing CBDM is yet to be determined. METHODS: Data of 154 patients with CBDM were collected and divided into two groups: with endoscopic retrograde cholangiopancreatography (with ERCP, n = 82) and without ERCP (n = 72). Clinical outcomes, including the incidence of unfavorable outcomes (UOs), such as cholangitis and pancreatitis, were observed and compared between the two groups. RESULTS: The incidence of UOs was significantly lower in the ERCP group than in the without ERCP group (3.7% vs. 23.6%, respectively, p < 0.001). Moreover, the total number of readmissions was also lower in the ERCP group than in the without ERCP group (p < 0.001). A multivariate analysis adjusted for age, sex, and the American Society of Anesthesiologists (ASA) class revealed that endoscopic sphincterotomy (EST) and cholecystectomy were associated with a lower risk of UOs. CONCLUSION: The high rate of UOs in CBDM patients without ERCP suggests that its natural clinical course may not be as favorable as previously suggested. This finding implies that efforts should be made to clear the bile ducts.

Evaluation of symptomatic small bowel stricture in Crohn's disease by double-balloon endoscopy.

PURPOSE: To assess the efficacy of double-balloon endoscopy (DBE) for the detection of small-bowel strictures in Crohn's disease (CD). METHODS: This tertiary-referral hospital cohort study was conducted between January 2018 and May 2022. CD patients with symptoms of small-bowel stricture were enrolled sequentially. All of the patients were subjected to both computed tomography enterography (CTE) and DBE, and their symptoms of stricture were assessed using the Crohn's Disease Obstructive Score (CDOS). The diagnostic yield of DBE was compared to that of CTE, and the relationship between the DBE findings and CDOS was investigated. The factors influencing the DBE diagnosis were examined using Cox regression analysis. RESULTS: This study included 165 CD patients. The CDOS scores were higher in 95 patients and lower in 70 patients. DBE detected 92.7% (153/165) and CTE detected 85.5% (141/165) of the strictures. The DBE diagnostic yields were 94.7% (90/95) in the high CDOS patients and 91.4% (64/70) in the low CDOS patients (P = 0.13). Patients with a history of abdominal surgery and abscess had a lower diagnosis rate in the multivariate analysis. CONCLUSION: DBE has been demonstrated to be an efficient diagnostic method for detecting small bowel strictures in CD patients. Additionally, there was no difference in the diagnostic yields between patients with low and high obstructive scores.

Melatonin attenuates monocrotaline-induced hepatic sinusoidal obstruction syndrome in rats via activation of Sirtuin-3.

Melatonin possesses potent hepatoprotective properties, but it remains to be elucidated whether melatonin has a therapeutic effect on monocrotaline (MCT)-induced hepatic sinusoidal obstruction syndrome (HSOS). In this study, male Sprague Dawley rats were intraperitoneally injected with melatonin or the same volume of vehicle at 0 and 24 h after MCT intragastric administration. Next, hematoxylin-eosin staining and electron microscopy were performed to evaluate the hepatic sinusoidal injury of rats. Endothelial cell marker RECA-1 was observed by immunohistochemistry. Hepatic oxidative stress was analyzed by detecting malondialdehyde, glutathione S-transferase, and reactive oxygen species. Assessment of liver function was carried out by analysis of serum aspartate aminotransferase, alanine aminotransferase, total bilirubin, and albumin levels. Real-time polymerase chain reaction and Western blot analysis were used to identify liver Sirtuin-3 (SIRT3) and active matrix metallopeptidase 9 (MMP-9) expression. Besides, liver sinusoidal endothelial cells (LSECs) were used for the in vitro functional verification experiment. Specifically, liver histology of the melatonin-treated groups showed that the pathological damages caused by MCT were significantly attenuated, total HSOS scores were decreased, and the elevation of serum hyaluronic acid observed in the model group was also reduced. Moreover, melatonin treatment also improved the survival of rats after partial hepatectomy. Administration of melatonin ameliorated MCT-induced LSECs injury, hepatic oxidative stress, and hepatic dysfunction. Furthermore, melatonin treatment increased SIRT3 expression while attenuating MMP-9 activity in liver tissues. Cell experiment also demonstrated that SIRT3 might mediate the protective effect of melatonin on LSECs. Collectively, our study provided the potential rationale for the application of melatonin for the prevention of MCT-induced HSOS.

Interobserver Agreement among Cytopathologists in False-Negative Cases by Cytological Diagnosis with Endoscopic Ultrasound-Guided Fine Needle Aspiration in Solid Pancreatic Lesions.

INTRODUCTION: Early detection and accurate pathological assessment are critical to improving prognosis of pancreatic cancer. EUS has been widely used in diagnosing pancreatic lesions and can obtain histological diagnosis by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). However, comprehensive assessment of the interobserver agreement (IOA) among cytopathologists evaluating EUS-FNA specimens is still limited. Therefore, this study evaluated IOA among cytopathologists for EUS-FNA specimens of solid pancreatic lesions, especially in false-negative cases of cytological diagnosis and analyzed the factors that influence cytological diagnosis of EUS-FNA so as to improve the diagnostic efficiency of EUS-FNA. METHODS: We retrieved EUS-FNA samples of pancreatic solid lesions from 2017 to 2021 and collected their clinical/cytological data. Two cytopathologists independently reviewed these cases using a quoted, novel standardized cytology scoring tool. Ultimately, we calculated IOA among cytopathologists and performed a binary logistic regression analysis to evaluate factors influencing the cytological diagnosis of EUS-FNA. RESULTS: 161 patients were included, and 60 cases with a clinical diagnosis of pancreatic cancer but a cytological diagnosis of benign and atypical constituted the false-negative group. IOAs for cytological diagnosis of overall patients and the false-negative group were in perfect/moderate agreement with Kendall's W values of 0.896 and 0.462, respectively. The number of diagnostic cells in the scoring tool had the highest level of agreement (κ = 0.721) for overall patients. There was at best moderate agreement on other quantity and quality parameters for both all cases and false-negative group. Logistic regression analysis showed the number of diagnostic cells (OR = 6.110, p < 0.05) and amount of blood (OR = 0.320, p < 0.05) could influence cytological diagnosis. CONCLUSIONS: The false-negative rate of our study as high as 37.26% (60/161) is mainly related to strict standards of cytopathologists, and their ability to standardize pancreatic cytology is still improving. Suboptimal agreement among cytopathologists for cytological diagnosis and the number of diagnostic cells may be associated with the occurrence of false-negative diagnosis. Further regression analysis confirmed that the number of diagnostic cells and obscuring blood were important factors in cytological diagnosis. Therefore, refinement of cytological diagnostic criteria, standardization of specimen quality evaluation, and training of cytopathologists may improve the agreement of cytopathologists, thus improving the repeatability of cytological diagnosis and reducing the occurrence of false-negative events.

The Mechanosensitive Ion Channel PIEZO1 in Intestinal Epithelial Cells Mediates Inflammation through the NOD-Like Receptor 3 Pathway in Crohn's Disease.

BACKGROUND: Crohn's disease (CD) is an incurable chronic intestinal inflammatory disease with no recognized cause. It has been reported that the mechanosensitive ion channel PIEZO1 initiates proinflammatory responses. However, little is known about the role of PIEZO1 in CD. METHODS: Ileum biopsies were obtained from 30 patients with CD and 15 healthy volunteers. Clinical data were collected to determine the relationship between CD and PIEZO1. First, HT29 cells were incubated with Yoda1 and GsMTx4 (Grammostola spatulata mechanotoxin 4) to activate and inhibit PIEZO1, respectively. Second, PIEZO1 knockdown was performed using small interfering RNA. Third, calcium imaging, flow cytometry, and immunofluorescence were used to detect intracellular calcium and mitochondrial function. Last, real-time quantitative polymerase chain reaction, immunoblotting, and enzyme-linked immunosorbent assay were used to quantify PIEZO1, proinflammatory cytokines, and NLRP3 (NOD-like receptor 3)-related compounds. RESULTS: PIEZO1 was highly expressed in the ileum of patients with CD and correlated positively with the Crohn's Disease Activity Index, platelet count, and hematocrit and fecal calprotectin levels. In HT29 cells, Yoda1 triggered calcium influx, which was inhibited by GsMTx4 treatment and small interfering RNA-mediated PIEZO1 knockdown. Increased calcium concentrations resulted in increased reactive oxygen species accumulation and decreased mitochondrial membrane potential, whereas decreased calcium concentrations caused by GsMTx4 and PIEZO1 knockdown had the opposite effect. Mechanistically, molecules in the NLRP3 pathway were activated in patients with CD and HT29 cells were stimulated by lipopolysaccharide; these effects were reversed by the knockdown of PIEZO1. Finally, PIEZO1 and NLRP3 knockdown decreased proinflammatory cytokine levels in HT29 cells. CONCLUSIONS: PIEZO1 in intestinal epithelial cells caused calcium influx, which resulted in mitochondrial dysfunction and activated the NLRP3 inflammasome, mediating intestinal inflammation.

PIEZO1 was highly expressed in patients with active Crohn's disease. Its expression was significantly increased in the ileum and was associated with intestinal inflammation. In intestinal epithelial cells, PIEZO1 triggered calcium influx, resulting in mitochondrial dysfunction, and activated the NLRP3 inflammasome, thereby mediating intestinal inflammation.

Efficacy and safety of esophageal submucosal tumors treated with internal traction method-assisted submucosal tunneling endoscopic resection: a single-center, single-blind, randomized controlled study.

BACKGROUND AND OBJECTIVES: Submucosal tunnel endoscopic resection (STER) is an effective technique for treating esophageal submucosal tumors, but the efficacy and safety of treating esophageal submucosal tumors with internal traction method-assisted STER have not been determined. The objectives of this study were to assess the feasibility, safety, and efficacy of internal traction method-assisted STER for the removal of esophageal submucosal tumors. PATIENTS AND METHODS: Eighty patients who underwent STER for esophageal submucosal tumors were included in the study. They were randomized and assigned to the two groups. The dual-knife method was used for STER. Forty patients underwent conventional STER (control group) and 40 underwent internal traction method-assisted STER in which self-made rubber band traction with clips was used (study group). In the study group, one end of the self-made rubber band was fixed on the surface of esophageal submucosal tumors with a clip, and the other end of the self-made rubber band was set on the anal side of the contralateral esophageal wall with a clip. RESULTS: STER was successful in all cases. Lesion features and demographics were similar between the two groups. In addition, broad exposure of the submucosal tissue was obtained by applying tension to the self-made rubber band traction with clips. The en bloc resection rate and complete resection rate were both 100% in the study group. However, the en bloc resection rate and complete resection rate were 85.0% and 100%, respectively, in the control group. Complications, such as perforation and pneumomediastinum, were significantly reduced in the study group, and there was a significant difference in the number of occurrences of bleeding, operation duration, fasting time, and patient length of stay between the study group and control group (P < 0.05). During the mean 13.7 month follow-up, there were no patients with esophageal fistula, recurrence, or distant metastasis in either group. CONCLUSIONS: This original study showed that esophageal submucosal tumors could be effectively and safely treated with internal traction method-assisted STER, and this technique might be superior to conventional STER due to its fewer complications, shorter operation duration, and shorter inpatient length of stay.

Association between triglyceride-glucose index and atrial fibrillation: A retrospective observational study.

Background: Insulin resistance is associated with atrial remodeling as well as atrial fibrillation (AF). However, there was limited evidence on the relationship of triglyceride-glucose index (TyG) index, a simple, valuable marker of insulin resistance, with AF. Thus, we aimed to investigate the association between TyG index and AF among hospitalized patients. Methods: A retrospective observational study was conducted in Daping Hospital, which included 356 hospitalized patients from the Department of Cardiology. Clinical and biochemical parameters were collected from electronic medical records and AF was diagnosed from electrocardiogram (ECG) findings. Results: We found that the TyG index was significantly higher in the AF group than in the group without AF. Multivariate logistic regression revealed that hypertension (OR = 1.756, 95%CI 1.135-2.717, P = 0.011) and TyG index (OR = 2.092, 95%CI 1.412-3.100, P<0.001) were positively associated with AF. The analysis of the area under the ROC curve was performed and revealed that area under curve (AUC) of TyG index was 0.600 (95%CI, 0.542-0.659, P = 0.001), the optimal critical value was 8.35, the sensitivity was 65.4%, and the specificity was 52.0%. Additional subgroup analyses of diabetic and non-diabetic subjects were also performed and found the TyG index was increased in non-diabetic subjects with AF. Furthermore, a logistic regression analysis showed TyG index was associated with AF (OR = 3.065, 95% CI, 1.819-5.166, P<0.001) in non-diabetic subjects. However, TyG index was not associated with AF in diabetic subjects. Conclusion: Elevated TyG index is an independent risk factor for AF among non-diabetic hospitalized patients.

Vitamin B5 rewires Th17 cell metabolism via impeding PKM2 nuclear translocation.

Metabolic rewiring is essential for Th17 cells' functional identity to sense and interpret environmental cues. However, the environmental metabolic checkpoints with specific regulation of Th17 cells, manifesting potential therapeutic opportunities to autoimmune diseases, remain largely unknown. Here, by screening more than one hundred compounds derived from intestinal microbes or diet, we found that vitamin B5 (VB5) restrains Th17 cell differentiation as well as related autoimmune diseases such as experimental autoimmune encephalomyelitis and colitis. Mechanistically, VB5 is catabolized into coenzyme A (CoA) in a pantothenate kinase (PANK)-dependent manner, and in turn, CoA binds to pyruvate kinase isoform 2 (PKM2) to impede its phosphorylation and nuclear translocation, thus inhibiting glycolysis and STAT3 phosphorylation. In humans, reduced serum VB5 levels are found in both IBD and MS patients. Collectively, our study demonstrates a role of VB5 in Th17 cell metabolic reprograming, thus providing a potential therapeutic intervention for Th17 cell-associated autoimmune diseases.

Expression of 5-hydroxytryptamine 7 receptor in intestinal mucosa correlates with the degree of intestinal inflammation in Crohn's disease.

BACKGROUND: Crohn's disease (CD), an inflammatory bowel disease (IBD), is a complex and heterogeneous disease characterized by nonspecific transmural inflammation of the gastrointestinal tract. CD has a variety of potential causes with no effective treatment available yet. Current clinical laboratory findings from patients do not provide direct indication of the status of mucosal inflammation in the intestine. Recently, it has been found that intestinal inflammation is generally associated with increased levels of 5-hydroxytryptamine (5-HT), which acts as an important gastrointestinal signaling molecule in intestinal homeostasis by stimulating specific receptors. Most previous researches were carried out in vitro or with animal models, and there was a lack of authentic clinical research. In this study, clinical specimens from patients with Crohn's disease were used to investigate the expression of 5-hydroxytryptamine 7 receptor (5-HT7R) in the induction and development of chronic non-specific inflammatory bowel disease. METHODS: Patients with CD admitted to the Department of Gastroenterology in the First Affiliated Hospital of Anhui Medical University between June 2014 and January 2018 were recruited, among which 28 were in active disease and 32 were in remission. In addition, 20 patients who had no obvious abnormality by colonoscopy in the hospital during the same time period were recruited into the control group. Data of clinical disease activity (CDAI), CD endoscopic score (SES-CD) and magnetic resonance score (MaRIA) were collected from those two groups of patients. The expression and distribution of 5-HT7R were investigated and their correlations with clinical CDAI, MaRIA, and endoscopic SES-CD scores were analyzed. RESULTS: Our study demonstrated that 5-HT7R is expressed in intestinal neurons and CD11C-positive cells in human colon. In CD11c/CD86 double-positive cells in the bowel, 5-HT7R expression was significantly increased in the inflammatory area in the bowel of CD patients, and it was closely related to disease severity, MaRIA, and SES-CD scores. CONCLUSION: The expression of 5-HT7R was significantly correlated with the degree of gut inflammation in CD patients and could be a potential biomarker for disease activity and the therapeutic efficacy in patients with Crohn's Disease.

LncRNA PSR Regulates Vascular Remodeling Through Encoding a Novel Protein Arteridin.

RATIONALE: Vascular smooth muscle cells (VSMCs) phenotype switch from contractile to proliferative phenotype is a pathological hallmark in various cardiovascular diseases. Recently, a subset of long noncoding RNAs was identified to produce functional polypeptides. However, the functional impact and regulatory mechanisms of long noncoding RNAs in VSMCs phenotype switching remain to be fully elucidated. OBJECTIVES: To illustrate the biological function and mechanism of a VSMC-enriched long noncoding RNA and its encoded peptide in VSMC phenotype switching and vascular remodeling. RESULTS: We identified a VSMC-enriched transcript encoded by a previously uncharacterized gene, which we called phenotype switching regulator (PSR), which was markedly upregulated during vascular remodeling. Although PSR was annotated as a long noncoding RNA, we demonstrated that the lncPSR (PSR transcript) also encoded a protein, which we named arteridin. In VSMCs, both arteridin and lncPSR were necessary and sufficient to induce phenotype switching. Mechanistically, arteridin and lncPSR regulate downstream genes by directly interacting with a transcription factor YBX1 (Y-box binding protein 1) and modulating its nuclear translocation and chromatin targeting. Intriguingly, the PSR transcription was also robustly induced by arteridin. More importantly, the loss of PSR gene or arteridin protein significantly attenuated the vascular remodeling induced by carotid arterial injury. In addition, VSMC-specific inhibition of lncPSR using adeno-associated virus attenuated Ang II (angiotensin II)-induced hypertensive vascular remodeling. CONCLUSIONS: PSR is a VSMC-enriched gene, and its transcript IncPSR and encoded protein (arteridin) coordinately regulate transcriptional reprogramming through a shared interacting partner, YBX1. This is a previously uncharacterized regulatory circuit in VSMC phenotype switching during vascular remodeling, with lncPSR/arteridin as potential therapeutic targets for the treatment of VSMC phenotype switching-related vascular remodeling.

Fecal calprotectin predicts endoscopic activity and mucosal healing of small bowel Crohn's disease evaluated by double-balloon endoscopy.

PURPOSE: Fecal calprotectin (FC) levels can reflect the level of intestinal inflammation. Crohn's disease (CD), which affects the small bowel, has not been linked to FC levels. We determined if FC levels and endoscopic activity were related by performing double-balloon endoscopy (DBE). METHODS: Herein, patients with small bowel CD diagnosed by DBE between January 2020 and January 2022 were prospectively observed. Feces and blood samples of patients were collected before performing DBE and checked for the levels of FC and serological biomarkers. The endoscopic activity and mucosal healing (MH) were evaluated using the partial simple endoscopic score (pSES-CD). RESULTS: In all 254 CD patients, FC levels were correlated with pSES-CD (r = 0.775, P < 0.001). Even in patients with isolated small bowel CD, FC levels were strongly correlated with pSES-CD (r = 0.753, P < 0.001). In all patients, FC as an endoscopic remission indicator was found to have an area under the curve (AUC) of 0.872, with a cut-off value of 156.09 µg/g. In patients with isolated small bowel CD, FC yielded a high AUC of 0.865 for predicting endoscopic remission, with a cut-off value of 211.48 µg/g, sensitivity of 73.95%, and specificity of 91.30%. FC was optimally cut-off at 76.99 µg/g to predict MH in accordance with the AUC of 0.877. CONCLUSIONS: Using DBE findings, FC was found to be significantly correlated with pSES-CD. Even in isolated small bowel CD, FC may be a more reliable marker of accurately predicting endoscopic remission and MH.

A Birth Cohort Study of Neurodevelopmental Outcomes from Birth to 2 Years of Age in Preterm Infants under 34 Weeks of Gestation.

Background: The tissues and organs of premature infants are immature and easily damaged by external adverse factors, leading to functional development disorders and abnormalities. Besides, the incidence of premature babies in various countries has an increasing trend, with the incidence rate exceeding 10%. Objective: This study aims to investigate the neurodevelopment and the incidence of various developmental delays, cerebral palsy, autism spectrum disorder, and audio-visual impairment in premature infants under 34 weeks of gestation from birth to 2 years of age, so as to provide the basis for early intervention of premature infants in the clinic. Methods: A cohort of premature infants was established using 263 premature infants with a gestational age of 28-33 + 6 weeks who were born alive from March 1, 2018, to February 28, 2019, in four tertiary hospitals in Shenzhen. In addition, 263 full-term infants of the same sex who were born in the same period in the four hospitals were randomly selected and paired in a ratio of 1 : 1 as the control group. The subjects were assessed for neurodevelopment using the Gesell test scale at 6, 12, 18, and 24 months after birth (premature infants were corrected for months). We calculated the neurodevelopmental indicators of children in each month of age and the incidence of various developmental delays, cerebral palsy, autism spectrum disorder, and audio-visual impairment in the two groups. Results: The results of this study showed that the cohort of premature infants with birth gestational age less than 34 weeks had higher adaptive, fine motor, and personal-social energy domain development quotient (DQ) values from the corrected gestational age of 6 months to the corrected gestational age of 24 months after birth compared with the full-term cohort. And it also achieved catch-up growth in neurological development, but the detection rates of neurodevelopmental abnormalities at the corrected gestational age of 12 and 24 months were higher than those in the full-term cohort. Conclusion: It is important to reduce the disability rate and degree of premature infants by strengthening the systematic management, early promotion and supervision, as well as early intervention for preterm infants with developmental abnormalities who were born at gestational age less than 34 weeks after birth.