Leucine-tRNA-synthase-2-expressing B cells contribute to colorectal cancer immunoevasion.

Immunoregulatory B cells impede antitumor immunity through unknown features and mechanisms. We report the existence of leucine-tRNA-synthase-2 (LARS2)-expressing B cell (LARS B) subset with a transforming growth factor-ß1 (TGF-ß1)-dominant regulatory feature in both mouse and human progressive colorectal cancer (CRC). Of note, LARS B cells exhibited a leucine nutrient preference and displayed active mitochondrial aminoacyl-tRNA biosynthesis. They were located outside the tertiary lymphoid structure and correlated with colorectal hyperplasia and shortened survival in CRC patients. A leucine diet induced LARS B cell generation, whereas LARS B cell deletion by Lars2 gene ablation or leucine blockage repressed CRC immunoevasion. Mechanistically, LARS2 programmed mitochondrial nicotinamide adenine dinucleotide (NAD+) regeneration and oxidative metabolism, thus determining the regulatory feature of LARS B cells in which the NAD-dependent protein deacetylase sirtuin-1 (SIRT1) was involved. We propose a leucine-dieting scheme to inhibit LARS B cells, which is safe and useful for CRC therapy.

Chondroitin polymerizing factor promotes development and progression of colorectal cancer via facilitating transcription of VEGFB.

Colorectal cancer (CRC) is a highly prevalent malignancy affecting the digestive system on a global scale. This study aimed to explore the previously unexplored role of CHPF in the progression of CRC. Our results revealed a significant upregulation of CHPF expression in CRC tumour tissues compared to normal tissues, with its levels correlating with tumour malignancy. In vitro experiments using CRC cell lines demonstrated that inhibiting CHPF expression suppressed cell proliferation, colony formation and cell migration, while promoting apoptosis. Conversely, overexpressing CHPF had the opposite effect. Additionally, our xenograft models in mice confirmed the inhibitory impact of CHPF knockdown on CRC progression using various cell models. Mechanistic investigations unveiled that CHPF may enhance VEGFB expression through E2F1-mediated transcription. Functionally, suppressing VEGFB expression successfully mitigated the oncogenic effects induced by CHPF overexpression. Collectively, these findings suggest that CHPF may act as a tumour promoter in CRC, operating in a VEGFB-dependent manner and could be a potential target for therapeutic interventions in CRC treatment.

Fluorogenic Rhodamine-Based Chemigenetic Biosensor for Monitoring Cellular NADPH Dynamics.

Ratiometric biosensors employing Förster Resonance Energy Transfer (FRET) enable the real-time tracking of metabolite dynamics. Here, we introduce an approach for generating a FRET-based biosensor in which changes in apparent FRET efficiency rely on the analyte-controlled fluorogenicity of a rhodamine rather than the commonly used distance change between donor-acceptor fluorophores. Our fluorogenic, rhodamine-based, chemigenetic biosensor (FOCS) relies on a synthetic, protein-tethered FRET probe, in which the rhodamine acting as the FRET acceptor switches in an analyte-dependent manner from a dark to a fluorescent state. This allows ratiometric sensing of the analyte concentration. We use this approach to generate a chemigenetic biosensor for nicotinamide adenine dinucleotide phosphate (NADPH). FOCS-NADPH exhibits a rapid and reversible response toward NAPDH with a good dynamic range, selectivity, and pH insensitivity. FOCS-NADPH allows real-time monitoring of cytosolic NADPH fluctuations in live cells during oxidative stress or after drug exposure. We furthermore used FOCS-NADPH to investigate NADPH homeostasis regulation through the pentose phosphate pathway of glucose metabolism. FOCS-NADPH is a powerful tool for studying NADPH metabolism and serves as a blueprint for the development of future fluorescent biosensors.

Expression of SOX4 Significantly Predicts the Risk of Lymph Node Metastasis for Patients With Early-Stage Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma stands as a notably aggressive malignancy within the digestive system. In cases of early esophageal cancer without lymph node metastasis, endoscopic surgical resection offers a viable alternative, often resulting in improved patient quality of life. However, the paucity of methods to preoperatively ascertain lymph node involvement complicates surgical planning. SOX4 gene was previously found to be highly associated with invasive metastasis in our work through single-cell RNA sequencing on 5 paired tumor/peritumor tissues. This research included the collection of 124 tissue samples from 106 patients (106 tumor and 18 lymph node specimens). Samples were methodically arranged into a tissue microarray and treated with immunohistochemical staining. Statistical analysis was conducted to assess the relationship between them. In the univariate analysis, 3 factors were identified as statistically significant in relation to lymph node metastasis: T category (P = .014), vascular invasion (P < .001), and SOX4 intensity (P = .001). Additionally, when evaluating SOX4 intensity alongside other clinical indicators, SOX4 was shown to independently influence lymph node metastasis. Further, the multivariate analysis revealed that vascular invasion (P < .001) and SOX4 intensity (P = .003) were significantly associated with lymph node metastasis, exhibiting hazard ratios of 10.174 and 7.142, respectively. The results of our study indicate that both SOX4 expression and vascular invasion serve as predictors of lymph node metastasis in patients diagnosed with category T1 esophageal squamous cell carcinoma, underscoring the potential utility of SOX4 in prognostic evaluations.

Whole-exome sequencing reveals common and rare variants in immunologic and neurological genes implicated in achalasia.

Idiopathic achalasia (IA) is a severe motility disorder characterized by neuronal degeneration in the myenteric plexus, but the etiology remains largely unknown. We performed whole-exome sequencing (WES) in 100 IA-affected individuals and 313 non-IA control subjects and validated the results in 230 IA-affected individuals and 1,760 non-IA control subjects. Common missense variants rs1705003 (CUTA, GenBank: NC_000006.11:g.33385953A>G) and rs1126511 (HLA-DPB1, GenBank: NC_000006.11:g.33048466G>T) at 6p21.32 were reproducibly associated with increased risk of IA (rs1126511: OR = 1.83, p = 2.34 × 10-9; rs1705003: OR = 2.37, p = 3.21 × 10-7), meeting exome-wide significance. Both variants can affect the expression of their target genes at the transcript level. An array-based association analysis in 280 affected individuals and 1,121 control subjects determined the same signal at 6p21.32. Further conditional analyses supported that the two missense variants identified in WES-based association study were potential causal variants of IA. For rare variants, the top genes identified by gene-based analysis were significantly enriched in nerve and muscle phenotypic genes in the mouse. Moreover, the functional rare variants in these genes tended to cooccur in IA-affected individuals. In an independent cohort, we successfully validated three rare variants (CREB5, GenBank: NC_000007.13:g.28848865G>T; ESYT3, GenBank: NC_000003.11:g.138183253C>T; and LPIN1, GenBank: NC_000002.11:g.11925128A>G) which heightens the risk of developing IA. Our study identified and validated two common variants and three rare variants associated with IA in immunologic and neurological genes, providing new insight into the etiology of IA.

YY1: a key regulator inhibits gastric cancer ferroptosis and mediating apatinib-resistance.

OBJECTIVE: Gastric cancer (GC) stands as a prevalent and deadly global malignancy. Despite its role as a preoperative neoadjuvant therapy, Apatinib's effectiveness is curtailed among GC patients exhibiting elevated YY1 expression. YY1's connection to adverse prognosis, drug resistance, and GC metastasis is established, yet the precise underlying mechanisms remain elusive. This study aims to unravel potential pathogenic pathways attributed to YY1. DESIGN: Utilizing bioinformatics analysis, we conducted differentially expressed genes, functional annotation, and pathway enrichment analyses, and further validation through cellular and animal experiments. RESULTS: Higher YY1 expression correlated with diminished postoperative progression-free survival (PFS) and disease-specific survival (DSS) rates in TCGA analysis, identifying YY1 as an independent DSS indicator in gastric cancer (GC) patients. Notably, YY1 exhibited significantly elevated expression in tumor tissues compared to adjacent normal tissues. Bioinformatics analysis revealed noteworthy differentially expressed genes (DEGs), transcriptional targets, factors, and co-expressed genes associated with YY1. LASSO Cox analysis unveiled Transferrin as a prospective pivotal protein regulated by YY1, with heightened expression linked to adverse DSS and PFS outcomes. YY1's role in governing the p53 signaling pathway and ferroptosis in GC cells was further elucidated. Moreover, YY1 overexpression dampened immune cell infiltration within GC tumors. Additionally, YY1 overexpression hindered GC cell ferroptosis and mediated Apatinib resistance via the p53 pathway. Remarkably, IFN-a demonstrated efficacy in reversing Apatinib resistance and immune suppression in GC tissues. CONCLUSIONS: Our findings underscore the pivotal role of YY1 in driving GC progression and influencing prognosis, thus pinpointing it as a promising therapeutic target to enhance patient outcomes.

New endoscopic closure technique, "internal traction-assisted suspended closure," for GI defect closure: a pilot study (with video).

BACKGROUND AND AIMS: After endoscopic full-thickness resection (EFTR), reliable closure of the perforation is critical. However, it is technically difficult to close some defects by using metal clips alone or by purse-string suturing, which may lead to unreliable closure. Inspired by the process of pulling up the 2 ends of the incision in the surgical suture, we developed a new endoscopic closure technique, the "internal traction-assisted suspended closure" technique. This pilot study was performed as an initial evaluation of the feasibility and safety of this new endoscopic closure technique. METHODS: Data from patients in whom this suspended closure technique was used to close full-thickness defects after EFTR were retrospectively reviewed. The primary outcome was successful closure rate. Secondary outcomes were closure time, length of postprocedural hospital stay, and incidence of postprocedural adverse events. Defect size and tumor characteristics were also analyzed. RESULTS: Eight patients who underwent the suspended closure technique after EFTR were included. All patients were successfully treated with the suspended closure technique, and no patient developed serious adverse events. The median length of the defect was 3.25 cm (range, 2.5-9.0) and the median width was 2.8 cm (range, 1.8-6.0). The median closing time was 13 minutes (range, 6-24). CONCLUSIONS: The internal traction-assisted suspended closure technique is a simple, reliable, and easy-to-use technique for large full-thickness defects after endoscopic resection.

Automatically optimized radiomics modeling system for small gastric submucosal tumor (<2 cm) discrimination based on EUS images.

BACKGROUND AND AIMS: The clinical management of small gastric submucosal tumors (SMTs) (<2 cm) faces a non-negligible challenge because of the lack of guideline consensus and effective diagnostic tools. This article develops an automatically optimized radiomics modeling system (AORMS) based on EUS images to diagnose and evaluate SMTs. METHODS: A total of 205 patients with EUS images of small gastric SMTs (<2 cm) were retrospectively enrolled in the development phase of AORMS for the diagnosis and the risk stratification of GI stromal tumor (GIST). A total of 178 patients with images from different centers were prospectively enrolled in the independent testing phase. The performance of AORMS was compared to that of endoscopists in the development set and evaluated in the independent testing set. RESULTS: AORMS demonstrated an area under the curve (AUC) of 0.762 for the diagnosis of GIST and 0.734 for the risk stratification of GIST, respectively. In the independent testing set, AORMS achieved an AUC of 0.770 and 0.750 for the diagnosis and risk stratification of small GISTs, respectively. In comparison, the AUCs of 5 experienced endoscopists ranged from 0.501 to 0.608 for diagnosing GIST and from 0.562 to 0.748 for risk stratification. AORMS outperformed experienced endoscopists by more than 20% in diagnosing GIST. CONCLUSIONS: AORMS implements automatic parameter selection, which enhances its robustness and clinical applicability. It has demonstrated good performance in the diagnosis and risk stratification of GISTs, which could aid endoscopists in the diagnosis of small gastric SMTs (<2 cm).

Validation and update of a clinical score model to predict technical difficulty of colorectal endoscopic submucosal dissection: a multicenter prospective cohort study.

BACKGROUND AND AIMS: The Zhongshan colorectal endoscopic submucosal dissection (CR-ESD) score model was proposed to grade the technical difficulty of CR-ESD. The objective of this study was to prospectively validate and update the score model. METHODS: A multicenter prospective cohort analysis of CR-ESD was conducted. Individual data on patients, lesions, and outcomes of CR-ESD were used to validate the original model and further refine the difficulty of the prediction model. Data were randomly divided into discovery and internal validation cohorts. A multivariate Cox regression analysis was conducted on the discovery cohort to develop an updated risk-scoring system, which was then validated. RESULTS: Five hundred forty-eight patients with 565 colorectal lesions treated by ESD from 4 hospitals were included. In the prospective validation cohort, the area under the receiver-operating characteristic (ROC) curve for the original model was .707. Six risk factors were identified and assigned point values: tumor size (2 points for 30-50 mm, 3 points for ≥50 mm), at least two-thirds circumference of the lesion (3 points), tumor location in the cecum (2 points) or flexure (2 points), laterally spreading tumor-nongranular lesions (1 point), preceding biopsy sampling (1 point), and NBI International Colorectal Endoscopic type 3 (3 points). The updated model had an area under the ROC curve of .738 in the discovery cohort and of .782 in the validation cohort. Cases were categorized into easy (score = 0-1), intermediate (score = 2-3), difficult (score = 4-6), and very difficult (score ≥7) groups. Satisfactory discrimination and calibration were observed. CONCLUSIONS: The original model achieved an acceptable level of prediction in the prospective cohort. The updated model exhibited superior performance and can be used in place of the previous version. (Clinical trial registration number: ChiCTR2100047087.).

Endoscopic resection of giant esophageal subepithelial lesions: experience from a large tertiary center.

BACKGROUND AND AIMS: Increased reports on endoscopic resection (ER) of esophageal giant subepithelial lesions (g-SELs) have emerged in recent years. The aim of this study was to evaluate the efficacy, technical difficulty, and safety through our single-center experience. METHODS: Seventy-five patients with g-SELs undergoing endoscopic resection were included in the training set. Clinicopathologic features, procedure-related characteristics, postprocedural outcomes, and follow-up data were analyzed. A predictive nomogram model for procedural difficulty was proposed based on the multivariable logistic regression analysis. Internal and external validations were conducted to verify the model performance. RESULTS: The overall en bloc resection rate was 93.3%. Intraoperative and postoperative adverse events occurred in 7 (9.3%) and 13 (17.3%) patients, respectively. No recurrence or metastasis was observed. Thirty-two (42.7%) patients underwent a difficult procedure. Age (adjusted odds ratio [aOR], .915; P = .004), maximal tumor diameter ≥8 cm (aOR, 9.896; P = .009), irregular shape (aOR, 4.081; P = .053), extraluminal growth pattern (aOR, 5.419; P = .011), and submucosal tunneling endoscopic resection (aOR, .109; P = .042) were found to be statistically or clinically significant factors for predicting endoscopic resection difficulty, based on which a nomogram model was developed. Internal and external validations of the nomogram via receiver-operating characteristic curves and calibration curves achieved favorable results. CONCLUSIONS: Endoscopic resection serves as a promising therapeutic option for esophageal g-SELs. A younger patient age, large tumor size, irregular shape, and extraluminal growth may indicate increased endoscopic resection difficulty, whereas a submucosal tunneling endoscopic resection procedure tends to be of lower difficulty. Our nomogram model performs well for predicting endoscopic resection difficulty for esophageal g-SELs.

Long-term outcomes of endoscopic resection for well-differentiated nonampullary duodenal neuroendocrine tumors.

BACKGROUND & AIMS: Nonampullary duodenal neuroendocrine tumors (NAD-NETs) are rare with limited evidence regarding endoscopic treatment. The study aimed to investigate the efficacy and safety of endoscopic resection of well-differentiated NAD-NETs and evaluate long-term outcomes, including local recurrence and metastasis. METHODS: A total of 78 patients with NAD-NETs who underwent endoscopic resection between January 2011 and August 2022 were included. The clinicopathologic characteristics and treatment outcomes were collected and analyzed. RESULTS: En bloc resection was achieved for 74 of the tumors (94.9%) and R0 resection was obtained in 68 of the tumors (87.2%). Univariate analysis identified tumors in the second part of the duodenum, tumor size ≥ 10 mm and muscularis propria invasion as risk factors for non-curative resection. Two patients with R1 resection (vertical margin involvement) and two patients with lymphovascular invasion underwent additional surgery. Four patients experienced adverse events (5.1%), including two cases of delayed bleeding and two cases of perforation, all successfully managed conservatively. During a median follow-up period of 62.6 months, recurrence and lymph node metastasis were only detected in one patient with R1 resection 3 months after the original procedure. CONCLUSION: Endoscopic resection is safe and effective and provides a favorable long-term outcome for patients with well-differentiated NAD-NETs without regional lymph node or distant metastasis.

A scoring system to predict the technical difficulty of endoscopic resection for cardial submucosal tumors.

BACKGROUND AND AIM: Endoscopic resection has been successfully used for the removal of digestive submucosal tumors (SMTs). However, the cardia has been considered a challenging location for endoscopic resection due to its narrow lumen and sharp angle. The objective of this study was to establish a clinical scoring model to grade the technical difficulty of endoscopic resection for cardial SMTs. METHODS: A total of 246 patients who suffered cardial SMTs and received endoscopic resection were included in this retrospective study. All of them were randomized into the training cohort (n = 123) or internal validation cohort (n = 123). Potential predictors were analyzed using univariate analysis. Then, covariates with P < 0.05 were selected for the multivariate logistic regression model. The ß coefficients from the logistic regression model were used to create a scoring system for technical difficulty prediction by rounding the score to the nearest integer of the absolute ß coefficient value. RESULTS: The clinical score consisted of the following factors: male gender (2 points), extraluminal growth (3 points), and maximum diameter ≥3 cm (3 points). The scoring model demonstrated good discriminatory power, with an area under the receiver operating characteristic curve of 0.860 and a 95% confidence interval of 0.763-0.958. The model also showed a good goodness of fit in the Hosmer-Lemeshow test (P = 0.979). In the training cohort, the probability of encountering technical difficulty in the easy (score = 0), intermediate (score = 1-3), difficult (score = 4-6), and very difficult (score >6) categories was 0, 6.8%, 33.3%, and 100.0%, respectively; similarly, in the validation cohort, it was 0, 5.6%, 22.2%, and 50.0%, respectively. CONCLUSIONS: This scoring system could serve as a valuable tool for clinicians in predicting the technical difficulty of endoscopic resection for cardial SMTs.

Feasibility and safety of endoscopic resection for the jejunoileal lesions.

BACKGROUND: Endoscopic resection (ER) for jejunoileal lesions (JILs) has been technically challenging. We aimed to characterize the clinicopathologic characteristics, feasibility, and safety of ER for JILs. METHOD: We retrospectively investigated 52 patients with JILs who underwent ER from January 2012 to February 2022. We collected and analyzed clinicopathological characteristics, procedure-related parameters, outcomes, and follow-up data. RESULTS: The mean age was 49.4 years. Of the 52 JILs, 33 ileal tumors within 20 cm from the ileocecal valve were resected with colonoscopy, while 19 tumors in the jejunum or the ileum over 20 cm from the ileocecal valve received enteroscopy resection. The mean procedure duration was 49.0 min. The en bloc resection and en bloc with R0 resection rates were 86.5% and 84.6%, respectively. Adverse events (AEs) included one (1.9%) major AE (delayed bleeding) and five (9.6%) minor AEs. During a median follow-up of 36.5 months, two patients had local recurrence (3.8%), while none had metastases. The 5-year recurrence-free survival (RFS) and disease-specific survival (DSS) were 92.9% and 94.1%, respectively. Compared with the enteroscopy group, overall AEs were significantly lower in the colonoscopy group (P < 0.05), but no statistical differences were observed in RFS (P = 0.412) and DSS (P = 0.579). There were no significant differences in AEs, RFS, and DSS between the endoscopic submucosal dissection (ESD) and the endoscopic mucosal resection (EMR) group. CONCLUSIONS: ER of JILs has favorable short-term and long-term outcomes. Both ESD and EMR can safely and effectively resect JILs in appropriately selected cases.

Peroral endoscopic myotomy is an effective treatment for achalasia combined with hiatal hernia.

PURPOSE: To explore the feasibility of peroral endoscopic myotomy (POEM) in patients with achalasia and hiatal hernia. MATERIALS AND METHODS: We performed a retrospective review of 2136 patients with achalasia between January 2016 and December 2022. Patients with achalasia and hiatal hernia were assigned into study group, and matched patients with achalasia but no hiatal hernia were assigned into control group. The preoperative baseline information, procedure-related adverse events (AEs) and follow-up data were compared between the two groups. RESULTS: Hiatal hernia was identified in 56/1564 (3.6%) patients with achalasia. All of these patients underwent POEM with success. The preoperative baseline characteristics were similar between the study and control group. The study group presented with a similar rate of mucosal injury (12.5% vs 16.1, P = 0.589), pneumothorax (3.6% vs 1.8%, P = 1.000), pleural effusion (8.9% vs 12.5%, P = 0.541) and major AEs (1.8% vs 1.8%, P = 1.000) compared with the control group. As for the follow-up data, no significant differences were observed in clinical success (96.4% vs 92.9%, P = 0.679; 93.6% vs 94.0%, P = 1.000; 86.5% vs 91.4%, P = 0.711) clinical reflux (25.0% vs 19.6%, P = 0.496; 31.9% vs 26.0%, P = 0.521; 35.1% vs 31.4%, P = 0.739) and proton pump inhibitor usage (17.9% vs 16.1%, P = 0.801; 29.8% vs 24.0%, P = 0.520; 32.4% vs 25.7%, P = 0.531) between the study group and control group at 1-year, 2-year and 3-year follow-ups. CONCLUSIONS: POEM is a safe and effective treatment for achalasia combined with hiatal hernia.

The safety and efficacy of endoscopic submucosal fenestration in the treatment of completely embedded upper gastrointestinal foreign body.

BACKGROUND: Upper gastrointestinal foreign body ingestion is a common digestive tract emergency, of which completely embedded ones were challenging for most endoscopists. We aim to evaluate the efficacy and safety of endoscopic submucosal fenestration in the treatment of completely embedded upper gastrointestinal foreign bodies. METHODS: From December 2018 to December 2021, 19 patients with completely embedded upper gastrointestinal foreign bodies who underwent endoscopic submucosal fenestration in Zhongshan Hospital, Fudan University were included. The safety, efficacy, and outcome were retrospectively reviewed. RESULTS: Among the 19 patients, 15 foreign bodies were embedded in the esophagus, 3 located in the gastric wall, and 1 located in the duodenal bulb. The foreign bodies were successfully managed in 12 cases, and 7 failed after attempts of repeated exploration. Two cases confirmed completely traversing into the mediastinum were successfully removed after transfer to surgery. One case had retrieval of a foreign body in a half-year examination. Till now, 3 failed patients had great relief of symptoms and only one patient claimed occasional thoracodynia. Of note, there were neither serious adverse events, nor long-term complications during the follow-up. CONCLUSION: In disposing of foreign bodies completely embedded in the upper gastrointestinal tract, ESF is a safe and effective alternative to surgery.

Clinical outcomes of endoscopic resection for the treatment of intermediate- or high-risk gastric small gastrointestinal stromal tumors: a multicenter retrospective study.

BACKGROUND AND AIMS: Many studies of gastric gastrointestinal stromal tumors (g-GISTs) following endoscopic resection (ER) have typically focused on tumor size, with most tumors at low risk of aggressiveness after risk stratification. There have been few systematic studies on the oncologic outcomes of intermediate- or high-risk g-GISTs after ER. METHODS: From January 2014 to January 2020, we retrospectively collected patients considered at intermediate- or high-risk of g-GISTs according to the modified NIH consensus classification system. The primary outcome was overall survival (OS). RESULTS: Six hundred and seventy nine (679) consecutive patients were diagnosed with g-GISTs and treated by ER between January 2014 and January 2020 in three hospitals in Shanghai, China. 43 patients (20 males and 23 females) were confirmed at intermediate-or high-risk. The mean size of tumors was 2.23 ± 1.01 cm. The median follow-up period was 62.02 ± 15.34 months, with a range of 28 to 105 months. There were no recurrences or metastases, even among patients having R1 resections. The 5-year OS rate was 97.4% (42/43). CONCLUSION: ER for intermediate- or high-risk gastric small GISTs is a feasible and safe method, which allows for a wait-and-see approach before determining the necessity for imatinib adjuvant or surgical treatment. This approach to g-GISTs does require that patients undergo close follow-up.

Bridging polyp in an anastomosis resected by endoscopic submucosal dissection (ESD).

A 60-year-old man was admitted to our hospital for routine postoperative review of colon cancer. He underwent a colonoscopy, which showed a bridge-like polyp located 13 cm from the anal verge, with the base of the polyp located 1.5 cm above the anastomosis and the head of it located on the anastomosis and fusion growth with the anastomosiz. The patient accepted ESD to remove the lesion. During the ESD procedure, the basal of the polyp was incised using an insulated-tip knife, when the polyp tip located at the anastomosis was gradually dissected with a hook knife, severe fibrosis and three staples was found in the submucosal. We carefully separated the scar tissue and pulled out staples with hook knife in electrocision mode. Finally, we removed the lesion completely.

Exosomal lncRNA HOTAIR induces PDL1+ B cells to impede anti-tumor immunity in colorectal cancer.

Regulatory B cells (Bregs) contribute to tumor immunosuppression. However, how B cells acquire their regulatory features in tumors remain unclear. Exosomes are important messengers that transmit tumor information to remodel tumor immunity. Here we revealed that tumor-derived exosomes drive Bregs to suppress anti-tumor immunity by delivering long non-coding RNAs (lncRNAs). HOTAIR was screened by lncRNA profiling in both colorectal cancer (CRC)-derived exosomes and infiltrating B cells. Tumor-derived HOTAIR polarized B cells toward a regulatory feature marked by programmed cell death-ligand 1 (PDL1) in CRC, and induced PDL1+ B cells to suppress CD8+ T cell activity. Exosomal HOTAIR bound to and protected pyruvate kinase M2 (PKM2) against ubiquitination degradation, resulting in STAT3 activation and PDL1 expression. Results from CRC patients showed a positive correlation between exosomal HOTAIR and tumor-infiltrating PDL1+ B cells. These findings reveal how B cells acquire PDL1-dominant regulatory feature in CRC, implying the clinical significance of exosomal therapy targeting HOTAIR.

Gastric Peroral Endoscopic Pyloromyotomy for Infants With Congenital Hypertrophic Pyloric Stenosis.

INTRODUCTION: Congenital hypertrophic pyloric stenosis (CHPS), the most common infantile disease requiring surgical intervention, is routinely treated with open or laparoscopic pyloromyotomy. Recently, gastric peroral endoscopic pyloromyotomy (G-POEM) has been used for adult gastroparesis. We aimed to evaluate the efficacy and safety of G-POEM in treating infantile CHPS. METHODS: We reviewed data from 21 G-POEM-treated patients at 3 tertiary children's endoscopic centers in China between January 2019 and December 2020. Clinical characteristics, procedure-related parameters, perioperative management, and follow-up outcomes were summarized. RESULTS: G-POEM was performed successfully in all patients. The median operative duration was 49 (14-150) minutes. The submucosal tunnels were successfully established along the greater curvature of the stomach in 19 cases, and 2 cases were switched to the lesser curvature because of difficulty. No perioperative major adverse events occurred. Minor adverse events included inconsequential mucosal injury in 5 cases and unsatisfactory closure of the mucosal incision in 1 case. Upper gastrointestinal contrast radiography in all patients showed smooth passage of the contrast agent through the pylorus on postoperative day 3. The growth curves of the patients reached normal levels 3 months after the procedure. No recurrent clinical symptoms occurred in any patient during the median follow-up period of 25.5 (14-36) months. DISCUSSION: G-POEM is feasible, safe, and effective for infants with CHPS, with satisfactory clinical responses over a short-term follow-up. Further multicenter studies should be performed to compare the long-term outcomes of this minimally invasive technique with open or laparoscopic pyloromyotomy.