Peptidyl arginine deiminase 4 (PAD4) plays a pivotal role in infection and inflammatory diseases by facilitating the formation of neutrophil extracellular traps (NETs). However, the substrates of PAD4 and its exact role in inflammatory bowel disease (IBD) remain unclear. In this study, we employed single-cell RNA sequencing (scRNA-seq) and substrate citrullination mapping to decipher the role of PAD4 in intestinal inflammation associated with IBD. Our results demonstrated that PAD4 deficiency alleviated colonic inflammation and restored intestinal barrier function in a dextran sulfate sodium (DSS)-induced colitis mouse model. scRNA-seq analysis revealed significant alterations in intestinal cell populations, with reduced neutrophil numbers and changes in epithelial subsets upon PAD4 deletion. Gene expression analysis highlighted pathways related to inflammation and epithelial cell function. Furthermore, we found that neutrophil-derived extracellular vesicles (EVs) carrying PAD4 were secreted into intestinal epithelial cells (IECs). Within IECs, PAD4 citrullinates mitochondrial creatine kinase 1 (CKMT1) at the R242 site, leading to reduced CKMT1 protein stability via the autophagy pathway. This action compromises mitochondrial homeostasis, impairs intestinal barrier integrity, and induces IECs apoptosis. IEC-specific depletion of CKMT1 exacerbated intestinal inflammation and apoptosis in mice with colitis. Clinical analysis of IBD patients revealed elevated levels of PAD4, increased CKMT1 citrullination, and decreased CKMT1 expression. In summary, our findings highlight the crucial role of PAD4 in IBD, where it modulates IECs plasticity via CKMT1 citrullination, suggesting that PAD4 may be a potential therapeutic target for IBD.

结直肠癌是全球较常见的恶性肿瘤之一，是现阶段我国消化系统发病率排名第一的恶性肿瘤，也是影响国民健康的重要公共卫生问题。早筛、早诊和早治能够有效改善结直肠肿瘤的预后。结肠镜是结直肠疾病最为准确的诊断、筛查和随访手段，但结肠镜检查的效果取决于其质控。本文主要从结直肠癌发病率、癌变途径、危险因素、诊断筛查方式和结肠镜检查质控标准等方面对该领域相关成果进行综述。

BACKGROUND & AIM:Exosomes are effective mediators of cell-to-cell interactions and transport several regulatory molecules, including microRNAs (miRNAs), involved in diverse fundamental biological processes. The role of macrophage-derived exosomes in the development of inflammatory bowel disease (IBD) has not been previously reported. This study investigated specific miRNAs in macrophage-derived exosomes in IBD and their molecular mechanism.METHODS:A dextran sulfate sodium (DSS)-induced IBD mouse model was established. The culture supernatant of murine bone marrow-derived macrophages (BMDMs) cultured with or without lipopolysaccharide (LPS) was used for isolating exosomes, which were subjected to miRNA sequencing. Lentiviruses were used to alter miRNA expression and investigate the role of macrophage-derived exosomal miRNAs. Both mouse and human organoids were co-cultured with macrophages in a Transwell system to model cellular IBD in vitro.RESULTS:LPS-induced macrophages released exosomes containing various miRNAs and exacerbated IBD. Based on miRNA sequencing of macrophage-derived exosomes, miR-223 was selected for further analysis. Exosomes with upregulated miR-223 expression contributed to the exacerbation of intestinal barrier dysfunction in vivo, which was further verified using both mouse and human colon organoids. Furthermore, time-dependent analysis of the mRNAs in DSS-induced colitis mouse tissue and miR-223 target gene prediction were performed to select the candidate gene, resulting in the identification of the barrier-related factor Tmigd1.CONCLUSION:Macrophage-derived exosomal miR-223 has a novel role in the progression of DSS-induced colitis by inducing intestinal barrier dysfunction through the inhibition of TMIGD1.

Disconnected pancreatic duct syndrome (DPDS) is an important and common complication of acute necrotizing pancreatitis. Endoscopic approach has been established as the first-line treatment for pancreatic fluid collections (PFCs) with less invasion and satisfactory outcome. However, the presence of DPDS significantly complicates the management of PFC; besides, there is no standardized treatment for DPDS. The diagnosis of DPDS presents the first step of management, which can be preliminarily established by imaging methods including contrast-enhanced computed tomography, ERCP, magnetic resonance cholangiopancreatography (MRCP), and EUS. Historically, ERCP is considered as the gold standard for the diagnosis of DPDS, and secretin-enhanced MRCP is recommended as an appropriate diagnostic method in existing guidelines. With the development of endoscopic techniques and accessories, the endoscopic approach, mainly including transpapillary and transmural drainage, has been developed as the preferred treatment over percutaneous drainage and surgery for the management of PFC with DPDS. Many studies concerning various endoscopic treatment strategies have been published, especially in the recent 5 years. Nonetheless, existing current literature has reported inconsistent and confusing results. In this article, the latest evidence is summarized to explore the optimal endoscopic management of PFC with DPDS.

Background Dietary management is considered a potential adjunctive treatment for inflammatory bowel disease (IBD). Short-video sharing platforms have enabled patients to obtain dietary advice more conveniently. However, accessing useful resources while avoiding misinformation is not an easy task for most patients. Objective This study aimed to evaluate the quality of the information in IBD diet–related videos on Chinese short-video sharing platforms. Methods We collected and extracted information from a total of 125 video samples related to the IBD diet on the 3 Chinese short-video sharing platforms with the most users: TikTok, Bilibili, and Kwai. Two independent physicians evaluated each video in terms of content comprehensiveness, quality (rated by Global Quality Score), and reliability (rated by a modified DISCERN tool). Finally, comparative analyses of the videos from different sources were conducted. Results The videos were classified into 6 groups based on the identity of the uploaders, which included 3 kinds of medical professionals (ie, gastroenterologists, nongastroenterologists, and clinical nutritionists) and 3 types of non–medical professionals (ie, nonprofit organizations, individual science communicators, and IBD patients). The overall quality of the videos was poor. Further group comparisons demonstrated that videos from medical professionals were more instructive in terms of content comprehensiveness, quality, and reliability than those from non–medical professionals. Moreover, IBD diet–related recommendations from clinical nutritionists and gastroenterologists were of better quality than those from nongastroenterologists, while recommendations from nonprofit organizations did not seem to be superior to other groups of uploaders. Conclusions The overall quality of the information in IBD diet-related videos is unsatisfactory and varies significantly depending on the source. Videos from medical professionals, especially clinical nutritionists and gastroenterologists, may provide dietary guidance with higher quality for IBD patients.

Peptidylarginine deiminases (PADs) are the only enzyme class known to deiminate arginine residues into citrulline in proteins, a process known as citrullination. This is an important post-translational modification that functions in several physiological and pathological processes. Neutrophil extracellular traps (NETs) are generated by NETosis, a novel cell death in neutrophils and a double-edged sword in inflammation. Excessive activation of PADs and NETs is critically implicated in their transformation from a physiological to a pathological state. Herein, we review the physiological and pathological functions of PADs and NETs, in particular, the involvement of PAD2 and PAD4 in the digestive system, from inflammatory to oncological diseases, along with related therapeutic prospects.

Background and Aims: Adequate bowel preparation is crucial for clear mucosal visualization during colonoscopy. We aimed to comprehensively compare oral sulfate solution (OSS) and 3-L split-dose polyethylene glycol (PEG) for bowel preparation before colonoscopy. Methods: This randomized, active-controlled, noninferiority study was performed in 10 medical centers. Eligible subjects were enrolled to receive OSS or 3-L PEG in a split-dose regimen. The quality of bowel preparation, adverse reactions, and acceptability were evaluated. The quality of bowel preparation was evaluated using the Boston Bowel Preparation Scale. Safety was evaluated by adverse reactions. The study population was divided into the full analysis set (FAS), the safety set, the modified FAS (mFAS), and the per-protocol set (PPS). Results: Three hundred forty-eight potentially eligible subjects were enrolled. Three hundred forty-four subjects were included in the FAS and safety set, 340 subjects were included in the mFAS, and 328 subjects were included in the PPS. Adequate bowel preparation of the OSS was not inferior to 3-L PEG in the mFAS (98.22% vs 97.66%) and the PPS (98.17% vs 98.78%). There was no significant difference in acceptability between the 2 groups (94.74% vs 94.80%, P = .9798). Overall adverse reactions were similar (50.88% vs 44.51%, P = .2370) between the 2 groups. Conclusions: The split-dose OSS regimen was not inferior to the split-dose 3-L PEG regimen for the quality of bowel preparation in a Chinese adult population. The safety and acceptability of the 2 groups were similar.

INTRODUCTION: Although the 9-minute mean withdrawal time (m-WT) is often reported to be associated with the optimal adenoma detection rate (ADR), no randomized trials of screening colonoscopy have confirmed the impact of a 9-minute m-WT on adenoma miss rate (AMR) and ADR. METHODS: A multicenter tandem trial was conducted in 11 centers. Seven hundred thirty-three asymptomatic participants were randomized to receive segmental tandem screening colonoscopy with a 9-minute withdrawal, followed by a 6-minute withdrawal (9-minute-first group, 9MF, n = 366) or vice versa (6-minute-first group, 6MF, n = 367). The primary outcome was the lesion-level AMR. RESULTS: The intention-to-treat analysis revealed that 9MF significantly reduced the lesion-level (14.5% vs 36.6%, P < 0.001) and participant-level AMR (10.9% vs 25.9%, P < 0.001), advanced adenoma miss rate (AAMR, 5.3% vs 46.9%, P = 0.002), multiple adenomas miss rate (20.7% vs 56.5%, P = 0.01), and high-risk adenomas miss rate (14.6% vs 39.5%, P = 0.01) of 6MF without compromising detection efficiency (P = 0.79). In addition, a lower false-negative rate for adenomas (P = 0.002) and high-risk adenomas (P < 0.05), and a lower rate of shortening surveillance schedule (P < 0.001) were also found in 9MF, accompanying with an improved ADR in the 9-minute vs 6-minute m-WT (42.3% vs 33.5%, P = 0.02). The independent inverse association between m-WT and AMR remained significant even after adjusting ADR, and meanwhile, 9-minute m-WT was identified as an independent protector for AMR and AAMR. DISCUSSION: In addition to increasing ADR, 9-minute m-WT also significantly reduces the AMR and AAMR of screening colonoscopy without compromising detection efficiency.

Neutrophils are the most abundant leukocyte population in the human circulatory system and are rapidly recruited to sites of inflammation. Neutrophils play a multifaceted role in intestinal inflammation, as they contribute to the elimination of invading pathogens. Recently, their role in epithelial restitution has been widely recognized; however, they are also associated with bystander tissue damage. The intestinal epithelium provides a physical barrier to prevent direct contact of luminal contents with subepithelial tissues, which is extremely important for the maintenance of intestinal homeostasis. Numerous studies have demonstrated that transepithelial migration of neutrophils is closely related to disease symptoms and disruption of crypt architecture in inflammatory bowel disease and experimental colitis. There has been growing interest in how neutrophils interact with the epithelium under inflammatory conditions. Most studies focus on the effects of neutrophils on intestinal epithelial cells; however, the effects of intestinal epithelial cells on neutrophils during intestinal inflammation need to be well-established. Based on these data, we have summarized recent articles on the role of neutrophil-epithelial interactions in intestinal inflammation, particularly highlighting the epithelium-derived molecular regulators that mediate neutrophil recruitment, transepithelial migration, and detachment from the epithelium, as well as the functional consequences of their crosstalk. A better understanding of these molecular events may help develop novel therapeutic targets for mitigating the deleterious effects of neutrophils in inflammatory bowel disease.

Pancreatic adenosquamous carcinoma (ASPC) is a rare subtype of pancreatic cancer with lethal malignancy, and few studies have focused on the heterogeneity of ASPC. Here, we performed a single-cell sequencing procedure on pancreatic tumor tissue from an ASPC patient and a patient with high-grade intraductal papillary mucinous neoplasm (IPMN). Through the combined analysis of single-cell sequencing data from five pancreatic ductal adenocarcinoma (PDAC) patients, one IPMN patient, and one ASPC patient in a public database, we identified 11 main types of cells, including macrophages, B cells, cancer stem cells, ductal cells, fibroblasts, endo/stellate cells, neutrophils, acinar cells, T cells, natural killer (NK) cells, dendritic cells, and mast cells. Then, the different characteristics and differentiation paths of the immune microenvironment among IPMN, ASPC, and PDAC in macrophages, T cells, and cancer-associated fibroblasts (CAFs) were identified through multiple bioinformatics analyses. Two novel special cancer-associated fibroblasts were identified as nCAFs and imCAFs. Then, cancer cells in duct cells were identified using the infercnv software. Two ASPC-specific subgroups of cancer cells with squamous cell features were identified. Finally, the identified specific CAFs and cancer cells were mapped to TCGA-PAAD cohort through the cibersoftx software. All of these identified subgroups were calculated to have a significant prognostic value in pancreatic cancer patients. These findings will promote the clinical application of single-cell sequencing data of pancreatic cancer and deepen our understanding of ASPC.

近年来，我国结直肠癌发病率和死亡率逐年上升，结直肠癌的早期筛查与早诊早治是遏制该趋势的有效措施。目前普遍应用的结直肠癌筛查手段还存在一定的局限性。肠道微生态在结直肠癌的发生发展中发挥重要的作用，通过粪便检测基于宏基因组学的微生物标志物有望成为结直肠癌早期筛查的新型无创检测手段。本文综述了粪便宏基因组学在结直肠癌早期筛查中多种微生物标志物的研究进展及其应用前景。

目的 分析开展结肠镜检查规范化培训对结肠镜检查质量控制水平的影响.方法 本次研究吸纳国内22家带教医院及136家地县级医院参与,采用国家消化内镜质控中心牵头制定的《结肠镜检查肠道准备督导与效果评价表》作为评价依据,评价带教医院结肠镜检查质量控制水平,由22家带教医院对地县级医院采用"一对多"模式的带教培训,比较地县级医院接受培训前后结肠镜检查质量控制水平,本次研究的观察指标为前述评价表的总分及腺瘤检出率(ADR).结果 22家带教医院的前述评价表总分均在80分以上,中位总分为91.5(88.9,95.3)分.因9家地县级医院未能按照计划参加培训而无法完成完整的两轮评价,故最终纳入127家地县级医院进行分析.在开展结肠镜检查规范化培训前,评价表总分低于60分的医院占比为16.5％,接受培训后无一家医院该总分低于60分;培训后,该总分为60～80分的医院占比较培训前下降,该总分高于80分的医院占比较培训前升高.127家地县级医院培训后的前述评价表中位总分为95(88,100)分,高于接受培训前的80(66,88)分,差异有统计学意义(P<0.05).培训后,ADR低于15％的医院、ADR为15％～25％的医院占比均较培训前下降,ADR高于25％的医院占比较培训前升高.结论 通过高水平医院"以点带面"对地县级医院进行结肠镜检查规范化培训,有助于提高地县级医院结肠镜检查质量控制水平.

Psychosocial stress is a vital factor contributing to the pathogenesis and progression of inflammatory bowel disease (IBD). The contribution of intestinal macrophage autophagy to the onset and development of IBD has been widely studied. Herein, we investigated the underlying mechanism of psychosocial stress in an IBD mouse model pertaining to macrophage autophagy. Corticotropin releasing hormone (CRH) was peripherally administrated to induce psychosocial stress. For in vivo studies, dextran sulfate sodium (DSS) was used for the creation of our IBD mouse model. For in vitro studies, lipopolysaccharide (LPS) was applied on murine bone marrow-derived macrophages (BMDMs) as a cellular IBD-related challenge. Chloroquine was applied to inhibit autophagy. We found that CRH aggravated the severity of DSS-induced IBD, increasing overall and local inflammatory reactions and infiltration. The levels of autophagy in intestinal macrophages and murine BMDMs were increased under these IBD-related inflammatory challenges and CRH further enhanced these effects. Subsequent administration of chloroquine markedly attenuated the detrimental effects of CRH on IBD severity and inflammatory reactions via inhibition of autophagy. These findings illustrate the effects of peripheral administration of CRH on DSS-induced IBD via the enhancement of intestinal macrophage autophagy, thus providing a novel understanding as well as therapeutic target for the treatment of IBD.

结肠镜检查是目前结直肠息肉筛查、诊断和随访手段中的"金标准",可在镜下检出病变、进行活检,并明确病变性质.随着我国结直肠癌发病率的不断升高和结直肠癌筛查的持续推进,结肠镜检查的应用在临床实践中具有越来越重要且不可替代的地位[1-2].但是,作为"金标准"的结肠镜检查并不能确保检出所有的结直肠癌及癌前病变.荟萃分析数据显示,即使是经验丰富的内镜医师在良好的肠道准备质量和充分的退镜时间(withdrawal time, WT)条件下,仍然会遗漏约26％的结肠腺瘤[3],而腺瘤漏诊则是结肠镜检查后所规定的筛查间期内仍然发生结直肠癌(即结直肠间期癌)的最主要原因,后者可占到所有结直肠癌病例的3.9％～9％,严重影响了结肠镜检查的质量控制,并直接威胁到受检者的生命健康[4-5].本文就结肠镜检查WT对结直肠息肉检出影响的研究现状进行综述.

Background & Aim: Exosomes are effective mediators of cell-to-cell interactions and carry many regulatory molecules, including miRNAs, that can play crucial roles in diverse fundamental biological processes. However, to date, no study has reported macrophage exosomal involvement in the development of inflammatory bowel disease (IBD). This study investigated the specific miRNAs in macrophage-derived exosomes in IBD and the potential molecular mechanism. Methods: Dextran sulfate sodium (DSS) was used to generate IBD mice. The supernatants of murine bone marrow-derived macrophages (BMDMs) with or without lipopolysaccharide (LPS) were collected for exome isolation and miRNA sequencing. Lentiviruses were used to modify miRNA expression and further investigate the role of macrophage-derived exosomal miRNAs. In vitro, both mouse and human organoids were applied to a Transwell system in co-culture with BMDMs as a cellular IBD-related challenge. Results: Here, we show that LPS-induced macrophages can release exosomes containing various miRNAs, aggravating IBD. We analyzed miRNA sequencing of macrophage-derived exosomes, and miR-223 was selected for further study. In vivo, exosomes with high miR-223 expression contributed to the exacerbation of intestinal barrier dysfunction, which was further verified in both mouse and human colon organoids. Furthermore, time-dependent analysis of the mRNAs of DSS-induced colitis mouse tissue combined with miR-223 target gene prediction was performed to select the candidate gene, and the barrier-related factor TMIGD1 was identified. Conclusion: Collectively, these data indicated that macrophage-derived exosomal miR-223 played a novel role in intestinal barrier dysfunction by inhibiting TMIGD1 in the progression of DSS-induced colitis.