Background and Aims nsedated colonoscopy is often associated with patient discomfort and may increase procedural difficulty for endoscopists. This study aimed to investigate the influence of perianal lidocaine application on the comfort level of patients and endoscopic operations during unsedated colonoscopy. Methods 122 patients aged 18-40 years were enrolled and randomly allocated to colonoscopy with 2% lidocaine (experiment group, n = 61) or normal saline (control, n = 61) smeared around the anus. The primary outcomes were anal pain score and abdominal pain score during and after colonoscopy, assessed using a visual analogue scale (VAS). Secondary outcomes included cecal intubation time, polyp detection rate, adenoma detection rate, and adverse events. Results There was no statistical difference between groups in terms of abdominal pain scores during unsedated colonoscopy. Abdominal pain scores after colonoscopy were significantly lower in the lidocaine group than in the saline group. (P < 0.001). However, the lidocaine group had significantly lower anal pain scores during and after colonoscopy (P < 0.001) and a shorter cecal intubation time (P < 0.001). Polyp and adenoma detection rates were higher in the lidocaine group (P < 0.05). Junior endoscopists achieved greater improvements in these outcomes compared to senior endoscopists. Conclusion Perianal application of lidocaine may reduce anal pain and may improve procedural efficiency during unsedated colonoscopy, particularly among junior endoscopists.

Chemical burns of the rectum are so rare that there are few cases reported about this situation. In fact, chemical burns of the rectum can cause severe serious consequence, such as bleeding, perforation and necrosis, even developing to persistent rectal stricture. Here we present a case report of a 12-year-old child with rectal stenosis who imitates the use of corkage and inserts rust remover into the rectum unsupervised by family members. He underwent endoscopic balloon dilation followed by submucosal injection of bleomycin at the stenosis point.

Duodenal perforation is the most serious complication of endoscopic retrograde cholangiopancreatography (ERCP), with an incidence of 0.09-1.67% but a high mortality rate of 8-23%. The Stapfer classification categorizes ERCP perforations into four types based on location: I) lateral/medial duodenal wall, II) perivaterian, III) distal bile duct related to instrumentation, IV) retroperitoneal air alone. While surgery is recommended for diagnosed perforations due to the mortality risk, there is no established treatment for resulting long-term retroperitoneal infections. We describe our experience managing such cases.

Celiac disease (CeD), triggered by gliadin exposure, necessitates therapeutic strategies that establish an antigen-specific immune tolerance. This study explores the therapeutic efficacy and mechanism of rapamycin-gliadin composite nanoparticles (PLN-GR) for CeD treatment. In vivo analyses demonstrated the efficient uptake of PLN-GR by antigen-presenting cells (APCs), particularly Kupffer cells and splenic dendritic cells (DCs), driving their tolerogenic phenotypic transformation. In a murine CeD model, PLN-GR administration significantly enhanced gluten tolerance and mitigated intestinal inflammation, as indicated by reduced paw edema and improved histopathological parameters. Mechanistically, PLN-GR induced macrophage metabolic reprogramming from glycolysis to oxidative phosphorylation, concomitant with elevated serum itaconate levels. This metabolic shift potentiated interorgan immunoregulatory crosstalk, expanding PD-L1+ tolerogenic splenic DCs while suppressing pathogenic Th1 cell populations. Bone marrow-derived macrophages (BMDMs) from Acod1-/- mice (deficient in itaconate synthesis) failed to induce DC tolerance upon PLN-GR treatment. However, supplementation with the itaconate derivative 4-octyl itaconate (4-OI) restored PD-L1 expression in DC2.4 cells in vitro, revealing that itaconate induces and stabilizes the tolerant DC phenotype. These findings underscore PLN-GR as a novel nanotherapeutic platform for CeD, achieving gliadin-specific tolerance through hepatic-splenic immunometabolic reprogramming and itaconate-dependent PD-L1 regulation, thereby offering a translatable strategy for autoimmune disease management.

Metformin (Met) is a pharmaceutical agent for the treatment of type 2 diabetes mellitus. Intriguingly, it may also play a role in the gastrointestinal tract, the gut microbial communities, and the tissue-resident immune cells. The present study aimed to investigate whether the administration of Met achieved protective effects on high-fat diet (HFD)-fed mice with colorectal adenomas (CRA) and elucidated its mechanism via the gut microbiota. AOM/DSS was administered in an HFD-induced diet to induce CRA in mice. 16 S rRNA sequencing was conducted to analyze the gut microbiota profile of mice. Met reduced the inflammatory response in the intestine and alleviated HFD-induced intestinal flora disturbances, and Roseburia intestinalis (R. intestinalis) colonization enhanced the efficacy of Met. Met suppressed CRA cell proliferation, which was further reduced by R. intestinalis. Met blocked NF-κB signaling by activating GILZ through increased R. intestinalis abundance. GILZ deletion in macrophages weakened the inhibition of CRA growth by Met and R. intestinalis, leading to increased macrophage M1 polarization. Inhibition of the NF-κB signaling reversed the activation of macrophage M1 polarization by knockdown of GILZ and reduced the proliferation of CRA cells. Our results shed light on the impact of Met on gut microbiome alteration in treating CRA.

Epithelial barrier impairment of intestinal inflammation leads to the leakage of bacteria, antigens and consequent persistent immune imbalance. Restoring the barrier function holds promise for management of intestinal inflammation, while the theragnostic strategies are limited. In this study, we developed a novel coating by catalase (CAT)-catalyzed polymerization of tannic acid (TA) and combined chelation network with Fe3+. 3 + . TA-Fe3+ 3 + coating was self-polymerized in situ along the small intestinal mucosa, demonstrating persistent adhesion properties and protective function. In enteritis models, sequential administration of TA-Fe3+ 3 + complex solution effectively restored the barrier function and alleviated the intestinal inflammation. Overexpressed CAT in inflammatory lesion is more favorable for the in situ targeting growth of TA-Fe3+ 3 + coating onto the defective barrier. Based on the high longitudinal relaxivity of Fe3+, 3 + , the pathologically catalyzed coating facilitated the visualization of intestinal barrier impairment through MRI. In conclusion, the novel TA-Fe3+ 3 + delivery coating proposed an alternative approach to promote theranostic intervention for intestinal diseases.

Background: Accurate diagnosis of patients with ulcerative colitis (UC) can reduce their risk of developing colorectal cancer. This study intended to explore whether moxifloxacin, an agent with fluorescence potential, could promote two-photon microscopy (TPM) diagnosis for mice with dextran sodium sulfate (DSS)-induced colitis, which could imitate human UC. Methods: 32 Balb/c mice were randomly divided into 4 groups: control, acute colitis, remission colitis and chronic colitis. Fluorescence parameters, imaging performance, and tissue features of different mouse models were compared under moxifloxacin-assisted TPM and label-free TPM. Results: Excitation wavelength of 720 nm and moxifloxacin labeling time of 2 min was optimal for moxifloxacin-assisted TPM. With moxifloxacin labeling for colonic tissues, excitation power was decreased to 1/10 of that without labeling while fluorescence intensity was increased to 10-fold of that without labeling. Photobleaching was negligible after moxifloxacin labeling and moxifloxacin fluorescence kept stable within 2 h. Compared with the control group, moxifloxacin fluorescence was reduced in the three colitis groups (P < 0.05). Meanwhile, the proportion of enhanced moxifloxacin fluorescence regions was (22.4 ± 1.6)%, (7.7 ± 1.0)%, (13.5 ± 1.7)% and (5.0 ± 1.3)% in the control, acute, remission and chronic groups respectively, with significant reduction in the three colitis groups (P < 0.05). Besides, variant tissue features of experimental colitis models were presented under moxifloxacin-assisted TPM, such as crypt opening, glandular structure, adjacent glandular space and moxifloxacin distribution. Conclusions: With unique biological interaction between moxifloxacin and colonic mucosa, moxifloxacin-assisted TPM imaging is feasible and effective for accurate diagnosis of different stages of experimental colitis.

Letter to: Underwater cap-suction pseudopolyp formation for endoscopic mucosal resection: a simple technique for treating flat, appendiceal orifice or ileocecal valve colorectal lesionsEndoscopy 2023; 55(11): 1045-1050DOI: 10.1055/a-2115-7797

Background The combination of endoscopy and laparoscopic assistance is gaining attention due to its minimally invasive approach and the potential to improve the safety of surgical treatment for potential malignant tumors at the base of the appendix. Methods Initially, we attempted an endoscopic resection for a patient with a large adenoma in the ileocecal region, with involvement of the appendiceal orifice. However, due to intraabdominal adhesions, a smooth resection was not possible. Therefore, in collaboration with the surgical team, we proceeded with the laparoscopic release of adhesions followed by endoscopic appendectomy. The surgical site was closed using endoscopic purse-string sutures, and intestinal and intraperitoneal dual drainage tubes were placed. Results The patient had a favorable recovery following the appendectomy, with no adverse complications. One year later, the follow-up endoscopy revealed excellent closure of the surgical site. Conclusions The integration of internal medicine and surgery has become an inevitable trend in the advancement of medical disciplines. The laparoscopic and endoscopic combined surgery enhances the cooperation between internal medicine and surgery, ultimately benefiting the patients. This significant attempt holds the promise of further supplementation and support from additional clinical data.

Epithelial barrier impairment of intestinal inflammation leads to the leakage of bacteria, antigens and consequent persistent immune imbalance. Restoring the barrier function holds promise for management of intestinal inflammation, while the theragnostic strategies are limited. In this study, we developed a novel coating by catalase (CAT)-catalyzed polymerization of tannic acid (TA) and combined chelation network with Fe3+. TA-Fe3+ coating was self-polymerized in situ along the small intestinal mucosa, demonstrating persistent adhesion properties and protective function. In enteritis models, sequential administration of TA-Fe3+ complex solution effectively restored the barrier function and alleviated the intestinal inflammation. Overexpressed CAT in inflammatory lesion is more favorable for the in situ targeting growth of TA-Fe3+ coating onto the defective barrier. Based on the high longitudinal relaxivity of Fe3+, the pathologically catalyzed coating facilitated the visualization of intestinal barrier impairment through MRI. In conclusion, the novel TA-Fe3+ delivery coating proposed an alternative approach to promote theranostic intervention for intestinal diseases.

Esophageal stricture is a debilitating condition that negatively impacts patients' quality of life after undergoing endoscopic mucosal resection (EMR). Despite its significance, this disease remains underexplored due to the lack of a stable animal model. Under direct visualization with choledochoscopy, we retrogradely damaged the esophageal mucosal layer through the gastrostomy to create a rat model of esophageal stricture. The development of histological defects in the mucosal layer was assessed over a 2-week period after model induction. Then the models were evaluated using X-ray barium radiography, Hematoxylin–Eosin, Masson’s trichrome, Sirius red, and Victoria blue staining, multiphoton microscopic imaging. Additionally, the molecular mechanisms of esophageal stricture were explored by conducting RNA transcriptome sequencing, PCR, immunohistochemistry, and immunofluorescence staining. We successfully established fifteen rat models of esophageal stricture by injuring the mucosal layer. In the model group, the mucosal defect initially occurs and subsequently repaired. The epithelium was absent and was plastically remodeled by collagen during the acute inflammatory phase (Day 1), proliferation phase (Day 7), anaphase of proliferation (Day 10), and plastic remodeling phase (Day 14). We observed increased expression of COL1A1, acta2, FGF, IL-1, and TGF-β1 pathway in the model group. We established a highly repeatable rat model of esophageal stricture, and our results suggest that the mucosal defect of the esophagus is a critical factor in esophageal stricture development, rather than damage to the muscularis layer. We identified Atp4b, cyp1a2, and gstk1 as potential targets for treating esophageal stricture, while the TGF-β pathway was found to play an important role in its development.

Since two-photon microscopy (TPM) can obtain high-resolution images at cellular and subcellular level and moxifloxacin has multiphoton fluorescence characteristic, our study aimed to explore the feasibility and diagnostic value of moxifloxacin-assisted TPM in different human colorectal diseases, including low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN) and cancer tissues. Excitation power for TPM imaging with and without moxifloxacin was (2.74 ± 0.16) mW and (0.28 ± 0.02) mW, respectively (p < 0.05). Whether labeled with moxifloxacin or not, images of normal, LGIN, HGIN and cancer tissues all reached the strongest signal at 30 μm from the mucosa. Normalized fluorescence intensity of TPM images with moxifloxacin was approximately 10 times stronger than that without moxifloxacin. Fluorescence signal was differed significantly in normal, LGIN, HGIN and cancer tissues with or without moxifloxacin (p < 0.05). Besides, moxifloxacin-assisted TPM could present variant tissue features with different colorectal diseases, such as the crypt opening, glandular structure, adjacent glandular space and fluorescence distribution.

Pancreaticoduodenal artery aneurysm (PDAA) is a rare visceral aneurysm with a high risk of rupture and mortality. Herein, we presented a case of duodenal obstruction associated with a ruptured PDAA during the postoperative course after successful embolization.

目的 设计制备搭载麦醇溶蛋白(Gliadin)-雷帕霉素(Rapamycin,Rapa)的复合纳米颗粒,经结构表征、稳定性、缓释特性等研究优选处方,测试其对乳糜泻相关过敏反应的免疫耐受治疗作用.方法 本研究利用沉淀自组装法制备聚合物脂质杂化纳米粒(PLNs),载药后超滤离心法得到浓缩纳米药物水溶液;透射电镜观察其形态;激光粒度分析仪考察粒径、Zeta电位和稳定性;BCA蛋白定量测试及分光光度计考察包封率;透析袋法考察其体外释药特性;迟发超敏反应考察其免疫抑制效应.结果 制备的PLNGliadin、PLNRapa及PLNGliadin+Rapa纳米粒形态规整,分布良好,粒径分别为(198.04±10.98)nm、(70.73±6.51)nm、(200.98±0.77)nm;Zeta 电位分别为(-29.71±5.67)mV、(-41.55±1.13)mV、(-44.80±4.93)mV;PLNGliadin 及 PLNGliadin+Rapa的Gliadin 包封率分别为(43.05±3.35)％与(41.79±4.93)％;PLNRapa及PLNGliadin+Rapa的 Rapa 包封率分别为(38.05±6.26)％和(26.13±1.30)％.三种PLNs纳米药物缓释特性明显;药效学试验结果表明三种PLNs纳米药物均能降低由Gliadin刺激造成的足底肿胀超敏反应,PLNGliadin+Rapa效果最显著,且两次预防治疗比单次预防治疗效果好.结论 搭载Gliadin-Rapa的PLNs递送体系结构稳定,缓释作用突出,能有效抑制乳糜泻相关的过敏反应,是治疗乳糜泻的潜在方法.

A case series recently published in REED again highlighted the importance of early diagnosis and treatment in preventing complications of esophageal fishbone impaction. As the most common foreign body (FB) in China, fishbone ingestion is frequently encountered in our daily clinical practice. Although the majority could be managed effectively with endoscopy, rare particular cases still present challenges. We described the case of esophageal fishbone in which the first two endoscopic examinations were negative, emphasizing the role of computed tomography in its management.

Benign esophageal strictures are a frequent complication after esophageal surgery or extensive endoscopic submucosal dissection. Endoscopic dilation is the preferred treatment in clinical practice. However, the allocation of time for each dilation is unclear. The aim of this study was to evaluate the appropriate duration of endoscopic dilation for benign esophageal strictures after esophageal surgery or endoscopic submucosal dissection. Patients with benign esophageal strictures after esophageal surgery or endoscopic submucosal dissection between July 2010 and July 2018 were retrospectively included in this study. According to the dilation time (1, 3, 5 min), patients were divided into three groups. The clinical effects and adverse events were compared among the three groups. Altogether, 57 patients, including 21 in the 1-min group, 18 in the 3-min group and 18 in the 5-min group, were included. All patients underwent endoscopic treatment successfully. The stricture recurrence rate was 76.19% in the 1-min group, 55.56% in the 3-min group and 61.11% in the 5-min group. The median overall dysphagia-free period was 2.60 (range, 0.80–12.00) months in the 1-min group, 6.60 (range, 1.80–12.00) months in the 3-min group and 6.25 (range, 2.40–12.00) months in the 5-min group (P < 0.05). For patients who developed stricture recurrence, the mean dysphagia-free periods were 2.26  ±  1.27 months, 4.00  ±  1.76 months and 4.23  ±  1.63 months, respectively (P < 0.05). The dysphagia-free periods were comparable between the 3- and 5-min groups and were longer than those in the 1-min group. Muscle layer damage occurred in two patients (11.11%) in the 5-min group and in no patients in the other two groups. Three minutes was considered a safe and effective dilation duration for benign esophageal strictures after esophageal surgery or endoscopic submucosal dissection.

目的 利用麦醇溶蛋白(gliadin)诱导小鼠乳糜泻模型,通过检测乳糜泻相关指标来评价该模型的可行性.方法 将健康的C57BL/6小鼠随机分成2组:正常组与乳糜泻组(CeD组).第1天对CeD组的小鼠腹部两侧皮下注射100μl的gliadin与完全弗氏佐剂的乳液(含100 μg gliadin),对正常组的小鼠腹部两侧皮下注射100μl的1×PBS溶液.第8天对CeD组的小鼠腹部两侧皮下注射100pl的gliadin与不完全弗氏佐剂的乳液(含50 μg gliadin),对正常组的小鼠腹部两侧再次皮下注射100μl的1×PBS溶液.第14天,测量注射25 pl gli-adin溶液(2.5 mg/ml)和DMSO溶液前后的CeD组,小鼠的足底厚度.连续测量灌胃0.2 ml gliadin的0.1 mol/L醋酸溶液的小鼠体重.造模结束后,处死小鼠,测量小肠长度.利用实时荧光定量聚合酶链式反应(RT-qPCR)检测小鼠十二指肠组织中的干扰素(IFN)-γ、白细胞介素-15(IL-15)、肿瘤坏死因子α(TNF-α)、组织转谷氨酰胺酶(TG2)的水平.结果 gliadin溶液刺激足底后,CeD小鼠足底的厚度明显高于刺激前[(3.25±0.05)mmvs(2.30±0.05)mm,P＜0.01],CeD组(gliadin)小鼠的足底肿胀程度为(0.95±0.05)mm,明显大于正常组的(0.54±0.08)mm及CeD(DMSO)组的(0.53±0.21)mm(P＜0.01).相对于对照组,CeD组小鼠出现体重下降、肠损伤.CeD组的TNF-α,TG2、IL-15和IFN-γ这4种乳糜泻发生的标志性产物的含量显著增加(P＜0.01).结论 该造模方法在肠损伤、肠道炎症等方面均能很好的模仿临床上乳糜泻的疾病特征,可为未来乳糜泻治疗的研究提供基础.

A 69-year-old male was referred to our center for further evaluation and treatment of a gastric mass. Esophagogastroduodenoscopy found a 30-mm submucosal tumor (SMT) in the gastric body. Endoscopic ultrasound revealed a hypoechoic lesion originating from the muscularis propria layer. Computed tomography showed that the tumor presented a predominately intraluminal growth pattern.

目的 探讨新型锂皂石/甘油磷酸钠复合纳米凝胶应用于黏膜下注射剂的可行性、有效性及安全性.方法 0.3％甘油磷酸钠粉末与不同体积的锂皂石粉末预先混合后加入纯水,合成不同浓度的水凝胶,观察其微观形态并测定其降解率和流变性能.在新鲜离体猪胃黏膜下注射2 ml生理盐水、0.4％透明质酸钠与不同浓度(2％～5％)水凝胶,观察胃黏膜隆起高度随时间的变化;注射相同面积后模拟内镜下黏膜下剥离术(ESD)进行电刀剥离,记录完整剥离的时间.并用CCK8法检测5％水凝胶浸提液对胃黏膜GES-1细胞存活率的影响.结果 各项表征实验表明,合成的水凝胶呈多孔结构,性质稳定,具备剪切变稀的能力,且随着锂皂石浓度提高,成胶速度更快.体外黏膜下隆起实验中,在90 min时生理盐水组隆起高度的维持率不足50％,0.4％透明质酸钠组约为55％,而2％～5％水凝胶组为68％～91％,差异具有统计学意义(P＜0.05).模拟ESD剥离平均时间也较对照组更短,差异具有统计学意义(P＜0.05).细胞毒性试验中,在加入5％水凝胶浸提液后的1～3 d内GES-1细胞活力与对照组无明显差异(P＞0.05).结论 锂皂石/甘油磷酸钠复合纳米凝胶配制简便,拥有剪切变稀的性质,在黏膜下可持久维持理想的隆起高度,且生物相容性好,有望成为一种新型的黏膜下注射剂.