A ghost epigastric pain.

A 16-year-old woman complained of intermittent epigastric pain for one year. The gastroscopy, colonoscopy and laboratory findings were normal. Physical examination was unremarkable other than upper abdominal tenderness. The symptom was not relieved in past medical treatment. The abdominal computed tomography (CT) scan revealed appendix wall swelling and suspected appendicitis. Endoscopic retrograde appendicitis therapy (ERAT) with eyeMax (Micro-tech, China) was proposed to perform after informed consent obtained. A colonoscopy with a transparent cap (Olympus, Japan) attached to the tip was inserted into the cecum, and advanced the level of appendicular orifice. Subsequently, the Gerlach's valve was pushed aside using the transparent cap. Finally, the eyeMax was placed in the appendicular orifice, slowly moved forward in appendicular lumen. The eyeMax showed a lot of appendicular stones, and irrigated repeatedly. The stones were expulsed smoothly. The patient was discharged two days later without recurrent epigastric pain on follow-up and to date.

Successful removal of a duodenal lesion in difficult location using "a sandwich method".

A 69-year-old woman was diagnosed with a duodenal adenoma near major duodenal papilla during cancer screening examination (Figure 1A). Therefore, endoscopic mucosal resection (EMR) was proposed to remove the duodenal lesion. Unfortunately, satisfactory visualization of the duodenal lesion was not obtained during gastroscopic operation. Unexpectedly, duodenoscopy provided optimal visualization of the duodenal lesion. Consequently, the "sandwich method" using duodenoscopy-gastroscopy-duodenoscopy was successfully performed to remove the challenging duodenal lesion. Firstly, the duodenoscopy was used to create a submucosal bleb through injecting saline containing 0.3 % indigo carmine. Subsequently, the gastroscopy with a transparent capwas used to remove the duodenal lesion with en bloc resection. Then, the duodenoscopy was reused to close the mucosal defect. Finally, pathologic examination showed a tubule-villous adenoma. The patient was recovered uneventfully, and discharged 2 days later.

TC2N inhibits distant metastasis and stemness of breast cancer via blocking fatty acid synthesis.

BACKGROUND: Tandem C2 domains, nuclear (TC2N) is a C2 domain-containing protein that belongs to the carboxyl-terminal type (C-type) tandem C2 protein family, and acts as an oncogenic driver in several cancers. Previously, we preliminarily reported that TC2N mediates the PI3K-Akt signaling pathway to inhibit tumor growth of breast cancer (BC) cells. Beyond that, its precise biological functions and detailed molecular mechanisms in BC development and progression are not fully understood. METHODS: Tumor tissues of 212 BC patients were subjected to tissue microarray and further assessed the associations of TC2N expression with pathological parameters and FASN expression. The protein levels of TC2N and FASN in cell lines and tumor specimens were monitored by qRT-PCR, WB, immunofluorescence and immunohistochemistry. In vitro cell assays, in vivo nude mice model was used to assess the effect of TC2N ectopic expression on tumor metastasis and stemness of breast cancer cells. The downstream signaling pathway or target molecule of TC2N was mined using a combination of transcriptomics, proteomics and lipidomics, and the underlying mechanism was explored by WB and co-IP assays. RESULTS: Here, we found that the expression of TC2N remarkedly silenced in metastatic and poorly differentiated tumors. Function-wide, TC2N strongly inhibits tumor metastasis and stem-like properties of BC via inhibition of fatty acid synthesis. Mechanism-wise, TC2N blocks neddylated PTEN-mediated FASN stabilization by a dual mechanism. The C2B domain is crucial for nuclear localization of TC2N, further consolidating the TRIM21-mediated ubiquitylation and degradation of FASN by competing with neddylated PTEN for binding to FASN in nucleus. On the other hand, cytoplasmic TC2N interacts with import proteins, thereby restraining nuclear import of PTEN to decrease neddylated PTEN level. CONCLUSIONS: Altogether, we demonstrate a previously unidentified role and mechanism of TC2N in regulation of lipid metabolism and PTEN neddylation, providing a potential therapeutic target for anti-cancer.

A case of achalasia associated with early esophageal cancer.

A 65-year-old man was admitted to our hospital complaining of reflux for more than 20 years. After endoscopy and barium-swallow examination, he was diagnosed with achalasia as well as a squamous cell carcinoma. Therefore, peroral endoscopic myotomy (POEM) combined with endoscopic submucosal dissection (ESD) was performed simultaneously. During the procedure, a mucosal erosion with a clear boundary was shown in the middle segment of the esophagus. ESD was first performed and the lesion was removed en-bloc. Subsequent POEM therapy was performed after marking the left esophageal wall 10cm above the cardia. After submucosal injection, the submucosal plane was created through a length 2cm longitudinal incision, then the muscle was cut a length of 10 cm into the esophagus and 2 cm below the cardia, and finally the incision was closed by clips. Pathological examination revealed high-grade intraepithelial neoplasia of squamous epithelium (carcinoma in situ) with a negative margin. The patient was recovered without complication four days after the procedure. The endoscopy showed perfect healing of the esophageal lesions during two-months follow-up , and the reflux symptom was resolved.

"Clip coupled with an elastic ring" internal traction for endoscopic submucosal dissection of a rectal neuroendocrine tumor: a junior endoscopist experience.

A 64-year-old female was found a rectal neuroendocrine tumor (NET) for cancer screening examination. Endoscopic ultrasonography (EUS) revealed a hypoechoic lesion (8.3*6.6 mm) originating from the submucosa layer. "Clip coupled with elastic ring" internal traction for endoscopic submucosal dissection (ESD) was used to remove the NET according to the procedure removal of a duodenal tumor1. The procedures are following: 1. Marking around the lesion with a margin of approximately 5 mm. 2. Submucosal injection and circumference incision around the lesion. 3. Applied clip coupled with elastic ring internal traction. 4. Submucosal injection. 5.Precise dissection was performed with the NET being en bloc resection. 5. Closed the mucosal defect. Finally, the Histopathology confirmed a neuroendocrine tumor.

An unpredictable gastrointestinal bleed.

A 65-year-old male complained of persistent melena for 6 days, and displayed anemia symptoms without hematemesis, vomiting, and abdominal distention. He was diagnosed as ruptured aneurysm of aortic sinus Valsalva, and had received coronary artery occlusion 1 month ago. After the operation, he was continually prescribed clopidogrel 75 mg once daily. The laboratory examination showed blood hemoglobin concentration was 60 g/L without other conspicuous abnormality. Unfortunately, neither esophagogastroduodenoscopy (EGD) nor colonoscopy found no obvious bleeding lesions. And abdominal computed tomography angiography (CTA) and enhanced computed tomography (CT) showed no obvious abnormal findings. Moreover, capsule endoscopy revealed small intestinal with mucosal erosion (Figure 1A). After discontinued clopidogrel, blood transfusion, and support therapy, his symptoms was resolved with negative fecal occult blood, continued clopidogrel 75 mg once daily, and uneventfully discharged 1 week later.

Clinical and endoscopic characteristics and management of 220 cases with serrated polyps.

BACKGROUND: Serrated polyps are considered the precursor lesions of colorectal cancer through the serrated pathway. In the present study, we aimed to evaluate and discuss the clinical and endoscopic characteristics and management of serrated polyps. METHODS: The data of 220 cases with serrated polyps between September 2018 and November 2021 in Shenzhen People's Hospital were retrospectively analyzed. RESULTS: Of all these cases, 32 were hyperplastic polyps, 36 were traditional serrated adenomas, 126 were sessile serrated lesions, 25 were SSLs with dysplasia, and one was an unclassified serrated adenoma. Although most patients were males aged ≥50 years and most serrated polyps were located in the distal colon and rectum with a size of 6-10 mm and the shape of type 0-Is, there was no significant difference (P > 0.05). Serrated polyps of ≤5 mm in size and type 0-IIa were mostly removed by cold biopsy forceps. Cold snare polypectomy was primarily used for those of 6-10 mm in size. Endoscopic mucosal resection was used for those of 6-20 mm, and endoscopic submucosal dissection was used for those of ≥20 mm (P < 0.05). All complications occurred in SSL patients with or without dysplasia (P < 0.05). CONCLUSIONS: Clinical and endoscopic characteristics were beneficial for distinguishing and diagnosing serrated polyps. In addition, management options were crucial to prevent recurrence and progression. However, the detection rate of serrated polyps was relatively low. Therefore, prospective multicenter studies with large samples are necessary to better assess colorectal serrated polyps.

Agromyces chromiiresistens sp. nov., Novosphingobium album sp. nov., Sphingobium arseniciresistens sp. nov., Sphingomonas pollutisoli sp. nov., and Salinibacterium metalliresistens sp. nov.: five new members of Microbacteriaceae and Sphingomonadaceae from polluted soil.

There are many unidentified microbes in polluted soil needing to be explored and nominated to benefit the study of microbial ecology. In this study, a taxonomic research was carried out on five bacterial strains which were isolated and cultivated from polycyclic aromatic hydrocarbons, and heavy metals polluted soil of an abandoned coking plant. Phylogenetical analysis showed that they belonged to the phyla Proteobacteria and Actinobacteria, and their 16S rRNA gene sequence identities were lower than 98.5% to any known and validly nominated bacterial species, suggesting that they were potentially representing new species. Using polyphasic taxonomic approaches, the five strains were classified as new species of the families Microbacteriaceae and Sphingomonadaceae. Genome sizes of the five strains ranged from 3.07 to 6.60 Mb, with overall DNA G+C contents of 63.57-71.22 mol%. The five strains had average nucleotide identity of 72.38-87.38% and digital DNA-DNA hybridization of 14.0-34.2% comparing with their closely related type strains, which were all below the thresholds for species delineation, supporting these five strains as novel species. Based on the phylogenetic, phylogenomic, and phenotypic characterizations, the five novel species are proposed as Agromyces chromiiresistens (type strain H3Y2-19aT = CGMCC 1.61332T), Salinibacterium metalliresistens (type strain H3M29-4T = CGMCC 1.61335T), Novosphingobium album (type strain H3SJ31-1T = CGMCC 1.61329T), Sphingomonas pollutisoli (type strain H39-1-10T = CGMCC 1.61325T), and Sphingobium arseniciresistens (type strain H39-3-25T = CGMCC 1.61326T). Comparative genome analysis revealed that the species of the family Sphingomonadaceae represented by H39-1-10T, H39-3-25T, and H3SJ31-1T possessed more functional protein-coding genes for the degradation of aromatic pollutants than the species of the family Microbacteriaceae represented by H3Y2-19aT and H3M29-4T. Furthermore, their capacities of resisting heavy metals and metabolizing aromatic compounds were investigated. The results indicated that strains H3Y2-19aT and H39-3-25T were robustly resistant to chromate (VI) and/or arsenite (III). Strains H39-1-10T and H39-3-25T grew on aromatic compounds, including naphthalene, as carbon sources even in the presence of chromate (VI) and arsenite (III). These features reflected their adaptation to the polluted soil environment.

Therapeutic potential of gene therapy for gastrointestinal diseases: Advancements and future perspectives.

Advancements in understanding the pathogenesis mechanisms underlying gastrointestinal diseases, encompassing inflammatory bowel disease, gastrointestinal cancer, and gastroesophageal reflux disease, have led to the identification of numerous novel therapeutic targets. These discoveries have opened up exciting possibilities for developing gene therapy strategies to treat gastrointestinal diseases. These strategies include gene replacement, gene enhancement, gene overexpression, gene function blocking, and transgenic somatic cell transplantation. In this review, we introduce the important gene therapy targets and targeted delivery systems within the field of gastroenterology. Furthermore, we provide a comprehensive overview of recent progress in gene therapy related to gastrointestinal disorders and shed light on the application of innovative gene-editing technologies in treating these conditions. These developments are fueling a revolution in the management of gastrointestinal diseases. Ultimately, we discuss the current challenges (particularly regarding safety, oral efficacy, and cost) and explore potential future directions for implementing gene therapy in the clinical settings for gastrointestinal diseases.

Endoscopic submucosal dissection coupled with "modified clip coupled with elastic ring" traction removing rectal neuroendocrine tumor.

A 50-year-old female complained of discomfort of lower abdomen, and a colonoscopy revealed a rectal neuroendocrine tumor (NET). Endoscopic ultrasonography (EUS) showed a hypoechoic lesion (8.5*7.6 mm) originating from the submucosa layer. Endoscopic submucosal dissection (ESD) coupled with "modified clip coupled with elastic ring" traction was performed to remove the NET. Following procedures previously described, we made a subtle change.

Application of Nanoparticles in the Diagnosis of Gastrointestinal Diseases: A Complete Future Perspective.

The diagnosis of gastrointestinal (GI) diseases currently relies primarily on invasive procedures like digestive endoscopy. However, these procedures can cause discomfort, respiratory issues, and bacterial infections in patients, both during and after the examination. In recent years, nanomedicine has emerged as a promising field, providing significant advancements in diagnostic techniques. Nanoprobes, in particular, offer distinct advantages, such as high specificity and sensitivity in detecting GI diseases. Integration of nanoprobes with advanced imaging techniques, such as nuclear magnetic resonance, optical fluorescence imaging, tomography, and optical correlation tomography, has significantly enhanced the detection capabilities for GI tumors and inflammatory bowel disease (IBD). This synergy enables early diagnosis and precise staging of GI disorders. Among the nanoparticles investigated for clinical applications, superparamagnetic iron oxide, quantum dots, single carbon nanotubes, and nanocages have emerged as extensively studied and utilized agents. This review aimed to provide insights into the potential applications of nanoparticles in modern imaging techniques, with a specific focus on their role in facilitating early and specific diagnosis of a range of GI disorders, including IBD and colorectal cancer (CRC). Additionally, we discussed the challenges associated with the implementation of nanotechnology-based GI diagnostics and explored future prospects for translation in this promising field.

A submucosal lesion of the rectum: an unexpected MALT.

A 57-year-old female was found a 12 mm × 10 mm submucosal lesion in the rectum with a smooth mucosa and telangiectasia The lesion was considered as a neuroendocrine tumor, and removed by endoscopic submucosal dissection (ESD) It was finally diagnosed with mucosa-associated lymphoid tissue (MALT) lymphoma with negative margin by pathological examination and histopathological test. MALT lymphoma in the rectum is rare and difficult to diagnose without histopathological test. In this case, the characteristic of this case is telangiectasia on the surface of lesion. Therefore, our findings suggested small lesion in rectum but big in impact.

Plant-derived exosomal nanoparticles: potential therapeutic for inflammatory bowel disease.

Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, is a chronic autoimmune disorder characterized by inflammation. However, currently available disease-modifying anti-IBD drugs exhibit limited efficacy in IBD therapy. Furthermore, existing therapeutic approaches provide only partial relief from IBD symptoms and are associated with certain side effects. In recent years, a novel category of nanoscale membrane vesicles, known as plant-derived exosome-like nanoparticles (PDENs), has been identified in edible plants. These PDENs are abundant in bioactive lipids, proteins, microRNAs, and other pharmacologically active compounds. Notably, PDENs possess immunomodulatory, antitumor, regenerative, and anti-inflammatory properties, making them particularly promising for the treatment of intestinal diseases. Moreover, PDENs can be engineered as targeted delivery systems for the efficient transport of chemical or nucleic acid drugs to the site of intestinal inflammation. In the present study, we provided an overview of PDENs, including their biogenesis, extraction, purification, and construction strategies, and elucidated their physiological functions and therapeutic effects on IBD. Additionally, we summarized the applications and potential of PDENs in IBD treatment while highlighting the future directions and challenges in the field of emerging nanotherapeutics for IBD therapy.

Stem Cell Therapy in Inflammatory Bowel Disease: A Review of Achievements and Challenges.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a group of chronic inflammatory diseases of the gastrointestinal tract. Repeated inflammation can lead to complications, such as intestinal fistula, obstruction, perforation, and bleeding. Unfortunately, achieving durable remission and mucosal healing (MH) with current treatments is difficult. Stem cells (SCs) have the potential to modulate immunity, suppress inflammation, and have anti-apoptotic and pro-angiogenic effects, making them an ideal therapeutic strategy to target chronic inflammation and intestinal damage in IBD. In recent years, hematopoietic stem cells (HSCs) and adult mesenchymal stem cells (MSCs) have shown efficacy in treating IBD. In addition, numerous clinical trials have evaluated the efficiency of MSCs in treating the disease. This review summarizes the current research progress on the safety and efficacy of SC-based therapy for IBD in both preclinical models and clinical trials. We discuss potential mechanisms of SC therapy, including tissue repair, paracrine effects, and the promotion of angiogenesis, immune regulation, and anti-inflammatory effects. We also summarize current SC engineering strategies aimed at enhancing the immunosuppressive and regenerative capabilities of SCs for treating intestinal diseases. Additionally, we highlight current limitations and future perspectives of SC-related therapy for IBD.

Ligation-assisted endoscopic resection to remove a small esophageal lesion (< 20 mm) originating from muscularis propria.

A 35-year-old female complained of slight dysphagia for 3 months. Her physical examination and laboratory tests were unremarkable. Esophagogastroduodenoscopy (EGD) revealed a submucosal tumor (SMT) in the lower esophagus. Then, endoscopic ultrasonography (EUS) revealed that a hypoechoic echo lesion (10mm*12mm) originated from muscularis propria. Subsequently, ligation-assisted endoscopic resection was performed to remove the esophageal lesion. The steps were briefly described as follows: Marking dots in the SMT, and injecting submucosally beneath the marking dots. Incising apical mucosal surface around the marking dots Assembling an endoloop and ligation device (MAJ-339; Olympus). Ligating the SMT with endoloop. Cold snare the SMT.Ligating the defect using another endoloop. Histopathology confirmed a leiomyoma). After 2 months follow-up, EGD revealed healing of the esophageal lesion.

Endoscopic mucosal resection with double band ligation versus endoscopic submucosal dissection for small rectal neuroendocrine tumors.

BACKGROUND: Endoscopic resection remains an effective method for the treatment of small rectal neuroendocrine tumors (NETs) (≤ 10 mm). Moreover, endoscopic mucosal resection (EMR) with double band ligation (EMR-dB), a simplified modification of EMR with band ligation, is an alternative strategy to remove small rectal NETs. AIM: To evaluate the feasibility and safety of EMR-dB for the treatment of small rectal NETs (≤ 10 mm). METHODS: A total of 50 patients with small rectal NETs, without regional lymph node enlargement or distant metastasis confirmed by endoscopic ultrasound, computerized tomography scan, or magnetic resonance imaging, were enrolled in the study from March 2021 to June 2022. These patients were randomly assigned into the EMR-dB (n = 25) group or endoscopic submucosal dissection (ESD) group (n = 25). The characteristics of the patients and tumors, procedure time, devices cost, complete resection rate, complications, and recurrence outcomes were analyzed. RESULTS: There were 25 patients (13 males, 12 females; age range 28-68 years old) in the EMR-dB group, and the ESD group contained 25 patients (15 males, 10 females; age range 25-70 years old). Both groups had similar lesion sizes (EMR-dB 4.53 ± 1.02 mm, ESD 5.140 ± 1.74 mm; P = 0.141) and resected lesion sizes(1.32 ± 0.52 cm vs 1.58 ± 0.84 cm; P = 0.269). Furthermore, the histological complete resection and en bloc resection rates were achieved in all patients (100% for each). In addition, there was no significant difference in the complication rate between the two groups. However, the procedure time was significantly shorter and the devices cost was significantly lower in the EMR-dB group. Besides, there was no recurrence in both groups during the follow-up period. CONCLUSION: The procedure time of EMR-dB was shorter compared with ESD, and both approaches showed a similar curative effect. Taken together, EMR-dB was a feasible and safe option for the treatment of small rectal NETs.

Nursing Cooperation Pattern for Patients With Advanced Pancreatic Cancer and Abdominal Pain Undergoing Endoscopic Ultrasound-guided Celiac Plexus Neurolysis.

Context: Patients with pancreatic cancer (PC) at a late stage often suffer from severe abdominal pain due to the invasion of celiac plexus, and the analgesics they receive often have intolerable side effects. Endoscopic, ultrasound-guided, celiac plexus neurolysis (EUS-guided CPN) can have a good therapeutic effect. Objective: The study intended to evaluate the ability of two nursing cooperation patterns to reduce patients' pain, decrease operation times, increase operational efficiency, and increase nurses' satisfaction, for patients with advanced PC and abdominal pain who received EUS-guided CPN. Design: The research team designed a retrospective controlled study. Setting: The study took place at the Shenzhen People's Hospital of the Second Clinical Medical College of Jinan University in Shenzhen, China, and at the Changhai Hospital of the Second Military Medical University in Shanghai, China. Participants: Participants were 40 patients with advanced PC who received EUS-guided CPN at one of the two hospitals between January 2019 and January 2020. Intervention: Twenty participants at Changhai Hospital received the traditional nursing cooperation pattern and became the control group, and 20 participants at the Shenzhen People's Hospital received the new nursing cooperation pattern and became the intervention group. Outcome Measures: The study measured clinical data, nursing measures, diagnostic significance, and key points for the two patterns as well as compared the effects of the new nursing cooperation method to that of traditional nursing. If the measurement data met the requirements for normality, the team used the two independent sample t-test for the intergroup comparisons. If normality wasn't satisfied, the team used medians and interquartile ranges (IQRs) for expression and the rank sum test for the intergroup comparisons. Counting data were expressed using the constituent ratio, and team used the chi-square test for comparisons between groups. P < .05 was considered to be statistically significant. Results: The operations were successful, and no complications occurred. No significant difference existed in the pain scores between the control group and the intervention group (P > .05), while a significant difference occurred in the nurses' operation times and satisfaction. Not only were the scores for operation times for the control group (97) and the intervention group (59) significantly different, but also the nurses' satisfaction was significantly higher for the intervention group postintervention, at 83.35 ± 5.25, than for the control group, at 62.25 ± 8.18 (P < .001). Such a new nursing cooperation method could assist in patient's rehabilitation and increase nurses' satisfaction. Conclusions: The new nursing cooperation method for patients with advanced PC and abdominal pain undergoing EUS-guided CPN can reduce operation time and improve nurses' satisfaction.

An unexpected gastric cardia submucosal lesion.

An esophagogastroduodenoscopy revealed a submucosal lesion in the gastric cardia of a 55-year-old man.Endoscopic ultrasonography showed a hypoechoic echo lesion originated from the muscularis propria layer considering a leiomyoma or stromal tumor.a submucosal tunneling endoscopic resection was successfully performed to remove the lesion and the diagnosis is hepatoid adenocarcinoma.This is the first report on a case of gastric HAC originated from submucous layer.

Endoscopic management of postoperative fistulas using purse-string suture combined with cyanoacrylate.

A 65-year-old man complained of choking and hoarseness for fifteen days, and was diagnosed with thyroid carcinoma infiltrating esophagus and trachea. Therefore, the patient underwent thyroidectomy, partial esophagectomy, and partial tracheal resection, and histopathology confirmed primary squamous cell carcinoma of the thyroid. Unfortunately, on the tenth postoperative day, an esophagogastroduodenoscopy showed a large fistula (25 mm*20 mm) in esophageal introitus, and diagnosed with tracheoesophageal fistula due to sustained choking. The patient failed to response to conservative treatment within 14 days. Consequently, endoscopic management was performed that the fistula was partly closed by purse-string suture using endoloop and hemostatic clips, then 1 ml of cyanoacrylate (Compon, China) was injected into the fistulous tract through a catheter. Interestingly, the patient's symptom was relieved after the procedure. And, esophagogastroduodenoscopy revealed healing of the fistula 14 days later.

Bortezomib inhibits ZIKV/DENV by interfering with viral polyprotein cleavage via the ERAD pathway.

Flaviviruses have posed a serious threat to human health in the past decades, and effective therapeutic drugs are lacking; thus, treatment of flavivirus infection is a great challenge. The flavivirus protease NS2B3 is an attractive target for antiviral drug screening. Here, we developed an intracellular Zika virus (ZIKV) NS2AB3 self-cleavage assay to identify inhibitors that interfere with viral polyprotein cleavage and block ZIKV/dengue virus (DENV) replication. Bortezomib was identified as the most potent inhibitor, with a half-maximal effective concentration (EC50) in the nanomolar range. We found that instead of directly inhibiting NS2B3 protease activity, bortezomib dramatically induced the ubiquitination and aggregation of NS3, leading to the attenuation of its protease activity in cells. Two E3 ligases, HRD1 and RNF126, were found to be responsible for NS3 ubiquitination. Our study identifies bortezomib as a potential drug for the treatment of ZIKV/DENV infection and reveals the central role of the ERAD pathway in the inhibition of flaviviruses by bortezomib.