an-obstructive-chronic-pancreatitis-model-established-through

An Obstructive Chronic Pancreatitis Model Established Through Electrocoagulation

Chronic pancreatitis (CP) is a severe inflammatory condition that can destroy the pancreas, lead to diabetes, and increase pancreatic cancer risk, ...

Naval Medical University

Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/FNB) is very safe and has a high diagnostic rate for upper gastrointestinal lesions, especially pancreatic lesions, but its application in the lower gastrointestinal tract has rarely been reported. Due to the tortuous course of the colorectum, with the sigmoid colon particularly prone to perforation, most endoscopists are reluctant to perform lateral-sector endoscopic ultrasound scanning without a water-bag protection for the puncture. The ultrasonic endoscopy and flexible puncture needle techniques recently introduced into clinical practice have made ultrasound-guided puncture safer and more convenient. In addition, endoscopists have carefully tested various protective measures to improve the safety of the lower gastrointestinal puncture, substantially increasing its clinical feasibility. In this article, we review the iterations of endoscopic ultrasound equipment introduced in recent years and the many ingenious ideas proposed by endoscopists regarding lower gastrointestinal puncture.

Diagnosis by Endoscopic Ultrasonography-Guided Sampling through the Lower Gastrointestinal Tract.

Ubiquitous pollution due to microplastics through the food chain is a major cause of various deleterious effects on the human health. The aim of this study was to determine the existence of microplastics and the internal mechanism of microplastics as accelerators of cholelithiasis. Gallstones were collected from 16 patients after cholecystectomy, and microplastics in the gallstones were detected through laser direct infrared and pyrolysis gas chromatographymass spectrometry examinations. Mice model of gallstone were constructed with or without different diameters of microplastic (0.5, 5 and 50 µm). The affinity between microplastic and cholesterol or bilirubin was tested by co-culturing and qualified using molecular dynamics simulations. Finally, altered gut microbiota among the groups were identified using 16 s rRNA sequencing. The presence of microplastics in the gallstones of all the patients were confirmed. Microplastic content was significantly higher in younger chololithiasis patients (age<50 years). Mice fed a high-cholesterol diet with microplastic drinks showed more severe chololithiasis. In terms of the mechanism, microplastics showed a higher affinity for cholesterol than for bilirubin. Significant alterations in the gut microbiota have also been identified after microplastic intake in mice. Our study revealed the presence of microplastics in human gallstones, showcasing their potential to aggravate chololithiasis by forming large cholesterol-microplastic heteroaggregates and altering the gut microbiota.

Microplastics are detected in human gallstones and have the ability to form large cholesterol-microplastic heteroaggregates.

Pancreatic ductal adenocarcinoma (PDAC) is one of the main types of malignant tumor of the digestive system, and patient prognosis is affected by difficulties in early diagnosis, poor treatment response, and a high postoperative recurrence rate. Carbohydrate antigen 19-9 (CA19-9) has been widely used as a biomarker for the diagnosis and postoperative follow-up of PDAC patients. Nevertheless, the production mechanism and potential role of CA19-9 in PDAC progression have not yet been elucidated.

Single-cell RNA sequencing reveals the process of CA19-9 production and dynamics of the immune microenvironment between CA19-9 (+) and CA19-9 (-) PDAC.

Artificial intelligence (AI) is an epoch-making technology, among which the 2 most advanced parts are machine learning and deep learning algorithms that have been further developed by machine learning, and it has been partially applied to assist EUS diagnosis. AI-assisted EUS diagnosis has been reported to have great value in the diagnosis of pancreatic tumors and chronic pancreatitis, gastrointestinal stromal tumors, esophageal early cancer, biliary tract, and liver lesions. The application of AI in EUS diagnosis still has some urgent problems to be solved. First, the development of sensitive AI diagnostic tools requires a large amount of high-quality training data. Second, there is overfitting and bias in the current AI algorithms, leading to poor diagnostic reliability. Third, the value of AI still needs to be determined in prospective studies. Fourth, the ethical risks of AI need to be considered and avoided.

The application of artificial intelligence in EUS.

Previous research has shown that the activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway in macrophages can promote severe acute pancreatitis through the release of inflammatory factors. The role of this pathway in pancreatic acinar cells, however, has not been studied, and understanding its mechanism could be crucial. We analysed plasma from 50 acute pancreatitis (AP) patients and 10 healthy donors using digital PCR, which links mitochondrial DNA (mtDNA) levels to the severity of AP. Single-cell sequencing of the pancreas during AP revealed differentially expressed genes and pathways in acinar cells. Experimental studies using mouse and cell models, which included mtDNA staining and quantitative PCR, revealed mtDNA leakage and the activation of STING-related pathways, indicating potential inflammatory mechanisms in AP. In conclusion, our study revealed that the mtDNA-STING-nuclear factor κB(NF-κB) pathway in pancreatic acinar cells could be a novel pathogenic factor in AP.

Mitochondrial DNA Leakage Promotes Persistent Pancreatic Acinar Cell Injury in Acute Pancreatitis via the cGAS-STING-NF-κB Pathway.

Autoimmune pancreatitis (AIP) is identified as a severe chronic immune-related disorder in pancreas, including two subtypes. In this study, pancreatic lesions in patients diagnosed as either type 1 AIP or type 2 AIP are examined, and these patients' peripheral blood at single-cell level. Furthermore, flow cytometry, immunofluorescence, and functional assays are performed to verify the identified cell subtypes. In type 1 AIP, there is a notable increase in the amount of B cells and plasma cells, and IgG4+ plasma cells are key pathogenic cells of AIP. The differentiation path of naïve-stage B cells into IgG4+ produced plasma cells is observed, and an increased amount of T helper cells and T follicular helper (Tfh) cells. This study also reveals that HIF-1α, an activated transcriptional factor, can directly bind to promoter site of NAMPT, promoting higher levels of visfatin production in HIF1A+ classical monocytes. Pancreatic stellate cells can be activated by extracellular visfatin and promote the development of fibrotic response in pancreatic lesions across both AIP subtypes. The current findings shed light on the exploration of dynamic alterations in peripheral blood cells and cell subgroups in pancreatic lesions of AIP, while elucidating a pathogenic cell subset and potential fibrosis mechanism of AIP.

Article	Year
Diagnosis by Endoscopic Ultrasonography-Guided Sampling through the Lower Gastrointestinal Tract. Diagnostics (Basel, Switzerland)\| PubMed ID: 38201373	2023
Microplastics are detected in human gallstones and have the ability to form large cholesterol-microplastic heteroaggregates. Journal of hazardous materials\| PubMed ID: 38335610	2024
Single-cell RNA sequencing reveals the process of CA19-9 production and dynamics of the immune microenvironment between CA19-9 (+) and CA19-9 (-) PDAC. Chinese medical journal\| PubMed ID: 38816396	2024
The application of artificial intelligence in EUS. Endoscopic ultrasound\| PubMed ID: 38947752	2024
Mitochondrial DNA Leakage Promotes Persistent Pancreatic Acinar Cell Injury in Acute Pancreatitis via the cGAS-STING-NF-κB Pathway. Inflammation\| PubMed ID: 39180578	2025
Unraveling the Microenvironment and the Pathogenic Axis of HIF-1α-Visfatin-Fibrosis in Autoimmune Pancreatitis Using a Single-Cell Atlas. Advanced science (Weinheim, Baden-Wurttemberg, Germany)\| PubMed ID: 39887620	2025

Chang Wu

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