Objective: This multi-center, randomized, double-blind, placebo-controlled study aimed to evaluate the clinical efficacy and safety of Elian Granule in treating chronic atrophic gastritis (CAG). Methods: Over a 24-week period, 240 CAG patients were randomized to receive either Elian Granule or placebo. Primary outcomes included histological improvement of gastric mucosa via biopsy, while secondary outcomes assessed dyspepsia symptom scores and quality of life (QOL) scores. Safety was monitored through physical examinations, laboratory tests (blood and urine tests, liver function, and renal function), and electrocardiograms (ECGs). Results: The Elian Granule group exhibited significantly higher improvement rates in gastric mucosal atrophy (76.29% vs. 48.96%, P < 0.001) and intestinal metaplasia (62.89% vs. 34.38%, P < 0.001) compared to the placebo group. Total dyspepsia scores improved at 4, 12, and 24 weeks (P < 0.001), the individual symptom scores showed significant improvement in epigastric pain, epigastric distension, epigastric discomfort, early satiety, heartburn, belching and acid reflux at both the 4-week and 12-week timepoints (P < 0.05, P < 0.01, P < 0.001), of these, epigastric pain, epigastric distension, early satiety, belching and acid reflux maintained their statistically significant improvement through the 24-week evaluation period (P < 0.05, P < 0.01, P < 0.001). The total effective rate for symptom relief was 85.57% in the Elian group versus 47.92% in the placebo group (P < 0.001). QOL scores for physical health (GH, PF, BP, and PCS total score) and mental health (VT, SF, MH, and MCS total score) also improved significantly (P < 0.05, P < 0.01). No adverse impact was observed. Conclusion: Elian Granule significantly improves gastric mucosal atrophy and intestinalization, alleviates dyspeptic symptoms, and enhances QOL in CAG patients, demonstrating a favorable safety profile. Clinical Trial Registration:: http://itmctr.ccebtcm.org.cn/zh-CN/Home/ProjectView?pid=7a00ecee-da6a-4939-bae1-e6a58cd97cdb, identifier ChiMCTR2000003929, 2020-9-13.

Precancerous lesions of gastric cancer (PLGC) are crucial for the progression to gastric cancer, and early intervention in PLGC is pivotal in preventing its development into gastric cancer. In order to illustrate the molecular mechanisms underlying PLGC and the roles of associated genes within these lesions, genetically engineered mouse models (GEMMs) have been developed. We systematically summarize the current GEMMs, and highlight the principal pathological mechanisms involved, including gastrin/gastric acid balance, inflammatory factors, the interplay between cancer-promoting and cancer-suppressing genes, and apoptotic pathways. We further discuss the mechanisms involved in the existing GEMMs of PLGC.

IntroductionFunctional dyspepsia (FD) is a prevalent functional gastrointestinal disorder associated with oxidative stress (OS) and dysbiosis. Chaihushugan powder (CHSGP) demonstrates efficacy in treating FD; however, the underlying therapeutic mechanism is not yet elucidated. This study aims to investigate the effects of CHSGP on OS and gut microbiota (GM) in FD rats, with a particular emphasis on the role of GM as a potential target for the antioxidant properties of CHSGP.MethodsThe FD rat model was established with a modified tail-clamp stimulation and the administration of the CHSGP decoction at a dosage of 9.6 g/kg via gavage for a duration of 4 weeks. The GM was depleted by the administration of a cocktail of metronidazole (200 mg/kg), ampicillin (200 mg/kg), neomycin sulfate (200 mg/kg), and vancomycin (100 mg/kg). Fecal microbiota transplantation (FMT) was performed with CHSGP-treated fecal supernatant at a dosage of 10 mL/kg. The gastrointestinal motility was measured using the rates of gastric emptying and small intestine propulsion. Hematoxylin and eosin staining was employed to elucidate the pathological changes, while the transmission electron microscope was used to examine the microstructures of the interstitial cells of Cajal (ICC). Chemiluminescence, colorimetric assay, immunofluorescence co-staining, and western blot assay were employed to identify the OS-related markers (ROS, SOD, NOX4, PRDX1, and TRX2). Sequencing of fecal microbiota was performed utilizing 16S rDNA.ResultsThe CHSGP decoction promoted gastrointestinal motility, protected the microstructure of ICC, and reduced OS in FD rats. The GM composition was also regulated by CHSGP. However, these effects disappeared after microbiota depletion. Fortunately, the FMT therapy reinstated them.ConclusionChaihushugan powder decoction might regulate the GM to alleviate mitochondrial OS in the gastric tissues of FD rats.

BACKGROUND:Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Currently, there is no suitable treatment for post-ERCP pancreatitis (PEP) prophylaxis. Few studies have prospectively evaluated interventions to prevent PEP in children.AIM:To assess the efficacy and safety of the external use of mirabilite to prevent PEP in children.METHODS:This multicenter, randomized controlled clinical trial enrolled patients with chronic pancreatitis scheduled for ERCP according to eligibility criteria. Patients were randomly divided into the external use of mirabilite group (external use of mirabilite in a bag on the projected abdominal area within 30 min before ERCP) and blank group. The primary outcome was the incidence of PEP. The secondary outcomes included the severity of PEP, abdominal pain scores, levels of serum inflammatory markers [tumor necrosis factor-alpha (TNF-α) and serum interleukin-10 (IL-10)], and intestinal barrier function markers [diamine oxidase (DAO), D-lactic acid, and endotoxin]. Additionally, the side effects of topical mirabilite were investigated.RESULTS:A total of 234 patients were enrolled, including 117 in the external use of mirabilite group and the other 117 in the blank group. The pre-procedure and procedure-related factors were not significantly different between the two groups. The incidence of PEP in the external use of mirabilite group was significantly lower than that in the blank group (7.7% vs 26.5%, P < 0.001). The severity of PEP decreased in the mirabilite group (P = 0.023). At 24 h after the procedure, the visual analog scale score in the external use of mirabilite group was lower than that in the blank group (P = 0.001). Compared with those in the blank group, the TNF-α expressions were significantly lower and the IL-10 expressions were significantly higher at 24 h after the procedure in the external use of mirabilite group (P = 0.032 and P = 0.011, respectively). There were no significant differences in serum DAO, D-lactic acid, and endotoxin levels before and after ERCP between the two groups. No adverse effects of mirabilite were observed.CONCLUSION:External use of mirabilite reduced the PEP occurrence. It significantly alleviated post-procedural pain and reduced inflammatory response. Our results favor the external use of mirabilite to prevent PEP in children.

Abstract Context Elian Granules have been applied in the treatment of precancerous lesions of gastric cancer (PLGC) and achieved good results. However, its exact mechanism remains unclear. Objectives To explore the mechanism of Elian granules in treating PLGC through the mitogen-activated protein kinase (MAPK) signalling pathway based on network pharmacology. Materials and methods Through network pharmacological methods, the targets of the active component of Elian granules against PLGC were obtained. Subsequently, Specific Pathogen Free (SPF) male Sprague Dawley (SD) rats were randomly divided into normal, model, and Elian granule groups. The N-methyl-N′-nitro-N-nitrosoguanidine comprehensive method was used to establish the PLGC rat model. The model and Elian granule groups were given normal saline and Elian granule aqueous solution (3.24 g/kg/d) intragastric administration, respectively, for 24 weeks. The pathological changes in gastric tissues were observed by hematoxylin-eosin staining. The protein expression of p-JNK and p-p38 was verified by western blotting. Results 394 and 4,395 targets were identified in Elian granules and PLGC, respectively. The 190 common targets were mainly enriched in MAPK signalling pathways. The gastric mucosal epithelium was still intact, the glands were arranged regularly, and no goblet cells or apparent inflammatory cell infiltration were observed in the Elian granule group. The expression of p-JNK and p-p38 protein of the Elian granule group (0.83 ± 0.08; 1.18 ± 0.40) was significantly higher than the model group (0.27 ± 0.14; 0.63 ± 0.14) (p < 0.01; p < 0.05). Discussion and conclusions Elian granules may play a critical role in the treatment of rat PLGC by up-regulating the expression of p-JNK and p-p38 proteins in the MAPK signalling pathway, thus providing a scientific basis for clinical application.

Background Multifocal atrophic gastritis and intestinal metaplasia are considered to be important links in the gastric precancerous cascade. However, there are no specific drugs for these conditions. Although many studies have shown that traditional Chinese medicine is effective with no serious side effects, these studies have not been scientifically rigorous trials. Our aim is to design a high-quality trial for a Chinese patent medicine, Elian Granules, to investigate its efficacy and safety in treating patients with chronic atrophic gastritis with or without intestinal metaplasia. Methods This is a phase II, randomized, double-blind, placebo-controlled, multicenter clinical trial. A total of 240 participants will be assigned to a treatment or placebo control group in a 1:1 ratio. The experimental drug or placebo will be taken with boiling water, two small bags (24.2 g) each time, twice a day, half an hour after a meal, for 24 weeks. The primary outcome is the observation of histological changes in the gastric mucosa of patients with atrophic gastritis with or without intestinal metaplasia after 6 months based on the OLGA/OLGIM staging systems. The secondary outcomes include the assessment of dyspepsia and quality of life based on the dyspepsia symptom score and the quality-of-life scale. Discussion This study is designed to evaluate the efficacy and safety of Elian Granules in a randomized, double-blind, placebo-controlled, multicenter manner. This trial may not only provide evidence for a phase III clinical trial, but also an alternative option for the treatment of chronic atrophic gastritis (CAG). Trial registration Registry Platform For Evidence-Based Traditional Chinese Medicine ChiMCTR2000003929 . Registered on 13 September 2020

Background Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP) in children. To date, there is no suitable medicine for post-ERCP pancreatitis prophylaxis in children and few study has prospectively evaluated an intervention to prevent post-ERCP pancreatitis in children. Mirabilite, a well-known traditional Chinese medicine(TCM) has good therapeutic effects on acute pancreatitis and no side effect for children by basic research and clinical studies. Our protocol is designed to assess the efficacy and safety of the external use of mirabilite to prevent post-ERCP pancreatitis in children. Methods/design: 520 patients planned for diagnostic and therapeutic ERCP will be enrolled according to the eligibility criteria‎. The patients will be randomly divided into two equal groups (Mirabilite and control, the external use of mirabilite in a bag on the projected abdominal area over the pancreas within 30 min before ERCP). The primary end point is incidence of post-ERCP pancreatitis. Secondary end points include abdominal pain scores, the levels of inflammatory markers [tissue necrosis factor (TNF)-α, IL-6, and IL-8] and intestinal barrier function markers (diamine oxidase, D-lactic acid, and endotoxin). Additionally, the side effects of topical mirabilite is investigated. Conclusion This trial would be the first experiment to determine mirabilite to prevent post-ERCP pancreatitis in children. Mirabilite maybe provide potential clinical benefits and a new avenue with tremendous potential for the future preventing of post-ERCP pancreatitis. Trial registration number: ChiCTR1900022642. Registered on 19 April 2019- Retrospectively registered, http://www.chictr.org.cn.

Zhijian Gu (  gogigian@hotmail.com ) Shanghai University of TCM: Shanghai University of Traditional Chinese Medicine https://orcid.org/0000-0002-7965-8280 Jun Cong Shanghai University of TCM: Shanghai University of Traditional Chinese Medicine Biao Gong Shanghai University of TCM: Shanghai University of Traditional Chinese Medicine Rong Cen Shanghai University of TCM: Shanghai University of Traditional Chinese Medicine Yongqi Chen Shanghai University of TCM: Shanghai University of Traditional Chinese Medicine Qingling Jia Shanghai University of TCM: Shanghai University of Traditional Chinese Medicine Chenheng Wu Shanghai University of TCM: Shanghai University of Traditional Chinese Medicine Jianghong Ling Shanghai University of TCM: Shanghai University of Traditional Chinese Medicine Xudong Tang China Academy of Chinese Medical Sciences

Patients with precancerous gastric conditions are at a high risk for gastric carcinoma. The Chinese medicine Weifuchun (WFC) is used in treating chronic superficial gastritis and in postoperative adjuvant treatment of gastric cancer. Both monotherapy and combination therapy of WFC with other drugs can result in a favorable therapeutic outcome. WFC can dramatically improve clinical outcomes in patients with gastric precancerous lesions by targeting multiple pathways including pathways involved in the pharmacological action of Radix Ginseng Rubra (red ginseng), Rabdosia amethystoides, and fried Fructus Aurantii, including regulation of NF-κB, RUNX3/TGF-beta/Smad, Hedgehog (Hh) and Wnt signaling pathways, modulation of the expression of oncogenes and tumor suppressor genes, and indirect inhibition of Helicobacter pylori (Hp) by maintaining gastric microbial ecosystem. In this review, we will discuss the clinical efficacy and therapeutic regimen of WFC for gastric precancerous lesions and the molecular mechanisms involved. This review will highlight WFC-based therapeutic strategies in disrupting progress to gastric cancer and provide more information on the pharmacological mechanisms of WFC and its clinical application for the treatment of precancerous gastric lesions.