Molecular knowledge of human gastric corpus epithelium remains incomplete. Here, by integrated analyses using single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and single-cell assay for transposase accessible chromatin sequencing (scATAC-seq) techniques, we uncovered the spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium. Specifically, we identified a stem/progenitor cell population in the isthmus of human gastric corpus, where EGF and WNT signaling pathways were activated. Meanwhile, LGR4, but not LGR5, was responsible for the activation of WNT signaling pathway. Importantly, FABP5 and NME1 were identified and validated as crucial for both normal gastric stem/progenitor cells and gastric cancer cells. Finally, we explored the epigenetic regulation of critical genes for gastric corpus epithelium at chromatin state level, and identified several important cell-type-specific transcription factors. In summary, our work provides novel insights to systematically understand the cellular diversity and homeostasis of human gastric corpus epithelium in vivo.
Humans ; Epigenesis, Genetic ; Gastric Mucosa/metabolism* ; Chromatin/metabolism* ; Stem Cells ; Epithelium/metabolism* ; Fatty Acid-Binding Proteins/metabolism*

Gastric acid suppressants, such as proton pump inhibitors, are one of the most widey used drugs worldwide. There is a very high frequency of abuse of gastric acid suppressants, leading huge waste of medical resources. Moreover, numerous studies have showed that acid suppressants were associated with a variety of adverse events, such as fractures and intestinal infections. Increasing guidelines and consensuses have been made to guide the appropriate use of acid suppressants. Gastrointestinal surgery is one of the fields with the largest prescriptions of acid suppressants. Acid suppressants are widely used for preventing anastomotic bleeding after upper gastrointestinal surgery, treating gastrointestinal bleeding and etc. However, most of these prescriptions are off-label uses lacking adequate evidentiary basis. Thus far, there is no guideline specific for appropriate use of acid suppressants in digestive surgeries. Therefore, Chinese Society of Upper Gastrointestinal Surgeons (CSUGS) and Chinese Gastric Cancer Association (CGCA) developed this clinical practice guideline based on the best research evidence and clinical expertise. The aim is to guide the appropriate use of gastric acid suppressants in gastrointestinal surgery, which in turn, increase the benefits of patients.
Humans ; Digestive System Surgical Procedures ; Gastric Acid ; Gastrointestinal Hemorrhage/prevention & control* ; Proton Pump Inhibitors/therapeutic use*

The most common cause of antibiotic-associated diarrhea is Clostridium difficile infection (CDI). Recurrent C. difficile infection (rCDI) often occurs after successful treatment of CDI. Due to the increased incidence and the difficulty in treating rCDI, it is becoming an important clinical issue. Identifying risk factors is helpful for early detection, treatment, and prevention of rCDI. Advanced age, use of antibiotics, gastric acid suppression, and infection with a hypervirulent strain are currently regarded as the major risk factors for rCDI. Several treatment modalities, including vancomycin, fidaxomicin, and fecal microbiota transplant (FMT), are suggested for rCDI treatment. However, there is currently no definitive treatment method with sufficient evidence for rCDI. Recent studies have focused on FMT and have shown positive results for rCDI. Prevention of rCDI by measures such as hand washing and isolation of patients is very important. However, these preventive measures are often overlooked in clinical practice. Here, we review the risk factors, treatment, and prevention of rCDI.
Anti-Bacterial Agents ; Clostridium difficile* ; Clostridium* ; Diarrhea ; Gastric Acid ; Hand Disinfection ; Humans ; Incidence ; Methods ; Microbiota ; Recurrence ; Risk Factors* ; Vancomycin

Peptic ulcer bleeding (PUB) is the most common cause of non-variceal upper gastrointestinal bleeding, and its frequency has been declining over the past decades. However, mortality from PUB persists, and it is still a serious challenge in clinical practice. Although endoscopic intervention is the basic treatment modality for PUB, pharmacological therapy is an important adjunct. The emergence of proton pump inhibitors (PPIs) enables maintenance of intragastric pH >6, which greatly helps in the treatment of PUB. Continuous intravenous infusion of high-dose PPI reduces the re-bleeding rate, thereby helping avoid additional surgery in patients with high-risk stigmata. Moreover, administration of PPIs prior to endoscopy may reduce the need for additional endoscopic intervention. Recently introduced gastric acid suppressants, such as potassium-competitive acid blockers, have shown promising results in further treatment of PUB.
Christianity ; Endoscopy ; Gastric Acid ; Hemorrhage ; Humans ; Hydrogen-Ion Concentration ; Infusions, Intravenous ; Mortality ; Peptic Ulcer ; Proton Pump Inhibitors

Helicobacter pylori (H. pylori), a causative agent of chronic gastritis and gastric cancer, has several virulent factors for own survival and progression toward gastric diseases in human stomach. Of those, H. pylori produces mainly urease (10~15% total protein weight) that neutralize the gastric acid for survival. Here, we identified the antigenic epitope of urease and then developed an ELISA using the antigen including the epitope of urease. We identified the antigenic epitope of urease that induces IgA antibodies in human using truncated mutants. Eight kinds of serially-truncated mutant of UreA and UreB were prepared and subjected to immunoblot using pooled sera of patients with gastric disorders. UreBEnd protein containing UreB epitope was produced and investigated its diagnostic value via ELISA in children. As a result, mutants having last 24 amino acid residues of UreB carboxyl terminus deleted did not show IgA-reactive band. The clones that contained the downstream of 448(th) amino acid in UreB showed IgA-reactive band. The serodiagnostic value of the UreBEnd recombinant protein including identified epitope was confirmed via IgA ELISA and shown to have 97% sensitivity and 100% specificity. These results demonstrated that carboxyl terminal region of UreB carries an antigenic epitope for IgA response in human. It may be useful for detecting H. pylori infection with improved test accuracy and minimum use of endoscopy.
Antibodies ; Child* ; Clone Cells ; Endoscopy ; Enzyme-Linked Immunosorbent Assay ; Epitopes* ; Gastric Acid ; Gastritis ; Helicobacter pylori* ; Helicobacter* ; Humans ; Immunoglobulin A* ; Sensitivity and Specificity ; Stomach ; Stomach Diseases ; Stomach Neoplasms ; Urea* ; Urease*

Ascorbic acid is one of the most well-known nutritional supplement and antioxidant found in fruits and vegetables. Calcium ascorbate has been developed to mitigate the gastric irritation caused by the acidity of ascorbic acid. The aim of this study was to compare calcium ascorbate and ascorbic acid, focusing on their antioxidant activity and effects on gastric juice pH, total acid output, and pepsin secretion in an in vivo rat model, as well as pharmacokinetic parameters. Calcium ascorbate and ascorbic acid had similar antioxidant activity. However, the gastric fluid pH was increased by calcium ascorbate, whereas total acid output was increased by ascorbic acid. In the rat pylorus ligation-induced ulcer model, calcium ascorbate increased the gastric fluid pH without changing the total acid output. Administration of calcium ascorbate to rats given a single oral dose of 100 mg/kg as ascorbic acid resulted in higher plasma concentrations than that from ascorbic acid alone. The area under the curve (AUC) values of calcium ascorbate were 1.5-fold higher than those of ascorbic acid, and the C(max) value of calcium ascorbate (91.0 ng/ml) was higher than that of ascorbic acid (74.8 ng/ml). However, their T(max) values were similar. Thus, although calcium ascorbate showed equivalent antioxidant activity to ascorbic acid, it could attenuate the gastric high acidity caused by ascorbic acid, making it suitable for consideration of use to improve the side effects of ascorbic acid. Furthermore, calcium ascorbate could be an appropriate antioxidant substrate, with increased oral bioavailability, for patients with gastrointestinal disorders.
Animals ; Ascorbic Acid ; Biological Availability ; Calcium* ; Fruit ; Gastric Juice ; Humans ; Hydrogen-Ion Concentration ; In Vitro Techniques* ; Models, Animal ; Pepsin A ; Plasma ; Pylorus ; Rats ; Ulcer ; Vegetables

In the present study, a gastric retention floating system for Brucea javanica oil, composed of alginate and carrageenan, was prepared using ionotropic gelation. Parameters for floatability, drug load, encapsulation efficiency, bead morphology, in vitro release, and in vivo gastric retention were evaluated. The optimized formulation via Box-Behnken design consisted of 1.7% alginate (W/V), 1.02% carrageenan (W/V), 1.4% CaCO (W/V), and a gelling bath of pH 0.8. The alginate-carrageenan-Brucea javanica oil beads had a porous structure and exhibited up to 24 h of in vitro floatability with a load capacity of 45%-55% and an encapsulation efficiency of 70%-80%. A 6-h sustained release was observed in vitro. The beads had a prolonged gastric retention (> 60% at 6 h) in fasted rats, compared to non-floating beads (15% at 6 h), as measured by gamma scintigraphy with single-photon emission tomography/computed tomography (SPET/CT). In conclusion, the alginate-carrageenan-Brucea javanica oil system showed enhanced oil encapsulation efficiency, excellent floating and gastric retention abilities, and a favorable release behavior.
Alginates ; chemistry ; Animals ; Biological Availability ; Brucea ; chemistry ; Carrageenan ; chemistry ; Delayed-Action Preparations ; administration & dosage ; chemistry ; pharmacokinetics ; Drug Carriers ; chemistry ; Drug Delivery Systems ; methods ; Drug Evaluation, Preclinical ; Gastric Mucosa ; metabolism ; Glucuronic Acid ; chemistry ; Hexuronic Acids ; chemistry ; Microspheres ; Plant Oils ; administration & dosage ; chemistry ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley

PURPOSE: Acid neutralization during chemical clearance is significantly prolonged in children with cystic fibrosis, compared to symptomatic children without cystic fibrosis. The absence of available reference values impeded identification of abnormal findings within individual patients with and without cystic fibrosis. The present study aimed to test the hypothesis that significantly more children with cystic fibrosis have acid neutralization durations during chemical clearance that fall outside the physiological range. METHODS: Published reference value for acid neutralization duration during chemical clearance (determined using combined impedance/pH monitoring) was used to assess esophageal acid neutralization efficiency during chemical clearance in 16 children with cystic fibrosis (3 to <18 years) and 16 age-matched children without cystic fibrosis. RESULTS: Duration of acid neutralization during chemical clearance exceeded the upper end of the physiological range in 9 of 16 (56.3%) children with and in 3 of 16 (18.8%) children without cystic fibrosis (p=0.0412). The likelihood ratio for duration indicated that children with cystic fibrosis are 2.1-times more likely to have abnormal acid neutralization during chemical clearance, and children with abnormal acid neutralization during chemical clearance are 1.5-times more likely to have cystic fibrosis. CONCLUSION: Significantly more (but not all) children with cystic fibrosis have abnormally prolonged esophageal clearance of acid. Children with cystic fibrosis are more likely to have abnormal acid neutralization during chemical clearance. Additional studies involving larger sample sizes are needed to address the importance of genotype, esophageal motility, composition and volume of saliva, and gastric acidity on acid neutralization efficiency in cystic fibrosis children.
Child* ; Cystic Fibrosis* ; Electric Impedance ; Gastric Acid ; Genotype ; Humans ; Reference Values ; Saliva ; Sample Size

Currently, proton pump inhibitors are used in a wide range of patients with gastroesophageal reflux disease, peptic ulcer, and upper gastrointestinal symptoms such as dyspepsia. In addition, the application of proton pump inhibitors for prevention of gastrointestinal complications induced by non-steroidal anti-inflammatory drugs is expected to increase their use in the future. The use of proton pump inhibitors promotes bacterial growth by reducing gastric acid concentration. If the acidity (pH) of the stomach fluid is lower than 4, most pathogens can be sterilized. However, patients who need to use a proton pump inhibitor should maintain a gastric acidity of at least 5 or 6, and can be at risk of infections such as pneumonia and Clostridium difficile infection. Several infectious diseases associated with the use of proton pump inhibitors were reviewed.
Bacterial Infections* ; Clostridium difficile ; Communicable Diseases ; Dyspepsia ; Gastric Acid ; Gastroesophageal Reflux ; Humans ; Peptic Ulcer ; Pneumonia ; Proton Pump Inhibitors ; Proton Pumps* ; Protons* ; Stomach

The first histamine H₂ receptor antagonists (H₂RAs) were developed in the early 1970s. They played a dominant role in treating peptic ulcer disease and gastroesophageal reflux disease (GERD). H₂RAs block the production of acid by H⁺, K⁺-ATPase at the parietal cells and produce gastric luminal anacidity for varying periods. H₂RAs are highly selective, and they do not affect H₁ receptors. Moreover, they are not anticholinergic agents. Sequential development of H₂RAs, proton pump inhibitors (PPIs), and discovery of Helicobacter pylori infection changed the paradigm of peptic ulcer disease with marked decrease of morbidity and mortality. PPIs are known to be the most effective drugs that are currently available for suppressing gastric acid secretion. Many studies have shown its superiority over H₂RAs as a treatment for acid-related disorders, such as peptic ulcer disease, GERD, and Zollinger-Ellison syndrome. However, other studies have reported that PPIs may not be able to render stomach achlorhydric and have identified a phenomenon of increasing gastric acidity at night in individuals receiving a PPI twice daily. These nocturnal acid breakthrough episodes can be eliminated with an addition of H₂RAs at night. The effectiveness of nighttime dose of H₂RA suggests a major role of histamine in nocturnal acid secretion. H₂RAs reduce secretion of gastric acid, and each H₂RA also has specific effects. For instance, nizitidine alleviates not only symptoms of GERD, but also provokes gastric emptying, resulting in clinical symptom improvement of functional dyspepsia. The aim of this paper was to review the characteristics and role of H₂RAs and assess the future strategy and treatment of upper gastrointestinal disease, including acid related disorders.
Cholinergic Antagonists ; Dyspepsia ; Gastric Acid ; Gastric Emptying ; Gastroesophageal Reflux ; Gastrointestinal Diseases ; Helicobacter pylori ; Histamine ; Mortality ; Peptic Ulcer ; Phenobarbital ; Proton Pump Inhibitors ; Rabeprazole ; Stomach ; Treatment Outcome* ; Zollinger-Ellison Syndrome