Proton pump inhibitors (PPIs) are indispensable in the treatment of gastro-esophageal reflux disease and peptic ulcers or for the prevention of stress ulcers after major abdominal surgery. However, long-term PPI therapy leads to several side effects such as delayed gastric emptying and distinct changes in mucosal histology. Therefore, this retrospective study aims to evaluate the impact of preoperative PPI therapy on the anastomotic leak rate after esophagectomy.

A retrospective, single-center analysis was conducted for all patients treated with esophagectomy and gastric conduit reconstruction between January 2016 and November 2024. Preoperative treatment with PPIs, as well as patient comorbidities, histopathological findings and surgical techniques were noted. Subsequently, a group-wise comparison was carried out for the differences in anastomotic leak rate and postoperative complications in patients with and without preoperative PPI therapy. Finally, a multivariate logistic regression analysis was conducted for the occurrence of anastomotic leak.

A total of 229 patients were included in the study. The group-wise comparison revealed a significantly higher rate of anastomotic leaks and postoperative complications in patients with preoperative PPI therapy compared to those without. The multivariate logistic regression analysis indicated a 2.5-fold increased risk of anastomotic leaks in patients with preoperative PPI therapy compared to patients without.

Preoperative PPI therapy may represent a modifiable risk factor for the development of anastomotic leaks after esophagectomy. Further prospective, interventional studies are necessary to verify the results.

The study was retrospectively registered in the German clinical trial database (Application number DRKS00035536, Registration date 03.12.2024).

Gastroesophageal reflux disease (GERD) is a prevalent chronic gastrointestinal disorder that affects a substantial proportion of the global population. It is characterized by the extensive backward flow of stomach contents into the esophagus, leading to troublesome symptoms and potential complications. Proton pump inhibitors (PPIs) have long been the cornerstone of pharmacological treatment for GERD, effectively suppressing gastric acid secretion. However, a substantial subset of patients, referred to as PPI-refractory GERD, experience inadequate symptom control despite optimal PPI therapy. GERD significantly impacts patients' quality of life, affecting domains, such as vitality, pain, and physical functioning. Consequently, there is an urgent need for alternative therapeutic strategies and novel pharmacologic agents to provide more effective, long-term relief. Emerging treatment options include potassium-competitive acid blockers (PCABs) like vonoprazan, which offer more potent and sustained inhibition of gastric acid secretion compared to traditional PPIs. Additionally, prokinetic agents such as itopride have gained attention due to their potential to improve GERD symptoms by enhancing gastrointestinal motility and accelerating gastric emptying. This article reviews the mechanisms of action, clinical efficacy, and potential of these novel therapeutic approaches in improving patient outcomes in GERD management. With the growing prevalence of PPI resistance and side effects, a personalized, multifaceted approach to treatment is becoming increasingly necessary to optimize care for patients with GERD.

Atrophic gastritis (AG) is characterized by atrophy of gastric glands-in particular, oxyntic glands-in the setting of chronic inflammation; it is often autoimmune. The diagnosis is confirmed by immunohistochemistry (IHC) for gastrin (to confirm biopsy site), and pathologists often use IHC for neuroendocrine markers to evaluate for enterochromaffin-like cell hyperplasia (ECL-H). The utility of neuroendocrine staining is unclear, and we undertook this study to determine whether ECL pattern provided any additional information in cases of Helicobacter-negative AG.

We reviewed clinicopathologic findings in 184 cases from 184 patients with histologic AG and no evidence of Helicobacter infection. Using neuroendocrine IHC markers, cases were divided into 3 groups: Group 1 showed complete ECL-H (both qualitative and quantitative criteria met), group 2 showed focal ECL-H (qualitative but not quantitative criteria met), and group 3 showed no ECL-H (neither criteria met).

Group 1 patients were more likely to have positive autoantibody serologies (73%, P = .0007 vs group 2) and higher mean gastrin levels (700 pg/mL, P = .017 vs group 3), and only these patients developed gastric neuroendocrine tumors. Group 2 patients were more likely to take proton pump inhibitors (64%, P = .0002 vs group 1). Group 3 patients were more likely to be male (70%, P = .008 vs group 1) and to have microcytic anemia (44%, P = .022 vs group 2) and less likely to have intestinal metaplasia (50%, P = .044 vs group 1).

Stratification based on degree of ECL-H is not necessary for diagnosis of AG but does lead to statistically significant clinical and pathologic differences among groups.

Gastric mucosal changes associated with long-term potassium-competitive acid blocker and proton pump inhibitor (PPI) therapy may raise concern. In contrast to that for PPIs, the evidence concerning the safety of long-term potassium-competitive acid blocker use is scant. Vonoprazan (VPZ) is a representative potassium-competitive acid blocker released in Japan in 2015. In order to shed some comparative light regarding the outcomes of gastric mucosal lesions associated with a long-term acid blockade, we have reviewed six representative gastric mucosal lesions: fundic gland polyps, gastric hyperplastic polyps, multiple white and flat elevated lesions, cobblestone-like gastric mucosal changes, gastric black spots, and stardust gastric mucosal changes. For these mucosal lesions, we have evaluated the association with the type of acid blockade, patient gender, Helicobacter pylori infection status, the degree of gastric atrophy, and serum gastrin levels. There is no concrete evidence to support a significant relationship between VPZ/PPI use and the development of neuroendocrine tumors. Current data also shows that the risk of gastric mucosal changes is similar for long-term VPZ and PPI use. Serum hypergastrinemia is not correlated with the development of some gastric mucosal lesions. Therefore, serum gastrin level is unhelpful for risk estimation and for decision-making relating to the cessation of these drugs in routine clinical practice. Given the confounding potential neoplastic risk relating to H. pylori infection, this should be eradicated before VPZ/PPI therapy is commenced. The evidence to date does not support the cessation of clinically appropriate VPZ/PPI therapy solely because of the presence of these associated gastric mucosal lesions.

This study aims to elucidate the relationship between gastric mucosal atrophy, cystic dilatation, and their associated histopathological characteristics.

A comprehensive analysis was conducted on endoscopic biopsy specimens from 527 cases exhibiting gastric mucosal cystic dilatation. Detailed histological observations and immunohistochemical analysis were performed.

This study included 527 endoscopic biopsy and ESD samples, with a male predominance of 313 cases (59.4%) and 214 female cases (40.6%). The age distribution was as follows: 207 cases (39.3%) were ≤ 60 years, while 320 cases (60.7%) were > 60 years. Regarding cystic dilatation types, 287 cases (54.5%) were identified as simple cystic dilatation, and 240 cases (45.5%) were classified as compound cystic dilatation. Gastric mucosal atrophy was observed in all cases of cystic dilatation, with the atrophic process initially disrupting the structural integrity of the gastric glands. This led to increased interstitial tissue and widening of glandular septa, followed by compensatory hyperplasia and cystic cavity formation. Simple cystic dilatation (54.5%) and compound cystic dilatation (45.5%) were distinguished based on the extent of cellular and structural changes. Simple cystic dilatation could progress to early gastric cancer, presenting as gastric papillary cystadenocarcinoma, while compound cystic dilatation could lead to tubular papillary adenocarcinoma. The progression from simple to complex lesions involved low- and high-grade intraepithelial neoplasia, ultimately resulting in mixed cystadenocarcinoma-glandular tube papillary carcinoma, indicative of early-stage gastric cancer.

The classification, grading, and histopathological characteristics of cystic dilatation in the gastric mucosa are crucial for guiding clinicians in precise treatment and vigilant monitoring of malignant transformation. This approach is significant for the prevention and control of gastric cancer progression.

To evaluate the efficacy and rationale of proton pump inhibitors (PPIs) for adverse drug reactions in elderly patients with heart failure (HF).

From February 2019 to September 2021, 120 elderly patients with chronic heart failure (CHF) treated at Jintan First People's Hospital were enrolled as subjects. The patients were classified into a control group (n=60) and a research group (n=60). In addition to clopidogrel, the control group received cimetidine, while the research group received lansoprazole. Clinical efficacy, oxidative stress markers, echocardiographic indices, vascular endothelial function, cardiac function indicators, and adverse reactions were compared between the two groups. A cost-effectiveness analysis was also performed, and risk factors affecting patient efficacy were examined.

The clinical efficacy of the research group was remarkably superior to that of the control group (88.33% versus 63.33%, P<0.05). The combination of clopidogrel and cimetidine was identified as a risk factor affecting patient efficacy (P=0.003). Besides, the research group showed significant elevation in superoxide dismutase (SOD), glutathione peroxidase (GPx), left ventricular ejection fraction (LVEF), and nitric oxide (NO) after treatment, all higher compared to the control group (all P<0.05). Additionally, significant reductions in malondialdehyde (MDA), left ventricular end diastolic diameter (LVEDD), left ventricular end systolic dimension (LVSD), endothelin-1 (ET-1), N-terminal pro-B-type natriuretic peptide (NT-proBNP), creatine kinase (CK), lactate dehydrogenase (LDH), and free fatty acids (FFA) were observed in the research group, all lower than the control group (P<0.05). The incidence of bradycardia, hypotension and electrolyte disturbances in the research group was remarkably lower (P<0.05). Additionally, the research group demonstrated greater cost-effectiveness compared to the control group.

The use of PPIs in elderly patients with HF not only improves efficacy but also enhances safety, making this drug treatment approach worth promoting.

Helicobacter pylori (H. pylori) infection has a protective effect on gastroesophageal reflux disease (GERD). Both of these diseases have a very high incidence and prevalence. As a result, GERD often recurs after anti-Helicobacter therapy. The problem of effective treatment of H. pylori infection and GERD is that the main groups of drugs [proton pump inhibitors (PPIs) and potassium-competitive acid blockers] have the possibility of side effects with use. Such supposed side effects have no evidence in randomized controlled trials that comply with the principles of evidence-based medicine. Morphological changes in the gastric mucosa after long-term use of antisecretory drugs should be considered as compensatory mechanisms of sanogenesis. The greatest concern for doctors who treat patients with antisecretory drugs is the risk of gastric carcinogenesis. This article presents an analysis of morphological and pathophysiological changes that occur after long-term use of antisecretory drugs (PPIs). Hypertrophy (hyperplasia) of G cells, enterochromaffin-like cells and possible fundic gland polyps (hyperplasia) are compensatory mechanisms of sanogenesis during long-term treatment with PPIs. These mechanisms are of primary importance for rehabilitation and prevention of complications in patients with GERD, non-steroidal anti-inflammatory drugs-gastropathy and other diseases during long-term treatment with PPIs. Understanding the pathophysiological and morphological mechanisms of compensation and adaptation, the mechanisms of sanogenesis and carcinogenesis will increase the number of indications for long-term use of PPIs with a high level of efficiency and safety of treatment. In addition, understanding the pathophysiological and morphological mechanisms of compensation and adaptation, the mechanisms of sanogenesis will allow us to forecast the side effects of long-term use of potassium-competitive acid blockers.

Autoimmune gastritis (AIG) leads to increased gastrin (G) levels due to hypo-achlorhydria, providing proliferative stimuli on the gastric mucosa.

To evaluate the incidence and characteristics of gastric polyps in AIG patients across six tertiary centers in Italy.

A multicentric, cross-sectional study enrolled patients with AIG diagnosed from January 2000 to June 2023, who underwent at least one endoscopy. Data on demographics, clinical history, biochemical profiles, and endoscopic and histopathological findings were systematically collected.

Among 612 AIG patients followed for a median of 4 years, 222 (36.3 %) developed at least one gastric polyp. Of these, 214 were non-endocrine lesions detected in 162 patients, including 151 inflammatory (70.5 %), 29 adenomatous (13.6 %), 18 fundic gland polyps (8.4 %), 13 adenocarcinomas (6.1 %), and one MALT lymphoma. Additionally, 108 patients had gastric neuroendocrine neoplasms (gNENs), with 48 also having non-endocrine polyps. Older age and higher gastrin and chromogranin A levels were associated with polyp occurrence. No differences in OLGA/OLGIM stages or Helicobacter pylori status were noted among patients with and without lesions.

This large multicentric study underscores the substantial occurrence of gastric polyps in AIG patients, including notable rates of gNENs and adenocarcinomas, emphasizing the importance of proactive endoscopic surveillance and histopathological examination for effective management.

Sometimes non-neoplastic changes of the gastric mucosa mimic diffuse-type gastric carcinoma, specifically signet-ring cell adenocarcinoma. In fact, gastric epithelial cells undergoing signet-ring cell change have a cellular morphology that is almost identical to signet-ring cell adenocarcinoma, often leading to misdiagnosis. Accurate recognition of signet-ring cell change is essential to avoid overdiagnosis and overtreatment of signet-ring cell adenocarcinoma. Research on this topic is limited and clinicians lack formal diagnostic tools when signet-ring cells are detected in biopsy specimens. The aims of this study are 3-fold. Firstly, to increase the awareness of both clinicians and pathologists of this rare but highly significant entity. Secondly, to report 4 additional examples of signet-ring cell change and analyze them alongside signet-ring cell adenocarcinoma to compare their morphological and phenotypic features and their evolution over time. Finally, to highlight the potential utility of endoscopic resection to confirm the diagnosis. Cells in signet-ring cell change strongly express E-cadherin, show a wild-type p53 expression, and have a low Ki67 index. In contrast, cells in signet-ring cell adenocarcinoma strongly express p53, have high proliferation rates, and show either no or weak E-cadherin staining. Genetic analysis may be useful in identifying patients at risk of hereditary early diffuse gastric adenocarcinoma, which can mimic signet-ring cell change.

Background/Objectives: Proton pump inhibitor (PPI) use has increased worldwide, including in continuous and longer-term users. Recent reports highlight PPI-related endoscopic gastric mucosal changes, including fundic gland polyps, hyperplastic polyps, multiple white and flat elevated lesions, cracked and cobblestone-like mucosa (CCLM), and black spots. PPI use elevates gastrin levels because of acid inhibition, and hypergastrinemia might be relevant to these findings. In this cross-sectional study, we retrospectively examined gastric mucosal changes in long-term PPI users, focusing on medication period and gastrin levels. Methods: We enrolled 57 patients who received a PPI (>1 year) at two clinics between January 2021 and March 2022. Participants were classified according to medication period: 1 < 5, 5-10, and ≥10 years. Gastrin levels were categorized as low, middle, and high (<250, 250-500, and ≥500 pg/mL, respectively). Odds ratios (OR) were estimated to assess the risk of endoscopic findings. Results: Of the 57 patients, 6 (10.5%), 25 (43.9%), and 26 (45.6%) were PPI users of 1 < 5, 5-10, and ≥10 years, respectively. There were no significant differences in the incidence of endoscopic findings among the medication periods. Low, middle, and high gastrin groups included 21 (36.8%), 21 (36.8%), and 15 (26.3%) patients, respectively. CCLM incidence was significantly elevated in higher gastrin level groups: middle (OR, 6.60; 95% confidence interval [CI], 1.46-29.75; p = 0.014) and high (OR, 9.00; 95% CI, 1.79-45.23; p = 0.0008) (p-trend = 0.0171). No significant differences were observed for other findings. Conclusions: No elevated risk of PPI-related gastric epithelial changes in long-term PPI users was observed time-dependently. Notably, higher gastrin levels were positively associated with CCLM development, irrespective of the medication period.

Polyps are defined as luminal lesions that project into the mucosal surface of the gastrointestinal tract and are characterized according to their morphological and histological features [...].

Gastro-oesophageal reflux disease (GERD) is a highly prevalent disorder worldwide and developing effective treatment strategies for GERD is a clinical priority. GERD is associated with anxiety and depression. Several approaches have been developed to improve GERD, although effectiveness is limited. Acupoint catgut embedding (ACE) is an established technique in traditional Chinese medicine for the treatment of anxiety and depression. This study will investigate the effects of ACE on anxiety, depression, acid reflux and heartburn in patients with GERD.

The ACE-GERD trial is a single-centre, prospective randomised controlled trial. 62 patients will be randomly assigned equally to the experimental and control groups. Patients will be treated with ACE or sham ACE. In the experimental group, absorbable polyglycolic acid sutures will be implanted at the acupoints using sterile disposable injection needles. The sham ACE treatment will exhibit similar surface characteristics but lack absorbable polyglycolic acid sutures. Treatments will be administered every 2 weeks for a period of 10 weeks. The main outcome measure is the Reflux Disease Questionnaire symptom score. Secondary outcomes are the endoscopic assessment, 24-hour pH/impedance monitoring test, oesophageal high-resolution manometer, Gastro-oesophageal Reflux Disease Questionnaire score, Gastro-oesophageal Reflux Disease Health-related Quality of Life, Self-rating Anxiety Scale and Self-rating Depression Scale scores.

The ACE-GERD trial aims to evaluate the efficacy of ACE treatment as a therapeutic tool for improving anxiety, depression, acid reflux and heartburn in patients with GERD and to provide the evidence base for future clinical studies.

The trial has been approved by the Ethics Committee of Guangdong Provincial Hospital of Chinese Medicine (ethics no. BF2023-113-01). Results will be published in peer-reviewed journals and presented at scientific conferences and meetings.

ChiCTR2300074643.

The effectiveness of vonoprazan (VPZ)-based regimens in enhancing Helicobacter pylori (HP) eradication rates is promising. This study evaluated the clinical efficacy of 14-day VPZ-based triple therapy in obese patients infected with HP. A total of 200 obese patients with gastric disorders, confirmed to be HP-positive via gastroscopy and the 13C urea breath test, were retrospectively analyzed. Among them, 118 patients received the 14-day VPZ-based triple regimen (Study group), while 82 patients were treated with the traditional 14-day bismuth-containing proton pump inhibitor-based quadruple regimen (Control group). Baseline characteristics, pretreatment inflammatory indicators, lipid profiles, and gastrointestinal function indicators recorded. The two groups were compared for treatment efficacy, HP eradication rate, gastrointestinal function improvement, and incidence of adverse reactions. The Study group demonstrated a higher overall effective rate compared to the Control group, particularly in HP-strong positive obese patients. No significant differences were observed between the two groups for HP-positive obese patients in terms of total effective rate, HP eradication rate, gastrointestinal function improvement, or adverse reactions incidence. In conclusion, the 14-day VPZ-based triple regimen exhibited superior therapeutic efficacy, higher HP eradication rates, enhanced gastrointestinal function, and reduced adverse reactions in HP-strong positive obese patients, indicating improved overall efficacy and safety.

Vonoprazan, a potassium-competitive acid blocker, is effective at treating acid-related gastrointestinal disorders but has been linked to gastric mucosal redness, a novel condition. This report describes two cases of vonoprazan-associated mucosal redness. Case 1 involved a 73-year-old woman who developed longitudinal erythema and mild mucosal changes after starting vonoprazan seven years ago. Case 2 involved a 70-year-old man who exhibited significant erythema and atrophic gastritis after seven months of treatment. In both cases, the pathological findings included hemorrhage in the superficial mucosa, highlighting that microhemorrhage may be the corresponding pathological finding for vonoprazan-associated mucosal redness.

Development of bioadhesives that can be facilely delivered by endoscope and exhibit instant and robust adhesion with gastric tissues to promote gastric ulcer healing remains challenging. In this study, an advanced bioadhesive is prepared through free radical polymerization of ionized N-acryloyl phenylalanine (iAPA) and N-[tris (hydroxymethyl) methyl] acrylamide (THMA). The precursory polymer solution exhibits low viscosity with the capability for endoscope delivery, and the hydrophilic-hydrophobic transition of iAPA upon exposure to gastric acid can trigger gelation through phenyl groups assisted multiple hydrogen bonds formation and repel water molecules on tissue surface to establish favorable environment for interfacial interactions between THMA and functional groups on tissues. The in-situ formed hydrogel features excellent stability in acid environment (14 days) and exhibits firm wet adhesion to gastric tissue (33.4 kPa), which can efficiently protect the wound from the stimulation of gastric acid and pepsin. In vivo studies reveal that the bioadhesive can accelerate the healing of ulcers by inhibiting inflammation and promoting capillary formation in the acetic acid-induced gastric ulcer model in rats. Our work may provide an effective solution for the treatment of gastric ulcers clinically.

Peptic ulcer disease (PUD) and postprocedural artificial ulcers are common ulcer disease. For them, proton pump inhibitor (PPI) and potassium-competitive acid blocker (P-CAB) are commonly used in clinical practice. PPI requires acid, time, and multiple doses, but P-CAB has fewer limitations. We compared the efficacy, safety, and prevention of PPI and P-CAB in PUD or artificial ulcer.

We searched PubMed, ClinicalTrials.gov , Embase, Cochrane Library, and Web of Science databases for all studies. All eligible randomized controlled trials up to August 5, 2023, were included. Healing rates, shrinking rates, treatment-emergent adverse events rates, and recurrence rates were measured. Risk of bias, sensitivity analyses, and heterogeneity were also performed.

Twenty researches that were selected from 926 screening studies and in total 6,551 participants were included. The risk ratio (RR) of healing rate with P-CABs vs PPIs of PUD at 4 weeks was RR 1.01 (95% confidence interval 0.98-1.04). In addition, the healing rate distinction of artificial peptic ulcer was RR 1.04 (0.89-1.22), and the shrinking rate was mean difference 0.10 (-1.30-1.51). The result of treatment-emergent adverse event rate of PUD was RR 1.11 (0.91-1.35), and the delayed bleeding rate of artificial ulcer was RR 0.35 (0.16-0.80). The RR for recurrence rate of drug-related ulcers was 0.45 (0.25-0.81).

P-CAB is noninferior in healing artificial ulcer and PUD, also the incidence of treatment-emergent adverse events. But, there may be a statistical advantage in holding back delayed bleeding and preventing drug-induced ulcers. More standardized experiments are needed for further applications and more precise conclusions.

Anisomeles indica (L.) Kuntze is a traditional herb with multiple medicinal properties and with potential for preventing or treating various diseases. Acteoside, one of the active ingredients in A. indica, is prepared into commercially available products of A. indica HP813 powder. In this study, the gastroprotective effects of A. indica HP813 powder were evaluated. Wistar rats were treated with A. indica HP813 powder at doses of 0, 207.5, 415, and 830 mg/kg body weight for 28 days. Then, gastric ulcers were induced by the oral administration of 70% ethanol (10 mL/kg body weight) on day 28. The rats were sacrificed at the end of the trial, and stomach tissues were collected. These stomach tissues were then used for macroscopic, microscopic, and immunohistochemical analyses. The results indicated that the area of gastric ulcer was 48.61%, 35.30%, and 27.16% in the ethanol-induced group, 415 mg/kg A. indica HP813 powder group, and 830 mg/kg A. indica HP813 powder group, respectively. In addition, the lesion scores were 2.9, 2.4, and 2.3 in the ethanol-induced group, 415 mg/kg A. indica HP813 powder group, and 830 mg/kg A. indica HP813 powder group, respectively. The immunochemical staining of the gastric tissue revealed that A. indica HP813 powder reduced the expressions of TNF-α and NF-κB proteins in the gastric tissue, which had been induced by ethanol. Finally, A. indica HP813 powder protected the gastric ulcer from ethanol damage through IκB-α induction. The present results demonstrated that A. indica HP813 powder has protective effects against ethanol-induced gastric ulcer.

Background: In the absence of Helicobacter pylori (HP) infection, a characteristic gastric mucus adhesion may appear during the use of vonoprazan. We named this novel characteristic mucus "web-like mucus" (WLM). This study aimed to determine the incidence and risk factors for WLM. Methods: Between January 2017 and January 2022, 5665 patients were enrolled in this study. The patients were divided into a proton-pump inhibitor (PPI)-prescribed group (n = 2000), a vonoprazan-prescribed group (n = 268), and a no-PPI/vonoprazan-prescribed (n = 3397) group, and the presence of WLM was examined. After excluding four patients with autoimmune gastritis, the remaining 264 patients in the vonoprazan group were divided into WLM and non-WLM groups, and their clinical features were analyzed. Results: A total of 55 (21%) patients had WLM, all in the vonoprazan-prescribed group. There were no significant differences in factors such as, sex, age, chronic kidney disease, diabetes mellitus, HP eradication history, smoking, or alcohol consumption between the WLM and non-WLM groups. The median duration from the start of vonoprazan administration to the endoscopic detection of WLM was 2 (1-24) months. Conclusions: WLM appears to be a characteristic feature in patients treated with vonoprazan.

Since the introduction of vonoprazan, a potassium-competitive acid blocker (P-CAB), it has been demonstrated to reversibly inhibit gastric acid secretion by engaging in potassium-competitive ionic binding to H+/K+-ATPase. In contrast, proton pump inhibitors (PPIs) achieve H+/K+-ATPase inhibition through covalent binding to cysteine residues of the proton pump. Reported cases have indicated an emerging trend of P-CAB-related gastropathies, similar to those associated with PPIs, as well as unique gastropathies specific to P-CAB use, such as the identification of web-like mucus. Pathologically, parietal cell profusions, which show a positively correlated with hypergastrinemia, have a higher incidence in P-CAB users compared to PPI users. Thus, this review aims to summarize the endoscopic and pathological findings reported to date concerning P-CAB-related gastric mucosal lesions. Additionally, it seeks to discuss the differences between the PPIs and P-CABs in terms of the formation and frequency of associated gastropathies. This review highlights the evident differences in the mechanism of action and potency of acid inhibition between P-CABs and PPIs, notably contributing to differences in the formation and frequency of associated gastropathies. It emphasizes the necessity to distinguish between P-CAB-related and PPI-related gastropathies in the clinical setting.

Aim Estimate the prevalence of gastric polyps linked to long-term use of proton pump inhibitor (PPI), determine the various risk factors that promote this association, and identify the characteristics associated with these polyps. Methods This prospective cross-sectional study was conducted on approximately 1000 patients presenting to the Gastroenterology Endoscopic Department for upper GI endoscopy at two hospital centers in Beirut, Lebanon, over a period of 12 months from September 2021 to September 2022. The demographic and clinical data of patients who had been taking PPIs for at least one month were collected via a questionnaire. All patients with a previous Helicobacter pylori (H. pylori) infection, presence of hypergastrinemia, or a personal/family history of gastric polyps were excluded from this study. Statistical analyses were performed using SPSS 20 software. Categorical variables were compared by Fisher's exact test; p-values of less than 0.05 were considered statistically significant. Results The prevalence of gastric polyps linked to long-term PPI use was 30%. The minimum duration of daily PPI use required for the formation of polyps is around 24 months. The dosage did not play a significant role in increasing this prevalence. A significant correlation was found between chronic PPI use and factors such as sex, age range, duration, and type of PPI used. These polyps were predominantly found in females (with an OR of 2.9), increased with age, were mostly of the fundic gland type, and their size was proportionally linked to both the dosage and duration of daily PPI use. No cases of dysplasia within the fundic gland polyps (FGPs) were demonstrated in our study. Conclusion To date, there is no current data that prove an association between gastric cancer and PPI-induced FGPs. Additionally, the incidence of FGPs has increased with the widespread chronic use of PPIs. Therefore, attention should be drawn to the potential risk of dysplasia. Thus, the present study highlights the importance of limiting the prescription of PPIs to globally well-defined indications and determining the various risk factors that promote the association between gastric polyps and PPI use. This abstract was recently presented as an E-poster at the ESGE Days 2024 Congress on April 25-27, 2024, in Berlin, Germany.

The efficacy and safety of potassium-competitive acid blockers (P-CABs) in the eradication of Helicobacter pylori (Hp) remains controversial when compared with proton pump inhibitors (PPIs).

The current study set out to compare the differences in the eradication rate and adverse reactions between eradication regimens based on P-CAB or PPI drugs and the differences between the vonoprazan-based and the tegoprazan-based regimens to explore the efficacy and safety of different Hp eradication regimens.

Databases including PubMed, EMBASE, Cochrane Library, and WOS were searched from the inception of these databases up to July 2023, and eligible randomized controlled trials (RCTs) were included. The outcome measures were the eradication rate and the incidence of adverse reactions of different regimens in treating Hp. The results were estimated as relative risk (RR) and its 95% confidence interval (CI), and R 4.2.1 software was used to perform the network meta-analysis (NMA).

A total of 20 studies were included in the analysis, involving 5815 patients with Hp. In terms of eradication rate, the 2-week vonoprazan-based triple regimen (V-Tri-2w) was the best, which was superior to the 2-week PPI-based quadruple regimen [P-Qua-2w, RR = 0.9, 95% CI: (0.85-0.95)] and the 1-week tegoprazan-based triple regimen [T-Tri-1w, RR = 0.79, 95% CI: (0.64-0.97)]; the 2-week tegoprazan-based quadruple regimen (T-Qua-2w) was superior to the 1-week PPI-based triple regimen [P-Tri-1w, RR = 0.82, 95% CI: (0.67-0.99)], and there was no difference between the remaining tegoprazan-based regimens and the PPI-based or vonoprazan-based regimens. In terms of the incidence of adverse reactions, the 2-week vonoprazan-based binary regimen (V-Bi-2w) was lower than that of the 2-week PPI-based quadruple regimen [P-Qua-2w, RR = 1.98, 95% CI: (1.57-2.52)]; there was no significant difference between 1 and 2 weeks for each regimen, such as the vonoprazan-based triple regimen [RR = 1.11, 95% CI: (0.82-1.52)].

In the eradication treatment of Hp, the efficacy and safety of vonoprazan-based regimens are generally better than those of PPI-based regimens. Among them, the V-Tri-2w regimen has the highest eradication rate and may be the preferred choice for Hp eradication.

Licorice is the dry roots and rhizomes of Glycyrrhiza uralensis Fisch., Glycyrrhiza glabra L. and Glycyrrhiza inflata Bat., which was first recorded in Shengnong's herbal classic. Licorice flavonoid (LF) is the main compound isolated from licorice with an indispensable action in treating gastric ulcer (GU). However, the underlying mechanisms need to be further explored.

This study aimed to investigate and further elucidate the mechanisms of LF against ethanol-induced GU using an integrated approach.

The anti-GU effects of LF were evaluated in an ethanol-induced gastric injury rat model. Then, the metabolomics approach was applied to explore the specific metabolites and metabolic pathways. Next, the network pharmacology combined with metabolomics strategy was employed to predict the targets and pathways of LF for GU. Finally, these predictions were validated by molecular docking, RT-qPCR, and western blotting.

LF had a positive impact on gastric injury and regulated the expression of GU-related factors. Upon serum metabolomics analysis, 25 metabolic biomarkers of LF in GU treatment were identified, which were primarily involved in amino acid metabolism, carbohydrate metabolism, and other related processes. Subsequently, a "components-targets-metabolites" network was constructed, revealing six key targets (HSP90AA1, AKT1, MAPK1, EGFR, ESR1, PIK3CA) that may be associated with GU treatment. More importantly, KEGG analysis highlighted the importance of the PI3K/AKT pathway including key targets, as a critical route through which LF exerted its anti-GU effects. Molecular docking analyses confirmed that the core components of LF exhibited a strong affinity for key targets. Furthermore, RT-qPCR and western blotting results indicated that LF could reverse the expression of these targets, activate the PI3K/AKT pathway, and ultimately reduce apoptosis.

LF exerted a gastroprotective effect against gastric ulcer induced by ethanol, and the therapeutic mechanism may involve improving metabolism and suppressing apoptosis through the PI3K-AKT pathway.

Gastroesophageal reflux disease (GERD) is a common disease affecting millions of people worldwide. Proton pump inhibitors (PPI) are the most common drugs used to treat this acid-related disorder due to their high efficacy and fewer side effects. However, long-term use of these drugs can cause histopathological changes, including cystic dilation of gastric fundic glands. The present report describes a 53-year-old man with chronic GERD and daily use of PPIs 20 mg once a day for over 15 years. This case demonstrates the association between PPI and the development of fundic gland polyps.

Preclinical and clinical evidence indicates that proton pump inhibitors (PPIs) may indirectly diminish the microbiome diversity, thereby reducing the effectiveness of immune checkpoint inhibitors (ICIs). Conversely, recent publications have shown that PPIs could potentially enhance the response to ICIs. The precise mechanism through which PPIs modulate the ICIs remains unclear. In this study, we discovered a novel molecular function of PPIs in regulating immune invasion, specifically through inducing PD-L1 translocation in various tumor cells.

C57BL/6 mice subcutaneous transplantation model is used to verify the potential efficacy of PPIs and PD-L1 antibody. Western blotting analysis and phosphorylated chip are used to verify the alteration of PD-L1-related pathways after being treated with PPIs. The related gene expression is performed by qRT-PCR and luciferase reporter analysis. We also collected 60 clinical patients diagnosed with esophageal cancer or reflux esophagitis and then detected the expression of PD-L1 in the tissue samples by immunohistochemistry.

We observed that the IC50 of tumor cells in response to PPIs was significantly higher than that of normal epithelial cells. PPIs significantly increased the expression of PD-L1 on cell membrane at clinically relevant concentrations. Furthermore, pre-treatment with PPIs appeared to synergize the efficiency of anti-PD-L1 antibodies in mouse models. However, PPI administration did not alter the transcription or total protein level of PD-L1 in multiple tumor cells. Using a phosphorylated protein chip, we identified that PPIs enhanced the phosphorylation of GSK3β, then leading to PD-L1 protein translocation to the cell membranes. The capacity of PPIs to upregulate PD-L1 was negated following GSK3β knockout. Furthermore, our clinical data showed that the PPIs use resulted in increased PD-L1 expression in esophageal cancer patients.

We mainly address a significant and novel mechanism that the usage of PPIs could directly induce the expression of PD-L1 by inducing GSK3β phosphorylation and facilitate primary tumor progression and metastasis.

Several features of drug-induced mucosal alterations have been observed in the upper gastrointestinal tract, i.e., the esophagus, stomach, and duodenum. These include pill-induced esophagitis, desquamative esophagitis, worsening of gastroesophageal reflux, chemotherapy-induced esophagitis, proton pump inhibitor-induced gastric mucosal changes, medication-induced gastric erosions and ulcers, pseudomelanosis of the stomach, olmesartan-related gastric mucosal inflammation, lanthanum deposition in the stomach, zinc acetate hydrate tablet-induced gastric ulcer, immune-related adverse event gastritis, olmesartan-asso-ciated sprue-like enteropathy, pseudomelanosis of the duodenum, and lanthanum deposition in the duodenum. For endoscopists, acquiring accurate knowledge regarding these diverse drug-induced mucosal alterations is crucial not only for the correct diagnosis of these lesions but also for differential diag-nosis of other conditions. This minireview aims to provide essential information on drug-induced mucosal alterations observed on esophagogastroduodenoscopy, along with representative endoscopic images.

A 37-year-old man with systemic lupus erythematosus underwent esophagogastroduodenoscopy as a screening examination for anemia and bloody stool. A semi-pedunculated edematous lobular polyp of 25 mm in size was detected in the greater curvature of the upper gastric body. At that time, a definitive diagnosis of cancer could not be made based on a biopsy specimen from the lesion. Since the patient was on proton pump inhibitor (PPI) for a long time to prevent peptic ulceration due to prolonged prednisolone administration for systemic lupus erythematosus, we diagnosed the lesion as a PPI-associated hyperplastic polyp and switched lansoprazole to famotidine. Two months later, esophagogastroduodenoscopy revealed that the polyp had decreased in size to 8 mm, whereas the biopsy specimen led to a histological diagnosis of gastric cancer. The polyp was removed by endoscopic submucosal dissection. Immunohistochemistry revealed that the tumor cells were positive for MUC5AC, but negative for MUC2 and MUC6, leading to a final diagnosis of foveolar-type gastric adenocarcinoma. In conclusion, we may suggest that PPI induces reversible morphological changes in foveolar-type gastric adenocarcinoma. Furthermore, short-term follow-up of polypoid lesions should be prepared, considering tumor comorbidity with morphological changes during long-term PPI usage.

To compare the detection rate and diagnostic accuracy of cardia polyps using endoscopy with blue laser imaging (BLI) and white-light imaging (WLI).

Patients were randomly divided into the BLI group and WLI group according to the endoscopic procedures. BLI followed by WLI was conducted in the BLI group, whereas WLI followed by BLI examination was conducted in the WLI group. The number, size, microstructure, and microvascular patterns of cardia polyps detected were recorded. Biopsy of the polyps was then performed.

The detection rate of cardia polyps in the BLI group was higher than that in the WLI group (7.87% vs 4.22%, P = 0.018). The rate of overlooked lesions in the BLI group was lower than in the WLI group (0.64% vs 3.38%, P = 0.003). The diagnostic coincidence rate between magnifying BLI and histopathology was 88.16%. The sensitivity, specificity, positive predictive value and negative predictive value for the diagnosis of neoplastic lesions by magnifying endoscopy with BLI were 90.91%, 87.69%, 55.56%, and 98.28%, respectively. The most remarkable patterns for predicting inflammatory polyps were the prolonged and fine network patterns (sensitivity 71.43%, specificity 93.75%). Small round combined with honeycomb patterns were the most common among fundic gland polyps (sensitivity 80.00%, specificity 98.48%). Neoplastic lesions presented as villous or ridge-like combined with core vascular or unclear pattern for both microvascular and microstructure patterns.

BLI is more effective than WLI in the detection and diagnosis of cardia polyps, and magnifying endoscopy with BLI may help diagnose such lesions.

Acid-suppressive drugs (ASDs) are widely used in many gastric acid-associated diseases. Nocturnal acid breakthrough has been a common problem of many ASDs, such as proton-pump inhibitors (PPIs) and H2 -receptor antagonists (H2RAs). Potassium-competitive acid blockers (P-CABs) are expected to solve this continuing conundrum. This article examined major ASDs and compared them with placebo in terms of nocturnal acid-inhibitory effects, using a network meta-analysis of randomized controlled trials (RCTs).

To compare the effectiveness of major ASDs, a Bayesian network meta-analysis (NMA) was applied to process data extracted from RCTs. The plausible ranking for each regimen and some subgroups were assessed by surface under the cumulative ranking curves (SUCRA).

Fifty-five RCTs were conducted with 2015 participants. In terms of nocturnal acid-inhibitory effects, the overall results showed that tegoprazan (SUCRA 91.8%) and vonoprazan (SUCRA 91.0%) had the best performance, followed by new PPIs (including tenatoprazole and ilaprazole) (SUCRA 76.6%), additional H2RAs once at bedtime (AHB) (SUCRA 61.3%), isomer PPIs (including esomeprazole and dexlansoprazole) (SUCRA 38.6%), revaprazan (SUCRA 34.7%), traditional PPIs (including omeprazole, rabeprazole, pantoprazole, lansoprazole) (SUCRA 32.6%), H2RAs (SUCRA 23.1%), and placebo (SUCRA 0.3%). In some subgroups, the nocturnal acid-inhibitory effect of vonoprazan or tegoprazan was better than most of the other regimens, even new PPIs and AHB.

This is the first study to compare the effect of ASDs on inhibiting nocturnal acid breakthrough. Overall, in terms of nocturnal acid-inhibitory effect, vonoprazan and tegoprazan had an advantage against other regimens including H2RAs, isomer PPIs, traditional PPIs, AHB, and new PPIs. Even in some subgroups, such as language classification (English), types of study design (crossover-RCT), age (≤40 years), BMI (18.5-24.9 kg/m2 ), continent (Asia and North America), disease status (health), the duration of therapy (2 weeks), and time of administration (at daytime or at night-time), the nocturnal acid-inhibitory effect of vonoprazan or tegoprazan were better than most regimens, even AHB and new PPIs.

Long-term consumption of pump inhibitors causes osteoporosis. Some possible mechanisms are gastrin over-secretion and hypochlorhydria. Octreotide is a somatostatin analog that inhibits the secretion of many hormones such as gastrin. This study aimed to assess the effects of pantoprazole on the bone when used with octreotide in an animal model.

Forty-eight male Wistar rats were randomly assigned into 4 groups: A) pantoprazole 3 mg/Kg/day orally; B) Sandostatin LAR 1 mg/month intramuscular injection; C) Pantoprazole and Sandostatin LAR; and D) Control group. After 90 days of the experiment, bone densitometry was done and serum and urine samples were collected for analysis.

The results indicated a significant decrease in the global, spine, femur, and tibia bone mineral density (BMD) and bone mineral content (BMC) in the pantoprazole group compared to the control group (P<0.05). There was a significant increase in the levels of PTH, gastrin, and alkaline phosphatase (ALP) in the pantoprazole group compared to the control group (P<0.05). There was no significant difference in the serum levels of gastrin, PTH, ALP, and also BMD in the rats that received sandostatin+ pantoprazole or sandostatin alone, compared to the control group.

This study showed that the pantoprazole-induced bone loss, through elevation of serum gastrin and PTH, was preventable by concomitant use of a long-acting somatostatin analog.

Multiple white and flat elevated lesions (MWFL) that develop from the gastric corpus to the fornix may be strongly associated with oral antacid intake. Therefore, this study aimed to determine the association between the occurrence of MWFL and oral proton pump inhibitor (PPI) intake and clarify the endoscopic and clinicopathological characteristics of MWFL.

The study included 163 patients. The history of oral drug intake was collected, and serum gastrin levels and anti-Helicobacter pylori immunoglobulin G antibody titers were measured. Upper gastrointestinal endoscopy was performed. The primary study endpoint was the association between MWFL and oral PPI intake.

In the univariate analyses, MWFL were observed in 35 (49.3%) of 71 patients who received oral PPIs and 10 (10.9%) of 92 patients who did not receive oral PPIs. The occurrence of MWFL was significantly higher among patients who received PPIs than in those who did not (p<0.001). Moreover, the occurrence of MWFL was significantly higher in patients with hypergastrinemia (p=0.005). In the multivariate analyses, oral PPI intake was the only significant independent factor associated with the presence of MWFL (p=0.001; odds ratio, 5.78; 95% confidence interval, 2.06-16.2).

Our findings suggest that oral PPI intake is associated with the presence of MWFL (UMINCTR 000030144).

The present study was conducted to evaluate the protective effect of milk kefir against NSAID-induced gastric ulcers. Male Swiss mice were divided into three groups: control (Vehicle; UHT milk at a dose of 0.3 mL/100 g), proton pump inhibitor (PPI; lansoprazole 30 mg/kg), and 4% milk kefir (Kefir; 0.3 mL/100 g). After 14 days of treatment, gastric ulcer was induced by oral administration of indomethacin (40 mg/kg). Reactive oxygen species (ROS), nitric oxide (NO), DNA content, cellular apoptosis, IL-10 and TNF-α levels, and myeloperoxidase (MPO) enzyme activity were determined. The interaction networks between NADPH oxidase 2 and kefir peptides 1-35 were determined using the Residue Interaction Network Generator (RING) webserver. Pretreatment with kefir for 14 days prevented gastric lesions. In addition, kefir administration reduced ROS production, DNA fragmentation, apoptosis, and TNF-α systemic levels. Simultaneously, kefir increased NO bioavailability in gastric cells and IL-10 systemic levels. A total of 35 kefir peptides showed affinity with NADPH oxidase 2. These findings suggest that the gastroprotective effect of kefir is due to its antioxidant and anti-inflammatory properties. Kefir could be a promising natural therapy for gastric ulcers, opening new perspectives for future research.

The natural history of short bowel syndrome involves intestinal adaptation wherein the remnant small intestine undergoes histologic and anatomic changes aimed at increasing absorption. Teduglutide-a glucagon-like peptide 2 analog approved for pediatric use in 2019-stimulates this process by causing proliferation of intestinal epithelial cells resulting in increased villous height and crypt depth. Food and Drug Administration approval for pediatric patients followed safety and efficacy studies in children that were limited to 24-week duration. Pediatric-specific postmarketing studies evaluating long-term safety and efficacy are underway. Formation of colorectal polyps has been repeatedly observed in studies of adult patients on long-term teduglutide, including in individuals without endoscopic evidence of polyps before treatment initiation. Recent studies, however, suggest increased risk of small bowel hyperplastic and dysplastic polyp formation with long-term glucagon-like peptide 2 analog use. We report 2 cases of small bowel foveolar hyperplastic polyps found during surveillance endoscopies after 1 year of treatment with teduglutide.

Long-term use of proton-pump inhibitors can induce fundic gland polyps in the human stomach. However, this phenomenon has not been described in the veterinary literature. A 5-year-old intact female Maltese dog was referred to our hospital with chronic intermittent vomiting. The dog had been administered omeprazole (0.7-1.0 mg/kg PO q24 h) for the management of hydrocephalus for over 4 years; the omeprazole dose was increased to 10 mg/kg PO q24 h 8 months prior to presentation at referring hospital. Abdominal ultrasonography revealed marked thickening of the gastric wall with multi-lobulated, thickened folds. Subsequent endoscopy revealed marked polypoid lesions, and histological examination of the biopsy samples was consistent with the fundic gland polyps associated with proton-pump inhibitor use in humans. The lesions resolved after cessation of omeprazole, as assessed by ultrasonography. This report describes a case of fundic gland polyps following the long-term administration of omeprazole in a dog.

Gastric polyps represent an abnormal proliferation of the gastric mucosa. Chronic atrophic autoimmune gastritis (CAAG) targets parietal cells and results in hypo-achlorhydria and hypergastrinemia, which exerts a proliferative effect on the gastric mucosa.

We investigate the incidence of gastric polyps in CAAG patients.

This is a single-center retrospective study examining patients with confirmed CAAG from January 1990 until June 2022. Demographic, clinical, biochemical, and serological data were collected for each included patient. The histopathological characteristics of the detected polyps were recorded.

A total of 176 CAAG patients were included. Eighty-nine (50.5%) had 163 incidental polyps. Seventy-six patients (85%) had 130 non-endocrine lesions, among which 118 (90.7%) were inflammatory, 6 (4.6%) adenomatous, and 4 (3%) fundic; 33 patients (37%) had gastric neuroendocrine neoplasms (gNENs), and 21 (23.6%) both; one had MALToma and one gastric adenocarcinoma. Higher circulating levels of gastrin and chromogranin A were observed among patients with polyps (median 668 vs 893 pg/ml p = 0.0237, 146 vs 207 ng/ml p = 0.0027, respectively).

CAAG implies a high incidence of gNENs and exocrine lesions. Gastrin plays a possible trophic role on the mucosa. Further evidence is needed to validate its predictive role for increased polyp risk in CAAG.

Helicobacter pylori (H. pylori) infection is the most important risk factor for gastric cancer. Eradication of H. pylori significantly reduces the incidence and mortality of gastric cancer. H. pylori resistance to antibiotics and a gradual decline in eradication rates are gaining more and more attention. Our study aimed to address the correlation between endoscopic manifestations and the eradication effect of H. pylori.

We retrospectively reviewed outpatients in our hospital with H. pylori infection undergoing eradication therapy from January 2022 to March 2023. Both the primary diagnosis and eradication of H. pylori after treatment were confirmed by a 13C urea breath test. Patients were treated with a proton pump inhibitor (PPI)-based quadruple therapy. Clinical characteristics and endoscopy manifestations within 7 days before or after patients were diagnosed with H. pylori infection were analyzed.

From January 2022 to March 2023, a total of 323 patients were enrolled in this study. There were 138 male patients and 185 female patients. The mean age of patients was 45.62 ± 13.04 years. The H. pylori initial eradication rate was 82.0%. Univariate analysis of factors affecting H. pylori eradication showed that sex, age, and endoscopic manifestations including diffuse redness, multiple white, and flat elevated lesions, and atrophy were significantly associated with the failure of H. pylori eradication therapy. A multivariable logistic regression model analysis of these five factors showed that patients aged over 60 years with multiple white and flat elevated lesions in the endoscopic examination are significantly less likely to eradicate H. pylori with empirical quadruple therapy. On the other hand, patients with diffuse redness were significantly more likely to eradicate H. pylori infection with empirical quadruple therapy.

Our study shows that age over 60 years old, multiple white and flat elevated lesions in endoscopic examination are independent risk factors of initial H. pylori eradication failure with empirical quadruple therapy, while diffuse redness in endoscopic examination is a protective factor of initial H. pylori eradication failure with empirical quadruple therapy, while diffuse redness in endoscopic examination is a protective factor. For patients with these risk factors, a drug sensitivity test or H. pylori resistance gene mutation detection may be more appropriate. However, further mechanism studies or prospective studies are needed to prove our findings.

Background: Long-term maintenance therapy with proton pump inhibitors (PPIs) is a common treatment strategy for acid-related gastrointestinal diseases. However, concerns have been raised about the potential increased risk of gastric cancer and related precancerous lesions with long-term PPI use. This systematic review and meta-analysis aimed to evaluate this potential risk. Methods: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for randomised controlled trials published before 1 March 2023, with no language restrictions. The primary endpoint was the occurrence and progression of gastric mucosal atrophy, intestinal metaplasia, Enterochromaffin-like (ECL) cell hyperplasia, gastric polyps, and gastric cancer during the trial and follow-up. Data were analysed using a random effects model. Results: Of the 4,868 identified studies, 10 met the inclusion criteria and were included in our analysis, comprising 27,283 participants. Compared with other treatments, PPI maintenance therapy for more than 6 months was associated with an increased risk of ECL cell hyperplasia (OR 3.01; 95% CI 1.29 to 7.04; p = 0.01). However, no significant increase was found in the risk of gastric mucosal atrophy (OR 1.01; 95% CI 0.55 to 1.85; p = 0.97), intestinal metaplasia (OR 1.14; 95% CI 0.49 to 2.68; p = 0.76), gastric polyps (OR 1.13; 95% CI 0.68 to 1.89; p = 0.64), or gastric cancer (OR 1.06; 95% CI 0.79 to 1.43; p = 0.71). Conclusion: This systematic review and meta-analysis does not support an increased risk of gastric cancer or related precancerous lesions with long-term PPI maintenance therapy. However, long-term PPI use should be monitored for potential complications such as ECL cell hyperplasia. Further studies are needed to confirm these findings and evaluate the safety of PPI maintenance therapy for acid-related gastrointestinal diseases. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, Identifier: PROSPERO (CRD42022379692).

A type of gastric mucosal injury disease known as gastric ulcer (GU) is clearly connected to the aberrant release of gastric acid. Traditional botanicals have the potential for anti-inflammation, anti-oxidation, and other multitarget therapies, as well as being safe.

The purpose of this study was to investigate the potential effects of Xiangshao Decoction (XST) on gastric mucosal injury in GU rats and to explore the possible molecular mechanisms.

After identifying XST and its components, we established GU rats and cell models by acetic acid and H₂O₂ induction, respectively. SOD and MDA indexes in gastric tissues and GES-1 cells, and the serum levels of BDNF, ALT, and AST were detected with relevant kits, changes of the gastric mucosa were observed and recorded, and gastric tissue pathology was observed by H&E staining. The production of ROS in GES-1 cells was detected by fluorescent probes. Cell transfection techniques were used to silence or overexpress NRF2. The mRNA or protein expressions of NRF2, KEAP1, NQO1, HO-1, SOD2, IL-1β, IL-6, TNF-α, IBA1, GFAP, or γ-H2AX in the gastric tissue, hippocampus, or GES-1 cells were measured via qPCR, Western blot, immunofluorescence staining, or immunohistochemical staining.

The pH of gastric acid, ulcer score, and pathological damage score in GU rats could be reversed by XST administration. Expressions of IL-1β, IL-6, and TNF-α in the gastric mucosal tissues and the hippocampus of GU rats after administration of XST were down. Expressions of NRF2, NQO1, HO-1, SOD2, etc. in the gastric mucosal tissues and BDNF in the hippocampus were up-regulated. The production of ROS and MDA and the expressions of IL-1β, IL-6, TNF-α, and KEAP1 in H₂O₂-induced GES-1 cells were significantly reduced after XST intervention, while the activities of SOD and the expression of NRF2, NQO1, HO-1, and SOD2 were significantly increased, and these could be blocked by silencing NRF2 expression.

XST can improve oxidative stress injury and inflammatory response in GU rats and cell models, and its mechanism is mediated by the NRF2 signaling pathway.