[Vitamin D3 alleviates the gastritis that associated with Helicobacter pylori infection in mice with hypercholesterolemia by enhancing the activity of vitamin D receptors in the liver tissue and blocking the signaling pathway of JAK/STAT3].

Objective To investigate whether vitamin D3 (VD3) can alleviate Helicobacter pylori (Hp) infection by reducing blood lipids and inhibiting the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathway. Methods High-cholesterol mouse model and Hp infected mouse model were established. Each was treated with VD3 via oral administration for 8 weeks. Real-time quantitative PCR was used to detect the expression of vitamin D receptor (VDR), insulin-induced gene 2 (Insig-2), and gastrin mRNA. Western blot analysis was used to examine the expression of JAK, STAT3, and cyclooxygenase-2 (COX2) proteins in gastric tissues. Biochemical analyses were performed to measure serum cholesterol levels, and ELISA was utilized to evaluate serum gastrin, interleukin 6 (IL-6), and IL-8 levels, along with histopathological examination of liver and gastric tissues using HE staining. Results After oral administration of VD3, the levels of VDR and Insig-2 in mouse liver tissue significantly increased in the high cholesterol group and the high cholesterol combined with Hp infection group. And the expression of serum gastrin decreased. The expression of JAK, STAT3 in gastric tissues reduced, as did the expression of COX2. Serum cholesterol levels decreased, with no significant changes in IL-6 levels, but a reduction in IL-8 levels. Compared to the control group, the high cholesterol combined with Hp infection group showed reduced hepatic ballooning degeneration and alleviated gastric tissue inflammation. In addition, inflammation in gastric tissue was also reduced in the cholesterol group and the Hp infection group. Conclusion VD3 alleviates gastritis by enhancing the activity of VDR in liver tissues, blocking the JAK/STAT3 signaling pathway, and inhibiting the expression of inflammatory factors.

Managing immune checkpoint inhibitor-associated gastritis: Insights and strategies.

Immune checkpoint inhibitors (ICIs) are widely used due to their effectiveness in treating various tumors. Immune-related adverse events (irAEs) are defined as adverse effects resulting from ICI treatment. Gastrointestinal irAEs are a common type of irAEs characterized by intestinal side effects, such as diarrhea and colitis, which may lead to the discontinuation of ICIs.

Impact of high-altitude hypoxia on Helicobacter pylori-induced gastritis pathological manifestations and inflammatory responses.

BACKGROUND: Chronic gastritis caused by Helicobacter pylori (Hp) infection is a common gastrointestinal disorder. Despite the high prevalence of Hp infection and chronic gastritis in the Tibetan Plateau, there is a lack of studies elucidating the influence of plateau hypoxia on Hp-induced gastritis. This study aimed to investigate the impact of high-altitude hypoxia on Hp-induced gastritis, particularly focusing on pathological manifestations and inflammatory responses. METHODS: This study was conducted from July 2023 to March 2024 at the Department of Gastroenterology, Affiliated Hospital of Qinghai University. Ninety patients diagnosed with chronic gastritis were enrolled in the study and divided into four groups based on their residential altitude and Hp infection status. Data on endoscopic and pathological characteristics were collected, along with serum oxidative stress and inflammatory markers. RESULTS: Patients with Hp gastritis exhibit distinctive features in the gastric mucosa, including diffuse erythema, enlarged folds, and white turbid mucus during endoscopy. Notably, individuals with Hp gastritis at high altitudes show a higher prevalence of diffuse erythema and enlarged folds. Pathological analysis reveals that these patients have elevated gastric mucosal inflammation scores and increased chronic and active inflammation. Furthermore, individuals with Hp gastritis at high altitudes demonstrate elevated levels of serum TNF-α, IL-1ß, IL-6, and MDA, as well as reduced serum SOD and GSH-Px activities. CONCLUSIONS: High-altitude hypoxia may exacerbate gastric mucosal damage by enhancing oxidative stress and inflammatory response induced by Hp infection.

Gastric microbiota transplantation as a potential treatment for immune checkpoint inhibitor-associated gastritis.

Immune-related adverse events (irAEs) are complications of the use of immune checkpoint inhibitors (ICIs). ICI-associated gastritis is one of the main irAEs. The gastric microbiota is often related to the occurrence and development of many gastric diseases. Gastric microbiota adjustment may be used to treat gastric disorders in the future. Faecal microbiota transplantation can alter the gut microbiota of patients and has been used for treating ICI-associated colitis. Therefore, we propose gastric microbiota transplantation as a supplementary treatment for patients with ICI-associated gastritis who do not respond well to conventional therapy.

A Systematic Review of Symptoms of Pernicious Anemia.

BACKGROUND: Pernicious anemia (PA) is a type of macrocytic anemia caused by autoimmune gastritis. To facilitate timely diagnosis and treatment of PA there is a pressing need for improved understanding among Healthcare providers of the condition's symptoms and diagnostic criteria. OBJECTIVE: This systematic review aims to extend existing clinical knowledge on the presentation of PA by determining which symptoms and clinical complications are reported in published adult case studies. METHODS: Relevant studies were identified through electronic searches of PsycINFO, Embase, and MEDLINE, via OvidSP. During data extraction symptoms were categorized according to the International Classification of Diseases and were grouped based on frequency. RESULTS: Symptoms were documented for 103 adults with a diagnosis of PA; the most frequent symptoms were fatigue (55%), loss of sensation in limbs (32%), excessive weight loss (27%), and a sore tongue (23%). CONCLUSIONS: This review highlights the diverse symptomology of adults who are diagnosed with PA. Most symptoms documented in case studies are consistent with the core signs of B12 and folate deficiencies. Research is needed to identify if there are common clusters of PA symptoms that can be used as prompts for diagnostic testing in patients with suspected B12 deficiency.

Plain language titleA Review of Symptoms of Pernicious AnemiaPlain language summaryThis study reviewed case studies that have been written about adults with pernicious anemia, it has documented the frequency of the core symptoms and the impact these have on health.

Risk of map-like redness development after eradication therapy for Helicobacter pylori infection.

BACKGROUND: Map-like redness is a newly identified endoscopic risk factor for gastric cancer in patients who received Helicobacter pylori eradication therapy. However, the incidence rate of map-like redness in patients who received eradication, and the risk factors for the development of map-like redness remain unclear. We hence aimed to investigate the incidence rate of map-like redness at 1-year post H. pylori eradication, and evaluated its associations with map-like redness and gastric cancer in relation with gastric condition. MATERIALS AND METHODS: Endoscopic severity of gastritis and map-like redness were retrospectively evaluated according to the Kyoto Classification of Gastritis in patients who had undergone endoscopy before and after H. pylori eradication therapy. RESULTS: The incidence rate of map-like redness for all 328 patients at a mean of 1.2 ± 0.6 years after eradication was 25.3% (95% confidence interval [CI]: 20.7%-30.4%). Patients who developed map-like redness were older, had more severe atrophy and intestinal metaplasia, a higher total score of the Kyoto Classification of Gastritis both before and after eradication, and a higher rate of gastric cancer history than patients who did not have map-like redness. On multivariate analysis, risk of map-like redness was increased in patients with intestinal metaplasia (odds ratio [OR]: 2.794, 95% CI: 1.155-6.757) and taking acid inhibitors (OR: 1.948, 95% CI: 1.070-3.547). Characteristics of H. pylori-positive patients with gastric cancer history were patients who were older (OR: 1.033, 95% CI: 1.001-1.066), taking acid inhibitors (OR: 4.456, 95% CI: 2.340-8.484), and with occurrence of map-like redness after eradication therapy (OR: 2.432, 95% CI: 1.264-4.679). CONCLUSIONS: Map-like redness is observed in one fourth of patients at 1-year post eradication. Patients who developed map-like redness were found to have severe intestinal metaplasia and taking acid inhibitors, and hence such patients require increased attention at surveillance endoscopy.

Asymptomatic cytomegalovirus gastritis in an immunocompetent COVID-19 patient: A case report.

A number of complications are associated with COVID-19 due to reduced immunity. Of these, opportunistic infections are of great significance because of their atypical presentation and low detection rates. Co-infection of various parts of the gastrointestinal system with cytomegalovirus (CMV) is a common occurrence in COVID- 19 patients. Dysphagia and odynophagia are the main complaints of oesophagitis caused by CMV. Colitis due to CMV presents with melena, diarrhoea, or constipation. However, gastritis due to the same agent can be asymptomatic or associated with atypical symptoms like fever and epigastric pain. Cytomegalovirus gastritis can be fatal if not detected early. Hence, continued monitoring of routine baseline investigations is imperative until the complete resolution of COVID-19, as prompt diagnosis improves the outcomes.

Unveiling early stage autoimmune gastritis: novel endoscopic insights from two case reports.

The predominant characteristic of autoimmune gastritis (AIG) is corpus-dominant advanced atrophy, which is mostly observed in the middle to late stages. More reports are needed on the endoscopic features of the early stage. In this report, we present two cases of early-stage AIG in which endoscopic examinations showed no atrophy of the gastric mucosa but displayed a transition of collecting venules from a regular to an irregular arrangement. In addition, yellowish-white cobblestone-like elevations were observed in the fundic gland region. Histologically, the observed manifestations included pseudohypertrophy and protrusion of parietal cells into the lumen, possibly along with hyperplasia of G cells, lymphocytic infiltration and potentially pseudopyloric gland metaplasia. Serologically, the anti-parietal cell antibody returned positive results, whereas the anti-intrinsic factor antibody yielded negative results. In this study, we summarized some endoscopic features of two patients, aiming to provide clues for endoscopists to detect early-stage AIG.

Long-term endoscopic gastric mucosal changes up to 20 years after Helicobacter pylori eradication therapy.

Helicobacter pylori eradication therapy reduces the risk of gastric cancer. However, it is unclear whether the severity of risk factors for gastric cancer such as atrophy and intestinal metaplasia are reduced after eradication in the long term. We aimed to study long-term changes in endoscopic risk factors for gastric cancer up to 20 years post-eradication. The endoscopic severity of gastritis according to the Kyoto Classification of Gastritis in 167 patients was retrospectively evaluated over an average follow-up 15.7 years. A significant improvement in mean total gastric cancer risk score (4.36 ± 1.66 to 2.69 ± 1.07, p < 0.001), atrophy (1.73 ± 0.44 to 1.61 ± 0.49, p = 0.004), and diffuse redness (1.22 ± 0.79 to 0.02 ± 0.13, p < 0.001) was observed compared to baseline in the Eradication group. However, there was no change in the never infection and current infection groups. The frequency of map-like redness increased over time until 15 years (3.6% to 18.7%, p = 0.03). The Cancer group had significantly higher risk scores at all time points. Endoscopic atrophy significantly improved in eradicated patients over long-term, suggested that eradication is one of the key elements in gastric cancer prevention. Individualized surveillance strategies based on endoscopic gastritis severity before eradication may be important for those at risk of gastric cancer.

Zinc supplementation alleviates oxidative stress to inhibit chronic gastritis via the ROS/NF-κB pathway in a mouse model.

Zinc (Zn) is an important trace element; it is involved in the regulation and maintenance of many physiological functions in organisms and has anti-inflammatory and antioxidant properties. Chronic gastritis is closely associated with damage to the gastric mucosa, which is detrimental to the health of humans and animals. There are few studies on the effects of zinc on, for example, gastric mucosal damage, oxidative stress, inflammation and cell death in mice. Therefore, we established in vivo and in vitro models of inflammatory injury and investigated the effects of zinc supplementation in C57BL/6 mice and Ges-1 cells and examined the expression of factors associated with oxidative stress, inflammation and cell death. In this study, the results of in vivo and in vitro experiments showed that reactive oxygen species (ROS) levels increased after sodium salicylate exposure. Malondialdehyde levels increased, the activity of the antioxidant enzymes catalase and superoxide dismutase decreased, and the activity of glutathione decreased. The NF-κB signaling pathway was activated, the levels of proinflammatory factors (TNF-α, IL-1ß, and IL-6) increased, and the expression of cell death-related factors (Bax, Bcl-2, Caspase3, Caspase7, Caspase9, RIP1, RIP3, and MLKL) increased. Zinc supplementation attenuated the level of oxidative stress and reduced the level of inflammation and cell death. Our study indicated that sodium salicylate induced the production of large amounts of reactive oxygen species and activated the NF-κB pathway, leading to inflammatory damage and cell death in the mouse stomach. Zinc supplementation modulated the ROS/NF-κB pathway, reduced the level of oxidative stress, and attenuated inflammation and cell death in the mouse stomach and Ges-1 cells.

Trained Immunity and Trained Tolerance: The Case of Helicobacter pylori Infection.

Trained immunity is a concept in immunology in which innate immune cells, such as monocytes and macrophages, exhibit enhanced responsiveness and memory-like characteristics following initial contact with a pathogenic stimulus that may promote a more effective immune defense following subsequent contact with the same pathogen. Helicobacter pylori, a bacterium that colonizes the stomach lining, is etiologically associated with various gastrointestinal diseases, including gastritis, peptic ulcer, gastric adenocarcinoma, MALT lymphoma, and extra gastric disorders. It has been demonstrated that repeated exposure to H. pylori can induce trained immunity in the innate immune cells of the gastric mucosa, which become more responsive and better able to respond to subsequent H. pylori infections. However, interactions between H. pylori and trained immunity are intricate and produce both beneficial and detrimental effects. H. pylori infection is characterized histologically as the presence of both an acute and chronic inflammatory response called acute-on-chronic inflammation, or gastritis. The clinical outcomes of ongoing inflammation include intestinal metaplasia, gastric atrophy, and dysplasia. These same mechanisms may also reduce immunotolerance and trigger autoimmune pathologies in the host. This review focuses on the relationship between trained immunity and H. pylori and underscores the dynamic interplay between the immune system and the pathogen in the context of gastric colonization and inflammation.

[Impact of primary duodenogastric reflux and Helicobacter pylori infection on gastritis and antibiotic resistance in children]. / å„¿ç«¥åŽŸå‘æ€§åäºŒæŒ‡è‚ èƒƒåæµä¸Žå¹½é—¨èžºæ†èŒæ„ŸæŸ“å¯¹èƒƒç‚Žå’ŒæŠ—ç”Ÿç´ è€è¯æ€§çš„å½±å“.

OBJECTIVES: To investigate the risk factors for Helicobacter pylori (HP) infection in children with primary duodenogastric reflux (DGR) and its impact on gastritis and antibioticresistance. METHODS: A retrospective analysis was performed on the clinical data of 2 190 children who underwent upper gastrointestinal endoscopy in Wuxi Children's Hospital from January 2019 to February 2022, among whom 308 children were diagnosed with primary DGR. According to the presence or absence of HP infection, the children were classified to HP infection group (53 children) and non-HP infection group (255 children). The risk factors for HP infection and its impact on the incidence rate and severity of gastritis were analyzed. According to the presence or absence of primary DGR, 331 children with HP infection were classified to primary DGR group (29 children) and non-primary DGR group (302 children), and then the impact of primary DGR with HP infection on antibiotic resistance was analyzed. RESULTS: The HP infection group had a significantly higher age than the non-HP infection group (P<0.05), and there was a significant difference in the age distribution between the two groups (P<0.05), while there were no significant differences in the incidence rate and severity of gastritis between the two groups (P>0.05). The multivariate logistic regression analysis showed that older age was a risk factor for HP infection in children with DGR (P<0.05). Drug sensitivity test showed that there were no significant differences in the single and combined resistance rates of metronidazole, clarithromycin, and levofloxacin between the primary DGR group and the non-primary DGR group (P>0.05). CONCLUSIONS: Older age is closely associated with HP infection in children with DGR. Primary DGR with HP infection has no significant impact on gastritis and antibiotic resistance in children.

Subacute combined degeneration of the spinal cord with cerebellar lesions: A case report.

RATIONALE: Subacute combined degeneration of the spinal cord is a degenerative disease of the central and peripheral nervous systems caused by vitamin B12 deficiency, mainly involving the spinal cord posterior, lateral, and peripheral nerves, but rarely involving the cerebellum. PATIENT CONCERNS: A 41-year-old woman presented with a 2-year history of walking unsteadily. Her hematologic examination revealed megaloblastic anemia and vitamin B12 deficiency. Electromyography showed multiple peripheral nerve damage (sensory fibers and motor fibers were involved). Imaging examination showed long T2 signal in the cervical, thoracic and lumbar spinal cord and cerebellum. Gastroscopy revealed autoimmune gastritis. DIAGNOSES: Subacute combined degeneration of the spinal cord. INTERVENTIONS: By supplementing with vitamin B12. OUTCOMES: The patient's symptoms of limb weakness, diet, and consciousness were improved, and the muscle strength of both lower limbs recovered to grade IV. LESSONS: The symptomatic people should seek medical treatment in time to avoid further deterioration of the disease. When esophagogastroduodenoscopy is performed as part of routine physical examination in asymptomatic people, it should be checked for the presence of autoimmune gastritis. Early diagnosis can prevent irreversible neuropathy.

Cytomegalovirus gastritis as a rare adverse event during combined ipilimumab and nivolumab in a patient with melanoma.

Immunotherapy has improved survival outcomes of patients with advanced melanoma. Lower gastrointestinal tract immune-related adverse events (irAEs) are common during treatment; however, gastritis is not frequently observed. Herein, we report a case of severe cytomegalovirus (CMV)-related gastritis in a patient treated with ipilimumab and nivolumab for metastatic melanoma. This report presents a 60-year-old woman with stage IV BRAF wild-type melanoma. After the second course of ipilimumab-nivolumab, the patient reported epigastric discomfort after meals, anorexia, and subsequent nausea, vomiting, epigastric pain, and weight loss. Disease staging with PET/CT scan showed very good partial response and diffuse gastroduodenitis. The patient underwent esophagogastroduodenoscopy, showing severe esophageal candidiasis and diffuse hemorrhagic, edematous, and ulcerative mucosa in the whole gastric wall. Biopsies of the gastric wall were obtained. Before receipt of the final pathology report, the patient was empirically started on corticosteroids based on the clinical suspicion of immune-related gastritis, without improvement of symptoms. The hematoxylin-eosin staining demonstrated active gastritis with diffuse nuclear cytopathic viral inclusions in epithelial and interstitial cells; CMV infection was confirmed with immunohistochemical staining. The patient started ganciclovir and fluconazole, with rapid improvement of symptoms. This case presents a rare instance of CMV gastritis in a patient receiving combined anti-PD1 and anti-CTLA4 , in the absence of immune-suppression to manage an irAE. In the case of suggestive symptoms of irAEs, a high index of clinical suspicion is required to rule out concomitant or isolated infective disease. Guidelines for prophylaxis and treatment of these patients are needed, to optimize treatment results.

Severe Unexplained Iron Deficiency Anemia in Children: High Yield of Upper Gastrointestinal Endoscopy Regardless of Gastrointestinal Symptoms.

In this retrospective study spanning 2016 to 2022, we aimed to evaluate the diagnostic utility of upper gastrointestinal endoscopy (UGE) in children under 18 years presenting with severe unexplained iron deficiency anemia (IDA), defined as microcytic anemia of hemoglobin ≤7 g/dL with low ferritin levels. Of 106 children hospitalized for severe anemia, 29 had unexplained IDA (mean hemoglobin level of 6.2 [3.2 to 6.9] gr/dL), and 25 of them underwent UGE. The mean age was 10.7 ± 3.9 years, with 76% being female. Ten children (40%) had gastrointestinal (GI) symptoms at presentation. The cause of IDA was found in 18 (72%) of 25 children who underwent UGE, of whom 12 were without GI symptoms. Gastric nodularity, erosions, or polyps were observed in 68%, and gastritis was evident in 72% based on histopathology. Helicobacter pylori was found in 50% of those with gastritis. Follow-up showed normalized hemoglobin levels in 92% of cases, with only 2 children requiring repeat iron therapy. Our findings underscore the importance of incorporating UGE into the diagnostic investigation of severe unexplained IDA in children, irrespective of the presence of GI symptoms.

Triple-drug combination therapy versus six-month proton pump inhibitor monotherapy in non-Helicobacter pylori Helicobacter eradication, and hyperacid environment preference of Helicobacter suis: a clinical study.

BACKGROUND: At present, eradication regimens for non-Helicobacter pylori Helicobacter (NHPH) have not been established yet. We investigated effectiveness of the standard triple-drug combination therapy for Helicobacter pylori eradication and of a proton pump inhibitor (PPI) monotherapy in eradication of NHPH. METHODS: Subjects were the patients who were diagnosed with NHPH-infected gastritis based on microscopic findings, helical-shaped organisms obviously larger than Helicobacter pylori, in the gastric mucosal specimens using Giemsa staining at Kenwakai Hospital between November 2010 and September 2021, whose NHPH species were identified by polymerase chain reaction (PCR) analysis of urease genes in endoscopically-biopsied samples, and who consented to NHPH eradication with either the triple-drug combination therapy for one week or a PPI monotherapy for six months. Six months after the completion of eradication, its result was determined with esophagogastroduodenoscopy, microscopic examination, and PCR analysis. In cases of unsuccessful eradication, a second eradication with the other therapy was suggested to the patient. RESULTS: PCR analysis detected NHPH in 38 patients: 36 as Helicobacter suis and two as Helicobacter heilmannii/Helicobacter ailurogastricus. Fourteen Helicobacter suis-infected and one Helicobacter heilmannii/Helicobacter ailurogastricus-infected patients requested eradication therapy. The triple-drug combination therapy succeeded in four of five patients, while the PPI monotherapy succeeded in five of 10 patients. Three of five patients who had been unsuccessful with the latter therapy requested the triple-drug combination therapy as the second eradication and all three were successful. In total, the triple-drug combination therapy succeeded in seven out of eight (87.5%) attempted cases, while the PPI monotherapy in five out of 10 (50%) attempted cases. CONCLUSIONS: In NHPH eradication, the triple-drug combination therapy was considered to be effective to some extent and to become the first-line therapy. While, although less successful, PPI monotherapy appeared to be a potentially promising option particularly for patients with allergy or resistance to antibiotics. Effectiveness of PPI monotherapy may be attributed to hyperacid environment preference of Helicobacter suis and PPI's acid-suppressive effect. Additionally, male predominance in NHPH-infected gastritis patients may be explained by gender difference in gastric acid secretory capacity. However, further evidence needs to be accumulated. STUDY REGISTRATION: This study was approved by the Research Ethics Committee of Kenwakai Hospital (No. 2,017,024).

Millingtonia hortensis L.f. ethanol extract exerts in vivo and in vitro anti-inflammatory activities through inhibition of Syk kinase in NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Millingtonia hortensis L.f., commonly known as tree jasmine or Indian cork tree, is native to South Asia and Southeast Asia. Traditionally, its stem bark, leaves, and roots are employed for pulmonary, gastrointestinal, and antimicrobial purposes, while the flowers are used in treating asthma and sinusitis. AIM OF THE STUDY: The underlying anti-inflammatory mechanisms of M. hortensis remain relatively unexplored. Therefore, we studied the anti-inflammatory effects of M. hortensis and the molecular mechanisms of its ethanol extracts (Mh-EE) both in vitro and in vivo. MATERIALS AND METHODS: Nitric oxide (NO) production was assessed using Griess reagent, while cell viability of RAW264.7 cell and HEK293T cells were determined via the MTT assay. Constituent analysis of Mh-EE using GC/MS-MS and HPLC, and mRNA expression of inflammatory cytokines was measured through PCR and RT-PCR. Protein levels were analyzed using western blotting. The thermal stability of Mh-EE was evaluated by CESTA. Lastly, a gastritis in vivo model was induced by HCl/EtOH, and protein expression levels were measured using western blotting. RESULTS: Mh-EE significantly reduced NO production in LPS-induced RAW264.7 cells without substantially affecting cell viability. Additionally, Mh-EE decreased the expression of proinflammatory factors, such as iNOS, IL-1ß and COX2. Furthermore, Mh-EE downregulated TLR4 expression, altered MyD88 recruitment, and suppressed phosphorylation of Syk, IKKα, IκBα and AKT. Simultaneously, Mh-EE also attenuated NF-κB signaling in HCl/EtOH-induced mice. CONCLUSIONS: Mh-EE exerts anti-inflammatory effects by suppressing p-Syk in the NF-κB pathway, and it has potential as a novel treatment agent for inflammatory diseases.