Gender features of the cytokine profile in patients with chronic atrophic gastritis

Background. Сhronic atrophic gastritis certainly remains an urgent problem of gastroenterology but data on sexual differences in the content of cytokines in this pathology are quite contradictory. The purpose of the study: to assess the gender chara­cteristics of the cytokine profile in patients with chronic atrophic gastritis. Materials and methods. The study included 120 patients with gastric atrophy, according to histological examination of biop­sies. The control group consisted of 20 healthy individuals, men and women equally. In all patients, we have evaluated the levels of interleukins (IL-8, IL-10, IL-18), tumor necrosis factor alpha (TNF-α), vasculoendothelial growth factor (VEGF) by enzyme-linked immunosorbent assay using appropriate reagent from Vector-BEST kits and the Stat Fax 303 Plus analyzer. Results. In men with chronic atrophic gastritis, there is a more pronounced imba­lance towards pro-inflammatory cytokines, in particular the level of IL-18 is 1.7 times higher (p < 0.05) than in women. In 46.2 % of cases, the content of IL-8 was also elevated in men by 1.3 times (p > 0.05) compared to women. The level of anti-inflammatory cytokine IL-10 does not have a significant gender difference in patients with precancerous conditions of the stomach. The median of IL-18/IL-10 ratio in men is 2 times higher than in women: 65.36 (21.67; 154.25) vs. 32.15 (12.76; 191.85) (p < 0. 05). In males, IL-8/IL-10 ratio is also 1.5 times higher, which is 2.25 (1.29; 7.68) vs. 1.49 (0.75; 9.78) but this difference was not statically significant. Serum content of VEGF in men exceeded the same indicator in women by 1.4 times (p < 0.05). Direct correlation between VEGF content and the levels of TNF-α (r = 0.47, p < 0.05), IL-8 (r = 0.42, p < 0.05), IL-18 (r = 0.58, p < 0.05) confirm the evidence of increased VEGF expression under the influence of many proangiogenic growth factors and proinflammatory cytokines. Conclusions. With an increase in the level of IL-18 and VEGF by more than 30 %, men require dynamic monitoring for early detection of precancerous structural changes in the gastric mucosa.

Metabolomic Study of Zuojin Pill in Relieving 1-Methyl-3-nitro-1-nitrosoguanidine-Induced Chronic Atrophic Gastritis

The classic prescription Zuojin Pill (ZJP) shows a good therapeutic effect on chronic atrophic gastritis (CAG); it is of great significance to clarify its specific mechanism. Therefore, we explore the mechanism of ZJP on MNNG-induced CAG by integrating approaches. First of all, through the pathological changes of gastric tissue and the expression level of PGI and PGI/II in serum, the expression of inflammation-related factors was determined by RT-PCR to determine the efficacy. Then, UPLC-Q-TOF/MS was used for plasma and urine metabolomic analysis to screen the specific potential biomarkers and metabolic pathway of ZJP in ameliorating CAG and to explore its possible mechanism. ZJP significantly ameliorate the pathological injury of gastric tissue, increase levels of PGI and PGI/II, and reduce the expression level of proinflammatory factors. Through metabolomic analysis, 9 potential metabolic differences were identified and 6 related metabolic pathways were enriched. These findings indicate for the first time the potential mechanism of ZJP in improving CAG induced by MNNG and are of great significance to the clinical development and application of ZJP-related drugs.

Interobserver agreement of estimating the extent of intestinal metaplasia in patients with chronic atrophic gastritis

The extent of gastric intestinal metaplasia (GIM) can be used to determine the risk of gastric cancer. Eleven international gastrointestinal expert pathologists estimated the extent of GIM on haematoxylin and eosin (H&E)- and Alcian blue-Periodic acid Schiff (AB-PAS)-stained slides of 46 antrum biopsies in 5% increments. Interobserver agreement was tested with the intraclass correlation coefficient (ICC). Correlation between standard deviation and extent of GIM was evaluated with the Spearman correlation. The interobserver agreement was very good (ICC = 0.983, 95% confidence interval (CI) 0.975–0.990). The use of AB-PAS did not increase the agreement (ICC = 0.975, 95% CI 0.961–0.985). Cases with a higher amount of metaplastic epithelium demonstrated a higher standard deviation (rs = 0.644; p < 0.01), suggesting lower diagnostic accuracy in cases with extensive GIM. In conclusion, estimating the extent of GIM on H&E-stained slides in patients with chronic atrophic gastritis can be achieved satisfactorily with high interobserver agreement, at least among international expert gastrointestinal pathologists.

A COMPLEX DIAGNOSTICS OF EARLY GASTRIC CANCER ASSOCIATED WITH HELICOBACTER PYLORI INFECTION IN THE ADULT POPULATION OF THE KRASNOYARSK TERRITORY

The aim of our study was to evaluate the clinical-anamnestic, serological, immunological and biochemical tests used for early diagnostics of gastric cancer associated with Helicobacter pylori infection in the adult population of the Krasnoyarsk Territory.Materials and methods: The control group consisted of 104 apparently healthy blood donors, the comparison group – 97 patients with chronic atrophic gastritis as well as a group of patients with early gastric cancer comprising 98 subjects. Assessment of monocyte and neutrophil spontaneous and induced chemiluminescence (CL) was carried out on a 36-channel biochemiluminometer "BLM - 3607". Phagocytosis was measured by using a Beckman Coulter FC 500 flow cytometer. A Varyan Cary Eclipse spectrofluorometer was used to study lipid peroxidation and factors of the antioxidant defense system.Results and discussion: While studying the phagocytic arm of immunity, it was found that all patients with early gastric cancer were reported to have parameters of the maximum intensity for neutrophil spontaneous CL from 17831 c.u. and lower, whereas induced CL reached at least 30,000 c.u.. Phagocytic activity of neutrophilic granulocytes in patients with early gastric cancer was 36% or less. While studying the indicators of monocytes, it was found that spontaneous and induced CL decreased from 454 c.u. and 1186 c.u., respectively, in the patients with early gastric cancer. Monocytic activity in early gastric cancer was 34% or less. In the study of lipid peroxidation, an antioxidant defense in patients with chronic atrophic gastritis and gastric cancer had increased malondialdehyde (MDA) level. Patients with gastric cancer had decreased activity of the enzyme catalase (CAT), whereas subjects with chronic atrophic gastritis had reduced glutathione peroxidase (GPO) level. In contrast, patients with early gastric cancer were featured with increased GPO activity. We have proposed coefficients for assessing the factors of the AOD system in patients: the ratio for superoxide dismutase to catalase activity (SOD / CAT) as well as the ratio for superoxide dismutase to glutathione peroxidase activity (SOD / GPO).Conclusion: During the study, threshold values of parameters were obtained for assigning groups at high risk of developing early gastric cancer, which can be used for screening in adult population.

The circular RNA hsa_circ_000780 as a potential molecular diagnostic target for gastric cancer

Background The present study aimed to identify a specific circular RNA (circRNA) for early diagnosis of gastric cancer (GC). Methods Totally 82 patients with GC, 30 with chronic nonatrophic gastritis and 30 with chronic atrophic gastritis were included in this study. Four of the 82 GC patients were selected for screening. Total RNA from malignant and adjacent tissue samples was extracted, and circRNAs in four patients were screened. According to the screening results, the eight most upregulated and downregulated circRNAs with a statistically significant association with GC were identified by real-time fluorescent quantitative polymerase chain reaction (PCR). Then, the most regulated circRNA was selected for further sensitivity and specificity assessments. CircRNA expression was examined by quantitative reverse transcriptase PCR in 78 GC (21 and 57 early and advanced GC, respectively) and adjacent tissue samples, as well as in gastric fluid samples from 30 patients with chronic nonatrophic gastritis, 30 with chronic atrophic gastritis, and 78 GC. Results A total of 445 circRNAs, including 69 upregulated and 376 downregulated circRNAs, showed significantly altered expression in GC tissue samples. Hsa_circ_000780 was significantly downregulated in 80.77% of GC tissue samples, with levels in GC tissue samples correlating with tumor size, tumor stage, T stage, venous invasion, carcinoembryonic antigen amounts, and carbohydrate antigen 19–9 levels. Strikingly, this circRNA was found in the gastric fluid of patients with early and advanced GC. Conclusions The present study uncovered a new circRNA expression profile in human GC, with hsa_circ_000780 significantly downregulated in GC tissue and gastric fluid specimens. These findings indicate that hsa_circ_000780 should be considered a novel biomarker for early GC screening.

Are physicians ready to comply with the guidelines for diagnosis and management of Helicobacter pylori-associated diseases: the survey results 2020–2021

Objective: To assess compliance of physicians with diagnostic and management guidelines for H. pylori-associated diseases with a question-naire-based survey.Materials and methods: We conducted an anonymous voluntary online survey of 775 physicians of the following specialties: internal medicine 459 (59.2%), gastroenterology 279 (36%), and endoscopy 34 (4.4%). The respondents expressed their level of agreement with the questionnaire items as follows: 0 – I do not know, 1 – disagree, 2 – partially agree, and 3 – fully agree.Results: 613 (79.4%) of the physicians fully agreed to diagnose and treat H. pylori in patients with chronic atrophic gastritis, 602 (78.0%) in the 1 st degree relatives of gastric cancer patients, 525 (68.0%) in patients with chronic superficial gastritis, 423 (54.8%) in peptic ulcer at remission, and 336 (43.4%) in those with dyspepsia syndrome. The physicians were equally compliant with eradication therapy in the patients, for whom long term use of proton pump inhibitors (PPI) or non-steroid anti-inflammatory drugs (NSAID) is being planned (386 (50.0%) and 397 (51.4%), respectively). Internists were less compliant with diagnosis and management of H. pylori in patients taking both PPI (χ2 = 66.525, p = 0.004) and NSAID (χ2 = 103.354, p = 0.003). Among the primary diagnostic tools for H. pylori the physicians preferred 13/14С-urease breath test (545 physicians, or 70.6%) and gastric bioptate morphology (574, or 74.4%), and among the control diagnostic methods they chose fаeces analyses (enzyme-linked immunosorbent assay and polymerase chain reaction). The respondents considered bismuth-enhanced standard triple therapy with clarithromycin to be the most effective regimen for the 1 st line eradication therapy (606, 78.5%). To increase the efficacy of eradication therapy, the physicians were more prone to administer esomeprazole or rabeprazole (70.6%), bismuth-based agents (79.4%), than to use rebamipid (35%), probiotics (44.9%) and/or to double PPI doses (44.2%). The respondents expressed their concerns with low patient compliance to treatment (59.4%) and limited diagnostic capabilities (49.4%).Conclusion: Physician's compliance with the guidelines on diagnosis and management of H. pylori-associated diseases is adequate and might depend on both their awareness and availability of the proposed diagnostic and therapeutic methods.

Efficacy and Safety of Elian Granules in Treating Chronic Atrophic Gastritis: Study Protocol For a Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Trial

Background: Multifocal atrophic gastritis and intestinal metaplasia are considered to be important links of the gastric precancerous cascade. But, there is a lack of definite therapeutic drugs for them. Many studies have shown traditional Chinese medicine is effective and no serious side effects have been identified. However, the studies that have been carried out were not scientifically rigorous trials. Our aim is to design a high-quality trial for a Chinese patent medicine, Elian granules, to investigate the efficacy and safety of this drug in treating chronic atrophic gastritis patients with or without intestinal metaplasia.Methods: This is a phase Ⅱ, randomized, double-blind, placebo-controlled, multicenter clinical trial. A total of 240 participants will be assigned to treatment group or placebo control group with a 1:1 ratio. Then, the experimental drug or placebo will be taken with boiling water,2 small bags (24.2g) each time, twice times a day, half an hour after each meal for 24 weeks. The primary outcome is to observe gastric mucosal histological changes after 6 months in patients with atrophic gastritis with or without intestinal metaplasia based on OLGA/OLGIM. The secondary outcome included dyspepsia symptom score and quality of life scale.Discussion: This study is designed to evaluate the efficacy and safety of Elian granule in a randomized, double-blind, placebo-controlled, multicenter manner. This trial may not only provide evidence for a phase III clinical trial, but also a vision of an alternative option for chronic atrophic gastritis(CAG) treatment.Trial registration: The registration number, ChiMCTR2000003929, was assigned by the Registry Platform For Evidence Based Traditional Chinese Medicine on 13 September 2020.