Сombination of two or more biological or immunosuppressive drugs in order to achieve a synergistic effect in patients with refractory inflammatory bowel disease (IBD) has been in the spotlight for many years. Combination therapy may include various medications, most often biological and immunosuppressants. Despite the fact that biological therapy of IBD has traditionally focused on drugs that block tumor necrosis factor-alpha, the development of new drugs that act on different targets, such as vedolizumab, ustekinumab, tofacitinib or ozanimod, has made it possible to use combined immunosuppressive therapy. The treatment algorithm suggests various combinations of dual biological therapy for 2 categories of patients with IBD: patients with well-controlled luminal IBD and uncontrolled extra-intestinal symptoms (indications such as arthritis or psoriasis) and patients with refractory, uncontrolled IBD. Thus, data on the efficacy and safety of dual biological therapy as a method of treating Crohn’s disease (CD) or ulcerative colitis (UC) remain very limited. In fact, the vast majority of literature consists of individual cases and a series of cases. Given the lack of studies with a high level of evidence, gastroenterologists have turned to larger studies of dual biological therapy in other areas of medicine, such as rheumatology and dermatology. The aim of this article is to demonstrate clinical experience of combination therapy with genetically engineered biological drugs and selective immunosuppressors in UC, to analyze potential adverse effects or risks associated with combination therapy, and to determine future directions in the use of this treatment.

The study of inflammatory bowel disease is characterized by dynamism and new discoveries. Subtle and new mechanisms of participation of genetic and environmental factors in the pathogenesis of inflammatory bowel diseases have been deciphered, as well as new classes of drugs have appeared that allow influencing many parts of the inflammatory process. However, the paradox of the situation lies in the fact that the more recent advances and discoveries in the field of biology and medicine, the more “gray spots” become in our understanding of the pathogenesis and approaches to the treatment of this category of patients. At the same time, the fundamental problems of IBD, related to reducing the risk of surgical interventions and restoring the quality of life of patients to the population level, are far from being resolved. The article discusses new methodological approaches to the treatment of patients with inflammatory bowel diseases using new classes of cytostatics and granulocyte-macrophage colony-stimulating factors.

Introduction. Inflammatory Bowel Disease (IBD) including Crohn’s Disease (CD) and Ulcerative Colitis (UC) representsis a challenge for gastroenterologists worldwide, due to its potential to cause life-threatening complications and lead to disability in patients. Aim: to develop a tool that can be used in clinical practice to predict the development of life-threatening complications of IBD through mathematical modeling. Methods. A historical cohort of 291 adult patients with a verified diagnosis of IBD (48% - CD, 52% - UC) who sought medical care from 2020 to 2022 comprised the study base. The outcomes were life-threatening complications including a subgroup of conditions that required urgent surgical intervention. Logistic regression, classification trees and neural network analysis were used to predict the studied outcomes. Results. Life-threatening complications occurred in 22.3% of CD- and in 9.9% of UC patients. The corresponding numbers for urgent surgical complications were 16.5% and 1.3%. Among the constructed mathematical models for both types of outcomes, neural network models demonstrated the highest sensitivity and specificity. Based on the neural network models, two software products named “IBD prognosis: risk of life-threatening complications” and “ IBD prognosis: risk of urgent surgical complications” were developed. For the former, the positive predictive value was 65.0% (95% CI 52.4-75.8) while the negative predictive value was 97.0% (95% CI: 93.9-98.5). For the latter, the corresponding numbers were 77.4% (95% CI: 60.2-87.4) and 99.2% (95% CI: 97.2-99.8). Conclusions. Two tools have been developed for use in clinical practice by gastroenterologists, therapists, and general practitioners to manage IBD patients. Identifying a high-risk IBD patient for developing a life-threatening complication can be used as a foundation for optimizing the therapy used in the treatment of a given patient, potentially saving lives.

Introduction: Currently, the possibilities in the treatment of Crohn’s disease (CD) are expanding. Various classes of genetically engineered biological therapy are available for the treatment of inflammatory bowel diseases (IBD). Vedolizumab, having a selective nature of action, has a higher safety profile of the drug, which suggests lower immunogenicity and, as a consequence, long-term efficacy. Materials and methods: A retrospective study was conducted on the basis of the National Medical Research Centre of Coloproctology named after A. N. Ryzhikh, which included 54 patients treated with vedolizumab. In the course of the work, the survival of therapy was evaluated, as well as the influence of demographic characteristics, localization, phenotype of the disease and other factors on the effectiveness of therapy. Results: The study showed 86.0% (95% CI 72.8-93.1) survival of therapy for 15 months and 75.9% (95% CI 58.8-86.7) for two years. No statistically significant differences were obtained when assessing the effect of gender, comorbidity, lesion localization, disease phenotype, smoker status and the use of glucocorticosteroids during vedolizumab induction. During the analysis, it was revealed that significant factors affecting the effectiveness of therapy are the age of CD debut less than 21 years and the SES-CD index index more than 7, as well as previous therapy with the use of two or more anti-TNF drugs. Discussion: Despite the small sample size, the findings allow us to predict the effectiveness of therapy, which may affect survival.

Introduction. The article is devoted to the identification of a marker of imbalance of oxidative stress and the antioxidant system in children with Crohn’s disease. The putative level of total bilirubin as an integrative method for assessing Crohn’s disease activity is highly correlated with indicators of oxidative stress and the antioxidant system (ischemia, modifying albumin, malondialdehyde, catalase, sulfhydryl groups and glutathione). Purpose: to explain the relationship between the level of total bilirubin and the activity of the inflammatory process in Crohn’s disease, which allows the introduction of the studied integrative indicator in clinical practice. Materials and methods. Based on the results of scientific studies of biomarkers of oxidative stress (albumin-modifying ischemia - plasma IMA, malondialdehyde - plasma MDA) and the antioxidant system (plasma SH-groups, catalase and reduced erythrocyte glutathione), as well as a simultaneous study of the level of total bilirubin in children diagnosed with Crohn’s disease. To search for a differential method for assessing the level of Crohn’s disease activity by the degree of bilirubin, use binary logistic regression. Results and survey. The results of the study showed a clear relationship between the increase in bilirubin levels and the severity of oxidative stress. It has been established that with a decrease in the level of total bilirubin, there is a predominance of oxidative stress over the antioxidant system, which leads to an increase in inflammation activity. It has been proven that the level of total bilirubin can be used in the complex activity of diseases as a minimally invasive, as well as an objective and acute marker. The sensitivity and specific sensitivity of this protocol is 90.9% and 93.3% respectively, which allows the use of total bilirubin as a marker of inflammation in Crohn’s disease.

Aim. To assess changes in the structure of the small intestine microbial community in the context of the “gut microbiota-immune system-brain axis” in healthy aging, depression and dementia. Materials and methods. 74 elderly people included in the groups: “Healthy ageing”, “Depression”, “Dementia” were investigated. Evaluation of 5 main types of microorganisms of the small intestine (Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria, Fusobacteria) by method of gas chromatography - mass spectrometry of microbial markers was carried out. For statistics, hierarchical cluster analysis with the construction of a heat map was used. Results. Reconstruction affected 15 out of 30 studied bacterial species of the phylums Firmicutes, Actinobacteria, Proteobacteria in the “Dementia” and “Depression” groups in relation to the “Healthy ageing” group. In depression, the number of all types of bacteria involved in the fermentation of food polysaccharides increased in relation to the “Healthy ageing” group. In dementia, low levels of Clostridium spp., Eubacterium spp., Bifidobacterium spp. was shown, in relation to depression, but number of C. perfringens, С. difficile and facultative anaerobes: Streptococcus spp., Enterococcus spp., Lactobacillus spp., S. aureus, S. epidermidis was increased, compared to “Healthy ageing” group. Conclusions. The indicators of the systems included in the axis “intestinal microbiota - immune system - brain” indicated a pronounced disintegration of the axis in dementia in relation to depression and healthy ageing. The results can be used as biological markers in the differential diagnosis of these pathologies (dementia/depression), which have common risk factors and clinical symptoms.

The aim of the study was to study the effect of salivary amylase on improving gastric protein digestion, as well as the effect of gastric protein hydrolysis on improving fat digestion. The work consisted of two parts, in the first part, in two series, the hydrolysis of proteins under the influence of gastric juice in the presence of starch and the effect of saliva amylase on the change in the total proteolytic activity of gastric juice when using substrates of a mixture of starch and proteins were investigated. In the second part of the work, the lipolytic activity of pancreatic juice with the studied proteins was studied in the presence and absence of bile. From the data obtained, it was found that the use of a mixture of starch with proteins helps to reduce the hydrolysis of proteins by gastric juice. The use of salivary amylase promotes an increase in protein hydrolysis by reducing the formation of starch-protein complexes that prevent the digestion of proteins by gastric juice. All the studied proteins, except gelatin, have an inhibitory effect on lipase in the pancreatic juice; the degree of inhibitory effect of each protein is expressed differently. It depends on their degree of digestion in gastric juice. Thus, the preliminary hydrolysis of proteins by pepsins in the stomach contributes not only to the further improvement of their hydrolysis under the influence of proteolytic enzymes of pancreatic juice, but also to the hydrolysis of fats under the influence of pancreatic lipase. It is concluded that the sequence of nutrient breakdown by enzymes of saliva, stomach and pancreas is primarily aimed at enzymatic disintegration between polysaccharides and proteins, as well as proteins and fats, in order to reduce their interaction and the formation of physical complexes. Thus, secondarily, improve the digestibility of nutrients in the upper gastrointestinal tract. The conceptual assumption of enzymatic disintegration of nutrients in the upper gastrointestinal tract allows us to substantiate the existing sequence of initial digestion of polysaccharides by saliva, as well as the initial digestion of proteins by gastric juice.

Purpose of the study. To determine the level of expression of motilin and vasoactive intestinal peptide (VIP) in the mucosa of the sigmoid colon in patients with diverticular disease (DD) of the colon and irritable bowel syndrome (IBS). Material and methods. 120 people were examined: 85 patients with DD and 35 with IBS. The patients were divided into 3 groups: group 1-40 patients with symptomatically uncomplicated DD (SUDD); group 2-45 people with an asymptomatic form of DD; the 3rd group of patients was represented by persons with IBS with constipation (IBSc). The control group consisted of 30 practically healthy people. All patients and healthy people were examined according to a single program, including clinical data, laboratory (general blood count with leukocyte formula, C-reactive protein), instrumental (colonoscopy, ultrasound examination of the abdominal organs) data. Primary antibodies to motilin and VIP were used to verify hormone expression. Results. The clinical picture in individuals with SUDD corresponded to the classical manifestations of IBS with the incidence of constipation in 87.5% and diarrhea in 12.5% of patients. Immunohistochemical analysis showed a significant decrease in the expression level of motilin and VIP in patients in this group of patients. The group with SUDD was statistically indistinguishable from the group with IBSc (p > 0.05), however, it was statistically significantly different from the group with asymptomatic DD (p < 0.05). Conclusions. The data obtained indicate the important role of the expression of motilin and VIP in the manifestation of the clinical manifestations of DD and IBS and give reason to assume that these hormones are involved not only in motor-evacuation disorders, but also in proliferative processes in the colon mucosa, which, possibly, initiate destructive processes, accompanied by the formation of diverticula.

Aim. To establish the prevalence of atherosclerotic lesions in the unpaired visceral artery branches of the abdominal aorta. To explore the features of clinical presentation, the state of the mucosa of the upper GI tract. Materials and methods. A total of 118 patients with atherosclerosis of the unpaired visceral artery branches of the abdominal aorta aged 45 to 89 years were examined. The comparison group included 120 patients without atherosclerosis in the unpaired visceral artery branches of the abdominal aorta. Patients in both groups had coronary atherosclerosis. Ultrasound dopplerography (USDG) as a screening technique, CT angiography, and MSCT aortography were used to verify occlusion-stenotic lesions in the unpaired visceral artery branches of the abdominal aorta. The diagnosis of erosion changes in the gastric mucosa was confirmed by clinical symptoms and endoscopic examination findings. Results. In our study, hemodynamically relevant stenosis (>70%) was identified in 28.8% of patients. The clinical presentation of atherothrombosis in mesenteric vessels was shown to be nonspecific. Abdominal pain was the most common symptom in the examined patients with abdominal angina (76.3%). The upper GI endoscopy in patients with a verified diagnosis of chronic abdominal ishemia (CAI) showed gastric mucosa atrophy (focal or diffuse) in 100% of cases. Gastric erosions are identified in 55.1% of patients. Gastric ulcers are observed in 27.1% of patients. Erosive and ulcerative lesions of the gastric mucosa are combined with atrophic changes in the mucosa. Erosive esophagitis was detected in 28.8% of patients. The frequency of detected focal abnormalities in the esophageal mucosa accounts for 27.3%, and those in the gastric mucosa is 54.2%, mainly due to intestinal metaplasia. Conclusion. Due to the increasing prevalence of obliterative vascular diseases, early detection of changes in the upper gastrointestinal tract remains an urgent challenge. The comprehensive endoscopic examination using additional endoscopic NBI and ZOOM techniques allows to identify all changes in the mucosa, including small focal abnormalities. Timely detection of the disease makes it possible to choose the right treatment method.

The aim. To evaluate the effectiveness of endoscopic techniques for gastrointestinal bleeding of unknown origin in the conditions of GBUZ “KKB No. 2” and to determine the most effective therapeutic tactics. Materials and methods. The basis for our study was the analysis of the results of treatment of 47 patients with suspected small intestine bleeding in the period 2018-2023 in the State Medical Institution “KKB No. 2” of the city of Krasnodar. The study group was dominated by men -25 patients (53%) compared with women - 27 patients (47%). The age of the patients ranged from 18 to 89 years. VCE was performed in 16 patients. In controversial and unconvincing cases, BAE-14 patients were performed. A comprehensive examination of VCE + BAE was performed in 17 patients. Results: The most rational method of endoscopic hemostasis in small intestine bleeding, according to our observation, is endoscopic clipping in combination with conservative therapy. Results. According to our observation, the most rational method of endoscopic hemostasis in small intestinal bleeding is endoscopic clipping in combination with conservative therapy. Conclusion. The capabilities of clinicians in the differential diagnosis of pathological conditions of the small intestine are enhanced by the availability of modern equipment in medical and preventive institutions, as well as to perform minimally invasive treatment, reducing the rehabilitation time due to the reduction of surgical trauma.

Purpose of the study. To find out the effectiveness of the use of angiotensin-converting enzyme (ACE) inhibitors in the complex therapy of erosive and ulcer lesions of the stomach and duodenum in unstable angina pectoris (UA). Materials and methods. A survey of 109 patients with UA with gastroduodenal erosions and ulcers was carried out, taking into account their clinical signs, endoscopic features and the parameters of gastric secretion. The patients were divided into two groups depending on the nature of the treatment of erosions and ulcers. The first group included 40 patients treated with standard therapy, and the second one included 69 patients who additionally received ACE inhibitor lisinopril at an average dose of 7.27±0.16 mg a day. Results. The therapy by lisinopril resulted in decreasing of pain and dyspeptic syndrome, especially in patients with acute erosions, compared with conventional treatment group. According to endoscopic examination, in patients treated with lisinopril, an acceleration of repair processes in the tissues of the gastroduodenal zone was observed. The depth and size of damages, a reduction in the period of persistence of microbleeding signs and inflammatory changes in the periulcerous zone were also less pronounced in lisinopril patient’s group. In patients with acute erosions a decrease in the number and size of erosive defects of the mucous membrane was observed. The study of the parameters of gastric secretion showed that gastroduodenal erosions and ulcers in UA revealed the activation of the acid-peptic factor and a decreasing in the production of gastromucoproteins. Increased production of pepsinogen and a sharply reduced formation of protective mucus was observed in patients after conventional treatment, despite some positive dynamics. Normalization in pepsinogen secretion with some inhibition of the production of mucopolysaccharides was observed in Lisinopril treated patients at the end of therapy. Acid production in both groups was reduced, which was associated with could be provoked by an uptake of antisecretory agents. Conclusion. The use of ACE inhibitor lisinopril in the complex therapy in patients with UA with gastroduodenal erosions and ulcers is pathogenetically justified and clinically effective. This combination helps to reduce the duration of clinical signs, accelerate the healing of defects and normalize the parameters of gastric secretion.

The frequency of achieving control as a result of taking antihypertensive drugs in women in the age group 55-64 years reaches 78.9%, the frequency of gastrointestinal symptoms occurring during treatment of hypertension is up to 62%. The aim: to analyze the probable causes of the development of symptoms of diseases of the gastrointestinal tract in postmenopausal patients receiving antihypertensive therapy. Material and methods. A comprehensive clinical examination of out-patient and in-patient patients of health care institutions of the Smolensk region with hypertension aged 50 to 84 years, (group AG, n=160) mean age 67.4 ± 17.4 years. Results. Complex examination and observation on the basis of standard methods with high probability shows the formation of gastroesophageal reflux disease, gastritis, simple erosions of the gastric mucosa, biliary dysfunction, chronic pancreatitis steatohepatosis in the observed patients. Conclusions: In postmenopausal women receiving antihypertensive therapy, there are major gastrointestinal symptoms of varying severity, arising in conditions of irrational nutrition, psycho-emotional and physical stress on the background of irregular medication. Based on the analysis of modern scientific sources, it can be argued that complex rational antihypertensive, antiplatelet, hypolipidemic, antisecretory and eradication therapy and the correction of modifiable risk factors ensures the achievement of remission of gastrointestinal and cardiovascular disease in the optimal time, improves the quality, life expectancy of patients and improves disease prognosis.

The purpose of this study is to conduct a clinical and morphological analysis of cases of chronic gastritis with a high risk of gastric cancer (GC). Materials and methods. The study included 26 cases of chronic atrophic gastritis of stages 3 and 4 with a high risk of developing GC according to the assessment using the OLGA system (Operative Link for Gastritis Assessment). The cases were diagnosed on material of gastric tissue biopsy in 2022. In total, 678 histological studies were performed during the year. Cases of chronic gastritis with a high risk of developing GC accounted for 3.8% of all chronic gastritis. Results. Cases of chronic gastritis with a high risk of developing GC were more often observed in older men (average age 67±12 years, ratio 2.25:1). Multifocal atrophic gastritis was in the first place in frequency of occurrence (61.5%), the connection with helicobacter infection was confirmed only in a third of cases (34.6%). Morphological changes were characterized by a predominant lesion of the antrum of the stomach and mixed complete and incomplete intestinal metaplasia. With the exception of one case in which pseudopancreatic metaplasia was detected in the antrum of the stomach, all cases of autoimmune gastritis (n=26) were assigned to stage 2 with a low risk of developing GC, which seems controversial to us. Conclusion. The results of our study showed a high percentage of pre-existing tumor lesions of the stomach in the group of chronic gastritis with a high risk of developing GC. Dysplasia was diagnosed in 5 out of 26 cases, GC with previously performed mucosectomy in 3 out of 26 cases. In addition, the patients had other tumor and precancerous lesions of the gastrointestinal tract. These data show the validity and practical value of using the OLGA system to identify high-risk groups for the development of tumors not only of the stomach, but also of gastrointestinal tumors of other localizations.

Objective. The work was performed with the purpose to study microbiota state of the gastro-intestinal tract (GIT) of C57Bl/6 mice with signs of metabolic dysbiosis (MD) induced with the use of fructose solution or with poloxamer 407 (P 407), during treatment with combination of sodium polyprenylphosphate (PPP) and beta-sitosterol (BSS). Materials and Methods. MD was induced in mice with drinking 20 per cent water fructose solution. MD was also induced in mice by intraperitoneal use of P 407 at the dose of 500 mg/kg two times per week during ten weeks. The mice of experimental groups received intragastrically combination of PPP and BSS preparations (0,2 ml of the suspension per mouse). Medical scheme consisted in use of preparations five times per week starting after one month from the first day of fructose drinking or of P 407 use and prolonging for one month else. The quantity of viable bacteria in the probes obtained was measured by the direct passage of the material tested on elective or selective nutritional media with following count of colonies grown. Results. The drink of fructose solution or use of P 407 caused the changes of GIT microbiota state that confirmed development of signs of MD in mice. Treatment with PPP and BSS combination was shown to cause actual tendencies to restore the normal GIT microbiota state. Conclusion. Combination of PPP and BSS preparations seemed to be efficient as a novel approach to correction of GIT microbiota state perturbed due to pathogenesis of MD considered as one of the primary signs of metabolic syndrome in mice.

Background. Due to the fact that inflammatory bowel diseases (IBD) are widespread among the population, the development of new drugs for the treatment of IBD is a public health priority. Preclinical drug testing is inextricably linked with the modeling of IBD in laboratory animals. This study purpose was to develop a model of chemically induced colitis in rabbits. Methods. The study was performed on male rabbits of the “Soviet Chinchilla” breed. Colitis was simulated by oral administration of dextran sulfate sodium (DSS) in a concentration of 0.1% to 2% solution for five consecutive days. Euthanasia of laboratory animals was carried out on the seventh day, after the end of taking the DSS solution. A histological examination of the intestine was performed. Results. It was found that using 0.1% DSS solution allows to obtain a model of mild erosive colitis. The use of 0.5% DSS solution gave the intermediate severity of erosive ulcerative colitis. DSS concentration of more than 1% led to the development of severe ulcerative colitis in rabbits and the death rate of 71.4% among them. Conclusion. The obtained results indicate that the use of 0.5% DSS solution makes it possible to create a model of erosive ulcerative colitis in rabbits suitable for studying human IBD.

Purpose. To obtain an image of the pancreas of a laboratory mouse by radiation imaging with different contrast agents. Materials and methods. Contrast-enhanced PET/CT was used to visualize the mouse pancreas. Gold nanoparticles were administered intravenously to C57/Bl6 female mice (22 g) as a contrast agent 48 h before PET/CT scanning. Amylum emulsion with “Ultravist-300” was administered through an oral gavage 1 day, 2 hours and 15 minutes before scanning. Official drug “Ultravist-300” was administered intravenously 10 minutes before scanning.¹⁸F-BPA was injected intravenously immediately before the study, and sequential CT and PET were performed using the MilLabs VECTOR6 trimodal imaging system for small laboratory animals. For image interpretation, reference images of Pirogov’s anatomical preparations of a laboratory mouse and atlases of CT and MRI imaging were used. Results. The pancreas of a laboratory mouse was visualized as a focus of increased¹⁸F-BPA uptake in the abdomen. Using the approach of sequential exclusion of syntopic organs from the analyzed area according to contrast-enhanced CT, it was proved that the observed focus corresponds to the pancreas, and its margins were determined. Conclusion. Using the PET/CT method with various contrast agents, a non-invasive in vivo image of the mouse pancreas was obtained. Its location in the abdominal cavity was precisely characterized, which will allow preclinical studies of new organotropic pharmaceuticals at a higher methodological level.

Introduction. Ulcerative colitis (UC) and Crohn’s disease (CD) belong to the category of inflammatory bowel disease (IBD) and are one of the most pressing problems of gastroenterology worldwide, including due to the development of specific life-threatening complications. Chronic inflammation in the colon in IBD is the cause of the development of one of these complications - colorectal cancer, which requires disabling colectomies and is also one of the leading causes of death among IBD patients. In the Russian population of IBD patients the prevalence of dysplasia and cancer of the colon mucosa has not been previously studied in large epidemiological studies. The aim of the study was to assess the incidence of colorectal cancer in patients with IBD in St. Petersburg. Materials and methods. Within the framework of this publication, the results of three studies were compared: a single-center retrospective cohort study conducted on the basis of the city center of IBD in St. Petersburg (516 patients with IBD who admitted to this medical institution for the period 2020-2023); a multicenter epidemiological study aimed at assessing the clinical features of IBD among the population of St. Petersburg (1072 patients with IBD who admitted to 42 outpatient clinics and 6 city hospitals in 2018-2020); registry study based on the general statistical module of the regional IBD Register of St. Petersburg, operating on the basis of a regional fragment of the unified healthcare state information system (12,858 patients with IBD, data collection period: 2019-2022). Results. As a result of comparing data from three studies, the incidence of IBD-associated colorectal cancer in St. Petersburg was calculated, which was 15.7 cases per 10,000 patients with UC per year and 11.5 cases per 10,000 patients with CD per year. Compared to the population of St. Petersburg as a whole, the likelihood of developing colorectal cancer in patients with UC was 2.9 times higher, in patients with CD - 2.4 times higher. At the same time, in a single-center study, when assessing the prevalence of IBD-associated colorectal cancer, it was found that compared with other life-threatening complications of IBD, it was much less common: toxic dilatation of the intestine occurred 3 times more often, intestinal perforation occurred 20 times more often, decompensated bowel stricture occurred 21 times more often, and severe anemia requiring blood transfusion occurred 36 times more common. Also, as a result of a single-center study, it was found that for 1 case of IBD-associated dysplasia of the colon mucosa, there were 5 cases of sporadic dysplasia. Conclusion. The selection of the most effective therapy and systematic endoscopic examination of patients with IBD will significantly reduce the likelihood of developing colorectal cancer, and systematic observation of the patient with regular endoscopic monitoring of the colon with multifocal biopsy will allow timely detection of dysplasia of the colon mucosa in accordance with current clinical guidelines. It can be assumed that within the framework of cancer prevention measures in the first years of follow-up of a patient with IBD from the onset of the disease, it is advisable to give priority to the risk of developing not only IBD-associated dysplasia, but also sporadic dysplasia of the colon mucosa.

Ultrasound of the intestine is a highly informative, accessible, harmless, mobile, common method of diagnosing inflammatory bowel diseases that does not require special training, has high specificity (95.6%) and sensitivity (89.7%) (depend on the examined area). In recent years, standardized methods have been developed to quantify the results of intestinal ultrasound in inflammatory bowel diseases, the most common of which are the Milan ultrasound criteria for ulcerative colitis, as well as the Sonographic Lesion Index for Crohn’s disease (SLIC), the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS), A simple Ultrasound Activity Score for Crohn’s Disease (SUS-CD) with a satisfactory correlation and an area under the curve. The use of echocontrast drugs (both oral - polyethylene glycol and intravenous - Sonovue) improves the visualization of a number of structures. Purpose: consider the current position of ultrasound for the diagnosis of inflammatory bowel diseases, research technique, specificity and sensitivity of the method, quantitative methods of evaluating indicators, applicability for monitoring the activity of the disease, the presence of complications and the effectiveness of therapy. Materials and methods: in February-June 2023, articles were searched in the databases PubMed, Cyberleninka, Wiley, Oxford University Press, Science Direct with the following keywords: inflammatory bowel disease (IBD), ultrasound, Crohn’s disease, ulcerative colitis, disease activity, ultrasonographic parameters, index, abdominal ultrasonography, sonovue, gastrointestinal Ultrasound (GIUS), Contrast-enhanced ultrasonography (CEUS), epidemiology. Practical guidelines on ultrasound diagnostics, clinical recommendations on Crohn’s disease [regional enteritis] and ulcerative colitis, guidelines of international medical associations, communities, etc. were also used. The search was not limited to years or languages. After reviewing the abstracts of articles or full texts, a decision was made on the suitability of the articles for inclusion in the review. The graphs, diagrams, figures of interest were used as a source for creating own illustrations. Conclusion: ultrasound methods of intestinal examination have a number of advantages, which include high information content, no need for preparation, high availability, prevalence, low cost and harmlessness. Of particular clinical importance is the possibility of evaluation at the patient’s bedside, the use of ultrasound criteria for assessing the activity of IBD and monitoring in dynamics.

The article discusses the high relevance of the problem of inflammatory bowel diseases (IBD). First of all, attention is drawn to the annual increase in the incidence of ulcerative colitis and Crohn’s disease. Factors that can influence the development of IBD are assessed. A diagram of the pathogenetic cascade of dysbiotic disorders is presented, manifested by an increase in the blood serum of metabolic products of the intestinal microflora, microvascular, metabolic and immune changes leading to the triggering of inflammation in the intestinal wall.

Introduction. One of the most prevalent functional disorders of the gastrointestinal system, irritable bowel syndrome (IBS), significantly affects patients’ quality of life. At the moment, only symptomatic drugs are used to treat this disorder. Although using melatonin can be thought of as a form of pathogenetic therapy, its efficacy has not yet been conclusively demonstrated. This systematic review of randomized placebo controlled clinical trials reviews current data on the evaluation of the efficacy of melatonin in patients with IBS. Material and research methods. The search and selection of publications was carried out in the PubMed, ScienceDirect, ClinicalTrials.gov, Cochrane Library, eLibrary, medRxiv and International Clinical Trials Registry Platform databases from their publication until October 30, 2022. Results. The inclusion criteria were met by four randomized placebo-controlled trials, totaling 155 participants, and these trials were included in the subsequent analysis. All investigations revealed a considerable reduction in the frequency and severity of bloating, as well as a tendency for other intestinal symptoms to regress. Two trials reported an improvement in patients’ quality of life, albeit one of the studies did not find these changes to be statistically significant, and the other did not assess them. This review demonstrates that melatonin is effective in treating IBS by lowering the frequency and severity of the condition’s symptoms in the vast majority of published RCTs. The poor number and sample size of clinical trials, along with their inadequate methodological quality, prevent us from drawing any firm conclusions about the contribution of melatonin to the improvement of IBS patients’ quality of life. To confirm melatonin’s significance in the treatment of IBS patients, larger studies are required to assess its efficacy and safety when used in various doses.

The synthesis of antibacterial drugs and their subsequent use in clinical practice contributed to saving a huge number of people’s lives in the global space. At the same time, they can cause significant harm, including Clostridium difficile infections, in the formation of antibiotic resistance and changes in the human microbiome, the consequences of which have yet to be assessed. Antibiotic management programs are becoming more and more commonplace in modern clinical practice, requiring extensive knowledge based on clinical, genomic and laboratory data. Increasing evidence suggests a role for antibiotics in the manifestation of allergic, inflammatory, metabolic, and functional diseases. On the other hand, there is more and more data on the role of antimicrobial drugs in cancer prevention and treatment of viral diseases.

Currently, the problem of diarrheal syndrome against the background of therapy with non-antimicrobial drugs, with a frequency of occurrence of up to 24%, has become particularly relevant. This is due to an increase in the number of people taking drug therapy for a long time, an increase in the population of older people, an increase in comorbidity, polypragmasia and hypersensitivity of this group of patients to medications. The mechanism of drug-induced diarrhea is complex and insufficiently studied. Many drugs are able to affect various pathogenetic links, causing disorders of the intestinal microbiome, motor evacuation dysfunction, layering on existing intestinal diseases with the development of functional disorders, catarrhal and erosive ulcerative lesions, which makes it difficult to diagnose and choose an adequate therapeutic tactic. The situation is often complicated by the impossibility of canceling the therapy of the underlying disease or changing the treatment regimen, which can lead to serious consequences for a patient with diarrhea syndrome. Thus, the issues of early diagnosis, differential diagnosis and approaches to the treatment of drug-induced diarrhea are becoming increasingly important in clinical practice.

The article discusses current ideas about the impact of HIV infection on the gut microbiome, microbial translocation, chronic inflammation, and immune activation. The gut microbiome is involved in systemic inflammation and immune activation, which contributes to the persistence of HIV infection. Although the exact pathogenesis of HIV infection and changes in the intestinal microbiome in the form of a decrease in bacterial diversity is still unclear, normalization of the intestinal microbiome in HIV infection can reduce inflammation, and thereby lead to a decrease in the possible reservoir for HIV infection. The authors of the article presented modern hypotheses about the interaction of the intestinal microbiome with systemic inflammation, as well as the relationship between the intestinal microbiome and the persistence of HIV infection. The inability of modern treatment methods to affect the hidden reservoir and deplete it is the main obstacle to the cure of HIV infection. The ongoing treatment efforts aimed at reducing the reservoirs of HIV infection in order to achieve stable remission and the possibility of a cure for HIV infection are discussed.

Despite certain success achieved in therapy and prevention, cardiovascular diseases (CVD) continue to be the leading cause of death of the population worldwide. One of the main reasons for this is that the pathophysiological mechanisms of the development of atherosclerosis, a disease that underlies most clinical forms of CVD, have not been fully understood yet, and therapy based on well-known concepts of pathogenesis, including lipid, does not provide the desired results. In this regard, search and identification of new molecular targets and therapeutic approaches is an important objective of modern medical science. In this direction, a completely new metabolic pathway identified by researchers, that links lipid consumption, gut microbiota (GM) and development of atherosclerosis, deserves interest. Thus, for the first time it was shown that GM uses food choline, as well as carnitine (found in red meat) for synthesis of trimethylamine (TMA), which, in turn, is rapidly oxidized by liver flavin monooxidases (FMO) to trimethylamine oxide (TMAO), that causes the development of atherosclerosis. Mechanisms of proatherogenic effect of TMAO, which, taken together, involve stimulation of inflow and suppression of outflow of cholesterol from the cell, have also been established. Another pathway of GM influence on the development or progression of atherosclerosis, that links the presence of bacterial infection and the degree of atherosclerosis development, has also been identified. It is believed that in this case, bacterial liposaccharides (LPS) interact with low-density lipoproteins (LDL), as a result of which LDL turn into atherogenic oxidized LDL. The article discusses possible therapeutic strategies for prevention and treatment of coronary atherosclerosis associated with both decreased production of TMAO and elimination of TMA from the intestines, and regulation of microbial metabolism (inhibition of microbial enzymes that produce TMA), as well as change in the structure of GM towards increase in the proportion of microorganisms beneficial to the human body (unable to produce TMA).

Epigenetic mechanisms play a crucial role in the regulation of gene expression. The underlying mechanisms include DNA methylation and covalent modification of histones by methylation, acetylation, phosphorylation, or ubiquitination. The complex interplay of various epigenetic mechanisms is mediated by enzymes operating in the cell nucleus. Modifications in DNA methylation are carried out primarily by DNA methyltransferases (DNMTs) and ten-eleven translocation proteins (TETs), while a variety of enzymes such as histone acetyltransferases (HATs), histone deacetylases (HDACs), histone methyltransferases (HMTs), and histone demethylases (HDMs)) regulate histone covalent modifications. In many pathological conditions such as cancer, autoimmune, microbial inflammatory, metabolic, allergic diseases and/or low vitamin D availability, the epigenetic regulatory system is often disrupted. Vitamin D interacts with the epigenome at several levels. First, critical genes in the vitamin D signaling system that encode for the vitamin D receptor (VDR) and the enzymes 25-hydroxylase (CYP2R1), 1α-hydroxylase (CYP27B1), and 24-hydroxylase (CYP24A1) have large CpG islands in their promoters. areas and therefore can be suppressed by DNA methylation. Second, the VDR protein physically interacts with coactivator and corepressor proteins, which in turn are in contact with chromatin modifiers such as HATs, HDACs, HMTS, and chromatin remodelers. Third, a number of genes encoding chromatin modifiers and remodelers, such as HDM from the Jumonji C (JmjC) domain containing proteins and lysine-specific demethylase (LSD) families, are primary targets for VDR and its ligands. Finally, there is evidence that certain VDR ligands have DNA demethylating effects. In this review, the authors discuss the regulation of the vitamin D system by epigenetic modifications and how vitamin D contributes to the maintenance of the epigenome and assess its impact on health and disease.

Human physical qualities represent a complex trait influenced by environmental and genetic factors, with most traits being polygenic in nature. The study of the relationship between molecular genetic data, physical characteristics and metabolic individuality (regulation of biogenesis, energy balance, lipid metabolism, glucose homeostasis, etc.) is a promising vector of research, both in the population as a whole and in various nosologies, primarily for hereditary and metabolic diseases characterized by impaired physical development and metabolic balance, including cystic fibrosis (CF), obesity, diabetes mellitus. The first studies were devoted to the study of these parameters in athletes. The genotype-phenotype study in CF has been actively studied for the past few years. It has been shown that environmental factors can determine clinical polymorphism in CF, which account for nearly 50% of lung function variability in this disease. However, CF patients with similar molecular genetic variants of the CFTR gene and in a single habitat (for example, in siblings) can have highly variable clinical manifestations. Genes whose products provide cell energy exchange (PPARA, PPARG, PPARD, PGC-1, UCP2, UCP3, ACTN, ACE) can also be “modifiers” and have an effect on the phenotype, the difference in clinical manifestations of the disease of patients with CF, the relationship of which in this category of patients has not been studied. The world has seen a steady increase in obesity and its complications. Patients with CF from the category of persons with nutritional deficiency in recent decades began to move into the category of overweight patients, which requires study. This review summarizes the recent achievements of studying genes whose products provide energy exchange of the cell, discusses the development of the relationship both with the physical characteristics of individuals and with pathological changes in the body as a result of the appearance of metabolic products in excess or with altered physicochemical properties and functional activity parameters leading to various diseases.

There are certain difficulties with diagnosing of poliarteritis nodoza, that is explained by the folllowung factors: non-specificity of the initial symptoms, polymorphism of clinical manifestations, the abcence of specific laboratory markers. Тhe diagnosis is made primarily on the basis of the clinical picture, that becomes apparent during the first three months of illness. The abcence of a detailed clinical picture does not exclude the presense of poliarteritis nodoza. It may be explained by the concomitant pathology, in this case periodic illness (familian mediterranean fever). Due to medical literature data, poliarteritis nodoza is surely associated with periodic illness. The prevalence of poliarteritis nodoza in general population is about 6 on 100 000 people.The prevalence of poliarteritis nodoza among the patients suffering from periodic illness is 1%. The patients when they are diagnosed polyarteritis nodosa in association with periodic illness are younger than the patients when they are diagnosed only polyarteritis nodosa. It turned out to be interesting that the treatment of patients with polyarteritis nodosa in association with periodic illness through glucocorticoid drugs in the combination with colchicines proved to be successful and resulted in remission.

Whipple’s disease is an infectious, systemic and recurrent disease caused by the gram-positive bacterium Tropheryma whipplei. The disease proceeds with a heterogeneous clinical picture, presenting difficulties of timely diagnosis and in the absence of antibacterial therapy can lethal outcome. This review is devoted to the etiology, pathogenesis, epidemiology, clinical picture, modern diagnosis and therapy of Whipple’s disease.

Coronary artery thrombosis in ulcerative colitis is a serious condition and can occur in the young population. The authors report a case of multifocal atherosclerosis complicated by acute myocardial infarction due to atherosclerotic coronary thrombosis in a young woman with ulcerative colitis.

The article presents a clinical observation of Whipple’s disease in a 42-year-old patient with a history of stage IIB Hodgkin’s lymphoma, in whom the disease debuted with articular syndrome, lymphadenopathy of the retroperitoneal and mesenteric lymph nodes, deep vein thrombosis of the leg. The diagnosis was confirmed by a morphological study of biopsy specimens of the duodenal mucosa, mesenteric lymph nodes 12 p. of the intestine, electron microscopic detection of accumulations of rod-shaped bacteria in the intestinal mucosa 6 years after the onset of clinical manifestations. Dynamic observation for 5 years was carried out using video gastroduodenoscopy, morphological assessment of changes in xanthoma macrophages proposed by A. Herbay, the percentage of damage by PAS-positive macrophages to the area of the lamina propria of the duodenal mucosa of the intestine. Conducted therapy with ceftriaxone for 14 days followed by taking co-trimaxosole for 4 years 7 months led to a stable remission.

The course of inflammatory bowel diseases can be complicated by damage to almost all organs and systems, including the eyes, skin, lungs, kidneys, liver, as well as hematopoietic organs and the cardiovascular system. In this case, skin diseases are most often affected, and skin extraintestinal manifestations occur in more than 10% of patients with inflammatory bowel disease. Among the cutaneous extraintestinal manifestations, the second place in prevalence after erythema nodosum is occupied by pyoderma gangrenosum - neutrophilic dermatosis, an idiopathic disease, most often associated with systemic immune-inflammatory conditions, such as rheumatoid arthritis, hemoblastoses or intestinal diseases. Also, this disease is one of the components of such genetically determined syndromes as PAPA, PASH, PAPASH and SAPHO. Difficulties in diagnosing and detecting this condition are due to the lack of a standardized approach to the appointment of these patients, the achievement of the results of randomized trials, and the identification of the reliability of the reliability of drug therapy for pyoderma gangrenosum. This article presents a review of the literature and, as a clinical manifestation, an observation in patients with the onset of inflammatory bowel disease complicated by pyoderma gangrenosum was identified.