An analysis of published data and the results of our own studies showed that activation of peripheral δ₂-opioid receptor (δ₂-OR) increases cardiac tolerance to reperfusion. It has been established that this δ₂-OR is localized in cardiomyocytes. Endogenous opioids are not involved in the regulation of cardiac resistance to reperfusion in non-adapted rats. The infarct-limiting effect of δ₂-OR agonist deltorphin II depends on the activation of following protein kinases: PKCδ, ERK1/2, PI3K, PCG. SarcK_ATP channel and MPT pore are hypothetical end effectors of the cardioprotective effect of deltorphin II.

Myocardial ischemia is the basis for many acute and chronic conditions with great social significance. Therefore, experimental models that describe ischemia development in humans are necessary for a better understanding of the pathophysiology of these conditions and the development of medical and surgical methods of treatment.

Aim: To compare current approaches to experimental modeling of myocardial ischemia considering the pathogenetic features of the simulated processes. The manuscript describes the main experimental models of myocardial ischemia: in vitro cellular models, ex vivo isolated heart models, in vivo animal models, the principal components of the ‘heart-on-chip’ model and the possibilities of in silico modeling. The criteria for choosing a specific model of ischemia by pathophysiological approach, advantages and limitations of the models are considered.

Antibiotic resistance poses a serious threat to public health. The problem of nosocomial infections is inextricably linked with antibiotic resistance. Nosocomial infections in most cases are caused by the formation and spread of hospital strains that are resistant to antibacterial drugs. Nosocomial infections caused by multidrug-resistant microorganisms increase healthcare costs, lengthen hospital stays, and lead to extremely poor patient outcomes. The article systematizes data on the prevalence of nosocomial infections and examines the problem of antibiotic resistance of leading nosocomial pathogens. Approaches to monitoring and management of antibiotic resistance and epidemiological surveillance of nosocomial infections are analyzed. A promising area of research in public health is considered – osocomial infections associated with previous hospitalization.

The intestinal microbiota (IMB) can indirectly affect the course of ostearthritis (OA) at the systemic level by stimulating a chronic nonspecific inflammatory reaction in the synovial membrane and subchondral bone, the cause of which is an increase in the amount of circulating lipopolysaccharides (LPS) of the bacterial wall, as well as provoke the development of metabolic syndrome, which links the two necessary components of the pathogenesis of OA. The result of direct exposure is the formation of leaky gut syndrome with the activation of LPS of the bacterial wall of mild inflammation, provoking the production of proinflammatory cytokines, the effect of which on synoviocytes and chondrocytes leads to their activation with subsequent production of IL-6 and IL-8, which contributes to the persistence of inflammation. By correlation analysis, the relationship of three taxa with OA joint damage was proved, namely, the order Desulfovibrionales and the genus Ruminiclostridium 5 – with knee joint OA, Methanobacteriaceae – with knee joint OA, and OA of any localization, and the appearance and degree of contamination with the genus Streptococcus correlated with the severity of pain syndrome. The metabolic syndrome itself can provoke the development of dysbiosis, so it can also be its consequence. A change in the composition of the microbiota in the form of the predominance of the genus Clostridium and the species Staphylococcus aureus with a decrease in the diversity of microorganisms is associated with an increase in the amount of adipose tissue in the body, dyslipidemia, insulin resistance with impaired carbohydrate metabolism. Low levels of LPS in the blood are found in obese patients even in the absence of an obvious focus of infection due to violations in the CMB, they signal TLR-4, triggering systemic inflammation. Studies have shown a positive effect of prescribing proand prebiotics on the course of OA, which makes IMB a promising target for the treatment and prevention of OA.

Introduction. More and more studies demonstrate the importance of determining the beta-adrenergic reactivity of erythrocyte membranes (beta-ARM) for predicting the severity of cardiovascular diseases, including chronic heart failure. But the presence of general patterns between the change in beta-ARM and the expression of beta1adrenergic receptors on the membranes of cardiomyocytes, depending on the left ventricular ejection fraction (LVEF) remains questionable.

Aim: To evaluate beta-ARM and expression of beta1-adrenergic receptors of cardiomyocytes in groups of patients with heart failure with preserved (≥ 50%) and reduced (< 50%) LV EF.

Materials and methods. The study included 100 patients with chronic heart failure of ischemic origin. Groups of 79 patients with LVEF ≥ 50% and 21 patients with LVEF < 50% were formed. The levels of epinephrine and norepinephrine in blood plasma and the expression of beta1-adrenergic receptors in myocardial samples were assessed using enzyme immunoassay. Beta-ARM was determined in whole blood by assessing the inhibition of hemolysis of erythrocytes placed in a hypoosmotic medium in the presence of a selective beta-blocker.

Results. In the group with LV EF < 50%, beta-ARM was increased (p = 0.037), amounting to 31.9% (23.2; 40.1), compared with the group with LVEF ≥ 50%, where beta-ARM was 21.4% (15.0; 31.7). At the same time, in patients with LV EF < 50%, the expression of beta1-AR on cardiomyocyte membranes was significantly lower than in the other group (p = 0.037): 2.7 (2.1; 3.0) ng/mg and 3.1 (2.4; 3.9) ng/mg total protein, respectively. However, plasma levels of epinephrine and noradrenaline were comparable in the study groups.

Conclusion. Patients with heart failure with LVEF < 50% were characterized by increased beta-ARM and reduced expression of beta1-AR on cardiomyocyte membranes compared with the group with LVEF ≥ 50% with comparable levels of circulating catecholamines.

During the first year after myocardial infarction, coronary artery restenosis, fatal arrhythmias, hospitalization for heart failure or cardiac death may occur. It is necessary to search for biomarkers to predict complications of myocardial infarction. As such predictors, it seems promising to introduce the ABCDE-SE echocardiographic protocol, as well as study the metabolism of vitamin D and proteins of the fibrinolysis system. Cardiospecific microRNAs-21, -29, -143 can be used as pathogenetic factors in the development of complications; it is proposed to study the ongoing pharmacotherapy and patients’ compliance with it as controllable factors.

Aim: To search for predictors of complications of myocardial infarction based on the assessment of echocardiographic parameters, vitamin D metabolism, components of the fibrinolysis system and cardiac-specific microRNAs.

Material and Methods. The PROMETHEUS study is designed as a prospective, open-label, non-randomized cohort study. It is planned to include 300 patients newly admitted to the vascular center with a preliminary diagnosis of ST-segment elevation ACS. All patients will have their vitamin D concentrations determined; genetic variants of polymorphisms of the vitamin D receptor gene and vitamin D binding protein; concentrations of urokinase and soluble urokinase receptor; microRNA-21, -29, -143, as well as echocardiography using the ABCDE-SE protocol at 1, 3, 6 and 12 months from inclusion. Pharmacotherapy will be assessed at all stages.

Expected results: Based on the results of the study, a comprehensive algorithm for optimizing the prediction and prevention of complications of myocardial infarction will be developed and introduced into practical healthcare.

Introduction. The prevalence of iron deficiency (ID) among patients with chronic heart failure (CHF) ranges from 50% to 80%. It has been established that ID is a significant predictor of adverse outcomes and mortality in CHF, and is also associated with a decrease in exercise tolerance. The use of oral iron preparations for the purpose of its correction is limited by the high frequency of adverse events and, in some cases, their ineffectiveness in CHF. Ferric carboxymaltose has a high potential in the correction of ID, which has proven itself well in the cohort of patients with CHF, but its effectiveness has not been precisely established in CHF.

Aim: To evaluate the effect of ferric carboxymaltose therapy on the quality of life, functional status, and clinical picture of CHF in patients with diagnosed iron deficiency.

Material and Methods. It is a prospective randomized cohort study. It is planned to include 70 adult patients with CHF (NYHA II-III) and diagnosed ID: group 1 (n = 35) – group of drug therapy with ferric carboxymaltose, group 2 (n = 35) – without drug therapy. A control group of patients without ID (n = 30) will also be recruited. The prospective part involves the observation of patients with repeated visits after 6, 12 months, during which the indicators of quality of life, functional status, clinical picture of CHF, structural and functional echocardiographic indicators of LV and right heart, as well as the presence of repeated hospitalizations for CHF and death from all causes will be evaluated.

The comorbidity of manifestations of psychological distress and cardiovascular diseases is complex. The degree of impact of psychological stress on the patient depends on the possibilities of the adaptive potential of the individual in the environment.

Aim: To study the cognitive assessment of stress, coping strategies and clinical and psychological associations in personality type D and depression in patients with coronary artery disease (CAD).

Material and Methods. The study included 112 CAD patients. The DS-14 questionnaire was used to determine personality type D.To determine the level of depression the hospital scale HADS (Hospital Anxiety and Depression Scale). To assess coping strategies, the questionnaires “Methods of Coping Behavior” and “Indicator of Stress Coping Strategies” were used. Difficult life situation (DLS) assessment was determined using the “Cognitive Assessment of DLS” methodology. The questionnaire “Types of Orientations in Difficult Situations” was used to study orientations in DLS.

Results. Patients were divided into groups based on manifestations of psychological distress: with type D (n = 40), without type D (n = 72); with depression (n = 48) without depression (n = 82). In type D, there was a more frequent assessment of the situation as out of control (12.0 ± 4.6 points versus 11.0 ± 4.6 points, p = 0.049) and orientation towards losses in difficult situations (17.0 ± 4.1 points 15.5 ± 5.1, points, p = 0.016). In depression, less pronounced desire for difficulties (19.0 ± 5.0 points versus 23.0 ± 5.9 points, p = 0.006), orientation towards opportunities (15.5 ± 3.2 points versus 18.0 ± 3.5 points, p < 0.001). In type D, the strategies “Escape-avoidance” (p = 0.05) and “Self-control” (p = 0.04) were used more often. In depression, the strategies “Problem resolution” (p = 0.02), “Search for social support” (p < 0.001) and “Avoidance” (p = 0.02) were more often used, less often – “Confrontational coping” (p = 0.001).

Conclusion. Differences in cognitive assessment and coping strategies were revealed in patients with coronary artery disease in personality type D and the development of depression symptoms. This study emphasizes the need for individualized behavioral interventions for patients with coronary artery disease with manifestations of psychological distress.

Aim: To analyze the features of clinical signs, quality of life and psycho-emotional state in patients with heart failure with preserved left ventricular ejection fraction (HFpEF) and non-obstructive atherosclerosis of the coronary arteries, depending on the presence of echocardiographic criteria for dysfunction of the right heart.

Material and Methods. Patients underwent an extended protocol of echocardiography with an assessment of the structure and function of the right heart; ultrasound examination of the lungs with the determination of the number of B-lines; a six-minute walk test, a test for the presence of a symptom of bendopnea with the determination of blood oxygen saturation (SpO₂) before and during the test. In addition, quality of life was assessed using the Minnesota questionnaire and the SF-36 questionnaire (The Short Form-36); the psycho-emotional state of patients was analyzed according to the HADS (Hospital Anxiety and Depression Scale), the level of adherence to treatment was analyzed according to the Morisky – Green questionnaire. Patients were divided into two groups depending on signs of right heart dysfunction: Tei index more than 0.54, tricuspid annulus systolic excursion (TAPSE) less than 17 mm, tricuspid annulus systolic velocity (RV S’) less than 9,5 cm/sec.

Results. Echocardiographic signs of right heart dysfunction in patients with HFpEF was associated with lower quality of life indicators according to the SF-36 questionnaire, in particular, general health status (p = 0.008) and role limitations due to emotional problems (p = 0.03). During the bendopnea test (p = 0.04), the majority of patients with signs of dysfunction of the right heart (66.7%) had a decrease in SpO₂, while in the comparison group the proportion of such patients was 36.7% (p = 0.04). The psycho-emotional state according to the HADS scale and adherence to treatment did not differ in both groups (p > 0.05). The frequency of detection of B-lines according to lung ultrasound was also comparable.

Introduction. Psychological stress and autonomic dysfunction are recognized as risk factors for cardiovascular diseases, but they affect cardiovascular risk differently in men and women.

Aim: To study gender differences in factors influencing the probability of detecting arterial hypertension (AH) from the perspective of the role of stress, autonomic dysfunction and nonspecific inflammation in rotational shift workers in the Arctic region.

Material and Methods. In the medical unit of the gas production company “Gazprom dobycha Yamburg” (polar settlement of Yamburg, 68°21’40”N) we simultaneously examined 99 men and 81 women with AH 1,2 degree of AH and normotensive persons comparable in age (p = 0.450), work experience in the Arctic (p = 0.956), number of years of rotational shift work (p = 0.824), level of office systolic (SBP) (p = 0.251) and diastolic blood pressure (DBP) (p = 0.579). Questionnaires were used to determine the level of general stress (PSM25 scale), occupational stress (Vaisman questionnaire); assessment of autonomic nervous system (ANS) function (Wayne A.M. questionnaire); 24-hour blood pressure monitoring was performed; biochemical blood test for biomarkers of inflammation, cortisol, brain natriuretic peptide precursor, homocysteine, folliclestimulating hormone was carrued out.

Results. Vegetative manifestations (asthenization, increased fatigue, meteorological dependence, headaches) were significantly more often observed in women. Among men with AH, individuals with high levels of neuropsychological tension predominated, every fifth M had a high level of occupational stress. The median scores on the Wayne A.M. questionnaire were significantly higher in women, regardless of BP, and moderate ANS disorders were significantly more prevalent. According to logistic regression data, a significant effect on the probability of AH in men was the number of stress scores (OR = 1.050; 1.029–1.171, p = 0.001), indicators of nocturnal DBP variability (OR = 1.295; 1.109–1.511, p = 0.001) and nonspecific inflammation: rise in high-sensitivity C-reactive protein (hs-CRP) increased the probability of AH by 1.5 times (OR = 1.532; 1.212–1.937, p = 0.001), IL-1β – by 7 times (OR = 7.275; 3.235–16.361, p = 0.001). The probability of AH in women increased by the values of the daily variability of SBP (OR = 1.154; 1.019–1.306, p = 0.024), hs-CRP by 1.5 times (OR = 1.479; 1.226–1.783, p = 0.001), tumor necrosis factor-alpha (TNF-α) (OR = 1.111; 1.001–1.244, p = 0.044), level of IL-6 increased the probability of AH by 1.7 times (OR = 1.676; 1.149–2.958, p = 0.035), the number of scores on ANS questionnaire had a significant effect (OR = 1.055; 1.006–1.107, p = 0.026).

Conclusion. In the conditions of the rotational shift work in the Arctic, gender differences were revealed in the stress perception and the severity of ANS dysfunction with a clear relationship between stress, inflammation and AH in men. ANS dysfunction in women was a trigger of nonspecific inflammation and AH. The identified gender differences will help to reveal vulnerable groups among men and women and develop targeted interventions for individuals in the Arctic region.

Aim: To develop an algorithm for personalizing the diet therapy of patients with obesity and atrial fibrillation (AF) based on the assessment of the metabolic status.

Material and Methods. The study included 100 patients with grade III obesity and paroxysmal AF. All subjects had nonvalvular AF. Anthropometric parameters, actual nutrition, bioimedance analysis of body composition, basal metabolic rate (BMR) were assessed.

Results. Changes in basal metabolism by gender were identified. In women – a decrease in the rate of carboydrate oxidation (CHO) (by 27 ± 12.2%, p < 0.05), an increase in fat oxidation (by 48,58 ± 14.6%, p < 0.01). In men – a decrease in BMR (by 26,23 ± 13.6%, p < 0.05), CHO (by 57,18 ± 18.1%, p < 0.01) and protein (by 28,06 ± 12.9%, p < 0.05), increased rate of fat oxidation (by 31,42 ± 10.0%, p <0.05). A hyperphagic pattern of actual nutrition has been established: excess daily energy intensity (by 16–44%), excess of daily intake of proteins (by 34–54%), fats (by 17% in women) and carbohydrates (by 57–72%, p < 0.05). An excessive amount of saturated fat, cholesterol, and added sugar was revealed in the diet. A deficiency in vitamin D intake was found (by 8–16%, p < 0.05). The maximum daily energy requirement for 95% of women is within 2250 kcal/day, for men – 2950 kcal/day.

Conclusion. Metabolic status disorders serve as factors of hemodynamic overload, humoral and electrical dysfunction of the heart. Diet therapy is a powerful component in the treatment and prevention of AF. It is advisable to carry out an algorithm for individual correction of the chemical composition and energy value of diet therapy taking into account the optimal metabolic corridor of needs, enriching the diet with vitamin D, eliminating added sugar, cholesterol, sodium, phosphorus, and sources of vitamin K.

The search for a method of perioperative pain control after coronary bypass surgery is relevant both from the point of view of safety and effectiveness of the methods used.

Aim: To evaluate the hemodynamic changes and effectiveness of erector spinae plane block (ESPB) for off-pump coronary artery bypass surgery.

Methodology and research methods. The prospective randomized single-center study included 45 patients equally distributed according to the applied methods of perioperative analgesia into 3 groups: general anesthesia with epidural anesthesia (GA + EA group, n = 15), general anesthesia with ESPB (GA + ESPB group, n = 15) and general anesthesia without any regional anesthesia techniques (GA group, n = 15). Assessment of hemodynamics and severity of pain syndrome was performed during the first postoperative day.

Results. The intraoperative dose of fentanyl was 0.4 (0.4–0.5) mg in the GA + EA group, and 0.4 (0.3–0.4) mg in the GA + ESPB group that is significantly less than in the GA group – 1.1 (1.0–1.1) mg (p < 0.001). Postoperatively, the dose of fentanyl was 0.10±0.04 mg in the GA + EA group and 0.23±0.05 mg in the GA group (p < 0.001), whereas in the ESPB group fentanyl was not used. The pain level assessed by the numeric rating scale (NRS) was 3.0 (2.0–4.0) points at one hour after tracheal extubation and 3.0 (0.5–3.5) points at the end of the first day of the postoperative period without difference between the groups. The systemic and pulmonary hemodynamics, respiratory and vasopressor support did not differ as well.

Conclusion. The use of regional anesthesia (EA and ESPB) provides similar quality of perioperative analgesia like general anesthesia, but leads to reduction in opioid doses. Postoperatively, the use of ESPB does not lead to a deterioration of the hemodynamic status of the patient.

Relevance. Among the studies during the COVID-19 pandemic, a special role is played by studies examining the prognostic value of clinical, laboratory and instrumental markers in patients. Biomarkers with absolute sensitivity and specificity for predicting the outcome of a new coronavirus infection have not been identified yet.

Aim: To identify early clinical and laboratory predictors of severity and mortality in hospitalized patients with COVID-19 and to evaluate the effectiveness of the pharmacotherapy in outpatient and early hospital settings.

Methodology and research methods. A retrospective, comparative study was carried out. Medical data from 745 adult patients with COVID-19, hospitalized in the respiratory hospital of the Siberian State Medical University (Tomsk) from 05/16/2020 to 09/30/2020 were included. The main group consists of patients who were discharged from the hospital. The comparison group included patients with a fatal outcome of the disease.

Results. The group of deceased patients was characterized by older age and a greater number of comorbid diseases (р < 0.0001), the presence of pneumonia during the year preceding COVID-19 (р < 0.0001) and risk factors for the development of Pseudomonas aeruginosa infection (р < 0.005). Early admission to the hospital (р = 0.0110), severe dyspnea (р < 0.0001) with a decrease in oxygen saturation below reference values (р < 0.0001) are also associated with the risk of a fatal outcome. Anosmia was significantly more common in the group of surviving patients.

The number of platelets, the absolute number of lymphocytes, amounts of total protein, albumin (р < 0.0001), sodium (р = 0.0013) in the first 48 hours of hospitalization in the main group were significantly higher. The number of leukocytes (p = 0.0078), neutrophils (p < 0.0001), neutrophil-lymphocyte ratio (p < 0.0001), concentrations of glucose, aspartate aminotransferase, urea, creatinine, C-reactive protein and lactate dehydrogenase were significantly lower in the main group. Serum procalcitonin levels > 0.5 ng/ml were 5 times higher in deceased patients during early period of hospitalization.

Conclusion. Clinical, anamnestic and laboratory factors were identified through this study. These factors may be useful in the early period of hospitalization for accurate assessment of risks of severe ill, effective disease management and reduction of mortality in hospitalized patients with COVID-19.

The general context of the study is to review the characteristics of the course of chronic heart failure (CHF) in persons infected with the human immunodeficiency virus (HIV) as a part of a single-stage screening clinical trial.

Aim: To determine the features of the CHF course in HIV-infected patients, depending on the presence of thrombocytopenia (TP).

Material and Methods. In a multidisciplinary hospital, 240 patients with HIV infection were examined for four years, where a cohort of patients with CHF (160 people) was identified, further divided into groups of patients with TP (107 people) and without TP (53 people). Patients underwent the same amount of research, including echocardiography, non-invasive arteriography, and a detailed laboratory examination.

Results. TP in patients with CHF and HIV infection is more common in smokers and people with alcohol dependence and is associated with hemodynamic disorders in the form of higher systolic and diastolic blood pressure, left atrium increase. With TP, the values of NT-proBNP in blood plasma are higher, and in the blood serum – tissue inhibitor of metalloproteinases-1, urea, bilirubin, while the concentration of sodium and potassium ions in the blood serum is lower. Anemia and leukopenia were more common in the group of patients with thrombocytopenia. Patients with TP are more adherent to taking protease inhibitors and non-steroidal anti-inflammatory drugs.

Conclusion. The frequency of CHF detection in patients with HIV infection against the background of TP is almost 2 times higher and is more often accompanied by dilatation of the left atrium, higher blood pressure, an increase in TIMP-1 and a decrease in the concentration of potassium ions in the blood serum. The concentration of NT-proBNP in blood plasma has a close inverse correlation with the number of platelets in patients with CHF and TP, and the presence of severe TP ≤ 30 × 109 cells/l increases the chances of developing CHF with low left ventricular ejection fraction by 10.8 times. Smoking, possible alcohol dependence and adherence to taking protease inhibitors and NSAIDs are significant factors associated with the development of thrombocytopenia in HIV-infected patients with CHF.

Aim: To study the content of tryptophan and the intermediate metabolites of kynurenine and serotonin pathways of its metabolism in the blood plasma of patients with type 2 diabetes mellitus (DM) and non-proliferative diabetic retinopathy as candidates for markers of the early stage of the pathological process.

Material and Methods. Three groups of people were analyzed: the first group of 10 patients with type 2 diabetes mellitus and without diabetic retinopathy; the second group of 10 people with type 2 diabetes mellitus and non-proliferative stage of diabetic retinopathy; and the control group of 10 healthy people. The features of the first group were a decrease of macula’s photosensitivity in the fundus and a slight increase in the central thickness of the retina. Patients with diabetic retinopathy tended to have a moderate number of microaneurysms and microhemorrhages, moderately presented intraretinal microvascular anomalies in one quadrant, vein dilatation, clearness of the central retinal vein and its branches. In the macular zone there was an edema with hard exudates in the center and lateral to the fovea centralis. All participants of the study gave blood on an empty stomach in the morning, and after that in we measured the content of tryptophan (TRP), kynurenins ((kynurenine (KYN), 3-hydroxykynurenine (3-HKYN), kynurenic acid (KYNA)) and the level of L-5-hydroxytyrptophan (5HTrp) in blood plasma by HPLC method with fluorimetric and spectrophotometric detection.

Results. The groups of people with type 2 diabetes mellitus showed the increasing of TRP level in blood relatively to healthy individuals: by 15.1% (p = 0.032) and 17.9% (p = 0.030) in the first and second groups, respectively. As for the patients of the first group, the content of their KYN was increased by 57.7% (p = 0.012) and KYNA by 33.6% (p = 0.012) relatively to the control and the concentration of 3-НKYN decreased by 18.1% (p = 0.020) relatively to healthy people. As for the patients in the second group, the changes in their level of kynurenines had the same direction, but were more visible. Thus, the concentration of KYN exceeded the same parameters of healthy individuals by 84.5% (p = 0.001) and the parameters of the first group by 18.0% (p = 0.049); the KYNA level increased by 56.6% (p = 0.001) relatively to the control and by 17.3% (p = 0.049) from that of the first group. There was a decrease in the content of 3-HKYN amounted to 18.6% of the control (p = 0.038) and an increase in the concentration of 5HTrp – 193,9% (p < 0.001).

Diabetic retinopathy is a complication of type 1 diabetes mellitus with high social significance, especially in childhood and adolescence.

Aim: To evaluate ultrasound indicators of retrobulbar blood flow at different durations of type 1 diabetes mellitus in childhood and adolescence.

Material and Methods. Ultrasound examinations were performed in 70 patients with type 1 diabetes mellitus aged from 5 to 18 years, with disease duration of up to 5 years, from 5 to 10 years, and more than 10 years. The analysis included an assessment of the linear velocity of blood flow and the index of peripheral resistance in the ophthalmic arteries, central arteries and retinal veins, posterior short ciliary arteries, and ophthalmic veins at different times of the duration of type 1 diabetes mellitus.

Results. The study revealed a decrease in blood flow velocity in the central retinal arteries, in the posterior short ciliary arteries with an increase in the duration of type1 diabetes mellitus. The greatest decrease in blood flow velocity was recorded in the group with duration of diabetes mellitus of more than 10 years.

Conclusion. The obtained data on a decrease in blood flow velocity in the retrobulbar arteries can be used for the assessment and dynamic monitoring of early disorders of the blood supply to the eye and orbit in patients with type 1 diabetes mellitus in childhood and adolescence.

Introduction. Peptic ulcer of the stomach and duodenum is a chronic recurrent multifactorial disease, the ethiopathogenesis of which is significantly contributed by hereditary predisposition. With this disease, a chronic inflammatory process develops, in which cell adhesion molecules take part. The incidence of peptic ulcer disease (PUD) depends on gender: men get sick 2-7 times more often than women. There are few works on the analysis of gender-specific features of associations of polymorphic loci of candidate genes of YB, therefore, further study of this issue is necessary.

Aim: To study the role of two groups of candidate genes of PUD specially selected for the study of 9 polymorphic loci (SNPs): the first – GWAS-significant for peptic ulcer disease (rs2294008 PSCA, rs505922 ABO), the second - genes of cell adhesion molecules pathogenetically significant for the development of PUD (rs6136 SELP; rs8176720, rs2519093, rs507666 ABO; rs651007, rs579459, rs649129 ABO/RF00019), - in the formation of peptic ulcer disease in men and women of the Central Chernozem region of Russia. The sample consisted of 305 men (188 patients, 117 controls) and 441 women (211 patients, 230 controls).

Methods. The regulatory potential of SNPs was assessed using Internet resources (HaploReg v4.1, PolyPhen-2, GTEx Portal), the analysis of associations was carried out by the method of logistic regression in the framework of allelic, additive, dominant and recessive genetic models.

Results. The allele T rs2294008 of the PSCA gene in the group of men is a protective factor in the development of peptic ulcer disease (OR = 0.39-0.64). This pattern was not revealed in women. The rs2294008 polymorphism of the PSCA gene is located in the regions of histone proteins marking promoters and enhancers in the gastric and esophageal mucosa, in the area of hypersensitivity to DNAse in the stomach, binding sites with the POL2 regulatory protein and the CTCF regulatory motif; it affects the expression of 10 genes, including 4 (LY6K, LYNX1, PSCA, THEM6) in the target organ (stomach), alternative splicing of 3 genes, including 2 genes (JRK, LYNX1) in the tissues of the stomach and esophagus.

Conclusions. The T allele of rs2294008 of the PSCA gene in the group of men is a protective factor in the development of ulcer disease. Polymorphism rs2294008 of the PSCA gene affects the expression of ten genes in the target organ (stomach), alternative splicing of three genes, including two genes in the stomach and esophagus tissues.

Breast cancer (BC) is the most common hormone-dependent genetically determined cancer among women. The level of “active” sex hormones in the body, the connection of which with breast cancer is beyond doubt, is determined by the content of the protein transporting sex hormones (SHBG).

Aim: To study associations of polymorphic loci linked with the level of SHBG at the full-genomic level of significance with the risk of developing breast cancer.

Material and Methods. The work was carried out on a sample of 1,498 women, 358 of whom were BC patients, the control was 1140 individuals. Genotyping of four single nucleotide polymorphic loci (SNP) associated with the level of SHBG was performed according to previously performed genome-wide studies (GWAS): rs7910927 JMJD1C, rs4149056 SLCO1B1, rs8023580 NR2F2-AS1, rs12150660 SHBG. The method of logistic regression was used to search for associations.

Results and Discussion. SNP rs8023580 of the NR2F2-AS1 gene is associated with the risk of BC developing. The presence of the CC genotype rs8023580 NR2F2-AS1in a woman has a protective value in the formation of the disease (CCvsTC+TT [recessive model]; OR = 0.58; 95%CI = 0.35–0.96; p = 0.033; p_perm = 0.042). SNP rs8023580 NR2F2-AS1 is functionally significant in the liver: it is localized in the enhancer region, affects the level of methylation of the cg01739960 (hg38) genome region, affects the expression of the RP11-327J17.2 gene, determines the interaction of DNA with six transcription factors (Fo xd1,Foxl1,Foxq1,Mef2,PLZF,STAT), which are located in the cis-regulatory region of RNA polymerase II, specific for the DNA binding sequence, and determine the activity of DNA-binding transcription factors specific for RNA polymerase II, are involved in the processes of cellular differentiation and tissue development.

Conclusion. The SHBG-enhancing CC genotype rs8023580 of the NR2F2-AS1 gene is a protective factor in the development of BC.

Introduction. Acute kidney injury is a common complication of cardiac surgery with cardiopulmonary bypass. Ischemic-reperfusion injury, systemic inflammation, oxidative stress, and other factors that occur during cardiopulmonary bypass lead to disruption of energy supply and death of kidney tissue cells. Delivery of nitric oxide is a promising method of nephroprotection during cardiosurgical operations with cardiopulmonary bypass.

Aim: To study the parameters of energy supply of the renal tissue during cardiopulmonary bypass with nitric oxide delivery in the experiment.

Material and Methods. A prospective controlled experimental study was performed on 12 rams. Animals were included in 2 equal groups at a ratio of 1:1. In the main group, nitric oxide was delivered at a dose of 80 ppm immediately after tracheal intubation and within 90 minutes of cardiopulmonary bypass (main group, n = 6). In the control group, mechanical ventilation and cardiopulmonary bypass were performed according to standard protocols (control group, n = 6). Biopsy specimens of kidney tissue were taken 1 hour after weaning from cardiopulmonary bypass. Energy supply was assessed (according to the tissue concentration of adenosine triphosphate (ATP) and lactate).

Results. Delivery of nitric oxide was not accompanied by tissue perfusion aberration during cardiopulmonary bypass (CPB). The level of free hemoglobin in both groups was statistically significantly higher 1 hour after cardiopulmonary bypass compared with the stages of intubation – p < 0.000... and the beginning of CPB – p < 0.000... The ATP value significantly differed between groups and amounted in the control group 3.7 ± 0.62 nmol/g; in the main group 6.8 ± 1.11 nmol/g, р = 0.00011. The lactate concentration did not differ statistically significantly between the groups and amounted to: in the control group 12.9 ± 3.71 nmol/g; in the main group 10.2 ± 2.14 nmol/g, р = 0.1502.

Conclusion: Delivery of nitric oxide improved the parameters of energy supply of the renal tissue during cardiopulmonary bypass in the experiment.

Background. Using numerical modeling to study biomechanics of implantable devices for cardiovascular healthcare can help specialists understand underlying mechanisms of clinical complications caused by these devices.

Aim: To describe the results of numerical modeling of aneurysm formation in vascular grafts based on the simulation of degradation of their mechanical properties.

Material and Methods. The simulation was carried out using a three-dimensional computer model obtained by high-resolution computed tomography of the vascular graft “KemAngioProtez” (CJSC “NeoKor”, Russia). Using the 3D model obtained with a specialized script in the Abaqus/CAE environment (Dassault systems, USA), we have simulated the decrease in the elastic modulus (from 100 to 10%) with post-threshold stresses in the material and the accumulation of plastic strain.

Results. Undergoing 150 loading cycles, the vascular wall in the model swelled up to 0.7 mm in the radial direction, and its mechanical properties degraded significantly (by 90% compared to baseline) due to prolonged pressure exposure. The value of maximum plastic deformation was 0.55%.

Conclusion. Numerical modeling of graft mechanical properties degradation can assist in qualitative and quantitative assessment of the areas of aneurysm formation. The method makes it possible to visualize the swelling areas and can be used as a valuable tool to complement the existing approaches to studying vascular grafts, and biografts in particular.

Regular exercise improves cognitive function, reduces the risk of premature death from cardiovascular disease, stroke, diabetes and improves quality of life.

Aim: To study the morphological parameters of cardiomyocytes of the left ventricle of the heart and the proliferative activity of rat cardiomyocytes during physical activity of different intensity.

Methodology and Research Methods. Outbred male rats (n = 30) were taken as experimental animals and divided into three series. The first series of rats were given light physical activity – the animals swam in the bath for 15 minutes. The animals of the second series were in the bath for 30 minutes (moderate severity), the third series were in the bath until they began to lose strength and sink (in 55–59 minutes). Animals were taken out of the experiment after 10 sessions of water loading. Some rats (5 animals per series) were slaughtered 30 days after the end of the experiment. After extraction, the heart was stained with hematoxylin and eosin, the amount of DNA in the nuclei of cardiomyocytes was determined, binuclear and Ki-67 positive cells were counted, and the diameter of cardiomyocytes was measured. Statistical analysis was carried out in the program “Statistica 10.0”.

Results. Histological examination revealed changes only in the myocardium of the left ventricle of rats of the third series: pronounced dystrophic changes in cardiomyocytes. There were cells with necrobiosis, focal necrosis of groups of cardiomyocytes. The highest level of cardiomyocyte polyploidy occurred in the second and third series (the ratio of diploid and tetraploid cardiomyocytes in the control corresponded to 91.6 ± 7.4%; 8.2±6.3%). In these series, there was also a change in the number of binuclear cells (in the control – 12.7 ± 1.9‰). In all series of Ki-67 positive nuclei were not detected.

Conclusion. Severe physical activity leads to structural disorders of the myocardium, persistent hypertrophy of cardiomyocytes and is accompanied by a decrease in the proliferative activity of cardiomyocytes.

Introduction. Porous TiNi alloys are widely used in medicine as osteoreplacement implants due to their unique properties of superelasticity and biocompatibility, but their clinical use is severely limited by time-consuming manual fabrication and the inability to create precise geometries. Reconstructive surgery for the replacement of bone defects requires biocompatible endoprostheses of individual shape and complex geometry. The use of porous 3D-TiNi implants can be a solution to many problems in traumatology and bone oncology.

Aim: To evaluate the possibility of using porous 3D-TiNi implants in osteoplastic surgery based on a study of the structure and biocompatibility of the material under in vivo conditions.

Material and Methods. Porous samples in the form of cones and a single implant for maxillofacial surgery were prepared from TiNi powder by selective laser melting. To print an individual implant for maxillofacial surgery, the personal data of the patient at the Oncology Research Institute were used. The macrostructure, elemental and phase composition of porous titanium nickelide samples were investigated using scanning microscopy and X-ray diffraction analysis. The biocompatibility of porous cone-shaped samples was evaluated in vivo using guinea pigs whose condition was analysed by CT scanning.

Results. Structural studies of porous titanium nickelide samples showed that selective laser melting can be used to obtain a continuous porous structure with strong contact bridges between particles of a three-phase powder. In vivo testing of the cone-shaped implants showed no local inflammatory changes, rejection or deformation of the hind limb axes of the experimental animals. The basic feasibility of fabricating a custom implant of complex geometry from TiNi powder using selective laser melting according to a patient’s MSCT data was demonstrated.

Conclusions. Porous 3D-TiNi implants obtained by selective laser melting showed high biocompatibility under in vivo conditions. An experimental study confirmed the efficacy and ease of use of 3D TiNi implants, their excellent self-fixation in bone tissue, and bone tissue augmentation at the interface with the implant. The macrostructure, chemical and phase composition of the implant material was found to be close to traditional porous TiNi alloys. It was shown that the method of selective laser melting makes it possible to create complex geometric defects in bone tissue from TiNi.

A clinical case of a patient with recurrent pulmonary embolism (PE) and non-ST elevation acute myocardial infarction (NSTEMI) is presented. Underestimation of the history data, the clinical course of non-massive pulmonary embolism under the mask of syncope, eventually led to the development of massive pulmonary embolism and clinical death of the patient. The article discusses non-massive PE masks, principles of treatment and secondary prevention of venous thromboembolic complications in a patient with acute NSTEMI.

Aim: To study the annual outcomes of patients with a confirmed diagnosis of myocardial infarction (MI), depending on its type.

Material and Methods. Of the 1,325 hospitalized patients, 1,293 (97.5%) were diagnosed with acute coronary syndrome; the rest had extra-cardiac causes of chest pain. Follow-up included examinations of patients in the hospital and interviewing by phone or email in 12 months after discharge. All patients with MI were tested for the presence of personality type D. After 12 months of follow-up, the total number of patients diagnosed with MI was 255 (92.1%) patients [180 (70.5%) patients with MI1, 75 (29.5%) patients with MI2].

Results. After 12 months of follow-up, in the general group of patients complications developed in 53 (20.7%) patients (27 (15.0%) patients in the IM1 group and 26 (34.6%) patients in the IM2 group). Overall mortality and the frequency of repeat- ed hospitalizations for heart failure were higher in MI2 compared to MI1 [8 (10.6%) vs. 2 (1.1%) (p = 0.001) and 9 (12.0%) vs. 8 (4.4%) (p = 0.03), respectively]. The main predictors of adverse events in patients with MI2 were: obesity, p = 0.005; diabetes mellitus, p = 0.006; two-vessel lesion, p = 0.001; three-vessel lesion, р = 0.001; low adherence to drug therapy (< 6 points) on the Morisky-Green scale, p = 0.007; personality type D, p = 0.040. In patients with MI1, the main predictors of adverse events were: obesity, p = 0.019; male, p = 0.009. There were no statistically significant differences in both groups in the frequency of mortality from MI, the development of recurrent MI, as well as complications such as subacute/late stent thrombosis and restenosis in the stent.

Conclusion. In patients with MI2, compared with MI1, after 12 months of follow-up the indicators of total mortality (10.6% vs. 1.1%) and repeated hospitalizations due to decompensation of heart failure (12% vs. 4.4%) are higher.