Aim. To investigate the associations of cell proliferation marker Ki-67 in estrogen receptor (ER) and progesterone receptor (PR) positive (ER⁺/ PR⁺) and negative (ER^-/PR^-) tumors with the ratio of antibodies against estradiol and progesterone (IgA₁-E2/IgA₁-Pg) in the serum of breast cancer (BC) patients.

Materials and Methods. Antibodies against steroid hormones were analyzed by ELISA in the serum of 432 healthy women and 1212 patients with BC (573 patients with I stage and 639 patients with II–IV stages). Expression of Ki-67, ER and PR in tumors was determined by immunohistochemical staining. Serum estradiol and progesterone were measured by enzyme-linked immunosorbent assay.

Results. In total, low IgA₁-E2/IgA₁-Pg (≤ 1) and high IgA₁-E2/IgA₁-Pg (> 1) ratio were revealed in 49.3% and 50.7% of healthy women; in 25.7% and 74.3% of stage I BC patients with tumor Ki-67 < 14 (р < 0.001; OR = 0.4 and OR = 2.8, respectively), and in 17.1% and 82.9% of stage I BC patients with tumor Ki-67 > 30 (р < 0.001; OR = 0.2 and OR = 4.7, respectively). The differences between patients with low and high tumor Ki-67 levels in relation to low and high IgA₁-E2/IgA₁-Pg ratio were statistically significant (p = 0.03). In stage I BC patients with ER⁺/PR⁺ and tumors with Ki-67 < 14, low and high IgA₁-E2/IgA₁-Pg ratio were found in 25.0% and 75.0% cases (р < 0.001; OR = 0.3 and OR = 2.9, respectively). In stage I BC patients with ER⁺/PR⁺ and tumors with Ki-67 > 30, low and high IgA₁-E2/IgA₁-Pg ratio were found in 12.9% and 87.1% cases (р < 0.001; OR = 0.2 and OR = 6.6, respectively). In patients with ER⁺/PR⁺ tumors, the differences between patients with low and high tumor Ki-67 levels in relation to low and high IgA₁-E2/IgA₁-Pg ratio were also statistically significant (p = 0.009). In patients with ER^-/PR^- tumors, the differences between patients with low and high Ki-67 levels in relation to low and high IgA₁-E2/IgA₁-Pg ratio were not revealed. The proportion of breast cancer patients with tumor Ki-67 > 30 increased from I to II–IV BC stages regardless of IgA₁-E2/IgA₁-Pg ratio.

Conclusion. IgA₁-E2/IgA₁-Pg ratio may serve as a predictor of tumor proliferative activity in stage I BC patients with ER⁺/PR⁺ tumors.

Aim. To evaluate the efficiency and safety of nitric oxide delivery for kidney protection in the simulation of cardiopulmonary bypass and circulatory arrest in the experiment.

Materials and Methods. We performed an experimental modeling of cardiopulmonary bypass with circulatory arrest in 20 sheep of the Altai breed weighing 30-32 kg. Circulatory arrest was performed at moderate hypothermia (30-32°C) for 15 minutes and was followed by reperfusion and warming up to 37°C. Animals were divided into 2 equal groups: 10 sheep which received nitric oxide (NO) through the inhalations supply and cardiopulmonary bypass machine at a dose of 80 ppm, and 10 control sheep. We further collected biological fluids and tissue specimens for subsequent assessment of the safety of NO use and its nephropro-tective properties.

Results. The proposed method of NO therapy during the cardiopulmonary bypass with circulatory arrest was safe and did not lead to an increase in toxic metabolites. In sheep which received NO therapy, the average concentration of NO2 throughout the entire period of the experiment was 1.2 ± 0.19 ppm (with a maximum allowable concentration of 3.0 ppm), and the concentration of methemoglobin (MetHb) was 2.3 ± 0.34% (with a maximum allowable level of 5.0%). Neutrophilic gelatinase-associated lipocalin (NGAL) was significantly lower in sheep which received NO therapy (0.67 ± 0.255 ng/mL versus 2.23 ± 0.881 ng/mL in the control group, p = 0.0001). Acute kidney injury was mitigated in sheep which received NO therapy.

Conclusion. Experimental delivery of NO at a dose of 80 ppm during the cardiopulmonary bypass and circulatory arrest is safe and is associated with reduced acute kidney injury.

Aim. To study the prognostic significance of abdominal aorta (AA) diameter in progression of peripheral atherosclerosis in patients aged 40-64 years and without abdominal aortic dilation.

Materials and Methods. The study included 157 outpatients aged 40-64 years who underwent Doppler ultrasonography of brachiocephalic arteries, lower extremity arteries, and abdominal aorta in order to assess cardiovascular risk. Upon the serum collection, we measured lipid fractions, creatinine, glycated hemoglobin, high-sensitivity C-reactive protein, pentraxin-3 and matrix metalloproteinases (MMP-1, MMP-2, MMP-9, and MMP-10). The criteria for the progression of peripheral atherosclerosis were: 1) the appearance of a new atherosclerotic plaque; 2) stenosis increase by ≥ 10%; 3) carotid plaque area increase by ≥ 0.106 cm².

Results. We found that 116 (73.9%) patients initially had low to moderate cardiovascular risk. Abdominal aortic diameter directly correlated with the level of glycated hemoglobin (r = 0.298; p = 0.003) and serum MMP-2 (r = 0.240; p = 0.041), whilst aortic size index directly correlated with serum MMP-9 (r = 0.319; p = 0.029). Repeated Doppler ultrasonography was performed in 120 (76.4%) patients, with the median period between two examinations was 14.4 (12.3; 20.8) months, and progression of peripheral atherosclerosis was identified in 26 (21.6%) patients. An increase in abdominal aortic diameter > 1.64 cm could predict atherosclerosis progression with sensitivity of 53.8% and specificity of 74.1%. According to Cox regression analysis, an increase in abdominal aortic diameter > 1.64 cm was associated with a 2.31-fold increased risk of atherosclerosis progression (95% CI = 1.06 - 5.00, p = 0.034).

Conclusion. Abdominal aortic diameter can be considered as a predictor of peripheral atherosclerosis progression.

Aim. To compare the clinicopathological features, the course of pregnancy and its outcomes with the results of histological examination of the uterine scar in women with a past medical history of a single caesarean section.

Materials and Methods. We analysed the associations between histological features of scarred myometrium and clinicopathological parameters of 48 pregnant women aged 19 to 40 years with a past medical history of a single caesarean section. All women were divided into two groups depending on the uterine scar condition. Tissue sampling for histological examination was performed during lower segment caesarean section from the scar area after fetal extraction.

Results. 26 women had non-defective uterine scar and 22 women had uterine scar dehiscence (an overstretched inferior uterine segment with little or no muscle fiber and disorganised connective tissue at histological examination). Clinicopathological parameters associated with a uterine scar dehiscence were are ≤ 2-year interval between deliveries (OR = 6.85, 95% CI = 1.27-36.90, p = 0.025) and obesity (OR = 3.5, 95% CI = 0.97-12.70, p = 0.056). Typical pregnancy complication in patients with uterine scar dehiscence was placental insufficiency (OR = 4.75, 95% CI = 1.39-16.2, p = 0.013).

Conclusion. Identification of the risk factors for uterine scar dehiscence may assist in selecting a method of delivery for women with a past medical history of caesarean section.

Aim. To assess the quality of preparation of patients with type 2 diabetes mellitus for elective percutaneous coronary intervention, which is aimed to achieving the target values of the modifiable cardiovascular risk factors.

Materials and Methods. We retrospectively analysed 100 electronic medical records of patients with type 2 diabetes mellitus who were admitted for elective percutaneous coronary intervention at Research Institute for Complex Issues of Cardiovascular Diseases from 2021 to 2022. We analysed clinicopathological data, the data from clinical laboratory tests, and pharmacological anamnesis.

Results. The average age was 65.19 ± 8.69 years, and the proportion of women was 59%. Smoking history and obesity were reported in 22% and 55% of patients, respectively, with average body mass index of 30.38 [27.66; 34.87] kg/m². All patients suffered from arterial hypertension, 55% had past medical history of myocardial infarction, and 15% had atrial fibrillation. The duration of type 2 diabetes mellitus was 10 [3; 12] years. Target blood pressure at the admission was achieved in 40% patients. Average total cholesterol and blood glucose were 4.15 [3.50; 5.10] mmol/L and 7.85 [6.15; 11.00] mmol/L, respectively. Beta blockers, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, and statics were received by 90%, 89%, and 97% of patients. Maximum statin dose was registered in 27% patients, combined therapy (statin + ezetimibe) was documented in 4% patients. 14% of patients did not take hypoglycemic drugs. Oral hypoglycemic agents were received in 65% (in most cases biguanides and sulphonylureas, in 7% patients they were combined with insulin). Sodium-dependent glucose cotransporter (SGLT2) inhibitors have been taken by 19% of patients.

Conclusion. Patients with type 2 diabetes mellitus recommended for elective percutaneous coronary intervention typically suffer from arterial hypertension and frequently had increased body mass index, total cholesterol, and blood glucose. The prevalence of using antihypertensive drugs, oral hypoglycemic agents, and lipid-lowering drugs should be increased.

Aim. To determine the predictors of left ventricular dysfunction in patients with ventricular ectopic beats without structural heart disease.

Material and Methods. We modeled ventricular ectopy in rats through early afterdepolarization (aconitine-induced arrhythmia) and delayed afterdepolarization (adrenaline arrhythmia). In addition, we modeled ventricular ectopy in rabbits and cats by delayed afterdepolarization (barium chloride-induced and strophanthin arrhythmias, respectively) and also modeled ventricular ectopy in dogs by re-entry hydrogen peroxide-induced arrhythmia. In addition to conventional electrocardiography parameters, we analyzed pre-ectopic interval, its variability, and the internal deviation index. Further, the study included 514 patients aged 16 to 34 years (mean 21.2 ± 0.2 years), and the number of premature ventricular contractions (PVCs) per day of observation ranged from 6,157 to 37,254 (mean 19,706 ± 656 PVCs). We registered the same parameters as in experimental arrhythmias but calculated them separately for mono- and polymorphic, left and right ventricular out-flow tract arrhythmias. The duration of follow-up of patients was up to 10 years. The endpoint was the detection or absence of cardiovascular and/or extracardiac pathology.

Results. We recorded polymorphic PVCs and early monomorphic PVCs when modeling ventricular arrhythmias by the mechanism of delayed post-depolarization and early post-depolarization, respectively. Both early and late monomorphic PVCs were documented when inducing ventricular arrhythmias by re-entry. When modeling hydrogen peroxide-induced and strophanthin arrhythmias, we observed significantly higher values of PVC-QRS complex and ventricular arrhythmia internal deviation index in comparison with aconitine-induced arrhythmia. Favourable outcome was registered in 50.97% of patients, whilst coronary artery disease, arterial hypertension, and mitral valve prolapse were documented in 7.98%, 16.73% and 2.92% patients. The rest of the patients had gastrointestinal diseases. In patients with favourable outcome, the signs of monomorphic PVCs correlated with those revealed during the modeling of ventricular ectopy by early afterdepolarization (r = 0.92), whereas those signs of polymorphic PVCs correlated with those observed at barium chloride-induced delayed afterdepolarization (r = 0.94). In patients with CAD, signs of PVCs correlated with those registered during re-entry hydrogen peroxide-induced arrhythmia (r = 0.93), Finally, in patients with arterial hypertension and mitral valve prolapse signs of PVCs correlated with those documented at strophanthin-(r = 0.92) and adrenaline-induced delayed afterdepolarization (r = 0.89). In these patients, the values for both monomorphic and polymorphic PVCs, ventricular arrhythmia internal deviation index, duration of PVC-QRS complex and PVC-QRS/QRS_average did not exceed 0.42 units, 149 ms and 1,44 units, respectively. The development of coronary artery disease and arterial hypertension well correlated with an increase in ventricular arrhythmia internal deviation index ≥ 0.56 units and QRS complex duration ≥ 157 ms. Mitral valve prolapse was associated with the duration of the QRS complex ≥ 159 ms of polymorphic PVCs.

Conclusion. In patients with ventricular ectopy but without structural heart disease, an increase in the values of ventricular arrhythmia internal deviation index and the duration of PVC-QRS complex was ≥ 0.48 units and 149 ms, respectively, associated with the development of cardiovascular pathology. Development of coronary artery disease and hypertension correlated with ventricular arrhythmia internal deviation index ≥ 0.56 units, and QRS complex duration ≥ 157 ms in monomorphic and polymorphic PVCs, whereas development of mitral valve prolapse correlated QRS complex duration ≥ 159 ms in polymorphic PVCs.

Aim. To assess the profile of lipid consumption in the population of Omsk Region, located in Western Siberia.

Materials and Methods. During 2019-2020, we have performed a cross-sectional survey in the adult population of the Omsk region (n = 441, age 18-83 years). Questionnaires included an information regarding the food intake, nutritional status, and health status. In addition, we measured body mass index, waist circumference and waist-to-hip ratio. Among the parameters, we evaluated average daily consumption of energy, fats, cholesterol, saturated, monounsaturated, and polyunsaturated fatty acids, phospholipids, linoleic acid, alpha-linolenic acid, and arachidonic acid. In addition, we assessed the ratio of omega-6 to omega-3 fatty acids in the diet, specific weight of vegetable fats, and the energy quotas of individual nutrients.

Results. In the population of Western Siberia, we found insufficient intake of alpha-linolenic acid (69.6 ± 2.2% population), arachidonic acid (55.3 ± 2.4%), polyunsaturated fatty acids (44.4 ± 2.4%), and phospholipids (37.6 ± 2.3%), as well as excessive consumption of cholesterol (74.1 ± 2.1%), total fats (61.9 ± 2.3%), saturated fatty acids (47.8 ± 2.4%), monounsaturated fatty acids (37.6 ± 2.3%), energy (34.7 ± 2.1%), and linoleic acid (31.1 ± 2.2%). In all groups of respondents, we registered high values of the omega-6/omega-3 ratio. The proportion of respondents with adequate consumption of energy and nutrients did not exceed 59.2 ± 2.3%.

Conclusion. The diet of the adult population in Western Siberia was characterized by dysbalanced lipid consumption (more than 60% of the population). We documented an insufficient consumption of polyunsaturated fatty acids and phospholipids in combination with excessive consumption of products containing cholesterol, saturated fatty acids, monounsaturated fatty acids, and linoleic acid.

Aim. To compare the efficiency of single arterial grafting (SAG) and multiple arterial grafting (MAG) at coronary artery bypass graft (CABG) surgery in the long term.

Material and Methods. To assess the angiographic outcomes, we evaluated the patency of 323 bypasses at 102 angiograms obtained during coronary angiography performed > 10 years post-CABG surgery.

Results. Out of 323 analyzed bypasses, 230 (71.2%) showed physiological functioning, whereas stenosis, occlusions, and other coronary artery alterations were found in 93 (28.8%) bypasses. The most common cause for the failure of anastomoses was competitive flow (most frequently registered in the anastomoses between left internal thoracic artery and left anterior descending artery, left internal thoracic artery and diagonal branches of left anterior descending artery, right internal thoracic artery and left anterior descending artery, and between right internal thoracic artery and right coronary artery), poor distal bed (most frequently revealed in the anastomosis between left internal thoracic artery and obtuse marginal artery, saphenous vein and diagonal branches of left anterior descending artery, saphenous vein and obtuse marginal artery, and between saphenous vein and right coronary artery), progression of atherosclerosis in combination with poor distal bed (most frequently detected in the anastomosis between right internal thoracic artery and obtuse marginal artery), and combination of poor distal bed, competitive flow, and graft degeneration (most frequently found in the anastomoses between radial artery and obtuse marginal artery and between radial artery and right coronary artery). In 5 (5.4%) cases, the cause of coronary bypass dysfunction was unclear.

Conclusion. The main causes for the coronary bypass failure included competitive flow (in case with multiple arterial grafting) and poor distal bed (in case with single arterial grafting).

The review presents a comparative analysis of scientific data on the structural and functional characteristics of subunits (HIF-1α and HIF-1β) of hypoxia-inducible transcription factor-1 (HIF-1). Differences between the main regulatory HIF-1α subunit and the constitutively expressed HIF-1β subunit, sensitivity to endo- and exogenous regulators of their stability, and intracellular content depending on the cell's oxygen supply state (normoxia and hypoxia conditions) are described. In normoxia, the intracellular content of HIF-1α is determined by oxygen-dependent and oxygen-independent mechanisms. Oxygen-dependent enzymatic degradation of HIF-1α occurs by PHD-dependent hydroxylation, VHL-dependent ubiquitination, and FIH-1-dependent hydroxylation. Oxygen-independent pathways of HIF-1α pool regulation include: 1) HIF-1α gene transcription (Notch and/or NF-KB-dependent, STAT3 and Sp1 cytokine-dependent), 2) mRNA translation (cap-dependent or IRES-dependent, as well as cytokine-dependent activation of the PI-3K/AKT pathway activation under the effect of growth factors and vasoactive hormones), 3) protein-protein interactions, 4) various mechanisms of post-translational modification. Changes in Krebs cycle enzyme activity and active oxygen forms confer HIF-1α stability through PHD activity inhibition and reduction of ubiquitin-proteasome degradation. PHD-independent post-translational stabilizers of HIF-1α are: cytosolic reductase NQO1, sirtuin-2, prostaglandin E2, activated protein kinase C1 receptor competing with heat shock protein 90, human Hdm2 (a natural inhibitor of p53), glycogen synthase kinase 3β, and negative modifiers are enzymes - methyltransferase SET7/9, lysine-specific demethylase-1, sex-like kinase 3, β-arrestin-2, casein kinase-1. Under hypoxic conditions, non-hydroxylated HIF-1α subunits migrate to the nucleus where they heterodimerize with HIF-1β, HIF-1α/β heterodimers bind the main 5'-(A/G)CGTG-3' consensus sequence within the hypoxia-reaction element (HRE) of the target genes, and recruit co-activators (p300, histone modifying enzymes, histone readers, chromatin remodeling proteins, and mediator proteins for target genes transcription enhancement with the aid of RNA polymerase II), resulting in the formation of HIF-1, acting as a transcription factor for the target genes providing metabolic reprogramming from oxidative phosphorylation to anaerobic glycolysis (genes encoding glucose transporters (GLUT1 and GLUT3), genes for glycolytic enzymes hexokinase 1 and 2 (HK1 and HK2), phosphoglycerate kinase 1), as well as genes for erythropoietin, vascular endothelial growth factor and its receptors FLT1 and FLK1, endothelin 1 and angiopoietin 1, resulting in adaptation to hypoxia.

Here we review current opportunities in pregnancy management in women with uterine fibroids, also known as leiomyoma. Uterine fibroids are associated with a number of complications already at planning for pregnancy and also during pregnancy and labour. We discuss vaginal delivery and caesarian section in such patients, considering safety issue with regards to myomectomy and its expediency before pregnancy and during caesarean section. Multiple controversies and debates emphasize the need for the further research in this direction.

Gestational diabetes mellitus (GSD) is defined as hyperglycemia of variable degree with onset or first recognition during pregnancy which does not meet the criteria of clinical diabetes mellitus (DM). The growing incidence of GSD is a global health problem, affecting from 9% to 12% of pregnancies worldwide. In this review, we focused on the key aspects of GSD prevention. Major risk factors of GSD development include family history, past medical history of GSD, fetal macrosomia in previous pregnancies, and obesity. At primary treatment, lifestyle interventions (e.g., change of the dietary pattern) may represent an efficient measure, and here we consider several types of diets and dietary supplements (e.g., myoinositol, folic acid, and probiotics) that might be useful to mitigate GSD. Physical activity and specialised psychological care during pregnancy planning, during the pregnancy and in the postpartum period has a number of positive effects. Adequate perception of GSD, which might be improved by psychotherapy, directly correlates with adherence to therapeutic and preventive measures. The complex of dietary interventions, increased physical activity, and psychological care can significantly reduce the risk of adverse pregnancy outcomes.

Diabetes mellitus is a leading endocrine disease with a steadily increasing incidence, and its complications impose a heavy burden on the healthcare. Although pathophysiology of diabetes mellitus has been extensively investigated through the recent decades, the role of circadian rhythms in this regard was vaguely described. Circadian rhythms comprise an autonomous system of neuroendocrine signals and transcription factors that enfold key physiological processes into a daily cycle. Circadian clocks are subdivided into central (located in the suprachiasmatic nuclei of the hypothalamus) and peripheral oscillators (located in organs and cells) which produce circadian variations in the activity of virtually all cells within the human body, including the β cells of the pancreas. Circadian rhythm disruption causes circadian desynchronization which is associated with impaired glucose metabolism and insulin secretion, thereby being considered as one of the triggers of diabetes mellitus. Production of melatonin, a master regulator of circadian rhythms and a potent antioxidant, is significantly reduced in patients with diabetes mellitus. Circadian desynchronization may be triggered by a jetlag or an eating disorder. At present, circadian disruption is viewed as an important cause for the development of diabetes mellitus, although the mechanisms of such link have not been fully elucidated hitherto and might include genetic predisposition and increased oxidative stress. Timely diagnosis and appropriate treatment of circadian disruption in patients with diabetes mellitus may ameliorate the severity or prevent diabetes complications.

Acquired heart defects have a high prevalence among patients of different age groups and represent a significant social problem. To date, surgery remains the only effective option to treat acquired heart disease, and replacement of the dysfunctional heart valves frequently relies on mechanical prosthetic heart valves which implantation requires lifelong anticoagulant therapy with vitamin K antagonists and constant monitoring of international normalised ratio. However, the optimal target range for international normalised ratio values remains poorly defined. Optimisation of the approaches to anticoagulant therapy for this category of patients is becoming increasingly important. This paper highlights the main problems and possible solutions for patients who have undergone implantation of mechanical heart valves and need constant intake of vitamin K antagonists.

Aim. Here, we provided an overview of artificial intelligence (AI) approaches for developing a system for prediction of infectious diseases and designed a respective step-by-step protocol.

Materials and Methods. Literature search in PubMed and Google Scholar and PubMed.

Key Points. Infectious diseases impose a heavy burden on a healthcare, demanding the development of novel and efficient approaches to prevention as well as sensitive and specific diagnostic tests. Evolution of data science have led to the emergence of promising artificial intelligence (AI) algorithms and tools for the forecasting of infectious diseases. Employing machine learning algorithms, AI systems can rapidly analyze a large amount of data, extract specific disease patterns, and screen for the most efficient AI instruments in relation to specific tasks, thus contributing to prevention, diagnostics, and treatment of infectious diseases in the context of personalized medicine. Importantly, such AI-based systems can determine specific human motor patterns from videos and/or photographs in order to assist physicians in primary diagnosis. Integration of AI tools into the existing healthcare algorithms can be especially useful for public health.