Aim. To develop methodological grounds for assessing the probability of breast malignancy in patients with noncancerous breast diseases (NCBD) by the following parameters: expression of markers of epithelial – mesenchymal transition (EMT) and proliferation and production of cytokines by samples of the breast tissue.

Materials and methods. In breast samples (BS) of patients with invasive carcinoma of no special type (ICNT) and patients with NCBD, immunohistochemistry was used to determine the expression of E-cadherin (CDH1), integrin β1 (CD29), type II collagen (CII), and proliferation of Ki-67. Using the enzyme-linked immunosorbent assay, concentrations of interleukin (IL)-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, tumor necrosis factor (TNF)α, interferon (IFN)γ, granulocyte colony-stimulating factor (G-CSF), granulocyte – macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF)-A, and monocyte chemoattractant protein (MCP)-1 were determined in the supernatant of the cultured breast tissue samples.

Results. It was shown that ICNT and NCBD differ in the expression of E-cadherin, CD29, Ki-67, and the production of IL-2, IL-4, IL-6, IL-17, IL-18, IL-1Ra, TNFα, IFNγ, and MCP-1. The ROC analysis found that the models characterizing the differences between the ICNT and NCBD samples were formed by the parameters of CD29 and Ki-67 expression and IL-17, IL-18, TNFα, VEGF-A, and MCP1 production. The neural network analysis revealed that CD29, IL-1Ra, TNFα, and VEGF-A had the greatest normalized importance for assessing the differences between the ICNT and NCBD samples. Clustering of the combined database of patients with NCBD and ICNT by the expression of E-cadherin, CD29, Ki-67 and by the production of IL-17, IL-18, TNFα, MCP-1, and VEGF-A resulted in a cluster which includes the parameters of 94.1% of patients with NCBD. The parameters of less than 10% of patients with NCBD who fell into other clusters practically coincided with the studied parameters of the ICNT group, which suggests that these patients may form a risk group with the malignancy probability of more than 90%.

Conclusion. The data obtained made it possible to develop methodological grounds for assessing the likelihood of breast malignancy in patients with NCBD.

Acute in-hospital stroke is a severe complication of the early recovery period after cardiovascular surgery with a probability of up to 15%. Unfortunately, in-time diagnostic neuroimaging (computed tomography and magnetic resonance imaging) in cases of severe brain damages is considerably hindered increasing the risk of an adverse outcome.

The aim of the study was to develop a method to evaluate the functional state of the human brain in patients with severe in-hospital stroke measuring parameters of electrical activity in the central nervous system.

Materials and methods. The sample was composed of 20 anonymous archived electroencephalograms obtained from volunteers with no neurological disorders, 10 records of patients without neurological symptoms during general anesthesia, 17 records of patients with out-of-hospital strokes obtained from the UCLH Stroke EIT Dataset, and 18 records from patients with acute in-hospital stroke during neuromonitoring in the early postoperative recovery period. A new integral coefficient of the functional state was introduced, and an algorithm to calculate the proposed measure of the functional activity of the central nervous system was developed and implemented.

Results. The proposed method to evaluate the functional state of the human brain was applied to analyze neurophysiological records obtained from people with different activity of the nervous system: from resting state to deep coma. It was shown that the integral coefficient naturally reflects the functional state of the human brain and can be used for early detection of brain dysfunction and damages caused by cerebral hemodynamic impairment.

Conclusion. The introduced integral criterion to evaluate the functional state of the human brain can be used for long-term postoperative monitoring in cardiac patients who underwent surgical treatment.

Aim. To evaluate the efficacy and safety of dexamethasone at various doses in an experimental model of direct acute lung injury (ALI).

Materials and methods. The study was performed on 80 white outbred male rats, in which ALI was modeled by intratracheal administration of lipopolysaccharide. The animals were divided into 4 groups: the control group and three experimental groups (groups 1–3), where the animals were intraperitoneally administered dexamethasone at doses of 0.52, 1.71, and 8.00 mg / kg / day, respectively, for 3 days. A complete blood count, blood biochemistry test, and hemostatic tests were performed to assess the efficacy and safety of dexamethasone on day 3 of the experiment The severity of pulmonary edema was assessed by changes in the lung weight coefficient and the wet / dry weight ratio.

Results. The use of dexamethasone in the ALI model increased the survival of rats in groups 1 and 2 by 35% (p < 0.05), and in group 3 only by 20% compared with control animals. The rat lung weight coefficient and the wet / dry weight ratio when using dexamethasone at all doses studied were equally reduced by an average of 28% (p < 0.05) and 17% (p < 0.05), respectively (p < 0.05). The severity of side effects of dexamethasone (hyperglycemia, hyperproteinemia, hyperkalemia, hypercoagulability, increased activity of creatine phosphokinase in the blood) was dose-dependent and was maximum in group 3 (dexamethasone dose 8.00 mg / kg / day).

Conclusion. The effectiveness of both low (0.52 mg / kg / day) and high (8.00 mg / kg / day) doses of dexamethasone in an experimental model of ALI in rats is characterized by the same anti-edematous effect. Based on the results of the blood tests and the analysis of rat survival, the use of dexamethasone at the lowest dose (0.52 mg / kg / day) should be considered the safest.

The aim. To conduct a comparative analysis of clinical and anamnestic data in women of reproductive age after ovarian cyst surgery and with occult premature ovarian insufficiency (POI) to predict a poor ovarian response to stimulation.

Materials and methods. We conducted a retrospective study of medical records of women (aged 18–40 years) with infertility at the Assisted Reproductive Technology Center of Siberian State Medical University from 2017 to 2020. The main group consisted of 84 patients who underwent ovarian cyst surgery. The comparison group consisted of 33 patients with biochemical signs of POI (follicle stimulating hormone (FSH) 10–12 mMU / ml) who did not undergo ovarian cyst surgery. Anti-Mullerian hormone (AMH), FSH, estradiol, the antral follicle count (AFC), and the ovarian response to stimulation were compared.

Results. A correlation was established between AFC and a poor ovarian response both in the main group (r = –0.7; p = 0.004) and in the comparison group (r = –0.620; p = 0.000) in women under 35 years of age. A correlation was found between the concentration of estradiol and a poor ovarian response in the comparison group in women over 35 years of age (r = –0.707; p = 0.001). A moderate negative correlation between AMH and a poor ovarian response was revealed only in the main group of women under the age of 35 years (r = –0.589; p = 0.021). A moderate negative correlation between AMH and a poor ovarian response was revealed in the comparison group in women under the age of 35 years (r = –0.648; p = 0.000), a weak negative correlation was found for women at the age of 35 years (r = –0.500; p = 0.004). In both groups, the level of FSH did not determine the ovarian response to stimulation.

Conclusion. The determination of AFC and AMH is more significant in predicting a poor ovarian response in women after ovarian surgery and in women with occult signs of POI under the age of 35 years, compared with FSH. In the group of women over 35 years with occult signs of POI, the concentration of estradiol may matter in predicting a poor ovarian response, which requires further research.

The aim was to investigate wound-healing properties of zinc-containing biocomposites based on humic ligands (humic substance (HS) – Zn) in the in vivo experiment on the aseptic wound model and to evaluate their resorptive properties.

Materials and methods. The objects of the study were 5 samples of HS-Zn in the form of complex salts comprising fine black powders synthesized in the Laboratory for Natural Humic Systems of the Faculty of Chemistry at Moscow State University. The wound-healing effect of the substances was studied on 70 male Wistar rats using a traumatic model of an excisional aseptic skin wound. The degree of affected skin healing was evaluated during 21 days by the planimetric method. The resorptive properties of the HS-Zn samples were studied by inductively coupled plasma mass spectrometry (ICP-MS) in the biomaterial (blood serum, fur, skin from the wound surface).

Results. It was found that course application of zinc-containing HS-Zn biocomposites to the wound surface led to a decrease in the wound area in comparison with ZnSO₄ with the equivalent concentration of elemental Zn (1.67 mg/ ml). Two samples FA-Zn and Peat1-Zn showed the most pronounced regenerating effect. We noted an increase in Zn level in the tested skin samples from the wound area, in fur, and in the blood serum, which indicates the resorptive effect of zinc-containing HS-Zn biocomposites during course application; however, the parameters did not exceed limiting permissible concentrations. The correlation between the tested samples was not equal, which indicates a significant impact of the initial HS matrix on the Zn bioavailability.

Conclusion. The observed reparative effect of zinc and HS complexes in the context of their low toxicity is of interest for further study to develop effective wound-healing preparations.

The aim was to study the prevalence of some common internal diseases in young people of working and childbearing age, depending on the levels of adipokines.

Materials and methods. The study included 1,340 people aged 25–44 years. The levels of leptin, adiponectin, adipsin, lipocalin-2, plasminogen activator inhibitor-1 (PAI-1), and resistin were determined by the multiplex analysis. Low-density lipoprotein hypercholesterolemia (LDL hypercholesterolemia), coronary artery disease (CAD), type 2 diabetes mellitus (T2DM), arterial hypertension (AH), renal dysfunction (RD), and chronic bronchitis (CB) were studied.

Results. With an increase in the level of adiponectin, the prevalence of CAD increased by 8.6 times. The highest quartile of the adipsin level was characterized by an increase in the prevalence of LDL hypercholesterolemia by 12.9%, AH by 3.9%, and RD by 17.9%. The quartiles of lipolkalin-2 showed higher prevalence of LDL hypercholesterolemia, AH, and RD in Q₄ compared to Q₁. The prevalence of CB was associated with a decrease in the level of lipocalin-2 and was higher by 35.9% within Q₁ compared to Q₄. In the quartiles of PAI-1, the prevalence of T2DM and LDL hypercholesterolemia was 2 and 1.5 times higher, respectively, and the prevalence of RD was 2.5 times lower in Q₄ than in Q1. In quartiles of resistin, the prevalence of LDL hypercholesterolemia, AH, and RD increased by 13–38%, while the prevalence of CB decreased by 20% in Q4, compared to Q₁. The prevalence of LDL hypercholesterolemia and RD was higher within Q₄ of leptin.

Conclusion. The results indicate the need for further research aimed at studying the molecular mechanisms underlying the effects of adipokines. This will allow to find a combined approach to restoring normal physiological levels of adipokines, which can have a positive effect in the studied internal diseases.

Aim. To conduct a clinical and morphological assessment of the characteristics of colon cancer depending on the dMMR / pMMR status of the tumor.

Materials and methods. A retrospective study included 66 patients with operable colorectal cancer (CRC) (T1-4bN0-2bM1), who were treated at Cancer Research Institute of Tomsk National Research Medical Center (NRMC). The average age of the patients was 64.4 ± 12.8 years. All patients underwent hemicolectomy or colon resection, as well as intraoperative resection of distant metastases, if present.

Results. We determined that in CRC patients with pMMR tumors, hematogenous metastases were detected in 27.3% of cases, while in patients with dMMR tumors, hematogenous metastases were detected only in 6.1% of cases (p = 0.021). A comparative analysis of dMMR and pMMR tumors also allowed to establish higher frequency of perineural invasion among the pMMR subgroup of carcinomas (p = 0.039). The sign of tumor budding was found both in dMMR carcinomas (36%) and in pMMR tumors (45%). This sign was associated with damage to regional lymph nodes (p = 0.0017). A more detailed analysis of the tumor budding phenomenon showed that in dMMR tumors, Bd1 low-grade budding (83%) predominated. In pMMR tumors, Bd2 intermediate-grade budding (33%) and Bd3 high-grade budding (26.7%) prevailed. Bd2 and Bd3 tumor budding types were associated with hematogenous metastasis (p < 0.001).

Conclusion. The obtained data demonstrate the differences in such pathomorphological parameters as perineural invasion and the degree of tumor budding depending on the dMMR / pMMR status of the tumor. These histologic parameters in tumor tissue are also associated with higher incidence of distant metastasis in patients with pMMR carcinomas as opposed to patients with dMMR tumors.

The aim of this work was to study the immunomodulatory effects of lithium salt gamma-lactone of 2,3-dehydro-Lgulonic acid (LiAc) on healthy blood leukocytes and leukemia cells in vitro.

Materials and methods. Peripheral blood lymphocytes and neutrophils obtained from healthy donors, as well as THP-1 cells (human monocytic leukemia) were used as test systems. To assess the proliferative activity, lymphocyte blast transformation was used. The antiproliferative effect was studied by the 3H-thymidine incorporation assay. Cytotoxic effects were studied using the Alamar Blue test. The effect on the phagocytic activity was studied using the method for assessing the neutrophil function during bacterial phagocytosis.

Results. LiAc exerted a dose-dependent effect on target cells, including antiproliferative and cytotoxic effects on leukemia cells and a stimulating effect on neutrophils in phagocytosis.

Conclusion. LiAc can be considered as a promising drug with immunomodulatory effects, including a suppressive effect on the proliferative activity of leukemia cells and a stimulating effect on immune mechanisms mediated by neutrophils and macrophages.

Aim. To study the effect of adipose tissue hormones on the level of metalloproteinases in men with verified coronary atherosclerosis and to assess associations between the studied biomarkers and abdominal obesity.

Materials and methods. The study included 96 men aged 58.9 ± 5.1 years: 80 men with angiographically verified atherosclerosis and class II–III angina pectoris and 16 men without atherosclerosis. Anthropometric parameters were measured in all patients, and their blood was taken on an empty stomach. The blood levels of adiponectin, leptin, resistin, adipsin, amylin, and metalloproteinases (MMPs) -1, -2, -3, -7, -9, -10, -12, -13 were determined by the multiplex analysis. Statistical processing of the results was carried out using the SPSS 13.0 software.

Results. In patients with severe atherosclerosis, lipocalin, MMP-1, MMP-7, and MMP-12 levels were higher than in the control group. The blood concentration of adiponectin in patients with atherosclerosis was reduced. Inverse correlations were revealed between waist circumference and concentrations of MMP-1 and MMP-12, as well as between body mass index and MMP-1. A moderate direct relationship was revealed between resistin and MMP-2 and MMP-3; between amylin and MMP-9; between adiponectin and MMP-12; between leptin and MMP-7.

Conclusion. The results obtained suggest a relationship between the level of damage markers and adipose tissue hormones, which lead to complications of cardiovascular diseases and explain the effect of obesity on atherosclerotic plaque destabilization.

Aim. To study the response of retinal glial cells to constant irradiation of various intensity and to develop a mathematical model allowing to evaluate the dynamics of damage to radial glial cells and predict their photodamage depending on the duration and intensity of irradiation.

Materials and methods. Outbred sexually mature white rats (n = 50) weighing 180–200 g were exposed to constant round-the-clock light (200, 3,500 lux, days 1, 2, 7, 14, 30). The control group consisted of 25 non-irradiated animals. Using semi-thin sections stained with toluidine blue, we counted the number of pycnomorphic cells in the radial glial cells. Ultrastructural changes in the glial cells were studied using the JEM-100 CX-II electron microscope.

Results. The study showed that after photodamage, oligodendrocytes and astrocytes were mainly characterized by mitochondrial swelling and expansion of endoplasmic reticulum cisterns. Microglial cells at the late stage of the experiment (day 30) were localized in the inner layers of the retina; their density depended on the intensity of irradiation. The earliest (days 1, 2) changes in the radial glial cells were noted in the subretinal space and were manifested by proliferation of scleral processes and phagocytosis of dead sensorineural cell fragments. The intensification of destructive changes in the radial glial cells led to disturbances in neuron – glia interactions in the retina and a decrease in regeneration of retinal neurons (day 7–14). The developed mathematical model allowed to assess the dynamics of damage to the radial glial cells in the retina and to predict photodamage depending on the duration and intensity of irradiation.

Conclusion. Glial responses in the retina after photodamage depend on the intensity and duration of light exposure. As the duration of irradiation increases, degenerative changes in glial cells intensify and are more pronounced after high (3,500 lux) irradiation intensity.

The aim of the study was to evaluate the role of polymorphic loci rs12524494, rs17883901, rs606548, rs636933, rs648595, and rs761142 in the GCLC gene in predicting the clinical course of acute alcoholic pancreatitis (AAP).

Materials and methods. The material of the study was blood DNA samples obtained from 547 patients with AAP and 573 healthy individuals. The average age of patients was 48.9 ± 13.1 years, the average age of healthy individuals was 47.8 ± 12.1 years. Genotyping was performed using the MassARRAY 4 Analyzer. Plasma levels of total glutathione were determined using the OxiSelect™ Total Glutathione (GSSG/GSH) Assay Kit STA-312. The level of reactive oxygen species (ROS) was determined using the OxiSelect™ In Vitro ROS/RNS Assay Kit (Green Fluorescence) STA-347 (Cell Biolabs Inc., USA). The kinetic colorimetric assay was used to determine the level of amylase in the blood serum. Statistical data processing was performed using the Statistica 10.0 and SNPStats software.

Results. It was found that the polymorphic loci rs606548 (genotype C/C, odds ratio (OR) = 3.34, 95% confidence interval (CI) 1.29–8.66, р = 0.007), rs648595 (genotype G/T, OR = 1.56, 95% CI 1.04–2.36, р = 0.029), and

rs12524494 (genotype A/G, р = 0.021) in the GCLC gene were predictors of an increased risk of necrotizing pancreatitis. For the genotype T/T of rs648595 (recessive model) in the GCLC gene, the lowest values of oxidized glutathione were found, whereas rs17883901 – G/A in the GCLC gene was associated with the highest ROS values in the blood. The rs761142 A/A genotype in the GCLC gene (OR = 1.70, 95% CI 1.12–2.59; р = 0.010) showed predisposition to acute peripancreatic fluid сollection, and the rs648595 G allele (OR = 1.47, 95% CI 1.01–2.13; р = 0.042) in the GCLC gene exhibited predisposition to the formation of acute pancreatic pseudocysts. Predisposition to massive bleeding was associated with rs17883901 (G/A genotype, OR = 6.20, 95%CI 1.3–28.81; р = 0.031) in the GCLC gene.

Conclusion. The established genotype – phenotype associations will make it possible to predict the clinical course of AAP in a particular patient, taking into account their genetic makeup, as well as to determine the treatment strategy in a timely manner.

Aim. To determine the role of the Notch signaling pathway in the regulation of Th1 / Th2 lymphocyte balance in patients with disseminated drug-sensitive (DS) and drug-resistant (DR) pulmonary tuberculosis (PT).

Materials and methods. Mononuclear leukocytes were isolated from the venous blood of 13 patients with disseminated PT by density gradient centrifugation. The cells were cultured for 72 h in the complete cell culture medium at 5% CO₂ and 37 °C. Preliminarily, CFP10 and ESAT6 mycobacterial antigens or γ-secretase inhibitor DAPT (5 μM / l; 10 μM / l) together with CFP10 and ESAT6 antigens were added to the culture medium. Immunophenotyping of Th1 and Th2 lymphocytes was performed by multicolor flow cytometry by determining the expression of CD4 receptor and intracellular transcription factors T-bet and GATA-3.

Results. In patients with disseminated DS and DR PT, an increase in the number of Th1 and Th2 lymphocytes was found in intact cultures. Stimulation of cells with mycobacterial antigens CFP10 and ESAT6 resulted in an increase in the number of CD4⁺T-bet⁺ and CD4⁺GATA-3⁺ cells in all comparison groups. Addition of CFP10 and ESAT6 antigens and DAPT (10 μM / l) to the incubation medium was accompanied by a decrease in the number of Th2 lymphocytes in PT patients in both groups. A rise in the number of Th1 cells was registered only in patients with DS PT. Suppression of the Notch signaling pathway with the γ-secretase inhibitor DAPT (10 μM / l) resulted in an increase in the Th1 / Th2 lymphocyte balance in both DS and DR variants of the disease.

Conclusion. The Notch signaling pathway has a modulating effect on the differentiation of the key lymphocyte populations that determine the balance between cell-mediated and humoral immune responses to PT. Suppression of the Notch signaling cascade by the γ-secretase inhibitor DAPT (10 μM / l) in vitro promotes an increase in the Th1 / Th2 ratio in patients with disseminated DS and DR PT. The positive regulatory effect on the Th1 / Th2 lymphocyte balance allows to consider the Notch signaling pathway as a promising potential target in the development of new approaches to the pathogen-specific therapy for PT.

Aim. To define the association of CDKN2A/B deletions in the 9p21 locus with survival of patients with diffuse large B-cell lymphoma.

Materials and methods. The study included 105 patients with diffuse large B-cell lymphoma who received firstline therapy with R-CHOP. A deletion of 9p21 was detected by fluorescent in situ hybridization of tumor tissue biopsy samples. Deletions of CDKN2A and CDKN2B were determined by real-time quantitative polymerase chain reaction. The overall survival and the progression-free survival were calculated by the Kaplan – Meier method with plotting of survival curves (the log-rank test). The risk of event occurrence was determined by the Cox regression analysis with the calculation of the risk ratio (RR) and 95% confidence interval (CI). The differences between the variables were considered statistically significant at p < 0.05.

Results. The deletion of the chromosomal region 9p21 was detected in the biopsy samples in 16.2% of patients. The CDKN2A deletions were detected in 23.8% of patients and CDKN2B loss – in 28.6% of patients. The progressionfree survival was significantly lower in patients with the 9p21 deletion than in those without this aberration: 29.4% vs. 62.5%, respectively (p = 0.012; RR = 2.26; 95% CI = 1.17–4.38). The risk of disease progression at low and low-intermediate values of the International Prognostic Index was 5.9 times higher in patients with the CDKN2B deletion than in patients without this abnormality.

Conclusion. Deletion of the chromosomal region 9p21 is associated with low progression-free survival in patients with diffuse large B-cell lymphoma. Loss of CDKN2B is associated with a high risk of disease progression in patients with low and low-intermediate risk according to the International Prognostic Index.

Background. There are different opinions about the effect of functional ovarian cysts on the duration of controlled ovarian hyperstimulation, the dose of gonadotropins, the number and quality of collected oocytes and produced embryos, and the frequency of pregnancy.

Aim. To analyze in vitro fertilization (IVF) programs in women with anovulatory infertility and ovarian retention.

Materials and methods. A prospective study included 71 women aged 18–44 years. The main group (I) included patients (n = 38) with anovulatory infertility and functional ovarian cysts (FOC) diagnosed by ultrasound before enrollment in the IFV program. Patients of this group underwent ultrasound-guided transvaginal puncture of ovarian cyst followed by cytology. The comparison group (II) (n = 33) encompassed patients with anovulatory infertility without FOC, who went through the IVF program. The control group (III) included apparently healthy individuals (n = 15). The study algorithm included collection of clinical and anamnestic data of the patients, data of laboratory and instrumental studies, parameters of a stimulated IVF cycle, characteristics of oogenesis and early embryogenesis, and assessment of IVF program effectiveness.

Conclusion. It was established that in FOC and anovulatory infertility, the number of collected oocytes was smaller; however, the number of the best quality embryos and the frequency of pregnancy did not differ.

Aim. To study the hydration status according to clinical parameters and laboratory and instrumental research findings at admission and discharge in patients hospitalized with acute decompensated heart failure (ADHF), depending on the severity of glucose metabolism disorder.

Materials and methods. The study included 280 patients (53% men, average age 70.1 ± 10.8 years) with ADHF. 72.5% of patients had arterial hypertension in the medical history, 60% of patients had coronary artery disease. In all patients, the level of glycated hemoglobin (HbA1c) was determined to assess the glucose metabolism status. The patients were divided into groups depending on the results obtained: at HbA1c values < 5.7%, patients were included in the group without glucose metabolism disorders, at HbA1c of 5.7–6.4% – in the prediabetes group, at HbA1c ≥ 6.5% – in the type 2 diabetes group. The patients underwent a standard physical examination at admission and at discharge, as well as a clinical and comprehensive assessment of congestion (determination of N-terminal pro B-type natriuretic peptide (NT-proBNP), lung ultrasound, liver Fibroscan testing, including calculation of a controlled attenuation parameter, bioimpedance analysis of the body).

Results. The frequency of glucose metabolism disorders in patients hospitalized with ADHF was 57.5% (n = 161), while prediabetes was detected in 17.1% of patients (n = 48) and type 2 diabetes – in 40.4% (n = 113) of cases. Congestion at admission was detected in all patients. A significantly higher frequency of residual (61%) and a lower frequency of subclinical congestion (10%) were revealed in patients with ADHF and type 2 diabetes, compared to patients without glucose metabolism disorders (39% for residual congestion, 27% for subclinical congestion) and prediabetes (40% for residual congestion, 25% for subclinical congestion), respectively. There were no significant differences in the frequency of euvolemia at discharge, depending on the glucose metabolism disorder.

Conclusion. Тo assess congestion phenomena at discharge, it is necessary to use clinical, laboratory, and instrumental assessments for patients with ADHF and glucose metabolism disorders. However, in patients with ADHF and prediabetes, it is preferable to focus on the laboratory and instrumental assessment of congestion, while in patients with ADHF and type 2 diabetes, both clinical and laboratory and instrumental assessment of congestion should be performed.

The aim of this study was to apply integrative physiological mathematical models to simulate physiological parameters in traumatic shock caused by lower limb blast injury.

Materials and methods. At the first stage of mathematical modeling, we applied lumped parameter integrative physiological models, and at the second stage we used neural networks.

Results. We developed a clinical decision support system that allows to determine the intensity of blood loss in lower limb blast injuries according to physiological monitoring data.

Conclusion. The developed approaches make it possible to partially solve the problem associated with the impossibility of accumulating a sufficient amount of medical data for a specific person to create an adequate personalized clinical decision support system.

Aim. To determine concentrations and identify the relationship of biomarkers (endocan / cell-specific molecule-1, fatty acid binding protein 4 (FABP 4), placental growth factor (PlGF), oncostatin M), with parameters of collageninduced platelet aggregation in patients with coronary artery disease (CAD).

Materials and methods. In patients with CAD (n = 51), serum levels of endocan, FABP 4, PlGF, oncostatin M, and platelet aggregation indices (collagen at concentrations of 2 and 10 mmol / l) were determined. Patients were divided into groups with and without high residual platelet reactivity (HRPR). Correlation coefficients between concentrations of proinflammatory biomarkers and platelet aggregation indices were determined in patients of both groups.

Results. In patients with HRPR, the concentrations of endocan and PlGF were significantly higher, and the concentrations of FABP4 and oncostatin M were lower than in the first group. In patients with HRPR, a correlation was found between the concentration of endocan and the degree of platelet aggregation in the presence of 2 mmol

/ l of collagen (ρ = 0.48; p = 0.01), between the concentration of PlGF and the degree of platelet aggregation in the presence of 10 mmol / l of collagen (ρ = 0.58; p = 0.01), as well as between the concentration of FABP 4 and the size of aggregates at both collagen concentrations (ρ = 0.42; p = 0.03) and (ρ = 0.70; p = 0.01) and the degree of platelet aggregation in the presence of 10 mmol / l of collagen (ρ = 0.43; p = 0.01).

Conclusion. In all examined CAD patients, regardless of the residual platelet reactivity, the levels of endocan and FABP 4 increased compared to the reference values. In patients with HRPR, the content of parameters (endocan, PlGF) contributing to plaque growth was elevated, and in patients without HRPR, the levels of platelet-activating factors (FABР 4, oncostatin M) were increased, which determines a personalized approach to prescribing therapy for these groups of patients. In patients with CAD, platelet aggregation indices were associated with concentrations of proinflammatory biomarkers (endocan, PlGF, and FABP 4), which contribute to the development of endothelial dysfunction.

Objective: using the clustering method, to determine and describe the clinical and pathogenetic phenotypes of the coronary microvascular obstruction phenomenon (CMVO) that occurs during percutaneous coronary interventions (PCI) in patients with myocardial infarction (MI).

Materials and methods: the study group included 190 patients with CMVO that occurred during PCI for type 1 MI. Participants admitted in 2013-2020. CMVO criteria: blood flow < 3 points in the infarct-related artery (IRA) according to TIMI flow grade (TFG); perfusion < 2 points for Myocardial blush grade; ST segment resolution < 70%. Median age – 64 [56; 70] years, 137 (72%) men, 53 (28%) women. MI with ST elevation (STEMI) in 170 patients (89%). Primary PCI in 127 (67%) cases. Nine patients (4.7%) have died. Phenotyping was performed using the EM (expectation-maximization) clustering algorithm.

Results: three phenotypes have been identified in a ratio of 56% (n = 106) / 27% (n = 52) / 17% (n = 32). The values of the parameters are respectively: age 62 [54; 67] / 73 [67; 79] / 59 [50; 65] years; women 8 (8%) / 39 (77%) / 6 (19%); STEMI 102 (96%) / 43 (83%) / 25 (78%); thrombolysis 46 (43%) / 6 (12%) / 11 (34%); acute heart failure 1 [1; 2] / 2 [1; 4] / 2 [2; 2] class; platelet to lymphocyte ratio 110 [78; 153] / 106 [85; 132] / 132 [100; 182]; glucose at admission 8,0 [6,9; 9,6] / 11,1 [8,8; 15,2] / 7,5 [6,1; 8,1] mmol/l; total cholesterol 4,7 [4,2; 5,4] / 5,3 [3,7; 6,2] / 5,1 [4,5; 6,2] mmol/l; glomerular filtration rate according to CKD-EPI 77 [64; 88] / 58 [46; 74] / 81 [64; 88] ml/min/1.73m²; Syntax Score 15 [10; 21] / 20 [14; 26] / 8 [5; 10] points; Syntax Score in IRA 9 [8; 15] / 12 [7; 16] / 6 [3; 7] points; collaterals according to Rentrop 0 [0; 1] / 0 [0; 1] / 0 [0; 0] degree; TIMI thrombus grade 5 [5; 5]/ 5 [3; 5] / 1 [0; 2] degree; TFG 0 [0; 0] / 0 [0; 1] / 2 [2; 3] degree; aspiration thrombectomy 30 (28%) / 7 (13%) /4 (13%); IRA diameter 3,5 [3,0; 3,5] / 3,0 [2,8; 3,5] / 3,5 [3,0; 3,5] mm; balloon angioplasty 99 (93%) / 45 (87%) /16 (50%); PCI of 2 or more arteries 0 (0%) / 4 (8%) / 3 (9). Deaths – 2 (1.9%), 7 (13.5%) and 0 (0%) patients, respectively (p = 0.002, χ2-Pearson).

Conclusion. Тhree phenotypes have been identified. First phenotype: severe IRA thrombosis, mostly men, moderate atherosclerotic lesions. Second phenotype: mostly elderly women, high hyperglycemia, severe atherosclerotic lesions, severe AHF, impaired renal function, IRA thrombosis. Third phenotype: mostly men, minor changes in the coronary arteries, absence of significant thrombosis and preserved blood flow in the IRA before PCI, elevated levels of inflammatory markers and total cholesterol.

Background. Antibiotic resistance is a global threat leading to ineffective treatment of many infectious diseases. One of the factors contributing to an increase in antibiotic resistance is over-the-counter sale of antibiotics.

The aim of this study was to establish the sources of antibiotic prescription and to determine the prevalence of self-medication and factors that cause it.

Materials and methods. The computer-assisted web interview (CAWI) methodology was used in the study. The questionnaire consisted of six blocks and 41 questions. For statistical analysis of the study results, Statistica for Windows version 10.0 and R-Studio software programs were used.

Results. The study involved 2,725 people. Only 50.9% of the respondents purchased antibiotics with a prescription or got them during hospitalization. Parameters associated with over-the-counter purchase of antibiotics included female gender (odds ratio (OR) = 1.4; 95% confidence interval (CI): 1.2–1.7), lack of higher education (OR = 1.6; 95% CI: 1.3–1.9), medical education (OR = 1.7; 95% CI: 1.2–2.5), lack of awareness of a ban on over-the-counter sale of antibiotics (OR = 1.6; 95% CI: 1.3–1.9), and relying on the knowledge (opinion) of family members or acquaintances as the main sources of information about the correct use of antibiotics (OR = 2.2; 95% CI: 1.7–2.9).

Conclusion. Antibiotic resistance can be reduced by propaganda and strict control over a ban on over-the-counter sale of antibiotics. It is also essential to update knowledge of medical professionals about antibacterial drugs and antibiotic resistance on a regular basis, also through raising their awareness of the development of antibiotic resistance in both patients and medical workers.

Aim. To evaluate the nature of changes in the expression of markers of endothelial progenitor cells (VEGFR2, CD34, CD14) and endothelial cells (CD146) in association with the expression of the leukocyte common antigen CD45 in the culture of blood mononuclear cells in the presence of M-CSF in patients with coronary heart disease (CHD) and healthy donors.

Materials and methods. The study included 12 patients with CHD with class III–V angina pectoris and 10 healthy donors, from whom 30 ml of venous blood was taken on an empty stomach in the morning and stabilized with heparin. Blood mononuclear cells were isolated by Ficoll density gradient centrifugation (1.077 g / cm³) and subject to immunomagnetic separation using CD14-MicroBeads and CD34-MicroBead Kit (Miltenyi Biotec B.V. & Co. KG, Germany). The resulting CD14⁺ and CD34⁺ culture of mononuclear cells was incubated for 6 days in a complete nutrient medium with and without M-CSF 50 ng / ml (Cloud-Clone Corp., USA) with complete replacement of the medium and repeated application of M-CSF on day 3. After 6 days, the proportions of CD45⁺, CD14⁺, CD34⁺, VEGFR2⁺, and CD146⁺ cells in the culture were assessed by flow cytometry using CD14-FITC, CD34-PE, VEGFR2-Alexa Fluor 647; CD45-FITC and CD146-PerCP antibodies (BD Biosciences, USA).

Results. It was shown that in healthy donors, the proportion of CD146⁺ cells in the co-culture of blood mononuclear cells with M-CSF exceeded their number in the sample without it, with comparable expression rates of CD45, CD14, and VEGFR2 markers between the control and stimulated cultures. In CHD patients, the number of CD146+ and VEGFR2⁺ cells did not change when M-CSF was added to the mononuclear cell culture; however, the proportion of CD14⁺ cells increased and the proportion of CD45⁺ cells decreased compared to the control sample. The number of CD34⁺ cells was comparable both between control and stimulated samples, and between the groups of examined individuals. At the same time, in patients with CHD, an increased proportion of VEGFR2⁺ cells was found in the control and stimulated samples compared to healthy individuals, while an increased proportion of CD14⁺ cells was detected only in the stimulated culture.

Conclusion. The development of CHD disrupts the response of blood mononuclear cells to the effect of M-CSF, increasing the number of CD14⁺ and reducing the proportion of CD45⁺ cells in the culture in the absence of stimulating effects on the expression of endothelial cell marker CD146. At the same time, M-CSF does not affect the expression of CD34 and VEGFR2 in endothelial progenitor cells both in patients with CHD and in healthy individuals.

The review summarizes and analyzes the results of major foreign studies on the role of adipokine imbalance in the development of a severe course and complications of novel coronavirus infection (COVID-19). Adipokines are biologically active compounds produced by adipose tissue cells and involved in the regulation of metabolism and the functioning of the immune system. 

Obesity is a proven risk factor for severe COVID-19 due to high hormonal and metabolic activity of visceral adipose tissue. A deep understanding of COVID-19 pathogenesis from the point of view of the role of adipokine imbalance in it can provide the grounds for the development of effective pathogenetic approaches to the prevention of a severe course and complications of novel coronavirus infection.

Obesity is considered as a chronic progressive disease, heterogeneous in its etiology and clinical manifestations, and characterized by excess in body fat mass and its deposition in the body. The term “morbid obesity” refers to excessive deposition of adipose tissue with a body mass index (BMI) ≥40 kg / m² or with a BMI ≥ 35 kg / m² in the presence of serious complications associated with obesity. Along with obesity, the frequency of type 2 diabetes mellitus and cardiovascular diseases closely associated with it has increased. It results from the progression of metabolic disorders, including insulin resistance, which is inextricably linked with the accumulation of visceral fat and plays a key role in the pathogenesis of obesity-related diseases.

The study of lipidomic signatures in obesity and associated conditions is a promising branch of fundamental medicine, which makes it possible to significantly and at a new conceptual level stratify a cohort of obese patients into various phenotypes, including a metabolically healthy and metabolically unhealthy obesity phenotypes. Dynamic changes in the lipidome both in the context of diet, drug treatment, and after various bariatric surgeries are of great interest for developing personalized strategies for the treatment of this disease. Currently available studies and their results suggest that we are only at the very start of studying this promising biomedical field.

The 2019 novel coronavirus infection (COVID-19) pandemic has been a great burden for all of humanity. Soon after it began, researchers noticed that elimination of the virus from the body and recovery are not the end of the disease, since many patients did not return to their previous state of health, continued to complain of pathologies of various organs and systems, could not work, and some of them developed mental disorders.

The aim of the review was to analyze and summarize published data on the quality of life and mental disorders in the post-COVID period. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, 7,374 scientific works were found, of which 176 English-language and 276 Russianlanguage relevant publications were selected for analysis. The review included 17 (including 2 Russian-language) articles relevant to the topic of this review. Complaints of decreased memory and attention, appearing no later than 6 months after recovery from COVID-19, were reported by 3.2–9.1% of patients. Asthenic symptoms during the first month after the elimination of the novel coronavirus infection occurred in 55–70% of patients, and six months later – in every fifth patient. At the same time, post-viral fatigue more often affected women discharged from respiratory hospitals and persons with chronic bronchopulmonary pathology. Quite often, those who recovered from COVID-19 experienced insomnia and emotional disturbances, the frequency of which also correlated with the female sex and the severe course of the disease, which required hospitalization in the intensive care unit (ICU). In the post-COVID period, the development of depressive symptoms is not excluded, but sufficient evidence for this has not been obtained. The quality of life in these patients decreased. After discharge from the hospital, some patients remained unable to work, and some began to experience difficulties with self-care. However, over time, there is a trend toward restoration of the quality of life, which is especially evident in young people. In patients who have been in the ICU for more than 7 days, the rehabilitation potential is much lower. Psychopathological symptoms contribute to a decrease in the quality of life along with physical factors (persistent dyspnea, decreased exercise tolerance).

This review deals with the current state of affairs in the diagnosis of cervical squamous intraepithelial lesions. Transformation of classifications of cervical pathologies is considered. The role of cytological (liquid-based and conventional cytology), molecular biological (Digene Hybrid Capture test), immunohistochemical (p16INK4α, Ki-67), and histologic methods in the diagnosis of cervical lesions is discussed. Particular attention is paid to the diagnosis of human papillomavirus infection. Performance indicators of screening programs based on primary determination of human papillomavirus (HPV) DNA in comparison with common cytological methods are presented. Tropism of HPV to various parts of the cervix, which predisposes to the formation of deep multifocal lesions, as well as the influence of the physical status of HPV on the treatment strategy and risks of relapse are considered.