Aim. To evaluate strength of magnesium ion complexes with levofloxacin and moxifloxacin.

Materials and methods. Complexation of levofloxacin, moxifloxacin, and reference ligands (ethylenediaminetetraacetate (EDTA), sodium citrate, and glycine) with magnesium ions in the range from 0.0 to 1.0 mmol / l was studied. The technique developed by the authors (patent RU 2680519 C1) was used to measure the rate of a model formation reaction of a magnesium phosphate coarse dispersion. Complexing activity of ligands was expressed in relation to EDTA activity and compared with the theoretical ion exchange equilibrium constants. The half maximal effective concentration (C50) calculated by the Michaelis − Menten equation was used to evaluate the dependence of the complexing activity on the dose.

Results. A correlation between the activity of EDTA, citrate ions, and glycine and the theoretical equilibrium constants (R = −0.87, p < 0.001) was found. In the range from 0.0 to 0.4 mmol / l, both levofloxacin and moxifloxacin showed a lesser complexing effect than EDTA (p < 0.001), and in the range from 0.6 to 1.0 mmol / l, their complexing effect was comparable (p > 0.050). The activity of fluoroquinolones did not differ at any concentration (p > 0.050), but moxifloxacin C50 (0.13 mmol / l; 95% confidence interval (CI) 0.11–0.15) was significantly lower than that of levofloxacin (0.22 mmol / l; 95% CI 0.19–0.26), (p < 0.001). Within the 0.4–1.0 mmol / l concentration range, the activity of levofloxacin was higher than that of citrate ions and glycine (p < 0.001). Complexing activity of moxifloxacin was higher than that of citrate ions within the range of 0.2–1.0 mmol / l, and in the range of 0.4–1.0 mmol / l, it was higher than that of glycine (p < 0.001).

Conclusion. The proposed method showed that the complexing activity of fluoroquinolones was close to that of EDTA and exceeded the activity of citrate ions and glycine. The complexation of fluoroquinolones may be associated with their ability to induce side effects associated with magnesium deficiency.

Aim. To identify early morphological changes in the heart and aorta of rats with experimental metabolic syndrome induced by a high-fat and high-carbohydrate diet (HFHCD).

Materials and methods. The study was carried out on male Wistar rats. The animals were divided into two groups: a control group (n = 10) and an experimental group (n = 10). The rats from the control group were fed with a standard laboratory diet. The rats from the experimental group received HFHCD for 12 weeks. Body weight, blood pressure (BP), and individual parameters of carbohydrate and lipid metabolism were assessed in the rats.   A histologic examination of the heart and aorta in the animals was performed.

Results. Feeding rats with HFHCD led to an increase in body weight, elevation of BP, obesity, hyperglycemia, and triglyceridemia. The histologic examination of the heart in the rats of the experimental group showed signs of vascular disease, lipomatosis, and focal myocardial degeneration. Lipid accumulation in the cells of the media, hyperplasia of adipocytes in the adventitia, and depletion and fragmentation of the elastic lamina were revealed in the aortic wall of the rats receiving HFHCD.

Conclusion. The study indicated that HFHCD is an effective way to model metabolic syndrome. Structural disorders in the heart and aorta may be the mainstay for the development of cardiomyopathy and arterial hypertension in diet-induced metabolic syndrome.

Aim. To perform a scintigraphic assessment of the bronchopulmonary system and pulmonary microcirculation in patients with connective tissue dysplasia.

Materials and methods. The study included 31 male patients of conscription age with connective tissue dysplasia (CTD), diagnosed according to the 2019 clinical guidelines (average age (19.6 ± 2.6 years)), and 25 practically healthy individuals comparable in gender and age, who formed a control group. All patients underwent planar pulmonary ventilation – perfusion scintigraphy with determination of pulmonary alveolar – capillary permeability.

Results. In patients with CTD, the apical to basal perfusion gradient (U/LQ) was on average 24% lower than in the control group (p = 0.046), and alveolar – capillary permeability was higher in both lungs, both at minute 10 and at minute 30.

Conclusion. Static pulmonary ventilation – perfusion scintigraphy allows to identify functional disorders in patients with CTD at the preclinical stage: a decrease in the perfusion gradient on average by 24% compared with the control group and an increase in alveolar – capillary membrane permeability.

Aim. To identify the differences in executive function (inhibitory control, working memory, cognitive flexibility) between patients with bipolar affective disorder and depressive episode.

Materials and methods. A total of 72 patients with affective disorders aged 20–40 years were examined. Of them, 30 patients had bipolar affective disorder, a current episode of mild or moderate depression, and 42 patients had a mild, moderate, and severe depressive episode without symptoms of psychosis. The executive function was evaluated using PsyToolkit, a set of software tools for programming psychological experiments. Computerized Go/ No–go tasks (assessment of inhibitory control and psychomotor functions), the Corsi block-tapping test (assessment of visual and spatial working memory capacities), and the Stroop Color and Word Test (assessment of cognitive flexibility) were used.

Results. An intergroup comparison of patients revealed that patients with bipolar disorder significantly more often demonstrated false button press in the Go/No–go task (p = 0.043); however, they exhibited a greater working memory capacity in the Corsi block-tapping test (p = 0.049) compared with patients with a depressive episode.

Conclusion. Important data were obtained regarding the specifics of executive dysfunction depending on the type of affective disorder. The presented data expand and supplement available information about the cognitive characteristics of patients with bipolar affective disorder and depressive episode, which may be useful in clinical practice and serve a focus of future research.

Background. 1.5 years after the registration of the first vaccine against COVID-19 in Russia, national herd immunity reached only 49.7%. It is obvious that the success of vaccination measures depends on the readiness of the population for immunization and their attitude to the vaccine.

The aim of the study was to research the attitude to vaccination against a new coronavirus infection among various socio-demographic population groups in Russia.

Materials and methods. The study was conducted online by distributing via social networks a direct link to an electronic form with questions about the attitude to the COVID-19 pandemic and vaccination. A total of 2,786 people (of whom 66.9% were women) aged 16 to 77 years took part in the online survey.

Results. It was shown that distrust of vaccination was more often expressed by women and younger people.  A targeted approach to these population groups can improve the results of awareness-raising and preventive measures in the context of an ongoing pandemic.

Background. A combination of different types of lung cancer and chronic obstructive pulmonary disease (COPD) is very common. COPD, accompanied by ventilation disorders and, often, respiratory failure, is a significant additional risk factor for mortality in these patients. Identification of risk factors for mortality in patients with lung cancer and COPD can potentially be associated with better long-term outcomes.

Materials and methods. Using a Cox regression model based on information about the outcome of the disease and life expectancy after treatment initiation, a survival analysis was performed with an assessment of the contribution of various clinical and anamnestic factors for a group of 118 COPD patients with primary diagnosed lung cancer. These patients received treatment at the Cancer Research Institute in Tomsk in 2013–2019.

Results. The study included 118 patients (87.3% men and 12.7% women). Among them, 77.97% of patients were active or former smokers with smoking index (SI) ≥ 10 pack-years, and 22% of patients had never smoked or had SI < 10 pack-years but had other risk factors for COPD. Peripheral lung cancer was detected in 45.8% of cases. Squamous cell carcinoma was noted in 54.2% of cases, adenocarcinoma – in 34.7%, large cell carcinoma – in 1.7%, small cell carcinoma – in 5.9%, and carcinoid tumors – in 2.5% of cases. Patients were characterized by varying degrees of severity of ventilation disorders in accordance with the GOLD classification: stage 1 was observed in 44% of patients, stage 2 – in 38.1 % of patients, stage 3 – in 16.9 % of patients, and stage 4 – in one patient. Threeyear mortality was 28.12%.

Conclusion. According to the results of the Cox regression analysis, factors that significantly reduced the survival rate of patients with lung cancer in combination with COPD were more severe stages in terms of the size of  the primary tumor and its localization, the prevalence of metastasis (according to TNM classification), more severe dyspnea (mMRC scale), lower oxygen saturation values, atelectasis, and episodes of pneumonia, including paracancrotic pneumonia, over the previous 12 months. The presence of certain types of metastases, such as metastatic lesions of the pleura, adrenal glands, distant non-regional lymph nodes, and bones should also be noted as negative factors for survival. It is worth noting that surgical treatment of the primary tumor was associated with an increase in the survival rate in patients with lung cancer in combination with COPD.

Aim. To create heterotopic and orthotopic patient-derived xenograft (PDX) models of colorectal cancer (CRC) by transplantation of patient’s tumor samples into immunodeficient BALB / c Nude mice.

Materials and methods. The study was performed on 15 female BALB / c Nude mice aged 6–8 weeks weighing 21–25 g. All animals underwent transplantation of the tumor material obtained from CRC patients into the following sites: heterotopic transplantation (under the skin of the thigh and into the omentum), orthotopic transplantation (into the descending and ascending colon and into the cecum). Weight and general condition of the animals and the size of the tumor nodule had been monitored for 80 days. The success of each model was assessed by the degree of engraftment, the dynamics of tumor growth, and the reproducibility of histopathologic characteristics. At the end of the experiment, the animals were euthanized by cervical dislocation.

Results. 100% survival of the animals and similar tumor growth dynamics in the xenograft models were observed throughout the experiment. The analysis of histologic specimens obtained from the xenografts and patient’s tumor showed their correspondence to moderately differentiated intestinal adenocarcinoma. The main advantages and disadvantages of different variants of PDX models were described.

Conclusion. Heterotopic and orthotopic PDX models reproduce the morpho-histologic characteristics of human tumors and demonstrate stable growth dynamics. Therefore, they are a suitable tool for the development, testing, and validation of potential anticancer drugs.

Aim. To study the potential use and information value of calprotectin in the blood plasma as a new biomarker for determining the activity of rheumatoid arthritis (RA).

Materials and methods. The study included 113 people. The treatment group consisted of 79 patients diagnosed with RA; the average age was 58 (± 11.66) years, the median duration of the disease was 10 [6; 15] years. The control group encompassed 34 healthy volunteers; the average age was 40 (± 11.14) years. RA activity was determined according to the Disease Activity Score (DAS) 28 and the Clinical Disease Activity Index (CDAI). The concentration of calprotectin in the blood plasma was determined by the solid-phase enzyme-linked immunosorbent assay. The obtained results were compared with laboratory and clinical parameters, as well as with composite indices (DAS28, CDAI) of RA activity. For mathematical data processing, Spearman’s rank correlation coefficient, linear discriminant analysis, and ROC analysis were used.

Results. In the group of patients with RA, the level of calprotectin in the blood was higher than in the control group. A statistically significant relationship was revealed between the level of calprotectin in the blood and all standard parameters of RA activity. The ROC analysis showed that the sensitivity, specificity, and diagnostic accuracy in assessing articular syndrome, as well as moderate and high RA activity according to the composite indices DAS28 and CDAI were higher for calprotectin than for erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). The linear discriminant analysis showed that a combination of ESR and calprotectin levels was the most informative; following it, the probability of correct classification of RA activity, according to the DAS28 index, was 71%. For the CDAI index, only one marker, calprotectin, resulted in a statistically significant classification with a probability of 70.5 %.

Conclusion. Сalprotectin in the blood plasma is a promising laboratory biomarker for assessing synovitis activity in RA demonstrating higher accuracy, sensitivity, and specificity than traditional acute-phase reactants.

Aim. To study the features of the functioning of innate immunity in children with chronic idiopathic urticaria.

Materials and methods. The study included 28 children of both sexes aged 6–16 years with chronic idiopathic urticaria (CIU). The median age of the patients was 8 years (p = 0.045). Clinical research methods included an analysis of complaints and anamnestic data, as well as an objective examination of the child (dynamics of urticaria, severity of itching, the presence of angioedema). Immunological techniques included determination of the number of monocytes expressing CD14⁺CD282⁺, CD14⁺CD284⁺, CD14⁺CD289⁺, the number of peripheral blood lymphocytes expressing CD3⁺CD16⁺, the levels of immunoglobulin (Ig) E, lactoferrin, interferon (IFN) γ, interleukin (IL)4, and IL-6, and a nitroblue tetrazolium test.

Results. In the course of the study, an increase in the expression of Toll-like receptors TLR2 and TLR4 by monocytes, a decrease in the expression of TLR9 by monocytes, a significant rise in lactoferrin levels, a slight decrease in the number of natural killer (NK) cells, a decrease in microbicidal activity and adaptive reserves, a rise in IgE levels, a decrease in IL-4 levels, and an increase in IFNγ and IL-6 were revealed in children with CIU.

Conclusion. The immunological changes revealed during the study indicate multidirectional expression of Toll-like receptors, disturbances in the work of the cellular components of innate immunity, and a launch of a proinflammatory cytokine cascade in children with CIU, which can serve as a mainstay for the development of new schemes for personalized therapy of CIU in children.

Aim. To identify the structural foundations of the pathogenesis of arterial hypertension and kidney disease associated with a high-fat, high-carbohydrate diet and age.

Materials and methods. The study was carried out on male Wistar rats aged 60 and 450 days. The animals were divided into 4 groups: group 1 (n = 14) – intact rats (60 days old) fed with a standard diet for 90 days; group 2 (n = 14) – rats (aged 60 days) receiving a high-fat, high-carbohydrate diet for 90 days; group 3 (n = 14) – intact rats (aged 450 days) receiving a standard diet for 90 days; group 4 (n = 14) – rats (aged 450 days) fed with a high-fat, high-carbohydrate diet for 90 days. Clinical and instrumental research methods, enzyme-linked immunosorbent assay, and immunohistochemistry and histology techniques were used in the study.

Results. Feeding 60-day-old animals with a high-fat, high-carbohydrate diet resulted in an increase in body weight and abdominal fat, a rise in systolic blood pressure, and moderately pronounced histologic changes in the kidneys. In intact 450-day-old rats, age-related changes prevailed: changes in the myocardial mass, an increase in TGF-β1, morphological changes in the renal tubules and glomeruli. In 450-day-old rats receiving a high-fat, highcarbohydrate diet, the most pronounced increase in both systolic and diastolic blood pressure, a significant rise in serum fibronectin, and destructive changes in the renal tissue were noted.

Conclusion. Functional and biochemical signs of arterial hypertension and morphological changes in the kidneys were the most pronounced in 450-day-old rats fed with a high-fat, high-carbohydrate diet.

Aim. To assess the effect of depressive disorder (DD) on the clinical presentation of coronary artery disease (CAD) and five-year survival rate of patients with chronic CAD.

Materials and methods. The study included 79 patients with functional class II–III exertional angina who experienced myocardial infarction more than 6 months before. The patients were divided into two groups: group 1 (n = 45) consisted of patients with CAD and depression and group 2 (n = 34) encompassed patients with CAD without depression. The clinical presentation of CAD was assessed by the results of filling out the angina pectoris self-control diary and exertion tests. The presence and severity of DD were determined using psychometric scales, such as Hospital Anxiety and Depression Scale (HADS) and Beck Depression Inventory (BDI), and verified by the psychiatrist. Information about five-year survival was obtained via telephone interviews with the patients and their relatives.

Results. Patients with CAD and DD were characterized by more frequent episodes of angina pectoris during a week (10 [8; 14] vs 6 [4; 7], p = 0.000004), an increased demand for nitroglycerin (4 [0; 10] tablets vs 0 [0; 4] tablets, p = 0.001), and lower exercise tolerance (50 [25; 75] W vs 75 [50; 75] W (p = 0.06), 350 [250; 400] meters vs 435 [350; 500] meters (p = 0.01) than CAD patients without DD. The five-year survival rate was significantly lower in group 1 than in group 2 (69 [62; 72] vs 71 [68; 72] months (p = 0.04)), 35 (77.8%) vs 32 (94.1%) patients survived. In group 1, a greater number of deaths from cardiovascular accidents (10 (22.2%) vs 2 (5.9%)) was noted (log-rank test, p = 0.03).

Conclusion. In patients with CAD, associated depression results in aggravation of the clinical course of CAD and poor disease prognosis, which requires timely diagnosis and treatment of DD.

Background. Inhibitory receptors and their ligands (also called checkpoint molecules) are important feedback regulators of the immune response. However, their role in immunological adaptation during pregnancy remains poorly understood.

The aim of the study was to evaluate the level of checkpoint molecule (PD-1, CTLA-4, Tim-3) expression in peripheral T cells in pregnant women compared with fertile non-pregnant women.

Materials and methods. The study included 36 women in the second half of pregnancy without pregnancy complications, 12 of whom had extragenital pathology. The control group consisted of 28 age-matched fertile non-pregnant women. The proportion of CD8⁺PD-1⁺, CD8⁺TIM-3⁺, CD8⁺PD-1⁺TIM-3⁺, CD4⁺PD-1⁺, CD4⁺TIM-3⁺, and CD4⁺PD-1⁺TIM-3⁺ was evaluated by flow cytometry using the corresponding monoclonal antibodies (BD Biosciences, USA).

Results. The proportion of CD4+Tim-3+ and CD8+PD-1+ Т cells and CD4+ and CD8+ Т lymphocytes co-expressing PD-1 and Tim-3 in the peripheral blood of pregnant women was statistically significantly higher than in non-pregnant women. An increase in CD4+Tim-3+ and CD8+PD-1+ T cells was observed both in pregnant women with and without extragenital pathology. However, pregnant women with extragenital pathology were characterized by a higher CD8+PD-1+ count and a smaller number of CD8+Tim-3+ cells, as well as by a lack of an increase in PD-1+Tim-3+ T cells typical of pregnant women. The number of comorbidities was directly correlated with the proportion of CD8+PD-1+ lymphocytes and inversely correlated with the proportion of CD8+Tim-3+ and CD4+ PD-1+Tim-3+ cells. In addition, the expression of checkpoint molecules was associated with gestational age (a direct correlation was found with the proportion of CD8+Tim-3+, CD4+PD-1+Tim-3+, and CD8+PD-1+Tim-3+ cells) and to a lesser extent – with the age of pregnant women (an inverse relationship was found with the proportion of CD8+Tim-3+ cells).

Conclusion. Pregnant women in the second half of pregnancy are characterized by increased expression of PD-1 and Tim-3 molecules in peripheral T cells. At the same time, concomitant extragenital pathology affects the expression of these molecules.

Background. Implementation of immunotherapy in clinical oncological practice has significantly improved the results of cancer treatment. It resulted in the need for seeking new markers to assess the effectiveness of therapy and the disease prognosis.

Aim. To analyze the content of soluble forms of PD-1 and PD-L1 immune checkpoint proteins in the blood serum of patients with non-small cell lung cancer and esophageal squamous cell carcinoma and their association with clinical and morphological characteristics of the disease and the disease prognosis.

Materials and methods. The study included tumor samples obtained from 43 patients with non-small cell lung cancer and 21 patients with esophageal squamous cell carcinoma. The concentration of sPD-L1 and sPD-1 in the blood serum was determined using enzyme-linked immunosorbent assay (ELISA). The Mann – Whitney test was used to determine statistically significant differences in independent groups. A correlation analysis was performed using the Spearman’s rank correlation coefficient. Overall survival was analyzed by constructing survival curves using the Kaplan – Meier method and a Cox proportional hazards model. The differences were considered statistically significant at p < 0.05.

Results. The study showed that sPD-1 and sPD-L1 were found in the blood serum of both cancer patients and healthy donors, and their concentrations did not differ significantly. It was shown that the high concentration of sPD-L1 in the blood serum of patients with non-small cell lung cancer was significantly associated with the late stage of the disease and was an independent unfavorable prognostic factor. It should be noted that for patients with esophageal cancer, an unfavorable prognostic marker was the high concentration of the soluble form of PD-1 protein, and not PD-L1 ligand, as in case of lung cancer.

Conclusion. The content of sPD-1 and sPD-L1 in the blood serum can have different prognostic significance for various types of cancer, and further studies are required to confirm their clinical usability.

Aim. To compare the frequency of genotypes for polymorphic variants of GRIN2A and GRIN2B genes in patients with schizophrenia and addictive behavior (alcohol / tobacco abuse) and in patients with schizophrenia without addictive behavior in the Slavic population of the Tomsk region.

Materials and methods. The study included 219 inpatients with the established diagnosis of schizophrenia who received treatment in the clinics of Mental Health Research Institute and Tomsk Clinical Psychiatric Hospital. A history of alcohol / tobacco abuse was identified during a clinical interview and objective data collection. DNA was isolated from peripheral blood leukocytes by standard phenol – chloroform extraction.

15 single nucleotide polymorphisms (SNPs) in the GRIN2A gene and 9 polymorphisms in the GRIN2B gene were selected for genotyping. Allelic variants were determined by real-time polymerase chain reaction (PCR) with specific primers. The SPSS 17.0 software package was used for statistical data processing. The distribution of genotype frequency was assessed using the Pearson’s χ2 test with the Yates’ correction and the Fisher’s exact test.

Results. Significant differences in the allele frequency for the rs9788936 polymorphism in the GRIN2A gene (χ2 = 4.23, p = 0.04) and for the rs10845838 polymorphism in the GRIN2B gene (χ2 = 4.27, p = 0.04) were reveled between the groups of patients with and without alcohol abuse. It was found that the polymorphic variant rs8049651 of the GRIN2A gene had a clear association (F = 8.06, p = 0.029) with the development of tobacco addiction in patients with schizophrenia.

Conclusion. The study identified the association between alcohol abuse and the rs9788936 polymorphism in the GRIN2A gene and the rs10845838 polymorphism in the GRIN2B gene in patients with schizophrenia. The association between the rs8049651 and rs7190619 polymorphisms in the GRIN2A gene and the development of tobacco abuse in patients with schizophrenia was revealed.

Persistent hyperglycemia resulting from diabetes mellitus causes microvascular lesions and long-term diabetic complications, such as nephropathy.

The aim of the study was to analyze the levels of insulin-like growth factors (IGFs), their carrier proteins (IGFBP), and markers of kidney tissue damage (IL-18, L-FABP, cystatin C, NGAL, and KIM-1) in male rats with diabetes mellitus, tumor growth, and their combination.

Materials and methods. The study included white outbred male rats (n = 32) weighing 180–220 g. The animals were divided into four groups (n = 8 each): group 1 – intact animals; controls (2) – animals with diabetes mellitus; controls (3) – animals with Guerin carcinoma; experimental group (4) – animals with Guerin carcinoma against the background of diabetes mellitus. Levels of IGF-1, IGF-2, IGFBP-1, IGFBP-2 and markers of acute kidney injury (IL-18, L-FABP, cystatin С, NGAL, and KIM-1) were determined in the kidney homogenates using enzyme-linked immunosorbent assay.

Results. Increased levels of acute kidney injury markers were found in the kidneys of male rats with diabetes mellitus alone and in combination with Guerin carcinoma. In the animals with diabetes mellitus, the levels of IGF-1, IGFBP-1, and IGFBP-2 were decreased on average by 1.3 times, and the level of IGF-2 was increased by 2.1 times compared with the values in the intact male rats. The elevation of IGF-2 / IGF-1 on average by 2.8 times indicated increasing hypoglycemia in the kidney tissue of the animals with diabetes mellitus and in the experimental group with diabetes mellitus and Guerin carcinoma. In the kidney tissues of the rats with Guerin carcinoma, IGF-1 and IGF-2 were elevated on average by 1.5 times, and IGFBP-2 was decreased by 1.7 times. In the animals with malignant tumors growing against the background of diabetes mellitus, IGF-2 and IGFBP-1 were increased by 2.3 and 1.7 times, respectively, and the levels of IGF-1 and IGFBP-2 were similar to those in the intact animals.

Conclusion. The study demonstrated abnormalities in the metabolic profile of the kidneys in male rats with experimental diabetes mellitus, Guerin carcinoma, and their combination.

Aim. To identify disturbances of differentiation and subpopulation composition of VEGFR2+ cells in the blood and bone marrow associated with the features of the cytokine profile in the blood and bone marrow in patients with coronary artery disease (CAD) with and without ischemic cardiomyopathy (ICM).

Materials and methods. The study included 74 patients with СAD with and without ICM (30 and 44 people, respectively) and 18 healthy donors. In all patients with СAD, peripheral blood sampling was performed immediately before coronary artery bypass grafting, and bone marrow samples were taken during the surgery via a sternal incision. In the healthy donors, only peripheral blood sampling was performed. In the bone marrow and blood samples, the number of VEGFR2⁺ cells (CD14⁺VEGFR2⁺ cells) and their immunophenotypes CD14⁺⁺CD16-VEGFR2⁺, CD14⁺⁺CD16⁺VEGFR2⁺, CD14⁺CD16⁺⁺VEGFR2⁺, and CD14⁺CD16-VEGFR2⁺ was determined by flow cytometry. Using enzyme-linked immunosorbent assay, the levels of VЕGF-А, TNFα, M-CSF, and IL-13, as well as the content of MCP-1 (only in the blood) and the M-CSF / IL-13 ratio (only in the bone marrow) were determined.

Results. The content of CD14⁺VEGFR2⁺ cells in the blood of CAD patients with and without ICM was higher than normal values due to the greater number of CD14⁺⁺CD16-VEGFR2⁺, CD14⁺⁺CD16⁺VEGFR2⁺, and CD14⁺CD16⁺⁺VEGFR2⁺. In the bone marrow of the patients with ICM, the content of CD14⁺⁺CD16-VEGFR2⁺, CD14⁺CD16⁺⁺VEGFR2⁺, and CD14⁺CD16-VEGFR2⁺ was lower than in patients with CAD without ICM, and the number of CD14⁺⁺CD16+VEGFR2⁺ cells corresponded to that in the controls. Regardless of the presence of ICM in CAD, a high concentration of TNFα and normal levels of VEGF-A and IL-13 were observed in the blood. In CAD without ICM, an excess of MCP-1 and deficiency of M-CSF were revealed in the blood. In the bone marrow, the levels of VEGF-A, TNFα, M-CSF, and IL-13 were comparable between the groups of patients against the background of a decrease in the M-CSF / IL-13 ratio in the patients with ICM.

Conclusion. Unlike CAD without cardiomyopathy, in ICM, no excess of VEGFR2⁺ cells and MCP-1 in the blood is observed, which hinders active migration of CD14⁺CD16⁺⁺VEGFR2⁺ cells from the myeloid tissue, and a decrease in the M-CSF / IL-13 ratio in the bone marrow disrupts differentiation of other forms of VEGFR2⁺ cells, preventing vascular repair.

HER2-positive breast cancer occurs in 15–20% of breast cancer patients and is associated primarily with a poor prognosis of the disease and the need for highly specific targeted therapy. Despite the clinical importance of determining HER2/neu, traditional diagnostic methods have their disadvantages and require the study of new additional research techniques.

The information presented in this review makes it possible to consider current trends in the radionuclide diagnosis of HER2-positive breast cancer using the latest class of alternative scaffold proteins and to consider various aspects of their use in clinical practice.

The review describes available modern radiological methods which are currently applied for a detailed and comprehensive anatomical and functional assessment of the viability of various coronary artery bypass grafts. In addition, it presents some aspects of the implementation of these methods and clinical interpretation of the results.

Liver fibrosis (LF) is an unfavorable event in the natural course of chronic liver diseases (CLD), therefore, early implementation and widespread use of antifibrotic therapy methods is a pressing issue in hepatology. The aim of the review was to describe current approaches to targeted therapy of LF.

PubMed database, Google Scholar search engine, Cochrane Database of Systematic Reviews, eLIBRARY.RU scientific electronic library, as well as reference lists of articles were used to search for scientific articles. The publications that corresponded to the aim of the study were selected for the period from 1998 to 2021 by the terms “liver fibrosis”, “pathogenesis”, and “treatment”. Inclusion criteria were restricted to targeted therapy of LF.

Despite the growing evidence for reversibility of LF, there are currently no effective or clinically approved regimens for its specific therapy. However, taking into account the relevance of the issue, scientific research in this area is necessary. Multiple drugs with a good safety profile have been studied, which, though intended for other purposes, can have a positive effect on LF. In addition, a number of innovative approaches that differ from pharmacotherapy inspire optimism about finding a solution to this problem. It is obvious that studies focused on well-characterized groups of patients with confirmed histologic, elastography, clinical, and radiological parameters are required. This is a challenging task, since the key point will be stratification of risk based on ethnicity, etiology, and clinical status, and very large samples will be required for a reliable assessment. Nevertheless, the solution will increase efficiency of treatment for patients with CLD, improve their prognosis and quality of life, and significantly reduce the need for liver transplantation, a demand for which remains extremely high worldwide.

The aim of this review was to provide extended information on current trends in the diagnosis of complicated diabetic foot syndrome (DFS), the most frequent and severe complication of diabetes mellitus, including hightech medical imaging methods and instrumental and laboratory predictors of the complicated course and risk of amputation in DFS.

The article provides an analytical review of modern publications over the past 5 years on diagnosis and therapy. Pilot data on the use of high-tech medical imaging methods, assessment of skin microbiota and ulcers in DFS, molecular testing methods in terms of predicting the amputation risk and survival of patients with DFS, as well as the effectiveness of biosensing systems have been systematized, summarized, and subjected to analytical evaluation.

The review provides an expert assessment of the capabilities of pathogen-specific molecular imaging using modern positron emission tomography (PET), single-photon emission computed tomography (SPECT), and highenergy radionuclides in bacterial infection to understand its pathogenesis, minimize diagnostic problems, improve antimicrobial treatment, and address fundamental and applied aspects of DFS. Literature data on the assessment of foot perfusion in diabetic patients with varying degrees of limb ischemia by hybrid technologies (SPECT / CT and PET / CT) and new modalities of magnetic resonance imaging (MRI) are also systematized, which contributes to new understanding of the response to revascularization, surgical shunting, and stimulation of angiogenesis within ischemic tissue, as well as potentially to healing of foot ulcers.

The review is aimed at substantiating a multidisciplinary approach in DFS, selection, development, and implementation of innovative strategies for diagnostic modalities to identify diabetic foot pathologies, and choice of an adequate method for treating and monitoring the results of therapy in the context of personalized medicine.

Unprecedented advances of recent decades in clinical pharmacology, cardiac surgery, arrhythmology, and cardiac pacing have significantly improved the prognosis in patients with chronic heart failure (CHF). However, unfortunately, heart failure continues to be associated with high mortality. The solution to this problem consists in simultaneous comprehensive use in clinical practice of all relevant capabilities of continuously improving methods of heart failure treatment proven to be effective in randomized controlled trials (especially when confirmed by the results of studies in real clinical practice), on the one hand, and in development and implementation of innovative approaches to CHF treatment, on the other hand. This is especially relevant for CHF patients with mildly reduced and preserved left ventricular ejection fraction, as poor evidence base for the possibility of improving the prognosis in such patients cannot justify inaction and leaving them without hope of a clinical improvement in their condition. The lecture consistently covers the general principles of CHF treatment and a set of measures aimed at inotropic stimulation and unloading (neurohormonal, volumetric, hemodynamic, and immune) of the heart and outlines some promising areas of disease-modifying therapy.

To date, the study of the role of proteases in the pathogenesis of various diseases remains relevant. The variety of cathepsin functions is associated with the peculiarities of their localization, expression, and regulation, due to which cathepsins are involved in development of many pathologies. Dysregulation of proteases, their inhibitors, and substrates can lead to the development of multiple organ dysfunction.

The review presents data on the characteristics of the entire family of cathepsins and cathepsin S, in particular. The pathophysiological role of cathepsin S in the formation of bronchopulmonary pathologies, as well as in bronchial asthma is described, and intraand extracellular implementation mechanisms are considered. The authors believe it is this enzyme that could be targeted in targeted asthma therapy to prevent airway wall remodeling at the earliest stages of the disease. The literature search was carried out in the search engines Medline, eLibrary, Scopus, the Cochrane Library, and RSCI.

The review analyzes variability of clinical manifestations of p.Arg870His in the MYH7 gene, which is repeatedly registered in patients with hypertrophic cardiomyopathy (HCM). The analysis involves the data from scientific publications obtained as a search result in the PubMed, СlinVar, and eLibrary.ru databases, as well as authors’ own results. A wide range of phenotypic manifestations have been revealed in carriers of p.Arg870His, from the asymptomatic to severe course, rapid progression, and early death. The review considers possible factors that modify the effect of the pathogenic variant (i.e. dosage of the pathogenic variant, the presence of other unfavorable genetic variants, etc.). The importance of accumulating information on the clinical features of HCM in the carriers of specific gene variants is emphasized in order to clarify their pathogenicity and to identify factors modifying the clinical outcome, which is important for the choice of the treatment strategy for HCM.

One of the most important functions of the skin, mechanical, is provided by collagen fibers and their interaction with other elements of the extracellular matrix. Synthesis of collagen fibers is a complex multistep process. At each stage, disturbances may occur, leading, as a result, to a decrease in the mechanical properties of the connective tissue. In clinical practice, disorders of collagen synthesis are manifested through increased skin laxity and looseness and premature aging. In addition to the clinical presentation, it is important for the cosmetologist and dermatologist to understand the etiology and pathogenesis of collagenopathies. The present review summarizes and systematizes available information about the role of genetic and epigenetic factors in the synthesis of collagen fibers in the skin. Understanding the etiology of collagen synthesis disorders can allow doctors to prescribe pathogenetically grounded treatment with the most effective results and minimize adverse reactions.