Background. One of the factors of the pathogenesis of atherosclerosis and other cardiovascular diseases is induced endothelial senescence. In this regard, the urgent task of molecular biology and medicine is the search for molecules that affect the process of vascular endotheliocytes senescence.
The aim. To assess the expression of Sirt-1,3,6 and chemokines IL-4, CXCL11 in the replicative and induced senescence of human endotheliocytes.
Materials and methods. The study was conducted on the primary culture of isolated human umbilical vein endothelial cells (HUVECs). HUVECs were cultured under conditions of replicative (natural) and lipopolysaccharide induced senescence.
Results. The synthesis of Sirt-1,3,6, IL-4 and CXCL11 was evaluated using western blot analysis. We revealed a decrease in Sirt-1,3,6 synthesis by 1.6–1.8 times (р < 0.05) in the conditions of HUVEC replicative senescence. Induced senescence of endotheliocytes is characterized by a more pronounced decrease (1.7–3.4 times; р < 0.05) in the Sirt-1,3,6 synthesis. CXCL11 synthesis increases by 1.4 times (р < 0.05) in replicative and by 3.4 times (р < 0.05) in induced HUVEC senescence. IL-4 synthesis increases by 4.7 times in conditions of induced HUVEC senescence and doesn’t have changes in replicative senescence of endotheliocytes.
Conclusion. These data obtained indicate that sirtuins and chemokines play an important role in the development of endothelial dysfunction observed in natural and induced senescence.

Background. Angiogenic endothelial dysfunction and progenitor endothelial cells (EPCs) in ischemic cardiomyopathy (ICMP) have not been studied enough.
The aim. To establish the nature of changes in the cytokine profile and HIF-1α in blood and bone marrow associated with impaired differentiation of monocytic progenitor cells of endotheliocytes (CD14+VEGFR2+) in the bone marrow and their migration into the blood in patients with coronary heart disease (CHD), suffering and not suffering from ICMP.
Materials and methods. A single-stage, single-centre, observational case-control study was conducted involving 74 patients with CHD, suffering and not suffering from ICMP (30 and 44 people, respectively), and 25 healthy donors. In patients with CHD, bone marrow was obtained during coronary bypass surgery, peripheral blood – before surgery. Healthy donors were taken peripheral blood. The number of CD14+VEGFR2+ in bone marrow and blood was determined by flow cytometry; the concentration of IL-6, TNF-α, M-CSF, GM-CSF, MCP-1 and HIF-1α – by the method of enzyme immunoassay.
Results. A high content of CD14+VEGFR2+ cells in the blood of patients with CHD without cardiomyopathy was established relative to patients with ICMP against the background of a comparable number of these cells in myeloid tissue. Regardless of the presence of ICMP in the blood, patients with CHD showed an excess of TNF-α, a normal concentration of IL-6, GM-CSF, HIF-1α and a deficiency of M-CSF, and in the bone marrow supernatant, the concentration of IL-6 and TNF-α exceeded that in the blood plasma (the level of GM-CSF – only in patients without cardiomyopathy). With ICMP, the normal concentration of MCP-1 was determined in the blood plasma, and with CHD without cardiomyopathy, its elevated content was determined.
Conclusion. The formation of ICMP is accompanied by insufficient activation of EPCs migration with the CD14+VEGFR2+ phenotype in blood without disruption of their differentiation in the bone marrow, which associated with the absence of an increase in the concentration of MCP-1 in blood plasma and not associated with the plasma content of M-CSF, GM-CSF, HIF-1α, IL-6 and TNF-α.

CYP2C and CYP3A cytochromes are induced by a variety of compounds and affect the pharmacokinetics and pharmacodynamics of a large number of drugs. Currently, the possibility of using copper coordination compounds in antitumor therapy is being actively studied. Evaluation of potential interactions between new molecules and P450 cytochromes is necessary at an early stage of drug design.
The aim. To study the modulating effect of Cu(II) complexes with enamine and tetrazole derivatives on CYP2C9, CYP2C19 and CYP3A4 and their cytotoxic and antiproliferative properties on normal human lung fibroblasts MRC-5 and a 3D model of hepatocellular carcinoma HepG2.
Materials and methods. Cytotoxic and antiproliferative activities of copper(II) complexes – [CuL2] (1), [Cu2(bipy)2(PT)4] (2), [Cu2(phen)2(PT)4] (3), {[Cu(phen)(MT)2]∙H2O}n (4) (L – anion of 2-anilinomethylidene-5,5-dimethylcyclohexane-1,3-dione; PT – 5-phenyltetrazolate anion; MT – 5-methyltetrazolate anion; bipy – 2,2’-bipyridine; phen – 1,10-phenanthroline) – were examined in 2D and 3D models using fluorescence-based phenotypic screening. The modulating effect on CYP2C9, CYP2C19 and CYP3A4 was studied using fluorescence-based targeted screening. The results of CYP3A4 expression were confirmed by real-time reverse transcription polymerase chain reaction (RT-PCR).
Results. Complex (1) increases the CYP3A4 expression and does not affect CYP2C9 and CYP2C19 expression. Complex (2) has no modulating effect on CYP2C and CYP3A. Complexes with 1,10-phenatrolin (3) and (4) induce CYP3A4, inhibit CYP2C9 and do not affect CYP2C19 expression. All compounds have a dose-dependent cytotoxic effect on HepG2 and MRC-5: the compound with 5-methyltetrazolate anion (4) has the same effect on cell lines, compounds with 5-phenyltetrazolate anion (2) and (3) have selective effect. Complexes with 1,10-phenatrolin are effective on both 2D and 3D models.
Conclusion. The [Cu2(phen)2(FT)4] complex (3) can be used as a basis for creating an antitumor compound, but further modification of the structure is required to increase the selectivity to tumor cells.

This article presents an overview of modern statements of the induced sputum method; detailed description of the methods and protocols for taking sputum in adults and children, methods for processing the obtained substance. The paper describes in detail the features of the cellular composition of induced sputum in healthy individuals and in patients with bronchial asthma, emphasizes the importance of the eosinophilia level as a prognostic and diagnostic criterion of asthma and also determines the functions of other induced sputum cells such as neutrophils, macrophages, basophils. The article is illustrated with photographs of sputum microscopy. In addition to sputum cytology, we give accent to the possibility of using other research methods such as an identification of viral and bacterial pathogens, genomics, proteomics, lipidomics, metabolomics, determination of the concentration of various mediators in the sputum supernatant. The paper presents the ideas on biochemical inflammatory markers and remodelling of the respiratory tract in asthma, which can be determined in sputum (C3a anaphylatoxin, clusterin, periostin, eosinophil-derived neurotoxin, folliculin). In addition, we summarize the information on inflammatory phenotypes of bronchial asthma, emphasize their variability and modification depending on the period of the disease, prescribed treatment, intercurrent respiratory infections, and smoking. The article also presents detailed characteristics of eosinophilic, neutrophilic, mixed and small granulocyte phenotypes of bronchial asthma, and describes the most frequent correlations of phenotypes with the severity and course of the disease, with lung function parameters and other indicators. The paper gives an account of the possibilities of using the induced sputum method for a comprehensive assessment of the course, asthma controllability and the effectiveness of drug therapy, as well as for a personalized selection of an antiinflammatory drug considering the inflammatory phenotype.

Bacterial ecosystem of the gut plays a fundamental role in the normal functioning of the metabolic and immune systems. Functional bowel disease and obesity are highly prevalent in the population and place a heavy burden on healthcare system. Both comorbidity and multimorbidity are considered to be common for obesity and intestinal functional disorders. Changes in the microbiota can be both the cause and consequence of each disease: intestinal functional disorder changes the composition of the microbiota, resulting in obesity, and vice versa. Intestinal functional disorders and obesity are characterized by a similar type of dysbiosis.
The aim of the review is to analyze the research findings available to date in order to establish the relationship between the gut microbiome, functional bowel disease and obesity. The researches have shown that patients with intestinal functional disorders have a different gut microbiome than healthy individuals. For intestinal functional disorders, the general patterns of the intestinal microbiota composition were described, and the characteristic taxonomic groups of bacteria were identified. On the other side, it must be noted that there is no clear correlation between intestinal functional disorders and obesity in terms of the microbiota. This can be explained by the high heterogeneity of intestinal functional disorders, as well as by the lack of a unified approach to creating a study design, by different sizes of population samples and also by different diagnostic criteria. The necessity to determine the criteria in the development of the design of future studies is discussed.

Background. The relationship between pathogens of new diseases and tick-borne infections is an underinvestigated direction in the problem of infectious diseases.
The aim. To show the features of identifying the markers of Borrelia burgdorferi, tickborne encephalitis and SARS-CoV-2 pathogens on the example of a case of a triple mixed infection (Lyme disease, tick-borne encephalitis and COVID-19) and using comprehensive studies.
Methods. In 2019–2021, a comprehensive study of 7 blood samples from a patient with mixed infection was carried out. We used real-time polymerase chain reaction (PCR), enzyme immunoassay (ELISA) and determined antigen, IgM, IgG antibodies, and avidity index (AI) of IgG antibodies.
Results. Ixodid tick-borne borreliosis was diagnosed in a patient 5 months after contagion. Only high-avid Lyme-IgG antibodies were detected. Low-avid Lyme- IgG antibodies appeared against the background of a reduced general condition. At the same time, high-avid IgG (cut-off index (COI) – 7.8) and IgM (COI = 1.2) antibodies to the TBE virus were detected. In July 2020, the patient was infected with SARSCoV-2. TBE virus which passed into the body simultaneously with Borrelia in the fall of 2019 was activated. Although the patient did not have specific symptoms of TBE, in subsequent blood samples (No. 4, 5, 6) we found TBEV antigen (optical density (OD) – 4.3; 1.9 and 2.0 respectively) and IgM (COI = 1.3; 0,9 and 0 respectively). These results were recognized as TBEV activation, which contributed to an increase in the avidity of IgG antibodies (AI = 65 %; 100 % and 63 % respectively). IgM antibodies to SARSCoV-2 virus were not detected, as opposed to the high levels of IgG (COI = 8.2; 8.1; 8.4 and 14.7 respectively).
Conclusions. Therefore, using not only the common methods of diagnosing (PCR and ELISA), but also the determination of the antibody avidity degree, we have shown that when analyzing a case of a triple mixed infection, B. burgdorferi dominates in the human body and causes a long-term chronic course of the disease.

Background. With the increased use of combination antiretroviral therapy, the mortality of people living with HIV has decreased significantly, which has led to an increase of comorbidity and secondary HIV-related pathology in both adults and also in children and adolescents living with HIV infection. The incidence of children and adolescents with HIV infection and those in the general population varies significantly.
The aim. To assess the frequency and range of chronic comorbidities in children and adolescents with perinatal HIV infection Methods. We carried out an observational study. Data on the incidence of 161 children with perinatal HIV infection registered in the Irkutsk Regional AIDS Center were copied.
Results. Overall incidence of tuberculosis (18633.5 per 100 000 children), diseases of the digestive system (24844.7 per 100 000 children), diseases of the eye and adnexa (28571.4 per 100 000 children), diseases of the nervous system (18012.4 per 100 000 children), mental and behavioral disorders (13,664.6 per 100 000 children) in children with perinatal HIV infection is the higher than in children of comparable age. The overall incidence values of the endocrine system diseases, eating and metabolic disorders, diseases of the ear and mastoid process, diseases of the circulatory system, diseases of the genitourinary system, as well as congenital disorders and chromosomal disorders in children and adolescents with and without perinatal HIV infection are comparable.
Conclusion. The prevalence of diseases of the circulatory, respiratory and genitourinary systems in children with perinatal HIV infection is comparable to that in the corresponding population. Prevalence of tuberculosis, anemia, diseases of the gastrointestinal tract, diseases of the eye and adnexa, diseases of the nervous system, mental and behavioral disorders is higher compared to children not exposed to HIV.

Background. Production of pro-inflammatory cytokines including interleukin 6 (IL-6) is activated in COVID-19. Using olokizumab which inhibits IL-6 production in treatment of COVID-19 is pathogenetically justified.
The aim. To study in real clinical practice the efficacy and safety of using the IL-6
inhibitor (olokizumab) in treatment of patients with confirmed COVID-19 pneumonia.
Materials and methods. The first group included 41 hospitalized patients with confirmed COVID-19 pneumonia having complex therapy including olokizumab. The control group consisted of 66 patients with confirmed COVID-19 pneumonia who did not have therapy with IL-6 inhibitor. We analyzed clinical (volume of lung involvement, respiratory failure degree, body mass index) and laboratory data (levels of T-troponin, lactate, procalcitonin, natriuretic peptide, C-reactive protein, fibrinogen, D-dimer, ferritin, erythrocyte sedimentation rate, glomerular filtration rate).
Results. The groups did not differ in gender, age, body mass index of patients, volume of lung tissue injury, and duration of hospitalization (p > 0.05). Respiratory failure of 2–3rd degree was more common in patients of the first group (χ2 = 6.3; p = 0.010). The initial levels of C-reactive protein (50.9 [34.2; 76.2] and 32.2 [9.9; 69.1] mg/L respectively; p = 0.009) and fibrinogen (6.0 [5.3; 6.7] and 5.2 [4.3; 6.2] g/l respectively; p = 0.005) in patients having therapy including olokizumab were significantly higher than in the control group. The levels of erythrocyte sedimentation rate, fibrinogen and ferritin, D-dimer, detected upon admission of patients to the hospital, didn’t have statistically significant differences. At discharge, the erythrocyte sedimentation rate in patients receiving olokizumab was statistically significantly lower (9.0 [5.5; 14.5] and 13.0 [7.0; 27.0] mm/h; p = 0.018).
Conclusions. Using olokizumab in the treatment patient with COVID-19 pneumonia has demonstrated a positive effect on clinical and laboratory parameters (erythrocyte sedimentation rate, fibrinogen level) in patients with pronounced inflammatory changes and respiratory impairment.

The COVID-19 pandemic has stimulated interest in the development of biotechnology, as well as in the search for new solutions in the diagnostics of immune processes. The response of immunoglobulins A, M and G had a significant role in the assessment of virus-specific immune responses. Later, it was understood that for a comprehensive assessment of adaptive immunity processes, it is reasonable to study its cellular component. One of the most affordable methods for assessing T cell immunity, which has proven itself in the diagnosis of other infectious diseases, such as latent tuberculosis infection, is IGRA ELISPOT.
The aim of the study. To determine SARS-СoV-2 specific immune response of T lymphocytes in vitro in the peripheral blood of volunteers from various groups using IGRA ELISPOT method. We evaluated the applicability of the method to assess T cell immune response to infection and vaccination. In addition, we determined the duration of the maintenance period of the SARS-CoV-2 specific T cells immune response induced by vaccination.
Materials and methods. The study was carried out on venous blood samples of volunteers from three groups: 1) hospital patients with COVID-19; 2) COVID-19 convalescents; 3) vaccinated against COVID-19. The T cell immune response was assessed using the TigraTest® SARS-CoV-2 test system, which determines in vitro the number of T cells secreting interferon-gamma in response to stimulation with SARS-СoV-2 peptides in two antigens panels: 1) peptides of the spike protein (S); 2) peptides of N, M, Orf3a and Orf7a proteins.
Conclusion. The IGRA ELISPOT assay is a specific and sensitive tool in the assessment of T cell immunity to the SARS-CoV-2 virus. The method makes it possible to assess SARS-CoV-2 specific T cell responses induced both by natural encounter with the pathogen and by vaccination. It is advisable to use the method in routine practice for comprehensive assessment of immunity to SARS-CoV-2.

Background. Molecular structures combining a phosphorus-containing counterpart and non-polar radicals are employed in design of pro-drugs as structural and functional groups necessary for transportation of drugs through cellular barriers. It is assumed that the carrier itself does not exhibit biological activity. However, the “organic phosphate – alkyl radical” complex may possess its own metabolic and pharmacological properties even in the absence of a drug moiety.
The aim. To study the effect of fluorinated alkyl phosphates on the growth of bacterial test cultures in an agar medium and to identify conjugated metabolic markers using UV/visible spectroscopy.
Materials and methods. The effect of six organyl phosphates on the growth of five types of bacteria under aerobic conditions was evaluated by the method of wells in an agar medium. For solutions containing cell metabolites of Pseudomonas aeruginosa, the absorption spectra were recorded at 250–280 nm. The principal component analysis (PCA) was used for multivariate comparative analysis of the spectra. Results. The studied organyl phosphates bearing the ethyl and propyl radicals are potential temporary carriers of the drug moiety, since they are capable of penetrating through cellular barriers. However, the fluorinated compounds exhibit bactericidal properties, the degree of which depends on the arrangement of fluorine atoms in the radical. The most active compounds are those exhaustively halogenated at the terminal carbon atom of the ethyl radical (-СН2-СF3), while non-fluorinated organyl phosphate is the least active. UV/visible spectra of P. aeruginosa cultivation products, according to PCA data, contain patterns reflecting the metabolic effects mediated by these structural features of the radicals.
Conclusion. In terms of practical application of the studied compounds, the activity of a proantibiotic based on organyl phosphate with a non-fluorinated ethyl(propyl) radical will be determined only by the specificity of the drug moiety. Exactly the same molecule, but exhaustively fluorinated at the terminal carbon atom of the alkyl radical, is likely to be characterized by lower specificity and higher activity under the additive (or synergistic) action of metabolically active groups.

The aim of the study is to evaluate the effect of R. uniflorum dry extract on morphofunctional state of mice thymus and spleen at cyclophosphamide immunosuppression.
Materials and methods. The experiments were carried out on F1 (CBAxC57Bl/6) mice 18–20 g of weight. Immune deficiency was simulated by a single intraperitoneal introduction of cyclophosphamide in the dose 250 mg/kg. R. uniflorum dry extract in the dose 100 mg/kg was administered per os for 14 days. The thymus and spleen were fixed for histological studies on day 16. The thymus total area, the cortex and medulla area, the connective tissue capsule thickness, the spleen white and red pulp area were used to measure on micropreparations stained with hematoxylineosin and azure-eosin. The cell density and the cellular composition were calculated in the thymus cortical substance.
Results. The R. uniflorum extract increased the thymus total area and the corticomedullary index by 37 and 26 % (p ≤ 0.05), respectively. The cells density increased in the cortical substance, it decreased in the medulla, as a result “layer inversion” is not observed in any animal of the experimental group. The number of proliferating lymphocytes, blasts and large lymphocytes increased; the number of destructive cells and macrophages decreased in the cortical substance. The spleen white pulp relative volume was 39 % higher than in the control.
Conclusions. The R. uniflorum dry extract had an immunocorrective effect on the thymus and spleen morphofunctional state at cyclophosphamid immunosuppression.

Background. Hepatic encephalopathy is an actual problem of modern medicine. However, its pathogenesis and histological picture are currently insufficiently studied. Less is known about the impact of the nature of primary liver disease on pathogenesis and histological picture of hepatic encephalopathy. This determines the relevance of further morphological studies of the brain in the late stages of liver cirrhosis of various etiologies.
The aim. To establish and compare the morphological changes in the brain in alcoholic liver cirrhosis and viral (hepatitis C virus (HCV)) cirrhosis.
Materials and methods. The morphological study of the brain of 40 deceased in outcome of HCV-associated cirrhosis and 23 patients died in outcome of chronic alcoholism was carried out. Histological changes in various parts of the brain were studied using survey and elective stains. The immunohistochemical study of HCV NS3 and CD68 expression in different brain regions was performed in cases of HCV-infection.
Results. The changes of neurons, glial cells and cerebral microvessels underlie in the basis of morphological picture of brain damage in both studied groups underlie that corresponds to the “classical” model of hepatic encephalopathy pathogenesis. At the same time, a number of morphological features were observed. The most prominent differences concerned the manifestations of the glial reaction. The productive changes of macroglial cells with the appearance of multiple Alzheimer’s astrocytes type 2 as well as spongious changes in subcortical white matter dominated in the observations of alcoholic cirrhosis. In contrast, microglia cells reaction (microgliosis) in white matter was noticed in HCV-associated cirrhosis.
Conclusions. The differences in histological signs of brain in the terminal stages of liver disease of viral and alcoholic etiology are shown. They broaden current idea of morphological picture of hepatic encephalopathy, and may be used to study its pathogenesis.

The aim of the study. To assess the influence of radiofrequency circumferential exposure modes on the morphological parameters of the pulmonary artery tissues in animal experiment (pigs).
Material and methods. In the experiments, we used outbred pigs divided into 3 groups (4 animals in each). The first experimental group included 188 histological samples of the pulmonary arteries (PA) after radiofrequency circumferential exposure on the PA using an ablator clamp. Two lines of exposure on the PA and two lines of exposure on each PA mouth were performed. Ablation was performed until the target level of tissue impedance between the ablator branches corresponding to the values at transmural damage was reached. The second experimental group included 162 histological samples of the PA after circumferential denervation of pulmonary trunk and both PA mouths. Ablation was completed upon reaching 50 % impedance level relative to the impedance values at transmural damage. The third group (control) included 55 histological samples of PA without radiofrequency exposure. The material obtained was studied using light microscopy, hematoxylin and eosin and van Gieson’s staining, and also by impregnation with silver salts according to S. Ramón y Cajal.
Conclusions. Morphological criteria for irreversible destruction of nerve fibers and ganglia of the pulmonary trunk adventitial layer and for PA bifurcation were obtained when using two studied ablation modes. Circumferential PA denervation using subthreshold power of radiofrequency exposure made it possible to avoid irreversible damage to the nerve endings and ganglia of the PA intimal layer and thus to preserve physiological neuroreflectory regulation of the PA and the entire pulmonary circulation. Turning off the cascade of pathological reflexes eliminates the factor of the progression of pulmonary hypertension associated with an increase in peripheral resistance of the pulmonary arterioles precapillary link.

In this review, we analyzed the domestic and foreign literature on the use of corneal lenticula obtained by keratorefractive surgery using the SMILE technology (SMall Incision Lenticula Extraction). Research is being actively carried out on the use of a lenticular tissue for refractive purposes: for the correction of hyperopia (LIKE – Lenticular Intrastromal Keratoplasty), for the correction of presbyopia (PEARL – PrEsbyopic Allogenic Refractive Lenticule). A significant amount of works are devoted to the use of lenticular tissue for the treatment of keratectasias of various origins. For example, a number of authors for the treatment of keratoconus suggest implantation of a lenticule into the recipient’s corneal pocket formed by a femtolaser (SLAK – Stromal lenticule addition keratoplasty). Clinical cases of combined treatment are described: implantation of a lenticule and corneal intrastromal segments for the treatment of corneal pellucid degeneration. A large number of works are devoted to the use of lenticules for tectonic coverage of ulcerative defects, marginal thinning in Mooren’s ulcer. Several clinical cases of the use of a corneal lenticule to cover a deep corneal defect in recurrent pterygium are described. This review also included articles on the storage and decellularization of corneal lenticules. The analyzed articles show a wide area of application of the corneal lenticule; however, more research is required in each of the areas of application, and it is also necessary to solve the problem of procurement and storage of lenticular tissue.

Background. Research and maintenance of an acceptable quality of life is considered to be the main aim of treating chronic incurable disease including glaucoma.
The aim. To perform a comprehensive assessment of the quality of life of patients with glaucoma when using various types of surgical and conservative treatment before treatment and 1 month after treatment.
Material and methods. We carried out a randomized controlled study which included 229 patients, divided into 2 groups. The first group of patients (133 people) received various types of surgical intervention for glaucoma, consisted of 6 subgroups. They had the following types of surgeries: sinus trabeculectomy with the use of “Glautex” drainage implant; classical sinus trabeculectomy; sinus trabeculectomy with implantation of drainage made of a collagen hemostatic foam; transscleral laser cyclocoagulation of the ciliary body; cataract phacoemulsification in comorbid primary open-angle glaucoma and in primary closed-angle glaucoma. The second group consisted of 96 patients who received conservative treatment; it consisted of 4 subgroups. Patients of subgroups of the 2nd group received various types of conservative therapy against the background of local antihypertensive therapy: complex treatment with the use of vasoprotectives, vitamins, nootropics in a hospital setting; neuroprotective therapy in the form of Retinalamin intramuscular injection. After receiving informed voluntary consent to participate in the study, all patients underwent a comprehensive assessment of the quality of life using universal, specific and psychological questionnaires (SF-36, visual analogue scale, EQ-5D, VFQ-25, GQL-15, VF-14 and HADS) before treatment and 1 month after treatment.
Results. The therapy had a positive effect on the quality of life in both groups of patients, however the most pronounced positive dynamics is registered in patients having conservative therapy as compared with those having surgical treatment. The use of valid, reliable questionnaires makes it possible to fully assess the quality of life in glaucoma.

The aim. To identify neuropsychological signs of a decrease in higher mental functions associated with professional exposure to physical factors.
Materials and methods. The study involved 40 patients with vibration disease caused by local vibration (Group 1), 50 patients with vibration disease caused by combined exposure to local and general vibration (Group 2), 71 civil aviation pilots with an established diagnosis of occupational sensorineural hearing loss (Group 3), and 38 healthy men (Group 4, control group). Methods of neuropsychological testing were used.
Results. In Groups 1–3 the state of functioning of the cognitive sphere is represented by a mildly pronounced nature of impairments. The results of MMSE and FAB tests in patients of Groups 1–2, when compared with Group 4, determine a decrease in the functional activity of the frontal lobes and subcortical structures (25 (24–27), 25 (22–26), 15 (14–16) and 15 (13–16) points respectively). The most informative feature associated with the fact of occupational exposure to local vibration is the indicator of long-term memory (F = 9.41; р = 0.003); with combined impact of local and general vibration – short-term memory (F = 11.0; р = 0.001); with aircraft noise – objective gnosis (F = 8.48; р = 0.001). The obtained features make it possible to track with a high degree of accuracy the development of a decrease in cognitive functions in this contingent (86.1 %, 84.8 % and 72.1 % respectively).
Conclusion. Common signs of changes in the cognitive sphere and lesions of the brain structures in patients with vibration disease are a decrease in praxis, impressive speech, for occupational sensorineural hearing loss – the lack of analytical-synthetic and conceptual thinking, object and finger gnosis, characterizing the inferiority of the functioning of the frontal and parietal regions of the left hemisphere.

Indicators of physical development appear to be environmentally sensitive and thus we can consider them the main characteristics of the population health.
The aim. To assess the line of physical development main variables in the ontogenetic aspect (data from the North born male subjects aged from 8 to 77).
Material and methods. Three thousand seven hundred and ninety-four male Caucasians from 17 age groups were examined to analyse their physical development.
Results. The study showed longer body length variables as the region-related somatometric picture which is characteristic of male Caucasian northerners in comparison with those from other regions of the Russian Federation, as well as from other countries. Besides, they exhibited significantly lower body mass index and reported to have had lower body weight since the age of 17. We can see the modern northerners’ somatotype being influenced by regional extremes. That also includes the end of the body growth processes by the start of ontogenesis in the youth. The line pattern of annual growth observed in the body length and weight variables indicates a combined pronounced dynamics in the 11 to 16 age period. By the age of 60–77 years subjects tend to decrease in the body length with a significant increase in the body weight and body mass index by the age of 31–36.
Conclusion. The study suggests that identifying risks for the development of noninfectious and cardiovascular diseases caused by accelerated BMI in older populations requires monitoring of the North inhabitants’ main physical development indicators as well as the body annual growth variables.

In this review, an analysis of modifiable risk factors for the development and progression of periodontal tissue diseases was carried out. The review highlights the data on the relationship of periodontal infection, tobacco smoking, diabetes mellitus, cardiovascular disease, drug-induced periodontal tissue damage, stress, and obesity with the risk of developing and progression of periodontal tissue diseases. A rather detailed analysis of the mechanisms of pathogenic influence of the microflora of the oral cavity, including in the subgingival plaque, was carried out. The mechanisms of the pathological effect of smoking on the state of periodontal tissues are described. Data on the effect of periodontal treatment on glycemic control in patients with diabetes mellitus are presented. The article emphasizes the importance of the presence of periodontal diseases as a risk factor for cardiovascular and cerebrovascular diseases, describes the mechanisms of the mutual influence of cardiovascular pathology and the inflammatory process in the periodontium. In addition, the article presents the possibilities of the iatrogenic effect of systemic drugs on the state of periodontal tissues. The data on the influence of stress loads on the development of dental diseases are presented. The review article describes in detail the mechanisms of influence of overweight and obesity on the risks of development and progression of periodontal tissue diseases. Based on the results of the scientific research publications presented in the article, it can be stated that not only the dentist, but also doctors of other specialties need to work to change the modifiable risk factors for the development and progression of periodontal diseases.

Biceps brachii distal tendon injury is rare, 2.55–5.35 per 100,000. This nosological form did not have a gender modality and was previously found mainly in middle-aged men (46.3 y.o.). By 2022, this injury “rejuvenated” and began to occur more often, covering the categories of juniors and young athletes, whose professional activities have expanded significantly with the advent of new power disciplines, contact sports and popularization of bodybuilding. The authors note the negative impact of smoking and the use of anabolic steroids, statins and obesity on the incidence of these lesions. The maximum supination force in this type of injury is reduced by an average of 40 %, and the maximum flexion force is reduced by an average of 20 %. Considering the significance of functional disorders not only of the elbow joint, but also of motor patterns of the entire upper limb girdle for professional athletes, sports-organized people and people involved in the physical aspects of labor, surgical treatment is recommended. Nonsurgical treatment can be aimed at suppressing edema and inflammation, limiting early movements in the elbow joint and increasing secondary muscle tension, and it is suitable for patients with low functional demand, poor compliance and high risks of both surgical treatment and anesthesia care. That is, the choice of treatment tactics is still based, in addition to anatomical changes and on the “subjective” patient data, his/her needs for physical activity and requires an algorithmic approach in order to avoid both known complications and confidently predict a positive result during the prehospital period. Based on ten years of clinical and practical experience adjusted by widely available scientific periodicals, we have developed a scheme that is understandable to every specialist in the field of traumatology, orthopedics or sports medicine, and is applicable regardless of the medical institution level. For the first time, this scheme was published in this work.

The reverse shoulder arthroplasty in the conditions of the modified anatomy of the glenoid is complex and often excludes the possibility of using the standard tactics of installing the glenoid component. There are no identical glenoids, each articular cavity of the scapula differs in height, width, angle of inclination, density of bone tissue, absence or presence of various defects of bone tissue. Given the variety of options for changing the structure and quality of the glenoid bone tissue in injuries and diseases of the shoulder joint, each case of endoprosthetics should be considered individually. In order to perform an adequate metaglen installation, these parameters must be normalized or standardized. The purpose of this work is to review the domestic and foreign literature devoted to the features of reversible shoulder joint replacement during deformation of the articular cavity of the scapula. Based on the analysis of literature data, the percentage of complications associated with unsatisfactory treatment results due to the instability of the glenosphere is quite large, which indicates the lack of elaboration of this topic and its relevance for practical traumatology and orthopedics. The paper considers eccentric non-standard methods of rimming the articular cavity of the scapula, methods of its bone grafting, the use of metaglens made taking into account the deformation of the glenoid, as well as indications for the use of technology for the individual manufacture of scapular components. The study and analysis of indications for the use of various types of techniques for solution glenoid deformities made it possible to systematize and differentially approach the issue of preoperative planning and choosing the correct, right treatment tactics in complex cases of reversible shoulder joint replacement.

Introduction. The search, development and introduction of new drugs with an immunotropic effect are one of the priority tasks of modern immunopharmacology. Numerous studies have proven the immunotropic activity of individual substances isolated from medicinal plants (flavonoids, polysaccharides, ecdysteroids, terpenoids, etc.). In the present study, it is of interest to determine the immunomodulatory effect of individual substances isolated from Silene jeniseensis Willd.
The aim of the study. Determination of the immunomodulatory activity of individual substances isolated from Silene jeniseensis: flavonoid isoorientin-2”-O-rhamnoside, polysaccharide arabino-3.6-galactan and ecdysteroid 20-hydroxyecdysone under conditions of cyclophosphamide induced experimental immunosuppression.
Methods. Experiments were carried out on F1 (CBAxC57Bl/6) mice. Immunodeficiency was modeled by intraperitoneal administration of cyclophosphamide to control group animals in the dose 250 mg/kg once. Experimental groups of mice received the test substances intragastrically once a day for 14 days against the background of immunosuppression in the following doses: isoorientin-2”-O-rhamnoside – 10 mg/ kg, arabino-3.6-galactan – 3 mg/kg, 20-hydroxyecdysone – 3 mg/kg. The effect of substances on cellular immunity was determined in a delayed hypersensitivity reaction, humoral immunity was determined in an antibody formation reaction by local hemolysis according to A.J. Cunningham. The phagocytic activity of peritoneal macrophages was studied in relation to colloidal ink particles.
Results. With the introduction of isoorientin-2”-O-rhamnoside, arabino-3.6-galactan and 20-hydroxyecdysone in experimental animals, there was an increase in the index of delayed-type hypersensitivity reaction by 1.3–1.4 times, the absolute and relative number of antibody-forming cells by 1.4–1.7 times, phagocytic index by 1.2–1.5 times compared with the data in the control group, which indicates the leveling of the suppressive effect of cyclophosphamide on cell-mediated immune response, antibody genesis and phagocytosis of macrophages.
Conclusion. Isoorientin-2”-O-rhamnoside and arabino-3.6-galactan have the most pronounced immunomodulatory effect. The obtained data allow us to consider the studied substances as promising plant immunomodulators.

Background. Urethral strictures are currently one of the most complex pathologies in reconstructive urology. The most promising direction in this area is the development of single-stage surgical interventions that meets modern requirements for the quality of life of patients.
The aim of the study. To evaluate the possibility and the effectiveness of surgical treatment of extended recurrent tuberculous urethral strictures in men using a combination of a skin flap and a buccal graft. In the literature, there is no description of the use of this technique in patients with urethral tuberculosis.
Materials and methods. We observed 44 patients with urethral tuberculosis. Three men from this group of patients were diagnosed with tuberculous (post-tuberculous) extended recurrent stricture of the anterior urethra and they underwent combined single-stage urethroplasty with a ventral fasciocutaneous flap and a buccal graft using the inlay method in the penile region and with a buccal graft using the ventral onlay method in the bulbous urethra. Ultrasound of the urethra served as a method that determines the possibility of performing this surgery in case of maintaining a sufficient width of the urethral plate with a moderate degree of spongiofibrosis.
Results. Patients were under observation for 34, 50 and 54 months and have good long-term functional results – all patients have unassisted urination and no residual urine. Post-micturition dribbling persists in 1 patient. The overall effectiveness of the treatment of these strictures, taking into account the treatment of repeated cases of the disease recurrence, is high.
Conclusion. This technique demonstrates the possibility of performing a single-stage reconstruction of the anterior urethra in patients with extended recurrent tuberculous (post-tuberculous) urethral strictures and is also applicable for the surgical treatment of urethral strictures of other origins.

The aim of the study. Description of the medical history and discussion of treatment tactics in a puerperal woman after a caesarean section against the background of pancreatic necrosis, panmetritis, abdominal sepsis, COVID-19.
Material and methods. A 30-year-old pregnant woman (30–31 weeks) was hospitalized in a perinatal center 5 days after the onset of girdle pain in the abdomen and uncontrollable vomiting, which did not bring relief. She had a history of caesarean sections 10 and 5 years ago. Sterile pancreatic necrosis was diagnosed. Successful caesarean section was performed. During the revision of the abdominal cavity, multiple plaques of fatty necrosis, omentobursitis were found in the upper abdomen. The treatment included pancreatic abdominization, cholecystostomy, abdominal drainage. Clinical roentgenologic examination and PCR-test verified COVID-19.
Infected pancreatonecrosis developed, complicated with necrotic omentitis, abscess of the omental bursa (Enterococcus faccilis 107 CFU, Acinobacter baumani 106 CFU), abdominal sepsis, successfully treated. During vaginal examination, hemorrhagic discharge appeared (Klebsiella pneumoniae 105 CFU, Pseudomonas aeruginosa 105 CFU). Extirpation of the uterus revealed the defect of the anterior wall, thrombosis of the uterine arteries and veins, peripheral vessels. The patient recovered. The body build index was 26.03 kg/m2 at admission, 18.22 kg/m2 – at discharge, 23.61 kg/ m2 – 3 months later.
Conclusion. 1. During the COVID-19 pandemic, pregnant women are often targeted by SARS-CoV-2. Prevention, diagnosis and treatment of coronavirus infection should be carried out according to the recommendations approved by the authorized health organ. 2. In the presented case report, the pathogenesis of complicated sterile pancreatonecrosis, cesarean section, abdominal sepsis were significantly influenced by changes due to organ ischemia in the result of peripheral vessels thrombosis. 3. The severity of the patient’s condition was certainly determined by the miscellaneous microbial profile – association of four agents of aggressive in-hospital infection in high concentration.

D-lactic acid stereoisomer (D-lactate) is produced by the intestinal microflora and can enter the bloodstream and cause in some cases a condition of acute D-lactic acidemia known as short gut syndrome. The level of D-lactate in blood and in the contents of the intestine is considered as a promising marker of the development of inflammation associated with microflora disorders, as well as with the development of a bacterial infection, while the mechanism of its entry into the blood of vertebrates from the intestine has not been studied in detail.
The aim of the study. To investigate the relationship between the level of D-lactate in blood and in the intestine, taking into account the permeability of the intestinal epithelium.
Materials and methods. As a model object of the study, we used juvenile rainbow trout O. mykiss. For 54 days, they were high-carbohydrate or high-protein fed. Since different types of bacteria prefer different substrates, it was expected that at the end of the experiment, the composition of the intestinal microflora would be significantly different in fish fed with different diets. The content of D-lactate in blood plasma in vitro was assessed by the Larsen method with modifications; intestinal permeability was assessed by the intensity of fluorescence of the FITС-Dextran stain in the blood of fish. The analysis of the metagenome of samples of the contents and epithelium of the fore and hind intestine was carried out. The hematological profile was partially characterized using blood smears taken immediately after fish blood sampling. By the means of a different diet, it was possible to obtain two groups of fish that differ significantly in the permeability of the intestinal epithelium and in the content of D-lactate in the intestine. At the same time, despite the differences between the experimental groups in the content of D-lactate in the intestine and in intestinal permeability, no significant differences in D-lactate level in blood were found between them. Analysis of the composition of the intestinal microbiome by metabarcoding for the 16S rRNA gene revealed the absence of lactobacilli in the production of D-lactate in fish.
Results. It was shown that the mechanism of accumulation of D-lactate in the blood plasma in fish is less associated with increased intestinal permeability or hyperproduction of this metabolite by the intestinal microflora and is more associated with the utilization of D-lactate in the body. In the experiment, it was not possible to achieve a significant change in the species composition of the intestinal microflora of trout under the influence of a highcarbohydrate diet for 54 days compared to fish that received high-protein diet. Some tendencies towards changes in the composition of the microflora were found in the contents of the hindgut, and perhaps with a longer exposure, these changes could reach a statistically significant level.

Background. A typical extreme factor is hypoxia, which significantly affects the ability to perform tasks of professional activity, in particular, physical activity of various intensity. Physical and neuro-emotional stress under conditions of hypoxia can cause the breakdown of compensatory and adaptive mechanisms with the development of extreme and critical conditions.
The aim of the study. Quantitative assessment of the effect of hypoxia on the physical performance of laboratory animals at different levels of their natural resistance.
Research methods. Modeling of hypoxia was carried out by the methods of pressure chamber rise of laboratory animals and the administration of a methemoglobin former. Resistance to hypoxic hypoxia was assessed by the criterion of the threshold elevation, to hemic hypoxia – by the lifetime. The criterion for the functional state of laboratory animals was their ability to perform physical activity, which was created by treadmill run or swimming with a load.
Results of the study. An altitude of 3500 m causes a decrease in the physical performance of male rats by a third of normoxia level; an altitude of 5000 m – decrease by two times; an altitude of 6500 m – decrease by four times, and at an altitude of 8000 m makes running physical activity by rats impossible. A mild degree of hemic hypoxia causes a decrease in swimming time by almost 2 times, which corresponds to the effect of an altitude of 5000 m on the working capacity; and a moderate degree of hemic hypoxia causes a decrease in swimming time by more than 3 times, which approximately corresponds to the effect of an altitude of 6000 m. The level of resistance to hypoxia has a moderate effect on physical performance, and the factor of a low level of physical performance has almost no effect on the resistance to hypoxia (28 % and 7 % of the trait variability respectively). In animals with an initially low level of resistance to hypoxia, there is also a decrease in working capacity by an average of 20 %.
Conclusion. Hemic hypoxia is an adequate model in studies with a complex effect of various extreme factors. Simulation of mild hypoxia caused by the administration of 30 mg/kg of sodium nitrite is an optimal method.

Background. The formation of a pseudarthrosis is one of the most severe complications of bone fractures. Pseudarthrosis occurs as a result of a disorder in the fracture union, has a poor prognosis and requires long-term treatment and repeated surgeries. A small number of representative pseudarthrosis models makes it difficult to conduct preclinical studies of promising pharmacological substances, bone replacement materials and surgical methods of treatment.
The aim. To develop and to validate an experimental model of normotrophic pseudarthrosis of a rabbit’s tibia by creating diastasis between bone fragments, forming local vascularization disturbance and using unstable fixation.
Materials and methods. The study was carried out on Soviet Chinchilla rabbits. The animals were divided into 2 groups: in experimental group, we formed tibial pseudarthrosis; in control group, we made a simple transverse tibial fracture. The pseudarthrosis was formed by segmental resection (5 mm) of the middle third of the tibia, bone fragments dilatation for 5 mm, removal of periosteum and bone marrow within 5 mm followed by daily destabilization of a fracture in an external fixation device. The duration of the experiment was 6 weeks. X-ray examination of the fracture area was carried out weekly, multi-layer spiral computed tomography (MSCT) and histological examinations were carried out at the end of the experiment.
Results. The survival value in the experiment was 100 %. According to weekly X-ray examination, fracture union was registered only in the control group and occurred on average on the 22,8 ± 5,1 day, while the formation of pseudarthrosis was observed only in the experimental group, and radiographic signs of a pseudarthrosis were noted on average on the 33,6 ± 3,5 day. The formation of a pseudarthrosis by the end of the experiment was confirmed by MSCT and histological studies.
Conclusions. The developed model of the normotrophic pseudarthrosis of a rabbit’s tibia can be used for experimental tests of various factors for stimulating reparative regeneration and methods for treatment of the pseudarthrosis.