The aim of the work was to study the effect of fractions from Saussurea controversa and Мeadowsweet extracts on hemopoiesis and regeneration of bone tissue, which are the main target indicators in experimental osteomyelitis.

Materials and methods. In the experiment we used butanol, water and element-organic fractions from the Saussurea controversa extract as well as ethyl acetate, butanol and water fractions from the Мeadowsweet extract, obtained by liquid extraction of the extracts from corresponding plants with the help of organic solvents. After modeling osteomyelitis of the right femur in rats and course treatment for 28 days, the state of bone marrow hemopoiesis was evaluated and morphological examination of the affected limb was performed.

Results. The butanol fraction (at a dose of 10 mg/kg) containing flavonol glycosides, the water fraction (at a dose of 80 mg/kg) containing polysaccharides in its composition and the element-organic fraction (at a dose of 10 mg/kg) represented by organic calcium showed the highest osteogenic activity in the Saussurea controversa extract. The water fraction from the Meadowsweet extract (at a dose of 50 mg/kg) demonstrated pronounced hemopoietic activity due to stimulating erythro-, granulo- and lymphopoiesis in the bone marrow of rats with experimental osteomyelitis. 

The goal is to study the mechanisms of linoleic acid-dependent oxidative damage to hemoglobin in blood erythrocytes of pregnant women with cytomegalovirus (CMV) infection during the first trimester.

Materials and methods. The study included 55 CMV-seropositive pregnant women at 8–11 weeks pregnant, aged 24,7 ± 0,18 years. 20 women had exacerbated cytomegalovirus infection and in 35 women a latent course of the disease was observed. The control group consisted of 20 CMV-seronegative pregnant women, comparable in age and gestational age with the group of pregnant women with cytomegalovirus infection. The levels of linoleic acid, superoxide dismutase, glutathione peroxidase and methemoglobin in the blood were studied by the spectrophotometry. Glutathione was determined by histochemical methods, the total amount of hemoglobin was measured using the automatic hematological analyzer, and hydrogen peroxide level was calculated by enzyme immunoassay.

Results. In cytomegalovirus infection, an increase in the indices of exogenous hydrogen peroxide and linoleic acid in blood erythrocytes of pregnant women is observed. During the period of acute disease in the first trimester of pregnancy it causes oxidative modification and a decrease in the level of not only superoxide dismutase, glutathione peroxidase and glutathione, the processes involved in the redox regulation of thiol-disulfide exchange of erythrocytes, but also hemoglobin with formation of large amount of methemoglobin, which contributes to reduction of oxygen metabolism and development of hemic hypoxia. In the latent course of the disease, the oxidative damage to hemoglobin in the erythrocytes of pregnant women is mitigated by the increase in the activity of redox enzymes, which maintains oxygen homeostasis at the level necessary for the development of pregnancy. 

Introduction. In the modern world people are exposed to the influence of adverse psychological and physical factors, escalating in intensity. The search for new pharmacodynamic effects of [1,3,5]-thiadiazine derivatives designated by significant biological activity of these compounds is an essential issue.

Aim. To research adaptogenic activity of tetrahydropyrido[2,1-b][1,3,5]thiadiazine derivatives using a modified Porsolt Forced Swim Test.

Materials and methods. Four substances from the group of 3-R-8-aryl-6-oxo-3,4,7,8-tetrahydro-2H,6Hpyrido[2,1-b][1,3,5]thiadiazine-9-carbonitriles were selected for the research. Rats were divided into a control group, 5 reference groups (amitriptyline, caffeine, thiotriazolin, thiocetam, ginseng) and 4 experimental groups according to the number of the studied original tetrahydropyrido[2,1-b][1,3,5] thiadiazine derivatives.

Results. Intragastric injection of substance 2 for 5 days in the modified forced swim test (forced swimming with freight) increased work capacity and endurance of the rats by 103.42% as opposed to the initial results. The detected adaptogenic activity of this tetrahydropyrido[2,1-b][1,3,5]thiadiazine derivative six times exceeds adaptogenic activity of ginseng and seven times that of amitriptyline. The rats in the control group were active for a bit longer time. Ginseng raised the time of activity by 17% at day 5. Caffeine essentially reduced work capacity and endurance. Amitriptyline showed adaptogenic activity at day 3 of the research (increase by 10.4%). Thiotriazolin also showed adaptogenic activity on day 3 of the research (increase by 30.17%). Thiocetam increased the time of activity by 78.55%. Substance 4 had adaptogenic activity too; it increased the time of activity in aversive conditions by 58.25%, which three times exceeds this parameter for ginseng and four times for amitriptyline. 

Objectives. To substantiate the effectiveness of the wound coating developed by us, which combines broad-spectrum antimicrobial effect, sorption activity, analgesic effect and prolonged action on a purulent wound.

Materials and methods. The material for the study was wound coating in the form of a film developed at Kursk State Medical University (Russian patent number 2605343). Experimental animals (Wistar rats) were divided into 2 groups (comparative and experimental) of 36 animals in each. In all the experimental animals a purulent wound was modeled according to the method proposed by P.I. Tolstikh. Local anesthetic activity was determined on rabbits of the Chinchilla breed (20 individuals in each group). In the course of the study, the following methods were used: microbiological method (identification of the areas of growth retardation and wound contamination), visual assessment of the wounds, planimetric method, pH evaluation of the wounds, and Renier’s technique (for determination of the anesthetic activity). The data were processed statistically, and the statistical significance of the differences was determined using the nonparametric Mann – Whitney test. The differences were considered statistically significant at p ≤ 0.05.

Results. Before the experiment on animals, high efficacy of the developed film was proven for the most common test strains of microorganisms capable of causing wound infection, using the microbiological method of investigation. Using the Renier’s method, the ability of the film to provide a local anesthetic effect was demonstrated, which was significantly higher than that of the 2% lidocaine ointment. Following visual evaluation of the wound, it was found that purification and regeneration of the wounds occurred earlier in the animals from the experimental group. The speed of wound healing in the experimental group was 1.3 times higher at 1–3 days, whereas at 5–8 days the situation was reversed in favor of the comparison group. In addition, at day 8 wound contamination in the experimental group was 1.2 times lower than in the comparison group. According to the results of the pH evaluation, significant differences between the groups were noted at days 5, 8, 15. Approximation of pH values to those of intact skin also proved the effectiveness of using the developed film.

Conclusion. The results of the conducted studies confirmed broad-spectrum antimicrobial activity of the developed film, its local anesthetic activity and efficacy in treatment of experimental purulent wounds, which allows to recommend it for further preclinical trials. 

The aim of this work was to study changes in mechanical lung properties in cases of COPD in general and in different zones depending on the body position.

Materials and methods. The research was performed in 37 patients with chronic obstructive pulmonary disease (COPD) in the vertical and horizontal positions (VP and HP).

Results. The analysis of integral respiration mechanics has revealed a reduction in dynamic lung compliance and an increase in total non-elastic lung resistance during expiration (TNRexp) in HP vs. VP. At the same time, despite the increase in TNRexp in HP, the total work of breathing did not increase. Unlike healthy individuals, the COPD patients were characterized by the absence of differences in regional mechanical properties in both VP and HP. There were no differences in the respiration mechanics of the left lung, and the zones of the right lung only differed in the parameters of regional non-elastic work of breathing (NWBr ) that was increasing from top downwards: the indicators of NWBr during expiration and NWBr in the lower zone were higher as opposed to those of the upper zone in VP. As for HP, NWBr during inspiration, NWBr during expiration and NWBr were higher.

Conclusion. The data obtained contradict the prevailing opinion about an escalation in regional differences in ventilation and respiration mechanics under the influence of emerging focal and diffuse inflammatorysclerotic pathological changes in lungs and emphysema. 

Purpose. In experiment in vivo to study the features of regeneration of the conjunctiva and sclera of rats after surgery with intraoperative application of a 0.05% Ciclosporin A.

Materials and methods. Еxperimental animals (rats) (n = 48) were divided into the main group, including the subgroups a (n = 16) and b (n = 16) and the comparison group (n = 16). Performed a through cut of the conjunctiva and damage to the surface layers of the sclera one of the eyes of all animals. Further on the surgical trauma zone in the main group, the intraoperative application of the cytostatic was performed. In the subgroup a with a duration of 3 minutes, in the subgroup b – 6 minutes. In the comparison group a hemostatic sponge without a cytostatic was used intraoperatively.

Results. In the comparison group postoperative period proceeds with a stereotyped dynamics of cell phase changes in damaged tissues. In the end the development of dense conjunctival-scleral fusion in the area of surgical trauma was noted. Intraoperative application of 0.05% Cyclosporine A leads to a slowing of regeneration, preventing formation of rough conjunctival-scleral scar.

Conclusions. Intraoperative applications of 0.05% Cyclosporin A change the stereotyped dynamics of the inflammatory-reparative regeneration in the surgical intervention zone, inhibiting the migration of cells almost in 3 times and significantly (in 2 times) prolonging the duration of the macrophage phase. This causes a slowdown of reparative regeneration, prevents excessive scarring in the operating area. 

An experimental model of the obesity and type II diabetes mellitus formation in C57BL/6 mice using a high fat diet was developed and tested. In the study, it was shown that mice feeding high-fat diet had a significant body weight gain during the 3rd week. By the end of the experiment, body weight has more than doubled. In mice that feed chow diet, body weight increased by 50%, by the end of the experiment It was shown that high fat diet also induced glucose tolerance, and the insulin concentration tripled. The data obtained confirm the adequacy of the experimental model of diabetes mellitus type II in mice.

The goal was to identify gender differences in the clinical features of antipsychotic-induced hyperprolactinemia in patients with schizophrenia.

Materials and methods. 98 patients from the Department of Endogenous Disorders of the Research Institute of Mental Health Clinic in Tomsk were examined. Persons aged 18–50 were included with followup treatment for at least 1 year, whose condition corresponded to the ICD-10 schizophrenia criteria. Prolactin levels were determined by ELISA using the PRL Test System reagent kit (MonobindInc., USA). The base map of sociodemographic and clinical-dynamic features for patients with schizophrenia was used. Statistical processing of data was performed using the Statistica 12.0 software package. Mann–Whitney U test, Pearson’s χ² criterion, including Yates correction, and Fisher’s two-sided test were used for comparing small samples.

Results. The average serum concentration of prolactin in women was 52.4 ± 39.1 ng/ml, in men it was 26.7 ± 19.7 ng/ml. Hyperprolactinemia was detected in 23 (47.9%) women and 25 (50%) men. Among women with hyperprolactinemia, statistically significant “Weight Gain” and “Headache” parameters were more common (p = 0.044 and p = 0.005, respectively). Men with hyperprolactinemia had higher BMI rates (p = 0.0066). For the rest of the UKU paragraphs, no significant differences were found in both men and women. Men presented fewer complaints and were less willing to discuss sexual dysfunction.

Conclusion. Antipsychotic-induced hyperprolactinemia in patients with schizophrenia does not always have a full range of specific clinical manifestations and needs careful examination of patients with account of gender characteristics, as well as regular monitoring of the prolactin level in the serum of patients. 

Currently the development of technologies for labeling somatostatin with technetium-99m for diagnosing radionuclide neuroendocrine tumors is under way. Somatostatin analogues are binded with technetium99m only by the preliminary addition of a chelating agent. Therefore, it is important to develop a method for preparation of an octreotide derivative by modifying octreotide with precursors: ligands with high chelating ability for its tight binding with technetium-99m. ω-Bis(pyridin-2-ylmethyl)amino)aliphatic acids can be used successfully as such precursors.

The purpose of the study was to develop a method for obtaining a new octreotide derivative for diagnosing neuroendocrine tumors.

Materials and methods. The somatostatin octreotide analogue was used as the object of the study; succinimid-1-yl 6-(bis(pyridin-2-ylmethyl)amino)hexanoate was used as a chelating agent. Methods of high performance liquid chromatography and mass spectrometry were used to separate and analyze the synthesized compounds.

Results. A method to produce an original octreotide derivative using a succinimid-1-yl 6-(bis(pyridin2-ylmethyl)amino)hexanoate as a chelating agent was proposed. The conditions of analytical and semipreparative HPLC for the analysis and purification of the active octreotide derivative (a monosubstituted derivative of the amino acid residue of D-phenylalanine) were suggested.

Conclusion. The synthesized derivative of octreotide has a chelating center for strong binding to technetium-99m in its structure, which can be useful for diagnosing neuroendocrine tumors. 

Objective. To identify and evaluate the relationship between the level of proadrenomedullin and clinical and anamnestic data of patients with chronic heart failure of ischemic genesis.

Materials and methods. 240 men with chronic forms of coronary heart disease (mean age 55.9 [43; 63] years) and past Q-forming myocardial infarction were examined. Of these, 110 patients had chronic heart failure and preserved left ventricular ejection fraction (group 1) and 130 patients had chronic heart failure and dilatation with a low left ventricular ejection fraction (group 2). In all patients the MR-proADM level in the blood serum was determined.

Results. In the control group, the level of MR-proADM was 0.49 [0.18; 0.58] nmol /l. In the meantime, it was statistically significantly higher in the studied groups of patients than in the control group (p < 0.001 and p < 0.001, respectively). And in the group of patients with chronic heart failure and dilatation with a low left ventricular ejection fraction, it was statistically significantly higher than in the group of patients with chronic heart failure and preserved left ventricular ejection fraction (1.72 [1.56; 1.98] nmol/l and 0.89 [0.51; 1.35] nmol/l, respectively, p < 0.038). The study demonstrated the presence of statistically significant associations between the level of MR-proADM and the severity of chronic heart failure and exertional angina pectoris as well as between the presence of a constant form of atrial fibrillation and the levels of systolic and diastolic blood pressure.

Conclusion. MR-proADM is a new promising marker, which will be possible to use as a diagnostic standard for assessing the effectiveness of treatment of cardiac patients. 

Tobacco smoking in patients with asthma can intensify the bronchi mucosa damage and significantly worsen the course of the disease.

Aim. To assess the influence of tobacco smoking on the clinical manifestations of the disease, airway response to cold air exposure and destructive-cytological processes in the goblet cells of bronchial epithelium in patients with asthma.

Materials and methods. In 145 patients with asthma their asthma control level was determined by the Аsthma Control Test, lung function (FEV1 , %) and airway response (∆FEV1 , %) to a 3-minute isocapnic hyperventilation (–20 °С) of cold air (IHCA) were evaluated, and induced sputum (IS) was collected. In cytograms of IS a percentage content, the index of cell destruction (ICD) and the index of cytolysis intensiveness (IC) were assessed; histochemically the activity of myeloperoxidase (MPO) and the contents of glycoproteins were identified. The 1st group included 102 non-smokers and the 2nd group included 43 smokers.

Results. In IS of patients of the 2nd group in comparison with the 1st one we found intensification of the destructive (ICD = 0.47 ± 0.02 and 0.40 ± 0.02, respectively, р = 0.044) and cytolytic activity of goblet cells (IC = 0.22 ± 0.03 and 0.15 ± 0.02, respectively, р = 0.047) with the domination of the number of completely destroyed cells (21.7 ± 2.4 vs. 14.5 ± 1.6%, р = 0.043) and the decrease in the number of cells with a normal structure (52.5 ± 2.1 vs. 60.5 ± 3.1%, р = 0.047). For smokers it was typical to have high contents of neutrophils in IS (34.1 ± 3.0 vs. 23.9 ± 1.4%, respectively, р = 0.0006) and high level of myeloperoxidase in granulocytes of bronchi (94.3 ± 5.4 vs. 80.7 ± 3.6 pixels, р = 0.037). Smokers responded more actively to IHCA (∆FEV1 was –13.7 ± 2.6 vs. –7.9 ± 1.2%, respectively, р = 0.032), and the degree of the response correlated with the indices of destructive-cytological activity of IS cells.

Conclusion. Tobacco smoking in patients with asthma leads to the disturbance of the structure of goblet epithelium in the bronchi with the intensification of destructive-cytological processes, which is accompanied by a decrease in the level of glycoproteins in cytoplasm, an increase in the secretory activity of the goblet cells, neutrophilia, growth of oxidative peroxidase activity of granulocytes, worsening of the bronchial conductance, and intensification of airway response to cold air. 

Background. Dihydroquercetin (DHQ) is a natural flavonoid. It has a wide range of pharmacological effects, which includes anti-inflammatory activity. There is a gap in our knowledge about the biochemical mechanisms of the therapeutic potency implementation of this compound. This fact slows down the process of the drug development using DHQ. Molecular modeling is designed to further translate the research from the fundamental experimentation to the real clinical practice. Purpose. The study objective was to estimate DHQ as a cyclooxygenase-2 (COX-2) inhibitor by using in silico analysis.

Materials and methods. The information about the COX-2 structure was obtained from the Protein Data Bank (code 5KIR). The 3D-models of DHQ were generated by using the ChemBioDraw Ultra software. Docking was carried out in the GOLD program after the corresponding validation of molecular modeling algorithms based on experimental data of X-ray diffraction analysis.

Results. The design of this study is based on the rational selecting of the virtual ligand structures. It gives an opportunity to optimize the quantum-mechanical calculation. By using in silico analysis, it was shown that DHQ and some of its metabolites demonstrate ability of binding to SER353, SER530, and ARG513 of COX-2 at the catalytic site.

Conclusion. Important α-amino acids for intermolecular interaction of DHQ and its metabolites with COX-2 were determined during this study. Our data can be used for the development of new antiinflammatory drugs on the base of DHQ. 

Purpose. Increasing of treatment efficiency for patients with acute pancreatitis by improving objective means of determining the severity of acute pancreatitis.

Materials and method. The study was based on a retrospective analysis of 130 cases of acute pancreatitis: 47 cases from «Krasnoyarsk Regional Clinical Hospital» and 83 cases from «Regional Interdistrict Clinical Hospital No 20 named after I.S. Berzon» in the period from 2015 to 2017. The raw data was pre-processed. In particular, different methods (median, linear regression) were used to fill the missing values in the observation matrix. The initial dataset contained features measured in various quantitative and categorical scales. For some features with a pronounced asymmetric distribution, a quantile transformation was applied to initial values. The quantile transformation allows features to be brought to a uniform distribution in order to reduce the risk of excluding significant features. Ridge regression was used in combination with an algorithm for sequential reduction of attribute space.

Results. The classifier of three degrees of acute pancreatitis severity was developed. This classifier can help to determine better treatment tactics. During validation, the method of determining the severity of acute pancreatitis classification has proven to be effective. The average accuracy was 92% compared to the experts’ decisions. This procedure for constructing a classifier can be used as part of the basis to the medical decision support system.

Conclusion. The results of this study will help to make the choice of a necessary starting therapy, assess the need for surgical intervention and in severe cases, prescribe enhanced antibacterial and detoxification therapy. This will predictably reduce the percentage of septic complications of acute pancreatitis, and consequently will reduce the frequency of fatal outcomes. 

Objective. The purpose of the research was to study the effect of DNA methylation modulators on the production of proinflammatory cytokines by fibroblast-like synovial cells (FLC).

Materials and methods. We used the cells derived from the synovial tissue of 6 patients with active rheumatoid arthritis (RA) after 3–7 in vitro culturing passages.

Results. There was an IL-1β-induced up-regulation of osteoprotegerin (OPG) synthesis in the RA FLC cultures. The addition of methylating compounds S-Adenosyl methionine (SAMe) and genistein into the cultures resulted in a statistically significant decrease in the production of OPG, while the addition of the demethylating agent hydralazine did not change the synthesis of the cytokine. All three DNA methylation modulators used at different concentrations significantly reduced the percentage of spontaneous migration and invasion of FLC in the Boyden chamber.

Conclusion. Enzymes and molecular complexes involved in DNA methylation could be potential therapeutic targets, and in vitro FLC cultures of RA patients can be used as a model for preclinical screening of new drug compounds. 

This review discusses a relatively new class of targeted molecules that is being actively studied for radionuclide diagnosis and treatment of malignancies. The full-size antibodies used so far have non-optimal pharmacological properties, slow distribution in the body, poor penetration into the tissue and kidney excretion, and high immunogenicity, which significantly complicates their use in clinical practice. Over the past decade, a new class of targeted molecules, called “non-immunoglobulin scaffolds” have become popular; they have all the requirements for optimal delivery of a radionuclide to tumor cells. Scaffolds usually are smaller in size in comparison with antibodies, but they are larger than peptides, and are characterized by high affinity and optimal biochemical, biophysical, biological, and economic features. The advantages of such proteins are their stable structure, good penetration into tissues, the possibility of additional functionalization and expression in the bacterial system, which ensures low production costs.

The results of preclinical and clinical studies for diagnosis of malignancies using such proteins as affibody, adnectin, DARPins, etc., have demonstrated their high specificity, affinity, good tolerance and low immunogenicity. 

The focus of the researchers’ attention today includes the recently discovered role of mitochondria in the immune response. Increasing evidence shows that mitochondrial DNA, in retaining some of their characteristics of the ancient α-proteobacteria’s genome, is a potent immune stimulus for inflammatory reactions. Systemic inflammatory response is a frequent complication in surgical interventions and various traumas, and its development cannot be explained using common conceptions. This review provides information on the current understanding of the development of inflammation mediated by mtDNA, including systemic inflammatory response, and on the mechanisms regulating mitochondrial homeostasis and mtDNA release in various pathological conditions.

To understand the current state of the issue of dental manifestations of primary immunodeficiencies, foreign literature on the problem has been analyzed. The article describes the dental manifestations of many primary immunodeficiencies, which can be both secondary and major symptoms. The article presents the data on the following syndromes: severe combined immunodeficiency, hyper IgE, Wiskott – Aldrich, DiGeorge, deficiency of STIM1 and ORAI1, NEMO deficiency and IκBα deficiency, common variable immunodeficiency, X-linked agammaglobulinemia, hyper IgM, selective IgA deficiency, autoimmune lymphoproliferative syndrome, autoimmune polyendocrine syndrome type 1, Chediak – Higashi syndrome, CD70 deficiency, severe congenital neutropenia syndromes, leukocyte adhesion deficiency, localized aggressive periodontitis, Papillon – Lefevre syndrome, chronic mucocutaneous candidiasis, Marshall syndrome, hyper IgD syndrome, Aicardi – Goutières syndrome type 7, cherubism syndrome, CANDLE (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature), PAPA (pyogenic arthritis, pyoderma gangrenosum and acne), chronic recurrent multifocal osteomyelitis, periodontal Ehlers – Danlos syndrome, and C1 inhibitor deficiency. The role of secretory immunoglobulins of salivary fluid is described.

The aim of the study was to study the available approaches to the formulation and quality control of forensic medical expert conclusions. We have studied the literature sources containing recommendations on drawing up expert opinions and improving their quality. After a selection of scientific publications and publications on the subject matter with the help of a descriptive method, the article presents the existing approaches to this problem. As a result of the conducted research, the absence of any general objective requirements for expert conclusions was revealed. The development of unified standards for writing and the definition of “signs of quality” of expert conclusions is a promising task of forensic science and practice, the solution of which will improve the quality of examinations.

Vascular access is the cornerstone of hemodialysis. With vascular access dysfunction, the results of treatment of patients with stage 5 chronic kidney disease significantly deteriorate. One of the most common causes of vascular access failure is peripheral venous stenosis. Despite the variety of initiating factors, the morphological substrate of stenotic damage to the arteriovenous fistula (or arteriovenous anastomosis) in most cases is neointimal hyperplasia. Stenotic lesions of the arterivenous fistula are strongly associated with an increased risk of thrombosis and loss of vascular access. There are 4 typical localizations of stenosis: arteriovenous or arteriograft anastomosis, stenosis of the juxta-anastomotic segment of the fistula, stenosis of the functional segment of the fistula, and stenosis of the cephalic arc.

The most common indication for surgical treatment is vascular access failure; less common indications are clinical symptoms of venous insufficiency.

There are various methods of open reconstruction of the stenotic segment of the fistula vein: resection, prosthetics with a synthetic vascular graft, prosthetics or plastic repair of the autologous vein wall, complete or partial drainage of the prestenotic segment of the vein, etc. Currently an alternative method of stenosis repair using endovascular interventions is gaining popularity. In contrast to central vein stenosis, where endovascular interventions are the gold standard, in peripheral vein stenosis it is only an adjuvant method. Complications of endovascular interventions are extremely rare.

Despite the fact that endovascular interventions have almost absolute probability of technical success, the primary patency is not high and is about 50% in six months. The use of bare stents is not accompanied by an increase in primary patency. The use of stent-grafts can increase the primary patency, especially in the plastic repair of challenging stenoses of the graft-vein anastomosis or cephalic arch.

Many issues related to endovascular interventions remain unresolved, which requires further research. 

The purpose of this work was the need to highlight the significance of the works of Professor Boris I. Alperovich and his students in creating unique cryosurgical instruments and the development of modern cryosurgical operations on the liver and pancreas. The article used documents confirming the priority of the authors in the creation of cryotherapy equipment and methods of cryosurgical treatment of diseases of the liver and pancreas.

The results of a large number of studies indicate the relationship of obesity and bronchial asthma in children. The review highlights the mechanisms of development of the so-called obese asthma: morphological changes in the respiratory tract, systemic inflammation, adipokine production, impaired glucose and insulin metabolism, genetic and epigenetic factors, changes in the microbiome of the respiratory tract and(or) intestines. The relationship of asthma and obesity can have both a genetic basis and can occur under the influence of a complex of pathogenic factors, and they can be especially important at the “early programming” stage. Obesity increases the risk of asthma development, and in patients with existing asthma due to a number of mechanisms it increases the severity or makes it difficult to achieve control of asthma. Studies showed that patients with obese asthma are distinguished by a more severe course of the disease, poor quality of life and a decreased response to therapy for asthma. Weight loss in children with asthma can lead to an improved well-being of patients, but data on the effectiveness of therapeutic interventions in these children is limited. Comorbidity of asthma and obesity is a complex multifactorial phenotype in children, which requires further study. Being overweight or obese needs to be taken into account as part of asthma treatment in this category of patients.

The review of the literature presents the content analysis of surgical treatment of large and giant hernia of the esophageal aperture of the diaphragm as well as the analyses of complications when using the main methods of hernioplasty. Alloplasty of the esophageal aperture of the diaphragm remains a large and unresolved surgical problem, as evidenced by the analyzed literature sources, mainly reviews and clinical recommendations.

Firstly, alloplasty can cause postoperative complications with a frequency of up to 20%, especially when using rigid polypropylene and composite polytetrafluoroethylene mesh implants with circular paraesophageal fixation. Modern biological nets now show high incidence of anatomical relapses, so most specialists continue to use synthetic implants, of which the most promising ones are lightweight, mesh, partially absorbable structures.

Secondly, clear indications for alloplasty have not been developed, for example, according to the size of the hernia of the esophageal opening in the diaphragm, which is the main risk factor for relapses.

Thirdly, it is still not clear what indicator should be used to estimate the size of hernia of the esophageal aperture of the diaphragm and, therefore, it is not clearly defined which hernias are considered small, which are large and which are giant, despite the fact that the three terms constantly appear in the medical literature.

Fourthly, the optimal technique for alloplasty has not been determined with large and especially giant hernias, which would prevent anatomical relapses, and at the same time would not cause postoperative complications.

It is necessary to outline the following ways to solve these problems: to develop effective and at the same time safe methods of alloplasty of large and giant hernias; to determine clear indications for alloplasty of the esophageal opening of the diaphragm, depending on the size of hernias; to create an appropriate, applied classification of hernias of the esophageal aperture of the diaphragm. 

This review presents analysis of experimental models of atopic dermatitis, psoriasis, skin symptoms of autoimmune systemic connective tissue diseases, and blistering skin diseases. Presented in the review are experimental models of atopic dermatitis which reproduce various stages and types of disease that allows the investigation of disease pathogenesis. Atopic dermatitis can develop spontaneously in Nc/Nga mice. There are atopic dermatitis models initiated by monoclonal IgE injection or epicutant sensitization under dermal barrier disfunction imitation. Genetically modified atopic dermatitis models - transgenic and knockout mice – are convenient for investigation of disease stages, cytokines, antigen-presenting cells and T-cells influence. We show that the psoriasis models created by genetic engineering methods are the most convenient for investigation of the role of particular cell types and specific factors in the disease development. Up-regulation of adhesion molecules, cytokines, transcription factors, inflammation mediators in both keratinocytes and immune cells of transgenic mice reveals their influence on psoriasis pathogenesis. There are descriptions of skin symptom models of autoimmune systemic connective tissue diseases and blistering skin disease models with and without genetic modifications. Each model demonstrates some peculiarities of pathogenesis and disease symptoms, whereas combined use of the models will allow to study the mechanisms of development of atopic dermatitis, psoriasis, blistering skin diseases and skin lesions under autoimmune systemic connective tissue diseases, that will contribute to the development of modern effective methods of treatment.

There is an increase in the prevalence of chronic, noncommunicable diseases, including allergic and autoimmune diseases in developed countries. In this regard, the study of factors modifying the population’s immune response is very important.

According to the “old friends” hypothesis , insufficiency of infectious stimulation and decrease in prevalence of helminthiasis are associated with development of noncommunicable diseases. Studies revealed that intestinal parasites modulate the host immune response and alter susceptibility to immunological diseases. It is suggested that one of the pathogenetic mechanisms of immune response modulation by parasites is an increase in the content of gastrointestinal bacteria with anti-inflammatory effect. Advanced technologies of microorganism identification provide a deep insight into the microbiota in different pathologies. The study of changes in the intestine and bile microbiota of the host in helminthiases provides new possibilities for prevention, diagnosis and control of such conditions as chronic inflammatory bowel diseases and allergic diseases. The purpose of this review is to analyze current experimental and clinical data on intestinal microbiota in helminth infections and possible association with development of chronic noncommunicable diseases. 

The paper provides a clinical description and analysis of two melanoma cases with mutations in the BRAF and NRAS gene within one tumor. Until recently, it was believed that mutations in the BRAF and NRAS genes are exclusive and do not occur within the same tumor. Later it was revealed that these mutations can exist within one tumor, but this is still quite a rare phenomenon. Molecular genetic analysis of the tumor obtained from both patients showed a mutation in the 15 exon of the BRAF gene c.1799T>A (V600E) and exon 2 of the NRAS p.G13S gene (p.37 G>A). The expression level of non-mutant NRAS protein was different in both cases. In conclusion, so in one patient, despite the presence of a mutation in the NRAS gene, the level of expression of the non-mutant protein was absent, which can be related to possible posttranscriptional disorders in the regulation of gene expression.

A description is given of a patient with a latent tumor process that has developed recurrent thrombosis of the superficial and deep veins of the lower extremities, common iliac veins, PE, a blood clot in the right ventricle, and a spleen infarction. The examination revealed bronchogenic lung cancer with metastases to the bronchopulmonary lymph nodes and liver, confirmed by an autopsy.

Introduction. Malignant skin tumors (MST) are an important interdisciplinary problem. Neoplasia data refer to tumors of apparent localization, therefore, they are found in the clinical practice of doctors of different profiles. The duration of the diagnostic period, as well as the prognosis, depends on the coordinated work of specialists.

Aim. Development, implementation and evaluation of the effectiveness of an interdisciplinary model for managing patients at risk for malignant skin tumors.

Materials and methods. A descriptive study included a study of the proportion of people at risk for developing MST, the nosological structure of the revealed MST among patients referred to the dermatological oncology room of the Sverdlovsk Regional Dermatovenerologic Dispensary for the period from 01.01.2016 to 31.12.2017 (total 3,275 patients), as well as 208 patients examined in the Sverdlovsk Regional Oncology Dispensary (SROD). The data of the “ONKOR” regional oncological information system were used.

Results. An interdisciplinary model of managing patients at risk has been developed, including patient routing andtraining of specialists in various fields. As a result of the implementation of the model, 208 patients were examined, 208 of whom were diagnosed with skin cancer, 123 of whom had skin cancer, 11 cases of melanoma, Kaposi’s sarcoma in 2 cases, skin lymphomas in 4 patients, lymphosarcoma in 1 patient, amounted to 67.8% of the diagnoses of MST confirmed in the Sverdlovsk Regional Dermatovenerologic Dispensary of the Sverdlovsk Regional Oncology Dispensary. 9.6% of patients had dysplastic nevi, confirmed histologically. 1987 patients at risk of developing MST were taken under the dispensary observation by a dermatologist and venereologist.

Conclusion. Тhe introduction of the algorithm of interdisciplinary interaction contributes to the improvement of the quality and accessibility of medical care to the population, the identification of patients at risk for the occurrence of MST, reducing the burden of non-core patients on oncology services. 

One of the most difficult categories of patients is patients with inflammatory bowel disease. A clinical case of the development of mesalazine-induced eosinophilic pneumonia in a 15-year-old boy with ulcerative colitis is presented. The patient suffered an acute respiratory disease, which caused the aggravation of ulcerative colitis and, accordingly, an increase in the dose of mesalazine. Against this background, the child had active complaints of heaviness in the chest to the left. Eosinophilia was noted in the blood. Analysis of clinical symptoms, X-ray data, microscopic examination of the pleural fluid, the results of spiral computed tomography of the chest allowed a differential diagnosis of the main symptoms and associated identified pulmonary lesions with mesalazine.