I n t r o d u c t i o n . The appearance of hematological abnormalities since the beginning of the HIV-infection epidemic has been associated with an increased risk of disease progression and death in these patients.

A i m . Determination of risk factors for an adverse outcome in patients with HIV infection and cytopenia.

M a t e r i a l s a n d m e t h o d s . Hemograms and myelograms were analyzed in 30 hospitalized patients with HIV infection and cytopenia. All patients had two- or three-lineage cytopenia according to hemogram (anemia and thrombocytopenia, anemia and leukopenia, pancytopenia). Two groups of patients were assigned: in 18 (60%) patients the hospitalization had fatal outcome – group 1 (adverse outcome of the disease); and 12 (40%) patients were discharged from the hospital – group 2 (favorable outcome of the disease).

R e s u l t s . While evaluating the hemograms in patients with HIV infection and cytopenia with diff erent outcomes of the disease, no statistically signifi cant diff erences were found. Analysis of the bone marrow cellularity showed that the hypocellular and normocellular bone marrow were more often recorded in myelograms of group 1 patients; hypercellular bone marrow was not detected in group 1 patients, in group 2 patients it was determined in 4 cases (33.3%). The cellularity of the erythroid lineage was more often decreased in patients of group 2, normal and increased – in patients of group 1. The granulocyte lineage was more often suppressed in patients of group 1, was normal in patients of group 2, stimulated more often in patients of group 1. The megakaryocyte lineage more often had a decreased cellularity in group 1 patients; normocellularity of the megakaryocyte lineage was in group 2 patients; hypercellularity of the megakaryocyte lineage was not registered in the study groups. When comparing the signs of myelodysplasia in 13 patients of group 1, signs of dyspoiesis were revealed.

C o n c l u s i o n . In patients with HIV infection and cytopenia, as the underlying disease progresses, severe hematological disorders develop, which, in turn, may be risk factors for an adverse outcome of HIV infection.

I n t r o d u c t i o n . For patients with the consequences of COVID-19 it seems relevant to undergo a rehabilitation program to restore the respiratory function, oxygen uptake by tissues, increase exercise tolerance, etc. Rehabilitation includes aerobic-based exercises adequate to the patient’s state and physical capabilities, breathing exercises and physiotherapy modalities.

A i m . To evaluate the effectiveness of the third stage rehabilitation in patients aged 18–45 years with the consequences of COVID-19 (U07.1) in a day hospital of multispecialty hospital.

M a t e r i a l s a n d m e t h o d s . One hundred and thirty-nine patients aged 18–45 years with a verified diagnosis of pneumonia associated with COVID-19 (U07.1) were examined in a day hospital of multispecialty hospital. The patients were divided into 2 groups: 107 patients of the 1st group underwent the third stage rehabilitation; 32 people from who made up the 2nd group refused rehabilitation. The severity of dyspnea was assessed using the Medical Research Council (MRC) Dyspnea Scale; functional impairment in the performance of activities of daily living – according to the Baseline Dyspnea Index and Transitional Dyspnea Index scales; exercise tolerance – according to the 6-minute walk test and the modified Borg Scale; the severity of anxiety and depression – according to the Hospital Anxiety and Depression Scale (HADS); pain intensity – according to the Visual Analogue Scale (VAS); quality of life – according to the EuroQoL Five-Dimension Questionnaire (EQ-5D). Statistical processing of the obtained results was carried out.

R e s u l t s . In the group of patients who completed rehabilitation, upon follow-up examination, there was a significant decrease in complaints, normalization of a number of hemodynamic parameters, an improvement in the 6-minute walk test scores, a decrease in the severity of dyspnea according to the MRC Dyspnea Scale by 1.8 times, a decrease in anxiety according to the HADS by 2.1 times, a decrease in pain according to the VAS by 3.2 times, an improvement in exercise tolerance according to the modified Borg Scale by 1.8 times and quality of life – according to the EQ-5D by 1.4 times. In the group of patients who refused rehabilitation, the change in these indicators was not significant.

C o n c l u s i o n . For patients who have had pneumonia associated with SARS-CoV-2, it is advisable to go through the third stage rehabilitation in a day hospital in order to restore the respiratory functions, increase exercise tolerance, reduce anxiety and improve quality of life.

I n t r o d u c t i o n . Maintenance of an adequate micronutrient status is one of the components of the children’s health with the formation of normal indicators of the physical and intellectual development.

A i m . To evaluate the influence of the microelement and vitamin D adequacy of 7–8-year-old children living in the Khabarovsk Territory on their physical and cognitive development.

M a t e r i a l s a n d m e t h o d s . An observational, analytical, cross-sectional study was performed with an analysis of the prevalence of micronutrient imbalances among apparently healthy children aged 7–8 years living in the Khabarovsk Territory (n = 60). The physical development of children was assessed by calculating the Z-scores of body weight, height and body mass index (BMI). The assessment of the children’s cognitive abilities was carried out using conventional methods. Quantifi cation of elements (Mg, Zn, Ca, Se, Cu, Fe, Mn, Cr) in the hair and blood serum of children was carried out by inductively coupled plasma mass spectrometry. The iodine adequacy in children was determined by its content in the first-morning urine using the cerium arsenite method. Determination of 25-hydroxyvitamin D (25(OH)D) in the blood serum of children was carried out by the enzyme-linked immunosorbent assay.

R e s u l t s . A slowing down in growth rates was revealed with a decrease in the content of Ca, Cu, Se, Zn, and an increase in the concentration of Fe; a decrease in BMI with deficiency of Ca, Cu, Zn, Cr, and an increase with an I and 25(OH)D intake inadequacy. A decrease in cognitive profile indicators was noted in children with deficiency of Mg, Ca, I, Cu, vitamin D, and an excess of Fe. The factor analysis using the multiple correlation method revealed a combined effect of Ca, Zn, and Fe equally on both indicators of growth and BMI parameters (p < 0.05). The cumulative eff ect of concentrations of Cu, Ca, I, and vitamin D in the blood serum of younger schoolchildren on the formation of short-term memory was shown (p < 0.01). A relationship was found between the level of development of verbal-logical reasoning and the concentration of Mg and Ca (p < 0.05), as well as Fe and Ca (p < 0.05), while the combination of elements with 25(OH)D in the blood serum increased the significance of correlations (p < 0.01).

C o n c l u s i o n . The study demonstrates the need for an integrated approach to evaluate the microelement and vitamin D adequacy in children, in connection with the presence of comorbidity of deficient and excess conditions, a combined effect on physical and cognitive development in order to prevent the development of nutritional diseases.

I n t r o d u c t i o n . An effective way to reduce the volume of infusion (restrictive strategy) in hypovolemic shock, in particular in burn shock, is invasive hemodynamic monitoring and choosing the appropriate regimen for the use of inotropic agents, considering the data obtained. However, the use of inotropic agents in hypovolemic shock is still controversial. The most cutting issue is the choice of effective doses of inotropic agents.

A i m . Justification of the need to use inotropic agents and assessment of the safety and effectiveness of dobutamine use in burn shock.

M a t e r i a l s a n d m e t h o d s . The pilot clinical study conducted in 2021–2022 included 9 patients aged 15–70 years who were admitted to the intensive care unit (ICU) of the Burn Center of the Novosibirsk State Regional Clinical Hospital with a total body surface area burned > 40% (II–III degree), in most cases – thermal inhalation injury, who were in the ICU for over 3 days. Intensive care of burn injury in the acute phase was performed according to conventional clinical recommendations. Myocardial samples for morphological and immunohistochemical studies were taken from 34 patients who died from burn shock (27 men and 7 women, aged from 21 to 51 years) from 2015 to 2019. The samples were taken post mortem, and with minimal atherosclerotic changes of the coronary arteries (lesions no more than 20–25%). The control group for morphological and immunohistochemical studies comprised samples which were taken from 25 individuals who died because of sudden circulatory arrest (19 men, 6 women).

R e s u l t s . Studies have shown a decrease in myocardial contractility in patients with burn shock. Morphological examination revealed contraction lesions of individual cardiomyocytes of varying degree, as well as foci of primary clumping of myofibrils’ cytoplasm and myocytolysis. The immunohistochemical study of myocardial sections showed a decrease in the actin expression by 2.4 times (p < 0.05) and desmin – by 2 times (p < 0.05) in comparison with the control group. The results of the clinical study showed that dobutamine at a rate of up to 5.0 μg/kg/min does not cause an arrhythmogenic effect and/or lactic acidosis.

C o n c l u s i o n . The data obtained on structural changes of the myocardium confi rm the need for the use of inotropic agent in burn shock. Dobutamine at a rate of up to 5.0 μg/kg/min allows for a restrictive strategy of fl uid resuscitation and rapid recovery from burn shock.

I n t r o d u c t i o n . Recently, a large number of diseases associated with an impairment of the neuroendocrineimmune system caused by an increase in psycho-emotional stress and a severe environmental deterioration has been registered. The epiphysis is central to the endocrine and immune systems.

A i m . To study of structural transformations of the epiphysis during immunostimulation.

M a t e r i a l s a n d m e t h o d s . The study was carried out on 60 mature male rats of the reproductive period weighing 240–280 g. Animals of the experimental group (n = 30) were injected with imunofan fivefold on the 1st, 7th, 15th, 30th and 60th day at a dose of 0.7 μg/kg of body weight. Animals of the control group (n = 30) received 0.9% NaCl in an equivalent volume and the same regimen. In animals of both groups, the absolute and relative weight of the epiphysis, its maximal and minimal diameter, volume, as well as the cell ratio, maximal/minimal diameter and volume of pinealocytes, the maximal/minimal diameter and volume of pinealocyte nuclei were determined.

R e s u l t s . Changes in the parameters of the epiphysis were observed on the 15th, 30th, and 60th day the experiment. So, in the experimental group, the maximal and minimal diameter of pinealocytes increased by 3.93, 8.24, 13.15 and 7.04, 9.37, 10.54%, respectively, compared with the same indicators in the control group. Similar changes were noted for the maximal and minimal diameters of cell nuclei as an indicator of functional activity by 4.48, 7.23, 4.45 and 4.05, 7.66 and 10.16%, respectively.

C o n c l u s i o n . The results obtained make it possible to judge the active reaction of the epiphysis of mature rats in response to imunofan-induced immunostimulation.

I n t r o d u c t i o n . Microsatellite instability is historically closely associated with the development of oncological processes. Early diagnosis of microsatellite instability as a marker for premalignancy, including in the case of endometrial hyperplasia (EH), which is recognized as a premalignancy lesion, is of interest. Identifi cation of the mutational profile characteristic of malignant tumors in benign disease makes it possible to improve prognostic models and therapeutic tactics.

A i m . Determination of clinical and anamnestic features of patients with EH and endometrioid adenocarcinoma in a comparative aspect, as well as structural features of microsatellite instability in the endometrium in patients with this pathology.

M a t e r i a l s a n d m e t h o d s . The study involved 120 women who were divided into 4 groups: group I – EH patients without atypia (n = 30); group II – patients with atypical EH (n = 30); group III – patients with endometrioid adenocarcinoma (n = 30); group IV – healthy women without somatic and gynecological pathology (n = 30). A comparative morphological study of endometrial samples was performed and levels of MLH-1, MSH-2, MSH-6 and PMS-2 expression were assessed.

R e s u l t s . It was revealed that most EH patients without atypia, patients with atypical EH, endometrioid adenocarcinoma complained of abnormal uterine bleeding; the history of patients of these groups is characterized by the presence of cardiovascular and endocrine diseases, and the gynecological history is characterized by the presence of uterine fibroids, benign breast diseases and pelvic infl ammatory diseases. There was found a decrease in the MLH-1, PMS-2, MSH-2 and MSH-6 expression in endometrial biopsies of women with EH.

C o n c l u s i o n . Decreased expression of MLH-1, PMS-2, MSH-2 and MSH-6 in endometrial biopsies can probably be considered as a predictor of premalignant transformation, which requires further study in order to develop a program of malignancy risk assessment.

I n t r o d u c t i o n . Despite significant advances in therapy of patients with chronic myeloid leukemia (CML), improved survival rates, development of resistance to tyrosine kinase inhibitors (TKIs) remains an urgent problem.

A i m . To study the correlation between the level of expression of regulatory proteins p53, c-myc, ki-67 and caspase-3 on the bone marrow cells and the concentration of certain pro- and anti-inflammatory cytokines in blood serum with the effectiveness of therapy in patients with CML.

M a t e r i a l s a n d m e t h o d s . Seventy-four CML patients with chronic phase of the disease receiving TKI therapy were examined. In all patients, the concentration of certain cytokines and growth factors (TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-17, IL-18, IFN-α, and VEGF-A) was determined in blood serum by enzyme immunoassay and immunocytochemical study of bone marrow smears with monoclonal antibodies against antigens of regulatory molecules ki-67, p53, c-myc, and caspase-3. To determine the role of the biomarkers in predicting the therapy effectiveness, a comparative analysis of their values in groups of patients with a major molecular response (MMR) (n = 50) and without MMR (n = 24) was performed.

R e s u l t s . A comparative analysis of the expression of regulatory molecules on the bone marrow cells and the blood serum concentration of cytokines and growth factors of CML patients, depending on depth of the response to TKI therapy, showed that patients who did not achieve MMR had a significantly higher level of caspase-3 expression and concentration of pro-inflammatory cytokines IL-1β, IL-2, IL-6 and IL-17, as well as growth factor VEGF-A compared with those in patients with MMR. In turn, the achievement of MMR was characterized by a higher level of expression of regulatory molecules p53 and c-myc, as well as an increase in the IL-10 concentration and a decrease in the IL-1β, IL-2, IL-6 and IL-17 concentration. Analysis of the correlation between the level of expression of regulatory molecules and the single cytokine concentration showed a negative correlation between c-myc and p53 with IL-2, IL-1β, IL-17 and a positive (direct) correlation between c-myc and p53 with IL-10, a positive correlation between caspase-3 and IL-2, IL-1β, IL-6, IL-17 and a negative correlation between caspase-3 and IL-10. Thus, the achievement of MMR in patients with CML is more likely with a higher expression of regulatory molecules c-myc and p53 on the bone marrow cells, low expression of caspase-3, and low serum concentrations of IL-2, IL-1β, IL-17, IL-6 and a high concentration of IL-10, which indicates synergism of the biomarkers in the pathogenesis of CML and its tumor progression. The ROC analysis results showed the high quality of predictive models characterizing the achievement of MMR at the level of expression of c-myc > 6%, p53 > 4% in the bone marrow, which correlates with a low serum concentrations of IL-2, IL-1β, IL-17 and a high concentration of IL-10, and indicates the possibility of using these indicators as potential biomarkers of effectiveness of CML therapy and achievement of MMR.

C o n c l u s i o n . The results of the study showed that the concentration of cytokines in the blood serum of CML patients correlates with the intensity of expression of c-myc, p53 and caspase-3 proteins and is important in predicting the effectiveness of therapy.

I n t r o d u c t i o n . Despite the availability and high effectiveness of modern anticancer drugs used to treat patients with multiple myeloma (MM), most patients inevitably develop disease relapses and refractoriness to the ongoing therapy. The prognosis in patients with relapsed MM and refractoriness to the main classes of anticancer drugs (proteasome inhibitors and immunomodulators) remains poor, and the median overall survival (OS) is only 8 months. Daratumumab is the first fully human IgG1-κ monoclonal antibody that binds with high affinity to the CD38 protein on the surface of myeloma cells, has a direct effect on the tumor, and also has an immunomodulatory mechanism of action. In clinical trials, daratumumab has been shown high effective and safety when used as monotherapy in patients with relapsed and double refractory MM.

A i m . To evaluate the effectiveness and safety of daratumumab monotherapy in patients with relapsed/refractory multiple myeloma (RRMM) in real-life clinical practice.

M a t e r i a l s a n d m e t h o d s . We analyzed 32 patients with RRMM (14 men and 18 women) aged 41–76 years (median 65 years) from two hematological centers in the city of Novosibirsk. In 65.6% of patients, stage IIIA according to Durie-Salmon, stage I–II according to the ISS (in 65.6 and 28.1% of patients, respectively), ECOG performance status 0–1 (in 37.5 and 43.7% of patients, respectively) were diagnosed. Bone-related soft tissue plasmacytomas were recorded in 56.3% of patients, high lactate dehydrogenase activity was noted in 12 (37.5%) patients. The median number of prior lines of therapy was 2 (range 2–4). All patients had previously received proteasome inhibitors (bortezomib) and immunomodulatory agents (lenalidomide). Autologous hematopoietic stem cells transplantation was performed in 34.4% of patients. Double refractory MM was registered in 24 (75%) of 32 patients. The median time from diagnosis of MM to initiation of daratumumab therapy was 73.1 months (range 18–144 months). Daratumumab was administered as monotherapy at a dose of 16 mg/kg intravenously weekly (cycles 1–2), every other week (cycles 3–6), and then monthly.

R e s u l t s . The median duration of therapy with daratumumab was 12.2 months (range 4–22 months). The overall response rate (complete response + very good partial response (vgPR) + partial response (PR)) was 67.7%; vgPR – in 9 (29%) patients, PR – in 12 (38.7%), stable disease (SD) was registered in 19.4% of patients, respectively. The median time to response was 3.5 months (range 2.5–6). The median duration of response was 7.9 months (95% confidence interval (CI) 4.7–11.5). The median progression-free survival (PFS) was 19.1 months (95% CI 15.3–23.6), and the 12- and 18-month PFS were 91% and 50%, respectively. The median OS was not reached, and the 12- and 18-month OS values were 100% and 96.3%, respectively. The depth of the response had a statistically significant effect on the PFS (18-month PFS was 100% in the vgPR and PR subgroups and 81% in the SD subgroup, respectively (χ2 = 19.207, p < 0.001)). Therapy with daratumumab was accompanied with a favorable toxicity profile. In 37.5% of patients, grade 1 and 2 infusion reactions were noted, in 6.2% grade ≥ 3, in one patient, therapy was discontinued due to an infusion reaction of the 3rd degree. Fatigue, upper and lower respiratory tract infections (15.6% and 12.5%, respectively), anemia (15.6%), thrombocytopenia (6.2%), and neutropenia (6.2%) were recorded in 15.6% of patients.

C o n c l u s i o n . Therapy with daratumumab is an effective and safe treatment for RRMM.

n t r o d u c t i o n . Hyaluronidase is an enzyme preparation widely used in medicine, including ophthalmology. Hyaluronidase, having a protein structure, carries a potential danger in the form of undesirable allergic reactions. To avoid allergenic effects, protein structures are modified by combining with a polymer carrier, for example, by polyethylene glycol (PEG).

A i m . To study the possible allergenic potential of hyaluronidase, PEGylated using the technology of electron beam synthesis, with various routes of administration.

M a t e r i a l s a n d m e t h o d s . The object of the study is PEGylated hyaluronidase (PEG-Hyal). Experimental animals are hybrid mice and guinea pigs. Seven types of experiments were carried out: anaphylactogenic activity; conjunctival challenge test; cutaneous applications; delayed-type hypersensitivity (DTH); active cutaneous anaphylaxis; indirect mast cell degranulation; inflammatory response to concanavalin A (ConA).

R e s u l t s . When studying anaphylactogenic activity, an anaphylactic reaction was not observed in guinea pigs. The conjunctival challenge test also revealed no signs of hypersensitivity to the drug. In the study of sensitization, no development of local allergic reactions was observed. In experiments to the study DTH in mice, there were no significant differences for the DTH index in the experimental and control groups. The assessment of active skin anaphylaxis has been showed that the diameter of the stained spot did not significantly differ in both experimental groups from the control one. In indirect mast cell degranulation experiments, it was found that there was no statistically significant change in the mast cell degranulation index. Evaluation of the allergenic potential of PEG-Hyal in the inflammatory response to ConA showed that there is no statistically significant difference between the experimental and control groups.

C o n c l u s i o n . Based on the results of the experiments, it can be concluded that PEG-Hyal does not have an allergenic potential in various routes of administration, which significantly expands the possibilities of its clinical use.

I n t r o d u c t i o n . The development of liver cirrhosis, regardless of etiology, is based on the process of fibrosis and structural alteration of the organ. Regulation of this process is associated with a high level of TGF-β expression and suppression of apoptosis in hepatocytes. Oxidized dextran (OD) has a high antifibrotic activity and is able to change the functional state of the phagocytic cell, thus preventing the development of fibrosis and stimulating reparative processes in organs with post-toxic hepatosis and liver cirrhosis.

A i m . To study the molecular and cellular mechanisms of the effect of OD on the expression of epithelial-mesenchymal transition (EMT)-associated proteins during fibrosis and the development of liver cirrhosis in rats with post-toxic hepatosis.

M a t e r i a l s a n d m e t h o d s . In the experiment, 30 male Wistar rats weighing 280–320 g were used. The animals were divided into 2 groups. In group 1 rats (hepatosis), the post-toxic hepatosis was modeled by administration of a solution of CCl4 and ethyl alcohol. In rats from group 2, the post-toxic hepatosis was modeled in the same way, and OD was administered. The numerical density (Nai) of liver nonparenchymal cells expressing TGF-β (Kupffer cells, endothelial cells, fibroblasts) was calculated. The expression of E-cadherin, vimentin, SNAIL + SLUG by fibroblasts and hepatocytes was evaluated.

R e s u l t s . The numerical density (Nai) of hepatocytes expressing vimentin prevailed in the liver of group 1 rats (hepatosis), compared with that of group 2 animals (hepatosis + OD) on the 30th and 60th days. In animals of the 1^st (hepatosis) group on the 60th day, a 3-fold lower numerical density of hepatocytes expressing E-cadherin was noted in comparison with that in rats treated with OD (group 2). In animals of the 1st (hepatosis) group on the 30th and 60th days, a 2-fold and 5-fold higher numerical density of hepatocytes expressing SNAIL + SLUG was noted in comparison with that in rats of the 2nd group. The numerical density of fibroblasts expressing vimentin prevailed in the liver of group 2 rats (hepatosis + OD), compared with that of group 1 animals (hepatosis) on day 30. In animals of the 1^st (hepatosis) group on the 60th day, a 6-fold higher numerical density of fibroblasts expressing E-cadherin was noted in comparison with that in rats treated with OD (group 2). In animals of the 1st (hepatosis) group on the 30^th and 60th days, the numerical density of fibroblasts expressing SNAIL + SLUG was 6 and 7 times higher than in rats treated with OD (group 2). In the liver of animals of the 2^nd group (hepatosis + OD), the numerical density of cells expressing TGF-β was lower in comparison with that of animals of the 1^st  group (hepatosis) by 2.5 times on the 30th day and 3.6 times on the 60th day of the experiment.

C o n c l u s i o n . In post-toxic hepatosis, the expression of TGF-β, SNAIL + SLUG and vimentin proteins increases in liver parenchymal and nonparenchymal cells, contributing to the acquisition of a mesenchymal immunophenotype by cells, which leads to increased profibrotic activity and the development of liver cirrhosis. The use of OD in post-toxic hepatosis reduces the expression of vimentin, TGF-β and EMT-associated proteins in liver parenchymal and nonparenchymal cells, which decreases the severity of fi broplastic processes and prevents the development of liver cirrhosis.

Based on literature data, the review presents current information on a wide range of clinical manifestations of Q fever, as well as on laboratory methods for diagnosing the disease. Q fever is a zoonotic disease with a variety of transmission routes of its pathogen – Coxiella burnetii. The main carriers of coxiellas are ixodid ticks; in anthropogenic foci their hosts are domestic and livestock animals. The Q fever foci in the Novosibirsk region were found back in the 90s of the last century, however, laboratory diagnostics was not performed over the past two decades. Due to the polymorphism of clinical symptoms, the clindisease has no pathognomonic signs. The main manifestations of acute Q fever are fever, myalgias, pneumonia. Confirmation of the diagnosis is possible only if genetic and serological markers of the causative agent Coxiella burnetii are identified, which makes it possible to differentiate Q fever from other infections and prescribe appropriate therapy in a timely manner.