Introduction. It is known that bitter taste receptors (TAS2R) are expressed on many cells of the respiratory system and their activation is accompanied by a wide range of potentially beneficial effects for the treatment of asthma.

Aim. To evaluate the influence of TAS2R3, TAS2R4 and TAS2R5 polymorphisms on the development of asthma, parameters of lung function and control of the disease.

Materials and methods. The study enrolled 240 patients with asthma of varying severity (mean age 43.9±1.03 years, 44.5% males) and 90 healthy volunteers (control group, mean age 38.0±1.09 years, 50% males). Lung function was assessed using standard spirometry, the disease control was determined by ACT questionnaire. Preliminary screening by minor allele frequency, prediction of functional significance and assessment of linkage disequilibrium allowed us to select TAS2R4 rs33920115 as a representative variant for the group of TAS2R3, TAS2R4 and TAS2R5 polymorphisms. Genotyping was performed by PCR with high-resolution melting analysis.

Results. rs33920115 polymorphism was significantly associated with asthma in codominant (p=0.01), dominant (p=0.006), recessive (p=0.03), log-additive (p=0.003) and multiplicative (p=0.003) genetic models. Carriage of the AA genotype was more often observed among patients with asthma (29.2% vs. 17.8%) while the GG homozygotes were prevalent in the control group (33.3% vs. 19.2%). The effect remained significant after adjustment for sex and age (OR 1.8; 95%CI (1.26-2.61), p=0.001 for log-additive model). We found no effect of rs33920115 on lung function and asthma control.

Conclusion. TAS2R4 rs33920115 polymorphism and associated variations in TAS2R3 and TAS2R5 genes may influence the predisposition to asthma development, probably due to changes in the expression of the corresponding receptors.

Introduction. Macrophages, matrix metalloproteinase-9 (MMP-9) and tumor necrosis factor-alpha (TNF-α) make a significant contribution to the pathophysiological mechanisms of development and course of bronchial asthma.

Aim. To evaluate the role of macrophages and MMP-9 regulated by TNF-α signaling in the formation of airway response of non-allergic bronchial asthma patients to cold air hyperventilation.

Materials and methods. Spirometric indices of forced expiratory flow, cellular composition of sputum, MMP-9 and TNF-α content in exhaled breath condensate (EBC) were measured in 66 patients with asthma before and after bronchoprovocation test with isocapnic hyperventilation with cold (-20°C) air (IHCA) were evaluated.

Results. Two groups of patients with presence (group 1) or absence (group 2) of cold airway hyperresponsiveness were formed. High macrophage and neutrophil counts and a significant decrease in the number of epithelial cells in sputum were recorded after the IHCA. Concentrations of TNF-α and MMP-9 in EBC after IHCA decreased to a greater extent in patients of group 2. The content of epitheliocytes in sputum was correlated with FEF₅₀ (r=-0.49, p=0.03), FEF₇₅ (r=-0.45, p=0.047) and MEF_25-75 (r=-0.47, p=0.038), and their content after IHCA test with ΔMEF_25-75 (Rs=0.31; p=0.018). We found a correlation between baseline MMP-9 content in EBC and ΔMEF_25-75 (Rs=-0.59; p=0.042), as well as between MMP-9 level after IHCA and severity of bronchospasm (ΔMEF_25-75) in response to IHCA test (Rs=-0.67; p=0.023).

Conclusion. In patients with cold airway hyperresponsiveness, uncontrolled course of asthma and more significant bronchial patency disorders are associated with productive-proliferative inflammation involving macrophages, MMP-9 and TNF-α, which contributes to bronchial remodeling.

Aim. To study the relationship between the probability and severity of dyspnea following COVID-19 pneumonia with the characteristics of lung ventilatory function (LVF), lung diffusion capacity (DCL), and respiratory muscle strength (RMS) impairments.

Materials and methods. A total of 108 patients (58% women, age 62 [52-66] years) who had recovered from COVID-19 pneumonia were examined. Spirometry, bodyplethysmography, DCL, and RMS assessments were conducted 75 (46-155) days after the onset of the disease. The severity of dyspnea was evaluated using the MRC (Medical Research Council Scale) and the 10-point Borg scale. Instrumental and laboratory data from the acute phase of COVID-19 were retrospectively obtained from medical records.

Results. The risk of dyspnea of any severity at the time of examination was statistically significantly higher in patients with reduced (z-score < -1.645) VC, FVC, FEV₁, DLCO, VA, and DLCO/VA. No correlation was found between the risk of dyspnea and acute COVID-19 indicators (maximum C-reactive protein, lactate dehydrogenase levels, lung tissue damage assessed by computed tomography, positive PCR test), sex, or body mass index. None of the patients had a Gensler index <70%; however, reduced FEV₁ was found in 10.3% of patients. Restrictive LVF impairments were observed in 8.3% of patients, and mixed impairments in 11.2%. Dyspnea severity was statistically significantly higher in patients with LVF impairments, especially with mixed type, compared to patients with normal respiratory biomechanics. The correlation between the risk of dyspnea and functional parameters persisted even when the sample was limited to patients with normal LVF (n=75) and without comorbidities (n=49). In patients with normal LVF and no comorbidities who did not report dyspnea, FEV₁, ITGV, DLCO, and DLCO/VA values (in % of predicted) were higher, and Raw and Rocc were lower than in those with any severity of dyspnea.

Conclusion. There is a correlation between the risk and severity of dyspnea and restrictive, obstructive VFL impairments, and reduced DCL in the post-COVID-19 period. Additionally, identified patterns suggest that subclinical bronchial obstruction and reduced RMS may be possible mechanisms of dyspnea in patients with a normal respiratory biomechanics pattern.

Introduction. Oxidative stress plays a key role in the pathogenesis of COPD. Cigarette smoke induces oxidative stress, which causes DNA damage in cells. Transient receptor potential (TRP) channels are capable of mediating the effects of tobacco smoke and reactive oxygen species.

Aim. Studying the level of H2AX histones phosphorylation (γH2AX) indicating DNA damage in leukocytes of COPD patients and establishing its relationship with TRPV1 and 

TRPV4 expression.

Materials and methods. The study included 47 patients with COPD of varying severity and 25 controls. All subjects underwent spirometry to assess lung function. Histone H2AX phosphorylation and TRPV1/TRPV4 expression on leukocytes were determined by flow cytometry. Spearman's rank correlation coefficient (ρ) was used to search for relationships between quantitative variables.

Results. Lymphocytes of COPD patients were characterized by higher level of γH2AX (%) than lymphocytes from the controls (p=0.04). Lymphocytes of smokers also showed a greater degree of DNA damage as compared to healthy non-smokers (p=0.02). Significant differences were observed when comparing γH2AX expression (%) between COPD patients and healthy non-smokers in lymphocytes (p=0.001) and monocytes (p=0.04). Smoking more than 20 pack-years was associated with higher γH2AX (%) in lymphocytes (p=0.04) of COPD patients. Expression of TRPV1 and γH2AX (%) showed significant correlations on granulocytes (ρ=0.76, p<0.001), lymphocytes (ρ=0.34, p=0.03) and monocytes (ρ=0.55, p<0.001).

Conclusion. COPD patients differ from the control group by more pronounced DNA damage, which is most evident in lymphocytes. Smoking is a factor that negatively affects the formation of DNA breaks. TRPV1 expression may play a role in oxidative DNA damage in leukocytes by increasing the production of reactive oxygen species.

Introduction. Thrombo-inflammatory changes in the alveolar-capillary membrane are significant links in the pathogenesis of respiratory failure in COVID-19. This study investigates whether leukocyte-platelet aggregates contribute to its development and, if so, the mechanisms involved.

Aim. To examine the quantitative changes in leukocyteplatelet aggregates in patients with COVID-19 receiving different levels of oxygen support.

Materials and methods. The study included 134 COVID-19 patients of varying severity and 20 volunteers examined in the pre-pandemic period. The criterion for dividing the studied patients into groups was the ratio of blood oxygen saturation to its inhaled fraction, investigated by pulse oximetry. Three groups were formed depending on the value of the index: in the first (n=48), the SpO2/FiO2 index was above 450%, in the second (n=55) it ranged from 370 to 449%, and in the third (n=51) the index was up to 369%. The enumeration of blood cells, major leukocyte populations, lymphocyte subpopulations, and plateletleukocyte complexes was performed using the CytoFLEX LX flow cytometer (Beckman Coulter, USA).

Results. In the third group, there was a decrease in the number of monocytic aggregates (p<0.001) and their subfractions, as well as the number of lymphocyte rosettes (p=0.015), while the number of lymphocytes (p<0.001) and neutrophil interactions (p=0.05) increased in parallel. In the second group, there was a statistically significant decrease in the total number of monocytic aggregates (p=0.038), and in the third, the number of aggregates with classical monocytes (p=0.012).

Conclusion. The number of lymphocyte-platelet and monocyte-platelet aggregates decreased in patients with different types of oxygen support, while neutrophil-platelet aggregates increased and correlated with the SpO2/FiO2 ratio.

Aim. This study aimed to evaluate red blood cell indices and examine erythrocyte morphology in pregnant women with mild to moderate COVID-19 during their third trimester.

Materials and methods. A total of 85 pregnant women who underwent COVID-19 in the third trimester of pregnancy were examined, of whom 44 had a mild course (Group 1) and 41 had a moderate course (Group 2) of the disease. A control group included 35 non-infected pregnant women. The total erythrocyte and hemoglobin counts were assessed, along with hematocrit levels using an automated hematology analyzer, and the morphological shapes of erythrocytes were evaluated using the "MEKOS-C2" automated microscopy system. Erythrocyte transformation indices were also calculated.

Results. The COVID-19 course severity-dependent decrease in the total number of erythrocytes, hemoglobin and hematocrit in the blood of pregnant women relative to the control group was determined. Cytometric analysis of blood smears indicate a reduction in discocyte content in both the mild and moderate COVID-19 groups, both relative to the control and within the groups. Increased numbers of echinocytes and platecytes were observed in both groups compared to controls. In cases with moderate disease severity, increases in elliptocytes, dacryocytes, and degenerative erythrocyte forms were noted. These alterations led to heightened poikilocytosis indices in pregnant women with COVID-19 compared to controls and between groups. The levels of anisocytosis and polychromatophilic erythrocytes did not change significantly. The development of anisochromia was noted in the moderate disease group. Transformation indices for both reversible and irreversible changes were elevated in groups 1 and 2.

Conclusion. The moderate COVID-19 in the third trimester of pregnancy compared to the mild course of the disease is associated with more pronounced changes in the red blood system, characterized by a decrease in the number of erythrocytes and hemoglobin, the development of anisochromia and poikilocytosis. indicating anemia whose severity correlates with the severity of COVID-19 among pregnant women.

Aim. To investigate the levels of interleukin 1β (IL-1β) and prostaglandin (PG) E2 in peripheral blood and their prognostic significance in predicting pregnancy miscarriage in women with cytomegalovirus (CMV) infection exacerbation.

Materials and methods. This case-control study included 98 women in the first trimester of pregnancy (710 weeks), of which 50 women with CMV infection exacerbation (main group) and 48 essentially healthy women (control group). CMV infection was diagnosed by the presence of class M and G antibodies using enzyme-linked immunosorbent assay (ELISA), as well as CMV DNA detected by PCR. The levels of IL-1β and PG E2 in serum of peripheral blood were determined by ELISA using kits from Vector-Best (Novosibirsk, Russia) for IL-1β and Cloud-Clone Corp. (USA) for PG E2.

Results. The study found that women in the main group had a significant increase in the level of IL-1β up to 284.20±20.25 pg/mL (p<0.001) compared with the control group (1.49±0.03 pg/mL). Similarly, the level of PG E2 was also higher than that of the control group, amounting to 929.62±38.0 pg/mL (p<0.001) and 1.29±0.08 pg/mL, respectively.

Conclusion. The results of the study establish the prognostic role of IL-1β and PG E2 concentrations in the pathogenesis of pregnancy miscarriage in women with exacerbation of CMV infection in the early stages of gestation. High concentrations of IL-1β and PG E2 may indicate the development of pregnancy complications and be used as a nonspecific markerpredictor of the threat of miscarriage during CMV infection exacerbation.

Introduction. The epidemiologic situation of tuberculosis (TB) in the Russian Federation (RF) challenges regional TB services to improve their performance.

Aim. To assess the epidemiological situation of TB and the work of the phthisiatric service in the Republic of Crimea (RC) and the RF between 2018 and 2022.

Materials and methods. The epidemiological situation and the work of the phthisiatric service were analyzed using data from the Crimean Republican Clinical Center of Phthisiology and Pulmonology, the FSBI "National Medical Research Center for Phthisiopulmonology and Infectious Diseases" of the Ministry of Health of the Russian Federation, and the Russian Research Institute of Health. Statistical processing included the analysis of dynamic series.

Results. In 2018-2022 among the whole population of the RC, as in the RF, there was a trend of decreasing TB incidence and prevalence with a higher level of the indicator in the region. In RC, the rate of decline in TB incidence in the general population was higher than in the 0-17 age group. The proportion of children aged 0-14 years sick with TB in the RC compared to the RF was on average higher, with a more pronounced growth trend. The coverage of preventive examinations of the population and the proportion of detected TB patients in the RC were on average lower than in the country (by 1.5 and 1.3 times, respectively). The rate of decrease of the indicator in the region exceeded the national one. The ratio of morbidity to mortality in general, both in the RF and in the RC, had a positive trend. The rate of decrease of the indicator in the region exceeded the national one. The ratio of morbidity to mortality in general, both in the RF and in the RC, had a positive trend. In general, the rate of TB recurrence was decreasing in the country and the region. On average, the level of TB relapses in the RC exceeded the national level, but the rate of decrease in the indicator in the region was 4 times higher than in the RF.

Conclusion. Between 2018 and 2022, the epidemiological situation of TB in the RC, along with certain positive trends, was characterized by a number of problems, which, in our opinion, were due to the difficulties of the primary link and the anti-tuberculosis service during the COVID-19 pandemic.

Introduction. Chronic rhinitis is one of the common ENT diseases characterized by nasal congestion, leading to intermittent hypoxia and, consequently, to a disturbance in the balance of prooxidants and antioxidants in the blood plasma, which may reduce the quality of life of patients.

Aim. To evaluate the impact of the "lipid peroxidation – antioxidant defense" system indicators on the quality of life of patients with chronic rhinitis of different phenotypes, using the SNOT-22 disease outcome assessment test.

Materials and methods. The study groups included 45 patients with chronic allergic rhinitis, 49 patients with chronic vasomotor rhinitis, 32 patients with chronic atrophic rhinitis, 39 patients with chronic infectious rhinitis, and 40 individuals in the control group. Spectrophotometric method in blood plasma determined the indicators of the "lipid peroxidation – antioxidant defense" (LPO-AOD) system: diene conjugates, malondialdehyde, catalase, superoxide dismutase, ceruloplasmin, reduced glutathione, glutathione-S-transferase, glutathione peroxidase, and surveyed using the Russian version of the SNOT-22 questionnaire.

Results. For all patients from the study groups with chronic rhinitis, a decrease in the concentration of antioxidant system components was characteristic. An increase in lipid peroxidation was found in chronic allergic, atrophic, and infectious rhinitis, with the most significant disturbance detected in chronic infectious rhinitis. A total of the highest number of disturbances in the LPO-AOD system was found in patients from the study groups with chronic infectious rhinitis – 7, with chronic atrophic rhinitis – 6, with chronic allergic rhinitis – 5, with chronic vasomotor rhinitis – 3. Patients with chronic rhinitis showed a decrease in quality of life across all compared indicators: physical (in all groups) and psychological (in chronic atrophic rhinitis) health components were impaired. A direct correlation (r=0.83; p=0.001) was established between the quality of life and the number of disturbances in the LPO-AOD system, with the most significant decrease in quality of life found in patients from the study groups with chronic infectious rhinitis with the maximum imbalance in the LPO-AOD system.

Conclusion. The quality of life of patients is an important health indicator that depends on the disease phenotype and the performance of the LPO-AOD system. Identifying potential mechanisms for the formation of quality of life as an indicator with a predominantly subjective character under the conditions of an objectively existing disease presents a promising approach for defining measures aimed at improving the quality of life.

Introduction. Atrial fibrillation (AF) is the most common type of supraventricular tachyarrhythmia. Despite the established link between hyperammonemia and cardiac rhythm disorders, data on ammonia levels in patients with AF are currently lacking in both domestic and international medical literature.

Aim. To assess the ammonia levels in the blood of patients with atrial fibrillation and evaluate the effectiveness of standard therapy combined with L-ornithineL-aspartate in patients with atrial fibrillation and hyperammonemia.

Materials and methods. The study involved 88 patients with permanent or persistent forms of AF (47 women, 41 men, aged 69.9±2.2 years), who underwent assessment of ammonia levels in capillary blood (using the portable analyzer PocketChem BA PA 4140), as well as levels of fatigue and active attention using validated "Fatigue Assessment Scale" and "Number Connection Test". Among 36 selected patients with AF and hyperammonemia, undergoing a 10-day treatment course, two randomized groups were formed: the first group (n=18) received standard therapy (angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, antiarrhythmic, diuretic, anticoagulant drugs), and the second group (n=18) received additional therapy (L-ornithine-Laspartate) to reduce hyperammonemia.

Results. Hyperammonemia was detected in 79.55% of the 88 patients, with an average value of 146±5.45 µg/dL (normal up to 75 µg/dL). Ammonia levels in women (115.97±6.78 µg/dL) were significantly lower than in men (150.90±6.62 µg/dL) (p=0.001). During the standard therapy, ammonia levels in the first group did not change significantly (153.63±7.45 µg/dL to 161.53±9.55 µg/dL; p=0.103), active attention levels worsened (p=0.031), and mental fatigue progressed (p=0.06). The second group of patients showed a decrease in ammonia levels from 158.44±8.91 µg/dL to 123.94±11.9 µg/dL (p=0.035), improved active attention (p=0.002), and decreased fatigue (p=0.02).

Conclusion. The results indicate the appropriateness of assessing ammonia levels in the blood of patients with atrial fibrillation and correcting hyperammonemia in this category of patients.

Non-gestational ovarian choriocarcinoma is an exceptionally rare malignant germ cell tumor characterized by a particularly aggressive course, difficult diagnosis, and the inability to predict outcomes at the early stages of the disease. Objective: To draw the attention to the possibility of pure non-gestational ovarian choriocarcinoma mimicking an ectopic ovarian pregnancy. We present the case history of a patient with diagnosed non-gestational ovarian choriocarcinoma mimicking ectopic pregnancy, recorded in the 3rd gynecological department of the State Budgetary Healthcare Institution of the Republic of Mordovia "Republican Clinical Hospital № 4" (Saransk). Our clinical observation adds to the already known information about this rare disease and, thus, we hope that the information provided will be an additional reason to increase the level of medical vigilance in terms of diagnosis of this disease.

Idiopathic multicentric Castleman's disease (iMCD) is one of the subtypes of a rare non-clonal lymphoproliferative disorder affecting lymph nodes of various groups. This article discusses the diagnostic features of iMCD using multislice computed tomography (MSCT) and suggests parameters for postprocessing. A case of iMCD complicated by broncholithiasis, with effective visualization of changes using MSCT technique including images of multiplanar reconstruction and volume rendering, is demonstrated.

Aim. To present our own experience in treating patients with chronic lymphocytic leukemia (CLL) during the COVID-19 pandemic.

Materials and methods. The first group included 20 patients receiving therapy according to the FCR (fludarabine, cyclophosphamide, rituximab) – 15 people and RB (rituximab and bendamustine) – 5 people. The second group consisted of 10 patients receiving ibrutinib at a dose of 420 mg/day continuously.

Results. Both groups of CLL patients showed a high incidence of COVID-19 associated pneumonia (90 and 80% respectively for groups 1 and 2, p=0.06) and a severe course of pneumonia (84% in patients of group 1 and 66.7% in patients of group 2, p=0.0052). At the same time, none of the patients receiving ibrutinib therapy required mechanical ventilation. Among the patients receiving rituximab therapy, mechanical ventilation was required in 10 cases. Among the patients in group 1, the mortality rate was 55.5%. Among the patients receiving ibrutinib therapy, no deaths due to pneumonia or progression of hematoblastosis were registered.

Conclusion. Bruton's tyrosine kinase inhibitors are the safest and most effective in treating patients with CLL during the COVID-19 pandemic. This is due to the immunomodulatory action of ibrutinib; a higher likelihood of achieving a complete response compared to patients receiving FCR and RB protocols; the possibility of outpatient treatment and minimizing the need to visit medical facilities.

Glutathione S-transferase superfamily genes (GSTT1, GSTM1) encode phase II detoxification system enzymes; their mutations increase the sensitivity of the organism to the impact of damaging factors and the development of various diseases. Objective: to present the ecological and ethnic features of the distribution of polymorphic variants of these genes based on the analysis of domestic and foreign literature. The article describes the functional effects of genetic polymorphisms and shows the different frequency of polymorphic variants of GSTM1 and GSTT1 genes depending on race in Russia and the world. Special attention is given to the prevalence features of detoxification gene polymorphisms among the indigenous and migrant populations of the Amur region. Based on the literature data analysis, the conclusion is made about the importance of considering ethnic background, living conditions, and the state of "predisposition" genes for developing a personalized approach to prediction, prevention, and treatment.

Introduction. Toll-like receptors (TLRs) are pattern-recognition receptors that are expressed in many immune and non-immune cells, playing a crucial role in the development of inflammation and associated infectious diseases.

Aim. To summarize the knowledge about the role of TLRs and their genetic variations in the development of cytomegalovirus (CMV) infection during pregnancy and congenital infection in newborns.

Materials and methods. A systematic literature search was conducted in PubMed and Google Scholar for relevant studies. A total of 42 English-language articles and a Russian-language article were reviewed, covering a period of 19 years from 2004 to 2023. The search was conducted using the keywords: Toll-like receptors, cytomegalovirus, polymorphisms, intrauterine infection. The potential role of TLRs and their genetic variability in the pathogenesis of CMV infection both in the general population and in pregnant women is demonstrated. Their possible involvement in the development of congenital CMV infection in newborns is also identified.

Conclusion. The results could be used to develop therapeutic targets aimed at potential application for immune correction of inflammation caused by CMV infection.

Results. The paper shows the knowledge on the structure and types of TLRs, revealing the main molecular mechanisms by which the receptors participate in the regulation of the immune system and the development of inflammation during infection.

Asthma is a global health problem affecting countries worldwide. Currently, there is an increasing prevalence of patients with asthma who also suffer from concomitant cardiovascular pathology. The most common comorbidity is the coexistence of asthma and chronic heart failure (CHF). Given the overlap in clinical symptoms, differential diagnosis of these diseases at onset can be quite challenging. This raises the question of the possibility of early diagnosis of CHF in patients with asthma and the need to continue searching for etiopathogenic markers, as most laboratory indicators do not have 100% pathognomonic value. An analysis of available literature data on potential CHF markers in patients with a history of asthma was conducted. Information queries included the following set of keywords: "markers of chronic heart failure, bronchial asthma, N-terminal pro-brain natriuretic peptide (NTproBNP)." It was found that NTproBNP, currently considered the "gold standard" for diagnosing CHF, does not have absolute prognostic value, indicating the need for further search for highly sensitive and more specific markers. The article presents new biological markers, such as the fibrosis marker galectin-3, gamma-glutamyltransferase, growth stimulating factor, pentraxin 3, and tenascin C, which could be used for forecasting and risk stratification of heart failure development. It is concluded that the search for new biological markers would facilitate earlier diagnosis of CHF, thereby enabling timely therapy initiation, which could help reduce hospitalizations and improve the quality of life of patients.