Aim. To study the intensity and correlation between the inotropic responses of myocardium in patients with chronic coronary heart disease (CHD) upon stimulation of β1-adrenergic receptors (β1-AR) and the expression levels of these receptors in cardiomyocytes.

Materials and methods. Isolated myocardium (fragment of the right atrial appendage) from 46 patients with chronic CHD was obtained during coronary artery bypass grafting. The inotropic response of muscle strips was evaluated in an isometric condition. To affect β1-adrenergic receptors (β1-ARs), norepinephrine (10^–7 M) was used under pre-blockade of α-adrenergic receptors (α-AR). The expression of β1-ARs was determined by Western blotting in the same myocardial samples.

Results. It has been established that the myocardium of this cohort of CHD patients demonstrated significant heterogeneity both in terms of the inotropic response to stimulation of β1-adrenergic receptors and the degree of their receptor expression. A significant positive correlation (r = 0.72; p < 0.001) was observed between the inotropic response of muscle strips and the expression level of β1-ARs in these patients’ myocardium.

Conclusion. These findings confirm that the extent of the inotropic response of the myocardium to activation of β1-ARs significantly depends on the number of β1-ARs present when chronic CHD develops. This dependency reflects the degree of cardiac remodeling occurring in this pathology.

Aim. To evaluate the incidence, clinical, anamnestic, and angiographic characteristics of patients with Wellens syndrome (WS) in the profile of non-ST segment elevation myocardial infarction (NSTEMI).

Materials and methods. A retrospective, single-center study was conducted at the Regional Vascular Center No. 2 of the Novosibirsk Regional Clinical Hospital. It included 147 patients hospitalized with a diagnosis of NSTEMI in 2024. Of those, 21 patients (14.3%) had a verified WS ECG pattern (8 had type A, 13 had type B). All patients underwent coronary angiography (CAG).

Results. The age of patients with WS was 64 [57; 72] years, 66.7% were men. All patients had a history of hypertension, 38% had type 2 diabetes mellitus, and 76% had dyslipidemia. Despite the high cardiovascular risk, only 47% of patients received regular antihypertensive therapy, 28% received antiplatelet agents, and 19% – statins before hospitalization. Troponin I levels were elevated in 85% of patients (2.55 [1.9; 3.3] ng/ml). Clinically, spontaneous resolution of chest pain was noted in 50% of cases, recurrence occurred in 60% of patients, and absence of pain was noted in 10% of cases. According to CAG findings, critical stenosis (>90%) of the anterior descending artery was detected in 90% of patients. In two-thirds of the patients, the GRACE score indicated a high risk of in-hospital mortality.

Conclusion. WS was detected in one out of seven patients with NSTEMI and was associated with an extremely high risk of adverse events. Key clinical features include severe polymorbidity due to inadequate basic drug therapy, frequent recurrence, or absence of pain, which complicates timely diagnosis. Detection of characteristic ECG changes is an absolute indication for emergency CAG and revascularization.

Aim. To analyze changes in gene expression of S100 calcium-binding protein A8 (S100A8), S100 calcium-binding protein A9 (S100A9), S100 calcium-binding protein A12 (S100A12), chitinase-3-like protein 1 (YKL40), chitinase3-like protein 2 (YKL39), stabilin 1 (STAB1), tumor necrosis factor α (TNFα), interleukin-1 beta (IL1B), interleukin-1 receptor antagonist (IL1RN), interleukin-6 (IL6), interleukin-10 (IL10), interleukin-12 subunit A (IL12A), C-X-C motif chemokine ligand 8 (IL8), C–C motif chemokine ligand 18 (CCL18), Toll-like receptor 2 (TLR2), Toll-like receptor 4 (TLR4), Toll-like receptor 7 (TLR7), mannose receptor C-type 1 (MRC1), neuropilin-1 (NRP1), transforming growth factor beta-1 (TGFβ1), and colony-stimulating factor 1 (CSF1) in monocytes of prostate cancer (PCa) patients and healthy men.

Materials and methods. The study included 35 patients with stage II–IV PCa and 11 healthy men. Monocytes were obtained from peripheral blood by magnetic sorting. Gene expression analysis and ROC analysis were performed, and the Pearson’s correlation was applied.

Results. In patients with PCa, decreased expression of the IL8 (p = 0.0001, q = 0.002) and YKL40 (p = 0.002, q = 0.017) genes was observed after the Benjamini – Hochberg correction. In contrast, TLR7 (p = 0.0054, q = 0.031) gene expression was significantly increased two-fold in the PCa group. The ROC analysis demonstrated the ability to statistically significantly differentiate patients with PCa.

Conclusion. The study revealed decreased expression of IL8 and YKL40 in monocytes obtained from prostate cancer patients, whereas TLR7 expression was elevated two-fold. The ROC analysis results confirm the diagnostic potential of these markers for differentiating prostate cancer patients.

The aim of this study was to investigate the counts of immunoregulatory cells localized in the peripheral blood and thymus tissue of patients with chronic coronary artery disease (CAD) depending on gender.

Materials and methods. A cross-sectional, single-center comparative study was conducted, including 47 men and 16 women with chronic CAD. The severity of coronary atherosclerosis was assessed by calculating the Gensini score based on selective coronary angiography data. The vascular age index (VAI) was also calculated. The counts of FoxP3+ T regulatory lymphocytes (Treg) and T helper lymphocytes types 1 and 17 (Th1, Th17) in thymus obtained during coronary artery bypass grafting and in peripheral blood were assessed by flow cytometry.

Results. Women had higher absolute counts of terminally differentiated Tregs (CD25^loFoxP3+ Tregs) in the blood and showed a trend toward an increased proportion of Tregs in the total CD4+ cell population in the thymus compared to men. Only in women was the number of Tregs in the blood correlated with both the Gensini score and the VAI.

Conclusion. Thus, the distribution of Tregs in the blood and thymus in CAD has gender-specific characteristics: women have signs of prior Treg activation, which may contribute to limited severity of coronary atherosclerosis compared to men.

Aim. To evaluate the role of genetic variants of the genes encoding signal transducer and activator of transcription 5 (STAT5B), interferon-gamma receptor 2 (IFNGR2), suppressor of cytokine signaling 5 (SOCS5), the GATA3 transcription factor, interleukin-10 (IL10), and the STAT4-inhibitory protein PIAS4 in the development of bronchial asthma and opisthorchiasis.

Materials and methods. The study included DNA samples from 85 children with bronchial asthma (BA) of varying severity (mean age 10.1 ± 8 years), 86 individuals with O. felineus infection (mean age 11.2 ± 4.5 years), and 140 control subjects (mean age 11.1 ± 5 years). Gene variants including rs16967593 (STAT5B), rs7880053 (IFNGR2), rs6737848 (SOCS5), rs10905277 (GATA3), rs1800872 (IL10), rs3760903 (PIAS4) were genotyped using real-time polymerase chain reaction.

Results. The rs10905277 variant of the GATA3 gene was associated with the risk of developing bronchial asthma in additive (p = 0.001; OR = 0.51; 95% CI; 0.34–0.77) and recessive models (p = 0.008; OR = 0.22; 95% CI; 0.07–0.68). The GATA3 gene variant under study was found to also affect the severity of atopic disease (p = 0.025). The rs16967593 variant of the STAT5B gene was associated with opisthorchiasis in both additive (p = 0.032; OR = 1.61; 95% CI: 1.04–2.51) and recessive (p = 0.035; OR = 2.82; 95% CI: 1.08–7.37) genetic models.

Conclusion. For the first time, the development of bronchial asthma in children from Tomsk population was shown to be associated with the rs10905277 polymorphism of the GATA3 gene, which is involved in the development of atopic inflammation. The GATA3 gene rs10905277 variant under study is also associated with disease severity. Homozygous genotypes for the G allele and heterozygotes were more frequent in patients with more severe disease compared to those with mild asthma (94.4% vs. 62.7% and 83.3% vs. 59.3%, respectively). The rs16967593 polymorphic variant of the STAT5B gene is associated with O. felineus infection.

The aim of the study was to analyze the dynamics of antibiotic resistance among major pathogens causing maxillofacial infections from 2020 to 2024.

Materials and methods. The study was based on the analysis of microbiological cultures from patients treated in the Dental Purulent-Surgical Unit at Vitebsk Regional Clinical Hospital between 2020 and 2024. Antibiotic susceptibility was determined using broth microdilution and disk diffusion methods, as well as the Biomérieux ATB Expression and BD Phoenix test systems. To evaluate the efficacy of antibacterial agents, the minimum inhibitory concentration (MIC₉₀) of antibiotics was compared between planktonic bacteria and those within biofilms (BF).

Results. K. pneumoniae exhibited a critical increase in resistance to carbapenems, reaching 50% in 2022, which alters approaches to empirical therapy with β-lactam antibiotics. The following changes were observed among Gram-positive pathogens: S. aureus showed a marked increase in resistance to amikacin and erythromycin. Coagulase-negative staphylococci showed an increase in the proportion of methicillin-resistant strains to 43.64% by 2024. An increase in resistance to third-generation cephalosporins was observed among α-hemolytic streptococci (cefotaxime: 31.58% in 2024). Vancomycin and linezolid remained fully active (100%) against all Gram-positive pathogens tested. Biofilm formation significantly increases antibiotic resistance, with MIC₉₀ values 4to 128-fold higher than those for planktonic bacteria.

Conclusion. These findings indicate the need to reconsider empirical therapy, favoring antibiotic combinations with anti-biofilm properties, and to enhance microbiological surveillance.

Aim. To study the co-expression patterns of molecular biological subtype (MBS) markers on individual circulating tumor cells (CTCs) in luminal subtypes of breast cancer (BC) and their association with the expression of stemness and epithelial – mesenchymal transition (EMT) markers.

Materials and methods. The study analyzed venous blood and primary tumor biopsies from 51 BC patients (N1– 4N0–3M0), including 21 cases with luminal A, 19 cases with luminal B (HER2–), and 11 cases with luminal B (HER2+) MBS. Flow cytometry was used to assess the expression of CD45, EpCAM, N-/E-cadherin, CD44, CD24, CD133, Her2neu, ER, PR, and Ki67 in CTCs before therapy initiation. Statistical analysis was performed using Statistica 10.0 (p < 0.05).

Results. In luminal A and B (HER2–) primary tumor MBS, phenotypic conversion of CTCs was observed, characterized by the emergence of HER2+ CTCs, which were often ER-negative and exhibited various coexpression patterns of stemness markers. The key practical finding was the identification of a metastasis-associated CTC phenotype in luminal HER2– MBS: CD45–EpCAM+ER–PR–Her2neu+Ki67–. This phenotype corresponds to the classical HER2+ subtype at the level of a single cell.

Conclusion. The study results support the feasibility of determining MBS marker expression on a single CTC for predicting the risk of hematogenous metastasis in luminal A and B (HER2–) primary tumor MBS and for optimizing treatment strategies.

The aim. To study the antioxidant, hepatoprotective, and anti-inflammatory properties of an aspen bark (Populus tremula L.) phenol glycoside complex (ABPG) in vitro.

Materials and methods. ABPG was obtained by solvent extraction and characterized by high-performance liquid chromatography (HPLC). Radical scavenging activity was assessed by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, and iron chelating capacity was evaluated by the colorimetric ferrozine-based assay. Cellular effects were studied in HepG2 cells in models of lipotoxicity (oleic and palmitic acids), paracetamol-induced injury, and inflammatory stimulation with lipopolysaccharide (LPS) and interferon γ (IFNγ). Intracellular reactive oxygen species (ROS), reduced glutathione (GSH), neutral lipid content, or cell viability served as endpoints.

Results. ABPG comprised more than 70 individual constituents; its dominant components (as a share of the total HPLC peak area) were dihydroxybenzoic acid (11.5%), methoxybenzoic acid (8.5%), luteolin (7.7%), salicin (5.4%), and hydroxybenzoic acid (1.88%). The complex showed pronounced radical scavenging activity (IC₅₀ = 87.6 µg/ml in the DPPH assay) and chelated Fe²⁺ ions in the amount equivalent to 14.07 mg ethylenediaminetetraacetic acid per gram of the sample. In HepG2 cells, ABPG lowered ROS levels under lipotoxic conditions by 47.6% and prevented intracellular lipid accumulation by 40.4%. In paracetamol-induced injury, it restored cell viability to 77.9%; and under LPS/IFNγ stimulation, it decreased ROS production by 19.2% while raising GSH levels by 42.9%.

Conclusion. The aspen bark phenol glycoside complex modulates the redox state and stress responses of hepatocytes, conferring cytoprotection through redox-dependent mechanisms. These effects underlie its antioxidant, hepatoprotective, and anti-inflammatory effects in vitro.

The aim of this pilot study was to assess the effect of salbutamol 400 µg on lung diffusing capacity (DLCO) and alveolar volume (VA) during bronchodilator test in patients with respiratory disorders, and to evaluate whether future studies with adequate statistical power are warranted.

Materials and methods. A prospective longitudinal study was conducted in 51 adult patients (82% men, median age 44 years) with respiratory diseases. All patients underwent spirometry and DLCO measurement before and  15 minutes after inhalation of 400 µg of salbutamol.

Results. No significant effect of salbutamol inhalation on mean DLCO values was observed (p = 0.39), whereas a significant increase in VA was noted (p = 0.03). Cohen’s d effect sizes were 0.026 and 0.056 for DLCO and VA, respectively, confirming the lack of a significant effect. In 10% of the patients, the DLCO change exceeded the test-retest repeatability threshold (±2 mL/min/mm Hg). The minimum sample size for future studies was  210 patients.

Conclusion. Inhaled salbutamol (400 µg) has no clinically significant systemic effect on DLCO. The observation of individual variability in DLCO response in 10% of the patients supports the need for larger studies (n ≥ 210) to definitively assess the impact of β₂-agonists on gas exchange.

The aim of the study was to develop a quantitative scoring system for fibrotic changes in pancreatic tissue (P), and to identify prognostic computed tomography (CT) parameters for assessing pancreatic fibrosis and the risk of specific postoperative complications.

Materials and methods. Between 2009 and 2022, 136 patients underwent surgery for complicated forms of chronic pancreatitis. The study population was predominantly male: 100 patients (73.5%) were men and 36 (26.5%) were women. Age ranged from 17.0 to 76.0 years, with a median of 45.0 [37.8; 53.0] years. The median disease duration was 36.0 [12.0; 84.8] months. All patients underwent contrast-enhanced multislice CT before surgery, and histological examination was performed after the intervention according to developed research protocols.

Results. To quantitatively assess the gland structure, the ratio of preserved functional parenchyma to stroma, obtained from histological examination, was used and expressed as the parenchymal-stromal ratio (PSR). Based on ROC analysis, a PSR value of < 1.561 was identified as the threshold corresponding to clinically significant fibrosis. Correlation analysis identified preoperative CT parameters that showed a strong (contrast enhancement coefficient) and moderate (native-phase pancreatic parenchymal density, pancreatic duct diameter, and pancreatic index) correlation with the histological marker, as well as high diagnostic significance according to ROC analysis. Based on the integration of CT parameters into a multivariate model using ROC analysis, a scoring system was developed to predict the risk of clinically significant fibrosis. The cut-off point was set at 1 point. We proposed a risk assessment scale for predicting specific postoperative complications. A score of >3 points was associated with a 12.3-fold increase in the risk of specific postoperative complications.

Conclusion. Morphometric analysis enables quantitative assessment of fibrotic changes in the pancreatic parenchyma. The analyzed CT parameters were effective in predicting the morphological structure of the pancreas. The obtained preoperative CT parameters allow for reliable prediction of the risk of specific postoperative complications.

Aim. To perform computer modeling and evaluate the interaction of Janus Kinase 3 (JAK3) with xanthotoxin.

Materials and methods. The 3D structures of JAK3 (PDB ID: 5LWM) and xanthotoxin PubChem (PubChem ID: 4114) were obtained from the Protein Data Bank (PDB) and the Chemical Compounds and Mixtures Database (CCM), respectively. PyMOL v. 2.5 was used to prepare the kinase structure for molecular docking, and OpenBabel was used to convert xanthotoxin to .pdb format. Molecular docking was performed using AutoDock Vina, and molecular dynamics simulations were performed using GROMACS 2023.3. The CHARMM36 force field was used to construct protein topology, and the CHARMM General Force Field (CGenFF) server was used for ligand topology. Xmgrace and PyMOL were used to analyze the results.

Results. Molecular docking of JAK3 and xanthotoxin yielded a stable complex with a binding energy of 7.043 kcal/mol. The amino acid residues of JAK3 involved in the intermolecular interaction were identified: leucine at position 828 (LEU828) and at position 905 (LEU905). The stability of the docked complex was confirmed by molecular dynamics simulations. Molecular dynamics simulations showed that the JAK3 complex maintained its structure throughout the simulation in the presence of xanthotoxin; the system reached an equilibrium state.

Conclusion. These data suggest a possible role for xanthotoxin in programmed cell death and can be used for further experimental studies.

Aim. To evaluate the profile of postoperative complications and the dynamics of transthoracic echocardiography parameters, physical performance, and myocardial injury markers in patients with frailty syndrome in the perioperative period of coronary artery bypass grafting (CABG), depending on the chosen rehabilitation program.

Materials and methods. The study included 80 patients with stable coronary artery disease, randomized into two groups. Patients in group 1 (early rehabilitation, n = 36) completed an early physical rehabilitation program on a treadmill lasting 14-18 days. Group 2 (control, n = 44) did not complete the early training program. Myocardial remodeling parameters using echocardiography and physical performance of the participants, assessed at days 5-6 and 21-23 after CABG, were analyzed. Additionally, the concentration of myocardial injury biomarkers, including N-terminal pro-brain natriuretic peptide (NT-proBNP), interleukin (IL) 33, and stimulating growth factor gene-derived 2 (ST2), as well as the incidence and nature of intraand postoperative complications were assessed.

Results. The incidence of complications was 18% among patients who completed the early rehabilitation program and 48% in the control group (p = 0.03). The odds of developing complications were significantly lower in patients who were engaged in the early training program compared to those who were not (OR 0.34; 95% CI 0.13-0.92; p = 0.03). Left ventricular ejection fraction decreased after surgery relative to baseline values both in group 1 (p < 0.001) and in the control group (p = 0.001). In the third week after CABG, patients with early rehabilitation showed a significant improvement in peak oxygen consumption (p = 0.041) and exercise tolerance (p < 0.001), as well as a decrease in NT-proBNP (p = 0.009) and ST2 (p = 0.002) levels. In the control group, either an increase in these parameters or persisting negative trends were observed.

Conclusion. Data were obtained on the impact of early physical training on the postoperative disease course in patients with frailty syndrome undergoing CABG. The examination of changes in laboratory markers of myocardial damage and instrumental signs of myocardial remodeling was performed.

Aim. To assess the profile of proteases with elastolytic activity (EA) in peripheral blood in the pathogenesis of pulmonary tuberculosis (PT) in relation to pulmonary ventilatory dysfunction and gas exchange abnormalities.

Materials and methods. A comprehensive assessment of the lung status was performed in 264 patients with verified PT without co-occurring chronic obstructive pulmonary disease. Chest computed tomography with em­physema progression quantification and pulmonary function testing (PFT) were performed, including spirometry, body plethysmography, and measurement of diffusing capacity of the lungs for carbon monoxide (DL_CO). Serum levels of matrix metalloproteinases (MMP-7, -9, -12) and their tissue inhibitor-1 (TIMP-1) were determined by ELISA using reagents from R&D Systems (Minneapolis, MN, USA), while neutrophil elastase (NE) and a₂-macroglobulin (MG) levels were measured by inhibiting synthetic substrates (ICN Biomedicals Inc., USA). Statistical analysis included the non-parametric Mann Whitney and Kruskal Wallis tests with Bonferroni correction and the Spearman’s rank correlation coefficient in Statistica 7.0. A multivariate analysis of variance (MANOVA) model was constructed in R.

Results. In the MANOVA model, a composite variable Y was derived from the biochemical markers, reflecting changes in proteases with EA in PT pathogenesis, considering the clinical form and patterns of pulmonary function impairment. In destructive disease without pulmonary function abnormalities, EA was determined predominantly by NE and MMP-12 levels. Fibrotic transformation with obstructive or mixed pulmonary dysfunction was ac­companied by a shift in the protease inhibitor balance towards increased concentrations of MMP-7 and MMP-9. Excess EA at early stages of the disease was compensated by MG, whereas at later stages, compensation was mediated by TIMP-1.

Conclusion. Alterations in the profile of proteases with elastolytic activity characterize shifts in tissue responses, reflect the development of distinct patterns of functional respiratory disorders and DL_CO reduction, and may there­fore serve as biochemical markers of evolving ventilatory dysfunction and gas exchange abnormalities in PT.

This lecture summarizes current evidence on the molecular and genetic mechanisms of resistance to HER2targeted breast cancer (BC) therapies. Despite marked improvements in HER2-positive BC treatment, the efficacy of targeted therapy remains suboptimal. Within the first two years after completing combined therapy, 10-15% of patients develop locoregional recurrences, and 15-25% of patients develop distant metastases within the first five years of follow-up, which is attributed to drug resistance.

The primary mechanisms of resistance are discussed, including impaired binding of targeted drugs to HER2, activating HER2 mutations, HER2 intratumoral heterogeneity, cross-talk between HER2 and estrogen receptors, alterations in intracellular signaling pathways, the role of HER2-HER3 heterodimer, and the tumor microenvironment. Particular emphasis is placed on factors limiting the efficacy of antibody drug conjugates, which are currently a subject of active investigation. Understanding the mechanisms of resistance to HER2-targeted therapies is crucial for optimizing treatment strategies for HER2-positive BC patients. This includes novel drug development, early resistance prevention, and personalized therapy to improve patient outcomes.

The review highlights modern mechanisms underlying the pathogenesis of diabetic ketoacidosis (DKA) based on the analysis of experimental and clinical data. It describes molecular pathways involving activation of the nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome, followed by the release of pro-inflammatory cytokines interleukin-ie (IL-1P) and interleukin-18 (IL-18), as well as the initiation of в-cell pyroptosis in the pancreatic islets of Langerhans. Mitochondrial dysfunction and increased oxidative stress are discussed as contributors to cellular damage and amplification of the inflammatory response.

The dysregulation of pancreatic а-cells with enhanced glucagon secretion, stimulating gluconeogenesis and keto­genesis, is analyzed. The role of the kidneys in maintaining ketone body levels is considered, including filtration, reabsorption, and interactions with lipid signaling pathways that influence insulin resistance and inflammation. Central neurohumoral mechanisms involving the hypothalamic pituitary axis and the sympathetic nervous system are described, as well as the distinctive features of DKA developing during therapy with sodium-glucose cotrans­porter type 2 (SGLT2) inhibitors.

The importance of osmotic stress and its interplay with counter-regulatory hormones is emphasized. An integrative model is presented that unites inflammatory, metabolic, endocrine, and renal components, providing a deeper understanding of the clinical manifestations of DKA and offering prospects for the development of new diagnostic and therapeutic strategies.

Lymphangitic carcinomatosis is one of the most severe forms of tumor progression. It is characterized by the massive spread of tumor emboli, composed of cells with reduced adhesive capacity to the endothelium, through the lymphatic vessels. Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta­Analyses) guidelines, 394 scientific papers were screened. Of those, 292 English-language publications met the criteria for analysis. A total of 39 articles (including three in Russian) relevant to the topic of this review were included.

Due to the highly diverse localization of lymphangitic carcinomatosis and its polymorphic symptoms, diagnosis remains challenging and is associated with the risk of erroneous and often delayed decision-making. Data on lymphangitic carcinomatosis are still scarce, and its developmental mechanisms are not fully understood. However, systematizing knowledge about its possible clinical and morphological manifestations and studying the molecular and genetic mechanisms of its development could serve as a basis for identifying key prognostic markers and developing targeted therapies for this currently prognostically unfavorable form of tumor progression.

Preeclampsia (PE) occupies a leading position in the profile of maternal morbidity and mortality. PE is also a common cause of neonatal mortality. Therefore, forecasting the progression of PE and its prevention are key directions in modern obstetrics aimed at reducing maternal and perinatal morbidity.

Platelets are multi-functional cell fragments that play an important role in the pathogenesis of PE, while platelet indices allow for the assessment of certain morphometric features of platelets and for the indirect assessment of their functional state.

The authors conducted a non-systematic, descriptive search of scientific publications in the PubMed, eLIBRARY. RU, and Google Scholar databases. This search was aimed at systematizing data on the use of accessible and easily measurable prognostic markers of PE, including platelet and hematological indices presented in clinical blood tests and performed on modern hematology analyzers. Priority was given to studies published within the past 10 years.

The review shows that mean platelet volume (MPV), plateletcrit (PCT), platelet distribution width (PDW), and the platelet-to-lymphocyte ratio (PLR) have the greatest prognostic value for PE. Moreover, the prognostic value increases with a combination of these indices, taking into account the gestational age (optimally 14-28 weeks) and integration with clinical risk factors. It is worth noting that for successful implementation of platelet indices into routine clinical practice, further studies are required, aimed at standardizing measurement methods, defining clinically significant threshold values and assessment times, conducting multicenter studies with large samples, and validating the prognostic value at different stages of pregnancy.

Atrial fibrillation and coronary artery disease (CAD) are a common and clinically significant comorbidity. Based on various epidemiological studies, it is believed that the relationship between atrial fibrillation and CAD is complex and much closer than a mere coincidence. These two diseases share common risk factors that influence the underlying mechanisms of their development, contributing to a vicious cycle of their onset and progression. In this case, CAD can be both a cause and a consequence of atrial fibrillation.

The aim of this systematic review was to evaluate and compare the opinions of authors of various publications on the interactions between atrial fibrillation and CAD, taking into account the epidemiology and pathophysiological interactions between them.

Materials and methods. The PRISMA (Preferred Reporting Items for Systematic Reviews and MetaAnalyses) 2020 methodology was used to select relevant publications. According to these guidelines, 597 articles on the stated topic were identified in the PubMed and eLibrary.ru search engines. At the final stage, 74 English-language publications and 16 Russian-language publications were included in the review. Existing opinions in various publications often complement one other, although they are sometimes contradictory, requiring further in-depth research in this area. The pathophysiological findings suggest that these two diseases can form a vicious cycle, exacerbating each other. Understanding these interrelated mechanisms allows for a transition from symptomatic treatment to a pathogeneticallyfocused strategy aimed at breaking the vicious cycles linking atrial fibrillation and CAD.

Overlap syndrome in rheumatology represents a significant clinical challenge, owing to diagnostic difficulties and the complexity of selecting appropriate therapy, which together may contribute to an unfavorable prognosis. In recent years, comorbidity including that underpinned by metabolic syndrome has emerged as one of the most im­portant features of human pathology. This symptom complex is regarded as the primary cause of the development, severe course, and complications of the most epidemiologically significant non-communicable diseases, including systemic connective tissue diseases. The presented clinical case illustrates the course of overlap syndrome in pro­nounced metabolic disorders.

Temporary placement of an intra-aortic balloon pump for the treatment of perioperative myocardial infarction in patients with severe peripheral artery disease and systemic hypoperfusion is associated with an increased risk of lower limb ischemia. In such clinical settings, it is particularly important to use methods that allow objective and continuous assessment of local tissue perfusion. This article presents a clinical case of using tissue oximetry based on near-infrared spectroscopy (NIRS) to monitor regional oxygenation in a patient with acute myocardial infarction and cardiogenic shock following coronary artery bypass grafting.

The patient had severe stenosis of the iliac artery (greater than 70%), which significantly increased the risk of isch­emic complications during catheter placement for intra-aortic balloon counterpulsation. The use of NIRS enabled continuous monitoring of regional oxygen saturation in the calf muscles and early detection of subtle changes in distal perfusion. As systemic hemodynamics stabilized, a consistent increase in regional oxygen saturation was observed, reflecting improved peripheral tissue perfusion.

The use of tissue oximetry in this clinical case ensured safe mechanical circulatory support without the risk of lower limb ischemia, demonstrating the high practical value of this method in the perioperative management of high-risk patients.

The aim was to demonstrate the potential of using artificial intelligence (AI) in pharmacology and the development of new drugs. This study reviews the key technological drivers shaping the market for generative design and AI applications in medicine, the dynamics of the global AI drug discovery market, the activities of leading players and startups, and the regulatory and legal aspects governing the industry. Particular focus is placed on the Russian market, including its maturity, growth barriers, and AI adoption case studies from 2022 to 2025.

This article is dedicated to the memory of Vyacheslav V. Novitsky, one of the most brilliant and internationally renowned Russian pathophysiologists, a prominent public and cultural figure, and the founder and editor-in-chief of the journal Bulletin of Siberian Medicine. Vyacheslav Novitsky served as Rector of Siberian State Medical University from 1997 to 2014 and as chair of the Pathophysiology Division from 2000 to 2017. As an academic visionary educator, he established a premier research school that continues the traditions of Tomsk school of pathophysiology. He was supervisor and mentor for over 150 PhD and DSc scholars. Vyacheslav V. Novitsky made an outstanding contribution to the development of Siberian State Medical University, significantly elevating its academic ranking and developing a modern campus infrastructure. Beyond academia, he was deeply engaged in civic and cultural life, serving as a deputy of the Tomsk Regional Duma and earning the title of Honored Worker of Culture of the Russian Federation. His achievements were recognized with numerous prestigious awards, including the Davydovsky Gold Medal of the Russian Academy of Medical Sciences. Vyacheslav Novitsky left behind a profound legacy as one of the greatest scientific minds and a goal-oriented, vibrant man of diverse interests and immense erudition.