Aim. To perform a pathomorphological and semi-quantitative assessment of lipid and calcific lesions of aortic valve leaflets in 12-month-old male and female ApoE^–/– mice in order to substantiate the feasibility of using this model in preclinical studies of preventive therapy for calcific aortic stenosis.

Materials and Methods. The study included 12-month-old male and female ApoE^–/– mice (n = 20). After euthanasia, complexes of the aortic arch with a fragment of the left ventricle containing the aortic valve and the descending aorta were isolated. For macroscopic evaluation of lipid and calcific lesions, whole-mount specimens were stained with 1% Oil Red O and 2% Alizarin Red. For detailed analysis, serial cryosections of aortic valve leaflets were prepared and stained with Oil Red O, Alizarin Red, and hematoxylin and eosin. Visualization was performed using light and fluorescence microscopy. Semi-quantitative analysis of the area of lipid and calcific lesions was carried out using ImageJ software.

Results. Macroscopic evaluation did not reveal lipid or calcific lesions in aortic valve leaflets. However, pathomorphological analysis of cryosections demonstrated multiple lipid inclusions of various sizes, sometimes forming extended clusters, as well as heterogeneous microcalcifications located in both superficial and deeper layers of the valve leaflets. Semi-quantitative analysis showed significantly more pronounced lipid lesions in male ApoE^–/– mice compared with females (p = 0.002), whereas calcification demonstrated comparable values between the groups with a tendency toward higher levels in females.

Conclusion. In 12-monthold ApoE^–/– mice, lipid and calcific lesions develop in aortic valve leaflets and morphologically resemble early changes described in the initial stages of calcific aortic stenosis in humans. Detection of these lesions requires pathomorphological analysis of cryosections using lipophilic and calcium-specific dyes in combination with fluorescence microscopy. The obtained results support the use of ApoE^–/– mice as an experimental model for studying early stages of aortic valve calcification and for conducting preclinical studies of preventive interventions.

Drug-induced kidney injuries are a preventable yet common cause of acute and chronic renal failure. Studying their mechanisms of development, diagnosis, and prevention is essential for improving renal outcomes.
Aim. To identify the dynamics and pathogenetic mechanisms of chronic tubulointerstitial kidney injury during prolonged administration of anti-tuberculosis drugs used for treating sensitive tuberculosis.
Materials and Methods. The experiment was conducted on 50 male outbred white rats weighing 250–260 g. Experimental and control groups (10 rats each) were formed. The control group comprised a baseline and two dynamic control subgroups. The experimental group received a combination of anti-tuberculosis drugs: isoniazid, rifampicin, ethambutol, and pyrazinamide. The study duration was 120 days. The following markers were assessed semi-quantitatively: CD3, CD20, and vimentin.
Results. In a previous study, prolonged administration of anti-tuberculosis drugs induced chronic tubulointerstitial nephritis in rats. To elucidate the underlying mechanisms, immunohistochemical analysis was performed. On day 60, the number of CD3+ cells in the interstitium of the experimental group was 17.9 [16.65; 20.35] compared to 3.1 [2.75; 3.4] in the control group (p < 0.01); by day 120, it increased to 19.6 [18.45; 21.1]. A similar trend was observed for CD20+ cells: 21.6 [19.6; 24.0] on day 60 and 26.5 [23.25; 28.65] on day 120 (p < 0.05). The proportion of vimentin-positive tubules increased to 35.4 % [31.9; 37.95] on day 60 and to 58.9 % [54.15; 63.4] on day 120. Functional impairment was confirmed biochemically.
Conclusion. Long-term anti-tuberculosis treatment induced progressive chronic tubulointerstitial renal injury in rats, characterized histologically by tubular epithelial dystrophy, inflammation, and necrosis. Injury progression was driven by activation of the epithelial-mesenchymal transition, marked by significantly increased vimentin expression in the interstitium and tubular epithelium.

Anaphylaxis is an acute life-threatening condition characterized by rapid onset of systemic disturbances and a high risk of adverse outcomes. Classically, the pathogenesis of anaphylaxis has been attributed to IgE-mediated activation of mast cells and basophils with subsequent release of inflammatory mediators leading to vasodilation, increased vascular permeability, and bronchospasm. However, in recent years, a new understanding of the multifactorial nature of this syndrome has emerged, incorporating systemic, cellular, and molecular mechanisms that extend beyond the traditional allergological paradigm. The aim of this article is to provide a comprehensive review of contemporary concepts of anaphylaxis pathogenesis with an emphasis on the integration of immune, vascular, neurogenic, and metabolic mechanisms. The paper analyzes key pathophysiological pathways, including IgE- and non-IgE-mediated mast cell activation, complementand contact-dependent cascades, neuroimmune interactions, endothelial dysfunction, as well as the role of mitochondrial dysregulation and oxidative stress. Particular attention is given to the phenotypic heterogeneity of anaphylaxis and its association with the development of arterial hypotension, vascular leakage, and shock. The presented data substantiate the need to revise classical views on the pathogenesis of anaphylaxis and provide a foundation for further fundamental research and the development of targeted diagnostic and therapeutic approaches

Aim. To assess the quality of life in patients with NAFLD at the stage of liver steatosis and the effect of a course of cognitive computerized training (CCT) and LOLA intake on changes in quality of life indicators.
Materials and methods. A prospective comparative study was conducted involving 86 patients with NAFLD at the steatosis stage (men, average age 36 years), randomized into two groups: LOLA (n = 42) and CCT (n = 44) for 4 weeks. Participants had to have normal liver function (absence of cytolysis according to biochemical blood analysis), a negative result according to the AUDIT questionnaire (less than 8 points), which excluded alcohol abuse, as well as the absence of hepatic encephalopathy according to the Reitan test and dementia or pre-dementia conditions according to the MMSE scale (score on a scale of 28-30). All patients gave informed consent to participate in the study. The quality of life was assessed twice (before and after treatment) using the SF-36 questionnaire. Standardized data from the MIRAGE study were used for comparison with population norms.
Results. Patients showed a significant decrease in quality of life on the scales of physical functioning (p<0.001), vital activity (p = 0.01), social (p = 0.032) and role-based emotional functioning (p = 0.014) compared with population norms. Both methods of therapy led to significant improvements: LOLA – mainly in vital activity (p = 0.032), CCT – in social (p = 0.012), emotional role (p = 0.004) and mental health (p = 0.038). An intergroup comparison showed the advantage of CCT in improving the psycho-emotional sphere (p<0.05), and LOLA in increasing the energy status (p = 0.041).
Conclusion. NAFLD at the stage of steatosis is accompanied by a decrease in the quality of life in the physical and psycho-emotional spheres. This justifies the need for early detection and comprehensive correction aimed not only at metabolic parameters, but also at improving the quality of life and restoring the ability to engage in daily activity.

Aim. Conduct an analytical review of current evidence regarding postoperative cognitive dysfunction (POCD) in cardiac patients and evaluate the potential of multitasking trainings as a way of cognitive rehabilitation.
Materials and methods. For this systematic review, contemporary domestic and foreign literature sources were searched in PubMed, Google Scholar, CyberLeninka, eLibrary databases, including original studies, systematic reviews, and meta-analyses addressing pathogenesis, diagnosis, POCD risk factors, and cognitive rehabilitation techniques, with a focus on computer-based multitasking trainings, including those with using virtual reality (VR) technologies.
Results. The pathogenesis of the interaction of cardiovascular diseases and cognitive disorders was analyzed, key risk factors for the development of POKD were identified. It has been shown that modern approaches to rehabilitation, in particular multitasking trainings (the method of "double tasks") and VR technologies, have significant potential. They contribute to the stimulation of neuroplasticity, activation of extensive neural networks, improvement of cognitive functions (attention, memory, control functions) and can reduce the frequency and severity of POKD. Data from studies demonstrating neurophysiological and biochemical improvements (e.g., increased BDNF) in patients following such trainings are presented.
Conclusion. The use of multitasking training, especially in the format of computer programs and the use of virtual reality technologies, is a promising non-pharmacological personalized approach to the prevention and correction of POCD in cardiac patients. For widespread implementation in clinical practice, the development of unified protocols and further research are necessary.

Aim. To study regulatory processes in the maternal-placental-fetal system in gestational diabetes mellitus to identify differences in their nature depending on the development of fetal macrosomia.
Materials and Methods. A study of heart rate variability was conducted using standard maternal-fetal methods in 100 women and their fetuses diagnosed with gestational diabetes mellitus and macrosomia detected by ultrasound at 28−29 weeks of pregnancy. The second group consisted of 100 women diagnosed with gestational diabetes mellitus but without macrosomia, according to ultrasound at 28−29 weeks of pregnancy.
Results. The study demonstrates fundamentally different patterns of adaptation in pregnant women with gestational diabetes depending on the development of macrosomia. A favorable scenario (without macrosomia): the body demonstrates effective adaptation – it responds adequately to stress, recovers quickly, and maintains a high energy potential. This indicates intact reserves of the regulatory system. An unfavorable scenario (with macrosomia): despite hyperadaptive efforts, regulation shifts toward autonomous mechanisms (more primitive and energy-consuming). Low energy status, inadequate responses to stress, and lack of recovery indicate a critical decline in adaptive potential. This creates a risk of decompensation and pregnancy complications. Fetuses without macrosomia exhibit a predominantly hyperadaptive state with an optimal balance of autonomic regulation (the ratio of sympathetic to parasympathetic influences is approximately 3:1), high heart rate variability, and rapid adaptation to stress, reflecting significant adaptive potential. With the development of macrosomia in the setting of gestational diabetes, compensatory mechanisms fail: adaptive reserves are suppressed, autonomic regulation is disrupted, and the dominance of the central component of regulation indicates overstrain of the fetal regulatory systems.
Conclusion. The study highlights the negative impact of macrosomia on the functional state of the mother's regulatory systems and points to the need to develop specific rehabilitation measures for women with this complication of gestational diabetes.

Chorionic villi ingrowth is a serious complication of pregnancy, which is a common cause of maternal mortality and postpartum hysterectomy. The prevalence of this pathological condition has increased significantly over the past 30 years due to an increase in the number of cesarean section operations. Diagnosis of chorionic villi ingrowth after curettage of the uterine cavity due to non-progressive pregnancy, spontaneous termination of pregnancy, and medical abortions is still a poorly understood problem, because there are great difficulties in recognizing this pathological condition. Our clinical case presents a situation of diagnosis of chorionic villi ingrowth in a patient after medical abortion, which clearly demonstrates the role of ultrasound examination performed by an expert doctor on a high-resolution ultrasound scanner in the diagnosis of this serious obstetric pathology.

The review presents current information about representatives of the domain Archaea, as part of the human gut microbiome. In the human gastrointestinal tract, 20 species of archaea have been found, the most common are Methanobrevibacter smithii, found in 95.7−100 % of people, Methanosphaera stadtmanae – in 29.4 % and Methanomassiliicoccus luminyensis – in 4 % of people. The species composition of archaea depends on age, with the highest diversity observed in individuals aged 25−60 years. The primary source of archaea colonization in newborns is the intestinal microbiome and the mother's breast milk.

Intestinal archaea are hydrogenotrophs that are unable to break down glycosides and have positive syntrophic relationships with bacteria of the genera Bacteroides, Prevotella, and Ruminococcus, which compete with members of the Desulfovibrionaceae family, indicating their significant contribution to the regulation of the intestinal microbiota.

There is conflicting evidence about the clinical significance of archaea in the gut microbiome. Methane, a metabolite of archaea, regulates the Keap1-Nrf2 system, which provides endogenous antioxidant protection. Some archaea can use pro-atherogenic trimethylamine molecules as electron acceptors, reducing the risk of atherosclerosis. However, archaea have been linked to the development of intestinal cancer and impaired motility, leading to constipation. There is also evidence of a link between archaea and metabolic disorders, as Methanobrevibacter smithii can activate lipogenesis and alter glucose tolerance through hydrogen consumption. Archaea have been implicated in the development of infectious myocarditis and urinary tract diseases. Additionally, there is evidence of the sensitivity of archaea to antibiotics.

In view of the increased attention to the intestinal archaeome, methods for studying methanogenic archaea in humans are described. The main methods are molecular genetic and cultural, but the latter requires complex nutrient media and special atmospheric conditions for cultivation. Data on deposited archaea strains in various microbial collections are provided.

Thus, research on the archaeome of the human intestinal microbiota has far-reaching prospects, both in further assessing the role of archaea for human health and in developing new methods for diagnosing, treating, and preventing microbiome-associated pathological conditions in humans.

Background. Laryngeal cancer is one of the most common malignant neoplasms of the head and neck region.
Aim. To study the characteristics of morbidity, mortality, morphology and survival in laryngeal cancer among the male and female population using the example of a megalopolis in North-West Russia.
Materials and Methods. An analysis of 4,809 newly diagnosed cases of laryngeal cancer was conducted based on data from the St. Petersburg Population Cancer Registry for the period 2001–2024. Epidemiological, clinical, and statistical methods were used in the study.
Results. The incidence rates of laryngeal cancer in men varied from 7.75 to 8.93 with a maximum level at the age of 60−69 years (34.41 per 100 thousand). The incidence rate in women was significantly lower, but from 2001 to 2024 there was an upward trend from 0.55 to 0.96 (p = 0.001), in the age groups of 40−49 and 60−69 years from 0.37 to 0.74 and 1.16 to 2.27 (p = 0.001) per 100 thousand, respectively. During the studied period, squamous cell carcinoma was detected in 75.3 % of men, while among women, an increase in the proportion of this form of cancer was noted from 60.6 % to 81.7 % (p > 0.05). Among men, the incidence of cases detected for the first time at stage IV of the disease increased from 14.0 % to 27.6 % (p = 0.001), among women from 14.0 % to 31.4 % (p = 0.037). Mortality rates among men varied from 4.32 to 5.56 (p > 0.05), among women they increased from 0.26 to 0.46 per 100 thousand (p = 0.018). Among men and women, 5-year overall survival rates in the early stages of the disease varied, respectively, at the level of 65.8−70.7 % and 76.7−89.2 %, in the late stages – 31.6−36.4 % and 36.0−55.8 %.
Conclusion. Laryngeal cancer is more commonly diagnosed in men; however, in recent years, incidence and mortality rates have increased among women. The high proportion of cases detected at late stages and the low survival rate indicate the need for improved early detection and prevention.

Aim. To characterize the incidence of malignant neoplasms (MN) of the digestive organs in the Republic of Karakalpakstan (Uzbekistan) and Astrakhan Oblast (Russian Federation) in 2014−2023.
Materials and methods. Data from the Ministry of Health of Uzbekistan Form No. 7 for 2014−2023 and annual publications "Malignant Neoplasms in Russia" for 2014-2023 were used.
Results. The average incidence rate of malignant neoplasms (2014–2023) in the Republic of Karakalpakstan was 69,6 per 100000 population, compared to 370,3 per 100000 in Astrakhan Oblast. The incidence of digestive system MN over the study period was 109,3 per 100000 population in Astrakhan Oblast, which is significantly higher than in the Republic of Karakalpakstan (28,5 per 100000). However, the prevalence of digestive system MN was higher in the Republic of Karakalpakstan (41 %) compared to Astrakhan Oblast (29,4 %). In the group of MN at three localizations (esophagus, stomach, liver, and intrahepatic bile ducts), the rates in the Republic of Karakalpakstan were 8,7 per 100000 population (95 % confidence interval [CI]: [7,4–10,1]), which was higher than in Astrakhan Oblast (6,8 per 100000; 95 % CI: [5,4–8,6]) only for esophageal MN (relative risk [RR] = 1,32; 95 % CI: [1,20– 1,46]).
Conclusion. The relative risk of mortality from MN of the digestive system (DS) in Astrakhan Oblast was more than three times higher (RR = 3,14; 95 % CI: [2,99–3,30]) than in the Republic of Karakalpakstan. Across all localizations, the incidence and mortality rates in the Republic of Karakalpakstan were higher in men, with the exception of esophageal MN, where higher values were observed in women.

Aim. To evaluate the epidemiological effectiveness of hip arthroplasty and the contingent of patients at the stage of prescribing surgical treatment for coxarthrosis.
Materials and methods. We used a retrospective descriptive study from 2008 to 2024 to analyze the number of HAP patients and patients with disabilities due to coxarthrosis in the Irkutsk region. A crosssectional study of a continuous sample of patients for 2017 (n = 704) was used to analyze the distribution of patients by sex, age, body weight, place of residence, and severity of joint damage in groups with different forms of coxarthrosis: degenerativedystrophic (DDK−56.1 %), dysplastic (DK−30.5 %), and posttraumatic (PTK−13.4 %).
Results. On average, 670 HAP were performed per year, or 3.6 (3.3−3.9) per 10,000 adults; the average disability rate was 7.6 (7.2−8.0), respectively. Over the analyzed period, the number of HAP increased by 2.7 times, and the disability rate decreased by 3.6 times. A weak inverse correlation between HAP and disability rates was revealed in dynamics by years (r = - 0.11, p = 0.68) and a moderate direct relationship (r = 0.27, p = 0.04) when comparing these indicators by territorial units (n = 41). Women predominated in the groups with DDC and DK (60 %), and men in the PTC group (72 %). City residents (69−74 %) and people of retirement and pre-retirement age (Me = 5−57 years) predominated in all three groups. Patients with different forms of coxarthrosis differed in the number of people with disabilities before surgery: odds ratio DDC/DC = 0.65 (0.45−0.95), DDC/PTC = 0.32 (0.22−0.56). Before HAP, 56−79 % of all patients had a disability and more than 96 % had severe joint damage (stages III-IV).
Conclusion. The weak statistical relationship between HAP and disability is explained by the influence of confounding factors, including a high proportion of elderly patients with disabilities before surgery, the presence of patients with contraindications to surgery in the region, and lower accessibility of specialized medical care in rural areas.

Aim. To assess the prevalence of MetS and identify factors associated with its presence among hospitalized patients.
Materials and methods. We conducted an observational analytical cross-sectional study on a sample of 187 patients from the therapeutic department of Sechenov University Clinical Hospital № 4 (study period: April 2024 – January 2025). Data included medical records and face-to-face interviewing. Participants were divided into two groups: 84 with MetS and 103 without. Categorical variables were compared using Pearson's chi-square and Fisher's exact tests. Logistic regression adjusted for sex and age was performed, followed by multivariate analysis.
Results. The prevalence of MetS among hospitalized patients was 44.92 %. MetS was significantly less common in individuals aged 18–44 years and more prevalent among women. In the MetS group, the most common combination (44.85 % of patients) was abdominal obesity combined with two additional criteria. According to logistic regression and multivariate analysis, the factors most strongly associated with MetS were: presence of hormonal disorders in first-degree relatives (OR = 2,92; 95 % CI: 1,07–8,29; p = 0,04), consumption of animal fats and foods containing hidden fats 4–5 times per week (OR = 8,73; 95 % CI: 2,65–33,29; p = 0,001), and salt intake 5 and more g/day (OR = 3,77; 95 % CI: 1,24–12,31; p = 0,02).
Conclusion. The identified association between MetS and hereditary predisposition, as well as excessive intake of fats and salt, underscores the necessity of thorough family history collection and its assessment at the patient's first visit to identify risk groups and enhance motivation for dietary correction. Further prospective studies are required to confirm causal relationships.

The aim of this study is to evaluate the distribution of working time among epidemiologists in healthcare organizations regarding their various functional responsibilities.
Materials and methods. A survey was conducted with the participation of 418 specialists, the method of confidence intervals was used.
Results. The majority of respondents, between 92% and 93%, consider infection prevention to be their most important task. However, only 60% to 67% prioritize their work in organizing and conducting microbiological monitoring. Overall, organizational and methodological work receives considerable attention, with an average of 75.1% dedicating between 1 to 5 hours per week to this aspect, while 12.3% spend between 6 to 9 hours, and 12.5% invest more than 10 hours per week. There is also ample focus on consultative work, as 84.6% of respondents spend between 1 to 5 hours weekly, while 6.8% devote 6 to 9 hours, and 8.4% invest more than 10 hours in this area. Additionally, the control functions are adequately fulfilled, with 85.6% of respondents conducting audits in healthcare facilities. On average, 76.9% allocate 1 to 5 hours per week to ensuring compliance with sanitary and epidemiological regulations, while 11.6% dedicate 6 to 9 hours, and 11.4% spend over 10 hours on it. However, there is insufficient time devoted to analytical work, as 76.7% only allocate 1 to 5 hours per week to this important function, which is crucial for infection prevention.
Conclusion. More than 10 hours per week should ideally be dedicated to analytical tasks by all respondents, highlighting a gap that could impact efforts in infection prevention.

The introduction of digital technologies into prosthetic dentistry has led to a transition from traditional clinical and laboratory stages to fully digital treatment protocols based on digital jaw models. Assessment of the identity of digital models makes it possible to evaluate how interchangeable different scanning methods are when solving clinical tasks. A pilot study demonstrated that dental arch models obtained by intraoral and laboratory scanning show a high degree of agreement, while the detected discrepancies are localised in the distal molar region and ranged from 139 to 282 μm (mean 186.6 ± 42.5 μm).
Aim. To evaluate the identity of digital dental arch models obtained by intraoral and laboratory scanning using the method of three-dimensional virtual model superimposition.
Material and methods. At the Department of Prosthetic Dentistry of Kemerovo State Medical University, 5 volunteers with intact dentitions were examined. Each participant underwent intraoral scanning (Shining3D Aoralscan 3) and laboratory scanning of a gypsum model obtained using a one-step A-silicone impression technique. In the DentalCAD software environment (ExoCAD, EU), three-dimensional virtual models were superimposed, and the maximum shortest distance between surfaces in areas of greatest mismatch was measured.
Results. The maximum discrepancies were localised in the distal molar region and ranged from 139 to 282 μm (mean 186.6 ± 42.5 μm), while in the anterior and anterolateral segments of the dental arch, model coincidence was visually more complete. The data obtained in this pilot study may serve as a starting point for further development of technical and algorithmic solutions aimed at reducing accumulated error during full-arch scanning.
Conclusion. The pilot study showed that dental arch models obtained by intraoral and laboratory scanning generally demonstrate a high degree of agreement, with discrepancies being local in nature and maximal in the distal molar region. The obtained results allow intraoral scanning to be considered a reliable source of digital data for planning and fabrication of prosthetic restorations spanning 4–6 teeth, while maintaining caution when dealing with more extensive prosthetic constructions.