During the preoperative planning of shoulder arthroplasty, the surgeon encounters bone defects of the glenoid in more than 39 % of cases. Ignoring the bone defect of the glenoid leads to the malposition of the glenoidal component of the endoprosthesis, scapular notching, excessive medialization of the center of rotation, which in turn can reduce the strength and leverage of the deltoid muscle. Accurate diagnosis, assessment and selection of the optimal method of bone defect replacement are necessary for the proper functioning of the endoprosthesis and the duration of its service life.

Aim of the study was to review the literature data over the past 10 years on reverse shoulder replacement in patients with glenoid bone defects, to consider diagnostic methods, indications, advantages and disadvantages, as well as complications with various methods of restoration of glenoid bone defects.

Material and methods. The search for publications from 2014 to 2024 was carried out in databases PubMed, ResearchGate, ScienceDirect upon request: (“glenoid bone loss” OR “glenoid bone deficiency”) and “shoulder arthroplasty”.

Results and discussion. The gold standard and mandatory method should be computed tomography examination, which is necessary for three­plane evaluation of the glenoid defect and component positioning planning. The review presents various classifications, however, an universal classification that not only describes the configuration and degree of the defect, but is also directly related to treatment tactics has not been developed at the moment. Various types of defect replacement are considered. The indications, limitations and disadvantages of each method are systematized in the table.

Conclusions. Nowadays, the world literature lacks not only large­scale long­term observations and meta­analyses on reverse shoulder arthroplasty for glenoid bone defects, but also comparative studies of different types of treatment for comparable groups, which emphasizes the relevance of conducting new research in this area.

Prostate cancer (PCa) has long been classified as an androgen­driven malignancy; however, mounting evidence underscores the pivotal role of estrogen in its initiation, progression, and therapeutic resistance. This review establishes that PCa exhibits intrinsic estrogen dependence through intratumoral aromatization, positioning it within the spectrum of estrogen­driven malignancies. Through integrative molecular analyses, we elucidate how estrogen orchestrates metabolic reprogramming, shifting prostate tumors toward enhanced lipid oxidation and glucose uptake a hallmark of glucolipotoxicity. Mechanistically, estrogen signaling, primarily via the PI3K/AKT pathway, drives the upregulation of carnitine palmitoyltransferase 1 and glucose transporter 1, fueling a metabolic storm characterized by oxidative stress, mitochondrial dysfunction, and chronic inflammatory signaling. This metabolic adaptation enables androgen­independent survival, presenting a critical vulnerability overlooked by conventional androgen­targeted therapies. Our findings necessitate a paradigm shift in the classification and treatment of PCa, advocating for a novel therapeutic framework targeting the estrogen–metabolic axis. We propose a precision strategy integrating aromatase inhibition, estrogen receptor blockade, and metabolic stress modulation to counteract castration­resistant disease. Recognizing PCa as an estrogen­driven, metabolically adaptive malignancy transforms its clinical understanding and therapeutic approach, demanding urgent reconsideration of current oncologic paradigms.

According to numerous data presented in the scientific sources, the use of minimally manipulated cellular products with their own mesenchymal stem cells (MSCs) improves the results of surgical treatment of bone injuries. However, there is currently no consensus on the preferred use of MSCs from bone marrow or from adipose tissue. This is due to the accumulation of positive experience of their use in the restoration of bone defect. The purpose of the work. Determination of the optimal source of mesenchymal stem cells for surgical reconstruction of a bone defect. Material and methods. The search for publications for the period 2021–2025 was carried out in the databases PubMed, eLIBRARY.RU, Google Scholar and other scientific sources. The selected studies contained data on the use of MSCs from bone marrow and adipose tissue, as well as on the technique of their use. According to the PRISMA criteria, 16 publications were screened, of which 10 did not contain the necessary data on the concentration of cellular components and the technique of their application. Thus, a quantitative analysis of the data from 6 publications was carried out. Results and discussion. Currently, the technique of obtaining and preparing minimally manipulated cellular products with bone marrow MSCs for surgical treatment in traumatology and orthopedics is technically simpler and requires less time than the technique with adipose tissue MSCs. This may be one of the reasons for the prevalence of publications describing the use of bone marrow MSCs in clinical practice. The use of mesenchymal stem cells in the area of surgical reconstruction of a bone defect is necessary, however, there is no consensus on the best source of MSCs. Conclusions. According to the conducted analysis of literary sources, the technique using bone marrow MSCs has an advantage due to the reduction of the duration of the operation, however, the effectiveness of the cellular fraction of the bone marrow aspirate can be significantly reduced by errors in the collection technique and the composition of the aspirate itself. Techniques using adipose tissue MSCs have fewer errors, but a longer intervention time. At the same time, reliably important factors for increasing the effectiveness of bone defects surgical treatment with using minimally manipulated cellular products with MSCs are: heterogeneity and a sufficient amount of cellular fraction (no more than 1 million cells), as well as the presence of a carrier matrix.

This article presents an analysis of the role of oxidative stress in the pathogenesis of COVID­19 caused by SARS­CoV­2. Both classical and alternative mechanisms of redox imbalance are discussed, including ACE2 inactivation, mitochondrial dysfunction, neuroimmune dysregulation, and microbiota­associated pathways. Oxidative stress in CODID­19 promotes activation of pro­inflammatory cascades, the NF­κB transcription factor, and suppression of the Nrf2­driven signaling pathway, enhancing cytokine production and promoting a cytokine storm. Impaired antioxidant defense is associated with immune and endothelial dysfunction, facilitating thrombosis and microvascular injury. Contradictory clinical and experimental data regarding the effectiveness of antioxidant therapy are presented. The article highlights the need for a stratified approach and further investigation of redox­related mechanisms in disease progression. Special attention is given to unresolved issues, including the patient’s baseline redox status and the mechanisms underlying persistent activation of NADPH oxidase and suppression of Nrf2 signaling. These aspects may offer new perspectives for the development of targeted therapies for severe forms of COVID­19.

The article provides a review of the modern literature devoted to the study of the relationship between the pathogenetic mechanisms of diabetes mellitus and chronic generalized periodontitis, as well as the effect of periodontal therapy on glycemic control in patients with both diseases. Special attention is paid to key aspects of the pathogenesis of inflammatory periodontal diseases and their relationship with metabolic disorders in diabetes mellitus. It has been established that chronic periodontal inflammation contributes to increased insulin resistance and impaired blood glucose control, while hyperglycemia, in turn, exacerbates the course of periodontitis, creating a vicious circle. The paper considers the main mechanisms of this interaction, including the role of microangiopathies, oxidative stress, and accumulation of glycation end products in tissues, as well as various methods of periodontal therapy, which are based on scaling and root planing with and without the use of antimicrobial medications. Their effectiveness in improving glycemic control, in particular, reducing the level of glycated hemoglobin in patients with diabetes mellitus, has been evaluated. It has been shown that complex periodontal treatment contributes not only to improving the condition of periodontal tissues, but also has a positive effect on carbohydrate metabolism. The results of the study emphasize the need for an interdisciplinary approach to the management of patients with diabetes mellitus and chronic generalized periodontitis, including joint efforts by endocrinologists and dentists. Further research in this area may contribute to the development of more effective strategies for the treatment and prevention of both diseases.

The aim of this review article is to systematize current data on materials and alloys used for the restoration of bone defects in the maxillofacial region, evaluate their advantages and limitations, and assess their prospects for clinical application. Titanium remains the “gold standard” in medical implants due to its high strength, biocompatibility, and durability. However, modern trends in medicine and materials science indicate a growing interest in bioresorbable materials and 3D technologies, which open new horizons for the development of more advanced and functional implants. These innovative approaches not only enhance implant integration with biological tissues but also minimize the risks of long-term complications, such as bone stress shielding or the need for secondary surgeries to remove the implant. One of the most crucial aspects of modern implantology is the necessity for a personalized approach to each patient. This includes considering not only anatomical features but also individual biological and physiological parameters. Interdisciplinary research that brings together the expertise of surgeons, material scientists, bioengineers, and biologists plays a key role in the successful development of new materials and technologies, which present immense opportunities for improving patients’ quality of life. However, to fully realize this potential, continued active research, strengthened interdisciplinary collaboration, and attention not only to technical aspects but also to ethical and economic considerations in the development and implementation of innovations are essential.

The brain­derived neurotrophic factor (BDNF) is abundantly expressed in nervous and immune systems, as well as in bronchopulmonary system and involves in cellular aging, which figures out interest in studying its role in asthma pathogenesis in the elderly (late asthma). BDNF activation can occur not only through its connection with cellular receptors (tropomyosin receptor kinase B (TrkB) and P75 neurotrophic receptor (p75NTR), but also through Keap1/ Nrf2 pathway. Both signalling pathways linked with asthma and aging. In addition, Keap1­independent pathways of Nrf2 activation were described, which are associated with the activity of BDNF and also participate in the aging process and pathogenesis of the asthma. Aging cells acquire senescence­associated secretory phenotype (SASP), which is involved in the progression of immunosenescence, inflammaging, lung aging and is capable of mediating the development of asthma in elderly. On the other hand, aging cells can express BDNF and TRKB, which support their viability through SASP. The fact that TRK inhibitors can reduce the viability of aging cells in the experiment allows us to look in a new way at the role of TRKB/BDNF as a target in the treatment of asthma. The role of Nrf2 is described in cellular aging and related SASP, which can also be of interest from the standpoint of studying its role in pathogenesis in the elderly. This review summarizes modern information regarding BDNF, its receptor and receptor­dependent action, as well as the role in inflammation, inflammaging and asthma pathogenesis in elderly.

Despite the extensive arsenal of antibacterial drugs and the diversity of new wound treatment technologies, it is fair to say that the problem of wound infection has not lost its relevance. As a rule, in patients with concomitant diseases (obesity, diabetes, sensory neuropathies, autoimmune diseases, etc.), the healing of wound defects is prolonged, which makes them especially vulnerable to infections. Wound infection is one of the decisive factors in the pathogenesis of chronic wounds associated with an increase in the number of multiresistant bacterial strains. Two most common wound pathogens are Pseudomonas aeruginosa and Staphylococcus aureus. Wound healing is mediated not only by complex coordinated cellular mechanisms, but also by the impact of the wound microbiome. Objective. Analysis of the mechanisms of pathogenicity and intermicrobial interactions of P. aeruginosa and S. aureus as a significant “instrument” of wound infection to identify priority strategies for antimicrobial therapy (combination antibacterial drugs, phage therapy, use of antimicrobial peptides etc.). Material and methods. A search and analysis of scientific literature for 2018­2025 was performed in the information resources PubMed, eLIBRARY.RU, Europe PMC, Web of Science, CyberLeninka. The search queries included the following combinations of words: for Russian­language publications chronic wound infection; biofilms in chronic wounds, pathophysiological mechanisms of wound healing; for English­language publications chronic wound infection, biofilms in chronic wounds, pathophysiological mechanisms of wound healing, chronic wound infection bacteria, acute and chronic wounds, P. aeruginosa, S. aureus, mechanisms of pathogenicity, virulent properties. Results and discussion. The review summarizes and presents the mechanisms of initiation of wound infection, determinants of virulence, pathogenicity, antibiotic resistance of P. aeruginosa and S. aureus, immune evasion strategies and features of intermicrobial interactions. Conclusions. Wound infections pose a significant global threat due to high rates of morbidity and mortality. P. aeruginosa and S. aureus remain the most common pathogens causing wound infections and form mixed biofilms that hamper their susceptibility to both antimicrobials and the host immune system. Both types of bacteria secrete a broad spectrum of virulence factors, including toxins and enzymes that facilitate their attachment to the wound surface and suppress the host immune response, leading to further tissue damage. Moreover, the spatial organization formed by these pathogens can influence their virulence properties and is key to understanding bacterial interactions within polymicrobial biofilms. Currently, combination antibacterial drugs, phage therapy, antimicrobial peptides, etc. are used to solve the problem of the growth of multidrug­resistant strains.

A literature review is presented using the eLIBRARY.RU, Google Scholar and PubMed information databases for the period 2000–2025. The selection criterion was information on the role of immunoregulatory blood proteins in the reproductive health of women living on the Northern and Arctic territories. The article presents modern data on the role of transferrin, haptoglobin, immunoglobulins, and lipoproteins in physiological pregnancy, infertility, and spontaneous labor. In middle­aged women living on northern and arctic territories, increase of transferrin, haptoglobin, IgM concentrations affect the content of immunocompetent cells, cytokines, and the extracellular pool of receptors, while low levels of apoproteins B, A­I cause insufficient antioxidant and anti­inflammatory protection in the body. Decrease in antioxidant protection and deregulation of the immune response contribute to the increase in reproductive health risks in women living in northern and arctic regions, including menstrual and ovarian cycle disorders and pregnancy complications. The study of the role of blood proteins with immunoregulatory, anti­inflammatory, and antioxidant properties in assessing women’s reproductive health is a promising area.

The gut microbiota is a complex biodiversity of microorganisms, including many different species, that colonize the human intestinal tract. The development and establishment of the gut microbiota in infants is subject to change over time as a result of multiple factors. As previously believed, the colonization of the infant’s intestine with microorganisms begins immediately after birth, however, a growing body of evidence suggests that the intrauterine environment is not sterile, and the transfer of microbiota from mother to fetus occurs during pregnancy. Many prenatal factors can modulate the composition and development of the infant’s intestinal microbiota, such as the characteristics of the mother’s diet, obesity, smoking, and the use of antibacterial drugs during gestation. The method of delivery and the type of feeding are fundamental factors for the subsequent development and establishment of the infant’s microbiota at birth and the postpartum period, respectively. The objective of this review is to identify and analyze the most significant modifiable factors (maternal nutrition, mode of delivery, feeding type) that determine the development of the infant’s intestinal microbiota based on a summary of literature data. This review is necessary to create a theoretical basis that can be used by physicians (neonatologists, pediatricians) to develop practical measures to optimize and correct the microbiocenosis, and prevent diseases in children associated with its disruption (allergy, obesity, diabetes mellitus, necrosing ulcerative colitis).

According to the current consensus published by the European Working Group in 2018, sarcopenia is considered not only as a geriatric syndrome caused by age-related degeneration of muscles, which are manifested by a decrease in strength, mass and functionality. A secondary form of pathology is also distinguished, which is a consequence of a wide range of diseases and conditions, which can develop regardless of age. Many respiratory diseases are currently known as possible causes of secondary sarcopenia, in which catabolic processes in muscle tissue were previously interpreted within the framework of systemic pathogenic effects. In 2021, a Japanese working group of researchers identified a separate phenotype – respiratory sarcopenia, which is associated with a decrease in strength, mass and functionality of the respiratory muscles, observed in a significant number of patients with various diseases, primarily of the respiratory tract, and with aging. The development of sarcopenia (both primary and secondary) has an important prognostic value, as a rule, it is associated with a severe course, a worse response to therapy, and unfavorable outcomes. The aim of the review was to accumulate and systematize the data of international open-access scientific publications since 2019 on sarcopenia and diagnostic approaches for its assessment in the most common respiratory diseases. The most relevant clinical and observational data are presented in the article. It was concluded that striated muscle damage in a wide range of respiratory tract diseases increases the risk of adverse patient outcomes, negatively affects the duration of hospitalization, and entails an increase in the costs of the healthcare system. Currently, a pressing problem in clinical medicine is the timely diagnosis of sarcopenia in conditions of comorbidity and the development of complex therapy programs, taking into account the involvement of muscle tissue and its significant role in long-term outcomes for patients.

Stroke remains one of the most disabling and socially significant diseases, which necessitates the development and implementation of comprehensive rehabilitation methods. The main challenges of recovery are associated with a wide range of neurological disorders, including motor dysfunctions, cognitive and psychoemotional disorders, and sleep disorders in patients after a stroke. Motor disorders have differences in development and rehabilitation of upper and lower limbs. Therefore, the recovery of upper limbs is the most complicated problem due to the specifics of the neural organization and features of movement coordination. Most modern methods of neurorehabilitation have proven their efficiency, but the availability of some of the most effective techniques may be limited. Cognitive and psychoemotional disorders, including depression and anxiety, significantly reduce patient motivation and worsen the prognosis for recovery. Sleep disorders, such as insomnia and obstructive apnea, also negatively affect the rehabilitation process. Prospects for solving these problems include the development of personalized rehabilitation programs, the integration of cognitive and motor rehabilitation methods, as well as their use to correct the psychoemotional state of patients and various sleep disorders.

The dura mater plays a key role in protecting the central nervous system by providing mechanical and barrier functions. Various injuries, surgical interventions, and pathological conditions may require its repair or replacement. The use of synthetic implants or autografts often carries risks, including infections, allergic reactions, and rejection. In recent years, bacterial cellulose has gained attention as a biomaterial with unique properties that could significantly improve surgical outcomes. This review explores the potential of bacterial cellulose as a dura mater substitute and analyzes its advantages. A literature search was conducted in PubMed and Google Scholar (2014–2024), focusing on key studies of biocompatibility and neurosurgical applications. Keywords included bacterial nanocellulose, properties of bacterial nanocellulose, dura mater defects, biocompatibility. Out of 127 sources (in vitro, in vivo, and clinical studies), 32 articles were selected based on novelty, depth of research (mechanical properties, immune response, tissue regeneration), and relevance to dura mater repair. Priority was given to publications from the last decade (2014–2024), experimental in vivo models (rabbits, rats), and reviews on neurosurgical applications. A literature review has shown that bacterial cellulose is a promising biomaterial with unique properties, including high biocompatibility, hypoallergenicity, and the ability to modulate the immune response toward an anti-inflammatory phenotype. A key factor in its efficacy is thorough endotoxin removal, which minimizes inflammatory reactions. Bacterial cellulose demonstrates particular potential in experimental and clinical neurosurgery as a potential medical device for dura mater defect repair.

Immunotherapeutic vaccines are a promising direction in the treatment of oncological diseases. In recent years, significant progress has been made in understanding the mechanisms of interaction between the immune system and tumor cells and in developing strategies to overcome tumor immunosuppression. Aim of the study was to systematize modern data on the development and clinical use of dendritic cell (DC) vaccines for the treatment of gynecological cancer, evaluate their effectiveness, identify key limitations and promising strategies for enhancing the antitumor response. Material and methods. The PubMed, Google Scholar and eLIBRARY.RU databases were used to write the literature review. Results. Clinical studies demonstrate that DC vaccines are capable of inducing a specific antitumor immune response, increasing relapse-free and overall survival in patients with gynecological cancers. The greatest efficiency is observed in combination with chemotherapy, especially when using personalized vaccines based on autologous tumor lysates or neoantigens. However, limitations to their widespread use include response heterogeneity, manufacturing complexity, and the need to optimize the timing of administration relative to other treatments. Conclusions. DC vaccines represent a promising direction for immunotherapy of gynecologic malignancies, but require further research to overcome current limitations. The development of personalized approaches and combination strategies could significantly improve their clinical effectiveness.

The COVID-19 pandemic has affected many aspects of human life, including accelerated aging of the population. Numerous scientific papers indicate the negative impact of SARS-CoV-2 on health, manifested in a number of changes: from shortening of telomeres and an increase in neurodegenerative diseases to cognitive impairment, depression and an increased risk of cardiovascular diseases, including myocarditis and arrhythmia. In addition, there are problems withcoagulation, changes in the expression of the angiotensin-converting enzyme 2 gene, signs of early vascular aging, early immunological aging, metabolic syndrome and external manifestations of premature aging. The list of consequences of COVID-19 is constantly expanding, including changes in blood biochemistry. In this regard, it is imperative to study the mechanisms underlying these changes and develop prevention strategies to maintain healthy aging in the post-COVID era. These features can be taken into account when developing projects to support the older generation.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the effective methods for treating hematological diseases. High accuracy of donor-recipient pair selection based on HLA-system reduces the risk of complications after allo-HSCT. Modern typing methods allow us to study HLA loci not only in high, but also in allelic resolution.

The aim of the study was to evaluate the effect of compatibility at five HLA loci in allelic resolution and mismatches at the HLADPB1 locus of donor-recipient pairs on the outcome of allogeneic unrelated HSCT.

Material and methods. The work included 38 donor-recipient pairs; before HSCT, HLA-typing at the HLA-A, -B, -C, -DQB1, -DRB1 loci was performed in high resolution. Retrospectively, all studied donor–recipient pairs were typed by NGS technology at allelic resolution using the AllType NGS II Loci Amplification Kit (One Lambda, USA) and NGSgo-MX11-3 (GenDX, Netherlands). Statistical data processing was performed using StatTech 4.8.3 software (developer – StatTech LLC, Russia). The DPB1 T-cell Epitope (TCE) Algorithm v2.0 calculator was used to classify the type of HLA-DPB1 mismatch.

Results and discussion. When assessing the overall three-year survival for recipients compatible with donors 10/10 at allelic resolution and less than 10/10, no statistically significant differences were found (p = 0.912). Mismatch in HLA-DPB1 according to the classification did not have a statistically significant effect on the overall three-year survival (p = 0.589). The analysis revealed that the odds of developing chronic graft-versus-host disease in recipients with TCE-incompatible mismatch were higher (p = 0.045) compared with recipients whose donor was incompatible with TCE-compatible mismatch or fully compatible.

Conclusion. Non-permissive HLA-DPB1 mismatch in donor-recipient pairs is one of the predictors of the development of chronic graft-versus-host disease in recipients. The model obtained by binary logistic regression had good discriminatory ability (area under the ROC curve 0.713; 95 % confidence interval 0.513–0.912).

In the forties of the XX century, it was stated by Rose what amino acids are essential that is they are not synthesized in the organism of man and animals if they cannot be found in food. Though threonine is considered an essential amino acid, nevertheless as far back as the eighties of the last century many papers and theses which described ways of mutual transformation of threonine and glycine, catalyzed by threonine aldolase, were published, which by definition contradicts the essentiality of threonine. In particular, an increase in threonine content in the tissues of human beings who were diagnosed with nonketotic hyperglycinemia was explained by its synthesis from glycine under the influence of threoninealdolase. Some authors even ascribed to serine hydroxymethyltransferase, an enzyme which catalyzes mutual transformation of two non-essential amino acids, serine and glycine, the identity to threonine aldolase. That was the reason why the view that threonine disintegrates under the action of serine hydroxymethyltransferase appeared. Later it was determined that threoninealdolase which is very active in bacteria is not present in animals’ tissues and that serine hydroxymethyltransferase does not affect threonine in mammals; thus in mammals the aldol cleavage of threonine is impossible, to say nothing about its reversibility. After that it seems there must not be any doubt that the synthesis of threonine in animals is impossible as both enzymes which catalyze disintegration of threonine (threonine dehydratase and threonine dehydrogenase) split threonine irreversibly; the fact has been known since the discovery of the enzymes. However, recently some papers in which transformation of glycine into threonine in human beings and mammals is ascribed to threonine dehydrogenase have appeared. It should be noted that threonine dehydrogenase in humans is absent. In the present paper impossibility of transformation of glycine into threonine in human beings and mammals is stated on the biochemical level which agrees with the fact that threonine is an essential amino acid.

Consumption of water from man-made reservoirs and groundwater contaminated with arsenic and antimony increases the risk of kidney damage.

The aim of the study was to investigate the spectrum of disorders of the excretory function of the kidneys in rats exposed to subthreshold, threshold, and effective doses of antimony and arsenic ingested with drinking water.

Material and methods. Male Wistar rats (n = 125) received water from a man-made reservoir contaminated with antimony and arsenic for 90 days. The excretory function of the kidneys was evaluated on days 40 and 90 using conventional methods.

Results and discussion. The specific effects of the combined action of antimony and arsenic on kidney function were studied, depending on the levels and duration of exposure, and the dose-response relationships were quantified. The predicted changes in kidney function indicators obtained using approximating curves were almost identical to the empirical data.

Conclusions. The combined contamination of man-made reservoirs and groundwater with arsenic and antimony, which have nephrotoxic effects, increases the risk of kidney damage in potentially exposed population groups.

Chemotherapy toxicity and tumor chemoresistance remain major challenges in modern oncology. One promising strategy to improve therapeutic efficacy and reduce adverse effects is the use of redox-active compounds that attenuate oxidative stress, in particular by activating the antioxidant-responsive Keap1/Nrf2/ARE signaling pathway.

The aim of this study was to evaluate the effects of the synthetic monophenol TS-13, which exhibits both direct and indirect antioxidant activity, on the development and metastasis of Lewis lung carcinoma in mice.

Material and methods. A total of 106 female C57BL mice were randomized into 12 groups. For one month, some groups received oral administration of TS-13 or the reference compound tert-butylhydroquinone (tBHQ) (100 mg/kg). Subsequently, selected groups were implanted intramuscularly with 2×105 Lewis lung carcinoma cells. Some animals then received two injections of doxorubicin (total dose 8 mg/kg). After 7 weeks, tumor and lung tissues were processed for standard histological analysis. Tumor growth activity was assessed by counting mitotic figures, and the general morphological characteristics of tumor and lung tissues were described.

Results. Both doxorubicin and TS-13 demonstrated marked antimitotic effects, which were further enhanced by their combined administration. Combination therapy with cytostatic and TS-13 more effectively suppressed metastatic activity and reduced the overall area of tumor lesions in the lungs compared to monotherapy with doxorubicin, TS-13, or tBHQ. Administration of either TS-13 or tBHQ equally inhibited the development of lung metastases, reducing the number of tumor cells and the formation of large metastatic foci. Notably, the use of TS-13 in combination with doxorubicin partially restored the integrity of the bronchial epithelium.

Conclusions. The synthetic monophenol TS-13, acting as both a direct antioxidant and an activator of the Keap1/Nrf2/ARE pathway, demonstrates potential for optimizing anticancer therapy by enhancing the effect of doxorubicin and suppressing tumor growth and metastasis. In addition, its combined use with doxorubicin helps reduce tissue damage and mitigates the adverse impact on the bronchial epithelium. These properties of TS-13 highlight its prospects for reducing side effects and improving the efficacy of standard chemotherapy regimens.

In the forties of the XX century, it was stated by Rose what amino acids are essential that is they are not synthesized in the organism of man and animals if they cannot be found in food. Though threonine is considered an essential amino acid, nevertheless as far back as the eighties of the last century many papers and theses which described ways of mutual transformation of threonine and glycine, catalyzed by threonine aldolase, were published, which by definition contradicts the essentiality of threonine. In particular, an increase in threonine content in the tissues of human beings who were diagnosed with nonketotic hyperglycinemia was explained by its synthesis from glycine under the influence of threoninealdolase. Some authors even ascribed to serine hydroxymethyltransferase, an enzyme which catalyzes mutual transformation of two non-essential amino acids, serine and glycine, the identity to threonine aldolase. That was the reason why the view that threonine disintegrates under the action of serine hydroxymethyltransferase appeared. Later it was determined that threoninealdolase which is very active in bacteria is not present in animals’ tissues and that serine hydroxymethyltransferase does not affect threonine in mammals; thus in mammals the aldol cleavage of threonine is impossible, to say nothing about its reversibility. After that it seems there must not be any doubt that the synthesis of threonine in animals is impossible as both enzymes which catalyze disintegration of threonine (threonine dehydratase and threonine dehydrogenase) split threonine irreversibly; the fact has been known since the discovery of the enzymes. However, recently some papers in which transformation of glycine into threonine in human beings and mammals is ascribed to threonine dehydrogenase have appeared. It should be noted that threonine dehydrogenase in humans is absent. In the present paper impossibility of transformation of glycine into threonine in human beings and mammals is stated on the biochemical level which agrees with the fact that threonine is an essential amino acid.

Currently, there is no doubt that type 2 diabetes mellitus (T2DM) is associated with local and systemic manifestations of meta-inflammation, which is considered as one of the variants of low-grade inflammation.

Aim of the study was to develop and test a scale for assessing chronic systemic meta-inflammation in patients with prediabetes and T2DM based on a comparative analysis of inflammation biomarker levels.

Material and methods. Two groups of patients were studied: prediabetes (n = 26, fasting serum glucose level of 6.1–6.9 mmol/L and/or postprandial glycemia 7.8–11.0 mmol/L, and glycated hemoglobin content <6.5 %) and T2DM (n = 63). The control group consisted of blood donors (n = 89). To verify meta-inflammation, an integral criterion was used, including blood plasma content of C-reactive protein, cytokines (IL-6, IL-8, TNFα), cortisol, D-dimers.

Results and discussion. Systemic meta-inflammation developed in 57.7 % of patients with prediabetes and in 74.6 % patients with T2DM, but was not detected in the control group. At the same time, in 7.7 and 19 % cases with prediabetes and T2DM, respectively, meta-inflammation in intensity can be characterized as systemic hyperinflammation, when the levels of individual proinflammatory cytokines increased by ten folds relative to the upper normal limit.

Conclusions. Systemic meta-inflammation develops in most, but not all patients with prediabetes and T2DM. In some patients, however, its intensity goes beyond low-grade inflammation and is rather characterized as systemic hyperinflammation, with its characteristic “cytokine storm” phenomenon.

Low birth weight remains one of the key causes of perinatal morbidity and mortality. Timely detection of intrauterine growth disorders requires tools capable of integrating multidimensional ultrasound and clinical data of a pregnant woman.

The purpose of the study was to develop and verify a machine learning model that predicts the risk of having an underweight fetus based on fetometric measurements and maternal factors, as well as to evaluate its diagnostic value compared to classical methods.

Material and methods. The study included 5,477 pregnant women (8,396 ultrasounds; 11–40 weeks gestation). The control group consisted of 5,161 women who gave birth to full–term newborns with normal weight, the case group consisted of 316 pregnant women with full-term babies weighing less than 10th percentile for the corresponding period of pregnancy. For each ultrasound study, standard fetometric parameters and 20 clinical/social variables of the mother were collected. After data purification, a stratified division by pregnant women (80 % train / 20% test), standardization of quantitative characteristics, and binary coding of categories were performed. The following methods were compared: gradient boosting (XGBoost, CatBoost, LightGBM), transformer network and multitasking (regression + classification) neural network. Hyperparameters were selected by Optuna; the quality was evaluated using mean squared error (MAE), root mean squared error (RMSE), area under curve (AUC), sensitivity (Se), specificity (Sp).

Results and discussion. Regression (assessment of gestational age): stacking three boosts gave MAE 0.29 weeks (≈ 2 days), RMSE 0.40 weeks, R2 = 0.989. The multitasking network reached MAE 0.32 weeks. Classification (LBW / norm): The multitasking model showed an AUC of 0.96, Se of 90 %, and Sp of 96 % at the optimal threshold. The greatest contribution to the prognosis was made by the circumference of the abdomen and the length of the femur of the fetus, and maternal factors included placental insufficiency, hypertensive complications, smoking and parity. The elimination of parity reduced AUC by ≈ 0.02, confirming its additional informative value. Calibration of probabilities after isotonic regression demonstrated proximity to the ideal line, which ensures interpretability of risk for the clinician.

Conclusions. A highly accurate system for predicting the risk of having a small fetus has been created and validated, combining ultrasound fetometry and clinical and social data. The accuracy (AUC 0.96) and high sensitivity make the model a promising screening tool for obstetric practice. The implementation of the algorithm in the form of an automated report can improve the early diagnosis of fetal growth disorders and optimize the routing of pregnant women at risk. The next steps are external validation based on multicenter data and analysis of clinical and economic efficiency.

Impaired intrarenal hemodynamics is one of the links in the pathogenesis of chronic kidney disease in type 2 diabetes (T2D); correction of these disorders is the target of drugs with nephroprotective activity, such as sodium-glucose cotransporter-2 (SGLT2) inhibitors.

The aim of our study was to evaluate the effect of the SGLT2 inhibitor empagliflozin on intrarenal blood flow parameters in patients with T2D.

Material and methods. In an open prospective cohort singlecenter study, clinical and laboratory data were monitored before the start of treatment, on the 7th, 28th, 90th, and 180th day of taking empagliflozin 10 mg/day. The study of renal blood flow parameters was carried out using Doppler ultrasonography, peak systolic (PSV), end-diastolic, and mean velocity (MV) of blood flow, as well as resistance index (RI) of intrarenal arteries were assessed.

Results and discussion. Forty patients with T2D and chronic kidney disease, chronic heart failure and/or atherosclerotic cardiovascular disease were included, 17 men and 23 women, aged 43 to 76 years. In the arteries of the cortex, on the 90th day of empagliflozin administration, a decrease in PVR and MV was observed compared to the period before the start of treatment (p < 0.001 and p = 0.004, respectively). This dynamics was maintained on the 180th day (p < 0.001). The lowest values of RI in the arteries of the renal cortex were observed on the 180th day (all p < 0.01 compared to the periods before treatment, on the 7th and 28th days of empagliflozin administration). IR of blood flow in the medulla decreased from the 7th to the 90th day (p = 0.003). The revealed changes in intrarenal hemodynamics were associated with the dynamics of serum creatinine and glycated hemoglobin A1c content, as well as of albuminuria.

Conclusions. In patients with T2D, a decrease in intravascular resistance and blood flow rates in the kidney is observed on the 90–180th day of empagliflozin use. Changes in intrarenal blood flow are associated with the hemodynamic and metabolic response to empagliflozin.

Accurate and fast segmentation of magnetic resonance (MR) images with volumetric brain formations, such as glioblastomas and meningiomas, helps plan surgical and radiation treatment, increase the safety and radicality of surgical intervention, which in turn allows to increase the overall life expectancy of patients and the disease-free period. It is required for the development and evaluation of the effectiveness of a deep convolutional neural network with transmission connections for automatic segmentation of volumetric brain formations (meningiomas and glioblastomas) on postoperative MR images, as well as analysis of its accuracy in comparison with manual expert segmentation and existing methods.

Material and methods. The paper considers the creation of an architecture inspired by the SegResNet model, training on BraTS2024-GLI and BraTS2024-MEN-RT, describes a method for compiling a training sample that reduces class imbalance, and analyzes the results in comparison with participants in the BraTS 2024 competition.

Results and discussion. The developed model was trained and tested on two datasets of postoperative images of glioblastoma and meningioma. Several metrics are analyzed to compare the model with the methods described in the literature, as well as to evaluate it in the context of the variability of manual segmentation by different experts. The model achieves a Sorensen coefficient 0.8299 for meningioma segmentation and 0.7028 for glioblastoma contrast-accumulating region segmentation. In addition, the segmentation of the model provides an accurate estimate of the volume of the tumor area, as evidenced by the high values of the coefficient of intra-class correlation – 0.9661 for meningioma and 0.8339 for glioblastoma. Overall, the developed model requires fewer resources for learning and getting results.

Conclusions. Model performs segmentation at least at the expert level, but with significantly less variability, especially when assessing the volume of the tumor after surgical treatment.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that leads to irreversible structural joint damage and disability. Even with modern therapeutic approaches, a subset of patients continues to exhibit persistent inflammatory activity, which underscores the importance of identifying prognostic markers of treatment efficacy. Increasing attention is currently being paid to the morphological features of synovial membrane remodeling and to the subpopulation composition of lymphocytes in the peripheral blood of RA patients.

The aim of our study was to investigate associations between the subpopulation profile of immunocompetent cells in the synovial membrane and in the peripheral blood of patients with rheumatoid arthritis of varying disease activity.

Material and methods. The study included 52 patients, including 40 with RA and 12 with osteoarthritis as a comparison group. All patients underwent standard clinical evaluation, disease activity assessment (ESR, C-reactive protein content, composite activity indices), and peripheral blood lymphocyte subpopulation analysis. In RA patients with knee synovitis, ultrasound-guided fine-needle aspiration biopsy of the synovial membrane was performed.

Results and discussion. A positive association between the number of CD4⁺ T cells in the synovium and clinical disease activity in RA is revealed, whereas an inverse relationship was observed in peripheral blood. These findings provide additional insights into local immune responses in RA and highlight the potential of synovial biopsy analysis for therapy personalization.

Conclusions. In patients with RA of varying disease activity, divergent associations were identified between the number of CD4⁺ T helper cells in the synovial membrane of affected joints and in peripheral blood.

In Russia, up to 470 thousand cases of stroke have been registered per year over the past five years. Stroke often leads to urination disorder which most often manifested by detrusor hyperactivity.

Aim of the study was to investigate the prevalence of urination disorders due to cerebrovascular disease (CVD) among persons recognized as disabled for the first time in the Kemerovo Region –Kuzbass in 2014–2023.

Material and methods. In persons recognized as disabled for the first time due to CVD in the Kemerovo Region – Kuzbass from 2014 to 2023, disability and morbidity parameters were analyzed, based on Rosstat data, including reporting forms No. 7-Д (social security) and morbidity reports. 3811 individual rehabilitation and habilitation programs for individuals with urinary incontinence, expert documentation from medical and social assessment institutions, and data obtained from the Unified Automated Vertically Integrated Information and Analytical System for Conducting Medical and Social Assessments in the Kemerovo Region – Kuzbass were analyzed.

Results. Urination disorders were found in 1/3 of all persons recognized as disabled due to CVD for the first time; most persons with impaired urination due to CVD were severely disabled persons and female patients.

Conclusions. Early detection and correction of urination disorders will improve the quality of life in persons disabled due to CVD and, coupled with the correct choice of treatment, will decrease the amount of absorbent underwear used, which will decrease the economic burden on the state.

The aim of the study is to assess the features of the epidemic process and clinical and virological characteristics of chronic hepatitis C (CHC) in Saint-Petersburg over a ten-year period (2015–2024).

Material and methods. A retrospective epidemiological analysis of the incidence and mortality of CHC in Russia and Saint-Petersburg for 2015– 2024 was carried out based on data from Federal Statistical Surveillance, government reports and reports from medical organizations of various forms of ownership (The Botkin Clinical Infectious Diseases Hospital, Saint-Petersburg, Russia; non-governmental medical clinic EXCLUSIVE, Saint-Petersburg, Russia). The study included 500 outpatient patients with CHC.

Results. In the Russian Federation and Saint-Petersburg, in the period from 2014 to 2024, there was a decrease in the incidence of CHC by 1.1 times (p < 0.05), the incidence of CHC in Saint-Petersburg exceeds the national values by 2.4 times. Over the past decade, there has been an increase in cases of hospitalization for both acute and chronic hepatitis C, in 2024 the proportion of patients with CHC was 8.5 %. HCV subtype 1b (53.6 %) and 3а (36.8 %) prevailed. Advanced stages of liver fibrosis (F3 and F4), which determine the need for priority start of antiviral therapy, were noted in 42.1 % of patients, which is almost 2 times more than the national level. Hepatitis C virus monoinfection and hepatitis B and C co-infection were the main causes of liver cirrhosis and hepatocellular carcinoma in hospitalized patients. In the etiological structure of hospital case-fatality, the leading place is occupied by the mixed infection of hepatitis B and C viruses (2024 – 33 %), which is more than 2 times higher than the indicators of the prepandemic period (p < 0.05).

Conclusions. The high epidemiological and clinical significance of the CHC burden for Saint-Petersburg in shown, which determines the need to optimize the epidemiological surveillance system, screening programs, as well as access to antiviral therapy.

ABCC8-MODY is caused by variants in the ATP-binding cassette transporter subfamily C member 8 (ABCC8) gene, which encodes sulfonylurea receptor 1 (SUR1), a subunit of the ATP-sensitive potassium channel (K-ATP) found in β-cell membranes. ABCC8 is responsible for the secretion of insulin, which controls blood sugar levels. We report on a 35-year-old female patient with diabetes regarding a likely pathogenic variant NM_001287174.3: c.970G>A, p. V324M (rs1328072266) in the ABCC8 gene. Based on the genetic test results, the patient was diagnosed with MODY12.

Conclusions. A personalized approach to diagnosis and treatment is especially important in identifying the “non-classical” course of diabetes in young people. The presented case demonstrates the features of the clinical course and difficulties in treating a rare form of monogenic diabetes – ABCC8-MODY.

Funicular myelosis (subacute combined degeneration of the spinal cord) is a clinical manifestation of vitamin B₁₂ deficiency, which is rarely diagnosed in children and is associated with damage to the posterior and lateral funiculi of the spinal cord. A clinical case of funicular myelosis with B₁₂ deficiency anemia in a child aged 11 years, which was manifested by sensory ataxia, lower paraparesis, hypotonia, areflexia and atrophy of the muscles of the lower extremities in combination with pyramidal insufficiency, is presented. The cyanocobalamin deficiency in the child’s blood, combined with other hematological indicators, allowed us to diagnose B₁₂-deficiency anemia and determine the cause of the development of neurological manifestations. The development of anemia was associated with dyspeptic disorders against the background of an unhealthy diet with a low content of animal products and the formation of progressive protein-energy deficiency. Neurological manifestations were reversible and regressed during treatment with cyanocobalamin. The case demonstrates the possibility of funicular myelosis developing as the only clinical manifestation of nutritional B₁₂ deficiency anemia in a child.

The emergence of new genovariants of SARS-CoV-2 leads to the need to monitor the epidemic potential of the virus, COVID-19 morbidity and to assess the effectiveness of vaccination against this infection.

Aim of the study was to assess the incidence of COVID-19 in unvaccinated and vaccinated population against this infection in different periods associated with the change in the leading SARS-CoV-2 genovariants.

Material and methods. The data of registration of laboratory-confirmed cases of COVID-19 in St. Petersburg, Leningrad, Kaliningrad, Pskov regions and the Komi Republic in 2020–2024 were used in this work. To assess the effectiveness of vaccination, data on 2 443 331 cases in the population with different vaccine status in 2021–2024 were included in the study. Research methods: epidemiologic analysis, real-time PCR, statistical methods. Data on molecular genetic studies of 14 033 samples were obtained from GISAID and VGARus databases.

Results. The incidence of COVID-19 among the fully vaccinated in different years in the regions was 5–9 times lower compared to the unvaccinated. During the period of circulation of different sublineages of the Omicron genovariant, a decrease in the efficacy of full vaccination was observed. In 2022, a decrease in the efficacy coefficient of 2.1–3.5 % and an increase in the odds of infection of 1.2–3.3 % were observed. In 2023, the efficacy coefficient decreased by 1.9–2.6 % and the odds of infection increased by 1.5–5.5 %. With an incomplete immunization scheme, there was a 28.3–36.6 % increase in the odds of infection, with 95 % lower odds of recurrence among those fully vaccinated. An increase in the probability of re-infection was found with an incomplete vaccination course. In 2024, an increase in the epidemiologic efficiency of vaccination was observed in the conditions of application of updated vaccines.

Conclusions. The results of the study indicate the efficacy of a full course of vaccination against primary and recurrent COVID-19 incidence. During the emergence of genovariant Omicron and its sublines, a decrease in the effectiveness of the full course of immunization was established; violation of the vaccination scheme also led to a decrease in its effectiveness.