Background. Vulvovaginal atrophy (VVA) following antitumor treatment is a common and clinically significant complication. At the same time, the immunoinflammatory mechanisms determining the severity and persistence of atrophic changes are yet to be sufficiently studied. The role of extracellular neutrophil traps (NETs) in the pathogenesis of genital tract mucosal damage remains virtually unexplored. Objective: To evaluate blood levels of NET markers – citrullinated histone H3 (CitH3), myeloperoxidase (MPO), cathepsin G (CatG) – in various VVA phenotypes after antitumor therapy and to determine their significance as potential biomarkers of atrophy severity. Material and methods . A cross-sectional comparative study enrolled 215 postmenopausal women divided into five groups as follows: VVA after surgical treatment (n=52), chemoradiotherapy (n=27), antiestrogenic therapy (n=48), VVA without a history of cancer (n=53), and control (n=35). Clinical symptoms, vaginal pH, vaginal health index (VHI), epithelial thickness, and plasma levels of CitH3, MPO, and CatG were evaluated. Statistical analysis was performed using the Mann–Whitney test with Bonferroni correction and calculation of the r effect size. Results . The NETs profile varied depending on the nature of the treatment received. Maximum levels of CitH3 (0,65 [0,50–0,80] ng/ml), MPO (24 [18–30] ng/ml) и CatG (14 [12–16] ng/ml) were found in women after chemoradiotherapy. Antiestrogenic therapy was accompanied by pronounced immunoinflammatory activation of NETs, while surgical menopause and VVA without a history of gynecological cancer were associated with moderate and minimal levels, respectively. Intergroup differences between the oncological groups and the control group were statistically significant (p<0.005) with a large effect size according to the Mann–Whitney criterion (r≥0.50). Conclusion . VVA after antitumor therapy is characterized by various immunoinflammatory phenotypes, which are reflected in specific NET profiles. CitH3, MPO, and CatG can be considered pathogenetically significant markers reflecting the degree of immunoinflammatory changes in VVA, thus representing candidates for further research aimed at patient stratification and the development of personalized therapy.

Background. The search for promising nonsteroidal anti-inflammatory drugs (NSAIDs) is aimed, in particular, at identifying molecules with multitargeted anti-inflammatory and analgesic effects (including through central mechanisms). Objective: To study the interactions of a candidate NSAID molecule (SV-1010) with opioid receptors and compare them with the effects of known agonist molecules (butorphanol and U-50488) using chemoreactomic analysis and docking. Material and methods. Chemoreactomic analysis of NSAID mechanisms of action was conducted in three stages: data sampling, establishment of lists of molecules with known properties, and calculation of Kd binding constants and EC50 activation constants. Docking of kappa opioid receptors was performed using MarvinSketch, MOPAC2012, and AutoDock Vina. A comparison of the results of chemoreactomic modeling and docking was performed. Results. Chemoreactomic analysis of the interactions of the studied molecules with opioid receptors showed that the median and average values ​​of the binding constants Kd of the SV-1010 compound are comparable with the estimates of the constants obtained for butorphanol and U-50488 (75–98 nM for delta receptors, 62–81 nM for kappa receptors, 198–244 nM for mu receptors). Among the studied opioid receptor subtypes, the lowest Kd values ​​were established for SV-1010 for kappa receptors (64.8±46.3 nM; delta and mu receptors: 79.9±77.6 and 243.8±246.9 nM, respectively). No significant difference in the binding of SV-1010 molecules to kappa-1 and kappa-2 opioid receptors was detected (Kd in the range of 23.7–54.5 nM). Docking of the studied molecules into the structure of the human kappa receptor allowed us to obtain Kd values ​​and formulate the mechanism of binding of SV-1010 to the kappa-opioid receptor site (potentially, the key binding amino acids of the kappa-opioid receptor site are ILE730, VAL667, MET579, ILE726, TRP723, ILE460 and TYR464). A comparison of the results of chemoreactomic modeling and docking made it possible to find a correlation expressed by the equation “35.8x – 4790” with a correlation coefficient close to unity. The results of chemoreactome modeling of EC50 constants confirmed the results of the Kd binding constant analysis, including the finding that SV-1010 exhibits greater affinity for kappa receptors than for mu receptors. Conclusion. Chemoreactomic and docking modeling of the SV-1010 molecule's effects support the hypothesis that this compound may be a kappa-opioid receptor agonist, indicating the potential for experimental and other studies of SV-1010 with a focus on kappa-opioid receptors.

Background. Nootropics are pharmacological agents that enhance such cognitive functions as memory and attention, as well as the overall mental performance. In recent years, global demand for these pharmaceuticals has significantly increased due to intensified psychological stress, a growing incidence of neurological disorders, and a growing public focus on mental health. In Uzbekistan, the nootropic drug market is experiencing active growth, underscoring the need for a comprehensive analysis of its structure and key trends. Objective: To analyze trends in the nootropic drug market in Uzbekistan from 2015 to 2024, to identify key trends and factors influencing its development, and to assess the dynamics of supply and demand. Material and methods. The available data on registered nootropic drugs in Uzbekistan, pharmaceutical company reports, sales statistics, and information on government policy and support measures were used. The dynamics of the number of registered trade names and their distribution by manufacturing country were studied. Leading companies playing a key role in the market were identified. The distribution of nootropics by composition (monodrugs and combination forms) and dosage forms (oral, injectable, etc.) was also examined. Results. The analysis revealed a steady growth in the nootropic drug market in Uzbekistan throughout the study period. This growth is primarily driven by the increasing demand for cognitive enhancers across various age groups. One evident trend consists in the expanding presence of domestic manufacturers, who are introducing novel drug forms, including combination and injectable formulations. Additionally, innovative compounds, such as citicoline that has shown considerable therapeutic potential across various neurological conditions, are increasingly attracting attention. Conclusion. The nootropic drug market in Uzbekistan is demonstrating positive growth dynamics, driven by rising consumer demand and reinforced by supportive government initiatives. The market is expected to continue to grow, with improvements in drug variety and accessibility. Both local and international pharmaceutical companies play a pivotal role in enhancing product quality and ensuring broad patient access.

Background. Identification of terminological and practical inconsistencies in the field of patent law in regulatory legal acts, including the Civil Code of the Russian Federation (CC RF) is important for lawmakers, regulators, stakeholders in the pharmaceutical market, and patent holders. Objective: To conduct a comprehensive analysis of Clause 5 of Article 1359 of CC RF, which provides an exception to patent holders’ exclusive rights regarding the compounding of drugs in pharmacies pursuant to physicians’ prescriptions, in terms of its consistency with current pharmaceutical legislation and international legal standards. Material and methods. The methods of historical-legal, semantic-linguistic, and comparative-legal analysis were applied. The Russian regulation was compared with that in the European Union (EU), the United States of America, Japan, Brazil, etc. Additionally, provisions of international agreements, including the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) and the EU Agreement on a Unified Patent Court, were analyzed. Results. The current wording of Clause 5 of Article 1359 of CC RF was found to suffer from insufficient terminological clarity regarding the concepts of “individual compounding” and “medicinal product”, thus leading to legal uncertainty and potential conflicts with existing pharmaceutical legislation. The analysis of international practices revealed common regulatory approaches to this exception: the individual (personalized) nature of compounding (for a specific patient), mandatory medical prescription, exclusion of industrial-scale manufacturing, and the professional status of the performer (a pharmaceutical specialist). The Russian norm appears to have been borrowed from regulatory models of EU countries. However, in the absence of clear criteria for its application, risks of a broader interpretation arise, including the preparation of active pharmaceutical ingredients, which contradicts the objectives of patent regulation and the current structure of the pharmaceutical market. Conclusion. Clause 5 of Article 1359 of CC RF is designed to protect pharmacy organizations and implements the principle of fair use of patented objects, provided that the medicinal products are lawfully obtained. It may serve as a negotiating tool in cases of drug shortages. To uphold constitutional obligations regarding public health protection and to eliminate legal uncertainty, the norm requires legislative clarification and refinement.

Backgr о und. Immunoglobulin A nephropathy (IgA-N) is a common form of chronic glomerulonephritis. Its basis is the accumulation of IgA immune complexes in the glomeruli, associated with impaired glycosylation of the IgA molecule. Exogenous antigens, such as gluten, play an important role in the development of the disease. It has been experimentally confirmed that oral immunization with gluten induces mesangial IgA deposits, and a gluten-free diet can improve the course of nephropathy, indicating the significance of the enterorenal axis in the pathogenesis of IgA-N. Objective: To study structural changes in renal tissue in IgAN patients and to evaluate the clinical and diagnostic significance of IgA antibodies to deamidated gliadin peptides (anti-DGP IgA) in the blood serum. Material and methods . The study involved 105 patients aged 18 to 64 years diagnosed with IgAN based on a lifetime nephrobiopsy with morphological examination according to the Oxford classification. Patients were divided into two groups: the main group (n=20) included IgAN patients with detected anti-DGP IgA, and the control group (n=85) included IgAN patients seronegative for anti-DGP IgA, IgA antibodies to tissue transglutaminase, and to endomysium. Results. When comparing fibrous-sclerotic changes, no statistically significant intergroup differences were obtained. However, a clear trend of predominance of irreversible light-optical changes within the area of the nephrobiopsy specimen was noted in patients of the main group compared to the control group: 82.4% and 56.9%, respectively (p=0.059). Conclusion. The obtained results reflect a high frequency of irreversible fibrous-sclerotic changes in the nephrobiopsy in patients with IgAN and anti-DGP IgA in the blood serum. Timely detection of anti-DGP IgA can improve the ability to predict the outcome of the disease and optimize therapeutic strategies.

Objective: Comparative analysis of modern computer programs (smartphone programs – mobile applications) using artificial intelligence (AI) for diagnosis and dynamic monitoring of skin pathologies. Material and methods. A total of 1,319 publications were identified for AI-powered computer programs using targeted searches in PubMed/MEDLINE and Google Scholar databases, as well as in the eLibrary and CyberLeninka electronic libraries for the period 2016–2025. Using queries focused on AI, convolutional neural networks (CNNs), computer programs (mobile apps), and dermatovenereology, a total of 1,319 publications were identified. After a multi-stage screening based on inclusion/exclusion criteria (including the availability of quantitative performance metrics), 9 key articles with specific descriptions of the computer programs (mobile apps) were selected. A search and subsequent analysis identified 9 computer programs (mobile apps): Google DermAssist, SkinIO, Melanoma Check, Derma Onko Check, SkinVision, Tibot, SkinScan, Aysa, and Skinive, which use AI to diagnose and monitor skin conditions. Results. Effectiveness of the programs varies: Google DermAssist and Derma Onko Check demonstrated high accuracy (96–97%) and sensitivity (97–98%), while Skinive showed improvement in metrics over time from 2020 to 2021 (maximum sensitivity of 97.9% and specificity of 97.1%). Limitations include dependence on photo image quality, low effectiveness for rare conditions and dark skin tones, and the need for a biopsy to confirm a diagnosis. Mobile apps using CNN demonstrate high sensitivity (87–97.9%), but specificity varies significantly (70–98%), which may increase the number of additional consultations with specialist doctors when using these programs in diagnostics. Conclusion. AI-based software (mobile apps) offer significant potential for increasing the accessibility and accuracy of skin pathology diagnostics, especially in remote areas and regions with a shortage of dermatovenereologists. Potential developments include integrating software with telemedicine, improving algorithms for diagnosing rare pathologies, and standardizing testing to improve the reproducibility of results.

Objective : To analyze foreign experience in the use of artificial intelligence (AI) in oncology, as well as examine current advances in AI and its impact on clinical practice. Material and methods. A systematic review of foreign literature was carried out, current AI programs and technologies in oncology were analyzed. The total number of identified records via the PubMed/MEDLINE search was 7680. After publication selection in accordance with the PRISMA guidelines, 32 studies that met all criteria were randomly included in the review and formed the basis for the analysis. Results . AI demonstrates high efficiency in cancer diagnostics, including early detection of tumors, analysis of medical images and pathological data. A literature review on the use of AI models in oncology revealed exponential growth from 2010 to 2022, confirming the active development of the field. Diagnostic and treatment reports generated by the AI technologies indicated a comparable level of accuracy to that of experienced oncologists; they also revealed the ability to improve clinical outcomes. Furthermore, the introduction of AI stimulates the development of personalized treatment, increased patient adherence to therapy and optimization of the work of medical organizations. AI’s impact was revealed on physicians (reduced diagnostic and treatment errors), patients (personalized support), and hospitals (smart management systems). Conclusion . AI is becoming an integral part of modern oncology, offering new opportunities to improve diagnostics, treatment, outcome prediction, and patient support. A study of the dynamics of publications and AI models indicates that the use of AI in clinical oncology is rapidly developing, opening up new prospects for the creation of smart hospitals, simplification of medical data exchange, development of personalized medicine, and improvement of the quality of patient care. The integration of AI with emerging technologies such as wearable devices and multimodal analysis promises to revolutionize oncology practice.

Background . Specialists in health technology assessment consider real-world evidence (RWE) a promising path for improving comprehensive drug assessment (CDA). Therefore, it is particularly important to elicit opinions from CDA experts on the necessity of incorporating RWE analysis into the assessment process. Objective : To present the results of a survey of CDA specialists demonstrating their views on the necessity and variability of incorporating RWE into the CDA process. Material and methods . The survey was conducted in the form of a specially developed original questionnaire between July 2024 and February 2025 among two groups: regulatory authority representatives and pharmaceutical industry representatives involved in CDA. Results . The survey involved 29 representatives from both regulatory authorities and pharmaceutical industry. The majority of respondents support the inclusion of RWE in CDA: 96.6% of regulatory authority representatives vs 75.9% of industry representatives. The most favored assessment areas using RWE were safety, efficacy, impact on economy, and the quality of evidence base for medicinal products. The predominant view was that in decision-making, the role of RWE should be informative rather than restrictive. Conclusion . The surveyed respondents specialising in CDA predominantly hold positive attitudes towards incorporating RWE into the assessment procedure. The support of this incorporation by experts implies that work on specific implementations of RWE in CDA is fully justified and promises to be successful.

Objective : To explore approaches to improving medical care for patients with chronic hepatitis С (CHC) at the national level. Material and methods. A Markov model was used to predict the direct medical costs and outcomes (e.g., number of cured and died patients, cases of complications) for the treatment of CHC for 6 years in 300,000 patients. Two modeling scenarios were considered: a basic scenario included therapy administered with drugs in accordance with clinical guidelines and the standard of medical care for CHC patients; an alternative scenario focused on therapy with pan-genotypic drugs only. Results . In the basic scenario, 298,034 people, or 99.3% of the cohort are treated over a period of 6 years. During this time, the disease develops into 236 cases of decompensated liver cirrhosis, 2,073 cases of hepatocellular carcinoma, 62 liver transplants required, and 430 deaths from complications of progressive liver decompensation. Total direct medical costs for this period are estimated at 105.3 billion rubles. Annual costs range from 16.5 billion rubles in the first year to 18.2 billion rubles in the sixth year. In the alternative scenario, a slight improvement in clinical outcomes is observed; however, the treatment cost increases from 105.8 billion rubles to 114.5 billion rubles (+8.7 billion rubles). It was found that decrease in the cost of drugs by 10%, 20%, 30%, or 40% can provide additional treatment for 31,706, 70,907, 120,615, and 185,707 patients, respectively. Conclusion . The study made possible to assess the efficiency of the proposed measures for treating patients with CHC over a 6-year horizon, as well as the financial requirements for their implementation. Furthermore, possible measures to improve the effectiveness of CHC control activities and prospective ways to realize the benefits that could be achieved by reducing the cost of drug therapy were considered.

Objective: An analysis of pharmaceutical information as a factor in self-medication and the loyalty of pharmacy visitors.Material and methods. Sociological survey was conducted with 2888 respondents, poll`s period February – March 2025 inclusive. The geographical coverage included 58 subjects of the Russian Federation. The questionnaire consisted of questions to identify the respondent's characteristics (gender, age, region of residence), frequency of self-medication, attitude of pharmacy visitors to pharmaceutical specialists and their recommendations. Kendall's and Spearman's rank correlation coefficients were used when processing the questionnaires.Results. 88,3% of respondents use self-medication, and 42,8% do it often and constantly. Factors that increase the tendency toward self-medication are the female sex and young age. There is no correlation between the high frequency of self-medication and visits to pharmacy organizations. The main criteria for choosing a pharmacy organization are the price of the desired product, proximity to home/work, and the range of products offered. Most often, respondents are interested in the drug as well as the assortment of goods. Internet ordering is also popular. Searching for information on the Internet about a drug, assortment, pharmacy, or online order correlates with more frequent self-treatment. Respondents indicated time and/or cash savings as the main reasons for searching for information. Only 37,1% of respondents always fully follow the recommendations of pharmacy workers, and patient compliance naturally negatively correlates with self-medication. 20,6% of respondents indicated distrust of the qualifications of a pharmacy specialist and/or considered, that their recommendations optional. Reluctance to change lifestyles, as well as a lack of belief in the outcome, correlated with male gender and younger age. Among the positive trends in pharmacies, the most often noted were an increase in the range of drugs, an improvement in equipment, and the number of organizations. Among the negative trends in the pharmaceutical industry, respondents noted an increase in self-interest (commercial interest) among pharmacy workers – 24,7% of respondents answered so. Only 38,4% of respondents noted the possibility of error or subjectivity in someone else's negative opinion about the pharmacy. A more positive attitude toward the pharmacy worker generally correlated with a lower frequency of self-medication.Conclusion. The results of the sociological study demonstrate the importance of pharmaceutical information and attitudes toward pharmacy workers as factors in self-medication. The data obtained can serve as the basis for targeted advertising, considering age and gender preferences, and popularizing the appeal to a specialist. It is also necessary to monitor and update information freely available on the Internet.