Objective: to investigate the antitumor effects of various forms of vitamin B12 in combination with various synergistic vitamins and evaluate the prospects for clinical applications.

Material and methods. Cell lines BT-474 (breast ductal carcinoma) and A549 (lung carcinoma) were used as an in vitro cell model, and transplantable epidermoid Lewis lung carcinoma (LLC) was used as an in vivo animal tumor model. Animal studies of LLC were carried out on 25 male F₁ hybrid mice (age 2.5–3 months, body weight 23–26 g). In silico research was conducted as a systematic computer analysis of 9,326 scientific sources.

Results. In vitro studies on cultures of two human tumor cell lines (BT-474 and A549) confirmed the cytotoxic effect of vitamin B12 (aquacobalamin). It has been shown that vitamin B12 has weak cytotoxic properties in the concentration range of 3.125–200 μg/L (IC50>200 nM), and its hydrophobic derivative (heptamethyl cyanoquacobyric acid ester) significantly reduces the survival of tumor lines. BT-474 and A549 cells at high concentrations (100–200 µg/l, IC50~100 nM). Experimental animals with an in vivo LLС model easily tolerated a drug based on vitamin B12. Exposure to the drug up to the 21^st day of LLС development was accompanied by an increasing tendency to inhibit tumor growth by 10–20% (р=0.059). The results of a systematic in silico review of the literature show that clinical data confirmed the significant antitumor effect of vitamin B12.

Conclusion. The cellular model indicated the antitumor properties of vitamin B12 and its hydrophobic derivative. With subchronic intragastric administration of B12 to tumor-bearing animals, a steady tendency to inhibit the LLС growth was observed. Analysis of clinical data confirmed the feasibility of the antitumor use of vitamin B12 individually and in combination with synergistic vitamins.

Objective: To analyze the legal and ethical aspects of regulating artificial intelligence (AI) in medicine in key jurisdictions (United States, European Union, China, Russia), to identify regulatory gaps, ethical dilemmas and prospects for harmonization of standards.

Material and methods. National and international regulatory documents (GDPR, AI Act, FDA, NMPA), scientific publications, clinical cases and regulatory initiatives (IMDRF, WHO) were reviewed. Methods for comparative legal analysis and systematization of ethical and legal norms were used.

Results. Considerable differences in approaches to AI regulation were identified, including flexibility in the US, the ethical centricity in the EU, centralization in China and an emerging framework in Russia. Key issues were emphasized, such as algorithmic bias, AI transparency, responsibility, and the conflict between innovation and security.

Conclusion. The harmonization of international standards, the introduction of dynamic regulation and the strengthening of interdisciplinary cooperation should be pursued to achieve a balance between innovation and the protection of patients' rights.

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. Breast cancer is a socially significant disease. In Russia, the drug provision of breast cancer patients at all stages of treatment is carried out within the public procurement (PP) system. A systematic risk analysis of the PPs of anticancer drugs is an essential requirement for the safety and effectiveness of chemotherapy treatment.

Objective: identification of the main stages in the PPs of anticancer drugs used in breast cancer therapy; study and assessment of possible risks at each stage, development of a heat map of such risks.

Material and methods. The methods of content and comparative analysis of scientific publications, legislative acts and protocols of open auctions, requests for quotations from four Russian oncological hospitals in the Southern and Central Federal Districts were used. In order to obtain a quantitative estimate of the overall risk for each group and to construct a risk heat map, the severity of consequences and the probability of risk occurrence were combined in a multiplicative model.

Results. The key stages in the PPs of anticancer drugs were established to include tender planning, PP realization, government contract conclusion, and its implementation. At the stage of tender planning, the following groups of the risks were identified: the risk of delaying the implementation of innovative chemotherapy treatment regimens into the real clinical practice; the risk of prescribing the chemotherapy treatment regimens classified as an increased risk of adverse reactions; the risk of excessive uniformity and/or variety of dosage regiments. At the stage of PP realization and contract conclusion, the risks are related to a cancellation of the purchase and forced procurements of more affordable analogues. The stage of contract implementation involves the risks of reduced patient compliance due to the transfer of tablet drug forms to the ambulatory release; emergence of an urgent need for particular medicines due to changes in the treatment strategy; reduced effectiveness of thermolabile drugs due to a violation of the temperature regime of their transportation. The risk of forced procurements of more affordable analogues was rated as the highest level, while the risks of purchase cancellation and the emergence of an urgent need for medicines were ranked among the lowest.

Conclusion. The results obtained may serve as a basis for improving the risk-based approach to PPs through minimizing negative consequences for patients, hospitals and the entire healthcare system.

Objective: To study the characteristics of population consumption of combined glucose-lowering drugs (GLDs) in pharmacy organizations of the Russian Federation (RF) for the period from 2021 to 2023.

Material and methods. Using the tools of pharmacoepidemiological monitoring, a multicenter study was conducted to assess the implementation of GLD fixed-dose combinations (FDCs) in the retail sector of the pharmaceutical market of 85 RF subjects. The range and volume of retail sales (in packages and rubles) of GLDs from 13 groups of the Anatomical Therapeutic Chemical Classification System (including FDCs) were analyzed using the database of the product range of medicines of the AlphaRM company (Russia). The content, comparative, systemic, retrospective, logical, and graphical analysis, as well as the methods of grouping and descriptive statistics were used.

Results. The structure of retail sales was found to be dominated by foreign FDCs. Thus, out of the 16 FDCs included in the State Register of Medicinal Products, 12 are produced by foreign companies. A list of combinations of GLDs that have no Russian analogues was compiled, which includes “alogliptin + metformin”, “alogliptin + pioglitazone”, “vildagliptin + metformin”, “dapagliflozin + metformin”, etc. By the end of 2023, the volume of pharmacy sales of FDCs had amounted to 4,677 billion rubles (about 98% are sales of imported drugs). In the period from 2021 to 2023, the average retail price of 1 package of a combined drug increased from 927 to 1261 rubles, while the average retail price of 1 package of an imported drug was 5.5 times higher than that of the respective domestic drug. The share of FDCs in the structure of retail sales of GLDs (in physical terms, i.e., the number of packages) was about 8%. The most popular among pharmacy customers are imported combined drugs with metformin (Galvus^® Met, Reduxin^® Forte, Glibomet^®, Glucovans^®, Vipdomet^®, Sigduolong^®, Sinjardi^®, Yanumet^®), domestic drugs of the “metformin + glibenclamide” combination (Metglib^® force, Metglib^®, Glibenclamide + Metformin^®), as well as with other combinations (Glidica M^® and Glimecomb^®). When compiling the marketing profile of GLD FDC group, it was found that triple combinations of GLDs are not registered in the RF. This limits the ability of physicians to prescribe rational pharmacotherapy regimens.

Conclusion. The results obtained can be used by healthcare managers when assessing the need for drugs prescribed for the treatment of diabetes; when planning funds allocated from federal and regional budgets for the provision of medicines to these categories of beneficiaries, as well as when developing measures for improving drug support for patients with diabetes. In addition, the results may serve as a basis for the development of programs aimed at supporting the domestic pharmaceutical industry.

Objective: To develop a method for assessing the effectiveness of diagnostics using differentiated algorithms based on opinion, obtained from AI models, compared to the effectiveness of conventional diagnostics.

Material and methods. Two routing scenarios for diagnosing malignant and benign skin neoplasms (MNs and BNs) were simulated. The first scenario involves diagnostics using algorithms based on the conclusions of the Derma Onko Check AI model. The second scenario involves standard diagnostic routing by general practitioners, internists, and dermatovenerologists. The diagnostic effectiveness indicators used in the simulation, including those of general practitioners, internists, and dermatovenerologists, were obtained from previous clinical studies. The modeling was conducted using clinical data and photographic images from 90 patients with skin cancer (39 melanomas and 51 basal cell carcinomas) and 291 patients with skin cancer (100 non-melanocytic skin tumors and 191 melanocytic skin tumors).

Results. To assess the relative diagnostic efficiency using algorithms based on AI model output, calculation formulas with visualization of the results in the form of a quadrant matrix were developed and proposed. An mobile app called “AI-diagnostic efficiency calculator” (CalcRDAI&RNDAI) was developed for practical use to automatically calculate diagnostic efficiency indicators using algorithms based on AI model output. When testing a method for evaluating the use of algorithms based on the findings of the Derma Onko Check software, a 1.9-fold increase in the detection of skin cancer cases and a 10.5-fold decrease in missed cases were observed. The evaluation results are located in quadrant I (more detected, fewer missed), confirming the value of the diagnostic algorithm using algorithms based on the findings of the Derma Onko Check AI model in providing medical care.

Conclusion. The proposed method for evaluating diagnostic effectiveness using the developed formulas for calculating effectiveness and visualizing the results in a quadrant matrix enables objective evaluation of the effectiveness of AI models in multi-stage diagnostic routing.

Background. Beta-adrenergic blockers, or beta-blockers (BBs), are a crucial class of medications. Given their extensive use in the management of cardiovascular diseases, regular analysis of BB availability and range in the pharmaceutical market is essential.

Objective: To analyze the range of BBs available on the pharmaceutical market of the Republic of Uzbekistan, taking their quantitative composition, countries of origin, and dosage forms into account.

Material and methods. The study utilized data from the State Register of medicines, medical devices and medical equipment approved for use in medical practice in the Republic of Uzbekistan. Methods employed included systematization, statistical and comparative analysis, and graphical representation of the results.

Results. The Uzbek pharmaceutical market is dominated by metoprolol, bisoprolol, and nebivolol, with the majority of products are manufactured in the countries such as India, Russia, and Germany. Solid dosage forms, specifically tablets and capsules, are prevalent in this sector, which is consistent with the therapeutic use of this drug class.

Conclusion. The range of BBs in the pharmaceutical market of Uzbekistan is extensive in terms of international nonproprietary names, trade names, and manufacturing origins. This reflects consistent demand and the clinical importance of this drug group in the management of cardiovascular conditions. The findings can be used to further improve the pharmaceutical supply system.

Background. Underreporting of adverse drug reactions is a pressing public health concern in the Russian Federation. Addressing this requires evaluating the pharmacovigilance system performance, analyzing stakeholder involvement (patients, healthcare and pharmaceutical professionals, and industry representatives), and refining existing approaches through the enhancement of interagency cooperation and digital solutions.

Objective: To assess the role and level of involvement of pharmaceutical professionals in the spontaneous reporting system of the Russian Federation, identify the primary barriers hindering their participation, and determine areas for improving pharmacovigilance.

Materials and methods. The study analyzes public statistical data from regulatory agencies in the Russian Federation (Roszdravnadzor), the United States (FAERS), and Germany (BfArM) to compare the reporting profiles of key groups. Due to the lack of aggregated national data for the Russian Federation, the authors conducted a survey in 2025 via the Yandex Forms platform, involving 101 respondents (consumers, healthcare professionals, and pharmaceutical professionals).

Results. The study analyzed the causes of underreporting across all target groups, evaluating awareness levels, reporting tool availability, motivation, and other contributing factors. A pronounced imbalance was identified in the Russian reporting system: unlike the multi-channel models of the United States and Germany, the majority of reports in the Russian Federation are submitted by healthcare professionals. The conducted survey revealed that pharmaceutical professionals account for only 8% of reports, which is inconsistent with their legal obligations. Healthcare professionals were found to be the primary contributors (61%), followed by pharmaceutical companies (17%) and patients or their relatives (14%). Notably, despite high pharmacovigilance awareness (88.9%), only 40.7% of pharmaceutical professionals reported encountering consumer complaints. Their preferred method of report submission is direct communication with pharmaceutical companies (51.9%), with online reporting forms being the most convenient format (51.9%). Analysis of comments identified key barriers, including insufficient feedback, procedural uncertainty, and a lack of confidence regarding the effectiveness of reports.

Conclusion. The study identified key problem areas and proposed strategies for improving the pharmacovigilance system in the Russian Federation. Pharmaceutical professionals represent a critical but under-involved category of reporters within the pharmacovigilance system. Improving the completeness and quality of drug safety data requires a comprehensive approach, encompassing educational reform, implementation of digital tools to streamline reporting, and the launch of awareness campaigns. Furthermore, it is essential to foster an environment where reporting adverse reactions is perceived as an integral part of professional responsibility.

Background. The introduction of immune checkpoint inhibitors (ICIs) and targeted therapies (TTs) has fundamentally changed the clinical management of melanoma, significantly improving survival outcomes both in unresectable disease and in the adjuvant setting. At the same time, these therapeutic innovations have substantially increased healthcare expenditures, which raises the importance of pharmacoeconomic evaluation in clinical and policy decision-making.

Objective: To analyze modern approaches to assessing the cost-effectiveness of pharmacotherapy using real-world data (RWD), to summarize international experience in their application, and to evaluate the prospects for implementing RWD-oriented pharmacoeconomic approaches in the healthcare system of the Russian Federation.

Material and methods. Pharmacoeconomic studies published between 2010 and 2025 were analyzed using data from randomized clinical trials and real-world evidence. Key outcomes assessed included costs, effectiveness, and utility, such as quality-adjusted life years and incremental cost-effectiveness ratios.

Results. In most international models, ICIs – particularly anti-рrogrammed cell death protein 1 (anti-PD-1) monotherapy – have more favorable cost-effectiveness profiles in the treatment of unresectable melanoma compared with TTs, whereas combination regimens are characterized by a substantially higher budget impact. The cost-effectiveness of adjuvant therapy largely depends on the risk of recurrence and the cost of subsequent treatment for disease progression. Several studies show the high economic value of preventive and screening interventions aimed at early melanoma detection. The review highlights the need for cautious extrapolation of international pharmacoeconomic data to the Russian setting, taking into account national pricing policies, reimbursement mechanisms, and the absence of a formally established willingness-to-pay threshold.

Conclusion. The performed analysis of published studies shows that the use of RWD in pharmacoeconomic evaluations of pharmacotherapy allows refinement of model parameters and improves the robustness of economic conclusions; however, the applied approaches vary substantially in study design and data quality. The applicability of these approaches within the Russian healthcare system requires consideration of limitations related to the availability and structure of domestic RWD.