Review
INTRODUCTION. Tumor-associated reactions, despite significant advances, remain understudied, which limits the use of immunotherapy.
OBJECTIVE. To analyze the immunopathogenesis of tumor-associated reactions and the prospects for immunotherapy.
MATERIALS AND METHODS. There was a review of scientific medical literature documenting immune homeostasis during the development of tumor-associated immune responses and immunotherapy methods for patients with tumors. The study is based on an analysis of 78 scientific publications from 1996 to 2025 in international and domestic scientific literature databases such as Google Scholar, PubMed, eLIBRARY, and Scopus. The literature search was conducted using keywords and various sequences of their combinations in Russian and English: antibodies; tumor antigens; immunotherapy; tumor-associated conditions; solid tumors; immunopathogenesis of tumors.
RESULTS. Neoantigens have been shown to facilitate evasion of immunological surveillance, with cytotoxic T lymphocytes, natural killer cells, and interferon-γ being the most important immune defense factors. The number of CD45RO+ memory T cells and cytotoxic T lymphocytes in tumors correlates with the likelihood of metastasis. Mast cells, neutrophils, and macrophages secrete factors that promote cell cycle progression and tumor cell survival. Th2 cells, regulatory T cells, and M2 macrophages promote tumor growth. Antibody blockade of cytotoxic T-lymphocyte-associated protein 4 and programmed cell death protein-1 enhances antitumor immunity. Adoptive therapy using T cells expressing chimeric antigen receptors has proven successful in hematological malignancies.
DISCUSSION. Most tumor antigens have weak immunogenicity but can be recognized by cytotoxic T cells, natural killer cells, and macrophages. Tumor antigens suppress the expression of major histocompatibility complex molecules, secrete immunosuppressive factors, and activate regulatory T cells. Antibodies specific to tumor cell antigens are used for both diagnostics and therapy. Tumor immunotherapy includes vaccination with tumor antigens, administration of cytokines, and blocking the signaling necessary to support tumor cell growth. Promising approaches to tumor immunotherapy include CAR T-cell therapy and enhancing T-cell activity.
CONCLUSION. The development of tumor-specific responses is primarily induced by neoantigens that suppress the activity of effector cells. Increased lymphocyte activity enhances antitumor immunity. The success of checkpoint blockade in many solid tumors and CAR-T cell infusion in hematological malignancies allows to develop more effective immunotherapies in the future.
Original articles
OBJECTIVE. To conduct a comprehensive analysis of the evolution and current state of hypobaric chambers as a tool for psychophysiological training of aviation personnel of the naval aviation of the Russian Navy (Navy), and to determine the prospects for their use in the Armed Forces.
MATERIALS AND METHODS. The study was conducted using a retrospective analysis and descriptive analytical methods. It examined data on the development of pressure chamber technologies, modern methods for using low-pressure pressure chambers, the technical characteristics of the Edelweiss hypobaric pressure chamber module (HPM), and the results of its practical application.
RESULTS. It has been established that hyperbaric chamber technologies have evolved from the first experiments in the 17th century to the modern high-tech HPM Edelweiss complex. From 2015 to 2017, an innovative hyperbaric complex was created and installed at the Yeisk Naval Aviation Center. The complex includes the SVBK-30 hyperbaric chamber for highaltitude (up to 30,000 m) research and the TD-1 breathing simulator for interval hypoxic training. Over 700 tests have been completed, and paratrooper training programs have been implemented.
DISCUSSION. The obtained results confirm the effectiveness of using low-pressure chambers in the psychophysiological training of aviation personnel and for conducting medical flight examinations. The Edelweiss HPM complex has unique characteristics and technical potential for further improvement: the introduction of digital technologies, integration into the medical monitoring system, and expanded diagnostic capabilities. The HPM can be used to develop new psychophysiological training methods and non-drug treatments for certain chronic diseases.
CONCLUSION. Hypobaric chambers have come a long way, from observing the effects of high altitude on humans to the rapid development of high-altitude chambers with unprecedented physiological research. Modern high-altitude chambers are high-tech systems with automated control systems that have become a key tool for ensuring the professional longevity of flight crews. Future developments are linked to improved technical specifications and expanded medical monitoring capabilities, as well as the emergence of new possibilities for hypobaric treatments for certain diseases.
INTRODUCTION. The article examines the problem of assessing occupational risks (OR) at nuclear ship repair enterprises in the context of the implementation of the Strategy for the Development of the Shipbuilding Industry until 2036 and beyond until 2050. Particular attention is paid to the complex impact of production factors on the health of workers.
OBJECTIVE. To conduct a quantitative assessment of OR levels for workers’ health at a nuclear ship repair enterprise under the complex influence of production factors.
MATERIALS AND METHODS. Instrumental measurements of the production environment (noise, vibration, chemical exposure, and ionizing radiation) were performed in the shipbuilding workshop. Priori estimate methods were used in accordance with current regulatory documents. Industrial monitoring data and a special assessment of working conditions for 2016–2023 were analyzed.
RESULTS. A significant excess of maximum permissible levels were detected for the main harmful factors: chemicals (up to 14.2 times), noise (up to 37.5 dBA), vibration (up to 32 times), and radiation factors (MADER up to 439.00 μSv/h). High risks of developing occupational diseases were identified in the main production groups.
DISCUSSION. Risk causes and their impact on worker health and productivity were analyzed. Priority areas for reducing risks were proposed: equipment modernization, improved working conditions and enhancement of industrial control systems.
COCNLUSION. The study results demonstrate the need for a comprehensive approach to occupational health and safety management at nuclear ship repair facilities. Implementation of the proposed measures will significantly reduce the risk of occupational diseases and maintain worker health.
OBJECTIVE. To explore features of the internal disease picture (IDP) in individuals with neurotic disorders.
MATERIALS AND METHODS. A total of 105 patients aged 25–47 years (mean age – 36 ± 2.7 years) were examined. Patients were divided into two groups. The first group consisted of 45 patients with neurotic disorders (ICD-10 code: F 40, F 41, F 42, F 44, F 48). The second group - 60 patients with somatic pathology (diseases of the circulatory system, respiration and diseases of the gastrointestinal tract). The methods used were «Type of Attitude Towards Illness» (TOBOL), «Freiburg Personality Inventory» (FPI), World Health Organization Quality of Life Questionnaire (WHO-100), «Lifestyle Index», «Treatment Satisfaction» questionnaire.
RESULTS. Patients with neurotic disorders compared to somatic patients have a reliably (p < 0.05) higher level of depressive feelings, being more prone to spontaneous aggression and more likely to use a psychological defense mechanism – compensation, that is, how to overcome their failures in the sphere of success in other areas. A lower level of treatment satisfaction is noted in patients with neurotic disorders. Patients with neurotic disorders are reliably (p < 0.001) more likely to be diagnosed with a sensitive illness attitude type.
DISCUSSION. In patients with somatic pathology, it is not uncommon to define a type of IDP, in which mental and social adaptation is not substantially impaired. Patients suffering from neurotic disorders have attitudes to diseases that are largely influenced by premorbid personality features. They are characterized by reactions according to the type of irritable weakness, anxious, depressed, depressed state, «withdrawal» into illness. Also, patients with neurotic disorders are more likely to define an internal disease picture (IDP), reflecting a sensitized attitude towards it: they are shy about their disease, use it to achieve certain goals, construct paranoid concepts of the nature and cause of their illness chronic course, exhibit heterogeneous aggressive tendencies, blaming those around them for their illness.
CONCLUSION. In patients with neurotic disorders, IDP is characterized by properties related to premorbid personality features or incorporated into the clinical structure of the disease. In order to improve therapy efficacy and adherence to treatment in these patients, it is necessary to take measures to correct their internal picture of the disease.
INTRODUCTION. Rehabilitation of special military operation (SMO) participants facing the effects of combat stress and chronic pain syndromes requires methods aimed at restoring basic regulatory functions. Cognitive flexibility (CF) and emotional regulation (ER) are key targets for intervention, as traumatic stress causes significant dysfunction in these areas, manifested in cognitive rigidity and emotional lability.
OBJECTIVE. To summarize the experience of using the method of personalized breathing training with biofeedback (BFB) in the rehabilitation program for SMO participants, using the example of a clinical case description.
MATERIALS AND METHODS. A method based on a telemetry monitoring system (video plethysmography, variational pulsometry) allows to create individual breathing programs synchronized with heart rate in real time. The introduction of breathing practice enables targeted optimization of physiological rhythms through controlled breathing to restore the neurophysiological foundation necessary for normalizing CF and ER.
RESULTS. The method’s application confirmed its high efficacy. In addition to a significant reduction in post-traumatic stress disorder symptoms, anxiety, and pain, positive dynamics in cognitive-emotional regulation were recorded: victims demonstrated reduced rigidity of thought, an increased ability to switch between tasks, and more effective management of emotional reactions. Objective heart rate variability data demonstrated restoration of autonomic balance, which is a physiological correlate of improved CF and ER mechanisms.
DISCUSSION. The obtained data indicate that the developed method is an effective tool not only for symptomatic correction, but also for strategic restoration of the mechanisms of CF and emotional regulation disrupted as a result of traumatic stress.
CONCLUSION. Targeted impact on fundamental physiological rhythms opens the way for preventing long-term negative changes in the psyche and promotes sustainable psychophysiological recovery of SMO participants.
INTRODUCTION. Students are at high risk of stress, which contributes to the development of diseases.
OBJECTIVE. To study the health risk of students under the combined influence of psychosocial stress and the Baltic climate based on the expression of the CDKN2A gene.
MATERIALS AND METHODS. Bioclimatic comfort was assessed using the wind chill index, the integrated body cooling conditions indicator, and monthly UV insolation levels. Quantitative expression of the CDKN2A gene was determined in first-year students: Group 1 (n = 90, fall) and Group 2 (n = 88, spring) using polymerase chain reaction (PCR). Results were compared across seasons among individuals with and without signs of stress, as measured by the Hospital Anxiety and Depression Scale (HADS).
RESULTS. In male and female students, the CDKN2A gene expression increases in spring compared to autumn in the absence of stress by 13.3 (p = 0.001) and 13.5 (p = 0.001) times, respectively, and in the presence of stress by 7.7 (p = 0.001) and 3.4 (p = 0.001) times. In female students, the number of transcript copies in the presence of stress in autumn is 3.6 (p = 0.029) times higher than in the absence of stress, an uncharacteristic feature among students, probably due to the lower emotional stability of girls. The relationship between CDKN2A gene expression with the season of the year and the presence of stress was confirmed by analysis of variance.
DISCUSSION. Exposure to hypothermia and vitamin D deficiency during winter and spring determine the development of anxiety and depression in students in the Baltics. CDKN2A gene expression may serve as an indicator of deteriorating student health.
CONCLUSION. Living conditions and lifestyle are risk factors for student health. These findings suggest that more preventative measures should be taken to help females adapt to learning conditions compared to males, as well as the implementation of health-improving measures to reduce stress levels during the winter and spring seasons for all cohorts of students.
OBJECTIVE. To determine the possibilities of using non-invasive portable individual sensors for monitoring the divers’ functional state when performing work underwater.
MATERIALS AND METHODS. The «Diving Automatic Optical Sensor-4» (VODA-4) functional state monitoring system was used in the experimental studies. The hardware and software system consists of a source and detector of visible and near-infrared radiation, equipped with a microprocessor for data processing and visualization. To address the problem of monitoring the divers’ functional state, modifications of the system in the form of wearable body sensors were used.
RESULTS. Conducted studies have shown that the VODA-4 hardware and software system possesses the necessary technical characteristics to ensure the recording of divers’ functional state indicators during underwater work. It has been proven that the VODA-4 hardware and software system enables rapid and non-invasive monitoring of a diver’s condition using backscattered radiation in biological tissue based on readings from 18 optical sensors in the visible and near-infrared wavelength ranges.
DISCUSSION. Individual typological characteristics of tissue blood flow were identified, reflecting the subjects’ compensatory responses to elevated hydrostatic pressure. It was shown that backscattered radiation intensity at selected wavelengths significantly decreases during immersion and recovers to values significantly above resting levels upon reaching a given depth. The difficulty in evaluating the obtained results lies in the virtual lack of understanding of the «norm» when recording cardiovascular and respiratory system performance indicators or changes in lactate and glucose levels during underwater work.
CONCLUSION. The hardware and software complex «VODA-4», which includes portable individual sensors for monitoring the functional state, allows monitoring changes in divers’ physiological parameters in hyperbaric conditions during diving operations.
OBJECTIVE. To examine the theoretical and methodological foundations for ensuring the population safety in the Arctic Zone of the Russian Federation (AZ RF) in emergency situations (ES) of a sanitary and epidemiological nature.
MATERIALS AND MEHODS. The study material was a set of organizational and methodological measures for providing outpatient care to 29,860 patients in the deployed Temporary Outpatient Center (TAC) during the acute coronavirus pandemic at the Murmansk City Polyclinic No. 1 for the period from January 2021 to February 2022.
RESULTS. There was a characteristic analysis of biological and social emergencies in the permafrost zone, including climatic, geographical, logistical, and demographic factors. The study identified shortcomings in the legal framework for protecting the population from emergencies in the Arctic.
DISCUSSION. The need to modify the current emergency classification system, taking into account transport accessibility factors and resource availability, is substantiated. An approach to optimizing medical evacuation measures by implementing the TAC as an element of the Unified State System for the Prevention and Elimination of Emergencies (RSES) is proposed.
CONCLUSION. TAC deployment reduces the risks of medical evacuation operations and optimizes the use of air ambulance resources. Therefore, the development of organizational and methodological approaches to TAC deployment is a relevant area for improving emergency safety systems in the Arctic zone of the Russian Federation.
INTRODUCTION. Traumatic brain injury (TBI) remains a significant cause of temporary loss of ability to work, disability and mortality among employees of the internal affairs bodies of the Russian Federation.
OBJECTIVE. To study the dynamics and structure of medical and statistical indicators reflecting the consequences of TBI among employees of the internal affairs bodies of the Russian Federation in 2008–2024.
MATERIALS AND METHOD. A retrospective medical statistical study was conducted based on aggregated data from departmental medical reporting of the Russian Ministry of Internal Affairs (MIA) for 2008–2024. The analysis included indicators of primary morbidity, cases and days of temporary loss of ability to work, primary disability, and mortality. Descriptive statistics and time series analysis were used.
RESULTS. A steady decline in primary morbidity (from 55.3 to 26.3 ‰), cases of temporary disability (from 52.6 to 25.1 ‰), the total number of days of incapacity (from 1128.0 to 648.0 ‰), primary disability (from 2.1 to 0.3 ‰) and mortality (from 42.5 to 13.8 per 100 thousand) were revealed. An increase in the average duration of one case of disability (from 21.4 to 25.8 days) and an increase in the mortality / disability ratio from 20.2 to 46.0 were established.
DISCUSSION. The decline in these indicators is due to a combination of organizational and medical factors, including improved professional selection, the development of medical care and rehabilitation systems, and the specifics of recording the consequences of injuries. The increase in the average duration of disability and the mortality/disability ratio reflect structural changes in injuries and the impact of the departmental military medical examination system.
CONCLUSION. The obtained data indicate a reduction in the medical and social consequences of TBI with a simultaneous transformation of their structure and confirm the importance of further improvement of prevention, medical support and rehabilitation of employees of the internal affairs bodies of the Russian Federation.
INTRODUCTION. Eye tracking, as a method for recording human oculomotor activity, is of great scientific and practical interest to aviation medicine specialists for diagnosing pilots’ functional status at various stages of their professional careers. Russian and international literature has already described studies that have established patterns of certain eye tracking indicators for various levels of cognitive activity in various mental work environments, including studies involving aviation specialists. A correlation between oculomotor activity dynamics and physiological and psychophysiological parameters of the human body has been identified.
OBJECTIVE. To justify the use of eye tracking for diagnosing pilot’s functional states using correlation analysis.
MATERIALS AND METHODS. The study assessed pilots’ heart rate regulation, central nervous system function, and oculomotor activity before and after performing a flight in a flight simulator. An emergency situation was simulated as an external stressor affecting the pilot’s functional state. The dynamics of functional state were assessed based on changes in physiological and psychophysiological indicators, as well as a correlation analysis of the time series of these indicators with oculomotor activity data and the success of actions in emergency situations.
The study involved 22 pilots from Southeast Asia who performed flights in Russian-made flight simulators.
RESULTS. Statistically significant changes in eye-tracking parameters, heart rate variability, and psychophysiological parameters characterizing changes in the pilots’ functional state and the degree of oculomotor activity strain were identified. Strong statistical correlations were established between the speed characteristics of gaze movements and the temporal characteristics of gaze fixations with the parameters of mathematical and spectral analysis of the cardiac rhythmogram, as well as with attentional properties and the speed of neural processes. Statistical correlations were also established between physiological and psychophysiological parameters and the pilots’ professional success.
DISCUSSION. The nature of the statistical relationships indicates that the basis for changes in heart rate variability, characteristics of attention, the nervous system, oculomotor activity of a person and the success of his professional activity in an emergency situation is the functional state of the pilot’s body.
CONCLUSION. Increased gaze velocity during cognitive tasks reveals the degree of stress on the pilot’s regulatory systems. Gaze fixation time indicators largely reflect the degree of cognitive activation and, to a lesser extent, the mobilization of physiological reserves. The nature of the statistical relationships between pilot oculomotor activity, physiological and psychophysiological responses, and professional performance allows eye tracking to be considered an informative method for assessing a pilot’s functional state.
INTRODUCTION. This article presents the results of an experimental study of combatant military personnel (UAV operators) using the PAK Eterno™ hardware and software system (PAK). PAK was tested using a VR headset with an algorithmic bilateral stimulation (BLS) method for self-management of post-traumatic stress disorder symptoms by combatants in the field.
OBJECTIVE. To evaluate the effectiveness, safety, and practical applicability of the virtual technology «PAK Eterno™» with the BLS method for self-treatment of symptoms of acute stress reaction by military personnel in combat conditions.
MATERIALS AND METHODS. In accordance with standards for medical and psychological rehabilitation of military personnel, methods were used to assess the physiological parameters and mental state of UAV operators. Their functional status and professional performance were also assessed (self-assessment and assessment by the crew/unit commander). A single independent therapy session using the PAK lasted an average of 25 minutes, followed by repeated screening.
RESULTS. The obtained results demonstrated a significant psychotherapeutic effect and an acceptable safety profile for independent use in combat conditions: 38% (n = 80) – improvement in functional state according to psychophysiological indicators after a single session; 51% (n = 80) – reduction in the number of complaints according to the self-assessment questionnaire scale (ACC-2) after the session; 32% of participants (n = 26) moved from the levels of «unsatisfactory» and «satisfactory» to the level of «good» subjective well-being.
DISCUSSION. The mechanisms (pathophysiological and neurobiological) of PAK action, which has clinically proven desensitization of traumatic memories, and the immersive VR environment, which ensures concentration of attention and elimination of external distractions while maintaining complete confidentiality, were confirmed.
CONCLUSION. The results indicate a reduction in the severity of the effects of combat stress in military personnel and normalization of subjective well-being even with a single use.
INTRODUCTION. Implant-associated infections are among the key postoperative complications of orthopedic surgery. A promising approach to their prevention is coating the implant surface with antimicrobial agents, such as peptides.
OBJECTIVE. To evaluate the efficacy of synthetic antimicrobial peptides and compositions based on them against current pathogens of orthopedic infections.
MATERIALS AND METHODS. Bacterial strains of Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus (MRSA), and S. epidermidis (MRSE) were isolated from patients with implant-associated infections. Peptides PR-39, RFR-ChBac3.4(1–14), protegrin-1, and G-Ar-2[W2L, V8R] were synthesized using solid-phase synthesis. Their antimicrobial activity was assessed by serial dilutions in a liquid nutrient medium and on the surface of titanium alloy metal plates for medical device production.
RESULTS. The most active peptides were protegrin-1 and G-Ar-2[W2L, V8R]. Their geometric mean minimum inhibitory concentrations in liquid medium were 0.3 μM and 0.4 μM, and the minimum concentrations for suppression of all studied bacterial strains on plates were ~3 μg/cm2 and ~15 μg/cm2. Protegrin-1 and PR-39 showed synergistic action in liquid medium, but the effect was not maintained in tests using plates.
DISCUSSION. The studied peptides demonstrated antibacterial activity both in the nutrient medium and on the surface of titanium plates. The protocol for peptide adsorption on the alloy surface can be further optimized; in particular, metal-binding sites can be introduced into their primary structure. PR-39 and PG-1 exhibited synergism in the liquid nutrient medium but exhibited independent antimicrobial activity in the compositions applied to the surface of the plates. This can be explained by a disruption in the peptide stoichiometry during their interaction with bacterial targets near the surface and during diffusion into the liquid phase.
CONCLUSION. The studied peptides can be recommended for further development of antibacterial coatings for medical metal structures to prevent implant-associated infections.
INTRODUCTION. The concurrent course of chronic hepatitis C (CHC) and chronic kidney disease (CKD) is a pressing clinical problem characterized by mutual aggravation, a high incidence of comorbid complications, and the difficulty of selecting antiviral therapy (AVT). The advent of direct antiviral drugs has dramatically changed the prognosis for this category of patients. However, in real-world clinical practice, there remains a need to evaluate the efficacy and safety of various treatment regimens in patients with multiple morbidities, including those on hemodialysis.
OBJECTIVE. To characterize the features of the СHC course and evaluate the efficacy and safety of interferon-free antiviral therapy in patients with CKD, including those receiving hemodialysis.
MATERIALS AND METHODS. A retrospective analysis of 21 medical records of patients with comorbidities was conducted. Twelve (57.1%) patients had stage 5D CKD on program hemodialysis. All patients were prescribed regimens based on direct acting antiviral agents. Efficacy was assessed by achieving a sustained virological response (SVR) 12 weeks after completion of therapy.
RESULTS. All patients who completed the full AVT course achieved SVR. The most commonly used regimens were glecaprevir/pibrentasvir (n = 8) and grazoprevir/elbasvir (n = 5). Therapy was well or satisfactorily tolerated in 76.2% of patients. Five (23.8%) patients experienced moderate adverse events (dyspepsia, weakness), which were successfully managed. No serious adverse events were reported.
DISCUSSION. The 100% SVR rate achieved in the study is consistent with data from large international studies and meta-analyses confirming the high efficacy of modern pangenotypic regimens in patients with end-stage renal disease. These results demonstrate that carefully selected therapy based on direct-acting antivirals, particularly glecaprevir/pibrentasvir and grazoprevir/elbasvir, is not only highly effective but also safe, even in the presence of severe polypharmacy and severe comorbidities, which has important implications for real-world clinical practice.
COCNLUSION. Modern AVT based on direct acting antiviral agents is highly effective and safe in patients with CHC and concomitant CKD, including dialysis patients, even in the presence of severe comorbidities. Glecaprevir/pibrentasvir and grazoprevir/elbasvir regimens can be considered the drugs of choice in this population.
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