Background. The effective functioning of the immune system in solid organ recipients against M. tuberculosis may be compromised due to the intensive action of immunosuppressive drugs. Identifying latent tuberculosis infection (LTBI) in patients on the heart transplant waiting list, as well as in heart transplant recipients, may help improve the epidemic situation. Objective. To determent the level of latent tuberculosis infection in patients before and after heart transplantation. Materials and Methods. A comparative prospective cohort study was conducted using immunodiagnostic data from individuals prior to heart transplantation ( n =14) and recipients of a transplanted heart ( n =28). The control group consisted of healthy individuals ( n =69) with no history of contact with TB patients. All participants underwent immunodiagnosis for tuberculosis infection. Results. Positive results were recorded significantly more frequently in recipients of a transplanted heart compared to the control group (53.6 % versus 4.4 %, p =0.001). In the pre-transplant patient group, the level of positive immunodiagnostic results was also significantly higher (35.7 %) than in the control group ( p =0.001). Despite this, there were no statistically significant differences between the recipient group and the transplant candidate group ( p =0.275). Conclusion. The LTBI rate in recipients of a transplanted heart (53.6 %) was determined to be 1.5 times more frequent compared to patients awaiting transplantation (35.7 %). Notably, both comparison groups demonstrated a significantly high level of LTBI relative to healthy individuals (4.4 %), which necessitates further examination of this patient cohort and investigation into the causes of these findings.
Background. Assessment of the reproductive potential of the subarctic territories of Russia is of high significance due to the specific climatic, geographical, socio-economic and ethno-demographic conditions that affect fertility. Despite national demographic trends, regional variability in fertility rates, infertility, reproductive behaviour and accessibility of assisted reproductive technologies remains insufficiently studied, which limits the development of targeted management decisions. Aim. To conduct a comprehensive assessment of fertility and reproductive potential in the subarctic regions of the Russian Federation (Murmansk and Arkhangelsk regions, Chukotka, Yamalo-Nenets, Khanty-Mansiysk and Nenets autonomous okrugs, Republics of Karelia, Komi and Sakha (Yakutia), Krasnoyarsk Krai) over the period 2014–2023, based on a system of demographic and medico-statistical indicators. Materials and methods. Data from official statistics (Rosstat, Federal State Statistics Service, fedstat. ru) as well as information from the State Budgetary Institution “Research Institute of Healthcare Organization and Medical Management of Moscow Health Department” were used. The following indicators were analysed: proportion of women of fertile age, crude birth rate and total fertility rate (TFR), including age-specific rates for groups 15–19, 20–24, 25–29 and 30–49 years; proportion of indigenous population; newly diagnosed and total infertility rates among men and women of fertile age; proportion of successful IVF cycles; abortion rate; maternal mortality rate; and numbers of marriages and divorces. Descriptive statistics, cluster analysis (by mean TFR) and Pearson’s correlation analysis were applied. Results. The median TFR over the 10-year period for the Russian Federation was 1.6. In the subarctic regions, values varied: cluster analysis identified three groups – with high (Nenets Autonomous Okrug, Yamalo-Nenets Autonomous Okrug, Republic of Sakha (Yakutia)), medium (Khanty-Mansiysk Autonomous Okrug, Chukotka Autonomous Okrug, Republic of Komi, Krasnoyarsk Krai) and low (Arkhangelsk Region, Republic of Karelia, Murmansk Region) fertility levels. Correlation analysis revealed the strongest statistically significant associations of TFR with the proportion of women of fertile age (r=0.84) and the proportion of indigenous peoples (r=0.79). The influence of infertility rates and abortion frequency on TFR variation in the studied sample was weak and not statistically significant. Conclusion. Interregional differences in fertility within the subarctic zone are primarily determined by structural (age and ethnic) factors rather than by medico-reproductive losses (infertility, abortions). The obtained results indicate the need for further in-depth analysis incorporating socio-economic and migration factors to substantiate regional demographic policy.
The aim of this review was to systematize current pathophysiological mechanisms of sepsis-associated acute kidney injury (SA-AKI) in children and their relevance for early recognition of renal dysfunction. A review of 44 literature sources, published predominantly between 2021 and 2026, was conducted. SA-AKI cannot be explained solely by arterial hypotension or reduced renal perfusion. Its pathogenesis involves systemic inflammation, endothelial dysfunction, endothelial glycocalyx damage, intrarenal microcirculatory disturbances, coagulopathy, mitochondrial insufficiency, and inflammatory-metabolic injury to the tubular epithelium. Even after macrohemodynamic stabilization, capillary stasis, local hypoxia, interstitial edema, and heterogeneous renal perfusion may persist. Glycocalyx degradation increases vascular permeability, leukocyte-platelet adhesion, and microthrombus formation. Impaired fatty-acid β-oxidation, reduced mitochondrial ATP synthesis, oxidative stress, and altered phospholipid metabolism contribute to tubular dysfunction before a marked rise in serum creatinine. Complement and inflammasome activation, apoptosis, pyroptosis, necroptosis, ferroptosis, and disturbances of autophagy, mitophagy, and tissue repair play a distinct role in sustaining renal injury. In newborns and young children, these mechanisms are important because of immature immune and vascular regulation, susceptibility to fluid overload, and limited functional renal reserve. The delayed rise in creatinine and the variable diagnostic value of urine output restrict early detection; therefore, risk assessment should consider age, baseline renal reserve, fluid exposure, and the severity of multiple organ dysfunction. SA-AKI should be regarded as an early manifestation of profound tissue dysregulation rather than only as a late laboratory complication of sepsis.
Background. Optimizing the duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) remains challenging, especially in patients with high bleeding risk and diabetes mellitus, where stent thrombosis risk is significantly increased due to delayed endothelialization. Objective. To demonstrate the safety of early DAPT discontinuation based on individual assessment of stent endothelialization using optical coherence tomography (OCT). Materials and Methods. We present a clinical case of a 71-year-old female with type II diabetes, atrial fibrillation (CHA2DS2-VASc score of 6), functional class II exertional angina, and a history of left anterior descending (LAD) artery stenting. Risk stratification indicated a high hemorrhagic status: HAS-BLED score of 3, PRECISE-DAPT score of 17, ARC-HBR score of 2, and a CRUSADE score of 49 (corresponding to an 11.9 % risk of major bleeding). Baseline OCT revealed significant narrowing: the minimal lumen area in the LAD was 3.51 mm² (56 % area stenosis), and 2.08 mm² in the right coronary artery (RCA) (72 % area stenosis). Stenting of LAD and right coronary artery was performed using amphilimus-eluting polymer-free stents. DAPT discontinuation was planned at 1 month contingent on sufficient endothelialization per control OCT. Results. Follow-up OCT at one month demonstrated neointimal coverage of 81.18 % of the struts in the LAD and 95.9 % in the RCA. No evidence of stent thrombosis or restenosis was observed. The patient was transitioned to clopidogrel monotherapy, alongside ongoing anticoagulant therapy for the prevention of thrombotic complications associated with atrial fibrillation. During the one-year follow-up period, no ischemic or hemorrhagic adverse events were registered, and there was no recurrence of angina symptoms. Conclusion. The application of OCT for the evaluation of stent strut endothelialization provides a robust rationale for shortening DAPT duration to 1 month in patients with high hemorrhagic risk. This strategy minimizes bleeding threats without escalating the incidence of ischemic events, even in the presence of concomitant diabetes mellitus and multiple comorbidities.
The high mortality rate of abdominal gunshot wounds (15–60 %), rising antibiotic resistance, and the need for accelerated innovation necessitate a systematic analysis of current approaches to diagnostics, surgical tactics, and translational medicine in military field surgery. The objective of this review is to develop a comprehensive scientific and practical paradigm for abdominal military field surgery that integrates epistemological, translational, and prognostic aspects. The methodology included searching the Russian Science Citation Index (RSCI), PubMed, Google Scholar, and CyberLeninka databases for the period 2023–2026, followed by narrative data synthesis. Thirty-six sources were analyzed, including national guidelines, original studies, clinical cases, and reviews. It was found that shrapnel and mine blast wounds predominate among abdominal gunshot wounds (65 %), with combined injuries occurring in 70 % of cases. Peritonitis is characterized by a polymicrobial landscape (80–85 %) with a high rate of multidrug resistance (30–60 %). Traumatic pancreatitis develops in 65 % of patients with direct pancreatic injury. Vacuum-assisted laparostomy reduces mortality from 45 % to 28 %. The FAST protocol reduces preoperative preparation time from 45 to 18 minutes. The translational model (stages T1–T4) enabled the introduction of vacuum-assisted laparostomy/vacuum-assisted laparostomy and endovideosurgical technologies into clinical guidelines within 3–5 years, confirming the high efficacy of the translational approach in extreme conditions. Conclusion. Translational medicine is an effective tool for accelerating the implementation of innovations in abdominal military field surgery; Vacuum-assisted technologies, artificial intelligence, and bioengineered methods for closure of abdominal wall defects remain priority areas.
Background. The aim of the study was to investigate the elastic properties of the neck vessels in 6-year-old children born with extremely low (ELBW), very low (VLBW) and low body weight (LBW) as predictors of the development of cardiovascular diseases in subsequent years. Objective. To study the elastic properties of the neck vessels in 6-year-old children born with ELBW, VLBW, and LBW as predictors of the development of cardiovascular diseases in subsequent years. Materials and methods. The elastic properties of the neck vessels were assessed in 173 6-year-old children using echotraking. The children were divided into the following subgroups based on their birth weight: those born with extremely low (ELBW) (n=15), very low (VLBW) (n=25), low (LBW) (n=54), and a control group (n=79). The systolic and diastolic diameters of the vessel, the stiffness of the common carotid artery wall, and the compliance, distensibility, Peterson elasticity modulus, Young’s modulus, Gosling pulsatility index, and Purlot’s resistance index were determined based on the analysis of the coefficients. Results. In 6-yearold children who were born with extremely low, very low and low body weight, there were statistically significant changes in the elastic properties of the vascular wall of the common carotid arteries compared to the control group. The compliance coefficient and the extensibility coefficient of the common carotid artery were significantly lower in six-year-old children who were born with extremely low, very low and low body weight. At the same time, the resistance coefficient and the stiffness index of the common carotid artery in the studied groups of children were significantly higher than in the control group. The median thickness of the intima-media complex in the control group was statistically significantly lower than in the groups of children born with extremely low, very low and low body weight. Conclusion. The results obtained indicate early preclinical vascular changes in children with extremely low, very low and low body weight at birth and the possibility of using ultrasound studies in order to detect them.
Background. Heart rate conversion during cardioversion has a mixed effect on the functional response of the cardiovascular system. According to impedance cardiography data, one month after electrical cardioversion, the most significant changes were in cardiac index, cardiac power index, total peripheral resistance, and total peripheral resistance index, exceeding echocardiographic parameters in sensitivity. These data suggest that bioimpedance cardiography is a useful and timely method for dynamically monitoring hemodynamic status in atrial fibrillation (AF). Objective. To assess hemodynamics in patients with atrial fibrillation after cardioversion, as well as to identify the real functional response of the cardiovascular system by analyzing bioimpedance indicators and ultrasound parameters of the heart. Materials and methods. To conduct a comparative analysis of hemodynamic parameters at baseline and one month later in 97 patients with persistent atrial fibrillation, followed by an assessment of the functional response of the cardiovascular system using two methods of bioimpedance cardiography and ultrasound diagnostics of the heart. Results. The study showed that the parameters measured by impedance cardiography did not change significantly, although the cardiac index, cardiac force index, total peripheral resistance, and total peripheral resistance index changed most clearly 1 month after cardioversion. Thus, the cardiac index changed from 2.93±1.25 to 2.64±0.99 l/min/m 2 at p=0.0001, the cardiac strength index – from 0.62±0.27 to 0.57±0.22 W/m 2 at p=0.0001, the total peripheral resistance – from 1536±736.97 to 1731±1515.6 din·s/cm 5 at p=0.0004, the index of total peripheral resistance increased from 3094±1464.3 to 3562±3709.9 din·s/cm 5 ·m 2 at p=0.0001. It is these indicators that reflect not so much the anatomical condition of the heart chambers, but rather the current organization of blood flow, the level of vascular load, and the ability of the cardiovascular system to operate in a more stable mode after the restoration of sinus rhythm. Echocardiographic indicators were less sensitive in the early stages, and after 6 months, only the peak blood flow velocity at the tricuspid valve showed significant changes (0.74±0.5 m/s to 0.64±0.4 m/s, p=0.028). The size of the right atrium changed from 4.21±0.7 cm to 4.01±0.71 cm at p=0.056, which indicates a positive trend, but does not reach the criteria of statistical significance. Conclusion. The obtained data allow us to consider bioimpedance cardiography as a useful and operational method of dynamic monitoring, which is not inferior to ultrasound examination of the heart in AF, and in a number of clinical situations, it detects functional changes earlier.
Background. The reliability and reproducibility of preclinical in vivo studies significantly depend on the quality of laboratory animals. Objective. To compare the variability of clinical laboratory and behavioral parameters, as well as the level of microbiological control, in rats obtained from four breeding facilities located in the Russian Federation. Materials and Methods. This paper presents coefficient of variation (CV %) values for complete blood count parameters, biochemical analysis parameters (alanine aminotransferase, aspartate aminotransferase (AST), creatinine, lactate dehydrogenase (LDH), total protein, urea), and hemostasis system parameters (activated partial thromboplastin time and prothrombin time), respiratory rate, and behavioral test parameters (number of rearings against the walls and number of squares visited). The study included 4 groups of 10 males and 10 females each. Results. Based on the data analysis, elevated leukocyte levels were detected in the blood of animals without SPF status; in group 1, rats showed deviations outside the reference intervals for creatinine (20 % higher in males and 7 % higher in females), urea (20 % higher in males and 12 % higher in females), and AST. The coefficient of variation for most parameters was below 20 %, indicating satisfactory homogeneity. High interindividual variability (CV > 20–30 %) was observed only for lactate dehydrogenase (LDH) and behavioral tests. A sex difference was observed: in males, the CV values for leukocyte count and differential leukocyte count ranged from 10 % to 20 %, whereas in females the CV exceeded 20 % in all groups. Respiratory rate and hemostasis parameters showed low biological variability in all groups. Conclusion. The variability of the studied parameters was not influenced by the source of the animals; rather, the method used to analyze the parameter was significant. An attempt was made to define acceptability criteria for variability of major vital parameters in biological test systems. For example, variability with CV < 5 % can be regarded as “too” low (high data homogeneity); CV < 10 % corresponds to low variability (homogeneous data); CV from 10 to 20 % indicates satisfactory variability (data homogeneity acceptable for most parameters); CV from 20 to 30 % reflects moderate variability (data with considerable scatter typical for biological test systems); and CV > 30 % indicates high variability (heterogeneous dataset).
This paper formulates the problem of developing a mathematical language intrinsically suited to the historicity and organized complexity of living systems. The challenge lies not in the insufficient expressive power of modern mathematics, but in its underlying ontological assumptions. The mathematical framework developed for describing inert physical systems encounters fundamental limitations when applied to living systems. Models formulated within this framework cannot adequately describe systems whose state space expands throughout their history and whose dynamics are governed by memory, as well as by relational and functional organization. Following the historical pattern whereby new mathematical languages often prove productive before acquiring rigorous foundations, we propose, as a first step, a conceptual framework assembled from existing theoretical building blocks. These include Diekmann’s models of physiologically structured populations, Rosen’s relational biology, Kauffman’s concepts of the expanding state space and the adjacent possible, fractional and non-Markovian dynamics, the Doi-Peliti and Schwinger-Keldysh field-theoretic formalisms, and homotopy type theory, which reimagines equality as a structure of paths. Studies of chronic inflammation, tumor evolution, and carcino-evo-devo theory demonstrate that none of these approaches, taken individually, is sufficient to address the questions that biology poses to mathematics. However, each shifts the analytical focus, in its own way, from individual entities to relations, processes, and reproducible patterns of organization, thereby aligning with process ontology. The aim of this article is to identify existing conceptual gaps, argue for the methodological importance of the ontological shift from the classical “substantial” perspective to a process-oriented one, and formulate the requirements for a future “algebra of life”. From the perspective of translational medicine, a reformed mathematical paradigm for living systems is of critical importance, as it offers a means to overcome the looming deficit of theoretical tools for the conceptual compression and interpretation of exponentially growing volumes of multi-omics and clinical data.
The cellular plasma membrane functions not only as a structural barrier but also as a dynamic regulatory platform, integrating stress, mechanical, and metabolic signals and coordinating intracellular and intercellular adaptive responses. It ensures the spatial organization of signaling complexes, promotes compartmentalization of biochemical processes, and creates conditions for rapid and selective reorganization of the cellular response to microenvironmental changes. This review proposes the concept of a membrane-associated epichaperome, organized in functional association with lipid microdomains and forming an epichaperome-lipid interface — a structurally and functionally integrated platform that unites proteostasis, membrane biophysics, and adaptive signaling. The membrane heat shock proteins HSP70 and HSP90 coordinate intracellular signaling cascades, serving as platforms for the assembly and stabilization of multiprotein complexes, including receptors and kinases. They support the activity of signaling pathways and regulate intercellular communication via exosomes, extracellular vesicles, and tunneling nanotubes. Furthermore, these proteins participate in the remodeling of the lipid environment, influencing the organization of lipid rafts and ensuring the functional plasticity of membrane domains, which facilitates cellular adaptation to changing conditions. In pathological conditions, including tumors, chronic inflammation, and neurodegenerative diseases, the epichaperome-lipid interface forms pathologically adaptive signaling platforms that promote cellular plasticity, drug resistance, invasion, and cooperative behavior. The proposed theory of the membrane-associated epichaperome expands the traditional understanding of cytoplasmic chaperone networks and provides a new conceptual basis for the development of diagnostic markers and translational therapeutic strategies aimed at the selective disruption of pathological membrane platforms. The aim of the work is to summarize modern data on the molecular organization and functions of the epichaperome-lipid interface and discuss its importance in the pathogenesis of socially significant human diseases.
The period of the Special Military Operation (2022–2026) marked an era of profound and comprehensive transformation for Russian military medicine, driven by unprecedented challenges: the high intensity of combat operations, the predominance of mine-blast trauma and polytrauma in the structure of sanitary losses, and the need to provide care under conditions of mass and irregular influx of the wounded. An analysis of 78 scientific publications demonstrates that the response to these challenges was not merely adaptation, but a fundamental restructuring of the entire medical evacuation and treatment system. The classical linear staging gave way to a network-centric model, where mobile forward medical groups and aeromobile units play a key role, while “vertical” evacuation by air ambulance has reduced the time for delivering severely wounded patients to multidisciplinary hospitals to 60–90 minutes. In clinical practice, a true technological breakthrough occurred: the principles of Damage Control Surgery became the standard for treating polytrauma, and in vascular surgery, priority shifted to endovascular and hybrid methods, fundamentally changing approaches to treating traumatic pseudoaneurysms and arteriovenous fistulas. Concurrently, massive transfusion protocols were standardized, becoming a key factor in reducing mortality from acute blood loss, and modern multimodal analgesia protocols were introduced, including the legalized use of narcotic analgesics at the pre-hospital stage. A continuous system of staged medical and psychological rehabilitation has been established, integrating high-tech prosthetics, including myoelectric prostheses, methods for managing phantom limb pain (botulinum therapy, mirror therapy), and robotic exoskeletons. The accumulated experience, grounded in the close integration of military and civilian medical services, has not only forged a new “gold standard” for managing severe combat trauma but has also acted as a powerful catalyst for innovation, with outcomes that hold strategic significance for the development of the entire healthcare system, particularly in the field of disaster medicine.
Relevance. Declining birth rates and the increasing prevalence of pregnancy complications remain major medical and demographic challenges in the Komi Republic, underscoring the need for continuous monitoring of maternal health indicators and evaluation of regional support measures. Objective . To analyze trends in key maternal health indicators in the Komi Republic in 2012–2024 and to assess the impact of organizational measures on maternal health and pregnancy outcomes . Materials and methods . The study was based on data from statistical reports of the Komi Republic Medical Information and Analytical Center and official data from the Federal State Statistics Service of the Russian Federation (Rosstat). A retrospective analysis was performed of birth rates, morbidity among pregnant women, complications of pregnancy, labor and the postpartum period, operative delivery rates, and the effectiveness of antenatal follow-up. Results . Over the past 12 years, the birth rate in the Komi Republic decreased by 52 %. Against the background of a declining number of births, there was an increase in the prevalence of anemia among pregnant women, with values exceeding the national average in several years, as well as a rise in diabetes mellitus and endocrine disorders. An upward trend was also observed in complications of labor and the postpartum period, including obstetric hemorrhage and infectious complications. At the same time, operative rates activity increased. Positive changes were noted in antenatal care coverege: the proportion of women registered in early pregnancy reached 91.5 %, and coverage with prenatal follow-up remained high. Conclusion . The findings indicate unfavorable trends in maternal health in the Komi Republic and support the need to improve prevention of extragenital diseases, optimize management of pregnancy and childbirth in high-risk women, and further strengthen the regional maternal and child health system.
The article presents two autopsy cases of systemic scleroderma that led to the death of patients, as well as a review of the literature on the etiology and pathogenesis of the disease, with a focus on the development of infectious complications in these cases. Scleroderma is a rare connective tissue disorder, and one of the most common causes of death is infectious complications, including sepsis. The aim of this study was to analyze two clinical cases of systemic scleroderma that resulted in the death of patients. Materials and methods. The results of autopsies of two patients with a diagnosis of systemic sclerosis are presented: a 63-year-old woman and a 59-yearold man. In each case, an autopsy was performed with a macroscopic examination of all organs and tissues. For histological examination, in case 1, samples were taken from the lungs, heart, liver, kidneys, skin, esophagus, small and large intestines, right lumbar muscle, and bodies of the I and III lumbar vertebrae; in case 2, samples were taken from the lungs, heart, liver, kidneys, skin, and esophagus.
The aim of the study was to quantify and compare the parameters of cerebral tumor blood flow in neuro-oncological neurosurgical patients with relapse-free course and recurrence of glial low-grade tumors using SPECT-CT with 99m Tc-Technetril as a tumorotropic radiopharmaceutical, and MRI in the arterial spin labelling (ASL) mode. Materials and methods. The study included 23 patients treated 2019-2020 with glial brain tumors (15 with grade 2‒4 anaplasia gliomas and 8 with glioblastomas). Of these, 16 with glial brain tumors (13 — gliomas and 3 — glioblastomas) after radical tumor removal followed by external gamma therapy, and 7 with inoperable formations were examined after chemoradiotherapy, without surgical removal. The patients were divided into groups 1 — with a relapse-free course, 11 people; of those who had a relapse/continued growth, 12 patients (group 2), five of them died during a two-year follow-up. All underwent MRI of the brain (MRI 3.0 T) in ASL mode with calculation of cerebral blood flow in absolute units — as ml/min/100 cm3, as well as SPECT-CT with 99m Tc-Technetril on a gamma camera with the ability to determine standardized uptake values (SUV), with calculation of blood flow in tumor formations ( РКрОп ОФЭКТ ), using the method KML (Krivonogov-Minin-Lishmanov), as РКрОп ОФЭКТ = СВП 99mTc-Технетрил * (МО/Body Weight) * 100, where СВП 99mTc-Технетрил is the standardized value of rfp uptake, MO is the minute volume, 100 is the conversion coefficient for representing the result in the usual units “ml/min/100 cm 3 of tissue”. Results. ASL MRI and SPECT-CT with 99m Tc-Technetril methods significantly correlate with each other and are interchangeable in terms of the obtained values of blood flow of malignant tumors, both maximum and average in the studied regions. If there is a visual nodular structure in the area of the removed brain tumor, and blood flow anywhere within it is more than 23 ml/min/ 100 cm 3 , the presence of continued growth or recurrence of a low-grade glial neoplasm is likely. Conclusion. As follows from the presented visual-semiotic and computational data of ASL MRI and SPECT CT with 99m Tc-Technetril, these methods should reasonably be used as widely as possible for early monitoring of the postoperative condition in patients after radical removal of glial low-grade brain tumors. It is advisable to further their comparative and joint study, including in inter-center studies.
Chronic heart failure with preserved ejection fraction (CHFpEF) is a multifactorial condition with various pathophysiological causes and morphological manifestations, which largely determines the use of therapeutic approaches adapted to the patient’s clinical phenotype. In recent years, CHF has been increasingly replacing chronic heart failure with a reduced ejection fraction (CHFrEF), and is an equally serious condition that reduces the quality of life of patients on a par with CHFrEF. Currently, CHFpEF affects approximately 9 % of individuals over the age of 60, and the 5-year survival rate for this form of heart failure is roughly 35 %. The contemporary pharmacological armamentarium for managing CHFpEF symptoms remains notably limited. One promising therapeutic avenue involves targeting the modification processes — and consequently the mechanical properties — of titin, a major protein of the muscle sarcomere. Active research is currently underway on the development and application of agents that influence titin modification, with ongoing preclinical and clinical trials. This review examines the structure and post-translational modification (predominantly phosphorylation) of titin. It also explores the various signaling pathways whose dysregulation is associated with CHFpEF pathogenesis, as well as data from studies investigating drugs that target these pathways in both animal models and human subjects. The review presents an analysis of domestic and international literature published between 2000 and 2026, sourced from platforms including PubMed, Elsevier, and Google Scholar. Current evidence indicates that modulating titin modification is a potentially effective strategy for treating chronic heart failure. These findings underscore the need for further investigation in this field. The ultimate goal is to identify novel pharmacological solutions and integrate them into clinical practice to enable personalized management of CHFpEF syndrome.
Obesity is a global health problem whose incidence is steadily increasing. Modern lifestyles, characterized by changing dietary preferences and low levels of physical activity, are key factors in the development of obesity and overweight. Obesity increases the risk of numerous gastrointestinal (GI) diseases, such as gastroesophageal reflux disease, inflammatory bowel disease, functional digestive disorders, and others. The pathogenesis of these conditions includes chronic low-grade inflammation, increased intestinal barrier permeability, and changes in the intestinal microflora. The purpose of this article is to describe and systematize high-calorie diets and to study the morphological and pathophysiological mechanisms by which these diets influence the gastrointestinal tract. This review examines the main types of diets used to model obesity in laboratory animals: high-fat, high-carbohydrate, with a choice of fats or carbohydrates, combined (“cafeteria diet”, “Western diet”), and models of psychogenic overeating. Histological features of the gastrointestinal tract wall of obese rats are represented by changes in the mucosa (a decrease in the number of PAS-positive goblet cells) and the lamina propria (an increase in the number of neutrophils, lymphocytes, macrophages, and collagen fibers). In addition, increased concentrations of IL-1β, IL-6, IL-8, TNF and monocyte chemotactic protein (MCP-1), and malondialdehyde (MDA) were detected in the colon wall. Obesity and excess body weight have been shown to impact structural components of the nervous system (hyperactivation of enteric ganglia, disruption of the autonomic nervous system, etc.), leading to impaired gastrointestinal motility. Experimental studies demonstrate that high-calorie diets alter the histological characteristics and motility of the gastrointestinal tract in laboratory animals, causing structural damage and disruption of innervation of the digestive organs. This indicates the need for further research to identify the mechanisms underlying the development of obesity complications and develop effective preventive measures.
Introduction. Endovascular treatment is currently the main treatment method of patients with peripheral arterial disease. The main disadvantage of this treatment method is the frequent development of restenosis in the long-term postoperative period, which necessitates the development of more advanced devices aimed at preserving the integrity of the inner layer of the artery. Objective. To study the effect of a new self-expanding nitinol stent on changes in the architecture of the vascular wall and cellular components of tissues adjacent to the implantation site by analyzing the vascular condition in laboratory pigs. Material and methods. Two Landrace pigs had stents with 5–20 % oversizing implanted in the common iliac artery. Vital signs were monitored during the follow-up; 3 days before the procedure and thereafter, dual antiplatelet therapy was used. After 3 months, angiography and ultrasound of the iliofemoral segment were performed, then the animals were euthanized. The extracted sections of the arteries with implanted stents were subjected to a thorough macroscopic and histological analysis. Results. For 3 months, the vital signs remained within the normal range. Angiography and ultrasound revealed patency of the stented area without significant restenosis. Morphological examination of the tissues demonstrated the integrity of the internal elastic membrane of the arteries. Conclusion. The implantation of the new domestic self-expanding nitinol stent caused a favorable reaction of the common iliac artery wall with minimal myointimal hyperplasia in the postoperative period. Thus, the new domestic self-expanding nitinol stent developed by us has successfully passed the stage of preclinical animal testing.
Genetic studies have shown associations between polymorphic regions of genes that determine the metabolic processes of xenobiotics, transcription factors, signaling pathways, membrane receptors and cytokines with a pleiotropic effect, as well as antigen-presenting molecules, with congenital heart defects (CHD). A significant problem in assessing the impact on the formation of congenital heart disease of a wide set of polymorphic variants of genes unrelated to each other by signaling pathways is their complex, combined interaction, which requires the use of a developed scheme for analyzing data from the binary system “sick — healthy”. Aim of the study: to assess the significance of a wide set of genes for the formation of congenital heart defects. Materials and methods. Genotyping of polymorphic loci of immune response genes, xenobiotic metabolism genes, and signaling pathway genes was performed and comparison of genetic profiles in children with sporadic (without family history) septal congenital heart disease with the absence of chromosomal pathologies with a control conditionally healthy group of children using various classifiers. Data analysis was performed on a wide range of polymorphic gene variants according to a developed scheme: assessment of the data structure; selection of significant polymorphic variants of genes associated with congenital heart disease; training and testing of nonlinear classifiers; repeated selection of associative variants of polymorphic gene regions with optimization of nonlinear classifiers; construction of a linear classifier. Results. The most significant polymorphic variants of genes that determine the formation of congenital heart defects were identified: GSTP rs1871042, GSTP rs1695, CYP1A2 rs7622551, GATA6 rs10454095, TREM1 rs4711668, TLR1 rs5743551, IL6R rs2228145, IL6R rs222923 8, IL8 rs4073, HLADRB1* . Models such as random forest (RF), support vector machines with a polynomial kernel (PSVM) and Gaussian processes for classification (GPC) were obtained with good accuracy both for individual classes and average accuracy. A method has been tested to increase classification accuracy by combining models into a simple voting system, which may be of (applied) practical interest for pilot studies of a wide range of polymorphic variants of genes with unrelated signaling pathways.
Background. Transformation of the morphology of the post-infarction myocardium changes the electrical characteristics of the heart muscle, increasing the risk of life-threatening arrhythmias. Objective . The aim of the study was to compare the structural and electrical features of the heart muscle in post-infarction patients. Design and methods. The study participants were 105 (85.4 %) patients who had suffered an MI, aged 56.7±8.4 years. Six months after the MI, the patients underwent cardiac magnetic resonance imaging (MRI) (GE SIGNA Voyager tomograph, GE HealthCare, USA) with the introduction of a contrast agent — gadoteric acid. Six and 12 months after the MI, the patients underwent multi-day electrocardiogram monitoring (MMEKG) for 72 hours. Results. According to MMEKG, unstable paroxysms of VT were registered in 9 (6.8 %) patients. Frequent (>30/h) ventricular extrasystoles (VE) were correlated with the percentage of scar zone — r=0.679 (p=0.0101), the mass of the heterogeneous zone — r=0.721 (p=0.00951). An association was established between polymorphic VE with the presence of areas of microvascular obstruction r=0.812 (p=0.0095) and intramyocardial hemorrhage r=0.798 (p=0.0114). Most parameters of autonomic regulation and heart rate turbulence showed a moderate negative relationship with the scar mass. According to the data of univariate regression analysis, risk markers of unstable VT were established: scar zone mass, end-diastolic size, turbulence slope, SDNN variability parameter. Conclusion. Predictors of unstable runs of ventricular tachycardias within 12 months after myocardial infarction are the mass of the scar zone, the values of the left ventricular end-diastolic diameter, the values of the turbulence slope and the SDNN variability parameter.
This clinical case report describes the surgical management of a shrapnel wound to the thigh with associated vascular damage. A 55-year-old male soldier sustained a shrapnel injury to his left thigh during a combat mission. A tourniquet was applied immediately at the point of injury to control life-threatening bleeding. Upon evacuation to the nearest military field hospital (MFH), ultrasound examination revealed a rupture of the superficial femoral artery (SFA) and superficial femoral vein (SFV), along with an embolism of the posterior tibial artery and anterior tibial artery. Acute ischemia of the left lower limb, classified as grade 2b according to the Fontaine-Pokrovsky classification, was diagnosed. The case was complicated by a multi-level vascular injury, combining a proximal rupture of major vessels and distal embolism, which posed a significant threat of irreversible ischemia. Given the imminent risk of limb loss and the impossibility of evacuation to a higher-level multi-specialty military hospital, a decision was made to perform emergency surgery at the MFH. The surgical strategy involved a comprehensive set of reconstructive procedures on both the arteries and the vein. The intervention included resection of the SFA with an end-to-end anastomosis, repair of the SFV wall defect, removal of a thromboembolus from the popliteal artery bifurcation, and popliteal-to-distal posterior tibial artery bypass grafting using a reversed great saphenous vein. The postoperative course was uneventful, with complete resolution of acute ischemic symptoms and primary healing of the surgical wounds. The successful outcome demonstrates the feasibility of performing complex revascularization procedures in a military field hospital setting, even without on-site angiographic support. The surgical care provided at the MFH stage ultimately prevented limb amputation and subsequent disability.
