Chloride channels play a fundamental role in cellular homeostasis, influencing ion balance, pH regulation, and apoptotic signaling. While glutamate-gated chloride channels (GluCl) are traditionally restricted to invertebrates, recent evidence suggests that functionally analogous chloride conductances may exist in cancer cells, contributing to tumor survival and metabolic adaptation. Notably, chloride intracellular channels (CLICs), particularly CLIC6, have emerged as strong candidates for chloride-mediated oncogenic signaling. CLIC6 is overexpressed in multiple malignancies, including breast, ovarian, lung, gastric, and pancreatic cancers, and is known to interact with dopamine D₂-like receptors. Patchclamp studies have confirmed its chloride-selective conductance, localization to the plasma membrane, and regulation by pH and redox potential. The unexpected anticancer effects of antiparasitic drugs such as ivermectin, which targets GluCl channels in parasites, suggest a possible chloride-mediated mechanism of cytotoxicity in tumors. Ivermectininduced chloride influx may disrupt ionic equilibrium, hyperpolarize the plasma membrane, and trigger mitochondrial dysfunction, leading to oxidative stress, cytochrome c release, and caspase activation. This ionic disruption may also interfere with key oncogenic pathways, including PI3K/AKT, Wnt/β-catenin, and NF-κB, impairing tumor proliferation and immune evasion. Given the structural and functional parallels between GluCl channels and CLIC6, ivermectin’s efficacy may be partially mediated through chloride channel dysregulation. This review synthesizes molecular, electrophysiological, and pharmacological evidence supporting the existence of GluCl-like chloride conductance in cancer cells and its therapeutic implications. Further research is needed to characterize chloride ion dynamics in tumors, validate CLIC6 as a potential GluCl channel analog, and explore chloride channel-targeting strategies for cancer treatment, opening new frontiers in oncology.

In this review, based on the analysis of specialized domestic and foreign literature allocated in the electronic libraries eLibrary and CyberLeninka, the database of medical and biological publications PubMed, a theoretical justification is presented for the problem of women’s reproductive health associated with species-specific transformation of the oral microbiome and changes in its taxonomic profile. Data on previously studied predictors affecting women’s reproductive function do not raise discussions. However, the role of the oral microbiome in the pathogenesis of reproductive dysfunction has not been fully studied. It is known that the oral microbiome consists of more than 700 species of bacteria, and its diversity can change under the influence of various factors, such as age, hormonal changes, diet and general health. These changes can have a significant impact on the overall physical condition of a woman and her somatic health. It has been proven that during pregnancy, an increase in the number of viable microorganisms is observed, which can have both positive and negative effects on the health of the mother and fetus. At the same time, imbalances in the oral microbiome can increase the risk of developing various dental diseases (gingivitis, periodontitis), as well as systemic diseases, which in turn can have a negative impact on reproductive health. Therefore, further study of the relationship between the oral microbiome and women’s reproductive function opens up new opportunities for its implementation and prediction of outcomes.

The work is an overview of the loop-mediated isothermal amplification (LAMP) method and its application to diagnostics of hemorrhagic fevers. Its objective was to briefly characterize isothermal amplification and systematize the available data on diagnostics by this method of hemorrhagic fevers caused by pathogens belonging to the first pathogenicity group. The review describes the principle of LAMP operation, which is based on the use of chain-displacing activity of DNA polymerase. The advantages of the method, such as high sensitivity and specificity, simplicity of implementation and cost-effectiveness, are considered in detail. Various methods for detecting LAMP results are also discussed, including the turbidimetric method, the use of fluorescent dyes and immunochromatographic analysis. It is noted that LAMP has some limitations, such as the complexity of primer selection and the possibility of false negative results in the presence of mutations in the genome. However, in general, the method seems promising for rapid detection of viruses in the field. The review provides information on the developed diagnostic test systems based on LAMP for detecting RNA of especially dangerous viruses belonging to the Filoviridae and Arenaviridae families. It is noted that despite the promise of the method, at present none of the described test systems are registered or produced on a commercial basis. The conclusion emphasizes the need to develop and implement new methods for diagnosing dangerous viral infections to control the epidemiological situation and develop a strategy for anti-epidemic measures. LAMP is considered a promising method for creating rapid and cost-effective tests.

In the modern world the refusal of spectacle correction for near vision due to the development of presbyopia after 40 years old is an increasingly common criterion of satisfaction among patients, especially those leading an active lifestyle and wishing to solve the problem by surgical methods. The only effective method of correcting this condition is multifocal intraocular correction. Although the majority of patients do not require spectacles or contact lenses after this type of surgery, every surgeon with an active surgical practice has a number of patients who are dissatisfied with their outcomes. This may occur both as a result of complications during surgical treatment, and due to the peculiarities of neuroadaptation processes, the state of brain plasticity in each individual patient. The most common complications of multifocal correction are blurred vision and the presence of optical phenomena (halo and glare) associated with residual ametropia, posterior capsule opacification, large pupil size, wavefront anomalies, dry eye and lens decentration. The main causes of this are lens dislocation, residual refractive error, lens opacification and disruption or difficulty of the patient’s neuroadaptation process. Understanding and assessing the neuroadaptation in patients who have undergone lens surgery to correct presbyopia and eliminate cataracts is a poorly studied aspect of cataract surgery in the CIS countries and somewhat more studied in foreign literature, which is a promising direction for research. This article will review the literature on the above topic.

This literature review demonstrates the current state of the problem of diagnosing cardiovascular autonomic neuropathy (CAN), the advantages and disadvantages of the techniques used, and the possibility of introducing an easily reproducible method.

Material and methods. English-language articles from 2020–2024 using the keywords “cardiac autonomic neuropathy”, “diagnosis” and “study” in Google Scholar, PubMed, Springer search engines were selected for analysis. Among the materials found, the area of interest was the works describing clinical studies on the pathology under study.

Results and discussion. Currently, CAN is rarely diagnosed in clinical practice, despite its prognostic significance. In the analyzed works, CAN diagnosis was performed due to scientific rather than clinical interest, and the diagnostic methods themselves are heterogeneous. Recognized “gold standard” cardiovascular tests are difficult to reproduce on a large scale and in patients with multiple pathologies.

Conclusions. The problem of CAN is not given due attention in practical medicine connectedly the lack of a single easily reproducible diagnostic standard. Spectral analysis of heart rate variability with orthostatic test seems to be a promising method of CAN diagnosis with the possibility to determine the severity of the condition and response to treatment.

Cerebral palsy (CP) is one of the leading causes of disability in childhood. In many cases, this condition significantly reduces patients’ quality of life and requires a comprehensive interdisciplinary treatment approach, therefore, early diagnosis, prevention, and correction of its complications are of great importance. Developing effective treatment strategies requires an understanding not only of the etiological factors but also of the pathogenetic mechanisms underlying the disease. In recent years, persistent inflammation due to microglial activation following organic brain damage has been recognized as a key factor in CP pathogenesis. Growing evidence suggests that an imbalance between proand anti-inflammatory cytokines in the brain exacerbates neuronal damage and worsens rehabilitation outcomes. Further research on neuroinflammation is essential for identifying key therapeutic targets and developing new approaches to the physical rehabilitation of patients with CP. This review aims to present current data on the problem of neuroinflammation in CP patients and potential intervention points for physical rehabilitation methods.

The stability and satisfaction of sexual relationships are vital for individual well-being and societal cohesion. Although psychological and social influences on these outcomes are well-documented, the study of their genetic underpinnings remains an emerging area of research. This review aims to synthesize and critically analyze genetic research findings related to the stability and satisfaction of sexual relationships, highlighting key genetic mechanisms and their implications.

Material and methods. This review synthesizes findings from 42 peer-reviewed publications published between 2003 and 2023, focusing on the genetic contributions to relationship stability and satisfaction.

Results. Evidence indicates that neuroticism, with a heritability estimate of approximately 40 %, strongly predicts relationship instability. In contrast, higher levels of agreeableness and extraversion are associated with greater satisfaction. The review examines how genetics influence personality traits, attachment patterns, emotional regulation, hormonal factors, sexual compatibility, communication behaviors, and mental health predispositions. It also highlights the interaction between genetic and environmental influences, supported by case studies and empirical research that demonstrate the complexity of these relationships.

Conclusions. This review discusses ethical implications and outlines future research opportunities, providing a comprehensive perspective on how genetics can shape successful sexual partnerships. By integrating genetic research with relationship science, it offers evidence-based insights to guide future interdisciplinary investigations.

Endometriosis is a common gynecological disorder. Nowadays, its etiology and pathogenesis remain unknown. Its diagnosis and treatment are one of the most urgent problems. Existing theories do not fully explain the causes and mechanisms of the disease development, so the most effective treatment has not yet been found. Due to this fact, we cannot effectively prevent this disease. Many researchers try to solve this problem. The most important issue is studying various biomolecules' role in endometriosis development. In this review, we summarized data on some molecules that may play an important role in endometriosis development, including factors of chronic inflammation (M2-associated markers, arginase 1, CD11b), neovascularization (VEGF, HIF-1α, decorin), invasion (RPLP1, H3K27me3, TWIST1, RON, CD47, TSP1, SIRPα), autophagy (LC3B-II, p62, Beclin, NLRC5), proliferative activity and active metabolism in ectopic endometrial cells (MCT, GLUT), neurogenesis (NFASC, CHL1, c-Fos). The study of these molecules will help to deepen the understanding of the nature and mechanism of the disease, develop a diagnostic set of its markers, as well as effective treatment methods, including targeted therapy.

In the literature, the size of the parotid gland is greatly averaged, and there is also little data on the description of the organ in the context of sexual and craniotypic features. Therefore, an intravital study of the parotid gland in women with different skull shapes looks promising and can amplify the overall anatomical picture of the organ. The aim of the study was to study the anthropometric parameters of the parotid gland in women with different skull shapes.

Material and methods. Tomograms of the head organs of 90 women aged 18 to 87 years were analyzed. The transverse-longitudinal index of the skull and the upper-facial index are calculated, groups are identified according to the shapes of the cerebral skull – dolichocranians, mesocranians and brachycranians, according to the shapes of the facial skull – euryprosopes, mesoprosopes and leptoprosopes. The vertical, sagittal, and frontal dimensions were studied, and the volume of the parotid gland was calculated. The comparative analysis of the group indicators was performed using the Kraskell – Wallis criterion, the Mann – Whitney method with the Bonferroni correction, and the nonparametric Spearman method.

Results. The sagittal size of the gland is larger in dolichocran women compared to brachycranians (p < 0.0167). There is negative relationship between the sagittal size of the gland and the shape of the cerebral skull (p < 0.0001, r = –0.34 on the right, p = 0.0004, r = –0.36 on the left). The frontal size of the gland in brachycranian is larger than in mesoand dolichocranian women (p < 0.0167), it positively correlates with different shapes of the cerebral skull (p < 0.0001, r = 0.7 on the right, p < 0.0001, r = 0.66 on the left). The vertical size of the gland increases from euryprosopes to leptoprosopes, and the frontal size is larger in euryand mesoprosopus than in leptoprosopus women. The vertical size of the gland positively depends on the shape of the facial skull (p = 0.0003, r = 0.37 on the right, p = 0.0004, r = 0.36 on the left), and the frontal ‒ negatively (p < 0.0001, r = –0.73 on the right, p < 0.0001, r = –0.77 on the right).

Conclusions. In women, the sagittal and frontal dimensions of the parotid gland have a significant difference in the transverse-longitudinal cranial index. The vertical and frontal dimensions of the gland in different shapes of the facial skull significantly differ.

The aim of the study was to investigate the possible relationship between the occurrence of sigmoid colon diverticula and morphometric parameters of the body in middle-aged, elderly and old people.

Material and methods. The data of 569 diagnostic colonoscopies performed with Fujifilm video colonoscopes and morphometric parameters of the body calculated according to the method of V.N. Shevkunenko on the basis of the relative height index of the trunk were used in the study. Non-parametric criteria were used for statistical analysis, as well as the regression probit model.

Results and their discussion. It has been established that the frequency of diverticulosis incidence enhances at the ‘age distance’; along with the increase in the number of diverticulosis cases, there is a tendency of growth of this pathology in the groups of brachymorphic and dolichomorphic body types. A decrease in the proportion of detected diverticula in the senile age group (11.36 %) compared to the group of patients with mesomorphic type of physique in the middle age group (21.88 %) was found. An increase in the number of patients with colonic diverticula on the ‘age distance’ in the group of patients with dolichomorphic type of physique from 34.38 % in the middle age group to 50.00 % in the old age group was determined.

Conclusions. The obtained data allow optimizing the diagnostic process. Knowing the patient’s body type and age group, a doctor can timely prescribe a set of diagnostic methods to detect colonic diverticula. This is especially important for timely diagnosis of asymptomatic diverticulosis.

The pineal gland is a neuroendocrine gland that synchronizes the functional activity of body organs with the light regime using the hormone melatonin, which is actively released into the bloodstream at night. Melatonin is synthesized by pinealocytes, the main cell population of the pineal gland, in addition to which there are also astroglia, microglia, and mast cells. Besides, the pineal gland contains psammoma bodies (calcifications), the functional significance of which and the mechanisms of formation have not been determined. The aim of this study was to investigate the occurrence of calcifications in different parts of the human pineal gland (parenchyma, connective tissue trabeculae and capsule) and to describe the relationship of calcifications with astroglial cells and their processes, microgliocytes, mast cells, as well as blood vessels and nerve fibers using appropriate immunohistochemical reactions.

Material and methods. For immunohistochemical examination, antibodies to glial fibrillary acidic protein (GFAP), vimentin, two microglia markers (Iba-1 and TMEM119), mast cell tryptase, tyrosine hydroxylase and von Willebrand factor were used.

Results. Our study revealed calcifications mainly in the central part of the pineal gland, in the lobules among pinealocytes, with their number and size being increased from young to middle age. Processes of astroglial (mainly GFAP-, but not vimentin-containing) cells tightly envelop psammoma bodies. No relationship was found between the location of calcium deposits and blood vessels, tyrosine hydroxylase-immunoreactive nerve fibers, microgliocytes or mast cells. Prevalence of activated microglia and degranulating mast cells was not observed. Tyrosine hydroxylase-immunoreactive nerve fibers were identified for the first time in the human pineal gland.

Conclusions. The obtained data indicate that psammoma bodies are normal and, apparently, obligatory components of the adult human pineal gland, the formation of which is associated with pinealocytes and/or astrocytes, but not with blood vessels, nerve fibers, microglia or mast cells. The possible functional role of calcifications in the human pineal gland may be associated with the functional activity of pinealocytes.

A model of induced polypharmacy in studies of drug-induced changes in blood parameters can be represented by the combined treatment of tuberculosis patients in accordance with current clinical guidelines. Against the background of anti-tuberculosis therapy (ATT), patients experience negative changes in hematological parameters, indicating undesirable effects of anti-tuberculosis drugs (ATD). It is quite difficult to distinguish between the myelosuppressive effect of the specific inflammatory process (tuberculosis) and that of chemotherapy alone. The hematotoxic effect of individual ATDs is known, but how the interaction of a combination of drugs can affect the severity of drug-induced adverse events has not been sufficiently studied. The aim of the study was to analyze the drug-induced effects of standard two-month combined anti-tuberculosis therapy on the hematological parameters of rats, excluding the factors of a specific disease, and to determine early laboratory criteria for detecting changes.

Material and methods. The study material was rat blood serum, in which the following parameters were assessed: iron level, hemoglobin concentration, red blood cell, white blood cell, platelet count and erythrocyte indices (mean corpuscular volume and mean corpuscular hemoglobin) after two months of combined ATT. Experimental group I (EGI) received first-line ATDs for drug-sensitive tuberculosis, while experimental group II (EGII) received second-line (reserve) ATDs for multidrug-resistant tuberculosis. The results were compared with a control group (CG).

Results and discussion. During the experiment, no statistically significant hematological changes were found in the blood of rats in EGI after standard two-month ATT. In contrast, in EGII, after 60 days of second-line ATD combination therapy, a significant decrease in hemoglobin level (by 38.2 %, р < 0.001), mean corpuscular volume (by 32.1 %, р < 0.001), and mean corpuscular hemoglobin (by 25.2 %, p < 0.001) was observed. These findings may serve as early diagnostic criteria for the development of adverse hematotoxic effects of ATDs and require further study to determine the optimal drug administration regimen.

Both the skin's own cellular components and physiologically active substances, such as cytokines, actively participate in the protracted and intricate process of skin burn wound healing. One of these molecules is angiogenin, a ribonuclease that encourages the development of a vascular network where tissue and organ damage has occurred. The study compared the effects of intradermal delivery of human skin fibroblast cells, EA.Hy926 endothelial cells, conditioned media from human bone marrow mesenchymal stem cells, and human recombinant angiogenin after thermal skin burn in female CD-1 mice.

Material and methods. Using a metal plate heated to 200–250 °C over the flame, a thermal skin burn in the back area was initiated. Treatment was started immediately after the initiation of the burn wound. Recombinant human angiogenin (1 ml of solution containing 10 μg of active agent) was administered once, twice, and three times with an interval of 7 days; conditioned media from human somatic cells (1 ml) were administered once. A caliper was used to measure the size of the wound on days 7, 14, and 21. Blood and a piece of skin from the burn wound were collected when the animals were removed from the experiment. Using spectrophotometry, the amounts of NO and cytokines (IL-1β, TNFα, IL-10, and VEGF) in blood serum and extract of skin samples were measured. The squamous epithelium, granulation tissue, blood vessel count, lymphocytes, neutrophils, macrophages, plasmocytes, and fibroblasts were all evaluated by histological analysis of skin samples.

Results and discussion. Human recombinant angiogenin or conditioned media derived from human somatic cells significantly accelerated the repair of wound skin defects in groups of mice with thermal burns. A conditioned media derived from human bone marrow mesenchymal stem cells is as effective as a single injection of human recombinant angiogenin. The wound defect's epithelialization, granulation tissue development, and increased angiogenesis were all facilitated by treatment with human recombinant angiogenin and conditioned media derived from human somatic cells. It has been demonstrated that variations in cytokine and NO levels in blood serum and skin occur depending on the type of treatment and the length of observation. The morphometric characteristics of skin samples taken from the burn site were found to correlate with these parameters.

Conclusions. Injections of the biomedical cell product into the area of thermal skin burns in female CD-1 mice accelerate wound defect healing.

The processes of biological integration of the implant and regeneration of surrounding tissues after surgery are sufficiently studied. A more detailed study of morphological changes at different stages of implantation and the postoperative period can contribute to: identifying possible causes of negative reactions to a particular type of implants, modifying existing materials, and, consequently, improving the quality of treatment and prognosis for patients. The aim of study is to investigate the integration process of synthetic and biological implants at the submicroscopic level in the early stages after surgery.

Material and methods. Surgeries were performed to implant a synthetic mesh and a xenopericardial plate into the anterior abdominal wall and the wall of the small intestine in 10 sexually mature male Chinchilla rabbits. Fourteen days after the surgery, tissue fragments with the implanted implants were sent for examination using a backscattered electron detector using a scanning electron microscope.

Results and discussion. Propylene mesh forms a less stable structure, since its iointegration results in “kinks” and “empty” areas not filled with new connective tissue. The stability of the xenopericardial plate is ensured by the similar direction of its own fibers and newly formed collagen fibers.

Conclusions. Polypropylene implants can become mobile in the surrounding tissues, which reduces the effectiveness of the surgery. In the early stages, the xenopericardium is better fixed to the tissues into which it was implanted.

Laboratory animals allow modeling infectious diseases to study pathogenesis and conduct drug trials. The creation of animal models that most accurately reproduce COVID-19 is promising for assessing the effectiveness of drugs and vaccines against the SARS-CoV-2 virus. The aim is to study the histological changes in the lungs and the other indicators of the infectious process in modeling COVID-19 in guinea pigs as a type of laboratory animals susceptible to SARSCoV-2 virus.

Material and methods. The experiments were carried out on 12 guinea pigs of both sexes infected with SARS-CoV-2 alpha variant. The dynamics of the viral load was determined in nasal washes by RT-PCR; SARS-CoV-2 antibody content in the blood serum were measured by ELISA; titers of neutralizing antibodies were estimated in the neutralization reaction in Vero E6 cell culture. As controls, 12 lung autopsies of patients infected with SARS-CoV-2 (confirmed by PCR analysis) and those who died as a result of pneumonia were studied. Structural changes in the lungs of autopsy and experimental samples were studied on paraffin sections stained with haematoxylin and eosin.

Results. After intranasal infection with SARS-CoV-2 alpha variant at a dose of 4 lg TCID₅₀ (the dose infecting 50 % of the cell culture and causing cytopathic effect in 50 % of the cell monolayer), a low level of viral load with high rates of elimination was detected in the nasal cavity and lungs of guinea pigs. On days 3 and 5, the viral load in nasal swab samples was significantly higher in males (p < 0.05). After 7 days, viral RNA was not detected in nasal swabs. Antibodies to SARSCoV-2 were detected in the blood serum of guinea pigs on the 15th day. With a neutralizing antibody titer of 1:100 for all animals, the positivity rate in females was 2 times higher. Histologically confirmed severe viral pneumonia was recorded in dead animals and at the end of the experiment, similar to changes in the autopsy material of patients with COVID-19.

Conclusions. Histological changes in the lungs of guinea pigs during modeling of SARS-CoV-2 infection indicate the susceptibility of this animal species to the studied pathogen with reproduction of the disease in patients, which allows us to consider guinea pigs as a promising animal model for the study and prevention of COVID-19.

Ovarian cancer remains one of the most common causes of death from gynecological cancer in women worldwide. Its course depends on many factors, including genetic and epigenetic disorders. MicroRNAs are currently considered one of the most promising prognostic and diagnostic markers for solid tumors. The aim of the study was to analyze the association of polymorphic loci of the microRNA-27a rs895819 and microRNA-146a rs2910164 genes with the risk of developing ovarian cancer.

Material and Methods. Genotyping was performed by determining single nucleotide polymorphisms using the KASP method. For pairwise comparison of the frequency of occurrence of genotypes and alleles in patients with ovarian cancer and in the control group, the χ2 test was used for 2×2 contingency tables. If there are statistically significant differences between the compared samples, the odds ratio (OR) and the boundaries of the 95 % confidence interval (95 % CI) were assessed. Quantitative characteristics were compared using the Mann – Whitney test (in the case of two groups) and the Kruskal – Wallis test (in the case of three groups).

Results. As a result of a comparative analysis of the distribution of frequencies of alleles and genotypes of the polymorphic locus rs2910164 of the miR-146a gene in a sample of patients with ovarian cancer and healthy individuals, it was shown that carriage of the homozygous genotype GG and allele G is a risk factor for women of Tatar ethnicity. No significant differences were detected in the distribution of allele frequencies and genotypes of the rs895819 polymorphic locus of the miR-27a gene.

Conclusions. The polymorphic locus of microRNA-146a rs2910164 is associated with an increased risk of ovarian cancer in women of Tatar ethnicity.

Currently, there is insufficient data in the literature on the efficacy and safety of platelet-rich plasma (PRP) therapy in patients with osteoarthritis (OA) of the knee. The aim of this study was to evaluate the efficacy and safety of local therapy with PRP and hyaluronic acid (HA) by intra-articular injection in patients with stage II-III knee OA.

Material and methods. Patients (n = 32, age 60.9 ± 7.7 years) were divided into 2 groups: the first (18 patients) received a combination of PRP and HA intra-articularly. PRP was injected according to the schedule (1, 7, and 14 days) and HA (1 day). In the second group (14 patients), HA was injected intra-articularly in isolation. Manipulations were performed on one knee joint. Prior to treatment, all patients underwent radiography of the knee joint and ultrasound in three zones (upper pole of the patella, lateral and medial condyles of the tibia) to evaluate changes in cartilage thickness in the dynamic range. Diagnostic arthroscopy of the affected joint was performed to objectify the severity of cartilage lesions one day prior to the first intra-articular drug injection. Control ultrasound was performed at 12 and 24 weeks of followup. The clinical efficacy of the therapy was assessed using WOMAC, Lequesne, and visual analog pain scale.

Results. Analysis of the dynamics of pain syndrome showed an analgesic effect of therapy and improvement of the functional status of patients in the first and second groups after 3 months. In both groups, after 3 months of observation, according to ultrasound data, a statistically significant increase in cartilaginous tissue in the area of the upper pole of the patella was revealed, as well as in the area of the lateral condyle of the tibia in the second group after 3 months with a further increase in cartilage thickness by the 6th month of observation. In the third localization, the medial condyle of the tibia, both groups showed no statistically significant increase in cartilage thickness.

Conclusions. PRP and HA are effective and safe in the treatment of stage II–III knee OA with chronic pain syndrome. Regression of clinical effects occurred 6 months after initiation of therapy, while the combination of therapy methods did not contribute to prolongation of positive results. Thus, the combination of the indicated treatment methods (PRP + HA) does not seem appropriate.

During leukemogenesis, there is a consistent accumulation of driver aberrations leading to the development of acute myeloid leukemia (AML). Since mutations in the NPM1 gene in the absence of a concomitant FLT3-ITD mutation have favorable prognostic value and can serve as independent targets for assessing minimal residual disorder in this disease, their rapid and accurate identification in patients with newly diagnosed AML is required. Currently, the literature contains the results of several domestic studies of the mutation spectrum of NPM1 in an adult cohort of patients with a “narrow” geography. The aim of the work was to study the frequency and spectrum of insertions in the 12th exon of the NPM1 gene in a sample of patients with de novo acute myeloid leukemia living in a large Siberian metropolis.

Material and methods. The study group consisted of 128 primary patients with AML in Novosibirsk. The PCR method with flanking primers was used for screening, and direct Sanger sequencing by capillary electrophoresis was used to establish the sequence and insertion site.

Results and discussion. The frequency of mutations in the 12th exon of the NPM1 gene in the study group was 14.8 %, 84.4 % of the findings were inserts of type A, in one case (5.2 %) an insert of type B. Two new insertions previously undescribed were identified, c.863_864insTGCT and c.868_869insAAGC. The first of them is similar in its functional effect to the changes observed with classical inserts of type A and B: it leads to an elongation of the encoded protein, a shift in the reading frame, and the loss of the nucleolar localization signal motif with the formation of a typical nucleophosmin export signal motif from the nucleus. A distinctive feature of c.868_869insAAGC insertion was the partial preservation of the nucleolar localization signal due to the presence of tryptophan in the 288th position.

Conclusions. Using the developed set of primers, it is possible to screen mutations in NPM1 exon 12 in patients with AML within one working day, as well as their further accurate identification by direct sequencing during the first induction treatment cycle.

The migration of immunocompetent cells plays a central role in the development of thyroid damage. It involves lymphocyte-platelet adhesion (LPA), which not only promotes cell movement through the vascular wall, but also the relationship between other cellular and humoral mechanisms engaged in the immune defense mechanism, as well as the response of the vascular endothelial wall. The aim of the study was to investigate the effect of associations of single nucleotide polymorphism (SNP) of P-selectin gene (SELP) (Thr715Pro), E-selectin gene (SELE) (Leu544Phe and Ser128Arg), the level of their soluble forms sPand sE-selectin and LPA in hyperthyroidism syndrome.

Material and methods. 63 patients with hyperthyroidism syndrome due to diffuse toxic goiter (56 %) and nodular/multi-nodular toxic goiter (44 %) were studied. The control group consisted of 48 practically healthy volunteers, matched for sex and age. The LPA, the polymorphism of the Pand E-selectin genes, the concentration of sPand sE-selectin was determined.

Results and discussion. It was found that in patients suffering from thyrotoxicosis syndrome, the ability of lymphocytes to form bundles with platelets decreases: the number of lymphocyte-platelet coaggregates (LTC) in them was 5.2 [3.9; 6.6] %, while in healthy people it was 14.0 [12.1; 15.2] % (p < 0.05). There is also a decrease in the number of platelets coming into contact with lymphocytes. In patients with thyrotoxicosis with a heterozygous Thr/Pro genotype for the Thr715Pro SNP of the SELP gene, the concentration of sP-selectin is two times lower than in homozygotes Thr/Thr (p < 0.05). The analysis of the sE-selectin content revealed no differences that could depend on the SELE Leu544Phe and Ser128Arg SNP, the effect of these polymorphisms on LPA has also not been established.

Conclusions. In patients with hyperthyroidism, there is a significant decrease in adhesion between lymphocytes and platelets. The concentration of sP-selectin varies depending on patient’s genotype at SELP gene SNP Thr715Pro, which in turn affects LPA to varying degrees.

Osteoporosis (OP) and sarcopenia are common complications of rheumatoid arthritis (RA). The bone and muscle tissue status may be related to the activity of various immunological factors. Aim of the study was to investigate the association between immunological factors and the bone and lean tissue status in women with RA.

Material and methods. The study included 163 postmenopausal women with confirmed RA (age 61.0 [52.0; 66.0] years, median [lower quartile; upper quartile]). A clinical and laboratory examination was performed including dual-energy X-ray absorptiometry to assess bone mineral density (BMD) and lean mass. The levels of C-reactive protein, rheumatoid factor, antibodies to cyclic citrullinated peptide, myostatin, follistatin, IL-6, IL-6 receptors, insulin-like growth factor 1, adiponectin, leptin, fibroblast growth factor 23, tumor necrosis factor SF12 and sclerostin in blood serum were determined.

Results. Persons with OP had higher level of sclerostin compared to those without it (р < 0.001). In sarcopenic patients IL 6, rIL 6, and sclerostin contents were lower (p = 0.038, p = 0.040, and p = 0.003, respectively), and insulin-like growth factor 1 concentration was higher (p = 0.014) than in those without sarcopenia. Multivariate linear regression revealed an independent positive association of sclerostin level with lumbar spine and femoral neck BMD (β = 0.28, p = 0.017 and β = 0.25, p = 0.028, respectively) and a negative association of adiponectin level with total and appendicular lean mass (β = –0.21, p = 0.045 and β = –0.25, p = 0.036, respectively) and appendicular lean mass index (β = –.30, p = 0.041).

Conclusions. In women with RA, BMD correlates with sclerostin level, and muscle mass – with adiponectin content. The effect of various cytokines on BMD and lean mass in patients with RA requires further study.

One of the development factors of primary open-angle glaucoma (POAG) is genetic predisposition to its occurrence, associated with the peculiarity of cytokine genes. However, mechanisms for the implementation of this phenomenon for different geographic regions remain unknown. The aim of the study analyze the distribution features of the single nucleotide polymorphisms of IL10 gene (rs1800896 and rs1800872) in groups of patients with POAG from four regions of the Russian Federation: Novosibirsk (NSR), Leningrad (LEN), Orenburg (ORE) regions and the Chuvash Republic (CHVSh).

Material and methods. The comparative multicenter genetic study on 499 patients with POAG from 4 branches of the S. Fyodorov Eye Microsurgery Federal State Institution (Novosibirsk – 199 people, Cheboksary – 100 people, Orenburg – 100 people, St. Petersburg – 100 people) was conducted. The control group – 530 individuals without this disease. Genotyping was performed by TaqMan (Syntol, Russia). Differences were considered statistically significant at p < 0.05, with Bonferroni correction.

Results and discussion. Statistically significant multidirectional interregional differences in the distribution of IL10 gene polymorphisms in POAG patients were revealed. The frequency of IL10-592 C allele in patients from the LEN region have increased to 87.00 % relative to patients from NSO (72.86 %, odds ratio (OR) = 2.50, p_cor = 0.0006) and from ORE (75.50 %, OR = 2.17, p_cor = 0.0276), as well as IL10-592 CC genotype. LEN region patients with this genotype have 3.57-fold higher chance of POAG developing than NSO patients (p_cor = 0.0006) and 2.86-fold higher chance – relative to ORE residents (p_cor = 0.0084). In LEN region patients the frequencies of IL10-592 A, IL10-592 CA and IL10-592CA / IL10-1082AA complex genotype were reduced relative to patients from the ORE (24.00 %, OR = 6.00, p_cor = 0,0016). This complex is, on the one hand, protective against POAG disease for residents of the LEN region, and on the other hand, a risk factor for the development of POAG in residents of the NSR and the ORE.

Conclusions. We have identified new factors of genetic predisposition to the POAG development in Russian Federation and identified both positive and negative associative links with this ophthalmopathology. The results can be used to develop polygenic risk indicators for the POAG development, taking into account regional ethnogeographic specifics.

Aim of the study was to investigate the morphological results of implantation with the introduction of fragments of autologous bone into soft tissues sutured over the device.

Material and methods. The condition of gum tissue in 95 patients before implantation and 4–6 months after the installation of screw dental implants using standard technology (n = 42) or with the placement of fragments of autologous bone, formed during the preparatory procedures, over the implant (n = 47) was study with morphological methods using immunohistochemistry to identify CD68+ cells.

Results. The addition of autologous bone particles to the tissue next to the intraosseous implant promotes the formation of thick and strong bone, reliably isolating the device from the oral cavity, damage during chewing and contamination by microorganisms. 4–6 months after implantation the signs of the inflammatory process (vascular reactions, leukocyte infiltration and formation of a connective tissue capsule) and macrophage response with migration of phagocytes and the formation of giant multinuclear forms are absent in the tissues near the foreign body and remaining bone fragments.

Conclusions. In the case of introducing small fragments of autologous bone, formed during the preparation of the implantation bed, into the soft tissue over the device during surgery, after 4–6 months a dense mass of compact bone with wide osteons and very sparsely located Haversian canals is formed. Bone fragments not included in the bone capsule either lyse with subsequent calcification, or gradually migrate via tissues, even bone, and are eliminated outward. During the formation of a bone dome over the implant, objects similar to dentin may appear.

Hypertension is a risk factor for myocardial and cerebral infarction. These conditions lead to cognitive impairment (CI) and emotional-volitional disorders (EVD), which subsequently can dramatically reduce the availability of industrial work activity and worsen health. Aim of the study was to conduct a comparative assessment of the frequency and relationship of cardiovascular risk factors, CI and EVD in patients with stage III hypertension, depending on the history of myocardial or cerebral infarction.

Material and methods. A total of 100 patients with verified hypertension stage III were examined, against the background of indicated hypotensive therapy. Patients, whose age was 62.7 ± 9.2 years (arithmetic mean ± error of the mean), were divided into two groups of 50 people. Group 1 included people with post-infarction cardiosclerosis, and group 2 included people with a history of acute cerebrovascular accident. The patients’ risk factors were analyzed, and their CI was assessed using the MMSE and MoCa scales. The Beck Depression Inventory was used to study the EVD.

Results and discussion. In patients with hypertension, the risk factors in the 2nd group were statistically significantly less likely to include alcohol and table salt abuse, and more often a sedentary lifestyle and COVID-19. In the 1st group, the frequency of individuals with increased level of glucose, high-density lipoproteins, triglycerides was significantly higher, and the frequency of individuals with elevated total cholesterol content and glomerular filtration rate less than 60 ml/min/1.73 m² was lower. Patients of the 2nd group were statistically significantly less likely to have chronic kidney disease stage C3a. CI according to the Mohs scale and MMSE were more pronounced in the 2nd group. In the 1st group, a direct correlation was found between CI and age, education, blood glucose level and a negative – with creatinine content. In the 2nd group, a positive correlation was found between CI and COVID-19, body mass index, systolic blood pressure and an inverse relationship – between CI and blood triglyceride and bilirubin content. EVD were manifested by subdepression and were significantly more common in the 2nd group. The severity of depression correlated with the total cholesterol content in the 1st group and with glomerular filtration rate in the 2nd group.

Conclusions. The obtained results showed a difference in the combinations of risk factors in the 1st and 2nd groups of patients, which depended on the disease associated with hypertension.

There is a lot of evidence about the role of free radical oxidation in homeostasis and in the development of many diseases. Of particular interest are pathological conditions that are accompanied by both activation of free radical oxidation processes and hemocoagulation, which leads to the development of disseminated intravascular coagulation syndrome. Diseases of the circulatory system have become one of the most common causes of death worldwide, which are accompanied by activation of the hemostasis system, intravascular coagulation and free radical oxidation. Aim of our study was to investigate spontaneous luminol-dependent chemiluminescence of whole blood and hemocoagulation parameters in patients with diseases of the circulatory system.

Material and methods. Free radical oxidation parameters (chemiluminescence intensity maximum, chemiluminescence intensity decay constant, and luminescence light sum) were determined using a BCLM 3606M biochemiluminometer. Free radical steady state concentration was determined using the Bouguer – Lambert – Beer formula. The rate constant for the transition of free radicals to an excited state, accompanied by the emission of light (k₂), was calculated using Yu.A. Vladimirov's equation in own modification. Platelet hemostasis parameter values were determined by direct impedance measurement using a Sysmex XN-550 analyzer, coagulogram parameter ‒ using a Sysmex CA-1500 analyzer.

Results. In patients with circulatory system diseases, an increase in the large platelets proportion (by 1.16 times, p = 0.05) and a decrease in the prothrombin according to Quick (by 1.22 times, p = 0.04) relative to the control group parameters are observed, an increase in the chemiluminescence intensity maximum (by 1.23 times, p = 0.05) is revealed. The steady state concentration of free radicals is 1.074·10-6 mol/dm3, the reaction rate constant is 3.068·10⁶ (mol/dm³)^-1·s^-1.

Conclusions. In patients with circulatory disorders, intensification of lipid peroxidation processes and activation of hemocoagulation processes are observed, as evidenced by an increase in the maximum intensity of blood spontaneous luminol-dependent chemiluminescence, the large platelets proportion and a decrease in prothrombin according to Quick. The value of the rate constant for the transition of free radicals to an excited state, accompanied by the emission of light (k₂), in the blood of patients is 3.068·10⁶ (mol/dm³)^-1·s^-1.

The aim of the study was to identify the association between polymorphism of the SLCO1B1 gene and virological efficacy in children receiving lopinavir as part of their antiretroviral therapy.

Material and methods. The study included 48 children with HIV infection aged 4 to 17 years receiving lopinavir as part of their antiretroviral therapy. The first group of 32 patients with virological efficacy included children with undetectable viral load <50 copies/ml, the second group of 16 patients without virological efficacy included children with detectable viral load >50 copies/ml. The libraries were prepared according to the DNA Flex protocol, following the manufacturer’s recommendations (Illumina, USA). Sequencing was performed on the NextSeq 550 platform.

Results. Targeted sequencing of the SLCO1B1 gene region revealed 37 polymorphisms. Analysis of the identified polymorphisms showed that rs4149056 of the SLCO1B1 gene is associated with virological efficacy in children with HIV infection. The carriage of TC/CC genotypes of the rs4149056 polymorphism was registered more often in the group with virological efficacy than without it (odds ratio 0.14, 95% confidence interval 0.01–0.812, p = 0.017).

Conclusions. The carriage of TC/CC genotypes of the rs4149056 polymorphism may serve as a predictor of virological efficacy in children with HIV infection receiving lopinavir therapy in combination antiretroviral therapy.

The problem of comorbidity is of great importance due to its severe medical and social consequences. In the etiopathogenesis of comorbid pathology in patients with somatic disease, a significant role is played by risk factors that tend to appear in the form of clusters. Aim of the study was to investigate the features of the severity and structure of comorbidity in patients with a therapeutic profile in the presence of each of the three clusters of risk factors for chronic non-communicable diseases (cluster 1: age over 52 years, obesity, hyperglycemia; cluster 2: arterial hypertension, hypertriglyceridemia, elevated serum concentration of C-reactive protein (CRP), hyperuricemia; cluster 3: low(LDL) and high-density lipoprotein (HDL) hypocholesterolemia).

Material and methods. The study included data from case histories of 4908 people, 2026 men (41.3 %) and 2882 women (58.7 %), aged 57.9 ± 0.2 years (arithmetic mean ± standard error of the mean). Three groups of patients were formed depending on the presence of a particular cluster of risk factors: Group 1 – age over 52 years, obesity, hyperglycemia (n = 434); Group 2 – arterial hypertension, hypertriglyceridemia, elevated serum concentration of CRP, hyperuricemia (n = 108); Group 3 – LDL hypercholesterolemia, HDL hypocholesterolemia (n = 363). The frequency of all available nosological forms was analyzed in accordance with ICD-10. Transnosological comorbidity was assessed by the number of nosological forms, transsystemic comorbidity – by the number of ICD-10 classes in one patient.

Results and discussion. A high level of transsystemic and transnosological comorbidity was revealed in patients with any of the considered clusters, which emphasizes their importance in the development of comorbidity. The highest comorbidity rates were found in patients with a cluster of factors: age over 52 years, obesity and hyperglycemia (transnosological comorbidity – 8.86 ± 0.19; transsystemic comorbidity – 4.60 ± 0.06). The most common nosologies in patients in all 3 groups were hypertension, deforming dorsopathy and non-alcoholic fatty liver disease, which may be due to the common pathogenetic mechanisms of these diseases (dysregulatory, vascular and metabolic disorders), which can be initiated by the considered risk factors.

Conclusions. Among the clusters of factors associated with comorbidity, the most significant are the following: age over 52 years, obesity, hyperglycemia; arterial hypertension, hypertriglyceridemia, hyperuricemia, increased serum concentration of CRP.

Aim of the study was to determine the association of polymorphic variants of lipid and carbohydrate metabolism genes with the risk of myocardial infarction.

Material and methods. 146 patients with myocardial infarction and 300 relatively healthy donors were recruited for the molecular genetic study including isolation of genomic DNA and genotyping of single-nucleotide polymorphic variants by real-time PCR. To assess the myocardial infarction risk, the frequencies of alleles and genotypes for 12 single-nucleotide polymorphic variants in the IGF1R, INS, LEP, LEPR, LIPC, LPA, APOE and APOB genes were studied.

Results. It was found that the increased myocardial infarction risk is associated with the genotypes T/T and G/T of rs6725189 variant in the APOB gene (p < 0.0001); G/G and A/G of rs1137100 variant in the LEPR gene (p < 0.0001) and T/T of rs1800588 variant in the LIPC gene (p = 0.0023) regardless of gender. In men, the myocardial infarction risk is 1.5-fold higher than in women when carrying a homozygous genotype for a rare allele of the polymorphic loci rs1800588 in the LIPC gene (p = 0.0064) and rs6725189 in the APOB gene (p < 0.0001). Carriage of the A allele of rs689 variant in the INS gene (p = 0.024) and the C allele of rs429358 variant in the APOE gene (p = 0.024) increases the myocardial infarction risk in men by two times. At the same time, the A/G and G/G genotypes of the rs1137101 polymorphic variant in the LEPR gene are associated with a reduced myocardial infarction risk (p = 0.0003). Myocardial infarction patients carrying the C/C genotype of rs7412 variant in the APOE gene are characterized by higher serum blood level of LDL (p = 0.0091), and this tendency is more pronounced in men (p = 0.044). In male patients with myocardial infarction carrying the homozygous for the rare allele A of the polymorphic variant rs689 in the INS gene, higher fasting glucose levels were recorded (p = 0.01).

Conclusions. Carriage of rare alleles in individual polymorphic sites of the genes of lipid (rs1137100 LEPR, rs6725189 APOB, rs1800588 LIPC and rs429358 APOE) and carbohydrate metabolism (rs689 INS) is associated with an increased risk of myocardial infarction.

In Russia, more and more attention is being paid to strengthening public health as a system that covers all spheres of human life. Meanwhile, the medical and social causes of human resources losses as a foundation of public health have not been sufficiently studied. The study aim is to determine structure, rank, and government regulation of medical, biological, and socio-economic causes of losses in quality of human resources (military, labor, reproductive) – the basis of public health as a medical and social resource of Russia caused by socially significant infectious diseases (SSID).

Material and methods. In the study an information-analytical method was used with search on leading websites of main regulatory legal acts and publications corresponding to study aim and analysis of them was conducted.

Results and discussion. The frequency of SSID registration in regulatory documents governing quality of country’s military reserve, as causes of medical and social losses, amounted to 9.0 % of ICD-10 class I diseases; labor reserve – 6.0 %, reproductive resources – 2.5 %. Among socially significant infections, active tuberculosis and its severe manifestations/ outcomes has become leading cause of medical and social losses of main components of public health: military, labor and reproductive reserves.

Conclusions. SSID, despite their small list or low frequency of registration in regulatory documents governing quality of individual components of public health, play significant role in medical and social causes of losses of strategically important public health structures, especially in military reserve.