Aim. To evaluate the temporal changes in circulating cytokines rallying systemic inflammatory response after a blast injury.
Material and Methods. Experiments were performed on 60 male Wistar rats (50 rats with blast-related soft tissue injury of the thigh and 10 intact rats). Blast injury was modeled under general anaesthesia using grater firecrackers stuffed with a pyrotechnic mixture. After 3, 7, 14 and 28 days post injury, we carried out a gross examination of the wound and its drainage, measured wound area, assessed local oedema severity, and evaluated serum potassium, myoglobin TNF-α, IL-1β, IL-6, and IL-10.
Results. Three to seven days post injury, therewas abundant serous and purulent exudate and pronounced local edema without considerable changes in the wound area. Serum myoglobin and potassium were raised 2.2-2.6-fold and 1.3-fold, respectively (p < 0.05); in addition, we documented the elevation of a major pro-inflammatory cytokine IL-1β. Fourteen days post injury, wound area reduced by 24%, (p < 0.05) along with the decreased wound drainage and local edema of the injured area. Although the levels of serum myoglobin and pro-inflammatory cytokines (in particular
IL-6) lowered, they were still significantly higher as compared with the intact rats. Twenty eight days post injury, fibrosis has been completed, epithelialization occurred and only a small scab remained on the wound surface. Yet, serum IL-1β still was 1.3-fold higher than in the intact animals (p < 0.05), albeit IL-6 and TNF-α returned to the reference values. The concentration of anti-inflammatory cytokine IL-10 reached its maximum values relative to the control (3.9-fold, p < 0.05) to the 14th day post injury that was followed by a considerable reduction (though not reaching the reference values) by the period of scar formation.
Conclusion. Blast injury in rats is accompanied by a dysregulated balance between pro-inflammatory and anti-inflammatory cytokines throughout all regeneration phases.

Aim. We aimed to evaluate levels of transforming growth factor β1 (TGF-β1) in the serum, lymph nodes, and primary tumour in patients with colorectal cancer.
Materials and Methods. Here we enrolled 44 patients with colorectal cancer and 25 patients with benign tumours of the colon admitted to Chita Regional Cancer Centre in 2019-2020. The control group included 25 patients with colon injury. The concentration of TGF-β1 in the serum, lymph nodes, and tumour homogenate was measured by flow cytometry (CytoFlex LX analyzer and LEGENDplex HU multiplex analysis kit).
Results. Serum level of TGF-β1 in patients with colorectal cancer was 1.58-fold lower than in those with benign colon tumours and 1.38-fold lower than in the control group. In contrast, TGF-β1 level in tumor tissue was 5.91 (3.86; 7.81) fold higher than in the injured colonic tissue from the control group, although there were no statistically significant differences between the cancerous tissue and benign neoplasms.
Conclusion. TGF-β1 is increased in tumour tissue but reduced in the serum of patients with colorectal cancer.

Aim. To develop an animal model of femoral head aseptic necrosis for studying Legg–Calvé–Perthes disease.
Materials and Methods. To induce the development of aseptic necrosis, we used Wistar rats (n = 8) which suffered from combined hypoperfusion of the femoral head and increased intra-articular pressure in the hip joint. Having employed isoflurane anesthesia, we performed an incision (≈ 3 cm length) on the outer surface of the thigh in the projection of the hip joint and then excised periosteum in the proximal third of the femur. A dense vicryl ligature was applied around the femoral neck to reduce blood perfusion of the femoral head. Further, 1.5 mL 2% rheopolyglucinum solution (10% isotonic dextran, 30-40 kDa molecular weight) was injected into the hip joint cavity to increase intra-articular pressure. Rats were sacrificed upon 8-week follow-up with subsequent X-ray and histological examination.
Results. Our animal model of femoral head aseptic necrosis includes two main components of Legg–Calvé–Perthes disease: an increase in the intra-articular pressure and insufficient blood perfusion of the femoral head. In all (8/8) cases, aseptic necrosis of the femoral head was achieved. Eight weeks post intervention, the condition of the proximal femur 8 was similar to impression fracture.
Conclusion. Our model of femoral head aseptic necrosis fully reflects the pathogenesis of LeggCalve-Perthes disease and can be therefore used in experimental studies.

Aim. To improve epidemiological surveillance in the neonatal intensive care unit.
Materials and Methods. We retrospectively examine case histories of 646 newborns delivered in Tyumen Perinatal Center and admitted to neonatal intensive care unit (310 with intrauterine infection and 336 without intrauterine infection). Predictors of intrauterine infection (odds ratio and 95% confidence interval) were determined by means of multivariate analysis and logistic regression analysis.
Results. According to the multivariate analysis, past medical history of abortions, urinary tract infections, preterm birth during previous pregnancy, colpitis, vaginitis, leukocytosis, elevated C-reactive protein, anemia, and impaired fetal blood supply were among the predictors of intrauterine infection. Stepwise logistic regression identified 7 significant features associated with intrauterine infection: leukocytosis, anemia, pathological alterations in amniotic fluid, preterm birth, impaired fetal blood supply, newborn respiratory distress syndrome, and injury of the newborn central nervous system. Sensitivity and specificity of the prognostic model were 87.7% and 83.9%.
Conclusion. Our prognostic model might be applicable for the prediction and verification of intrauterine infection during the prenatal and perinatal observation.

Aim. As the activity of bacteriophages is species- and strain-specific, it is necessary to study bacteriophage sensitivity in distinct geographic regions with various disease patterns. Here, we aimed to study the lytic activity of specific commercially available bacteriophages against Klebsiella spp., Proteus spp., and Staphylococcus aureus isolated from the intestines of children with gut dysbiosis.
Materials and Methods. Bacteriophage sensitivity was assessed in 315 opportunistic microorganisms (125 Staphylococcus aureus strains, 120 Klebsiella spp. strains, 70 Proteus spp. strains) isolated from the intestinal microbiota of 300 children < 4 years of age with gut dysbiosis. Bacteriophage preparations were produced by Microgen (Russian Federation). The lytic activity of bacteriophages was studied by a drip method on a Muller-Hinton medium by calculating the area of bacterial culture lysis.
Results. We found low sensitivity of Klebsiella spp. (37.5% sensitive strains) and Proteus spp. (41.4% sensitive strains) to specific bacteriophages, albeit there were considerable differences between distinct Klebsiella species (Klebsiella pneumoniae, 56.7% sensitive strains; Klebsiella oxytoca, 18.3% sensitive strains, p = 0.03) and Proteus species (Proteus vulgaris, 52.0% strains; Proteus mirabilis, 35.6% strains, p = 0.04). Nevertheless, sensitivity to Staphylococcus aureus was considerably higher (78.4%). In addition, lytic activity of bacteriophages reduced along with the increasing severity of gut dysbiosis.
Conclusion. Klebsiella spp. and Proteus spp. isolated from children with dysbiosis have low sensitivity to commercially available bacteriophages. Bacteriophage sensitivity positively correlated with gut dysbiosis.

Aim. To study impact of ethylmethylhydroxypyridine succinate, an antioxidant, on the efficacy of photodynamic therapy (PDT) of kraurosis vulvae (vulvar lichen sclerosus).
Materials and Methods. The study enrolled 90 patients with kraurosis vulvae who were randomised into 3 groups receiving: 1) PDT and ethylmethylhydroxypyridine succinate 1 week after the start of the PDT for 1 month; 2) PDT without ethylmethylhydroxypyridine succinate; 3) low-level laser therapy on the perineal region. Clinical manifestations of kraurosis vulvae were dynamically assessed before the treatment and 1, 6, and 12 months post treatment. The severity of vulvar itching was evaluated using visual analogue scale. LS-A index was calculated to determine the disease activity, whilst LS-S index was applied to quantify the affected vulvar area.
Results. PDT demonstrated higher therapeutic efficacy in treatment of kraurosis vulvae than low-level laser therapy. Addition of ethylmethylhydroxypyridine succinate to the treatment protocol improved the results of PDT, as remission of vulvar itching within 12 months was achieved in 73% of patients who received PDT in conjunction with ethylmethylhydroxypyridine succinate and only in 47% of participants receiving PDT alone (p = 0.042). One month post treatment, the intensity of itching according to visual analogue scale was 2.0 points in patients who received combined treatment and 4.5 points in those receiving PDT alone (p < 0.001). Vulvar epithelialization also occurred earlier in patients receiving combined treatment (48 ± 5 days versus 54 ± 3 days in those receiving PDT alone, p < 0.001). Upon 12 months of observation, disease activity and affected vulvar area were significantly lower in patients receiving combined treatment (LS-A 4.0; LS-S 1.0) as compared to the PDT alone (LS-A 6.5; LS-S 3.0, p = 0.004 and < 0.001, respectively).
Conclusion. Addition of ethylmethylhydroxypyridine succinate to photodynamic therapy demonstrated high efficacy against kraurosis vulvae and can be recommended for its treatment.

Antibiotic resistance represents an urgent and unresolved issue due to a rapid spread of multidrug-resistance organisms (MDROs). An alternative approach is the medical use of bacteriophages which have selective and lytic activity against specific bacterial strains, in contrast to broad-spectrum antibiotics. Isolation of bacteriophages is a multi-step, tedious, and labour-intensive technique, and physiology of various bacteriophages has been vaguely studied. These drawbacks hamper the flow production of bacteriophage preparations and require a stringent quality control. Here, we review the existing literature on genetically modified bacteriophages, in particular studies which examined efficacy of such bacteriophages for the treatment of multidrug-resistant infections. Genetically modified bacteriophages showed high efficiency in patients with multidrug-resistant infections applied either as a main treatment modality or as an adjuvant therapy added to the antibiotic treatment protocols. The key advantage of genetically modified bacteriophages is broader and higher lytic activity, as they can target antibiotic resistance genes such as efflux pumps, and low immunogenicity which delays their elimination by immune cells. We propose that genetically modified bacteriophages are able to overcome the shortcomings of natural bacteriophages and can be implemented for the prevention and treatment of bacterial infections, in particular those caused by MDROs.

Acute cerebral insufficiency is a life-threatening condition defined by a loss of basic and higher nervous activity, as well as neuronal regulation of vital organs. Along with the signs and symptoms of brain damage, acute cerebral insufficiency is often accompanied by manifestations from other vital organs (i.e., respiratory, cardiovascular, gastrointestinal, urinary and immune systems as well as haemostasis), significantly complicating the disease course. Among the critical consequences following acute cerebral insufficiency are: 1) neurogenic endocrine disorders including hypopituitarism and impaired secretion of antidiuretic hormone which are notable for electrolyte imbalance; 2) healthcare-associated infections such as congestive pneumonia, ventriculitis, and pressure ulcers. In the worst-case scenario, acute cerebral insufficiency results in a multiple organ dysfunction syndrome. Here we describe epidemiology, pathophysiology, signs, symptoms, prevention, and treatment of vital organs in patients with acute cerebral insufficiency.

Despite numerous efforts of healthcare, the incidence of COVID-19 and its fatal complications remains unacceptably high. As COVID-19 pathophysiology is notable for an uncurbed immune response, its treatment protocols routinely include immunosuppressive drugs such as corticosteroids, cytostatic drugs, calcineurin inhibitors, and monoclonal antibodies. Here we review the efficacy of the latter 3 drug classes, in particular inhalation preparations, in COVID-19 treatment and SARSCoV-2 elimination as well as their potential advantages and drawbacks. Efficacy of cytostatic drugs and calcineurin inhibitors in the treatment of airway inflammation in COVID-19 remains unconfirmed. Promising agents in this regard are biologics, including monoclonal antibodies and purinergic agents.

Numerical abnormalities of karyotype are the result of genome mutations. Unlike gene and chromosomal abnormalities, genome mutations do not disrupt the structure of DNA or chromosomes. The cause of numerical changes in the karyotype is a violation of the mechanism of chromosome segregation during meiosis or mitosis. Like other mutations, genome mutations are a natural mechanism for increasing of genetic diversity in offspring. At the same time, humans usually have negative effects of any numerical deviations from the norm, for this reason, cytogenetic examination of aneuploidies is an important diagnostic tool in medical genetics.
A change in the number of sex chromosomes is usually not lethal. The spectrum of detected deviations in the carrier is from inconstant impairment of reproduction but a normal phenotype to malformations of some internal organs, infertility and severe intellectual disabilities. Aneuploidies of autosomes are always a threat to life and health. Only autosomal trisomies on chromosomes 13, 18, 21 and 22 are compatible with live birth, there are solitary reports of the birth of children with polyploidies. At the same time, the prognosis of life is relatively favorable only in the case of trisomy 21, leading to the formation of Down syndrome. Other aneuploidies usually lead to spontaneous termination of pregnancy in the early stages and are discovered in samples of abortion material.
In this regard, cytogenetic analysis of chromosomal aneuploidies is used to establish the genetic cause of anomalies and malformations in the postnatal period, delays in speech and psychomotor development, reproduction disorders in adults. Of particular importance is the cytogenetic analysis of the karyotype of embryos in the prenatal period. The proposed lecture analyzes the mechanism of formation of genomic mutations and their diversity. The possible medical consequences of the presence of various types of aneuploidies are considered. To the reader attention is offered syndromes associated with a change in the number of chromosomes in the karyotype. The description is illustrated by real images of patient karyotypes.
The lecture is aimed primarily at students of medical and biological specialties, young specialists who plan to use cytogenetic research methods in their practical activities, and doctors who are faced with the need to analyze and interpret the results of cytogenetic analysis. To assimilate the material under discussion, it is recommended to familiarize yourself with the previous lecture of the cycle.

A multimodal approach to prevent the cognitive impairment in patients with cardiovascular diseases combines the control of major cardiovascular risk factors, cognitive recovery, and physical training. Here we discuss current advances in computer-aided (also called computer-assisted) cognitive recovery to prevent the cognitive impairment in patients with cardiovascular diseases, as this approach has a number of advantages in comparison with the conventional tools. We describe a cognitive training software to stimulate perception, attention, short-term memory, executive functions, speech, and thinking. Baseline neurological examination and neuropsychological testing are mandatory before starting a cognitive recovery. A particular attention is paid to the high prevalence of cognitive impairment in cardiac surgery patients. Around half of them have pre-operative cognitive impairments, and almost half of the patients suffer from a postoperative cognitive dysfunction. Among the brain regions, prefrontal and parietal cortex and hippocampus are the most sensitive to circulatory disorders as they are supplied by the terminal branches of the cerebral arteries. Therefore, cognitive rehabilitation of cardiac surgery patients should include computer-aided cognitive training tasks activating these brain regions.