Purpose of the study. An analysis of the changes in components of the urokinase system in the brain of urokinase gene-knockout mice (uPA-/-) with B16/F10 melanoma growing alone and together with chronic neurogenic pain (CNP).

Materials and methods. The study included male and female C57BL/6-PlautmI.IBug-ThisPlau6FDhu/GFDhu mice (uPA-/-) (n = 48) and C57BL/6 mice (uPA+/+) (n = 80) with transplanted B16/F10 melanoma growing solitarily and together with CNP. Levels of the urokinase receptor (uPAR) and plasmin (PAP) and activity and levels of the PAI-I inhibitor were measured in the brain of animals by ELISA.

Results. Levels of uPAR, PAI-I and PAP in the brain differed only in intact uPA-/- males, being on average 1.6 times higher (p < 0.05) than in uPA+/+ mice. Among animals with CNP, uPA-/- males showed increased PAI-I by 1.3 times (p < 0.05) and decreased PAP by 2.6 times (p < 0.05), while in uPA+/+ males, changes in PAI-I and PAP were opposite; in uPA-/- females, levels of all indicators increased by 1.6–2.1 times (p < 0.05), unlike uPA+/+ females. Among animals with melanoma only, changes in the levels of uPAR, PAI-I and PAP in the brain tissues in uPA-/- males differed from the group with CNP and from uPA+/+ males; in uPA+/+ females, levels of uPAR and PAP increased by 1.7 and 3.0 times (p < 0.05), and only PAP increased in uPA-/- females by 3.2 times (p < 0.05). Combination of CNP with melanoma in uPA-/- mice, regardless of their gender, down-regulated levels of uPAR and PAI-I on the average by 1.5 and 2.0 times, respectively (p < 0.05), and up-regulated PAP on the average by 2.2 times (p < 0.05) compared to the levels in animals with CNP; in uPA+/+ animals, similar decline of uPAR by 3.7 times (p < 0.05) was registered only in males, and an increase of PAI-I by 2.0 times (p < 0.05) was noted in all mice.

Conclusion. Changes in the studied parameters in the brain tissue of urokinase gene-knockout animals in response to stress factors indicate the role of the brain urokinase system in the response to both CNP and melanoma growth, and the gender specificity of these changes may be another factor that conditions gender differences in the risk of occurrence and course of cutaneous melanoma.

Purpose of the study. Analysis of the effect of DM on levels of sex hormones and their receptors in tumor and perifocal tissues in outbred white female rats.

Materials and methods. Outbred white female rats were divided into 2 groups, 18 rats each: control group – with transplantable Guerin’s carcinoma, main group – with transplantable Guerin’s carcinoma growing in presence of DM. DM was reproduces in animals by the single intraperitoneal alloxan injection (150 mg/kg body weight). Animals were killed after 10 days of the tumor growth. Levels of hormones (estradiol, testosterone, progesterone and prolactin) and their receptors (RЕα, RЕβ, RA and RP4) were measured by ELISA in tumor and perifocal tissues in animals of the control and main groups.

Results. Female rats with Guerin’s carcinoma growing in presence of DM showed an increase in glucose in tumor and perifocal tissues by 1.8 times (р < 0.05) and 7.6 times, respectively, compared to the levels in the control group. Levels of E2 were increased, respectively, by 2.4 and 9.5 times; P4 – by 2.1 and 3.0 times; PRL – by 2.7 and 4.4 times. T was increased in perifocal tissues by 2.2 times and was unchanged in tumor tissues. RЕα and RP4 were elevated by 3.9 and 3.0 times, respectively, only in tumor tissues, and RA by 3.9 times only in perifocal tissues. The REα/RЕβ ratio was increased only in the tumor by 3.2 times. The Е2/RЕβ ratio was increased in tumor and perifocal tissues by 2.0 and 9.6 times, respectively. The T/RA ratio was decreased in the tumor and its perifocal area by 1.4 (р < 0.05) and 2.0 times, respectively. The opposite changes were observed in the Е2/RЕα and P4/RP4 ratios: a decrease in the tumor by 1.6 and 1.4 times, respectively (р < 0.05), and an increase in the perifocal area by 9.8 and 2.5 times, respectively.

Conclusion. Female rats with Guerin’s carcinoma growing in presence of DM demonstrated local hyperglycemia, changes in the levels of sex steroids and a misbalance in their receptors in tumor and perifocal tissues causing active metastasis and reduced average survival of animals.

Purpose of the study. Was to analyze antitumor efficacy of the XAV 939 Wnt signaling pathway inhibitor and its combination with 5 fluorouracil in subcutaneous xenografts derived from patients with colorectal cancer.

Materials and methods. Antitumor efficacy of the agents and their combination was studied in xenografts derived from patients with colorectal cancer and subcutaneously implanted in immunodeficient Balb/c Nude mice. All animals with tumors were divided into 4 groups (n = 5): group 1 received 5 fluorouracil 25 mg/kg, group 2 – XAV 939 25 mg/kg, group 3–5 fluorouracil and XAV 939 combination at the same dosages, group 4 was control. Criteria for the efficacy of the tested agents and their combination included tumor growth rate and tumor growth inhibition rate (TGI %).

Results. The mean volumes of xenografts and tumor growth rate in the group receiving a combination of 5 fluorouracil and XAV 939 were 335.2 ± 40.7 mm3 , being lower than the averages of xenografts in controls – 609.3 ± 69.5 mm3 (p < 0.05). The mean volumes of xenografts in the group receiving 5 fluorouracil monotherapy were 601.9 ± 45.5 mm3 , in the group with the XAV 939 monotherapy – 527.9 ± 258.6 mm3 . The highest TGI (44.99 %) was registered in the group receiving a combination of 5 fluorouracil and XAV 939.

Conclusion. The study revealed the ability of combined XAV 939 Wnt signaling pathway inhibitor and 5 fluorouracil to inhibit the growth of subcutaneous xenografts derived from patients with colorectal cancer.

Purpose of the study. Investigation of morphological characteristics of changes in the epithelium of foregut in experimental animals put under conditions of provoked carcinogenesis.

Materials and methods. The method of chronic experiment on animals is applied: 40 female non-linear white rats, which are divided into 4 equal groups (n = 10). The first (I) and second (II) control groups of animals were exposed to mechanical trauma of the oral mucosa with additional application of 0.9 % NaCl solution and 1 % aqueous dimethyl sulfoxide (DMSO) solution with a frequency of 2 times a week. The third group of animals, i.e. the main group (4-NQO), was subjected to mechanical traumatization of the oral mucosa with additional application of 1 % DMSO aqueous solution containing 0.1 mg/ml of 4 nitroquinoline-N-oxide, with a frequency of 2 times a week. The fourth group of animals was intact. On the 1st, 7th, 10th, 14th day from the beginning of the experiment, and then every 14 days, cytological material was taken from the oral mucosa and stained with Papanicolaou stain. To compare the emerging changes, the histological picture of the organs of the foregut was studied.

Results. Animals from the main group (4-NQO) showed a lag in body weight gain over the standard variance in the control (I and II) and intact groups. Atypical cells of indeterminate significance appeared in smears starting from 42 days of the experiment. Starting from the 56th day of the experiment, atypical cells (1–2 in the field of view), described in Bethesda terms as low-grade intraepithelial lesions, were detected in smears obtained from the main group of animals (4-NQO). Parabasal cells of the squamous epithelium with atypical large (more than 3 times compared to the reference) nuclei, anisonucleosis, with variable contours of the nuclear membrane within one cell, coarse chromatin were recognized as diagnostically significant.

Conclusion. The severity of morphological changes in foregut epithelium in the direction of the precancerous state is significantly higher in the main group with prolonged exposure to carcinogenic factor, compared with the control and intact groups (р < 0.05). Thus, the effectiveness of modeling the conditions of provocation of carcinogenesis of the epithelium of the upper digestive tube in experimental animals was studied and proved by mechanical traumatization of the oral mucosa with additional application of carcinogen (4-NQO). This model of provocation of carcinogenesis will be used in the next study of neoplastic processes of the female reproductive system.

Purpose of the study. This work is devoted to the study of blood plasma miRNA patterns in blood plasma using high-throughput sequencing of the Omnibus Gene Expression base and the search for candidate miRNA molecules for the development of a minimally invasive diagnostic panel.

Materials and methods. Basing on the open dataset of Omnibus Expression of the NCBI GSE150956 Gene, groups of samples with glioblastoma and conventionally healthy donors were formed. For each sample, information on the levels of miRNA expression was extracted. Determination of significant miRNAs using machine learning algorithms of the R 4.0.4 project. For significant miRNAs, target genes have been performed, an analysis of the improvement of functional characteristics and interactome analysis of target genes of miRNA were performed.

Results. The study analyzed the data of 131 samples, where 35 samples with glioblastoma and 96 samples of the conditionally healthy group. Differential expression data were obtained for 945 miRNA. Two panels were obtained using machine learning methods, common miRNA – hsa-miR 3180, hsa-miR 3180-3p, hsa-miR 6782-5p, hsa-miR 182-5p, hsa-miR 133b and hsa-miR 670-3p. For significant miRNAs, information was obtained on experimentally confirmed target genes, a gene ontology demonstrating their participation in enzyme binding, participation in the regulation of primary cellular metabolic processes, and the development of glioblastomas and cancer in general.

Conclusion. As a result of layer-by-layer filtering and application of machine learning algorithms, significant miRNAs were identified that are candidates for a diagnostic panel of a minimally invasive method of high-grade glial tumors.

Purpose of the study. To find out the abilities of multispiral computed tomography (MSCT) using intravenous bolus injection in detecting and preoperative esophago-gastric junction cancer staging in order to improve preoperative diagnosis of this pathological condition.

Materials and methods. The patients, diagnosed esophago-gastric junction cancer (n1 = 76), esophagus (n2 = 27) and medically fit people’s (n3 = 30) findings of investigating have been analyzed. All patients went through computed tomography on Light Speed VEX Plus and Light Speed RT 16 ("GE", The USA). The findings of MSCT have been compared with anatomical data, which were got after histomorphologic study of post-operation and endoscopic recruitment material.

Results. Characteristic MSCT signs of the wall of the esophageal-gastric junction (EGJ) were revealed in healthy individuals, with esophagitis and cancer. The thickness of esophagus paries in normal conditions and in case of esophagitis and EGJ cancer is: 5.4 ± 1.01 mm, 10.36 ± 1.85 mm, 22.53 ± 8.19 mm (p < 0.001). The external diameter of the abdominal part of esophagus in the normal condition is 14.2 ± 1.68 mm, in case of esophagitis is 17.96 ± 3.7 mm, EGJ cancer is 27.9 ± 9.48 mm (p < 0.001). The main statistically significant (p < 0.001) qualitative character of esophago-gastric junction canser were: non-visualization of mucic in afflicted areas (96.8 %), bosselated upper and lower contours of narrowing (75.2 %), dissymmetric parries pachymenia (70.4 %), blunt-edged outer contours (58.4 %), cotyloid suprastenotic esophageal distensibility (45.6 %). The delicacy depended on the degree of damage delicacy and was at the stage Т1 – 66.7 %, Т2 – 76.5 %, Т3 – 77.8 %, Т4а – 86.2 %, Т4b –100.0 %, in general, diagnostic accuracy of the method in EGJ cancer Т-staging was 81.6 %.

Conclusion. The results of the work showed that the inclusion of MSCT with intravenous bolus contrast in the algorithm of the study of patients with suspected tumor pathology of the EGJ will improve the diagnosis of cancer of the EGJ.

Purpose of the study. Analysis of the effectiveness of cryoprecipitate – antienzymatic with common soft tissue phlegmon and sepsis.

Patients and methods. To achieve the intended goal, a study of the results of treatment of 92 patients with a diagnosis of advanced soft tissue phlegmon and sepsis was performed. All patients underwent a comprehensive diagnostic study with an in-depth study of the indicators of the hemostasis system. For a comparative assessment, 2 groups of patients were identified. Group 1 (46 (50 %) patients – the main one) – received cryoprecipitate-antienzymatic therapy as part of complex treatment, group 2 (46 (50 %) patients – comparisons) – received only the generally accepted basic treatment.

Results. An in-depth study of the hemostasis system in patients with widespread soft tissue phlegmon and sepsis indicated the development of thrombohemorrhagic syndrome, which was manifested by depletion of both the coagulation and anticoagulation systems of the blood, a drop in AT III, an increase in thrombinemia and fibrinolysis depression. In order to correct thrombohemorrhagic syndrome, a cryoprecipitate-antienzymatic complex was included in the complex treatment of patients with widespread soft tissue phlegmons and sepsis, aimed at unblocking microcirculation in inflammatory foci and parenchymal organs, to improve the penetration of antibacterial drugs and other drugs into these foci, thereby stopping inflammation and preventing the increase of multiple organ failure. The effectiveness of the cryoprecipitate-antienzymatic complex was evaluated based on clinical data of the course of the purulent – inflammatory process and the results of indicators of the hemocoagulation and fibrinolysis system on 8–10 days from the start of therapy.

Conclusion. The use of cryoprecipitate-antienzymatic complex, which includes freshly frozen plasma (FFP), heparin, proteinase inhibitors, in patients with widespread soft tissue phlegmon and sepsis effectively eliminates thrombohemorrhagic syndrome, which improves microcirculation in purulent – inflammatory foci and affected parenchymal organs, improving the flow of antibacterial drugs into these foci. At the same time, there is an improvement in the course of the wound process, so the wounds are cleaned faster from necrotic masses and filled with healthy granulation tissue, which makes it possible to perform plastic closure of the wound defect 1.6 times faster. Mortality is reduced by 2.2 times and the number of thrombotic and thromboembolic complications in the structure of deaths is reduced.

Purpose of the study. was to improve the technology of prosthetic repair of the anterior abdominal wall patients with hernias by means of pharmacological regulation of the local and systemic inflammatory response and stimulation of reparative regeneration.

Materials and methods. The study was carried out on 52 pure line rats in vivarium. All animals have on-lay implantation of a polypropylene mesh imlantant. Group I have no specific pharmacological treatment receive (0.9 % sodium chloride solution); group II – receive solution of xymedon, group III – potassium orotate, group IV – methyluracil.

Results. Identified that all investigated drugs of the pyrimidine series (xymedon, potassium orotate, methyluracil) have a significant effect on the local and systemic inflammatory process. The growth of IL 10 and TNF-a are associated with an increase in the area of liquid inclusions. The use of potassium orotate and methyluracil in the postoperative period is inappropriate, as it is associated with an increased risk of hemorrhage and acute paraprosthetic fluid accumulations. Taking xymedon after surgery is associated with an accelerated growth of blood vessels and granulation tissue, a decrease in fluid inclusions, but is associated with an insignificant increase in the risk of tissue hemorrhage.

Conclusion. Pharmacological regulation of inflammatory and regenerative processes with xymedon in the perioperative period of prosthetic repair could guide the development of surgical treatment of patients with abdominal hernias, which requires further clinical study.

More than 1.8 million of new cases of lung cancer (LC) are registered each year worldwide. LC is the leading cause of cancer death in both developing and developed countries, and the 5 years survival rate is as low as 19 %. Many factors explain such unsatisfactory outcomes, including the LC diagnosis at an advanced stage, when the currently available treatments can rarely provide cure. Biomarkers are used to assess the development risks, screening, diagnosis, monitoring, and prognosis, and to personalize the LC treatment. Clinical use of biomarkers is essential for the identification of a high-risk group for screening for LC and differentiating early LC from benign pulmonary lesions. Current trends in the development of LC biomarkers involve the integration of molecular biomarkers with clinical and radiological characteristics using artificial intelligence for the development of imaging biomarkers, and using highly sensitive technologies such as next-generation sequencing for molecular research. LC biomarkers are now at all stages of development, from discovery to clinical trials requiring high-quality clinical validation. Reliable biomarkers are especially needed to differentiate malignant and benign lesions in the lung tissue and to identify those at greatest risk of developing lung cancer. Scientific advances in understanding LC have led to the development of biomarkers that demonstrate sufficient accuracy in clinical validation studies. Promising trends in the development of LC biomarkers include highly sensitive and increasingly accessible NGS and radiomics technologies, along with the use of easily collected biomaterials, which in combination with other tumor characteristics contribute to the development of biomarkers for assessing the LC development risks, diagnosis, monitoring, prognosis and personalized therapy. This review focuses on the development, current application, and future trends in the use of LC biomarkers.

The proportion of men with impaired sperm fertility is increasing every year, which is one of the factors in the decline in fertility and is becoming both a medical and social problem. Modern diagnostic methods make it possible to recognize many factors of male infertility: genetic, endocrine, infectious, extra-genital, etc. However, despite all modern biomedical advances, 1/3 of patients remain with an unrecognized cause (idiopathic) of male infertility. At the same time, we must not forget that most patients from this category do not want to resort to assisted reproductive technologies to realize paternity, and they strive to achieve pregnancy in a natural way. Therefore, the search for the causes of male infertility remains an urgent issue in modern urology field. This article reviews the literature on the role of mast cells in the formation of fibrosis in tissues, including the testis. Mast cells affect the proliferation, functioning and phenotype of fibroblasts put under hypoxic conditions. Fibroblast activation enhances collagen fibrillogenesis. Studies by Russian and foreign scientists have shown that with sperm pathology, the number of mast cells in the connective tissue of the testicle increases sharply. Against the background of an increase in the number of mast cells in the interstitium of the testis, fibrosis of the wall of the convoluted seminiferous tubules increases. Moreover, in severe spermatogenesis disorders (Sertoli cell-only syndrome, Germ cell aplasia), mast cells were found both in the peritubular space and in the lumen of the convoluted seminiferous tubules. Most infertile men have significant amounts of significant amounts of mast cells in their ejaculate. There are sporadic data on the negative correlation between the presence of mast cells in seminal plasma and the concentration and motility of spermatozoa. Conclusion. The negative effect of mast cells on spermatogenesis remains unknown to the end. Mast cells have a high ability to migrate to connective tissue, which levels increase during inflammation, and the production of many mediators, proteases and histamine, cytokines, which can be both a trigger in the formation of sperm pathology and the cause of the formation of fibrosis in the testicle.

Inflammatory myofibroblastic tumors (inflammatory myofibroblastic tumors) IMT in the clinical practice of an oncologist are very rare diagnostic findings. Currently, the bulk of scientific publications about IMT are devoted to reviews of clinical cases. If initially IMT were considered as pseudo-tumors, now they are classified as intermediate fibroblastic/myofibroblastic tumors according to the WHO histological classification. Management of patients with hepatic IMT are debatable today. Hepatic IMT are mostly benign lesions and characterized by spontaneous regression without any treatment. However, sometimes therapeutic and surgical treatment of these lesions is necessary. Many authors recommend surgical treatment, as with conservative treatment, some patients develop relapses. This rare observation demonstrates our experience of liver resection for inflammatory myofibroblastic liver tumor in 76 year-old patient.

Purpose of the study. To describe the theoretical foundations and practical application of design thinking technology in the activities of a medical organization as a tool for managing interaction with patients to improve the provision of medical care for cardiovascular diseases.

Materials and methods. The work was carried out on the basis of the Research Institute for Complex Issues of Cardiovascular Diseases (Kemerovo). When using methods of sociological research (questioning, content analysis). In the period from 2015 to 2020, 43865 patients were treated at the institution, of which 16886 were questioned. The analysis of domestic and foreign literature, as well as regulatory documents was carried out for the period from 2015 to 2020 using the keywords: "design thinking", "Service design", "design thinking in medicine."

Results. The possibility of adapting the technology of design thinking to medical and diagnostic activities in research institutes, namely to the process of assessing patient satisfaction, is shown. Due to the presence of an effective mechanism for managing interaction with patients, in the research institute in the period from 2011 to 2020, there was a decrease in justified complaints (more than 2 times), and the level of patient satisfaction reaches target values.

Conclusion. Design Thinking is part of the patient management process as an initial step in assessing patient satisfaction. The described technology can be used by any medical organization.