Aim. To study the analgesic effect of a new 1,4-benzodiazepine-2-one derivative (codenamed PAV-0056) in pain models in mice, its anti-inflammatory effect in experimental exudative inflammation in rats, and its potential ulcerogenic effect.

Materials and methods. A 1,4-benzodiazepine-2-one derivative (codenamed PAV-0056) was orally administered in polyvinylpyrrolidone (PVP) solution to 192 CD-1 mice weighing 20–25 g and 140 Sprague – Dawley rats weighing 250–300 g. The analgesic effect of the PAV-0056 compound at a dose of 0.01, 0.1, and 1 mg / kg was studied in murine acute thermal pain models (hot plate test, hot water immersion tail-flick test), acute chemogenic pain models (formalin test), and visceral spasticity-related pain models (acetic acid-induced writhing test). The anti-inflammatory effect of PAV-0056 at doses of 0.01, 0.1, and 1 mg / kg was studied in an experimental rat model of inflammation induced by subplantar administration of bradykinin and histamine. The potential ulcerogenic effect was studied in intact rats, who were injected with PAV-0056 at doses of 1 and 50 mg / kg four times. The analgesic effect of the PAV-0056 compound was compared to that of diclofenac sodium at a dose of 10 mg / kg and tramadol at a dose of 20 mg / kg. Its anti-inflammatory and potential ulcerogenic effects were compared to those of diclofenac sodium at a dose of 10 mg / kg.

Results. In the hot plate test, the PAV-0056 compound at a dose of 0.1 mg / kg increased response latency in mice by 36%, and at a dose of 1 mg / kg, it increased response latency by 46% (p < 0.05). In the tail-flick test, the PAV-0056 compound at a dose of 1 mg / kg increased response latency to heat stimulation in mice by 46% (p < 0.05). After subplantar administration of formalin, PAV-0056 at doses of 0.01–1 mg / kg had a pronounced analgesic effect, as shown by a decrease in the number of pain responses by 39–55% (p < 0.05). When mice were intraperitoneally injected with an acetic acid solution, the PAV-0056 compound at doses of 0.1 and 1 mg / kg reduced the frequency of writhings by 46 and 57%, respectively; at a dose of 0.1 mg / kg, it delayed the onset of the first writhing by 21% (p < 0.05). In experiments on rats, the PAV-0056 compound prevented the development of exudative inflammation induced by subplantar administration of bradykinin and did not have an anti-inflammatory effect in histamine-induced inflammation. PAV-0056 did not cause formation of gastric ulcers and gastric mucosal bleeding.

Conclusion. A 1,4-benzodiazepine-2-one derivative, PAV-0056, has a pronounced analgesic effect in models of thermal, chemogenic, somatic, and visceral pain in a wide range of doses (0.01–1 mg / kg). Its analgesic effects are the same as those of diclofenac sodium at a dose of 10 mg / kg and tramadol at a dose of 20 mg / kg. The analgesic effect of the PAV-0056 compound is selective, depends little on suppression of inflammatory exudation, and is caused by bradykinin antagonism. This substance has low toxicity and does not damage the gastric mucosa.

Aim. To study the morphofunctional state of the colonic wall in rats when using the N–terminal analog of the adrenocorticotropic hormone (ACTH) ACTH6-9-Pro-Gly-Pro (ACTH_6-9-PGP) peptide under chronic stress.

Materials and methods. The study was performed on 55 male Wistar rats, which were divided into 5 groups (n = 11): group 1 – control group (administration of saline solution without stress); group 2 – chronic restraint stress (CRS) + administration of saline solution; group 3 – CRS + administration of ACTH_6-9-PGP at a dose of 5 μg / kg; group 4 – administration of ACTH_6-9-PGP at a dose of 50 μg / kg; group 5 – administration of ACTH_6-9- PGP at a dose of 500 μg / kg. A histologic examination of the rat colon was performed. The histologic architecture of the colonic wall, the depth of crypts, and the number of goblet cells were assessed. Furthermore, the number of granulocytes, plasma cells, lymphocytes, macrophages, and mast cells was counted.

Results. The study demonstrated that chronic (14 days) restraint stress resulted in the development of inflammations in the colonic wall of the animals. Intraperitoneal administration of ACTH_6-9-PGP at doses of 50 and 500 μg / kg daily throughout the entire time of stress exposure prevented the development of stress-induced alterations observed in the control animals. At the same time, anti-inflammatory effects of the peptide in the colonic wall and a decrease in the level of corticosterone in the blood serum were noted.

Conclusion. The results of this work and data from other studies on the effects of N-terminal analogs of ACTH indicate the need for studying the mechanisms of their effect on inflammation and searching for targets of ACTH_6-9-PGP. 

Aim. To study anatomical variations of the intra–trunk pathways in the thoracodorsal nerve bundles and to develop a system for their coding.

Materials and methods. After fixation in a 2% solution of acetic acid using the MBS-10 stereomicroscope, we performed macro- and microscopic intra-trunk dissection of thoracodorsal nerve bundles in 121 specimens obtained from 105 corpses of males and females who died at the age of 40–97 years. Using the obtained findings, we compiled a database in the MS Excel 12.0 software and determined the number of anatomical variations in absolute and relative (% from 121 specimens) units.

Results. The study revealed that the thoracodorsal nerve is a mixed nerve, which consists of 1 motor and 1– 3 sensory bundles that variously pass through the spinal nerves, trunks, and the axillary nerve with the formation of 20 intra-trunk pathways. In 77% of cases, sensory bundles arising from the thoracodorsal nerve pass through the posterior bundle, the posterior division, the middle trunk, and the C7 spinal nerve or the inferior trunk and the C8 spinal nerve. In 22% of cases, the thoracodorsal nerve has one or, rarely, two duplicate sensory pathways besides the main one. In 93% of cases, the motor bundle to the thoracodorsal nerve passes through the C7 spinal nerve and the middle trunk, the posterior division, and the posterior bundle. Coding the anatomical variations of the intra-trunk pathways in the direction of sensory bundle «posterior bundle → posterior division → trunk → spinal nerve; motor bundle ← posterior bundle ← posterior division ← trunk ← spinal nerve allows to briefly yet clearly and fully display the morphological diversity of the nerve anatomy.

Conclusion. The identified anatomical variations of the intra-trunk pathways can be useful in the diagnosis of injuries and diseases. They expand indications for the use of spinal nerves, trunks of the brachial plexus, and the thoracodorsal nerve in reconstructive surgery.

Aim. To evaluate the role of heart rate variability in the pathogenesis of chronic heart failure with preserved ejection fraction (HFpEF) in patients with non-obstructive coronary artery disease (CAD).

Materials and methods. The cross-sectional study included 65 patients (55.4% were males) with non-obstructive CAD. Non-obstructive CAD (stenosis < 50%) was confirmed by coronary computed tomography angiography. Heart rate variability (HRV) was evaluated by 24-hour Holter monitoring; parameters of time series and spectral analysis were analyzed.

Results. Depending on the presence of HFpEF, the patients were divided into 2 groups: group 1 (n = 48) included patients with HFpEF, and group 2 (n = 17) encompassed patients without it. In patients with HFpEF, a statistically significant decrease in the total HRV and parasympathetic effects on the heart rate, mainly at night, as well as increased activity of cerebral ergotropic systems were revealed. In group 1, the values of the time series analysis of HRV and QT dispersion based on the study of RR interval duration (SDANN and SDNNidx) had a significant direct relationship with the level of myocardial stress in diastole, the value of vascular resistance, and the E / e’ ratio. The cut-off values of SDNNidx and pNN50 were identified, that may be used as markers for early diagnosis of HFpEF.

Conclusion. In patients with non-obstructive CAD and HFpEF, it is advisable to perform 24-hour Holter monitoring and assess HRV parameters by the time series analysis, which, compared with the spectral analysis, has a closer relationship with the characteristics of left ventricular diastolic function and afterload.

Aim. To study new molecular genetic markers of Gilbert’s syndrome (GS).

Materials and methods. It was a case – control study. The GS group included 125 people (mean age 38.5 ± 11.9 years, 58.9% were men) with unconjugated hyperbilirubinemia; known causes of unconjugated hyperbilirubinemia were excluded. The control group (n = 323, mean age 48.9 ± 11.9 years, 53.2% were men) was a random sample of individuals from the DNA bank of participants of the HAPIEE and MONICA projects. DNA was isolated by phenol – chloroform extraction from venous blood. Genotyping of groups by rs3064744, rs34993780, rs56059937, rs4148323, and rs4124874 single nucleotide polymorphisms (SNPs) in the UGT1A1 gene was performed by polymerase chain reaction followed by the polyacrylamide gel analysis according to the author’s protocols.

Results. For rs34993780 and rs56059937, no carriers of a rare allele were found in the GS group and the control group. In the GS group, two carriers of a heterozygous mutation rs4148323 were found. Statistically significant differences between the groups were found in the frequencies of rs4124874: homozygous GG was statistically significantly more common in the GS group than in the control group (odds ratio (OR) = 11.8, 95% confidence interval (CI) 6.9–20.3, p < 0.001).

Conclusion. The GG genotype of rs4124874 in the UGT1A1 gene is associated with an increased risk of GS. Carriers of the rare heterozygous mutation rs4148323 were found in the GS group.

Aim. To evaluate the viability of mononuclear cells (MNCs) in leukocyte concentrates (LCs) at the stages of their preparation, freezing, and thawing.

Materials and methods. The study material included 44 LCs from donors of allogeneic hematopoietic stem cells (HSCs) and 189 autologous LCs from patients with oncohematological disorders. LCs were obtained from donors and patients by leukocytapheresis after mobilization of HSCs. LCs from patients were frozen with dimethyl sulfoxide (DMSO) used as a cryoprotectant at a final concentration of 5% and stored in liquid nitrogen. LCs were thawed before transplantation. A total of 161 LCs were immediately transfused to the recipient after thawing, and 28 LCs were washed from DMSO before transfusion. Flow cytofluorometry was used to determine the percentage of MNC populations that excluded 7-aminoactinomycin D (7-AAD).

Results. The viability of peripheral blood MNCs in donors and patients was close to 100%. It was found that leukocytapheresis and cryopreservation with DMSO did not affect the viability of MNCs. The freezing of LCs with DMSO, storage in liquid nitrogen, and thawing resulted in a significant decrease in the content of viable MNCs (p = 0.0025), while no effect of LC storage duration on the viability of MNCs was revealed. Following DMSO removal from LCs, significantly more HSCs remained in a viable state than without washing (94.4 [94.5; 95.2] % vs. 86.7 [67.6; 92.9] %, (p = 0.0051); for other MNC populations, except monocytes, the differences in the viability index were also statistically significant.

Conclusion. The viability of MNCs in LCs is recommended to be used as an independent characteristic of the transplant quality. In obtaining LCs and mixing them with the cryoprotectant DMSO, the viability of MNCs does not decrease, while in thawed LCs, it decreases significantly. Thawing of LCs with removal of DMSO allows to achieve the best viability of HSCs and most MNC populations.

Aim. To assess the frequency, dynamics, and prognostic value of renal venous congestion using Doppler ultrasound in patients with decompensated heart failure (DHF).

Materials and methods. A prospective, single-center study included 124 patients with DHF (mean age 70 ± 12 years, 51.6% were males), left ventricular ejection fraction (LVEF) 44 [34; 55] %, N-terminal pro B-type natriuretic peptide (NT-proBNP) 1,609 [591; 2,700] pg / ml. All patients underwent a standard physical examination and laboratory and instrumental tests, including the assessment of the NT-proBNP level. Renal venous blood flow was assessed using pulsed-wave Doppler ultrasound. The presence of continuous renal blood flow was considered as the absence of venous congestion, while intermittent blood flow (two-phase and single-phase flow) indicated venous congestion. Rehospitalization for DHF and reaching a composite endpoint (rehospitalization for DHF and cardiovascular mortality) within 12 months after discharge were selected as endpoints.

Results. At admission, continuous renal venous blood flow was observed in 34 (27.4%) patients, intermittent renal venous blood flow was found in 90 (72.6%) patients: two-phase flow in 62 (50%) and single-phase flow in 28 (22.6%) patients with DHF. At discharge, 66 (53.2%) patients had intermittent renal venous blood flow: two-phase flow in 50 (40.3%) and single-phase flow in 16 (12.9%) patients. Correlations of renal venous congestion with the levels of NT-proBNP, serum iron, uric acid, creatinine, LVEF, systolic pressure in the pulmonary artery (SPPA), and the development of acute kidney injury (AKI) were revealed. Persistent renal venous congestion at discharge was significantly associated with a higher probability of rehospitalization for DHF (hazard ratio (HR) 1.93 95% confidence interval (CI) (1.017–3.67); p = 0.044) and a composite endpoint (HR 2.66, 95% CI (1.43–4.96); p = 0.002).

Conclusion. In patients with DHF, it is necessary to evaluate renal venous blood flow using pulsed-wave Doppler ultrasound to stratify patients with development of cardiovascular complications within 12 months.

Aim. To study the blood microbiome taxonomy in patients with metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO).

Materials and methods. The study included healthy donors without obesity (n = 116) and obese patients who were divided into subgroups with MHO (n = 36) and MUHO (n = 53). Bacterial DNA isolated from blood samples was subject to metagenomic sequencing of the v3–v4 variable region in the 16S rRNA gene. We compared the frequency of isolating certain taxa from the samples and the proportion of these taxa in the total pool of bacterial DNA in the blood.

Results. MUHO patients showed an increase in Lachnospiraceae, Ruminococcaceae, and Prevotellaceae, which are the main taxa in gut microbiota. This may indicate greater intestinal permeability in such patients. Obese patients, regardless of the metabolic phenotype of obesity, more often had Rhodobacteraceae, Streptomycetaceae, Leuconostocaceae, and Burkholderiaceae DNA in their blood. Nocardioidaceae, Flavobacteriaceae, Hyphomicrobiaceae, and Gaiellaceae DNA were more frequently present in the blood microbiome of patients with MHO, whereas MUHO patients more often had S24-7, Nocardiaceae, and Helicobacteraceae DNA in their blood. Many members of these families inhabit soil and water, which may indicate increased skin barrier permeability in obese patients. Additionally, a higher number of Helicobacteraceae-positive blood samples in the MUHO patient group may indicate increased translocation from the stomach.

Conclusion. Obesity is accompanied by changes in the taxonomic composition of the blood microbiome. Moreover, the nature of the changes depends on the metabolic phenotype of obesity and the permeability of external barriers.

Background. Due to diversity of cancer, the functional role of galectin-3 is rather controversial; however, for many types of neoplasms, the marker acts as a tumor growth promoter.

Aim. To perform a comparative analysis of galectin-3 levels in the blood serum of healthy individuals and patients with benign, borderline, and malignant bone tumors divided into two age groups (under and over 18 years of age) based on the main clinical and morphological characteristics of the disease and prognosis.

Materials and methods. The study included 201 patients with benign, borderline (giant cell tumors, locally aggressive tumors), and malignant bone tumors and 31 healthy donors. The galectin-3 level was determined in the blood serum before treatment with Human Galectin-3 ELISA kit (R&D, USA).

Results. The level of galectin-3 in the blood serum of patients with benign and malignant bone tumors was statistically significantly higher than that in the control group of patients both under and over 18 years. In patients with borderline bone tumors, a trend toward an increase in the galectin-3 concentration compared with the controls was revealed. The ROC analysis for galectin-3 in patients with bone sarcomas showed that the area under the curve (AUC) comprised 0.795 (р < 0.0001) in the group of patients over 18 years and 0.868 (р = 0.0008) in the individuals under 18 years. For malignant bone tumors in patients over 18 years, the sensitivity of this method was 71.3%, and specificity was 71.43% (optimal cut-off level was 8.09 ng / ml; р < 0.0001), while in patients under 18 years, the sensitivity of the method was 80%, and specificity was 90% (optimal cut-off level was 5.49 ng / ml; р < 0.001). No significant associations between the serum galectin-3 level and the clinical and morphological characteristics of bone neoplasms were found both in patients under and over 18 years of age. However, it could be noted that the highest concentration of the marker was found in chordomas and at earlier stages of the disease. In patients over 18 years with chondrosarcoma and osteosarcoma, no correlation between the marker and the disease prognosis was found.

Conclusion. An increase in the galectin-3 level in the blood serum was observed in all age groups of patients with both benign and malignant bone tumors. However, the sensitivity and specificity of the method assessed by the ROC analysis do not allow to apply this marker for the diagnosis of bone tumors.

Aim. To analyze the mRNA level of genes encoding antioxidant enzymes and the transcription factors Nrf2 and Foxo1 regulating their expression and the activity of glucose-6-phosphate dehydrogenase (G6PDH) and NADPdependent isocitrate dehydrogenase (NADP-IDH) and assess the correlation between these parameters, oxidative status, and motor coordination parameters in rats with rotenone-induced parkinsonism.

Materials and methods. The study was performed on male Wistar rats aged 4–6 months and weighing 200–250 g. Parkinsonism was modeled by subcutaneous administration of rotenone for 10 days at a dose of 2.5 mg / kg. To confirm the development of the pathology, motor coordination tests and histological staining of the cerebral cortex and striatum with hematoxylin and eosin were used. The oxidative status was analyzed based on the levels of conjugated dienes, carbonyl amino acid residues in proteins, and α-tocopherol. The enzyme activity was studied spectrophotometrically by the formation of NADPH. Real-time PCR was used to analyze the level of gene mRNA.

Results. During the study, an increase in serum and brain concentrations of conjugated dienes, carbonyl amino acid residues, and α-tocopherol was observed in the experimental group of rats compared to the controls. It could be associated with the redistribution of this compound between tissues during pathology development. The animals with experimental parkinsonism, in addition, were characterized by a decrease in the mRNA level of the Sod1, Gpx1, Gsr, Gsta2, Nfe2l2, and Foxo1 genes, as well as the activity of G6PDH and NADP-IDH. In the rats with experimental parkinsonism, a negative correlation of NADPH-IDH activity in the brain with serum α-tocopherol level and a positive correlation with Gpx1 and Foxo1 mRNA levels in the striatum were found. The level of oxidatively modified proteins in the brain of the animals with PD was negatively correlated with the concentration of Gsta2 mRNA in the striatum, while the specific activity of G6PDH in the serum was characterized by the positive relationship with grip strength.

Conclusion. The data obtained indicate that the inhibition of transcription of the genes encoding antioxidant enzymes and regulatory factors Nrf2 and Foxo1 contributed significantly to the development of oxidative stress in PD. A decrease in the activity of G6PDH and NADP-IDH led to a decrease in the availability of NADPH, which is a limiting factor in the functioning of the glutathione antioxidant system. Obviously, the inhibition of G6PDH and NADP-IDH was also an important pathogenic factor in the progression of the pathology. Along with a decrease in the content of antioxidant gene mRNA in the brain tissues, the level of α-tocopherol increased in the rats with parkinsonism, which could be the result of an imbalance in the functioning of antioxidant system.

Aim. To study the comparative dynamics of left ventricular (LV) remodeling after on-pump and off-pump coronary artery bypass grafting.

Materials and methods. The study included 129 patients with verified coronary artery disease (CAD) who underwent coronary artery bypass grafting (CABG) with cardiopulmonary bypass (on-pump CABF) or beating heart surgery (off-pump CABG). All patients underwent transthoracic echocardiography (TTE) and volumetric compression oscillometry (VCO) before surgery, as well as one week and four months after it. The results were compared in groups divided according to the surgical technique and the presence of previous myocardial infarction using variation series, the Tukey’s post-hoc test, the Pearson correlation coefficient, and the Spearman’s rank correlation coefficient.

Results. According to TTE data, no difference in hemodynamic parameters between the groups in the postoperative period was noted. According to VCO data, a significant difference was revealed in the off-pump group without previous MI one week after surgery: an increase in cardiac output (CO) (p < 0.001), an increase in stroke volume (SV) and stroke index (SI) (p = 0.005), LV power (LVP) (p = 0.015), and also a rise in cardiac index and LVP four months after the surgery. In the on-pump group of patients with previous MI a week after CABG, a decrease in the LVP (p < 0.001) and dynamic changes of energy expenditure (p < 0.001) were observed. The correlation analysis revealed moderate correlations between the inotropic parameters of cardiac hemodynamics SV, SI, CO, LVP and blood pressure (BP) (rπ = 0.33–0.47; p < 0.001) and strong correlations between SV, SI, CO, LVP and ejection fraction (EF) (rπ = 0.63–0.68; p < 0.001).

Conclusion. Seven days after the off-pump CABG, an improvement in some hemodynamic parameters and all inotropic parameters of the heart was revealed compared with the on-pump group. Four months after the off-pump surgery, positive hemodynamic remodeling was observed compared with the postoperative period after the onpump CABG.

Background. Childhood obesity is one of the pressing problems in modern healthcare, since it is associated with a high risk of non-communicable diseases, such as bronchial asthma (BA). The aim. To determine the features of cytokine profiles in children with and without BA, depending on body weight and visceral fat area.

Materials and methods. At the first stage, 506 Tomsk schoolchildren underwent anthropometry with the calculation of the body mass index (BMI) and measurement of the visceral fat area (VFA) using the InBody 770 analyzer. Fiftyone (51) children from the first stage were included in the second clinical and diagnostic stage. The children were divided into four clinical groups: “Obesity” (n = 17), “Visceral Obesity” (n = 7), “Asthma” (n = 15), and “Healthy Children” (n = 12). In all study participants, the levels of interleukin (IL)-6, IL-8, IL-4, IL-10, and immunoglobulin (Ig) E in the blood serum were determined by the multiplex assay (MagPix and Luminex 200 c analyzers). Statistical data analysis was carried out using the Statistica 10.0 software package and the 4.2.2 version of R.

Results. The levels of IL-10 in the “Asthma” (p < 0.006) and “Obesity” (p < 0.008) groups were significantly higher than in the “Visceral Obesity” group. Significantly higher levels of IL-8 were found in patients with asthma (p < 0.003) and obesity (p < 0.003) compared to the “Visceral Obesity” group. Higher concentrations of IL-6 were found in the “Asthma” (p < 0.001) and “Obesity” (p < 0.028) groups compared to the “Visceral Obesity” group.

Conclusion. Similar upward changes in IL-6, IL-8, and IL-10 in children with asthma and obesity without a history of asthma may explain the contribution of obesity to a risk of asthma in children, possibly through excessive production of these proinflammatory cytokines that contribute to the implementation of Th2-mediated allergic inflammation.

Aim. To develop a computer program to determine the probability of colorectal cancer based on the assessment of the levels of CTLA-4 and its ligand B7.2.

Materials and methods. The study included 44 patients with colorectal cancer (CRC) and 25 patients with benign tumors of the colon. The control group consisted of 25 individuals who had been operated for colon injury. We determined the levels of CTLA-4 and B7.2 in the blood serum and in the supernatants of tumor tissue and lymph node homogenates using flow cytofluorometry.

Results. We found that the level of CTLA-4 in the blood serum increased by 2.77 times in CRC patients compared to the control group (p < 0.001). The concentration of CTLA-4 in the tumor tissue in patients with CRC was 2.34 times higher than in the control group (p = 0.007). The concentration of the B7.2 ligand in the blood serum of patients with CRC exceeded this parameter in the control group by 2.51 times (p = 0.002). The concentration of B7.2 in the tumor tissue of CRC patients was 1.68 times higher (p = 0.004) than in the control group. The analysis of the obtained data determined the parameters that have prognostic value in the structure of the diagnostic model. Using these parameters, we developed a computer program to determine the probability of CRC in the patient.

Conclusion. The data obtained demonstrate an increase in the levels of CTLA-4 and its ligand B7.2 in the serum and tumor tissue of patients with CRC.

The review considers the molecular structure of inflammasomes, routes of inflammasome activation, appropriate downstream effects, and their association with autoinflammatory, autoimmune, neurodegenerative, and allergic diseases and malignancies with a focus on the involvement of the skin in these pathologies. Inflammasome activation is interpreted as an early pathophysiological event before the onset of inflammation, and, especially, if inflammasome dysregulation occurs. All research aspects related to the NLRP3 inflammasome are described in detail. The review also considers promising directions for therapeutic interventions in NLRP3-associated diseases.

Ovarian cancer is considered to be the most malignant and aggressive tumor of the female reproductive system, which is largely associated with early development of malignant ascites and peritoneal carcinomatosis. Cancer cells representing the primary focus, as well as those contained in the ascitic fluid, are extremely heterogeneous in terms of morphological, immunohistochemical, and molecular genetic aspects. Cancer stem cells play a significant role in tumor self-renewal, differentiation, metastasis, and development of chemoresistance.

This literature review is aimed at summarizing the available data on cancer stem cells in ovarian cancer and their role in tumor progression. A bioinformatic search was carried out in the PubMed, NCBI, Google Scholar, and eLibrary databases using the keywords “cancer stem cells”, “ovarian cancer”, “malignant ascites”, “chemoresistance”, etc.

The data presented in the review make it possible to comprehensively characterize the role of stem cell properties of ovarian cancer cells. The review presents up-to-date information on the molecular and biological parameters of cancer stem cells in ovarian cancer, which are the cellular component of malignant ascites, as well as data from the authors’ studies. Along with this, the article describes modern ideas about the mechanisms of formation of cellular spheroids and their contribution to cancer progression.

Cancer stem cells are an extremely promising target in the development of future therapeutic strategies based on the study of signaling pathways in ovarian cancer stem cells, the mechanisms of spheroid formation, and the contribution of immune cells to the acquisition of cancer stem cell properties. 

The aim of the review is to highlight the main factors affecting the development of liver fibrosis and possible mechanisms of liver damage in patients who have experienced COVID-19. A search was carried out using keywords in the Scopus, Web of Science, and PubMed databases in literary sources of the last three years on factors associated with fibrogenesis in novel coronavirus infection.

The review presents the main mechanisms of liver damage in COVID-19: direct effects on hepatocytes and cholangiocytes, hypoxia, and immune-mediated and drug-induced damage. We analyzed the significance of factors affecting fibrosis development in patients with COVID-19: chronic diffuse liver diseases, against which COVID-19 occurs, such as non-alcoholic fatty liver disease, alcohol-associated liver disease, chronic hepatitis B, C, and cirrhosis of the liver.

Damage to the liver in coronavirus infection develops by several mechanisms. The development of COVID-19 against the background of diffuse liver pathology of various genesis is associated with progression of these diseases (increased fibrogenesis) and a poorer prognosis.

The article discusses modern ideas about cervical carcinogenesis as a multi-stage process of multifactorial genesis. Currently, ideas about the pathogenesis of cervical cancer (CC) are based not only on understanding the role of high-risk oncogenic human papillomavirus (HPV) in this process and accumulation of genetic changes caused by it, but also on formation of a complex HPV interactome, or a network of intermolecular interactions of HPV oncoproteins with host cell proteins. Carcinogenesis also involves a wide range of epigenetic events and, above all, impairment of the regulatory function of miRNAs. An important role in cervical carcinogenesis is attributed to the concept of cancer stem cells (CSCs) formulated in recent years, which is closely related to the explanation of disease recurrence and treatment resistance, as well as to new approaches to treatment. The cervicovaginal microbiome and cervical microenvironment, which are responsible for natural clearance of HPV, regression of epithelial lesions, and modeling of the immune response, are becoming promising objects for research.

The aim of the review was to present up-to-date information on the most important mechanisms of cervical carcinogenesis, as well as on new approaches to the treatment of CC, based, in particular, on the use of knowledge about regulatory miRNAs, CSC markers, and the state of the cervicovaginal microbiota.

In recent years, there has been an increase in the number of women undergoing coronary artery bypass grafting (CABG). Although the evidence of gender effects on outcomes is controversial, a number of publications have reported less favorable outcomes of CABG in women. The aim of this paper was to review the literature regarding factors that worsen short- and long-term prognosis in women undergoing surgical myocardial revascularization.

Gender differences in early outcomes of CABG are largely explained by gender distribution of baseline clinical characteristics. Women, compared to men, undergo CABG at an older age and have a worse profile of cardiovascular disease (CVD) risk factors (RF), comorbidity burden, structural and functional cardiac pathology, and coronary lesions. In women, complete myocardial revascularization is less frequent than in men, venous shunts are used more frequently, and the left internal mammary artery is less frequently used as a conduit. In addition to the baseline characteristics, higher incidence of perioperative myocardial infarction (MI), higher prevalence of anxiety and depression, lower quality of life and social adaptation after CABG, and lower involvement of women in rehabilitation programs, compared to men, may contribute to a less favorable long-term prognosis after CABG in women.

There is a need for more information for physicians about the specifics of CVDs and anatomical and surgical aspects of CABG in women. It is also necessary to raise patients’ awareness of RF correction and to involve them in educational technologies. Recommendations for diagnosis and treatment of CVDs should be developed taking into account gender. Further research is also required to develop and implement sex-specific models for predicting surgical risks. Long-term follow-up is appropriate in women with recent MI and a history of diabetes mellitus. To further improve clinical outcomes of CABG in women, development of approaches that facilitate more complete revascularization and reduce the incidence of perioperative complications, such as MI and pneumonia, is needed. More answers to questions regarding gender differences in long-term outcomes of CABG may be obtained by analyzing further studies involving a larger number of female patients.

An anomalous course of coronary arteries is fairly rare pathology, which, however, may underlie clinical manifestations of coronary artery disease. Expanding the possibilities of diagnostic coronary angiography makes it possible to detect numerous types of congenital anomalies of the coronary arteries.

However, if earlier they were considered as angiographic findings and were characterized as benign, now this attitude has been changed due to reports of cases of syncope, angina pectoris, and sudden cardiac death associated with their presence. In this regard, a trend emerged to consider such anomalies as “potentially malignant”, which explains special caution at their detection. The article presents a clinical case of an anomalous retroaortic course of the circumflex artery from the right coronary artery.

The article presents a clinical case of a rare autoinflammatory disease – a family case of Muckle – Wells syndrome. The diversity of clinical manifestations and the impossibility of confirming the diagnosis without a genetic study by DNA sequencing determine the complexity of and delay in the diagnosis. The development of severe complications and, as a consequence, a fatal outcome necessitates early diagnosis. The described clinical case demonstrates the importance of DNA sequencing for the timely diagnosis of the disease, the features of the disease course, and the familial nature of the disease. The diagnosis of Mackle – Wells syndrome in young family members before the development of severe complications will allow to start adequate and timely treatment and prevent the development of amyloidosis.

Migrainous stroke is a rare combination of frequently occurring diseases; only a few cases have been described in the domestic literature. The complexity of differential diagnosis is due to the fact that at the stage of initial manifestations, these two conditions can mimic each other. Treatment strategy and further prevention for each of these diseases is different, so timely and convincing early diagnosis is crucial. The presented clinical case describes a case of ischemic stroke in a young woman who had been suffering from migraine for a long time, which did not fully meet the criteria for migrainous infarction. The patient was treated at the regional vascular center of the Tomsk Regional Clinical Hospital, there was a positive trend in the neurological status. The catamnesis of the disease was tracked. It was suggested that endothelial dysfunction is the main pathogenetic factor in the formation of an ischemic focus against the background of a protracted migraine attack.

The global digitalization has become one of the most significant challenges in the field of medicine and healthcare. The rapid development of digital technologies determines the growing demand for constant access to big data in real time Their use is in need for research and technological projects in the sphere of artificial intelligence technologies development. Siberian State Medical University developed the first Russian-language repository of clinical data “SibMed Data Clinical Repository” (https://dataset.ssmu.ru/). The article describes the structure, functions of the repository, and perspectives of its use.