The data on the protective properties of the Prunella grandiflora L. extract were obtained when used together with the anticancer drug etoposide on the experimental strain of Drosophila melanogaster. The combined use of etoposide and 10% extract of P. grandiflora decreased mortality in D.  melanogaster individuals to 15% and doubled the average individual fertility compared to the use of this cytostatic drug without the extract. Using the SMART method, the presence of the antigenotoxic effect was identified,  which manifests itself through the absence of chromosomal aberrations. 

 Aim. To summarize the experience of organizing and evaluating the efficiency of the Medical Center for Remote Monitoring of patients with COVID-19 and community-acquired pneumonia in Tomsk.

Materials and methods. The project of the Medical Center for Remote Monitoring was developed on the basis of data from theoretical and empirical analyses of the current state of the healthcare system in the Tomsk region and the epidemiological situation with regard to COVID-19. The Center efficiency was assessed based on the analysis of quantitative and time indicators of the load on the emergency medical service and outpatient service. Statistical processing of the results was carried out using the Statistica 12.0 software package.

Results. On October 20, 2020, in Tomsk, on the premises of the “Emergency medical unit”, a Medical Center for Remote Monitoring was established. It was aimed at providing remote consultations for patients with COVID-19 and community-acquired pneumonia. According to its algorithm, operators  of the Center assessed a patient’s condition on a point scale using standardized speech modules to make a decision on the tactics of their support. During the second wave of COVID-19, when the Center operated, a statistically significant decrease in the load on the ambulance service (average number of calls per day, average waiting time for all calls and  coronavirusrelated calls) as well as on the outpatient service (average  number of house calls per day, including calls for acute respiratory diseases) was registered.

Conclusion. The work of the Medical Center for Remote Monitoring based on the described model is associated with a decrease in the load on the healthcare system in an unfavorable epidemiological situation due to high COVID-19 incidence. This experience can be spread to other regions of  Russia and adapted for other categories of citizens. 

 Aim. To identify the relationships between structural proteins of myocytes, as well as indicators of antioxidant defense and metabolites of glycolysis against the background of using statins in animals in the experiment for clarifying the diagnosis of statin-associated myopathy.

Materials and methods. The study was conducted on outbred male rats, which were divided into 3 groups. The control group consisted of intact animals, and there were two experimental groups: group 1 – animals with induced hypercholesterolemia, group 2 – animals with induced  hypercholesterolemia treated with simvastatin. In the muscles of animals from the studied groups, the content of structural proteins of the sarcomere, titin and nebulin, was analyzed, and the concentration of glycolysis metabolites (pyruvic acid and lactate) and the activity of antioxidant defense enzymes (superoxide dismutase (SOD) and catalase) were determined.

Results and discussion. The use of simvastatin in the animals led to a  decrease in the content of NT- and N2Atitin isoforms and an increase in the  content of the T2-proteolytic fragment. Complete absence of nebulin was also noted, which reflects the presence of dystrophic changes in the muscle  tissue. Long-term administration of simvastatin caused metabolic changes in the rats, characterized by impaired supply of cells with molecular oxygen. However, as opposed to the animals with hypercholesterolemia that were not given statins, a decrease in hypoxia-induced shifts was observed. Abnormalities in the performance of the antioxidant defense (AOD) system and multidirectional changes in the activity of the antioxidant pair “SOD –  catalase” were noted. The correlation analysis revealed a positive relationship between the content of the NT-titin isoform and the SOD activity and negative correlations between the content of the N2A-titin isoform and the level of lactate, as well as between the T2-proteolytic fragment of titin and the level of lactate.

Conclusion. The study revealed a complex set of biochemical changes in the muscles that underlie myotoxicity of statins during their long-term use. Additional biochemical parameters were found – SOD activity and lactate concentration, changes in which, along with the determination of titin and  nebulin concentrations, indicating tissue hypoxia, will make it possible to more accurately diagnose statin-associated myopathy. 

 Aim. To study the effect of eplerenone on the activity of free radical oxidation and renal function in rats with experimental diabetes mellitus induced by streptozotocin.

Materials and methods. Experiments were carried out on 36 male Wistar rats. Diabetes mellitus (DM) was simulated by a single intraperitoneal injection of streptozotocin at a dose of 65 mg/kg. Eplerenone was injected into the stomach at a dose of 50 mg/kg.

Results. It was found that eplerenone in experimental diabetic nephropathy (DN) significantly attenuated proteinuria: the concentration of protein in the urine became 4 times lower than in untreated DN (p < 0.001). In the kidneys, eplerenone therapy normalized the structure and function of renal glomeruli and restored the podocyte number, which was reduced by 37.8% in the DN model. Free radical oxidation (FRO) in the kidneys of rats treated with eplerenone increased – the concentration of thiobarbituric acid reactive substances rose by 1.5 times (p = 0.009), and changes in the activity of antioxidant enzymes, such as superoxide dismutase (a decrease by 2.4 times, p = 0.002), catalase (an increase by 1.8 times, р < 0,001), and glutathione peroxidase (an increase by 1.5 times, р < 0.001) were observed, as opposed to the values in the controls.

Conclusion. In streptozotocin-induced experimental diabetic nephropathy in rats, eplerenone had a nephroprotective effect, but increased oxidative stress in the kidneys. The increase in FRO could be determined by the nongenomic effect of aldosterone, which accumulates under conditions of prolonged mineralocorticoid receptor (MR) blockade. The nephroprotective effect of eplerenone can be associated with the weakening of the genomic effects of aldosterone, realized with the participation of MR. 

 Aim. In an in vivo experiment, to study the effect of local intraoperative application of 0.05% cyclosporin A solution on the conjunctival and scleral regeneration after surgery on the rabbit eyes with steroid-induced  glaucoma.

Materials and methods. At the first stage of the experiment, a model of steroid-induced glaucoma was reproduced for 29 male Californian rabbits by injecting 0.5 ml of a 0.4% solution of dexamethasone subconjunctivally in both eyes once a week for 3 months (12 subconjunctival injections for each rabbit). At the second stage of the experiment, after the development of  steroid glaucoma, the rabbits were divided into the main group, consisting  of the subgroup «a» (n = 8) and the subgroup «b» (n = 8), and the comparison group (n = 8). All animals were performed a penetrating incision of the conjunctiva and a non-penetrating incision of the sclera of one of the eyes. A hemostatic sponge impregnated with 0.05% cyclosporin А solution was applied to the intervention area in the main group, in the subgroup «a» – for 3 minutes, in the subgroup «b» – for 6 minutes. In the comparison group, the cytostatic was not used.

Results. The use of 0.05% cyclosporin А solution led to a decrease in the  infiltration of fibroblasts and inflammatory cells into the area of surgical  injury. On the 4th day after the surgery, cell density in the intervention area  in the subgroup «a» with 3-minute application of cytostatic-antimetabolite solution was 2.7 times lower (p = 0.043) than in the comparison group, while exceeding the values in the subgroup «b» by 3.2 times (p = 0.036). The number of fibroblasts in the subgroups «a» and «b» was 3.6 (p = 0.043) and 12.8 times (p = 0.031) less than in the comparison group, and a shift in the cellular composition of the infiltrate towards the fibroblastic population occurred only on the 14th day after the surgery.

Conclusion. Intraoperative application of 0.05% cyclosporin А solution significantly slows down the course of regeneration, reducing infiltrative inflammation in the intervention area, which prevents excessive scarring. 

 Background. Peritoneal carcinomatosis (PC) is one of the most unfavorable factors of ovarian cancer progression. It is often accompanied by accumulation of fluid in the abdominal cavity, which is called ascites. However, prognostic factors associated with malignant ascites are not well understood.

The aim of this study was to evaluate dissimilar populations of EpCAM-positive cells in ascitic fluid and their relationship with the presence of invasive peritoneal implants and the prevalence of carcinomatosis on the Predictive Index Value (PIV) scale in ovarian cancer patients.

Materials and methods. The prospective study included 22 patients aged 36–76 years with newly diagnosed FIGO stage Ic–IV ovarian cancer, who were admitted for treatment to Cancer Research Institute of Tomsk NRMC. The study material included EDTA-stabilized ascitic fluid sampled during laparoscopy. Various populations of ascites tumor cells were identified by laser multicolor flow cytometry. The degree of carcinomatosis was determined according to the PIV scale.

Results. The study identified twelve populations of EpCAM-positive cells in the ascitic fluid of ovarian cancer patients. Epcam+CD45-CD44-CD24+CD133-Ncadherin+ cells (r = 0.58; p = 0.004) and atypical (hybrid) EpCam+CD45+CD44+CD24+/-CD133+/-Ncadherin+/- cells (r = = 0.51; р = 0.01) had a positive correlation with the PIV index.

Conclusion. The obtained results show a high degree of heterogeneity of tumor cells in the ascitic fluid of ovarian cancer patients. Identified atypical (hybrid) forms of EpCam-positive cells are of great interest for cell biology and require further investigation. 

 Background. Despite the progress in diagnosis and treatment of chronic rheumatic diseases in children, the choice of anti-inflammatory drugs in case of the onset of oligoarticular juvenile idiopathic arthritis (JIA) still remains relevant. Till present, pediatric rheumatologists have not reached a  consensus on this issue yet.

The aim of this study was to search for predictors of early failure of local steroid therapy and assessment of its feasibility in patients with oligoarticular JIA.

Materials and methods. In a retrospective study, 92 children aged 11 months – 9 years with chronic oligoarticular JIA without extra-articular manifestations were monitored. The features of the clinical, instrumental and laboratory diagnosis during the disease onset were studied, along with the dynamics of the articular syndrome and the effectiveness of intra-articular administration of corticosteroid drugs.

Results and discussion. The data on 92 children with 164 active joints who received 218 local intra-articular injections of triamcinolone acetonide at the onset of the disease were analyzed. Intra-articular injections of triamcinolone acetonide at a dose of 20–40 mg were performed with an interval of 3, 6, and 12 months, depending on the intensity of the disease. In about one third of children with oligoarticular JIA, arthritis became inactive on average after two intra-articular injections of triamcinolone acetonide. The study did not reveal the predictors of early ineffective topical corticosteroid monotherapy in children. No clinical, instrumental, and laboratory signs were identified that would directly indicate the need for early therapy with  methotrexate.

Conclusion. Triamcinolone acetonide is an effective and safe drug for children with oligoarticular JIA. Despite the widespread use of biological, gene, and other innovative therapies, application of local corticosteroids as  the firstline therapy in children with oligoarticular JIA should not be  neglected. 

 Aim. To identify the presence and the correction method of decreased heart rate variability (HRV) in patients with chronic coronary artery disease (CAD) and comorbid depressive disorders (DD).

Materials and methods. 79 patients with CAD (with class II–III angina pectoris and myocardial infarction that occurred more than 6 months ago) were divided into two groups. The first group included 50 CAD patients with depression, and the second – 29 CAD patients without depression. 17  patients received agomelatine (1st subgroup), 12 patients received fluvoxamine and fluoxetine (2nd subgroup), and 21 patients refused to take antidepressants (3rd subgroup). Initially and after 6 months, the HRV parameters were evaluated using the SCHILLER MT-200 Holter-ECG apparatus (Switzerland).

Results. A significant decrease in HRV was revealed in the patients with depression compared to the patients without it: SDNN (96 [83; 117] ms vs. 110 [98; 127] ms; p = 0.02), SDANN (80.5 [67; 94] ms vs. 91 [79; 102] ms; p = 0.03), SDNNindex (46.5 [38; 56] ms vs. 55 [48; 66] ms; p = 0.006), rMSSD (29 [23; 38] ms vs. 33 [29; 45] ms; p = 0.04), pNN50% (3.9 [2.4; 5,7] vs. 5.7 [2.9; 12.6]; p = 0.03). Initially, the 1st, 2nd, and 3rd subgroups did not differ in all HRV parameters. Against the background of antidepressant therapy, there  were significant differences between the 2nd and 3rd subgroups in SDNN  (110 [96; 140] ms vs. 85.5 [75; 103] ms; p = 0.008), SDANN (93.7 ± 22.9 ms vs. 72.7 ± 21.4 ms; p = 0.02), SDNNindex (55.8 ± 16.4 ms vs. 42.4 ± 10.8 ms; p = 0.01) and pNN50% (7.8 ± 6.7 vs. 3.6 ± 1.8; p = 0.02), as well as between the 1st and 3rd subgroups (SDANN (93.6 ± 28.5 ms vs. 72.7 ± 21.4 ms; p = 0.03), rMSSD (36.5 [28.5; 51] ms vs. 26.5 [25; 32] ms; p = 0.02)).

Conclusion. In patients with CAD with comorbid DD, significant impairment of heart rhythm regulation occurs due to a pronounced decrease in HRV, which can seriously affect the course and prognosis of CAD. Prescribing modern antidepressants can be used as a method of correcting autonomic  dysfunction in patients with CAD with comorbid depression. 

 Background. Neutrophils can play a significant role in the formation of bronchial inflammation in asthma  exacerbation in patients with cold-induced airway hyperresponsiveness (CIAHR).

Aim. To evaluate the role of neutrophils in the dynamics of the inflammatory pattern of bronchi in the exacerbation of asthma in patients with CIAHR.

Materials and methods. In 31 patients (average age (37.2 ± 2.7) years) with persistent bronchial asthma (BA) with moderate exacerbation and previously established cold-induced airway hyperresponsiveness during cold air isocapnic hyperventilation (– 20 ºC, 3 min) (CAIH), the level of asthma  control (Asthma Control Test (ACT), score) and external respiration (forced expiratory volume in the first second (FEV1), forced expiratory flow between 25% and 75% of the vital capacity (FEF25–75)) were assessed; induced  sputum (IS) was examined initially and after 24 weeks of follow-up. At the time of the examination, the patients were additionally prescribed prednisone orally (at a maximum dose of 30 mg) for the first 10 days in order to stop the exacerbation, and then they continued treatment with a combination of budesonide / formoterol (640 / 18 μg per day) for 24 weeks.

Results. At the time of the initial examination, the ACT score was 17.0 (13.0; 19.5), FEV1 was 89.1 ± 3.9%, and the number of neutrophils in the sputum was 55.9 ± 5.6%. At the end of treatment, the ACT score was 22.0 (17.0; 24.5) (p = 0.037), FEV1 was 96.2 ± 2.9% (p = 0.038), the number of neutrophils in IS decreased, but remained high enough (40.0 ± 5.5%; p = 0.048); and the number of eosinophils did not change. A linear regression equation was made reflecting the relationship between the initially high number of neutrophils in the sputum, other cellular elements in the sputum, the level of asthma control, and the degree of severity of the bronchial response after a bronchoprovocation test with CAIH.

Conclusion. Asthma exacerbation in patients with CIAHR is associated with  an increase in the neutrophil pool of the bronchial inflammatory infiltrate and correlates with the degree of severity of the airway reaction to cold bronchoprovocation and the level of asthma control.  

 Aim. To determine the nosological and clinical features of mood disorders (MD) with comorbid alcohol use disorder (AUD) and efficiency of antidepressant therapy.

Materials and methods. We examined 88 patients with MD and comorbid AUD – 33 females (37.5%) and 55 males (62.5%). The first group included 31 patients with AUD without comorbid affective symptoms, the second group contained 29 patients with MD without AUD, the third group included 28 patients with AUD and MD. In the study, we applied clinical-psychopathologic, clinical-dynamic, and statistical methods with Pearson’s χ2 test, Mann – Whitney U-test (for comparison of independent samples), Kruskal – Wallis test (for more than two independent samples), and Wilcoxon test (for comparison of dependent samples). At the level of statistical  significance, no differences between the groups according to the gender – age composition were revealed (p = 0.115 – according to gender composition, р = 0.248 – according to age composition, Pearson’s χ2 test).

Results. The patients with the diagnosis of AUD with comorbid MD showed worse dynamics of the reduction of depressive [from 24.0 (18.3; 33.0) to 9.0 (4.3; 12.0) points according to the Structured Interview Guide for the Hamilton Depression Rating Scale – Seasonal Affective Disorder (SIGH-SAD)  (р = 0.001, Wilcoxon test)] and anxiety [from 20.5 (12.5; 25.0) to 5.5 (3.3; 8.0) points according to the Hamilton Anxiety Rating Scale (HARS) (р = 0.001, Wilcoxon test)] symptoms against the background of the therapy with initially lower indices compared to the group with MD alone [from 27.0 (21.0; 36.0) to 6.0 (5.0; 11.0) points according to SIGH-SAD (р = 0.001, Wilcoxon test) (intergroup differences upon admission р = 0.046; upon  discharge р = 0.683, Mann – Whitney U-test) and from 21.0 (14.0; 29.0) to 5.0 (3; 10.5) points according to HARS (р = 0.001, Wilcoxon test) (intergroup differences upon admission р = 0.082; upon discharge р = 0.825, Mann –  Whitney U-test)]. The course of AUD is characterized by a larger extent of malignancy in the group with a comorbidity: decrease in pathological  alcohol craving from 31.5 (16.3; 43.5) points to 8 (2.3; 14.8) (р = 0.001, Wilcoxon test) in the group with a comorbidity and from 29.5 (21.8; 37.0) to 7 (3.0; 11.3) points with AUD alone (р = 0.001, Wilcoxon test) (intergroup  differences upon admission р = 0.058; upon discharge р = 0.04, Mann – Whitney U-test on the Obsessive Compulsive Drinking Scale (OCDS).

Conclusion. Clinical-dynamic characteristics of MD with comorbid AUD  result in therapeutic difficulties associated with comparatively worse dynamics of reduction of the symptoms of both diseases.  

 Background. The calpain proteolytic system plays an important role in the development of cancer. Detection of early cancer in the upper respiratory tract is often challenging, as symptoms are largely non-specific, and most cases are diagnosed at an advanced stage.

Aim. To identify candidate markers of transition from premalignant lesions to invasive carcinoma, we studied mRNA expression levels of CAPN1 and CAPN2 and the total activity of calpains in the tumor tissues of patients with head and neck squamous cell carcinoma (HNSCC) and in the epithelial dysplasia-affected tissues of patients with chronic diseases of the upper respiratory tract.

Materials and methods. The study included 32 patients with HNSCC (Т1-3N0-1М0) and 12 patients with chronic diseases of the upper respiratory system associated with epithelial dysplasia. The expression levels of CAPN1 and CAPN2 were assessed using real-time polymerase chain reaction (PCR). The calpain activity was determined by hydrolysis of the fluorogenic Suc-LLVY-AMC oligopeptide.

Results. The mRNA expression levels of CAPN1 and CAPN2 were respectively 3 and 4 times higher in the tumor tissue of patients with HNSCC than in the tissue of patients with endothelial dysplasia in the upper respiratory tract. The level of calpain activity was 4.4 times higher in patients with HNSCC than in patients with epithelial dysplasia of different severity.

Conclusion. The elevated mRNA expression levels of CAPN1 and CAPN2 and their activity in the tumor tissues of patients with HNSCC compared to patients with chronic respiratory diseases associated with epithelial dysplasia are likely to characterize a high potential for transition from precancerous lesion to cancer. To clarify the role of calpains in the carcinogenesis of HNSCC, further studies of intact tissues using animal models are required.  

 The aim of the study was to evaluate the immunoregulatory activity of an experimental drug based on ultra-high dilutions of antibodies to MHC I and MHC II molecules against Salmonella enteritidis rif92.

Materials and methods. The drug tested: a sample of ultra-high water-alcohol dilutions of antibodies to MHC I and MHC II molecules applied to lactose powder (the theoretical level of the initial antibody concentration reduction is at least 1024 times). A model of non-lethal Salmonella infection  in chickens was induced by administering a virulent strain of Salmonella enteritidis rif92 with a concentration of 2.5 × 109 CFU/g in the volume of 0.5 ml/bird. The following groups were formed (n = 15 in each group): 1 – drug; 2 – drug + antibiotic at the median effective dose (ED 50); 3 – placebo; 4 – placebo + antibiotic at ED50; 5 – intact control. The duration of the experiment was 12 days. The studied parameters included the survival rate during the observation period; daily body weight; feed consumption for the entire period; pathogen concentration in the litter on day 3, 6, and 9; the presence and concentration of the pathogen in the liver and cecum on day 12; and the index of antimicrobial activity on day 12.

Results. In the groups receiving the experimental drug, the infectious process proceeded in a milder form and the bacterial load in chickens was lower. The bacterial count in the litter was reduced by two orders compared to the respective control when the drug was added both alone and in combination with the antibiotic. A protective effect of the experimental drug on the liver of the infected chickens was detected.

Conclusion. A pronounced immunoregulatory activity of the studied drug against Salmonella enteritidis rif92 in chickens was demonstrated for the first time. The results obtained allow to consider the drug as a promising agent
for the treatment of Salmonella infection.  

 Aim. To study the relationship of obstructive respiratory disorders during sleep with subclinical development of right ventricular dysfunction and pulmonary hypertension, as well as with the risk of an adverse course of chronic heart failure (CHF) with preserved left ventricular ejection fraction (LVEF).

Materials and methods. The study included 86 men with moderate and severe forms of obstructive sleep apnea syndrome (OSAS) (with an apnea/hypopnea index (AHI) > 15 per hour). All patients had abdominal obesity and hypertension. Upon inclusion in the study, all patients underwent polysomnography and echocardiography according to the  standard protocol with an additional assessment of the fractional area  change in the right ventricular myocardium (ΔSRV) and the right ventricular  stroke work index (RVSWI). Also, the content of the N-terminal brain natriuretic peptide precursor (NT-proBNP) in the blood serum was  determined by enzyme immunoassay analysis. A six-minute walk test (6MWT) was performed after inclusion in the study and after 12 months of  follow-up. Depending on the course of CHF during the follow-up,  retrospectively, the patients were divided into 2 groups: with an unfavorable (n = 33) and favorable (n = 53) prognosis.

Results. A significant relationship between AHI and ΔSRV, RVSWI, NT-proBNP, and 6MWT was revealed. Based on the results of one-way correlation analysis, it was found that ΔSRV (odds ratio (OR) 2.51; 95%  confidence interval (CI) 2.42–3.24; p = 0.0009), NT-proBNP (OR 1.92; 95% CI  1.32–2.78; p = 0.003), and AHI (OR 3.93; 95% CI 2.87–4.11; p = 0.018) were predictors of an adverse course of CHF. In a multivariate analysis, it was found that AHI was an independent predictor of an adverse course of CHF (OR 3.49; 95% CI 2.17–11.73; p = 0.0008), while the addition of NT-proBNP improved risk stratification of an adverse course of CHF (OR 4.66; 95% CI 3.87–13.11; p < 0.0001).

Conclusion. The fractional area change in the right ventricular myocardium (ΔSRV) can be considered as a non-invasive marker for determining the  emerging right ventricular dysfunction and predicting adverse cardiovascular events in patients with preserved LVEF and OSAS. Moreover, the combined use of echocardiographic (ΔSRV) and laboratory (NT-proBNP) markers can improve risk stratification of CHF progression.  

 Aim. To develop a new methodological approach to assessment of collagen-induced platelet aggregation in patients with coronary artery disease (CAD) and to determine the quality of various methods for detecting high residual platelet reactivity (HRPR) to predict the risk of myocardial perfusion disturbance.

Materials and methods. 36 patients (10 men and 26 women) aged 41–83 years and having stable CAD were examined. All patients had been undergoing continuous antiaggregation therapy for 6 months. We evaluated platelet aggregation using a laser analyzer with collagen as an aggregation inducer by the standard method 1 and our own patented method 2. The degree of platelet aggregation (%) and the size of aggregates in relative units (r.u.) in platelet-rich plasma were estimated. Myocardial perfusion scintigraphy with 99mTc-methoxy-isobutylisonitrile was performed according to a two-day stress-rest protocol. The summed stress score (SSS) values were used for analysis. SSS < 4 was regarded as normal myocardial perfusion.

Results. The degree of platelet aggregation according to method 1 was 12 (5; 64)%, the aggregate size was 3 (2; 7) r.u. The degree of platelet aggregation according to method 2 was 44 (13; 78)%, and the aggregate size was 5 (4; 8) r.u. Method 2 allowed to diagnose the presence of myocardial ischemia with an aggregation degree ≥ 44.9% with sensitivity of 84% and specificity of 92% (area under the curve (AUC) = 0.89; p < 0.0001; odds ratio (OR) 2.18; 95% confidence interval (CI) 0.57–0.98) and an increase in aggregate size ≥ 4.80 r.u. with sensitivity of 84% and specificity of 84% (AUC = 0.95; p < 0.00001; OR 5.83; 95% CI 0.72–0.99).

Conclusion. In patients with CAD, detection of high rates of collagen- induced platelet aggregation using the patented technique is associated with the risk of impaired myocardial perfusion. The developed new  methodological approach to detection of HRPR allowed to determine high risk of atherothrombotic complications in additional 22% of the examined patients. 

 Aim. To determine the diagnostic value of positron emission tomography (PET)/computed tomography (CT) with F-18 fluorodeoxyglucose (18F-FDG) for monitoring the effectiveness and prognosis of lymphoma therapy.

Materials and methods. Retrospective data of 18F-FDG PET/CT (before treatment (PET1), after two cycles (PET2), and after completion of chemotherapy (PET3)) in 30 people with lymphomas were analyzed.

Results. A complete metabolic response in PET2 (PET2–) was observed in 21 patients (70%). In 9 patients in PET2–, a partial metabolic response (6 people), lack of metabolic response (2 people), or metabolic progression (1
person) were detected. These patients comprised the PET2+ group.
After chemotherapy, a complete metabolic response (PET3–) was diagnosed in 26 patients (87%). This effect was achieved in 21 patients (100%) with PET2– and in 5 patients (66%) with PET2+. Of the 9 patients in the PET2+ group, in 4 (44%) patients, a partial metabolic response or no metabolic response was diagnosed. Further monitoring of these patients showed that progression was diagnosed in 2 cases, and in 2 patients, further treatment resulted in complete remission. A two-year follow-up of patients revealed that remission was observed in 20 (67%) patients. The analysis of the results of PET2 showed that a relapse of the disease was observed in 6 (67%) PET2+ patients and remission was noted in 3 (33%) patients. In PET2– patients, a relapse was diagnosed in 4 (19%) persons, and remission was established in 17 (81%) patients.

Conclusion. Early PET/CT with 18F-FDG allows to predict the effect of  lymphoma treatment. The method can be recommended for monitoring lymphoma therapy. 

 The causes of ulcerative colitis are still unknown. Scientists made important  advances in understanding the pathogenesis of this disease in the 21st century.  Complex involvement of an impaired immune response in relation to antigens  of the intestinal microbiota in genetically predisposed individuals under the  influence of certain environmental factors was revealed. The factors that disrupt  the epithelial barrier and alter the composition of the intestinal  microbiota trigger the onset of the disease, thereby stimulating an impaired  immune response. Recent studies have discovered completely new hypotheses  of its origin and development, gradually interpreting the already known pathogenetic mechanisms of the disease. In this review, we focused on the new concepts in the pathogenesis of ulcerative colitis. We examined genetic, environmental, barrier, and microbial factors. We went into detail on the structure and role of the epithelial barrier, identified specific genes that are  involved in the regulation of the intestinal epithelial barrier function in ulcerative  colitis. We studied the literature containing information on relevant  studies in PubMed and Google Scholar citation systems, using such key words  as ulcerative colitis, colon microbiota, barrier function, genetic predisposition, and predisposing factors. 

 This literature review is devoted to the molecular mechanisms of oogenesis and depletion of the ovarian reserve. One of the factors in this process is constantly changing environment of the ovaries, both during intrauterine development and the postnatal period. Numerous mechanisms and factors  affecting the internal environment of the female gonad are described, such as stem cell factor (SCF), which regulates migration of primordial germ cells and survival of early oocytes, insulin-like growth factor I (IGF-I), and leukocyte migration inhibitory factor (LMIF). The capabilities of the endocrine system, namely sex steroids, which can both replenish the number of germ cells and deplete the ovarian reserve through the expression of apoptotic markers, were shown. Apoptosis causes degeneration of most of the germ cells formed during oogenesis. The molecular mechanisms and factors involved in this process are numerous.
Pathways mediated by mitochondria of germ cells and external pathways mediated by receptors of the cell surface were described. A mediator between two apoptotic pathways was established – the Bid protein (BH3-interacting domain death agonist), the activation of which triggers the apoptosis mechanism of the intrafollicular microenvironment. Some other factors were identified that mediate programmed germ cell death and result in diminished ovarian reserve: eukaryotic elongation factor 2 kinase (eEF-2 K), PUMA and NOXA genes, the absence of growth factors and members of tumor necrosis factor (TNF) family. Changes in the epigenetic modification of chromatin in the follicular and germ cells, oxidative stress, decreased DNA repair, and the involvement of the genes BRAC1, RAD51, ERCC2, and H2AX associated with this process can also affect reproductive health and the ovarian reserve. A significant role of mitochondrial dysfunction of follicular cells in depletion of the ovarian reserve is of great interest, which leads to impaired oocyte competence, deteriorates the gamete quality, and depletes  the ovarian reserve. Therefore, oogenesis depends on a huge number of factors and the internal environment of the ovaries, the knowledge of which  can maintain the stability of the reproductive function and preserve the quality of the ovarian reserve.  

 The review systematizes modern data on the biochemical markers that can clarify the nature and the course of chronic bronchitis. The article describes markers associated with bronchopulmonary pathology, such as tumor necrosis factor alpha (TNFα), interleukin 1 (IL-1), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 10 (IL-10), tissue factor, type 1 plasminogen activator inhibitor (PAI-1), and monocyte chemoattractant protein-1   (MCP-1). For each biomolecule,  its properties, functions, direct role in body processes, and associations with 
bronchopulmonary pathology are described. The use of these markers for early  diagnosis of bronchopulmonary pathology and monitoring of the treatment effectiveness is promising and requires further in-depth study. 

 The ubiquitin-proteasome system (UPS) controls the activity, subcellular localization, and stability of many cellular proteins that affect cellular homeostasis by regulating multiple signaling cascades. The activity of this system is associated with the emergence and progression of oral squamous cell carcinoma, since specific proteolysis of most intracellular proteins involved in the pathogenesis of cancer is implemented by this system.
The review article presents data on the characteristics of proteasomes and the process of substrate protein ubiquitination. The role of the ubiquitin-proteasome system in the pathogenesis of oral squamous cell carcinoma is shown, and the prospects of its use in precancerous diseases are described. The  literature search was carried out in the search engines Medline, eLIBRARY, Scopus, The Cochrane Library, and RSCI. 

 Gastric cancer (GC) is the 5th most common type of cancer in the world and the third leading cause of death from cancer. GC is a multi-factorial and morphologically heterogeneous disease. Currently, several morphological classifications of GC are used, however, for diagnosis, it is necessary to take into  account not only the morphological type of the tumor, but also its molecular subtype. According to the literature, the intestinal type of GC is most often associated with effects of environmental factors and is usually found in older  age groups in men, while diffuse gastric cancer (DGC) is a genetically determined disease which is more common in younger patients, with the same 
frequency among men and women.
This review covers in detail GC, its classification by P.A. Lauren (1965), and its molecular subtypes characterized during the Cancer Genome Atlas project and examines the impact of certain risk factors on the pathogenesis of the disease, such as: H. pylori infection or Epstein – Barr virus. A separate section in this analytical work is dedicated to expression of the PD-L1 marker by tumor cells and the use of this parameter for prognosis and therapy of this disease. An essential part of the work is discussion of the features of intestinal and diffuse types of gastric cancer, which reflect not only the differences in classifications used in modern diagnosis, but also the relationship between the pathological pattern and the molecular subtype of gastric cancer. 

 Given a persistent global trend towards an increase in the number of patients with bronchial asthma (BA) over the past decades, researchers are facing challenges related to a comprehensive study of the pathogenesis of BA. Numerous studies have shown that BA is associated with long-term persistence of leukocytes (lymphocytes, macrophages, and eosinophils) in the bronchial tissues. However, the causes of this phenomenon remain understudied. The article provides an overview of modern research on the mechanisms of disorders of lymphocyte apoptosis in patients with BA.

Our study considers the main mechanisms of molecular regulation of  lymphocyte apoptosis, including transcription factors, the Fas/FasL system, and bcl-2/bcl-XL factors. We present the data on the role of reduced lymphocyte apoptosis in the formation of a severe BA phenotype. Taking into account high  prevalence of obesity among patients with BA, we analyzed a few existing articles on the apoptosis of immunocompetent cells in obesity. In addition, the article highlights the key mechanisms of development of lymphocyte plasma membrane blebbing (PMB) with formation of microvesicles, as well as their influence on the course of pathological processes in BA.

The authors believe that further in-depth study of apoptosis, lymphocyte  necrosis, and plasma membrane blebbing can help improve the principles of diagnosis and treatment of BA. 

 The problem of atherosclerosis, which forms the pathological basis of coronary artery disease (CAD), is one of the most discussed ones in development of cardiovascular diseases. This chronic inflammatory disease involves interactions between different cells, and an atherosclerotic plaque is a complex immunological environment. Modern  quantitative methods  increase the understanding of the pathophysiological processes responsible  for progression of atherosclerotic plaques. Flow cytometry is a powerful modern method that allows for a complex and simultaneous cell analysis. This review is devoted to studies on atherosclerosis and CAD performed  using flow cytometry.  

 The use of quantitative mapping of diffusion characteristics carries great potential for diagnosis and therapy of brain diseases, since it potentially allows to classify tumors, determine the degree of their malignancy, differentiate various morphological structures of tumor and non-tumor pathologies (such as  tumor stroma, necrotic zones, cysts, various types of edema, etc.), and predict the course and outcome of diseases, in particular, a clinical response to treatment. Based on diffusion weighted magnetic resonance imaging (MRI), it is possible to perform 3D modeling of the white matter pathways of the brain, which is called tractography. In addition to a unique ability to visualize the location of tracts in relation to intracranial pathologies, this technology allows to build and analyze complex maps of communication networks in the brain (connectomics).
The review is devoted to the discussion of the physical and technical concept of diffusion weighted MRI, the key ways of its application in tumor and non-tumor processes, and problems that complicate correct interpretation of results. Since the problem of developing software for diffusion MRI data remains relevant, this review presents our own experience in developing an application as part of a project on creating effective methods for processing diffusion MRI data and modeling white matter tracts. 

 Endothelial dysfunction as a crucial factor in the pathogenesis of cardiovascular diseases requires precise and effective diagnostic methods. The review highlights the currently used methods which can be divided into morphological, instrumental, and laboratory ones. Special attention is paid to the so called jar  test, which was  introduced by Professor V.A. Valdman in 1936. The jar test may  serve as a prototype of modern methods for endothelial function assessment.
These diagnostic methods can help to identify functional endothelial disorders at the earliest stage. It will significantly expand the possibilities of primary prevention of cardiovascular and a number of other diseases through non-pharmacological and pharmacological correction of endothelial dysfunction. 

 Vertebral artery compression is a syndrome that occurs as a result of hemodynamically significant partial or complete obstruction of vertebral arteries by extravascular structures. In clinical practice, this condition is most often called vertebral artery syndrome. Any vertebral segments can be  compressed, but most often the lesion is determined at the level of C1–C2. Russian authors consider vertebral artery compression to be a common cause of a wide range of patient complaints, including dizziness, headaches, and subjective tinnitus. In some studies, it is reported that vertebral artery syndrome develops in 50% of patients with degenerative changes in the cervical spine.
In the world literature, vertebral artery compression syndrome which is often referred to as “bow hunter’s syndrome” is called a rare pathology. Such a pronounced difference in the frequency of detection of vertebral artery compression in Russian and world literature may be associated with a lack of  common diagnostic criteria, low awareness of alternative diagnoses, and incorrect interpretation of patient complaints. It is obvious that these factors need to be corrected in order to reduce the likelihood of overdiagnosis of  vertebral artery compression syndrome and improve the quality of medical care. 

 The review presents the analysis of data proving the role of platelets in the mechanisms of regulation of reparative tissue regeneration. The influence of platelets on damage, apoptosis, and proliferation of cells, as well as on extracellular matrix remodeling, angiogenesis, and neurogenesis is shown. Their  interaction with macrophages in restoring the structure of damaged tissues is assessed. Several regenerative properties of platelets are characterized. 

 The article presents a case of pulmonary embolism with comorbid acute inferior myocardial infarction in the 54-year-old patient who was admitted to the Regional Center for Percutaneous Coronary Interventions. Coronary angiography revealed a multivessel lesion with angiographic signs of instability  in the proximal third of the right coronary artery. Pulmonary angiography revealed signs of pulmonary embolism with moderate impairment of pulmonary perfusion.
The described combination is challenging in terms of both diagnosis and subsequent treatment strategy. A feature of this case is the use of a double surgery, consisting of revascularization of the infarct-related artery and fragmentation of thrombotic masses in the pulmonary artery, in combination with thrombolytic therapy. 

 Aim. To study a rare sporadic case of metastatic gastrinoma associated with mutations in the MEN1 and TSC2 genes in a 25-year-old male.

Materials and methods. A retrospective analysis of the history of a 25-year-old patient with sporadic gastrinoma with a highly aggressive clinical course and high metastatic potential was performed. Sequencing of the DNA  extracted from the surgical tumor biopsy was performed on the Illumina  NextSeq 550 sequencer (Illumina Inc., USA) with the mean coverage of at least 100× using the AmpliSeq target panel for Illumina Comprehensive Cancer Panel for studying exons of 409 genes, mutations in which are associated with oncopathology.

Results. The article presents the results of complex diagnosis and treatment of metastatic gastrinoma using modern locoregional therapy and drugs from the group of somatostatin analogues. Using next generation sequencing and Sanger sequencing, sporadic mutations in the MEN1 and TSC2 genes with pronounced clinical significance were identified in the extracted DNA.

Conclusion. The identified mutations, being the drivers of the tumor process, apparently determined the atypical development of the presented clinical case – the sporadic Zollinger – Ellison syndrome. Complete morphological and immunohistochemical validation of the neuroendocrine tumor before treatment determined a successful treatment strategy, including the use of somatostatin analogues in adjuvant and neoadjuvant therapies in combination with chemoembolization of hepatic metastases. 

 The article presents a clinical case of comorbid pathology – development of migraine against the background of systemic mastocytosis. The classification and clinical manifestations of systemic mastocytosis, a rare blood disease, are given.
This clinical case illustrates an example of excessive mast cell degranulation (with the release of proinflammatory and vasodilating agents as a result of mast cell pathology). In this regard, in addition to the pathogen-specific therapy for systemic mastocytosis (including prevention of mast cell degranulation), it seems important to describe the effectiveness and the possibility of prescribing preventive and emergency therapy for migraine against the background of the underlying hematological disease – systemic mastocytosis.
Treatment of cephalalgia in patients with mastocytosis is a complex clinical task, in the solution of which it is necessary to take into account serious limitations in prescription of acetylsalicylic acid and other non-steroidal anti-inflammatory drugs.