Introduction. Disturbances of trace element hemostasis are the causes of trace element imbalance, which often lead to the development of such major human diseases as iron defi ciency anemia (IDA) and diabetes mellitus.

Aim. Study of the trace element composition of fruits of the Vacciniaceae family plants and determination of their prospects for use in the prevention of trace element imbalance.

Materials and methods. The content of 37 elements, including essential (Mn, Fe, Cu, Cr, Co, Zn) and toxic elements (Pb, Hg, As, and Cd), was determined by inductively coupled plasma mass spectroscopy.

Results. The content of toxic elements in all the studied samples is below the reference values. The content of essential microelements diff ers, which must be taken into account in the prevention of specifi c imbalance of trace elements.

Conclusion. The collected raw materials are environmentally safe and can be used for medicinal purposes. The combination of cranberry and blueberry is optimal in terms of manganese and zinc content and can be used to prevent diabetes. From the point of view of the IDA prevention, it is preferable to use blueberry fruits, which have equimolar concentrations of iron and manganese and the maximum content of cobalt.

 Introduction. Increasing the eff ectiveness of chemotherapy for ovarian cancer is an important task of modern oncogynecology. A serious disadvantage of chemotherapeutic drugs used in the treatment of malignant ovarian neoplasms is a low selectivity and the associated high systemic toxicity which manifests itself as a combination of undesirable side effects of chemotherapy (functional disorders of the gastrointestinal tract, toxic eff ects on various organs and the blood system). In recent years, the role of dysbiosis as a factor aff ecting the tolerability of chemotherapy has been studied.

Aim. To compare the severity of the developing adverse events in patients with malignant ovarian neoplasms receiving chemotherapy with the use of probiotics and without them.

Materials and methods. The study involved 25 patients diagnosed with stage II–IV ovarian cancer. The patients of the study group (10 women) underwent combined treatment (cytoreductive surgery + 6 courses of chemotherapy). During 3 cycles of chemotherapy, the patients of this group received VedaBiotic, an innovative domestic multisynbiotic drug containing 11 strains of probiotics a prebiotic, vitamin C, and a natural sorbent. The comparison group consisted of 15 patients diagnosed with stage II–IV ovarian cancer, who received the same treatment as the patients in the study group but without taking probiotic preparations. To study the eff ectiveness of taking probiotics, the following were assessed: condition of patients according to the Karnofsky Performance Scale (indicator – Karnofsky performance score); quality of life of patients according to the EORTC QLQ-C30 questionnaire (version 3.0); results of full blood count and blood chemistry.

Results. The assessment of patients’ general status on the Karnofsky Performance Scale showed a signifi cant improvement in the well-being of patients in the study group. Patients who took VedaBiotic had signifi cantly less pronounced subjective complaints such as dyspnea, pain, sleep disturbance, asthenia, loss of appetite, nausea, vomiting, diarrhea. According to the results of blood chemistry, the level of liver enzymes was signifi cantly lower in the study group.

Conclusion. These data may indicate the possibility of a chemoprotective eff ect on the part of the microbiota of the large intestine. In the authors’ opinion, VedaBiotic can be recommended for the inclusion into the diet of oncological patients receiving anticancer therapy to eff ectively restore the microbiota of the large intenstine.

   Introduction. Nowadays, a wide range of environmental, social, behavioral and medical factors infl uence somatic and reproductive health of women, which leads to the development of specifi c characteristics of the course of various gynecological diseases, i.e. pathomorphosis in the clinical (narrow) sense.

   Aim. Analysis of the medical and social profi le, and clinical and anamnestic specifi c characteristics of patients with endometrial polyps (EPs) of different morphological types in the light of the doctrine of pathomorphosis.
   Materials and methods. To investigate the pathomorphosis of EPs, a retrospective study of 393 patients with EPs was performed: 207 women were treated in 2016–2018 (1st group), and 186 women – in 2006–2008 (2nd group).
   Results. In patients of the 1st group, changes of the medical and social profi le and clinical course of the disease were revealed: a later age of manifestation of atrophic and earlier age of functional and hyperplastic EPs; in women with atrophic EPs, hypertension is more often observed, with functional EPs – disorders of the digestive system and anemia; patients with functional and hyperplastic EPs have a lower number of pregnancies, childbirths and surgical abortions, and with atrophic EPs have a greater number of pregnancies, therapeutic abortions and miscarriages; in the past medical history of
patients with atrophic EPs, cervical polyps, endometrial hyperplasia, cervicitis are more often observed, with hyperplastic EPs – endometrial hyperplasia and ovarian cysts, with functional EPs – cervicitis and infertility. The incidence of abnormal uterine bleeding (AUB) decreased signifi cantly, the incidence of asymptomatic course of the disease increased in atrophic EPs, while the incidence of AUB in the form of intermenstrual bleeding and asymptomatic course increased statistically signifi cantly in hyperplastic EPs, and infertility – in functional EPs.
   Conclusion. Formed over a period of 10 years, the changes in the age of EPs manifestation, somatic and reproductive health of women with EPs, clinical manifestations of EPs of various morphological types can be interpreted as pathomorphosis in the clinical (narrow) sense. These changes must be taken into account when developing diagnostic, therapeutic and reconstructive treatment of this pathology.

   Introduction. Coronary artery disease (CAD) remains the main cause of disability and mortality among workingage people. A signifi cant part of stable angina patients are patients with intermediate (40–70 %) coronary artery stenosis.

   Aim. To study cardiovascular risk factors and make a comparative assessment of the clinical angiographic picture and vascular stiff ness in stable angina patients with intermediate coronary artery stenosis, depending on the chronological age / biological age ratio, as well as to determine the level of long-term metabolites of nitric oxide (NO) – nitrites (NO₂).
   Materials and methods. 40 stable angina class I–III patients (36 men) aged 33–68 years with intermediate coronary artery stenosis were examined. Depending on the values of the chronological age / biological age coeffi cient (K), the patients were divided into two groups. The 1st group included patients with a biological age exceeding the passport age (K < 1.0 [0.53; 0.98]), the 2nd group included patients with a biological age equal or inferior to the chronological age (K ≥ 1.0 [1.1; 1.5], p < 0.01 ).
   Results. Stable angina patients with intermediate coronary artery stenosis represent a rather challenging group of people in terms of prognosis. Patients with increased biological age are characterized by an unfavorable course of the disease and a less favorable cardiometabolic profi le compared to patients whose biological age corresponded to the chronological one. At the same time, the level of long-term metabolites of nitric oxide (NO) – nitrites (NO₂) in plasma did not depend on the biological age of patients.
   Conclusion. The study of the biological age and level of long-term metabolites of nitric oxide (NO) – nitrites (NO₂) in stable CAD patients with intermediate coronary artery stenosis is of great interest and requires further research.

   Introduction. The anticonvulsant drug range expansion, the change in the treatment strategies, and person-oriented approach to choosing the optimal drug dictates the need for marketing research to update and systematize data on the state of the national pharmaceutical market of anticonvulsants. Carrying out a marketing analysis of the antiepileptic drugs (AEDs) market, including determining the market situation and the qualitative characteristics of this group of drugs, is necessary to prescribe optimal and rational pharmacotherapy regimens for patients with epilepsy, as well as to meet the
demand and needs of consumers.
   Aim. To perform an analysis of the national market of AEDs and determine its main parameters and development trends.
   Materials and methods. The methodology for research of the AEDs market included methods of content-analysis and ATC/DDD methodology, structural-logical, graphic-analytical, and statistical methods of analysis. The objects of content analysis were: the State Register of Medicines; the unified structured directory-catalog of medicines; Internet sites; price-lists of the main distributors of medicines. The objects of the study were the sales data on AEDs in the Russian Federation for 2020 provided by the IQVIA agency (IMS Health).
   Results. An analysis of the AED range in the Russian market showed suffi cient assortment saturation of AEDs of the 1st and 2nd generations, and an insuffi cient number of the latest AEDs. It has been established that the largest share (50 %) of the AEDs in the home pharmaceutical market is represented by Russian manufacturers. At the same time, India makes the maximum contribution to the structure of imports (11 %). In 2020, the leading positions in consumption continued to be held by valproates (36 %) and carbamazepine (27 %), however, the AEDs’ consumption structure has been changing in recent years, the share of the newest anticonvulsants was 13% in physical terms (in volume) and 23 % in monetary terms (in values), respectively, an increase in the cost of the newest anticonvulsants amounted to 19 %.
   Conclusion. The growth driver of the AED market is the subsidized segment. The growth of public antiepileptic therapy spending, despite the entry of ever cheaper generic drugs, was provided by medicines of the new and newest generations, the price of which diff ers up to a hundred times from traditional AEDs. The revealed dynamics of sales of AEDs, the social orientation of the policy of the Russian state, and the legal norms for subsidized drug provision of patients with epilepsy with all drugs, suggest a further increase in government expenditures on AEDs in the coming years.

   Introduction. Left ventricular diastolic dysfunction (LV DD) is associated with the development of chronic heart failure (CHF) with preserved ejection fraction. This CHF phenotype is most common in patients with type 2 diabetes mellitus (T2DM). It is relevant to study the relationship between LV DD in patients with T2DM and the level of N-terminal pro-B-type natriuretic peptide (NT-proBNP), as a CHF biomarker, and other clinical, laboratory and echocardiographic parameters.
   Aim. To determine the signifi cance of NT-proBNP and other factors in the development of LV DD in T2DM in the long-term follow-up period.
   Materials and methods. The study included 94 patients with T2DM aged 40 to 65 years (65 % women). All patients had arterial hypertension (AH), obese or overweight and had no signs of NYHA class III–IV CHF, LV ejection fraction (EF) < 50 %. 37 patients had stable coronary artery disease (SCAD). Patients underwent clinical and laboratory examination, echocardiography. The concentration of NT-proBNP was determined. After 8.8 ± 0.72 years, 41 patients with T2DM were examined again with an assessment of clinical, biochemical and echocardiographic parameters. At baseline the 2009 National Guidelines of the Society of Cardiology of the Russian Federation and the Society of Heart Failure Specialists for the diagnosis and treatment of CHF were used for the diagnosis of LV DD. After 8.8 ± 0.72 years, the 2020 Clinical Guidelines of the Russian Society of Cardiology (RSC) for CHF were used for the diagnosis of LV DD. The search for factors that determine the presence of LV DD in the long-term period was carried out using logistic regression and ROC analysis.
   Results. At baseline LV DD was detected in 81.9 % of cases in patients with T2DM and correlated with the presence of SCAD and the duration of AH. T2DM patients with LV DD compared with patients without LV DD did not differ in the level of NT-proBNP (30.6 pg/ml [20; 83.4] vs 36.7 pg/ml [20; 71.1]), p = 0.7). After 8.8 ± 0.72 years, LV DD was detected in 51.2 % of patients with T2DM according to the 2020 Clinical Guidelines of the RSC. Patients with T2DM were divided into 2 groups: with LV DD (group 1) and without LV DD (group 2). Patients of the first and second groups differed in duration of diabetes (20 years [16; 25] vs 17.5 years [14.5; 20.5], р = 0.04), body mass index (BMI) (33.9 kg/m² [31.2; 37.4] vs 32.2 kg/m² [27.4; 34.7], р = 0.03), left ventricular mass index (LVMI) (94.8 g/m 2 [82.5; 107] vs 73.9 g/m² [71; 82.7], p < 0.01) and were comparable in terms of carbohydrate, lipid metabolism, and kidney function. Compared to the second group, the first group had the higher baseline level of NT-proBNP (47.3 pg/ml [23.4; 111] vs 20 pg/ml [20; 20.3], p < 0.01), higher baseline BMI (34.6 kg/m² [30; 38] vs 31.2 kg/m² [29.6; 33.7], р = 0.04) and higher baseline LVMI (101.1 ± 1 g/m² vs 86.3 ± 14.1 g/m² , р = 0.02). The logistic regression revealed that in patients with T2DM the presence of LV DD in the long-term period is associated with the level of NT-proBNP (p = 0.03), baseline BMI (p = 0.04), baseline LVMI (p = 0.01). The baseline level of NT-proBNP > 31.2 pg/ml showed a sensitivity of 66.7 % and a specificity of 100 % for the presence of LV DD in patients with T2DM after 8.8 ± 0.72 years of follow-up.
   Conclusion. In the long-term follow-up period the presence of LV DD in patients with type 2 diabetes mellitus is associated with the increased baseline level of NT-proBNP, especially in combination with the increased baseline LVMI and BMI values, while the level of NT-proBNP > 31.2 pg/ml can be considered as a prognostic marker of LV DD in patients with T2DM after 8.8 ± 0.72 years of follow-up with a sensitivity of 66.7 % and a specifi city of 100 %.

   Introduction. More than 18 million people die every year from complications (the most common of them are thrombosis of the cerebral, coronary and peripheral vessels) caused by diseases of the cardiovascular system. Optimal prevention of thrombosis (antiplatelet therapy) requires the use of drugs that would be able to eff ectively prevent thrombus formation without increasing the risk of bleeding. A new indolinone derivative (codenamed GRS) has potent antiaggregant action and low toxicity (LD 50 for rats > 5000 mg/kg). However, selecting the effective dose and dosage regimen for GRS requires data on its pharmacokinetics in oral and intravenous administration.
   Aim. To determine the pharmacokinetics of a new antiplatelet agent, an indolinone derivative (GRS) after a single intravenous and oral administration to rats.
   Materials and methods. The GRS compound was administered as a 1 mg/kg aqueous solution into the tail vein or as a 10 mg/kg suspension in carboxymethyl cellulose aqueous solution for oral (intragastrical) administration. Blood samples were taken at 5, 10, 20, 40 min, 1, 2, 4, and 8 h, and urine samples were collected at 2, 4, 8, 12, and 24 h after administration. GRS was detected in biological samples using high-performance liquid chromatography with ultraviolet detection.
   Results. The study has demonstrated that with both routes of administration, the antiaggregant eff ect of GRS lasts for at least 8 hours, being lipohpilic, GRS is rapidly distributed in organs and tissues by passive diffusion, undergoes biotrans-formation and is excreted in the urine mostly as metabolites, since at most 2.5 % of the initial compound is excreted in the urine. Bioavailability of GRS does not exceed 12 %.
   Conclusion. After intravenous and oral administration to rats, the GRS compound is excreted in the urine mostly as metabolites; metabolic clearance is more prominent after GRS oral administration.

   Introduction. Despite the signifi cant financial resources for pharmaceutical care in the constituent entities of the Russian Federation, differences remain in ensuring the availability of drugs to the citizens eligible for social support. In this regard, the development of organizational and pharmaceutical measures to optimize the system of subsidized provision of medicines for the population (in the example of the Novosibirsk Region (NR)) is an important area of modern pharmaceutical science.
   Aim. Analysis of the provision of medicines to benefi ciaries in the Novosibirsk Region.
   Materials and methods. The sources of information were materials of the Novosiboblpharm, State Public Institution of Novosibirsk Region, the database of the Novosibirskoblpharm on the cost and number of provided and defferred prescriptions during 2019–2021 for 35 municipal entities (MEs) of the NR. Content analysis, expert assessment method, logical, non-parametric (rank), economic and statistical, and cluster analysis were used.
   Results. Monitoring of the number of citizens, eligible to receive medicines on preferential terms for the analyzed period in the federal segment revealed an increase in benefi ciaries by 13.96 %, and in the regional segment – a decrease by 5.19 %. Analysis of the number and cost of provided prescriptions and medicines supplied during this period showed that pharmaceutical care to regional benefi ciaries has improved, while to federal benefi ciaries – worsened in all indices. As a result of an assessment of structural similarity of the Provision of Essential Medicines (PEM), during 2019–2021, the territorial systems of subsidized provision of medicines of MEs of the NR were separated into the federal and the regional segments. It was found that in the federal segment, only 18 (51.4 %) MEs in 2019, 20 (57.14 %) MEs in 2021 of 35 MEs of the NR have a rational structure of subsidized provision of medicines, and the increase was 11.16 %. In the regional segment, only 21 (60.0 %) MEs in 2019, 22 (62.80 %) MEs in 2021 of 35 MEs in the NR had a rational structure of subsidized provision of medicines, the increase was 4.76 %.
   Conclusion. An irrational structure of subsidized provision of medicines has been identifi ed, which consists in its substantial structural similarity in clusters, and asymmetry in the federal and regional segments, that requires an in-depth research and revision of the subsidized provision of medicines structure, substantiation of new directions for the future development of the PEM system.

   Introduction. The rate of recurrence of respiratory tuberculosis is one of the indicators characterizing the effectiveness of anti-tuberculosis measures. Timely detection of patients with relapses is one of the priority approaches in solving the problem. Currently, with the introduction of big data processing technologies, namely artifi cial intelligence, various classifiers are used that take into account the totality of signs identifi ed in patients. The decision tree algorithm has proven itself widely in medical analytics. By analyzing these data, it is possible to classify the state of health and identify the first signs of tuberculosis recurrence.
   Aim. To develop and evaluate models for predicting a recurrence in patients with pulmonary tuberculosis caused by multidrug-resistant pathogen (MDR-TB), using logistic regression and decision tree.
   Materials and methods. The study included clinical and epidemiological, age, sex, social, medical and biological data of 346 patients with MDR-TB who successfully completed chemotherapy. Two observation groups were formed depending on the onset of recurrence of the disease in patients at least in the five-year follow-up period. The first group consisted of 35 patients with relapse, and the second one had 311 patients with no relapse. Statistical data processing for logistic regression was performed by IBM SPSS Statistics 23.0, the decision tree classifier was designed in the Scikit-learn 0.24.2 library in an interactive cloud environment with the Google Colaboratory code, using K-fold stratifi ed validation. The quantitative interpretation of the prediction results was carried out according to the ROC-curves (receiver operating characteristic) with the assessment of the AUC indicator (the area under the ROC-curve).
   Results. The sensitivity and specifi city of the logistic regression model and the decision tree classifi er for predicting tuberculosis recurrence were 98.7 %, 88.6 % and 74.0 %, 97.0 %, respectively.
   Conclusion. The created models can become a tool for predicting the recurrence of MDR-TB in cured patients.

   Introduction. Current approaches used to predict the recurrence of diffuse large B-cell lymphoma (DLBCL) with involvement of the central nervous system (CNS) need to be improved. Data from national studies on the incidence and clinical and laboratory characteristics of primary CNS DLBCL and secondary CNS involvement in systemic DLBCL are fragmentary and do not allow us to assess the overall picture.
   Aim. An assessment on the territory of the Siberian metropolis of data on the incidence and clinical and laboratory characteristics of DLBCL patients with primary CNS lymphoma (PCNSL) and secondary CNS involvement, as well as validation of the CNS-International Prognostic Index (CNS-IPI) on this sample.
   Materials and methods. The study group consisted of 47 patients with PCNSL and 35 with secondary CNS involvement in systemic DLBCL, the comparison group consisted of 202 patients with DLBCL without CNS involvement.
   Results. All patients with secondary CNS involvement in DLBCL belonged to the medium and high risk groups (p = 0.007) according to the CNS-IPI, which confi rms its prognostic value. The risk factors for secondary CNS involvement in DLBCL were ECOG performance status ≥ 2, HIV infection, age over 60 years, a history of chronic kidney disease, ≥ 2 extranodal sites, and high expression of Ki-67 (> 75 % positive tumor cells), non-GCB subtype of lymphoma, and presence of anemia. When assessing the characteristics of the clinical course of the disease, a number of peculiarities of the primary and secondary CNS involvement in DLBCL were identifi ed. In particular, in terms of overall survival, the PCNSL group had a more favorable prognosis (p = 0.051).
   Conclusion. The results of the study confi rm the importance of the CNS-IPI as a tool of a hematologist to determine the group of patients needing prevention of recurrence of DLBCL in the CNS. New data on a higher incidence of chronic kidney disease, arterial hypertension and thyroid disorders in the group of patients with PCNSL require further study.

   Introduction. The maternal mortality (MM) rate is a direct indicator of the quality of the healthcare system, primarily the obstetric and gynecological services, and at the same time makes it possible to judge the socio-economic development of a country or regions.
   Aim. An analysis of the main causes of MM and the structure of defects in the quality of medical care to the population of the Turkestan Region of the Republic of Kazakhstan.
   Materials and methods. The study was carried out in 2020 based on the material of 16 autopsies performed at the Turkestan Regional Anatomic Pathology Bureau and the Laboratory of Pathomorphology of the Clinical
Diagnostic Center of the Akhmet Yassawi International Kazakh-Turkish University (Republic of Kazakhstan). A complex of modern research methods was used: pathoanatomic, medical-statistical and retrospective.
   Results. The main primary causes of MM in the Republic of Kazakhstan in 2015–2020 were extragenital pathology, obstetric hemorrhage, preeclampsia and eclampsia, septic infections and complications of abortions. In the structure of medical care defects, those of treatment prevailed (47.2 %). In 31.5 % of cases, there were diagnostic defects, in 23.6 % incomplete examination of patients was noted, in 7.9 % – incorrect or untimely diagnosis. Organizational defects in the provision of medical care were observed in 6.3 % of cases. In 15.0 % of cases, there were no defects in the quality of medical care.
   Conclusion. The analysis of the identifi ed defects in the quality of medical care will allow the healthcare authorities of Kazakhstan to improve the quality of medical and preventive care for pregnant women.

   The article is devoted to the global problems of modern medicine – HIV infection and the COVID-19 pandemic. The review of the literature highlights current ideas about the pathogenesis and course of COVID-19 in patients with HIV infection, and also touches upon the problems of concomitant pathology and mental health of patients with HIV in the setting of the COVID-19 pandemic. It has been shown that HIV-positive patients are a risk group for the severe course of COVID-19, in particular, individuals with severe immunodefi ciency (CD4+ T lymphocytes ≤ 200 cells/μl) due to the development of synergetic lung damage by SARS-CoV-2 and secondary infectious agents such as cytomegalovirus and Pneumocystis carinii. It has been proven that one of the targets of the SARS-CoV-2 virus is CD4+ T cells, which in COVID-19 leads to a more rapid progression of immunodefi ciency in patients with HIV infection and, thus, signifi cantly increases the risk of secondary diseases and death. Particular attention should be paid to middle-aged and elderly people living with HIV, who, compared with HIV-negative patients, are more likely to have concomitant pathology – arterial hypertension, cardiomyopathy and diabetes mellitus, which are the risk factors for severe COVID-19. The results of studies on the eff ect of antiretroviral drugs on the course of COVID-19 showed that HIV-infected patients receiving tenofovir + emtricitabine have a lower risk of severe COVID-19 and associated hospitalization than patients receiving other HIV treatment regimens. Clinical and preclinical data support the potential use of tenofovir in the treatment of novel coronavirus infection.