Introduction. The main demographic indicators in the country depend on the characteristics of the reproductive behavior of today’s children and adolescents. Sex education, usually realized in the family, plays a key role in the formation of reproductive behavior, and should not only be timely but also informative, which cannot be achieved without the health care system support.

Aim. To determine trends in the reproductive behavior of adolescent girls and the degree of involvement of medical professionals in the process of sex education for girls and adolescent girls.

Materials and methods. An anonymous survey was conducted among 400 girls aged 15 to 18 years (average age 16.3 years) who had applied to the Clinical Center for Family Health and Reproduction, and of 34 obstetrician-gynecologists providing care to minors.

Results. According to the survey results, to maintain reproductive and sexual health, adolescent girls need information and comprehensive preventive education on reproductive health issues which will give them the knowledge and skills to determine their behavior. According to estimates of obstetrician-gynecologists, there is a popular request for online consultation of parents of girls and adolescent girls on issues of reproductive health and behavior, but doctors do not always have the opportunity to render this type of consultation, although they consider these measures one of the ways for the reproductive health promotion of children and adolescents.

Conclusion. The development of an electronic resource containing prevention-focused information on reproductive behavior and health issues will optimize preventive work with girls and adolescent girls, and will also make the adolescent health care system as effective and available as possible, thus allowing the formation of models of normal reproductive behavior of children and adolescents and preserving the reproductive potential of the population.

Introduction. It is difficult for primary care physicians to use, under conditions of limited consultation time, multi-page orders for prevention and outpatient follow-up, clinical guidelines on arterial hypertension (AH) in adults. At the same time, compliance with the basic time characteristics of orders and clinical guidelines is important for effective management of hypertension patients.

Aim. To study some aspects of the work of a general practioner in real life outpatient practice in screening and following-up of patients with hypertension and to present simple algorithms for routing such patients, which are a synthesis of clinical guidelines for hypertension and basic orders.

Materials and methods. A survey of patients waiting for an attendance of a general practioner was performed simultaneously, once in three outpatient clinics of Khabarovsk. The survey included all patients waiting for an appointment at the time of the study, regardless of gender, age and purpose of the visit. A questionnaire contained 5 questions: about the presence of blood pressure (BP) up to 140/90 mm Hg and higher; established diagnosis of AH; administered medications (without specifying which ones and their dosage) to correct high BP; by which specialist he is followed-up with the diagnosis of AH, and what the purpose of this visit to the outpatient clinic is. From the outpatient records of the interviewed patients, information about BP measurement that day at the attendance was obtained; presence of a previously established diagnosis of AH; adding AH to the diagnosis structure that day; previously prescribed treatment for AH; achieving BP targets; compliance with the standard of examination for AH; date of last visit due to hypertension.

Results. The responses of 149 patients were analyzed. A male/female ratio was 1:4 (31:118 people), average age was 64.4 ± 1.3 years. In 77.2% (115 people), BP had ever increased to 140/90 mm Hg and higher, of which the diagnosis of hypertension was established in 103 (69%) respondents. 87 (84.5%) patients diagnosed AH are followed-up by a doctor. At the doctor’s appointment, BP was measured in 95 people out of 149 (63.8%), and in 74 people (71.8%) out of 103 diagnosed with AH. On the appointment day, AH was included in the diagnosis structure only in 42.7% patients with an already established diagnosis of AH. In 39% of cases, non-compliance with the minimum required frequency of visiting a doctor for AH was revealed, which was less than once a year.

Conclusion. To achieve the target BP level in AH management is important to comply with the time intervals while working with AH patients: establishing a diagnosis, excluding secondary AH, initiating the outpatient follow-up, achieving the BP targets and timely referral to a cardiologist. The algorithms proposed for a general practitioner will help ensure the correct routing of patients with AH, compliance with the standard of management of such patients, achieving BP control and reducing the risks of development and progression of cardiovascular diseases.

Introduction. Over the past 10 years, there has been an increase in HIV-1 resistance to antiretroviral drugs worldwide. HIV infection patients with low adherence to antiretroviral therapy (ART) are most often at risk of developing acquired HIV-₁ resistance. The identification of key factors affecting the degree of adherence will allow timely detection of patients with a high risk of poor adherence to ART and treatment defaulting, and develop individual management tactics for such patients to reduce the risk of resistance development.

Aim. To study the factors influencing adherence to ART in patients with virological failure and the  effect of adherence on the risk of developing acquired HIV-₁ resistance to  first-line antiretroviral drugs.

Materials and methods. Two hundred and seventy one patients with an confirmed diagnosis of HIV infection, with di ff erent stages of the disease, aged 21 to 59 years, who were followed-up from March 2018 to August 2022 at the Center for the Prevention and Control of AIDS (City Infectious Clinical Hospital No. 1, Novosibirsk) and received ART, were enrolled in a study. The criterion to include patients in the study was a virological breakthrough during previously effective ART with  first-line drugs (when an undetectable level of HIV RNA load was recorded for 3–6 months). A retrospective analysis of the degree of adherence to ART of the studied patients with HIV infection and virological break-through was performed, considering various factors. The HIV-₁ drug resistance testing was carried out based on the State Research Center of Virology and Biotechnology VECTOR.

Results. Men predominated among the patients – 56.4% (n = 153). The average age was 35.4 ± 2.85 years. Hetero-sexual transmission of HIV was dominant – 64.8%. Parenteral transmission of HIV (intravenous drug abuse) accounted for 31.5% of cases. According to the results of the retrospective analysis of the degree of adherence to ART, it was found that  48.3% (131 out of 271) of patients had missed medications, including low adherence in 31.7% (86 out of 271) patients; aver-age – in 16.6% of patients (45 out of 271). Most often, poor adherence was reported in people with parenteral HIV transmission– 75.3% compared with sexual transmission – 36% (p < 0.001), and in rural residents – 62.5% compared with urban residents – 34.1% (p < 0.001). Among men, missed medication was detected more often than in women – 57.5 and 36.4%, respectively ( p < 0.001). Also, a significant factor was the lack of permanent employment – poor adherence was in 69.5% of patients in this group compared with patients having permanent employment – 26.3% ( p < 0.05). On the contrary, high adherence was more often observed in female patients – 63.6% compared with male ones – 42.5%; in the presence of permanent employment – 73.7% compared with 30.5% in it’s absence; in the case of sexual transmission – 64.0% compared with parenteral transmission – 24.7%; in urban residents – 65.9% versus 37.5% in rural residents (p < 0.05).According to the totality of all mutations revealed, HIV drug-resistant variants were found in 54.6% of the patients with virological ART failure (148 out of 271). Of the 148 HIV-1 drug-resistant variants, a combination of drug resistance mutations from the group of nucleoside reverse transcriptase inhibitors (NRTIs) was most often detected and non-nucleoside reverse transcriptase inhibitors (NNRTIs) – in 60.1% (89 cases). Isolated mutations to NRTIs were found in 15.5% (23) cases, for NNRTIs – in 12.2% (18). A combination of mutations of resistance to NRTIs + integrase inhibitors (IIs) was found in 4.1% (6) patients. The proportion of patients with resistance to NRTIs and PIs (protease inhibitors) was 2% (3); to NRTIs + IIs – 1.4% (2). A combination of mutations to three classes of drugs at once was detected in 6 patients: NRTIs + NNRTIs + IIs – 2.7% (4) and NRTIs + NNRTIs + PIs – 1.4% (2). An isolated mutation to IIs was in one patient (0.6%).

Conclusion. The analysis showed that non-adherence was reported in a significant part of patients – 48.3% (low – 31.7%, moderate – 16.6%). Factors contributing to poor adherence to ART were: parenteral transmission of HIV (in 75.3% of people with poor adherence); living in rural areas (in 62.5%); lack of permanent employment (in 69.5%); male sex (in 57.5%). Among patients with detected HIV drug resistance (n = 148), individuals with poor adherence prevailed (70.9%) compared with patients who did not have HIV drug resistance (23.6%) (p < 0.001). Taking into account the data obtained, when choosing the initial ART regimen, it is necessary to analyze the degree of risk of non-adherence depending on social and other factors. The high frequency of registration of HIV drug-resistant mutations found in the Novosibirsk Region necessitates timely testing for drug-resistant HIV patients with virological ART failure and the introduction of screening for primary drug resistance in patients at risk of poor adherence.

I n t r o d u c t i o n. The reproducibility of the effect of any herbal medicinal product or its effectiveness depends on the quantitative variability of the chemical composition of medicinal plant raw materials (MPRM).

A i m. A study of the individual variability of biologically active compounds (BAC) of the phenolic complex of Nonea (N.  rossica Steven) herb and the determination of statistically valid quality criteria for MPRM.

M a t e r i a l s  a n d  m e t h o d s . The objects of the study were specimens of N. rossica Steven herb obtained from plants collected at different points of the range in its typical habitats during the flowering phase in 2017–2022. The content of BAC markers – flavonoids, cinnamic acids and lactone compounds was determined by spectrophotometry.

R e s u l t s. As a result of the analysis of the content of BAC markers of 12 plants growing in one cropping area, it was found that the coefficient of variation does not exceed 24%, so, the studied sample is uniformed. The homogeneity of the sample makes it possible to statistically correctly combine individual specimens and form a combined sample for plants collected within the cropping area. An analysis of the content of BAC markers in raw materials collected at various points of the range (combined samples) showed that the coefficient of variation increased slightly and did not exceed the critical value of 33%. Here, the combined samples under consideration are also homogeneous, which makes it possible to determine confidence intervals for varying the content of BAC markers.

C o n c l u s i o n. The criteria for the quality of raw materials have been established: the content of flavonoids in terms of rutin should be at least 0.68%, cinnamic acids in terms of caffeic acid – at least 1.9%, lactones in terms of 2-hydroxycinnamicacid – at least 0.25%.

Introduction. Thanks to magnetic resonance imaging (MRI), a detailed study of the structure of the cervical  intervertebral discs is possible.

Aim. To identify the morphometric features of the cervical intervertebral discs during the development of degenerative  and dystrophic changes.

Materials and methods. A total of 203 MR images were analyzed, obtained during the examination of  volunteers from 18 to 84 years using conventional methods on 1–1.5 T MR scanners. The height of the intervertebral discs  was measured at C7–C3 segments. The obtained data were grouped into tables and statistical analysis was carried out using  Microsoft Excel 2007.

Results. Three groups were formed according to the severity of changes in the cervical spine and gender: 1st – with-out substantial changes in the cervical spine; 2nd – moderate changes; 3rd – pronounces changes in the cervical spine. The  greatest changes in the vertical dimension of intervertebral discs are observed in men. The mean intervertebral disc height  at the level from C6/7 to C4/5 decreases in men from the 1st to the 3rd group; in women, on the contrary, the height of the  C4/5 disc decreases from the 3rd group. The height of the C2/3 intervertebral disc was the largest in the 3rd group.

Conclusion. The presented results indicate a decrease in the intervertebral disc height due to the progression of  degenerative and dystrophic changes. The opposite dynamics were noted for C2/3 and C4/5 intervertebral discs among  women – a decrease in the height from the 3rd to the 1st group. The data obtained complete the information on the dynamics of changes in morphometric parameters taking into account the degenerative and dystrophic state of the studied structures and the gender of patients, which makes it possible to develop tools for computational analysis of diagnostic data,  improving the quality of medical care.

Introduction.  The methodology of pharmaceutical development provides for the preparation and analysis of experimental samples, in particular by the amount of an active substance in the dissolution/release medium. Modern spectral and chromatographic methods are used to standardize the quality of pharmaceutical substances, which significantly complicates testing samples. The development and validation of an accessible method for the spectrophotometric determination of trimetazidine dihydrochloride (TMD) is necessary to assess the release kinetics in the samples studied.

Aim. Development and validation of a spectrophotometric method for the quantitative determination of TMD.

Materials and methods. Pharmaceutical substances of TMD and excipients met the quality requirements of regulatory documents.  The certified devices, equipment and methods used complied with the requirements of the State Pharmacopoeia of the Russian Federation, 14th ed. and the recommendations of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH).

Results. To develop a method for the spectrophotometric determination of TMD, the maximum absorbance was detected at 269 ± 2 nm. Due to the need to quantify the release profiles of the active substance from experimental samples (granulates and tablets) of TMD in acidic medium and phosphate buffer (pH = 6.8 ± 0.05), the method was validated under such conditions. The constructed calibration curve showed that the linear range of the method is 5.0–25.0  μ g/ml with a correlation coefficient of 0.9994 in acidic medium (HCl 0.1 M) and 10.0–50.0 μ g/ml with a correlation coefficient of 0.9997 in phosphate buffer. Such characteristics of the method as specificity, accuracy and precision were within reference limits. The determination of TMD using this method in mixture models formulated into granules and tablets showed coincidence with the reference values within the limits of acceptable deviations.

Conclusion. A spectrophotometric method for the quantitative determination of TMD within the maximum absorbance at 269 ± 2 nm was developed and validated, which makes it possible to use it during pharmaceutical development.

Introduction.  The coronavirus disease (COVID-19) pandemic has prompted the study of problems of comorbidities, including widespread and highly pathogenic comorbid infectious diseases. Tuberculosis continues to be major infectious disease in terms of social life and epidemiology that can have a negative impact on the outcomes of patients with COVID-19 and other infectious diseases, including because of the association of pathogenetic mechanisms of these infectious diseases is still unclear. The study of risk factors for adverse outcomes of tuberculosis and COVID-19 co-infection will improve managing these diseases.

Aim. To evaluate the impact of changes in immunocompetent cell subsets and speci fi c treatment regimens on SARS-CoV-2 clearance in the respiratory tract of patients with COVID-19 and tuberculosis co-infection.

Materials and methods. In a retrospective cohort clinical study we have analyzed the clinical characteristics and duration of elimination of coronavirus (SARS-CoV-2) from the respiratory tract of 76 hospitalized patients with COVID-19 and active tuberculosis. The first group included 37 patients with COVID-19 and active pulmonary or extrapulmonary tuberculosis without signs of lymphogenous or hematogenous spread of Mycobacterium tuberculosis infection (TB P/EP). The second group included 39 patients with COVID-19 and disseminated tuberculosis (DTB).

Results. When constructing multiple regression models, the CD4⁺ count less than 80 cells/ μ l was the strongest determinant of delayed elimination of SARS-CoV-2 from the respiratory tract with a regression coefficient  ( β ± m) of 21.762 ± 6.250 (p = 0.002) and 10.853 ± 4.220 ( p = 0.015) in the  first and second groups, respectively. In combination with the duration of anti-tubercular therapy, antiretroviral therapy, anemia, and platelet count, these factors made it possible to predict a 68.1% variances in the duration of elimination of SARS-CoV-2 from the respiratory tract of patients with TB P/EP, and a 42.7% variances of this indicator in patient with COVID-19 and DTB co-infection.

Conclusion. A decrease in the CD4⁺ count less than 80 cells/μl, the duration of the intensive phase of anti-tubercular therapy, antiretroviral therapy, anemia, peripheral blood platelet count have a comprehensive impact on prolongation of SARS-CoV-2 elimination from the respiratory tract of patients with COVID-19 and tuberculosis co-infection.

Introduction. Luminal breast cancer (BC) occupies the largest proportion in the structure of the entire molecular landscape of this disease. During the ongoing treatment, most often hormone therapy, in part of patients, the disease progression develops, which makes necessary the search for new molecular predictors.

Aim of the research. To study the clinical and morphological features of the disease depending on BMI-1 and ROR1 expression in the primary tumor in luminal breast cancer patients during aromatase inhibitors therapy.

Materials and methods. The study included 80 patients with T1-2N0-1M0 operable primary breast cancer at the age of 62.1 ± 8.1 years. The primary tumor tissue was studied using immunohistochemistry. Antibodies to ROR1 and BMI-1 were used. The presence and degree of immunostaining, and the percentage of positively stained tumor cells were assessed. The expression parameters of the studied markers were assessed in relation to various clinical and pathological data of the disease.

Results. 70 patients had the luminal A subtype, 10 patients had the luminal B/HER2-negative subtype. Positive BMI-1 expression was observed in 64% of cases, ROR1 expression was less common and amounted to 24%. As tumor grade increases, the number of cases with positive ROR1 expression increases ( p < 0.05). The level of proliferative activity (Ki67) correlated with positive ROR1 expression ( ρ = 0.312, p = 0.03) and BMI-1 ( ρ = 0.310, p < 0.031). In presence of metastases to regional lymph nodes, the expression of both markers was significantly higher. The occurrence of distant metastases is associated with high levels of BMI-1 expression by primary tumor cells ( p < 0.05).

Conclusion. The study clearly demonstrates the correlation of ROR1 and BMI-1 proteins with the clinical and morphological parameters of the primary tumor and the course of the disease in luminal subtypes of breast cancer.

I n t r o d u c t i o n . Recent literature shows that exposure to heavy metals is an important and underestimated risk factor related to the development of atherosclerosis and its consequences.

A i m . To study the effect of chronic intoxication with different heavy metal salts (cadmium sulfate, nickel nitrate, and cobalt nitrate) on lipid metabolism in experimental atherosclerosis.

M a t e r i a l s  a n d  m e t h o d s . The experiments were conducted on 110 outbred male albino rats. Atherosclerosis was modeled according to I.V. Savitsky. After modeling atherosclerosis, the animals were chronically exposed to heavy metal salts (cadmium sulfate – 1 mg/kg, nickel nitrate – 2 mg/ kg and cobalt nitrate – 2 mg/kg) via drinking water for 60 days in four experimental series. The comparison group consisted of intact animals. To assess lipid metabolism, total cholesterol (TCH), triglycerides (TG), low-density lipoproteins (LDL), high-density lipoproteins (HDL) and the values of the atherogenic coefficient (AC) were determined.

R e s u l t s . After intoxication with various heavy metals of rats with modeled atherosclerosis, a marked aggravation of lipid metabolism disturbances – a significant increase in the level of TCH, TG, LDL and AC with a simultaneous decrease in the level of HDL in the blood serum is revealed. The maximal changes in the parameters of lipid metabolism are observed by the 60th day after intoxication in experimental atherosclerosis.

C o n c l u s i o n . Long-term exposure to heavy metals (cadmium sulfate, nickel nitrate and cobalt nitrate) exacerbates lipid metabolism disorders occurring in experimental atherosclerosis. According to the severity of pathological changes, the following are in descending order: cadmium sulfate → nickel nitrate → cobalt nitrate. Despite the fact that cobalt is one of the essential microelements, long-term exposure to it also leads to an aggravation of lipid metabolism disorders in experimental atherosclerosis.

Researches aimed at studying the role of TP53 gene variability in the tumor progression of diff use large B-cell lymphoma(DLBCL) are among the most in-demand in both the fields of fundamental and applied oncohematology. However, until recently, the knowledge about the specific mechanisms of dysfunction of this gene and their clinical significance in DLBCL was largely limited.

This article is dedicated to the 300th anniversary of the Russian Academy of Sciences and describes the main scientific results of research of the molecular genetic mechanisms and the significance of p53 deregulation in DLBCL, conducted jointly by Novosibirsk State Medical University and the Research Institute of Therapy and Preventive Medicine – the Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences for many years.

A comprehensive study of TP53 variability due to functionally significant polymorphisms and haplotype structure, somatic mutations, promoter methylation, as well as allelic imbalance was carried out. A two-hit mechanism for dysfunction of this anti-oncogene in the formation of lymphoma has been established. The current underestimation of the frequency of aberrations in TP53 in DLBCL is shown due to ignoring synonymous mutations and changes in non-coding regions of the gene.

The deep involvement of TP53 in the processes of predisposition to development, initiation, progression and response of DLBCL to therapy has been proven.

The results obtained suggest that assessment of the function of the TP53 gene and understanding the specific mechanisms of its inactivation in each of the diagnosed cases of DLBCL may soon have direct access to personalized selection of therapy.

In recent decades, for the treatment of patients with moderate to severe psoriasis, biologics have been actively developed, the use of which is recommended when the psoriasis systemic treatment is insufficiently effective or if there are contrain dications to it. However, in recent years, experts have increasingly raised the question of the use of biologics at an early stage of the aggressive course of the disease, especially in cases where psoriasis causes significant psychosocial maladjustmentin the patient, problems with establishing interpersonal and social relationships, a feeling of stigmatization and a decrease in the quality of work. Palmoplantar psoriasis which is associated with great difficulties in daily and occupational life requires special attention in this regard.

The article presents a case report that shows of the successful early use of therapy with biologics in a patient to relieve symptoms of palmoplantar psoriasis and distal interphalangeal psoriatic arthritis which began in the early stages of the disease due to a significant decrease in the quality of life and work activity, as well as of an emphatic refusal of systemic basic therapy with methotrexate.

After a 4-week initial course of secukinumab, almost complete regression of psoriatic eruptions and symptoms of psoriatic arthritis was noted. The patient’s psychoemotional state has stabilized. Performing manipulations related to one’s occupational duties does not cause any difficulties due to the disease.

Biologics for the treatment of moderate and severe forms of the disease has become a major advance allowing not only to obtain a high level of therapeutic response but also to successfully correct the psychosocial consequences of the disease.

Russian clinical guidelines use a stepwise approach to the treatment of psoriasis. The first-line systemic therapy includes basic anti-inflammatory drugs – methotrexate, retinoids for the treatment of psoriasis, cyclosporine, ultraviolet irradiation of the skin. In the case of their ineffectiveness, intolerance or the presence of contraindications, prescribing biologics is considered. The presented case report demonstrates that the patient’s emphatic refusal of systemic basic therapy for psoriasis can also be considered as a possible reason for the early use of biologics which allows recovering both the physical and psychosocial status of the patient.