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To date, the pathogenesis of COVID-19 associated multisystem inflammatory syndrome (MIS-C) remains unclear. Despite this, it becomes obvious that the pathogenesis of MIS-C is directly related to a certain immune dysregulation, however, a clear understanding of the mechanisms of this dysregulation has not yet been formulated. In order to identify the cytokine profile in patients with MIS-C, spontaneous and stimulated production of certain cytokines in cell culture was identified. Materials and methods. The study was conducted in the following study groups: group 1 — patients with MIS-C (n = 52); group 2 (comparison group) — patients with COVID-19 associated pneumonia (n = 15); group 3 (control group) — conditionally healthy patients (n = 23). The following stimulating agents were used: S58 — recombinant antigen Spike_SARS-Cov-2; NP is a recombinant NP antigen of the coronavirus SARS-CoV-2 and a standard mitogen. Results. Тhe absence of the initially expected hyperproduction of the main pro-inflammatory cytokines (IL-6, IL-8, TNF-α, etc.) was recorded. Statistically significant developments were recorded between patients of the study groups in the spontaneous production of MCP-1, in particular, the indicated indicator was 40010.82 (19698.1; 64812.1); 643.7 (214.6; 1695.4) and 622.7 (214.6; 1068.1), respectively. The indicated spontaneous hyperproduction of MCP-1 in patients with MIS-C allows us to consider as a probable completely new theory of the pathogenesis of MIS-C associated with dysregulation of the type 2 immune response. The presence of statistically significant differences, primarily in the spontaneous production of this cytokine, can apparently be explained by the presence of genetically determined determinants associated with subsequent dysfunction of the Th2 helper immune response, a potential trigger for which is a previous COVID-19 infection. Thus, further study of the immunopathogenesis of COVID-19 associated MIS-C is required.

Chronic heart failure (CHF) is a common complication of many cardiovascular diseases. It is important to study the clinical and functional features of CHF to clarify the further prognosis of this disease due to the unfavorable course and high mortality rate. Diagnosis and treatment of CHF is an issue for doctors of various specialties, in particular when it comes to geriatric patients with multiple concomitant diseases. Various physiological and morphological transformations in the aging population contribute to heart failure. The most common type of HF in older people is HF with preserved ejection fraction. Atypical clinical symptoms of CHF are much more common in elderly people than in young people. The prevalence of HF with age is associated with a longer period of influence of damaging factors on the heart, such as arterial hypertension, metabolic stress or ischemia-related damage. Due to the unfavorable course and high mortality rate, it is important to study the clinical and functional characteristics of CHF to clarify its prognosis. However, the data available on this issue vary significantly; the mechanisms, issues of diagnosis and treatment of patients with heart failure in different age groups have not been sufficiently studied, which determined the purpose of this study ‒ to investigate the features of the clinical and functional characteristics of CHF depending on age. Material and methods. The study included 90 male and female patients with diagnosed CHF stages I-IIB, NYHA functional class I-IV, aged 40–86 years, who underwent echocardiography, general and biochemical blood tests. The patients were divided into two groups: group 1 – patients of working age (women 16–54 years old and men 16–59 years old, n = 20), group 2 – patients older than working age (women 55 years and older, men 60 years and older, n = 70). Results and its discussion. According to the data obtained, the average age of all surveyed was 68.1 ± 9.8 years. The second stage of CHF prevailed in both the first and second groups of the studied categories of participants. Atypical symptoms prevailed, which creates difficulties in its diagnosis and treatment. The frequency of CHF decompensation in patients over working age, as well as the concentration of natriuretic peptide, is higher compared to the group of CHF patients of working age, which is probably due to the presence of comorbid pathology and cognitive deficit. The data obtained can be used to develop an approach to stratify the risk of CHF.

Among the many diseases that affect potato plants, viral infections are the most common and cause significant damage to farms, affecting both the yield and quality of potatoes. In this regard, an important condition for preserving the potato seed fund in Russia is systematic monitoring and early highly specific detection of potato viral infections. The purpose of the work is to study samples of potato varieties collected in the Novosibirsk region for the presence of viral infections using RT-PCR. 130 potato plants from three districts of the Novosibirsk region (NR) were studied. As a result of monitoring, the following viruses were identified: PVY (potato virus Y), PVS (potato virus S), PVM (potato virus M) and PVX (potato virus X). The quarantine pathogen potato spindle tuber viroid (PSTVd) was not detected in any of the samples analyzed. The maximum frequency of occurrence in the region was noted for three viruses: PVY, PVM and PVS. A significant proportion of the samples were mixed viral infections: the occurrence of the combination of infection PVY + PVM in plants was 25.0 %, and PVY + PVS, 22.6 %. To develop methods for determining the strain affiliation of the studied samples, the nucleotide sequences of the capsid protein genes of 10 Y-virus isolates were sequenced. Phylogenetic analysis of the studied sequences of NR isolates was carried out with a set of sequences of reference strains 261-4, Eu-N, N:O, NE-11, NTNa, NTNb, N-Wi, O, O5, SYR_I, SYR_II and SYR_III retrieved from GenBank. As a result of phylogenetic analysis, it was established that NR viral samples fell into two groups of strains: group 1, which also includes isolates of the reference strains 261-4/SYR_III, and group 2, NTNa. The obtained results of the strain affiliation of NR samples lay the basis for the development of DNA and immunodiagnostic systems for identifying PVY circulating in NR, as well as for elucidating the source and routes of entry of specific virus strains.

The impact of the new coronavirus COVID-19 infection on the course of pregnancy, maternal and child health is largely unclear and controversial. The presented literature review analyzes changes in the immune, cardiovascular, and endocrine systems in women in physiological pregnancy. The peculiarities of the course of infection caused by SARS-CoV-2 virus in pregnancy, depending on the virus variant, are presented, the issues of infection pathways into immune and non-immune cells, including placental cells, as well as the issues of transplacental transfer of the virus – the key moment of infection of the embryo or fetus, on which the outcome of pregnancy also largely depends, are considered. Promising approaches to COVID-19 therapy are presented: use of inhibitors of transmembrane serine protease 2 (TMPRSS2), furin, angiotensin-converting enzyme (ACE2) and RNA-dependent RNA polymerase, amnion epithelial cells and their exosomes. At the same time, the potential use of mesenchymal stem cells in patients with severe COVID-19 pneumonia is reviewed. Difficulties and questions regarding the use of the above therapeutic methods in pregnant women are highlighted. Aspects of the use of surfactant preparations in newborns at risk of new coronavirus infection are considered.

To conduct a study of the quality of life of children who have suffered from multisystem inflammatory syndrome (MIS‐C) associated with SARSCoV‐2 in the post‐rehabilitation period against the background of correction of microecological imbalance.The study involved 49 children aged 2 to 12 years who underwent MIS‐C associated with SARS‐CoV‐2 and received treatment in a hospital (DGKB No. 3 in Novosibirsk), and then underwent rehabilitation on an outpatient basis. The duration of rehabilitation was 7–8 weeks. All children were prescribed a course of additional rehabilitation for 30 days in order to correct microecological imbalance, which included: Biovestin, a dietary supplement in liquid form, containing bifidobacteria of the Bifidobacterium longum MC‐42 strain; the official drug, Kudesan, (active ingredient Coenzyme Q10); and the official drug, Succinic Acid. The assessment of physical, social, educational, emotional and psychological functioning, as well as quality of life as an integrating indicator before and after a comprehensive rehabilitation course using the parental form of the Reds OL Generic Core Scales questionnaire (Russian version) was carried out.After the rehabilitation course, children who underwent MIS‐C associated with SARS‐CoV‐2 showed signs of dysfunction of various organs and systems, which may be the result of an imbalance in the microbial ecosystem and requires mandatory correction. The introduction of a probiotic product and drugs affecting metabolic processes into the rehabilitation course led to a decrease in inflammatory reactions, as well as normalisation of metabolic processes and increased oxygenation, which improved the condition of the children and their quality of life.Federal Research Center for Fundamental and Translational Medicine (FRC FTM), Siberian Branch, Russian Academy of Sciences

Adaptogens are a category of herbal medicinal products that enhance the adaptive reserves of the body, resistance to extreme factors and survival under stress. Adaptogenic properties have been revealed in dozens of plants, in particular, preparations based on raw materials from the Lady’s Mantle (Alchemilla vulgaris L.), a perennial herbaceous plant from the family Rosaceae, have a wide range of biological activity, including antioxidant, antiinflammatory, neuroprotective, anticancer and other, which allows them to be used for prevention and supportive therapy in the treatment of many pathological processes. The results of the authors’ own research and a number of literature data substantiate the presence of adaptogenic properties in this plant. The review analyzes the information in the scientific literature on the chemical composition of compounds included in preparations based on A. vulgaris raw materials, the modern interpretation of the concept of “adaptogen” and criteria for evaluating the adaptogenic properties of plants, and discusses possible molecular and cellular mechanisms that ensure the presence of such properties in the Lady’s Mantle.

Aim. To study risk factors for fatal cardiovascular events in patients with non-small cell lung cancer over two years of standard treatment.Material and methods. This pilot retrospective non-randomized cohort study included 179 patients who were consecutively admitted to the chemotherapy department of City Clinical Hospital 1 from January to December 2020 with a confirmed diagnosis of non-small cell lung cancer based on the comprehensive examination and morphological verification according to the 2018 clinical guidelines on bronchial and lung cancer. Diagnosis and treatment of cardiovascular diseases were carried out according to national clinical guidelines. The follow-up period for non-small cell lung cancer and cardiovascular disease was 2 years. Logistic regression models were considered to assess the risk of cardiovascular death. The model accuracy was assessed by a cross-validation.Results. The best model in terms of the sensitivity and specificity sum according to a cross-validation was the model with the following explanatory variables: sex, cancer stage, platinum-based chemotherapy, etoposide, immunotherapy, surgical treatment. This model showed a sensitivity of 70,1% and a specificity of 82,1%.Conclusion. This approach is easy to implement and may optimize treatment for patients with non-small cell lung cancer.

Currently the “rejuvenation” and an increase in the number of components of the metabolic syndrome (MS) determine its clinical significance in the earlier development of diabetes mellitus, cardiovascular diseases and related complications. Aim of the study was to investigate the features of the MS clinic picture in a population of young men and womenliving in the Khanty-Mansiysk autonomous region – Yugra.Material and methods. The study included 863 young people between 18 and 44 years of age, including 344 men and women with MS and 519 people in the comparison group. Studied subgroups are represented by non-indigenous men and women living in urban and rural areas, and indigenous rural residents. The analysis of MS clinical and laboratory parameters was carried out and its clinical variants in ethnic groups were identified.Results and its discussion. According to the results of the survey of young people with metabolic syndrome, it was revealed that the combination of abdominal obesity and two components of MS were most common in young people with MS (in 50.0 % men and in 55.5 % women). The study defined regression models for each MS group and threshold values for waist circumference were set, which changes in lipid and carbohydrate metabolism were predicted.Conclusions. In groups with MS, hypertriglyceridemia was determined as its most common component. The study identified the most frequent association of abdominal obesity with hyper-LDL cholesterol and hypertriglyceridemia in patients with metabolic syndrome, in ethnic groups, this combination is more common in indigenous rural men (53.3 %) and in non-indigenous urban women (54.3 %).

The pandemic of a new corona virus infection (NCVI) has worsened the already unfavorable demographic situation in the Russian Federation. Aim of the study was to assess the changes in the demographic situation in the country and the Siberian Federal District and the causes contributing to them. Material and methods. Statistical data of the Ministry of Health of the Russian Federation, Rosstat, regional ministries of health of subjects belonging to the Siberian Federal District, and literature on the problems of demography were used. The following methods were used: analytical, historical, statistical, including statistical observation, summary and grouping of materials, absolute and relative statistical values, sampling. Results and discussion. The pandemic period of the new coronavirus infection in RF and SFD is characterized by a substantial increase in the mortality rate, which became the maximum in the newest history of Russia, i.e. since 1991. The structure of the main causes of death has changed. Diseases of the circulatory system, neoplasms, diseases of the digestive organs and external causes, accounted for 76.6 % of all causes in 2019, in 2021 they accounted for only 60.1 %, with NCVI taking second place among causes of death (19.1 %). The birth rate remains at a low level, and in 2021 was 9.6 per 1000 population, which is 16.5 % lower than in 2017, due to which the natural decline in population has significantly increased (to –6.3 in Russia and to –7.0 per 1000 population in SFD) and the average life expectancy has decreased. Conclusions. All of the foregoing points to the ineffectiveness of measures to prevent and forestall the adverse effects of the pandemic, which is practically inevitable in the case of new, poorly studied infectious diseases. The measures taken to organize medical care to the population in the conditions of the pandemic have not been adequate. This is evidenced by the higher rates of total mortality of the population, compared to the probable ones (caused by the increase in mortality from NCVI), a significant increase in natural population decline and a reduction in life expectancy.

Abstract Metabolomic analysis of blood plasma samples from COVID-19 patients is a promising approach allowing for the evaluation of disease progression. We performed the metabolomic analysis of plasma samples of 30 COVID-19 patients and the 19 controls using the high-performance liquid chromatography (HPLC) coupled with tandem mass spectrometric detection (LC–MS/MS). In our analysis, we identified 103 metabolites enriched in KEGG metabolic pathways such as amino acid metabolism and the biosynthesis of aminoacyl-tRNAs, which differed significantly between the COVID-19 patients and the controls. Using ANDSystem software, we performed the reconstruction of gene networks describing the potential genetic regulation of metabolic pathways perturbed in COVID-19 patients by SARS-CoV-2 proteins. The nonstructural proteins of SARS-CoV-2 (orf8 and nsp5) and structural protein E were involved in the greater number of regulatory pathways. The reconstructed gene networks suggest the hypotheses on the molecular mechanisms of virus-host interactions in COVID-19 pathology and provide a basis for the further experimental and computer studies of the regulation of metabolic pathways by SARS-CoV-2 proteins. Our metabolomic analysis suggests the need for nonstructural protein-based vaccines and the control strategy to reduce the disease progression of COVID-19.

Multisystem inflammatory syndrome (MIS-C) is a new childhood disease associated with coronavirus SARS-CoV-2 that manifests itself 3–4 weeks after infection. The development of MIS-C is possible, despite the asymptomatic course of coronavirus infection. The pathogenetic features of MIS-C remain unclear. The aim of the study was to investigate the state of peripheral blood parameters in children with multisystem inflammatory syndrome associated with SARS-CoV-2 upon admission to a hospital. Material and methods. We examined 52 children with MIS-C from 1 to 14 years old, hospitalized in Children`s Clinical Hospital No. 3 in Novosibirsk in October–December 2020. Testing for the isolation of SARS-CoV-2 RNA in scrapings from the nasopharynx and oropharynx was carried out using real time PCR (test systems of DNA-Technology, Russia). The presence of specific IgM and IgG antibodies to SARS-CoV-2 in blood serum was determined by ELISA using Vector-Best kits (Russia). Results and discussion. It was noted that SARS-CoV-2 virus RNA was found only in 12.8 % of cases, while specific IgG antibodies in blood serum were detected in 100 % of children. IgM to SARS-CoV-2 antigens were detected in the blood serum only in 53.85 % of children with MIS-C. It has been established that unexpressed leukocytosis was found both in children under the age of 7 and in children of 8–14 years old. However, the leukocytes content in children of the older age group was significantly lower than in children aged 1–7 years. At the same time, in both age groups, some children had extremely low values of the indicator. The causes of severe leukopenia against the background of excessive inflammation remain unclear. Age groups (1–7 and 8–14 years) do not differ statistically significantly in the relative content of lymphocytes and neutrophils. In the study of individual values of the relative content of lymphocytes within the age groups, it was noted that only some children had lymphopenia of varying severity. Conclusions. Against the background of minor leukocytosis in children with MIS-C, upon admission to the hospital, there is a tendency to develop both relative and absolute lymphopenia, regardless of age. The study noted an extremely pronounced variability of individual values of the evaluated peripheral blood parameters, regardless of age, which, with similar clinical symptoms, characterized as MIS-C, requires further study in dynamics, taking into account the initial values of the indicators.There is no pronounced relationship between the leukocytes content and specific IgM antibodies to SARS-CoV-2 antigens in the blood.

The transformations of domestic healthcare carried out in the last three decades have not led to the planned results, and in some areas the consequences have turned out to be negative. Rural healthcare suffered the most significantly. The aim of the study was based on the analysis of the situation in the rural health care of the country to propose measures to improve it. Material and methods. The statistical data of the Ministry of Health of Russia, Rosstat, Central Research Institute of Organization and Informatization of Healthcare, as well as data on the Siberian Federal District for the period from 1990 to 2020 were used. Scientific publications on the problem under consideration have been studied. Results and their discussion. The course taken in the early 90s of the last century towards the commercialization of medicine remains. So for the period from 2005 to 2018 in the structure of the country’s medical personnel, the number of people employed in the public sector decreased from 93.6 to 86.8 % (by 237 000), whereas in private medical organizations it increased by 2.3 times. In 2020, 38.4 % of medical organizations were already private. The most significant changes have occurred in rural healthcare. The number of paramedic and obstetric stations decreased by 21.1 %, the provision of beds in hospitals is 2 times lower than the national average, and doctors are 3 times fewer than in cities. In the age structure, the share of doctors over the age of 60 increased from 13.5 % (2017) to 18.1 % (2020). The implementation of the programs “Zemsky Doctor” and “Zemsky paramedic” did not lead to an increase in the provision of medical workers in rural areas. Today, medical care is geographically available only to 49 % of villagers, for 40 % it is difficult to access, and 9 % is practically inaccessible (2 % of respondents could not answer the question). This has led to the fact that the average life expectancy of the villagers is 1.5 years lower than that of the townspeople, and the total mortality is 1.2 % higher than the national average. Conclusion. The problem of accessibility of medical care to the rural population has worsened in the last three decades. The implemented programs aimed at improving its accessibility and quality, including for rural residents, have not led to a significant positive result.

BACKGROUND: The prevalence of Type 2 diabetes mellitus (T2DM) has reached epidemic proportions and it is estimated to affect over 400 million people worldwide. Moreover, the incidence of diabetes is expected to continue to rise and it is projected to affect nearly one of the three individuals by the year 2050. These alarming projections suggest that there is an urgent need for the development and implementation of novel prevention and treatment strategies to combat the rise in T2DM.AIM: To study the possibility of using polymorphisms of genes SLC30A8 and MC4R as markers for predicting the development of T2D in the population of Novosibirsk.MATERIALS AND METHODS: On the basis of prospective follow-up of a representative population sample of residents of Novosibirsk (The HAPIEE Project), 2 groups were formed according to the “case-control” principle (case — people who had diabetes mellitus 2 over 10 years of follow-up, and control — people who did not developed disorders of carbohydrate metabolism). T2D group (n = 443, mean age 56.2 ± 6.7 years, men — 29.6%, women — 70.4%), control group (n = 532, mean age 56.1 ± 7.1 years, men — 32.7%, women — 67.3%). DNA was isolated by phenol-chloroform extraction. Genotyping was performed by the method of polymerase chain reaction with subsequent analysis of restriction fragment length polymorphism, polymerase chain reaction in real time. Statistical processing was carried out using the SPSS 16.0 software package.RESULTS: Genotype TT rs13266634 of the SLC30A8 gene was associated with the risk of developing T2D (relative risk — RR 1.51, 95% confidence interval — CI 1.11–2.05, p =0.008). The CC genotype rs13266634 of the SLC30A8 gene was associated with a protective effect against T2D (RR 0.57, 95% CI 0.35–0.92, p=0.026). No significant effect of rs17782313 of the MC4R gene on the risk of developing T2D was found.CONCLUSION: The rs13266634 polymorphism of the SLC30A8 gene confirmed its association with the prognosis of the development of T2D, which indicates the possibility of considering it as a candidate for inclusion in a diabetes risk score. The association between polymorphisms rs17782313 of the MC4R gene and the prognosis of the development of T2D was not found.

The Russian Society of Cardiology (RKO)With the participation of: The National Society for the Study of Atherosclerosis (NOA), the Russian Association of Endocrinologists (RAE), the Russian Society of Cardiosomatic Rehabilitation and Secondary Prevention (RosOKR), the Russian Scientific Medical Society of Therapists (RNMOT), the Eurasian Association of Cardiologists, the Eurasian Association of Therapists (EAT), the Russian Association of Gerontologists and Geriatricians

Objective: to establish associations of cognitive functions (CFs) and professional level in an open population of Novosibirsk aged 25–44 years.Patients and methods. The subject of the study was a random representative sample of one of the Novosibirsk districts population aged 25–44 years (463 men, mean age 35.94±5.957 years, and 546 women, mean age 36.17±5.997 years) in 2013–2016. CFs were screened using: A.R. Luria 10 words learning task – immediate and delayed recall after the interfering task; Bourdon Test (BT); exclusion of “the fifth extra” test; verbal fluency test (naming animals in 1 min). Education level and professional status were assessed according to the criteria of the WHO international program MONICA protocol.Results and discussion. The analysis showed that the management and engineering and technical staff (ETS) coped significantly better with cognitive tests than manual labor workers. The analysis of memory using the A.R. Luria test showed that the differences in the first recall of 10 words between manual labor workers and managers reached 0.849 words, in the mean number of correctly remembered words it reached 0.735 words, and in delayed recall – 1.096 words (p

Aim. To investigate polymorphisms of 18 genes as possible molecular genetic markers of predisposition or resistance to development of non-infective (NE) or infective endocarditis (IE).Materials and methods. The study encompassed 81 patients with NE and 94 patients with IE. The control group included 225 conditionally healthy people. Polymorphisms of 18 genes were tested using polymerase chain reaction (PCR).Results. For the first time, a statistically significant relationship was identified between gene polymorphisms and valvular vegetations: for genes in the hemostatic system – rs6025 (1691 G > A) of the F5 gene (AG genotype), rs1126643 (807 C > T) of the ITGA2 gene (TT genotype); for folate pathway genes – rs1805087 (2756 A > G) of the MTR gene (AG genotype) and rs11697325 (–8202 A/G) of the MMP9 gene (AA genotype) and rs2476601 (C1858T) of the PTPN22 gene (TT genotype). The protective effect of gene polymorphisms was revealed: for the NOS3 gene (4b / 4b genotype) and G (–572) C of the IL6 gene (CC genotype). For two polymorphisms, an association with thromboembolic complications in NE was revealed: rs1126643 (807 C > T) of the ITGA2 gene and rs1799889 (–675 5G > 4G) of the PAI (SERPINE1) gene. In IE, such an association was detected for the polymorphism rs11697325 (–8202 A/G) of the MMP-9 gene.Conclusion. The polymorphisms of candidate genes were revealed, that are associated with the clinical and hemostasiological characteristics of IE and NE. In NE, for the first time, the association with thromboembolic complications was identified for two polymorphisms: rs1126643 (807 C > T) of the ITGA2 gene and rs1799889 (– 675 5G > 4G) of the PAI-1 (SERPINE1) gene. In IE, such a relationship was detected for one polymorphism – rs11697325 (8202 A/G) of the MMP-9 gene.

Introduction. The COVID-19 pandemic has become a huge challenge for the entire healthcare system, medical institutions and doctors. The results of the industry’s activities turned out to be insufficiently effective, and therefore it is necessary to analyze not only what is directly related to the coronavirus infection, but also the consequences that the pandemic has led to. Goal. To analyze the results and consequences of health care activities and the health status of the population of the Siberian Federal District during the COVID-19 pandemic. Material and methods. The statistical data of the Ministry of Health of the Russian Federation, Rosstat, the Central Research Institute for the Organization and Informatization of Healthcare (TSNIIOIS), the Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, as well as data for the Siberian Federal District were used. Scientific publications on the problem under consideration have been studied. Results and discussion. In connection with the beginning of the COVID-19 pandemic in Russia, as in all countries of the world, serious anti-epidemic measures were carried out, the procedure for providing medical care to the population changed, the consequences of which did not have the best effect on their health, including in the Siberian Federal District. The number of visits per resident of the district as a whole decreased by 16.2 %, in the polyclinic by 19.5 %, at home increased by 44.4 %. The number of visits for preventive purposes decreased by 6 %, and the coverage of dispensary observation by 11.2 %. The proportion of patients with oncological diseases in stages 3-4 increased to 40.6 %. Hospitalization of the SFO declined by 17.2 %, the number of operated patients 17.8 %, and postoperative complications have increased by 43.7 % from 1.07 to 1.54 %. Total mortality amounted to in 2020 for 14.5 per 1,000 population, i.e. increased by 18 % compared to 2019 year, while only 1/3 was due to COVID-19. In 2020, the number of Russians decreased by 510 thousand people. Conclusions. The results of health care activities, a significant deterioration in the health of the population and the complication of the demographic situation in the country during the pandemic, indicate serious shortcomings in the organization of medical care to the population, primarily in extreme situations, and requires a deep analysis and adequate measures to improve the structure and functioning of the industry in any conditions.

Most young patients with hyperglycemia have type 1 diabetes and type 2 diabetes but up to 10% of all cases of the disease occur in MODY (Maturity Onset Diabetes of the Young). Published abstracts show features of the debut, laboratory and genetic characteristics of MODY in the Russian population. However there is a small amount of data on the clinical course of this nosology in the Russian Federation.Aim: To investigate the characteristics of the 3-year course of GCK-MODY diagnosed after 18 years.Materials and methods: 85 probands and 46 relatives of the first and second degrees of kinship with a clinical diagnosis of GCK-MODY were examined: biochemical and hormonal blood tests, ultrasound, molecular genetic studies. Patients were invited for a follow-up visit 3 years after verification of the pathogenic mutations associated with GCK-MODY. Examination, biochemical and hormonalanalyzes , ultrasound were done in second visit.Results: The diagnosis GCK-MODY was verified by a molecular genetic study in 25 probands (29.4%). In 33 of 46 (71.7%) relatives of patients with GCK-MODY were diagnosed identical mutations. In 31 patients with GCK-MODY diagnosed after 18 years, a dynamic observation was performed for three years. Most patients over 18 years of age did not have clinical manifestations of carbohydrate metabolism disorders when diagnosing GCK-MODY and follow up visit. Skin rashes and allergic reactions prevailed among concomitant pathologies. Patients with GCK-MODY had preserved β-cell secretion, HbA1c targets were achieved. Low fasting hyperglycemia prevailed which persisted even after treatment correction. Among the characteristics of carbohydrate metabolism, biochemical, lipid and hormonal parameters during GCK-MODY verification and after three years of observation no significant differences were obtained, which indicates a stable course of the disease. Half of the patients achieved normoglycemia by rational nutrition, two people with GCK-MODY within three years after determining the diagnosis were transferred from insulin therapy to oral glucose-lowering drugs. Among oral glucose-lowering drugs prior to GCK-MODY verification most patients used metformin, 3 years later — dipeptidyl peptidase-4 inhibitors.Conclusion. The results of a three-year follow-up of a group of patients with GCK-MODY demonstrate a non-progressive course of this type of diabetes with stable indicators of carbohydrate metabolism and low fasting hyperglycemia that persists after 3 years of observation. With the verification of GCK-MODY and the achievement of the target values of glycated hemoglobin and postprandial glycaemia by rational nutrition, even if a low level of fasting hyperglycemia is determined, the prescription of oral glucose-lowering drugs is not indicated in most cases.

Стандартные протоколы ультразвукового исследования включают исследования всех сосудов анализируемой области, во всех режимах сканирования, с полным набором измерений, и требуют высокой квалификации специалистов и больших временных затрат. Однако для ряда клинических задач достаточно выполнения фокусированного протокола ультразвукового исследования, т.е. ориентированного на решение конкретной проблемы и, следовательно, сокращенного по времени, тем самым позволяющего увеличить число обследуемых. Оценка сердечно-сосудистого риска с помощью выявления атеросклеротических бляшек в сонных и бедренных артериях, скрининг на наличие аневризмы аорты, выявление проксимального тромбоза глубоких вен нижних конечностей – это те направления в медицине, где фокусированные протоколы ультразвукового исследования могут повысить долю обследуемых и способствовать своевременной диагностике и профилактике заболеваний. Доступность фокусированного ультразвукового исследования и развитие образовательных структур позволят расширить круг специалистов, способных выполнять подобные исследования (кардиологи, терапевты, врачи общей практики, сосудистые хирурги). Сегодня существует много вопросов по организации проведения фокусированных протоколов в клинической практике. Данный консенсусный документ направлен на повышение информированности широкого круга специалистов о задачах, принципах проведения и применении фокусированного УЗИ.

Purpose of the study: the aim of this work is to assess the association of 7 SNPs (rs499818 of the PHACTR1 gene, rs619203 of the ROS1 gene, rs10757278 (xr. 9), rs1376251 of the TAS2R50 gene, rs2549513 (xp. 16), rs4804611 of the ZNF627 gene and rs17465637 гена MIA3) with the severity of myocardial infarction. Materials and methods. Three samples were taken as objects of research. A population sample of patients with non-fatal MI (200 people: men – 129, women – 71), a sample of participants in the HAPIEE project with developed MI during the study (94 people: men – 56, women – 38). A sample of patients with myocardial infarction admitted to the intensive care unit of the city clinical hospital № 1. The sample size was 159 people (112 men, 47 women). The following SNPs were taken into the study: rs499818 (xp. 6), rs619203 of the ROS1 gene, rs10757278 (xr. 9), rs1376251 of the TAS2R50 gene, rs2549513 (xr. 16), rs4804611 of the ZNF627 gene and rs174653. To assess the association of SNP and the severity of the disease, we compared a population sample of patients with non-fatal MI versus a joint group from a sample of HAPIEE project participants with developed MI during the study, and a sample of MI patients admitted to the intensive care unit of City Clinical Hospital No 1. Results. For two SNPs, statistically significant differences in genotype frequencies were obtained: rs10757278 AA vs AG + GG OR = 0.61 CI 0.39–0.94; p = 0.027 and rs619203 of the ROS1 gene in a group of men for genotype GG vs CG + CCOS = 0.59 CI 0.37–0.94; p = 0.033. Conclusions. The associations of seven SNPs were studied, which, according to international studies, are associated with the risk of development, poor prognosis and the severity of myocardial infarction in the population of residents of the city of Novosibirsk. Two SNPs (rs10757278 and rs619203) were identified, which are associated with the severity of myocardial infarction.

The innate Iнн\mmune system is the first to respond to invading pathogens. It is responsible for invader recognition, immune-cell recruitment, adaptive-immunity activation, and regulation of inflammation intensity. Previously, two single-nucleotide polymorphisms of innate-immunity genes – rs5743708 (Arg753Gln) of the TLR2 gene and rs8177374 (Ser180Leu) of the TIRAP gene – have been shown to be associated with both pneumonia and tuberculosis in humans, but the data are contradictory among different ethnic groups. It has also been reported that rs10902158 at the PKP3-SIGGIR-TMEM16J genetic locus belongs to a haplotype race-specifically associated with tuberculosis. Meanwhile, a gradient of its frequency is observed in Asia. The aim of this work was to assess the effect of selection for the genotypes of the above-mentioned SNPs on the gene pools of populations living in harsh climatic conditions that contribute to the development of infectious lung diseases. We estimated the prevalence of these variants in white and Asian (Chukchis and Yakuts) population samples from Northern Asia and among patients with community-acquired pneumonia (CAP). Carriage of the rs5743708 A allele was found to predispose to severe CAP (odds ratio 2.77, p = 0.021), whereas the GG/CT genotype of rs5743708/rs8177374 proved to be protective against it (odds ratio 0.478, p = 0.022) in white patients. No association of rs10902158 with CAP (total or severe) was found among whites. Stratification of CAP by causative pathogen may help eliminate the current discrepancies between different studies. No significant difference in rs5743708 or rs8177374 was found between adolescent and long-lived white samples. Carriage of the alleles studied is probably not associated with predisposition to longevity among whites in Siberia. Both white and Asian populations studied were different from Western European and East Asian populations in the variants’ prevalence. The frequency of the rs8177374 T (Ser180Leu) variant was significantly higher in the Chukchi sample (p = 0, χ2 = 63.22) relative to the East Asian populations. This result may confirm the hypothesis about the selection of this allele in the course of human migration into areas with unfavorable climatic conditions.

Over the past two decades, the availability of medical personnel in Russia’s healthcare sector has continued to deteriorate. Over the period from 2000 to 2018, it decreased by about 11 % for both doctors and specialists with secondary medical education. This is due to several reasons: the rejection of the previously existing system of training and saturation of the industry with specialists, the unsuccessful optimization of the country’s health system, the lack of attention of the authorities to young professionals, the creation of favorable conditions for them to live and work, etc. An important role is played by insufficient work on career guidance, including in medical specialties with students of General education organizations and the reluctance of medical workers to do this. The article provides recommendations for the organization of career guidance among high school students, describes the forms in which it can be carried out. This includes specialized medical classes, clubs for studying the basics of medical knowledge, and volunteering. The experience of the regional clinical hospital, which for 5 years has been supervising a specialized medical class, 78–96 % of whose graduates have chosen the medical profession is of considerable interest. Teachers of the Novosibirsk Medical College actively work with General education organizations, and therefore the competition among applicants is from 2 people per place in the specialty «Nurse» to 12–14 in the specialties «Pharmacy» and «Orthopedic dentistry». The effectiveness of career guidance largely depends on how systematically and methodically it is carried out. To successfully conduct it, you need to organize a three-level system: career guidance office (level I), career guidance point (level II), career guidance center (level III). The joint work of representatives of General education and medical organizations, medical schools, will help to ensure that school graduates will come to medicine, confident in the correctness of their chosen profession. After graduation, they will return to their native land, to their familiar environment, and with a high degree of probability will remain there forever.

The meeting of the expert council of cardiologists-lipidologists, organized with the support of Novartis and dedicated to the discussion of the existing system of medical care for patients with familial hypercholesterolemia / mixed dyslipidemia, the modern evidence base for lipid-lowering therapy and the practical value of the strategy of early combined lipid-lowering therapy for doctors and these categories of patients was held in Moscow on November 11, 2020.

Background. The annual reporting forms for malignant neoplasms do not provide for the division of lymphomas into variants. In international publications and statistical reference books of the Russian Federation, variants of non-Hodgkin’s lymphomas (NHL) are also not separated. For these reasons, a detailed assessment of the epidemiology of NHL in Russia is difficult, and data for individual variants of the disease are not provided.Purpose: to present the clinical and epidemiological characteristics of Diffuse Large B-cell Lymphoma (DL BCL ) in Novosibirsk according to the data of the City Hematology Center (CHC).Material and Methods. A retrospective analysis of primary medical documentation (case histories, outpatient charts, and immunohistochemical study reports) of 271 patients with DL BCL was performed in the period from January 1, 2013 to December 31, 2018.Results. The calculated registered primary morbidity and mortality from DL BCL in Novosibirsk for the analyzed years fluctuated slightly. The average incidence and mortality rates were 2.85 and 1.98 per 100,000 population, respectively. When analyzing the dynamics of the prevalence of DL BCL in Novosibirsk, a positive trend of annual increase in the indicator was revealed: 1.87 times over the past 6 years. In men, the tumor developed 2.6 years earlier than in women. In General, the risk of getting DL BCL after 50 years was 3 times higher than at the age of 30 years. Among patients diagnosed with primary lymphoma who underwent treatment at the Hematology department of CHC, half of the patients had DL BCL .Evaluation of the clinical characteristics showed a pronounced severity of the analyzed cohort.Conclusion. The updated quantitative and qualitative indicators of clinical and epidemiological characteristics of DL BCL in Novosibirsk for 2013–18 were obtained. These indicators can be used for further monitoring, development and implementation of measures for the prevention, diagnosis and treatment of this form of hemoblastosis.

Primary congenital glaucoma (PСG) is a visual organ pathology that leads to progressive blindness and poor vision in children. Its main cause is an anomaly of the anterior chamber angle. Most cases of PСG are sporadic, but familial cases with an autosomal recessive (predominantly) and autosomal dominant (rare) type of inheritance have been described. Congenital glaucoma is a rare condition (1 case per 10,000–20,000 newborns), but its prevalence is substantially higher (up to 1 case per 250 newborns) in countries where consanguineous marriages are common. Mutations in the CYP1B1 gene, which encodes cytochrome P450 1B1, are the most common cause of autosomal recessive primary congenital glaucoma. This enzyme is known to be involved in retinoic acid metabolism and is necessary for normal eye development. The aim of this work was to assess the polymorphism of the CYP1B1 gene among West Siberian patients with primary congenital glaucoma. Direct automatic Sanger sequencing of exons and adjacent splicing sites of the CYP1B1 gene was carried out in 28 people with the PCG phenotype from a West Siberian region. As a result, in the sample of the white population we examined, pathogenic variants previously described in other ethnic groups were revealed: E387K (rs55989760), R444* (rs377049098), R444Q (rs72549376), and P437L (rs56175199), as well as novel single-nucleotide deletion p.F114Lfs*38 in the CYP1B1 gene. The latter can cause a frame shift, changed amino acid composition, and a formation of truncated in the protein. None of the detected mutations were found in the control sample of ophthalmologically examined individuals without PCG (100 people). Variants R444* (rs377049098) and R444Q (rs72549376) were not found in the general population sample either (576 randomly selected West Siberia residents). All the detected mutations caused the development of the autosomal recessive form of primary congenital glaucoma. The most severe clinical phenotype was observed in carriers of mutations in codon 444 of the gene. Consequently, in children with signs of increased intraocular pressure, molecular genetic analysis of the CYP1B1 gene is advisable for early diagnosis and timely initiation of PCG therapy.

Aim.To study the possibility of using polymorphisms of genesTCF7L2,FABP2,KCNQ1,ADIPOQas markers for predicting the development of type 2 diabetes mellitus (T2D) in the population of Novosibirsk. Materials and methods.On the basis of prospective observation of a representative population sample of residents of Novosibirsk (HAPIEE), 2 groups were formed according to the case-control principle (case people who had diabetes mellitus 2 over 10 years of observation, and control people who did not developed disorders of carbohydrate metabolism). T2D group (n=443, mean age 56.26.7 years, men 29.6%, women 70.4%), control group (n=532, mean age 56.17.1 years, men 32.7%, women 67.3%). DNA was isolated by phenol-chloroform extraction. Genotyping was performed by the method of polymerase chain reaction with subsequent analysis of restriction fragment length polymorphism, polymerase chain reaction in real time. Statistical processing was carried out using the SPSS 16.0 software package. Results and discussion.No significant effect of rs1799883 of theFABP2gene, rs2237892 of theKCNQ1gene, and rs6773957 of theADIPOQgene on the risk of developing T2D was found. Genotypes TT and TC rs7903146 of theTCF7L2gene are genotypes for the risk of developing T2D (relative risk RR 3.90, 95% confidence interval CI 2.316.61,p0.001; RR 1.86, 95% CI 1.422.43,p0.001, respectively). The CC genotype rs7903146 of theTCF7L2gene is associated with a protective effect against T2D (RR 0.37, 95% CI 0.290.49,p0.001). When theTCF7L2gene is included in the model for assessing the risk of developing T2D rs7903146, it retains its significance in both men and women. Conclusion.The rs7903146 polymorphism of theTCF7L2gene confirmed its association with the prognosis of the development of T2D, which indicates the possibility of considering it as a candidate for inclusion in a diabetes risk meter. Variants of risk meters have been developed to assess the prognosis of the development of diabetes mellitus 2 in men and women aged 4569 years during 10 years of follow-up. The association with the prognosis of the development of T2D polymorphisms rs1799883 of theFABP2gene, rs2237892 of theKCNQ1gene and rs6773957 of theADIPOQgene was not found.

Objective: isolation of coronavirus SARS-CoV-2 from clinical sample of patient with COVID-19 in Novosibirsk; obtaining a purified and inactivated viral antigen and study of its antigenic properties. Materials and methods: virus isolation was carried out in Vero cell culture from nasopharyngeal swab positive on SARS-CoV-2 RNA. The efficiency of SARSCoV-2 replication in cell culture was assessed on the appearance of cytopathic effect (CPE) and the presence of viral RNA in cultural medium with reverse transcription – polymerase chain reaction (RT-PCR). Purification, concentration and inactivation of the viral preparation were carried out according to standard methods. The purity of the purified preparation and the profile of viral proteins were determined by electrophoresis in 10% polyacrylamide gel (PAG) with the addition of sodium dodecyl sulfate (SDS). The presence and specificity of viral proteins were detected using COVID-19 convalescent’s sera with enzyme-linked immunosorbent assay (ELISA) and immunoblotting. Results: SARS-CoV-2/human/ RUS/Nsk-FRCFTM-1/2020 isolate was obtained after passage on Vero cells from a virus-containing clinical sample. A purified, concentrated, inactivated, whole-virion antigen was obtained. It contains three structural proteins: glycoprotein S (approximately 200 kDa), nucleoprotein N (48 kDa), and matrix protein M (20-25 kDa). All viral proteins were detected with serum antibodies of COVID-19 convalescents. Conclusion: SARS-CoV-2 coronavirus can be isolated in Vero cell culture. The antigenic specificity of the three structural viral proteins (S, N, and M) is preserved in the purified inactivated viral preparation. The inactivated whole-virion antigen of SARS-CoV-2/human/RUS/Nsk-FRCFTM-1/2020 isolate can be used to study the antigenic immunomodulating properties of viral proteins, to obtain immune sera of laboratory animals, and also as a component of test systems for the detection of specific antibodies with ELISA and immunoblotting.

Every year, about six million people die from tobacco use. Respiratory epithelium is the first line of defense against exogenous invasion, in particular, harmful inhaled particles, pathogens and allergens. However, the epithelium of the respiratory tract is also a regulator of immunological and inflammatory reactions through secretion of inflammation and immune cell recruitment mediators. An important component of the pulmonary immune system is the surfactant, and, in particular, its proteins SP-A and SP-D, synthesized mainly by type II pneumocytes.Aim. To assess the levels of surfactant proteins SP-A and SP-D in the blood of smoking patients without bronchopulmonary diseases.Materials and мethods. The study included 59 patients admitted to the department of internal medicine with hypertension. The general group was divided into subgroups: non-smoking patients (n = 31) and healthy smokers (n = 28). All patients underwent clinical, functional, diagnostic and laboratory tests. The content of surfactant proteins SP-A and SP-D in the blood was determined by enzyme immunoassay.Results. The subgroups did not differ in sex, age, height, body weight, blood pressure, heart rate, respiratory rate, and the distribution of comorbidities. The subgroups differed in the platelet level; in other main parameters of complete blood count and blood biochemistry no differences were revealed. It was found that the blood levels of surfactant proteins SP-A and SP-D in the subgroup of healthy smokers were significantly higher in comparison with the subgroup of non-smoking patients. The correlation analysis revealed a direct relationship between surfactant proteins SP-A and SP-D and smoking (R = 0.360, p = 0.006, R = 0.274, p = 0.037), a negative correlation between SP-D protein and age (R = –0.315, p = 0.016), and a direct relationship between SP-A protein and diastolic blood pressure (R = 0.271, p = 0.039). In the non-smoking subgroup, a negative correlation between SP-D and age (R = –0.438, p = 0.016) and between SP-D and systolic blood pressure (R = –0.433, p = 0.017) was identified.Conclusion. The direct relationship between higher levels of the surfactant proteins SP-A and SP-D and smoking in the group of healthy smokers is justified (inflammatory changes, structural abnormalities in the lung parenchyma under the influence of cigarette smoke). The SP-D protein is more significant in comparison with the SP-A protein in vascular wall remodeling, lung tissue matrix, oxidative lung tissue damage, and apoptosis, which explains its negative correlation with age and systolic blood pressure.

Disclaimer РThe EAC/RNAS Guidelines represent the views of the EAC and RNAS, and were produced after careful consideration of the scientific and medical knowledge, and the evidence available at the time of their publication. The EAC and RNAS is not responsible in the event of any contradiction, discrepancy, and/or ambiguity between the EAC/RNAS Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies. Health professionals are encouraged to take the EAC/RNAS Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic, or therapeutic medical strategies; however, the EAC/RNAS Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient’s health condition and in consultation with that patient and, where appropriate and/or necessary, the patient’s caregiver. Nor do the EAC/RNAS Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient’s case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations. It is also the health professional’s responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.Members of the Working Group confirmed the lack of financial support / conflict of interest. In the event of a conflict of interest being reported, the member (s) of the Working Group was (were) excluded from the discussion of sections related to the area of conflict of interest.

Aim of the study was to investigate glomerular filtration rate in population of 25–45 years old young people of Novosibirsk city. Material and methods. A survey of Novosibirsk typical district’s population has been carried out by the Institute of Internal and Preventive Medicine since 2013 to 2016. 1074 people (467 males and 607 females of 25–45 years old) have been included into the survey. The levels of glomerular filtration rate (GFR) were chosen according to KDIGO (2012) recommendation, such as: GFR more than 90 ml/min/1.73 cm2 – high or optimal, 60–89 ml/min/1.73 cm2 – slightly reduced, 45–59 ml/min/1.73 cm2 – moderately reduced, 30–44 ml/min/1.73 cm2 – vastly reduced, 1529 ml/min/1.73 cm2 – highly reduced, lower than 15 ml/min/1.73 cm2 – terminal renal failure. Results and discussion. Average GFR(CKD-EPI) level in all age groups was 99,9 ml/min/1.73 cm2 . Average GFR(CKD-EPI) was 104.41 ml/min/1.73 cm2 in 25–34 age group. Male average GFR(CKD-EPI) levels in appropriate age groups were reliably higher comparing to female levels. Both male and female analyzed indicators turned out to be reliably lower in older group than in the younger one. 95.1 % of male participants at the age from 25 to 34 years old had GFR ≥ 90 ml/min/1.73 cm2 , while female indicator was 76.9 %. The indicators in the age group from 35–45 years old were: for males – 86.4 %, for females – 58.3 %. Both male and female groups at the age from 35 to 45 contained people with GFR < 60.ml/min/1.73 cm2 (2 men – 0,8 %; 1 woman – 0.4 %). While GFR calculating according to MDRD and CKD-EPI formulas two dissimilar results were revealed. The advantages of CKD-EPI formulas calculating for higher GFR indicators have been evidenced.

The TRPM8 gene encodes the ion channel, which is a cold receptor in afferent neurons of the mammalian somatosensory system. We studied the frequency of haplotype distribution from six SNPs in the TRPM8 gene in Eurasian human populations, including Russians, Kazakhs and Chukchi. Four of the six SNPs are located in exon 7 (rs13004520, rs28901637, rs11562975, rs17868387), rs7593557 is in exon 11. These exons encode parts of the N-terminus, which is necessary for channel functioning in the plasma membrane of neurons. The rs11563071 is in exon 23 encoding part of the C-terminus. The primary difference in population distribution of haplotypes determines the SNP from exon 11 which leads to Ser419Asn substitution in protein. The most pronounced dif­ferences in the patterns of diversity and frequencies of haplotypes were observed between Chukchi and Russians. The frequency of major H1 haplotype encompassing the 419Ser gene variant differs in examined populations; 0.738 (Russians), 0.507 (Kazakhs) and 0.337 (Chukchi), p < 0.001. The TRPM8 gene variants encoding 419Asn and carrying the minor alleles of rs28901637 (P249P) and rs11562975 (L250L) in exon 7 are characteristic of Asian populations. The frequency of all 419Asn variants in Chukchi is comparable to that in Africans, however, the minor allele frequencies of rs28901637, rs11562975 in Africans is low. Apparently in the process of human colonization of Eurasia, minor alleles of these SNPs diverged depending on rs7593557 structure in exon 11. We analyzed sequences of five TRPM8 mRNA isoforms extracted by researchers from different tissues. Sequence analysis demonstrates that they are transcribed from major H1 variant of the TRPM8 gene but contain different translation start codons, which are generated by alternative splicing from pro-mRNA.

The article presents a variant of maturity onset diabetes of the young type 2, caused by a rare mutation in the GCK gene. Maturity onset diabetes of the young (MODY) is a hereditary form of diabetes with an autosomal dominant type of inheritance, an onset at a young age, and a primary defect in pancreatic β-cell function. This type of diabetes is different from classical types of diabetes mellitus (DM1 and DM2) in its clinical course, treatment strategies, and prognosis. Clinical manifestations of MODY are heterogeneous and may vary even among members of the same family, i. e., carriers of identical mutations. This phenotypic variation is due to the interaction of mutations with different genetic backgrounds and the influence of environmental factors (e. g., lifestyle). Using next-generation sequencing technology, the c.580–1G>A substitution (IVS5 –1G>A, rs1554335421) located in an acceptor splice site of intron 5 of the GCK gene was found in a proband. The identified variant cosegregated with a pathological phenotype in the examined family members. The GCK gene encodes glucokinase (hexokinase 4), which catalyzes the first step in a large number of glucose metabolic pathways such as glycolysis. Mutations in this gene are the cause of MODY2. The illness is characterized by an insignificant increase in the fasting glucose level, is a well-controlled disease without medication, and has a low prevalence of micro- and macrovascular complications of diabetes. The presented case of MODY2 reveals the clinical significance of a mutation in the splice site of the GCK gene. When nonclassical diabetes mellitus is being diagnosed in young people and pregnant women, genetic testing is needed to verify the diagnosis and to select the optimal treatment method.

Pulse wave amplification and augmentation are considered as new indicators of arterial stiffness. It is of interest to study their association with electrocardiographic pro-arrhythmic patterns in the male population of Novosibirsk. Material and methods. We used data from a representative sample of 145 men aged 25-44 years from a population of inhabitants of Novosibirsk. Applanation tonometry of the radial artery and pulse wave analysis were performed using the SphygmoCor system (AtCorMedical, Australia). The Brugada pattern, the pattern of early ventricular repolarization and fragmentation of the QRS complex were determined on a resting electrocardiogram according to generally accepted current criteria. When analyzing the data, descriptive statistics methods and the general linear model (GLM) were used. Results. Fragmentation of the QRS complex in the in the area of the inferior wall of the left ventricle, regardless of age, body mass index and heart rate, was associated with a decrease in the ratio of amplification of pulse pressure (F = 5.34; p = 0.022), amplification of pulse pressure (F = 5.91; p = 0.016) and amplification of systolic pressure (F = 5.02; p = 0.027). Conclusion. In the Novosibirsk male population, a decrease in pulse wave amplification was associated with fragmentation of the QRS complex. The results of this study demonstrate the relevance of an integrated assessment of prognostically significant indicators of arterial stiffness and ventricular pro-arrhythmia to study the possible cumulation of cardiovascular risk.

Community-acquired pneumonia is one of the most common infectious diseases and remains one of the leading causes of death in this group of diseases. Studies of community-acquired pneumonia are extremely relevant for modern clinical practice. One of the important role in the pathogenesis of bacterial, viral, fungal invasion in the system of a human lung system belongs to the pulmonary surfactant, in particular, its proteins SP-A and SP-D. This article reviews the well-known mechanisms of important biological properties of immunomodulatory activity of the proteins SP-A and SP-D in response to microbial infection in the lungs. The mechanisms of participation of surfactant proteins SP-A and SP-D in the cascade of reactions that lead to severe life-threatening complications in community-acquired pneumonia are considered. The use of serum levels of surfactant proteins SP-A and SP-D can help finding new diagnostic and prognostic approaches in patients with community-acquired pneumonia.

The Russian Federation is among countries with high cardiovascular risk. Hypercholesterolemia is a leading risk factor for the development of atherosclerotic cardiovascular diseases. To achieve low-density lipoprotein cholesterol (LDL-C) targets, such approaches as lifestyle changes and pharmacological correction, based on the use of statins, are applied. At the same time, a significant proportion of the population has moderate hypercholesterolemia and is characterized by low or moderate cardiovascular risk. Although first-line recommendations should be followed, a healthy lifestyle alone is not enough to achieve target levels of LDL-C, which means that even people with low to moderate risk may end up with the prospect of lifelong therapy with lipid-lowering drugs. These individuals do not have an indication for lipid-lowering therapy, and they are usually recommended a change in diet and supplementation. Innovative nutritional strategies have been developed to manage dyslipidemia. They were based either on changing some “risky” food components or on encouraging the consumption of “healthy” functional foods and/or nutraceuticals. Nutraceuticals (registered as food supplements in Russia) is an innovative way to help control LDL-C at low and moderate risk individuals without lipid-lowering drugs and as nutritive support for the cholesterol-lowering diet. Red yeast rice (RYR) based preparations have been already developed and available at the moment. RYR based preparations can be considered in patients with low and moderate cardiovascular risk, who have not reached the target level of LDL-C and have no indications for statin therapy or have statin intolerance. RYR based preparations contains a statin-like substance monacolin K in a dose of 3 mg. In randomized clinical trials, it was proved that the use of high-quality RYR nutraceutical leads to a decrease in LDL-C by an average of 20% without increasing the risk of side effects like for statins. Evaluation of dietary supplements and functional foods should necessarily include not only evidence of beneficial effects with respect to effects on the lipid profile and atherosclerosis, but also proven good tolerability. The manufacturing standard for these products is also important, guaranteeing component standardization and quality. RYR analogues should guarantee the absence of mycotoxin in their composition. In Russia, programs are needed for the primary prevention of atherosclerotic cardiovascular diseases with effects on hypercholesterolemia at the population level.

Background. the presence of functionally significant intron mutations in the TP53 gene was demonstrated in experiments in vitro and on samples of patients with some variants of non-Hodgkin’s lymphomas. to date, the studies of TP53 in tumor tissue of patients with diffuse large B-cell lymphoma (dlBCl) have been focused on the mutations in 5–8 exons of the gene. For these reasons, further studies of the spectrum of changes in the intron sequences of the TP53 gene and the determination of their functional effect in dlBCl are required.Description. We present two case reports that are of interest as the cases for detection of functionally significant intron TP53 mutations in dlBCl tissue, first published in the Russian scientific literature. the first clinical case of dlBCl was clinically characterized by extranodal tumor at the onset of the disease, severe symptoms of tumor intoxication, high paraclinical tumor activity, and early hemoblastosis recurrence. the second case of dlBCl was characterized by initially massive tumor lesion, rapidly progressive course of the disease, severe symptoms of tumor intoxication, high paraclinical tumor activity and poor response to therapy with subsequent generalization of lymphoma. Conclusion. Mutations in the TP53 gene are the driver of the tumor process, serve not only as a marker of aggressive tumor progression, but also as an independent predictor of reduced sensitivity to treatment. the presented clinical cases show that an in-depth analysis of the results of the TP53 sequencing in tumors and functional assessment of all detected changes, including changes in the introns of the gene and involving in silico analysis techniques, are necessary.

The primary objective of personalized vaccination is to induce an efficient immune defense while avoiding excessive immunization. Hence, it necessitates the development of methods for predicting the magnitude of the immune response prior to vaccination. Telomere length can be considered as a promising prognostic parameter for assessing the immune response to vaccination. The aim of the work was to analyze the possible association between leukocyte telomere length and specific antibody levels after vaccination against tick-borne encephalitis. The study included 55 men and 40 women who had not previously been vaccinated against tick-borne encephalitis and had no contacts with ticks. Vaccination was carried out with the EnceVir vaccine. One month after vaccination, the level of specific IgG antibodies against tick-borne encephalitis virus was analyzed using the VektoVKE-IgG-strip test system and leukocyte telomere length was measured using real-time quantitative PCR. According to the intensity of vaccine-elicited immune responses, patients were divided into three groups: unresponsive (IgG level 0–100 IU/ml), slightly responsive (IgG level 101–200 IU/ml) and highly responsive (IgG level above 200 IU/ml). The telomere length, at least at trend level (p < 0.1), correlated with the response to vaccination as well as age, educational level and the presence of emotional stress. Using a general linear model, an association between telomere length and immune response to vaccination against tick-borne encephalitis at trend level (p < 0.1) was found only in women. Using a pairwise comparison, it was found that telomere length was significantly higher in highly responsive women than in unresponsive women. Hence, an association between leukocyte telomere length and specific antibody levels after vaccination against tick-borne encephalitis was identified in women. Therefore, peripheral blood leukocyte telomere length can be considered as a promising marker for predicting lymphocyte proliferative responses and the magnitude of vaccine-elicited cellular immune responses.

Development of new drugs able to decrease the level of “bad” cholesterol, in particular, based on antisense oligonucleotide derivatives (ASOs), remains relevant for the patients with familial hypercholesterolemia and/or intolerant to statins. The goal of the work was to assess the changes in the lipid metabolism caused by variants of joint impact of the ASOs targeted to the mRNAs of its key genes: apoB, PCSK9, and apoCIII. Female C57BL/6J mice; nuclease-protected 13- and 20-nucleotide ASOs, and standard protocols for quantification of lipoproteins (HDL CHL, non-HDL CHL, and total CHL) and ALT in the blood serum were used in the work. The following combinations of ASOs were four times injected to the mouse caudal vein: 1) ASO to apoB, 2) ASO to apoCIII, 3) ASO to apoB and ASO to PCSK9, 4) ASO to apoB, ASO to PCSK9, and ASO to apoCIII, 5) ASO to apoB (three doses), ASO to PCSK9, and ASO to apoCIII (two doses), 6) ASO to PCSK9 and (ASO to apoCIII – only in the fourth administration). Triple weekly administration of these ASO combinations resulted in a decrease in non-HDL CHL by 25, 16, 35, 47, 60, and 7 %, respectively, as compared with the control and 1.8-, 1.5-, 1.9-, 2.4-, 3.1, and 1.24-fold higher HDL CHL/ non-HDL CHL ratio. The subsequent ASO injection with concurrent switching to a high-fat diet after 1 week resulted in a decrease in the non-HDL CHL by 28, 2, 28, 70, 33, and 49 % for ASOs (1–6), respectively, as compared with the control; the HDL CHL/non-HDL CHL ratio was 1.5-, 1.1-, 2-, 3.7-, 1.9-, and 2-fold better. The ALT concentration for all ASO combinations remained within the norm for the control animals, demonstrating the absence of any hepatotoxic effect. The best efficiency of ASOs requires selection of concentrations for single ASOs and their combinations as well as of the order and timing of administration. Thus, a new antisense approach is proposed.

Project of the Russian National Atherosclerosis SocietyIn 2016, Guidelines on the medical care organization to the patients with hereditary atherogenic lipid disorders in the regions of Russia were published, which described and presented the principles of routing patients with hereditary dyslipidemia and the organization of medical care for them within the current regulatory documents. In December 2018, the Russian Ministry of Health approved clinical guidelines for the diagnosis and treatment of familial hypercholesterolemia. Thus, persons with a severe hereditary dyslipidemia were able to get free medication with expensive lipid-lowering drugs and receive apheresis. Following the European ones, the Russian guidelines on the management of lipid metabolism disorders were updated: lower target low density lipoprotein cholesterol levels were adopted. In the Russian population, there is a high prevalence of hypercholesterolemia, including familial monogenic and polygenic types. Therefore, timely detection and routing to a lipid center or an office to a specialist (cardiologist, lipidologist), adequate and modern prescription of lipid-lowering therapy will make an important contribution not only to secondary, but also to primary prevention of atherosclerotic cardiovascular complications.

The aim of the research is to verify the association with sudden cardiac death (SCD) of single nucleotide polymorphisms rs7172856 and rs61999948, identified as new molecular genetic markers of SCD in the own genome-wide pooled allelotyping. Material and methods. Case-control study. The SCD group is formed using the criteria of the European Society of Cardiology from the DNA bank of suddenly deceased residents of the Oktyabrsky district of Novosibirsk (n = 437, average age – 53.1±9.0 years, men – 73.5 %, women – 26.5 %) The control group (n = 405, average age 53.2±9.2 years, men 70.0 %, women 30.0 %) is formed from the DNA bank of participants of MONICA and HAPIEE projects. DNA was isolated by phenol-chloroform extraction from myocardial tissue in the SCD group and venous blood in the control group. Genotyping was performed by the PCR-RFLP method. Results. No statistical significance was found in allele and genotype frequencies of rs7172856 between groups, even in separating in sex and age (p > 0.05). The proportion of male carriers of the TT genotype rs61999948 in the SCD group (6.3 %) is statistically significantly less than the proportion of male carriers of the TT genotype rs61999948 in the control group (12.6 %) (OR = 0.47, 95 % CI 0.26-0.85, p = 0.011). The identified significance is reserved in the group under 50 years old (p = 0.007) and in the group of men under 50 years old (p = 0.002). The proportion of carriers of the CC genotype rs61999948 is statistically significantly higher in the SCD group (59.0 %) compared with the control group (42.5 %) (OR = 1.94, 95 % CI 1.21–3.12, p = 0.006) for people under 50 years old. The identified association of the CC genotype with the SCD is reserved in the group of men under 50 years old (p = 0.001). Conclusions. Single nucleotide polymorphism rs7172856 is not associated with SCD. The TT genotype of the single nucleotide polymorphism rs61999948 is associated with a protective effect against SCD and the CC genotype of rs61999948 is associated with an increased risk of SCD for men under 50 years old.

The review presents an analysis of studies on the role of armolipid in the primary prevention of cardiovascular diseases. Armolipid is the nutraceutical that combines the lipid-lowering components of red yeast rice (monocalin K, policosanol) and antioxidants (coenzyme Q, astaxanthin and folic acid). The multifactorial evolution of atherosclerotic plaque with dyslipidemia, inflammation and genetic markers and practicability of primary prevention is shown. The presented data demonstrated that the intake of nutraceuticals is well tolerated. It also reduces the levels of total cholesterol, low-density lipoprotein cholesterol and inflammatory markers and improves vascular endothelial function. Nutraceuticals with lipid-lowering effects can be used as an alternative method of primary prevention in people with low and borderline cardiovascular risk before statin therapy, with poor adherence to statin therapy, as well as with statin intolerance or side effects.

Aim. To confirm the association between sudden cardiac death (SCD) and single nucleotide polymorphisms rs7164665, rs71461059, rs74765750, rs6762529, identified in own genome-wide associative study as new molecular genetic markers of SCD.Material and methods. As design we used case-control study. The SCD group was formed using the SCD criteria of the European Society of Cardiology (n=438, average age 53,2±9,1 years, male — 72,7%, women — 28,3%). The control group (n=435, average age 53,2±8,9 years, men — 70,0%, women — 30,0%) was selected by gender and age for the SCD group from the DNA bank of the international projects MONICA and HAPIEE. DNA was isolated by phenol-chloroform extraction from myocardial tissue in the SCD group and venous blood in the control group. Genotyping was performed by polymerase chain reaction followed by analysis of estriction fragment length polymorphism. The results are statistically processed using the SPSS 16.0 software package.Results. No carriers of the rare allele A of the single nucleotide polymorphism rs74765750 were found in the SCD group and the control group. No statistically significant differences were found between the SCD group and the control group relating to frequencies of genotypes and alleles of single nucleotide polymorphisms rs7164665 and rs71461059. In the age group older than 50 years, the proportion of carriers of the heterozygous CT genotype of the single nucleotide polymorphism rs6762529 in the SCD group is statistically significantly lower compared to the control group (CT vs CC+TT: OR=0,686, 95% CI 0,483-0,967 p=0,035).Conclusion. The CT genotype of the single nucleotide polymorphism rs6762529 is associated with a protective effect on SCD for people over 50 years of age. The association with single nucleotide polymorphisms rs7164665, rs71461059, rs74765750 with SCD has not been confirmed.

Aim. To identify genetic markers of risk for ST-elevated myocardial infarction (STEMI).Material and methods. The study included 210 patients (119 men, 91 women) with STEMI, hospitalized from December 21, 2016 to June 16, 2017 The average age of men was 55,5±9,5 years, women — 57,5±9,1 years. The diagnosis of STEMI was verified according to the criteria of the European Society of Cardiology (2015, 2017). During hospitalization, patients underwent clinical and instrumental examination, stipulated by medical care standards and clinical guidelines We also conducted a genetic study of single nucleotide polymorphisms (SNPs), which showed their association with the risk of coronary artery disease (CAD) and acute myocardial infarction (AMI) according to the GWAS: rs2820315 of the LMOD1 gene (Leiomodin 1, mapped on chromosome 1), rs9349379 of the PHACTR1 gene (regulator 1 of actin and phosphotase, localized on chromosome 6p241), rs867186 of the PROCR gene (Protein C receptor, located on chromosome 20q11.22), rsi1799883 of the FABP2 gene (Fatty acid-binding protein 2, located on chromosome 4q26). Statistical data analysis was performed using the SPSS 170.5 software package and authorial odds ratio (OR) calculator.Results. Carriage of the CC genotype of rs2820315 polymorphism of the LMOD gene is associated with an increased risk of STEMI by 1,87 times (95% CI 1,2862,722, p=0,016). Carriers of the CT genotype of rs2820315 polymorphism have a reduced risk of STEMI (OR 0,633; 95% CI 0,436-0,918, p=0,016).Conclusion. In order to identify risk groups for STEMI development, the study of the rs2820315 polymorphism of the LMOD gene is recommended. This will define the high-risk group for STEMI for developing of personalized programs for primary and secondary prevention of cardiovascular events in practical health care, which will contribute to reducing of STEMI mortality.

Aim. To determine the genetic predictors of five-year outcomes in patients with acute coronary syndrome (ACS).Material and methods. The study included patients admitted to the City clinical hospital № 1 (CCH №1) in Novosibirsk with a diagnosis of ACS in the period 2010-3 2011 (n=280). All patients were examined in accordance with clinical guidelines and standards of care, genetic markers were assessed. Genotyping included determination of single nucleotide polymorphisms (SNPs), confirming its association with the development of the ACS according to the results of an international genomeassociated studies: rs1376251, rs4804611, rs 1333049, rs619203, rs10757278, rs2549513, rs499818, rs17465637. All patients are kept in touch from the moment of initial contact to the present time, with the help of available means of communication and annual examinations in order to assess the end points. “End points” included: repeated nonfatal myocardial infarction (MI), hospitalization for myocardial ischemia, re-revascularization or chronic heart failure (CHF), nonfatal acute cerebrovascular accident (NACA), cardiovascular death.Results. We revealed SNPs, which play a role in predicting long-term outcomes of ACS: rs10757278, rs 4804611, rs 1333049, rs 2549513. The genotype of rs2549513 as 2,9-fold (95% CI 1,06-8,03; p=0,041) increases the risk of unfavorable long-term prognosis in the subgroup of men older than 55 years. The AA genotype rs10757278 and GG genotype rs1333049 are associated with a favorable long-term prognosis (OR=0,47, 95% CI 0,23-0,96; p=0,042 and OR=0,41, 95% CI 0,22-0,78; p=0,049, respectively) in the group of patients older than 55 years. For the GG genotype rs1333049 association was characteristic only for women. The AA genotype rs4804611 is associated with a favorable outcome of ACS at the age of 55 years (OR=0,036, 95% CI 0,14-0,96; p=0,053), significant differences were obtained in the group of men (p=0,36).Conclusion. The use of identified genetic predictors to assess the risk of five-year outcomes will strengthen a personalized approach to patients and, together with conventional prevention measures, will reduce cardiovascular mortality.

The purpose of the study was to assess the associations of proteins of pulmonary surfactants A (SP-A) and D (SP-D) with the severity of community-acquired pneumonia. Material and methods. A survey of 188 patients diagnosed with community-acquired pneumonia (CAP). The average age of the examined patients was 54.3 ± 16.5 years (M ± SD). In 102 patients (54.3 %) severe CAP was verified. All patients underwent clinical, functional, diagnostic and laboratory studies. Results and discussion. It was determined that SP-A and SP-D content was significantly higher in patients with severe CAP compared to patients with a mild course of this disease. The direct association of severe CAP with an elevated SP-AP level, directly associated with an increase in the concentration of C-reactive protein in the blood and erythrocyte sedimentation rate, have been confirmed in early studies. Using partial correlation analysis, it was established that the severe course of CAP is directly related to SP-A (r = 0.221; p = 0.003) and SP-D content (r = 0.262; p < 0.001) regardless of age, smoking, and body weight. Thus, direct associations of SP-A and SP-D with a severe course of CAP reflect the high pathogenetic significance of these protective factors in infectious lung damage.

The aim of the study was to investigate the association of SNPs in the TRPA1 (rs13268757) and TRPV1 (rs222747) genes with myocardial infarction. Material and methods. Myocardial infarction (MI) (200 individuals) and control (420 individuals) groups were formed as a part of international HAPIEE project. Genotyping the groups for the studied rs13268757 and rs222747 polymorphisms was performed by a real-time PCR on a StepOnePlus device (Applied Biosystems, USA) using TaqMan probes (Applied Biosystems, USA) according to a standard protocol. Intergroup comparison of the allele/genotype frequencies for each of the studied polymorphisms was calculated using Fisher's exact test and the SPSS 11.0 program. The correspondence of genotype frequencies to Hardy-Weinberg equilibrium was tested using the χ2 method. The relative risk of MI for a particular allele or genotype was calculated as an odds ratio (OR) using Fisher’s exact two-sided test and Pearson chi-square test. Differences were considered statistically significant with a significance level p

In opinion the Expert council provides management tactics for patients with hypertriglyceridemia (HTG). It is demonstrated that HTG is a common condition in overweight patients and is an important component of residual risk. HTG creates additional conditions for the progression of atherosclerosis, so the level of triglycerides (TG) is recommended to be measured in patients with a high, very high and extremely high risk level. An indication for the appointment of drugs that reduce the concentration of TG is its level of more than 2,3 mmol/L. Statins are the agents of choice to reduce the risk of cardiovascular disease in high-risk patients with hypercholesterolemia and HTG. Fenofibrate is used to correct HTG, and in case of intolerance to it or when the target level of TG is not reached, omega-3 ethers of polyunsaturated fatty acids in a dose of 2-4 g/day are recommended. In patients with HTG with a TG level >5,6 mmol/L, fenofibrate is the agent of choice.

Aim. To study the prevalence of coronary artery disease (CAD) according to epidemiological criteria in the Novosibirsk population of 25-45 years, to identify its associations with lipid and non-lipid risk factors.Material and methods. Cross-sectional survey of the Novosibirsk population aged 25-45 was carried out. The study included 650 people (268 men and 382 women). The epidemiological diagnosis of CAD (“Certain CAD” — CCAD, “Possible CHD” — PCAD) was made according to epidemiological (according to Rose questionnaire) and clinical functional (ECG recording with the Minnesota code) criteria. Blood levels of total cholesterol, triglycerides, cholesterol of low and high density lipoproteins (LDL-Ch, HDL-Ch) were determined. Blood pressure were measured (SBP, DBP), the presence of arterial hypertension (AH), body mass index and the smoking status were assessed.Results. CCAD was detected in 3,8% people, including in 2,6% men and in 4,7% women. PCAD was detected in 6,1% people, including 78% men and 5,0% women. The results of univariate analysis showed that the relative risk of PCAD in the population is higher in people with low HDL-Ch (OR 2,136), in smokers (OR 1,925) and in AH subjects (OR 2,235). The results of logistic regression analysis showed that the relative risk of PCHD in the population, independently of other factors, is associated with lower level of HDL-Ch (OR 0,180) and higher SBP (OR 1,026). The relative risk of CCAD developing in the female population is higher in women with low HDL-Ch (OR 3,800) and in AH women (OR 4,572).Conclusion. In the Novosibirsk population of 25-45 years, CAD, determined by epidemiological criteria, independently of lipid and non-lipid risk factors, is associated with AH presence and reduced HDL-Ch.

Cardiovascular diseases, in particular myocardial infarction (MI), are one of the most common causes of death in the world. Today, a significant problem for assessing of MI and post-infarction complications risks is the insufficient sensitivity and prognostic values of modern methods and markers. Therefore, the identification of new markers with high specificity and sensitivity is an important task. Recently, much attention has been paid to the study of extracellular RNAs, which are relatively stable in biological fluids. In this article, we overviewed some miRNAs, which are considered as potential markers for the diagnosis of MI and prediction of its adverse effects.

Purpose of research – to assess the feasibility and effectiveness of informatization of practical health care medical organization. Material and methods: timing, statistical analysis, systematization, sociological (questionnaire) survey, the object of the study is a medical information system. Results and discussion. The main characteristics and principles of the medical information system, as well as the technology of its implementation in the institution of practical health care are described. The results of the use of the system for 5 years, important changes in the organization of the diagnostic and treatment process and management of the medical organization are presented. The introduction of the electronic medical card helped to reduce the time for its filling and delivery from the registry to the specialist’s office. The rational schemes of routing of citizens at carrying out of preventive examinations within the framework of the examination have been developed. At the same time, the main set of measures envisaged by it is currently carried out during 2–3 hours within one day (previously, citizens spent up to 4 hours for examination, sometimes two days). The medical disability electronic certificate used in the center, reduced the time of its registration, has ruled out re-visits of patients to clinics because of the wrong filling out, allowed us to realize the remote control over filling correctness. The module «Pharmacy» and the creation of a single nursing post contributed to a more rational accounting and use of medicines in the hospital Center, to reduce the cost of this article by 15 %. The use of the system in the transition to an effective contract allows quickly and objectively assessing the activities of employees and taking into account the cost of one point to calculate the amount of incentive payments, which employees can see in person. Conclusion. The results show that the informatization of medical organizations is the most important factor in the successful development of the institution, improves the quality and availability of medical care to the population.