Aim. To evaluate the associations of VEGFR2 rs2305948 polymorphism with the occurrence of cardiovascular events during long-term follow-up in patients with myocardial infarction. Material and methods. The study included 218 patients with acute infarction (MI), mean age 57.7 ± 9.9 years (M ± SD). After clinical examination and preparation, patients urgently underwent coronary angiography followed by percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). All patients underwent determination of the rs2305948 VEGFR2 allelic variant by polymerase chain reaction. The duration of long-term follow-up of these patients was 9 years (from 2015 to 2024). Results. It was determined that during long-term follow-up, patients with rs2305948 VEGFR (C/T and T/T), in contrast to patients with rs2305948 VEGFR (C/C), were more likely to experience cardiovascular death, recurrent acute coronary syndrome (ACS), recurrent revascularization and a combined end point (cardiovascular death, recurrent ACS, coronary stent/bypass thrombosis, acute ischemic cerebrovascular accident, repeated myocardial revascularization). Using multivariate analysis, it was determined that the occurrence of cardiovascular death during long-term follow-up is directly influenced by the Charlton comorbidity index (p < 0.001) and rs2305948 VEGFR2 (C/T and T/T) (p = 0.030). The onset of a combined endpoint is directly determined by the Charlton comorbidity index (p = 0.014) and rs2305948 VEGFR2 (C/T and T/T) (p = 0.034) and vice versa by subsequent outpatient treatment with high doses of statins (p < 0.001). Conclusions. The presence of rs2305948 VEGFR (C/T and T/T) in patients with MI increases the likelihood of cardiovascular death by 2.82 times and the combined endpoint by 2.10 times during long-term follow-up (9 years).

Histamine intolerance is a disorder associated with impaired ability to absorb ingested histamine. Histaminosis occurs in 1-3% of the population. This condition was described at the beginning of the 21st century. This article provides an overview of histamine intolerance, mainly devoted to clinical manifestations, diagnosis and treatment.

Iron overload in non-alcoholic fatty liver disease (NAFLD) is a fairly common phenomenon that receives very little attention in clinical practice. However, iron overload, leading to hemosiderosis (deposition of “indigestible” nanodispersed iron oxides in various tissues) significantly aggravates NAFLD, stimulating increased chronic inflammation, insulin resistance and hemosiderosis of other organs. As a result, ferroptosis of hepatocytes occurs (apoptosis caused by iron overload and hemosiderosis), which accelerates the transformation of non-alcoholic steatosis into non-alcoholic steatohepatitis (NASH) and, subsequently, into liver cirrhosis. Iron overload is aggravated by micronutrient deficiencies and pathogenic intestinal microbiota. The paper presents the results of a systematic analysis of this issue, describes the prospects for therapy using micronutrients and human placenta hydrolysates (HPP), which contribute not only to the regeneration of liver tissue, but also to the normalization of iron homeostasis.

Currently, special attention is drawn to the phenomenon of comorbidity of chronic non-infectious diseases. The emergence of comorbidity is facilitated by the high incidence of coexisting diseases. One such combination is GERD and metabolic syndrome (MS). GERD and MS are multifactorial diseases, the pathogenesis of which is intertwined and mutually aggravates each other. Every year throughout the world and the Russian Federation, there is a clear trend towards an increase in the incidence of pathology of the upper gastrointestinal tract, namely gastroesophageal reflux disease (GERD). The prevalence of obesity in Russia over 40 years of observation has increased 4 times among men and 1.5 times among women. Despite the high incidence, to date there is no diagnosis of “metabolic syndrome” (MS) in ICD-10. MS is coded based on its constituent pathologies (obesity, dyslipidemia, insulin resistance, arterial hypertension). Treatment of this comorbid pathology requires a multidisciplinary approach, thereby placing a high burden on the healthcare system. This article displays the features of the pathogenesis and clinical picture of GERD, as well as the combination of this pathology with the components of MS.

Nonalcoholic fatty liver disease (NAFLD) is a rapidly progressive disease in terms of prevalence. It is most common in male individuals, with an average age of onset around 50 years of age. People suffering from overweight, obesity, type 2 diabetes mellitus are particularly susceptible to the development of NAFLD due to common pathophysiological processes of development. Genetic and epigenetic factors determine the occurrence and progression of NAFLD. Among genes there are those that predominantly affect the development of NAFLD: PNPLA3, TM6SF2, GCKR, MBOAT7, HSD17B13. There are also ongoing studies on the following genes: APOB, PCSK9, APOC3, MTP, SOD2, TNF-a, TGF-b. Among the factors associated with the development of NAFLD, special attention is paid to insulin resistance and obesity, mitochondrial dysfunction, lipotoxicity and release of pro-inflammatory cytokines. The common mechanisms of development of NAFLD, hypertension (HT) and cholelithiasis (CHD) explain their frequent concurrent course. The modern presentation of pathogenesis excludes the possibility of further use of the diagnosis «nonalcoholic fatty liver disease», as it has become clear that liver damage is multifactorial and cannot be defined as a «diagnosis of exclusion». The need to optimise the term NAFLD into «metabolically associated fatty liver disease» is being actively discussed.

Aim. To evaluate the efficacy of P2Y12 receptor inhibitors (clopidogrel and ticagrelor) in patients with myocardial infarction (MI) living in the northern region of Russia (Khanty-Mansi Autonomous Okrug — Yugra), depending on the carriage of various CYP2C19 allelic variants.Material and methods. This prospective observational study included 218 patients with acute MI who underwent percutaneous coronary intervention (PCI). The patients also underwent determination of allelic variants of the CYP2C19 gene. Patient were divided into groups receiving clopidogrel (n=164, 75%) and ticagrelor (n=54, 25%). Using biostatistical analysis methods, a comparison of clinical and genetic characteristics was performed, as well as an assessment of the risk of ischemic events between the groups in the long-term (108 months, 9 years) post-infarction period.Results. Reduced (*1/*2, *2/*2, *1/*3) and increased (*1/*17, *17/*17) metabolizer CYP2C19 genotypes, as well as severe comorbidity, are reliable independent predictors of composite outcome (cardiovascular death, recurrent acute coronary syndrome, coronary stent/bypass thrombosis, myocardial revascularization, acute ischemic cerebrovascular accident) during a long-term (9 years) follow-up. The advantages of ticagrelor over clopidogrel in terms of the effect on the incidence of ischemic events in the long-term period were established without a significant difference for bleeding both in the general cohort of patients and among carriers of CYP2C19 allelic variants (*1/*2, *2/*2, *1/*3) and (*1/*17,*17/*17) in patients with MI.Conclusion. Ticagrelor is significantly more effective than clopidogrel in reducing the risk of ischemic events in the general cohort of patients, as well as in carriers of reduced (*1/*2, *2/*2, *1/*3) and increased (*1/*17, *17/*17) metabolizer CYP2C19 genotypes during 9-year follow-up after the index MI.

Celiac disease (CD) is a well-studied disease among disorders associated with human leukocyte antigen (HLA). The prevalence of CD is about 0.7–1.4% of the population. CD is accompanied by atrophy of the villi of the mucous membrane of the small intestine in response to the effects of gluten. As a result of atrophy, the surface area of the mucous membrane of the small intestine decreases. Malabsorption is one of the main causes of insufficient intake of various vitamins, macro- and microelements into the body. This article contains various deficient states accompanying CD. Key words: celiac disease, vitamin D, vitamin A, vitamin B12, iodine, vitamin K, copper, iron, folic acid, zinc, malabsorption syndrome

Antibodies against the receptor-binding domain of the SARS-CoV-2 spike protein (RBD S-protein) contribute significantly to the humoral immune response during coronavirus infection (COVID-19) and after vaccination. The main focus of the studies of the RBD epitope composition is usually concentrated on the epitopes recognized by the virus-neutralizing antibodies. The role of antibodies that bind to RBD but do not neutralize SARS-CoV-2 remains unclear. In this study, immunochemical properties of the two mouse monoclonal antibodies (mAbs), RS17 and S11, against the RBD were examined. Both mAbs exhibited high affinity to RBD, but they did not neutralize the virus. The epitopes of these mAbs were mapped using phage display: the epitope recognized by the mAb RS17 is located at the N-terminal site of RBD (348-SVYAVNRKRIS-358); the mAb S11 epitope is inside the receptor-binding motif of RBD (452-YRLFRKSN-459). Three groups of sera were tested for presence of antibodies competing with the non-neutralizing mAbs S11 and RS17: (i) sera from the vaccinated healthy volunteers without history of COVID-19; (ii) sera from the persons who had a mild form of COVID-19; (iii) sera from the persons who had severe COVID-19. Antibodies competing with the mAb S11 were found in each group of sera with equal frequency, whereas presence of the antibodies competing with the mAb RS17 in the sera was significantly more frequent in the group of sera obtained from the patients recovered from severe COVID-19 indicating that such antibodies are associated with the severity of COVID-19. In conclusion, despite the clear significance of anti-RBD antibodies in the effective immune response against SARS-CoV-2, it is important to analyze their virus-neutralizing activity and to confirm absence of the antibody-mediated enhancement of infection by the anti-RBD antibodies.

Aim. To determine the associations of allelic variants of the CYP2C19 gene with coronary atherosclerosis and ischemic events in patients with myocardial infarction (MI) living in the Khanty-Mansi Autonomous Okrug — Yugra. Material and methods. This prospective observational study included 203 patients with acute MI who underwent percutaneous coronary intervention. Patients also underwent genetic testing using real-time polymerase chain reaction to determine allelic variants of the CYP2C19 gene. Using biostatistical analysis methods, associations were established between the genotypes of patients with MI, their clinical characteristics and major ischemic events over 7-year follow-up. Results. Significant associations were identified between allelic variants of CYP2C19*2 (*1/*2 and *2/*2) and smoking, right ventricular volume and glomerular filtration rate (GFR). The presence of the allelic variant CYP2C19*3 (*3/*3) was associated with GFR ³90 ml/min/1,73 m 2 and impaired glucose tolerance. A significant association was established between the CYP2C19*17 alleles (*1/*17, *17/*17) with coronary atherosclerosis, smoking, levels of troponin T, aspartate aminotransferase, total cholesterol, left ventricular posterior wall thickness, and a history of myocardial infarction. Data from multivariate analysis showed a clear association of allelic variants of CYP2C19*2 (*1/*2 and *2/*2) with the composite endpoint of 7-year follow-up (death, recurrent myocardial infarction, stent/bypass thrombosis, myocardial revascularization). A significant influence of CYP2C19*17 genotypes (*1/*17 and *17/*17) on myocardial revascularization in patients in the post-infarction period was also determined. Conclusion. CYP2C19*2 genotypes (*1/*2 and *2/*2) in MI patients living in Khanty-Mansi Autonomous Okrug — Yugra are clearly associated with ischemic events during a 7-year follow-up. CYP2C19*17 genotypes (*1/*17 and *17/*17) are clearly associated with coronary atherosclerosis and myocardial revascularization in the long-term post-infarction period.

Целью данной статьи является обобщение сведений о связях наиболее значимых психосоциальных факторов с сердечно-сосудистыми заболеваниями и приверженностью к медикаментозному лечению у пациентов, перенесших инфаркт миокарда. В многочисленных исследованиях установлены прямые ассоциации депрессии, личностной тревожности, а также враждебности и невротических расстройств с риском развития инфаркта миокарда и наступлением сердечно-сосудистых событий. Жизненное истощение способствует развитию ишемической болезни сердца и является одним из наиболее важных факторов риска как для мужчин, так и для женщин, а также относительно кратковременным прогностическим маркером возникновения инфаркта миокарда. Определено, что изолированные и одинокие люди подвержены повышенному риску инфаркта миокарда и инсульта, а среди лиц с инфарктом миокарда или инсультом в анамнезе – повышенному риску смерти. Представлены убедительные сведения о том, что узкое социальное окружение и неудовлетворительная социальная поддержка повышают риск развития сердечно-сосудистых заболеваний и ухудшают их прогноз. В ряде исследований установлено, что депрессия и тревожность прямо ассоциированы с низкой приверженностью к медикаментозной терапии у лиц, перенесших инфаркт миокарда. Определено, что социальная поддержка пациентов, перенесших инфаркт миокарда, прямо связана с приверженностью к выполнению рекомендаций по вторичной профилактике и медикаментозному лечению.

Aim. To identify and rank factors predisposing to angina relapse in Buryat patients who underwent percutaneous intervention for acute coronary syndrome. Material and methods. The study included 142 Buryat patients who underwent coronary stenting for acute coronary syndrome. All patients received clopidogrel. The CYP2C19*2 and CYP2C19*3 alleles were determined. Efficacy endpoints were assessed according to the Academic Research Consortium-2 criteria. Laboratory parameters and concomitant omeprazole therapy were assessed. Results. This study examined in detail a group of patients with short-term angina relapse without formal signs of unstable angina. A logistic regression model was obtained that makes it possible to identify and rank independent risk factors for recurrent angina in Buryat patients. Risk factors were ranked as follows: carriage of CYP2C19*2 and/or CYP2C19*3 alleles (coefficient b1=3,489, 95% confidence interval (CI) (3,096-346,213)), treatment with omeprazole (b2=2,816, 95% CI (2,745-101,616)), male sex (b3=2,749, 95% CI (1,425-163,458)) and blood glucose level (b4=0,354, 95% CI (1,141-1,779)). Conclusion. Thus, angina pain relapse in Buryat patients is facilitated by signs significant for recurrent myocardial infarction. This study suggests that patients with recurrent angina pain without electrocardiographic deterioration and biomarker elevation may require more careful personalization of therapy.

Antibody-dependent enhancement (ADE) has been shown previously for SARS-CoV-1, MERS-CoV, and SARS-CoV-2 infection in vitro. In this study, the first monoclonal antibody (mAb) that causes ADE in a SARS-CoV-2 in vivo model was identified. mAb RS2 against the SARS-CoV-2 S-protein was developed using hybridoma technology. mAb RS2 demonstrated sub-nanomolar affinity and ability to neutralize SARS-CoV-2 infection in vitro with IC50 360 ng/mL. In an animal model of SARS-CoV-2 infection, the dose-dependent protective efficacy of mAb RS2 was revealed. However, in post-exposure prophylaxis, the administration of mAb RS2 led to an increase in the viral load in the respiratory tract of animals. Three groups of blood plasma were examined for antibodies competing with mAb RS2: (1) plasmas from vaccinated donors without COVID-19; (2) plasmas from volunteers with mild symptoms of COVID-19; (3) plasmas from patients with severe COVID-19. It was demonstrated that antibodies competing with mAb RS2 were significantly more often recorded in sera from volunteers with severe COVID-19. The results demonstrated for the first time that in animals, SARS-CoV-2 can induce antibody/antibodies that can elicit ADE. Moreover, in the sera of patients with severe COVID-19, there are antibodies competing for the binding of an epitope that is recognized by the ADE-eliciting mAb.

Celiac disease (CD) is a well-studied disease among disorders associated with human leukocyte antigen (HLA). The prevalence of CD is about 0.7–1.4% of the population. This condition is multi-organ, because in addition to intestinal symptoms, there are a large number of extra-intestinal manifestations. CD occurs in people with a genetic predisposition. The disease is characterized by hypersensitivity to grain gluten proteins. The diagnosis can be made by detecting highly specific autoantibodies to transglutaminase 2 in the blood. All patients with CD should follow a gluten-free diet throughout their lives. Key words: celiac disease; gluten-free diet; gluten; transglutaminase 2

Modern medicine has successfully used the N-terminal pro-brain natriuretic peptide (NT-proBNP) as a biomarker for many cardiovascular diseases (CVDs). According to a number of studies, NT-proBNP may also play a role in the development of resistant hypertension (RH), but the existing work addresses this issue only indirectly. In turn, RH causes serious damage to the economic and social spheres, worsening the quality of life of patients. Thus, the complexity of verification and treatment of RH, the inconsistency of the described associations of NT-proBNP and RH makes this topic more relevant than ever.

The incidence of gallstone disease (GSD) and metabolic syndrome (MS) is increasing every year. The ICD-10 does not have the diagnosis of “metabolic syndrome” and it has been coded on the basis of the diseases despite its wide prevalence now. These are multifactorial diseases, the pathogenesis of which is intertwined and mutually aggravate their courses. There are both external and internal reasons of forming the stones in the biliary tract. Genetic factors play a significant role in the internal causes of cholelithiasis. The genetic characteristics of the patient allow to work out a personalized approach. It increases the success of drug therapy. MS is one of the main predisposing factors for the development of cholelithiasis. It also leads to more severe course of the latter. The pathogenetic mechanisms of the patologies developments are considered in the article presented with the special attention paid to the genetic component of cholelithiasis.

The aim of the work was to study the clinical significance of the genetic polymorphism of the adhesion factor - the genetic locus rs602662 FUT2 in Helicobacter pylori-associated diseases. Methods: The study included 91 patients. The study for the presence of the polymorphic locus rs602662 of the FUT2 gene was carried out by the standard TaqMan PCR method on a “Real-Time CFX96 Touch” amplifier. The duration of the study was 6 months. Results: When assessing the contribution of the genotype of the rs602662 locus of the FUT2 gene as a risk factor for the occurrence of clinical manifestations in H. pylori infection, it was found that the A allele has a protective effect on the occurrence of clinical symptoms of dyspepsia. The odds ratio (OR) for allele “A” carriers (genotypes A/A and G/A versus G/G) to have clinical symptoms with a positive H. pylori status was 0.175 (CI=[0.049-0.625] chi2=7.79 p=0.0053). Conclusion. As a result of the study, it was revealed that the carriage of the “A” allele has a significant associative relationship with the absence of clinical symptoms in patients with H. pylori infection 0.175 (C.I.= [0.049-0.625] chi2=7.79 p=0.0053).

The aim of the investigation was to study the level of vitamin D in the blood of adolescents with obesity/overweight compared with a normal body mass index of this age category. Methods. The study included 36 patients of a pediatrician or an endocrinologist who had a deficiency or insufficiency of vitamin D levels in the blood. After a month the therapy the patients included into the study passed the control analysis of the vitamin D levels. The duration of the study was a month. Results. The main group included 18 patients aged from 10 to 18 years, the control group included 18 patients of the same age. The average baseline of vitamin D in the main group in the start of the study was lower (18.39±1.31 nmol/l) compared to the control group (23.83±0.96 nmol/l, p<0.005). The initial concentration in the study groups, didn't show the clear relationship in terms of insufficiency and deficiency. Regardless body weight, the frequency of the pathology encountered did not have significant differences in the study groups, with the exception of allergic pathology, which is probably due to the randomness of the study group sampling. When comparing the normalization of vitamin D levels in the study groups, it was found that the index had risen higher in the control group, the Mann-Whitney U-test was 96 (p <0.05). Comparing the achievement of the target level of vitamin D after a month of the therapy in the compared groups, we obtained the data that in the control group all children fully reached the target levels, regardless the form of the drug received while in the main group, only 72.2% patients achieved the target level, 27.8% adolescents did not reach it, Fisher's exact test (two tailed) is 0.022, p<0.05. In the main group, inadequate dosages of vitamin D were taken by 72.2% of patients. Among them 55.5% of patients took higher dose and 16.7% of patients had lower one. In the control group, inadequate dosages of vitamin D were observed in 61.1% of patients: including, 22.2% higher and 38.9% were lower. Conclusion. As a result of the study, it has been found that the levels of vitamin D in overweight or obese adolescents are significantly lower than in adolescents with normal body weight living in the same region and having the similar lifestyle. The most effective method of correcting vitamin D insufficiency and deficiency is the use of vitamin D medicines at the recommended dosage and regularity.

Aim. To study the influence of atrial fibrillation on the severity of cognitive impairment in patients with arterial hypertension.Methods. The study included 25 patients with atrial fibrillation and arterial hypertension, the control group of 25 patients with arterial hypertension, but without cardiac arrhythmias. All patients underwent general clinical and instrumental examination of the cardiovascular system. The Montreal Cognitive Assessment test was used to assess memory and attention, the degree of mastering visual-constructive skills, abstract thinking and speech.Results. Cognitive functions in patients with atrial fibrillation were significantly worse than in patients in the control group (testing to assess indicators: 22.7 ± 3.2 and 25.6 ± 2.2 points, respectively, p < 0.001). Cognitive indicators such as memory, speech and abstract thinking are most severely affected in patients with arrhythmia.Conclusion. Atrial fibrillation creates conditions for the development of cognitive deficits. Cerebral hypoperfusion, the occurrence of "silent" cerebral infarctions and hypercoagulation are important pathogenetic factors of cognitive impairment in patients with atrial fibrillation. Received 29 July 2021. Revised 11 September 2021. Accepted 20 September 2021. Funding: The research was carried out within the state assignment of the Siberian Branch of the Russian Academy of Sciences (No. 121031300045-2). Conflict of interest: Authors declare no conflict of interest. Contribution of the authors: The authors contributed equally to this article.

Background . Clopidogrel is often used in patients undergoing coronary stenting for acute coronary syndrome. However, the CYP2C19 variants rs4244285(*2), rs4986893 (*3) affect the metabolism of clopidogrel. These alleles occur with different frequencies in patients of different nationalities, so the clopidogrel efficacy may differ in ethnic groups living in Russia. Objective . to assess the associations between genetic determinants of the risk of thrombotic complications during clopidogrel treatment and the clinical characteristics of Buryat and Russian patients, in order to search for personalized informative prognosis markers. Design and methods . The study included 142 Buryat and 150 Russian patients undergoing coronary stent placement for acute coronary syndrome. All patients received clopidogrel. Patients were stratified by the presence of CYP2C19*2 , CYP2C19*3 alleles. In all patients efficacy endpoints were assessed, as well as corresponding therapy. Results . In Buryat patients CYP2C19*3 allele was significantly more common (11,6 % versus 1,3 %, p < 0,001) than in Russian. In Buryat patients, recurrence of anginal pain during exercise was associated with the CYP2C19*3 and/ or CYP2C19*2 genotypes (p = 0,015), as well as with the taking omeprazole (p = 0.015). In Russian patients, efficacy endpoints in clopidogrel treatment were associated with the presence of CYP2C19*2 and/or CYP2C19*3 alleles (p = 0.036). Conclusion . The presence of minor CYP2C19*3 and CYP2C19*2 alleles, along with the reports of recurrence of anginal pain during moderate and light exercise in Buryat patients may be considered as a prognostic sign of thrombotic complications.

The article discusses the development of cognitive deficit in patients with atrial fibrillation (AF) and provides data on mechanisms of the development of cognitive disorders in AF. Under discussion are a possibility of reducing the risk of cognitive disorders with the anticoagulant therapy for prevention of stroke in AF and different properties of different anticoagulants, which may be important for patients. Thus, patients with cognitive disorders are more prone to missing the dose, which may entail serious, possibly fatal consequences. Therefore, the convenience of dosing may be essential. The drug rivaroxaban that has once-a-day dosing schedule and a calendar package, may help the patient better adhere to the doctor's recommendations. Therefore, rivaroxaban may help improving the compliance, which is the major condition for comprehensive, necessary protection of an elderly patient with AF, including the protection, with high safety, from stroke, from the risk of coronary complications, and from the impairment of kidney function.