In the modern conditions of unfavourable environmental situation in most cities, the problem of reproductive disorders (infertility and miscarriage) is becoming increasingly important. Oft en this can occur due to diseases of the endocrine system, in particular, due to autoimmune damage to the
thyroid gland. Th e most modern method of combating infertility today is the programme of assisted reproductive technologies (ART), although its eff ectiveness may decrease due to the presence of autoimmune thyroiditis (AIT). Research data on the eff ectiveness of ART in females with AIT are extremely
contradictory. However, most evidence suggests that superovulation induction in ART programmes elevates the risk of thyroid dysfunction in women with
AIT. Patients with AIT are always at risk of hypothyroidism development in early pregnancy. Th erewith only L-thyroxine treatment is presently provided for
women with infertility or miscarriage in combination with AIT who decide to use the in-vitro fertilisation (IVF) programme, which does not always show
high effi cacy. Further studies are required to assess the role of AIT in reproductive disorders, as well as to develop alternative methods for AIT correction, including the condition of euthyroidism

Th is literature review addresses a number of modern concepts of aetiopathogenetic mechanisms in placental dysfunction and their role in development
of CNS pathology in the foetus. A complex analysis of literature data has made it possible to understand the complexity and multifaceted nature of placental
disorders modulating brain development from the moment of trophoblast implantation. Th e eff ects of prenatal factors on the foetus are limited to the protective
function of the placenta retaining the placental reserve. Nevertheless, gestation pathology beginning from embryogenesis defi nes genetic and epigenetic impairments confi rming the concept of the placenta being “the third brain” connected to the maternal brain and the foetus’s developing brain and conditioning the
severity of hypoxic-ischaemic injury and the nature of further neurological impairments. Th e review has been written based on analysis of literatures presented in
eLIBRARY.RU, Cyberleninka, PubMed, ScienceDirect and Web of Science databases published in 2005-2021 (predominantly within the past 5-7 years) using the
following keywords: molecular and genetic predictors, preeclampsia, angiogenesis, neurogenesis, vascular endothelial growth factor and VEGF.

Th e condition of collagen fi bres in the skin directly aff ects its mechanical properties, which in turn aff ects the external condition of the skin, refl ecting
the age of a person. Th at is why the genetic aspects of the synthesis, functioning and degradation of collagen fi bres are of great interest in cosmetology and
dermatology. Quite a large number of patients turn to cosmetologists in order to correct the external manifestations of aging. Classically, procedures are
carried out to correct collagen synthesis, but development of personalised pathogenetically based therapy of involutional skin changes requires understanding
of features of the main links of exchange in collagen fi bres, including the processes of collagen degradation. Knowing clinical and genetic features of collagen
metabolism in a particular subject, it is possible to assess the risk of premature skin ageing and develop a personalised patient management scheme. Th is
review is devoted to genetic aspects of functioning of skin collagen fi bres and the features of their degradation.

Aim of study. To study the relationship between the thickness of the parenchyma of the aff ected kidney and the nature of its morphological changes.
Material and methods. Archival medical records of 350 patients operated on for congenital hydronephrosis within the period 1990-2020 were processed. Th e
age of patients at the time of surgery ranged from two months to 18 years. Based on the protocols of ultrasound examination of the kidneys before surgery,
the parenchymal thickness defi cit was calculated. Morphological analysis of parenchymal tissue was carried out on the basis of its histological conclusion.
Results. An increase in the loss of the parenchymal layer of all segments of the aff ected kidney with increasing age at the time of surgery has been revealed.
Atrophic processes of the parenchyma tissue of the hydronephrotic kidney are intensified with a decrease in its parenchymal thickness.
Conclusion. Th e thickness of the parenchyma of the aff ected kidney decreases and the degree of its atrophic changes increases with increasing duration of
the disease.

Aim of study. To conduct a study of pathomorphological changes in the colon of patients with severe forms of pseudomembranous colitis and evaluate the
possibilities in conservative and surgical treatment.
Material and methods. Th e paper presents analysis of pathomorphological changes in the colon in patients with pseudomembranous colitis (PMC). Th e effectiveness of treatment with pseudomembranous colitis was evaluated for 45 patients, among which 30 (67 %) with moderate course underwent conservative
therapy, including vancomycin and metronidazole, and 15 (33 %) patients with severe and complicated forms of PMC underwent surgical treatment. A total
of 10 patients underwent organ-preserving surgeries with ileostomy (including its combination with sigmostomy) to exclude the colon from the passage with
retrograde and its antegrade irrigation with vancomycin solution.
Results. Histological examination revealed signifi cant changes in the intestinal wall in patients with PMC, characterised by cystic dilatation of crypts and
glands, hypersecretion of mucus, followed by desquamation of the mucous membrane against the background of deep lymphocytic infi ltration. Th e duration
of conservative treatment was 35.3±1.4 days. Along with the main laboratory parameters (signifi cant leukocytosis, stab shift to the left , an increase in the
level of creatinine, C-reactive protein, a decrease in the amount of total protein), additional predictors of the failure of conservative therapy for PMC were
identifi ed, including shock and the need for inotropic support, the need for mechanical ventilation, acute renal failure, organ dysfunction. Th e mortality rate
amounted to 30 %. A total of 5 patients with a complicated course of the disease (toxic dilatation, perforation of the colon) underwent resection operations
(colectomy – 4 and hemicolectomy – 1) according to vital indications. A total of 3 (75 %) patients died.
Conclusion. It has been established that it is worth expanding the indications for surgical treatment of PMC if conservative therapy is ineff ective, and it is
possible to perform organ-preserving surgery aimed at shutting off the colon via ileostomy in the absence of severe surgical complications

Th e aim of the research. To improve treatment outcomes for patients requiring formation of entero-colonic anastomoses using a new method for prevention
of their leakage.
Material and methods. A total of 60 patients operated on for peritonitis who potentially required entero-colonic anastomosis were divided into 2 groups. Th e
retrospective comparison group included 33 subjects and 27 subjects were enrolled into the prospective main group. Anastomoses for patients in the main
group were formed according to the proprietary method that improves blood fl ow along the suture line. Th e method consisted in the following: the leading
segment of the small intestine was crossed at an angle of 50-60° to its mesenteric edge. Th e colon stump was also formed by crossing at an angle of 50-60° to
its mesenteric edge; a “window” was cut in the antimesenteric part of the colon wall: an oval-shaped area with an area corresponding to the cross-sectional
area of the small intestine, the end of the small intestine was connected to the oval hole in the colon “end to side” using a single-row continuous intestinal
suture. Primary endpoint: development of leakage in the formed entero-colonic anastomosis. Secondary endpoint: mortality of patients in the postoperative
period until discharge from the hospital.
Results. Th e proportion of leakage amounted to 3.7% in the main group, and 33.3 % in the comparison group (p=0.007). Th e mortality was 7.4 % and 36.3 %,
respectively (p=0.012).
Conclusion. Th e proposed technique for entero-colonic anastomosis formation has advantages due to a signifi cant reduction in the frequency of fi stula
leakage and mortality.

Th e aim of the research. To study the eff ects of lead intoxication on blood parameters in battery factory workers with dust bronchitis and bronchial asthma.
Material and methods. Th e study was conducted on battery factory workers (45 subjects) aged 30 to 60 years who came into contact with lead and on healthy
volunteers (15 subjects). Blood parameters were evaluated in hematological analyser XT-2000i using a unique technology of fl uorescent fl ow cytometry.
Results. Employees of the battery plant develop occupational diseases: dust bronchitis and bronchial asthma. In all studied groups of patients, laboratory
blood parameters changed compared with the control group: anemia, leukocytosis, haemoglobinopathy, a change in the qualitative characteristics of the leukocyte formula, an increase in the percentage of micro and macrophages were observed. Activation of intravascular coagulation is characteristic to all groups
of patients, which indicates a tendency to DIC syndrome. Comparative characteristics of blood parameters revealed deeper changes in BA patients who were
exposed to lead in their professional activities. It has been established that the technique of fl ow cytometry for determining functional blood parameters is
informative and can be used to characterise the condition of persons with occupational diseases based on lead intoxication.
Conclusion. For the fi rst time, it has been revealed that the total number of platelets increases with the growth of their size in battery factory workers, which
indicates a trend toward DIC syndrome. For the fi rst time, a decrease has been fi rst found in the concentration of haemoglobin, the number of red blood
cells, an increase in the total number of leukocytes due to lymphocytes with a decrease in neutrophils and eosinophils in patients with dust bronchitis. Th ere
is a correlation between the amount of haemoglobin and the number of leukocytes. It has been found for the fi rst time that employees of a battery factory suff ering from bronchial asthma have an increase in the amount of haemoglobin, erythrocytes, leucocytosis due to lymphocytes, but the linear associations
between leukocyte parameters are very weak. Based upon this, we recommend repeating medical examination with shorter intervals in between. Th e timing
of periodic inspections depends on the nature of production and types of work with lead and its compounds. When applying for a job, such contraindications
as blood diseases and diseases of the respiratory and cardiovascular systems should be a principal factor.

Th e aim of the research. To study the infl ammation pattern, myeloperoxidase activity and the content of the epithelium in the bronchi of patients with bronchial asthma (BA) with diff erent forms of airway hyperresponsiveness to physical stimuli.
Material and methods. Th e degree of asthma control, pulmonary function, and cellular composition of induced sputum were studied in 142 BA patients
with various forms of airway hyperresponsiveness to indirect provoking triggers. In cytological smears, the number of neutrophils, eosinophils, bronchial
epithelial cells was counted. A cytochemical study of myeloperoxidase activity in sputum neutrophils was carried out.
Results. It has been established that BA patients with combined airway hyperresponsiveness to various physical stimuli have lower asthma control, a higher
number of eosinophils in sputum, a higher level of myeloperoxidase in neutrophils, and a lower percentage of intact bronchial epithelium compared to patients with isolated cold airway hyperresponsiveness. A close relationship was found between the level of eosinophils and the number of intact epitheliocytes
(Rs=-0.52, p<0.001). In patients with combined airway hyperresponsiveness, a relationship was found between the activity of myeloperoxidase in neutrophils
and the severity of the bronchial response to isocapnic hyperventilation with cold air (R=-0.33; p<0.05).
Conclusion. Activation of the peroxidase function of neutrophils and stimulation of the eosinophil activity, which leads to destruction of the epithelium and
a decrease in the content of normal epitheliocytes, are associated with a greater severity of airway hyperresponsiveness to cold and the addition of reactions
to other stimuli.

Th e aim of the research. To assess baseline clinical parameters of patients with atrial fi brillation and to analyse the whole variety of drugs they receive at the
time of the development of cardioembolic stroke from the standpoint of evidence-based cardiology.
Material and methods. Th e study was conducted at the premises of the neurological department for patients with acute cerebrovascular accidents of the
Samara Regional Clinical Hospital named aft er V.D. Seredavin within the period from 2016 to 2019. In total, 139 patients were enrolled, of which 59 were
male. Th e average age of the patients was 72.25±6.33.
Results. Patients with atrial fi brillation admitted to the primary vascular department due to cardioembolic stroke were characterised by polymorbidity, namely: arterial hypertension was detected in 99.28 %, chronic kidney disease in 53.96 %, coronary heart disease in 30.94 %, diabetes mellitus in 19.42 % of the
cases. Subjects with chronic atrial fi brillation prevailed among the studied patients (62.6 % of the cases). Th e risk of thromboembolic complications according
to the CHA2DS2-VASc scale before admission to the hospital averaged at 4.37±1.2 points, while 97.84 % of the patients had indications for anticoagulant
therapy. However, in real clinical practice, the prevention of thromboembolic complications was only carried out in 13.67 % of the cases and its quality was
in compliancy with modern requirements in 3.60 % of the cases only.
Conclusion. Th e data obtained attest to cardioembolic stroke developing in polymorbid patients with atrial fi brillation against the background of low quality
management of patients with atrial fi brillation at the outpatient-polyclinic stage. Th is may indicate incomplete awareness of doctors about the possible risks
of developing a feasibility study in patients with atrial fi brillation, as well as low patient adherence to treatment.

Th e aim of the research. Assessment of changes in immune response factors during antiviral therapy of cervical intraepithelial neoplasia of severity grades
I and II against the background of human papillomavirus.
Material and methods. An outpatient examination of 232 female subjects of reproductive age was carried out. Among these, 172 women were with a histologically confi rmed diagnosis of mild to moderate cervical intraepithelial neoplasia (CIN I-II) associated with papillomavirus infection. During the work,
each patient underwent cytological and colposcopic examination as well as real-time HPV typing with viral load evaluation. To establish the fi nal diagnosis,
if necessary, a multifocal biopsy of the cervix was used. Within the framework of the designated goal, changes in the cervical zone were studied and analysed
by means of assessing caspase-3, caspase-9, IFN-γ, IL-18.
Results. As part of the study, changes in the caspase and cytokine profi le were analysed in HPV-associated cervical intraepithelial neoplasia of grades
I-II, which substantiated the use of immune system correction for successful treatment of patients with mild to moderate dysplastic processes.
Conclusion. Th e results obtained in the study make it possible to optimise management of patients with HPV-associated cervical intraepithelial neoplasia of severity degrees I-II.

The aim of the research. To analyse the relation between gender and age characteristics and various anthropometric parameters of obesity with impaired lipid metabolism among residents of the industrial region of Siberia
Material and methods. A total of 1,600 subjects aged 35-70 were enrolled. Th e mean age was 54.9±9.75 years and 52.6±10.0 years. Th e study was carried out
in accordance with Good Clinical Practice and Declaration of Helsinki principles. Prior to inclusion, all respondents signed an informed consent form approved by the institution’s local ethics committee. Th e studied indices of lipid blood spectrum were evaluated using standard tests by Th ermo Fisher Scientifi c,
Finland. Th e change in lipid level was assessed according to the “Diagnosis and correction of lipid metabolism disorders for the prevention and treatment
of atherosclerosis recommendations, revision 5, 2012. Obesity was assessed based on fi ve anthropometric parameters: body mass index (BMI), waist-to-hip
ratio (W/H), waist circumference (WC), skeletal muscle mass-to-visceral fat area ratio (SVR), and visceral adiposity index (VAI). Statistical processing was
carried out using Statistica 6.0. Quantitative variables are presented as a median (Me), percentiles (25 %; 75 %) were used as scattering measurements; frequencies (percentages) were used to describe qualitative characteristics. Th eir comparison was carried out using Mann Whitney and Pearson’s Chi-squared
test. As an indicator of the contribution of the risk factor (obesity, assessed according to various criteria) to the prevalence of dyslipidemia variants, the values
of the predictor signifi cance ranking was used (when using classifi cation trees, discriminant univariate branching was selected and the signifi cance of the
predictors was evaluated during the classifi cation process).
Results. Hypercholesterolemia was detected in 66.2% of the subjects, hypertriglyceridemia – in 36.3 %. A high level of LDL was found in 75.6 %, and a low level
of HDL – in 38.7 % of the respondents. Among men aged 35-49 years, total cholesterol, TG and LDL were higher than in women (p <0.001). At the age of 50-59
years, total cholesterol and LDL cholesterol were higher in women (p <0.001). At the age of 60-70 years, the mean level of total cholesterol and TG was also higher
in women than in men (p <0.001). Th e frequency of detection of dyslipidemia, depending on the presence of obesity, diff ered when using all the studied obesity
criteria, especially for WC. According to such criteria as BMI, WC, VAI, the prevalence of obesity was higher among women and in men when using the criterion
of the area of visceral fat. Th e presence of obesity according to the criteria of WC, W/H and VAI demonstrated the presence of associations with indicators of
the entire lipid spectrum. Th e highest values were demonstrated by the presence of obesity according to VAI: it was associated with an increase in TG by 1.23
mmol / l and with a decrease in HDL cholesterol by 0.49 mmol / l (p <0.001). At a younger age, indicators characterising a poorer lipid profi le (high values of TC
and LDL, low HDL) were found in males, while with increasing age, these changes in lipid metabolism were observed in the female patients. When performing
linear regression analysis, the greatest infl uence was demonstrated by age (rank 100 for hypercholesterolemia and high LDL cholesterol) and VAI (rank 100 for
hypertriglyceridemia and low HDL). Th e rest of the studied obesity criteria demonstrated approximately the same value of the ranks for all studied parameters
characterising lipid metabolism. It should be noted that the sex showed the lowest values for all the studied parameters of the lipid spectrum.
Conclusion. When analysing the relationship between gender and age characteristics and various anthropometric parameters of obesity with impaired lipid
metabolism, the following patterns were revealed among the inhabitants of a large industrial region of Siberia, according to the data of this epidemiological
study. Th us, such parameters as VAI, WC, W/H, which characterise obesity, are more reliable while assessing the risk associations for development of dyslipidaemia, in contrast to the classical assessment of obesity by BMI. It should be noted that VAI was a more signifi cant criterion in assessing the risk of hypertriglyceridemia and low HDL levels. Considering the gender and age of the surveyed respondents, the following diff erences were revealed. Male subjects of
younger age were characterised by higher results of LDL, total cholesterol and HDL. With increasing age, this trend changed and a more unfavourable course
of dyslipidaemia was observed in females. Th is study proves the need to take into account the extended parameters of obesity when assessing dyslipidaemia.
Th e use of extended criteria for assessing obesity will provide additional information in the management of patients with dyslipidaemia. However, further
research is needed to find out whether the identifi ed patterns are regional features or may be projected on all residents of our state

Tne aim of the research. To evaluate the main parameters of neutrophil extracellular traps formation (NETosis) and their dynamics in rheumatoid arthritis
(RA) patients associated with the transition from remission to active autoimmune infl ammation.
Material and methods. A total of 37 patients (6 males and 31 females) with verifi ed RA according to the ACR/EULAR 2010 criteria were enrolled in the study
and formed the main group. Th e comparison group was constituted by 30 healthy volunteers. Circulating neutrophils were isolated with one-step density
gradient centrifugation using double layers of iohexol gradient in the original modifi cation. Th e quantitative composition of neutrophils was assessed through
microscopy of smears stained according to May-Grunwald. Cell viability as well as non-specifi c activation were evaluated microscopically using trypan blue
exclusion assay and nitroblue tetrazolium test, respectively. Neutrophil extracellular trap (NETs) formation was induced by 50 nM phorbol-12-myristate-13-
acetate and assessed using fl uorescence microscopy.
Results. Neutrophils isolated from RA patients in clinical remission have been revealed to have a higher ability for spontaneous and induced NETs formation
than neutrophils from the comparison group. Th e transition from remission to active RA was characterised by a signifi cant increase in induced and, especially,
spontaneous formation of NETs. Th e growth rate of spontaneous NET formation was 3.9-fold higher than the induced NETs formation. Spontaneous
formation of NETs above 16.4 % may serve as a possible RA activation indicator. Neutrophils from ACPA-positive RA patients were found to have increased
spontaneous and induced NETs formation compared to ACPA-negative RA patients.
Conclusion. We have studied the main parameters of NETs formation and their dynamics associated with the transition from remission to active autoimmune
infl ammation in RA patients. Th e activity of RA has a more pronounced eff ect on the intensity of NETs formation than the presence of ACPA. NETs may be
considered a new potential diagnostic and prognostic biomarker

Th e aim of the research. To study markers of angiogenesis and infl ammation in dominant fi broids and myometrium.
Material and methods. Myomectomy in 226 patients of reproductive age with uterine myoma was carried out. Th e resected samples of dominant myomatous
nodules and perifocal myometrium of 35 females including 12 treated using selective progesterone receptor (PgR) modulator were examined for the content
of granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF) and 17-hydroxyprogesterone in the incubation
medium using enzyme-linked immunosorbent assay (ELISA). Spontaneous and stimulated by polyclonal activators (PA) levels of the markers were studied.
Additionally, the expression of PgR and VEGF was analysed through immunohistochemistry (IHC). Nonparametric statistics methods were used. Th e
Wilcoxon test was used for intragroup comparison, the Mann-Whitney test was used for intergroup comparison. Th e correlations between biomarkers were
studied using the Spearman correlation coeffi cient.
Results. In the surgical specimens of leiomyoma and myometrium treated without hormone therapy, statistically signifi cant diff erences were revealed for
PA-stimulated GM-CSF production incubated in vitro (2-fold lower in the nodule than in the myometrium), as well as for VEGF expression in tissue samples
(2-fold higher in the nodule than in the myometrium). PgR expression in the myometrium directly correlated with the infl ammatory infi ltration of the
nodule. Th e use of the selective PgR modulator contributed to the downregulation of GM-CSF production and VEGF expression in the nodule with no
eff ect on the myometrium, as well as to a decrease in 17-OH-progesterone in the myometrium without changes in the nodules, and to a negative correlation
between PgR expression and VEGF production in leiomyomas.
Conclusion. For the dominant fi broid, application of the selective PgR modulator contributed to a downregulation of VEGF expression and to the decrease
of in-vitro production of GM-CSF without infl uence on the perifocal myometrium, which demonstrates its proangiogenic and proinfl ammatory potential
in patients with uterine myoma

Drug-induced liver injury is a rare but life-threatening phenomenon. Paracetamol is referred to as a drug with a direct dose-dependent hepatotoxic
eff ect. Th e use paracetamol, even in therapeutic doses, is essentially safe, but requires a sensible approach while prescribing it to the risk groups and “off -
label”. Th e use of paracetamol in children is limited at the age of less than 3 months. Signifi cant damage to hepatocytes by paracetamol in children is relatively
rare and only occurs in 10% of the cases while taking potentially toxic doses of the drug. We have recorded a clinical case of toxic hepatitis development in
a newborn aft er intravenous “off -label” administration of therapeutic doses of paracetamol in order to relieve the pain syndrome. Th is case is indicative of the
fact that even therapeutic doses of paracetamol, as well as the predominantly sulfate pathway of drug biotransformation, which is typical for children under
14 years of age, does not rule out the possibility of toxic drug-induced liver damage. Taking into account the described case, there is a need to determine clear
indications for “off -label” use of the drug in view of the possible toxic eff ect development.

The article considers preoperative diagnosis of a rare disease: arterial malformation of the lower lobe of the lung in a child aged 1 year (no
descriptions of similar cases found in Russian literature and only scarce data thereon in foreign papers). The stages of differential diagnosis, the results of
radiological diagnosis methods and the result of surgical treatment are presented. The importance of a joint examination of the patient with the attending physician (surgeon) during diagnostic procedures to minimise possible complications is shown