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Fundamental and Clinical Medicine

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Vol 8, No 4 (2023)
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EDITORIAL

ORIGINAL RESEARCH

8-15 342
Abstract

Aim. To study of serum magnesium in women with a history of adverse pregnancy outcomes.

Materials and Methods. 74 women of child-bearing age, subject to voluntary informed consent, participated in a prospective cohort study. The main group (n = 31) included non-pregnant women who had a history of unfavorable gestation outcomes: premature birth, spontaneous miscarriage, habitual miscarriage, undeveloped pregnancy. The comparison group (n = 43) consisted of non-pregnant women with a history of two or more urgent deliveries. In all women, in preparation for pregnancy, the content of serum magnesium was determined by colorimetric method with xylidine blue.

Results. 77.6% of women with a burdened obstetric history of miscarriage (the main group) had various menstrual cycle disorders (FIGO, 2018). When analyzing the levels of magnesium in the blood serum of the examined women, it turned out that the obtained indicators in women of both groups corresponded to the established reference range of normal values of serum magnesium levels. At the same time, in the women of the main group, the average magnesium content in the blood serum was significantly lower and was closer to the lower limit of the range of normal values, and in the comparison group – in the middle of the range of normal values: 0.719 (0.672-0.767) mmol/l and 0.844 (0.778-0.922) mmol/l, respectively, p<0.001.

The optimal threshold value of the serum magnesium index in the study was 0.796 mmol/l with the sensitivity and specificity of the proposed prognostic model of 80.6% and 81.4%, respectively.

Conclusion. Determination of the level of magnesium in the blood serum of women at the stage of pre-pregnancy counseling is of particular importance. Despite the fact that all the examined women had serum magnesium levels within the range of its normal values, significantly lower serum magnesium levels were found in women with adverse pregnancy outcomes in the anamnesis, which necessitates prescribing magnesium-containing medications to such patients at the stage of pregnancy planning. For the prevention of miscarriage within the framework of preconception preparation with serum magnesium values ≤0.796 mmol/l, the intake of organic magnesium salts is recommended.

16-23 280
Abstract

Aim. To study the clinical and anamnestic characteristics of patients with endometrial hyperplasia (EH) and endometrial polyps (PE).

Material and Methods. a retrospective study was conducted, which included 267 sick women of reproductive and perimenopausal age who sought gynecological care at «Euromed» in 2022-23, who, before receiving the examination results, were diagnosed with N92 - heavy, frequent and irregular menstruation. Depending on the results of the pathomorphological examination, the patients were divided into 3 groups: group A included 89 patients with GE; group B – 99 women with PE; Group B (control) included 79 patients in whom endometrial pathology was excluded.

Results. Among all women who came to the clinic with heavy menstrual bleeding, 33.3% had GE, 37.1% had PE, 29.6% had BUN-O ovulatory dysfunction. GE without atypia was detected in 72 (80.9%) cases of group A, GE with atypia – in 7 (19.1%), in group B PE was diagnosed in 91 (91.9%) cases, PE with atypia – in 28 (8.1%).

In group B, in 22 (27.8%) cases, the endometrium was identified in the proliferation phase, in 57 (72.2%) cases, the endometrium was identified in the phase of incomplete secretion.

Conclusion. Women with GE are characterized by early menarche, absence of pregnancies and childbirth during life associated with the woman’s choice, contraception, endocrine diseases, obesity, polycystic ovary syndrome, ovarian tumors, heavy bleeding with clots during menstruation, menstruation for more than 8 days, chronic iron deficiency anemia. Women with endometrial polyps are characterized by arterial hypertension, uterine fibroids, adenomyosis, infertility, dysmenorrhea, chronic endometritis, a history of cervicitis and vaginitis; clinical manifestations include intermenstrual bleeding.

24-36 221
Abstract

Aim. To develop a method for noninvasive diagnosis of external genital endometriosis based on plasma microRNA concentrations.

Materials and Methods. 80 women of reproductive age who were admitted to the gynecological department for routine laparoscopy were retrospectively examined, according to the results of which and histological examination, the patients were divided into 2 groups: the main group — 54 patients with laparoscopically and histologically confirmed external genital endometriosis (EGE); the control group — 26 patients without EGE. Before laparoscopy, a blood sample was taken from all patients for a molecular-biological study of the expression of 10 microRNAs: miR-183, miR-125b, miR-126, miR-16, miR-15a, miR-200a, miR-20a, miR-21, miR-222 and miR-29b. Identification of the studied and normalizing RNAs (U6 RNA and 103a microRNA) was performed according to the method of Chen et al. The presented values of the expression of the studied microRNAs are given in the form of 2-ΔCt. The expression ratio is given in the form of 2-ΔCt (main)/2-ΔCt (control), if the expression in the group of patients with endometriosis exceeded that in the control group, and in the form of 2-ΔCt (control)/2-ΔCt (main), if vice versa.

Results. Comparison of the expression of 10 mi-croRNAs between the two groups revealed statistically significant differences only in miR-183: its expression in patients with EGE was statistically 1.5 times higher than that in women of the control group (p=0.017).

We have not detected a difference in the expression of mir-200a, while according to other researchers, representatives of the mir-200 family are among the most frequent whose expression changes with endometriosis. MIR-16 expression also did not differ statistically among the patients we examined, whereas a group of American colleagues revealed its increase in patients with endometriosis and with endometriosis-associated ovarian tumors. We found no difference in mir-21 expression. The results of other researchers are contradictory: some found its increase in endometrioid cysts compared with eutopic endometrium, an increase in the epithelium of the fallopian tubes with their endometriosis compared with unaffected; others did not reveal a difference between the eutopic endometrium of endometriosis patients and healthy women, but showed a decrease in expression in peritoneal foci and foci of deep infiltrative endometriosis compared with eutopic endometrium.

The expression of mir-222 was reduced in the patients we examined with endometriosis, which goes against the existing ideas about the pro-oncogenic role of this microRNA. An increase in its expression in cancer of the stomach, bladder, liver, lungs, breast, endometrium, ovaries is described. At the same time, the oncosuppressive effect of mir-222 is also known in prostate cancer, squamous cell carcinoma of the oral cavity.

Conclusion. Taking into account the revealed statistically significant difference in microRNA expression by ROC analysis, we determined their effectiveness and specificity in the diagnosis of EGE. Of course, further studies with a large contingent of patients are needed to confirm the diagnostic value of these biomarkers. In addition, our study did not allow us to establish a statistical difference in microRNA expression in patients with impaired fertility. But it is the test that makes it possible to differentiate female infertility — associated with endometriosis and without it, as a rule, tubal-peritoneal genesis — that will become a key tool in the personalized management of patients with infertility.

In our work, the distribution of patients by stages of EGE turned out to be uneven (there were no women with stage I at all) and it was not possible to establish a statistical difference in microRNA expression depending on the "length of service" of the disease.

37-53 299
Abstract

Aim. To validate ECFC culture as a candidate culture for vascular tissue engineering using comparative analysis of the proteomic and gene expression profiles in comparison with cultures of human umbilical vein endothelial cells (HUVEC) and human coronary artery endothelial cells (HCAEC).

Materials and Methods. ECFC culture was obtained by cultivating peripheral blood mononuclear cells of patients with coronary artery disease. Commercial HCAECs produced by Cell Applications, and HUVECs cultured according to the modified protocol of Jaffe were used as controls.

The cells were lysed with TRIzol, and total RNA was isolated using a Purelink RNA Micro Scale Kit with concomitant DNase treatment. Next, rRNA depletion was carried out, followed by the creation of DNA libraries. DNA libraries were quantified using quantitative polymerase chain reaction on a CFX96 Touch Bio-Rad amplifier. DNA libraries were equimolarly mixed and sequenced on HiSeq 2000 (Illumina) with a paired-end reads of 2x125 nucleotides.

Conventional western blotting was performed using pan-endothelial markers CD31, vWF, VEG-FR2/KDR, marker of endothelial progenitor cells CD34, markers of epithelial-mesenchymal transition Snail and Slug, and markers of endothelial specification: arterial HEY2, venous COUP-TFII and lymphatic LYVE1, VEGFR2. Dot blotting against 55 angiogenesis-related proteins was performed using Proteome Profiler Human Angiogenesis Array Kit in accordance with the manufacturer's protocol.

Results. ECFC overexpresses markers of all three endothelial lineages (KDR, VWF, CD34, NRP2, FLT4 and LYVE1 compared to HCAEC; NOTCH4, DLL2) and LYVE1 compared to HUVEC. Proteomic profiling indicated ECFC as an intermediate population between HCAEC and HU-VEC in term of the expression of HEY2, LYVE1, VEGFR3, Snail and Slug. 261 DEGs were detected between ECFC and HUVEC, and 470 DEGs between ECFC and HCAEC.

Conclusion. The gene expression profile of endothelial colony-forming cells corresponds to mature endothelial cells and indicates ECFC as an intermediate population between HCAEC and HUVEC. ECFC culture can be recommended for tissue vascular engineering.

54-64 249
Abstract

When performing operations on the abdominal and thoracic organs, the main share of postoperative complications is represented by the formation of adhesions or the development of an infectious process, which leads to a decrease in the quality of life of patients, the need for reoperation and often causes deaths. A solution to this problem can be the use of intraoperative biodegradable anti-adhesion membranes that have their own antibacterial activity.

Aim. Development of polymer anti-adhesion membranes with their own anti-inflammatory and antibacterial activity, assessment of their biocompatibility and biodegradation in in vivo experiments

Materials and Methods. The membranes are made by electrospinning from a composition of biodegradable polymers: polylactide-co-glycolide copolymer (50:50) and polylactide-co-glycolide (85:15). To impart antibacterial properties to the membrane, the antibiotic Tigacil was added to the polymer solution in various dosages - 0.125; 0.25 and 0.5 mg/ml polymer solution. The antibacterial activity of the membranes in vivo was assessed. The physical and mechanical properties were studied and the surface structure of the membranes was assessed using a scanning electron microscope. Biocompatibility and dynamics of biodegradation were assessed in vivo by implantation into laboratory animals (rats) for periods of 14 days, 1, 2 and 3 months, followed by histological examination of explanted samples.

Results. Polymer membranes made by electrospinning, without the inclusion of Tigacil, consist of threads whose thickness was 1.63 microns (1.422.85 microns); when Tigacil is included in the fiber composition, the fiber thickness decreases to 1.2 microns (0.977 - 1.89 pm), while the threads are more densely and orderly located. The strength and elasticity modulus of membranes with Tigacil are almost 2 times higher than those of samples without the inclusion of the drug. The maximum antibacterial effect was achieved at a Tigacil dosage of 0.5 mg/ml - the zone of inhibition of Staphylococcus aureus at a Tigacil concentration of 0.125 mg/ ml was 146%, 0.25 mg/ml - 152% and at a concentration of 0.5 mg/ml - 11 .5 mm 177%. The inclusion of Tigacil led to a decrease in the rate of biodegradation of samples in vivo. The samples underwent biodegradation without signs of acute and chronic inflammation.

Conclusion. The inclusion of Tigacil in the membrane gives it antibacterial properties, and the optimal concentration of Tigacil was 0.5 mg/ml of the polymer solution. The inclusion of Tigacil in the polymer composition affects the morphology of the membranes, increases the strength and elastic modulus, which led to a decrease in the rate of degradation when implanted subcutaneously in rats. The absence of signs of inflammation confirms the biocompatibility of the developed membranes.

65-72 238
Abstract

Aim. Assessment of the content of trans-fatty acids in foods consumed by the population of the Omsk region and the values of their actual consumption.

Materials and Methods. The results of laboratory studies of food products from the following groups were analyzed: fast food (hamburgers, french fries, chips); confectionery; oils, fats; meat products; dairy products (n=438). In product samples, the mass fraction of trans-fatty acid isomers was determined by gas chromatography. An assessment was made of the actual nutrition and consumption of trans fats by the inhabitants of the region using the method of analyzing the frequency of food consumption (n=441).

Results. The median content of trans fats in the main food groups was 0.67% of total fat, which does not exceed the values recommended by WHO. There was a decrease in the content of trans-isomers in food products from 2.7% in the period 2016−2017. up to 1.0% in the period 2020−2021 However, there remains a significant health risk associated with the consumption of trans-fatty acids, due to the high proportion of samples exceeding the recommended levels (24.5±2.1%), to a greater extent the risk was determined by the consumption of confectionery. The median consumption of TFAs in the study population was 1.16 g, which is in line with the recommended norms. The proportion of people with excess recommended consumption was 10.2%.

Conclusion. The results indicate an improvement in the situation related to the consumption of trans fats in 2016-2021 due to stricter requirements for their content in food products. It is necessary to conduct further research related to the assessment of the content of trans-isomers of fatty acids in the diet of various population groups to identify risk groups and priority food products - sources of trans fats.

73-84 499
Abstract

Aim. To identify the epidemiological features of HAIs in all patients admitted for surgery from 2018 to 2022. in a cardiac surgery hospital for the implementation of a risk-based prevention strategy.

Materials and Methods. A descriptive retrospective epidemiological study of the HAI epidemic process was performed from 2018 to 2022. in patients of a large cardiac surgery hospital (n = 6179). Stratified indicators were calculated. To display unknown relationships and make a forecast, Fourier spectral analysis was performed, followed by the use of artificial intelligence technology - neural networks. The STATISTICA Automated Neural Networks (SANN) tool was used, as well as the StatTech v. 3.0.5.

Results. The average rate of HAIs incidence over a 5-year period was 4.22 per 1000 patient days. We revealed decreasing trend of HAIs. Incidence of HCAI cardiopulmonary bypass surgery (CBS) was 3 times higher than without CBS (4.68 and 1.51 per 1000 patient-days, respectively). Fourier analysis revealed 10, 20, 30 cyclicity due to the dominant Klebsiella pneumoniae without the same time-series for other pathogens. The technology of neural network modeling did not reveal neural networks suitable for describing the forecast. Klebsiella pneumoniae showed properties typical of the hospital population and caused 35.49% of all cases of HAIs, had multidrug resistance to antibiotics in 74.45% of cases, with more than half of the strains having extended resistance, and 10.21% were pan-resistant. Acinetobacter baumanii also showed high epidemic activity, causing almost a fifth of all cases of HAIs, although its antimicrobial resistance characteristics were less pronounced than those of Klebsiella pneumoniae.

Conclusion. The epidemiological characteristics of the epidemic process of HCAI is one of the mandatory components of risk identification. The identified features of the dynamics of the epidemic process of HCAI in a cardiac surgery hospital, risk groups and time, the structure and characteristics of the microbiota should be taken into account in the HCAI risk management system.

REVIEW ARTICLES

85-100 392
Abstract

This review presents current information on the role of hypoxia-inducible factor-2 (HIF-2) under conditions of physiological tissue hypoxia and pathological hypoxic conditions. The structural and functional features of HIF-2 subunits (HIF-2α and HIF-β) and methods of their regulation under conditions of normoxia and hypoxia are described. The spectrum of cells expressing HIF-2α is quite diverse: endothelial cells of blood vessels, kidney fibroblasts, hepatocytes, interstitial cells (telocytes) of the pancreas, epithelial cells lining the intestinal mucosa, type II alveolocytes, glial cells, derivatives of neural crest cells (chromaffinocytes of the adrenal gland). HIF-2α -dependent transcriptional effects are highly locus specific and occur only under certain circumstances. Regulation of HIF-2α translation can be accomplished by two classes of regulatory molecules (RNA-binding proteins and mR-NAs) by altering the rate of translation due to binding to the 3' or 5' untranslated region of mRNA (3' or 5' UTR) of specific targets. HIF-2α activity is regulated primarily at the post-translational level by various signaling mechanisms at the level of mRNA expression, mRNA translation, protein stability, and transcriptional activity. Under normoxia, the canonical regulation of HIF-2α activity is determined by oxygen-dependent mechanisms, and under hypoxia conditions - by non-canonical (oxygen-independent) mechanisms, through phosphorylation, SUMOlyated, acetylation, methylation, etc., causing positive and negative effects. It has been established that HIF influences signaling pathways affecting embryonic development, metabolism, inflammation and the physiology of functional systems, and also works in long-term responses to chronic hypoxia, during which it regulates angiogenesis, glucose, iron, lipid metabolism, cell cycle, metastasis and other processes. Studying changes in the intracellular content of HIF-2α and the transcriptional activity of HIF-2 will allow us to develop effective methods for correcting various diseases accompanied by systemic and local oxygen deficiency.

101-114 435
Abstract

The “aging” of the population increased the importance of researches in the field of the epidemiology of chronic diseases, including Alzheimer's disease (AD) -the most common cause of dementia in the population.

Aim. The role of potential risk factors for AD through a systematic review and meta-analysis. The “aging” of the population has updated research in the field of the epidemiology of chronic diseases, incl. Alzheimer's disease (AD) is the most common cause of dementia in the population. The aim of the study was to assess the role of potential risk factors for AD through a systematic review and meta-analysis.

Materials and Methods. Using the electronic databases PubMed, Scopus, E-library, a search was made for articles in Russian and English, published from 1995 to 2022. In accordance with the clinical question, using the PECO formula, papers were selected in which the authors investigated the role of various risk factors in groups with and without AD. The study was carried out in accordance with the international guidelines for writing systematic reviews and meta-analyses "PRISMA". Study quality was analyzed using the Newcastle-Ottawa scale for cohort and case-control studies. The degree of heterogeneity was assessed using the chi-square test and the I2 coefficient. Publication bias was analyzed using a funnel plot. We used the software Review Manager 5.3 and Microsoft Office Excel 2010.

Results. Initially, 3197 articles were retrieved from the databases; After screening and eligibility analysis, 17 studies were included in the me-ta-analysis (11 case-control studies and 6 cohort studies). Totally, these publications included data from 134,732 people with a confirmed diagnosis of AD and 1,058,143 respondents without AD (control group). According to the results of the meta-analysis, significant risk factors were: heredity (odds ratio (OR) 1.82; 95% confidence interval (95% CI) 1.66-1.99), arterial hypertension (OR 1.65; 95% CI 1.29-2.13), hypercholesterolemia (OR 1.25; 95% CI 1.13-1.38), obesity (OR 1.13; 95% CI 1.09-1.17), presence of diabetes mellitus 2 type (OR 1.36; 95%; CI 1.15-1.62), low level of education (OR 1.61; 95% CI 1.18-2.18), depression (OR 1.35; 95% CI 1.03-1.76). There was no relationship with alcohol consumption, smoking, a history of myocardial infarction and / or coronary heart disease, a history of acute cerebrovascular accident, insomnia, female gender, traumatic brain injury.

Conclusion. The conducted meta-analysis allowed to obtain confirmation of the role of various potential risk factors for AD; at the same time, many of them are modifiable and are associated with metabolic disorders, which can probably be involved into the process of accumulation and deposition of beta-amyloid in the cells of the nervous system. Continued research on this issue could contribute to the development of prognostic scales and personalized recommendations for the prevention of this currently incurable disease.

115-123 292
Abstract

Despite the wide arsenal of chemotherapeutic agents, the search and study of new compounds with an alleged antitumor effect is relevant. Morphological diagnostics of pathological processes occurring under the action of pharmacologically active substances is the most important component of preclinical research of compounds with an alleged antitumor effect. It is advisable to use information about the possible cytotoxic effect of candidates for antitumor drugs using an immunohistochemical method for studying organs and systems of experimental animals at different stages of the development of the tumor process by indirect markers of tumor progression activity. Morphological examination of parenchymal organs and tumor tissue in the dynamics of the development of malignant neoplasm is more informative and evidence-based than biochemical research. The aim of the study is to conduct a comparative analysis of markers of tumor process activity for more effective use of morphological and immunohistochemical research methods in the preclinical study of compounds with suspected antitumor activity to assess the prospects for their use with the detection of tumor process activity. The literature search was carried out using the Scopus, Web of Science, PubMed and eLIBRARY databases. The paper presents an overview of current molecular biological markers for assessing the activity of the malignant process in the experiment: Transforming Growth Factor beta 1 (TGF-β1), Ki-67, Tumor necrosis factor alpha (TNF-α), p53, Poly-ADP-ribose polymerase 1 (PARP-1) and Anti-8-Hydroxy-2'-deoxyguanosine (8-OHdG), beta III Tubulin, p120 Catenin, Beta Actin. The listed markers are indirect and can be used in a single mode only for screening studies of antitumor and antimetastatic activity in which a large number of compounds are sorted according to the principle of effectiveness. When conducting an in-depth study of the pharmacological activity of the leader compounds it is necessary to perform a comprehensive immunohistochemical study. Our analysis of the literature data confirms the importance of selecting optimal, sensitive, economically feasible and affordable markers, which in turn leads to the improvement of diagnostic panels and their standardization to simplify their transition into clinical practice.

124-132 338
Abstract

Using information technologies at all stages of patient care is necessary at the current state of medical development. It is particularly important to implement innovative information technologies in the management of patients with cardiovascular diseases in the outpatient setting, in secondary prevention and rehabilitation that continues throughout life. Various wearable devices for hemodynamic monitoring, electrocardiographic and physical activity assessment, that help the patient`s condition during rehabilitation, have been widely used in clinical practice all over the world. However, considering the outpatient setting, a cardiologist or rehabilitologist should to be able to monitor the data obtained using a single source, and to communicate with the patient in order to adjust treatment. Applications for mobile devices providing feedback can be a convenient tool in this regard. To date, many applications have been developed for smartphones, including those that synchronize with wearable devices, to record patient parameters, including the level of physical activity. Most of them are limited by self-control. Both in Russia and in other countries, a number of problems and limitations associated with the use of these technologies are related to the patient, the imperfection of the health care system, and problems with the devices themselves. The present article is devoted to an overview of existing remote rehabilitation technologies focusing on the applications for mobile devices. The authors present a short summary on domestic and international development in information technologies, identify the problems and future development of this area in health care.

133-141 241
Abstract

Considering the progressive decrease in the number of women of fertile age, as well as children and adolescents, the primary medical and social task at the present stage is to preserve the reproductive health and life of women, preserving every desired pregnancy. The concept of demographic policy of the Russian Federation for the period until 2025 defines the global national goals, i.e. to increase the total fertility rate by 1.5 times, to reduce maternal and infant mortality by at least 2 times, and to improve the reproductive health of women, children and adolescents. Today every fifth desirable pregnancy ends in early loss, and the rate of miscarriage does not tend to decrease and, in fact, increases every year. Carriage of susceptibility or candidate genes can alter the course of biochemical processes in women and cause early pregnancy losses. According to the literature, the cytochrome P-450 gene (CYP1A1, CYP1B1), xenobiotic detoxification genes (GSTT1, GSTM1, GSTP1) and many others are recognized as candidate genes (genetic markers) associated with reproductive losses. Adverse pregnancy outcome is usually multifactorial; in turn, the combination of polymorphic variants of different candidate genes can increase the risk of early losses. A detailed study of the role of candidate genes with clarity and confirmation of the interest of candidate genes in the development of pregnancy loss is undeniable. In this regard, the interest of many researchers in studying the polymorphism of genes of the xenobiotic biotransformation enzyme system as one of the causal factors of pregnancy failure is understandable. The study of this group of genes is of particular relevance in regions with developed industry and high anthropogenic load. The article is devoted to the analysis of the existing data of foreign and domestic literature sources concerning the relationship between polymorphism of xenobiotic biotransformation system genes and reproductive losses.



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ISSN 2500-0764 (Print)
ISSN 2542-0941 (Online)