Bulletin of RSMU

ISSN Print 2500–1094 ISSN Online 2542–1204

Bulletin of RSMU

BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)

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Goryainova AYu, Usman NYu, Rubanovich AV, Borinskaya SA, Mescheryakov AA

Tamoxifen therapy results in endometrial thickening in some patients with hormone-sensitive breast cancer (HSBC). The data on the impact of polymorphic variants of the CYP2D6 gene encoding the CYP2D6 enzyme of the cytochrome P450 family on the efficacy and safety of treatment with tamoxifen are controversial. A prospective cohort study was aimed to explore the association of CYP2D6*3, *4, *6 polymorphisms with the risk of endometrial thickness during adjuvant tamoxifen therapy for HSBC. A total of 145 patients with resectable HSBC, who received 20 mg of oral tamoxifen per day, were enrolled. The CYP2D6*3, *4, *6 polymorphisms were identified by real-time PCR. Endometrial thickness was measured by ultrasonography after 3, 6 and 9 months of endocrine therapy. The study showed that endometrial hyportrophy was more often found in patients having no alternative alleles after 3 months of follow-up (40% against 23.2% in the group of “poor” metabolizers; p = 0.034). Meta-analysis of all follow-up periods has revealed that “normal” metabolizers show a significantly higher rate of endometrial thickness than “poor” metabolizers (OR = 1.88; 95% CI = 1.27–2.79; p = 0.002). A lack of significant differences in indicators of the state of endometrium between groups of patients with different CYD2D6 genotypes and menopausal status requires further investigation.

Received: 2023-09-28

Published online: 2023-10-29

DOI: 10.24075/brsmu.2023.041

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VIEWS 1898

Solovyova JuV, Paunova SS, Semicheva VR, Skoblina NA, Milushkina OYu

Uncontrolled screen time is a worldwide menace to health of the population. Today, the state of neuropsychiatric health of schoolchildren depends on various factors, including screen time, i.e., the time they spend using mobile electronic devices. This study aimed to investigate how different screen time durations affect the said neuropsychiatric health of this population group. In the 2022–2023 academic year, we surveyed 109 Moscow schoolchildren (35 boys and 74 girls) using questionnaires compiled by A.M. Vane (identification of signs of vegetative symptoms) and S.K. Kulakov (identification of internet addiction). The mean age of the participants was 14.9 ± 0.12 years. The children were divided into two groups: those staying within the regulated limit of mobile screen time (group 1, n = 11), and those exceeding that limit (group 2, n = 98). In group 1, the average mobile screen time, as measured for one month, was 110.50 ± 10.00 minutes per day, in group 2 — 345.00 ± 15.00. The average Vane questionnaire scores differed significantly between the groups (p ≤ 0.01): 12.30 ± 1.89 points in group 1 and 22.54 ± 1.16 points in group 2. Signs of vegetative symptoms were registered in 45.9% of group 1 participants and 63.6% of group 2 participants (p ≤ 0.01). The average Kulakov questionnaire scores differed significantly between the groups (p ≤ 0.05): 28.7 ± 1.88 points in group 1 and 37.1 ± 1.09 points in group 2. Schoolchildren who exceed the regulated mobile screen time limit are at risk of developing vegetative disorders and internet addiction.

Received: 2023-10-02

Published online: 2023-10-29

DOI: 10.24075/brsmu.2023.040

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VIEWS 2013

Markarov AE, Eremin DA, Martirosov AV, Khandzratsyan AS, Orazvaliev AI, Bugayan SA, Khalifaev OI

There are no actual statistical data on maxillofacial trauma, nor is there a published analysis addressing morbidity patterns, including cases requiring admission to maxillofacial surgery departments. Such data and the respective analysis could help to assess effectiveness of the maxillofacial trauma and diseases prevention and treatment measures, improve the emergency care approaches, identify problems in the medical aid system's maxillofacial surgery domain. This study aimed to analyze the aspects of emergency admission to hospitals for reasons requiring maxillofacial surgery. We processed hospital records of 15,227 patients admitted from 2018 through 2022. The analysis revealed the number of emergency maxillofacial cases to be at a fairly high level and show no downward trend. The majority of the patients are young, able-bodied men. Of all the admitted persons, 28.6% came to the hospital on their own; 22.9% were nonresidents and foreigners. The average hospital stay was 3.85 days, it did not change significantly during the studied period. The prevailing types of trauma were maxillofacial injuries and mandibular fractures. For 29.9% of patients with the latter type, the treatment method of choice was osteosynthesis. Up to 70% of all the patients needed to be followed-up by a maxillofacial surgeon after discharge. The mortality rate in maxillofacial surgery departments is extremely low; all such cases involved concomitant pathologies.

Received: 2023-08-09

Published online: 2023-10-23

DOI: 10.24075/brsmu.2023.038

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VIEWS 2259

Orlova EV, Berdalin AB, Reshetarov ID, Lelyuk VG

Currently, there are no clearly defined optimal diagnostic strategies of detection of dissections. This study aimed to analyze and compare the results of comprehensive examinations of people who suffered an ischemic stroke (IS) with and without brachiocephalic artery (BCA) dissections. Dissections group, formed based on the results of multispiral computed tomography angiography that confirmed dissections, included 53 patients, and control group — patients without BCA dissections — comprised 1451 people; examination of all patients involved duplex scanning (DS) of BCA and transcranial part, transthoracic echocadiography (TTE), multispiral computed tomography angiography (msCTA) and/or magnetic resonance imaging (MRI). Patients with dissection were younger (p < 0.0005) and had a lower body mass index (p < 0.0005) than participants from the control group; according to echocadiography, they were less likely to have left (p = 0.014) and right (p = 0.018) atrial dilation and aortic stenosis (p = 0.017). Also, dissections were significantly less often associated with atherosclerotic plaques in the common carotid artery (CCA) (p < 0.002), and BCA deformations (p < 0.05). Duplex scanning of BCA revealed that in patients with dissections, differentiation of the intima-media complex in CCA was compromised significantly less often, and signs of thrombosis of the internal carotid artery were registered significantly more often (p = 0.021 and p = 0.004); according to MRI, such patients had less pronounced changes in the periventricular and deep white matter of the brain (p < 0.0005 and p = 0.001) and never suffered strategic infarcts affecting the thalamus area (p < 0.0005). Comparison of the results of examinations of IS patients with and without BCA dissections revealed differences that are probably conditioned by the younger age of those who had said dissections.

Received: 2023-08-04

Published online: 2023-10-20

DOI: 10.24075/brsmu.2023.037

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VIEWS 1861

Stepanov AI, Putlyaeva LV, Didych DA, Galiakberova AA, Gurskaya NG, Lukyanov KA

The study of human induced pluripotent stem cells (iPSCs) and developing the technology for their practical use is one of the most knowledge-intensive areas of modern biomedical research. Despite the potential of using iPSCs in personalized medicine and to build cell-based models for disorders of various etiology, iPSC utilization remains challenging. Thus, the iPSC intercellular heterogeneity and the lack of effective identity determination and assessment methods considerably hamper reproducibility of such studies. The study was aimed to generate an iPSC line carrying the gene encoding the ATOH1 transcription factor controlled by the Tet-One expression induction system, along with TagBFP2 fluorescent protein and the puromycin resistance gene for cell selection. Molecular cloning, lentiviral transduction, cell culturing, immunofluorescence staining, and fluorescence microscopy were used during the study. The created cell model will allow analyzing the state of single cells and, therefore, has great practical potential for both laboratory and medical research.

Received: 2023-08-01

Published online: 2023-09-22

DOI: 10.24075/brsmu.2023.036

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VIEWS 1951

Mukhamedzhanov RK, Grigoryeva ES, Tashireva LA, Perelmuter VM, Zavyalova MV, Savelieva OE

Nowadays, great attention is paid to the study of circulating tumor cells (CTCs) due to their key role in distant metastasis. At the same time there is little data on the properties of circulating cells showing simultaneous expression of the leukocyte and epithelial markers and their possible role in tumor progression and chemotherapy resistance. The study was aimed to assess subpopulations of cells with hybrid epithelial/leukocyte phenotype and estimate the features of stemness, epithelial–mesenchymal transition (EMT), and integrin interface, which determine the cells’ possible metastatic properties in breast cancer (BC). The survey data from 128 patients with invasive breast carcinoma of no special type were included. Multicolor flow cytometry was used to assess the population structure and metastatic potential of the cells circulating in blood and primary tumor cells with hybrid phenotype. The primary tumor cell suspension was prepared by mechanical disaggregation. The high degree of heterogeneity was noted in the population of cells with hybrid phenotype, including the combination of the stemness and EMT features, and diverse integrin interface. Cells with hybrid phenotype are involved in the mechanisms underlying lymph node and distant metastasis. In lymph node metastasis, metastatic potential of these cells is associated with the stemness features (р = 0.0422) and co-expression of β3-, β4-, and αVβ5-integrins (р = 0.0338). In distant metastasis, metastatic potential of hybrid cells is associated with the stemness features (р = 0.015) and is not associated with the EMT features and integrin expression.

Received: 2023-07-04

Published online: 2023-08-31

DOI: 10.24075/brsmu.2023.033

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VIEWS 2177

Korshunov AS, Vagner VD, Belskaya LV, Kuryatnikov KN, Serov DO, Krasnov VA, Tigranyan GO, Bondar IA

Studying the mechanism underlying tooth eruption is an important and promising area due to the increased incidence of the diseases associated with tooth eruption abnormalities or difficulties that can result in purulent and septic complications. The study was aimed to explore variability and structural features of the hard tissue mineral component and organic matrix in mandibular third molars being at different stages of tooth eruption. Microscopic examination and biochemical testing of the enamel, dentin, and dentin–enamel junction of the study participants’ (n = 67; females aged 14–36) mandibular third molars were performed by scanning electron microscopy and Fourier transform infrared (FT-IR) spectroscopy. The association of the tooth eruption stage with the hard tissue structural features, such as the degree of mineralization and the size of dentinal tubules, orientation and size of the enamel prisms, was revealed. There were significant differences in the mandibular third molar hard tissue water content, which was demonstrated by metabolic processes and maturation rate (p < 0.05). According to the IR spectroscopy data, intensity of the collagen absorption bands in the enamel increases with age, while in dentin it decreases (1202, 1249, and 1342 cm–1). Furthermore the combination of the reduced intensity of the 1202 cm–1 band with the increase in the 1342 cm–1 dentin–enamel junction band confirms the important role it plays as a link between the enamel and dentin due to its metabolic, shock-absorbing, protective, and nutritional functions. The findings demonstrate significant changes in the wrapping and orientation of the collagen fibrils and fibers in the hard tissue, which affect primary spatial orientation and mandibular dental topography.

Received: 2023-07-31

Published online: 2023-08-31

DOI: 10.24075/brsmu.2023.035

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VIEWS 2111

Baranova NS, Gris MS, Baranov AA, Spirin NN, Artyuhov AS, Shakirova KM, Nasonov EL

There are persistent infections that contribute to the emergence and development of multiple sclerosis (MS) exacerbations; they are triggered by the Epstein–Barr, herpes type 6, herpes simplex types 1 and 2, varicella-zoster viruses. Cytokines are crucial to arresting the spread of a herpes infection in a body. If their production is out of balance, MS can progress faster. This study aimed at determining the level of cytokines in the blood serum of MS patients, assessing their clinical significance and how they affect reactivation of herpes infection. We examined 36 patients (12 male and 24 female) with confirmed MS (McDonald criteria) in remission. In 18 of them, we diagnosed reactivation of peripheral herpes virus. Serum levels of 15 cytokines (IL1ß, IL4, IL6, TNF-a, INF-γ, IL10, IL17A, IL17F, IL21, IL22, IL23, IL25, IL31, IL33, sCD40L) were determined with the help of xMAP multiplexing. Compared to the control group, MS patients had increased levels of IL10, IL33 (p < 0.001), with high IL33 identified most often (20 patients; 52.8%). During exacerbations, the average level of IL10 grew up (p < 0.01), as did that of IL31, the high levels of which were detected significantly more often (42.8 and 6.9%, respectively; p = 0.04). In addition, a prevailing scenario was the increased levels of IL33 and other cytokines (IL17A, IL17F, IL21, IL31) (57.1 and 6.9% of cases, respectively; p = 0.008). Reactivation of herpes translated into higher levels of IL1ß, IL23 and IL33 compared to cases without reactivation (p < 0.05 and p < 0.01, respectively). High levels of IL33 were significantly more frequently recorded in this group of patients (77.7 and 33.3%; p = 0.008). We discuss involvement of IL10, IL31, IL33 and other cytokines in the pathogenesis of herpes-associated MS.

Received: 2023-07-24

Published online: 2023-08-31

DOI: 10.24075/brsmu.2023.032

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VIEWS 2257