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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Poydasheva AG, Sinitsyn DO, Bakulin IS, Zabirova AH, Lagoda DYu, Suponeva NA, Piradov MA

Personalization of selecting a target for rTMS is a problem, solving which can significantly increase the method efficacy. Stimulation of the key hubs of individual-level resting-state networks represents an approach to personalization. The study aimed to develop an rTMS personalization method based on the selection of individual frontoparietal control network (FPCN) hubs and assessment of their localization variability. To determine the FPCN hubs, individual maps were built using the FPCN group mask as a seed. The searchlight algorithm with the sphere radius of 5 mm was used to select targets within the dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex (PPC). The target spatial localization variability and correctness of using the routine “5 cm rule” for the DLPFC localization were analyzed. In 24 healthy volunteers (9 males, average age 29±7 years), high interindividual variability of targets was demonstrated. In no area is there a universal position of the stimulation coil that would effectively stimulate targets in all volunteers. Spatial dispersion of points is higher in the DLPFC (volumes of the polyhedra containing the point sets are 2095 mm3 in the DLPFC and 739 mm3 in the PPC). All individual targets in the DLPFC are located within the FPCN mask, while in the PPC some targets are outside this mask. The average distance between the М1 zones and DLPFC is 64±13 mm. In 75% of the subjects, this exceeds 5 cm, which confirms that it was incorrect to use the routine “5 cm rule” for coil positioning in the majority of subjects. An algorithm to select personalized targets for rTMS based on the resting-state fMRI data in the DLPFC and PPC being the key FPCN hubs has been developed.

Received: 2025-11-14

Published online: 2025-12-20

DOI: 10.24075/brsmu.2025.081

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VIEWS 329

Solovyova NV, Chuprova NA, Kochergina KV, Mitrofanov AA, Chausova SV, Kichuk IV

In psychiatric practice, there is a need to develop simple, pathogenetically substantiated biomarkers for prediction of the patient’s current affective status and his/ her status short-term perspective. The study aimed to analyze the association of the affective status of patients with mood disorders with the peripheral blood catecholamine and serotonin levels. The Hospital Anxiety and Depression Scale (HADS) was used for affective status evaluation. Concentrations of catecholamines (adrenaline, norepinephrine, and dopamine) in blood plasma and serotonin in blood serum were assessed by high-performance liquid chromatography (HPLC). The study included 114 individuals with affective disorders, the average age was 34.57 (SD = 10.36) years, the share of females was 64%. We revealed no significant prognostic effects of peripheral blood neurotransmitter levels relative to the current affective status. The serotonin/norepinephrine ratio, the increase in which significantly decreases the risk of clinical depression according to HADS-D considering the patient's sex and age (p = 0.059), turned out to be the only marker at the level of trends. In patients diagnosed with recurrent depressive disorder or depressive episode, a slight decrease in serotonin levels (p = 0.068) compared to the patients diagnosed with the disorders beyond the category of mood disorders is reported. In the same group a negative correlation has been found between the HADS-A scores (anxiety) and norepinephrine levels (Rs = ‒0.410, p < 0.05). The findings suggest that it will be possible to confirm the preliminary results obtained and acquire new data in the expanded clinically homogenous samples.

Received: 2025-10-30

Published online: 2025-12-19

DOI: 10.24075/brsmu.2025.080

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VIEWS 364

Bilyalov AR, Chugunov SS, Akhatov ISh, Tikhonov AA, Shangina OR, Pavlov VN, Danilko KV, Galautdinov MF, Akbashev VN

The use of allogenic bone material as a ceramic filler for DLP printing makes it possible to obtain personalized complex-shaped implants combining the matrix biomimetic nature with the additive technology benefits. The study aimed to assess the possibility of using the calcined cortical bone allograft powder as part of photopolymerizable suspension for DLP printing and producing bioceramics with the characteristics comparable to that of synthetic hydroxyapatite by sintering. The bone allograft was subjected to multi-stage specialized treatment involving complete removal of cells with preservation of the intercellular matrix and collagen fiber structure. The calcined medical allograft was crushed, introduced into a photopolymerizable matrix, and used for DLP printing of the samples that were further sintered and analyzed by X-ray diffraction and energy-dispersive spectroscopy methods before and after additive production. The sintered material specific gravity was 81.5%, compressive strength — 75.8 MPa, tensile strength — 12 MPa, Young's modulus — 3.08 GPa, and Vickers hardness — 0.55 GPa, which was within the range of values for porous hydroxyapatite. After DLP printing and sintering the sample phase and elemental composition did not change considerably compared to the source calcined material. The calcined bone allograft powder is suitable for preparing photopolymerizable suspensions and subsequent DLP printing of ceramic samples without deteriorating the material phase and chemical stability. The resulting mechanical properties make it possible to consider this allogenic bone material as a promising candidate for production of personalized implants with sophisticated geometry.

Received: 2025-11-03

Published online: 2025-12-18

DOI: 10.24075/brsmu.2025.068

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VIEWS 382

Danilko KV, Solntsev VA, Plotnitsky RV, Mikhailova AV, Bilyalov AR, Chugunov SS, Galautdinov MF, Akbashev VN, Akhatov ISh

Scanning electron microscopy (SEM) enables the analysis of surfaces of various materials, including eukaryotic cells. The ability of cells of various body tissues to attach and grow on the surface of implantation materials is an important characteristic of their biocompatibility. SEM visualizes how cells adhere to the surfaces. However, sample preparation for SEM analysis traditionally requires extensive dehydration and the use of toxic osmium tetroxide. This study aimed to optimize the process of preparing animal cells grown on the surface of bioceramic samples for SEM analysis. We propose a new SEM analysis preparation method for mesenchymal stem cells derived from human adipose tissue cultured on the surface of three types of bioceramics. The method includes fixation with aldehyde, alcohol dehydration, staining with Giemsa dye, drying, and gold spraying. We also propose an algorithm for detecting cells attached to the surface of a porous and rough material. This approach accelerates the preparation of cells for SEM analysis and eliminates the need for highly toxic reagents.

Received: 2025-11-13

Published online: 2025-12-17

DOI: 10.24075/brsmu.2025.072

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VIEWS 334

Neznamov AN, Baykova YuP, Korshunov EN, Isaeva EM, Bruter AV, Kubekina MV

Atherosclerosis being the main cause of myocardial infarction and stroke remains a global medical and social problem. Despite the fact that it is recognized as a chronic inflammatory disorder, the intracellular molecular mechanisms that drive the disease progression are poorly understood. The CDK8 and CDK19 cyclindependent kinases being the key regulators of transcription and inflammation can potentially play an important role in the atherosclerosis pathogenesis. The study aimed to assess the impact of the Cdk8 and Cdk19 gene knockout on the development of atherosclerotic lesions in apolipoprotein E-deficient mice (ApoE⁻/⁻). It has been shown that both endothelium-specific and systemic Cdk8 knockout significantly reduce the area of atherosclerotic aortic lesions, and the total knockout has a more prominent anti-atherogenic effect. This suggests a pleiotropic role of CDK8 in the atherosclerosis pathogenesis mediated by its function not only in endothelial cells, but probably also in macrophages. In contrast to Cdk8, the systemic Cdk19 knockout had no significant effect on the development of atherosclerosis. Thus, CDK8, but not CDK19, has been identified as a pro-atherogenic regulator, which makes it a promising target for the development of novel therapeutic strategies.

Received: 2025-10-31

Published online: 2025-12-16

DOI: 10.24075/brsmu.2025.078

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VIEWS 257

Savelieva OE, Krivolesova TA, Zhigalina AS, Sigareva LP, Saburov AV, Reznik VA

Chronic endometritis (CE) is the most significant endometrial disease in terms of its impact on reproductive potential. Thus far, pathogenetically significant inflammatory markers — cytokines, inflammatory proteins, and hematological indices — have not been widely used in medical practice for the diagnosis of CE. This study aimed to evaluate indicators of systemic inflammation, including hematological parameters and inflammatory indices, in patients with infertility, and to determine their diagnostic significance for CE. We analyzed the data of examinations of 50 patients with infertility. The standard hematological method was used to determine the leukocyte count. Based on the blood cell composition, we calculated the inflammatory indices NLR, MLR, PLR, and SII. The concentration of CRP in the blood serum was determined by enzyme immunoassay. In patients with CE-associated infertility, the absolute and relative numbers of lymphocytes were lower (p = 0.0451 and p = 0.0089, respectively), whereas the relative numbers of monocytes and basophils were higher (p = 0.0469 and p = 0.0005, respectively) than in patients without CE. In the study group, the concentration of CRP in the blood was almost four times higher than in the control group (p = 0.0191), but all indicators remained within the normal range. A comparative analysis of the NLR, MLR, PLR, and SII indices revealed their significant growth in CE-associated infertility cases (p = 0.0387, p = 0.0058, p = 0.0335, and p = 0.0333, respectively). ROC analysis established the predictive significance of NLR (0.871 (95% CI: 0.767–0.974); p < 0.0001) and MLR (0.848 (95% CI: 0.737–0.958); p < 0.0001) indices for detecting CE in infertility patients.

Received: 2025-10-29

Published online: 2025-12-15

DOI: 10.24075/brsmu.2025.071

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VIEWS 329

Melamud MM, Ermakov EA, Tolmacheva AS, Sizikov AE, Klyaus NA, Nevinsky GA, Buneva VN

The high-mobility group protein B1 (HMGB1) belongs to alarmins — a group of molecules involved in inflammatory responses. HMGB1 is actively studied in the context of certain rheumatic diseases (RDs), including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA), but the accumulated knowledge remains insufficient. HMGB1 can also act as an antigen, yet the level of anti-HMGB1 antibodies is poorly understood in RDs. The aim of this study was to investigate the concentrations of HMGB1 and anti-HMGB1 antibodies in four RDs. Using enzyme-linked immunosorbent assay (ELISA), plasma samples from patients with RA (n = 60), AS (n = 60), SLE (n = 24), PsA (n = 30), and healthy donors (HD) (n = 60) were analyzed. After adjustment for age and disease duration, it was shown that the concentration of HMGB1 was significantly increased in SLE (p < 0.01), RA (p < 0.01), and AS (p = 0.017), while a statistically non-significant increase in HMGB1 was observed in PsA (p = 0.07) compared to HD. Among the four diseases, the highest level of HMGB1 was found in SLE (p < 0.01). The concentration of anti-HMGB1 antibodies was also elevated in SLE (p < 0.01), RA (p = 0.026), and AS (p = 0.028). Using correlation and regression analysis, a strong direct association was established between the level of HMGB1 and the DAS28 index in RA (p < 0.01 for both analyses). The results of the study describe characteristic changes in HMGB1 and anti-HMGB1 antibody levels in RDs and indicate the involvement of HMGB1 in the pathogenesis of these diseases.

Received: 2025-10-29

Published online: 2025-12-14

DOI: 10.24075/brsmu.2025.074

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VIEWS 298

Zornikov DL, Bekhter AA, Kornilov DO, Simarzina VM, Nechaeva DM, Karyakina AE, Leshukova MA, Amineva PG, Voroshilina ES

The risk of contamination by cervical microbiota during transcervical sampling represents a fundamental methodological challenge in endometrial microbiome research. This study aimed to experimentally evaluate the efficacy of Pipelle and Endobrush endometrial sampling catheters in preventing this contamination. An in vitro cervix model with two anatomically distinct canal types (cylindrical and slit-like) was developed and filled with a synthetic cervical mucus containing a defined quantity of bacterial DNA. After catheter passage through the model cervical canal, a simulated ‘endometrial’ sample (sterile air) was collected and subjected to quantitative PCR analysis. Both catheter types facilitated substantial transfer of bacterial DNA from the cervical mucus into the endometrial sample. The median transfer of total bacterial DNA was 81.6% [54.4–107] for the Pipelle catheter and 29.8% [14.8–56.3] for the Endobrush catheter (p = 0.009), indicating that neither device provided sufficient protection for reliable characterization of the endometrial microbiota. Catheter efficacy was further dependent on cervical canal morphology and the specific microbial group analyzed. These findings demonstrate that transcervical sampling with either catheter type introduces a significant and variable degree of cervical contamination, thereby confounding the interpretation of endometrial microbiota data and underscoring the need to conceptualize and study a combined cervico-endometrial microbiota.

Received: 2025-11-18

Published online: 2025-12-13

DOI: 10.24075/brsmu.2025.073

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VIEWS 395