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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Kornilov DO, Simarzina VM, Bekhter AA, Maslakov GP, Nechaeva DM, Karyakina AE, Fadeev FA, Voroshilina ES, Zornikov DL

The PI3K/AKT/mTOR signaling pathway is a key regulator of cell growth, and its dysregulation is involved in oncogenesis. Existing methods for assessing mTOR activity have design flaws. The aim of this work was to develop and validate a novel multiplex RT-qPCR assay for relative quantification of mTOR gene expression normalized to RPLP0 and TBP. Primers and probes were designed in silico. Validation was performed using the human SCP-1 cell line. Specificity was assessed in 10 separate and 10 multiplex runs. Analytical sensitivity and efficiency were determined from 27 technical replicates using a protocol without an elongation step. Specificity of amplification was assessed by agarose gel electrophoresis, and quantitative analysis was performed in real-time PCR using FAM (mTOR), HEX (RPLP0), and ROX (TBP) fluorescence channels. The assay showed 100% specificity. Stable detection was achieved at 125,000 cells/mL. Amplification efficiencies were 73–81%. The variation of mTOR expression normalized to RPLP0 ranged from –21.5% to 26.4%, and normalized to TBP from –14.3% to 19.2%. Normalization to the geometric mean of both reference genes provided the best reproducibility, with an interquartile range from –9% to 23.4%. The developed assay demonstrates high specificity, sensitivity, and reproducibility, making it a reliable tool for subsequent clinical research.

Received: 2026-03-11

Published online: 2026-03-25

DOI: 10.24075/brsmu.2026.011

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VIEWS 72

Chichelnitsky AK, Savchenko DA, Kostina AS, Raklov DA, Zhuk ER, Buimova ES, Negodaeva AI, Ivanenko AO, Aduchieva VI

Hepatocellular adenoma is a rare benign liver tumor with the potentially unfavorable course due to the risk of hemorrhage and malignant transformation. Treatment depends on the mass subtype and size. Here we present a clinical case of hepatocellular adenoma in a woman of reproductive age developed against the background of the long-term use of oral contraceptives. The tumor sized 8 cm was detected accidentally during instrumental examination; morphological and immunohistochemistry assessment confirmed that it was a benign one without β-catenin mutation. Liver resection was performed. The case highlights the importance of careful monitoring of the patients during the long-term use of oral contraceptives, as well as of the timely surgical interventions in individuals with large hepatocellular adenomas to prevent hemorrhage and malignization.

Received: 2026-02-12

Published online: 2026-03-28

DOI: 10.24075/brsmu.2026.010

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VIEWS 76

Dementev IM, Gabitov MV, Timoshin SS, Kuzovlev AN, Grebenchikov OA

Hypoxic-ischemic encephalopathy remains a leading cause of neonatal mortality and disability. Experimental data suggest potential neuroprotective properties of xenon; however, the mechanisms and extent of its effect are not fully understood. The study aimed to evaluate the neuroprotective properties of a xenon-oxygen mixture in a neonatal ischemia-hypoxia rat model using MRI and follow-up neurological assessment. The experiment involved Wistar rat pups (n = 16). Neonatal ischemia-hypoxia was induced by the Rice–Vannucci method. Thirty minutes post-hypoxia, animals received the 60-min inhalation of either nitrogen-oxygen (control, n = 8), or 50/50 xenon-oxygen mixture (n = 8). Brain MRI was performed on day 7. In the xenon group, brain lesion volume was significantly reduced by 25% compared to controls on day 7 (p = 0.001). Neurological development was assessed from day 3 to 28 using a combination of behavioral tests. Xenon-treated animals demonstrated earlier formation of forelimb and hindlimb grasping reflexes (p = 0.025 and p = 0.005), better hindlimb placement and cliff avoidance on day 7 (p = 0.045 and p = 0.03), and better preserved auditory startle response on day 14 (p = 0.035). Thus, early administration of a xenon-oxygen mixture after ischemia-hypoxia exerts pronounced neuroprotection in newborn rats, confirmed by reduced brain damage and improved neurological outcomes.

Received: 2026-02-25

Published online: 2026-03-17

DOI: 10.24075/brsmu.2026.009

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Razenkova VA, Korzhevskii DE

The cerebrovascular disorder associated with arterial hypertension results in neuroinflammation, in which microglia and macrophages of the brain are actively involved. The study aimed to assess functional activity and immunophenotype of microglia and macrophages in the areas of brain barriers in spontaneously hypertensive rats (SHR). Specimens of the brain of male Wistar rats and SHR (age 3–4 months, n = 10) were used. The study involved the use of immunohistochemistry analysis and confocal laser microscopy. The presence of М2 activation (CD206) and phagocytic activity (CD68) markers in the population of microglia and macrophages was assessed. It was shown that the CD206 protein was present in perivascular cells, the counts of which were considerably increased in SHR (40.69 ± 4.87 cells per 1 mm2 vs. 28.73 ± 1.39 in Wistar rats; t-test, р = 0.0007). The quantitative analysis conducted allowed us to identify the upward trend of the share of phagocytic cells in the brain of SHR compared to Wistar rats. No changes in the CD68 protein distribution were found in SHR, therefore, activation of microglia and macrophages is not accompanied by the phagocytic activity increase. The findings suggest alternative activation of brain macrophages in neuroinflammation caused by arterial hypertension.

Received: 2026-02-04

Published online: 2026-02-28

DOI: 10.24075/brsmu.2026.008

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VIEWS 239

Petrash EA, Nikishina VB, Yunina-Pakulova NYu, Minaev AS, Melkonyan GG, Lytkina KA, Karpenko AS

Assessment of phantom pain linguosemantic descriptors in patients with traumatic amputation during the use of mirror visual feedback is conditioned by the need to find criteria for the psychological phantom pain adjustment effectiveness. The study aimed to assess the dynamic changes in linguosemantic pain descriptors in patients with traumatic amputation showing manifestations of phantom pain syndrome as a criterion for evaluating the effectiveness of mirror visual feedback. The total sample size was 87 males post traumatic amputation of one lower limb (age 23–55 years). The research methods were as follows: Mini Mental State Examination (MMSE), original form for registering linguosemantic descriptors of phantom painful sensations, Visual Analog Scale (VAS) for phantom pain. The detected dynamic changes in linguosemantic descriptors of phantom painful sensations in patients with traumatic amputation of the limb showing manifestations of phantom pain syndrome during treatment involving the use of mirror visual feedback makes it possible to consider the following as effectiveness criteria: an increase in the number of pain descriptors represented mainly by concrete and tangible nouns (makes it possible to reduce phantom pain severity rated using a 10-point scale), as well as the increase in the number of descriptors that characterize non-painful unpleasant sensations at the linguosemantic level.

Received: 2026-01-29

Published online: 2026-02-26

DOI: 10.24075/brsmu.2026.007

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VIEWS 255

Ilina AA, Lakman IA, Bikmeyev AT, Enikeeva AR, Badykova EA, Zagidullin NSh, Bryukhanova OA

Tortuosity of the coronary, cerebral arteries, aorta and its branches remains an important vascular problem, which, on the one hand, complicates selection of the X-ray surgical treatment tactics, and on the other hand worsens the disease outcome. The lack of common standards for assessment of tortuosity of the coronary, cerebral arteries, aorta and its branches reduces the diagnosis accuracy in patients at high risk of cardiovascular events. The use of machine learning for automated tortuosity assessment represents one possible solution to this problem. The study aimed to analyze and compare accuracy, feasibility, and limitations of the available methods for automated assessment of tortuosity of the coronary, cerebral arteries, aorta and its branches using the machine learning tools. The systematic review was conducted in accordance with the PRISMA protocol. The search for papers published in 2015–2025 in the PubMed, Scopus, and eLibrary databases was performed using the following keywords: deep learning, machine learning, artificial intelligence, vessel tortuosity, curvature. Six papers out of 240 were included in the analysis. The analysis has shown that 80% of approaches are based on convolutional neural networks, and skeletonization aimed to isolate small blood vessels from the artery represents an essential preprocessing phase. In 50% of papers, tortuosity was determined qualitatively based on the presence of bending angles over 45°. Quantitatively, tortuosity was determined as a distance coefficient and a measure of curvature. In three studies out of six, verification of estimates was carried out by comparing the results with expert opinions (accuracy was 0.92–0.94). The study limitations are as follows: monocentricity, the use of data from one type of equipment.

Received: 2025-12-22

Published online: 2026-02-05

DOI: 10.24075/brsmu.2026.005

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VIEWS 315

Kozin SA, Lysikova EA, Yakovlev RYu, Mukhina KA, Soloveva AE, Shmigol TA, Makarov AA, Mitkevich VA

High efficacy of the synthetic Ac-His-Ala-Glu-Glu-NH2 (HAEE) peptide in suppression of the congophilic amyloid plaque formation was earlier shown in the animal model of Alzheimer's disease. The study conducted as part of the pre-clinical trial aimed to determine the optimal therapeutic dose of this peptide when used as an anti-amyloid agent for treatment of this disorder. The APP/PS1 transgenic mice randomized into four experimental groups and one control group (eight males and eight females per group) were used as model animals. Mice of experimental groups 1, 2, 3, and 4 twice a week throughout eight weeks received subcutaneous injections of drugs with the following HAEE dosage: 0.18 mg/kg, 0.30 mg/kg, 1.50 mg/kg, 3.00 mg/kg. Mice of the control group were administered saline. The Congo red stain was used to determine amyloid plaques in the hippocampus of all animals. Quantification of such plaques showed a significant (p < 0.001) decrease in the number of plaques in mice of experimental groups (the average plaque number per brain slice was 7.5 ± 2.1, 3.2 ± 0.9, 3.1 ± 0.6, and 3.3 ± 0.7 in mice of groups 1, 2, 3, and 4, respectively) compared to control mice (15.7 ± 4.6). Since the number of plaques in groups 2, 3, and 4 did not change significantly, the minimal HAEE dose, with which the lowest number of amyloid plaques is observed in the studied mice, is 0.3 mg/kg. This is roughly equivalent to the dose of 1.75 mg in terms of one adult human. Thus, the optimal therapeutic HAEE dose for clinical trials has been experimentally substantiated.

Received: 2025-12-09

Published online: 2026-02-04

DOI: 10.24075/brsmu.2026.006

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VIEWS 464

Minasov BSh, Yakupov RR, Akbashev VN, Evgrafov IO, Malsagov YuM, Karimov KK, Minasov IB, Akhmeldinova AA, Shveykin AA

The study is relevant due to persistent postural control impairment and gait disorder in patients post total knee arthroplasty (TKA), despite pain relief and restoration of the range of motion. The study aimed to assess the effects of kinesiotherapy in suspension on the patients’ stabilometry and gait phase parameters in the long term after TKA. A prospective comparative study was conducted that involved 93 patients (39 males and 54 females; average age 62.3 ± 5.1 years) enrolled 36 months after surgery. The patients were randomized into the index group (standard rehabilitation involving kinesiotherapy in suspension) and comparison group (standard program). The efficacy was assessed using stabilometry and gait phase analysis before and after the 3-week rehabilitation course. In the index group, a significant decrease in the normalized vectorogram area from 320 ± 60 to 190 ± 40 mm2 (p = 0.001) and mean center of pressure movement linear speed from 15.5 ± 2.8 to 8.7 ± 2.1 mm/s (p = 0.002) was revealed. The stance phase duration increased by 18%, and the walking phase symmetry increased from 74 ± 5 to 90 ± 4% (p < 0.01). In the comparison group, the changes were non-significant (p > 0.05). The decrease in WOMAC scores was reported for both groups, there were no intergroup differences. The data obtained confirm the efficacy of using kinesiotherapy in suspension to adjust postural and locomotor disorders after TKA.

Received: 2026-01-05

Published online: 2026-02-03

DOI: 10.24075/brsmu.2026.003

Comments 0

VIEWS 432