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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Issue 3, 2026

Topic Meckel's diverticulum

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Issue 4, 2025

Topic Chronic cerebral ischemia

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Issue 5, 2025

Topic Age-related alterations in the immune system

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Issue 6, 2025

Topic Anxiety and depressive disorders

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Issue 1, 2026

Topic Miscarriage

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Issue 2, 2026

Topic Postmenopause

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New articles

Sharko FS, Prokopenko AV, Izotova AO, Toshchakov SV

Genotype imputation makes it possible to considerably reduce the cost of whole-genome data acquisition preserving the information value, but its accuracy depends directly on the availability of a high-quality phased reference panel of haplotypes. The existing panels for Macaca mulatta cover mostly the Indian species lineage and do not reflect the genetic structure of laboratory populations of mixed origin. This retrospective bioinformatics study aimed to produce and validate a phased reference panel based on the consolidation of publicly available whole-genome datasets from 618 M. mulatta individuals of both geographic lineages processed in accordance with the common standardized protocol. The resulting panel includes 33,457,491 SNP markers. Validation on samples of Indian and Chinese origin with ultra-low coverage (0.1x–0.9x) confirmed high imputation accuracy, which was highest for the Indian lineage dominant in the panel. Testing on 10 independent samples with the 0.6x coverage showed a high average imputation reliability score (INFO = 0.898). The created resource opens the prospects for cost-effective genotyping of large M. mulatta cohorts and provides the basis for whole-genome association and population genetic studies in domestic and foreign primate research centers.

Received: 2026-07-14

Published online: 2026-08-21

DOI: 10.24075/brsmu.2026.045

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VIEWS 94

Yusef OV, Ibragimov BR, Klimenko MP, Gerasimova AA, Aimetdinova AB, Marnat EG, Abramov DD, Klimenko PA, Kurtser MA

Missed abortion is one of the most prevalent forms of early pregnancy loss that remains a pressing issue of obstetrics and gynecology. Despite advances in reproductive medicine, the molecular mechanisms underlying the embryo development termination in early gestation are poorly understood. A comparative singlecenter study aimed to assess the expression of TGF-β and MMP-9 genes in peripheral blood of women with physiological and missed abortion and assess their potential prognostic value for evaluation of the risk of early pregnancy loss. A total of 40 pregnant women were included in the study: 20 patients with the 9–11 week physiological pregnancy (control group) and 20 women diagnosed with missed abortion (index group). The TGF-β and MMP-9 gene expression was determined by the real-time polymerase chain reaction method after the total RNA isolation from peripheral blood. The Mann‒Whitney U-test and ROC analysis were used for statistical data processing. No significant differences in the TGF-β and MMP-9 gene expression between the studied groups were revealed. At the same time, ROC analysis made it possible to determine the threshold values of the studied indicators having some diagnostic information content. As for MMP-9, the threshold value Ct ≤ 29 ensuring the 80% sensitivity and 60% specificity turned out to be the most informative. As for TGF-β, the threshold value Ct ≤ 27.4 was characterized by the 75% sensitivity and 70% specificity. The findings suggest the potential prognostic value of the studied genes for evaluation of the risk of missed abortion.

Received: 2026-06-24

Published online: 2026-08-18

DOI: 10.24075/brsmu.2026.043

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VIEWS 155

Romanovskaya-Romanko EA, Ozhereleva OO, Plotnikova MA, Altuhov AS, Stukova MA

The use of live attenuated influenza vectors requires a balance between decreasing virulence and preserving immunogenicity. One possible approach to enhancing immunogenicity and protective efficacy of such attenuated strains is the integration of transgenes capable of activating the innate and adaptive immunity in the viral genome. The experimental study aimed to construct recombinant attenuated influenza viruses capable of expressing human IL1β and conduct comparative analysis of their replication properties, immunostimulatory activity, and safety profile in vivo. Recombinant strains with different transgene localization were generated by the reverse genetics method; their growth characteristics and transgene expression levels were assessed. Activation of the innate immunity genes in response to infection with recombinant strains was assessed in the А549 cell culture. The attenuated phenotype was confirmed in the mouse model. In the reported study, recombinant attenuated influenza viruses having the NS1 protein truncated to 124 amino acid bases and expressing human IL1β were constructed and produced. It was confirmed that recombinant strains could express the functionally active IL1β; the increase in relative expression of the innate immunity genes (RIG-I, MDA5, OAS1) and pro-inflammatory cytokines (IL6 and TNFα) in response to the infection of cells with recombinant strains compared to the empty vector NS124 was shown. Thus, the IL6 gene expression increased more than 10-fold (p < 0.0001) and that of the TNFα gene increased 3–4-fold (p < 0.0001). The attenuated phenotype of the recombinant strains produced was confirmed in in vivo experiments, which suggests preservation of the safety profile along with the enhanced immunostimulatory activity.

Received: 2026-07-02

Published online: 2026-08-17

DOI: 10.24075/brsmu.2026.044

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VIEWS 212

Seredin PV, Ippolitov YuA, Ippolitov IYu, Goloshchapov DL, Litvinova TA

The relevance of the study is associated with the search for minimally invasive molecular signatures of the dentogingival complex tissue condition in children. A pilot study aimed to identify spectral signatures of protein conformational changes in gingival crevicular fluid from children aged 8–14 years with dental caries and gingival inflammation (gingivitis) based on analysis of the IR spectral Amide III band in a pilot cohort. Gingival crevicular fluid samples collected from 20 children aged 8–14 years with different dental status were analyzed. FTIR spectra were acquired using synchrotron-based Fourier transform infrared spectroscopy in a Bruker Vertex 80/v spectrometer in the range of 3800–700 cm–1 with a focus on the Amide III region. Spectral deconvolution combined with multivariate analysis was used to estimate the contribution of protein secondary-structure elements. In the pilot cohort, dental caries was associated with a directed increase in the total contribution of components related to β-sheet structures. Based on the summed contributions of the main secondary structure elements, the β-sheet contribution exceeded 50% across the four analytical groups, the disordered component ranged approximately from 21 to 31%, and the contributions of β-turns and α-helical components remained below 10–11%. Inflammatory gingival changes showed a tendency toward a decreased contribution of β-turns and a relative increase in disordered conformations. Thus, the Amide III profile may reflect integral physicochemical changes in proteins of gingival crevicular fluid in individuals with caries and gingivitis. The reported features should be regarded as candidate spectral signatures of a hypothesis-generating nature that require further clinical validation.

Received: 2026-06-15

Published online: 2026-07-31

DOI: 10.24075/brsmu.2026.042

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VIEWS 300

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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: 2026-03-31

DOI: 10.24075/brsmu.2026.011

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VIEWS 936

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 849

Special Project Author's Work

Secrets of a quality research study and a good manuscript

At the end of 2015, Bulletin of RSMU saw an important change in its typographic design and content. We formulated new editorial policies and established strict ethical standards for submitted manuscripts in accordance with the guidelines of reputable international bodies. As a result, about a quarter of the submitted works have been rejected, the primary reason being the author trying to submit a previously published article. Sometimes authors believe that by making slight changes to the introduction, excluding a few people from the study, performing a new statistical analysis, and thus obtaining totally new results they will turn their old manuscript into a novel work. That is why we would like to talk about scientific integrity, honesty, plagiarism, and self-plagiarism in our special project “Author’s work”.

American physicist Richard P. Feynman, a Nobel laureate, was always very scrupulous about the quality of a research study. During his commencement address at the California Institute of Technology in 1974, he talked about scientific integrity and honesty and warned young researchers “not to fool” themselves. A must-read for anyone who believes he/she is a true scientist.

In 1918, Russian physiologist Ivan Pavlov, a Nobel laureate, delivered two lectures: on the mind in general and the Russian mind in particular; on those mind qualities that determine the success of a research work and on how these qualities are present in the Russian mind. Pavlov's thoughts are an effective vaccine against poor intellectual work.