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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Abdulrazzaq S

Acinetobacter baumannii is a high priority pathogen, rapidly acquiring multidrug resistance. Limited temporal resolution at the proteomic and transcriptomic levels has constrained our understanding of real-time resistance acquisition, thus hindering the development of strategies to combat resistance. The study aimed to unveil the resistance acquisition processes. A total of 45 clinical A. baumannii strains from three geographic locations were exposed to sub-inhibitory levels of carbapenem, aminoglycoside and β-lactam antibiotics for 72 hours. Kinetic resistance acquisition was simultaneously monitored by Western blot for expression of resistance proteins (β-lactamases, efflux pumps, porins) and quantitative PCR (qPCR) for mRNA using custom TaqMan probes with highest temporal resolution (13 timepoints at 6h intervals). Western blot analyses identified novel biphasic induction of resistance proteins: early phase (0–18h) with 3.4-fold induction of OXA-23, and late phase (24–72h) with 7.8-fold induction of NDM-1. qPCR results found mRNA levels reached their peak 4–8 hours prior to peak protein expression, suggesting robust post-transcriptional regulation. New discovery: AdeB efflux pump protein showed 12.6-fold increase with only 2.1-fold mRNA increase, suggesting extreme translational amplification with protein/mRNA ratio of 6.1. Machine learning algorithm categorized response into three distinct patterns with profound clinical implications: early responders (89% treatment failure); late responders (45% failure); constitutive expressors (67% failure). Thus, integrative analyses identified novel temporal dynamics of resistance development, key 4–8 hour windows for intervention before resistance is irreversible. Post-transcriptional regulation is much more important than previously thought, and may be exploited for the development of new combination therapies and individualised anti-microbial therapies.

Received: 2026-07-31

Published online: 2026-10-31

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Ershov DS, Egiazaryan KA

PemAvascular necrosis (AVN) of the humeral head worsens the outcomes of treatment of proximal humeral fractures. This study aimed to evaluate the frequency of AVN in patients with three- and four-part fractures of the proximal humerus and to improve treatment outcomes using a new reduction technique. By design, this work was a retrospective–prospective cohort study. We recruited 357 patients with three- and four-part fractures of the proximal humerus. In the main group, 200 patients (147 women [73.5%] and 53 men [26.5%]) underwent surgery with a condylus–plate system (RF patent No. 2705234). In the comparison group, 157 patients (120 women [76.4%] and 37 men [23.6%]) had surgery that relied on conventional techniques. At two years, 329 patients were available for follow-up. The designed reduction technique reduced the incidence of Cruess stage II–IV AVN from 28.8% to 17.3% (p = 0.015). The risk of AVN increased with age, diabetes mellitus, osteoporosis, and multimorbidity.

Received: 2026-10-21

Published online: 2026-10-31

DOI: 10.24075/brsmu.2026.066

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Shpilevaya MV, Arbuzova NV, Khodak YuA, Vorobiev II, Nosov NYu

Pemphigus vulgaris is a severe autoimmune disorder resulting from production of anti-desmoglein 3 (Dsg3) antibodies. An accessible standardized antigenic component, the recombinant Dsg3 extracellular component, is necessary to develop domestic diagnostic ELISA kits. The retrospective experimental study aimed to produce a recombinant Dsg3 ectodomain (ЕС1-ЕС5 domain) in the heterologous expression system and assess its immunoreactivity with autoantibodies of patients having pemphigus vulgaris when used as a target antigen in ELISA. The synthetic gene encoding the Dsg3 ЕС1-ЕС5 domains was cloned into eukaryotic expression vectors p1.1-Tr2 and p1.2-GS. The resulting constructs were used for transfection of CHO-4BGD cells. The target protein was purified by affinity chromatography on the Ni-Sepharose FF sorbent. Immunoreactivity of the recombinant Dsg3 as an antigenic substrate was assessed by ELISA using sera from patients with pemphigus vulgaris (n = 12) and healthy donors (n = 5) under two buffer conditions: with EDTA (Dsg3-EDTA) and with added Ca2+ ions (Dsg3-Ca2+). The Euroimmun commercially available ELISA kit (target antigen: Dsg3 ectodomain) was used for reference. As a result, transient cultures of the cells producing the Dsg3 ЕС1-ЕС5 domains were obtained. The protein with the purity > 90% was isolated by affinity chromatography. When performing ELISA in the Dsg3-EDTA buffer, 33.3% of samples were classified as positive, while 50.0% were considered positive when using the Dsg3-Ca2+ buffer; the effect of adding Ca2+ was heterogeneous: 58.3% of samples showed the signal increase and 41.7% showed the decrease. The findings suggest the need to switch to the Dsg3 expression in human cells (HEK293).

Received: 2026-05-12

Published online: 2026-10-27

DOI: 10.24075/brsmu.2026.065

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VIEWS 87

Larionova IV, Rakina MA, Kalinchuk AYu, Sudarskikh TS, Vasilchuk VN, Yatskovskyi AM, Villert AB, Kolomiets LA, Tashireva LA

High-grade serous ovarian carcinoma (HGSOC) remains a major challenge in oncology. This study aimed to assess the spatial and phenotypic heterogeneity of EpCAM, HER2, TROP2, and pan-cytokeratin expression in primary tumor cells, peritoneal metastases, and the ascitic tumor compartment (ascites), comprising spheroids and single cells, and to determine whether the identified subpopulations were associated with neoadjuvant chemotherapy (NACT) and disease progression. The study is prospective, single-center; it involved 27 patients with histologically confirmed HGSOC; EpCAM, HER2, TROP2, and pan-cytokeratin expression were assessed by immunofluorescence. The proportions of EpCAM−HER2− cells were different in the primary tumor, peritoneal metastases, and ascites, and were highest in single cells from ascitic fluid and metastatic tissue (p = 0.0012). CK–TROP2– cells were more frequent among single cells (73.50% [51.00–91.25%]; p = 0.0249). The proportion of CK+TROP2– cells was higher in solid tumor lesions, accounting for 83.00% [65.00–95.00%] of cells in primary tumors and 94.50% [47.00–98.00%] in metastatic tissue (p < 0.0001). In patients who received NACT, the proportion of EpCAM+HER2+ cells in primary tumors and metastatic lesions was higher than in patients who did not undergo pre-surgery therapy (42.50% [6.25–71.25%] vs. 0.00% [0.00–5.00%]; p = 0.0333). The clinical significance of the EpCAM−HER2− subpopulation depended on its organization within ascites. An increased proportion of EpCAM−HER2− cells among single ascitic cells, but not within spheroids, was independently associated with a higher likelihood of progression (OR [95% CI], 1.256 [1.010–7.769]; p = 0.0322) and shorter progression-free survival (OR [95% CI], 1.118 [1.001–1.518]; p = 0.0459). HGSOC is characterized by pronounced phenotypic heterogeneity across tumor compartments. The ascites may reflect the phenotypic state of disseminated tumor cells.

Received: 2026-09-14

Published online: 2026-10-26

DOI: 10.24075/brsmu.2026.062

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VIEWS 105

Proskokova SV, Korolenkova MV, Gusova YuV, Proskokov NA, Enikeev AM

Pre-eruptive intracoronal resorption is a lesion of the unerupted tooth coronal dentin detected during X-ray examination. Cone-beam computed tomography revealed lesions in teeth 4.5 and 4.7 of a 13-year-old girl. Tooth 4.5 was partially erupted at presentation; cold-induced pain developed two weeks later. Coronal pulpotomy was performed using Biodentine after detecting communication between the defect and the pulp chamber. The tooth was asymptomatic at 3 months, and continued root development was observed at 6 months. Tooth 4.7 was followed-up: at 6 months of follow-up, eruption had begun without any apparent changes in lesion dimensions; restorative treatment was planned once access became possible. In an 11-year-old boy, lesions were identified in unerupted teeth 3.5 and 3.7. Fissurotomy and restoration were performed without pulp chamber exposure once tooth 3.5 became accessible; the tooth was asymptomatic at 1.5 months. Tooth 3.7 remained under observation, with restoration planned after eruption. Comparable serial measurements of all lesions were not available. The cases illustrate the need for personalized management based on the lesion depth and progression, pulp status, root development, and tooth accessibility. Monitoring may be appropriate for small, stable lesions when regular follow-up is feasible; extensive or progressive lesions require reconsideration of the intervention timing. The long-term clinical and radiographic follow-up is required after vital pulp therapy and restoration. Two case reports make it impossible to establish a universal treatment algorithm.

Received: 2026-09-11

Published online: 2026-10-25

DOI: 10.24075/brsmu.2026.064

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VIEWS 81

Plisetskaya BS, Nikishina VB, Petrash EA, Karpenko AS

In the modern world, writing by hand is increasingly being replaced by typing on a keyboard. However, the available evidence on the neural mechanisms underlying these writing modalities comes primarily from international studies. This comparative study aimed to test the hypothesis that writing by hand elicits a greater increase in oxygenated hemoglobin concentration in the motor cortex and in regions overlying the angular and supramarginal gyri than keyboard typing. We used a within-subject repeated-measures design with two levels of each independent variable: stimuli reproduction modality (writing vs. typing) and stimuli presentation modality (visual vs. auditory). Brain oxygenation was recorded using functional near-infrared spectroscopy (fNIRS). The sample consisted of 62 individuals aged 18–35 years; data from 38 participants were included in the analysis: 8 men (21.1%) and 30 women (78.9%), with a mean age of 21.2 years. Group comparisons were performed using the Wilcoxon signed-rank test with Holm–Bonferroni correction. In the initial analysis, differences in oxyhemoglobin concentration in the motor region were close to statistical significance: handwriting vs. keyboard typing, p = 0.034; handwriting vs. keyboard typing under visual stimulation, p = 0.010; and visual vs. auditory stimulation during handwriting, p = 0.015. However, after correction for multiple comparisons, these differences no longer reached statistical significance (p = 0.068, 0.080, and 0.105, respectively). No significant differences were observed in the region of the angular and supramarginal gyri. Thus, the hypothesis was not supported. Nevertheless, the observed near-significant effects and the sensitivity of fNIRS to differences between writing modalities may be regarded as preliminary findings and a promising direction for future research.

Received: 2026-09-06

Published online: 2026-10-24

DOI: 10.24075/brsmu.2026.063

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VIEWS 70

Gorin IO, Koshel SM, Shlykov AG, Voronina MM, Ponomarev GYu, Pokrovskaya MS, Borisova AL, Adamov DS, Balanovska EV

A broad range of pharmacogenes identified when analyzing continental datasets characterizes the world's population as a whole. As for local regions, not all DNA markers from the general palette of pharmacogenes can be equally important for pharmacogenetics. The study aimed to identify the regionally important pharmacogenes. Frequencies of 24 pharmacogenes of cardiovascular diseases (CVDs, 1541 genomes) and seven pharmacogenes of tuberculosis (TB, 1437 genomes) in the indigenous population of Central Russia were determined. A total of 19 populations of 10 ethnic groups were included in the analysis: Bashkirs, Komi-Permyaks, Mari, Mishar Tatars, Kazan Tatars, Udmurts, Chuvash people, Moksha, Shoksha and Erzya of Mordovia, nine populations of Russians. Gene geographic maps of the spread of pharmacogenes across the region were plotted; these were subjected to the cartographic and statistical analysis by the principal components and genetic distance methods, correlation analysis. It has been shown that in the studied set of pharmacogenes, only a quarter of DNA markers (five CVD; two TB) play a key role in the genetic basis of the CVD and TB response to drugs in this region. There was no correlation between the spread of CVD and TB DNA markers (correlation r = 0). The history of the formation of the gene pools of the Central Russian population proved to be the leading factor for the CVD pharmacogenes. This conclusion has been confirmed by the highest correlation (r = 0.9) between DNA markers of CVDs and selectively neutral DNA markers (eye color, hair color, Y-haplogroups) reflecting the region's population ethnogenesis. The lack of patterns in the spread of TB pharmacogenes suggests predominance of social and medical and sanitary factors. With insufficient funding and the inability to identify individual genotypes, pharmacogenetics can focus on the regionally important pharmacogenes.

Received: 2026-09-01

Published online: 2026-10-23

DOI: 10.24075/brsmu.2026.056

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VIEWS 76

Demin NA, Shishkin AA, Perevoshchikov DV, Lyakhmun DN, Shafigullin RR, Ostanin OE, Polyaev BA, Pleshchev IE

Determination of capillary blood lactate levels remains a standard invasive method to assess the metabolic response to physical exertion, but requires repeated sample collection and laboratory analysis. This increases the procedural burden on the athlete and makes the continuous monitoring during the training or functional testing almost impossible. Eccrine sweat represents an accessible noninvasive medium suitable for integration with wearable sensor systems. The technical feasibility of continuous lactate monitoring in sweat has been already demonstrated in a number of studies. The study aimed to assess the potential of using wearable skin sensor systems for continuous lactate level determination in eccrine sweat during physical exercise. Operating principles of sensor systems, physiological characteristics of lactate dynamics in sweat, and requirements for the measurement reliability and reproducibility were considered. In our opinion, the eccrine sweat lactate monitoring should be considered as not only an alternative for the conventional capillary blood lactate monitoring, but also an independent approach to non-invasive monitoring when performing the functional testing of athletes. However, it is necessary to determine the method diagnostic accuracy and reproducibility for its full implementation.

Received: 2026-09-22

Published online: 2026-10-22

DOI: 10.24075/brsmu.2026.061

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VIEWS 78