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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Pashkina EA, Boeva OS, Borisevich VI, Abbasova VS, Skachkov IP, Lazarev YaA, Denisova VV

Multiple myeloma (MM) is a B-cell malignant tumor, the morphological substrate of which are plasma cells that produce monoclonal immunoglobulin. This is one of the most common tumors of lymphoid origin. It is known that during oncogenesis, the immune balance shifts towards suppression of the antitumor immune response. Innate lymphoid cells (ILC) are one of the key factors influencing the said balance. This study aimed to assess the features of ILC in MM patients. The peripheral blood levels of ILC1, ILC2, and ILC3, as well as the expression of HLA-DR on ILC 2, were measured with the help of flow cytometry. We found that MM patients (n = 14; 7 male and 7 female, mean age 59.2 ± 2.08) had significantly more ILC2 in the peripheral blood, with the content thereof amounting to 63.1 ± 4.51% among "helper" ILC, while in donors the proportion of ILC2 was 43.2 ± 6.17% (p = 0.03). MM patients were also found to have a decreased amount of ILC2 that express HLA-DR: the proportion of such cells was only 2.2 ± 1.53%, compared to 15.6 ± 5.29% in donors (p = 0.003). The results of this study point to the shift in the immune balance and polarization of the immune response towards type 2 (T2), which may contribute to the suppression of the antitumor immune response.

Received: 2024-12-02

Published online: 2025-02-25

DOI: 10.24075/brsmu.2025.006

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VIEWS 236

Vanakova AI, Dolgushina NV, Denisov PA, Goncharuk OD, Muravieva VV, Priputnevich TV

Endometrial polyps (EPs) represent the most common form of benign intrauterine disorder. Microbial factor is one of the possible etiological factors of EPs. Investigation of endometrial microbiota can provide new opportunities for improvement of the EP diagnosis and treatment. The study is aimed to assess intrauterine microbiota composition in patients with endometrial polyps. A total of 84 patients with endometrial polyps based on histology assessment data were enrolled. The comparison group included 44 patients having no endometrial abnormality. Endometrial microbiota composition was assessed by the culturomics method using the extended set of selective and nonselective growth media. The endometrium sample was obtained before performing hysteroresectoscopy. In patients with EP, growth of bacterial microflora in the uterine cavity was observed 2.4 times more often compared to patients having no endometrial abnormality (OR — 2.4, 95% CI — 1.1; 5.5). In cases of EP, intrauterine microbiota composition was characterized by larger species and taxonomic diversity. Microorganisms of the genera Staphylococcus and Lactobacillus prevailed. Further research focused on endometrial microecology can provide new opportunities for further improvement of the EP diagnosis and treatment strategies.

Received: 2025-01-21

Published online: 2025-02-24

DOI: 10.24075/brsmu.2025.007

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VIEWS 229

Osikov MV, Telesheva LF, Konashov AG, Konashov VA, Gusev AV, Boyko MS

Mortality among patients with various forms of sepsis is 36.2–47.7%. Predicting the likelihood of death associated with sepsis is critically important for clinical decision-making, stratifying patient risk, and improving overall survival. The study aimed to develop a mathematical model for predicting the outcome of sepsis in patients with abdominal surgical pathology. The study involved 64 patients diagnosed with abdominal sepsis (AS). Based on the AS outcomes, group 1 (n = 46) with favorable outcomes and group 2 (n = 18) with fatal outcomes were allocated. Clinical scales and laboratory testing methods were used to evaluate parameters on days 1, 3, and 7 since the AS diagnosis. On days 3 and 7, SOFA scores of the group with adverse AS outcomes were significantly higher, than that of the group with favorable outcomes. Complete blood counts of patients in group 2 showed the decrease in absolute lymphocyte counts on day 1 compared to group 1. As for blood biochemistry parameters, elevated serum levels of C-reactive protein, urea, creatinine, lactate, procalcitonin, direct bilirubin, as well as aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase activity were observed. Furthermore, a decrease in respiratory index on days 3 and 7 and venous oxygen saturation on days 1 and 7 was observed. A logistic regression model was constructed, and a software tool "Calculator for Predicting Mortality in AS" was developed. A model to predict the probability of fatal outcome in patients with AS was created. High serum CRP and creatinine levels, as well as the decrease in venous oxygen saturation serve as significant prognostic markers of fatal outcome in patients with AS.

Received: 2025-01-31

Published online: 2025-02-23

DOI: 10.24075/brsmu.2025.008

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VIEWS 208

Meyer AV, Thorenko BA, Imekina DO, Dutchenko AP, Pyanzova TV, Karabchukov KB, Lavryashina MB

Pulmonary tuberculosis (TB) is a socially significant disease and a global challenge faced by public health. The NF-kB signaling pathway is involved in differential expression of the genes involved in immune responses and regulation of inflammation in response to infection. The study aimed to assess associations of the NFKB1 allelic variants with TB based on the panel of SNPs (rs4648050, rs4648051, rs4648055, rs4648058, rs4648068, rs1609993) located within the NF-kB1 р105→р50 processing region. Total DNA was extracted from blood samples (phenol-chloroform extraction) of patients with TB (n = 93) and the population control group (n = 96) consisting of residents of the Kemerovo Region. Genotyping was performed by real-time PCR, and the results were processed using the resources of the Statictica, SNPStats, Arlequin software packages. Ethnic features (p < 0.05) of the Russian population of Siberia (population control group) were demonstrated based on the rs4648050 and rs4648051 allele frequencies. Differences (p < 0.05) of the genetic profile of the sample of patients with pulmonary tuberculosis throughout the entire SNP complex, except for rs1609993, were noted. We showed differences (p < 0.05) in the rs4648068 allelic frequencies between the population control sample and patients with pulmonary tuberculosis. The association with susceptibility to pulmonary tuberculosis was determined for genotypes АА*rs4648055 (OR = 2.51; p = 0.05) and GG*rs4648068 (OR = 2.16; p = 0.03). The findings are indirect evidence of modifying effects of the SNP located within the processing zone in the gene NFKB1 and its possible contribution to the NF-kB1 р105/р50 protein balance and immune response to mycobacterial infection.

Received: 2024-12-23

Published online: 2025-02-19

DOI: 10.24075/brsmu.2025.004

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VIEWS 254

Kotova EA, Sumarokova EV, Belilovsky EM, Monchakovskaya ES

The COVID-19 pandemic necessitated making timely managerial decisions when providing medical care to patients with tuberculosis (TB). The study aimed to develop a system for monitoring of TB combined with COVID-19 and estimate the prevalence of COVID-19 among TB patients, along with the efficacy of the measures applied. A registry of TB/COVID-19 patients was developed based on the Barclay-SV Medical Database Management System. It was used to perform comparative analysis of the information about 1837 patients with active TB forms and confirmed COVID-19 for two periods of the pandemic, 2020–2021 and 2022–2023, and against the data on all new TB cases and TB relapses registered in Moscow in 2020–2023: 7812 and 1243 individuals respectively, from the TB surveillance registries, excluding those identified posthumously. The socio-demographic structure of patients with TB/COVID-19 co-infection identified in 2020–2023 did not change and corresponded to that of TB patients. In the second period analyzed, mild COVID-19 cases were registered more often (60.9% vs. 41.6%; p < 0.01), the share of moderate COVID-19 cases decreased from 48.2% to 20.6% (p < 0.01), and the share of severe cases decreased from 6.4% to 4.9% (p = 0.19). In 2022–2023, the share of individuals with COVID lung damage decreased from 45.1% to 17.6%, while the number of cases of COVID upper respiratory tract lesion increased from 47.1% to 64.5% (p < 0.05). The fact of having HIV infection, CAD and hypertension, kidney and genitourinary diseases increased the chance of developing COVID-19 by TB patients 1.5–2-fold, and disseminated pulmonary tuberculosis, caseous pneumonia, lung tissue destruction and bacterial excretion increased it 1.4–1.6-fold. The registry made it possible to control routing of TB/COVID-19 patients, as well as treatment outcomes: the total share of individuals cured reached 90.1%.

Received: 2024-12-11

Published online: 2025-02-11

DOI: 10.24075/brsmu.2025.003

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VIEWS 254

Fokin VF, Ponomareva NV, Shabalina AA, Konovalov RN, Medvedev RB, Boravova AI, Lagoda OV, Krotenkova MV, Tanashyan MM

Cognitive reserve (CR) is characterized by the ability to engage neural networks for adaptive reorganization of brain functions in response to damage or stress. This study aimed to identify the structural and functional organization of neural networks in patients with chronic cerebral ischemia (CCI) having different CR. The study involved 137 women aged 50–85 years suffering from CCI without diabetes. The average duration of CCI was 10.1 ± 0.7 years. CCI patients were divided into two groups: with secondary (SE) and higher (HE) education. Salivary cortisol levels were measured before and after cognitive load, along with the differences in brain connectivity organization based on fMRI data in two patient groups. Connectivity patterns were primarily found in the auditory areas, different in two groups after applying multiple comparison correction (FDR) and were responsive to cortisol levels. Patients with greater CR developed CCI later, showed significantly more positive connectivity values, had lower baseline cortisol levels, and displayed larger shifts in cortisol levels during cognitive load.

Received: 2024-11-28

Published online: 2025-01-31

DOI: 10.24075/brsmu.2025.002

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VIEWS 337

Pisklova MV, Baulina NM, Matveeva NA, Favorova OO

The role of miRNAs (small non-coding RNAs) in regulation of gene expression is reported. By binding with target mRNAs miRNAs control expression of the genes encoding these mRNAs at post-transcriptional level taking part in physiological and pathological processes, from embryogenesis to neoplastic disorders. Various research teams have been studying the miRNA functions and mechanisms of action since the discovery of these molecules in 1993. The paper reports miRNA biogenesis pathways, modes of interaction between miRNAs and target mRNAs, and the mechanisms underlying suppression of translation and mRNA degradation. The results of numerous studies have shown that miRNAs can be used in medicine as biomarkers for diagnostic and prognostic purposes. Developments in miRNA therapeutics hold promise for the treatment of diseases, in which gene dysregulation plays a key role.

Received: 2024-11-24

Published online: 2025-01-28

DOI: 10.24075/brsmu.2025.001

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VIEWS 342

Valieva YM, Popov KV

Gene therapy is subdivided into in vivo and ex vivo according to the tactics of delivery of therapeutic constructions. In vivo therapy, a vector containing a therapeutic construction is injected into the patient. In ex vivo therapy, cells are removed from the patient's body, genetically modified, and then returned. In ex vivo therapy for inherited diseases, hematopoietic stem cells are most often subjected to modification. Despite the advantage of in vivo therapy, which consists in the possibility of scale-up of production and convenience of use of ready-to-use drug, therapy based on transplantation of genetically modified hematopoietic stem cells remains relevant for a number of genetic diseases.

Received: 2024-12-25

Published online: 2024-12-31

DOI: 10.24075/brsmu.2024.074

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VIEWS 289