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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Vladimirsky GM, Zhuravleva MA, Dashieva AE, Korneeva IE, Nazarenko TA

Currently, in vitro fertilization (IVF) with embryo transfer is the main method of treatment of all forms of infertility, but successful cases ending in pregnancy still account for only a third of all cycles performed. It is necessary to take into account many parameters and investigate the connections between them in order to properly evaluate the results of IVF. Over the past decades, a number of IVF prediction models have been developed with the aim at assessing the outcomes in individual cases, but, given the generally poor prognostic capacity, only a few of them have proven to be clinically significant. This study aimed to create nonlinear IVF outcomes prediction models and identify the most significant factors affecting the said outcomes. Using a database containing information on more than 700 indicators of 7004 women aged 18 to 45 years who participated in the IVF program in Russia from 2010 to 2020, we trained a random forest model that predicted pregnancy in the IVF cycle with ROC-AUC = 0.69. This paper describes 20 most successful predictors of the resulting model and interprets their contribution to the prognosis. Of these, body mass index (BMI) and the number of received and fertilized oocytes have been covered in the scientific literature previously as predictors of IVF outcomes, but other parameters, such as anamnestic data, previous participation in an IVF program (number of cases and their results), as well as serum concentration of AMH, rarely appear in foreign prognostic models.

Received: 2023-11-24

Published online: 2023-12-31

DOI: 10.24075/brsmu.2023.057

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VIEWS 2103

Radaeva OA, Simbirtsev AS, Kostina YuA, Iskandiarova MS, Negodnova EV, Mashnina SV, Yeremeev VV, Krasnoglazova KA, Babushkin IO

In spite of a vast number of trials devoted to quantitative characteristics of the cytokine profile in patients with various diseases, no exact reference intervals are presented. It is just as important that there is a limited number of trials analyzing circadian rhythms of cytokine synthesis in patients with arterial hypertension. The purpose of the work was to analyze the characteristics of circadian rhythms of cytokines (IL18, IL18 BP, LIF, sLIFr, M-CSF, MCSFR) in patients with Grade II essential arterial hypertension, and to detect pathogenetically significant characteristics developed following Covid-19. Blood samples were taken at 7.00–8.00, 12.00–13.00, 19.00–20.00.00, 00.00–1.00 to determine the levels of IL18, IL18 BP, LIF, sLIFr, M-CSF, MCSFR in 18 patients (56 (95% CI (54–69) years) with essential arterial hypertension (EAH) within three days prior to and following Covid-19. For this, the immunoenzyme method was used. The obtained data demonstrated altered circadian expression of cytokines in the peripheral blood of patients with essential hypertension depending on whether they have EAH or not, and their additional distortion following Covid-19, which is stable in the majority of cases. It is preserved for six months as low IL18 BP (р < 0.001), and twofold increase of sLIFr and MCSF (р < 0,001) at 18.00. A significant association is determined between the circadian rhythms of sLIFr and altered systolic BP resulting in the abnormal rhythm with BP rise at night (night peaker) in patients with EAH following COVID-19. The obtained fundamental data offer prospects for new research of immunopathogenesis following COVID-19 in patients with hypertension taking into account circadian rhythms of cytokines in the blood.

Received: 2023-11-29

Published online: 2023-12-31

DOI: 10.24075/brsmu.2023.056

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VIEWS 1656

Macular rupture is among major vitreoretinal disorders resulting in significant visual function decline. In recent years, the use of platelet-rich autoplasma in the macular rupture surgery is considered to be promising. However, despite high rate of macular rupture closure (78–96%), the development of new technology for foveal microarchitectonics restoration and visual function improvement currently remains a pressing issue. The study was aimed to develop a new foveal reconstruction technique for macular rupture involving the use of autologous conditioned plasma. The reported study involved 9 patients (10 eyes) with idiopathic macular hole, who underwent standard three-port 27G vitrectomy involving the use of autologous conditioned plasma in accordance with the technique developed. The proposed technique makes it possible to achieve good clinical and functional surgical treatment outcome and ensures optimal and more manageable reconstruction of foveal microarchitectonics.

Received: 2023-12-04

Published online: 2023-12-31

DOI: 10.24075/brsmu.2023.055

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VIEWS 1685

Minasov BSh, Yakupov RR, Bilyalov AR, Minasov TB, Valeev MM, Mavlyutov TR, Nigamedzanov IE, Akbashev VN, Karimov KK

Preoperative planning of hip arthroplasty provides surgeons with a unique opportunity of thorough investigation of the patient’s anatomy, allows them to determine optimal implant size and position, as well as to prevent potential complication. Advances in digital technology enable expansion of opportunities of preoperative planning due to using three-dimensional modeling. The study was aimed to compare precision of the three-step preoperative planning of hip arthroplasty and the standard method. Methods: The study involved 224 patients with various forms of degenerative and dystrophic diseases of the hip joint, who were divided into the index and control groups based on the planning method. In the index group, preoperative planning of arthroplasty was conducted in three steps: assessment of bone density in the zones of fixation based on CT; virtual design involving the use of automated programs; 3D model construction based on the computer model. X-ray images and endoprosthesis templates were used in the comparison group. The results showed that there were no significant differences between planning methods in patients with osteoarthrosis and avascular necrosis of the femoral head (p > 0.05), in contrast to the group with traumatic hip joint pathology showing significant differences (рс = 0.002). Conclusions: the three-step algorithm for preoperative planning of hip arthroplasty showed higher efficacy in patients with various nosological forms of degenerative and dystrophic diseases of the hip joint compared to the standard method.

Received: 2023-11-12

Published online: 2023-12-31

DOI: 10.24075/brsmu.2023.052

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VIEWS 1932

Shepelkova GS, Reshetnikov VV, Avdienko VG, Sheverev DV, Yeremeev VV, Ivanov RA

Vaccination is among the most effective measures to reduce tuberculosis morbidity and mortality. In 1974, BCG vaccination was included in the Expanded Program on Immunization. Today, it covers 80% of all children around the globe. Unfortunately, BCG vaccine provides no protection against pulmonary tuberculosis, the most prevalent form of tuberculosis. It is necessary to urgently develop new vaccination strategies to stop large-scale dissemination of infection caused by the multidrugresistant pathogen. The study was aimed to compare the capabilities of three variants of mRNA vaccines encoding Esat6 epitopes of stimulating adaptive immune response formation in C57BL/6 mice (ELISpot, delayed hypersensitivity, IgG titers), as well as of protecting I/St mice against M. tuberculosis infection. Efficacy of mRNA vaccines comprising different untranslated regions packaged in lipid nanoparticles was compared with that of BCG vaccine. The 5'-TPL-Esat6-3'-Mod vaccine demonstrated the highest efficacy in our experimental model. Thus, the 5'-TPL-Esat6-3'-Mod mRNA vaccine can be considered as a candidate vaccine for further optimization, improving efficacy and subsequent use for prevention of tuberculosis.

Received: 2023-11-17

Published online: 2023-12-31

DOI: 10.24075/brsmu.2023.054

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VIEWS 2006

Pukaeva NE, Zalevskaya VN, Deykin AV, Taubinskaya MI, Kukharskaya OA, Ovchinnikov RK, Antohin AI, Kukharsky MS

NEAT1 long non-coding RNAs play an important role in the central nervous system (CNS) and are associated with a number of pathological conditions. Increased levels of NEAT1 in the brain have been observed in neurodegenerative and psychiatric diseases — the significance of such an increase is still poorly understood. Functionally, NEAT1 is associated with cellular stress pathways in the nervous system. The aim of the current study was to evaluate the effect of increased levels of the short isoform NEAT1_1 on survival of mice primary hippocampal cultures under ER-stress induced by MG132 proteasome inhibitor. Primary cultures were obtained from transgenic animals expressing human NEAT1_1. Cellular composition and apoptosis were assessed using immunocytochemical staining. The expression of apoptosis signaling pathway genes was analyzed by quantitative PCR with reverse transcription. No differences in cellular composition and morphological characteristics of neurons were observed in primary neuronal cultures obtained from transgenic animals as compared to wild type cultures. Induction of ER-stress resulted in a more significant increase in apoptotic death of cells including neurons in NEAT1_1 expressing cultures in comparison with the wild type cultures. ER-stress signaling pathway genes Atf4 and Ddit3 were less expressed in transgenic cultures under stress. Expression of Bcl2l2 and Mcl1 anti-apoptotic genes was reduced as well. Thus, high levels of NEAT1_1 in primary neuronal cultures increased apoptotic cell death under ER-stress.

Received: 2023-11-08

Published online: 2023-12-31

DOI: 10.24075/brsmu.2023.053

Comments 0

VIEWS 1684

Kubekina MV, Filatov MA, Silaeva YY, Sitnikov DS

Impaired hatching of the embryo from the zona pellucida (ZP), the specialized protective shell, immediately before implantation is one of the factors of infertility. Hatching impairment is often due to the ZP hardening or thickening. In such cases, the laser assisted hatching procedure is used to overcome infertility. During this procedure a hole is drilled in the ZP facilitating the embryo release. The question of the safe use of laser for assisted hatching remains open, since laser beam can heat the environment and cause thermal shock in embryos. The study was aimed to assess safety of the mouse embryo femtosecond laser exposure during the assisted hatching procedure using the embryo viability and HSP gene expression assessment methods. A new type of pulsed laser was used in the study for the ZP dissection — the femtosecond laser. The energy of such pulses was two orders of magnitude lower than the energy of laser dissectors currently used in the clinics. To assess the femtosecond laser exposure to the embryo, the house mouse (Mus musculus) embryos were stained with fluorescence dyes, and expression of the genes encoding heat shock proteins (Hsp90aa1 and Hspa5) was assessed. The embryonic cells remained viable after the laser assisted hatching procedure involving the use of a femtosecond laser, while expression levels of the genes encoding heat shock proteins were slightly increased compared to the negative control group (p = 0.408).

Received: 2023-11-07

Published online: 2023-12-26

DOI: 10.24075/brsmu.2023.046

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VIEWS 1914

Roumiantsev SA, Kirilina IV, Gaponov AM, Khusnutdinova DR, Grigoryeva TV, Teplyakova ED, Makarov VV, Yudin SM, Shestopalov AV

Adipose tissue, being a source of chronic low-grade inflammation, activates cells of the immune system by producing cytokines and chemokines. The balance between pro- and anti-inflammatory molecules and their relationship with blood bacterial DNA in obese children and adolescents has not been studied sufficiently. This study aimed to find patterns of interaction between fractions of bacterial families in healthy and obese children, analyze cytokine levels and their relationship with blood bacterial DNA content, evaluate alpha diversity of blood microbiome and similarities of blood and fecal microbiomes. We examined 163 individuals (children and adolescents), who were divided into 2 groups, obese (n = 80, obesity classes I through III) and healthy (n = 83). The material sampled and studied was venous blood. Only individuals that have not been taking antibiotics, pro- and prebiotics for at least 3 months before the study were included. The methods employed were multiplex ELISA (enzyme immunoassay) and 16S rRNA gene sequencing (region V3–V4). From the angle of bacterial families, we found differences in their content (fractions) in blood microbiome and the frequency of isolation of their DNA therein. Nineteen families accounted for over three quarters of all bacterial DNA identified in the blood. In obese children, one of the dominating roles was played by Ruminococcaceae, with their DNA a key part of the microbiome's alpha diversity, while in healthy participants this could be said about Bacteroidaceae. Analyzing beta diversity, we found that in obese children, fecal and blood microbiomes differed significantly, which indicates, mainly, extra-intestinal translocation of bacterial DNA. Obese children exhibited increased content of IL17A (p = 0.017) and PD-L1 (p = 0.021); there were differences in blood microbiome between groups. We identified the patterns of interaction between bacterial DNA fractions, and assessed cytokine levels.

Received: 2023-10-13

Published online: 2023-12-23

DOI: 10.24075/brsmu.2023.049

Comments 0

VIEWS 1824