Bulletin of the Russian Military Medical Academy

The therapeutic effect of fibroblast-like cells obtained from the stromal vascular fraction of subcutaneous adipose tissue of mice and cultured for the treatment of bone marrow form of acute radiation syndrome was studied on a mouse experimental model. The cells were identified as multipotent mesenchymal stem (stromal) cells, owing to adhesion to plastic, confluent monolayer formation during cultivation, and the fact that osteogenic differentiation in vitro resulted in osteoblast maturation and calcium deposit formation, which indicated their multipotent nature. Irradiation of laboratory rodents was conducted using the X-ray therapy unit “RUM-17”. Stromal cells were obtained from subcutaneous adipose tissue of a mouse and grown in a culture of 3–4 passages and used as a cell product. Cell transplantation was performed 24 h after uniform X-ray irradiation of mice at a dose of 7.8 Gy. This is the first study to compare the therapeutic efficacy of allogeneic transplantation of multipotent mesenchymal stem cells with the different routes (intravenous and intraperitoneal) of cell suspension administration. A significant increase was found in the survival rate of mice during the 30-day follow-up period after lethal dose irradiation, which depended on the number of injected cells and delivery method of the biomedical cell product. Thus, with intravenous administration of 30 and 60 × 10³ multipotent mesenchymal stem cells, the 30-day survival rate of mice after irradiation at a dose of 7.8 Gy increased by 54.5% and 40%, respectively, compared with that of untreated animals (p = 0.03). An increase in the number of cells in the cell product to 120 × 10³/mouse led to a decrease in therapy effectiveness. In intraperitoneal administration, the protection of animals from death was 57% after transplantation of 30 and 60 × 10³ cells (p = 0.039) and 50% after application of 120 × 10³ cells. On day 30 after irradiation, in the introduction of a cellular product in different schemes, 70%–80% of animals showed restoration of the values of the main indicators of the hematopoiesis system to initial levels. Thus, cell therapy using multipotent mesenchymal stem cells isolated from adipose tissue with intravenous and intraperitoneal delivery routes of the cellular product to the irradiated body protects mice from death after exposure to X-ray radiation in lethal doses, decreasing the severity of radiation damage to the hematopoietic system in mice, and provides prospects for further research as an effective and safe treatment for acute radiation sickness.

The associations between the main non-lipid genomic biomarkers and coronary heart disease occurrence and the unstable course of the disease with the development of myocardial infarction in 164 patients with stage I–III hypertension were investigated. The study was conducted in two stages. At the first stage, the non-lipid genetic predictors of coronary heart disease were determined without considering the characteristics of its clinical course. At the second stage, the possibility of identifying genetic predictors of the complicated course of coronary heart disease with the development of myocardial infarction was studied. In hypothesis testing, the difference was considered significant at p < 0.05. It was found that the presence of coronary heart disease in patients with hypertension was associated with a significant predominance of genetic biomarkers in four single-nucleotide polymorphisms: in the hemostasis system (4G4G SERPINE 1), pro-inflammatory cytokines (T allele IL-1b-511, C allele IL-1b-1473), and innate immunity (FF TLR3-412). The development of myocardial infarction was associated with two genetic polymorphisms: pro-inflammatory cytokine system (CC IL-6-174) and hemostasis (4G4G SERPINE 1). In general, among the single-nucleotide polymorphisms studied, statistically significant results in predicting coronary heart disease were demonstrated by genetic biomarkers of the hemostatic system, pro-inflammatory cytokines, and innate immunity. In relation to myocardial infarction, genetic biomarkers of the hemostatic system and pro-inflammatory cytokines may have prognostic value. The use of genetic biomarker data as unfavorable prognosis predictors in patients with hypertension enables better risk stratification and assessment of the prognosis in these patients, which will significantly reduce the costs of conducting a genome-wide study.

The effectiveness of the use of oxygen, zinc bisvinylimidazole diacetate, and ascorbic acid for the treatment of powder gas poisoning was evaluated using an intoxication model of laboratory animals (mice) with thermal destruction products of nitrocellulose. Mice were subjected to intoxication with thermal destruction products of nitrocellulose in an average lethal concentration. Oxygen therapy (proportion of inhaled oxygen: 0.3; 1 ata) was performed immediately after exposure and once for 30 min. Zinc bisvinylimidazole diacetate (9 mg/kg, intraperitoneal) and ascorbic acid (40 mg/kg, intraperitoneal) were administered to mice once after exposure. Survival rate, hemoglobin derivative concentrations, pulmonary coefficient, and histological changes in the lung tissue were determined. The effectiveness of the use (protection, antidote power, and guaranteed protection indices) of a combination of zinc bisvinylimidazole diacetate and ascorbic acid was assessed. The survival rate of mice that received oxygen after intoxication with thermal destruction products of nitrocellulose was lower (20 ± 13%; p < 0.05) than that of animals that did not receive treatment (60 ± 16%); 3 h after exposure, the pulmonary coefficient was 22.5 [21.9; 23.8] rel. units and 13.1 [12.5; 13.7] rel. units respectively. The protection index of the combination of zinc bisvinylimidazole diacetate and ascorbic acid was 1.39 rel. units, antidote power indicator was 0.95 rel. units, and guaranteed protection coefficient was 0.65 rel. units. The use of the study combination resulted in decreased carboxyhemoglobin (9.3 [7.8, 12.9]%; p < 0.05) and methemoglobin (2.4 [1.5, 4.1]%; p < 0.05) concentrations compared to animals that did not receive treatment (24.5 [22.9; 28.3]% and 8.9 [7.3; 11.1]%, respectively). The pulmonary coefficient of mice receiving the study drug combination was lower (p < 0.05) than that of animals not receiving treatment at 3 and 6 h after exposure. Moreover, 6 h after exposure, signs of the alveolar phase were determined in mice that did not receive treatment, and in animals that were administered the study drug combination, signs of the interstitial phase of toxic pulmonary edema were observed. Thus, the use of oxygen after intoxication with products of thermal destruction of nitrocellulose leads to early formation of toxic pulmonary edema. As a pathogenetically based approach to the treatment of intoxication, the use of zinc bisvinylimidazole diacetate and ascorbic acid should be considered, the mechanism of action of which is aimed at relieving hemic and respiratory hypoxia.

Presently, an increasing volume of laboratory tests performed by sanitary and preventive organizations of the Russian Ministry of Defense (centers of state sanitary and epidemiological supervision) are carried out directly in the field during various combat training activities and special tasks and the localization and elimination of epidemic foci of infectious diseases in organized military collectives. Thus, non-staff mobile sanitary-epidemiological groups are formed. However, the regular special military equipment—medical field laboratory—used to equip such groups, is outdated and does not provide the basic principles of their autonomous functioning (mobility, autonomy, multidisciplinarity, high manufacturability, zoning of workplaces, compliance with biological safety requirements). Hence, the need for and prospects of developing a new automotive laboratory complex for equipping sanitary and prophylactic organizations of the Russian Ministry of Defense are investigated. This study analyzes the experience of military sanitary-preventive organizations for the period 2011–2021. The tactical and technical characteristics of the staff laboratory of the medical field laboratory of the state sanitary and epidemiological supervision centers of the Russian Ministry of Defense are compared with available analogues, including those in the institutions of other ministries and departments. As the number of long visits of military sanitary specialists and preventive organizations significantly increases to the extent of providing temporary accommodation for military units to ensure the sanitary and epidemiological well-being of the personnel, the need for laboratory research in isolation from the network of stationary laboratories to objectify the activities of the state sanitary and epidemiological supervision and ensure the anti-epidemic protection of troops also significantly increases. Moreover, the drawbacks of the standard medical field laboratory and its analogues and hence their limited use in the interests of the Russian Ministry of Defense in existing configurations were identified. The obtained results enabled reasoning for the need for a new automotive laboratory complex for equipping sanitary and preventive organizations of the Russian Ministry of Defense considering the successful solutions in laboratory complexes of other ministries and departments.

Based on the annual statistical reports for 2018–2023 and the cumulative median prevalence of various studies in 2009–2020 in Russia, the prevalence of peptic ulcer with uncomplicated and complicated course and various forms of gastritis in servicemen of the Regardie of the North Caucasian District was estimated, and the current trends are explained. The incidence of peptic ulcer with uncomplicated and complicated course and various forms of gastritis among the servicemen of the Regardie of the North Caucasian District for the specified period ranged from 11.521% to 16.351% (confidence interval: 10.515–12.588 and 15.233–17.517, respectively) and from 27.212% to 51.889% (confidence interval: 25.791–28.669 and 50.316–53.460, respectively). Random effects analysis has demonstrated different true effect sizes relative to the overall average. The revealed statistical patterns are only the first stage in an ongoing study on the prevalence of upper gastrointestinal diseases among the servicemen of the Regardie of the North Caucasian District. In general, the prevalence of peptic ulcer disease, including with a complicated course, and various forms of gastritis among military personnel was 13.270% and 37.679%, respectively (confidence interval: 10.617–16.170 and 24.292–52.102, respectively), showing an upward trend. The expected prevalence of peptic ulcer and gastritis in 2023 was 16,351 and 51,889%, respectively, which is not accidental and depends on the impact of specific risk factors. The identification of risk factors enables the development of measures to prevent delayed complications of the pathology under study and improvement of health in servicemen of the Regardie of the North Caucasian District. Thus, the study of the health status of the general population and military personnel, in particular, and the effect of various environmental factors determines their social significance both in military medicine and the structure of the healthcare system.

The treatment result of a patient with spontaneous rupture of the Achilles tendon and features of diagnosing alkaptonuric ochronosis, a rare disease, are presented, providing doctors beneficial information for the prevention and/or delay of possible complications. On March 8, 2021, at about 20:50, while at his workplace, getting up from his chair from the table, patient K, 52 years old, felt a sharp pain in the lower third of his right shin and was urgently taken to the hospital. He was examined by a traumatologist and was initially diagnosed with rupture of the right Achilles tendon. His right lower limb was immobilized with a plaster splint. On March 11, 2021, he entered the military traumatology and orthopedics clinic of the Kirov Military Medical Academy for surgical treatment. Upon admission, the patient complained of pain in the right lower leg and impaired support function of the right lower limb. Based on complaints, medical history, laboratory results, and instrumental studies, subcutaneous rupture of the right Achilles tendon was diagnosed. On March 12, 2021, anchor suture of the right Achilles tendon was performed. Anesthesia — combined, access: two separate incisions on the posterior surface of the lower third of the right leg and in the area of the calcaneal tubercle, each 5 cm long, intraoperatively revealed a complete subcutaneous rupture of the right Achilles tendon. Notably, the tendon was black in color when cut. The postoperative period proceeded without complications, and postoperative wounds of linear shape in the right Achilles tendon healed by primary intention. No signs of disturbances were observed in peripheral circulation and innervation of the right lower limb. To confirm the diagnosis, a simple laboratory test was performed: a change in the color of urine during the day, after its additional alkalization. The color change is due to the polymerization of homogentisic acid, which is excreted in large quantities in the urine. To verify the diagnosis, a molecular genetic technique was performed: sequencing of the clinically significant HGD gene and encoding the enzyme homogentisate-1,2-dioxygenase, which are mutations that lead to alkaptonuria. The analysis results confirmed the presence of an amino acid substitution at the pGLy161Arg position, indicating pathogenicity. The use of simple methods of additional laboratory diagnostics and molecular genetic analysis enabled the diagnosis of alkaptonuric ochronosis. Thus, characteristic diagnostic signs were damage to the Achilles tendon in combination with the obtained anamnestic, clinical, and laboratory data of alkaptonuria.

The genetic associations between single-nucleotide polymorphisms of genes and chronic heart failure in phenotypically similar groups of patients were examined. The known information about single-nucleotide polymorphisms associated with the main pathogenetic links of chronic heart failure is systematized. Using electronic databases (PubMed, Web of Science, eLibrary), a search and synthesis of scientific works was conducted, followed by the formation of groups of genes homogeneous in their functionality (i.e., genes of the metabolic cascade, coagulation cascade, and neuroendocrine cascade). From >50 literary sources analyzed, 15 of the most specific genes were identified (ApoA1, ApoE, ApoC3, GNB3, FTO, PON-1, ET(A), EDNRA, F13, ITGB3, PAI-1, VEGF, ACE, AGT, AGTR1), contributing in metabolic processes, the hemostatic system, endothelial function, and regulation of the renin–angiotensin–aldosterone system and associated with the development of chronic heart failure. The most significant contribution of these genes in the development of regulatory and structural disorders characteristic of the pathogenetic phenotype of chronic heart failure has been proven. The results are ambiguous. Thus, in individuals who have a polymorphic gene variant in their genotype associated with the risk of developing a disease, the possibility of its manifestation is considerably higher; however, this does not confirm the development of the disease. Moreover, a correlation was noted between ejection fraction in patients with chronic heart failure and gene polymorphisms associated with renin–angiotensin–aldosterone system dysfunction and metabolic cascade. Chronic heart failure is a polygenic disease. Hence, this allows for further research into groups of coordinately functioning genes that are part of genetic regulatory networks, enabling a more complete understanding of the etiology and pathophysiological mechanisms of this nosology with the aim of subsequent early identification of individuals belonging to the risk group and the creation of a set of measures for individual prevention diseases. We believe that the development of chronic heart failure with low ejection fraction is primarily responsible for gene polymorphisms associated with disorders of the renin–angiotensin–aldosterone system and for the development of chronic heart failure with preserved ejection fraction — gene polymorphisms associated with metabolic cascade disorders.

One of the main molecular mechanisms of viroids that cause disease in plants is the blocking of ribonucleic acid functions of host cells by viroid ribonucleic acid. The variety of splicing options is due to viroid replication, which requires ribonucleic acid polymerase, ribonuclease, ligase, and deoxyribonucleic acid working on ribonucleic acid matrices. Viroids with faster replication are preferred. Identifying host proteins that interact with viroid ribonucleic acid is critical in the pathogenesis of viroid infections, which leads to gene expression changes of host plants. The study of the pathogenesis of plant infections caused by satellite viruses has shown that they have a common ancestor and that the satellite viruses suppress the reproduction of the helper virus. Satellite viruses require accessory viral proteins to encode capsid proteins for genome encapsulation and reproduction. Replication occurs in the cytoplasm and is induced by ribonucleic acid polymerase of the helper virus. Hepatitis D virus ribonucleic acid replication requires cell ribonucleic acid polymerase II. When the viral and endosomal membranes fuse, the ribonucleic acid of the hepatitis D virus moves into the nucleus, and antigenomic ribonucleic acid is produced, which is the template for the synthesis of matrix ribonucleic acids encoding delta protein. The minor delta antigen regulates ribonucleic acid editing, and the large delta antigen inhibits viral replication and induces a signal for the transport of ribonucleic acid from the cell nucleus to the cytoplasm, which ensures the assembly of new viral particles. Large and small delta antigens have been detected in the brain, liver, lungs, kidneys, and spleen of snakes by reverse transcriptase polymerase chain reaction, Western blotting, and immunohistochemical assays, indicating that all delta viruses possibly share a common ancestor that arose before the divergence of reptiles and mammals.

The key milestones in the life and main scientific achievements of the famous Russian histologist Alexander A. Maksimov (January 22, 1874–December 3, 1928), a graduate and gold medalist of the Imperial Military Medical Academy, who headed its Histology Department with a course of embryology for 20 years, were studied (1903–1922). A.A. Maximov was born in St. Petersburg into a merchant family and spent his childhood years in Vasilyevsky Island. Some buildings where the A.A. Maximov family lived have survived to this day. A.A. Maximov had three older sisters: Vera, Evgenia, and Claudia. The gymnasium in which A.A. Maximov also studied in Vasilyevsky Island. The director of the educational institution (one of the best in St. Petersburg) was the famous teacher–organizer Karl I. May. The archives preserve information about the progress of Maximov’s essay, which testifies to his excellent studies. Maximov graduated with a gold medal. One of his classmates at the Imperial Military Medical Academy was Vladimir A. Oppel, who later became a famous surgeon. He left interesting memories of Maximov during the years of joint study at Imperial Military Medical Academy. While in exile, Maximov constantly remembered his homeland, colleagues, and native places where he spent most of his life. His works remain relevant today. Emphasis is placed on the key scientific developments of A.A. Maximov — unitary theory of hematopoiesis, identifying the morphological basis of inflammatory reactions, and neoplasm of connective tissue in experiment. The results of a search for previously unpublished St. Petersburg addresses related to the life of A.A. Maximov are presented. Based on recently discovered archival documents, new information is provided that complements the biography of the outstanding Russian histologist who pioneered the study of stem cells.

May 12, 2024, marked the 70^th birthday of the Honored Scientist of Russia, corresponding member and honorary doctor of the Kirov Military Medical Academy, Prof. Vasily N. Tsygan. He is a brilliant embodiment of the traditions of academic scientific schools, having gone from being a member and chairman of the Military Scientific Society of Cadets and Students to an adjunct to the deputy head of the academy for scientific work. After graduating from the academy with a gold medal and serving 3 years in the military, Vasily N. Tsygan entire subsequent scientific, pedagogical, and organizational activity has been connected with the academy. The topic of his candidate dissertation, related to changes in homeostasis in mechanical trauma, and performing special assignments from the command in Afghanistan and in the zone of the counter-terrorist operation in the Chechen Republic determined a crucial vector of research into the extreme impacts on the human body during military professional activity. V.N. Tsygan contributed to the study of immunophenotyping problems, the modern concept of molecular remission in oncohematology, and immunodeficiency in various types of pathology and methods for their correction. He is an experienced organizer of science and many large international scientific events. His activities involved the study of the history of Russian medicine, relations with the Nobel Committee, and defending the priority of Russian scientists. V.N. Tsygan’s contribution to the creation and development of the Military Medical Academy journals, where he worked for decades as executive secretary and deputy editor-in-chief, is invaluable. The Academy, the Ministry of Defense, the Academy of Medical Sciences, and the state have highly appreciated the merits of Prof. V.N. Tsygan, honoring him with state and departmental awards, prizes, and honorary titles.