[Prevention and treatment of COVID-19 based on post-genomic pharmacological analysis: Systematic computer analysis of 290,000 scientific articles on COVID-19].

The COVID-19 pandemic has highlighted pressing challenges in biomedical research methodology. It has become obvious that the rapid and effective development of treatments for "new" viral infections is impossible without the coordination of interdisciplinary research and in-depth analysis of data obtained within the framework of the post-genomic paradigm. Presents the results of a systematic computer analysis of 290,000 scientific articles on COVID-19, with an emphasis on the results of post-genomic studies of SARS-CoV-2. The futility of the overly simplified approach, which considers only one "most important receptor protein", only one "key virus gene", etc., is shown. It is shown how post-genomic technologies will make it possible to find informative biomarkers of severe coronavirus infection, including those based on complex immune disorders associated with COVID-19.

[Rehabilitation program of post-COVID-19 syndrome with the use of nitric oxide and molecular hydrogen].

Рost-COVID-19 syndrome (PS) is one of the medical and social problem. According to WHO, 10-20% of COVID-19 patients suffer from PS. The use of medical gases - inhaled nitric oxide (iNO) and molecular hydrogen (iH2) - may influence on the mechanisms of development PC. AIM: To evaluate the safety and efficacy of the combined inhalation of NO and H2 (iNO/iH2) in patients with respiratory manifestations of PS. MATERIALS AND METHODS: 34 patients with PS (11 men/23 women, 60.0±11.7 years) were included in the prospective open-label controlled study in parallel groups: the main group (n=17) received iNO/iH2 for 90 minutes once a day for 10 days (concentration of NO 60 ppm, H2<4% in the gas mixture), the control group (n=17) didn't receive inhalations. The period from the confirmation of COVID-19 to the start of the study was 641.8±230.5 days. The groups did not differ in the baseline parameters. The clinical symptoms (from the self-observation diary and mMRC questionnaires, "dyspnea language"), FAS, HADS, SF-36 scores, 6-minute walk test, the blood serum parameters of oxidative stress, the dynamics of the microcirculation in the eye bulbar conjunctiva were evaluated. The individual dose of iNO has chosen during a 15-minute test (the positive dynamics of the microcirculation have indicated that the dose was selected correctly). RESULTS: The decrease the symptoms severity, such as dyspnea, cough, fatigue and palpitations (p<0.005), the increase in SF-36 questionnaire scores (p=0.006) and a reducing of FAS score (p=0.001), as well as the anxiety component of HADS (p=0.02) were revealed at the end of treatment in the main group compared to the control group. We observed an improvement in distance walked (p=0.01) and the values SpO2 (p=0.04) in 6-minute walk test, the increase in the volumetric blood flow velocity in venules (p<0.001), and the date in oxidative damage (p<0.001) and antioxidant activity (p=0.03) parameters in the blood serum. CONCLUSION: The results of the study demonstrate clinical efficacy iNO/iH2 on clinical indicators, parameters of oxidative stress and microcirculation in patients with PS.

[New clinical guidelines for COPD - a paradigm shift: A review].

Chronic obstructive pulmonary disease is now one of the most common noncommunicable diseases and the main causes of morbidity, disability and mortality in the world. In recent years, new approaches to epidemiology, diagnosis, classification (categorization), evaluation of phenotypes, as well as characterization and assessment of the severity of сhronic obstructive pulmonary disease exacerbations have emerged. Modern approaches to starting and subsequent drug therapy have changed significantly. This is largely due to the results of recently conducted major clinical trials, demonstrated high efficacy of triple fixed combinations, including inhaled glucocorticosteroids, long-acting beta-agonists and long-acting anticholinergic drugs. The use of non-medication methods (smoking cessation, physical activity and respiratory rehabilitation) and modern approaches to the treatment of respiratory failure and antibiotic therapy remain important. In terms of their significance, all these updates have a significant impact on real clinical practice and can be considered as a novel paradigm of the approaches to the diagnosis and management of this disease.

[Pulmonary heart: A review].

The review on the problem of the pulmonary heart pursues two goals: firstly, to restore historical justice and to show the priority studies of doctor Dmitry D. Pletnev on such problems as diagnosis of right ventricular myocardial infarction, clinical characteristics of congestive heart failure of the right ventricle; secondly, to outline the modern concept of the pulmonary heart. The review provides an analysis of the pathogenetic mechanisms of the development of heart failure in the pulmonary heart. Much attention is paid to echo cardiography data and biological markers are emphasized in assessing the function of the right atrium, right ventricle, tricuspid valve regurgitation, pulmonary artery pressure. Prognostically unfavorable signs of the course of the pulmonary heart have been identified, which include a high degree of tricuspid valve regurgitation, the amplitude of movement of the fibrous valve ring (TAPSE) and atrial fibrillation developing with dilation of the right atrium.

[Heart Diseases by Professor Dmitry D. Pletnev (for the reprint of D.D. Pletnev's monograph "Heart Diseases", 1936)].

The article presents a brief review of Heart Diseases (1936), the monograph by one of the founders of domestic and world cardiology Dmitry Dmitrievich Pletnev. In the monograph, he summarized his clinical and experimental approach to the issues of heart diseases, addressed several fundamental problems of modern physiology and healthcare, introduced the concept of "functional unit" and "functional unity of the whole body", the concept of the extracardiac genesis of the chest frog, differential diagnosis of left and right ventricle myocardial infarction, semiotics and treatment of chronic heart failure, functional diagnosis of heart arrhythmias. All these approaches and concepts have long been included in the classics of world cardiology.

[Molecular mechanisms of the effect of standardized placental hydrolysate peptides on mitochondria functioning].

BACKGROUND: Human placenta hydrolysates (HPH), the study of which was initiated by the scientific school of Vladimir P. Filatov, are currently being investigated using modern proteomic technologies. HPH is a promising tool for maintaining the function of mitochondria and regenerating tissues and organs with a high content of mitochondria (liver, heart muscle, skeletal muscles, etc.). The molecular mechanisms of action of HPH are practically not studied. AIM: Identification of mitochondrial support mitochondrial function-supporting peptides in HPH (Laennec, produced by Japan Bioproducts). MATERIALS AND METHODS: Data on the chemical structure of the peptides were collected through a mass spectrometric experiment. Then, to establish the amino acid sequences of the peptides, de novo peptide sequencing algorithms based on the mathematical theory of topological and metric analysis of chemographs were applied. Bioinformatic analysis of the peptide composition of HPH was carried out using the integral protein annotation method. RESULTS: The biological functions of 41 peptides in the composition of HPH have been identified and described. Among the target proteins, the activity of which is regulated by the identified peptides and significantly affects the function of mitochondria, are caspases (CASP1, CASP3, CASP4) and other proteins regulating apoptosis (BCL2, CANPL1, PPARA), MAP kinases (MAPK1, MAPK3, MAPK4, MAPK8, MAPK9 , MAPK10, MAPK14), AKT1/GSK3B/MTOR cascade kinases, and a number of other target proteins (ADGRG6 receptor, inhibitor of NF-êB kinase IKKE, pyruvate dehydrogenase 2/3/4, SIRT1 sirtuin deacetylase, ULK1 kinase). CONCLUSION: HPH peptides have been identified that promote inhibition of mitochondrial pore formation, apoptosis, and excessive mitochondrial autophagy under conditions of oxidative/toxic stress, chronic inflammation, and/or hyperinsulinemia.

[Pulmonary fibrosis in patients with COVID-19: A review].

The viral infectious disease pandemic caused by SARS-CoV-2 has affected over 500 million people and killed over 6 million. This is the official data provided by the WHO as of the end of May 2022. Among people who have recovered from COVID-19, post-COVID syndrome is quite common. Scattered epidemiological studies on post-COVID syndrome, however, indicate its high relevance. One of the manifestations of post-COVID syndrome is the development of pulmonary fibrosis (PF). This article is devoted to the analysis of literature data on epidemiology, immunomorphology, as well as X-ray morphological and functional characteristics of PF in patients with post-COVID syndrome. Attention is drawn to the various phenotypes of the post-COVID syndrome and the incidence of PF, which, as clinical practice shows, is most common in people who have had severe COVID-19. This article discusses in detail the molecular biological and immunological mechanisms of PF development. The fibrotic process of the lung parenchyma is not an early manifestation of the disease; as a rule, radiomorphological signs of this pathological process develop after four weeks from the onset of acute manifestations of a viral infection. The characteristic signs of PF include those that indicate the process of remodulation of the lung tissue: volumetric decrease in the lungs, "cellular" degeneration of the lung parenchyma, bronchiectasis and traction bronchiolectasis. The process of remodulating the lung tissue, in the process of fibrosis, is accompanied by a violation of the lung function; a particularly sensitive test of functional disorders is a decrease in the diffusion capacity of the lung tissue. Therefore, in the process of monitoring patients with post-COVID syndrome, a dynamic study of the ventilation function of the lungs is recommended. The main clinical manifestation of PF is dyspnea that occurs with minimal exertion. Shortness of breath also reflects another important aspect of fibrous remodulation of the lung parenchyma - oxygen dissociation is disturbed, which reflects a violation of the gas exchange function of the lungs. There are no generally accepted treatments for PF in post-COVID syndrome. The literature considers such approaches as the possibility of prescribing antifibrotic therapy, hyaluronidase, and medical gases: thermal helium, nitric oxide, and atomic hydrogen. The article draws attention to the unresolved issues of post-covid PF in people who have had COVID-19.

[Dyspnea: neurobiological and clinical aspects].

An analysis of the results of studies carried out by specialists of the Russian Respiratory Society over the past 15 years is given. The article also includes the main provisions set out in the III Guidelines for dyspnea. A significant part of the manual is devoted to the recent achievements in studying neurophysiological processes in the brain structures during the development of dyspnea. These achievements were driven by image-diagnosis methods. An important aspect of this series of works for the clinical practice was identifying dyspnea domains and developing the instruments to assess severity. Analysis of the data on dyspnea from the clinical practice showed a highly heterogenic clinical picture, which must be taken into account in the management of individual patients. A diagnostic algorithm for long-term follow-up of patients with dyspnea syndrome is also discussed. The attention of doctors is drawn to the features of dyspnea during COVID-19; the disproportion between the sensory perception of respiratory discomfort and the degree of oxygen desaturation is emphasized. It was concluded that in the Russian-speaking environment of patients, doctors should actively use a verbal characteristic of dyspnea the language of dyspnea.

[Human placenta hydrolysates: from V.P. Filatov to the present day: Review].

Works of V.P. Filatov and his school laid the foundation for the study and clinical use of human placenta hydrolysates (HPH). To date, the PubMed database contains more than 5,000 publications on basic and clinical research on HPH. Studies of the peptide composition of HPH, carried out using the methods of modern proteomics, have made it possible to propose a complex of molecular mechanisms of the action of HPH in various pathologies. The article discusses the effects of HPH on the treatment of liver diseases, atopic dermatitis, viral infections (herpes, COVID-19, viral hepatitis), iron overload and chronic fatigue syndrome. Stimulation of HPH regenerative capabilities of the body is important for accelerating and improving the quality of wound healing, treatment of diseases of the joints and the reproductive system.

[Hydrogen effect on the mechanisms of mucosal immunity in patients with COVID-19].

AIM: To study the inhalation of an active form of hydrogen effect to mucosal and system immunity in a rehabilitation program for health workers. MATERIALS AND METHODS: The study involved patients that survived COVID-19 after therapy with inhaled hydrogen for 90 minutes (n=30), and a control group of patients treated according to standard protocol for managing patients that survived COVID-19 during the rehabilitation period (n=30). Biomaterial was carried out in 2 stages: on the first day of the study, before the accepted therapy and on the 10th day of the study. The indicators of humoral and cellular immunity were studied. The levels of secretory immunoglobulin A (sIgA) and IgG were investigated using the method of enzyme-linked immunosorbent assay. Phagocytosis was assessed on a Beckman Coulter FC-500 flow cytometer. Statistical data processing was carried out in the GraphPad Prism 7.00 software using nonparametric methods. RESULTS: It was shown that the phagocytic index (PI) of monocytes in nasal scrapings after inhaled hydrogen treatment did not significantly change relative to the first day of treatment and control, while the PI of granulocytes in nasal scrapings significantly increased relative to the first day by 2.5 times (p=0.000189), as well as relative to the control by 1.1 times (p=0.047410). PI of monocytes in pharyngeal scrapings showed a significant increase relative to the first day of treatment by 2.8 times (p=0.041103), however, did not differ relative to the control. PI of granulocytes of pharyngeal scraping did not differ significantly relative to the first day and control. PI of granulocytes and blood monocytes of the studied group did not change significantly. PI of granulocytes and monocytes of peripheral blood relative to control during therapy did not change. The sIgA level in nasal scrapings significantly increased by 2.9 times, while in pharyngeal scrapings the level of sIgA significantly decreased by 2 times. Сonclusion. We have shown an increase in granulocytes PI in the nasal cavity and oral monocytes, as well as in the level of sIgA in the nasal cavity during therapy with active hydrogen. The data obtained indicate the effectiveness of therapy, which can be used both in the treatment of COVID-19, and in post-COVID syndrome as an additional therapy. The absence of changes in blood parameters, as well as individual links in nasal and pharyngeal scrapings, requires further study to develop ways to overcome treatment tolerance.

Thermovaccination: Thermoheliox as an Immune Response Stimulant. Kinetics of Antibodies and C-Reactive Protein Synthesis in Coronaviral Infection.

The high efficiency of using thermoheliox (inhalation with a high-temperature mixture of helium and oxygen) in the treatment of patients affected by COVID-19 was shown. The dynamics of accumulation of IgG, IgM, and C-reactive protein (CRP) in patients with coronavirus infection in the "working" and control groups was studied experimentally. It was shown that thermoheliox intensifies the synthesis of IgG, IgM, and CRP antibodies, while eliminating the induction period on the kinetic curves of the synthesis of specific antibodies in the IgG form and transfers the synthesis of CRP to a fast phase. The results of experiments confirm the previously obtained data based on the analysis of the kinetic model of the development of coronaviral infection in the human body.

[COVID-19 and human security].

The article was prepared after materials of the report at the 22.12.2020 International Scientific Forum COVID-19 and Human Safety in partnership with the World Academy of Arts and Science and the Rome Club on the virtual platform of the Faculty of Global Processes of the Federal State Budgetary Educational Institution of Higher Education Lomonosov Moscow State University.

[Consent. Modern interpretation: "Voluntary Informed Consent"].

The article is devoted to voluntary informed consent. It considers the historical issues of the formation of this concept in modern health care and medical science. The article highlights a historical role of the Nuremberg Code which was taken as the basis for the Universal Declaration of Human Rights, the World Medical Association (WMA) Code of Ethics, the Declaration on Bioethics and Human Rights, i.e. documents that defined the world order after the end of World War II.

[Roles of active forms of vitamin D in supporting innate immune systems and in reducing excess inflammation in COVID-19].

A reduced supply of micronutrient vitamin D leads to a more severe course of coronavirus infection (COVID-19). Vitamin D deficiency is combined with a decrease in innate antiviral immunity and excess of inflammation. Vitamin D supplementation stimulates the synthesis of antibacterial peptides and is important for weakening the cytokine storm, reducing excessive acute and chronic inflammation, and also for compensating for chronic comorbid pathologies. Active forms of vitamin D (alfacalcidol, etc.) are of particular importance for compensating for vitamin D deficiency in elderly patients, endocrine-immune dysfunction, sarcopenia, chronic renal failure (in which the metabolism of vitamin D in the kidneys is disturbed).

[UNESCO: bioethical initiatives in 2019].

The Universal Declaration on Bioethics and Human Rights was adopted at the UNESCO General Conference on October 19, 2005. From today's perspective, it must be recognized that it was adopted at a historically important period in the development of civilization; It has always been seen as a document that significantly expanded the declaration on human rights, as it gave a new interpretation of human activity in modern society. Next year marks 25 years of active implementation of the main provisions of the declaration in the field of education, research and cultural heritage. Scientific ideas about the world were changing dynamically, new pedagogical technologies developed, society more than ever began to perceive cultural heritage more acutely. Under the influence of these processes, our ideas about moral values ​​and ethical principles changed. An idea of ​​bioethics has formed; The term implies versatile human activities, including not only the doctor-patient relationship, but also the active participation of a person in the field of industry, climate change, as well as new areas such as editing the human genome, transplantology and much more.

[Thermal heliox proteome. High-temperature heliox does not cause destruction of human respiratory system cells].

AIM: Conducting a pilot study to assess the effect of thermal heliox on the state of the respiratory tract by studying of the exhaled breath condensate protein composition before the thermal heliox procedure, immediately after and after three hours of relaxation Materials and methods. A comparative study of the exhaled breath condensates (EBC) protein composition of five non-smoking healthy donors was carried out. The EBC was taken before the respiratory procedure, immediately after a 20-minute inhalation by mixture of He/O2 gases (70/30) heated to 70C and 3 hours later. The protein composition was determined by chromatography-mass spectrometric analysis after selective tryptic hydrolysis. The results were processed using the Mascot program and the UniProt database. RESULTS: After the heliox procedure, the volume of the collected condensate (11.5 ml) decreases by an average of 32% and is practically restored after three hours of relaxation. Most proteins were consistent for all samples, regardless of the thermal heliox procedure. These are keratins, several proteins of the immune system (immunoglobulins, compliment proteins), tubulin. In samples after thermal heliox, the appearance of small amounts of additional proteins is observed. These are proteins of muscle metabolism (actin and calmodulin), fibrinogen, traces of hemoglobin, apolipoprotein, type B creatine kinase. After three hours of relaxation, tubulin disappears in the EBC. CONCLUSION: Most exhaled proteins are the same before, after the procedure, and for three hours of relaxation. The results obtained demonstrate the relative safety of the use of high temperature heliox as a therapeutic agent.

[Chronic obstructive pulmonary disease and cardiovascular comorbidity].

In recent years, a greater understanding of the heterogeneity and complexity of chronic obstructive pulmonary disease (COPD) has come from the point of view of an integrated clinical assessment of severity, pathophysiology, and the relationship with other pathologies. A typical COPD patient suffers on average 4 or more concomitant diseases and every day about a third of patients take from 5 to 10 different drugs. The mechanisms of the interaction of COPD and cardiovascular disease (CVD) include the effects of systemic inflammation, hyperinflation (hyperinflation) of the lungs and bronchial obstruction. The risk of developing CVD in patients with COPD is on average 2-3 times higher than in people of a comparable age in the general population, even taking into account the risk of smoking. The prevalence of coronary heart disease, heart failure, and rhythm disturbances among COPD patients is significantly higher than in the general population. The article discusses in detail the safety of prescribing various groups of drugs for the treatment of CVD in patients with COPD. Achieving success in understanding and managing patients with COPD and CVD is possible using an integrated multidisciplinary approach.

Disease associated with immunoglobulin g.

Diseases associated with disorders of immunoglobulin g synthesis and its subclasses are described. The analysis of the role of both deficiency and its increased production in the diagnosis and treatment of a number of diseases in humans.

Morbidity and mortality of the Russian population from acute respiratory viral infections, pneumonia and vaccination.

AIM: In order to assess the impact of influenza vaccination and pneumococcal infection (PI) were studied seasonal morbidity and mortality because of influenza, acute respiratory viral infections (ARVI) and pneumonia among the population of the Russian Federation during 2012-2016 timeframe. MATERIALS AND METHODS: There were analyzed the data of Federal service for surveillance in consumer rights protection and human welfare (Rospotrebnadzor) on influenza vaccination and PI and ARVI morbidity (including influenza), diseases of the respiratory system (DRS). The information on mortality of the population of Russia because of these diseases received from official publications of the Federal State statistics service (Rosstat) and The Ministry of health of the Russian Federation (Ministry of Health of Russia) on the mortality rates of the population of Russia because of these illnesses. RESULTS: the analysis revealed that compared to 2015, in 2016 the incidence rate of ARVI in total Russian population was increased to 5,7%. The incidence rate of influenza in 2016 reached 60,5 cases per 100 thousand of the total population and was higher than the 1,8 times than in 2015 (34,01 on 100 thousand people). The incidence rate of pneumonia in total population was increased by 24,0% in 2016 compared to 2015. According to Rosstat data, the increase of deaths because of influenza and ARVI was mainly in the first semester of 2016, which was associated with influenza epidemic. Mortality because of pneumonia dropped by 10,8% and from other DRS - by 6,9%, which might indicate on the improvement of the quality of medical care and prevention of DRS. Reduction in the mortality rate because of pneumonia also was due to significant influenza vaccination coverage and the increasing number of children and adults vaccinated against PI.

[Bronchiectasis]. / Bronkhoektazy.

The paper presents information on possible approaches to the classification, pathogenesis, and determination of the etiological causes of bronchiectasis. It discusses a group of bronchiectasis-associated diseases. It gives a detailed diagnostic algorithm aimed to establish the etiology of bronchiectasis and the markers of the efficiency of different treatment options. Much attention is paid to genetically predetermined bronchiectasis. Universal approaches to treating patients with bronchiectasis as a whole, as well as treatments for certain entities of bronchiectasis are discussed.