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РОЛЬ ФЕНОТИПИЧЕСКОГО РАЗНООБРАЗИЯ КЛЕТОК КОЖИ В ПРАКТИКЕ ДЕРМАТОЛОГА

РОЛЬ ФЕНОТИПИЧЕСКОГО РАЗНООБРАЗИЯ КЛЕТОК КОЖИ  В ПРАКТИКЕ ДЕРМАТОЛОГА
INTRODUCTION

In 2017, the Presidential Council for Strategic Development and Priority Projects outlined the main performance criteria for the healthcare sector - accurate and fast diagnosis, effective treatment, friendly attitude to the patient, availability, quality and effectiveness of medicines. They were enshrined in the Presidential Decree No. 254 of June 6, 2019 "On the Strategy for the Development of Healthcare in the Russian Federation for the period until 2025". Moreover, accurate diagnostics was specified as a priority.

At the same time, in 2016 it was noted that in terms of prevalence, skin diseases in the Russian Federation were among the top five among all diseases. The incidence was recorded in every 25th of the adult population. In absolute numbers, 8,604,183 cases of skin and subcutaneous tissue diseases were registered, with 6,240,955 cases registered for the first time [123].

Chapter 1: ACTUALITY OF DEVELOPMENT OF DIAGNOSTIC AND RESEARCH APPROACHES IN DERMATOLOGY

The chapter raises the relevance of the development of dermatology as a practical field of medicine. The judgement reveals the existing contradictions in dermatology that hinder its further development as a practice. At the same time, the trends in the development of science clearly demonstrate that its achievements are associated with new technologies of research activity and with progressive types of researchers' thinking. The latter is dictated by the high demand for the accelerated emergence of both individual scientific discoveries and their rapid introduction into practice, and the generation of classes of discoveries that form the frontline of solutions to current medical problems.

1.1. Human skin as a cognitive complexity

The chapter reflects on the role of the empirical approach in the clinical thinking of the dermatologist. At the same time, the complexity of the subject of study - human skin and its unique structure - is demonstrated. As a consequence, information about the dynamics of skin disease, the degree of skin response to environmental influences, and the evaluation of the effectiveness of applied external medications and cosmetics remain beyond the limits of understanding

1.2. Relevance of the flow cytometry method for detecting phenotypic diversity of skin cells

The chapter argues that numerous known methods of skin research do not solve the issues of distinguishability of skin states at the cellular level and this does not allow dermatologists of the present day to fully assess the functional activity of cell subpopulations of the skin under conditions of norm and pathology. Such a situation forms challenges to dermatology, which allowed me to formulate a number of questions impossible to raise earlier. On this basis, the scientific problem, object, subject and purpose of the study are shown.

1.3. Current data on the incidence of some common skin diseases in the context of their diagnostic problems

Improvement of the system of early detection of skin diseases is of high social importance and is one of the priority goals of the state policy in the field of health protection of citizens of the Russian Federation, which is reflected in the Decree of the President of the Russian Federation V.V. Putin dated May 7, 2018 No 204 "On national goals and strategic objectives of development of the Russian Federation for the period up to 2024", according to which an important task of diagnostics is to detect diseases at early stages of the process, through the introduction of new diagnostic technologies.

Chapter 2: MATERIALS AND RESEARCH METHODS

A total of 100 volunteers were involved in the study, including 80 conditionally healthy individuals to evaluate the application of flow cytometry, 6 patients with socially significant chronic skin diseases based on immune mechanisms to demonstrate new diagnostic capabilities of skin cytoimmunograms and 4 patients to demonstrate the application of the developed utility model - amplifier of reparative potencies ...

Chapter 3: METHOD OF FLOW CYTOMETRY FOR DETECTION OF PHENOTYPIC DIVERSITY OF SKIN CLETS

The chapter summarizes the history of the discovery of the skin cytoimmunogram and details the method of obtaining it. The practical application of the discovery demonstrates the need for profound changes in diagnostic and therapeutic approaches in dermatology as a scientific discipline and practice.

3.1. Conceptual justification of the problem of skin cell phenotype research

The issues outlined expose a problem that is formulated as follows: how is it possible to see and understand the picture of skin conditions revealed at the level of the study of its cellular phenotypes, with practical...

3.2. Possibilities of practical application of the method of obtaining skin cytoimmunograms

Based on two dozen examples, various possibilities of pragmatic application of the skin cytoimmunogram method are demonstrated. It is shown that quantitative and functional assessment of skin condition indicators opens the way to a new understanding and study of the processes taking place in human skin at the level of cell subpopulations. Phenotyping of cell suspension was carried out by the method of flow cytometry using specific markers CD3, CD4, CD8, CD14, CD16, CD19, CD34, CD44, CD45, CD49, CD54, CD63, CD80, CD146, CD203c, CD207, CD249, with the help of which subpopulations of cells were identified ...

Chapter 4. REALISING THE DEVELOPMENT OF DIAGNOSTIC AND RESEARCH PRACTICE IN DERMATOLOGY
4.1. Critical comparison of diagnostic criteria on visual inspection with actual results of cytoimmunograms of the skin of patients

Critical comparison of diagnostic criteria for visual examination of the rash recommended by the Federal Clinical Guidelines (2016) with the actual results of skin cytoimmunograms from inflammatory infiltrates of the rash of patients with socially significant skin diseases (red squamous lichen planus, psoriasis, atopic dermatitis, parapsoriasis, eczema, skin lymphoma) substantiates the necessity of quantitative and functional assessment of the state of cells of the main skin subpopulations in each individual patient, with his unique life history, age features of the skin and the whole organism, accumulated comorbid background, peculiarities of immunity and taking into account the treatment received earlier. Translated with www.DeepL.com/Translator (free version)

4.2. Practical realization of conceptualization on the example of the invention of an amplifier of reparative potencies of skin cells

Classical dermatologic approaches to wound healing are based on various types of external therapies aimed at rapid closure of the tissue defect "at any cost", including scar formation. And since the main links in the evolution of the wound are interpreted from the perspective of hidden chronic autoimmune pathology, therapeutic measures are often reduced to antibacterial and immunosuppressive effects....

4.3. Dependence of cell viability and apoptosis on the concentration of activator

A number of scientists have shown that apoptosis plays an important role in tissue regeneration processes during wound healing. If apoptosis does not occur, inflammatory processes continue, as proinflammatory factors such as, for example, lysosomal proteolytic enzymes and metabolites of arachidonic acid continue to flow from necrotic cells. The slowing of apoptosis processes, however, leads to the replacement of granulation tissue by definitive scar tissue....

4.4. Examples of activation of reparative processes at the level of human skin cells

It is known that fibroblasts and keratinocytes retain the ability to synthesize extracellular matrix components - collagen, tropoelastin and fibronectin, as well as the ability to retain hyaluronic acid due to a high level of CD44+ receptor expression on the surface. Their isolation in a viable state, as an object of subsequent activation, allowed not only to quantitatively and functionally characterize each cell subpopulation separately from all others, but also to further affect the isolated subpopulations with various substances, including an activator of xenogeneic origin....

4.5. Clinical demonstration of the use of a reparative process amplifier for skin repair of skin damage

Demonstrated patient A., 35 years old with the diagnosis: Thermal flame burn of the face of IIIA degree, S = 5%. Expected results from traditional treatment: the average period of granulation formation in IIIA degree burn wounds is 21 days and the average period of hospital stay in patients with deep burns is 30-35 days.

CONCLUSION

Assessment of the subpopulation composition of cells already today allows us to proceed to the study of skin diseases accompanied by significant changes in the number of cells and the appearance of unique membrane events on their surface, in their totality characterizing certain clinical conditions. The ability to examine cryopreserved samples allows repeat studies to be done some time later for those who might have doubted the results obtained....

FINDINGS

The synthesis of the methods of experimental dermatology, technologically raised to the level of studying and operating skin cell complexes, with the methods of conceptual analysis of experimental results has shown its productivity in generating a large number of classes of new concepts in the branch of medicine, which has clearly exhausted the potential of the existing scientific paradigm. The chapter derives implications from the presented observations, demonstrating new research, inventive and diagnostic possibilities of methods for determining the subpopulation composition of skin cells and obtaining skin cytoimmunograms. 

PRACTICAL RECOMMENDATIONS

The developed approach to the application of flow cytometry for the study and evaluation of individual subpopulations of skin cells allows to apply the obtained data in the daily research and diagnostic practice of a dermatologist.

THEORY OF PHENOTYPIC DIVERSITY OF SKIN CELLS

The chapter proposes a scientific theory of phenotypic diversity of human skin cells, the application of the basis of which will allow solving most practical problems of dermatology. On this basis, the practical necessity of applying the methods of conceptual analysis to solve theoretical problems of dermatology, technologically raised to the research of phenomena at the level of human skin cells, is shown.

In the presented provisions the theory brings isolated facts about the role of human skin cell phenotypes into logical interrelation, and the main thing is that it endeavours to deduce them by deductive rules from general premises, which serve as empirical and theoretical knowledge.

HYPOTHETICAL SOLUTION TO A SCIENTIFIC PROBLEM

In ancient Greek, the term "problem" means a difficulty or obstacle to which practical or theoretical efforts are being made to overcome.

REFERENCE LIST
APPENDICES