Purpose of the study. To determine the quantitative parameters of the molecular markers Ki‑67 and p16/INK4a at CIN 1–3 and to establish the possibility of using them to improve the quality of diagnosis by histological samples.

Patients and methods. Biopsy material of the cervix was studied in 71 patients who were carriers of HPV infection. Immunohistochemical method (IHC) in biopsy specimens determined the expression of Ki‑67 and p16/INK4a markers.

Results. According to the results of a standard histological examination, the distribution of patientsinto groups occurred as follows: CIN 1–18, in CIN 2–39, in CIN 3–14 patients. It was found that the expression of the studied markers is associated with the severity of dysplastic changes in the tissue of the cervix. By the studied marker, the most characteristic molecular profiles for the degrees of dysplasia were determined: CIN1 – Ki‑67–15–25%, p16/INK4a 10–15%; CIN2 – Ki‑67–70–80%, p16/INK4a – 65–70%; CIN3 – Ki‑67–85–90%, p16/INK4a – 90–95%. Heterogeneity was revealed in the expression of these markersin the CIN 2 group: in 7 cases (22,6%), the molecular profile corresponded to CIN 1, in 1 case (3,6%) to CIN 3. Clinical examples of using the IHC profile to clarify the degree of CIN are given.

Conclusion. The use of an IHC study with Ki‑67 and p16/INK4a, in addition to the standard histological examination, makes it possible to objectify the initial diagnosis of the degree of CIN, as well as to identify patients with a high and low risk of developing severe injuries. This is especially true for the CIN2 group, the most problematic in terms of histological evaluation and tactics of clinical management of patients. The use of IHC in the initial diagnosis will contribute to: improving the information content of multiple aimed and loop excisional biopsies; reduction in relapse due to inadequate treatment; eliminating the unreasonable use of such a traumatic method as conization (especially in women of childbearing age).

Purpose of the study. To conduct a comparative analysis of the expression of the following markers: Ki‑67, cyclin D1, E‑cadherin, CD44, MMP‑9, VEGF, P53, vimentin in renal tumor tissue in clear cell kidney cancer depending on the prevalence of the tumor process.

Materials and methods. The material for the study was the operating material of 100 patients with light cell kidney cancer who were treated at the National Medical Reseaгch Centгe fог Oncology of the Russian Federation Health Ministry from 2015 to 2018. 50 patients were diagnosed with local cancer (T1–3an0m0), 50 – generalized cancer (T1–4N0M1). For the immunohistochemical (IHC) study, the material was fixed in 10% neutral formalin for 24 hours and encased in paraffin. Dewaxing and restoration of antigenic activity of the material was carried out in the RT module (Thermo Fisher Scientific) using Tris buffer pH=9, for 20 minutes at 98 °C. the Formulation of the IGC reaction was carried out in the immunohistostainer «Autostainer 480S» (Thermo Fisher Scientific). Used system detection UltraVision Quanto Detection System (Thermo Fisher Scientific), and the Chromogen DAB. Antibodies used: E‑cadherin (EP700Y) Cell Marque, 1: 100; CD 44 (EPR1013Y) Cell Marque 1:150; Ki‑67 (SP6) Spring Bio, 1:200; P53 (DO‑7) Cell Marque, 1:200; cyclin D1 (EP12) Dako, 1:200; VEGF Termo Fisher, 1:100; Vimentin (V9) Dako, 1:150; MMP‑9 (EP100902) Epitomics, 1:100. The results of the reactions with markers were evaluated by counting the number of colored cells in each 3rd field of view of the entire drug at magnification of the X200 lens in the AXIO Scope microscope. A1 (Carl Zeiss). The results were expressed as a percentage-the proportion of stained cells in relation to all tumor cells in the field of vision. Parametric methods of statistics were used for statistical processing of the results. The reliability of the difference between the two averages was determined by the student's t‑test for unrelated populations.

Results. In clear cell kidney cancer, a low level of proliferative activity was observed in General, but in generalized, compared with local, it was significantly higher (P<0.05) (8±0.5% and 5±0.6%, respectively), and in generalized cancer, there was an overexpression of Cyclin D1–70±3.9%, compared to 14.4±2.3% in local stages, P<0.05. In generalized kidney cancer, epithelial-mesenchymal transformation processes are more pronounced in comparison with local cancer (a significant increase in Vimentin expression by 28% and CD44 by 16.6% (P<0.05), a decrease in E‑cadherin expression by 24% (P<0.05), and activation of neoangiogenesis processes (a significant increase in VEGF expression by 32%, P<0.05). The P53 protein was absent in local kidney cancer cells and was extremely low when generalized – 3.8±0.7%. One of the main markers of extracellular matrix degradation MMP‑9 was approximately at the same level at both stages: at local‑50±6% and 49.6±7.2% at generalized, the difference in indicators is not reliable (P<0.05).

Conclusion. Progression of clear cell kidney cancer from local to generalized forms is accompanied by hyperexpression of cyclin D1, a decreased e‑cadherin expression while increasing vimentin expression (increasing signs of epithelial-mesenchymal transformation), an increase in CD44 and VEGF expression.

Purpose of the study. Studying characteristics of the growth factor dynamics in the intact skin, tumors and perifocal tissues of melanoma in urokinase (uPA) gene-knockout mice.

Materials and methods. The study included male and female С57 ВL/6 mice (n=47) and C57BL/6‑Plautm1.1BugThisPlauGFDhu/GFDhu mice with uPA gene-knockout (n=31). В16/F10 melanoma was transplanted subcutaneously at a dose of 0.5 mL (1:10 in normal saline). Intact mice of the same strain served as controls. Levels of VEGFA, VEGFC, sVEGFR1, sVEGFR3, IGF1, IGF2, TGFβ1 and FGF21 were determined by ELISA in the skin, tumor and perifocal tissues isolated on the 21st day of the tumor growth.

Results. uPA gene-knockout inhibited the growth (mostly in females) and metastasis (predominantly in males) of melanoma in mice. Inhibition of the migration of malignant cells in males could be due to low levels of TGF-β1 compared to С57 ВL/6 mice: in the skin – by 5.0 times, in tumors – by 1.8 times and in perifocal tissues – by 6.1 times. In uPA gene-knockout females, lower levels of TGF-β1 were observed in tumors – by 1.4 times inhibited metastasis, but not completely, and solitary metastatic foci were registered in the lungs. Нigh levels of IGF1 in tissues of all uPA gene-knockout mice (males: in tumors by 1.4 times, in perifocal tissues by 2.6 times, in the skin by 3.6 times; females: in tumors by 2.6 times, in perifocal tissues by 25.0 times, in the skin by 13.9 times, compared to С57 ВL/6 mice) could maintain the metastatic phenotype of cancer cells (in females) or hiher proliferative activity of melanoma cells (in males). Lower levels of FGF‑21 in tumors (males – by 5.3 times, females – by 18.4 times), perifocal tissues (males – by 9.6 times, females – by 8,5 times) and skin (males – by 6.7 times, females – by 3.3 times) in uPA gene-knockout animals could be due to the IGF‑1 growth, as their reciprocal interaction is known. Interestingly, a significant, although lesser than in mice with a normal genotype, accumulation of VEGFA in melanoma tissues was observed: in males – in tumors by 44.9 times, in perifocal tissues by 6.8 times, in the skin by 2.4 times; in females – in tumors by 5.6 times, in perifocal tissues by 2.6 times, in the skin by 3.3 times, compared to the corresponding intact controls, due to the probable involvement of the uPA receptor (uPAR) in the implementation of VEGF-induced processes.

Conclusion. Changing the activity of a system of some growth factors, uPA gene-knockout modifies melanoma metabolism by inhibiting its growth and eliminating or reducing its metastatic activity.

Purpose of the study. To analyze prevalence and characteristics of the cardiovascular diseases (CVD) in patients with urolithiasis, revealed for the first time

Materials and methods. In a period between 2009 and 2018, was made a retrospective analysis of medical histories of 2311 patients with urolithiasis, which were treated in in the urology departments of the branch No. 1 of the MCHG named after N.N. Burdenko (n=1487) and GBUZ MO Krasnogorsk City Hospital No. 1 (n=824). In 67,6% of the cases (1562 patients) the diagnosis of urolithiasis was diagnosed for the first time on admission. Isolated urolithiasis was recorded in 676 cases (43,3%), in other 154 cases (9,8%) nephrolithiasis was combined with different variants of cardiovascular diseases (CVD) and diabetes. From 732 respondents with urolithiasis and associated cardiovascular diseases (CVD), were formed 3 groups, in the first group (I) were included patients (n=363) with hypertension and arterial hypertension: the second group (II; n=79) was formed from patients with isolated coronary heart disease. In the third group (III) were included 290 patients which had urolithiasis combined with hypertension, arterial hypertension and coronary heart disease. The stages of hypertension and degree of expression of arterial hypertension were given according to the recommendations of Russian science society of cardiology (2004). Stages of congestive heart failure were defined according to c NYHA (New York Heart Association) classification. Functional class of stable angina was defined according to Canadian Cardiovascular Society classification (1970,1976). The obtained data was analyzed using descriptive statistics methods.

Results. Average age of patients was 65,4 +– 3,27; 78% of the patients were men. On an emergency basis were hospitalized 30,9% from group I, 27,6% from group 2, and 31,3% from group III. In group I more often were recorded hypertension I + arterial hypertension I (32,5%) and hypertension II + arterial hypertension II (40,2%). In group II effort angina was recorded in 30 cases (38%). Congestive heart failure occurred among 153 patients (20,9%); most often it occurred among patients from III – in 102 cases (35,2%). In the whole sample, congestive heart failure of I and II degrees prevailed – in 88 (12%) and 57 (7,9%) patients. Kidney stones were found in 59,4% of patients, in the ureters – in 30,9% of patients, in kidneys and in the ureters – in 9,9% of patients. Share of the patients with kidney stones in the shape of corals is 3,4% of the whole sample. Average sizes of kidney stones of the patients with congestive heart failure are 9,2–11,8 mm which is different from the sizes in whole sample – 6,9–9,5 mm.

Conclusion. During the observation period, share of the patients with first time revealed urolithiasis, complicated with the cardiovascular diseases (CVD) increased in 1,9 times (16,7 versus 31,7%). Congestive heart failure, which was registered in 20,9% of patients, was charged with I and II degrees. The presence chronic cardiovascular diseases (CVD), especially complicated by congestive heart failure in patients with first time revealed nephrolithiasis, implies changes in the algorithms of metaphylactic of nephrolithiasis (regime of water loads, selection of diuretics and anticoagulants).

In women aged from 20 up to 60 years paraurethral cysts occur in 1–6%. In most cases, the clinical course of paraurethral cysts is asymptomatic, so their diagnosis can cause difficulties. Women who have paraurethral cysts may complain of pain, dyspareunia, and urinary disorders. The size of a cyst more than 2 cm can affect the quality of patient’s life, and very often causes symptoms of the lower urinary tract, including obstructive ones. Paraurethral cysts need to be differentiated other perineal formations. This article presents a review of the literature on the etiology, clinical course and diagnosis of paraurethral cysts. The main points of differential diagnosis of paraurethral cyst with urethral diverticulum, adenocarcinoma are also consecrated. Taking into consideration the anatomical location and the specifics of the treatment of paraurethral cysts, this problem has an interdisciplinary nature and requires the attention of specialists such as: urologist, gynecologist, surgeon.

By far the most aggressive subtype of breast cancer is triple negative cancer. The purpose of this review is to analyze current ideas about the pathogenesis, clinical characteristics of different subtypes of triple negative breast cancer, the nature of its metastasis, mechanisms of chemoresistance. The review presents the results of modern regimens of drug therapy of triple negative breast cancer according to the publications of domestic and foreign oncologists. On the basis of various clinical studies, the effectiveness of the use of anthracyclines, taxanes in the dose-dense regime, platinum preparations and other chemotherapy drugs for the treatment of triple-negative cancer has been shown. The presented treatment regimens allow to achieve a complete morphological response in 85% of patients, to increase the rates of relapse-free and overall survival, comparable with other subtypes of breast cancer. The review highlights the possibilities of modern targeted drugs-PARP inhibitors, chk1 inhibitors UCN‑01, immunotherapy possibilities for the treatment of this aggressive subtype of breast cancer.

Your attention is given to the clinical observation of a patient with recurrent liposarcoma of the left upper limb. According to vital indications with palliative purpose, the patient underwent surgery in the Oncology Department of surgical methods of treatment of FSBI SSC FMBC named after A.I. Burnazyan, FMBA of Russia. The operation was carried out in the amount of interscapularthoracic amputation on the left with resection of the left clavicle, plasty of the defect of rotary musclefat flap on a vascular pedicle after previous surgical treatment previous year in the amount of assertional the left upper extremity with the plastic of the wound defect myofascial flap on a vascular pedicle. Attempts to palliative embolization of blood vessels supplying the tumor node were unsuccessful, and the only option to provide medical care at this stage was surgical treatment. It should also be noted that the patient has a history of cancer of the left breast, in connection with which she was treated about 10 years ago. Currently, the patient is under our dynamic control and is undergoing adjuvant radiotherapy. The postoperative period was uneventful.

The article describes the results of applying the combined correction of the consequences of childhood traumatic experience, which served as the trigger that launched the onset of cancer distress. A patient with oncopathology (breast cancer) had signs of a sensitive, anxious-phobic personality. In the absence of the ability to cope with children's fears, a distress associatively occurs – a negative emotional state that did not allow finding a way out of the created conditions. The main prerequisite for the development of distress can be considered children's traumatic experience gained in the early stages of ontogenesis, amplified by negative memories of the loss of parents, loss of moral support for loved ones; the formation of a chronic state of loneliness, continuous anxiety regarding personality changes, depressed mood and mental activity. The clinical example described in the article illustrates the close pathological relationship of childhood traumatic experience and the occurrence of the disease, and also confirms the presence of a nonspecific psychosomatic disease in the framework of the diathesis-stress model. The psychological rehabilitation of the patient included the initiation of post-traumatic growth, self-knowledge, development of stress tolerance, activation of creative potential, finding a life goal, and finding harmonious interpersonal relationships. It is shown that the psychotherapeutic techniques used in the framework of the adapted diathesis-stress model (psychosynthesis, short-term analytical psychodrama, cognitive-behavioral psychotherapy) allow us to determine a behavior strategy in overcoming the traumatic situation that occurred in the early stages of childhood, in order to form the skills of the correct expression of our emotions, avoiding this deconstructive "coping" – strategy.

Purpose of the study. Substantiation of organizational principles of development of the health system of the population of the megalopolis in emergency situations. The article analyzes the stages of creation, testing and practical implementation of the modern organizational and staff structure of mobile medical formation and its functioning to meet the needs of the peaceful population of Moscow in Moscow pre-hospital period (2013-2017).

Materials and methods. A survey of 112 respondents from 57 industry-specific metropolitan organizations and enterprises of the state healthcare system was conducted on the main indicators of the activities of institutions involved in the formation of a mobile medical unit. The result of this questionnaire was an assessment of the personnel potential of outpatient polyclinic establishments-shapers of mobile medical units, as well as the provision of full-time property and material resources of organizations and enterprises of the Moscow City Health Department involved in their formation. 24 research exercises were conducted on the formation and use of mobile medical teams to eliminate the health consequences of emergencies.

Results. The article considers the issues of resource support of organizations and enterprises of the state healthcare system of Moscow. The calculation of the internal reserves of outpatient clinics of the Moscow Department of Health has been prepared, reflecting the personnel potential of the medical organizations that form the units. Research exercises have been carried out on the formation of mobile medical units, the issuance of medical equipment and sanitary equipment for them from medical warehouses, as well as the functioning of the units of mobile medical units during the mass arrival of people of various profiles.

Conclusion. The study showed that the organizational foundations in the field of medical support for the population in emergencies make it possible to ensure the formation of a mobile medical unit with labor and material resources with the maximum use of internal reserves of regional health care. The proposed model of the organizational structure of a modern medical formation is an alternative to the bulky and inactive first aid unit that has existed for more than 40 years.

Purpose of the study. To evaluate the level of detail, the amount of visualized data and the levels of navigation systems of primary medical organizations.

Materials and methods. The object of this study was 33 primary care medical organizations located on the territory of 7 constituent entities of the Russian Federation. The subject of the study was all the internal and external navigation elements of the MO. The assessment was based on the ALIDS checklist (version 1.0) of 72 indicators, united by five characteristics in general characteristics: architectural-planning and design solutions, transmitted information, levels and navigation elements. The “Levels” block was represented by 19 parameters with a separate assessment of the internal level (9 indicators), the intermediate level (5 indicators) and the external level (5 indicators) of navigation. For each criterion, a nominal dichotomous point score was set with the possibility, if necessary (doubt, clarification, question, etc.) of indicating an expert comment.

Results. A full-time study of the navigation systems of 33 primary medical organizations found that the levels of intermediate and external visualization are not used enough. Unlike architectural and planning solutions, various levels of navigation are maximally represented in medical institutions of the Tyumen and Kaliningrad regions, Krasnoyarsk Territory. The lack of an external level of navigation contributes to the main losses of lean production: unnecessary movement, unnecessary transportation and expectations from patients and visitors. Among the objects of internal navigation, cabinets and safety signs are most often placed on the navigation elements. The maximum percentage of compliance among the intermediate navigation category has been established for the main entrances for visitors, including entrances for patients with limited mobility.

Conclusion. The navigation system of a medical organization is an important part of the visualization system and one of the criteria for the quality of space. The qualimetry of navigation systems not only of medical organizations, but also of any other buildings and premises, is currently not conclusively presented. Using the author's ALIDS method of audit of navigation systems allows us to give a quantitative and qualitative assessment of the navigation elements used in medical institutions. While improving the navigation systems of existing medical organizations and designing/building new ones, especially with complex mixed or section planning, in order to reduce the main losses of lean manufacturing, it is necessary to create the most detailed and understandable general navigation schemes.