Original Articles. Оncology
Purpose of the study. Studying the dynamics of factors of apoptosis in mitochondria of skin and tumors cells in female mice with melanoma growth stimulated by chronic neurogenic pain.
Material and methods. The study included female С57ВL/6 mice (n=56) with a model of chronic neurogenic pain (CNP) produced by the bilateral sciatic nerve ligation and with transplanted B16/F10 melanoma. After 1–3 weeks of the tumor growth, levels of cytochrome C, caspase‑9 (Bioscience, Austria), Bcl‑2 (Thermo Fisher Scientific, Austria), and AIF (RayBiotech, USA) were determined by ELISA, and levels of calcium (Са2+) were determined by the Arsenazo III method (Abris+, Russia) in mitochondria of tumors cells and skin not affected by the tumor growth.
Results. In the CNP state, mitochondria of the skin cells showed a significant increase in Са2+ by 96.7 times, AIF by 1.4 times and Bcl‑2 by 5.9 times, while caspase‑9 decreased by 2.6 times, compared to the levels in intact mice. In the CNP‑stimulated melanoma growth, mitochondria of cells of the skin not affected by the tumor growth demonstrated a decrease in all studied indices, except caspase‑9 – its levels increased by 4.6 times after 3 weeks of the tumor growth. In mitochondria of the tumor cells within 1–3 weeks, levels of Са2+ decreased over time by 37.2–96.1 times, respectively, AIF by 49.4–2.0 times, Bcl‑2 by 3.0–1.5 times, cytochrome C by 15.3–8.8 times, and caspase‑9 increased by 1.7–4.4 times compared with the level in animals with pain.
Conclusions. In general, the growth of melanoma stimulated by chronic pain and the standard melanoma growth were characterized by the opposite dynamics of levels of apoptosis factor both in mitochondria of skin cells and in mitochondria of tumor cells, with the exception of cytochrome C. Mitochondria of melanoma cells and of the unchanged skin have a similar tendency to change the levels of apoptosis factors, which may indicate their functioning in the conditions of the mitochondrial network at the level of one organ. Mitochondria of tumor cells provide the anti‑apoptotic state of the tumor itself and of the skin not affected by the malignant process, probably due to the stress state of the skin.
Purpose of the study. To analyze the calcium levels in mitochondria of cells in different organs in standard and stimulated growth of experimental В16/F10 melanoma.
Materials and Methods. The study included female С57ВL/6 mice (n=168). Experimental groups: intact group (n=21), group with a model of chronic neurogenic pain (CNP) (n=21), group M – B16/F10 melanoma (n=63), group M+CNP – mice (n=63) with transplantation of B16/F10 melanoma 3 weeks after CNP model creation. The concentration of calcium in mitochondrial samples was determined by a biochemical method (Abris+, Russia). Results were statistically analyzed using the Statistica 10.0 program.
Results. CNP decreased calcium levels in mitochondria of cells in the brain by 1.4 (р=0.00153) times, liver by 2.6 times and heart by 3.2 times and increased the levels in the skin by 97.1 times. In standard growth of experimental melanoma, levels of calcium in cell mitochondria in most of the studied organs increased at the initial stage of the melanoma growth, and decreased to intact values and lower by the terminal stage. In the mitochondria of tumor cells, calcium levels were stably high at all stages of standard tumor growth. At the initial stage of CNP‑stimulated tumor growth, a decrease in calcium in the mitochondria of the skin by 5.7 times and its accumulation in the mitochondria of the brain by 6.6 times, heart, and kidneys were recorded by 1.5 times. At the terminal stage of stimulated melanoma growth, extremely low calcium values were recorded in the mitochondria of all organs. A stably low level of calcium was registered in the mitochondria of tumor cells at all stages of stimulated melanoma growth.
Conclusions. The growth of experimental B16/F10 melanoma in female mice is accompanied by mitochondrial dysfunction affecting most organs. Stimulation of the growth of experimental melanoma with chronic neurogenic pain, unlike the standard growth variant, changes accumulation of calcium in the mitochondria of cells both in organs and in the tumor itself. The chronic pain syndrome accompanying a malignant process can influence its course with the involvement of mitochondria and the modification of their functions.
Purpose of the study. In order to create the basis for prospective wound coatings the wound healing effect of xerogel based on neutral hydrosol of titanium dioxide was studied.
Materials and methods. After modeling the Wistar outbred runoff in 40 male rats, the wound defect on the skin of the intertropatular region was closed with a bandage. The animals were divided into four groups: Four groups: a control group, (10 rats) in which no drugs were applied to the burn surface; 2 – the group of the comparison preparation, 10 males to whom after the modeling of the burn on the wound surface was applied daily the preparation of comparison argosulfan 3 – experimental group № 1, included 10 males to whom after the modeling of the burn on the wound surface was applied daily the xerogel, in a dose of 0.1 ml/100 g of animal body weight, 4 – experimental group № 2, included 10 males, who after modeling the pathology were daily copied on the wound surface, in a dose of 0.2 ml/100 g of animal body weight.
Results. The complex of morphofunctional changes in experimental groups included changes in the epidermis – restoration of a more complete epidermal layer with skin appendages. Probably, it is provided not only by direct stimulation of cell proliferation of basal and studded layers, but also by other mechanisms, as indicated by the nuclear cytoplasmic ratio. In the connective tissue base of the wound effect of experimental groups it was noted the formation of a more extensive network of blood vessels of the hemomicrocirculatory channel and a decrease in the signs of venous hyperemia.
Conclusions. Thus, the effective dose of xerogel is 2 ml/kg. The revealed complex of local morphofunctional rearrangements allows the xerogel to be used in diseases and conditions characterized by the disturbance of the skin integrity, including a burn lesion.
Original Articles. Surgery
Purpose of the study. To analyze the causes of unsatisfactory results after laparoscopic repair of hiatal hernia, complicated by gastroesophageal reflux disease.
Materials and methods. A retrospective analysis of the treatment of 171 patients, who underwent laparoscopic hiatal hernia repair for the period 2009–2018 was carried out. In case of hiatal hernia defect 5 or more cm 29 (29.6%) of 98 patients performed the mesh hiatal hernia repair. Nissen fundoplication was used in 109 (63.7%) patients, Toupet fundoplication – in 62 (36.3%) patients. Intra‑abdominal esophagus segment length was measured intraoperatively after mediastinal mobilization, and after desuflation before the creation of the fundoplication wrap. In the long‑term postoperative period in patients, who did not have complaints the length of fundoplication wrap was measured. The causes of reoperations were analyzed.
Results. In the long‑term period, recurrence was noted in 34 (19.9%) patients, persistent dysphagia was noted in 10 (5.8%) patients, the overall unsatisfactory result was 22.8% (39 patients). 26 (15.2%) patients were unsatisfied their present condition (according to the GERD‑HRQL questionnaire). The use of mesh repair in comparison with simple suture repair not affected on frequency of recurrence in case of hernia 5 cm or more – 4 (13.8%) versus 14 (20.3%), CI: 0.19–2.1, p=0.44. The choice of fundoplication method (Nissen or Toupet) not affected on recurrence rate – 17.4% (19/109) versus 24.2% (15/62), CI: 0.71–3.24, p=0.39. The length of the fundoplication wrap at uppercontrastradiographswas 3.2 cm (2.3–3.7 cm). Intraoperativly after desuflation, the shortening of the esophagus was 1.3 cm (0.5–2 cm). 12 (7%) patients were reoperated. The shortening of the esophagus was revealed in all cases of reoperations.
Conclusion. Unreduced during the first operation short esophagus, which was diagnosed during all reoperations, was one of the possible factors, affecting the frequency of recurrence in the long term. Further studies are needed to evaluate the use of lengthening esophagus procedure on the long-term outcomes.
Review
The analysis of the current evidence base concerning the use of oral nutritional supplements (ONS) in gastric cancer (GC) has been made. Databases of scientific information eLIBRARY.ru and PubMed were used. Emphasis is placed on randomized clinical trials and meta‑analyses. The application of ONS is suggested for all patients who undergo to surgical treatment for GC. Its use allows increasing protein and energy consumption, improving the quality of life, some parameters of nutritional status and immunity (albumin, blood lymphocytes etc.). In patients with severe malnutrition (SM) ONS can significantly reduce the incidence of clinically important postoperative complications. The use of this type of medical nutrition in the first 5 days after surgery is safe and does not increase the rate of anastomotic leak. After gastrectomy (GE) its administration reduces the time of recovery of bowel motor function and the duration of hospitalization. After distal GE delay of gastric emptying may occur. In patients with SM, early start of enteral nutrition should be considered. After discharge from the hospital ONS can decelerate the progression of malnutrition, improve the tolerance of adjuvant chemotherapy and improve the quality of life. These effects are most clear after GE and in patients with a high risk of malnutrition (NRS‑2002 ≥ 3). There are no evident advantages of any particular type of ONS in patients with GC. When choosing a specific product, preference should be given to formulas with optimal nitrogen: non‑protein kilocalories ratio, osmolarity closest to physiological and individually selected organoleptic properties. It is recommended that the patient consume at least 200–250 ml of the mixture per day, and in the early postoperative period focus have to be made not on the target volume, but on signs of tolerability.
Clinical Case Reports
Breast cancer (BC) remains one of the most common diseases of the female population. According to statistics, breast cancer is detected in every eighth woman. Approximately 20‑24% of breast cancer patients are diagnosed with triple negative breast cancer. Triple‑negative breast cancer is characterized by an aggressive clinical course, a higher relapse rate, and low overall survival. According to statistics, the median survival rate for women with metastatic triple‑negative breast cancer is less than one year. We demonstrate a successful case of treatment of a 60‑year‑old woman diagnosed with triple negative breast cancer on the right, edematous‑infiltrative form, St IIIC cT4bN3M0 on the background of metabolic syndrome. Antitumor treatment lasted 1 year and consisted of three stages: systemic chemotherapy, surgical treatment (radical mastectomy), and adjuvant radiation therapy. After the treatment, remission was achieved. The patient is alive and has a relapse‑free period of 3 years.
Conclusion. Despite the severe concomitant pathology in the observed patient, we received a positive result of multi‑ stage therapy, where cytotoxic chemotherapy was the basic treatment for a woman with triple negative breast cancer.
Paraurethral cysts develop on the site of the paraurethral glands (Skin glands), and are a fairly rare pathology in women. The clinical course of paraurethral cysts is often asymptomatic. However, with an increase in the size of the cyst, women have complaints of frequent urination, dyspareunia, painful sensations in the perineum. Persistent microflora contributes to the aggravation of symptoms, up to the formation of an abscess. With inflammation of the paraurethral cyst, there is still no clear treatment algorithm. In this article, we present an observation of a 29‑year‑old woman with signs of an infected paraurethral cyst. We believe that the administration of antimicrobial drugs to women with signs of skinitis in combination with lower urinary tract infection is necessary for the purpose of preoperative preparation. Surgical treatment of an infected paraurethral cyst consisted of opening the abscess, followed by laser ablation of the inner surface of the cyst capsule. In the postoperative period, the patient also received antimicrobial therapy. We did not detect a recurrence of the paraurethral cyst, observing the patient for 1 year.
Conclusion. Combined treatment (a combination of medical and surgical treatment) of an infected paraurethral cyst demonstrates high efficiency.
Health Organization
The review is devoted to the analysis of the capabilities of modern navigation systems of healthcare facilities to supply an acceptable level of accessibility to the perception of navigation information for various categories of citizens. The hospitals’ navigation system is considered to be the most important part of the visualization system and one of the basic criteria for the quality of the space of health facilities when forming a new model of a medical organization providing primary health care in the framework of the federal project «Development of a primary health care system» of the national project «Healthcare». From the viewpoint of the management concept of lean production, the hospitals navigation system should be aimed at the complete elimination or reduction of unnecessary movements of visitors, as well as other types of basic and additional losses. The accumulated experience in implementing projects with the implementation of the concept of lean production in outpatient medical institutions of the Russian Federation suggests that a rationally designed and deployed navigation system can be an effective tool for visualization in a lean production methodology. Structural and technological solutions of an effective hospitals navigation system introducing the concept of lean production should take into account the possibility of perceiving navigation information by all population groups, including people with limited mobility: people with disabilities, people with disabilities, people with prams, etc. Technical means of informing, orienting and signaling for people with limited mobility is a complex of various technical means for providing visual, tactile, sound information, orientation in space. In addition, they indicate possible directions of movement and places of receipt of services that contribute to the accessibility, safety, information content and comfort of the healthcare facility. Modern hospitals must meet the requirements of ensuring accessibility and safety for people with disabilities and other people with limited mobility due to the implementation of a complex of architectural and planning, engineering, ergonomic, structural and organizational measures of the state program «Accessible Environment». The navigation system can be a key tool for these activities.
Purpose of the study. To study the comparative state and variability of cognitive capabilities, the degree of their correlation with the subjective and objective state of health among students of a medical university.
Materials and methods. The study was carried out during the year from 01.12.2018 to 01.12.2019 at the Far Eastern Federal University and the Pacific State Medical University. The sample size is 394 respondents. The response rate is 91.9%. The state of co‑cognitive functions was determined according to the Montreal scale for assessing cognitive functions (IOC‑test; MoCA, Montreal Cognitive Assessment). For the self‑assessment of the quality of life, the “Brief form of self‑assessment of the quality of life related to health MOS SF‑36” (MOS SF – Medical Outcomes Study‑Short Form) was used. To collect information on social, economic, physiological, behavioral status, a specialized questionnaire Pozdeeva (2008) and standard medical documentation were used.
Results. The total indicator of the assessment of cognitive functions in students was 26.1 points, in senior students it was slightly higher (26.8/25.5, p≥0.05). It was found that in the learning process, students significantly increase the level of executive functions (3.1/3.8, p≤0.05), attention, concentration and working memory (4.2/4.8, p≤0.05). The final assessment of physical health among primary students was 69 points, for senior students – 72 points. The indicator of mental health among students of the initial period of study was estimated at 52 points, among graduates – at 62 points (p≤0.05). The composite indicator of the quality of life associated with health was equal to 60 points for 1–3 year students, 67 points for 4–6 year students, (p≤0.05). The students of both age cohorts had a high incidence of chronic somatic pathology, the comorbidity index was 0.6, however, the number of visits to the doctor among senior students was significantly lower, in junior years (3.2/2.1, p≤0.05). The total indicator of the students' cognitive function was most strongly associated with physical activity (r=0.85, p≤0.05) and the state of physical health (r=0.73, p≤0.05).
Conclusions. Cognitive functions in medical students correspond to normal values. The activity of executive functions, attention, concentration and working memory significantly improves in the process of studying at a medical university. Medical students value their health‑related quality of life highly, but most of them have chronic medical conditions. Senior students assess their psychological status more highly by optimizing the emotional component. The total indicator of the cognitive function of students is interrelated with the frequency of physical activity, the state of physical health, quality of nutrition, self‑assessment of mental health and psychological comfort.
Currently, researchers face with various situations related to the moral situation in healthcare. This article is based on the results of a sociological reasearch conducted by specialists of the Krasnoyarsk Regional Center for Health and Medical Prevention in 2015–2019.Given the relevance of this topic, researchers compare the opinions of modern doctors and patients to ethical principles.
Purpose of the study. To study the attitude of modern doctors and patients of medical institutions to the classical norms of medical ethics.
Materials and methods. For the selection of respondents was used the representative sample based on gender and age of respondents (for the selection of patients), and by specialty of a medical workers (for doctors). Information collected by survey. Descriptive statistics were used to interpret the results, statistically significant differences between the rates were determined by Fischer`s exact test.
Results. The results indicate that there are statistically significant differences in the attitude of doctors and patients to some classic norms of medical ethics. In general, doctors often have an unambiguous opinion about the principles of bioethics; patients are more lenient about the principles of bioethics. However, sometimes patients are more categorical about some aspects of the principles of bioethics. In particular, these include the ambiguous opinions of doctors regarding the judgment that “if the doctor realizes that the patient has been harmed as a result of unlawful acts, he must report this to the internal affairs bodies”, as well as the opinions of doctors about the admissibility of accepting gifts from the patient.
Conclusions. The classical principles of bioethics preserve functionality and form the necessary attitude of doctors and patients to the ethical foundations of the doctor’s professional activities. Nevertheless, some aspects of these relationships are partially dysfunctional and can become a source of negative behavior in the system of relations between a doctor and a patient.