FEATURES OF THE FORMATION OF PRODUCTIVITY AND ADAPTIVE REACTIONS IN LEGUMINOUS CROP VARIETIES WITH RECESSIVE ALLELES OF GENES

Researches were carried out on varieties, hybrids, isogenic lines and mutants of peas of various use developed from the beginning of the 1980s up to 2013. Experimental material was investigated under field conditions in the collection, hybridization and breeding nurseries as well as in the process of competitive variety testing in Orel Province. It is shown that one or several recessive alleles of the genes introduced into the genotypes of new varieties of grain, fodder and vegetable peas, blue lupin and soybean can influence the changees in a great number of morphological and physiological parameters determining plant growth, development and also characteristics in the system of yield formation. Reduction of leaf area in leafless pea varieties and lupin varietitts with limited branching is connected with the weakening of root system growth, which is caused by trophic interaction between these organs

THE RUSSIAN DATA OF INTERNATIONAL ENDORSE REGISTER (EPIDEMIOLOGIC INTERNATIONAL DAY FOR THE EVALUATION OF PATIENTS AT RISK OF VENOUS THROMBOSIS IN ACUTE HOSPITAL CARE SETTING)

Aim. To estimate a risk factor frequency of venous thromboembolism (VTE) in patients urgently hospitalized in hospitals, and also to estimate of patients part having effective prevention of VTE.Material and methods. ENDORSE (Epidemiologic International Day for the Evaluation of Patients at Risk of Venous Thrombosis in Acute Hospital Care Setting) is the international register. Patients of 40 years and older hospitalised in therapeutic departments as well as patients of 18 years and older hospitalised in surgical departments (358 hospitals in 32 countries) were included in the register. The case history analysis of all patients was performed for estimation of risk VTE and evaluation of preventive therapy quality according to American College of Chest Physicians (ACCP) Recommendation 2004.Results. Totally 68 183 patients (including 30 827 (45%) surgical patients and 37 356 (55%) therapeutic patients) were enrolled in Global ENDORSE Register. Russian centers enrolled 4 788 patients (including 2 829 (59%) surgical patients and 1 959 (41%) therapeutic patients). Totally 35 329 (51,8%) patients enrolled in Global ENDORSE Register (64,4% of surgical patients (19 842) and 41,5% of therapeutic patients (15 487)) had VTE risks. In Russia 2 188 enrolled patients (45,7%) had VTE risks (52% of surgical patients (1 470) and 36,7% of therapeutic patients (718). Totally 17 732 (50,2%) patients enrolled in Global Register ENDORSE and having VTE risks received VTE preventive therapy according to АССР Recommendations 2004. In Russia 521 (23,8%) patients enrolled in Global ENDORSE Register and having VTE risks received VTE preventive therapy according to АССР Recommendations 2004. It is more than 2 times less in comparison with world level (р<0.001).Conclusion. There are a lot of patients with VTE risks in hospitals. It is necessary to improve preventive therapy of VTE due to better hospital management and more active use of АССР Recommendations 2004

Клинико-анамнестические и молекулярно-генетические критерии синдрома Линча

Lynch syndrome is the most common cancer-prone syndrome associated with a high risk of colorectal cancer (CRC), neoplasms of the upper gastrointestinal system, the urinary tract, the female reproductive system, brain tumours and others. The only known form of hereditary endometrial cancer is also diagnosed as part of Lynch syndrome. One or more pathogenic germline mutations in one of the mismatch repair (MMR) genes are the cause of Lynch syndrome. Mapping of MMR genes and the discovery of microsatellite instability (MSI) have given rise to the possibility of using these clue characteristics of the pathogenic process for the elaboration of a screening test for Lynch syndrome. Being highly accurate and superior to all previously developed clinical criteria and guidelines, MSI-testing along with the assessment of the expression patterns of MMR proteins by immunohistochemistry has taken the leading role in the early diagnosis of Lynch syndrome. This article focuses on a brief review about the main evolutionary stages of clinical, anamnestic, molecular and genetic criteria for Lynch syndrome together with the results of our own research on the accuracy of the Amsterdam criteria, the Bethesda guidelines and MSI-diagnostics in the determination of the indications for MMR-genotyping in colorectal cancer patients suspected for Lynch syndrome.Синдром Линча (СЛ) – самый частый наследственный онкологический синдром, ассоциированный с высоким риском развития рака толстой кишки, злокачественных новообразований верхних отделов желудочно-кишечного тракта, мочевыделительной системы, головного мозга, женской репродуктивной системы. В составе СЛ диагностируется единственно известная форма наследственного рака тела матки. Этиологическим фактором развития СЛ являются герминальные мутации в генах системы репарации неправильно спаренных оснований ДНК (DNA mismatch repair (MMR)). Картирование данных генов, а также открытие феномена микросателлитной нестабильности (microsatellite instability, MSI) расширило наши представления о патогенезе линч-ассоциированных опухолей и стало основой для молекулярных скрининговых исследований. Превышая в диагностической точности все разработанные ранее клинические критерии и рекомендации, MSI-тестирование наряду с оценкой экспрессии MMR-белков при иммуногистохимическом исследовании уверенно занимает лидирующее место в ранней диагностике СЛ. В данной статье приведен краткий обзор литературы, отражающий основные эволюционные этапы развития клинико-анамнестических и молекулярногенетических критериев СЛ, а также собственные данные, демонстрирующие точность амстердамских критериев, рекомендаций Бетезда и MSI-диагностики при определении показаний для MMR-генотипирования у больных с формально-генетическим диагнозом рака толстой кишки в составе СЛ

Impact of growing conditions on the gum properties of different genotypes of guar (Cyamopsis tetragonoloba (L.) Taub.)

Galactomannan (gum), a water-soluble polysaccharide, is widely used as a gelling agent in liquids, including in the oil and gas industry for hydraulic fracturing. The most effective source of this valuable plant material is seeds of guar (Cyamopsis tetragonoloba (L.) Taub.), a legume crop new for Russia. Although in recent years progress has been made in the selection of guar varieties adapted to the conditions of the Russian Federation, the question of the most appropriate region for the cultivation of this crop remains open. The purpose of the study was to investigate how a region and technology of guar cultivation can affect the main indicators of the final target product: the content and viscosity of guar gum extracted from the seeds of various guar genotypes. To understand this, ecogeographical tests of 13 guar accessions from the VIR collection were conducted at the experimental stations of the Vavilov Institute (VIR), where climatic conditions correspond to the temperature requirements of the crop. To compare the properties of gum extracted from the seeds of various genotypes, a fast-tracked laboratory method was suggested allowing gum extracts to be obtained for assessing their viscosity. The method allows fast screening of the breeding material and selecting guar genotypes with beneficial properties of guar gum which are in demand by the oil industry. Applying the fast laboratory method for assessing the properties of gum in seeds of 13 guar varieties showed that the content and viscosity of gum of the same variety vary greatly depending on growing conditions. The same set of 13 guar accessions was grown in 2018 at the Volgograd, Astrakhan, Dagestan and Kuban VIR experimental stations. As a result, the maximum viscosity values were obtained for the seeds reproduced at the Astrakhan region, where the guar was grown on irrigated lands. On the other hand, the maximum gum content in the seeds of all accessions was recorded when they were grown in the Volgograd region. The results showed that the guar gum extracted from seeds of guar plants grown in the Russian Federation can be used as a gelling agent in the processes of intensification of oil production by the method of hydraulic fracturing. This experience is new to the Russian Federation

Оценка рациональности затрат на лечение тяжелой внебольничной пневмонии в условиях многопрофильног о стационара

Purpose — to study rationality of financial expenses on the treatment of patients with the severe pneumonia.Materials and methods. It was selected 30 medical histories of patients with severe community-acquires pneumonia passing hospitalization in pulmonology department and department of intensive care in 2004, 2011 and 2014. The frequency analysis was applied to studying the structure of the carried-out drug treatment and identification of frequency of the separate medicinal preparations. We have data about the cost of drug which were received from the database of «1C: Drugstore» of regional clinical hospital.Results. Expenses on the treatment of severe community-acquires pneumonia according to 2014 year are rational, 92.23% of expenses are vitally necessary drug entering into modern clinical references. According to the ABC/VEN analysis during the period from 2004 till 2014 we found positive dynamics of increase of expenditure of money at category V. The appreciable attention should be paid to the treatment of accompanying pathology in the therapy of severe communityacquires pneumonia which can make heavier a current of basic disease and become the reason of complications, often fatal. Costs of the medicinal preparations for treatment of the accompanying pathology in 2014 year was made 6.27% that it is necessary to consider at advance planning of provision of medicines in pulmonology department.Conclusion. The results received by us testify about rational use of financial costs on treatment of patients with severe community-acquires pneumonia.Цель — изучить рациональность финансовых затрат на лечение пациентов с тяжелым течением пневмонии.Материалы и методы. Было отобрано по 30 историй болезни пациентов с тяжелой внебольничной пневмонией, проходивших стационарное лечение в отделении пульмонологии и реанимации в 2004, 2011 и 2014 гг. Для изучения структуры проводимого медикаментозного лечения и выявления частоты назначения отдельных лекарственных препаратов применялся частотный анализ. Провести анализ рациональности лекарственной терапии и затрат на нее позволил ABC/VEN-анализ. Сведения о стоимости лекарственных препаратов получены из базы данных ККБ «1С: Аптека».Результаты. Затраты на лечение тяжелой внебольничной пневмонии, по данным 2014 г., рациональны, 92,23% затрат приходится на жизненно-важные лекарственные препараты, входящие в современные клинические рекомендации. В ходе проведенного ABC/VEN-анализа за период с 2004 по 2014 г. выявлена положительная динамика увеличения расходования денежных средств на катергорию V. В терапии тяжелой внебольничной пневмонии значительное внимание должно уделяться лечению сопутствующей патологии, которая может утяжелять течение основного заболевания и стать причиной осложнений, зачастую фатальных. Затраты на лекарственные препараты для лечения сопутствующей патологии в 2014 г. составили 6,27%, что необходимо учитывать при перспективном планировании лекарственного обеспечения отделения пульмонологии.Заключение. Полученные нами результаты свидетельствуют о рациональном использовании финансовых затрат на лечение пациентов с тяжелым течением пневмони

СПЕКТР СОМАТИЧЕСКИХ МУТАЦИЙ ПРИ ЗАБРЮШИННОЙ НЕОРГАННОЙ ЛЕЙОМИОСАРКОМЕ: КЛИНИЧЕСКИЙ СЛУЧАЙ И ОБЗОР ЛИТЕРАТУРЫ

Retroperitoneal leiomyosarcomas (RpLMS) are highly aggressive tumors, which are characterized by poor prognosis and resistance to chemotherapy. Targeting tumor-specific molecular pathways have become a rapidly expanding field in drug development to increase efficacy of treatment of LMS. Here we present a case report of rapidly progressive RpLMS with gene mutations of key molecular pathways, which have not previously described in the literature. A 61-year-old man was admitted to our hospital with complaints of abdominal pain and fever. Radiological examination revealed retroperitoneal leiomyosarcoma, which was histologically confirmed by core-biopsy. The patient underwent radical (R0) en-bloc resection of tumor with left hemicolectomy, left total nephrectomy, left total adrenalectomy and distal subtotal pancreatectomy. Pathological assessment of the tumor revealed G3 leiomyosarcoma. The patient did not receive adjuvant therapy. Disease progression (local recurrence and pulmonary metastases) occurred 3 months after surgery, and the patient died 6 months after surgery. Immunohistochemical study revealed positive PD -L1 expression in tumor cells. The percentage of PD -L1- expressing cells was 30 %. Molecular-genetic testing allowed identification of somatic mutations in genes, such as PIK3CA, ALK, EGFR, ERBB, ESR1 and PD GFRA and confirmation of microsatellite stable status (MSS) of the tumor. Further studies to investigate spectrum of mutations in RpLMS are of great interest, since they can allow identification of potential targets for more effective antitumor therapy and to improve treatment results.Забрюшинные неорганные лейомиосаркомы являются высокоагрессивными опухолями и характеризуются неблагоприятным прогнозом, обусловленным низкой чувствительностью к химиотерапии. В настоящее время проводится поиск новых мишеней для лекарственного воздействия. В данной статье мы приводим клинический случай забрюшинной неорганной лейомиосаркомы с агрессивным течением, при которой был выявлен ряд ранее не описанных в литературе активирующих мутаций в генах, играющих важную роль в регуляции клеточной пролиферации. Больной в возрасте 61 года обратился в нашу клинику с жалобами на эпизодические боли в животе, повышение температуры тела. При обследовании был выявлен забрюшинно расположенный многоузловой опухолевый конгломерат, размерами 12×10 см. Пациенту было выполнено радикальное (R0) оперативное вмешательство в объёме удаления забрюшинной опухоли, левосторонней гемиколэктомии, нефрэктомии и адреналэктомии слева, дистальной субтотальной резекции поджелудочной железы. По данным патоморфологического исследования операционного материала опухоль соответствовала лейомиосаркоме III степени злокачественности (по системе FNCLCC). В послеоперационном периоде адъювантная химиотерапия не проводилась. В ранние сроки после операции (безрецидивный период – 3 мес) отмечено прогрессирование заболевания в виде локального рецидива опухоли и появления метастазов в лёгких, проводилась симптоматическая терапия. Спустя 6 мес после операции пациент скончался от прогрессирования заболевания. При иммуногистохимическом исследовании было выявлено, что в опухоли определяется экспрессия PD L1, уровень которой составил 30 %. Молекулярно-генетическое профилирование позволило выявить ряд соматических мутаций в генах PIK3CA, EGFR, ERBB2, PD GFRA, а также подтвердить стабильную систему репарации (MSS). Изучение мутационного профиля лейомиосарком представляет большой интерес, поскольку это может позволить определить новые механизмы лекарственного воздействия и улучшить результаты лечения

Inhibition of SOC/Ca2+/NFAT pathway is involved in the anti-proliferative effect of sildenafil on pulmonary artery smooth muscle cells

<p>Abstract</p> <p>Background</p> <p>Sildenafil, a potent phosphodiesterase type 5 (PDE5) inhibitor, has been proposed as a treatment for pulmonary arterial hypertension (PAH). The mechanism of its anti-proliferative effect on pulmonary artery smooth muscle cells (PASMC) is unclear. Nuclear translocation of nuclear factor of activated T-cells (NFAT) is thought to be involved in PASMC proliferation and PAH. Increase in cytosolic free [Ca²⁺] ([Ca²⁺]_i) is a prerequisite for NFAT nuclear translocation. Elevated [Ca²⁺]_iin PASMC of PAH patients has been demonstrated through up-regulation of store-operated Ca²⁺channels (SOC) which is encoded by the transient receptor potential (TRP) channel protein. Thus we investigated if: 1) up-regulation of TRPC1 channel expression which induces enhancement of SOC-mediated Ca²⁺influx and increase in [Ca²⁺]_iis involved in hypoxia-induced PASMC proliferation; 2) hypoxia-induced promotion of [Ca²⁺]_ileads to nuclear translocation of NFAT and regulates PASMC proliferation and TRPC1 expression; 3) the anti-proliferative effect of sildenafil is mediated by inhibition of this SOC/Ca²⁺/NFAT pathway.</p> <p>Methods</p> <p>Human PASMC were cultured under hypoxia (3% O₂) with or without sildenafil treatment for 72 h. Cell number and cell viability were determined with a hemocytometer and MTT assay respectively. [Ca²⁺]_iwas measured with a dynamic digital Ca²⁺imaging system by loading PASMC with fura 2-AM. TRPC1 mRNA and protein level were detected by RT-PCR and Western blotting respectively. Nuclear translocation of NFAT was determined by immunofluoresence microscopy.</p> <p>Results</p> <p>Hypoxia induced PASMC proliferation with increases in basal [Ca²⁺]_iand Ca²⁺entry via SOC (SOCE). These were accompanied by up-regulation of TRPC1 gene and protein expression in PASMC. NFAT nuclear translocation was significantly enhanced by hypoxia, which was dependent on SOCE and sensitive to SOC inhibitor SKF96365 (SKF), as well as cGMP analogue, 8-brom-cGMP. Hypoxia-induced PASMC proliferation and TRPC1 up-regulation were inhibited by SKF and NFAT blocker (VIVIT and Cyclosporin A). Sildenafil treatment ameliorated hypoxia-induced PASMC proliferation and attenuated hypoxia-induced enhancement of basal [Ca²⁺]_i, SOCE, up-regulation of TRPC1 expression, and NFAT nuclear translocation.</p> <p>Conclusion</p> <p>The SOC/Ca²⁺/NFAT pathway is, at least in part, a downstream mediator for the anti-proliferative effect of sildenafil, and may have therapeutic potential for PAH treatment.</p

Молекулярно-биологические подтипы рака молочной железы у носителей мутаций в гене BRCA1

Background. According to the literature, BRCA1-associated breast cancer (BC) most often belongs to the triple negative (TNBC) molecular subtype. The data on the contribution of other molecular subtypes to this group of patients differ among different studies.The study objective is to evaluate the frequency of different tumor molecular subtypes in BC patients with BRCA1 gene mutation treated in N. N. Blokhin National Medical Research Center of Oncology in the period from 2017 to 2020.Materials and methods. The study included BC patients with a mutation in the BRCA1 gene (n = 209) identified as a result BRCA1 mutation screening of patients with BC. DNA diagnostics was carried out on blood samples of patients using the real-time polymerase chain reaction method. After analyzing the patients primary documentation clinical and morphological data were taken into account: the age of diagnosis, the stage of the disease, the results of immunohistochemical studies (estrogen receptor status, progesterone receptor status, HER2 expression, Ki-67 proliferation index). The assignment to the particular molecular tumour subtypes was performed according to estrogen receptor status, progesterone receptor status, HER2 status and Ki67 value.Results. Clinical and pathomorphological data of 209 patients with BRCA1-associated BC were analyzed. The age at diagnosis ranged from 23 to 72 years, the median age was 40 years, the mean age was 41.46 ± 9.82 years. BC associated with BRCA1 was found to be TNBC in 71.3 % and luminal B, HER2 negative (LumB–) in 19.1 % of the cases. Other tumour subtypes were much less common: luminal B, HER2 positive (LumB+) in 7.2 %, luminal A (LumA) in 1 % and HER2-positive (HER2+) in 1.4 % of the cases. The frequency of subtypes was estimated in different age groups (1st – patients 23–34 (n = 53), 2nd – 35–49 (n = 111), and 3rd – 50–72 (n = 45) years old). TNBC frequency was 81.1 % in the 1st group, 73.9 % in the 2nd and 53.4 % in the 3rd group; LumB– frequency was 15.1, 15.3 and 33.3 % respectively. Using the Fisher test it was shown that the differences in frequencies were statistically significant between groups 1st and 3 rd, as well as between groups 2 nd and 3 rd (p &lt;0.05).Conclusion. TNBC was the main molecular subtype in all age groups of BC patients with BRCA1 germinal mutation, TNBC frequency was lower in the older age group. LumB– subtype was also common in BRCA1-associated tumors especially in older women.Введение. По данным опубликованных исследований, BRCA1-ассоциированный рак молочной железы (РМЖ) наиболее часто относится к тройному негативному молекулярному подтипу (triple-negative breast cancer, TNBC). Данные о соотношении других молекулярных подтипов среди этой группы пациентов различаются у разных авторов.Цель исследования – оценить частоту различных молекулярно-биологических подтипов опухолей в российской группе больных РМЖ с мутацией в гене BRCA1, находившихся на лечении в НМИЦ онкологии им. Н. Н. Блохина в период с 2017 по 2020 г.Материалы и методы. В исследование были отобраны пациенты с РМЖ с наличием мутации в гене BRCA1 (n = 209), выявленной в результате ДНК-диагностики при скрининге больных РМЖ. Для выявления герминальной мутации использовали ДНК пациентов, выделенную из лимфоцитов периферической крови, анализ проводили методом полимеразной цепной реакции в реальном времени. При анализе первичной документации больных были учтены клинико-морфологические данные: возраст постановки диагноза, стадия заболевания, результаты иммуногистохимического исследования (статус рецепторов эстрогена и прогестерона, HER2 и индекс пролиферации Ki-67). На основании оценки статуса рецепторов эстрогена и прогестерона, экспрессии HER2 и значения Ki-67 определена частота 5 молекулярных подтипов опухолей.Результаты. Проведен анализ клинических и патоморфологических данных 209 пациентов с BRCA1-accоциированным РМЖ. Возраст постановки диагноза варьировал в диапазоне 23–72 лет (медиана 40 лет; среднее значение 41,46 ± 9,82 года). РМЖ, ассоциированный с BRCA1, в 71,3 % случаев относился к TNBC, в 19,1 % – к люминальному В, HER2-отрицательному (LumB–). Другие подтипы опухолей встречались значительно реже: люминальный В, HER2-положительный (LumB+) – в 7,2 % случаев, люминальный А (LumA) – в 1,0 %, HER2-положительный (HER2+) – в 1,4 %. Проведена оценка встречаемости подтипов в разных возрастных подгруппах: 1-я – больные в возрасте 23–34 лет (n = 53); 2-я – 35–49 лет (n = 111); 3-я – 50–72 лет (n = 45). Частота TNBC составила 81,1 % в 1-й подгруппе, 73,9 % – во 2-й и 53,4 % – в 3-й; частота LumB– составила 15,1; 15,3 и 33,3 % соответственно. При использовании критерия Фишера показано, что различия в частотах между 1-й и 3-й, а также между 2-й и 3-й подгруппами статистически значимы (p &lt;0,05).Заключение. Во всех возрастных подгруппах пациентов с РМЖ, имеющих герминальную мутацию в гене BRCA1, основным молекулярным подтипом является TNBC, частота встречаемости которого ниже в старшей возрастной подгруппе. Подтип LumB– также характерен для BRCA1-ассоциированных опухолей, особенно у женщин старшего возраста