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Association of the Estrogen Receptors Beta Expression with the Ki-67 Proliferative Index in Breast Cancer 乳腺癌中雌激素受体β表达与Ki-67增殖指数的关系
Pub Date : 2023-07-18 DOI: 10.37489/0235-2990-2023-68-3-4-39-45
T. Bogush, P. D. Potselueva, A. Scherbakov, E. Bogush, A. B. Ravcheeva, N. Vikhlyantseva, V. Kosorukov
Background. Estrogen receptors beta (ERβ) are an important biological regulator and target of antiestrogens, however, unlike estrogen receptors alpha (ERɑ), their significance in the prognosis and treatment of breast cancer remains unclear. Purpose. Evaluation of the ERβ prognostic value in the comparative assessment of frequency and level of the marker expression in groups with good and poor prognosis by Ki-67 proliferative index score in breast cancer. Methods. ERβ expression level (% of cells expressing the marker) in 68 breast tissue samples was quantified by immunofluorescence and flow cytometry. Primary antibodies to ERβ (clone 14C8, ab288) and secondary antibodies conjugated with DyLight650 (ab98729) were used. In the same samples, the Ki-67 expression level was assessed by the immunohistochemical method. Results. The ERβ and Ki-67 were detected in 100% breast tissue samples with high heterogeneity of the markers’ expression in different patients. Statistical analysis of good and poor prognosis in accordance with the Ki-67 proliferative index score (Ki-67≤20% and Ki-67>20%) showed the prognostic value of the ERβ expression level of 50%. There was no association between the Ki-67 and ERβ expression levels in the same tumor sample (Spearman's rank correlation coefficient R=–0,16; P>0,05). At the same time, high expression of ERβ≥50% was 2,3 times more frequently detected in the good vs poor prognostic group by Ki-67 — 41% vs 18%, P=0,02. Conclusion. The ERβ expression level ≥50% in the tumor can be considered as a factor of good prognosis of breast cancer.
背景。雌激素受体β (Estrogen receptor β, ERβ)是一种重要的生物调节因子和抗雌激素靶点,但与雌激素受体α (Estrogen receptor α, ERβ)不同,其在乳腺癌预后和治疗中的意义尚不清楚。目的。用Ki-67增殖指数评分比较预后良好组和预后不良组标志物表达频率和水平评价ERβ的预后价值方法。用免疫荧光和流式细胞术测定68例乳腺组织标本中ERβ的表达水平(表达ERβ的细胞百分比)。采用ERβ的一抗(克隆14C8, ab288)和与DyLight650偶联的二抗(ab98729)。免疫组化法检测Ki-67的表达水平。结果。ERβ和Ki-67在100%的乳腺组织样本中检测到,不同患者的标志物表达具有很高的异质性。根据Ki-67增殖指数评分(Ki-67≤20%和Ki-67>20%)对预后好坏进行统计分析,ERβ表达水平为50%的预后价值。同一肿瘤样本中Ki-67与ERβ表达水平无相关性(Spearman等级相关系数R= - 0,16;P > 0。05)。同时,Ki-67检测到预后良好组ERβ≥50%高表达的频率是预后不良组的2,3倍,分别为41%和18%,P= 0.02。结论。ERβ在肿瘤中的表达水平≥50%可视为乳腺癌预后良好的因素。
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引用次数: 0
Antibacterial Resistance. The Challenge of Modernity 抗菌耐。现代性的挑战
Pub Date : 2023-07-18 DOI: 10.37489/0235-2990-2023-68-3-4-66-75
A. Daudova, Ju. Z. Demina, G. N. Genatullina, R. O. Abdrakhmanova, G. R. Baeva, A. Yasenyavskaya, O. V. Rubalsky
Antimicrobial resistance is considered by WHO as one of the most important threats to public health in the twenty-first century. According to forecasts, by 2025, many first-line antimicrobials will lose their effectiveness and the «post-antibiotic era» will begin. Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and representatives of the genus Mycobacterium are classified by the American Society of Infectious Diseases as microorganisms that play a predominant role in the development of infections associated with medical care and leading to fatal consequences. The review highlights the mechanisms of antibiotic resistance and many variants of microbial resistance to antibiotics. Knowledge of the molecular mechanisms of the formation of resistance of microorganisms allows us to develop strategic directions for overcoming it. The search for new ways to prevent and overcome the formation of resistance of pathogens to antibiotics is an extremely important task of modern medical science. The effectiveness of hybrid antibiotics associated with chemical compounds with various specific effects is presented. The use of the main active factor of the bacterial virus, endolysin, both in its pure form and as part of homodimers, for example, lysoprotein, which is a complex of endolysin with human immunoglobulins, is considered promising. Phage therapy of the future is a personalized phage therapy that requires the creation of a library or bank of phages.
世卫组织认为抗菌素耐药性是21世纪公共卫生面临的最重要威胁之一。据预测,到2025年,许多一线抗微生物药物将失去效力,“后抗生素时代”将开始。屎肠球菌、金黄色葡萄球菌、肺炎克雷伯菌、鲍曼不动杆菌、铜绿假单胞菌、肠杆菌和分枝杆菌属的代表被美国传染病学会归类为在与医疗保健相关的感染发展中起主要作用并导致致命后果的微生物。这篇综述强调了抗生素耐药的机制和许多微生物对抗生素耐药的变异。微生物耐药性形成的分子机制的知识使我们能够制定克服它的战略方向。寻找预防和克服病原菌对抗生素产生耐药性的新途径是现代医学的一项极其重要的任务。介绍了与具有不同特异效应的化合物相关的杂交抗生素的有效性。利用细菌病毒的主要活性因子,内溶素,无论是纯形式还是作为同型二聚体的一部分,例如溶酶蛋白,它是内溶素与人类免疫球蛋白的复合物,被认为是有希望的。未来的噬菌体治疗是一种个性化的噬菌体治疗,需要建立一个噬菌体库或噬菌体库。
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引用次数: 0
Evaluation of the Antiseptic Effect of the Anolyte Solution on Laboratory Rats 阳极酸盐溶液对实验大鼠防腐作用的评价
Pub Date : 2023-07-18 DOI: 10.37489/0235-2990-2023-68-3-4-35-38
S. Styazhkina, N. Kiryanov, D. Kuklin, Kh S Kutbedinov, O. N. Eykina, D. V. Strashnov
An experimental study of the antiseptic properties of the Anolyte solution was carried out. The developed anolyte solution has an antiseptic effect, especially active against Escherichia coli, which indicates the possibility of its use in the complex therapy of purulent wounds.
对阳极酸盐溶液的防腐性能进行了实验研究。所研制的阳极液溶液具有抗菌作用,对大肠杆菌尤其有效,这表明其在化脓性伤口的复杂治疗中有应用的可能性。
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引用次数: 0
Substantiation of the Combined Use of Negative Pressure Therapy and Meglumine Sodium Succinate in the Treatment of Wounds of Various Etiologies 负压疗法联合琥珀酸甲胺钠治疗各种病因性创面的临床观察
Pub Date : 2023-07-18 DOI: 10.37489/0235-2990-2023-68-3-4-76-83
M. Varganov, A. A. Miklichev, I. V. Svidersky
The review presents a theoretical rationale for the effectiveness of including topically NPWT therapy and meglumine sodium succinate intravenously in the complex therapy of wounds of various etiologies. The biochemical pathways accompanying the formation of normoxia and hypoxia of varying severity, the significance of succinate in their formation, including depending on the form of its intake into the body (exogenous and endogenous pathways), are given. Thus, when endogenous production of succinic acid is decompensated, the tricarboxylic acid cycle is inhibited and anaerobic glycolysis is activated. At this moment and before the onset of irreversible biochemical damage, the restoration of energy exchange processes begins to depend on succinate, including its exogenous intake. Additional, but no less important, antihypoxic effects of exogenous succinate include stimulation of succinate oxidase oxidation of succinic acid with the restoration of its consumption in the mitochondrial respiratory chain and an increase in the activity of the antioxidant function of glutathione, as well as stimulation of protein metabolism. Reamberin (meglumine sodium succinate) significantly accelerates tissue recovery during hypoxia due to its antihypoxic, cytoprotective and other effects due to the activation of HIF-1ɑ biologically active factors.
本文综述了包括局部NPWT治疗和静脉滴注琥珀酸甲胺钠在内的各种病因性伤口复杂治疗的有效性的理论基础。给出了伴随不同程度的常氧和缺氧形成的生化途径,琥珀酸盐在其形成中的重要性,包括取决于其进入体内的形式(外源性和内源性途径)。因此,当内源性琥珀酸生产失代偿时,三羧酸循环被抑制,厌氧糖酵解被激活。此时,在不可逆生化损伤发生之前,能量交换过程的恢复开始依赖于琥珀酸盐,包括其外源性摄入。此外,但同样重要的是,外源性琥珀酸的抗缺氧作用包括刺激琥珀酸氧化酶氧化琥珀酸,恢复其在线粒体呼吸链中的消耗,增加谷胱甘肽抗氧化功能的活性,以及刺激蛋白质代谢。Reamberin (meglumine sodium琥珀酸钠)通过激活HIF-1生物学活性因子,具有抗缺氧、细胞保护等作用,在缺氧时显著加速组织恢复。
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引用次数: 0
Long-term results of chemotherapy of tuberculosis with a widespread drug-resistant pathogen using bedaquiline 使用贝达喹啉治疗广泛存在耐药病原体的结核病的长期疗效
Pub Date : 2023-04-30 DOI: 10.37489/0235-2990-2023-68-1-2-27-32
A. Chernikov, D. D. Polyansky, A. Dyakov, K. D. Rotenko, D. V. Panfilova
Relevance. Long-term results of treatment of patients with widespread drug-resistant tuberculosis are not presented in the medical literature. Objective. Study the efficacy and long-term results of treatment of patients with widespread drug-resistant tuberculosis using bedaquiline. Material and methods. Two groups of patients with widespread drug-resistant tuberculosis were formed, who received bedaquiline as the base drug of the chemotherapy course: bedaquiline in the main group (49 people) and moxifloxacin in the control group (76 people). The results of treatment at the end of the course of chemotherapy and after three years of follow-up were studied. Results. 87.8±9.2% of patients from the main group completed an effective course of treatment with sputum culture control. In 67.3±13.1%, the cessation of bacillus excretion was achieved at 1–2 months of treatment. Undesirable effects of chemotherapy were noted in 10.2–32.7% of cases, with prolongation of the QT interval only in 8.2±7.7% of patients. After a three-year dispensary follow-up, there was no recurrence of tuberculosis in the main group, chronic obstructive pulmonary disease was less common for the fifirst time, no cases of treatment by a cardiologist and gynecologist were found, the transfer of patients from the second disability group to the third was more often observed. Conclusion. The use of bedaquiline for the treatment of patients with widespread drug-resistant tuberculosis makes it possible to achieve early cessation of bacillus excretion with transfer to outpatient treatment, reduce the frequency of adverse reactions of chemotherapy. The long-term results of dispensary observation indicate a low risk of reactivation of tuberculosis, a significant reduction in the need for dispensary observation by other specialists, including a cardiologist, and improvement in the results of complex rehabilitation.
的相关性。广泛的耐药结核病患者的长期治疗结果尚未在医学文献中提出。目标。研究贝达喹啉治疗广泛性耐药结核病的疗效和远期效果。材料和方法。广泛性耐药结核病患者分为两组,以贝达喹啉为化疗基础药物:主组(49例)贝达喹啉,对照组(76例)莫西沙星。观察化疗结束时及随访3年后的治疗结果。结果:主组87.8±9.2%的患者在痰培养控制下完成了有效疗程。67.3±13.1%的患者在治疗1-2个月时停止了芽孢杆菌的排泄。10.2-32.7%的患者出现化疗不良反应,仅8.2±7.7%的患者出现QT间期延长。经过三年的药房随访,主要组无结核复发,慢性阻塞性肺病首次出现较少,未发现由心脏病专家和妇科医生治疗的病例,从第二残疾组转移到第三残疾组的患者较多。结论。贝达喹啉用于广泛耐药结核病患者的治疗,可以实现芽孢杆菌排泄的早期停止,并转移到门诊治疗,减少化疗不良反应的发生频率。药房观察的长期结果表明,结核病复发的风险较低,其他专家(包括心脏病专家)对药房观察的需求显著减少,复杂康复的结果有所改善。
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引用次数: 0
The potential role of micro- and nanoplastics in the spread of viruses 微塑料和纳米塑料在病毒传播中的潜在作用
Pub Date : 2023-04-30 DOI: 10.37489/0235-2990-2023-68-1-2-33-44
B. Andryukov, N. Besednova, T. Zaporozhets, A. A. Yakovlev, E. Matosova, S. Kryzhanovsky, M. Shchelkanov
The review presents recent materials about the growing influence of micro- and nanoplastics (MP/NP) on the spread of pathogenic viruses in humans and animals. The issue of the interaction of viruses with the plastisphere, the role of the virus envelope in the preservation of these microorganisms on microparticles in the composition of the biofilm has been elucidated. The issues of synergism of the pathogenetic action of MP/NP and viruses, studied on various models, are discussed. The article shows the negative effect of MP/NP on the permeability of the body's natural barriers, which can create favorable conditions for the penetration of viruses and the development of an infectious process. The authors draw attention to the need to expand interdisciplinary research in this area, given the fact that viruses residing on MP/NP can increase their infectivity and, possibly, form new genovariants.
本文综述了关于微纳米塑料(MP/NP)对致病性病毒在人类和动物中传播的影响越来越大的最新材料。阐明了病毒与塑料球的相互作用,以及病毒包膜在生物膜组成中的微颗粒上保存这些微生物的作用。本文讨论了在不同模型上研究的MP/NP与病毒的协同作用问题。本文显示了MP/NP对人体天然屏障渗透性的负面影响,这可以为病毒的渗透和感染过程的发展创造有利条件。作者提请注意,鉴于驻留在MP/NP上的病毒可以增加其传染性,并可能形成新的基因变异,需要扩大这一领域的跨学科研究。
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引用次数: 0
Molecular mechanisms of microbial resistance to disinfectants 微生物对消毒剂耐药性的分子机制
Pub Date : 2023-04-30 DOI: 10.37489/0235-2990-2023-68-1-2-45-56
S. Kovalchuk, L. Fedorova, E. Ilina
Dissemination of microbial resistance to biocides, including disinfectants, is one of the acute problem, which poses biological and economic threats to all countries in the world. Understanding the mechanisms of microbial resistance to disinfectants is a necessary scientific basis for searching ways to overcome it. Despite the wide use of disinfectants, developing bacterial resistance to them has been less studied than to antibiotics. This review presents data on the main molecular mechanisms of microbial resistance to disinfectants.
微生物对杀菌剂(包括消毒剂)的耐药性的传播是一个严重问题,对世界各国构成生物和经济威胁。了解微生物对消毒剂的耐药机制是寻找克服方法的必要科学依据。尽管消毒剂被广泛使用,但与抗生素相比,对细菌产生耐药性的研究较少。本文综述了微生物对消毒剂耐药的主要分子机制。
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引用次数: 0
On the issue of screening and prevention of chronic and opportunistic infections in rheumatology 关于风湿病慢性和机会性感染的筛查和预防问题
Pub Date : 2023-04-30 DOI: 10.37489/0235-2990-2023-68-1-2-69-76
B. Belov, G. Gridneva, E. Aronova, N. Muravyeva
The problem of comorbid infections in rheumatology still remains relevant. Against the background of immunosuppressive/immunomodulatory therapy of immuno-inflammatory rheumatic diseases (IIRD), chronic and opportunistic infections (COI) often develop. Some of these infections can be prevented by performing timely screening procedures and preventive measures. A group of experts from the European Alliance of Rheumatology Associations (EULAR) has prepared recommendations on screening procedures and prevention measures for the most common COI (tuberculosis, chronic viral hepatitis B and C, infections caused by the human immunodeficiency virus and Herpes zoster, pneumocystis pneumonia) within the framework of the IIRD. This article presents the main provisions of this document. The need for periodic review of screening and preventive procedures is emphasized as new scientific data are accumulated.
风湿病学中合并症感染的问题仍然具有相关性。在免疫炎症性风湿病(IIRD)的免疫抑制/免疫调节治疗的背景下,慢性和机会性感染(COI)经常发生。其中一些感染可以通过及时的筛查程序和预防措施加以预防。来自欧洲风湿病协会联盟(EULAR)的一组专家在IIRD框架内就最常见的COI(结核病、慢性病毒性乙型和丙型肝炎、由人类免疫缺陷病毒和带状疱疹引起的感染、肺囊虫性肺炎)的筛查程序和预防措施提出了建议。本文介绍了该文件的主要规定。随着新的科学数据的积累,强调有必要定期审查筛查和预防程序。
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引用次数: 0
Succinate and succinate dehydrogenase as a «foothold» in the Krebs cycle in critical conditions 琥珀酸盐和琥珀酸脱氢酶作为克雷布斯循环的“立足点”在临界条件下
Pub Date : 2023-04-30 DOI: 10.37489/0235-2990-2023-68-1-2-57-68
Y. Orlov, A. Butrov, S. Sviridov, V. Afanasiev, A. Kondratiev, L. Tsentsiper, N. Govorova, A. Kondratiev, G. A. Baytugaeva, E. N. Kakulya
Purpose. Search and presentation of data from experimental and clinical studies reflecting the central role of succinate and succinate dehydrogenase in the regulation of adaptation mechanisms in critical conditions. Material and methods. The search for literature sources was carried out using the electronic resources of the Russian scientific electronic library eLIBRARY.ru, with the use of the following keywords: «Krebs cycle, succinate, succinate dehydrogenase, critical conditions», as well as in the English-language text database of medical and biological publications on medical sciences PUBMED, where similar keywords «Krebs cycle, succinate, succinate dehydrogenase, critical conditions» were used. Results. Taking into account the data presented in the review, it can be stated that the complex of succinate and succinate dehydrogenase is the central link in the Krebs cycle and the main structure of the antihypoxic ensemble of all body cells during the adaptation period under critical conditions. Conclusion. The data of experimental and clinical studies reflecting the central role of succinate and succinate dehydrogenase not only in the mechanisms of adaptation to hypoxia, but also in the regulation of inflammation, thermogenesis, hemostasis disorders, acid-base state, electrolyte metabolism, vascular tone and trophism of intestinal tissues, as well as in immunological reactions of the body, allow us to consider the substrate and enzyme as the central link of the Krebs cycle and the main structure of the antihypoxic ensemble of all body cells. The data presented in the review open up new prospects for the use of succinates in critical conditions.
目的。从实验和临床研究中检索和展示反映琥珀酸盐和琥珀酸脱氢酶在关键条件下调节适应机制中的核心作用的数据。材料和方法。文献来源的搜索使用俄罗斯科学电子图书馆eLIBRARY.ru的电子资源,使用以下关键词:«Krebs循环,琥珀酸盐,琥珀酸脱氢酶,临界条件»,以及医学科学医学和生物学出版物的英文文本数据库PUBMED,其中使用了类似的关键词«Krebs循环,琥珀酸盐,琥珀酸脱氢酶,临界条件»。结果。综上所述,琥珀酸盐和琥珀酸脱氢酶的复合物是克雷布斯循环的中心环节,是机体细胞在临界条件下适应期抗缺氧集合的主要结构。结论。实验和临床研究数据表明,琥珀酸盐和琥珀酸脱氢酶不仅在机体缺氧适应机制中发挥核心作用,而且在机体炎症、产热、止血障碍、酸碱状态、电解质代谢、血管张力和肠道组织营养的调节以及机体免疫反应中发挥核心作用。使我们认为底物和酶是克雷布斯循环的中心环节,也是所有身体细胞抗缺氧集合的主要结构。综述中提出的数据为琥珀酸盐在临界条件下的应用开辟了新的前景。
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引用次数: 0
Development of the screening conditions in vitro effective drugs against the causative agent of Сhikungunya fever 对Сhikungunya发热病原菌体外有效药物筛选条件的探讨
Pub Date : 2023-04-29 DOI: 10.37489/0235-2990-2023-68-1-2-11-15
S. Loginova, V. N. Schukina, S. Savenko, R. V. Sakharov, I. V. Surovyatkina, S. Borisevich
The Сhikungunya virus (CHIKV) is a member of the Flavivirus genus, the Flaviviridae family, and is a zoonotic arbovirus infection transmitted by Aedes mosquitoes. Chikungunya fever causes explosive epidemics involving millions of cases. There is an urgent need to develop broad-spectrum antivirals. Actual is the development of a model of screening in vitro effective drugs. To select the optimal screening conditions, a comparative analysis of cell cultures sensitivity to Сhikungunya virus, strain FN198/66 was carried out. The dynamics and level of virus accumulation at different infectious doses were estimated. It is shown that the Сhikungunya virus, strain FN198/66, well propagated in transplantable cell cultures Vero V, Сl008 Vero, BHK-21/13 and TC-17. All studied cell lines can be used to screen for effective non-specific medical defenses against Сhikungunya virus.
Сhikungunya病毒(CHIKV)是黄病毒科黄病毒属的一员,是一种由伊蚊传播的人畜共患虫媒病毒感染。基孔肯雅热引起爆炸性流行病,涉及数百万病例。目前迫切需要开发广谱抗病毒药物。实际是开发一种筛选体外有效药物的模型。为了选择最佳筛选条件,对细胞培养物对Сhikungunya病毒株FN198/66的敏感性进行了比较分析。估计了不同感染剂量下病毒积累的动态和水平。结果表明,Сhikungunya病毒株FN198/66在可移植细胞培养物Vero V、Сl008 Vero、BHK-21/13和TC-17中繁殖良好。所有研究的细胞系都可用于筛选针对Сhikungunya病毒的有效非特异性医疗防御。
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引用次数: 0
期刊
Antibiotics and Chemotherapy
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