卷 28, 编号 2 (2020)

Original study

基因多态性在结直肠癌发展中的重要性

Kulikov E., Sudakov A., Nikiforov A., Mertsalov S., Grigorenko V.

摘要

目的:测定MTHFR (Ala222Val), XPD (Lis751Gln), XRCC1 (Arg194Trp), XRCC1 (Arg399Gln), XRCC1 (Arg208His), APE1 (Asp148Glu), hOGG1 (ser326Ces), P53 (Pro47Ser), VEGF (C654G), EGFR(A2073T), TNF(G308A), CHEK2 (Ile157Thr), MMP1 (1607 1G>2G), TIMP1(C53CT) 基因多态性在结直肠癌发生发展中的意思。

材料与方法。我们分析了106例在Regional Clinical Oncology Center 梁赞地区的国家预算机构接受治疗的结肠直肠癌患者。所有患者采用静脉血白细胞DNA提取、聚合酶链反应(PCR)进行基因分型,电泳检测结果。

结果:确诊时患者的年龄与任何被研究基因的多态性均无相关性(p> 0.05)。TNF基因多态性(G308A)与肿瘤分期有统计学意义:其主要纯合基因型G/G在III-IV期患者中更为常见(p=0.047)。G / G TNF等位基因(G308A)与MMP1基因纯合突变等位基因(1607 1G/2G)的存在,与III-IV期诊断患者比例的增加有直接关系。两种多态性的结合在研究组中具有统计学差异(p=0.025)。在10例IV期患者中,有8例发现VEGF基因(C654G)中存在G / G多态性。这种突变的纯合子变异在I期(37.5%)、II期(40%)和III期(37.5%)患者中更少见(p = 0.0147)。

结论。所研究的基因并不影响结肠直肠癌的年龄相关标准,而且在男女患者中发现的频率是一样的,无论年龄组。肿瘤的定位和分化程度也与所研究基因的多态性无关。TNF基因(G308A)的G / A多态性应被认为是有助于降低肿瘤侵袭性的有利标准(p <0.05)。G/G主要基因型的鉴定,特别是结合MMP1基因纯合突变等位基因(1607 1G/2G)是不利因素(p <0.05)。G/G VEGF纯合突变基因型(C654G)的存在与肿瘤快速进展和转移活性直接相关(p <0.05)。

I.P. Pavlov Russian Medical Biological Herald. 2020;28(2):127-134
pages 127-134 views

体外研究孕激素对糖蛋白- P活性的影响

Erokhina P., Abalenikhina Y., Shchulkin A., Chernykh I., Popova N., Slepnev A., Yakusheva E.

摘要

研究现实性。糖蛋白- P(Pgp,ABCB1)是一种参与药物药代动力学和肿瘤细胞化疗耐药发展的转运蛋白。

目的:目的:研究黄体酮对体外培养的人小肠上皮细胞模型中Pgp活性的影响。

材料与方法:对Caco-2细胞系进行了研究。在特殊的Transwell体系中,通过非索非那定转运评价Pgp的活性。高效液相色谱法测定非索非那定的浓度。采用免疫酶测定法测定Pgp的含量。我们进行了四个系列的实验:对照组细胞在不添加任何物质的清洁运输介质中孵育;预孵育3天,10 mcmol / L浓度利福平对Pgp活性及合成的影响(诱导控制);孕酮在1、10和100 mol / L预潜伏30分钟时对Pgp活性的影响;孕酮在1、10、100 mcmol / L预潜伏3天后对Pgp活性及合成的影响。

结果:黄体酮与细胞潜伏30 分钟时,浓度为1和10的黄体酮对Pgp的活性没有显著影响,但浓度为100的黄体酮会降低转运蛋白的活性。

将Caco-2细胞与黄体酮浓度分别为1,10和100微米的水杨酸潜伏3天后,Pgp的活性没有变化。与对照指标相比,孕酮在潜伏3天后,浓度为100微米的孕酮可显著提高肠上皮细胞Pgp的合成,提高114.3%,但在剩余的使用浓度(1和10微米)中效果不显著。

结论:体外实验中,在Caco-2细胞系细胞中,孕激素浓度为100微米时,对Pgp活性有直接抑制作用,但在潜伏3天后,孕酮增加了转运蛋白的合成,使其抑制活性减弱。

I.P. Pavlov Russian Medical Biological Herald. 2020;28(2):135-142
pages 135-142 views

子宫内甲醛对新生大鼠胸腺结构的影响

Vash I.

摘要

目的:妊娠期暴露于甲醛(FA)的雌性新生大鼠胸腺结构的研究。

材料与方法:这项研究是对72只出生后第一天发育的白杂种大鼠进行的。第一组由幼鼠(n=37)组成,其是6只大鼠的后代,在整个妊娠期暴露于2.766 mg/m3的甲醛中。每天1次,在一平方米的种子室中进行60分钟的甲醛暴露。第二组包括对照动物(n=35)6只大鼠的后代,其在实验过程中均在与实验组相似的条件下进行,除了甲醛的作用以外。测定新生大鼠体重、胸腺绝对质量和相对质量。在光学水平上研究胸腺的结构。在2500µm2的面积上进行了胸腺皮层和大脑物质中的细胞数量计算。

结果:第一组新生大鼠的体重和胸腺绝对质量明显低于对照组的数值。比较组相对胸腺质量值之间的差异不显著。在甲醛作用下胸腺皮层和脑内物质细胞数无明显变化。

结论:甲醛在整个妊娠期对妊娠大鼠身体的吸入作用导致新生大鼠体重和胸腺绝对质量下降。与此同时,胸腺的相对质量没有发生明显变化。胸腺的结构在光学水平上在甲醛的作用下也没有发生显著的变化。

I.P. Pavlov Russian Medical Biological Herald. 2020;28(2):143-152
pages 143-152 views

心脏药物过量医院登记试点(HRCDO)的结果:主要是药物介导的心动过缓

Yakushin S., Nikulina N., Filippov E., Seleznev S., Lygina E., Chernysheva M.

摘要

目的:分析了药物介导性心动过缓(DMB)作为一个医学和社会问题的相关性,其主要规律及确定了该问题的进一步研究必要性。

材料与方法:注册研究2017年1月1日至2018年6月3日(18个月)在Regional Clinical Cardiology Dispensary梁赞地区国家预算机构进行。纳入标准:1)在服用至少一种具有心动过缓作用(BCA)的药物制剂(MP)的同时出现心动过缓律失常综合征;2)签署知情同意书。在对登记在案的患者进行诊断或治疗时,没有进行额外的干预。

结果:18个月后,191例患者住院(年龄为77.0[69.0;82.0]岁,26.7%男生)在所有因用药过量而住院的病人中,有52.6%的人被证实患有药物性心动过缓。在分析期间,由于过量使用心脏病药物(1.7倍,p <0.001),特别是心动过缓作用药物(1.8倍,p <0.001),住院人数有所增加。药物引起的心动过缓的主要临床表现:降低心率(< 50次/分钟—80.0%,< 40次/分钟—51.1%)、窦房结(30.4%)和房室的(1型—8.2%,2型—10.4%,3型—14.1%)封锁,晕厥(32.6%),心脏停顿> 3秒(7.4%)。94.8%的患者住院接受紧急护理,40.7%在麻醉科接受复苏;17.8%的病例需要植入起搏器;医院死亡率为5.2%。超过半数(54.5%)的住院患者服用2种以上的药物具有心动过缓的作用,15.7%的患者服用3种以上的药物,3.14%的患者服用4种以上的药物(单一疗法和联合用药)受体阻滞剂—68.4%,抗心律失常药物—38.9%,地高辛—25.8%,非二氢吡啶钙拮抗剂—10.5%,l1-咪唑啉受体激动剂—9.5%,其他心动过缓药物—7.4%。为分析药物性心动过缓的原因,我们收集了135例患者的临床资料(年龄为77.0岁[69.0;82.0],20.7%男生),其能准确说出有心动过缓作用的药物的剂量。其中,有14.1%的病例记录了绝对超过推荐剂量的情况,有85.9%的病例记录了几种具有心慢效应的药物的效应总和/增强情况,每种药物都以治疗剂量服用。

结论。该研究证实了药物性心动过缓问题的高度医学和社会意义,这需要实际医生、药理学家和临床药理学家以及医疗保健组织者的关注,并继续其研究。

I.P. Pavlov Russian Medical Biological Herald. 2020;28(2):153-163
pages 153-163 views

稳定缺血性心脏病和冠状动脉旁路移植术患者心理状态指标的动态变化

Solodukhin A., Trubnikova O., Barbarash O.

摘要

目的:冠状动脉旁路移植术(CABG)对缺血性心脏病(CHD)患者心理状态指标的动态评估和分析。

材料与方法:对58例从40到74岁稳定型缺血性心脏病的男性患者进行冠状动脉旁路移植前后心理状态指标,即疾疾病的内部图像、应对策略和生活取向的研究。患者入院后2-3天,冠状动脉旁路移植后7-8天由临床心理学家对各项指标进行评估。临床和心理诊断采用TOBOL问卷对疾病的态度(L.I.Wasserman)、《生活取向》(D.A. Leontiev)、《应对行为策略》(R. Lazarus,S. Folkman, T. A. Kryukova的改编版)。采用Statistica 10.0计算机软件进行统计分析。

结果:缺血性心脏病患者冠脉搭桥术后,采用TOBOL问卷、应激克服行为评估中的《积极重估》应对策略,以及《目的》在评估神经质根据《生活取向》测试中的量表水平都已确定指标的显著下降。

结论:研究结果表明,缺血性心脏病患者在冠状动脉旁路移植后,由于行为障碍和难以制定进一步的康复目标,对疾病的适应程度有所下降。为了增加术后适应,心理矫正影响的《目标》可能是《积极重估》应对策略及目标设定有助于患者在冠状动脉旁路移植后阶段制定目标。

I.P. Pavlov Russian Medical Biological Herald. 2020;28(2):164-170
pages 164-170 views

标准疗法及有机硒营养支持治疗Q-心肌梗塞患者的心率变异性

Radchenko E., Nizov A., Lapkin M., Yudin V., Zorin R., Aksentiev S., Mazo V.

摘要

目的:在使用有机硒进行标准药物治疗和膳食校正的背景下,评价Q-心肌梗塞患者不同病程时期、心率变异性指标、血液生化及流变学特征的关系。

材料与方法:对90例诊断为急性冠状动脉综合征、节段抬高、结果为Q-心肌梗死的患者(平均年龄为58.3±1.4岁,其中男生71例,女生19例)进行了开放的比较临床研究。患者被分成两组:对照组接受标准治疗,主要的治疗—另外,一种富含有机硒的饮食产品。在Q型心肌梗死的急性期、亚急性期和瘢痕期,采用Varicard 2.51复合材料对动态心脏间隔进行登记和数学分析,并对血液生化指标、硒状态和血液流变学特性进行评价。

结果:在住院治疗阶段,主组患者的心率下降(从68.8±1.7次降至64.0±1.3次/分;p < 0.05)。一开始,两组的SDNN水平均在临界值(25.0±1.3毫秒)内,压力指数(SI)比正常值高出数倍(1356.2±390.6标准单位),观察结束时,两组均未达到正常值。在整个治疗过程中,两组的变异系数(CV)均低于正常值,但动态上有轻微上升趋势。对照组心脏隔动态范围(HF)曲线谱的功率增加近2倍(p <0.05)。通过对血液生化指标、血清凝血和硒水平与心律数学分析的各个参数的相关性分析,发现它们在水平和方向上存在着不同的联系。

结论。使用富含硒的膳食产品,积极影响机体的滋养功能,结合标准疗法,可降低适应机制的张力,增加机体的适应潜力,有助于改善预后,降低风险。

I.P. Pavlov Russian Medical Biological Herald. 2020;28(2):171-182
pages 171-182 views

合成人工血管细胞毒性的比较

Kalinin R., Suchkov I., Mzhavanadze N., Korotkova N., Nikiforov A., Surov I., Ivanova P., Bozhenova A., Strelnikova E.

摘要

目的:研究并比较用于动脉重建手术的主要合成假体的细胞毒性,包括聚四氟乙烯(PTFE)和聚对苯二甲酸乙二醇酯(涤纶)。

材料与方法。在人脐静脉内皮细胞(英文:human umbilical vein endothelial cells,HUVEC)培养3代中,进行了MTS检测,用于实验室研究,利用细胞技术研究药物和医疗器械的细胞毒性。测试涉及使用MTS试剂,即3-(4,5-二甲基噻唑2-基)-5-(3-羧基甲氧基)-2-(4-磺苯基)- 2h -四唑;此外,还使用了吩嗪硫酸甲酯(PMS),其起到了电子结合试剂的作用。在实验中,细胞与聚四氟乙烯和涤纶在37℃,5% CO2含量下孵育24小时。在标准生长培养基中培养人脐静脉内皮细胞作为对照。经吩嗪硫酸甲酯存在时,内皮细胞线粒体脱氢酶将MTS降低为甲瓒,其中有蓝色染色。使用Stat Fax3200分析仪(microplate reader)Awareness technology Inc.Palm City Fl.(美国)进行细胞培养上清液光热测定。

结果。涤纶组光密度的最低平均值平为0.21(0.20-0.22)个光密度单位,对照组平均光密度最高,为0.36(0.35-0.38)个光密度单位;聚四氟乙烯组指标为0.35(0.33-0.36)。实验组比较,对照组与涤纶(p<0.001)、对照组与聚四氟乙烯(p=0.037)、涤纶与聚四氟乙烯(p<0.001)差异有统计学意义。与对照组相比,涤纶潜伏期导致细胞代谢活性下降41.7%(p<0.001)。暴露于聚四氟乙烯的细胞代谢活性与对照组接近,即符合内皮细胞体外培养的最佳条件。

结论。与聚对苯二甲酸乙二醇酯(涤纶)相比,聚四氟乙烯(PTFE)是体外内皮细胞代谢活动最不明显的抑制剂。

I.P. Pavlov Russian Medical Biological Herald. 2020;28(2):183-192
pages 183-192 views

Research of physical and mechanical characteristics of suture material in experiment in operations on liver

Lipatov V., Severinov D., Denisov A., Lazarenko S., Grigor’yev N.

摘要

Taking into account the peculiarities of the blood supply to the liver and the structure of its parenchyma, and, as a result, considerable difficulties in providing reliable hemostasis without additional traumatization, a surgeon needs to be careful when performing a surgical manipulation. Despite a large number of modern methods for stopping parenchymal bleeding, many practi-tioners give preference to classic methods of hemostasis, including ligation of bleeding vessels in the bulk of the organ using specialized sutures. One of the most serious complications of the use of suture material is cutting of organ tissue, which leads to enhanced bleeding and expansion of the area of damage. At the moment, the tactics of choosing suture material for surgical procedures is empirical. In this context, the aim of this study was to assess the physico-mechanical properties of suture material regarding its structure, and to develop a criterion for choosing surgical sutures for surgical procedures. For the study, the liver was removed out of corpses of males of 35 to 40 years of age, after which separate sections of 7.5×7×4 cm in size were obtained from it. Then a wound 3 cm long and 2 cm deep was made. The wound was sutured with a simple interrupted suture without tightening, but with application of one simple half-node. For suturing, catgut, twisted capron and polyglycolide thread were used. Attention was paid to the maximal force applied at the moment of cutting (Fmax) and the degree of pulling the thread at the moment of cutting (Lu). The analysis of the data was based on comparison of Fmax and Lu parameters. This method permits to refuse from the empirical approach to the choice of suture material for operations on the liver, and to develop a criterion for choosing surgical sutures.

I.P. Pavlov Russian Medical Biological Herald. 2020;28(2):193-199
pages 193-199 views

在严重下肢缺血情况下采用人工假体复腘胫骨段效果的改善

Matyushkin A., Lobachev A.

摘要

目的:目的分析人工假体在严重下肢缺血患者行股骨远端腘窝及胫骨旁路手术的近期及远期效果。

材料与方法:在2009-2017年期间,下肢慢性动脉供血不足严重危重阶段109例在D.D.Pletnev City Clinical Hospita国家预算机构的莫斯科大学外科诊所接受了手术。他们进行了股骨远端腘动脉旁路移植术或股骨胫骨旁路移植术,使用人工植体的聚四氟乙烯(PTFE)。33例(30.3%)患者搭桥手术是用人造假体进行的,76例(69.7%)采用外植体结合自体静脉,44例(40,4%)采用人工假体+自体静脉,32例(29.3%)采用根据补片或袖口类型进行远侧吻合口。两组患者中有14例(12.8%)在干预过程中辅以术中小腿动脉球囊血管成形术。对手术后5年的长期结果进行评估。Kaplan-Meyer生存分析用于计算结果。

结果:人工假体5年累计通行性为42.9%。然而,使用假体联合自体静脉,其采用联合分流或远侧吻合口,可显著提高累计通行性(54.5%),以及保肢功能(83.6%)。

结论。所获得的结果允许推荐在没有完全自体静脉发生的情况下,使用人工假体联合远侧吻合口的自体静脉成形术,或者把假体和小的自体静脉结合起来。为了改善长期效果,有必要对此类分流进行长期定期监测,并及时实施反复干预。

I.P. Pavlov Russian Medical Biological Herald. 2020;28(2):200-212
pages 200-212 views

Methods of pharmacological correction of intrauterine growth restriction syndrome

Klycheva O., Khuraseva A.

摘要

Aim. Comparative analysis of the effectiveness of pharmacological correction of intrauterine growth restriction syndrome (IGRS) by monotherapy with diosmin and dipiridamol.

Materials and Methods. Retrospective and prospective examination of 80 pregnant women with singleton pregnancy with gestational age from 28 to 36 weeks with confirmed diagnosis of IGRS of 1 or 2 degree asymmetric form was conducted. 75.0% Of pregnant women that participated in the study, were of the average reproductive age (23-29 years of age). The share of young first-time-mother in I group was 10.0%, in II group – 15.0%, the share of age first-time-mothers was 17.5 and 10.0%, respectively. Extended history taking and history analysis, general clinical and obstetric-gynecological examination were conducted, laboratory and ultrasound methods were used. Newborns were evaluated on Apgar scale at birth and in 5 minutes. In the early neonatal period, inborn and transient pathological syndromes were evaluated.

Results. In patients receiving diosmin (n=40), reduction  of the resistance index of the right and left uterine arteries  to 0.440±0.004 and 0.460±0.004, respectively,  and of the umbilical artery to 0.56±0.02 was achieved, that is lower than in the group of patients taking dipiridamol (n=40). A positive influence of diosmin on the intrauterine condition of the fetus was found that was manifested by its increased compensatory capacities for adaptation  to chronic hypoxia in reliably higher percent of cases as compared to dipiridamol. After pharmacological correction, a tendency to normalization of the main parameters of the system of hemostasis was found in higher percent in women taking diosmin. This, in turn, produced a favorable influence on the volume of blood loss in physiological deliveries. Thus, in I group the average amount of blood loss was 180±15 ml, while in II group it was 265±15 ml (р<0.05). However, in operative delivery no such differences were obtained. In I group immediately after deliveries 10.0% of newborns were transferred to the resuscitation and intensive care unit, in II group transfer to resuscitation department was required in 37.5% of infants (<0.05). All the rest of children immediately after birth in the satisfactory condition were placed to one ward with mother, and they did not require resuscitation measures. 

Conclusion. Increase in the compensatory capacities of the fetus was shown in the conditions of chronic intrauterine hypoxia in a reliably higher percent of cases after pharmacological correction with diosmin. This, in turn, produced a favorable influence on perinatal outcomes, birth of children with a higher parameters of mass and height and health index.

I.P. Pavlov Russian Medical Biological Herald. 2020;28(2):213-222
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Reviews

Epidemiological safety as a component of the operational management unit of the infocenter in introduction of lean manufacturing in a medical organization that provides primary health care

Kurmangulov A., Reshetnikova Y., Brynza N.

摘要

Currently, the primary health care system is undergoing active reformation. Lean manufacturing technologies are being introduced into the activities of medical organizations that help reduce the loss of medical and auxiliary processes. One of the main methods of lean production is visualization, which is implemented in the operational management of a medical organization in the form of creating information centers (InfoCenters) that reflect the main parameters of the activity of a medical organization in the SQDCM system: safety, quality, order execution, costs and a comfortable environment. Criteria of safety of medical activity most relevant for the national healthcare system are parameters of epidemiological safety. A parameter most difficult for indication, but necessary for reflection of epidemiological diagnostics in the InfoCenter is the accident rate at work.

Aim. Generalization of literature data on the possibility of including epidemiological safety parameters into the operational assessment of the InfoCenter.

Epidemiological studies conducted in our country in medical organizations of various profiles show an increasing rate of emergency situations among the medical personnel. With this, the system of indication and identification of all emergency cases still remains imperfect, and medical personnel often hide cases of emergency situations.

Conclusion. Introduction of criteria of epidemiological safety into the practical activity of a medical organization as a component of the operational management unit of the InfoCenter will contribute to the formation of functioning and constantly improving system of analysis of the activity of medical organizations, to the control of provision of medical care, and  to standardization of invasive procedures to ensure epidemiological safety. The key tasks of the InfoCenter are: focusing the attention of medical organization employees on problems, prompt response to emerging problems and risks, and also ensuring effective communication of all participants of operational meetings in a single information space.

I.P. Pavlov Russian Medical Biological Herald. 2020;28(2):223-233
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Disadaptive genetic-evolutionary processes in human populations of industrial cities

Artemenkov A.

摘要

Aim. Generalization of literature and proprietary data on genetic-physiological and evolutionary processes occurring in human populations in environmentally neglected industrial cities.

In the review information is given about damage to the genetic apparatus of cells of a human organism under influence of unfavorable environmental factors and disadaptations of different
genesis. To denote the totality of alterations induced by the given exposure, a new term is introduced – ‘genetics of disadaptations’. The information of mutagenic factors of the environment of industrial cities associated with growth of oncological diseases and of malformations resulting from chromosomal aberrations in cells is generalized. The problem of genetic burden of human populations
in environmentally neglected territories and of the influence of disadaptive factors on this process is discussed. Information of the ecological situation and morbidity of the population in Cherepovets industrial city is given. A role of disadaptations in genetic-evolutionary processes occurring in
human populations is shown. The cause of different manifestations of disadaptation in the population is stated to be divergence of traits. A hypothesis is proposed and evidences are given in favor of the existence of natural selection for a disadaptive trait in human populations. It is suggested that being accumulated in a human organism, disadaptive disorders may be transmitted to the next
generations reducing vital ability of organisms and inducing different diseases.

Conclusion. Within the topic, examples of different prophylactic measures for improving the health of the population of industrial cities are given to prevent unfavorable alterations of human genome under the influence of unfavorable ecological and related disadaptive factors.

I.P. Pavlov Russian Medical Biological Herald. 2020;28(2):234-248
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Consanguineous marriage as socio-medical problem

Bobdjonova O., Abdurakhmanova F.

摘要

Despite the availability of a large amount of scientific data on the negative impact of consanguineous marriages on the health of children born in such families, the significance of this problem is not decreasing in a number of countries.

Aim. Analysis of the modern scientific base on the problem of consanguineous marriages, assessment of their impact on the development of a particular pathology in children.

The article reflects the position of modern clinical recommendations, the results of recent studies, and some controversial and unresolved issues. Despite the emerging trend of declining consanguineous marriages in recent decades, this problem involves at least 20% of the population and dozens of countries around the world. The prevalence of consanguineous marriages in the world varies significantly, ranging from 0.1-0.4% in the United States and European countries to more than 50% in North Africa, the Middle East and West Asia. The most common form of consanguineous marriage is a marriage between first cousins. In general, rural residents who have a lower level of education are more likely to enter into consanguineous marriages.

Conclusion. Despite a number of positive social and economic aspects of consanguineous marriages, from the point of view of genetics and medicine, it is necessary to take into account the negative impact of consanguineous marriages, which consists in an increased genetic risk to offspring and a high incidence of congenital pathology in newborns. An assessment of the socio-demographic aspects of consanguineous marriages shows that their greater prevalence is often due to poor economic conditions, lack of education, and low social security.

I.P. Pavlov Russian Medical Biological Herald. 2020;28(2):249-258
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