卷 29, 编号 1 (2021)

Aim. This investigation seeks to determine the incidence of phenylketonuria in the Ryazan region, assess the spectrum of mutations in the PAH gene (phenylalanine hydroxylase), investigate the interrelationship between the disease’s clinical course, the phenylalanine blood level, and the patient’s genotype.

Materials and Methods. The incidence of phenylketonuria was studied based on the data of massive neonatal screening for the period from 2000 to 2019. Molecular genetic examination of mutations was conducted in 39 patients using the allele-specific multiplex ligation method. The interrelationship between the phenylalanine blood level on the fifth day of life and retest, the disease’s clinical course, and the patient’s genotype was assessed according to the medical record data of 33 patients under dispensary observation in a medico-genetic clinic. The patients were divided into two groups. The first group (n=21) had two «severe» mutations (residual activity of phenylalanine hydroxylase <10%). The second group (n=12) had one «severe» and one «mild» mutation (the residual activity of the enzyme >10%).

Results. The incidence of phenylketonuria in the Ryazan region was one in 5054 newborns, exceeding the Russian Federation’s average parameters. Eighteen mutations were discovered in the PAH gene. The most frequent was the R408W mutation (56.4% alleles). The second most frequent mutations were the IVS10-11G>A (6.4%) and P281L (5.1%). The R158Q and Y418C mutations occurred with a frequency of 4.1% and Е280К mutation of 2.7%. All the rest of the
mutations occurred as single cases. Investigation of the interrelationship between the phenylalanine blood level, the disease’s clinical course, and the patient’s genotype revealed a reliably higher content of amino acid in the first group on retest (32.1±1.7 mg/% vs. 17.7±1.5 mg/% in the second group, р<0.001) and predomination of more severe forms of phenylketonuria (90.5% vs. 41.7%, respectively, р<0.001). Disorders in neuropsychic and speech development were present in 28.6% of patients in the first group but were absent in the second group.

Conclusion. By conducting the study, the incidence of phenylketonuria was determined in the Ryazan region. The spectrum of mutations in the PAH gene was defined. The interrelationship between the disease’s clinical portrait, the phenylalanine blood level, and the patient’s PAH genotype was revealed.

Aim. To evaluate the potential utility of fibrin matrices containing 10, 20, and 25 mg/ml of fibrinogen (fibrin-10, fibrin-20, and fibrin-30, respectively) in vascular tissue engineering (VTE).

Materials and Methods. Fibrinogen was isolated using the method of ethanol cryoprecipitation and polymerized using a solution of thrombin and CaCl₂. The fibrin structure was studied in a scanning electron microscope, and the physical and mechanical properties of the material were tested on a Zwick/Roell test machine. The metabolic activity of endothelial cells (EC) on the fibrin surface was evaluated by the MTT assay, and the viability of fibroblasts in the thickness of fibrin and possibility for migration by in fluorescent and light microscopy. Percent of fibrin shrinkage was determined from the difference in the sample volumes before and after removal of moisture.

Results. The fiber diameter did not differ among all fibrin samples, but the pore diameter in fibrin-30 was smaller than those in fibrin-10 and fibrin-20. A possibility for migration of fibroblasts into the depth of the fibrin matrix and preservation of 97-100% viability of cells at a depth 5 mm was confirmed. The metabolic activity of EC on the surface of fibrin-20 and fibrin-30 exceeded that on collagen, fibronectin, and fibrin-10. All fibrin samples shrank in volume to 95.5-99.5%, and the highest shrinkage was seen in fibrin-10. The physical and mechanical properties of fibrin were inferior to those of human A. mammaria by a factor of 10.

Conclusion. Fibrin with fibrinogen concentrations of 20 and 30 mg/ml maintains a high metabolic and proliferative activity of EC on the surface and also a high viability of fibroblasts in the matrix. Its availability, ease of preparation, and a number of other favorable properties make fibrin a promising material for VTE. However, the problem of insufficient strength requires further investigations.

目的：用于局灶性和颞叶性癫痫研究自主调节和自主支持的机制。

材料和方法。我们检查了对照组中的36人（19名男性和17名女性，平均年龄33.7±1.4岁）（无癫痫发作史，脑电图上癫痫样活动的患者）， 68例（32例男性和36例女性，34.1±1.5岁）患有局灶性癫痫（额叶癫痫36例，颞部癫痫32例）。对心率变异性和皮肤交感力的生理指标进行了评估。

结果。两组患者均发现了交感神经的患病率，而根据诱发的皮肤交感神经电位的分析，癫痫患者组中的超节律性自主神经活动活跃。根据颞叶癫痫患者组的相关分析结果，初始状态的特征是系统内压力增加，这反映出较高的生理成本。对数回归分析模型可基于自主神经活动支持指数将局灶性癫痫患者分为不同病程的人群。

结论。焦点性癫痫患者群体中，交感效应占主导地位，而且在营养调节的超段中心中也有很大的活动性。系统内的植物调节比率表明，系统内的压力增加，并限制了颞部患者的功能储备。癫痫一套营养指标通过逻辑回归分析法，可以将病人分为不同的焦点性癫痫群体。

在外科动脉内膜切除术中，需要颈动脉交叉夹持以进行动脉切开和斑块清除。颈动脉阻断减少了流向Willis环的血流量，一些患者对颈内动脉（ICA）暂时性闭塞表现出不耐受。

目的。本研究论证了颈动脉交叉钳位不耐受（CCI）患者局部麻醉的安全性以及预测这种情况的危险因素。

材料和方法。回顾性分析发现，2019年1月至2020年12月期间接受颈动脉内膜切除术的所有患者（n=53，29名男性，年龄56-90岁（中位数78）），手术适应症为70%-99%的ICA狭窄或症状性狭窄。

外科手术。在胸锁乳突肌的前缘做一个切口。颈总动脉（CCA）从周围组织中分离出来，并向分叉处延伸。之后，分离颈内动脉和颈外动脉。静脉注射肝素（5000U），收缩压升高并保持在160mm Hg以上。接着，进行交叉钳位耐受性试验60s。使用夹钳期间，对患者的神经系统进行仔细观察。若出现颈动脉交叉钳位不耐受（CCI），插入临时分流器并继续手术。动脉切开术从颈总动脉开始，持续到颈内动脉。完全清除斑块，用补片覆盖动脉切开处。在完成缝合之前，夹钳被部分移除，利用血流冲洗碎屑后可松开外动脉和总动脉。最后移除颈内动脉钳。

结果。8例接受交叉钳夹耐受试验的患者表现为不耐受。所有这些病例的手术均通过分流继续进行。进一步的手术过程并不复杂。院内死亡率为零，仅1例发生短暂性脑缺血发作。冠状动脉疾病（CAD）[优势比（OR）12.65，95% 置信区间（CI）1.43–112.50]、脑血管事件史[OR 10.50，95% CI 1.83–60.30]、对侧狭窄70%或以上[OR 26.66，95% CI 2.29–304.37]与CCI和分流的必要性有显著关联。其余因素与不耐症无明显关联。

结论。区域麻醉是鉴别CCI患者和安全手术的安全方法。对侧ICA狭窄和脑血管事件史是预测CCI的重要因素。

Aim. This study aimed to investigate potential use of radiofrequency obliteration (RFO) of angiomatous tissues in patients with venous malformations.

Materials and Methods. A single-center study retrospectively involved 42 clinical cases [57.1% of men (n=24), aged 18-44 years; 42.8% of women (n=18) aged 18-56 years] of venous angiodysplasia, with a total of 46 interventions using RFO. Clinical manifestations of the disease were primarily characterized by pain syndrome (71.4%), cosmetic defect (100%), and edema syndrome (95.2%).

Results. Clinical improvement was possibly achieved with the reduction of the intensity of manifestations of angiomatous processes in 37 patients (88.1%). Stable and partial obliterations of caverns in the zone of exposure to radiofrequency were recorded in 37 (88.0%) and 5 (12.0%) patients, respectively. In caverns with small diameter, obliteration was achieved in 100% of the cases. Postoperative complications included bleeding (2.4%), burns in the zone of electrode introduction (2.4%), lymphorrhea (2.4%), and hypesthesia (2.4%). With this, according to the results of duplex scanning performed on control visits, no significant disease progression was observed. In the same patient, several complications could occur. All complications regressed within a month and required no treatment in hospital conditions.

Conclusion. RFO showed advantage as a minimally invasive treatment method of venous angiodysplasias. Results suggest that RFO can be recommended for use in patients with >1 cm depth of lesion with caverns of medium and large diameter as an independent treatment method and in combination with standard resection methods.

Aim. This study aimed to compare the effectiveness of conservative treatment methods, namely, estriol-containing cream and non-hormonal drug, in girls with labial adhesion (LA) in the clinical and diagnostic center of N.V. Dmitrieva Regional Children’s Clinical Hospital.

Materials and Methods. A retrospective analysis of pediatric clinical cases of labial adhesion (n=300) was carried out in N.V. Dmitrieva Regional Children’s Clinical Hospital in the period from 2016 to 2018. The study included 150 girls diagnosed with labial adhesion who were treated with estriol-containing cream (study group) and 150 girls with the same diagnosis (control group) who were treated with a non-hormonal gel containing onion extract 10 g, heparin 5000 IU, and allantoin. The age of the participants ranged from 4 months to 2 years and 2 months. Informed consent was obtained from the girls’ parents for the examination of the child, use of estriol-containing drug or a drug of non-hormonal composition, and processing of personal data. Recovery was considered the absence of recurrent synechiae for 2 years, improvement as not more than one recurrence not earlier than 6 months after the previous treatment, and no effect as two or more recurrences earlier than 6 months.

Results. In the main group, recovery, improvement, and no effect were achieved in 108 (72%), 39 (26%), and 3 (2%) girls, respectively. In the control group, recovery, improvement, and no effect was achieved in 30 (20%), 75 (50%), and 45 (30%) girls, respectively.

Conclusion. The results revealed the effectiveness and safety of using estriol-containing drugs in young girls diagnosed with labial adhesion.

钝性胸部创伤导致的气管支气管损伤很少见。颈部气管钝性损伤是一种更为罕见的病理表现，对临床医生来说是一个严重的诊断问题。喉和气管损伤的死亡率为40-80%。气管的颈部虽然被颈部、脊柱、锁骨和下颌骨的肌肉所覆盖，但仍然很脆弱。刺伤中颈部气管的损伤常与邻近结构一起发生。钝性创伤中由于创伤剂的直接作用，会发生运动 可移动的气管到颈椎。它伴随着气管软骨，其膜部分和周围软组织的损伤，同时保持皮肤的完整性。

不超过4%的气管破裂发生在离环状软骨最远的1厘米处。气管完全破裂或与喉部分离是一种极为罕见的病理现象。由于明显的呼吸系统紊乱，相当一部分受害者死于受伤部位。

本文报告一位41岁的Z.病人，气管与喉部完全分离，治疗成功的临床病例。原因的气管损坏在一次交通事故中脖子钝伤。这一临床病例的一个特点是，受害者在受伤后2天被送往专门的胸部外科，并进行了功能性气管造口术。

结论。气管损伤是一种潜在的致命疾病，因此，早期诊断气管支气管损伤是非常重要的，它可以及时手术，降低死亡风险。头、颈、胸外伤患者临床资料不合适，推荐的标准治疗程序效果不佳，临床医生应提高警惕，排除气管、支气管损伤。

X线计算机断层扫描和纤维支气管镜检查是诊断气管支气管损伤的可靠方法。手术过程中应尽量进行一期气管缝合，避免预防性气管切开和延迟干预，这与预后较差和并发症发生率高有关。

很少有报告涉及慢性淋巴细胞白血病（CLL）和急性髓细胞白血病（AML）在同一患者中共存的情况，而这种现象经常是由化疗药物导致的。癌症患者的血液参数变化可能被解释为疾病进展或与积极治疗相关的医源性影响，从而导致诊断延迟。在本文中，我们呼吁大家留意AML在CLL患者中的进展及对其诊断的挑战。

全身性炎症对动脉粥样硬化的发病机理有重要贡献，并且是众多研究的主题。旨在分析动脉粥样硬化发展机制的作品，通常包括动物实验。描述、论证和选择适当的模型是每项此类研究的首要任务。

目的：慢性阻塞性肺疾病（COPD）动脉粥样硬化动物模型脂质代谢和全身炎症特征的评价。

材料和方法。对小鼠、大鼠和家兔的脂质代谢和免疫应答的物种特异性特征进行了交叉连接分析，并对Toll样受体4（TLR4）与人类的差异进行了生物信息学分析。在国家生物技术信息中心（NCBI）和通用蛋白质资源（UniProt）的GenBank国际数据库中，对人、小鼠、大鼠和兔TLR4受体的氨基酸序列进行了搜索和分析。多受体氨基酸序列比对在Clustal Omega软件1.2.4版中执行。分子系统发育树的重建与可视化使用MEGA7程序根据最近邻居的方法（英语：Neighbor-Joining）和最大经济性的方法（英语：Maximum Parsimony）。

结果。研究结果表明，人类、小鼠和家兔在脂代谢特征上存在种属特异性差异，在分析研究结果时应予以考虑。

结论。由固有免疫系统介导的脂质代谢异常和全身性炎症与COPD的动脉粥样硬化的发病机制有关，在分析研究结果时必须考虑到特定物种的特征。

This article contains a literature review of the results of experimental and clinical studies of the influence of physical exercise on the clinical course of bronchial asthma (BA) and presents the pathophysiological mechanisms of this influence. A high prevalence of sedentary lifestyle among patients with BA, its cause, and consequences are considered. Some studies have shown that patients with BA more rarely perform physical activity, and their physical exercises are less intensive and/or take shorter time. Effects of different variants of physical exercise on patients with BA are also discussed. Regular aerobic and mixed exercises of moderate intensity reliably lead to an improvement of the quality of life, reduction of exacerbations, use of inhalators «on demand», nocturnal symptoms, and sleep; to a reduction of the hyperresponsiveness of the bronchi, eosinophil count in the sputum, levels of interleukin-6, and monocyte chemotactic factor-1; and to an increase in the level of interleukin-10. SOCS-JAK-STAT plays a role in the mechanism underlying the influence of aerobic exercises on inflammation, remodeling, and hyperresponsiveness of the airways by decreasing the expression of Th2 cytokines, chemokines, adhesion molecules, growth factors, NF-kB, and P2X7 receptors by the epithelium of the airways and by an increase in interleukin-10 level.

Conclusion. Data available in the literature are obtained on small cohorts of foreign patients. Clinical data devoted to the influence of aerobic exercises on control of BA and parameters of the respiratory functions are contradictory. Further investigations are required in this field.

本封致编辑的信将继续《物质诱发精神病和精神分裂症：相互作用点》（Fedotov I.A., Quattrone D., Shustov D.I. Substance-induced psychosis and schizophrenia: the interaction point. I.P. Pavlov Russian Medical Biological Herald. 2020;28(4):593-604. doi:10.23888/PAVLOVJ2020284593-604)一文的作者发起的讨论，探讨继发性精神病和精神分裂症之间的异同。