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Efficacy and safety of dual therapy - biological and small molecules in patients with ulcerative colitis 溃疡性结肠炎患者接受生物和小分子双重疗法的疗效和安全性
Pub Date : 2024-01-17 DOI: 10.31146/1682-8658-ecg-217-9-5-12
O. Knyazev, A. Kagramanova, A. Lishchinskaya, I. Li, E. Sabelnikova, T. .. Shkurko, B. Nanaeva, T. Baranova, M. Timanovskaya
Сombination of two or more biological or immunosuppressive drugs in order to achieve a synergistic effect in patients with refractory inflammatory bowel disease (IBD) has been in the spotlight for many years. Combination therapy may include various medications, most often biological and immunosuppressants. Despite the fact that biological therapy of IBD has traditionally focused on drugs that block tumor necrosis factor-alpha, the development of new drugs that act on different targets, such as vedolizumab, ustekinumab, tofacitinib or ozanimod, has made it possible to use combined immunosuppressive therapy. The treatment algorithm suggests various combinations of dual biological therapy for 2 categories of patients with IBD: patients with well-controlled luminal IBD and uncontrolled extra-intestinal symptoms (indications such as arthritis or psoriasis) and patients with refractory, uncontrolled IBD. Thus, data on the efficacy and safety of dual biological therapy as a method of treating Crohn’s disease (CD) or ulcerative colitis (UC) remain very limited. In fact, the vast majority of literature consists of individual cases and a series of cases. Given the lack of studies with a high level of evidence, gastroenterologists have turned to larger studies of dual biological therapy in other areas of medicine, such as rheumatology and dermatology. The aim of this article is to demonstrate clinical experience of combination therapy with genetically engineered biological drugs and selective immunosuppressors in UC, to analyze potential adverse effects or risks associated with combination therapy, and to determine future directions in the use of this treatment.
多年来,两种或两种以上生物或免疫抑制剂的联合治疗一直是难治性炎症性肠病(IBD)患者的关注焦点。联合疗法可包括多种药物,最常见的是生物制剂和免疫抑制剂。尽管 IBD 的生物疗法传统上以阻断肿瘤坏死因子-α 的药物为主,但随着作用于不同靶点的新药(如维多珠单抗、乌斯特库单抗、托法替尼或奥扎尼莫德)的开发,使用联合免疫抑制剂疗法成为可能。治疗算法建议对两类 IBD 患者采用不同的双重生物疗法组合,一类是管腔型 IBD 控制良好且肠道外症状(关节炎或银屑病等适应症)未得到控制的患者,另一类是难治性、未得到控制的 IBD 患者。因此,有关双重生物疗法作为治疗克罗恩病(CD)或溃疡性结肠炎(UC)的方法的有效性和安全性的数据仍然非常有限。事实上,绝大多数文献都是由个别病例和系列病例组成的。鉴于缺乏高水平证据的研究,胃肠病学家转而在风湿病学和皮肤病学等其他医学领域开展更大规模的双重生物疗法研究。本文旨在展示基因工程生物药物和选择性免疫抑制剂联合治疗 UC 的临床经验,分析联合治疗可能带来的不良反应或风险,并确定该疗法的未来使用方向。
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引用次数: 0
Molecular-genetic foundations of energy exchange and physical qualities of man. Research perspectives 人类能量交换和身体素质的分子遗传基础。研究视角
Pub Date : 2024-01-17 DOI: 10.31146/1682-8658-ecg-217-9-222-230
T. Maksimycheva, E. Kondratyeva, V. M. Popova
Human physical qualities represent a complex trait influenced by environmental and genetic factors, with most traits being polygenic in nature. The study of the relationship between molecular genetic data, physical characteristics and metabolic individuality (regulation of biogenesis, energy balance, lipid metabolism, glucose homeostasis, etc.) is a promising vector of research, both in the population as a whole and in various nosologies, primarily for hereditary and metabolic diseases characterized by impaired physical development and metabolic balance, including cystic fibrosis (CF), obesity, diabetes mellitus. The first studies were devoted to the study of these parameters in athletes. The genotype-phenotype study in CF has been actively studied for the past few years. It has been shown that environmental factors can determine clinical polymorphism in CF, which account for nearly 50% of lung function variability in this disease. However, CF patients with similar molecular genetic variants of the CFTR gene and in a single habitat (for example, in siblings) can have highly variable clinical manifestations. Genes whose products provide cell energy exchange (PPARA, PPARG, PPARD, PGC-1, UCP2, UCP3, ACTN, ACE) can also be “modifiers” and have an effect on the phenotype, the difference in clinical manifestations of the disease of patients with CF, the relationship of which in this category of patients has not been studied. The world has seen a steady increase in obesity and its complications. Patients with CF from the category of persons with nutritional deficiency in recent decades began to move into the category of overweight patients, which requires study. This review summarizes the recent achievements of studying genes whose products provide energy exchange of the cell, discusses the development of the relationship both with the physical characteristics of individuals and with pathological changes in the body as a result of the appearance of metabolic products in excess or with altered physicochemical properties and functional activity parameters leading to various diseases.
人的身体素质是一种受环境和遗传因素影响的复杂特征,大多数特征具有多基因性。研究分子遗传数据、身体特征和代谢个体性(生物生成调节、能量平衡、脂质代谢、葡萄糖稳态等)之间的关系,是一项很有前景的研究方向,既适用于整个人群,也适用于各种疾病,主要是以身体发育和代谢平衡受损为特征的遗传性和代谢性疾病,包括囊性纤维化(CF)、肥胖症、糖尿病等。最初的研究致力于研究运动员的这些参数。在过去几年中,CF 的基因型-表型研究一直在积极进行。研究表明,环境因素可决定 CF 的临床多态性,这种多态性占该病肺功能变异的近 50%。然而,具有类似 CFTR 基因分子遗传变异的 CF 患者,在单一生境中(如兄弟姐妹)的临床表现可能会有很大差异。其产物提供细胞能量交换的基因(PPARA、PPARG、PPARD、PGC-1、UCP2、UCP3、ACTN、ACE)也可能是 "修饰因子",对 CF 患者的表型、疾病临床表现的差异有影响,但这类患者与这些基因的关系尚未研究清楚。肥胖症及其并发症在全球持续增加。近几十年来,CF 患者从营养缺乏者类别开始进入超重患者类别,这需要进行研究。这篇综述总结了最近在研究其产物为细胞提供能量交换的基因方面取得的成就,讨论了这些基因与个体的身体特征以及因代谢产物过量或理化性质和功能活动参数改变而导致各种疾病的机体病理变化之间的关系发展。
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引用次数: 0
Diagnostic and therapeutic possibilities of balloon-assisted enetroscopy in clinical practice 球囊辅助内窥镜在临床实践中的诊断和治疗可能性
Pub Date : 2024-01-17 DOI: 10.31146/1682-8658-ecg-217-9-85-88
A. T. Kortieva, V. S. Krushelnitskiy, S. A. Gabriel, V. Dynko, A. Y. Guchetl
The aim. To evaluate the effectiveness of endoscopic techniques for gastrointestinal bleeding of unknown origin in the conditions of GBUZ “KKB No. 2” and to determine the most effective therapeutic tactics. Materials and methods. The basis for our study was the analysis of the results of treatment of 47 patients with suspected small intestine bleeding in the period 2018-2023 in the State Medical Institution “KKB No. 2” of the city of Krasnodar. The study group was dominated by men -25 patients (53%) compared with women - 27 patients (47%). The age of the patients ranged from 18 to 89 years. VCE was performed in 16 patients. In controversial and unconvincing cases, BAE-14 patients were performed. A comprehensive examination of VCE + BAE was performed in 17 patients. Results: The most rational method of endoscopic hemostasis in small intestine bleeding, according to our observation, is endoscopic clipping in combination with conservative therapy. Results. According to our observation, the most rational method of endoscopic hemostasis in small intestinal bleeding is endoscopic clipping in combination with conservative therapy. Conclusion. The capabilities of clinicians in the differential diagnosis of pathological conditions of the small intestine are enhanced by the availability of modern equipment in medical and preventive institutions, as well as to perform minimally invasive treatment, reducing the rehabilitation time due to the reduction of surgical trauma.
目的评估在 "KKB 2 号 "GBUZ 条件下采用内窥镜技术治疗不明原因消化道出血的效果,并确定最有效的治疗策略。材料和方法。我们研究的基础是对克拉斯诺达尔市 "KKB 2号 "国立医疗机构2018-2023年间47名疑似小肠出血患者的治疗结果进行分析。研究对象以男性为主--25 名患者(占 53%),女性为 27 名患者(占 47%)。患者年龄从 18 岁到 89 岁不等。16名患者进行了VCE检查。在有争议和难以令人信服的病例中,14 名患者接受了 BAE 检查。17名患者进行了VCE+BAE综合检查。结果:根据我们的观察,小肠出血时最合理的内镜止血方法是内镜下剪切术结合保守疗法。结果根据我们的观察,小肠出血最合理的内镜止血方法是内镜下剪切术结合保守疗法。结论由于医疗和预防机构拥有现代化设备,临床医生鉴别诊断小肠病变的能力得到了提高,同时还能进行微创治疗,减少了手术创伤,缩短了康复时间。
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引用次数: 0
Vitamin D and the epigenome: basic definitions, mechanisms and clinical effects 维生素 D 和表观基因组:基本定义、机制和临床效果
Pub Date : 2024-01-17 DOI: 10.31146/1682-8658-ecg-217-9-209-221
A. I. Khavkin, E. Loshkova, I. V. Doroshenko, E. Kondratyeva, M. I. Erokhina
Epigenetic mechanisms play a crucial role in the regulation of gene expression. The underlying mechanisms include DNA methylation and covalent modification of histones by methylation, acetylation, phosphorylation, or ubiquitination. The complex interplay of various epigenetic mechanisms is mediated by enzymes operating in the cell nucleus. Modifications in DNA methylation are carried out primarily by DNA methyltransferases (DNMTs) and ten-eleven translocation proteins (TETs), while a variety of enzymes such as histone acetyltransferases (HATs), histone deacetylases (HDACs), histone methyltransferases (HMTs), and histone demethylases (HDMs)) regulate histone covalent modifications. In many pathological conditions such as cancer, autoimmune, microbial inflammatory, metabolic, allergic diseases and/or low vitamin D availability, the epigenetic regulatory system is often disrupted. Vitamin D interacts with the epigenome at several levels. First, critical genes in the vitamin D signaling system that encode for the vitamin D receptor (VDR) and the enzymes 25-hydroxylase (CYP2R1), 1α-hydroxylase (CYP27B1), and 24-hydroxylase (CYP24A1) have large CpG islands in their promoters. areas and therefore can be suppressed by DNA methylation. Second, the VDR protein physically interacts with coactivator and corepressor proteins, which in turn are in contact with chromatin modifiers such as HATs, HDACs, HMTS, and chromatin remodelers. Third, a number of genes encoding chromatin modifiers and remodelers, such as HDM from the Jumonji C (JmjC) domain containing proteins and lysine-specific demethylase (LSD) families, are primary targets for VDR and its ligands. Finally, there is evidence that certain VDR ligands have DNA demethylating effects. In this review, the authors discuss the regulation of the vitamin D system by epigenetic modifications and how vitamin D contributes to the maintenance of the epigenome and assess its impact on health and disease.
表观遗传机制在基因表达调控中起着至关重要的作用。其基本机制包括 DNA 甲基化以及通过甲基化、乙酰化、磷酸化或泛素化对组蛋白进行共价修饰。各种表观遗传机制的复杂相互作用是由细胞核中的酶介导的。DNA 甲基化的修饰主要由 DNA 甲基转移酶(DNMTs)和十-十一转位蛋白(TETs)进行,而组蛋白乙酰转移酶(HATs)、组蛋白去乙酰化酶(HDACs)、组蛋白甲基转移酶(HMTs)和组蛋白去甲基化酶(HDMs)等多种酶则调节组蛋白的共价修饰。在许多病理情况下,如癌症、自身免疫性疾病、微生物炎症、代谢性疾病、过敏性疾病和/或维生素 D 不足时,表观遗传调控系统往往会受到破坏。维生素 D 在多个层面上与表观基因组相互作用。首先,维生素 D 信号系统中编码维生素 D 受体(VDR)、25-羟化酶(CYP2R1)、1α-羟化酶(CYP27B1)和 24-羟化酶(CYP24A1)的关键基因在其启动子中有较大的 CpG 岛,因此会受到 DNA 甲基化的抑制。其次,VDR 蛋白与辅助激活蛋白和核心抑制蛋白发生物理作用,而辅助激活蛋白和核心抑制蛋白又与 HATs、HDACs、HMTS 和染色质重塑因子等染色质修饰因子发生接触。第三,一些编码染色质修饰因子和重塑因子的基因,如含 Jumonji C(JmjC)结构域的 HDM 蛋白和赖氨酸特异性去甲基化酶(LSD)家族,是 VDR 及其配体的主要靶标。最后,有证据表明某些 VDR 配体具有 DNA 去甲基化作用。在这篇综述中,作者讨论了表观遗传修饰对维生素 D 系统的调控,以及维生素 D 如何促进表观基因组的维护并评估其对健康和疾病的影响。
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引用次数: 0
Microbial community structure in dementia and depression as a mirror of ageing “intestinal microbiota - immune system - brain” axis 痴呆症和抑郁症中的微生物群落结构是 "肠道微生物群--免疫系统--大脑 "轴老化的一面镜子
Pub Date : 2024-01-17 DOI: 10.31146/1682-8658-ecg-217-9-49-55
A. Burmistrova, M. E. Cazaux, Y. Filippova
Aim. To assess changes in the structure of the small intestine microbial community in the context of the “gut microbiota-immune system-brain axis” in healthy aging, depression and dementia. Materials and methods. 74 elderly people included in the groups: “Healthy ageing”, “Depression”, “Dementia” were investigated. Evaluation of 5 main types of microorganisms of the small intestine (Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria, Fusobacteria) by method of gas chromatography - mass spectrometry of microbial markers was carried out. For statistics, hierarchical cluster analysis with the construction of a heat map was used. Results. Reconstruction affected 15 out of 30 studied bacterial species of the phylums Firmicutes, Actinobacteria, Proteobacteria in the “Dementia” and “Depression” groups in relation to the “Healthy ageing” group. In depression, the number of all types of bacteria involved in the fermentation of food polysaccharides increased in relation to the “Healthy ageing” group. In dementia, low levels of Clostridium spp., Eubacterium spp., Bifidobacterium spp. was shown, in relation to depression, but number of C. perfringens, С. difficile and facultative anaerobes: Streptococcus spp., Enterococcus spp., Lactobacillus spp., S. aureus, S. epidermidis was increased, compared to “Healthy ageing” group. Conclusions. The indicators of the systems included in the axis “intestinal microbiota - immune system - brain” indicated a pronounced disintegration of the axis in dementia in relation to depression and healthy ageing. The results can be used as biological markers in the differential diagnosis of these pathologies (dementia/depression), which have common risk factors and clinical symptoms.
目的评估健康老龄化、抑郁症和痴呆症患者在 "肠道微生物群-免疫系统-脑轴 "背景下小肠微生物群落结构的变化。材料与方法。将 74 名老年人分为不同组别:"健康老龄化 "组、"抑郁症 "组和 "痴呆症 "组的 74 名老人进行了调查。采用气相色谱-质谱微生物标记法对小肠中的 5 种主要微生物(类杆菌、固着菌、放线菌、变形菌、镰刀菌)进行了评估。在统计方面,采用了构建热图的分层聚类分析。结果显示与 "健康老龄化 "组相比,在 "痴呆症 "组和 "抑郁症 "组的 30 个研究细菌物种中,有 15 个受重建影响,包括固醇菌门、放线菌门和蛋白菌门。在抑郁症患者中,与 "健康老龄化 "组相比,参与食物多糖发酵的各类细菌数量均有所增加。在痴呆症患者中,与抑郁症患者相比,梭状芽孢杆菌属(Clostridium spp.)、优杆菌属(Eubacterium spp.)和双歧杆菌属(Bifidobacterium spp.)的数量较少,但产气荚膜杆菌(C. perfringens)、艰难梭菌(С. difficile)和兼性厌氧菌(facultative anaerobes)的数量较多:与 "健康老龄化 "组相比,链球菌属、肠球菌属、乳酸杆菌属、金黄色葡萄球菌、表皮葡萄球菌的数量有所增加。结论肠道微生物群--免疫系统--大脑 "轴中各系统的指标表明,与抑郁症和健康老龄化相比,痴呆症患者的这一轴明显解体。这些结果可作为生物标记用于这些病症(痴呆症/抑郁症)的鉴别诊断,因为它们具有共同的风险因素和临床症状。
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引用次数: 0
Drug-induced diarrhea: a diverse problem in clinical medicine 药物引起的腹泻:临床医学中的一个多样化问题
Pub Date : 2024-01-17 DOI: 10.31146/1682-8658-ecg-217-9-186-194
A. M. Osadchuk, I. D. Loranskaya, M. A. Osadchuk
Currently, the problem of diarrheal syndrome against the background of therapy with non-antimicrobial drugs, with a frequency of occurrence of up to 24%, has become particularly relevant. This is due to an increase in the number of people taking drug therapy for a long time, an increase in the population of older people, an increase in comorbidity, polypragmasia and hypersensitivity of this group of patients to medications. The mechanism of drug-induced diarrhea is complex and insufficiently studied. Many drugs are able to affect various pathogenetic links, causing disorders of the intestinal microbiome, motor evacuation dysfunction, layering on existing intestinal diseases with the development of functional disorders, catarrhal and erosive ulcerative lesions, which makes it difficult to diagnose and choose an adequate therapeutic tactic. The situation is often complicated by the impossibility of canceling the therapy of the underlying disease or changing the treatment regimen, which can lead to serious consequences for a patient with diarrhea syndrome. Thus, the issues of early diagnosis, differential diagnosis and approaches to the treatment of drug-induced diarrhea are becoming increasingly important in clinical practice.
目前,在使用非抗菌药物治疗的背景下,腹泻综合症的发生率高达 24%,这一问题变得尤为重要。这是由于长期接受药物治疗的人数增加、老年人口增加、合并症增加、多发性瘫痪以及这类患者对药物过敏。药物诱发腹泻的机制复杂,研究不足。许多药物能够影响各种致病环节,导致肠道微生物群紊乱、运动排空功能障碍、在原有肠道疾病基础上发展出功能性紊乱、卡他性和侵蚀性溃疡病变,这使得诊断和选择适当的治疗策略变得十分困难。由于无法取消基础疾病的治疗或改变治疗方案,情况往往变得更加复杂,这可能会给腹泻综合征患者带来严重后果。因此,药物性腹泻的早期诊断、鉴别诊断和治疗方法等问题在临床实践中变得越来越重要。
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引用次数: 0
The use of melatonin in the treatment of irritable bowel syndrome: a systematic review of randomized placebo-controlled clinical trials 使用褪黑素治疗肠易激综合征:随机安慰剂对照临床试验的系统回顾
Pub Date : 2024-01-17 DOI: 10.31146/1682-8658-ecg-217-9-168-176
D. S. Mironov, I. A. Spirin, T. N. Trubeckaya, N. S. Shitova, V. A. Postoev
Introduction. One of the most prevalent functional disorders of the gastrointestinal system, irritable bowel syndrome (IBS), significantly affects patients’ quality of life. At the moment, only symptomatic drugs are used to treat this disorder. Although using melatonin can be thought of as a form of pathogenetic therapy, its efficacy has not yet been conclusively demonstrated. This systematic review of randomized placebo controlled clinical trials reviews current data on the evaluation of the efficacy of melatonin in patients with IBS. Material and research methods. The search and selection of publications was carried out in the PubMed, ScienceDirect, ClinicalTrials.gov, Cochrane Library, eLibrary, medRxiv and International Clinical Trials Registry Platform databases from their publication until October 30, 2022. Results. The inclusion criteria were met by four randomized placebo-controlled trials, totaling 155 participants, and these trials were included in the subsequent analysis. All investigations revealed a considerable reduction in the frequency and severity of bloating, as well as a tendency for other intestinal symptoms to regress. Two trials reported an improvement in patients’ quality of life, albeit one of the studies did not find these changes to be statistically significant, and the other did not assess them. This review demonstrates that melatonin is effective in treating IBS by lowering the frequency and severity of the condition’s symptoms in the vast majority of published RCTs. The poor number and sample size of clinical trials, along with their inadequate methodological quality, prevent us from drawing any firm conclusions about the contribution of melatonin to the improvement of IBS patients’ quality of life. To confirm melatonin’s significance in the treatment of IBS patients, larger studies are required to assess its efficacy and safety when used in various doses.
简介肠易激综合征(IBS)是最常见的胃肠道功能性疾病之一,严重影响患者的生活质量。目前,治疗这种疾病只能使用对症药物。虽然使用褪黑素可被视为一种病因疗法,但其疗效尚未得到确证。这篇随机安慰剂对照临床试验的系统性综述回顾了褪黑素对肠易激综合征患者疗效评估的现有数据。材料和研究方法。在 PubMed、ScienceDirect、ClinicalTrials.gov、Cochrane Library、eLibrary、medRxiv 和 International Clinical Trials Registry Platform 等数据库中搜索并筛选了自发表至 2022 年 10 月 30 日期间的出版物。结果符合纳入标准的有四项随机安慰剂对照试验,共有 155 人参加,这些试验均纳入了随后的分析。所有调查都显示,腹胀的频率和严重程度都有显著降低,其他肠道症状也有减轻的趋势。有两项试验报告称患者的生活质量有所改善,不过其中一项研究发现这些变化在统计学上并不显著,另一项研究也没有对这些变化进行评估。本综述表明,在绝大多数已发表的 RCT 中,褪黑素可降低肠易激综合征症状的频率和严重程度,从而有效治疗肠易激综合征。由于临床试验的数量和样本量较少,而且方法质量不高,因此我们无法就褪黑激素对改善肠易激综合征患者生活质量的贡献得出任何肯定的结论。要确认褪黑素在治疗肠易激综合征患者方面的重要性,还需要进行更大规模的研究,以评估褪黑素以不同剂量使用时的疗效和安全性。
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引用次数: 0
Colorectal cancer in inflammatory bowel diseases in St. Petersburg: results of an analytical study 圣彼得堡炎症性肠病中的结直肠癌:分析研究结果
Pub Date : 2024-01-17 DOI: 10.31146/1682-8658-ecg-217-9-138-149
Y. Uspenskiy, S. V. Ivanov, Yu. A. Fominykh, A. V. Kokorev
Introduction. Ulcerative colitis (UC) and Crohn’s disease (CD) belong to the category of inflammatory bowel disease (IBD) and are one of the most pressing problems of gastroenterology worldwide, including due to the development of specific life-threatening complications. Chronic inflammation in the colon in IBD is the cause of the development of one of these complications - colorectal cancer, which requires disabling colectomies and is also one of the leading causes of death among IBD patients. In the Russian population of IBD patients the prevalence of dysplasia and cancer of the colon mucosa has not been previously studied in large epidemiological studies. The aim of the study was to assess the incidence of colorectal cancer in patients with IBD in St. Petersburg. Materials and methods. Within the framework of this publication, the results of three studies were compared: a single-center retrospective cohort study conducted on the basis of the city center of IBD in St. Petersburg (516 patients with IBD who admitted to this medical institution for the period 2020-2023); a multicenter epidemiological study aimed at assessing the clinical features of IBD among the population of St. Petersburg (1072 patients with IBD who admitted to 42 outpatient clinics and 6 city hospitals in 2018-2020); registry study based on the general statistical module of the regional IBD Register of St. Petersburg, operating on the basis of a regional fragment of the unified healthcare state information system (12,858 patients with IBD, data collection period: 2019-2022). Results. As a result of comparing data from three studies, the incidence of IBD-associated colorectal cancer in St. Petersburg was calculated, which was 15.7 cases per 10,000 patients with UC per year and 11.5 cases per 10,000 patients with CD per year. Compared to the population of St. Petersburg as a whole, the likelihood of developing colorectal cancer in patients with UC was 2.9 times higher, in patients with CD - 2.4 times higher. At the same time, in a single-center study, when assessing the prevalence of IBD-associated colorectal cancer, it was found that compared with other life-threatening complications of IBD, it was much less common: toxic dilatation of the intestine occurred 3 times more often, intestinal perforation occurred 20 times more often, decompensated bowel stricture occurred 21 times more often, and severe anemia requiring blood transfusion occurred 36 times more common. Also, as a result of a single-center study, it was found that for 1 case of IBD-associated dysplasia of the colon mucosa, there were 5 cases of sporadic dysplasia. Conclusion. The selection of the most effective therapy and systematic endoscopic examination of patients with IBD will significantly reduce the likelihood of developing colorectal cancer, and systematic observation of the patient with regular endoscopic monitoring of the colon with multifocal biopsy will allow timely detection of dysplasia of the colon muc
导言。溃疡性结肠炎(UC)和克罗恩病(CD)属于炎症性肠病(IBD),是全球肠胃病学领域最紧迫的问题之一,其中包括危及生命的特定并发症。IBD 患者结肠内的慢性炎症是其中一种并发症--结肠直肠癌--发生的原因,结肠直肠癌需要进行致残性结肠切除术,也是 IBD 患者死亡的主要原因之一。在俄罗斯的 IBD 患者群体中,结肠粘膜发育不良和结肠癌的发病率以前从未在大型流行病学研究中进行过研究。本研究旨在评估圣彼得堡 IBD 患者的结直肠癌发病率。材料和方法在本出版物的框架内,对三项研究的结果进行了比较:以圣彼得堡市 IBD 中心为基础进行的单中心回顾性队列研究(2020-2023 年期间该医疗机构收治的 516 名 IBD 患者);旨在评估圣彼得堡人口 IBD 临床特征的多中心流行病学研究(1072 名 IBD 患者)。彼得堡 42 家门诊诊所和 6 家市立医院收治的 1072 名 IBD 患者);基于圣彼得堡地区 IBD 登记处一般统计模块的登记研究,该登记处在国家统一医疗信息系统地区片段的基础上运行(12858 名 IBD 患者,数据收集期:2019-2022 年)。研究结果通过比较三项研究的数据,计算出圣彼得堡与IBD相关的结直肠癌发病率为:每万名UC患者每年15.7例,每万名CD患者每年11.5例。与整个圣彼得堡的人口相比,UC 患者罹患结直肠癌的几率高出 2.9 倍,CD 患者则高出 2.4 倍。同时,在一项单中心研究中,在评估与 IBD 相关的结直肠癌发病率时发现,与 IBD 的其他危及生命的并发症相比,结直肠癌的发病率要低得多:肠道中毒性扩张的发病率是其他并发症的 3 倍,肠穿孔的发病率是其他并发症的 20 倍,失代偿性肠狭窄的发病率是其他并发症的 21 倍,需要输血的严重贫血的发病率是其他并发症的 36 倍。此外,一项单中心研究发现,1 例与 IBD 相关的结肠粘膜发育不良病例中,就有 5 例散发性发育不良病例。结论选择最有效的治疗方法并对 IBD 患者进行系统的内镜检查将大大降低罹患结直肠癌的可能性,而对患者进行系统的观察,定期进行结肠内镜监测并进行多灶活检,可以根据现行的临床指南及时发现结肠粘膜发育不良。可以认为,在对 IBD 患者从发病开始的最初几年进行随访的癌症预防措施框架内,最好不仅优先考虑患 IBD 相关性发育不良的风险,而且优先考虑患散发性结肠粘膜发育不良的风险。
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引用次数: 0
The role of serum bilirubin in the pathogenesis of Crohn’s disease in children and assessment of its activity 血清胆红素在儿童克罗恩病发病机制中的作用及其活性评估
Pub Date : 2024-01-17 DOI: 10.31146/1682-8658-ecg-217-9-42-48
E. Fedulova, M. S. Vagin, A. I. Khavkin
Introduction. The article is devoted to the identification of a marker of imbalance of oxidative stress and the antioxidant system in children with Crohn’s disease. The putative level of total bilirubin as an integrative method for assessing Crohn’s disease activity is highly correlated with indicators of oxidative stress and the antioxidant system (ischemia, modifying albumin, malondialdehyde, catalase, sulfhydryl groups and glutathione). Purpose: to explain the relationship between the level of total bilirubin and the activity of the inflammatory process in Crohn’s disease, which allows the introduction of the studied integrative indicator in clinical practice. Materials and methods. Based on the results of scientific studies of biomarkers of oxidative stress (albumin-modifying ischemia - plasma IMA, malondialdehyde - plasma MDA) and the antioxidant system (plasma SH-groups, catalase and reduced erythrocyte glutathione), as well as a simultaneous study of the level of total bilirubin in children diagnosed with Crohn’s disease. To search for a differential method for assessing the level of Crohn’s disease activity by the degree of bilirubin, use binary logistic regression. Results and survey. The results of the study showed a clear relationship between the increase in bilirubin levels and the severity of oxidative stress. It has been established that with a decrease in the level of total bilirubin, there is a predominance of oxidative stress over the antioxidant system, which leads to an increase in inflammation activity. It has been proven that the level of total bilirubin can be used in the complex activity of diseases as a minimally invasive, as well as an objective and acute marker. The sensitivity and specific sensitivity of this protocol is 90.9% and 93.3% respectively, which allows the use of total bilirubin as a marker of inflammation in Crohn’s disease.
导言。文章致力于确定克罗恩病儿童氧化应激和抗氧化系统失衡的标志物。作为评估克罗恩病活动性的综合方法,推测的总胆红素水平与氧化应激和抗氧化系统指标(缺血、修饰白蛋白、丙二醛、过氧化氢酶、巯基和谷胱甘肽)高度相关。目的:解释总胆红素水平与克罗恩病炎症过程活性之间的关系,从而在临床实践中引入所研究的综合指标。材料与方法。根据对氧化应激生物标志物(白蛋白修饰缺血--血浆 IMA、丙二醛--血浆 MDA)和抗氧化系统(血浆 SH 组、过氧化氢酶和还原型红细胞谷胱甘肽)的科学研究结果,以及对确诊为克罗恩病的儿童总胆红素水平的同步研究。为了寻找通过胆红素程度评估克罗恩病活动程度的鉴别方法,使用二元逻辑回归法。结果与调查。研究结果表明,胆红素水平的升高与氧化应激的严重程度有明显的关系。现已证实,随着总胆红素水平的降低,氧化应激会超过抗氧化系统,从而导致炎症活动增加。事实证明,总胆红素水平可作为一种微创、客观和急性标志物用于复杂疾病的检测。该方案的灵敏度和特异灵敏度分别为 90.9% 和 93.3%,因此可以将总胆红素作为克罗恩病的炎症标志物。
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引用次数: 0
Modern ideas about the influence of the gut microbiome on the persistence of HIV infection 关于肠道微生物群对艾滋病毒感染持续性影响的现代观点
Pub Date : 2024-01-17 DOI: 10.31146/1682-8658-ecg-217-9-195-200
A. A. Khryanin, V. K. Bocharova, E. V. Pushkarev
The article discusses current ideas about the impact of HIV infection on the gut microbiome, microbial translocation, chronic inflammation, and immune activation. The gut microbiome is involved in systemic inflammation and immune activation, which contributes to the persistence of HIV infection. Although the exact pathogenesis of HIV infection and changes in the intestinal microbiome in the form of a decrease in bacterial diversity is still unclear, normalization of the intestinal microbiome in HIV infection can reduce inflammation, and thereby lead to a decrease in the possible reservoir for HIV infection. The authors of the article presented modern hypotheses about the interaction of the intestinal microbiome with systemic inflammation, as well as the relationship between the intestinal microbiome and the persistence of HIV infection. The inability of modern treatment methods to affect the hidden reservoir and deplete it is the main obstacle to the cure of HIV infection. The ongoing treatment efforts aimed at reducing the reservoirs of HIV infection in order to achieve stable remission and the possibility of a cure for HIV infection are discussed.
文章讨论了目前关于艾滋病病毒感染对肠道微生物组、微生物转运、慢性炎症和免疫激活的影响的观点。肠道微生物组参与了全身炎症和免疫激活,而这正是导致艾滋病病毒感染持续存在的原因。虽然艾滋病病毒感染和肠道微生物群以细菌多样性减少的形式发生变化的确切发病机制仍不清楚,但艾滋病病毒感染者肠道微生物群的正常化可减少炎症,从而导致艾滋病病毒感染的可能储库减少。文章作者提出了肠道微生物群与全身炎症相互作用的现代假说,以及肠道微生物群与艾滋病病毒感染持续存在之间的关系。现代治疗方法无法影响隐藏的储库并将其耗尽,这是治愈艾滋病毒感染的主要障碍。本文讨论了目前旨在减少艾滋病毒感染储库的治疗努力,以实现稳定缓解和治愈艾滋病毒感染的可能性。
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引用次数: 0
期刊
Experimental and Clinical Gastroenterology
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