Aim: to study the structure and species composition, incidence of gut microbiota dysbiotic disorders using a new technique based on real-time polymerase chain reaction (PCR) – enteroflor®Kiddy – in children with pulmonary TB on TB treatment. Materials and methods. The study enrolled 63 children aged 2–12 years. We carried out a one-step cross-sectional study of gut microbiota in 49 patients (the median age was 5 years [3; 8]) with newly diagnosed active pulmonary TB: 13 children were examined before, and 36 children – at various time points of TB treatment; 14 children without focal TB did not receive TB treatment (the median age was 7.5 years [5,5; 10]). A specialized study of gut microbiota was performed using the enteroflor®Kiddy test system. Results. There was no difference in gut microbiota composition and incidence of dysbiotic disorders between children without focal TB and children with TB before TB treatment. We determined differences in gut microbiota in children with TB before TB treatment and during treatment monitoring: lower frequency of detection of Bifidobacterium spp. (100 and 61.1%, p < 0.05); Butyricimonas spp. (92.3 and 58.3%, p < 0.05); Desulfovibrio spp. (100 and 50.0%, p < 0.05); Clostridium perfringens gr. (92.3 and 22.2%, p < 0.001), higher frequency of detection of markers for pathogenicity and resistance of Clostridioides difficile (7.7 and 38.9%, p < 0.05), and lower frequency of detection of Staphylococcus aureus (23.1 and 0%, p < 0.05), respectively. We established that increased duration of TB treatment (more than 3 months vs. 2-3 months) led to higher frequency of gut microbiota dysbiotic disorders: complete absence of normobiota species Bifidobacterium spp. and Coriobacteriia was established in 52.4% and 14.3% of cases, respectively; pathogenic microbiota species Clostridioides difficile were detected 2.4 times more frequently (47.6%), Candida spp. fungi were detected 1.7 times more frequently (р > 0.05). In children on TB treatment containing second-line drugs as compared to children only receiving first-line drugs dysbiotic disorders associated with Bifidobacterium spp. were significantly more frequent (69.2 and 30% respectively) (χ2 = 4.573, р = 0.05), up to complete absence in 50% of children receiving second-line drugs; and pathogenic microbiota species Clostridioides difficile were detected 4.6 times more frequently (46.2 and 10%, р = 0.059); cdtA, cdtB were detected twice as often (46.2 and 20.0%, р > 0.05). The Candida genus fungi Candida spp. (р > 0.05) were detected twice as often in the microbiota of children only receiving first-line drugs. Conclusion. TB treatment produces pronounced negative effect on gut microbiota. The increase in chemotherapy duration and inclusion of second-line drugs leads to increasing incidence of dysbiotic changes of specific representatives of normobiota, their decreasing amount, and significant increase in detection of markers for pathogenicity and resistance.

The study revealed no effects of pregnancy and childbirth on the course of tuberculosis in female BALB/c mice after aerosol infection with Mycobacterium tuberculosis. However, we demonstrated a negative effect of tuberculosis infection on the fertility of infected females, which manifested in a longer period from mating to pregnancy and in a smaller litter size. Impaired reproductive function in response to the effect of the systemic infectious process was accompanied by the development of immunosuppression confirmed by an immunological test (delayed-type hypersensitivity to tuberculin) and the formation of genital tract dysbiosis during pregnancy and postpartum period.

Fecal microbiota transplantation (FMT) is a promising therapy for a variety of diseases involving the gastrointestinal (GI) tract. The purpose of our study is to evaluate the effectiveness of FMT for the treatment of different GI complications after allogenic hematopoietic stem cell transplantation (steroid-refractory and steroid-dependent graft versus host disease (SR/ SD GVHD) and infectious enterocolitis) in children from 1.5 to 18 years old. The study was approved by the Local Ethics Committee of the Morozov Children's Clinical Hospital of the Department of Health of Moscow (No. 176 dated 24.05.2022). The patients' parents gave their informed consent to the participation of their children in the study and the publication of the study results. SR/SD GVHD group included 14 patients and GI infections group – 11 patients. In total, 38 FMTs were performed. Eleven children underwent repeated FMTs due to the lack of effect after the first FMT. The resolution of diarrhea followed by the withdrawal of corticosteroids was recorded in 11 out of 14 patients with SR/SD GVHD. Ten out of 11 patients with GI infections also achieved relief of diarrhea. The clinical effect correlated with changes in the microbiome structure: for both groups of patients, the median proportion of normal microbiota before FMT was 6%, after FMT – 92% (p = 0.043). The median number of different taxa for both groups of patients before and after FMT were 3 and 10 taxa, respectively (p = 0.0016).

We evaluated the vaccine properties of a novel attenuated strain of M. tuberculosis BN (Mtb BN) and its impact on the gut microbiota in inbred female mice in comparison with a virulent strain Mtb H37Rv and a vaccine strain BCG. The Mtb BN strain demonstrated the highest anti-tuberculosis vaccine effect in I/St mice highly susceptible to tuberculosis infection and the same effect as BCG in mice of the recombinant strain B6.I-100 and in β2 microglobulin gene knockout mice. No adverse effects of the new Mtb BN strain on the gut microbiota of BALB/c mice were revealed. The virulent strain Mtb H37Rv and the vaccine strain BCG decreased the main indicators of normocenosis (Bifidobacterium spp., Bifidobacterium animalis subsp. lactis, Akkermansia, and Erysipelotrichaceae) and led to disappearance of Clostridium perfingens, E. coli, Pseudomonas spp., which contributed to reduction of species diversity and the development of dysbiosis.

Currently, cervicitis of nonspecific etiology is one of the urgent problems of modern gynecology due to the extremely high frequency of their occurrence, a tendency to a chronic relapsing course, a negative impact on reproductive health, and the risk of developing a number of complications. The role of violations of vaginal microbiocenosis and local immune status in the development of CNC has been convincingly shown. The replacement of lactobacilli with predominantly anaerobic microorganisms (Ureaplasma, Mycoplasma, Gardnerella vaginalis, Prevotella, Peptostreptococcus spp. and Bacteroides spp.), characteristic of bacterial vaginosis, is extremely often detected in patients with CNC. Of particular importance from the point of view of clarifying the pathophysiological mechanisms of development and the development of new diagnostic and prognostic markers, as well as the personalization of CNC therapy, is the study of the cytokine status. Cervicitis and other inflammatory diseases of the lower genital tract are characterized by an increase in the expression of pro-inflammatory cytokines with simultaneous inhibition of the formation of anti-inflammatory cytokines. Significant multidirectional changes in the balance of pro- and anti-inflammatory cytokines were revealed in active and chronic sluggish cervicitis. It should be noted that, despite the variety of proposed approaches to CNC therapy, this problem is still far from being solved to date. One of the promising directions is the personalization of CNC therapy based on molecular genetic markers (polymorphisms of cytokine genes, Toll-like receptors, genes of the detoxification system). The use of such a personalized approach can significantly increase the effectiveness of CNC treatment and reduce the risk of disease recurrence.

Introduction. Vitamin D administration is recommended for women with vitamin D insufficiency, who are planning to undergo assisted reproductive treatment (ART). The action of the active form of vitamin D is mediated through its vitamin D receptor (VDR). The presence of VDR in the cells and tissues of the female reproductive system suggests that vitamin D plays an important role in human reproduction. However, the effect of VDR gene polymorphisms on human reproduction has not been adequately studied.Aim. To assess the effect of VDR gene polymorphisms on the folliculogenesis, embryogenesis and clinical outcomes of assisted reproduction programs.Materials and methods. The cross-sectional study included 300 patients without complications during the assisted reproduction cycle. The number of follicles, oocyte-cumulus complexes, mature and immature oocytes, the presence of oocyte dysmorphisms, number of zygotes, fertilization rate, and the number of obtained blastocysts were evaluated. The determination of three polymorphisms of the VDR gene (FokI – rs2228570, BsmI – rs1544410, TaqI – rs731236) was performed by real-time polymerase chain reaction.Results. The incidence of perivitelline space pathology of oocytes in FokI A/A genotype patients was 5.7%, in A/G genotype patients – 14.7%, in G/G genotype patients – 16.3% (p = 0.041 when comparing A/A genotype with A/G + G/G genotypes). Depending on the genotype, the pregnancy rate ranged from 38.5 to 52.8%, but no statistically significant differences were found.Conclusion. It was shown that the perivitelline space pathology of oocytes in the FokI A/G genotype patients is 2.6 times higher, and in the G/G genotype patients – 2.9 times higher than in the A/A genotype patients. However, there were no differences in pregnancy rate among patients with different genotypes of FokI, BsmI and TaqI gene polymorphisms of VDR.

It is a common fact that children are less susceptible to COVID-19 than adults, and they usually have milder forms often without symptoms, due to the age-related characteristics of their immune response and the features of the renin-angiotensin system (RAS). The recent studies have shown that the RAS elements are widely represented in the lungs, and they actively participate in the inflammation process in addition to their main vasoregulatory function. The cascade of RAS reactions is one of the key links in the pathogenesis of COVID-19, and it is analyzed from two positions: expression of ACE2 receptors and polymorphisms of certain genes of this system. The studies have demonstrated that the ACE2 transmembrane protein is both the “entry gate” for the virus, and it also plays a regulatory role, turning the pro-inflammatory vasoconstrictor angiotensin II into anti-inflammatory angiotensin (1—7) with vasodilating properties. A higher content of ACE2 in children as compared to that in adults maintains the RAS system balance and prevents the development of complications. It has been also found that certain genetic polymorphisms (AGTR1, AGTR2, ACE2, ACE) can cause the imbalance of RAS components, leading to more pronounced reactions of alveolocytes, vascular endothelium and smooth muscle fibers in response to SARS-CoV-2 infection due to a shift of the vasoconstrictor, proliferative and profibrotic mechanisms. The patients with certain genetic polymorphisms of NOS genes regulating vascular tone, cell growth and proliferation may have a genetic predisposition to the development of severe forms of COVID-19.

Infectious process even at the initial stage after aerosol infection with Mycobacterium tuberculosis induced rapid changes in vaginal microbiota in mice. Rapid decrease in both the quantity and diversity of microbiota was noted, and then, partial recovery of normal flora was observed. Changes in vaginal microbiota was detected as soon as in 3-7 days after lung infection, while inflammatory changes appeared by day 35. At the early stage of infection, no signs of inflammation were observed, neither M. tuberculosis nor its DNA were detected in mouse genital organs.

To determine the most informative markers for assessing the functional state of endometrium during the 'window of implantation' and creating a model for assessment of the readiness of endometrium for embryo implantation. Forty-seven women with tubal infertility and a successful IVF pregnancy participated in the study. Pipelle endometrial sample was performed during the supposed 'window of implantation' in natural cycle with subsequent histological study, and transcriptional profile of genes GPX3, PAEP, DPP4, TAGLN, HABP2, IMPA2, AQP3, HLA-DOB, MSX1, POSTN determined by real-time quantitative polymerase chain reaction (qRT-PCR). Differences in the level of mRNA expression of all the studied genes in the receptive endometrium were found in comparison to the prereceptive one, which allowed us to classify two functional states of the endometrium. The results of histological examination responded to the stage of maturation of the endometrium in 78.7% of cases. Receptive endometrial status can be determined based on the integral evaluation of mRNA expression level of 4 PAEP, DPP4, MSX1, and HLA-DOB genes. The model for determining a personalized `window implantation' is offered for practical application in ART.

Host immunity against Candida albicans is crucial in controlling C. albicans infection. The innate immunity is believed to be the first line of host defense, such as the direct killing of yeasts through phagocytosis by neutrophils and macrophages. In addition to innate immune cells, an adjunctive protective effect is played by cellular adaptive immunity represented by Th lymphocytes. The balance of various Th cell subpopulations plays a crucial role in regulating the prognosis of C. albicans infection. Yeasts cell recognition by pattern recognition receptors leads to proinflammatory cytokines synthesis, cause immune system activation and yeast cells killing. However it was demonstrated that C. albicans inhibits immune response which cause infection. Aim - studying vaginal microbiota and the local immune response in women with recurrent vulvovaginal candidiasis for improving the tactics of their management. Results. Our date demonstrates that vaginal disbiosis are risk factor for RVVC and leads to more active innate immune system response.

Vulvovaginal candidiasis (VVC) frequently occur in women of childbearing age. 5-10% of these women experience recurrent vulvovaginal candidiasis (RVVC), which is characterized by at least 4 episodes of infection in 12 months. In addition to known risk factors such as antibiotics, diabetes, or pregnancy, host genetic variation and antifungal immune response play a substantial role in the pathogenesis of RVVC. The aim of this study was to identify a molecular-genetic factors of recurrence of VVC. Our results shows that single nucleotide polymorphisms (SNP) in cytokine genes such as IL4, IL1b and CCL2 were associated with recurrent vulvovaginal candidiasis and effect on susceptibility to disease.

Relevance: According to the literature, Vulvovaginal candidiasis (VVC) is diagnosed in 75% of women during life, and in 5-8% of women its recurrent course is developed (four or more episodes of exacerbation during 12 months). Recurrent vulvovaginal candidiasis (RVVC) is often observed in the presence of development risk factors, but often the recurrent course of the disease is developing among women without obvious risk factors. The literature shows that the development of a recurrent fungal infection is often caused by a violation of the local immune response, which is associated with the polymorphism of the immune system genes.Objective of the study: To develop criteria for forecasting the recurrent current volvovaginal candidiasis to improve the effectiveness of therapy.Study results: As a result of our study, it has been found that C. albicans remains the leading fungal species in the acute and recurrent VVC, but women with the recurrent course of VVC the prevalance of non-C. Albicans fungi is reliably higher than the patients with acute VVC (P = 0.037). Also, the sensitivity data obtained shows that most of the studied yeast fungi (97.5%) are sensitive to fluconazole. However, only in 10.5% of the non-C.Albicans strains resistance was detected. The determination of genetic predisposition to develop the recurrent current VVC, using the prediction model derived from our study, revealed that 77.8% of women with a genetic predisposition are developing a relapse of VVC. In view of these results and based on international recommendations (CDC, WHO, 2011) that it is appropriate to indicate the anti-recurring antifungal treatment to RVVC, it can be concluded that for patients with genetic predisposition to the development of recurrent VVC it is advisable to indicate the anti-recurrent antifungal therapy.

Цель исследования — изучение эффективности монотерапии (локальная деструкция очагов поражения) и комбинированного лечения (этиотропный препарат суперлимф и радиоволновая деструкция) у пациенток с папилломавирусной инфекцией и плоскоклеточной цервикальной интраэпителиальной неоплазией с поражением низкой степени. Материал и методы. Под наблюдением находились 160 женщин с выявленными методом полимеразной цепной реакции высокоонкогенными вирусами папилломы человека. Всем пациенткам проведено комплексное обследование, включающее цитологическое и бактериологическое исследования, метод полимеразной цепной реакции, определение профиля экспрессии генов матричной рибонуклеиновой кислоты, экспрессии наиболее информативных маркеров воспалительного процесса в соскобе эпителия цервикального канала, расширенную кольпоскопию. После получения результатов цитологического исследования была сформирована группа из 60 пациенток с цервикальной интраэпителиальной неоплазией низкой степени, которая была разделена на две группы: основную (36 больных), где применялось комбинированное лечение — препарат суперлимф и радиоволновая деструкция, и контрольную (24 пациентки), в которой проводилась только локальная монодеструкция. Результаты. Применение суперлимфа в комплексной терапии способствовало более быстрой нормализации цитологической картины на шейке матки после деструктивного лечения, более эффективной элиминации вируса папилломы человека, снижению локального воспаления по сравнению с этими показателями в контрольной группе. Заключение. Показана эффективность применения суперлимфа у пациенток с интраэпителиальным поражением шейки матки низкой степени, ассоциированным с папилломавирусной инфекцией, что позволяет рекомендовать этот препарат к широкому использованию при данной патологии.

Вульвовагинальный кандидоз (ВВК) зачастую встречается у женщин репродуктивного возраста. У 5-10% женщин ВВК развивается рецидивирующий ВВК (РВВК), который характеризуется развитием 4 и более эпизодов ВВК в течение 12 мес. Есть данные, что наряду с известными факторами риска, такими как антибактериальная терапия, сахарный диабет, беременность, в патогенезе развития РВВК важную роль принадлежит генетическим особенностям пациенток и противогрибковому иммунному ответу. Целью настоящего исследования явилось выявление молекулярно-генетических факторов рецидивирования ВВК. Результаты нашего исследования показали, что однонуклеотидный полиморфизм генов IL4, IL1b и CCL2 ассоциирован с рецидивирующим вульвовагинальным кандидозом и является предрасполагающим фактором для его развития.

More than 50% of pregnant women after the programs of assisted reproductive technologies (ART) face the problem of recurrent miscarriage (RMC), especially in the first trimester. Significant role in the development of RMC has infectious factor and chronic inflammation in the endometrium. The aim: to reveal the peculiarities of immune response mRNA genes of the inflammatory component expression in the period of the tentative implantation window (TIW) in women with RMC in ART programs. Material and methods. The main group consisted of 240 patients with RMC in ART programs; the control group included 100 conditionally healthy fertile women. On the ground of PCR reverse transcription, the mRNA of the IL-1β, IL-2, IL-10, Foxp3, TLR9, IL-2Rα cytokine genes was examined in endometrial samples obtained with the help of biopsy on the TIW day. Results. Analysis of the transcriptional profile of the immune response genes in the endometrium on TIW day revealed that the relative level of mRNA expression of the IL-1β, IL-2, Foxp3, TLR9, IL-2Rα genes did not differ significantly in the main and control groups. Statistically significant decrease in mRNA expression of IL-10 gene was observed in women with RPL. Conclusions. A feature of mRNA expression of the inflammatory component of the immune response in TIW period in women with RMC in ART programs is a decrease in the expression level of the IL-10 gene mRNA, which may be one of the reasons for the unfavorable outcomes of the onset pregnancy.

The article describes the history of development of the concept of primary prevention of congenital malformations of the fetus via periconceptional receiving of multivitamin preparations containing folic acid. The results of Hungarian studies on the use of multivitamins are also given below as well as the current understanding of the mechanism of the prophylactic action of folic acid from a position of pharmacogenetics. The data on the use of different biochemical forms of folate is presented as well.

Цель: Изучить эффективность золедроновой кислоты в терапии постменопаузального остеопороза (ПМО) с учетом полиморфизма гена фарнезилдифосфат-синтетазы (FDPS). Методы исследования: клинический, определение биохимических маркеров костного метаболизма (БМКР) - электрохемилюминесцентным методом («Хоффманн-Ла Рош ЛТД», Швейцария). Измерение МПК проводили с помощью двухэнергетической рентгеновской абсорбциометрии позвонков поясничной области (L1-L4) и шейки бедренной кости (Neck left, Neck total left). Молекулярно-генетический (определение однонуклеотидного полиморфизма гена FDPS (rs2297480) - методом «примыкающих проб» с анализом кривых плавления (ЗАО «НПФ ДНК-Технология, Россия)). Результаты. Обследовано 225 женщин с постменопаузальным остеопорозом. Средний возраст составил 59 (5466) лет. Средняя продолжительность периода постменопаузы 7 (2-13) лет. ИМТ=27,2(23,6-29,05) кг/м2. Распределение аллелей (АА:АС:СС) составило 55,1(n=144):39,5(n=103):5, 4(n=14). Базальные уровни биохимических маркеров костного ремоделирования (БМКР) соответствовали периоду постменопаузы и статистически значимо не различались в зависимости от генотипа FDPS. Средние показатели МПК в поясничном отделе позвоночника и/или шейке бедра соответствовали остеопорозу. Всем пациенткам проводили терапию золедроновой кислотой (zol) в дозе 5 мг в виде внутривенной инфузии 1 раз в 12 месяцев в течение 2 лет. Дополнительно все пациенты получали кальций 1000 мг/сут и витамин Д3 800МЕ/сут. Реакция БМКР на инфузию zol различалась в зависимости от генотипа FDPS. Через 6 месяцев после 1-ой инфузии достоверно более выраженное снижение B-Crosslaps 92 (91-93)% отмечено у пациентов с С/С генотипом (p=0,056), по сравнению с 82% у носителей аллеля А (p=0.07). Через 9 месяцев после инфузии B-Crosslaps у носителей аллеля А повышались до 75%, остеокальцина - 44,4% от исходного. Тогда как у носителей генотипа C/C как B-Crosslaps - (87%), так и osteocalcine -(53,6%) оставались по-прежнему низкими (р=0,056). К 12 месяцу после инфузии уровни B-Crosslaps и osteocalcin у носителей аллеля A повышались и соответствовали премено-паузальным значениям, тогда как у носителей С/С генотипа оставались в пределах ниже нижней границы нормы для пременопаузы. У пациентов с СС генотипом на фоне выраженного снижения БМКР после 2ой инфузии золедроновой кислоты произошло снижение МПК на 5,6%. Выводы. Различная реакция на терапию золедроновой кислотой у пациенток с ПМО связана с полиморфизмом гена FDPS (rs2297480). Для пациентов с генотипом С/С характерно «гиперторможение» костного обмена в ответ на терапию золедроновой кислотой, что возможно, было причиной отрицательной динамики МПК в поясничном отделе позвоночника на втором году терапии золедроновой кислотой.

Studies of collagen gene polymorphisms associated with predisposition to early recurrent miscarriages revealed significant differences in the distribution of COL1A1 C-1997A C>A (rs1107946) genotypes and alleles in the group of pregnant patients with early miscarriages in comparison with controls (normal pregnancy). Identification of COL1A1 C-1997A C>A (rs1107946) collagen gene polymorphisms at the stage of pregnancy planning will make it possible to form early miscarriage risk groups for more thorough preparation to gestation and optimization of follow up of this patient population.

An increasing number of hormonal contraceptives and their varying system effects on the body of a woman makes it necessary to personify their prescription and search for means of predicting their safety and tolerability. The article presents the research data and shows the various informative clinical predictors in the development of adverse reactions in the background. It was found that the most significant clinical predictors of occurrence of side effects and complications on the background of the use of the HC are the existence of gynecological diseases associated with menstrual cycles and poor portability of HC in history; an independent predictor of adverse effects on the background of the COC are chronic cholecystitis and dysfunction of the sphincter of Oddi; dynamics of lipid parameters, biochemical blood spectrum, as well as some parameters of hemostasis with the use of different variants of HC; genotype women polymorphic locus rs2414096 aromatase gene (CYP19A1) is a significant predictor of complications and side effects when using HC.