Andrey E. Donnikov

Aim : to conduct a cross-sectional study to assess a relationship between the expression levels of innate immunity genes and medical history in pregnant women with tuboperitoneal infertility. Materials and Methods . A cross-sectional, single-site study was conducted. The 84 women examined were divided into two groups: Group 1 included 62 pregnant women with a history of tuboperitoneal infertility, Group 2 consisted of 22 healthy pregnant women without any gynecological or obstetric complications as a control group. The study protocol included collection of gynecological and obstetric histories, assessing messenger RNA (mRNA) expression profiles for innate immunity-related genes collected by cervical canal mucosa scrapings, followed by calculating integrated inflammation index (II). Results . In Groups 1 and 2, differences were found in the expression patterns of mRNAs encoding interleukin (IL) IL-18, IL-10 , GATA-binding protein 3 ( GATA3 ) , cluster of differentiation 68 ( CD68 ) genes. Correlation analyses revealed significant associations between major infectious/inflammation-related complications in both obstetric (cervical insufficiency, recurrent pregnancy loss, preterm birth) and gynecologic histories (chronic endometritis) and the expression of IL-18, IL-10 , GATA3 mRNAs , CD68 genes highlighting common inflammatory pathways underlying these unfavorable pregnancy outcomes among patients with tuboperitoneal infertility. Conclusion . Differences in the mRNA expression profiles of the genes of the main pro- and anti-inflammatory interleukins IL-18, IL-10 , transforming factor G ATA3 , and cluster of differentiation CD68 in the cervical canal of pregnant women with former reproductive dysfunction and women without a history of infertility, as well as some relationships between complications in obstetric and gynecological histories and expression of innate immunity gene mRNAs in the group of impaired fertility points at the importance of a multidisciplinary approach in assessing a role of the infectious and inflammatory factor in this cohort of patients.

Fungi of the genus Malassezia are involved in the development of seborrheic dermatitis, atopic dermatitis and pityriasis versicolor. The use of molecular genetic methods for their detection represents a promising diagnostic approach. Objective is to determine the detection rate and species composition of Malassezia fungi using real-time PCR in patients with seborrheic dermatitis and pityriasis versicolor. Materials and methods. A total of 35 patients aged 10 to 76 years (median 25 years) were examined: 17 with seborrheic dermatitis and 18 with pityriasis versicolor. Skin scrapings were analyzed by RT-PCR for the detection and quantification of Malassezia spp., M. restricta, M. globosa, M. sympodialis, and M. pachydermatis. Results. The majority of samples from patients with seborrheic dermatitis and pityriasis versicolor were positive for Malassezia spp., M. restricta, and M. globosa. The detection rates of Malassezia spp. (M. restricta, and M. globose) in seborrheic dermatitis were 100 % (100 %, and 82.4 %, respectively); in pityriasis versicolor, they were 94.4 % (72.2 %, and 83.3 %, respectively). In contrast, M. sympodialis was detected in only one patient (5.9 %) with seborrheic dermatitis and one patient (5.6 %) with pityriasis versicolor. M. pachydermatis was not detected in any patient in the study group. Conclusions. The use of real-time PCR allowed the detection of Malassezia spp. in the majority of patients with seborrheic dermatitis and pityriasis versicolor. M. restricta predominates in seborrheic dermatitis, whereas mixed communities of M. restricta and M. globose are frequently found in pityriasis versicolor.

Цель исследования – представить характеристику биоценоза толстого кишечника и показателей экспрессии генов врожденного иммунитета в цервикальном канале у пациентов с гингивитом/в отсутствии гингивита с учетом течения и осложнений беременности. Проведено проспективное когортное исследование среди 98 беременных без отягощенного акушерского и гинекологического анамнеза, обратившихся для наблюдения в период 2023–2024 гг. в ФГБУ «НМИЦ акушерства, гинекологии и перинатологии имени В.И. Кулакова» Министерства здравоохранения Российской Федерации, г. Москва. Разделение на четыре группы осуществлено по наличию/отсутствию воспаления пародонтальных тканей (гингивита) и величине индекса воспаления (ИВ: ИВ≤60% и ИВ>60%), основанного на оценке экспрессии матричной РНК (м-РНК) генов врожденного иммунитета в соскобе из цервикального канала: группа А – отсутствие гингивита, ИВ≤60%; группа Б – наличие гингивита, ИВ≤60%; группа В – отсутствие гингивита, ИВ>60%; группа Г – наличие гингивита, ИВ>60%. В схему исследования входили оценка осложнений гестационного процесса и определение количества геном-эквивалентов представителей микробиома содержимого толстого кишечника методом ПЦР. Статистическая обработка проведена с использованием однофакторного дисперсионного анализа (ONE WAY ANOVA). При проверке гипотез статистически значимыми считали различия при р<0,05. Для выявления статистически значимых ассоциаций тестированных микроорганизмов использовался кластерный анализ методом К-средних. Анализ биоценоза содержимого толстого кишечника у беременных проведен при сравнении групп Б, В, Г с женщинами группы А (определена в качестве условной группы контроля, характеризующейся отсутствием гингивита и локальной воспалительной реакции в соскобе слизистой цервикального канала). Установлено статистически значимое снижение представительства таксонов в составе филотипа бактерий Firmicutes (вид Lactococcus lactis для групп Б, В, Г, семейство Peptoniphilaceae для групп Б, В), Bacteroidetes (род Prevotella для групп Б, В), Actinobacteria (Bifidobacterium longum subsp. longum для группы Б), изменение количества грибов рода Candida (группы Б, В, Г), увеличение представительства Actinobacteria (виды Bifidobacterium adolescentis для групп Б, Г), Proteobacteria (род Desulfovibrio, вид Escherichia coli для групп Б, Г). Использование метода К-средних позволило выделить две ассоциации микроорганизмов: в составе кластера 1 представлены микроорганизмы Prevotella spp. и Desulfovibrio spp., в составе кластера 2 – Desulfovibrio spp., Escherichia coli, Bifidobacterium longum subsp. longum, Candida spp. Установлена статистически значимая корреляционная взаимосвязь (r = 0,669; р<0,001) между принадлежностью к кластеру 2 и развитием в последующем гестационного сахарного диабета (ГСД). Для подтверждения прогностической значимости этих данных был использован ROC-анализ: площадь под кривой (AUC) для сопоставления частоты встречаемости ГСД у женщин, кишечный микробиом которых во втором триместре беременности принадлежал к кластеру 2, составила 0,813. Исследование микробиома кишечника беременных является важным этапом поиска патогенетических механизмов развития патологий гестационного процесса, среди которых ведущее место занимает ГСД, для которого характерно повышение риска неблагоприятных исходов беременности как для матери, так и для плода. Представленные сведения о возможной связи микроорганизмов Desulfovibrio spp., Escherichia coli, Bifidobacterium...

The objective: to study the species and quantitative composition of fecal microbiota in children undergoing chemotherapy for drug-resistant respiratory tuberculosis. Subjects and Methods. The study included 17 children from 2 to 12 years old with respiratory tuberculosis who received treatment for drug-resistant respiratory tuberculosis from 2022 to 2024 at Central Tuberculosis Research Institute. Fecal microbiota was tested by real-time PCR using the ENTEROFLOR® Children reagent kit at the following time points: before the start of chemotherapy, after 2 and 4 months of chemotherapy. Results. The most pronounced disturbances in the intestinal microbiocenosis among representatives of normobiota were noted after 2 months of chemotherapy; by 4 months, those parameters did not deteriorate either in quantitative terms or frequency of deviations from reference values: for representatives of the phylum Actinomycetota (Actinobacteria) – in Bifidobacterium spp. and Coriobacteriia , for representatives of the phylum Bacteroidota (Bacteroidetes) – in Butyricimonas spp. , Parabacteroides spp., Prevotella spp. Changes in the composition of normobiota were associated with the elevated proportion of opportunistic microbiota by 2 months and persistence of these values by 4 months of chemotherapy. Representatives of pathogenic microbiota, which were not present before chemotherapy, appeared by 2 months of chemotherapy with the following frequency: Streptococcus agalactiae – in 35.3% of cases, Clostridioides difficile , with the toxigenic genes cdtA and cdtB – in 58.9%, and increasing to 71.5% by 4 months of chemotherapy. Conclusion. Treatment with chemotherapy regimens for drug-resistant tuberculosis has a statistically significant negative impact on intestinal microbiota in children: the proportion of normobiota decreases, the proportion of opportunistic microbiota increases, and pathogenic microbiota develops.

Allergic reactions of the lower genital tract in women cause significant chronic vulvovaginal discomfort and require active diagnosis and treatment. Modern approaches to therapy, which combine allergen elimination and anti-inflammatory therapy, can achieve improvement or cure in most cases. Obstetricians-gynecologists are recommended to involve dermatovenerologists and allergists for joint management of patients in case of non-standard cases of vaginitis. From a scientific point of view, further studies of immune mechanisms in the genital tract and the development of new methods of specific therapy and prevention remain relevant. In the future, the results of such studies will help to develop more accurate clinical guidelines and improve the effectiveness of care for these patients. Successful treatment of allergic diseases of the vulva and vagina significantly improves the quality of life, restores a woman's confidence and comfort in everyday and intimate life. Developing an interdisciplinary approach, education, and a thoughtful method for addressing symptoms can help overcome many difficulties in diagnosing and treating this condition. The identified unresolved issues will serve as the starting point for new research and progress in this field of medicine.

Aim: to conduct a comprehensive analysis of clinical, anamnestic and immunological characteristics of women with infertility and/or a history of recurrent pregnancy loss. Materials and Methods. A cross-sectional study included 302 women of reproductive age with a history of infertility and/or recurrent pregnancy loss by enrolling those who was planning pregnancy and directed for preconceptional councelling in 2023–2024. Patients were divided into 3 groups depending on whether they had experienced infertility (n = 108), recurrent pregnancy loss (n = 141), infertility and recurrent pregnancy loss (n = 53). The study flowchart included the collection of gynecological and obstetric histories, as well as ultrasound examination of the pelvic organs in follicular phase. Expression of innate immunity gene mRNAs was carried out: interleukins (IL) IL-1 β , IL-10 , IL-18 , tumor necrosis factor-alpha ( TNF- α ), Toll-like receptor 4 ( TLR4 ), GATA-binding protein 3 ( GATA3 ), cluster of differentiation 68 ( CD68 ), β ₂ -microglobulin. Based on the mRNA expression profiles of the studied genes, the integral inflammation index (II) was calculated automatically using binary logistic regression software. A local inflammatory reaction in the cervical mucosal scraping was recorded when the II value exceeded 60 %. Statistical analysis was performed using R v 4.4.3. In hypothesis testing, differences were considered statistically significant at p < 0.05. Results. The prevalence of inflammatory endometrial pathology (chronic endometritis diagnosed by ultrasound) was comparable among groups 1, 2, 3 (16.7; 19.9; 18.9 %; p > 0,05). A greater incidence of ultrasound detected intrauterine adhesions was found in group 2 with combined infertility and recurrent pregnancy loss (17,0 %) compared to infertility group 1 (4.6 %; p = 0,022) and comparable to recurrent pregnancy loss group 3 (14.9 %; p > 0,05). Uterine septal removal was performed more often in group 2 (17.0 %) than in group 1 (1.9 %; p = 0,003). Endometriosis was diagnosed more often in group 2 (24,5 %) than in group 3 (7.8 %; p = 0,009). Reproductive history in combined pathology group 2 compared to infertility group 1 showed higher number of pregnancies (4.0 [3.0; 4.0] vs. 1.0 [0.0; 1.0]; p < 0.001), proportion of spontaneous miscarriages (50.9 % vs. 5.6 %; p < 0.001), prevalence of secondary infertility (24.5 % vs. 11.1 %; p < 0,001) and in vitro fertilization attempts (1.0 [0.0; 3.0] vs. 0.0 [0.0; 2.0]; p = 0.002). We found the difference in IL-1 β gene expression in group 1 and group 3 (4.6 [3.5; 5.3]) vs. 4.9 [4.1; 5.8]; p = 0,044). This may suggest different mechanisms underlying endometrial-embryonic dialogue disorders with common inflammatory background: the general index of local inflammation was high in all groups (more than 60 %). Conclusion.  Prevalence of ultrasound chronic endometritis signs in groups 1, 2, 3 was up to 20 %. Patients with infertility and/or recurrent pregnancy loss, with chronic endometritis, concomitant dysbiotic disorders and activated local immunity need to correct vaginal microbiocenosis before pregnancy in order to prevent infectious and inflammatory complications. It is necessary to develop a screening program based on the characteristics of gynecological, obstetric, reproductive history, morbidity and local inflammatory gene expression levels. Our data confirm the importance of an integrated approach in assessing a role of infectious factor in origin of reproductive disorders.