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Introduction. Most pelvic tumors originate from reproductive organs. Even using the up-to-date imaging techniques, radiologists experience difficulties in determining the source of the lesion since a wide range of tumors look similar to each other on the distorted backdrop of pelvic anatomy, large invasive formations, and an active inflammatory reaction of the pelvic peritoneum.Aim: to evaluate “pitfalls” in the preoperative noninvasive diagnosis of female pelvic tumors by applying the clinical diagnostic tools.Materials and methods. Four rare clinical cases were analyzed; all of them posed difficulties in interpreting the diagnostic examination due to their atypical characteristics. There were 2 cases of ovarian cancer, initially identified by an experienced team of radiologists as benign pelvic pathology. Also, there were fibroids with degeneration, marked proliferative activity, and a massive inflammatory reaction of the peritoneum – that was diagnosed as a malignant ovarian tumor. Tumor biopsies were examined using morphological and immunohistochemical methods (with the р16, Ki-67, p53, CD 117, S 100, CD 34 markers). Immunohistochemical (IHC) studies were performed with formalin-fixed paraffin materials using the avidin-biotin-peroxidase method. Antibodies to estrogen receptor (ER), progesterone receptor (PR), cytokeratin 7 (CK7), cytokeratin 20 (CK20) and Wilms tumor protein 1 (WT1) were also used.Results. A thorough analysis of the clinical picture and a joint multidisciplinary discussion (gynecologist, oncologist, radiologist, etc.) made it possible to avoid diagnostic errors.Conclusion. These observations demonstrate the difficulties of differential diagnosis between ovarian metastases of uterine cancer and primary multiple ovarian and uterine cancer, as well between leiomyosarcoma and uterine myoma with high mitotic activity. Obviously, the change in diagnosis calls for a change in the treatment strategy.

Extensive studies of the rudimental tissues taken from patients with aplasia of the uterus and vagina are aimed at elucidation of the mechanisms of the genesis of these malformations and at the search of the ways of their correction. We performed a histological examination of human uterine rudiments and immunohistochemical analysis of the expression of estrogen and progesterone receptors, VEGF, and stem/progenitor cell markers in these tissues. We found that the rudimental tissues show signs of disorganized histogenesis, but retain activity and contain cells expressing estrogen and progesterone receptors and VEGF as well as poorly differentiated precursor cells or stem cells. The presented data contribute to the in-depth studies of the mechanisms of formation of uterine rudiments and development of methods of their correction.

Aim. To conduct a retrospective analysis and evaluate the morphological methods for HPV-related intraepithelial lesions detection in women of reproductive age. Materials and methods. The data of cytological diagnosis, as well as the results of histological reports were analyzed for the period from 2018 to 2019. A comparative analysis was performed in 415 patients with HPV-related intraepithelial lesions, who applied to the scientific and polyclinic department of the Kulakov National Research Medical Center at the age of 19 to 45 years. Morphological examination was carried out by specialists of the 1st pathology department of the Center. Results. According to the results of a comparative analysis of cytological and histological conclusions, 3 groups were formed: 1 the group of coincidence (agree) of cytological and histological conclusions; 2 group of minor discrepancies (minor under/ over) between cytological and histological finding; 3 group of major discrepancies (major under/ over) between cytological and histological findings. Cytological and histological compliance was achieved in 194 (46.74%) patients. The total number of minor nonconformities was 192 (46%) cases. The total number of significant discrepancies between cytological and histological findings was 29 (6.9%) patients: 20 (4.8%) cases were found in the group NILM, hr. cervicitis HSIL and 9 (2.1%) cases in the group HSIL hr. cervicitis according to the results of histological examination. Conclusion. Cervical screening reduces the risk of breast cancer due to cytological examination of the cervix, but histological examination is crucial in making a correct diagnosis, since its result determines the choice of treatment method. The comparative analysis showed that in all groups there were cases of hypo- and hyperdiagnostics during cytological examination although the major discrepancies which can change treatment algorithm, were found only in 6.8% cases.

ObjectiveIn vitro maturation of oocytes collected from oophorectomy samples might be a promising approach in the field of oncofertility. In this study, we evaluate the feasibility of in vitro maturation of oocytes collected from oophorectomy samples in patients with ovarian tumors.MethodsThis prospective observational study included 27 patients with malignant ovarian tumors. Patients underwent oophorectomy and ovarian tissue was examined for the presence of immature cumulus-oocyte complexes. These were matured in vitro for 48 hours. Mature oocytes were vitrified or used for fertilization. Serum anti-müllerian hormone (AMH) levels were analyzed in 11 patients and cancer antigen 125 (CA125) levels in 16 patients.ResultsIn this study, 99 cumulus-oocyte complexes were obtained from 17 patients (63%). The mean (SE) age of the patients was 33.47±1.86 years (range 16–44). A total of 14 patients had ovarian cancer (IA–IVB), one patient had ovarian cancer IC and endometrial cancer IA, one patient had endometrial cancer stage IA with metastasis into the ovary, and one patient had cervical cancer stage IIB with metastasis in the ovary. Oocytes were not obtained in 10 patients who had diminished ovarian reserve due to age (>38 years), chemotherapy, or previous surgical treatment. On average, 5.8 cumulus-oocyte complexes were obtained per patient. The maturation rate was 40.4% with an average of 2.8 metaphase II oocytes per patient. As a result of the study, 3 blastocysts in 3 patients and 22 oocytes in 9 patients were vitrified.ConclusionsIn vitro maturation of oocytes collected from oophorectomy samples in patients with malignant ovarian tumors may result in oocyte and blastocyst vitrification. However, it should be offered to patients before surgery and chemotherapy. This method might be most beneficial in patients younger than 38 years, with AMH serum levels >1 ng/mL and without a large tumor burden.

Ovarian cystadenofibroma (CAF) is a rare ovarian tumor originating both from epithelial and stromal components being, however, classified as epithelial tumors. CAF prevalence among all ovarian tumors does not exceed more than 1.7 %. CAFs are commonly asymptomatic, in extremely rare cases of large tumor or ovarian torsion pain sensation may be noted. External genital endometriosis (EGE) is a chronic gynecological disorder that occurs in women of reproductive age and cause infertility and pelvic pain. EGE prevalence comprises around 10 % in women of reproductive age, 20–50 % in women with infertility, and almost 90 % in women with chronic pelvic pain. Magnetic resonance imaging (MRI) is method of choice in diagnostics of such pathology due to the high natural soft tissue contrast and functional techniques such as diffusion-weighted images (DWI) and dynamic contrast enhancement (DCE). Surgery planning, necessity for systemic therapy or follow-up directly depend on imaging and diagnostic laparoscopy results. Here we present a clinical case of rarely combined serous papillary CAF with extended EGE accompanied with consequences of intra-tumoral hemorrhage. Case study demonstrates main visualization characteristics that provide correct differential diagnosis and exclude malignancy transformation.

Aim. To evaluate the endometrial glyotype in the implantation window in patients with infertility in assisted reproductive technologies (ART) programs and to develop criteria for assessing endometrial receptivity based on the analysis of complex changes in the functional groups of glycans in the main endometrial epithelial to use in clinical practice. Materials and methods. The study included 32 infertile patients who took part in ART programs. Pipelle endometrial biopsy was performed during the implantation window in the cycle preceding the cycle of ovarian stimulation and embryo transfer. Using lectin histochemistry and immunohistochemistry, glycans levels in the glycocalyx of endometrial surface epithelium (SE) and glandular epithelium (GE) was studied. Results. Differences in the expression of mannose-rich glycans in SE and N-acetylgalactosamine--terminated glycans in the GE of the endometrium were revealed, as well as the link between the expression of lectin staining glycans: ConA, VVL, UEA-I, SNA, MAL-II, ECL and monoclonal antibodies: anti-MECA -79 mAb and anti-LeY mAb in SE and GE of the endometrium was assessed in patients with infertility, depending on the outcome of the ART program. The estimated threshold levels in glycan expression and the odds ratio for pregnancy occurrence allow to characterize the diagnostic value for the studied glycomarkers and to develop criteria for assessing endometrial receptivity. Conclusion. Based on a comprehensive evaluation of glycans in the main endometrial epithelial structures in the cycle preceding the ART cycle, criteria for assessment of the likelihood of pregnancy have been developed, which can increase the effectiveness of ART programs in patients with infertility.

Septoria leaf spot is the most serious blackcurrant disease in Western Siberia. Two Bacillus subtilis strains BZR 336g and BZR 517 isolated in geographically distant locality (south of Russia) were evaluated for the blackcurrant disease suppression in field experiments (Western Siberia). The field trials were conducted on two cultivars differed by their susceptibility to Septoria ribis in two consecutive years differed by environmental conditions. As a rule, plant treatment with bacterial suspensions (105 and 106 CFU/ml) significantly (P

Chronic inflammation underlies the progression of many human systemic disorders, including a number of gynecological diseases such as endometriosis and chronic endometritis. Inflammasomes play a special role in the regulation of intercellular interactions under physiological and pathological conditions. The pathogenesis of chronic inflammation assumes a gradual course, accompanied by prolonged maintenance active state of inflammasomes due to the excessive accumulation of intracellular and extracellular endogenous molecules released from destroyed cells – DAMPs (damage-associated molecular patterns), their ineffective utilization by autophagy and stress-reducing cell systems, local production of pro-inflammatory cytokines (IL-1β, IL-18), as well as ROS (reactive oxygen species), accumulation of macrophages and T-lymphocytes, tissue damage and the development of fibrosis. The proteins of the inflammasome complex can serve as targets for drugs, which will increase the efficiency of therapy for inflammation-associated diseases. This review presents the current data on the role of NLRP3-inflammasomes in immune regulation and the molecular mechanisms underlying the pathogenesis of endometriosis and chronic endometritis. Understanding the molecular mechanisms of inflammasome activation and the discovery of their effective inhibitors, as well as the assessment of the therapeutic potential in these pathologies, is an important direction of future research. Keywords: inflammasome, inflammation, innate immunity, endometriosis, chronic endometritis

We studied the association of polymorphic markers of cell cycle control genes (Arg72Pro of the TP53 gene, T(-410)G of the MDM2 gene, and Ser31Arg of the CDKN1A gene) in ovarian cancer and progression-free survival following platinum-based chemotherapy. Tumor tissue samples obtained from 49 patients who had undergone chemotherapy were examined. Patients received standard platinum-based chemotherapy and were observed until disease progression. Polymorphic markers of genes were evaluated by PCR-RFLP and real-time PCR. In patients carrying the G allele of the T(-410)G marker of the MDM2 gene, a decreasing trend was observed in median progression-free survival. An increase in the median progression-free survival was observed in carriers of the Pro allele of the TP53 gene (p=0.045). Furthermore, a stronger association was noted with carriers of the minor Pro/Pro homozygous genotype relative to the Arg/Arg genotype (p=0.007). In the subgroup of patients who underwent optimal or complete cytoreductive surgery, carriage of the minor Arg allele of the Ser31Arg marker (CDN1A gene) was associated with a decrease in the median progression-free survival time (p=0.004).

In the period from 2012 to 2015 on Kalym winter wheat variety plants there were carried out field tests of the liquid culture of B. subtilis BZR 336g and BZR 517 strains isolated from natural sources that exhibit antifungal activity against phytopathogenic fungi Fusarium graminearum, F. culmorum, Microdochium nivale and Pyrenophora tritici-repentis, and are also able to have a positive effect on the growth and development of plants. Pre-sowing seed treatment and two preventive treatments during the growing season of the plants were carried out with the liquid culture of the strains. Comparison variants - treatment with water (control), with chemical (Raxil, KS; Alto Super, KS) and with biological (Fitosporin-M, L) standards. Biological efficacy against the complex of fusarium root rots was noted in the shooting stage of winter wheat and during ripening, and in some years reached 22.8 % for B. subtilis BZR 336g strain and 17.2 % for B. subtilis BZR 517 strain. In variants with presowing seed treatment and treatment of vegetative winter wheat plants with B. subtilis BZR 336g strain for three years of field trials the yield was from 5.0 to 7.4 t / ha, and when treated with B. subtilis BZR 517 strain - from 4.2 to 7.6 t / ha. The maximum additional yield was obtained in 2013 - a reliable yield increase was 1.6 t / ha for B. subtilis BZR 336g strain and 0.8 t / ha for B. subtilis BZR 517 strain. The ability of liquid cultures of the studied strains to protect winter wheat against harmful diseases at the same level and above the biological and chemical standards will help to expand the range of microbial biological products in the segment of the Russian market of environmentally friendly plant protection products.

Currently, there is an active development of environmentally friendly methods of farming. However, the range of products for this type of farming system is limited. Growth stimulation is one of the mechanisms ensuring plant resistance to diseases that reduce crop yields. The aim of the work is to study the effect of laboratory samples of new biological products based on B. subtilis BZR 336 g, B. subtilis BZR 517, P. chlororaphis 245 F strains and organo-mineral fertilizers PRK White Pearl Brown (WPB) and PRK White Pearl Universal” (WPU) on plant growth and development of plants, as well as study of the possibility of their joint use for subsequent inclusion in organic farming systems or integrated plant protection. Growthpromoting ability was assessed in winter wheat and sunflower plants grown in sand in a climatic chamber. As comparison variants there were seed treatment with water (control), chemical (Dividend Star, KS) and biological (Fitosporin-M, F, B. subtilis 26 D) standards. In two plant cultures there was an expected retardant effect of the chemical standard and the growth-promoting effect of the biological standard. Statistically significant data were obtained for such a parameter as the shoot length. On winter wheat, laboratory samples provided the shoot length of 24.1-25.2 mm (an addition to the control of 3.4-8.2%), organic and mineral fertilizers - 23.9-24.5 mm (2.6-5.2%), mixtures with WPU - 23.2-24.4 mm (-0.4-4.7%), mixtures with WPB - 24.1-25.9 mm (3.4-11.2%), a significant increase in root length was not observed in this culture. On winter wheat, it is advisable to use the studied products separately. Sunflower is more responsive to the action of laboratory samples. They provided a shoot length of 13.6-14.6 mm (20.9-27.0%) and a root of 9.2-10.2 mm (4.5-15.9%). Organo-mineral fertilizers provided a shoot length of 14.2-14.5 mm (23.5-26.1%) and the root length of 10.8 mm (22.7%). Mixtures with WPU provided shoot length of 14.7-15.4 mm (27.8-33.9%), mixtures with WPB provided shoot length of 11.9-14.5 mm (3.5-26.1%), and no significant increase in root length was noted. The data obtained indicate the presence in the laboratory samples of fungicidal biological products growth-promoting properties, which vary depending on the culture and additionally used organic and mineral fertilizers. To confirm the results, additional experiments are necessary. Research in this direction will allow the rational use of the studied means of protection and increase plant yields in systems of organic, ecologized and integrated farming, and can help reduce the pesticidal pressure on agrocenoses.Conflict of interest: the authors stated that there was no conflict of interest.

Simple Summary Vulvar squamous cell carcinoma (VSCC) is the most frequent malignant vulvar tumor, with a peak incidence in the 7–8th decades of life. However, VSCCs can also occur in young women. This unfortunate event is even rarer and more worrisome in pregnant women, being hard to manage for gynecologists, oncologists, and radiotherapists. Very few cases have been reported and we felt the need for an updated review on this topic. Thus, we performed a systematic literature review of VSCCs diagnosed during pregnancy, discussing the clinic-pathologic features, the implications in pregnancy outcomes, and the effects of such a diagnosis in the management of mothers and their babies. Abstract According to our systematic literature review (PRISMA guidelines), only 37 vulvar squamous cell carcinomas (VSCCs) were diagnosed during pregnancy (age range: 17–41 years). The tumor size range was 0.3–15 cm. The treatment was performed after (14/37, 38%), before (10/37, 27%), or before-and-after delivery (11/37, 30%). We found that 21/37 (57%) cases were stage I, 2 II (5%), 11 III (30%), and 3 IVB (8%). HPV-related features (condylomas/warts; HPV infection; high-grade squamous intraepithelial lesion) were reported in 11/37 (30%) cases. We also found that 9/37 (24%) patients had inflammatory conditions (lichen sclerosus/planus, psoriasis, chronic dermatitis). The time-to-recurrence/progression (12/37, 32%) ranged from 0 to 36 (mean 9) months. Eight women died of disease (22%) 2.5–48 months after diagnosis, 2 (5%) were alive with disease, and 23 (62%) were disease-free at the end of follow-up. Pregnant patients must be followed-up. Even if they are small, newly arising vulvar lesions should be biopsied, especially in women with risk factors (HPV, dermatosis, etc.). The treatment of VSCCs diagnosed in late third trimester might be delayed until postpartum. Elective cesarean section may prevent vulvar wound dehiscence. In the few reported cases, pregnancy/fetal outcomes seemed to not be affected by invasive treatments during pregnancy. However, clinicians must be careful; larger cohorts should define the best treatment. Definite guidelines are lacking, so a multidisciplinary approach and discussion with patients are mandatory.

Aim. To analyze the literature data on modern approaches to morcellation of myomatous nodes in laparoscopic surgery and to highlight this area in a historical aspect. To form an idea of the main difficulties associated with morcellation, which contributed to and contribute to the improvement of the technique of this manipulation. Materials and methods. The review includes data from foreign articles published in the elibrary.ru and PubMed databases on this topic. Results. It describes both modern trends in the surgical treatment of patients with uterine myoma, and historical aspects of improving methods aimed at reducing risks, reducing the time of surgical intervention and improving its safety. Analyzed data on the use of electromorcellation, carried out both with the use of plastic containers, and without them. Conclusion. High requirements for surgical interventions contributed to the emergence of such a method of intracorporeal fragmentation of drugs, such as morcellation, which led to a significant reduction in the proportion of laparotomic operations in the treatment of patients with my uterus. The introduction of laparoscopy in the surgical treatment of uterine myoma allowed to achieve a fundamentally new high level of rehabilitation of patients. Removing removed drugs from the abdominal cavity is associated with a certain risk. Despite the significant number of proposed methods and devices for morcellation, they all require further improvement, since it is necessary to completely exclude contact of the myoma node tissue with abdominal organs in the extraction process. Currently, active research continues on ways to realize all the benefits of minimally invasive technologies in compliance with the rules of oncological safety.

Background Low endometrial receptivity is one of the major factors affecting successful implantation in assisted reproductive technologies (ART). Infertile patients with thin endometrium have a significantly lower cumulative clinical pregnancy rate than patients with normal endometrium. Molecular pathophysiology of low receptivity of thin endometrium remains understudied. We have investigated composition of glycocalyx of the apical surface of luminal and glandular epithelial cells in thin endometrium of infertile women. Methods Thirty-two patients with tubal-peritoneal infertility undergoing in vitro fertilization (IVF) were included in the study. Endometrial samples were obtained in a natural menstrual cycle. Patients were divided into two groups: patients with normal endometrium (≥8 mm) and with thin endometrium (Y and MECA-79 monoclonal antibodies (MAbs). Results Complex glycans analysis taking into account the adjusted specificity of glycan-binding MAbs revealed 1.3 times less expression of MECA-79 glycans on the apical surface of the luminal epithelial cells of thin endometrium compared to normal endometrium; this deficiency may adversely affect implantation, since MECA-79 glycans are a ligand of L-selectin and mediate intercellular interactions. The glycans containing a type-2 unit Galβ1-4GlcNAcβ (LacNAc) but lacking sulfo-residues at 6-OH of GlcNAcβ, and binding to MECA-79 MAbs were found; they can be considered as potential markers of endometrium receptivity. Expression of the lectins-stained glycans on the apical surfaces of the luminal and glandular epithelial cells did not differ significantly. Correlation between the expression of difucosylated oligosaccharide LeY on the apical surfaces of the luminal and glandular epithelial cells was found in patients with thin endometrium and recurrent implantation failure. A similar relationship was shown for mannose-rich glycans. Conclusions Specific features of key glycans expression in epithelial compartments of thin endometrium may be essential for morphogenesis of the endometrial functional layer and explain its low receptivity.

Bacillus velezensis strain BZR 277 is a rhizobacterium isolated from the rhizoplane of a winter oilseed rape plant from the Krasnodar region in Russia. This study presents the genome sequence of the rhizobacterium Bacillus velezensis BZR 277, which exhibited high antagonistic activity against the root-knot nematode Meloidogyne incognita Kof., Bacillus velezensis strain BZR 277 is a rhizobacterium isolated from the rhizoplane of a winter oilseed rape plant from the Krasnodar region in Russia. This study presents the genome sequence of the rhizobacterium Bacillus velezensis BZR 277, which exhibited high antagonistic activity against the root-knot nematode Meloidogyne incognita Kof. The data on the genome sequence can help to identify pathways for the biosynthesis of metabolites responsible for nematicidal activity in order to improve crop protection against plant-parasitic nematodes.

Bacillus velezensis strain BZR 517 is a prospective plant growth-promoting rhizobacterium with known biocontrol properties, which may be used to improve soil quality. The genome sequencing was conducted as part of new biological agent development in order to determine the biocontrol potential of the strain, including the production of biologically active compounds.

Bacillus velezensis strain BZR 336g is a plant growth-promoting rhizobacterium isolated from a winter wheat rhizoplane from the Krasnodar region in Russia. In this study, we report the genome, including genes with known phenotypic function, i.e., the biosynthesis of secondary metabolites with fungicidal and plant growth-promoting activities. We sequenced and analyzed the complete BZR 336g genome using two different DNA preparation methods to help us better understand the origin of the antimicrobial and antifungal abilities and to weigh the biocontrol properties of this strain.

The article presents some aspects of the interaction between biocontrol Bacillus subtilis strains and phytopathogenic fungi Fusarium and Pyrenophora. The presence of antifungal metabolites complexes in the culture fluid of the strains, including surfactin and iturin A has been found. The nature of the changes in the mycelium of phytopathogenic fungi is examined when co-cultivated with B.subtilis strains.

Stem canker and black scurf caused by Rhizoctonia solani are the important diseases in potato, while spur blight caused by Didymella applanata is a major disease in red raspberry. In Western Siberia, both crops are grown predominantly in small-scale farming that requires maximal usage of biological products for plant protection instead of chemicals. We evaluated two promising Bacillus velezensis strains BZR 336 g and BZR 517 isolated in the south of Russia (45°1′N, 38°59′E) for their biological control potentials against the potato and red raspberry diseases under the more severe weather conditions of Western Siberia (55°1′N, 82°55′ E). We tested two techniques to apply biocontrol agents: (1) coating the seeds (potato tubers) and (2) spraying over the plants (raspberry canes). In each case, we estimated B. velezensis strains on two plant cultivars differed by the disease resistance. The degree of B. velezensis influence on disease incidence and severity depended on the bacterial strain, the protected plant, and its cultivar. We also demonstrated that two B. velezensis strains significantly stimulated plant growth of potato, which contributed to the plant productivity on both cultivars. The BZR 336 g strain affected the potato productivity more than the BZR 517 strain. Under the influence of both bacterial strains, raspberry yield was significantly higher compared to the control on the susceptible cultivar. These findings indicated that two southern B. velezensis strains had proved their efficacy as biological control agents in the control of the serious fungal infection of potato and raspberry plants under the more severe ecological conditions of Western Siberia. For the first time, we demonstrated B. velezensis strains potential for use as biological control agents against R. solani on potato, and against D. applanata on red raspberry.

As a result of a series of experiments to study the entomopathogenic activity of bacteria and viruses from the “State Collection of Entomoacariphages and Microorganisms”, it was revealed that the large wax moth Galleria mellonella L. it is sensitive to new strains of bacteria and viruses. In the future, the strains can be used in the subsequent stages of screening of microorganisms that are promising as agents of biological pest control. The maximum biological efficacy on the fifth day against the tested insect was observed when using bacterial strains Bacillus spp. BZR 1159 (94.6%) and BZR 936 (95.0%) and a granulovirus strain of the codling moth (CpGV) BZR L-5 (100%). Larvae of G. mellonella L were susceptible to melanization in the process of infection with new bacterial and viral agents.

to investigate the frequency of the types of fallopian tubal secretory cell expansion (SCE) in diseases of the reproductive organs and to determine the immunophenotype and biological role of the cells in the early stages of the pathogenesis of high-grade ovarian serous carcinomas (HGOSC).The investigation enrolled 287 patients with extraovarian diseases and ovarian serous tumors varying in grade, whose fallopian tubes were morphologically and immunohistochemically examined using p53, Ki-67, PAX2, Bcl-2, beta-catenin, and ALDH1 markers. The material was statistically processed applying the Mann-Whitney test and χ2 test.The rate of secretory cell proliferation (SCP) (more than 10 consecutive secretory cells) and that of secretory cell overgrowth (SCO) (more than 30 consecutive secretory cells) increase with age in all investigated reproductive system diseases. The rate of SCP in the corpus fimbriatum of the patients with HGOSC was 5.9 times higher than that in those with extraovarian disease (p0.01); when comparing the same patient groups, that of SCO was 3.4 times higher (p0.05). The immunohistochemical characteristics of the investigated lesions (in scores) were as follows: PAX2 was expressed in the intact epithelium (2.8), in SCP (1.3), in SCO (1.2), in serous tubal intraepithelial carcinoma (STIC) (1.0), and in HGOSC (0.9); Bcl-2 was in the intact epithelium (2.2), in SCP (2.1), STIC (0.9), and in HGOSC (0.6), β-catenin was in the intact epithelium (0.5), in SCP (2.85), in SCO (2.95), in STIC (0.6), and in HGOSC (0.5); ALDH1 was in the intact epithelium (0.5), in SCP (2.91), in SCO (2.92), in STIC (1.2), and in HGOSC (0.6). There were statistically significant differences with a 95% confidence interval (p0.05) for: 1) PAX2 between the intact epithelium and pathology (fallopian tube lesions and HGOSC); 2) Bcl-2 between the intact epithelium and SCE (SCP and SCO) and between SCE and HGOSC; 3) beta-catenin between the intact epithelium and SCE (SCP and SCO) and between SCE and HGOSC; 4) ALDH1 between the intact epithelium and SCE, between and SCE and STIC, and between STIC and HGOSC.SCE was shown to be an independent intraepithelial lesion. The incidence of this abnormality increased with age and significantly differed in the patients with fallopian tubal lesions in extraovarian diseases from that in those with malignant ovarian serous tumors (by 5.3 times), while these groups showed a three-fold difference in SCO. Thus, SCP may serve as a more sensitive marker for the early stages of the pathogenesis of ovarian serous carcinoma. The studied types of SCE demonstrated multiple molecular events (loss of PAX2 expression and increased Bcl-2, beta-catenin, and ALDH1 expressions), some of which underwent considerable changes, by increasing the severity of a pathological process (loss of ALDH1, and beta-catenin, and bcl-2 expressions). Thus, therapeutic exposure in the early stages of pathogenesis may have a few points of application and just several molecules can serve as independent markers for early pathological changes in the fallopian tubal epithelium.Цель исследования - изучить частоту возникновения вариантов экспансии секреторных клеток эпителия маточной трубы при патологии органов репродуктивной системы, определить их иммунофенотип и биологическую роль на ранних этапах патогенеза серозных карцином яичника высокой степени злокачественности (СКЯВСЗ). Материал и методы. В исследование включены 287 пациенток с экстраяичниковой патологией и серозными опухолями яичника разной степени злокачественности, маточные трубы которых исследованы морфологически и иммуногистохимически (с маркерами р53, Ki-67, PAX2, Вcl-2, β-catenin, ALDH1). Статистическая обработка материала выполнена с использованием критериев Манна-Уитни и χ2. Результаты. Частота возникновения пролиферации секреторных клеток - ПСК (более 10 секреторных клеток подряд) и разрастания секреторных клеток - РСК (более 30 секреторных клеток подряд) возрастает с возрастом при всех изученных патологиях репродуктивной системы. В фимбриальном отделе частота ПСК в маточных трубах пациенток СКЯВСЗ в 5,9 раза выше, чем у пациенток с экстраяичниковой патологией (p0,01), частота РСК при сопоставлении тех же групп была в 3,4 раза выше (p0,05). Иммуногистохимическая характеристика изученных поражений была следующей (в баллах): экспрессия PAX2 составила в нормальном эпителии 2,8, в ПСК 1,3, в РСК 1,2, в серозной трубной интраэпителиальной карциноме (СТИК) 1,0, в СКЯВСЗ 0,9, экспрессия Вcl-2 составила в нормальном эпителии 2,2, в ПСК 2,1, в СТИК 0,9, в СКЯВСЗ 0,6, экспрессия β-catenin составила в нормальном эпителии 0,5, в ПСК 2,85, в РСК 2,95, в СТИК 0,6, в СКЯВСЗ 0,5, экспрессия ALDH1 составила в нормальном эпителии 0,5, в ПСК 2,91, в РСК 2,92, в СТИК 1,2, в СКЯВСЗ 0,6. Статистически значимые различия с доверительным интервалом 95% (p0,05) выявлены: 1) в отношении PAX2 между нормальным эпителием и патологией (поражениями маточной трубы и СКЯВСЗ); 2) в отношении Вcl-2 между нормальным эпителием и экспансией секреторных клеток (ПСК и РСК), а также между экспансией секреторных клеток и СКЯВСЗ; 3) в отношении β-catenin между нормальным эпителием и экспансией секреторных клеток (ПСК и РСК), а также между экспансией секреторных клеток и СКЯВСЗ; 4) в отношении ALDH1 между нормальным эпителием и экспансией секреторных клеток, между экспансией секреторных клеток и СТИК, а также между СТИК и СКЯВСЗ. Заключение. Показано, что пролиферация секреторных клеток является самостоятельным интраэпителиальным поражением. Частота данной патологии увеличивалась с возрастом, а также достоверно различалась у больных с поражением маточных труб при экстраяичниковой патологии от таковой у пациенток со злокачественными серозными опухолями яичника (в 5,3 раза), при этом уровень разрастания секреторных клеток в данных группах больных различался в 2 раза. Таким образом, пролиферация секреторных клеток может служить более чувствительным маркером ранних этапов патогенеза серозной карциномы яичника. Для изученных типов экспансии секреторных клеток продемонстрированы множественные молекулярные события (утрата экспрессии PAX2, усиление экспрессии Вcl-2, β-catenin и ALDH1), некоторые из которых претерпевали значительные изменения с усилением тяжести патологического процесса (утрата экспрессии ALDH1, β-catenin, Вcl-2). Таким образом, терапевтическое воздействие на ранних этапах патогенеза может иметь несколько точек приложения и сразу несколько молекул могут служить независимыми маркерами ранних патологических изменений эпителия маточной трубы.

We studied the antifungal activity of the Bacillus subtilis BZR 336g strain against the test culture of the fungus Fusarium oxysporum var. orthoceras App. et Wr. BZR 6, depending on the addition of citric acid crystalline hydrate, a microelements solution and corn extract to the liquid nutrient medium. It was found that citric acid at a concentration of 15 g/l improves the bioavailability of microelements and increases antifungal activity. Corn extract and microelements without the formation of a chelate form with citric acid do not affect the fungicidal properties of B. subtilis BZR 336g. However, the corn extract at a concentration of 3 g / l increases the titer of bacteria in the liquid culture from 2 ± 0.1 × 108 to 1 ± 0.08 × 108 CFU/ml. The combined use of the studied components allowed us to achieve a significant increase in the antifungal activity of B. subtilis BZR 336g by 3.1 times. At the same time, the effect of synergism in their complex interaction was noted, which is probably due to a qualitative and quantitative change in the composition of B. subtilis BZR 336g antifungal metabolites.

to study the incidence of fallopian tube lesions (secretory cell proliferations (SCP), p53 signature, serous tubal intraepithelial lesions (STIL), and serous tubal intraepithelial carcinomas (STIC) in ovarian epithelial tumors and to propose their pathogenetic association with a certain histotype of the ovarian tumor.The investigation enrolled 136 patients with ovarian epithelial tumors, whose fallopian tubes were morphologically and immunohistochemically (IHC) examined using p53, Ki-67, and PAX2. Statistical analysis was carried out applying the Mann-Whitney test and χ(2) test.Lesions meeting the STIC criteria were found in 14.7% of cases (only in ovarian serous carcinoma (OSC)), those suspecting STICs were in 25.7%, and those without signs of STICs were in 59.6%. IFC examination diagnosed STIC in 10% of cases (only in OSC), STIL in 13.3%, p53 signature in 11.7% (only in serous tumors), and the normal/reactively changed tubal epithelium in 65%. The incidence of STILs correlated with the malignant potential of serous tumors significantly (p0.05). There were significant differences in the incidence of STILs in patients with different histotypes of ovarian carcinomas (p0.05). PAX2-negative SCP was detected in 75% of OSC, 60% of serous borderline tumors, and 40% of serous cystadenomas. The differences in the incidence of SCP between serous tumors of varying grade, between serous tumors and non-serous carcinomas, between OSC and non-serous carcinomas were significant (p0.05).The investigation has shown that IHC examination should be used for the accurate diagnosis of STILs. It has also provided evidence for the pathogenetic association between STIC and high-grade OSC and revealed significant differences in the incidence of other fallopian tubal intraepithelial lesions in serous cystadenomas, borderline tumors, and OSC, in different ovarian carcinomas. The findings may suggest that the earliest stage in the pathogenesis of OSC is the development of SCP, followed by the formation of p53 signatures that may further give rise to STIL, and finally STC (due to the acquisition of additional mutations).Цель исследования - изучить частоту возникновения поражений маточной трубы (разрастаний секреторных клеток (РСК), p53-signature, серозных трубных интраэпителиальных поражений (СТИП), серозных трубных интраэпителиальных карцином (СТИК) при эпителиальных опухолях яичника) и высказать предположение об их патогенетической связи с определенным гистотипом опухоли яичника. Материал и методы. В исследование включены 136 пациенток с эпителиальными опухолями яичника, маточные трубы которых исследованы морфологически и иммуногистохимически (ИГХ) (р53, Ki-67, PAX2). Статистическая обработка материала выполнена с использованием критериев Манна-Уитни и χ2. Результаты. Поражения, соответствующие критериям СТИК, выявлены в 14,7% случаев (только при серозной карциноме яичника - СКЯ), подозрительные в отношении СТИК - в 25,7% случаев, не имеющие признаков СТИК - в 59,6%. После ИГХ-исследования СТИК диагностирована в 10% случаев (только при СКЯ), СТИП - в 13,3%, р53-signature - в 11,7% (только при серозных опухолях), нормальный/с реактивными изменениями трубный эпителий - в 65% случаев. Частота возникновения интраэпителиальных поражений маточной трубы достоверно коррелировала со злокачественным потенциалом серозных опухолей (p0,05). Достоверные различия в частоте возникновения интраэпителиальных поражений маточной трубы выявлены среди пациенток с карциномами яичника разных гистотипов (p0,05). PAX2-негативные РСК диагностированы при 75% СКЯ, 60% серозных пограничных опухолей, 40% серозных цистаденом. Достоверно значимыми были различия во встречаемости РСК между серозными опухолями различной степени злокачественности, серозными опухолями и несерозными карциномами, СКЯ и несерозными карциномами (p0,05). Заключение. Показано, что для точной диагностики интраэпителиальных поражений маточной трубы необходимо применение ИГХ-исследования. Подтверждена патогенетическая связь между СТИК и СКЯ высокой степени злокачественности и выявлены значимые различия во встречаемости других интраэпителиальных поражений маточной трубы при серозных цистаденомах, пограничных опухолях и СКЯ, при различных карциномах яичника. На основании полученных результатов можно предположить, что наиболее ранним этапом в патогенезе СКЯ является развитие РСК, далее образуются р53-signature, которые в дальнейшем могут дать начало развитию СТИП и, наконец, СТИК (при приобретении дополнительных мутаций).

Stratified mucin-producing intraepithelial lesion (SMILE) is a rare premalignant cervical lesion that combines the structural features of cervical intraepithelial neoplasia (CIN) and endocervical adenocarcinoma in situ (AIS).to analyze archival materials for the detection of SMILE and its subsequent morphological and immunohistochemical characterization.Cervical cone specimens from 53 women with histologically verified CIN3 were examined. The diagnosis of SMILE was based on the positive mucicarmine staining and weak focal expression of p63. The samples containing SMILE were further immunohistochemically examined using the biomarkers P16, Ki-67, Oct4, CD117, CD34, p53, EMA, and CK15. SMILE was detected in 2 of the 53 patients and concurrent with CIN3 in both cases. SMILE was characterized by the stratified arrangement of atypical cells containing mucin, the positive mucicarmine staining of the entire layer of the atypical epithelium, weak focal p63 expression, high Ki-67 expression, and diffuse р16Іnk4а staining. Both SMILE samples showed weak diffuse p53 expression in the presence of single cells with the pronounced nuclear staining pattern for p53 in one female patient. Weak focal CK15 expression was visualized in SMILE. The expression of the stem cell markers Oct4 and CD117 and the angiogenic marker CD34 was absent in the examined cervical epithelial preparations. The diffuse and intense expression of the marker EMA, which was not different from that in the endocervical and stratified squamous epithelium, and CIN3 was established in SMILE.The findings suggest that SMILE is morphologically and immunohistochemically similar to CIN3. In this investigation, these abnormalities differed only in the mucicarmine staining and expression of p63. This may be indicative of the underdiagnosis of SMILE, attendant СIN3 in the routine practice of a clinical pathologist, as the diagnosis of CIN3 is primarily based on the results of assessment of only the preparations stained with hematoxylin and eosin; the expression of p16 and Ki-67 is evaluated in some cases, which fails to differentiate SMILE and CIN3 in a number of preparations.The diagnosis of SMILE can be made only by immunohistochemical examination.Многослойное муцинпродуцирующее интраэпителиальное поражение (SMILE) относится к редким предраковым изменениям шейки матки, сочетающим структурные особенности цервикальной интраэпителиальной неоплазии (CIN) и эндоцервикальной аденокарциномы in situ (AIS). Цель - анализ архивного материала для обнаружения SMILE с последующей его морфологической и иммуногистохимической характеристикой. Материал и методы. Исследованы гистологические препараты конусов шейки матки с верифицированным диагнозом CIN3 от 53 женщин. Образцы, содержащие SMILE, подвергались дальнейшему иммуногистохимическому исследованию с использованием биомаркеров. SMILE обнаружено у 2 из 53 пациенток и в обоих случаях сопровождало CIN3. SMILE характеризовалось многослойным расположением атипических клеток, содержащих муцин, позитивным окрашиванием на муцикармин всего пласта атипического эпителия, слабой очаговой экспрессией р63, высокой экспрессией Ki-67, диффузным окрашиванием р16Ink4a. В обоих образцах SMILE наблюдалась диффузная слабая экспрессия р53, с присутствием единичных клеток с выраженным ядерным окрашиванием р53 у одной пациентки. В SMILE визуализировалась слабая очаговая экспрессия ck15. Экспрессия маркеров стволовых клеток okt4 и CD117 и маркера ангиогенеза CD34 отсутствовала в эпителии изучаемых препаратов шейки матки. В SMILE установлена диффузная, интенсивная экспрессия маркера EMA, не отличающаяся от таковой в эндоцервикальном и многослойном плоском эпителии, и CIN3. Результаты. Полученные результаты свидетельствуют о морфологическом и иммуногистохимическом сходстве SMILE с CIN3. В настоящем исследовании данные патологии различались лишь по окрашиванию муцикармином и экспрессии р63. Это может свидетельствовать о гиподиагностике SMILE, сопутствующих СIN3, в рутинной практике клинического патолога, так как диагноз CIN3 преимущественно устанавливается на основании результатов оценки только препаратов, окрашенных гематоксилином и эозином, в части случаев оценивается экспрессия р16 и Ki-67, что в ряде препаратов не позволяет дифференцировать SMILE и CIN3. Заключение. Диагноз SMILE может быть поставлен только при применении иммуногистохимического исследования.