[Comprehensive analysis of population mortality by cause: regional features].

Chronic non-communicable diseases (CNCDs) are the main most common causes of death both in the Russian Federation and in the Republic of Tatarstan. Thus, in the traditional structure of mortality in the Republic of Tatarstan in 2022, a "classical triad" is defined: diseases of the circulatory system are in first place (46% of all deaths), neoplasms are in second place (15%), and external causes are in third place. (7.3%). As throughout the world, during the coronavirus infection there was an increase in population mortality from all causes, mainly from diseases of the circulatory system (hereinafter referred to as CVD), as well as directly from coronavirus infection, which is the cause of almost every fifth death in the Republic of Tatarstan in 2021. The peak of coronavirus infection reduced the average age of death from cardiovascular causes by 4.5 years in men and by 4 years in women. It was revealed that in the Republic of Tatarstan the probability of death from diseases of the circulatory system and endocrine system in women is higher than in men; In men, on the contrary, there is a higher probability of death from respiratory diseases, cancer and external causes.

[The use of «growing¼ endoprostheses in the complex treatment of children with post-resection mandibular defects]. / Primenenie «rastushchikh¼ endoprotezov v kompleksnom lechenii detei s postrezektsionnymi defektami nizhnei chelyusti.

THE AIM OF THE STUDY: To develop and implement a comprehensive algorithm for the rehabilitation of patients after partial resection of the mandible using a titanium «growing¼ endoprosthesis. MATERIAL AND METHODS: The study included 16 patients aged 2 to 7 years, with benign (6 cases) and malignant (10 cases) tumors of the mandible. The patients were divided into 2 groups depending on the time of fixation of the endoprosthesis. Group 1 included patients with simultaneous installation of a prosthesis (7 people). Group 2 included patients with delayed installation of an endoprosthesis (9 people). For the reconstruction of the mandible, «growing¼ titanium endoprostheses made of Ti6Al4V alloy of various designs were used. Removable orthodontic devices of mechanical and functional type of action, standard elastic mouthguards were used in the process of dental treatment. RESULTS: A comprehensive algorithm has been developed for the rehabilitation of children after partial resection of the mandible, depending on the time of fixation of the prosthesis and the volume of surgical intervention. CONCLUSION: The developed algorithm of complex rehabilitation using a «growing¼ endoprosthesis and dental support at the pre and postoperative stages allows to reduce the volume of secondary deformation of facial structures and dentition.

Voltage-tunable Q factor in a photonic crystal microcavity.

A photonic crystal microcavity with a tunable quality factor (Q factor) has been implemented on the basis of a bound state in the continuum using the advanced liquid crystal cell technology platform. It has been shown that the Q factor of the microcavity changes from 100 to 360 in the voltage range of 0.6 V.

[Repair stimulator alpha-glutamyl-tryptophan in the complex therapy of chronic atrophic gastritis: results of histological examination]. / Stimulyator reparatsii al'fa-glutamil-triptofan v kompleksnoi terapii khronicheskogo atroficheskogo gastrita: rezul'taty gistologicheskogo issledovaniya.

OBJECTIVE: To study the effect of the repair stimulator alpha-glutamyl-tryptophan on the morphological characteristics of the gastric mucosa and the expression of CXCL-12 and CDX-2 in chronic atrophic gastritis associated with Helicobacter pylori. MATERIAL AND METHODS: Biopsy samples of 116 patients with a verified diagnosis of chronic atrophic gastritis associated with Helicobacter pylori were analyzed in a multicenter double-blind randomized placebo-controlled study. During the morphological study, the parameters characterizing the process of atrophy were evaluated: the number of glands per 1 mm2 of the gastric mucosa, the depth of the gastric mucosa glands, the number of parietal cells per 100 epithelial cells of the gastric mucosa, and the presence of signs of intestinal metaplasia. Primary antibodies Anti-CXCL-12 (MA5-23759) and Anti-CDX-2 (EP25) were used to set up immunohistochemical reactions to verify the expression of CXCL-12 and CDX-2. RESULTS: In patients taking the studied drug, a statistically significant increase in the number of glands per 1 mm2 of the gastric mucosa was revealed when compared with the initial screening indicators by 26.1% (p=0.028) and with the placebo group (p=0.026), a tendency to decrease the signs of intestinal metaplasia was determined. There was a statistically significant increase in the expression in the relative area of CXCL-12 expression in patients taking placebo when compared with the parameters of the initial data (p=0.045) and the absence of statistically significant changes in the main group. A statistically significant increase in the relative area of the CDX-2 expression was revealed in the group taking alpha-glutamyl-tryptophan in comparison with the baseline data (p=0.015), no statistically significant dynamics of this indicator was found in the placebo group. CONCLUSION: A statistically significant positive effect of the study drug on regenerative mechanisms leading to stabilization and/or improvement of the histological picture in the atrophic area of the gastric mucosa was found in comparison with the control of the initial state and with placebo. The results of an immunohistochemical study to increase CDX-2 expression while taking the study drug can also be regarded as an indicator of improvement in reparative processes.

[Endoscopic and morphometric analysis of the reduction of acute inflammatory process in the gastric mucosa after therapy with Regasthym Gastro].

AIM: To analyze the anti-inflammatory efficacy of Regasthym Gastro (alpha-glutamyl-tryptophan) in the treatment of patients with chronic atrophic gastritis according to endoscopic and morphometric studies. MATERIALS AND METHODS: As part of a double-blind placebo-controlled study, the results of gastroscopy and histological (morphometric) studies were retrospective analyzed in 80 patients diagnosed with chronic atrophic gastritis associated with Helicobacter pylori in exacerbation: 43 patients took Regasthym Gastro, 37 patients - placebo. The conclusions of the gastroscopy were structured in the form of a standardized scale, which included an assessment of criteria in points (from 0 to 3): thickness of folds, hyperemia, edema of the gastric mucosa, the signs of atrophy, metaplasia; the severity of the erosive process. The sum of points according to all criteria was used to assess the dynamics of the inflammatory process: positive dynamics; lack of dynamics; the pathological process is progressing. The results of the endoscopic examination were compared with morphometry data (the number of inflammation pool cells per 1 mm2 of gastric mucosa). Statistical processing of the results was carried out using the Statistica 12 application software package. RESULTS: According to the gastroscopy, before therapy, hyperemia of the gastric mucosa was present in 82.5%, edema - in 53.8%, erosion - in 17.5%, signs of metaplasia - in 12.5% of patients. After therapy with the investigated drug a statistically significant decrease in the severity of edema of the gastric mucosa (p=0.008), the total set of signs of acute inflammatory process (p=0.006), a decrease in the proportion of outcomes with negative dynamics of the inflammatory process (p=0.038) was revealed. Statistically significant (p<0.05) correlations were found between gastroscopy data of inflammation and the number of neutrophil, eosinophil granulocytes, macrophages and lymphocytes per 1 mm2. CONCLUSION: Regasthym Gastro contributes to a significant decrease in the severity of the inflammatory process according to the evaluation of the results of gastroscopy and morphometry. It is possible to recommend the inclusion of this drug in the complex therapy of chronic gastritis to increase the effectiveness and reduce the risks of progression of inflammation.

[The relationship between penile hemodynamic parameters in cavernous rteries and penile rigidity].

INTRODUCTION: Blood flow parameters in cavernous arteries during full-erection phase on Doppler ultrasonography are associated with intracavernosal pressure and, consequently, with penile rigidity. AIM: To examine the relationship between blood flow parameters in cavernous arteries and the penile rigidity. MATERIALS AND METHODS: A total of 54 healthy men and patients with erectile dysfunction of various degrees of severity, with mean age of 43,0 +/- 2,2 years ranging from 18 to 74 years, were included in the study. Erectile function was examined and 81 Doppler ultrasonography were performed after intracavernosal injection of alprostadil (10 mcg). In full-erection phase, peak systolic velocity (PSV) and systolic acceleration (SA) were measured, as well as resistive index (RI). Mean values were calculated for both cavernous arteries. Penile rigidity was assessed in three ways: clinical evaluation according to I. Goldstein, measurement of surface rigidity and evaluation of longitudinal rigidity. RESULTS: During Doppler ultrasonography a strong correlation of penile rigidity with RI (0,71-0,85) and SA (0,63-0,69) was found. Indirect assessment of penile rigidity using PSV values was less precise. With RI values close to 1,0, SA is a more reliable method for indirect rigidity assessment. CONCLUSION: Penile blood flow parameters, RI and SA, allow to evaluate a degree of rigidity and to eliminate subjectivity of the specialist performing the examination, as well as to obtain a range of penile rigidity values.

[The Drosophila CG9890 Protein is Involved in the Regulation of Ecdysone-Dependent Transcription].

Previously we showed that the CG9890 protein, which has zinc finger domains, interacts with ENY2-containing complexes and is localized mainly on the promoters of active genes. The CG9890 protein is involved in the regulation of the expression of some of the genes on the promoters of which it is located, and among these genes there are genes for the ecdysone cascade. In this work, the role of the CG9890 protein in the regulation of ecdysone-dependent inducible transcription was studied. For this, 12 ecdysone-dependent genes on the promoters of which the CG9890 protein is localized were identified. Their activation was studied after the addition of 20-hydroxyecdysone to cells, both in normal conditions and after RNA interference of CG9890. The expression of ecdysone-dependent genes is significantly increased in response to the treatment of cells with ecdysone, in contrast to the control genes. Moreover, in the cell line after RNA interference CG9890, the transcription of 8 out of 12 genes was significantly higher than in the control line. Thus, the CG9890 protein is involved in the regulation of transcription of ecdysone-dependent genes, and, in most cases, acts as a repressor.

INFLUENCE OF ADDING ZINC ARGINYLE-GLYCINATE TO IMPROVE EFFICACY OF BIOREGULATORY PEPTIDES OF THE PROSTATE GLAND IN TREATMENT OF PATIENTS WITH IMPAIRED SPERM PARAMETERS.

The drug Prostatilen® AC, rectal suppositories were developed on the basis of the previously registered medicine containing bioregulatory peptides of the prostate gland - Prostatilen® rectal suppositories, 3 mg, from whom it differs by the addition of аctive pharmaceutical ingredient zinc arginyle-glycinate dihydrochloride (ZAG). The aim of this study was to analyze the positive effect of adding ZAG to the drug in patients with impaired spermatogenesis. A total of 98 men aged 25-45 years (an average of 35.2±4.3 years) with a verified diagnosis of chronic abacterial prostatitis and related reproductive dysfunctions in the phase III, randomized, multicenter, open-label clinical trial was examined. The duration of participation of patients in the study was 14-16 days, the screening period was 2-3 days, the duration of therapy was 10 days, and the final examination was 2-3 days. A study group (n=49) received therapy with Prostatilen AC once daily, a control group (n=49) had Prostatilen once daily. All patients underwent conventional semen analysis before and after treatment. The obtained parameters were compared. During the analysis of the average statistical data in the comparison groups, it was found that treatment with Prostatilen AC leads to an increase in the total population of motile spermatozoa (cells A + B + C) by 14.3%, and the reference drug Prostatilen contributes to an increase in this indicant by 4.1% compared with the results of a screening examination with significantly higher efficiency in increasing the relative count of spermatozoa with a fast progressive motility (After therapy Prostatilen/Prostatilen AC p=0.0004). Prostatilen AC showed significantly higher efficiency in terms of increasing the count of normal forms of spermatozoa in the ejaculate than the reference drug Prostatilen (After therapy Prostatilen/Prostatilen AC p=0.0118). In patients who received the drug Prostatilen AC the number of abnormal forms of spermatozoa decreased by 12.4% (After therapy - 55.57%), and in the comparison group (drug Prostatilen) by 6.5% (After therapy - 58.90%) with significant decrease in forms of abnormal spermatozoa with head, acrosome, or neck pathology for Prostatilen AC compared to control. Prostatilen AC compared to Prostatilen had a statistically significant and clinically significantly superior efficacy in relation to initially impaired sperm parameters (improve of sperm motility, restoration of morphologically normal sperm, decrease in forms of abnormal spermatozoa with head, acrosome or neck pathology). This drug could be recommended to use in the treatment of patients in whom chronic prostatitis occurs with concomitant disorders of sexual and reproductive functions.

MLE Helicase Is a New Participant in the Transcription Regulation of the ftz-f1 Gene Encoding Nuclear Receptor in Higher Eukaryotes.

MLE helicase is an evolutionarily conserved eukaryotic protein involved in a wide range of processes in the regulation of gene expression. Previously, we studied the properties of MLE on the Drosophila melanogaster model. In the present work we continue studying the functions of MLE and show that MLE interacts with the components of the SWI/SNF chromatin remodelling complex. To clarify the work of MLE, the profile of MLE binding to the regulatory elements of the SWI/SNF-dependent ftz-f1 gene was analyzed. The effect of MLE on the expression of this gene, the transcription of which occurs by the RNA polymerase II pausing mechanism, was investigated. The data obtained indicate the important role of MLE in ensuring timely activation and high level of expression of the ftz-f1 gene in vivo.

Multifunctional ENY2 Protein Interacts with RNA Helicase MLE.

ENY2 protein of Drosophila melanogaster was previously discovered and characterized in our laboratory [1, 2]. It was found that ENY2 is a subunit of several multiprotein complexes and connects various stages of gene expression [3-5]. This work is devoted to studying the interaction of ENY2 with RNA helicase MLE. This interaction was confirmed by independent methods. Data indicating that this interaction is conserved in evolution and is important for the functioning of MLE in both sexes were obtained.

The Development of Reporter System for the Investigation of Molecular Mechanisms of Ecdysone Response.

To study the mechanisms of transcriptional regulation, a convenient experimental approach is to use the artificial chimeric constructs carrying the regulatory elements of interest. In the present work, we describe the creation and characterization of a novel genetic construct that makes it possible to study the transcriptional regulation of the early-late gene of the ecdysone cascade. Using the data of genome-wide experiments, we have isolated the main regulatory region of the hr4 gene, which was successfully used to create a chimeric reporter construct expressing a fluorescent protein upon the treatment with the ecdysone hormone. This reporter system can be used to study the mechanisms of the ecdysone response, both in cell culture and in tissues, at various stages of the Drosophila development.

[Focal laser coagulation in the treatment of a patient with kidney cancer and prostate cancer].

The article describes the clinical observation of the patient 84 years old with prostate cancer T2bNxM0, left kidney cancer T1N0M0 and severe comorbidity. Stepwise interstitial laser coagulation was performed using the Russian microsecond Nd: YAG laser surgical complex.

Insulator Protein Su(Hw) Is Indispensable for Amplification of Part of Drosophila Amplicons in Follicular Cells (DAFCs) during Early Oogenesis.

We found that the Su(Hw) insulator protein binds to all known Drosophila amplicons in follicular cells (DAFCs). Su(Hw) binding is required for ORC replication complex positioning on part of DAFCs during early oogenesis. Our data allow us to expand the current view on the role of the Su(Hw) protein in Drosophila oogenesis as a transcription repressor. We assume that Su(Hw) is involved in the coordination of transcription and replication processes during oogenesis in Drosophila.

[Interstitial laser coagulation in the management of urothelial papillary carcinoma of the renal pelvis].

This article presents a case of a 59-year-old patient with a primary tumor of the right kidney with bladder and liver metastases. The patient was treated in three-stages. In the first stage, he underwent ureteral stone extraction, laser resection of the tumor with subsequent vaporization. In the second stage, a repeat laser resection and vaporization of the tumor was performed. During the third stage, the patient underwent TUR of the bladder wall with the tumor, followed by laser vaporization of the tumor bed. During a 9-year follow-up, no signs of tumor growth or metastasis were observed.

[Murine and human hematopoietic progenitor cultures grown on stromal layers expressing Notch ligands].

The ex vivo maintenance and expansion of hematopoietic stem cells and early progenitors is necessary for the successful treatment of hematopoietic and immune diseases. Multiple attempts to improve the expansion of hematopoietic stem cells (HSCs) by their cultivation in the presence of growth factor cocktails have so far failed. Novel approaches aimed at conserving the earliest precursors in their undifferentiated state are needed. These approaches should take into account local regulatory factors that are present in the HSC microenvironment and the three-dimensional architecture of their niche. In the present study, we compared the effects of two Notch ligands, i.e., Jagged1 and DLL1, on murine and human hematopoiesis in vitro. Our observations indicate that the stromal expression of Notch ligands increases the production of both the total and phenotypically early murine and human hematopoietic cells in the co-culture. On one hand, this study demonstrates the similarity of effects of stromal expression of Notch ligands on murine and human hematopoiesis in vitro. On the other hand, our study revealed a number of cell type and ligand-specific variations that are systematically described below. It seems that the effects of SCF cytokine addition on murine hematopoiesis in vitro depend on the stromal context and are oppositely directed for Jagged1 and DLL1.

[Coactivator complexes participate in different stages of the Drosophila melanogaster hsp70 gene transcription].

The objective of this study was to identify transcriptional coactivators participating in transcription elongation of the hsp70 gene induced by heat shock. We found that all investigated coactivator complexes participate in transcription of this gene, as significant level of them were present at the gene promoter in its active state. For most of the coactivators (except for p300/CBP, Set2, and Mediator complex), we also observed a considerable increase of their binding level at the coding region of the gene after activation of its transcription by heat shock. We assume that coactivators CHD1, ISWI, Brm, Kismet-L, INO80, Mi-2, Gcn5, Lid/KDM5, Set1, DART1, DART4, SSRP1, PAF1, and Fs(1)h/Brd4 bind to the promoter of the active hsp70 gene and migrate to its coding region together with elongating RNA polymerase II. It can be suggested that some of these coactivators play an important role in stimulating the transition of the RNA polymerase II complex from transcription initiation to elongation stage.

Nuclear receptors EcR, Usp, E75, DHR3, and ERR regulate transcription of ecdysone cascade genes.

We found that an increase in the expression level of E75, DHR3, and ERR increases the degree of activation of dhr3 and hr4 genes in Drosophila S2 cells. We also detected a repressing effect of these nuclear receptors on the basal transcription level of these genes. This is the first study to show the ability of nuclear receptors E75, DHR3, and ERR to function as activators or repressors depending on external conditions. We also confirmed the existence of the interaction of all studied nuclear receptors with the promoters of dhr3 and hr4 genes of the ecdysone cascade in vivo.

Studying a novel ecdysone-dependent enhancer.

Earlier [4], we developed a two-stage scheme of the activation of expression of the ecdysone cascade gene ftz-f1 in Drosophila melanogaster S2 cells. In the first intron of the ftz-f1 gene, we found a binding site for the transcription activator DHR3. In this work, we studied the properties of this genomic element: the change in the histone modification level at different stages of transcription activation were analyzed, and data indicating the interaction of the intron element with the promoter were obtained. Taken together, the results of this study indicate that the studied genomic element exhibits the properties of an enhancer and functions at the stage of active gene transcription.

[Investigation of mechanisms of action of growth factors of autologous platelet-rich plasma used to treat erectile dysfunction].

AIM: To determine the quantitative and qualitative composition of growth factors (PDGF-AA, PDGF-BB, VEGF, VEGF-D, FGF-acid, FGF-basic) and platelets in various modifications of APRP. MATERIALS AND METHODS: Blood of 12 male volunteers (control group) and 12 patients with ED was used to prepare APRP and the subsequently determine the concentration of growth factors. The growth factor concentrations (FGF acid, FGF basic, PDGF-AA, PDGF-BB, VEGF, VEGF-D) was determined using a flow cytometry-based xMAP Luminex (Gen-Probe) system. RESULTS: Concentration of platelets in APRP obtained by two stage centrifugation, reached 1480 (1120-1644) in the control group and 1232 (956-1502) in patients with ED. The concentration of growth factors in the samples prepared without preliminary freezing was: PDGF-AA 842 (22-3700), PDGF-BB 2837 (1460-4100), FGF-basic 7.9 (0.28-127), FGF-acid 3, 4 (0.14-11), VEGF 19 (4.6-46), VEGF-D 21 (14-38). After thawing, the concentration of all growth factors in the samples increased. DISCUSSION: The study findings suggest that the mechanism of erectile function recovery following the use of APRP is through the active substances detected in APRP, i.e. FGF-basic, PDGF-AA, PDGF-BB, VEGF, VEGF-D and FGF-acid. Also, the study showed that the content of growth factors in APRP after of freezing/thawing is higher than in APRP that has not been frozen. This is due to the cell membrane destruction at extremely low temperatures during freezing.

[Age-related androgen deficiency. The current state of the problem].

This paper reviews the modern concept of age-related androgen deficiency. The authors discuss the prevalence of androgen deficiency and its relationship with age, concomitant diseases, pharmacotherapy and other factors.