[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.

[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.

[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.

[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.

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.

[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.

[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.

[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.

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.

[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.

[Cell technologies' application in practical andrology].

The article is devoted to new methods for treating men's erectile dysfunction using platelet-rich auto plasma and adipose tissue stromal vascular fraction. Recently, there has been increased interest in these methods due to their high level of efficiency and safety. Platelet-rich auto plasma and adipose tissue stromal vascular fraction have been successfully applied in different medical fields - traumatology, orthopedics, plastic surgery, etc. At the same time, efficacy and safety of these technologies has not yet been clinically studied from the perspective of evidence-based medicine.

[Large urethral stones: a case report].

The article describes a clinical observation of a 68 y/o patient with large stones of the urethra, reaching 5 cm in length and located in the penile urethra. The patient underwent a three-stage treatment: the first stage consisted of drainage of the urinary bladder, the second stage of the urethrolithotomy and a double-barreled fistula, the third was an anastomotic urethroplasty. After removing the cystostomic drainage tube, normal urination was restored.

[THE EFFECTIVENESS OF INTRACAVERNOUS AUTOLOGOUS PLATELET-RICH PLASMA IN THE TREATMENT OF ERECTILE DYSFUNCTION].

This article deals with using autologous platelet-rich plasma (APRP) as a new treatment for erectile dysfunction in men. In recent years there was a significant interest in regenerative medicine technology due to its high effectiveness with a good safety and low cost. Currently APRP has been used successfully in various fields of medicine (surgery, traumatology and orthopedics, sports medicine, cosmetics). However, until now there have been no studies consistent with evidence-based medicine verifying the effectiveness and long-term results of APRP application for ED treatment. This article presents the results of a clinical study on the use of APRP in men with ED with a comparative effectiveness analysis of different ways of APRP administration and in combination with PDE5 inhibitors. Possible mechanisms of action of APRP in restoring erectile function are discussed.

[Prospects for application of stem cells from adipose tissue in treating erectile dysfunction].

Although phosphodiesterase type 5 inhibitors are the first-line treatment of ED, some patients remain unresponsive to any pharmacotherapy. To date, the use of stem cells is considered as a new treatment modality for erectile dysfunction. The validity of this assumption has been experimentally proved in preclinical and clinical studies. The main focus is on the stem cells derived from adipose tissue, due to advantages over other sources.

[The development of strategic management of high-tech surgical medical care].

The high-tech surgical medical care is one of the most effective types of medical care in Russia. However high-tech surgical treatment very often is inaccessible for patients. The development of basics of strategic management of high-tech surgical care makes it possible to enhance availability of this type of care and to shorten the gap between volumes of rendered care and population needs. This approach can be resulted in decrease of disability and mortality of the most prevalent diseases of cardio-vascular diseases, malignant neoplasms, etc. The prerequisites can be developed to enhance life quality and increase longevity of population.

[Correction of complement system failure in patients with chronic prostatitis].

The aim of the study was detection of local and systemic changes in the complement system in patients with chronic abacterial prostatitis (CAP) and chronic bacterial prostatitis (CBP) and to assess a relevant corrective efficacy of the hardware and software complex Andro-Gin (KAP-ELM-01 Andro-Gin). Before treatment, blood plasma of CAP patients contained elevated concentrations of all studied components of the compliment system and factor H but subnormal concentration of C1-inhibitor. Locally, all the compliment indices were high including C1-inhibitor and factor H except component C5. Initial blood plasma compliment fractions in CBP patients were elevated but regulatory proteins concentrations were low. Local compliment components C3, C4, C5 and C5a and factor H were significantly higher. Standard treatment of CAP partially corrected the level of C3, C3a, C4 components, locally normalized concentration of C3 component and corrected C4 component, while in CBP standard treatment normalized concentration of C3 component and reduced C3a, C4, C5 and C5a components, locally normalized the levels of C3, C4 components, corrected concentration of C3a, C5, C5a components, raised regulatory factors. Combination of the standard treatment with Andro-Gin unit compared to standard treatment alone, in CAP corrected plasma concentrations of C3, C3a, C4 compliment components and significantly raised levels of regulatory factors, locally--partially normalized the level of factor H. In CBP additional use of Andro-Gin more significantly improved concentrations of C3a and C5a components , locally--C5a component, raised significantly concentration of regulatory factors C1-inhibitor and factor H. Thus, KAP-ELM-01 Andro-Gin administration in CAP and CBP patients promotes more effective correction of systemic and local disorders in the compliment system, the improvement being more pronounced in CBP.

[Correction of local immunometabolic disturbances combined with chronic prostatitis in prostatic adenoma].

We compared local immunometabolic effects of two dosage forms of longidase in patients with prostatic adenoma (PA) in combination with chronic prostatitis (CP) in the postoperative period. Transurethral resection (TUR) of the prostate was conducted in 81 patients aged 50-70 years suffering from PA and CP. All the patients after TUR were divided into three groups by postoperative treatment: group 1 (n = 25) received standard pharmacotherapy, group 2 (n = 28)--standard pharmacotherapy and longidase injections, group 3--standard pharmacotherapy plus longidase suppository. Immunological parameters were studied in biological material (urine) obtained before operation, after it and after treatment course. By changes in immunometabolic status (concentrations of cytokines TNFalpha, IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-18, receptor antagonist IL-1 Ra, complement components C3-, C3a-, C4-, C5-, C5a, regulators of the complement system factor H, C1-inhibitor) and sIgA, content of acylhydroperoxides, malonic dialdehyde, stable metabolites of hitric oxide, catalase and superoxiddismutase activity it is shown that PA patients with CP have pretreatment disturbances of local immunity and oxidant status (high levels of proinflammatory cytokines, subnormal IL-10, activated complement system, lipid peroxidation, low sIgA, NO-synthetic activity of capillary endothelial activity). TUR aggravates shifts of local immunometabolic status. Standard postoperative pharmacotherapy does not correct the disturbances adequately. The addition of longidase to standard postoperative treatment was effective in correction of immune and oxidant status. Thus, longidase injections and, especially, suppositories correct disturbances of local immunity and oxidant status in patients with PA and CP in postoperative period.

[Study of the Drosophila melanogaster trf2 gene and its protein product].

The Drosophila melanogaster TRF2 protein regulates transcription of several genes. The trf2 gene structure was studied. The gene proved to code for two protein isoforms, a known 75-kDa isoform and a newly identified 175-kDa isoform. The new isoform combines the known isoform sequence with an extended N end containing a coiled-coil motif. The long TRF2 isoform was found to act as a component of a multiprotein complex, including ISWI ATPase as well.