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Temozolomide resistance is a major cause of recurrence and poor prognosis in neuroglioma. Recently, growing evidence has suggested that mitophagy is involved in drug resistance in various tumor types. However, the role and molecular mechanisms of mitophagy in temozolomide resistance in glioma remain unclear. In this study, mitophagy levels in temozolomide-resistant and -sensitive cell lines were evaluated. The mechanisms underlying the regulation of mitophagy were explored through RNA sequencing, and the roles of differentially expressed genes in mitophagy and temozolomide resistance were investigated. We found that mitophagy promotes temozolomide resistance in glioma. Specifically, small ubiquitin-like modifier specific protease 6 (SENP6) promoted temozolomide resistance in glioma by inducing mitophagy. Protein-protein interactions between SENP6 and the mitophagy executive protein PTEN-induced kinase 1 (PINK1) resulted in a reduction in small ubiquitin-like modifier 2 (SUMO2)ylation of PINK1, thereby enhancing mitophagy. Our study demonstrates that by inducing mitophagy, the interaction of SENP6 with PINK1 promotes temozolomide resistance in glioblastoma. Therefore, targeting SENP6 or directly regulating mitophagy could be a potential and novel therapeutic target for reversing temozolomide resistance in glioma.

Introduction: Every year in Russia, more than 200 thousand whole body PET/CT are performed for various diseases in patients without clinical and laboratory manifestations of chronic kidney disease (CKD). However, only the "area of interest" of the attending physician is analyzed, while the rest of the organs or rather their metabolic activity is neglected during the standard procedure of this contemporary and high-tech research method., Aim: To perform a retrospective study of whole-body PET/CT as a tool for prophylactic clinical examination of the population in order to identify subclinical manifestations of chronic kidney disease MATERIALS AND METHODS: The results of whole-body PET/CT with 11C-choline were retrospectively analyzed for the detection of CKD in 100 patients of the Tyumen region who underwent a study for various indications outside the genitourinary system without history, clinical and laboratory manifestations of CKD., Results: According to the results, 22% of patients had different manifestations of 11C-choline hypometabolism, indicating a decrease in the viability of the parenchyma. In 14% of patients, there was a local decrease in the uptake of 11C-choline without CT-signs of kidneys damage, and in 8% of cases there was a total decrease in their metabolism, coinciding with X-ray signs of renal scarring., Conclusions: The possibility of early molecular study of nephropathy can be used for wider retrospective PET/CT clinical examination as one of the highly effective methods for detecting CKD, which needs further research.

The article is devoted to the interaction of a gynecologist and a urologist in a gynecological hospital, based on the experience of the gynecological department at the Clinic of obstetrics and gynecology of the Clinical Center of Sechenov University. The most common clinical scenarios were identified when the participation of a urologist in evaluation and treatment is urgently needed, including large pelvis mass, endometriosis with an involvement of pelvic organs, genital prolapse, small pelvis adhesions as a result of previous surgical procedures and postoperative urinary disorders. A close interaction between two specialties, which are dedicated to pelvic organs disorders, namely gynecology and urology, is extremely popular in modern clinical practice and allows to significantly reduce the number of intra- and postoperative complications, carry out a comprehensive examination and determine individual treatment tactics in a gynecological hospital, which increases quality of medical care.

Available data indicate a worse prognosis in cancer patients with COVID-19. Surgical treatment of lung cancer in the conditions of the COVID-19 pandemic poses new challenges to ensure the perioperative safety of patients., Objective: To prevent infection of patients in the perioperative period and, in case of infection, to prevent the severe course of COVID-19., Material and Methods: In the conditions of the COVID-19 pandemic within two months (March-April 2020) 138 patients underwent surgical treatment for malignant tumors, including 22 videothoracoscopic operations: 3 (13.6%) segmentectomies, 16 (72.7%) lobectomies, and 5 (22.7%) bilobectomies for non-small cell lung cancer., Results and Conclusions: Following the principles that ensure the prevention of infection and the prevention of severe COVID-19, we managed to avoid the first stage of the pandemic (March-April 2020) cases of infection with a new coronavirus infection in patients who underwent surgical treatment for lung cancer.

A review of the literature dedicated to the economic aspects of drug and surgical treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) is presented in the article. Currently, symptomatic therapy, which usually leads to an increase in the financial costs associated with the complications and surgical treatment, is most commonly used. The pathogenetic treatment of BPH (5-alpha reductase inhibitors), including combination therapy, requires an increase in costs, but it is also considered the most cost-effective approach. Despite the continuous growing of therapeutic armamentarium, the surgical treatment is still relevant and holds an important place. A lot of studies have shown that open procedures are inferior to endoscopic and minimally invasive interventions by both clinical and cost-effective results. At the same time, transurethral interventions on the prostate does not exclude economic losses due to the necessity of expensive laser technologies and the development of complications in the early postoperative period. Thus, currently, the best treatment option should be chosen not only on individual basis, but also depending on economic aspects based on a balanced medical and economic analysis of each treatment method.

Three basic theories of the development of an overactive bladder that have experimental and clinical evidences have been described, including neurogenic, myogenic, and urothelial. Based on the results of the literature analysis, the authors suggested the existence of detrusor ischemic disease as a result of compressive impairment of its blood flow due to incomplete or short-term relaxation under overactivity or hydraulic compression of the vessels by excessive urine volume in case of hypoactive bladder.

Aim: The aim of this study was to determine the possibilities of volumetric dynamic voiding multispiral computed cystourethrography (VDMMCT) for assessment of the lower urinary tract during voiding., Materials and Methods: VDMMCT was performed in a series of 22 patients with various urethral pathologies using 320 detector rows (640 unique slices; row width 0,5 mm). This method allows to cover the scan area of 16 cm per one rotation of the X-ray tube. In all patients, the cross-sectional area of the various urethral parts was estimated and the urinary bladder volume and average urine flow rate during all voiding phases were calculated., Results: VDMMCT was performed for dynamic evaluation of bladder volumes changes and analyzing a passage of contrasted urine throughout the urethra. The average volume of the urinary bladder was 356.3+/-179.9 ml, while the voiding volume was 299.5+/-154.8 ml. The average pre- and postoperative urine flow rate was 4.1+/-1.1 ml/s and 7.9+/-5.1 ml/s, respectively. The maximum urine flow rate was 19 ml/s. The average urethral diameter according to the VDMMCT after urethroplasty was 7.6+/-2.1 mm. The minimum length of urethral strictures was 17 mm, while the maximum length was 32 mm., Conclusion: Our results demonstrate the efficiency of the VDMMCT for assessing of the urethra throughout its length. VDMMCT can multidimensionally and dynamically represent the change of the bladder volume and the urine flow rate.

Objective: To identify the expression of the molecular markers p53 and p16INK4A in head and neck squamous cell carcinoma (HNSCC) and to assess their impact on its clinical and morphological characteristics and overall survival (OS) rates in patients with HNSCC., Material and Methods: Histological blocks were immunohistochemically studied using anti-p16 and p53 monoclonal antibodies in Krasnodar Clinical Oncology Dispensary One in 2011 to 2016. Overexpression of p16INK4A was established in the presence of 3 and 4 staining points (nuclear and/or cytoplasmic staining in 40% or more tumor cells). That of p53 was determined in the presence of nuclear staining (3+) in more than 50% of tumor cells., Results: Overexpression of p16 was found in 15 (27%) patients (9 (60%) men and 6 (40%) women). The p16-positive tumor status was associated with the female sex (p=0.023), which was characteristic of tonsil cancer (p<0.001) and represented by the nonkeratinizing type (p=0.008). Overexpression of p16 was associated with more frequent regional lymph node metastases (p=0.029). Overexpression of p53 was related to G2 tumor (p=0.021) and expression of p53 was less than 50% associated with tongue body cancer (p=0.004). Kaplan-Meier analysis showed that the 3-year OS in p16-positive HNSCC patients was significantly higher than that in p16-negative ones (p=0.048). Significantly higher OS rates were observed in p16-positive HNSCC patients than in p16INK4A-negative ones for Stage III-IV (p=0.021). OS rates in HNSCC patients with co-expression of p16INK4A (3 and 4 points) and p53 (3+) were significantly higher than in the absence of a combination of these molecular markers (p=0.049). At the same time, OS in HNSCC patients with co-expression of p16INK4A (3 and 4 points), p53 (3+) was significantly higher than in the absence of a set of these molecular markers for stage III-IV (p=0.01). OS in patients with Stages I-II HNNSCC and co-expression of p16INK4A (3 and 4 points) and p53 (3+) did not significantly differ from that in the absence of a set of these molecular markers (p=0.960)., Conclusion: Overexpression of p16INK4A (3 and 4 points) can be used as a prognostic marker to divide patients into subgroups with different clinical and morphological characteristics. The data on the correlation of p53 overexpression as a marker of mutations in the TP53 gene are contradictory and the study has not revealed the worst overall survival rates. A set of markers for the expression of p16 (≥40%) and p53 (≥50%) has been proposed for use as a favorable prognostic sign.

In modern rhinosurgery it is generally accepted that the framework of the nasal septum dyring septoplasty should be preserved or, if it is possible, restored. The article presents a literature review of various techniques of reinforcement and replacement of septal framework. Each of them has its own advantages and disadvantages, while universal, common technology is lacking. Analysis of the literature shows that the improvement of the replacement technique is still relevant.

Introduction: Early detection of malignant laryngeal tumors is crucial but still challenging. And 5-year survival rate depends on a stage of revealing. The aim of the study - assessment of the effectiveness of combined application of narrow band imaging and contact endoscopy in visualization of neoangiogenesis., Material and Methods: 102 patients were included in this study. All the patients were evaluated by means of narrow band imaging and contact endoscopy., Results: Combined application of narrow band imaging and contact endoscopy gained a high level of effectiveness: accuracy - 93.9%, sensitivity - 96%, specificity - 93.4%, positive predictive value - 94.3%, negative predictive value - 93.4%., Conclusion: Combined application of narrow band imaging and contact endoscopy may contribute to early detection of malignant laryngeal tumors.

A case of benign proliferative formation of the mammary gland of a rare histological form - subareolar sclerosing ductal hyperplasia in combination with papillomatosis of the nipple is presented. Pathology belongs to the group of complex sclerosing lesions. When setting the morphological (cytological, histological) diagnosis, it is necessary to take into account the clinical picture - the state of the nipple-areola complex, in particular, the presence / absence of nipple discharge and its involvement in the pathological process., Competing Interests: The authors declare no conflict of interest.

The review article presents information from foreign and domestic authors on the relevance of studying the incidence of men with bening prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). Complex urodynamic studies (CUDS) remains the most informative test of the degree of expression of LUTS and bladder outlet obstruction () caused by BPH. The difficulty in interpreting the results, the invasiveness and inaccessibility of CUDS in the routine practice of most medical institutions makes it necessary to perform relatively simpler and more accessible methods of research, which do not always objectively reflect the degree of urinary incontinence in older men. This fact causes a large number of complications and adverse outcomes of surgical treatment with the rapid development of BPH and obstructive symptoms. Taking into account the results of world research, the study of the urine proteome and urinary exosomes will improve the quality of diagnosis in patients with BPH and help in assessing the prognosis of the development of the disease.

Introduction: The globalization observed in the modern world contributes to the increasing rate of the delivery of "exotic" bacterial and parasitic infections from the tropic countries to Russia and the European countries., Aim: To analyze the modern early diagnostic tools of premalignant changes and malignant tumors of urinary bladder of schistosome origin in the residents of endemic areas., Materials and Methods: The current study included an analysis of examination and treatment of 181 patients with bladder schistosomiasis who lived in Benguela province in Angola. In 39 cases (21.5%) bladder cancer associated with schistosomiasis was detected. All patients were undergone to surgical treatment. 142 patients (78.5%) were divided into two groups. In Group 1 (n=74) patients had uncomplicated bladder schistosomiasis and in Group II (n=68) the patients with granulomatous inflammatory changes in the urinary bladder were included., Results: The patients with bladder schistosomiasis (n=142) were undergone to outpatient examination. In 38 cases (26.8%) the cytologic study of urinary sediment (CSUS) revealed the schistosomes eggs. With ultrasound study, the specific granulomatous changes in the mucous membrane of urinary bladder were detected in 28 cases (19.7%) while hydronephrosis, calcifications and thickening of bladder wall was diagnosed in 7 (4.9%), 10 (7%) and 99 (69.7%) patients, respectively. During cystoscopy the granulomatous changes in the bladder were found in 68 cases (47.9%). In Group I patients received "Praziquantel" in combination with oral antibiotic therapy, which resulted in resolution of gross hematuria and dysuria. All patients in Group II (n=68) were also administered antibacterial and antiprotozoal therapy. An additional 35 patients (24.6%) were undergone to transurethral bladder resection. Of 33 patients in Group II (23.2%) who received only antibacterial and antiprotozoal therapy the granulomas persisted in 7 cases (4.9%) and, therefore, TURB was performed. The subsequent studies showed the regression of the lesions in these patients., Conclusion: CSUS and ultrasound study are not sufficient for diagnosis of bladder schistosomiasis. Cystoscopy is recommended for all patients, since it allows to evaluate bladder volume and to determine the indications for TURB in addition to antiprotozoal and antibacterial therapy.

The search for and use of alternative biomarkers of the hyperactive bladder has garnered increasing attention in recent years because they may be considered pathogenetically significant and used as surrogate biomarkers. Promising agents that have met these criteria include proteins cytokines, neurotrophins, tumor necrosis factor (TNF), nerve growth factor (NGF), fibrinopeptides A and B, C-reactive protein, membrane-bound ATPase. Analysis of current scientific literature has demonstrated that specialists in many fields of medicine show interest in endogenous proteins that do not belong to neurotransmitters but affect the contractile ability of myocytes. The presented data indicate the feasibility and prospects of their use, but further studies and evaluation are needed. Based on the present literature review, the authors conclude that endogenous proteins activating myocyte contractility are of great clinical value as promising markers for detecting detrusor overactivity, its severity, and evaluation of the treatment effectiveness. The authors suggest that proteins of this group can play an important role not only in the pathogenesis of bladder function disorders but also in the physiological process of urination as an additional non-neurogenic humeral component.

MicroRNA-218 (miR-218) is a short, noncoding RNA, with multiple biological functions. In this study, we aimed to investigate the potential effects of miR-218 on the apoptosis of human ovarian carcinoma cells and the underlying mechanisms by which miR-218 exerted its actions. After over-expressing miR-218 in human ovarian carcinoma (OVCAR3) cells, cell viability was determined by MTT method, cell apoptosis was observed by flow cytometry (FCM), mRNA expression of miR-218, Bcl2, Bax was measured by RT-PCR and protein expression levels of Wnt, tankyrase and β-catenin were quantified by Western blots. Over-expression of miR-218 potently suppressed cell viability and promoted the apoptosis of human ovarian carcinoma cells in a time-dependent manner. In addition, the down-regulation of tankyrase expression level was detected in miR-218-over-expressed cells. Following the block of the Wnt/β-catenin signaling pathway using the inhibitor XAV-939, the effects of miR-218 on the proliferation and apoptosis of human ovarian carcinoma cells were significantly suppressed. Augmenting expression of miR-218 and/or miRNA-218 mimicking therapeutics may provide viable avenue for the treatment of ovarian cancer.

Aim: To substantiate and to prove the advantages of the new method of gastroplasty in comparison with traditional loop reconstruction of digestive tract after gastrectomy., Material and Methods: It was performed prospective comparative study of surgical treatment of 431 patients with gastric cancer who underwent gastrectomy with different variants of digestive tract reconstruction. The main group (146 patients) consisted of patients in whom original technique including establishment of food reservoir in initial jejunal part during reconstruction was applied. The control group consisted of patients with traditional loop reconstruction of the digestive tract (285 patients)., Results: Early dumping syndrome (within 1 year) was diagnosed in 9 (13.2%) patients of the main group and 16 (21.6%) patients of the control group. Mild and moderate degrees of this syndrome were observed in 7 (77.8%) and 10 (62.5%), 2 (22.2%) and 4 (25.0%) patients in the main and control groups respectively. Severe dumping syndrome occurred in 2 (12.5%) patients only in the control group. Late dumping syndrome was revealed in 7 (10.3%) and 11 (14.9%) patients, respectively. Body mass index was 18.7±0.8 and 17.4±0.6 (p<0.05), respectively. After 2 years early dumping syndrome was diagnosed in 6 (14.3%) and 10 (21.3%) patients, mild degree in 5 (83.3%) and 5 (50.0%) patients; moderate degree in 1 (16.7%) and 3 (30.0%). Severe dumping syndrome was confirmed in 2 (20.0%) patients from the control group. Late dumping syndrome occurred in 4 (9.5%) and 7 (14.9%), respectively. Body mass index was 21.2±0.7 and 19.0±0.9 (p<0.05), respectively. After 3 years, early dumping syndrome in mild form was diagnosed in 2 (10.5%) cases and late syndromy in 1 (5.3%) patient of the main group. There were 5 (21.7%) patients with the syndrome in the control group including mild and moderate severity in 3 (60.0%) and 2 (40.0%) patients respectively. Late dumping syndrome occurred in 3 (13.0%) patients. Body mass index was 21.9±1.0 and 19.7±0.6 respectively., Conclusion: Food reservoir in the initial part of jejunum after gastrectomy creates better conditions for the normalization of metabolic exchange resulting early functional digestive adaptation, especially in long-term period.

The current trend for decreased exposure to medical ionizing radiation sources contributes to the introduction of novel technologies into radiation diagnosis. The aim of this study was to compare the informative value of interactive digital X-ray study and routine enlargement fluorography. The study covered 316 individual without the complaints typical of lung diseases. Three roentgenologists assessed X-ray images by 7 major signs. The sensitivity, specificity, and accuracy of the methods in question were defined. The final stage was the construction of routine operating curves (ROC). When there were diffuse changes in the lung, the sensitivity of interactive digital X-ray study was 14% higher. The higher informative value of interactive digital X-ray study is also attested by the higher position of a respective ROC. The fact that lung tissue function in combination with low radiation load may be estimated assumes the use of interactive digital X-ray study in patients with pneumosclerosis and emphysema.

The article discusses the possible mechanisms of the antineoplastic effect of hypoxic bioreducing agents (HBA) when they are used in low nonhypoxic doses. Experimental and clinical studies provide evidence of the occurrence of stages which in administration of HBA into the organisms of the tumor-carrier may develop in succession, leading to stimulation of antineoplastic immunity: GBA activation in the hypoxic neoplastic tissue, conjugation of HBA metabolites with the macromolecules of the tumor cells, and presentation of the epitopes of neoantigens in association with the main complex of class I histocompatibility (MCH) cytolysis of these cells by T-killers. This process may be similar to that in contact sensitivity to low-molecular compounds (a variant of the reaction of delayed hypersensitivity [DH]) in the neoplastic focus. It is suggested that direct control of the effect of HBA on the immunocompetent and/or tumor cells may occur additively to or synergically with this process as the result of interaction of these compounds with the surface or intracellular receptors. It cannot be excluded that the activated HBA may force the endogenic ligands out of the nucleophilic centers of these receptors and realize receptor-mediated control of gene expression.