


Vol 106, No 2 (2025)
- Year: 2025
- Articles: 21
- URL: https://journals.rcsi.science/kazanmedj/issue/view/19279
Theoretical and clinical medicine
Alterations of phospholipid fractions in patients with HIV/tuberculosis coinfection under different treatment regimens
Abstract
BACKGROUND: Alterations in phospholipid fraction balance represent one of the mechanisms underlying lipid metabolism disorders in HIV infection.
AIM: To investigate the dynamics of phospholipid fractions in patients with HIV/tuberculosis coinfection undergoing monotherapy with antitubercular agents versus combined antiretroviral and anti-tuberculosis therapy.
MATERIAL AND METHODS: A comparative study of phospholipid fractions (sphingomyelin, phosphatidylcholine, lysophospholipids, phosphatidylethanolamine) was conducted using chromatography in two groups of patients with HIV-associated tuberculosis: Group 1 (100 patients) received tuberculosis chemotherapy (isoniazid, rifampicin, pyrazinamide, ethambutol), while Group 2 (100 patients) received antiretroviral therapy (tenofovir, lamivudine, efavirenz) alongside treatment with antitubercular agents. The control group consisted of 50 healthy individuals. CD4 lymphocyte counts and HIV RNA viral load were measured in all patients. Assessments were performed before treatment initiation and after 1 and 2 months of therapy. Statistical analysis was conducted using parametric methods, with differences considered significant at p <0.05.
RESULTS: Before treatment initiation, both groups of patients with HIV/tuberculosis coinfection had higher levels of sphingomyelin, lysophospholipids, and phosphatidylcholine compared to healthy individuals (p=0.001). In Group 1, receiving only anti-tuberculosis therapy, levels of sphingomyelin, lysophospholipids, and phosphatidylcholine significantly increased (p=0.001), with no change in the number of patients exhibiting bacterial shedding. In Group 2, after one month of antiretroviral therapy combined with anti-tuberculosis treatment, levels of sphingomyelin, lysophospholipids, and phosphatidylcholine decreased below those of the control group (p=0.001). A significant reduction in patients with bacterial shedding was observed (from 100% to 18%, p=0.001).
CONCLUSION: In the group of patients receiving combined antiretroviral and anti-tuberculosis therapy, a reduction in sphingomyelin and lysophospholipid levels was observed, along with a decrease in the number of patients exhibiting bacterial shedding.



Prognostic role of inflammatory response markers in gastric adenocarcinoma
Abstract
BACKGROUND: Prognostic assessment of survival in patients with cancer is essential for guiding treatment strategies, particularly in gastric cancer, which is associated with high morbidity and mortality.
AIM: The study aimed to evaluate the association between inflammatory response markers and survival outcomes in patients with gastric adenocarcinoma.
MATERIAL AND METHODS: The study included 152 patients with histologically confirmed gastric adenocarcinoma. Patients were distributed by stage as follows: 25 (16.45%) with stage I, 25 (16.45%) with stage II, 34 (22.4%) with stage III, and 68 (44.7%) with stage IV disease. Inflammatory response parameters were collected, calculated, and evaluated. The resulting data were analyzed and compared to identify statistically significant associations with overall survival. The inflammatory response parameters included the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), as well as two specific indices, systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI), which reflect the activity of inflammatory response in cancer patients and may serve as additional independent prognostic factors. The Mann–Whitney U test was used for two-group comparisons and the Kruskal–Wallis test for comparisons across more than two groups. Spearman’s rank correlation coefficient was used to assess the relationship between inflammatory markers and overall survival. Statistical analysis was performed using MedCalc version 20.104.
RESULTS: No significant associations were observed between inflammatory markers and patients’ age or sex. All inflammatory markers were significantly associated with overall survival (p < 0.001 for NLR, PLR, SII, and SIRI; p = 0.013 for MLR). Elevated levels of these markers correlated with shorter overall survival and a higher probability of stage IV disease.
CONCLUSION: Changes in hematologic markers reflecting systemic immune inflammation and inflammatory response are significantly correlate with survival outcomes in patients with gastric cancer.



Comparative analysis of quantitative parameters of structural components in the femoral and great saphenous veins across age groups
Abstract
BACKGROUND: Quantitative data on structural remodeling of the lower limb veins are limited and primarily concern changes associated with varicose vein disease.
AIM: This study aimed to investigate and compare age-related changes in the quantitative parameters of structural components in the femoral and great saphenous veins.
MATERIAL AND METHODS: A total of 120 vein specimens were analyzed, including 60 from the great saphenous vein and 60 from the femoral vein, obtained from 60 deceased individuals aged 25–98 years. According to the World Health Organization classification, the individuals were divided into five age groups: young adults (n = 10), middle-aged adults (n = 15), older adults (n = 15), elderly (n = 15), and the oldest-old (n = 5). Morphological and quantitative assessments of the femoral and great saphenous vein walls were conducted on hematoxylin and eosin-stained sections, including the volume fraction of the intima and the volume fractions of smooth muscle and connective tissue components in the media and adventitia. Statistical analysis was performed using the Kruskal–Wallis and Mann–Whitney nonparametric tests.
RESULTS: In older adults, the volume fraction of the intima was significantly lower in the great saphenous vein compared with the femoral vein (p < 0.0001). In all age groups except the oldest-old, the volume fraction of subintimal longitudinal smooth muscle cells in the media of the great saphenous vein was significantly higher than in the femoral vein (p ≤ 0.00017). No age-related changes in the volume fraction of circularly arranged smooth muscle cells were observed in the great saphenous vein (p = 0.36). The volume fraction of longitudinal smooth muscle cells in the adventitia was significantly greater in the great saphenous vein compared with the femoral vein in the young (p = 0.046), middle-aged (p < 0.0001), and older (p = 0.017) groups. In the oldest-old, the volume fraction of connective tissue in the adventitia was significantly reduced in both veins (p < 0.005), with a lower proportion found in the great saphenous vein compared with the femoral vein (p < 0.05).
CONCLUSION: In the great saphenous vein, a reduction in the volume fraction of the intima begins in older adulthood. In the femoral vein, a decline in the subintimal longitudinal smooth muscle layer is observed in the elderly. In both the femoral and great saphenous veins, a decrease in longitudinal smooth muscle bundles and connective tissue stroma in the adventitia occurs during longevity.



Length characteristics of C₇ spinal nerve, middle trunk, and its anterior division
Abstract
BACKGROUND: Contralateral transfer of donor nerves in cases of brachial plexus injury requires a detailed anatomical understanding of the C₇ spinal nerve.
AIM: This study aimed to identify distinctive length characteristics of the C₇ spinal nerve, middle trunk, and its anterior division before and after epineurium removal.
MATERIAL AND METHODS: To identify significant differences, the lengths of the C₇ spinal nerve, middle trunk, and its anterior division were measured twice in the anterior projection, before and after epineurium removal, in 121 brachial plexus specimens from male and female cadavers aged 40 to 97 years. Minimum and maximum values, medians, and quartiles (Q1; Q3) were recorded in the database. Statistical significance of differences in absolute nerve lengths and in the proportion of brachial plexus specimens with measured changes after epineurium removal was determined using the Mann–Whitney U test and Pearson’s χ2 test.
RESULTS: The median lengths before epineurium removal were as follows: C₇ spinal nerve, 25 (20; 30) mm; middle trunk, 22 (17; 28) mm; anterior division, 20 (15; 26.5) mm. After epineurium removal, the respective values were 28 (25; 32) mm, 20 (15; 27) mm, and 25.5 (20; 37) mm. The total length of the C₇ spinal nerve, middle trunk, and its anterior division ranged from 30 to 111 mm before epineurium removal (median: 71 [63; 78] mm), and from 30 to 146 mm after removal (median: 75 [66; 85] mm). After epineurium removal, the total length of the C₇ spinal nerve, middle trunk, and its anterior division remained unchanged in only 3.3% of cases, decreased by 1–35 mm in 15.7%, and increased by 1–72 mm in 81%. Lengths exceeding 100 mm were found in 1.6% of specimens before and in 11.6% after epineurium removal.
CONCLUSION: In 81% of cases, removal of the epineurium resulted in an increased total length of the C₇ spinal nerve, middle trunk, and its anterior division, which may reduce the distance required for contralateral nerve transfer by up to 72 mm.



Age-related changes in hair structure in the parietal region of men
Abstract
BACKGROUND: The study of age-related changes in the hair bulb and shaft is relevant due to the lack of data distinguishing normal from pathological hair characteristics across different age groups.
AIM: This study aimed to assess changes in hair bulb and shaft parameters in the parietal region across different male age groups.
MATERIAL AND METHODS: The study was based on microscopic examination of hair samples from 77 men who underwent evaluation at a medical center in Perm,in 2022–2023, specializing in the treatment of hair and scalp conditions. Participants were divided into three groups based on age. group 1 included 25 men aged 21 to 35 years (young adults). group 2 consisted of 27 men aged 36 to 59 years (middle-aged adults). group 3 included 25 men aged 61 to 74 years (elderly). Hair samples were obtained from the parietal region by gently extracting hairs in the late telogen phase, which were easily detached from the scalp and had fully developed bulbs and shafts. The width of the hair bulb and shaft was measured under a microscope. The width of the hair bulb was measured under a microscope as a line perpendicular to the shaft connecting the most distant points of the bulb. To determine shaft width, the height of the bulb was first measured as the distance from the most prominent point of the hair root to a perpendicular line connecting the narrowest part of the bulb. The shaft width was then measured at a distance from the narrowest point of the bulb equal to its height. It was defined as a line parallel to the bulb width, connecting the opposite sides of the hair shaft. Statistical analysis was performed using Student’s t test. Differences were considered statistically significant at p < 0.05.
RESULTS: A 1.3% decrease in hair bulb width was observed from young to middle adulthood (p = 0.7597). A similar trend was observed from middle to older adulthood, with a 3.3% reduction in hair bulb width (p = 0.4853). No significant age-related changes in shaft width were observed. A 3.8% decrease was noted from young to middle adulthood (p = 0.4995), and a 2.2% decrease from middle to older adulthood (p = 0.6488).
CONCLUSION: Despite age-related vascular changes, the thickness of the hair bulb and shaft in the parietal region remains largely stable.



Evaluation of the effectiveness of osteopathic treatment in the acute stage of Osgood–Schlatter disease in male athletes aged 10–15 years
Abstract
BACKGROUND: Osgood–Schlatter disease affects up to 20% of adolescents involved in running and jumping sports, predominantly males. There is a need for individualized rehabilitation programs to ensure full return to athletic activity.
AIM: This study aimed to evaluate the impact of combined treatment (osteopathic therapy and rehabilitation) on the frequency of ultrasound-detected signs of patellar tendon inflammation in 10- to 15-year-old male athletes with Osgood–Schlatter disease.
MATERIAL AND METHODS: In this randomized study, patients with acute-stage Osgood–Schlatter disease were divided into two groups: the main group received combined osteopathic and rehabilitation treatment, and the control group received identical rehabilitation alone. Each group included 15 boys aged 10–15 years, matched by age and disease duration. Treatment effectiveness was assessed using a visual analog scale for pain, the step-down test, ultrasound examination of the patellar tendon, and osteopathic assessment. Statistical analysis was performed using the Mann–Whitney U test and Wilcoxon signed-rank test. Changes in categorical variables before and after treatment were assessed using the Pearson χ2 test. Statistical significance was set at p = 0.05.
RESULTS: After 1 month of treatment, both groups showed reduced pain intensity (intervention group: p = 0.00063; control group: p = 0.003; between-group comparison: pre-treatment p = 0.443, post-treatment p < 0.001) and improved functional test performance (main group: p = 0.00055; control group: p = 0.04108; between-group comparison: pre-treatment p = 0.44012, post-treatment p = 0.00001). At 3-month follow-up, the frequency of ultrasound-detected inflammatory signs significantly decreased in the main group (p < 0.001), with no significant change in the control group (p = 0.143). Post-treatment reduction in inflammation was significant in the main group (p = 0.00004).
CONCLUSION: A 1-month course of combined treatment led to a significant reduction in the frequency of ultrasound-detected signs of patellar tendon inflammation in male athletes aged 10–15 years with Osgood–Schlatter disease at 3-month follow-up.



Experimental medicine
Effect of a novel thienopyridine derivative on liver structure in rats with diet-induced obesity
Abstract
BACKGROUND: The search for novel compounds that exert a positive impact on liver morphology and function having a beneficial effect on carbohydrate and lipid metabolism remains an urgent research priority.
AIM: This work aimed to evaluate the effect of a novel thienopyridine derivative on liver structure in rats with diet-induced obesity.
MATERIAL AND METHODS: A novel thienopyridine derivative AZ-020 was selected through in silico screening using online platforms based on its potential effects on the liver, as well as carbohydrate and lipid metabolism. An in vivo study was conducted in Wistar rats, which were randomized into five groups (8 per group): an intact group (maintained under standard conditions), control group (received excess palm oil 30 g/kg for 8 weeks), two reference groups (rats on high-fat diet received either metformin 300 mg/kg or vildagliptin 8 mg/kg during 2 weeks), and a test group (received AZ-020 1 mg/kg for 2 weeks under the same diet). Liver structure was assessed using histological and morphometric analyses, including hepatocyte count, binucleated hepatocyte count per field of view, hepatocyte size, hepatocyte cytoplasmic and nuclear area, and hepatocyte nuclear-to-cytoplasmic ratio. Statistical evaluation was performed using the fourfold table method with Pearson’s χ2 test, normalized Pearson’s test, Yates’ correction, and Fisher’s exact test. Parametric statistical methods and Student’s t-test were applied to morphometric data with normal distribution.
RESULTS: Administration of AZ-020 normalized liver histoarchitecture disrupted by prolonged dietary overload and confirmed a positive trend in key morphometric parameters of hepatocytes compared with the control group. A statistically significant 1.7-fold increase (66%) in binucleated hepatocyte count (an essential marker of liver regeneration) was observed following AZ- 020 administration. Treatment with AZ-020 led to normalization of the nuclear-to-cytoplasmic ratio, which showed a statistically significant 16% decrease compared with the control group. In the test group (treated with AZ-020), hepatocyte cytoplasmic area was 76.04 ± 0.35 μm2 (vs. 75.54 ± 0.31 μm2 in the control group, p = 0.0186); nuclear area was 11.13 ± 0.24 μm2 (vs. 13.9 ± 0.3 μm2, p < 0.001); and average hepatocyte area was 87.17 ± 0.59 μm2 (vs. 89.44 ± 0.61 μm2, p < 0.001).
CONCLUSION: The novel thienopyridine derivative with the laboratory code AZ-020, which belongs to the cyanothioacetamide class, demonstrated hepatoprotective effects in an experimental model of liver damage and metabolic disturbances.



Effects of amitriptyline, risperidone, and nooclerin on the behavior of male and female rats in the valproate model of autism
Abstract
BACKGROUND: Autism spectrum disorder is characterized by anxiety and stereotypical behaviors and is more commonly diagnosed in boys. Therefore, developing behavioral correction strategies for autism spectrum disorder with consideration of sex differences is especially relevant.
AIM: To assess the effects of amitriptyline, risperidone, and nooclerin on anxiety-like and stereotypical behaviors in male and female rats in the valproate model of autism.
MATERIAL AND METHODS: Anxiety-like and stereotypical behaviors were studied in 32 male and 32 female rats prenatally exposed to valproic acid and treated subcutaneously for 30 days with amitriptyline (4 mg/kg), risperidone (1 mg/kg), or nooclerin (20 mg/kg). Control groups included 8 males and 8 females. Behavioral testing included the elevated plus maze, extrapolative escape test, and marble burying test. Statistical analysis was performed using one-way ANOVA in GraphPad Prism 8.0.1.
RESULTS: In the elevated plus maze, rats in the autism model showed increased anxiety: time spent in the open arms decreased by 3.0-fold in females (p = 0.00001) and 1.9-fold in males (p = 0.00001); the number of open-arm entries decreased by 1.9-fold in females (p = 0.002) and 4.2-fold in males (p = 0.0001), compared with controls. In male rats, administration of amitriptyline and nooclerin reduced anxiety: time spent in the open arms increased by 3.7-fold (p = 0.001) and 3.9-fold (p = 0.0001), respectively, and the number of open-arm entries increased by 5.3-fold (p = 0.0001). In female rats, only nooclerin demonstrated an anxiolytic effect, with a 2.5-fold increase in the number of open-arm entries (p = 0.003). In the extrapolative escape test, female rats with autism exhibited increased anxiety, as evidenced by a 3.3-fold increase in jump duration (p = 0.0004) and a 2.3-fold increase in jump count (p = 0.004), compared with controls. All treatments normalized these parameters. Stereotypical behavior was observed in both sexes in the autism model, indicated by a 4.8-fold reduction in the number of untouched marbles in males (p = 0.00002) and a 4.2-fold reduction in females (p = 0.003), compared with controls. All treatments normalized this parameter.
CONCLUSION: Nooclerin showed anxiolytic effects in both male and female rats in the model of autism, whereas amitriptyline was effective only in males. Under high-stress conditions, anxiety developed only in females, and all tested drugs demonstrated anxiolytic effects.



Effect of p38 MAPK inhibition on the severity of intestinal dysfunction in suppurative peritonitis under antibacterial therapy
Abstract
BACKGROUND: Identifying new treatment strategies aimed at restoring intestinal wall integrity and preventing the development of abdominal sepsis remains a pressing issue in modern medicine.
AIM: This study aimed to examine the course of experimental peritonitis and the resulting intestinal dysfunction during etiotropic antibacterial therapy combined with pathogenetic treatment using a p38 MAPK inhibitor.
MATERIAL AND METHODS: Male Wistar rats were divided into control groups 1 and 2 and experimental groups 1, 2, and 3. All animals underwent induction of postoperative diffuse peritonitis via intraperitoneal injection of a suspension containing 109 microbial bodies/mL of Escherichia coli and Bacteroides fragilis. One day after peritonitis modeling, rats in the control groups received 3 mL of saline intraperitoneally, while rats in the experimental groups received 3 mL of an aqueous solution of the p38 MAPK inhibitor (a conjugate of 4-[4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-1H-imidazole-5-pyridine] with poly-1-vinylimidazole). All animals received antibacterial therapy (cefoperazone + sulbactam, 47 mg/day intramuscularly) starting on day 1 post-modeling. In control group 1 and experimental group 1, the duration of antibiotic therapy was 5 days; in control group 2 and experimental groups 2 and 3, it was 10 days. Animals were euthanized on days 3, 7, 14, and 28. Peritoneal fluid underwent microbiological analysis, and intestinal wall samples were examined histologically. Statistical analysis was performed using Statistica 10 for Windows. The significance of differences between the compared samples (p values) was assessed using the Wilcoxon (W) test and the Mann–Whitney U test. Differences were considered statistically significant at p < 0.05.
RESULTS: Administration of the p38 MAPK inhibitor alongside 5-day antibiotic therapy significantly reduced the severity of intestinal dysfunction on days 3 (pu = 0.005), 7 (pu = 0.005), and 14 (pu = 0.003), compared with control group 1. With 10-day antibiotic therapy, both early (group 2) and delayed (group 3) administration of the inhibitor resulted in reduced intestinal wall damage on days 14 (pu = 0.001) and 28 (pu = 0.003), compared with control group 2.
CONCLUSION: The p38 MAPK inhibitor attenuated the severity of destructive changes in the intestinal wall when administered alongside antibacterial therapy.



Reviews
Modern applications of 3D technologies for the treatment of bone tissue defects
Abstract
The use of 3D technologies offers more precise planning of surgical procedures in complex cases of localized bone tissue deficiency, allowing adaptation to individual anatomical features, improved outcomes, reduced risk of complications, and faster postoperative recovery. To analyze the current capabilities of three-dimensional printing in the surgical management of pelvic and hip bone defects, we reviewed scientific literature available in open-access databases including PubMed, eLibrary.Ru, Scopus, and Dimensions, with a search depth of up to 10 years. This review highlights major trends and advances in the medical application of 3D technologies aimed at reducing perioperative risks and improving patients’ quality of life in the context of bone tissue defects. Particular focus is placed on revision hip arthroplasty and pelvic oncologic conditions, where modern additive manufacturing technologies can enhance treatment quality and surgical outcomes. The methodology of 3D scanning for designing patient-specific implants is described. The review also demonstrates current and promising applications of 3D printing in clinical practice. Modern 3D technologies, particularly additive manufacturing, play an important role in improving surgical outcomes for skeletal deficiencies by enabling personalized treatment, expediting recovery, and improving patient prognosis. Emerging directions significantly expand the range of available reconstructive procedures, reduce the risk of complications, and ultimately improve patient quality of life and surgical efficiency.



Liquid biopsy in pancreatic ductal adenocarcinoma and precancerous lesions
Abstract
Pancreatic ductal adenocarcinoma ranks seventh among all cancer-related causes of death and has an overall 5-year survival rate of no more than 15% across all stages. This high mortality rate is largely attributed to delayed diagnosis: due to late clinical manifestation and early metastasis, only about 5% of pancreatic ductal adenocarcinoma cases are detected at stage I. Another important issue is the risk of overtreatment in patients with benign or non-neoplastic pancreatic conditions that mimic pancreatic ductal adenocarcinoma, often resulting in unnecessary and invasive surgeries. A diagnostic approach capable of detecting pancreatic ductal adenocarcinoma with high sensitivity at early stages and distinguishing it from benign pancreatic diseases could improve survival rates and reduce the number of unwarranted high-risk procedures. One of the most promising technologies for early and noninvasive cancer detection is liquid biopsy. This term refers to a set of analytical methods designed to identify tumor-specific genetic, epigenetic, and antigenic alterations by analyzing tumor-derived materials in biological fluids such as plasma, bile, or urine. Liquid biopsy may be used not only for early detection of pancreatic ductal adenocarcinoma and its precursors in high-risk individuals but also for differential diagnosis. This review summarizes current research evaluating the diagnostic potential of liquid biopsy through the detection of extracellular tumor DNA and RNA, as well as circulating tumor cells in blood, pancreatic juice, and bile in patients with pancreatic neoplasms.



Clinicopathological features of glomerulopathies and their prognostic significance in cancers of different sites
Abstract
This review analyzes international studies from the past five years that focus on glomerulopathies associated with malignant neoplasms of different sites. This study aimed to conduct a comparative analysis of histological and immunohistochemical features of morphological characteristics in glomerulopathies in cancer of different localizations, as well as identification of the specificity of the revealed features. Relevant publications were identified through Scopus, PubMed, and the Cochrane Library, with a search limited to studies published from 2019 to 2024. The review provides a detailed analysis of histological and immunohistochemical alterations in the glomerular apparatus in glomerulopathies associated with carcinomas of different sites. The identified morphological changes were assessed for their specificity. Particular attention is given to pathogenetic mechanisms that may underlie the development of glomerulopathies associated with carcinomas of different sites. A detailed analysis of the available literature demonstrates that understanding the histological and immunohistochemical features of glomerulopathies associated with malignant tumors contributes to improving diagnostic approaches for these conditions. Research in this area is of considerable importance, as it may offer new insights for the development of innovative strategies aimed at advancing prognosis and quality of life in patients with malignancies. Malignant cells are capable of expressing various substances, including proteins, that may contribute to the pathogenesis of glomerulopathies. Morphological evaluation of the glomerular apparatus enables the identification or exclusion of a pathogenetic association between the tumor and glomerulopathy, thereby allowing adjustment of the patient’s treatment plan. The review also discusses potential pathophysiological mechanisms of tumor-associated glomerulopathies, contributing to more accurate interpretation of glomerular changes and enabling differentiation between specific and paraspecific morphological features. In summary, this review presents an analysis of the histological and immunohistochemical features of glomerulopathies associated with malignant tumors of different sites, highlighting the importance of an interdisciplinary approach to diagnosing this condition as one of the clinical manifestations of malignancy.



Molecular mechanisms of berberine action on tumor cells
Abstract
Malignant tumors remain one of the leading causes of mortality worldwide, highlighting the urgent need to develop novel and effective therapeutic strategies. In recent years, the scientific community has actively pursued agents that combine high efficacy with minimal adverse effects and offer the potential to induce complete remission. In this context, berberine is a natural phytochemical derived from various Berberis species. It has garnered considerable interest due to its diverse pharmacological properties. Berberine, known as a nutraceutical, exhibits a broad spectrum of biological activity, including anti-inflammatory, antioxidant, and antitumor effects. In vitro and in vivo studies have shown that berberine exerts inhibitory activity against several cancer types, including breast, lung, liver, and colorectal cancers. Its antitumor properties are associated with several key molecular mechanisms through which it exerts effects on tumor cells. This review provides a detailed overview of the molecular pathways through which the antitumor effects of berberine are mediated. In particular, berberine activates the caspase cascade, leading to the induction of apoptosis in tumor cells, and inhibits cell proliferation by blocking key signaling pathways such as PI3K/Akt/mTOR. It also modulates the expression of genes involved in cell migration and invasion, including matrix metalloproteinases and E-cadherin, highlighting its potential as a promising therapeutic candidate. Additionally, berberine’s anti-inflammatory effects may contribute to cancer prevention by protecting cells from oxidative stress and chronic inflammation associated with tumor development. These pharmacological properties make berberine a promising agent for further investigation and clinical application, both as monotherapy and in combination with standard anticancer therapies. Thus, berberine represents a promising subject for further investigation of its molecular mechanisms of action and potential use in oncology, which may lead to the development of more effective and safer therapeutic strategies for patients with malignant tumors.



Morphological assessment of dental implantation outcomes
Abstract
Numerous publications have addressed gingival and bone augmentation involving both the alveolar processes of the jaws and the floor of the maxillary sinuses. In some cases, patients require not only dental restoration but also complex reconstruction of facial skeletal regions damaged by trauma, radiation exposure, cancer surgery, and other factors. Dental implantation is an essential component in the correction of extensive defects not only of the jaws but also of the paranasal sinuses. Additionally, various techniques have been described for covering the outer part of dental implants immediately after insertion to enhance integration. At the same time, certain disagreements remain regarding gingival manipulation during dental implantation and preparatory procedures. Some sources recommend covering implants with a flap of autologous soft tissue, whereas others support flapless approaches. Reports also differ on the source of soft tissue used for coverage: ranging from autologous grafts to allogeneic transplants, such as porcine-derived monolayer collagen matrices. There is no consensus on the optimal bone augmentation method for implant placement. Morphological data on the processes of lysis, replacement, or consolidation of autologous bone fragments that are placed into or left within tissues damaged during preparation and implantation are clearly insufficient, and existing publications lack detailed descriptions of these processes. All of this indicates that none of the challenges in dental implantation have been definitively resolved, including the need for a step-by-step understanding of the pathomorphological processes involved in bone graft consolidation or resorption.



The role of the NLRP3 inflammasome in the pathogenesis of bronchial asthma: inflammatory mechanisms and emerging therapeutic perspectives
Abstract
This article explores the pathophysiological mechanisms and therapeutic potential for treating bronchial asthma, a significant global public health issue. Immune-mediated inflammation is central to asthma pathogenesis and involves the formation of inflammasomes—molecular complexes that regulate inflammatory responses. The NLRP3 inflammasome plays a pivotal role in disease progression by interacting with allergens and triggering signaling cascades that lead to the production of proinflammatory cytokines, such as interleukin-1β (IL-1β) and IL-18. These cytokines recruit immune cells, including mast cells, eosinophils, and T lymphocytes, which contribute to airway inflammation, hyperresponsiveness, and bronchial obstruction. The article discusses asthma phenotypes, including infection-induced and atopic asthma, and the link between NLRP3 inflammasome activation and impaired lung function, steroid resistance, and neutrophilic inflammation. Special attention is given to the cellular and molecular pathways involved in the inflammatory response, including interactions between the inflammasome and T helper cells, macrophages, eosinophils, and mast cells. These interactions lead to the release of histamine, heparin, lysosomal enzymes, reactive oxygen species, nitric oxide, prostaglandins, and leukotrienes. Inflammatory mediators such as IL-4, IL-5, and IL-13 contribute to airway remodeling, mucus hypersecretion, and bronchospasm. Additionally, inflammasome activation can impair epithelial barrier integrity, further exacerbating allergic inflammation. The article emphasizes the chronic changes in the bronchial tree caused by sustained inflammation and highlights the importance of regulating inflammasome activity. In particular, the selective NLRP3 inflammasome inhibitor MCC950 has demonstrated efficacy in reducing inflammation and shows promise as a novel therapeutic approach. The article concludes that integrating inflammasome research into clinical practice (particularly through the use of targeted therapies such as MCC950) may transform the approach to asthma treatment. This underscores the importance of transitioning toward personalized medicine in the management of chronic inflammatory diseases such as bronchial asthma.



Clinical experiences
Prediction of paroxysmal atrial fibrillation based on 24-hour Holter electrocardiographic monitoring
Abstract
BACKGROUND: Predicting and detecting paroxysmal atrial fibrillation at an early stage is a key priority for preventing cardioembolic complications.
AIM: This study aimed to develop a predictive tool for paroxysmal atrial fibrillation in patients with sinus rhythm.
MATERIAL AND METHODS: A single-center case-control study was conducted involving 6630 patients. The main group comprised 97 individuals with newly diagnosed paroxysmal atrial fibrillation. The control group included 99 patients without atrial fibrillation, matched for anthropometric and comorbidity parameters. Standard laboratory and instrumental methods were used. During 24-hour Holter ECG monitoring, the following parameters were analyzed: sex, age, monitoring duration, and rhythm driver. Special attention was given to early ectopic beats of the “P on T” and “R on T” types. Differences were considered statistically significant at p ≤ 0.05.
RESULTS: Holter ECG parameters (extrasystole, ectopy, and paroxysmal tachycardia) were significantly more frequent and had higher values in the main group. A specific type of early atrial extrasystole (“P on T”) was observed in 97.9% of the main group, compared with 4.0% of the control group (odds ratio, 8461.648; 95% CI, 382.1983–187336). The number of supraventricular extrasystoles (isolated, paired, grouped) was significantly higher in the main group. Interval durations were also significantly longer in this group. No significant differences between groups were found in the frequency of ventricular extrasystoles or ST-segment depression. A logistic regression model was developed based on the most significant predictors: sex; number of atrial and atrioventricular supraventricular extrasystoles; number of isolated and paired ventricular extrasystoles; presence of allorhythmia in ventricular ectopy; and presence of early “P on T” ectopic beats. The model yielded an area under the curve (AUC) of 0.996, with an optimal risk threshold of 0.5 and prediction accuracy of 97.45%.
CONCLUSION: A predictive tool for paroxysmal atrial fibrillation in patients with sinus rhythm was developed, demonstrating high predictive performance.



Treatment experience in patients with recurrent ovarian cancer
Abstract
BACKGROUND: In patients experiencing recurrence of ovarian cancer, the choice of treatment strategy is crucial—whether to perform secondary cytoreduction followed by chemotherapy or to administer chemotherapy alone.
AIM: The analysis aimed to assess the effectiveness of treatment strategies based on clinicopathological factors in patients with a first recurrence of ovarian cancer.
MATERIAL AND METHODS: A retrospective analysis was conducted on medical records of 446 female patients with first recurrent ovarian cancer treated at the Primorsky Regional Oncology Center. Among them, 53 (11.9%) had platinum-refractory recurrence, 110 (24.7%) had platinum-resistant recurrence, and 283 (63.5%) had platinum-sensitive recurrence. BRCA1/2 mutation testing was performed in 197 patients, revealing mutations in 62 (31.5%) cases, while 135 (68.5%) had no detected mutations. The primary endpoints were overall survival and progression-free survival. The impact of clinicopathological factors was assessed using univariate and multivariate analyses and Kaplan–Meier survival curves.
RESULTS: In patients with first recurrence of ovarian cancer, overall survival and progression-free survival were significantly improved in cases of platinum-sensitive recurrence (p = 0.0010 for both overall and progression-free survival), stage I disease (p = 0.0030 for overall survival; p = 0.0010 for progression-free survival), the presence of BRCA1/2 mutations (p = 0.0010 for overall survival; p = 0.0070 for progression-free survival), secondary cytoreduction followed by chemotherapy (p = 0.0010 for both overall and progression-free survival), a single recurrent tumor (p = 0.0010 for overall survival; p = 0.0040 for progression-free survival), and complete primary cytoreduction (p = 0.0010 for both overall and progression-free survival), with the extent of initial cytoreduction being a significant factor (p = 0.0100 for overall survival; p = 0.0010 for progression-free survival). According to multivariate analysis, the risk of progression decreased by 30% in the presence of BRCA1/2 mutations (p = 0.0160) and by 30% in cases of a single recurrent tumor (p = 0.0040). Independent risk factors for progression included tumor histological type, the extent of primary cytoreduction, platinum-free interval duration, treatment strategy for the first recurrence, chemotherapy regimen, and maintenance therapy approach.
CONCLUSION: Complete secondary cytoreduction followed by antitumor drug therapy significantly improves overall survival and progression-free survival in patients with platinum-sensitive recurrence, increasing the likelihood of subsequent platinum-sensitive recurrences.



A rare case of coexisting vascular anomalies and developmental variant of the brachiocephalic vessels
Abstract
This article presents a rare case of coexisting vascular anomalies and developmental variants of the brachiocephalic vessels in a female patient who reported headaches triggered by food intake. The anomalies included: arteria lusoria, an aberrant right subclavian artery arising directly from the aortic arch and passing posterior to the esophagus; origin of the right vertebral artery from the right common carotid artery; origin of the left vertebral artery from the aortic arch; high vertebral artery entry points with hypoplasia; and excessive S-shaped tortuosity of the left internal carotid artery. This case is of particular interest due to the exceptional rarity of coexisting vascular anomalies and developmental variants in a single patient, qualifying it as a clinical curiosity. Variations in the origin and course of aortic arch branches may lead to altered cerebral hemodynamics and be associated with cerebrovascular disorders or neurological symptoms. Identifying atypical courses of the brachiocephalic vessels is crucial during preoperative assessment, as anomalous vascular anatomy may result in serious complications during surgical or endovascular interventions.



History of medicine
Professor Vladimir Onisimovich Kler — the founder of the histology department of the Ural State Medical University
Abstract
This article is dedicated to Professor Vladimir Onisimovich Kler, a prominent physician-histologist, regional geographer, biologist, geologist, and paleontologist—a remarkably versatile scholar. A well-known figure in Yekaterinburg (called Sverdlovsk from 1924 to 1991), he also made a notable contribution to the scientific and academic life of Kazan, where he worked from 1915 to 1921 as an assistant at the departments of zoology and histology at Kazan University. His first known publications, focused on determining the age of fish from bone structures, appeared during this period. It was in Kazan that he developed a strong interest in medical histology and chose to devote his life to it. In 1931, Professor Kler established the Department of histology, cytology, and embryology at the newly founded Sverdlovsk Medical Institute (now Ural State Medical University) and headed it for 20 years. A series of outstanding works in medical histology earned him recognition as one of the leading Russian morphologists. This article was written as a tribute to Professor Kler, not only as a prominent scientist, educator, and organizer of science, but also as an exceptionally remarkable individual, and to honor his contribution to the development of Russian medicine.



TO THE 80ᵗʰ ANNIVERSARY OF VICTORY IN THE GREAT PATRIOTIC WAR
Warriors of the Invisible Front during the Great Patriotic War
Abstract
This article presents biographic data of the employees of the Department of Microbiology at Kazan State Medical University who took part in the Great Patriotic War. It describes their military and labor feats, their scientific contributions, and work in the post-war peacetime. The aim of this article is to highlight the backgrounds of microbiologists and epidemiologists, employees of the Kazan State Medical University, veterans of the Great Patriotic War as perfect examples of their devotion to duty and patriotism. The article describes the feats of doctors providing qualified medical care to the wounded at the front, conducting diagnostic microbiological research and epidemic control measures, and eliminating outbreaks of infectious diseases in military units. The article was prepared using the primary sources such as autobiographies, memoirs of employees, archives of the Department of Microbiology, personal files from the archives of the Personnel Department of Kazan State Medical University, documents from the archives of the Kazan Research Institute of Epidemiology and Microbiology, as well as the website Memory of the People presenting documents from the archives of the Ministry of Defense of the Russian Federation.



Cochrane Review Summaries
Renin inhibitors versus angiotensin receptor blockers for primary hypertension
Abstract
This publication is the Russian translation of the Plain Language Summary (PLS) of the Cochrane Systematic Review: Wang GM, Li LJ, Fan L, Xu M, Tang WL, Wright JM. Renin inhibitors versus angiotensin receptor blockers for primary hypertension. Cochrane Database of Systematic Reviews. 2025. Issue 2. Art. No.: CD012570. DOI: 10.1002/14651858.CD012570.pub2


