I n t r o d u c t i o n . Differences in the frequency and spectrum of mutations in acute myeloid leukemia (AML) may be related to regional environmental factors (ionizing radiation or chemical mutagens) and the genetic predisposition of the population, while data on the Russian population are limited and presented in isolated publications with a “narrow” geography and a small sample size.
A i m . Comprehensive analysis of mutations in the hot spots of the DNMT3A, NPM1, FLT3, IDH1 and IDH2 genes in AML patients living in Novosibirsk.
M a t e r i a l s a n d m e t h o d s . Genomic DNA isolated from the bone marrow of 128 patients with newly diagnosed AML was studied. p.W288Cfs*12 mutations of the NPM1 and FLT3-ITD genes were screened by polymerase chain reaction (PCR) with flanking primers; screening for the p.R882 mutation of the DNMT3A gene, p.D835 of the FLT3 gene, p.R132 of the IDH1 gene, and p.R140 of the IDH2 gene was performed by PCR with analysis of restriction fragment length polymorphism (PCR-RFLP). Exact verification of the mutation was carried out by direct capillary sequencing according Sanger.
R e s u l t s . In the study group, in 42,2% of cases revealed some clinically, prognostically, and therapeutically significant findings. In total, 22,6% of the patients in the study group had mutations in the hot spots of the genes of epige netic genome regulation: IDH1, IDH2 and DNMT3A. At the same time, mutations in two or more analyzed genes occurred in half of the cases (51,9%) with findings. In the study group, the mutation rate was 9,3% for p.R882 of the DNMT3A gene, 14,8% for p.W288Cfs*12 in the NPM1 gene, 18,0% for FLT3-TKD and FLT3-ITD, 5,5% for p.R132 of the IDH1 gene, and 10,2% for p.R140 in the IDH2 gene, which corresponded to data from the cBioPortal for Cancer Genomics (p > 0,05). In an isolated variant, the p.W288Cfs*12 mutation of the NPM1 gene was detected in 7 out of 19 (36,8%) patients with this mutation.
C o n c l u s i o n . For the first time, a comprehensive picture of the spectrum of mutations in the analyzed hot spots of the DNMT3A, IDH1, IDH2, FLT3, and NPM1 genes was obtained in de novo AML in patients living in the Siberian region. In more than a third of cases, the analysis of the hot spots of the studied genes provides information important for making clinically significant decisions.

I n t r o d u c t i o n . Estimation of wound vitality is one of the most challenging and urgent tasks in forensic medicine, having undeniable significance. Conventional histological methods, based on the assessment of inflammatory response elements, are often insufficiently sensitive for diagnosing injuries inflicted shortly before death. The development and implementation of highly sensitive molecular morphological methods is an important direction for advancing expert practice.
A i m . To evaluate the diagnostic value of such immunohistochemical marker as tumor necrosis factor-alpha (TNF-α) and the method of quantitative digital analysis for the objective determination of the vitality of skin blunt force injuries.
M a t e r i a l s a n d m e t h o d s . Skin samples from 14 cadavers with documented antemortem injuries (28 sections, 140 fields of view) were analyzed. Samples were taken from the area of external injury, and a control tissue sample was also taken from an undamaged area. Paraffin-embedded sections were stained with monoclonal antibodies to TNF-α. Digital images were analyzed using Fiji software using color deconvolution to isolate DAB staining and subsequently determine the area of marker expression in the epidermis and dermis separately.
R e s u l t s . A statistically significant increase in the area of TNF-α expression was found in the damaged area compared to intact skin in control samples. In the epidermis, the difference in medians was –16,66% (p = 0,0002), and in the dermis –7,93% (p = 0,0072).
C o n c l u s i o n . Immunohistochemical detection of TNF-α in combination with quantitative analysis of digital image is highly informative and objective method for ascertaining the skin wound vitality. This approach allows for the identification of early molecular signs of alteration preceding morphological changes and minimizes the subjective factor during the interpretation of results, which increases the evidentiary value of the forensic medical report.

I n t r o d u c t i o n . Bacterial infections are a common pathology in patients with liver cirrhosis (LC) among which urinary tract infections (UTIs) are widely spread. A i m . To study the incidence, features of the course, risk factors of UTIs in hospitalized patients with LC, and the disease prognosis depending on the presence of UTIs.
M a t e r i a l s a n d m e t h o d s . A prospective observational study involving 338 hospitalized patients with LC aged 30 to 84 years (median, 55,00 (45,00; 63,00) years), 189 (55,92%) men and 149 (44,08%) women was conducted. Child-Pugh class A liver cirrhosis was diagnosed in 78 (23,08%) patients, class B – in 118 (34,91%), class C – in 142 (42,01%). Bacterial infections were detected in 172 (50,89%) patients with LC. Clinical examination, clinical investigations and laboratory tests, urine culture with antimicrobial susceptibility testing using conventional microbiological methods were performed in all the patients. 
R e s u l t s . In patients with LC, the incidence of UTIs was 37,87%, and the incidence of asymptomatic bacteriuria – 23,96%. UTIs were more common in women with LC (female to male ratio was 57,81% vs. 42,19%, p < 0,001), in patients with decompensated LC (p < 0,001), and in those with LC duration of less than 5 years (p = 0,016). UTIs co-existed with other infections in 45,31% of cases. In patients with LC, UTIs with systemic manifestations (79,69%), with anatomical and structural changes of the urinary tract according to imaging studies (79%), healthcare-associated infections (44,53%), catheter-associated infections (56,25%), and infections with risk factors (RFs) (94,5%), including more than one RF in 75% of cases, predominated. Among the patients with LC and UTIs 70% died within 45 months of follow-up, which was significantly higher compared to patients without UTIs – 34% (p < 0,001).
C o n c l u s i o n . The high incidence of UTIs in hospitalized patients with LC, the complicated course with the presence of RFs, systemic inflammatory response, co-infections, and the association with an unfavorable prognosis of the disease indicate the need for their timely diagnosis and medical prevention.

I n t r o d u c t i o n . Cerebral stroke (CS) remains a leading cause of disability, accompanied by persistent motor impairments, particularly in the upper extremities. The effectiveness of recovery depends largely on the accessibility and motivational value of the techniques used. Eastern practices such as Tai Chi Chuan (Tai Chi) and Qigong, which combine physical and psycho-emotional components, offer a great potential for the development of promising neuromotor exercises for the rehabilitation of various groups of patients.
A i m . To evaluate the effectiveness of an adapted sequence of neuromotor exercises (SNE) based on Tai Chi and Qigong (Zhang Zhuang) and performed in a sitting position, in the rehabilitation of upper extremity function in patients after CS.
M a t e r i a l s a n d m e t h o d s . Forty-four patients suffering from the consequences of CS, who were randomly assigned to the study group (n = 24) and the control group (n = 20), were enrolled in the study. Patients in the study group received a Tai Chi and Qigong (Zhang Zhuang)-based SNE, which included movement trajectories relevant to everyday activities, instead of the standard set of physical therapy, which was used in the control group. The effectiveness of rehabilitation was evaluated using the Fugl-Meyer Assessment (FMA) for the upper extremity, the DASH (Disability of Arm, Shoulder and Hand) questionnaire, and the fine motor test. Statistical analysis was performed using non-parametric methods (p < 0,05).
R e s u l t s . The study group demonstrated more significant improvement according to the FMA (p < 0,01) and a reduction in subjective limitations according to the DASH (p < 0,001). A positive effect of the SNE on fine motor skills was also noted.
C o n c l u s i o n . The Tai Chi and Qigong (Zhang Zhuang)-based SNE performed in a sitting position promotes upper extremity function recovery and can be recommended as an effective and available method of post-stroke rehabilitation.

I n t r o d u c t i o n . Synovial sarcoma (SS) occupies a prominent place in the group of soft tissue sarcomas (STS) in terms of prevalence and clinical and biological aggressiveness, remaining one of the key nosologies in the adult population and a significant cause of cancer in adolescents and young adults.
A i m . To perform a comparative analysis of the clinical, morphological and immune characteristics of SS in children and adults, to describe the immunoarchitectural patterns of the tumor microenvironment and determine their relations with the disease course, risk of metastasis and survival rates, comparing the results obtained with data from international s tudies.
M a t e r i a l s a n d m e t h o d s . A single-center retrospective study of 140 patients (74 males and 66 females, aged 4 to 84 years) with morphologically confirmed SS, diagnosed in 2012–2024 based on the results of pathomorphological examination of primary (biopsy and surgical) and non-primary (“consultative”) tumor samples, was performed. Data from medical records, pathomorphological examination, and archival slides and paraffin blocks were analyzed.
R e s u l t s . The results obtained are generally consistent with the known epidemiological and morphological characteristics of SS: a peak in childhood and adolescence, a predominance of localized stages, frequent monophasic morphology, and a high rate of SS18::SSX-positivity. The analysis confirms that the “classic” risk factors – tumor size ≥5–7 cm, deep anatomical location of tumors in soft tissue, high mitotic activity, extensive areas of necrosis, FNCLCC grade 3, and positive resection margins – continue to determine the prognosis.
C o n c l u s i o n . A comprehensive pathological assessment of SS, including clarification of the morphological variant, standard prognostic parameters, and characteristics of the tumor microenvironment, appears to be appropriate for more accurate risk stratification in children and adults. This study, with complete morphological, immunohistochemical, and molecular verification of the diagnosis, can serve as a reference for the development of standardized pathological reports and prognostic models, as well as for planning multicenter studies for validating immune patterns and assessing their predictive value in the context of new approaches to immuno- and targeted therapy of SS.

I n t r o d u c t i o n . Prolonged-release formulations are designed to minimize the problems of traditional dosage forms, such as fluctuations in plasma concentration of a drug and the need for frequent dosing. Trimetazidine dihydrochloride (TMD), an antianginal drug, is a suitable candidate to develop prolonged-release formulations, although this is a rather challenging task due to its high water solubility.
A i m . To investigate the possibility of preparing prolonged-release solid dispersions (SDs) of TMD using different ratios of Eudragit® RSPO or POLYOX™ WSR coagulant as polymers that prolong the drug release.
M a t e r i a l s a n d m e t h o d s . SD variants with active pharmaceutical ingredient (API) to polymer ratios of 1:2, 1:4, and 1:8 were prepared by the solvent (isopropanol) evaporation method, and were evaluated on such characteristics as: API content uniformity, flowability and compressibility, weight loss on drying, dissolution. X-ray diffraction analysis and microscopy were also performed.
R e s u l t s . The API was evenly distributed in the SDs prepared, and its content ranged from 96,91 to 103,16%. The weight loss on drying was 1,08–2,24%, the flowability and compressibility ranged from good to excellent. The dissolution rate was reduced due to an increase in the proportion of polymer, with the possibility of extending the drug release to 17 h using Eudragit® RSPO. However, it was not possible to obtain а prolonged-release profile in SDs prepared with POLYOXTM WSR coagulant. The X-ray diffraction analysis and microscopic sexamination showed the formation of SDs, in which the API is dispersed within the polymer.
C o n c l u s i o n . By the solvent evaporation method using a suitable polymer in suitable proportions SD of water-soluble API – prolonged-release TMD – can be obtained with the characteristics required for further pharmaceutical investigation.

I n t r o d u c t i o n . In the context of macroeconomic instability and emergencies associated with social threats that may arise, an extended study and design of community-focused technologies (CFTs) in the drug provision (DP) for patients with type 2 diabetes mellitus (T2DM) in the Novosibirsk region (NR) is necessary.
A i m . Development of a model for designing CFTs in DP for T2DM patients at the regional level.
M a t e r i a l s a n d m e t h o d s . For an expert assessment of CFT priority areas of activity and measures in DP for T2DM patients, a survey was conducted among heads of regional and federal pharmacy chains, employees of the Ministry of Health of the NR, and Roszdravnadzor for the NR (in total, 30 specialists). The following methods were used: content analysis, analytic hierarchy process, expert assessment, hierarchic synthesis method, and modeling.
R e s u l t s. According to the resulting vector of priorities, the most significant areas of CFTs in DP for T2DM patients were recognized as follows (in descending order): optimization of organization and improving the mechanism of DP for T2DM patients; ensuring the availability of pharmacotherapy for T2DM patients (specific categories of citizens) based on the use of the criteria and regional information services; developing organizational and functional forms and technologies to improve interagency collaboration between healthcare professionals and their communication with T2DM patients. Research and practical activities for designing areas of CFTs in DP for T2DM patients should be carried out as follows: a sociological study of satisfaction of the population suffering from T2DM with the organization of DP in the NR; formation of an optimal assortment, positioning and stratification of medicines in the system of essential DP; a sociological study of the opinions of healthcare professionals and pharmacists on the organization of the DP for T2DM patients in the NR; micro-segmentation of T2DM patients based on aim and subjective criteria, T2DM patient profiling; development of DP infrastructure: opening the drug dispensing outlets in municipal formations of the region, specialized (commercial) pharmacies.
C o n c l u s i o n . The results obtained can serve as a basis for further optimization of the healthcare system of the NR to increase the effectiveness of steps to improve the quality of DP for T2DM patients.

I n t r o d u c t i o n . Arterial hypertension (AH) is a serious problem of modern medicine. High blood pressure significantly increases the risk of dangerous cardiovascular complications.
A i m . To perform a pharmacoeconomic cost-effectiveness analysis of angiotensin-converting enzyme inhibitors (ACE inhibitors) – captopril, enalapril, and lisinopril using data from the State Register of Maximum Selling Prices. 
M a t e r i a l s a n d m e t h o d s . Data on the clinical effectiveness of the studied ACE inhibitors was obtained from literature sources. The level of reduction of elevated blood pressure (systolic and diastolic) was considered as the criterion of clinical efficacy. The costs of pharmacotherapy were calculated based on the data from the State Register of Medicines. To perform a cost-effectiveness analysis (CEA), the cost-effectiveness ratio (CER) was calculated for captopril, lisinopril, and enalapril in order to determine the most cost-effective ACE inhibitor with the minimum CER value. The CEA was performed in 3 variants: CEA No. 1 – calculation of CER for 20 subgroups (CER separately for each dose that demonstrated clinical effectiveness); CEA No. 2 – calculation of CER separately for each dose, the price of which was used to calculate the costs; CEA No. 3 – calculation of CER for all doses simultaneously.
R e s u l t s . The CER values for enalapril at a daily dose of 20 mg, achieved by taking four 5 mg tablets, were statistically significantly lower than the CER values for captopril and lisinopril when assessing clinical effectiveness by normalizing systolic blood pressure (SBP). It was also found that the CER values for enalapril at a daily dose of 20 mg (8 tablets at a dose of 2,5 mg) were statistically significantly lower than the CER values for captopril and lisinopril when assessing clinical effectiviness by normalizing diastolic blood pressure (DBP).
C o n c l u s i o n . A cost-effectiveness analysis of ACE inhibitors showed that enalapril 20 mg/day is more costeffective than captopril and lisinopril for normalizing SBP and DBP.

I n t r o d u c t i o n . The bacille Calmette-Guérin (BCG) vaccine, developed by French scientists Albert Calmette and Camille Guérin in 1921, remains an effective method for the specific prevention of tuberculosis. However, post-vaccination complications are possible when using the BCG/BCG-M vaccines, which is one of the reasons of parental vaccination refusal. The number of such refusals increases annually, creating a pressing medical problem. Furthermore, non-BCG vaccinated children are at increased risk of tuberculosis.
A i m . Analysis of cases of complications following anti-tuberculosis vaccination in 2008–2022 among children of the Orenburg region and demonstration of possible clinical manifestations of complications of BCG vaccination in children using two case reports as an example.
M a t e r i a l s a n d m e t h o d s . A clinical and epidemiological analysis of all cases of complications following anti-tuberculosis vaccination in children in the Orenburg region from 2008 to 2022 was performed. Data from the personal register at the Orenburg Regional Clinical Anti-Tuberculosis Dispensary were used. Data from the follow-up of children and medical records (primary diagnostics and verification of diagnosis) were analyzed. Two clinical cases of complications were examined: BCG lymphadenitis and BCG osteitis.
R e s u l t s . The complication rate per 100 000 of vaccinated ranged from 21,6 in 2008 to 19,6 in 2022, showing a fluctuating trend with a downward trajectory. The most common complications following BCG vaccination (51,3% of cases) were inflammation in the regional lymph nodes (lymphadenitis), cold abscesses (31,3% of cases), and specific osteoarticular inflammation (BCG osteitis) – 12,5% of cases.
C o n c l u s i o n . Post-BCG/BCG-M vaccination reactions and complications are possible, and it is essential to spread the actual information regarding the extremely low risk of post-BCG complications in children. The reason for the population’s refusal of BCG vaccination is the lack of active anti-tuberculosis campaigns among pregnant women and new mothers, who need to be educated about the necessity of BCG vaccination and introduced to the features of vaccination in newborns. The increase in BCG vaccination refusals in the region is not related to possible post-vaccination complications. The case reports presented may be useful for primary pediatric care specialists (primary care pediatricians and pediatric surgeons).

I n t r o d u c t i o n . High rates of effectiveness of the treatmen t for malignant neoplasms, an increase in the population requiring blood component transfusion, and the formation of a pool of donors residing in the Novosibirsk region and included in the Federal Registry of Bone Marrow and Hematopoietic Stem Cell (HSC) Donors have necessitated the need of a functional and structural restructuring the provision of medical care in the field of transfusiology.
A i m . To develop a new organizational model for the provision of medical care in the field of transfusiology and evaluate its effectiveness.
M a t e r i a l s a n d m e t h o d s . A retrospective study of the performance of the Novosibirsk Clinical Blood Center was conducted – from 2020 to 2024 for indicators of procurement and delivery of blood components as well as immunohematologic and immunogenetic labs; from 2017 to 2024 – for indicators a day hospital and the HSC procurement center. The study included the results of 217 857 blood component donations and the procurement of 170 761,1 liters of whole blood; blood substitution performed in 1 877 cases of day hospital stay; 32 883 laboratory tests performed on 10 276 patients with the presence of alloantibodies to red blood cell (RBC) antigen systems and 138 immunological studies in 28 patients with established platelet transfusion refractoriness; immunogenetic testing of 3000 donors included in the local database of typed donors and 76 patients from the Novosibirsk region who was in need of bone marrow and HSC transplantation; examination of 10 HSC donors and quality control of 10 therapeutic doses of allogeneic HSC.
R e s u l t s . The growth of overall production indicators by 11,3% made it possible to increase the total output of blood components under the state assignment by 9,3%, to reduce the write-off of expired blood components. Blood transfusion was carried out in patients with thrombocytopenia, hemorrhages, and anemias in the setting of a specialized transfusion day hospital. The total volume of RBC components transfused to patients amounted to 6495 doses, platelet concentrate – 986 doses. Clinical effectiveness was 99,5% of cases for RBC components and 91,1% for platelet concentrate. No posttransfusion complications were recorded. A total of 22 385 doses of RBC components were individually selected for patients with detected anti-RBC antibodies; the effectiveness of individual RBC selection was 99,8%. Individual selection of platelet concentrate was required in 28 patients with platelet transfusion refractoriness; the effectiveness of individual selection for patients with HLA antibodies was 71,4%, and for all the recipients with refractoriness was 92,8%. Immunogenetic study on 76 patients from the Novosibirsk region who was in need of bone marrow and HSC transplantation resulted in the identification of a matched related donor for 19 (25%) of them. Eighteen cytaphereses were performed in 10 donors, 10 therapeutic doses of HSC were harvested.
C o n c l u s i o n . The new organizational model for the provision of medical care in the field of transfusiology allows to increase the provision of medical facilities with blood components, the availability of transfusion care, improve the immunological safety of allogeneic transfusions, introduce high-tech methods for harvesting HSC, and lay the foundation for the development of the transplantation potential of the Novosibirsk region.

Neuroinflammation is a condition characterized by a wide range of differences both in the cellular elements involved in this process (microglia, astrocytes) and in its pathogenesis as a whole. The lack of consensus on the pathogenetic models of neuroinflammation only highlights the insufficient study of this pathological phenomenon. This review examines the characteristics of neuroinflammation as a phenomenon using infectious diseases of the central nervous system, such as meningitis. Despite the specific peculiarities of neuroinflammation itself, its effector mechanisms involve the same cytokines as those found in “classical” inflammation (IL-6, IL-8, IL-1β, TNF-α, MCP-1, IFN-γ, etc.). This allows these molecules to be considered as potential targets, enabling the prevention of both acute inflammation and chronic processes associated with long-term neurological and cognitive impairment.