Institute of Clinical and Experimental Lymphology

BACKGROUND : Obesity is considered one of the leading global health issues. According to a meta-analysis published in the Lancet, in 2024 there were 880 million adults and 159 million children with obesity worldwide. Surgical treatment is one of the main methods for managing morbid obesity. There are several options for surgical treatment, but mini-gastric bypass is gaining popularity among bariatric surgeries. The operation is considered effective in reducing body mass and achieving remission of obesity-related comorbidities. The main advantage of this type of surgical intervention is the combination of relative simplicity and safety of the operation compared to other shunting bariatric interventions with sufficient efficacy on the course of type 2 diabetes mellitus. Despite the advantages of this technique, there is limited research published in this area. AIM : Assess the long-term outcomes of mini-gastric bypass in patients with morbid obesity. MATERIALS AND METHODS: The study presents the results of a 2-year follow-up of 30 patients who underwent mini-gastric bypass surgery. The patients' average age was 52.5 [50–56.5] years, and their preoperative BMI was 50.0 kg/m 2 [46.2–59.6]. Follow-up assessments were conducted at 6, 12, 18, and 24 months over a two-year period post-surgery. During the observation period, anthropometric data (BMI, waist circumference, hip circumference, excess weight loss percentage — EWL, total weight loss percentage — TWL), fasting blood glucose level, glycated hemoglobin (HbA1c), and postoperative adverse events were evaluated. RESULTS: After two years post-surgery, the median BMI value was 33.6 kg/m2 [28.4–36.5] (p<0.001) with an excess weight loss of 33.6% [28.4–36.4] (p<0.001). The greatest excess weight loss of 35.6% [26.6–54.2] (p<0.001) and 56.0% [39.0–56.0] (p<0.001) was observed at 6 and 12 months of the study, respectively. Similar results were also noted for other parameters. During the study period, remission of type 2 diabetes was achieved in 40% of patients (n=12) at 12 months of observation and in 80% of patients (n=24) at 24 months of observation. A significant reduction in adverse events was observed in the second year of the study compared to the first year. CONCLUSION : Therefore, mini-gastric bypass surgery is an effective bariatric procedure that leads to weight loss and remission of type 2 diabetes.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that leads to irreversible structural joint damage and disability. Even with modern therapeutic approaches, a subset of patients continues to exhibit persistent inflammatory activity, which underscores the importance of identifying prognostic markers of treatment efficacy. Increasing attention is currently being paid to the morphological features of synovial membrane remodeling and to the subpopulation composition of lymphocytes in the peripheral blood of RA patients. The aim of our study was to investigate associations between the subpopulation profile of immunocompetent cells in the synovial membrane and in the peripheral blood of patients with rheumatoid arthritis of varying disease activity. Material and methods . The study included 52 patients, including 40 with RA and 12 with osteoarthritis as a comparison group. All patients underwent standard clinical evaluation, disease activity assessment (ESR, C-reactive protein content, composite activity indices), and peripheral blood lymphocyte subpopulation analysis. In RA patients with knee synovitis, ultrasound-guided fine-needle aspiration biopsy of the synovial membrane was performed. Results and discussion . A positive association between the number of CD4⁺ T cells in the synovium and clinical disease activity in RA is revealed, whereas an inverse relationship was observed in peripheral blood. These findings provide additional insights into local immune responses in RA and highlight the potential of synovial biopsy analysis for therapy personalization. Conclusions . In patients with RA of varying disease activity, divergent associations were identified between the number of CD4⁺ T helper cells in the synovial membrane of affected joints and in peripheral blood.

Impaired intrarenal hemodynamics is one of the links in the pathogenesis of chronic kidney disease in type 2 diabetes (T2D); correction of these disorders is the target of drugs with nephroprotective activity, such as sodium-glucose cotransporter-2 (SGLT2) inhibitors. The aim of our study was to evaluate the effect of the SGLT2 inhibitor empagliflozin on intrarenal blood flow parameters in patients with T2D. Material and methods . In an open prospective cohort singlecenter study, clinical and laboratory data were monitored before the start of treatment, on the 7th, 28th, 90th, and 180th day of taking empagliflozin 10 mg/day. The study of renal blood flow parameters was carried out using Doppler ultrasonography, peak systolic (PSV), end-diastolic, and mean velocity (MV) of blood flow, as well as resistance index (RI) of intrarenal arteries were assessed. Results and discussion . Forty patients with T2D and chronic kidney disease, chronic heart failure and/or atherosclerotic cardiovascular disease were included, 17 men and 23 women, aged 43 to 76 years. In the arteries of the cortex, on the 90th day of empagliflozin administration, a decrease in PVR and MV was observed compared to the period before the start of treatment (p < 0.001 and p = 0.004, respectively). This dynamics was maintained on the 180th day (p < 0.001). The lowest values of RI in the arteries of the renal cortex were observed on the 180th day (all p < 0.01 compared to the periods before treatment, on the 7th and 28th days of empagliflozin administration). IR of blood flow in the medulla decreased from the 7th to the 90th day (p = 0.003). The revealed changes in intrarenal hemodynamics were associated with the dynamics of serum creatinine and glycated hemoglobin A1c content, as well as of albuminuria. Conclusions . In patients with T2D, a decrease in intravascular resistance and blood flow rates in the kidney is observed on the 90–180th day of empagliflozin use. Changes in intrarenal blood flow are associated with the hemodynamic and metabolic response to empagliflozin.

INTRODUCTION. Plants of Boraginaceae family (Pulmonaria mollis, Nonea rossica, Onosma simplicissima, and Cynoglossum officinale) are widespread over the Russian Federation and are promising sources of phytomedicines with important pharmacological properties, such as antimicrobial, antianaemic, anticoagulant etc. Currently, Boraginaceae are not classified as officinal plants, presumably due to pyrrolizidine alkaloids (PA) that can cause hepatotoxic effect. AIM. This study aimed to assess safety using Boraginaceae plants based on acute toxicity and content of pyrrolizidine alkaloids. MATERIALS AND METHODS. The research objects were dried herbs of Pulmonaria mollis, Nonea rossica, Onosma simplicissima, and Cynoglossum officinale , collected from flowering plants in Novosibirsk region over 2023–2024. The composition and amount of alkaloids in alcohol extracts were determined by high-performance liq­uid chromatography with diode array and mass-spectrometry detection with electrospray ionisation. Acute toxicity was tested in vivo in 102 mature male and female CD-1 mice weighing 24.0±2.0 g, aged 12 weeks, taken from Conventional Animal Vivarium of Scientific Center of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences. The animals received a single dose of dried study extracts diluted in distilled water at 5 g/kg. RESULTS. The absence of PA in P. mollis herb was established, alongside with its trace amounts (0.01 μg/g) in P. mollis leaves. In other studied plant species, PA, such as enantiomers of intermedine, lycopsamine and their deriva­tives were found: O. simplicissima herb — 1.07±0.03 μg/g, N. rossica herb — 8.25±0.08 μg/g; in C. officinale herb — 676.3±7.4 μg/g. Assessed acute toxicity made it possible to classify dry extracts from P. mollis herbs and leaves , N. rossica herb and O. simplicissima herb as toxicity class 5, and C. officinale herb as toxicity class 4. CONCLUSIONS. Study doses of extracts taken from herbs and leaves of P. mollis are non-toxic. For extracts from O. simplicissima and N. rossica herb, further research is relevant to determine toxicity in prolonged use. Extracts from C. officinale herb are toxic and cannot be used per os .

Mitochondria are crucial for energy metabolism and the regulation of apoptosis and the inflammatory response in acute myeloid leukemia (AML). This study examined key mitochondrial characteristics in apoptosis-resistant AML cells during in vitro aseptic pro-inflammatory activation utilizing spectrofluorimetry, quantitative reverse transcription PCR, Western blotting, differential gene expression analysis, flow cytometry, transmission electron microscopy, and cellular respiration analysis. Under conditions of aseptic inflammation simulated in three-dimensional high-density cultures, apoptosis-resistant AML cells exhibited a significant reduction in the transcriptional activity of genes linked to oxidative phosphorylation and the tricarboxylic acid cycle; demonstrated diminished mitochondrial respiration activity; and decreased levels of the mitophagy regulatory proteins PINK1 and Parkin. Furthermore, pathogenic alterations in mitochondrial morphology were observed. These cells demonstrated enhanced intracellular generation of reactive oxygen species, lactate accumulation in the culture media, elevated levels of DRP1 protein, and an increased fraction of small and medium-sized mitochondria. The acquired data demonstrate that aseptic pro-inflammatory activation results in metabolic remodelling of acute myeloid leukemia cells, integrating characteristics of mitochondrial dysfunction. This condition may facilitate the persistence of leukemic cells during inflammatory stress and potentially contribute to the development of an apoptosis-resistant phenotype. The established in vitro model is crucial for examining both the characteristics of energy metabolism and the anti-apoptotic mechanisms in leukemic cells.

Background. Primary open-angle glaucoma (POAG) is optic neuropathy, the etiology of which is associated with genetic and non-genetic factors. IL-10 and MMP2 SNPs are associated with POAG, but the nature of the association depends on the ethnic profile of the population. For the Russian Federation, whose population includes 190 nationalities, this issue is relevant.Aim. To perform a multicenter comparative analysis of the IL-10 and MMP2 SNPs as potential factors for predicting the development of POAG in patients in four regions of the Russian Federation: the Novosibirsk, Leningrad, and Orenburg Regions, and the Chuvash Republic.Materials and мethods. We examined 499 POAG patients from 4 branches of S. Fyodorov Eye Microsurgery Federal State Institution (main group), 530 people without visual pathology (control 1), and 100 patients with cataracts (control 2). Genotyping of IL10 (rs1800896 and rs1800872 SNPs) and MMP-2 (rs243865) was performed by real-time polymerase chain reaction (RT-PCR) according to the manufacturer’s instructions (Lytex and Syntol, Russia). The differences were considered statistically significant at the Bonferroni-corrected p < 0.05.Results. An increase in the incidence of IL-10-1082 A was revealed in POAG patients compared to patients with cataract and healthy individuals. An increase in the incidence of IL-10 AA in both regions and a decrease in the frequency of MMP2-1306 TT were found. Similar patterns were established for interlocus IL-10 and MMP2 genotypes. The group of patients in the Leningrad Region differed the most compared to other regions, which may be due to their long-term residence together with the indigenous Finno – Ugric peoples.Conclusion. The data obtained should be taken into account when developing additional criteria for predicting predisposition to POAG, which is important in case of POAG in the family history.

Objective. To study early postoperative period in patients with chronic thromboembolic pulmonary hypertension (CTEPH) with concomitant supraventricular arrhythmias. Material and methods. We analyzed 133 patients with CTEPH who were admitted for pulmonary endarterectomy. Mean age was 52.8 (43.2—64.1) years. The 1st group (31 people) consisted of patients with concomitant supraventricular arrhythmias (atrial fibrillation, sinus tachycardia), the 2nd group (102 people) — without rhythm disturbances. Between-group analysis of clinical and functional data, as well as early postoperative period was carried out. Results. In the general group of patients, supraventricular rhythm disturbances were observed in 23.3% of cases. According to clinical data, the 1st group was characterized by older age (p=0.03), concomitant type 2 diabetes (p<0.001), higher incidence of obesity (p<0.001) and higher comorbidity index (p=0.02). Early postoperative period was more severe in the 1st group, where we observed ischemic stroke (p=0.01), larger proportion of patients with prolonged mechanical ventilation (p=0.03) and prolonged in-hospital period (p=0.04) compared to the 2nd group. There were no between-group differences in in-hospital mortality (p=0.19). Conclusion. Concomitant supraventricular arrhythmias in patients with CTEPH are associated with more severe early postoperative period with registration of ischemic stroke, larger proportion of patients with prolonged artificial ventilation and in-hospital period compared to patients without concomitant supraventricular arrhythmias. There was no effect of concomitant supraventricular arrhythmias on in-hospital mortality.

The importance of cytokines, including TNF, in development of uterine fibroids (UF) or leiomyomas (LM) is well proven. The number of polymorphic sites in promoter region of TNF gene is established, and their relationship with the gene expression level has been shown, thus potentially affecting the evolution of the disease. The aim of our research was to analyze the distribution of TNF-238, TNF- 308 and TNF-863 structural variants at the regulatory region of the TNFA gene in a representative group of Caucasian patients with UF compared with a matched group of healthy women followed by assessment of personalized prognostic significance of suggested differences. 180 patients diagnosed with uterine fibroids and 98 practically healthy women were examined. Genotyping of TNF gene polymorphisms (-863 C/A, TNF- 308 G/A, TNF-238 G/A, IL1B-31 T/C, IL4-590 T/C, IL6-174 C/G, IL8-251 T/A, IL10-592 A/G, IL10-1082 A/G and IL17A-197 G/A) was performed by RT-PCR using the SYBR Green intercalating dye. Statistical processing was carried out using multifunctional programs – IBM SPSS Statistics 23, SNPStats. We did not reveal significant differences between the compared groups when analysing distribution of TNF allelic variants and their combinations in genotypes. When comparing the combined SNP variants of the TNF gene at the studied nucleotide positions with the polymorphisms of other genes encoding proinflammatory cytokines, an increased frequency of TNF-238 GG:TNF-308 GG:IL17A-197 AA complex was found in the group of patients with uterine fibroids. The diagnostic specificity of this index was 100%, and the predictive value of this quotient reached 13.3, thus implying a 99.9% probability of a correct prediction. At the same time, the combination of TNF-863 CC genotype with IL-6-174 GG and IL-17-197 GG was significantly reduced in the patients. The frequencies of the anti-inflammatory cytokine genes IL4-590 T/C, IL10-592 A/G and IL10-1082 A/G analyzed n our study did not differ in the both compared groups and they were not considered either predisposing or protective for the disease. The magnitude of the revealed differences in occurrence of these allelic combinations reaches a significant level, thus assuming these traits as potential genetic factors for predicting a predisposal or resistance of women with a certain genotype to development of uterine fibroids, being prognostic criteria for early detection of this disorder.

Axial spondyloarthritis is characterized by activation of innate immune cells, which manifested in elevation of classical monocytes and predominance of the proinflammatory phenotype. However, the immunosuppressive potential of monocyte/macrophages remains practically unexplored. We evaluated the expression of Mer tyrosine kinase (MerTK) and arginase-1 (Arg1) in monocyte subsets in patients with axial spondyloarthritis, considering different clinical features. The expression of MerTK and Arg1 in intermediate and non-classical monocytes from patients with axial spondyloarthritis was reduced in comparison with the normal. The most pronounced decrease in monocyte expression of MerTK and Arg1 was associated with a more aggressive course of the disease (presence of coxitis, high disease activity, HLA-B27 positivity) and lack of response to conventional therapy. These data demonstrate an important role of MerTK and Arg1 in limiting myeloid-driven inflammation.