Kazan medical journal

BACKGROUND: Rheumatoid arthritis, gout, and fibromyalgia are common diseases; however, data on tolerance to psychomotor, intellectual, and communicative load in these patient groups are limited.

AIM: This study aimed to conduct a comparative analysis of the regulatory systems stress index, as well as hormonal and immunological serum parameters, in patients with rheumatoid arthritis, gout, and fibromyalgia under complex load conditions.

METHODS: The study included 21 patients with rheumatoid arthritis, 23 patients with gout, and 12 patients with fibromyalgia (age range 20–54 years). Diagnoses were established according to generally accepted criteria. The complex load lasted 4 hours and consisted of sequential psychomotor, intellectual, and communicative tasks. Load tolerance was assessed based on task performance, as well as on hormonal (cortisol, epinephrine, norepinephrine, serotonin, dopamine) and immunological (interleukin4, interleukin6, interleukin10, tumor necrosis factor) serum levels, and heart rate variability parameters. Statistical analysis was performed using general linear modeling (GLM, multivariate test), Wilcoxon W test, Mann–Whitney U test, Kruskal–Wallis H test, and Spearman rank correlation coefficient.

RESULTS: Patients with rheumatoid arthritis tolerated physical, intellectual, and communicative load satisfactorily (SI: 98.87, 91.07, and 95.01 arbitrary units, respectively). Patients with gout showed better tolerance of communicative load (SI = 116.46) compared with physical (SI = 139.36) and intellectual (SI = 171.61) loads. Patients with fibromyalgia tolerated prolonged complex load poorly, which caused overstrain of regulatory systems during physical (SI = 321.28), intellectual (SI = 400.95), and communicative (SI = 166.23) tasks. After complex load, a significant increase in serum interleukin4 levels was observed in men with rheumatoid arthritis (from 24.32 to 33.3 pg/mL; p = 0.023) and in men with gout (from 11.26 to 17.87 pg/mL; p = 0.007), as well as a decrease in interleukin10 levels in women with fibromyalgia (from 5.93 to 5.25 pg/mL; p = 0.035).

CONCLUSION: Differences were identified in the regulatory systems stress index during physical, intellectual, and communicative loads, as well as in the dynamics of hormonal and immunological serum parameters, in patients with rheumatoid arthritis, gout, and fibromyalgia.

BACKGROUND: Depressive disorders are the most common mental health conditions among patients on maintenance hemodialysis and may directly affect the outcomes.

AIM: To evaluate the effect of antihypertensive therapy on depression severity in patients with stage 5D chronic kidney disease.

METHODS: A threeyear cohort study was conducted in 377 patients on maintenance hemodialysis. The mean age was 55.3 ± 10.8 years, and the dialysis duration was 1–28 years (Me = 3; IQR: 2–6). Based on additional inclusion criteria (controlled hypertension, regular use of mono or twodrug antihypertensive therapy for >3 months), subgroups were formed according to drug class: calcium channel blockers (n = 25), reninangiotensinaldosterone system inhibitors (n = 21), beta-blockers (n = 20), calcium channel blockers with beta-blockers (n = 99), beta-blockers with renin-angiotensin-aldosterone system inhibitors (n = 34), calcium channel blockers with an imidazoline receptor agonist (n = 46), and calcium channel blockers with reninangiotensinaldosterone system inhibitors (n = 70). Patients completed the Beck Depression Inventory on their own. Depression levels were assessed according to outcomes. Statistical analysis included paired ttests, stepwise multivariable regression analysis, and Pearson chisquare test with Bonferroni correction. Differences were considered significant at p < 0.05.

RESULTS: Survivors showed a decrease in depressive symptoms over 3 years (p = 0.001), whereas patients who died showed progressive worsening (p = 0.019). In patients on calcium channel blockers, depression scores decreased (p = 0.001). With betablockers, the increase in depression scores was driven by the cognitiveaffective subscale. Regression analysis found no difference in the effect of antihypertensive monotherapy on depression severity. In the calcium channel blocker + betablocker group, depression improved (p = 0.001) due to a decrease in the somatic subscale (p = 0.001). With betablockers + reninangiotensinaldosterone system inhibitors, no significant changes were found. Regression analysis showed that use of a calcium channel blocker with an imidazoline receptor agonist or a reninangiotensinaldosterone system inhibitor was associated with more severe depressive symptoms (p = 0.001).

CONCLUSION: Calcium channel blocker monotherapy was associated with a reduction in depressive symptoms, while betablocker therapy was associated with an increase, mainly in the cognitiveaffective subscale.

BACKGROUND: The search for diagnostic markers reflecting muscle function, protein catabolism, and adipose tissue metabolism in sarcopenia is an important medical problem.

AIM: To assess the levels of asprosin (adipokine), meteorinlike protein (myokine), and proteinaseinhibitory activity in blood plasma, and their relationship with metabolic parameters and sarcopenia criteria in sarcopenic obesity and during the presarcopenic phase.

METHODS: The study included 50 participants (38 women, 12 men) aged 45–85 years. Of these, 11 had sarcopenia (reduced strength and mass), 16 had presarcopenia (reduced strength), and 23 served as controls (no strength or mass loss). We measured asprosin, meteorinlike protein, elastase and trypsinlike proteinase activity, and alpha1proteinase inhibitor in plasma.

RESULTS: In sarcopenic obesity, asprosin correlated positively with fat mass (r_s = 0.73, p = 0.012) and negatively with muscle strength (r_s = −0.81, p = 0.023). Asprosin was higher in sarcopenia without obesity than in sarcopenic obesity: 9.200 (8.500; 9.300) vs 7.100 (6.000; 7.900) ng/mL (p = 0.045). Meteorinlike protein exceeded the upper reference limit (179–1990 pg/mL) in 50% of controls (up to 2191–2871 pg/mL) and 25% of presarcopenic participants (up to 2275–4647 pg/mL). In sarcopenic obesity, meteorinlike protein correlated negatively with Cpeptide (r_s = −0.74, p = 0.005) and HOMAIR (r_s = −0.79, p = 0.011). In controls, meteorinlike protein was lower in hypertensive participants, while both meteorinlike protein and asprosin were lower in type 2 diabetes. Proteinaseinhibitor imbalance in presarcopenia included increased trypsinlike activity (1.5fold) and decreased elastaselike activity (23%). Trypsinlike activity correlated with SARCF score (r_s = 0.69, p = 0.02) and reduced performance. Higher alpha1proteinase inhibitor was associated with lower strength (r_s = −0.62, p = 0.03) and muscle mass (r_s = −0.63, p = 0.04) in controls, and with slower gait speed (r_s = −0.9, p = 0.02) in presarcopenic obese participants.

CONCLUSION: Adipomyokine dysfunction and plasma proteinaseinhibitor imbalance, combined with metabolic disturbances, may play a role in the development of sarcopenic obesity.

BACKGROUND: The increasing number of minimally invasive and open surgeries on upper abdominal organs highlights the importance of detailed study of the topographicanatomical features of the hepatopancreatobiliary area.

AIM: To identify key spatial landmarks indicating the origin of the human dorsal pancreatic artery.

METHODS: The study was based on computed tomography angiography of the abdominal cavity in 68 patients (29 men, 39 women). Data are presented as medians with the 25th and 75th percentiles. For each patient, the origin coefficient (K_о) was calculated. Statistical analysis included assessment of associations using the Kruskal–Wallis test; for post hoc pairwise comparisons, Dunn's test was used. The relationship between the distance from the center of the abdominal aorta to the pancreatic head and other variables was assessed using Spearman rank correlation coefficient. Differences were considered significant at p < 0.05.

RESULTS: A correlation was found between the origin coefficient (K_о) and the origin of the dorsal pancreatic artery (p < 0.0001). The most significant differences were observed when comparing origins from the splenic and common hepatic arteries, and from the common hepatic and superior mesenteric arteries. The significance levels according to Dunn’s test were 0.0004 and 0.0053, respectively.

CONCLUSION: The origin of the dorsal pancreatic artery is closely related to the position of the pancreas and the origin levels of the extraorgan arteries supplying it.

BACKGROUND: The development of new domestic oral anticoagulants is an urgent task. During a search for anticoagulant compounds among heterocyclic derivatives, a compound designated NAR0273b was identified, exhibiting antithrombin activity.

AIM: To study the mechanism of anticoagulant action of compound NAR0273b.

METHODS: The antithrombin activity of the 5,7di(thiophen2yl)4,5dihydro[1,2,4]triazolo[1,5a]pyrimidine derivative NAR0273b and the comparator drug dabigatran etexilate was evaluated using the Ecarin time assay in vitro on rabbit blood. The study included three groups: control, NAR0273b, and comparator, with five replicates per group. Experiments were performed on six male Chinchilla rabbits weighing 3–3.5 kg. The binding of NAR0273b to factor IIa was assessed using chromogenic substrate S2238 in vivo. The effect of NAR0273b on factor IIa levels was studied in male outbred white rats by enzymelinked immunosorbent assay. Experiments were performed on 35 animals weighing 250–270 g. The study included a control group, NAR0273b groups at 2.5, 5.5, and 11.0 mg/kg, and dabigatran etexilate groups at 3, 6, and 12.0 mg/kg, with five replicates per group. Statistical analysis was performed using GraphPad Prism 8.0 (GraphPad Software Inc., USA). EC₅₀ and ED₅₀ values were calculated by regression analysis.

RESULTS: In the Ecarin time assay, NAR0273b showed direct antithrombin activity comparable to dabigatran in terms of EC₅₀. In vivo, after intragastric administration, NAR0273b bound factor IIa on a chromogenic substrate and was comparable to dabigatran in ED₅₀. ELISA confirmed the ability of NAR0273b to bind thrombin: bound thrombin in controls was 187.2 ng/mL, whereas in the NAR0273b group (5.5 mg/kg) it reached 401.4 ng/mL, a 2.2fold increase over control. Thus, the ability of NAR0273b to block thrombin (factor IIa) was confirmed quantitatively by ELISA.

CONCLUSION: The anticoagulant mechanism of NAR0273b is associated with thrombin (factor IIa) blockade.

Melanoma is one of the most aggressive and therapy-resistant cancers, characterized by a high metastatic potential and a steadily increasing incidence. This review analyzes current approaches to cellular immunotherapy for melanoma, including tumor-infiltrating lymphocyte (TIL) therapy, TCR- and CAR-T-cell technologies, the use of NK cells, NKT cells, B cells, dendritic cells, macrophages, and immune checkpoint inhibitors.

TIL therapy and PD-1/PD-L1 and CTLA-4 immune checkpoint inhibitors have demonstrated the greatest clinical efficacy, improving overall and progressionfree survival in a subset of patients with advanced melanoma. TCR and CARTcell approaches have high potential due to their specific recognition of tumor antigens; however, their use is limited by toxicity, poor infiltration of solid tumors, and the difficulty of target selection. NK and NKTcell therapies have favorable safety profiles but require further optimization to increase antitumor activity and cell persistence in vivo. Bcell and dendriticcellbased vaccine strategies can induce antigenspecific immune responses and are considered promising adjuvant treatments. The development of CARmacrophages is a new direction in cellular therapy for solid tumors.

An analysis of clinical trial data shows that combination approaches that combine cellular therapy with immune checkpoint inhibitors or standard treatments are the most effective. Despite progress, the issues of toxicity, durability of the antitumor response, and overcoming the immunosuppressive tumor microenvironment remain unresolved, highlighting the need for further research in personalized immunotherapy for melanoma.

In recent years, the amount of scientific data indicating the key role of the gut microbiome in modulating immune responses that influence myocardial remodeling and the progression of chronic heart failure has been growing. Modulating the composition and function of the gut microbiome to reduce the severity of lowgrade inflammation and slow the progression of chronic heart failure appears to be an innovative approach.

This review aimed to analyze the role of the gut microbiome in cytokine-dependent inflammation in heart failure.

Fifty-two sources containing data on associations between cytokine levels and gut microbiome bacterial genera in patients with heart failure, published from 1999 to 2025 in journals indexed in PubMed and eLibrary.ru, were analyzed. The review includes a description of modern molecular methods for studying the gut microbiome, along with their advantages and disadvantages. Changes in the taxonomic and quantitative composition of the gut microbiome and in the cytokine profile of patients with heart failure are presented. The data presented in the analyzed publications demonstrate a link between specific bacterial taxa and cytokine levels in certain phenotypic groups of chronic heart failure; however, the mechanisms underlying these relationships often remain the subject of further research.

The identified limitations in the design of the reviewed studies, such as the presence of comorbidities, medication use, and unadjusted analyses that do not always account for confounding variables (diet and physical activity), underscore the need for further research to confirm these associations. Promising directions include research into diseasemodifying treatment for chronic heart failure, including the development of methods to modulate the microbiota in order to reduce cytokinemediated myocardial damage.

Over the past 40 years, the incidence of ischemic stroke in young adults (18–44 years) has tripled worldwide. Recent Russian and international studies on ischemic stroke in young patients demonstrate the significant role of genetic factors in embolism. Among the most common hereditary causes of thrombosis are thrombophilias, one of whose manifestations is hyperhomocysteinemia (9.5%). We present a clinical case of a 41yearold woman. Her history included smoking and alcohol abuse; she denied hereditary and chronic diseases and had never taken combined oral contraceptives. In 2021, at age 37, under severe stress (heavy workload) and a sharp rise in body temperature to 40 °C, she suffered an ischemic stroke. During hospitalization, hyperhomocysteinemia (326.0 µmol/L) was detected for the first time. With treatment, her condition stabilized with minimal neurological sequelae. She was discharged with recommendations for continuous antiplatelet, antihypertensive, and lipidlowering therapy, as well as B vitamins. She demonstrated poor compliance: she did not see a neurologist or hematologist and did not have her blood homocysteine level monitored for three years. In 2024, she stopped antiplatelet therapy on her own, leading to a recurrent ischemic stroke. After repeat hospitalization, her condition stabilized with minimal neurological sequelae, and her adherence improved. Young patients often demonstrate poor compliance to medical recommendations and followup, which underscores the need for an active monitoring system for this cohort. Recommendations for primary care physicians on managing such patients are provided.

This publication is the Russian translation of the Plain Language Summary (PLS) of the Cochrane Systematic Review: Gordon M, Sinopoulou V, Akobeng AK, Freeman SC, Moran GW, Cherayath R, Masitara M, Sherafat A, Khan MI, Alqusous F, Elleithy A, Phlananthachai S. Biologic drugs for induction and maintenance of remission in Crohn's disease: a network meta-analysis. Cochrane Database of Systematic Reviews. 2026, Issue 6. Art. No.: CD012751. DOI: 10.1002/14651858.CD012751.pub2.