CARDIOVASCULAR MEDICINE
Myocardial repolarization disturbances resulting in an increased value of dispersion of ventricular repolarization (DR) are associated with the development of life-threatening ventricular arrhythmias. The main tool for detection of repolarization disorders is electrocardiography (ECG).
This review is devoted to the new knowledge regarding the physiological and clinical significance of DR and its ECG-reflection.
The search for scientific literature was performed using e-LIBRARY, CyberLeninka and Pubmed data bases and the keywords (dispersion of repolarization, QT interval dispersion, Tpe interval, Tpe interval dispersion, Tpe/QT ratio) in different Russian and English spellings. The analysis of experimental, clinical and in silico studies demonstrated that the interval between the peak and the end of T-wave (Tpe) and its derivatives (relatively new ECG-indices, not yet widely used in clinical practice — Tpe interval dispersion and Tpe/QT ratio) provide information of both global and local dispersion of ventricular repolarization, being the proven useful predictors of life-threatening arrhythmias associated with the increased repolarization heterogeneity and the total mortality, while the dispersion of QT interval (the most “traditional” index of DR) is the least accurate measure of DR and arrhythmic risk. The threshold values of the considered ECG-indices of DR are given, and the age- and sex-dependence of them is discussed. The peculiarities of T-wave parameters measuring as well as the problems and the prospects of searching for the new arrhythmogenic ECG-indices are discussed.
Background. The course of arterial atherosclerosis, especially against the background of an increase in the biological age of a person, is associated not only with severe disorders of somatic, but also cognitive status. Conducting operations aimed at restoring blood circulation is associated with the progression of cognitive impairment or the appearance of postoperative cognitive dysfunction.
Objective. To determine the incidence and dynamics of cognitive impairment and anxiety in patients with arterial atherosclerosis in the perioperative period.
Design and methods. The study included 60 patients with arterial atherosclerosis admitted for planned surgical interventions to the cardiovascular surgery department. The main surgical interventions were carotid endarterectomy and reconstructive operations on the arteries of the aortofemoral-tibial segments. Depending on the initial cognitive status, the patients were divided into two groups: A — 38 patients with cognitive impairment and B — 22 patients without cognitive impairment. The primary neuropsychological examination was conducted 24 hours. Repeated diagnostics were performed by a neuropsychologist on the 5–7th day after the operation. General data of the patients, the structure of the primary and concomitant diagnoses, and the operations performed were studied. Neuropsychological diagnostics included the Montreal Cognitive Assessment Scale (MoCA), the Amsterdam Preoperative Anxiety and Information Scale (APAIS), and the Spielberger-Khanin test.
Results. Patients in Group A had signs of cognitive dysfunction, the average MoCA test score was 21.9 ± 3.4 points, versus 27.4 ± 1.2 points in Group B. Most patients in Group A were diagnosed with carotid artery atherosclerosis, arterial hypertension, and coronary heart disease. Multiple correlations were found, confirming the influence of factors on the cognitive status and anxiety level of patients.
Conclusion. The study found that 38 (63.3 %) patients were diagnosed with cognitive decline for the first time in the preoperative period. The main factors that lead to cognitive deficit are old age, carotid artery atherosclerosis, high comorbidity, social and work status.
Clonal Hematopoiesis of Indeterminate Potential (CHIP) is a widely studied age-related phenomenon associated with both hematological malignant neoplasms and an unfavorable prognosis of atherosclerotic cardiovascular diseases and chronic heart failure (HF), as well as related to other conditions in the pathogenesis of which low-grade systemic inflammation is involved.
This article outlines current knowledge about the CHIP. Results of a long-term clinical follow-up of two men with cardiometabolic risk factors, coronary artery disease (СAD), post-infarction cardiosclerosis and HF with mildly reduced ejection fraction, who carrying clonal hematopoiesis — driver mutations in DNMT3A gene with high clone sizes (VAF 15.4 % and VAF 8.7 %) are presented. CHIP- DNMT3A mutations in patients were detected at the ages of 47 and 65 years. Genetic testing was performed by next-generation sequencing using a targeted gene panel for CHIP. Over a 7-year period, despite having CHIP, these patients experienced a relatively favorable course of CAD and HF. However, they developed other non-cardiovascular conditions: bilateral coxarthrosis with total hip arthroplasty (in a younger patient) and gastric cancer.
The paper discusses methodological nuances of CHIP detection and unresolved clinical aspects regarding long-term patient management strategies. The authors consider a multidisciplinary approach to managing patients with CHIP appears optimal, potentially within the framework of specialized outpatient clinics as part of preventive personalized medicine.
HEMATOLOGY AND BLOOD TRANSFUSION
Hematopoietic stem cell transplantation (HSCT) is a modern method of treatment for oncohematological and other severe blood diseases. To prepare transplants, HSC mobilization is mainly used, followed by leukapheresis and assessment of CD34+ cells; the minimum required number for reliable repopulation is 2×106 CD34+ cells/kg, while an increase in the cellularity of the transplant >5×106 CD34+ cells/kg is associated with more positive clinical outcomes. The review presents the most relevant profile of surface markers for HSCs, describing the role of each marker in the proliferation and mobilization of CD34+ cells. The biological mechanisms of HSC retention and exit from the bone marrow niche, such as the CXCR4/SDF-1 (CXCL12) axis and interactions between VLA-4 and VCAM-1/fibronectin, have been analyzed. The review presents current approaches to pharmacological mobilization of HSCs, with a detailed discussion of the mechanisms involved. Classical agents, such as granulocyte colony-stimulating factor (G-CSF) and plerixafor, demonstrate effectiveness in most patients, but are associated with side effects and mobilization failures in ~10–15 % of donors. Promising drugs, including selective CXCR4 antagonists (motixafortide, balixafortide), CXCR2 agonists (MGTA-145), and approaches targeting the microenvironment of HSCs, such as inhibition of heparan sulfate synthesis, activation of the neurogenic axis through capsaicin-stimulated nociceptive neurons, and MMP-mediated matrix remodeling are discussed. The review analyzes the advantages (rapid and productive mobilization, potentially more functional transplants) and limitations (safety, translation of preclinical data, and requirement of clinical validation). The review addresses the potential of using the latest drugs and alternative targets in practice. Also emphasized the need for comparative clinical studies, development of biomarkers, and personalized mobilization algorithms to optimize the outcomes of HSC transplantation.
MEDICINAL CHEMISTRY
Background. Liposome size and polydispersity index are key factors determining the subsequent use of nanoparticles. Traditional synthesis methods do not allow the creation of liposomes of the required size and homogeneity; therefore, post-processing is performed using ultrasound or extrusion.
Objective. To compare two methods of liposome post-processing: ultrasound and extrusion. To compare the efficiency of two different extruders: Liposofast LF-50 and a proprietary extruder. To compare the efficiency of three membranes made of different materials: polycarbonate, polyethersulfone, and porous anodic alumina, using the extrusion post-processing method.
Materials and Methods. Commercially available reagents were used for liposome synthesis: phospholipids, cholesterol, and vitamin E (all from Sigma Aldrich, Germany). The physicochemical properties of liposomes were studied using a Zetasizer Ultra (Malvern Instruments, UK). Ultrasonic post-processing was performed using a UZG13-0.1/22 disperser (Russia), extrusion processing was carried out using one of two extruders: Liposofast LF-50 (Avestin, Canada) and an extruder of our own design (Nanotechnologies). The following membranes were used: polycarbonate (PC) 200 nm (Nuclepore, Whatman), polyethersulfone (PES) 200 nm (FMPES-0.20, Vladisart), and experimental membrane samples based on porous anodic aluminum oxide (PAO). To determine differences in membrane morphology, they were examined using a Quanta Inspect scanning electron microscope (FEI, USA).
Results. PC-based membranes are the most uniform, while PES is the least uniform. All membranes have a declared pore diameter of 200 nm, but only for PAOA is this parameter close to the actual value. PAOA membranes have the highest porosity, while polycarbonate membranes have the lowest. Differentpressures are required for the liposomal colloidal solution to pass through the membranes: 1.5–2 atm is sufficient for PES membranes, 5 atm for PC membranes, and 4–6 atm for PAOA membranes, which significantly affects the extrusion rate.
Conclusion. A comparison of existing liposome homogenization methods demonstrated the advantage of extrusion. The extruder developed by the authors is comparable to a commercial version. The effectiveness of PAOA membranes compared to commercial analogues is demonstrated.
NEUROLOGY
Schwannomas are the most common benign tumors of peripheral nerves and spinal nerve roots. Sectoral schwannomatosis, in turn, is a rare condition (0.58 cases per 1 million people) characterized by multiple tumors affecting a single nerve trunk, with no pathological lesions in other anatomical areas. Unlike systemic forms of neurofibromatosis, sectoral schwannomatosis typically lacks cutaneous manifestations and bilateral vestibular nerve involvement, making diagnosis particularly challenging. Over the past decade, only a few cases of sectoral schwannomatosis involving the sciatic nerve have been reported in the literature. Herein, we present a rare clinical case of a female patient with sectoral schwannomatosis of the sciatic nerve and its branches requiring surgical intervention. Neuroimaging (MRI and ultrasound) revealed multiple mass lesions extending along the sciatic nerve in the distal third of the thigh, as well as along the tibial nerve in the proximal third of the lower leg and the popliteal region. The total length of the involved nerve segment reached up to 20 cm, with tumors exhibiting heterogeneous structure and pronounced vascularization on Doppler imaging. The clinical presentation featured intractable neuropathic pain. No tumors were found in other nerves. The patient underwent surgical removal of five tumor nodules using direct nerve stimulation (intraoperative neuromonitoring), which allowed for clear differentiation between functionally significant nerve fascicles and tumor tissue, thereby preventing their damage. Postoperatively, nerve function was fully preserved, and pain regressed to 1 point on the visual analogue scale within the first five days. A review of the relevant literature is also provided. Given the rarity of this pathology, accumulation of clinical experience is essential; therefore, each identified case of sectoral schwannomatosis warrants a detailed description.
COMPUTER MODELING AND EPIDEMIOLOGY
A brief-n-clear synopsis of major trends in infrastructure development along with the expert groups activities within Shanghai Cooperation Organization (SCO), 2020–2025, has been presented and discussed following by an accent on both support and control over the national public health programs and, respectively, the translational medicine related innovation projects. An additional emphasize is made on attention expressed by the SCO expert community towards the arsenal of the In Silico mathematical models taking into account their role as the tools sustainable for optimization of the new drugs preclinical trial algorithms. Thus, announced for 2025–2030 ongoing SCO reform promotes an essential possibilities spread-out for its community of experts as this deals with both financial support and scientific expertise performance in case of the international research projects proposed by scientists from member-countries working in such areas as pharmacology/pharmacy and healthcare administration. Taking this into account, a scheme of interactions between the SCO Committees, Commissions and Expert Councils is under discussion, while a special attention to juridical and financial aspects was paid. As per peculiarities of planning and conduction of these SCO activities, this issue was studied within a context of comparison to analogical potential revealing in preclinical and clinical trials on new medicines carried out according to ACS (American Chemical Society) adopted protocols. Giving an example of achievements and perspectives of the SCO criteria fitting innovation projects: the results of preclinical studies (experimental and In Silico tracks) on PMC16-nanocationites designed for tumor cells targeting with a following release of paramagnetic isotopes (25Mg, 43Ca, 67Zn) which promotes the corresponding magnetic isotope effects (MIE) and, hence, the MIE-induced cytostatic (anti-tumor) consequences. In conclusion, a data supported prove makes a lot of sense in attentive studies on both SCO experience and the current trends of its applications to pharmacological research including the use of the SCO-developed programs in mathematical modeling in medicine and, in particular, in upgrade of In Silico models.
Experimental studies
Background. Enzyme-linked immunosorbent assay (ELISA) is widely used in the study of pharmacological safety, pharmacokinetics, pharmacodynamics of both original and reproduced (biosimilar) drugs; it is the method of choice for the evaluation of various biomarkers in clinical and preclinical studies. A feature limiting the use of this method is its species specificity.
Objective. The article discusses the use and adaptation of ELISA sets specific for humans for the analysis of biomaterial from laboratory animals.
Design and methods. The materials of several studies performed in the organization using rats as one of the most common test systems in preclinical studies, and including the use of ELISA kits for the determination of steroid hormones in the blood (testosterone, estradiol), stress hormones (cortisol, corticosterone) and cardiac biomarkers (myoglobin, troponin).
Results. Examples of using reagent kits without any changes are shown (cortisol), after various optimization options (corticosterone, testosterone, estradiol). On the myoglobin cardiomarker example an algorithm for biomaterial type choosing is presented, which allows expanding the initial field of reagent kit use and unifying the biomaterial selection in an experimental study, and troponin I turned out to be an example of the unsuitability of the kit for analyzing rat biomaterial.
Conclusion. Based on experimental experience, an algorithm and decision-making scheme for approbation and adaptation of ELISA reagent kits specific for humans in the analysis of laboratory animal biomaterial are formulated.
ISSN 2410-5155 (Online)




















