CLINICAL AND EXPERIMENTAL MEDICINE
An important place in the pathogenesis of systemic lupus erythematosus (SLE) is given to the immune mechanisms, many aspects of which, despite intensive study, remain unclear. As a result of the activation of T and B cells, the production of antibodies (including autoantibodies) increases, hypergammaglobulinemia occurs, and immune complexes are formed. The use of mesenchymal stem cells (MSCs) as the basis of a biomedical cell product for SLE cell therapy is justified due to the fact that this type of stem cells has a wide immunomodulatory activity range. In recent years, more and more data have appeared that the pooled cultures of allogeneic MSCs have more pronounced and stable immunomodulatory properties in relation to immunocompetent cells, in comparison with allogeneic MSCs obtained from a single donor.
The aim of the study was to develop a biomedical cell product based on pooled cultures of MSCs to increase the effectiveness of the existing methods of treating SLE.
The object of the study was the venous blood of SLE patients with clinical and laboratory lupus nephritis signs included in the trials (n = 6). Blood sampling and analysis were carried out before cell therapy and 1-1.5 months after. Immunophenotyping of blood cells was performed using flow cytometry.
The immunological efficacy of SLE cell therapy, which was expressed in a decrease of the number of immunocompetent cells associated with the inflammation process in the peripheral blood (decrease in the content of cytotoxic lymphocytes, activated and terminally differentiated TEMRA T cells, decrease in the number of antibody-producing plasma cells) with the use of poolMSC was shown. Clinical efficacy consisted in stopping the progression and reducing the SLE activity (doubling the SELENA-SLEDAI index from 10.43 to 5.14), as well as in achieving the complete LN remission (n = 4) and restoring the normal kidney function.
The aim of the study is to develop a method for predicting the complicated course of the early neonatal period in the large newborns for gestational age in order to optimize and increase the efficiency of medical care for this category of children.
A survey of 157 large newborns large for gestational age was carried out. The study group consisted of 105 large newborns for gestational age. The control of the correct operation of the regression model was carried out on an examination sample of children with large birth weight (n = 52). The control group consisted of 221 newborns with the physical development corresponding to the gestational age (appropriate for the gestational age). The anamnestic, clinical, laboratory, instrumental, morphological data were analyzed with a subsequent determination of the most significant factors associated with early adaptation disorders in newborns. The predicted event was considered to be a complicated course of the early neonatal period, which was determined by the presence of one or more diseases in a newborn.
Based on the multivariate regression analysis, it was found that the most significant prognostic factors associated with the disadaptation risk of large newborns were the pregravid maternal body weight of more than 70 kg, the delivery mode, the harmonicity coefficient (ponderal index) at a birth of 26.5 kg/m3 or more, the neutrophils level in the complete blood count on the 1-2 days of life. A mathematical model was developed for determining the probability of a complicated course of the early neonatal period in the large newborns large for gestational age. The threshold value was calculated and a classification scheme was created, allowing one to calculate the infant's belonging to the risk group of the complicated course of the early neonatal period based on the calculation of points for timely correction. It is shown that the developed multivariate mathematical model and the classification scheme based on it work steadily on the examination sample and can be used in practice in health care organizations at all levels of perinatal care.
The study topicality was conditioned by a need to find potential predictors of gastric cancer (GC) clinical progression in view of a high probability of long-term gastric cancer development in the post-surgery period.
The study was conducted during 2008-2018 and involved 345 radically operated gastric cancer patients (pT4a-bN0-3M0, types III-IV according to the R. Bormann classification). Out of this cohort, 68 patients underwent intraoperative hyperthermic chemoperfusion (cisplatin 50 mg/m2, doxorubicin 50 mg/m2, 1 hour, 42 °C). Long-term treatment results (progression-free survival (PFS)) were assessed by means of the Kaplan-Meier estimator method and the Cox multivariate analysis.
The unfavorable factors resulting in the GC progression included the metastatic damage of the regional lymph node (pN1-2 - RR 1.7 (95 % CI 1.2-2.5), pCox = 0.003; pN1-2 - RR 3.6 (95 % CI 2.5-5.1), pCox < 0.001), the extent of the tumor process requiring either a standard or combined gastrectomy or a combined distal stomach resection in comparison with a standard subtotal stomach resection (RR 1.4 (95 % CI 1.1-1.8), pCox = 0.017), and the situations where the patient treatment volume was limited to only radical surgery (RR 1.6 (95 % CI 1.1-2.2), pCox = 0.012). Based on the results of the Cox regression analysis, the nomogram was developed to predict PFS using the evaluation of the pN category and the volume of administered therapeutic procedures (surgical intervention extent and administration or non-administration of hyperthermic chemoperfusion). The nomogram demonstrated a highly predictive performance scoring a concordance index of 0.67.
The proposed nomogram provides a fairly high accuracy of predicting PFS in the infiltrative GC patients (pT4a-bN0-3M0) proceeding from the tumor morphology evaluation and the radical treatment extent.
Remote postconditioning (RPost) has a great therapeutic potential for protecting the myocardium during ischemiareperfusion in clinical practice. At the same time, an important problem limiting the use of conditioning effects in the clinic is the presence of metabolic disorders in the patient. The aim of this work was to assess the effect of induced metabolic syndrome (iMetS) on the efficacy of the infarct-limiting effect of remote ischemic postconditioning (RPost) in rats and to study the mechanisms of this effect.
The study was carried out on Wistar rats. MetS was induced by high-carbohydrate high-fat diet. Criteria of metabolic syndrome were an increase in the weight of animals, abdominal fat volume, the development of arterial hypertension, hypercholesterolemia, an increase in triglycerides in serum, hyperleptinemia, hyperglycemia, the development of a state of insulin resistance by a significant increase in the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index and glucose tolerance. All animals were subjected to 45 min coronary occlusion and 120 min reperfusion.
RPost led to a twofold reduction of infarct size in rats with intact metabolism (р < 0.0001), while in rats with iMetS a decrease in infarct size during RPost was 25 % (p = 0.00003), which was significantly lower than in animals without iMetC (р < 0.0001). A direct correlation was found between of infarct size during RPost and the serum leptin level of rats with iMetC.
The presented data suggested that a decrease in the efficiency of remote postconditioning in rats with diet-induced metabolic syndrome depends on leptin content in blood.
Classical homocystinuria is caused by a genetic mutation in the CBS gene, which leads to low levels or absence of an enzyme called cystathionine beta-synthase.
The purpose of the study was to analyze the clinical features and molecular and genetic data of patients with classical homocystinuria in Belarus.
The study group included patients with classical homocystinuria and their healthy siblings (3 probands and 2 siblings) from three unrelated families. Diagnosis of homocystinuria was made on a quantitative determination of the total homocysteine level in plasma. The next-generation sequencing was performed for the molecular genetic analysis of the CBS gene. The presence of the identified variants in probands and their siblings was confirmed by the Sanger sequencing.
All probands had specific clinical signs of classic homocystinuria: ectopia lentis, skeletal pathology, intellectual, psychiatric, behavioural problems and seizures (in 2 of 3 probands).
Homozygous missense-mutations c.430G>C (p.Glu144Gln, rs121964966), c.473C>T p.(Ala158Val, rs1376851289) and 1064C>T p.(Ala355Val, rs772384826) were identified in proband 1, 2 and 3 respectively. Healthy siblings of probands 1 and 3 were the heterozygous carriers of the corresponding mutations.
Classical homocystinuria is a very rare disease in the Republic of Belarus. All cases of the disease in Belarus are caused by very rare mutations not registered in the neighboring countries and are the result of marriages between the relatives or the natives of the same area. We have described for the first time the phenotypic manifestations of the p.Glu144Gln and p.Ala355Val mutations, expanded the description of the spectrum of clinical manifestations of the Ala158Val substitution, and assessed the clinical significance of the identified variants in accordance with the modern criteria.
The changes in the expression of the lipogenic Fasn and Sirt4 genes and the Fasn and Sirt4 proteins they encode in the visceral adipose tissue of Wistar rats against the background of excess fat intake were studied.
In addition to the standard vivarium diet, the rats received the animal fats (45 % of daily caloric value) for 8 weeks. A relative gene expression was determined by real-time PCR, protein content in the visceral adipose tissue - by the ELISA method.
It was found that the excess animal fat intake leads to a decreased expression of lipogenic Fasn and Sirt4 genes and the proteins they encode in the visceral adipose tissue of Wistar rats, which indicates the formation of the adipose tissue dysfunction, which may result in the impared lipid and carbohydrate metabolism, the insulin resistance development.
The purpose of this study was to determine the value of apparent diffusion coefficient (ADC) in various morphological variants of lymphomas, to study dependence of ADC on the anatomical location of lesions and technical scanning parameters to establish the usefulness in differentiating normal and involved lymph nodes (LN).
Whole body MRI with diffusion-weighted imaging (DWI) was performed in 209 patients with lymphoma before treatment. A target LN was selected and ADC determined in each patient.
The ADC value does not depend on the use of the parallel imaging technique (p = 0.56), higher when using built-in compared to superficial coil (p < 0.0001), higher when using respiratory triggering than free breathing (p < 0.02). The highest ADC values (х10-3 mm2/s) were obtained in the involved LN of the lung hilar (1.429 ± 0.396) and mediastinum (1.338 ± 0.313), lower values (p < 0.01) - in the LN of the abdomen (1.011 ± 0.298), axillary (0.840 ± 0.196), neck (0.834 ± 0.259), inguinal (0.753 ± 0.128) and iliac (0.738 ± 0.129). Depending on the morphological variant of lymphoma, the highest ADC value was obtained in Hodgkin lymphoma - 1.168 ± 0.372 (p < 0.0002). ADC in diffuse large B-cell non-Hodgkin lymphoma was 0.951 ± 0.320, indolent non-Hodgkin lymphomas - 0.756 ± 0.246, mantle zone non-Hodgkin lymphoma - 0.759 ± 0.211.
In conclusion, DWI in lymphoma should be performed using surface coil, parallel imaging, and free breathing. Statistically significant differences in ADC were found depending on the anatomical location of the lesions and the morphological variant of lymphoma. Given the dependence of ADC on various technical and clinical factors, it is not possible to establish a single threshold value for differentiating involved and normal LN. The use of the LN size criterion for this purpose is the most optimal in lymphoma.
One of the main complications of congenital pneumonia in premature newborns, leading to high mortality, is the development of hemorrhagic syndrome. Objective - to determine the prognostic significance of blood clotting indicators and the probability of developing hemorrhagic syndrome in premature newborns with congenital pneumonia.
The assessment of hemostasis indicators in 221 premature newborns who were treated and cared for in the State Institution RSPC “Mother and Child” in the period from 2017 to 2019 was carried out. A comparative analysis of the parameters of the coagulogram of the first day of life was performed with the allocation of the percentile range and the translation of absolute values into binary variables is made. Based on the results of the ROC analysis, a mathematical model was developed with a universal coefficient equal to χ2 = 24.19, p = 0.004, with a sensitivity of 92.9 % and an area under the ROC-curve AUC = 0.69 ± 0.039 (0.62-0.76), p < 0.001, and a computer support program for doctors. The prognostic significance of blood clotting parameters was calculated: activated partial thromboplastin time - 0.366, coefficient R - 0.208, prothrombin time - 0.321, prothrombin index according to Quick - 0.330, international normalized ratio - 0.242, thrombin time - 0.319, fibrinogen -0.295, D-dimer - 0.448, platelets - 0.478, which makes it possible to allocate premature newborns with congenital pneumonia with a threshold value of ≥0.293 to the risk group for the development of hemorrhagic syndrome.
Only 60-70 % patients with stage I and 35-40 % with stage II of non-small cell lung cancer (NSCLC) overcome the 5-year survival. The reason for such a high mortality rate is almost always a disease recurrence due to the presence of hidden metastases. This indicates a different course of the disease within one stage. There is a need to develop indicators that would allow predicting the tumor progression in patients at the early tumor development stages in order to correctly build the strategy and tactics of their treatment.
The objective of the study is to find and substantiate the possibility of using the laboratory parameters characterizing the level of blood proteins involved in carcinogenesis when predicting the NSCLC progression in patients with early disease stages.
In 1250 patients (839 men and 411 women) who were first diagnosed with NSCLC in the early stages (I and II), the duration of the recurrence-free period after treatment was analyzed according to the one-year observation results. In 103 patients (56 ± 22.5 years), the level of CYFRA 21-1, SCC, TPA, M2 of pyruvate kinase, chemokines CXCL5, CXCL8 and the concentration of HIF1a and hyaluronic acid in blood serum were determined by the enzyme immunoassay and that of the receptors CXCR1, CXCR2, CD44v6 in blood granulocytes, lymphocytes and monocytes - by flow cytometry. 62 persons had stage I (G1 - 20, G2 - 23, G3 - 19) and 41 - stage II (G1 - 14, G2 - 15 and G3 - 12).
Based on the results of the one-year observation and the graphic analysis of Kaplan-Meier, the groups of low (stage I, G1-2 + stage II, G1) and high (stage I, G3 + stage II, G2-3) risk of tumor progression were identified. In high-risk patients, compared with low-risk patients, the level of CYFRA 21-1, the fluorescence intensity of the receptor CXCR1 in granulocytes, the relative content of the receptor CXCR2 in lymphocytes and the receptor CD44v6 in monocytes were higher (p < 0.05). With their participation, according to the results of logistic regression analysis, an equation was constructed, the calculation of which allows predicting the risk of tumor recurrence. The threshold for the equation is 0.467. The sensitivity of the forecasting model is 84.8 %, the specificity is 84.2 %, the predictive values of positive and negative results are 81.2 and 87.3 % respectively.
The study results showed that a set of laboratory parameters, including blood CYFRA 21-1 level in combination with CXCR1, CXCR2, CD44v6 can be used in patients with early stages of NSCLC to assess the risk of tumor progression.
The article discusses the evaluation of the effectiveness of the influence of thermal vibration effects on the bending strength and surface hardness of composite filling materials.
The study was conducted on the basis of the Department of Therapeutic Dentistry of the Kuban State Medical University, as well as at the Krasnodar Instrument Plant “Cascade”. The samples under study were made according to the group affiliation from three different composite materials: Estelite Sigma Quick, Filtek Bulk Fill Posterior Restorative and DentLight. The bending strength was evaluated on the “MIP-10” testing machine of the company “NPK TECHMASH”. Determination of the surface hardness according to Vickers was carried out on the device PMT-3 of the company “LOMO”.
According to laboratory studies, a statistically significant increase in flexural strength and surface hardness according to Vickers was determined for all samples of composite materials subjected to thermal vibration before polymerization.
The data obtained indicate an increase in the strength characteristics of composite filling materials as a result of thermal vibration exposure before their polymerization, which increases the service life of composite fillings and reduces the risks of secondary caries formation after filling.
Coronavirus infection is a clinical syndrome caused by a mutational RNA virus (SARS-CoV-2). In severe cases, it is characterized by the development of a “cytokine storm”. The latter leads to the multiple organ dysfunction, ARDS and causes high mortality. To suppress the cytokine aggression in patients with severe COVID-19, the drug suppression is recommended; however, the use of hemosorption can be pathogenetically justified as an alternative method.
The aim of the study was to assess the effectiveness of hemosorption using the hemosorbent “Hemo-Proteazosorb” in the severe COVID-19 infection course in comparison to the drug suppression with tocilizumab.
We studied the clinical and laboratory parameters of 88 patients who were treated at the anesthesiology and intensive care department. All patients were divided into 2 groups: Hemo-Proteazosorb (n = 53) and Tocilizumab (n = 33).4
Against the background of hemosorption using the Hemo-Proteazosorb sorbent, statistically the level of procalcitonin, C-reactive protein, leukocytes, fibrinogen, D-dimers significantly decreases, the number of lymphocytes increases, as well as the respiratory index earlier grows in comparison with the group receiving tocilizumab therapy. The study found that the use of hemosorption through the domestic sorbent “Hemo-Proteazosorb” has a number of advantages over the drug suppression of the “cytokine storm” with tocilizumab due to the more pronounced effects of immunomodulation, improvement of the oxygen transport function of blood, its rheological properties and the possibility of effective use in persons with viral bacterial infection.
The lesion of the lower extremities vessels is one of the most dangerous complications of diabetes mellitus. The prognosis is bad in case of the development of critical ischemia.
The aim of the study is to assess the effect of autological red bone marrow aspirates on the microcirculation in the soft tissues of the lower extremities of patients with diabetic angiopathy.
The study included 36 patients with diabetic angiopathy of the lower limbs. The main group of 20 people consisted of the patients, whose treatment was added by revascularizing automyelotransplantation. The comparison group (16 people) included the patients who received standard complex conservative treatment.
All patients underwent pulse oximetry on the 1st toe before the treatment start and within the control times. The painless walking distance was also assessed and the chronic arterial insufficiency stage was determined.
In the main group, 18 patients retained their lower limbs, in the comparison group - 10 patients (pCox-Mantel = 0.015).
There was an increase in the painless walking distance in 15 out of 18 patients in 3-6 months after treatment in the main group. There was no improvement in the comparison group. Chronic wounds healed in 4 out of 7 patients.
The median SpO2 in the main group was 96 [92; 97] %, in the comparison group - 90 [88; 92] % (pMann_Whitney = 0.0035).
The inclusion of revascularizing automyelotransplantation in the complex treatment of patients with diabetic angiopathy of the lower extremities contributes to the lower extremity preservation, as well as the relief of critical ischemia signs and the healing of chronic wounds.
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