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Two new species of Agaricales, Deconica flavum and Entocybe roseoalbus, are described from Mount Tianmu, Zhejiang Province, Eastern China. Two new species are distinct and monophyletic based on morphology and phylogenetic analyses. Deconica flavum differs from other Deconica species in that the pileus is brow shallow in the center and stipe with yellowish white fibrils, scatted on litter under coniferous and broad-leaved mixed forest at 1162 m. Entocybe roseoalbus is distinguished from other species of Entocybe by nearly blue pileus and pinkish-white stipe, scatted on humus in similar forest conditions at 1025 m. The differences are discussed between the two new taxa and their similar species morphologically, and related species phylogenetically.

Upper Permian Longtan Formation transitional shale has become an important exploration layer, but the Longtan Formation shale (LFS) has a complex mineralogical composition, which affects the subsequent diagenesis and diagenetic evolution, and restricts the subsequent geologic exploration of shale gas. In this article, the observation of drilling cores, argon ion polishing-scanning electron microscope, Vitrinite reflectance, and X-ray diffractometer were used to analyze the type and characteristics of diagenesis of the LFS and clarify the stage of diagenetic evolution. The results show that the main diagenesis in the LFS is compaction, cementation, thermal maturation of organic matter (OM), dissolution, and transform of clay minerals. Among them, OM hydrocarbon generation, clay mineral transformation, and dissolution are pore-enhancing diagenetic events. Compaction and cementation are pore-reducing diagenetic events. The transitional and marine shales have similar characteristics of diagenesis, but there are big variations in the diagenesis of OM hydrocarbon, authigenic quartz, and siderite. The complex depositional environments of the marine-continental transition environment have resulted in a variety of rock types, which in turn influenced the diagenesis types and diagenetic evolution process. Compared with the transitional shales of the Shanxi and Taiyuan formations in the South China North Basin, the LFS are characterized by high clay content, low quartz content, complex mineral compositions, and a higher degree of thermal evolution.

Aim – to analyze the current literature on the role of single nucleotide polymorphism (SNP) of human genes in shaping the clinical course of the new coronavirus disease (COVID-19). Results. Based on the results of the analysis and synthesis of the current literature on the role of SNP in shaping the clinical course and outcome of COVID-19, the clinical and prognostic significance of SNP of genes encoding receptors responsible for the penetration of SARS-CoV-2 into target cells has been demonstrated. The presence of the D-allele of the ACE gene (DD and ID genotypes) is associated with the highest risk of severe COVID-19, which makes it possible to offer it as an informative prognostic marker of COVID-19 severity. SNP of the TMPRSS2 co-receptor gene, known as the androgen responsive gene, at certain loci is prognostically important, as it leads to an increase in TMPRSS2 expression in men, which promotes virus fusion with the target cell membrane and has an unfavorable effect on the course of COVID-19 in men. The data accumulated in the current literature on the clinical and prognostic value of SNP host genes encoding the immune response has also been analyzed. The role of HLA SNP genes, genes encoding innate immunity factors (TLR), as well as genes encoding pro-inflammatory cytokines (IL-6, TNF-α, etc.) and acute-phase inflammatory components (CRP) in the development of severe COVID-19 and the risk of death has been demonstrated. Attention has been paid to the determined role of SNP in the ACE gene in the development of pulmonary embolism in patients with severe COVID-19. The article has analyzed publications on the SNP role of host genes in the development of clinical events that are currently interpreted as long COVID. The prognostic role of the IL-10 gene SNP and its receptor gene in the formation of long-term consequences of the new coronavirus infection has been demonstrated. Conclusions. SNP of host genes encoding receptors responsible for the entry of SARS-CoV-2 into target cells and SNP of genes encoding immune response have some prognostic value in assessing the risk of severe course and adverse effects of COVID-19. The accumulation of data on genetic risk factors for adverse outcomes of the new coronavirus disease will allow us to enhance the understanding of this infection pathogenesis, improve patient stratification and individualize therapeutic interventions.

Abstract Objective As the global use of extracorporeal membrane oxygenation (ECMO) treatment increases, survival rates have not correspondingly improved, emphasizing the need for refined patient selection to optimize resource allocation. Currently, prognostic markers at the molecular level are limited. Methods Thirty-four cardiogenic shock (CS) patients were prospectively enrolled, and peripheral blood mononuclear cells (PBMCs) were collected at the initiation of ECMO (t0), two-hour post-installation (t2), and upon removal of ECMO (tr). The PBMCs were analyzed by comprehensive epigenomic assays. Using the Wilcoxon signed-rank test and least absolute shrinkage and selection operator (LASSO) regression, 485,577 DNA methylation features were analyzed and selected from the t0 and tr datasets. A random forest classifier was developed using the t0 dataset and evaluated on the t2 dataset. Two models based on DNA methylation features were constructed and assessed using receiver operating characteristic (ROC) curves and Kaplan–Meier survival analyses. Results The ten-feature and four-feature models for predicting in-hospital mortality attained area under the curve (AUC) values of 0.78 and 0.72, respectively, with LASSO alpha values of 0.2 and 0.25. In contrast, clinical evaluation systems, including ICU scoring systems and the survival after venoarterial ECMO (SAVE) score, did not achieve statistical significance. Moreover, our models showed significant associations with in-hospital survival (p

INTRODUCTION. Methotrexate (MTX) is the main disease-modifying antirheumatic drug (DMARD) and the gold standard for the safety and efficacy evaluation of biologicals and targeted small molecules. However, its narrow therapeutic range, interpatient variability in pharmacokinetics and pharmacodynamics, and potential clinically relevant drug–drug interactions (DDIs) may lead to treatment failure and increase the risk of adverse drug reactions (ADRs).AIM. The study aimed to describe the main clinically significant DDIs associated with MTX used in rheumatic disease therapy and determine possible approaches to addressing this issue based on a literature review.DISCUSSION. MTX is characterised by pharmacokinetic DDIs during absorption, cell penetration, and elimination. Some non-steroidal anti-inflammatory drugs (NSAIDs), theophylline, sulfasalazine, antibacterial agents, and proton pump inhibitors (PPIs) affect MTX elimination and therapeutic effects. The main ADRs associated with MTX include haematotoxicity, hepatotoxicity, lung tissue damage (interstitial pneumonitis and pulmonary fibrosis), and renal dysfunction. The severity of these ADRs depends on the dose, comorbidities, and concomitant therapy. The toxicity of MTX may be increased by the concomitant administration of medicinal products that exhibit haematotoxicity and affect renal function (impair the elimination of medicines). When co-administering MTX and medicines having clinically significant DDIs described in the literature, healthcare providers should consider the risk factors for each individual patient. The most significant risk factors include moderate to severe renal and hepatic impairment, older age, polypharmacy, and hypoalbuminemia.CONCLUSIONS. This article describes potential clinically significant interactions between MTX and certain NSAIDs, antibacterial agents, and PPIs that depend on individual patient characteristics and may increase the toxicity or decrease the effectiveness of MTX. MTX deprescribing, short-term withdrawal, and dosing optimisation may be considered as approaches to DDI risk mitigation.

Purpose of the study. Is to determine the features in the content and activity of some components of the plasminogen activation system in the blood of patients of different ages with leiomyomas (LM) and uterine corpus endometrial cancer (UCEC).Patients and methods. The study was carried out in patients with LM (n = 35) and UCEC T1a-2N0M0 (n = 56) of reproductive, perimenopausal and postmenopausal ages. Using ELISA methods, the content and activity of urokinase (u-PA), tissue plasminogen activator (t-PA), their inhibitor PAI-1, as well as the content of the soluble form of the u-PA receptor (su-PAR) were determined in the blood of patients. The Student´s test was used for statistical processing.Results. Regardless of the nature of the uterus tumor, it has been noted a significant increase in the activity and blood level of PAI-1 (up to 8 times, p < 0.01), especially pronounced in patients with UCEC of reproductive age. It was combined with the absence of changes or with a decreasing in blood level of su-PAR by more than 40 % (p < 0.05). We observed a rise of u-PA blood level without changes in one´s activity in patients with LM of perimenopausal age. And in patients with LM and UCEC of postmenopausal age an increase in u-PA blood level as well as elevation of u-PA activity (up to 3.9 times, p < 0.01–0.05) were noted. There was an increase in the calculated t-PA index (activity per unit mass) by 1.4–2.8 times (p < 0.05) in the most patients. The indicators of LM patients were characterized by the minimum value of the ratio “t-PA activity/u-PA activity in the blood” among all studied subgroups of patients. Age-related features of the researched parameters were observed more often in the cases of LM than in the cases of UCEC. The most pronounced differences between LM and UCEC were observed in patients of reproductive and postmenopausal age, characterized by stable hormonal levels.Conclusion. The participation of the plasminogen activation system in the pathogenesis of tumor lesions of the uterine body has been shown. The system’s “response” to the development of tumors in the uterus has both general characteristics and features that depend on the nature of the tumors and on the age-specific hormonal regulation of the body, which are most pronounced in postmenopausal women. The results obtained can be used in research aimed at clarifying the targets of targeted therapy for LM and UCEC in accordance with the age of patients.

Objective: to assess the incidence of newly diagnosed subclinical and manifest hypothyroidism in patients with ST-segment elevation myocardial infarction (STEMI) and to identify angiographic features of coronary artery lesions in this combined pathology.Materials and methods: in all patients with STEMI, the level of thyroid-stimulating hormone (TSH) was determined, and thyroid function was assessed if the TSH level deviated from the norm. Stage I of the study included 441 patients, stage II included 133 patients with STEMI. Depending on the presence of newly diagnosed hypothyroidism, patients were divided into 3 groups: 1st — patients without hypothyroidism (n = 57), 2A group — with subclinical hypothyroidism (n = 42) and 2B group — with manifest hypothyroidism (n = 34). All patients underwent coronary angiography and percutaneous coronary intervention.Results: newly diagnosed hypothyroidism occurred in 27.44% of patients with STEMI: subclinical — in 19.73%, manifest — in 7.7% of cases. Patients with concomitant overt hypothyroidism had significantly more severe atherosclerotic lesions of the coronary arteries compared to patients without hypothyroidism.Conclusion: a high incidence of newly diagnosed hypothyroidism in patients with STEMI was established (27.44% of cases). Multivessel coronary lesions were recorded more often in patients with overt hypothyroidism than in patients with subclinical hypothyroidism and without hypothyroidism.

Introduction. Infertility affects tens of millions of men and women across the globe. In approximately half of cases, male factors are the cause of infertility. In recent decades, there has been a significant decline in the quality of male ejaculate, which is characterized by reduced sperm concentration and motility. The insufficient diagnostic and prognostic value of routine semen analysis results highlights the challenge of developing effective diagnostic tools and searching for reliable biomarkers of male infertility. One of the most promising approaches may be assessing sperm microRNA expression.Objective. To study the role of sperm exosomal microRNAs miR-34a and miR-210 in the development of male infertility.Materials & methods. The retrospective study included 150 men aged 25 – 49 years; of these, 96 patients were diagnosed with idiopathic infertility. The comparison group consisted of 54 fertile men. To assess the structure and motility of sperm, the results of a standard ejaculate study (WHO, 2021) and computer data analysis using MMC Sperm (MMCSoft, St. Petersburg, Russia) software were used. The degree of DNA fragmentation was assessed using the TUNEL method. To analyze the expression of miR-34a and miR-210, quantitative real-time PCR was performed using the miRCURY LNA SYBR Green PCR Kit («Qiagen» GmbH, Hilden, Germany) and the Rotor-Gene Q PCR product detection system («Qiagen» GmbH, Hilden, Germany).Results. The study of ejaculate using the Computer Assisted Sperm Analysis System (CASA) method revealed a statistically significant relationship between the level of DNA fragmentation of sperm and indicators of the speed of their movement: rectilinear (VSL) (r = -0.522726; p < 0.01), curvilinear (VCL) (r = -0.499096; p < 0.01), along the middle path (VAP) (r = -0.429533; p < 0.01), as well as with the amplitude of lateral head displacement (ALH) (r = -0.294779, p < 0.01), the linearity of their curvilinear path (LIN) (r = -0.385796; p < 0.01), the degree of straight-line movements (STR) (r = -0.268248; p < 0.05) and their progressive mobility (r = -0.411547; p < 0.01). A study of the level of microRNA expression in sperm exosomes revealed a statistically significant decrease in its miRNA-34a pool (p = 0.0116). According to the Chaddock scale, the strength of the correlation between miR-210 expression and the effectiveness of ART programs was moderate (0.437993). The inverse relationship between miR-34a expression and IVF and ICSI results was weak (0.135314).Conclusion. The analysis of exosomal microRNA-34a and microRNA-210, which are involved in the regulation of spermatogenesis, reveals a direct correlation between their variations and changes in the kinetic and morphological parameters of gametes. It also indicates a relationship with the state of DNA fragmentation. These findings suggest varying levels of gene expression among infertile patients, men with proven fertility, and those undergoing assisted reproductive technology (ART) treatments, both with successful and repeated unsuccessful outcomes.

Background/purpose: This study addresses the delicate balance between healthcare personnel burnout and medical accessibility in the context of endovascular thrombectomy (EVT) services in urban areas. We aimed to determine the minimum number of hospitals providing EVT on rotation each day without compromising patient access. Methods: Employing an optimization model, we developed shift schedules based on patient coverage rates and volumes during the pre-pandemic (2016–2018) and pandemic (2019–2021) periods. Starting with a minimum of two hospitals on duty per day, we gradually increased to a maximum of eight. Patient coverage rates, defined as the proportion of patients meeting bypass criteria and transported to rotating hospitals capable of EVT, were the primary outcomes. Sensitivity analyses explored the impact of varying patient transport intervals and accumulating patients over multiple years. Results: Results from 7024 patient records revealed patient coverage rates of 92.5% (standard deviation [SD] 2.8%) during the pre-pandemic and 91.4% (SD 2.8%) during the pandemic, with at least two rotating hospitals daily. No significant differences were observed between schedules based on the highest patient volume and coverage rate months. A patient coverage rate of 98.99% was achieved with four rotating hospitals per day during the pre-pandemic period, with limited improvement beyond this threshold. Changing patient transport intervals and accumulating patients over six years (p = 0.83) had no significant impact on coverage rates. Conclusion: Our optimization model supports reducing the number of daily rotating hospitals by half while preserving a balance between patient accessibility and alleviating strain on medical teams.

Background: This study aims to determine whether end-stage renal disease (ESRD) is a true contraindication for extracorporeal membrane oxygenation in adult patients. Materials and methods: Adult patients who received VA-ECMO at National Taiwan University Hospital between January 2010 and December 2021 were included. Patients who received regular dialysis before the index admission were included in the ESRD group. The primary outcome was in-hospital mortality. Results: 1341 patients were included in the analysis, 121 of whom had ESRD before index admission. The ESRD group was older (62.3 versus 56.8 years; P

Abstract Beige fat activation involves a fuel switch to fatty acid oxidation following chronic cold adaptation. Mitochondrial acyl-CoA synthetase long-chain family member 1 (ACSL1) localizes in the mitochondria and plays a key role in fatty acid oxidation; however, the regulatory mechanism of the subcellular localization remains poorly understood. Here, we identify an endosomal trafficking component sortilin (encoded by Sort1) in adipose tissues that shows dynamic expression during beige fat activation and facilitates the translocation of ACSL1 from the mitochondria to the endolysosomal pathway for degradation. Depletion of sortilin in adipocytes results in an increase of mitochondrial ACSL1 and the activation of AMPK/PGC1α signaling, thereby activating beige fat and preventing high-fat diet (HFD)-induced obesity and insulin resistance. Collectively, our findings indicate that sortilin controls adipose tissue fatty acid oxidation by substrate fuel selection during beige fat activation and provides a potential targeted approach for the treatment of metabolic diseases.

Nowadays, doctors of almost all specializations have to deal with patients who have one or another voluminous formations of the skin and subcutaneous tissue with localization in the head and neck region, which are heterogeneous in their etiology. It’s important to remember that sometimes neoplasms can turn out to be a manifestation of an infectious disease, in particular helminthosis. One of the representatives from this group of diseases is dyrofilariasis, is a zoonotic transmissible tropical helminth disease caused by roundworms – filarias of the genus Dirofilaria, which parasitize in humans mainly in the subcutaneous tissue and lymphatic system. A single filariasis of the Dirofilaria repens type is found in humans in temperate regions of Russia. Generally, dirofilariosis imitates the clinical picture of some other non-parasitic disease. Because of the lack of awareness of this disease among doctors, the process of making a diagnosis is almost always difficult. Often the correct diagnosis is only made during surgical treatment.The article presents a clinical observation of dirofilariosis with lesions subcutaneous tissue of the dorsum nose.

Multiple sclerosis (MS) is an autoimmune-inflammatory and neurodegenerative disease of the central nervous system. The article analyses the ability of cladribine, which due to its selective lymphotoxic effect on activated cells and central effect on immunomodulation in brain tissue underwent successful clinical trials in 2010, when it was (temporarily) approved in Russia.Objective: to analyse the effect of cladribine tablets in daily practice on the course of MS over 3–4 year observational period after immune reconstitution therapy (IRT) in several neurological clinics from different regions of Russia.Material and methods. We collected data on 235 patients from 12 neurological clinics and regional MS centres who were followed for an average of 3.4 years after starting cladribine treatment.Results. An independent analysis of cases in which cladribine tablets were prescribed showed that the reason for prescribing cladribine was highly active MS (HARS) in 159 (67.7%) patients, rapidly progressive MS (RPMS) in 20 (8.5%), active relapsing-remitting MS – in 50 (21.3%) and secondary progressive MS with exacerbations – in 6 (2.5%). Only 12 (5.1%) of these patients had not previously received disease-modifying therapies (DMTs), i.e. in these cases the drug was the first DMT prescribed. Among patients who had received a second-line DMTs before switching to cladribine, 22 had previously received natalizumab, 5 had received ocrelizumab and only 1 had received fingolimod. Remaining patients (n=195) were switched from first-line DMTs. In all cases, a decrease in the frequency of exacerbations was observed during and after completion of the IRT course. Exacerbations between the first and second course of cladribine were observed in 36 patients (15.3% of all treated patients), including in almost half of the cases those who were switched from natalizumab (17 exacerbations or 47.2% of all exacerbations, that developed between the first and second course of therapy) and in three cases – from ocrelizumab (8.3 % of exacerbations that developed between the first and second course of therapy, or 60 % of all those switched from ocrelizumab to cladribine). After completion of full cladribine treatment during the four-year observation period, exacerbations occurred in 14 patients (6% of all patients included in the analysis), six of which occurred after switching from natalizumab.Conclusion. The results are generally consistent with the results of recently published meta-analyses and reviews, but the high likelihood of exacerbations in patients switched from second-line therapies such as natalizumab and ocrelizumab is noteworthy. Both drugs are prescribed for aggressive types of MS with exacerbations (highly active and rapidly progressive) who had a high frequency of exacerbations and an increase in Expanded Disability Status Scale (EDSS) scores prior to being prescribed these drugs. The switch from natalizumab is usually due to an increased risk of developing progressive multifocal encephalopathy with a high titre of antibodies against the JC-virus and the duration of natal izumab use of more than 2 years. It is likely that the resumption of MS activity after discontinuation of natalizumab is quite pronounced, and replacement with treatment with cladribine in tablet form is not able to completely prevent this. In this respect, such a switch does not appear to be optimal, in contrast to cases where first-line drugs are switched to cladribine.

The aim of the research is to determine the clinical-pathogenetic and prognostic value of nitrotyrosine levels in the blood serum of patients with COVID-19 with pneumonia in the development of oxygen dependence and the risk of fatal outcome. Materials and methods. 123 patients with COVID-19 with pneumonia were examined, who were examined and treated according to the Order of the Ministry of Health of Ukraine dated March 28, 2020 No. 722. Patients were divided into groups: I group – 32 patients with a moderate course without oxygen dependence; II group – 91 patients with a severe course with the presence of oxygen dependence. Patients in the II group were additionally divided into subgroups: II-A subgroup – 45 patients who recovered; II-B subgroup – 46 patients who died. The content of nitrotyrosine (Hycult Biotech, the Netherlands) was determined in the blood serum by the immunoenzymatic method. Statistical data processing was carried out in the program Statistica for Windows 13 (StatSoft Inc., No. JPZ804I382130ARCN10-J). Results. The content of nitrotyrosine in the blood serum of patients with COVID-19 with pneumonia in a severe course with the development of oxygen dependence is higher (p < 0.001) than in patients with a moderate course of the disease without signs of oxygen dependence. The level of its increase has an inverse correlation with the oxygen saturation index (r = -0.53, р < 0.05). When hospitalized for 9.0 [7.0; 12.0] day of the disease, under the condition of nitrotyrosine level >481.97 nmol/ml (AUC = 0.909, p < 0.001), the probability of developing oxygen dependence is significant. And under the conditions of nitrotyrosine level >521.96 nmol/ml during this observation period, the probability of a fatal outcome of the disease is significant (AUC = 0.842, p < 0.001). The established correlations confirm the clinical-pathogenetic role of nitrotyrosative stress in the development of the “cytokine storm” and multiorgan failure. The content of nitrotyrosine correlates with the level of C-reactive protein (r = +0.25, p < 0.05), the ratio of absolute neutrophil count to absolute lymphocyte count (r = +0.26, p < 0.05), alanine aminotransferase activity (r = +0.26, p < 0.05) and glomerular filtration rate (r = -0.27, p < 0.05). The diagnostic value of determining the level of nitrotyrosine in predicting the course of COVID-19 with pneumonia against the background of treatment after 7 days lies in the possibility of predicting the probability of a fatal outcome of the disease. Namely, the preservation of the level of nitrotyrosine >507.98 nmol/ml (AUC = 0.681, p < 0.001) during the specified period of observation indicates a high probability of a fatal outcome of the disease. Conclusions. In patients with COVID-19 with pneumonia, the level of nitrotyrosine elevation in the blood serum depends on the appearance of oxygen dependence and the outcome of the disease. The highest level of nitrotyrosine is in patients with COVID-19 with pneumonia with a severe course, and the degree of increase of this indicator has diagnostic value in predicting the probability of an unfavorable disease course.