bluuebunny/crossref_metadata_2025_split huggingface dataset:
Individual Compounds of <i>Rhodoila quadrifida</i> Rhizomes and Roots: Isolating and Establishing Structure
Authors: Lezina A. V. , Whaley A. K. , Whaley A. O. , Terninko I. I. 
Published: November 2022

Introduction. Medicinal plant raw materials, containing a wide range of various biologically active compounds, are of considerable interest as a likely source of new, pharmacologically active biologically active substances. One of the promising plants is Rhodiola quadrifida (Pall.) Fisch. & C.A. Mey, since the raw materials contain phenolic compounds and their derivatives, which cause anti-inflammatory, antioxidant and anticarcinogenic effects. In addition, this plant has considerable popularity in folk medicine as a dietary supplement.Aim. Isolation of individual compounds from rhizomes and roots of Rhodiola quadrifida and subsequent determination of their structure by NMR and mass spectrometry for phytochemical profiling.Materials and methods. Rhizomes and roots of Rhodiola quadrifida, purchased in the pharmacy of St. Petersburg (place and time of procurement according to the information on the package – Altai (near Barnaul), in March 2019. The ethanol extract fractions (ethanol, hexane, butanol, and water) obtained during sequential liquid-liquid extraction were examined on a LC-20 Prominence instrument (Shimadzu, Japan) with an SPD-M20A diode array detector to determine the chromatographic profile. The most promising ethyl acetate fraction was purified by column chromatography on open glass columns with sorbents of different selectivity and preparative chromatography [Smartlina (Knauer, Germany)] with a spectrophotometric detector. The structure of the obtained individual compounds was determined by NMR (Bruker Avance III 400 MHz, Germany) and confirmed by low-resolution mass spectrometry [Flexar FX-15 (PerkinElmer, USA)].Results and discussion. During the study, 7 individual compounds were isolated from the rhizomes and roots of Rhodiola quadrifida, namely 3,4-dihydroxybenzoic acid, 4-hydroxybenzoic acid, caffeic acid, ethyl gallate, catechin, epicatechin and tyrosol. These compounds were isolated for the first time from the raw materials of Rhodiola quadrifida. They are the major compounds and can characterize the phytochemical profile of raw materials, as well as determine the direction of pharmacological activity.Conclusion. For the first time, Rhodiola quadrifida was isolated from raw materials and the structure of 7 majority compounds was proved by NMR spectroscopy and mass spectrometry, which can serve as a foundation for further study of this species of Rhodiola and targeted study of its pharmacological activity in vitro and in vivo, considering the individual phytochemical profile.
Approbation of a Model of Fat Liver Disease Induced by Orotic Acid
Authors: Kovanskov V. V. , Ivkin D. Yu. , Semivelichenko E. D. , Plisko G. A. , Kopacheva E. A. , Sidorov K. O. 
Published: November 2022

Introduction. For the treatment of non-alcoholic fatty liver disease (NAFLD), hepatoprotective drugs are actively used. The existing models of non-alcoholic fatty liver disease used to study the effectiveness of medicinal products are characterized by a long duration of recovery and high mortality of test systems, in connection with which, the actual task is to test the screening model of this pathology. A number of studies have shown the hepatotoxic activity of orotic acid (OK), species-specific for rats, leading to the development of NAFLD.Aim. Approbation of the NAFLD model induced by orotic acid on 2 rodent species (mice and rats), research of the reversibility of pathology under the action of a reference drug (ursodeoxycholic acid – UDCA).Materials and methods. The reseacrh was conducted on outbred male rats weighing 260–265 g (n = 21) and inbred male mice of the C57BL/6 line weighing 16–18 g (n = 30). By randomization, the rats were divided into 3 groups (7 rats each): group 1 – intact animals; group 2 – NAFLD model; group 3 – NAFLD + UDCA model, mice were divided into 2 groups (10 and 20 mice, respectively): group 1 – intact animals; group 2 – NAFLD model. NAFLD was modeled by a high-carbohydrate diet with orotic acid (75 % standard feed, 24 % fructose and 1 % potassium orotate). UDCA was administered after the first control point 1 time a day through a probe in terms of 150 mg/kg. Biochemical and histological examination was carried out.Results and discussion. It was revealed that a high-carbohydrate diet with the addition of 1 % potassium orotate for 4 weeks causes moderate balloon dystrophy, mild hepatitis and an increase in the content of alanine aminotransferase and aspartate aminotransferase in the blood of rats and less significant changes in mice. Low animal mortality was also noted. The use of UDCA on the claimed model causes a decrease in the severity of liver dystrophy and a decrease in the level of liver enzymes in the blood.Conclusion. Based on the conducted experiments, rats turned out to be the optimal test system on the reproduced model, and a high-fat diet with the addition of orotic acid allows screening studies of drugs with hepatotropic activity.
Chelidonic Acid and its Derivates: General Spectrum of Biological Activity and Osteogenic Properties (Review)
Authors: Miroshnichenko L. A. , Polyakova T. Yu. , Avdeeva E. Yu. , Krivoshchekov S. V. , Khlusov I. A. , Belousov M. V. 
Published: November 2022

Introduction. The development and implementation of new effective and safe drugs with osteogenic activity is an urgent problem of modern medical and pharmaceutical sciences. This is due to the wide prevalence and complexity of the treatment of diseases of the musculoskeletal system, which entails significant economic costs for the treatment and recovery of this group of patients. Recently, standard therapy regimens are increasingly being supplemented with drugs derived from medicinal plants, which is associated with their rather pronounced therapeutic effect and the absence or mild side effects compared to more expensive modern medical analogues. In this regard, the development of new directions in the strategy for the development of pharmacological agents from plant sources becomes relevant. The study of plant secondary metabolites is one such area that has already yielded good results in relation to the development of such drugs, and holds great promise. The review provides information on the biological properties of chelidonic acid and its possible derivatives in order to demonstrate the prospects for the use of these objects for the development of drugs, including those with osteogenic activity.Text. Chelidonic acid is a substance present in many medicinal plants and has a wide range of pharmacological effects – analgesic, antimicrobial, anti-inflammatory, oncostatic and sedative. At the moment, methods have been developed for obtaining chelidonic acid and its derivatives from natural sources. In addition, chelidonic acid belongs to the so-called “small” molecules with osteogenic properties, which makes it promising in the creation of drugs for the treatment of diseases of the musculoskeletal system caused by impaired formation and regeneration of bone tissue. Native chelidonic acid has a low osteogenic activity, but given its ability to form complex compounds, it can act as a delivery system for osteoprotective micro- and macroelements. So, calcium chelidonate in experiments in vitro and in vivo shows a pronounced osteogenic activity: it stimulates the viability, adhesion and osteogenic differentiation of mesenchymal stem cells, enhances the mineralization of the extracellular matrix.Conclusion. Taking into account the wide range of biological activity of chelidonic acid, its use in the complex therapy of allergies, depression, diabetes mellitus, inflammatory diseases, malignant neoplasms and other pathological conditions seems relevant. Calcium chelidonate is a promising drug candidate that can be used to accelerate regeneration processes and in bone tissue engineering.
Association of admission serum calcium level with left ventricular dysfunction in patients with acute coronary syndrome
Authors: Wang Hong , Wang Rongrong , Tian Junping 
Published: November 2022

BackgroundThe relationship between serum calcium and left ventricular function in patients with acute coronary syndrome (ACS) has not been explored. Our aim was to investigate the correlation of admission serum calcium with left ventricular dysfunction in ACS patients.MethodsIn this cross-sectional study, 658 ACS patients who were admitted in the Department of Cardiovascular Disease from June 1st, 2019 to December 31st, 2019 were enrolled in the present study. Serum calcium and B-type natriuretic peptide (BNP) were measured at admission. Left ventricular ejection fraction (LVEF) was assessed using echocardiography. The correlation between admission serum calcium and left ventricular dysfunction was analyzed.ResultsWhen stratified by serum calcium quartiles calculated from all patients, patients with lower serum calcium quartile showed a markedly higher BNP and lower LVEF (P &lt; 0.05). Patients with LVEF ≤ 50% showed a significantly lower serum calcium and higher BNP compared to those with LVEF&gt; 50% (P &lt; 0.05). Admission serum calcium was positively correlated with LVEF (P &lt; 0.01) but negatively correlated with BNP (P &lt; 0.01). Multivariate logistic regression analysis showed that lower serum calcium (adjusted OR: 0.720, 95% CI: 0.519–0.997, P = 0.048) was independently associated with BNP ≥ 300 pg/ml in ACS patients. Using LVEF as a dependent variable, no significant correlation between low serum calcium and left ventricular systolic dysfunction was found in ACS patients.ConclusionsIn patients with ACS, admission serum calcium was positively correlated with LVEF and negatively with BNP. Lower admission serum calcium was an independent risk factor for elevated BNP.
Case report: Different clinical manifestations of the rare Loeffler endocarditis
Authors: Zhao Yuanyuan , Jiang Peiqing , Chen Xiangyun , Yao Guihua 
Published: November 2022

BackgroundLoeffler endocarditis is a rare and fatal disease, which is prone to be misdiagnosed, owing to its various clinical manifestations. Consequently, an early identification of Loeffler endocarditis and its effective treatment are crucial steps to be undertaken for good prognosis.Case presentationThis report describes two cases of Loeffler endocarditis with different etiologies and clinical manifestations. Case 1 was caused by idiopathic eosinophilia and presented with a thrombus involving the tricuspid valve and right ventricular inflow tract (RVIT). The patient suffered from recurrent syncope following activity. After the patient underwent tricuspid valve replacement and thrombectomy, he took oral prednisone and warfarin for 2 years, consequent to which he discontinued both drugs. However, the disease recurred 6 months later, this time manifesting as edema of both legs. Echocardiography showed that a thrombus had reappeared in the RVIT. Thus, oral prednisone and warfarin therapy was readministered. Three months later, the thrombus had dissolved. Low-dose prednisone maintenance therapy was provided long term. Case 2 involved a patient who presented with recurrent fever, tightness in the chest, and asthma, and whose condition could not be confirmed, despite multiple local hospitalizations. In our hospital, echocardiography revealed biventricular apical thrombi. After comprehensive examinations, the final diagnosis was eosinophilic granulomatosis polyangiitis (EGPA) involving multiple organs, including the heart (Loeffler endocarditis), lungs, and kidneys. After administration of corticosteroid, anticoagulant, and immunosuppressive agents along with drugs to improve cardiac function, the patient's symptoms improved significantly.ConclusionIn Loeffler endocarditis due to idiopathic eosinophilia, long-term corticosteroid use may be required. Diverse and non-specific symptoms cause Loeffler endocarditis to be easily misdiagnosed. So, when a patient shows a persistent elevation of the eosinophil count with non-specific myocardial damage, the possibility of this disease, should always be considered. Furthermore, even when an invasive clinical procedure such as endomyocardial biopsy (EMB) is not available or acceptable, corticosteroids should be administered promptly to bring the eosinophil count back to the normal range, thereby halting the progression of disease and reducing patient mortality.
Impact of severe valvular heart disease in adult congenital heart disease patients
Authors: Graziani Francesca , Iannaccone Giulia , Meucci Maria Chiara , Lillo Rosa , Delogu Angelica Bibiana , Grandinetti Maria , Perri Gianluigi , Galletti Lorenzo , Amodeo Antonio , Butera Gianfranco , Secinaro Aurelio , Lombardo Antonella , Lanza Gaetano Antonio , Burzotta Francesco , Crea Filippo , Massetti Massimo 
Published: November 2022

BackgroundThe clinical impact of valvular heart disease (VHD) in adult congenital heart disease (ACHD) patients is unascertained. Aim of our study was to assess the prevalence and clinical impact of severe VHD (S-VHD) in a real-world contemporary cohort of ACHD patients.Materials and methodsConsecutive patients followed-up at our ACHD Outpatient Clinic from September 2014 to February 2021 were enrolled. Clinical characteristics and echocardiographic data were prospectively entered into a digitalized medical records database. VHD at the first evaluation was assessed and graded according to VHD guidelines. Clinical data at follow-up were collected. The study endpoint was the occurrence of cardiac mortality and/or unplanned cardiac hospitalization during follow-up.ResultsA total of 390 patients (median age 34 years, 49% males) were included and S-VHD was present in 101 (25.9%) patients. Over a median follow-up time of 26 months (IQR: 12–48), the study composite endpoint occurred in 76 patients (19.5%). The cumulative endpoint-free survival was significantly lower in patients with S-VHD vs. patients with non-severe VHD (Log rank p &lt; 0.001). At multivariable analysis, age and atrial fibrillation at first visit (p = 0.029 and p = 0.006 respectively), lower %Sat O2, higher NYHA class (p = 0.005 for both), lower LVEF (p = 0.008), and S-VHD (p = 0.015) were independently associated to the study endpoint. The likelihood ratio test demonstrated that S-VHD added significant prognostic value (p = 0.017) to a multivariate model including age, severe CHD, atrial fibrillation, %Sat O2, NYHA, LVEF, and right ventricle systolic pressure &gt; 45 mmHg.ConclusionIn ACHD patients, the presence of S-VHD is independently associated with the occurrence of cardiovascular mortality and hospitalization. The prognostic value of S-VHD is incremental above other established prognostic markers.
Identification of glycolysis genes signature for predicting prognosis in malignant pleural mesothelioma by bioinformatics and machine learning
Authors: Xiao Yingqi , Huang Wei , Zhang Li , Wang Hongwei 
Published: November 2022

BackgroundGlycolysis-related genes as prognostic markers in malignant pleural mesothelioma (MPM) is still unclear. We hope to explore the relationship between glycolytic pathway genes and MPM prognosis by constructing prognostic risk models through bioinformatics and machine learning.MethodsThe authors screened the dataset GSE51024 from the GEO database for Gene set enrichment analysis (GSEA), and performed differentially expressed genes (DEGs) of glycolytic pathway gene sets. Then, Cox regression analysis was used to identify prognosis-associated glycolytic genes and establish a risk model. Further, the validity of the risk model was evaluated using the dataset GSE67487 in GEO database, and finally, a specimen classification model was constructed by support vector machine (SVM) and random forest (RF) to further screen prognostic genes.ResultsBy DEGs, five glycolysis-related pathway gene sets (17 glycolytic genes) were identified to be highly expressed in MPM tumor tissues. Also 11 genes associated with MPM prognosis were identified in TCGA-MPM patients, and 6 (COL5A1, ALDH2, KIF20A, ADH1B, SDC1, VCAN) of them were included by Multi-factor COX analysis to construct a prognostic risk model for MPM patients, with Area under the ROC curve (AUC) was 0.830. Further, dataset GSE67487 also confirmed the validity of the risk model, with a significant difference in overall survival (OS) between the low-risk and high-risk groups (P &lt; 0.05). The final machine learning screened the five prognostic genes with the highest risk of MPM, in order of importance, were ALDH2, KIF20A, COL5A1, ADH1B and SDC1.ConclusionsA risk model based on six glycolytic genes (ALDH2, KIF20A, COL5A1, ADH1B, SDC1, VCAN) can effectively predict the prognosis of MPM patients.
Association of geriatric nutritional risk index with the risk of osteoporosis in the elderly population in the NHANES
Authors: Huang Wei , Xiao Yingqi , Wang Hongwei , Li Kaixiang 
Published: November 2022

BackgroundOsteoporosis is common in the elderly, and malnutrition is considered a major risk factor for osteoporosis. This study investigated the relationship between the Geriatric Nutrition Risk Index (GNRI) and osteoporosis based on a large cross-sectional study of the National Health and Nutrition Examination Survey (NHANES).MethodsWe included 7405 older adults from NHANES (2005 to 2018) and divided them into the High-GNRI and Low-GNRI groups based on GNRI levels to compare the prevalence of osteoporosis among the two groups. A multi-factor logistic regression analysis was used to determine whether GNRI was an independent risk factor for osteoporosis. Spearman’s rank correlation coefficient was computed to investigate the linear relationship between geriatric nutritional risk index (GNRI) and bone mineral density (BMD) T-score. Finally, a generalized additive model (GAM) revealed whether there was a non-linear relationship between GNRI and osteoporosis.ResultsThe prevalence of osteoporosis was higher in the Low-GNRI group than those in the High-GNRI group (12.2% vs. 8.2%; P = 0.001). Similarly, the femoral neck BMD T-scores (-1.09 ± 1.42 vs. -0.91 ± 1.31; P = 0.003). However, there was no significant difference between Low-GNRI group and High-GNRI group in lumbar BMD T-scores (1.700 ± 1.69 vs 1.85 ± 1.72; P&gt;0.05). The multi-factor logistic regression analysis identified low GNRI as an independent risk factor for osteoporosis (OR: 1.544; 95% CI: 1.179-2.022; P &lt; 0.001). Besides, GNRI showed a positive linear correlation (P &lt; 0.001) with femoral neck BMD T-scores in older adults, with a progressive trend towards higher BMD as GNRI increased. By contrast, there was no linear correlation between GNRI and lumbar BMD T-score (P = 0.978). Lastly, the dose response curve revealed the non-linear negative correlation between GNRI and the risk of osteoporosis in the elderly (non-linear P &lt; 0.001). With the increase of GNRI, the risk of osteoporosis gradually decreased, especially when GNRI was greater than 100, the downward trend was more significant.ConclusionGNRI is an independent risk factor for osteoporosis in the elderly and is negatively and non-linearly associated with the risk of osteoporosis in the elderly population.
Case Report: A novel KNCH2 variant-induced fetal heart block and the advantages of fetal genomic sequencing in prenatal long-term dexamethasone exposure
Authors: Huang Huiping , Jing Siyuan , Wu Shaoying , Wei Li , Zhang Qian , Hua Yimin , Li Yifei , Yu Haiyan , Zhou Kaiyu 
Published: November 2022

Background: Fetal bradycardia is a common but severe condition. In addition to autoimmune-mediated fetal heart block, several types of channelopathies induce high-degree atrioventricular block (AVB). Long QT syndrome (LQTS) is a major cause of non-autoimmune-mediated fetal heart block. Due to the limitations of prenatal diagnostic technologies, LQTS is seldom identified unless fetal genetic screening is performed. Thus, long-term prenatal dexamethasone (DEX) exposure can become a challenge for these patients. We report on a rare case of a novel KCNH2 variant related to LQTS and associated with high-degree fetal AVB with long-term DEX exposure. This case led us to review our prenatal administration strategy for such patients.Case Presentation: A fetus was identified with high-degree AVB (2:1 transduction at 28 + 2 gestational weeks). Typical tests of immune function in the pregnant woman were conducted including tests for thyroid function, rheumatic screening, autoimmune antibodies (such as anti-Ro/SSA and anti-La/SSB), and anti-nuclear antibodies (anti-ANA). Following the recommended protocol, the pregnant patient received DEX (0.75 mg/day) during pregnancy. Subsequently, the fetal AVB changed from 2:1 to prolonged AV intervals with ventricular tachycardia, which suggested a therapeutic benefit of DEX in some respects. However, a high-degree AVB with a significantly prolonged QTc interval was identified in the neonate following birth. Genetic testing revealed that a KCNH2 c.1868C&gt;A variant induced LQTS. The body length remained approximately -3.2 SD from the reference value after prenatal long-term DEX exposure, which indicated a developmental restriction. Additionally, the functional validation experiments were performed to demonstrate the prolonged duration of calcium transit both in depolarization and repolarization with the KCNH2 c.1868C&gt;A variant.Conclusion: Genetic screening should be recommended in fetuses with autoimmune antibody negative high-degree AVB, especially for 2:1 transduction AVB and in fetuses with changes in fetal heart rhythm following initial DEX treatment. Genetic screening may help identify genetic variant–related channelopathies and avoid unexpected prenatal exposure of DEX and its possible long-term adverse postnatal complications.
Exploring the causal relationship between gastroesophageal reflux and oral lesions: A mendelian randomization study
Authors: Shu Linjing , Tong Xu 
Published: November 2022

Background: Clinical observations and retrospective studies have observed that patients with gastroesophageal reflux disease (GERD) have an increased probability of dental erosion, periodontitis and oral mucosal lesions and other common oral lesions. However, whether there is a genetic causal relationship between GERD and the occurrence of oral lesions has not been reported.Methods: In this study, we extracted instrumental variables from the largest published summary statistics of the oral lesion phenotype GWAS in UK Biobank (UKBB) and GERD GWAS. Then, we performed a causal inference analysis between GERD and common oral lesions by mendelian randomization (MR) analysis with the R package “TwoSampleMR”.Results: We observed a significant causal relationship between GERD and several common oral lesion phenotypes (painful gums, loose teeth, toothache, and mouth ulcers). GERD showed a positive correlation with the occurrence of these oral lesions. After removing outlier SNPs via the MR-PRESSO package, our conclusions were still robust.Conclusion: Our findings provide the first evidence for a genetic causal effect of GERD on oral lesion pathogenesis. For patients with confirmed GERD, attention should be paid to taking interventions to prevent the occurrence of oral lesions.