Search

Background: Epigenetic variants carried by circulating tumor DNA can be used as biomarkers for early detection of hepatocellular carcinoma (HCC) by noninvasive liquid biopsy. However, traditional methylation analysis method, bisulfite sequencing, with disadvantages of severe DNA damage, is limited in application of low-amount cfDNA analysis., Results: Through mild enzyme-mediated conversion, enzymatic methyl sequencing (EM-seq) is ideal for precise determination of cell-free DNA methylation and provides an opportunity for HCC early detection. EM-seq of methylation control DNA showed that enzymatic conversion of unmethylated C to U was more efficient than bisulfite conversion. Moreover, a relatively large proportion of incomplete converted EM-seq reads contains more than 3 unconverted CH site (CH = CC, CT or CA), which can be removed by filtering to improve accuracy of methylation detection by EM-seq. A cohort of 241 HCC, 76 liver disease, and 279 normal plasma samples were analyzed for methylation value on 1595 CpGs using EM-seq and targeted capture. Model training identified 283 CpGs with significant differences in methylation levels between HCC and non-HCC samples. A HCC screening model based on these markers can efficiently distinguish HCC sample from non-HCC samples, with area under the curve of 0.957 (sensitivity = 90%, specificity = 97%) in the test set, performing well in different stages as well as in serum α-fetoprotein/protein induced by vitamin K absence-II negative samples., Conclusion: Filtering of reads with ≥ 3 CHs derived from incomplete conversion can significantly reduce the noise of EM-seq detection. Based on targeted EM-seq analysis of plasma cell-free DNA, our HCC screening model can efficiently distinguish HCC patients from non-HCC individuals with high sensitivity and specificity., (© 2023. The Author(s).)

Background: Previous studies have reported that there may be a close relationship between elevated serum uric acid (UA) levels and metabolic syndrome. However, the association between these two factors has not been explored explicitly. Therefore, we carried out this study to investigate the association between UA and lipid profiles., Methods: A total of 2,482 subjects participated in this cross-sectional study using a multistage stratified sampling method. Lipid profile, glucose metabolism, and other metabolic factors were measured and classified into UA-stratified and age-stratified groups to investigate the relationship between hyperuricemia and metabolic factors. Pearson correlations and logistic regressions were utilized to further explore the association between UA and lipid profile., Results: The individuals aged 18 to 29 years presented with high serum UA concentrations. Moreover, the prevalence of hyperuricemia was higher among men than in women. Furthermore, statistically significant positive correlations were found between UA and serum triglycerides (TG), serum total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-c). Conversely, only high-density lipoprotein cholesterol (HDL-c) was negatively correlated. Moreover, TG group status (1.70≤ TG <2.30 mmol/L) was an independent risk factor for hyperuricemia in both univariate and multivariate models., Conclusions: This study found significant positive associations between TG, TC, LDL, and UA but an inverse relationship with HDL-c. Thus hyperuricemia may be a risk factor for abnormal lipid metabolism.

In this paper, a new class of rational quadratic/linear trigonometric Hermite functions with two shape parameters is proposed. Based on these Hermite functions, new improved first class of Side-Side (FCSS), second class of Side-Side (SCSS), first class of Side-Vertex (FCSV) and second class of Side-Vertex (SCSV) interpolation operators are proposed respectively, which can be used to construct C1 Coons surfaces over triangular domain. By altering the values of two shape parameters, the shape of the Coons surface patch can be adjusted flexibly, but without affecting the function values and partial derivatives of the boundaries. For constructing the triangular surface patches with the center of mass passing through a fixed point, we also give a center of mass function value control method, by which we can solve the corresponding shape parameter values. Moreover, we also apply these four improved interpolation operators to image interpolation. Compared with some widely used image interpolation methods, our methods achieve competitive performance., Competing Interests: The authors have declared that no competing interests exist.

Objective: To determine the therapeutic effect and potential mechanism of Huatan Tongluo decoction on rats with collagen-induced arthritis., Methods: Forty specific pathogen-free Wistar rats were selected, and 10 were randomly selected as the control (group 1). The remaining rats were injected intradermally with emulsified type II bovine collagen at the tail base and back, followed by a booster 7 d post first immunization. After establishing collagen-induced arthritis (CIA), rats were randomly divided into three groups (n = 10). The rats were treated orally for 30 d as follows: group 1, saline; group 2, model (saline); group 3, tripterygium polyglycoside (TP; 7.81 mg/kg, positive control); group 4, Huatan Tongluo decoction (HTTL; 7.5 g/kg). Body weight, ankle swelling and arthritis index were measured over the course of the study. The rats were sacrificed 30 d after treatment. Morphological changes in the synovium were observed by hematoxylin and eosin staining. Pannus formation and synovial thickness in the left ankle were observed by color Doppler ultrasoundVascular endothelial growth factor (VEGF) and VEGFR2 protein levels were measured by immunohistochemistry. VEGF/VEGFR2 mRNA levels were measured by real-time quantitative polymerase chain reaction., Results: Compared with the model group, a significantly lower arthritis index was observed in the positive control group (P < 0.05) and HTTL group (P < 0.01), after treatment. Both positive control and HTTL reduced intra-articular pannus formation and synovial thickening. Furthermore, VEGF mRNA, and VEGFR2 protein and mRNA levels were significantly downregulated (P < 0.05) in the treatment groups., Conclusion: Inhibition of the expression of VEGF and VEGFR2 in synovial tissues and the formation of pannus and synovial hyperplasia may be part of the mechanism of HTTL for relieving the symptoms of rheumatoid arthritis in CIA rats.

Huatan Tongluo Fang (HTTLF) is a traditional herbal formula that can resolve phlegm and dredge collaterals. HTTLF has also been used to treat rheumatoid arthritis (RA); however, the mechanism underlying the therapeutic effects of HTTLF on RA has not been clearly elucidated at the molecular level. In the present study, an integrated model of system pharmacology containing chemical space analysis, potential active compound prediction and compound-target-disease network was constructed to investigate the molecular mechanisms of HTTLF. The compounds from HTTLF dispersed well in the chemical space. Most of the compounds from HTTLF had similar chemical spaces to drug/drug-like compounds associated with RA, according to the MDL Drug Data Report. A total of 127 potentially active compounds and 17 targets of RA were identified. Among them, 50 compounds interacted with ≥2 targets, while 77 compounds interacted with only one target. In addition, 17 targets were associated with 82 diseases that belonged to 26 categories. These results indicate that HTTLF has diverse chemical spaces and polypharmacology with regards to the treatment of RA. In addition, HTTLF demonstrated therapeutic potential against diverse diseases other than RA, including osteoarthritis, atherosclerosis and brain cancer. This study provides a novel platform for understanding how HTTLF treats RA; this is beneficial for explaining the diverse functions of HTTLF with regards to RA, and may help develop novel compounds with desirable therapeutic targets to treat RA.