Development and validation of a nomogram for predicting specific mortality risk: A study of competing risk model based on real endometrial cancer patients.

OBJECTIVE: This study aimed to construct a competing risk prediction model for predicting specific mortality risks in endometrial cancer patients from the SEER database based on their demographic characteristics and tumor information. METHODS: We collected relevant clinical data on patients with histologically confirmed endometrial cancer in the SEER database between 2010 and 2015. Univariate and multivariate competing risk models were used to analyze the risk factors for endometrial cancer-specific death, and a predictive nomogram was constructed. C-index and receiver operating characteristic curve (ROC) at different time points were used to verify the accuracy of the constructed nomogram. RESULTS: There were 26 109 eligible endometrial cancer patients in the training cohort and 11 189 in the validation cohort. Univariate and multivariate analyses revealed that Age, Marriage, Grade, Behav, FIGO, Size, Surgery, SurgOth, Radiation, ParaAortic_Nodes, Peritonea, N positive, DX_liver, and DX_lung were independent prognostic factors for specific mortality in endometrial cancer patients. Based on these factors, a nomogram was constructed. Internal validation showed that the nomogram had a good discriminative ability (C-index = 0.883 [95% confidence interval [CI]: 0.881-0.884]), and the 1-, 3-, and 5-year AUC values were 0.901, 0.886 and 0.874, respectively. External validation indicated similar results (C-index = 0.883 [95%CI: 0.882-0.883]), and the 1-, 3-, and 5- AUC values were 0.908, 0.885 and 0.870, respectively. CONCLUSION: We constructed a competing risk model to predict the specific mortality risk among endometrial cancer patients. This model has favorable accuracy and reliability and can provide a reference for the development and update of endometrial cancer prognostic risk assessment tools.

Self-powered molecularly imprinted photoelectrochemical sensor based on Ppy/QD/HOF heterojunction for the detection of bisphenol A.

As an emerging porous material, hydrogen-bonded organic framework materials (HOFs) still pose application challenges. In this work, the designed type "I + II" heterojunction extracted hot electrons from HOFs using quantum dots (QDs) and polypyrrole (Ppy), improving the stability and photoelectrochemical performance of materials. In addition to serving as a potential well, electropolymerized Ppy was used as a recognition element for bisphenol A (BPA), and a novel self-powered molecularly imprinted photoelectrochemical (MIP-PEC) sensor was designed. The sensing platform showed a linear relationship from 1 × 10-10 to 1 × 10-7 mol∙L-1 and from 1 × 10-7 to 1 mol∙L-1 with an acceptable detection limit of 4.2 × 10-11 mol∙L-1. This is the first application of HOFs in constructing MIP-PEC sensors and a new attempt to improve the stability of HOFs for the application of porous crystal materials in the sensing field.

The Separation, Purification, Structure Identification, and Antioxidant Activity of Elaeagnus umbellata Polysaccharides.

In order to investigate the antioxidant activity of Elaeagnus umbellata polysaccharides, the physicochemical characteristics of purified Elaeagnus umbellata polysaccharides (EUP, consisting of two fractions, EUP1 and EUP2) were investigated using UV spectrophotometry, high-performance liquid chromatography (HPLC), high-performance gel permeation chromatography (HPGPC), and Fourier transform infrared spectroscopy (FT-IR). This revealed that EUP1 and EUP2 were acidic polysaccharides with an average molecular weight (MW) of 63 and 38 kDa, respectively. EUP1 mainly consisted of L-rhamnose and D-galactose in a molar ratio of 2.05:1, and EUP2 consisted of D-mannose, L-rhamnose, D-galactose, and D-arabinose in a molar ratio of 2.06:1:2.78:1. Furthermore, EUP exhibited considerable antioxidant potential for scavenging hydroxyl, superoxide anion, DPPH, and ABTS radicals. Therefore, EUP can be developed as a potential antioxidant for the functional food or pharmaceutical field.

Semaphorin3A Exacerbates Cardiac Microvascular Rarefaction in Pressure Overload-Induced Heart Disease.

Microvascular endothelial cells (MiVECs) impair angiogenic potential, leading to microvascular rarefaction, which is a characteristic feature of chronic pressure overload-induced cardiac dysfunction. Semaphorin3A (Sema3A) is a secreted protein upregulated in MiVECs following angiotensin II (Ang II) activation and pressure overload stimuli. However, its role and mechanism in microvascular rarefaction remain elusive. The function and mechanism of action of Sema3A in pressure overload-induced microvascular rarefaction, is explored, through an Ang II-induced animal model of pressure overload. RNA sequencing, immunoblotting analysis, enzyme-linked immunosorbent assay, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and immunofluorescence staining results indicate that Sema3A is predominantly expressed and significantly upregulated in MiVECs under pressure overload. Immunoelectron microscopy and nano-flow cytometry analyses indicate small extracellular vesicles (sEVs), with surface-attached Sema3A, to be a novel tool for efficient release and delivery of Sema3A from the MiVECs to extracellular microenvironment. To investigate pressure overload-mediated cardiac microvascular rarefaction and cardiac fibrosis in vivo, endothelial-specific Sema3A knockdown mice are established. Mechanistically, serum response factor (transcription factor) promotes the production of Sema3A; Sema3A-positive sEVs compete with vascular endothelial growth factor A to bind to neuropilin-1. Therefore, MiVECs lose their ability to respond to angiogenesis. In conclusion, Sema3A is a key pathogenic mediator that impairs the angiogenic potential of MiVECs, which leads to cardiac microvascular rarefaction in pressure overload-induced heart disease.

Dysregulated expression of microRNA involved in resistance to osimertinib in EGFR mutant non-small cell lung cancer cells.

Background: An increasing amount of evidence has confirmed that the altered expression of microRNAs (miRNAs) is critical to the mechanism underlying primary and even acquired resistance to tyrosine kinase inhibitors (TKIs). However, studies on the linkage between the altered miRNAs expression and osimertinib resistance are few, and the effect of miRNAs in this context is still unclear. In the light of this, we hypothesized that the differential expression of multiple miRNAs is the driver in the osimertinib resistance process. Thus, the aim of our study was to find differentially expressed miRNAs in non-small cell lung cancer cells resistant to osimertinib. Methods: An AZD9291(Osimertinib)-resistant cell line model was constructed, and the differential miRNAs between epidermal growth factor receptor (EGFR)-sensitive cell lines A549 and H1975 and the corresponding drug-resistant cell lines were identified via biosynthesis analysis. Results: In the A549 osimertinib-resistant cell line, 93 miRNAs were upregulated and 94 miRNAs were downregulated. In the H1975 osimertinib-resistant cell line, 124 miRNAs were upregulated and 53 miRNAs were downregulated. Finally, 7 significantly different miRNAs were screened using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Conclusions: This study on the mechanism of target therapy in lung cancer systematically and comprehensively examined the miRNAs involved in osimertinib resistance. It was found that miR-708-5p, miR-708-3p, miR-10395-3p, miR-7704 miR-34a-5p, miR-19b-1-5p, and miR-219a-5p may play key roles in osimertinib resistance.

Structure, physicochemical properties, antioxidant, and hypoglycemic activities of water-soluble polysaccharides from millet bran.

This study aimed to investigate the composition, structure, in vitro antioxidant, and hypoglycemic activities of a novel water-soluble MBP-1, an extract from millet bran, isolated by DEAE-52 cellulose and purified by Sephadex G-100. The results showed that MBP-1 was mainly composed of xylose, mannose, galactose, rhamnose, and arabinose with a molar ratio of 0.72:0.59:76.26:1.04:0.83 and a molecular weight of 6.6×104  Da, and its purity was 98%, and the yield was 3.76%. MBP-1 has an irregular granular structure by atomic force microscopy and scanning electron microscopy, and the anomeric carbon in MBP-1 molecule has α-configuration and ß-configuration by NMR and FTIR. The in vitro scavenging abilities of MBP-1 for·OH, DPPH, O2·- , and ABTS+ were 73.5%, 80%, 69.8%, and 75.2%, respectively, and the chelating activity for Fe2+ was 50%, and the inhibition rates of α-glucosidase and α-amylase were 78.5% and 74.6%, respectively, which indicated that MBP-1 possessed strong antioxidant and hypoglycemic activities. The results indicated that MBP-1 have certain application prospects in food-related fields.

Effect of Limited Enzymatic Hydrolysis on Structural and Functional Properties of Elaeagnus mollis Oil Meal Protein.

Elaeagnus mollis oil (EMO) meal, a by-product of oil production with plentiful protein, is considered a cheap and good quality source of plant protein for use in the food industry. In this study, the influence of limited enzymatic hydrolysis of EMO meal protein on the structure, solubility, foaming and emulsifying capacities was investigated in detail. The hydrolysates with different DH values (5, 10, 15, and 17) were obtained by controlling the time of enzymatic hydrolysis with alcalase. The results showed that enzymatic hydrolysis decreased molecular weight and increased flexibility and surface hydrophobicity. At the given range of pH and concentration of NaCl, the solubility, foaming and emulsifying capacities of hydrolysates were significantly improved, especially in the area of isoelectric point, and increased with the increase of DH. It was also found that the hydrolysate with DH10 had better foaming and emulsifying stability. In general, appropriate enzymatic hydrolysis could improve the functional properties in favor of their potential use as food ingredients.

Nε-carboxymethyl-lysine and Nε-carboxyethyl-lysine contents in commercial meat products.

The objective of this work was to investigate Nε-carboxymethyl-lysine (CML) and Nε-carboxyethyl-lysine (CEL) contents in commercial meat products. The results showed that sauced beef and Chinese smoked-cured sausage had the highest CML content (570.38 mg/kg protein) and lowest level of CML (42.18 mg/kg protein), respectively. The CEL level was the highest in stewed pork-hock in soy sauce (868.99 mg/kg protein), and lowest in Korean barbecue (37.95 mg/kg protein). Higher levels of CML and CEL were observed in meat products prepared with sucrose and sauce. Irradiation sterilization had a stronger promoting effect on CML and CEL formation, while smoking could lead to a decrease in CML and CEL. Formation pathway of CML and CEL might be different at different processing temperature due to the different trends of CML and CEL levels in commercial meat products. Furthermore, additions of spices, sodium nitrite and tomato juice in meat products had stronger inhibitory effects on CML and CEL formation. These data could provide a crucial guide for consumers to select meat products, and reduce CML and CEL intake.

The antibacterial mechanism of perilla rosmarinic acid.

Rosmarinic acid (RosA) is a phenolic acid compound extracted from perilla. In this experiment, the Oxford cup method was used to verify the antibacterial activity of PerillaRosA against Escherichia coli, Staphylococcus aureus, Salmonella, and Bacillus subtilis. By polyacrylamide gel electrophoresis, the effect of RosA on bacterial nucleic acid and bacterial Na+ /K+ -ATP-ase activity, and scanning electron microscope to exploration of its antibacterial mechanism preliminarily. The results showed that RosA had antibacterial properties against all four bacteria. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of E. coli were 0.8 and 0.9 mg/ml, respectively. The MIC and MBC of Salmonella were 0.9 and 1.0 mg/ml, respectively. The MIC and MBC of S. aureus and B. subtilis were both 1.0 and 1.1 mg/ml. RosA has the bacteriostasis function, which can destroy bacterial cells and cell proteins and inhibit the activity of Na+ /K+ -ATP-ase in cells.

Bone marrow mesenchymal stem cells derived from juvenile macaques reversed ovarian ageing in elderly macaques.

BACKGROUND: Female sex hormone secretion and reproductive ability decrease with ageing. Bone marrow mesenchymal stem cells (BMMSCs) have been postulated to play a key role in treating ovarian ageing. METHODS: We used macaque ovarian ageing models to observe the structural and functional changes after juvenile BMMSC treatment. Moreover, RNA-seq was used to analyse the ovarian transcriptional expression profile and key pathways through which BMMSCs reverse ovarian ageing. RESULTS: In the elderly macaque models, the ovaries were atrophied, the regulation ability of sex hormones was reduced, the ovarian structure was destroyed, and only local atretic follicles were observed, in contrast with young rhesus monkeys. Intravenous infusion of BMMSCs in elderly macaques increased ovarian volume, strengthened the regulation ability of sex hormones, reduced the degree of pulmonary fibrosis, inhibited apoptosis, increased density of blood vessels, and promoted follicular regeneration. In addition, the ovarian expression characteristics of ageing-related genes of the elderly treatment group reverted to that of the young control group, 1258 genes that were differentially expressed, among which 415 genes upregulated with age were downregulated, 843 genes downregulated with age were upregulated after BMMSC treatment, and the top 20 differentially expressed genes (DEGs) in the protein-protein interaction (PPI) network were significantly enriched in oocyte meiosis and progesterone-mediated oocyte maturation pathways. CONCLUSION: The BMMSCs derived from juvenile macaques can reverse ovarian ageing in elderly macaques.

The effects of BMMSC treatment on lung tissue degeneration in elderly macaques.

BACKGROUND: Age-associated lung tissue degeneration is a risk factor for lung injury and exacerbated lung disease. It is also the main risk factor for chronic lung diseases (such as COPD, idiopathic pulmonary fibrosis, cancer, among others). So, it is particularly important to find new anti-aging treatments. METHODS: We systematically screened and evaluated elderly senile multiple organ dysfunction macaque models to determine whether BMMSCs inhibited lung tissue degeneration. RESULTS: The average alveolar area, mean linear intercept (MLI), and fibrosis area in the elderly macaque models were significantly larger than in young rhesus monkeys (p < 0.05), while the capillary density around the alveoli was significantly low than in young macaque models (p < 0.05). Intravenous infusion of BMMSCs reduced the degree of pulmonary fibrosis, increased the density of capillaries around the alveoli (p < 0.05), and the number of type II alveolar epithelium in elderly macaques (p < 0.05). In addition, the infusion reduced lung tissue ROS levels, systemic and lung tissue inflammatory levels, and Treg cell ratio in elderly macaque models (p < 0.05). Indirect co-cultivation revealed that BMMSCs suppressed the expression of senescence-associated genes, ROS levels, apoptosis rate of aging type II alveolar epithelial cells (A549 cells), and enhanced their proliferation (p < 0.05). CONCLUSIONS: BMMSC treatment inhibited age-associated lung tissue degeneration.

Relationship between senescence in macaques and bone marrow mesenchymal stem cells and the molecular mechanism.

The relationship between bone marrow mesenchymal stem cells (BMSCs) and aging, as well as the antiaging effects of BMSCs, was observed. An aging macaque BMSC model was established. We isolated BMSCs from young and aged macaques and used RT-PCR and Western blot to confirm the aging-related mRNAs and their expression, revealing that TERT, SIRT1 and SIRT6 expression was decreased in the aged BMSCs. The morphology, immunophenotype, differentiation potential, proliferation potential, and antiaging effects of aged and young BMSCs on 293T cells were compared. The expression of aging-related genes and the difference between the secreted cytokines in natural aging and induced aging BMSCs were observed. The transcriptome of peripheral blood mononuclear cells from macaques was analyzed by high-throughput sequencing. Finally, the transcriptional characteristics and regulatory mechanisms of gene transcription in aging macaques were investigated.

Isolation, purification and identification of antioxidants in an aqueous aged garlic extract.

An aqueous aged garlic extract (AGE) was prepared by soaking sliced garlic in water for 20days at room temperature (23-25 °C). In order to locate the antioxidant ingredients of the aqueous AGE, an activity-guided fractionation approach using ABTS assay, DPPH assay and FRAP assay were conducted to guide the fractionation by means of extraction, column chromatography and semi-preparative HPLC. Some phenols and organosulfur compounds were identified as antioxidants in AGE by GC-MS. Furthermore, UV, IR, ESI-MS, NMR and specific rotation experiments led to the identification of l-phenylalanine, l-tryptophan, (3S)-1,2,3,4-tetrahydro-ß-carboline-3-carboxylic acid, (1S,3S)-1-methyl-1,2,3,4-tetrahydro-ß-carboline-3-carboxylic acid, and (1R,3S)-1-methyl-1,2,3,4-tetrahydro-ß-carboline-3-carboxylic acid as the major antioxidants in the AGE. The EC50 values of these purified tetrahydro-ß-carboline derivatives were 0.625-1.334 µmol/mL and 1.063-2.072 µmol/mL in ABTS assay and DPPH assay, respectively. It is the first time for us to identify (3S)-1,2,3,4-tetrahydro-ß-carboline-3-carboxylic acid as an in vitro antioxidant in AGE.

Sensitive and selective electrochemical determination of quinoxaline-2-carboxylic acid based on bilayer of novel poly(pyrrole) functional composite using one-step electro-polymerization and molecularly imprinted poly(o-phenylenediamine).

A facile and efficient molecularly imprinted polymer (MIP) recognition element of electrochemical sensor was fabricated by directly electro-polymerizing monomer o-phenylenediamine (oPD) in the presence of template quinoxaline-2-carboxylic acid (QCA), based on one-step controllable electrochemical modification of poly(pyrrole)-graphene oxide-binuclear phthalocyanine cobalt (II) sulphonate (PPY-GO-BiCoPc) functional composite on glassy carbon electrode (GCE). The MIP film coated on PPY-GO-BiCoPc functional composite decorated GCE (MIP/PPY-GO-BiCoPc/GCE) was presented for the first time. The synergistic effect and electro-catalytic activity toward QCA redox of PPY-GO-BiCoPc functional composite were discussed using various contrast tests. Also, the effect of experimental variables on the current response such as, electro-polymerization cycles, template/monomer ratio, elution condition for template removal, pH of the supporting electrolyte and accumulation time, were investigated in detail. Under the optimized conditions, the proposed MIP sensor possessed a fast rebinding dynamics and an excellent recognition capacity to QCA, while the anodic current response of square wave voltammetry (SWV) was well-proportional to the concentration of QCA in the range of 1.0×10(-8)-1.0×10(-4) and 1.0×10(-4)-5.0×10(-4) mol L(-1) with a low detection limit of 2.1 nmol L(-1). The established sensor was applied successfully to determine QCA in commercial pork and chicken muscle samples with acceptable recoveries (91.6-98.2%) and satisfactory precision (1.9-3.5% of SD), demonstrating a promising feature for applying the MIP sensor to the measurement of QCA in real samples.

Association between interleukin-10 gene polymorphism -592 (A/C) and peritoneal transport in patients undergoing peritoneal dialysis.

AIM: The aim of this analysis was to know whether these three cytokine polymorphisms, including interleukin-6 (IL-6; -572 G/C), tumour necrosis factor-α (TNF-α; -308 G/A), and IL-10 (-592 A/C) have an effect on baseline peritoneal transport property and longitudinal evolution of peritoneal function. METHODS: A total of 141 stable peritoneal dialysis (PD) patients with mean treatment duration of 84.4 ± 34.2 months were enrolled. We genotyped these three cytokine polymorphisms, together with clinical parameters that were included as factors affecting longitudinal change of property of peritoneal transport over the first 3 year period after commencing therapy. RESULTS: There was no significant association between genotypes and baseline peritoneal transport property. The -592 A/C polymorphism of IL-10 was associated with longitudinal change of peritoneal transport. The ratio of D/P creatinine was significantly higher in patients with AA than those with CC/CA genotypes at 12 months (0.65 ± 0.11 vs 0.62 ± 0.09, P = 0.048) and 24 months (0.64 ± 0.12 vs 0.59 ± 0.09, P = 0.018). In addition, patients with increased peritoneal transport have greater frequency distribution of AA genotype and A allele. Logistic regression analysis revealed that -592 A allele was an independent predictor for the increase in D/P creatinine over the first 12 month period (odds ratio: 2.482, P = 0.017). There was no correlation between either polymorphism of IL-6 -572 (G/C) or TNF-α-308 (G/A) and longitudinal change of peritoneal function. CONCLUSIONS: Single nucleotide polymorphism of IL-10 -592 (A/C) was associated with longitudinal evolution of peritoneal transport rate in PD patients rather than the baseline peritoneal characteristics.

Proinflammatory cytokines, hepatocyte growth factor and adipokines in peritoneal dialysis patients.

Chronic inflammation is a well-recognized complication in dialysis patients and a potential role of the adipose tissue as an important tissue of origin contributing to inflammation has been proposed. Stable peritoneal dialysis (PD) patients were enrolled to investigate the relationship between serum levels of proinflammatory cytokines and adipokines. Our results revealed that there was a strong association between high sensitivity C-reactive protein and interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-alpha) but not with IL-10 and IL-18. IL-6 correlated with TNF-alpha, IL-10, and IL-18. No association was found between IL-10 and IL-18. Adiponectin was positively correlated with all proinflammatory cytokines, except IL-10. No significant association was found between resistin and proinflammatory cytokines. Hepatocyte growth factor (HGF) was directly related to proinflammatory cytokines but not with adipokines. The presence of residual kidney function (RKF) affected IL-6, TNF-alpha, and HGF levels. The peritoneal transport property did not influence inflammatory cytokine and adipokine levels. In conclusion, there was a close relationship between proinflammatory cytokines and adipokines. HGF correlated with proinflammatory cytokines but not with adipokines. The PD-related factors such as RKF, peritoneal property and dialysis glucose load affected levels of proinflammatory cytokines. Body mass index was an important determinant of leptin and adiponectin in PD patients.

Factors associated with blood concentrations of indoxyl sulfate and p-cresol in patients undergoing peritoneal dialysis.

BACKGROUND: Accumulating evidence supports the important role of protein-bound uremic toxins such as indoxyl sulfate and p-cresol in uremic syndrome. They exert direct deleterious effects on a variety of cells and could link to clinical outcome. Factors relevant to indoxyl sulfate and p-cresol levels in peritoneal dialysis (PD) patients have rarely been investigated. We conducted a cross-sectional study to analyze the factors that correlate with both total and free indoxyl sulfate and p-cresol. METHODS: 182 stable PD patients with mean PD therapy duration 38.5 +/- 33.3 months were enrolled. Their mean age was 48.9 +/- 13.5 years; 62.6% (114/182) were female patients. Demographic data, including age, gender, and PD therapy duration, were reviewed and recorded. PD-associated features such as residual kidney function (RKF), peritoneal transport property, and dialysis modality were also recorded. Hemoglobin, blood urea nitrogen (BUN), serum creatinine, C-reactive protein, interleukin (IL)-6, and IL-10 were measured. Levels of total and free indoxyl sulfate and p-cresol were determined. RESULTS: Patients without RKF had lower Kt/V and weekly creatinine clearance and higher serum creatinine and IL-6 levels. These patients also had higher total and free indoxyl sulfate levels. There was no difference in indoxyl sulfate or p-cresol levels compared to patients with different peritoneal transport properties or with different treatment modalities. Multivariate regression analysis revealed that weekly creatinine clearance and serum creatinine were independent associates of total indoxyl sulfate level; IL-6, total indoxyl sulfate, and free p-cresol were associated with free indoxyl sulfate level. Weekly creatinine clearance and free p-cresol level independently correlated with total p-cresol; while gender, total p-cresol, and free indoxyl sulfate were associated with free p-cresol level. CONCLUSION: The free forms of indoxyl sulfate and p-cresol constituted a small portion of their total forms. The presence of RKF affected levels of free and total indoxyl sulfate. IL-6 level was significantly associated with free indoxyl sulfate level. There was a close relationship between indoxyl sulfate and p-cresol levels in their free forms in PD patients.