A novel four-gene signature for predicting the prognosis of hepatocellular carcinoma.

OBJECTIVE: To identify and utilize gene signatures for the prognostic evaluation of postoperative patients with hepatocellular carcinoma (HCC). METHODS: The gene mRNA expression profiles and corresponding clinicopathological data of postoperative patients with HCC were downloaded from The Cancer Genome Atlas (TCGA) database. Highly differentially expressed genes (DEGs) in tumor tissues compared to adjacent tissues were identified, and their associations with the overall survival (OS) of HCC patients were analyzed. The strongly associated genes were used to develop a prognostic score for the survival stratification of HCC, and the underlying mechanisms were analyzed using bioinformatics. RESULTS: A total of 376 DEGs were identified and four DEGs (ADH4, COL15A1, RET and KCNJ16) were independently associated with OS. A prognostic score derived from the four genes could effectively stratify HCC patients with different OS outcomes, independent of clinical parameters. Patients with high scores exhibited poorer OS than patients with low scores (HR 5.526, 95% CI: 2.451-12.461, p < .001). The four genes were involved in cancer-related biological processes and were independent of each other in bioinformatics analyses. CONCLUSION: Four genes strongly associated with the prognosis of postoperative patients with HCC were identified, and the derived prognostic score was simple and valuable for overall survival prediction.

[Protective effect of Longxue Tongluo capsule on oxidized low-density lipoprotein damage to human umbilical vein endothelial cells].

To observe the protective effect of Longxue Tongluo capsule (LTC) on human umbilical vein endothelial cells (EAhy.926 cells) injury induced by oxidized low-density lipoprotein (ox-LDL, 100 mg·L⁻¹). The effect of the cell viability of LTCin alleviating OX-LDL-induced endothelial cell injury was determined by MTT and LDH assay. The effect of LTC on lactic dehydrogenase (LDH), nitric oxide (NO), super oxide dlsmutase (SOD) and malondialdehyde (MDA) levels were detected by corresponding assay kits according to manufacturer's instruction. The effect of LTC on the protein expressions of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), p65, p-p65, IKB and p-IKB were detected by Western blot. The results showed that compared with the normal control group, the activity of EAhy.926 cells was significantly decreased, LDH leakage (P<0.01) increased, NO content and SOD activity significantly decreased (P<0.01, P<0.05), and the expressions of ICAM-1, VCAM-1, p-p65/p65 and p-IKB(P<0.05)increased.This study demonstrated that LTC had no significant effect on the growth of normal cells. The treatment with LTC significantly promoted the proliferation of vascular endothelial cells damagedby ox-LDL, decreased MDA content and LDH release, andincreased the activity of SOD and NO content. Meanwhile, ox-LDL significantly increased the expressions of ICAM-1, VCAM-1, p-p65/p65, p-IKB/IKB in Eahy.926 cells; these effects were suppressed by LTC at 1, 2 mg·L⁻¹. In conclusion, LTC has a significant protective effect on human umbilical vein endothelial cells caused by ox-LDL. This study suggested that LTC has a certain therapeutic effect on AS.

Utility of Assessing Cytokine Levels for the Differential Diagnosis of Pneumonia in a Pediatric Population.

OBJECTIVES: Although pneumonia is easily diagnosed, determining the causative agent is difficult due to low pathogen detection rates. We performed a prospective observational study to evaluate the utility of measuring inflammatory cytokine levels to discriminate between pneumonia caused by typical bacteria, respiratory syncytial virus, or Mycoplasma pneumoniae in a pediatric population. DESIGN: Serum inflammatory cytokine levels at early stages of the disease were evaluated for pneumonia caused by the three different pathogenic microorganisms. SETTING: The Children's Hospital of Zhejiang University School of Medicine, China. PATIENTS: One hundred sixty-six patients with bacterial pneumonia, 182 with M. pneumonia, and 167 with respiratory syncytial virus pneumonia. MEASUREMENTS AND MAIN RESULTS: The levels of interleukin-6 for pneumonia were significantly higher with typical bacteria than with either Mycoplasma pneumoniae or respiratory syncytial virus (p < 0.001). The area under the curve for serum concentrations of interleukin-6 was 0.997. A serum interleukin-6 level of greater than or equal to 93.0 pg/mL had 100.0% sensitivity and 99.14% specificity in discriminating bacterial pneumonia from respiratory syncytial virus pneumonia and Mycoplasma pneumoniae pneumonia. The interleukin-6 levels were higher in patients with Mycoplasma pneumoniae pneumonia than in those with respiratory syncytial virus pneumonia (p < 0.001). They also simultaneously had lower interleukin-10 levels than patients with respiratory syncytial virus pneumonia who had interleukin-10 levels comparable to those of patients with bacterial pneumonia, indicating a significant difference in the interleukin-6/interleukin-10 ratio between patients with Mycoplasma pneumoniae pneumonia and respiratory syncytial virus pneumonia (median interleukin-6/interleukin-10 ratio, 2.5 vs 0.5; p < 0.001). At an optimal cut-off value of 0.8, the interleukin-6/interleukin-10 ratio showed 90.3% sensitivity and 88.0% specificity. CONCLUSIONS: These results suggest that interleukin-6 is a good biomarker for identifying bacterial pneumonia and that the interleukin-6/interleukin-10 ratio is an effective biomarker for discriminating Mycoplasma pneumoniae pneumonia from respiratory syncytial virus pneumonia.

[Pharmacology research on PXR as a potential target in screening bioactive components of Chinese material medica].

Pregnane X receptor (PXR) is key transcription factors which mainly regulate the expression of CYP3A genes. At the molecular level, PXR has been revealed the protection mechanism of the body against xenochemicals and a major mode of the drug-drug interactions. Besides playing an important role in drug metabolism and interactions, PXR and its target genes also play an important role in maintaining normal physiological function and homeostasis. Therefore, it is necessary to study the regulation of PXR and its related pharmacological effects of TCM and natural products, and to provide new clues for the new pharmacological pathway.

[Development and identification of monoclonal antibodies of cape jasmine proteins in Reduning injection].

Liposoluble cape jasmine proteins were used to immunize BALB/C mice. Indirect ELISA was utilized to develop one monoclonal antibody by integrating SP2/0 cells and spleen cells from immunized BALB/C mice. The subclass of the monoclonal antibody was identified as IgG2b, with Kappa chain as its light chain. The ascite titer of 2H8 monoclonal antibody was 1:204 080. Western-blot analysis proved that 2H8 reacted with cape jasmine proteins to identify specific liposoluble protein with molecuar weight of around 58.5 kDa. Dot-ELISA was established with 2H8 ascites as the primary antibody, showing the minimum detectable amount of 19.5 ng. This study lays a foundation for the development of protein kits of Reduning injection.

Association between vitamin D level and pediatric inflammatory bowel disease: A systematic review and meta-analysis.

Background: Previous studies have reported that the incidence of pediatric inflammatory bowel disease (IBD) is related to vitamin D, but it is still unclear. This study intends to calculate the relationship between pediatric IBD and vitamin D. Methods: A comprehensive literature search from inception to January 2023 was performed in the PubMed, EMBASE, Medline, Web of Science, and Google Scholar databases. Relevant data were extracted as required and used for subsequent calculations. Results: Sixteen papers were included, and there was no significant difference between the average vitamin D level in IBD patients and healthy controls. In addition, the overall pooled results showed that C-reactive protein (CRP) was 2.65 higher before vitamin D supplementation than after supplementation [SMD = 2.65, 95% CI = (2.26, 3.04)]. Moreover, patients with IBD in remission were 0.72 higher before vitamin D supplementation than after supplementation [OR = 0.72, 95% CI = (0.52, 1.00)]. Conclusion: This study suggested that there was no obvious relationship between pediatric IBD and vitamin D, while vitamin D supplementation can improve disease activity. Therefore, follow-up still needs many prospective studies to confirm the relationship between pediatric IBD and vitamin D.

Aptamer-Based Triple Serum Fluorescence Intensity Assay: A Novel and Feasible Method for the Clinical Diagnosis of Primary Hepatic Carcinoma.

Background and Aims: Aptamers are artificial ligands that bind to biological targets with high specificity and affinity. We previously selected a group of aptamers against the serum of primary hepatic carcinoma (PHC) via systematic evolution of ligands by exponential and enrichment (SELEX) method, and some of the aptamers were valuable for PHC diagnosis in polyacrylamide gel electrophoresis (PAGE) analysis. Here, we used aptamers to develop a novel method suitable for the clinical diagnosis of PHC. Methods: The intensities of serum autofluorescence, cell-free DNA (cfDNA)-related fluorescence and aptamer-related fluorescence, named the aptamer-based triple serum fluorescence intensity (ATSFI), were sequentially measured at 8 °C and 37 °C in one tube by using a real-time polymerase chain reaction (PCR) system as a fluorimeter in patients with PHC (n=346) or liver cirrhosis (n=321). The diagnostic performances of ATSFI indicators alone and in combination were evaluated by area under the receiver operator characteristic curve (AUROC), and the underlying clinical mechanisms were analyzed by bivariate correlation. Results: The measurement of ATSFI was high throughput, rapid, convenient, and low cost. The aptamer-related fluorescence indicator SEA-SE37 was the most valuable for PHC diagnosis among all fluorescence indicators and superior to alpha-fetoprotein (AFP) (AUROC 0.879 vs. 0.836). The logistic model of ATSFI indicators exhibited excellent diagnostic performance for PHC, including AFP-negative, early and small PHCs, with AUROCs of 0.935-0.950 and accuracies of 86.8-88.3%. The diagnostic performance was further improved when ATSFI indicators were combined with AFP, with AUROCs of approximately 0.95 and accuracies of approximately 90%, suggesting ATSFI was independent of but complementary to AFP in PHC diagnosis. ATSFI models were highly valuable in clinical decision-making. The aptamer-related fluorescence intensity was generally independent of the clinicopathological characteristics of PHC but correlated with laboratory characteristics of PHC serum. Conclusions: The ATSFI assay is a novel, robust and feasible method for the clinical diagnosis of PHC.

[Galaxy/quasar classification based on nearest neighbor method].

With the wide application of high-quality CCD in celestial spectrum imagery and the implementation of many large sky survey programs (e. g., Sloan Digital Sky Survey (SDSS), Two-degree-Field Galaxy Redshift Survey (2dF), Spectroscopic Survey Telescope (SST), Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) program and Large Synoptic Survey Telescope (LSST) program, etc.), celestial observational data are coming into the world like torrential rain. Therefore, to utilize them effectively and fully, research on automated processing methods for celestial data is imperative. In the present work, we investigated how to recognizing galaxies and quasars from spectra based on nearest neighbor method. Galaxies and quasars are extragalactic objects, they are far away from earth, and their spectra are usually contaminated by various noise. Therefore, it is a typical problem to recognize these two types of spectra in automatic spectra classification. Furthermore, the utilized method, nearest neighbor, is one of the most typical, classic, mature algorithms in pattern recognition and data mining, and often is used as a benchmark in developing novel algorithm. For applicability in practice, it is shown that the recognition ratio of nearest neighbor method (NN) is comparable to the best results reported in the literature based on more complicated methods, and the superiority of NN is that this method does not need to be trained, which is useful in incremental learning and parallel computation in mass spectral data processing. In conclusion, the results in this work are helpful for studying galaxies and quasars spectra classification.

AFP-L3 for the diagnosis of early hepatocellular carcinoma: A meta-analysis.

BACKGROUND: The present study aimed to systematically evaluate the diagnostic value of an isoform of alpha-fetoprotein (AFP), AFP-L3, for early hepatocellular carcinoma (HCC) by a meta-analysis. METHODS: Diagnostic reports of AFP-L3% in early HCC were searched in the PubMed, Web of Science, Cochrane Library, and Embase databases up to December 2019. The retrieved literature was reviewed, and eligible articles were selected. Data were extracted from the eligible articles, and the risk of bias was evaluated according to the Quality Assessment of Diagnostic Accuracy Studies scale. Statistical analyses were conducted by MetaDiSc1.4 and RevMan5.3 software. The sensitivities, specificities, and diagnostic odds ratios were pooled. The summary receiver operating characteristic curve was drawn, and the area under the curve was calculated. RESULTS: Six studies with acceptable quality were included in the meta-analysis involving 2447 patients. No threshold effect was observed among the 6 studies, but there was obvious heterogeneity. The pooled sensitivity, specificity, and positive and negative likelihood ratios of AFP-L3% for the diagnosis of early HCC were 0.34 (95% CI 0.30-0.39, P < .0001), 0.92 (95% CI 0.91-0.93, P < .0001), 4.46 (95% CI 2.94-6.77, P = .0033), and 0.71 (95% CI 0.61-0.82, P = .0004), respectively. The diagnostic odds ratio was 6.78 (95% CI 4.02-11.44, P = .0074). The the area under the curve of the summary receiver operating characteristic was 0.755 (95% CI 0.57-0.94). CONCLUSION: AFP-L3% has high specificity but low sensitivity for diagnose early HCC, suggesting that AFP-L3% is more valuable for excluding HCC in conditions with elevated AFP than for diagnosing early HCC. In addition, a hypersensitive detection method can improve the diagnostic accuracy of AFP-L3% for early HCC.