E2F2 stimulates CCR4 expression and activates synovial fibroblast-like cells in rheumatoid arthritis.

AIM OF THE STUDY: E2F transcription factor 2 (E2F2) has increased expression in synovial tissues of rheumatoid arthritis (RA) and stimulates interleukin (IL)-1 α and IL-ß production in cultured RA synovial fibroblast-like cells (RASF), which supports the importance of E2F2 in RA pathogenesis. This study investigated the effect and mechanism of E2F2 in RA. MATERIAL AND METHODS: Cultured RASF were transfected with anti-E2F2 siRNA, and the expression profile was analyzed with an inflammatory response and autoimmunity PCR array loaded with 84-relative genes to explore the pathogenic pathway of E2F2. Apoptosis, migration and tube-like structure formation in the RASF with transfection of anti-E2F2 siRNA or E2F2-expressing plasmids were examined using flow cytometry, transwell assays and Matrigel assays, respectively. RESULTS: Significantly decreased expression of chemokine receptor 4 (CCR4) was detected in RASF with inhibited E2F2 expression, and the CCR4 expression was increased in RASF with transfection of E2F2-expressing plasmids. Silencing E2F2 expression stimulated apoptosis, but retarded migration and tube-like structure formation in RASF. The opposite observation was obtained in RASF with E2F2 overexpression. CONCLUSIONS: High E2F2 expression decreases apoptosis and increases migration and tube-like structure ability in RASF and might perform this role by up-regulating CCR4 expression, which ultimately contributes to the disease progression of RA synovial tissues.

Diagnostic value of alpha-fetoprotein-L3 and Golgi protein 73 in hepatocellular carcinomas with low AFP levels.

This study aimed to investigate the clinical values of serum alpha-fetoprotein-L3 (AFP-L3) and Golgi protein 73 (GP73) in the diagnosis of hepatocellular carcinoma (HCC) with low alpha-fetoprotein (AFP). From January 2011 to December 2013, 50 low-AFP HCC patients confirmed by the color Doppler flow imaging (CDFI) and pathological examinations were collected. Forty-five patients with chronic liver diseases were also selected, including 29 liver cirrhosis patients, 15 chronic hepatitis B patients, and one severe hepatitis patient. Furthermore, 100 health volunteers with no evidence of benign or malignant liver diseases were included. The enzyme-linked immunosorbent assay (ELISA) method was applied to the GP73 quantitative assay. Serum AFP concentrations were determined using immunoassays utilizing enhanced chemiluminescence. Diagnostic accuracy of GP73 and AFP-L3 assays for low-AFP HCC was evaluated using receiver operating characteristic (ROC) curve analysis. Statistical analyses were conducted with the GraphPad Prism 5.0 software. Low-AFP HCC patients (35/50) exhibited higher positive rates of AFP-L3 than non-HCC patients (5/45) and healthy controls (2/100) (both P < 0.05). There were also significant differences in the positive rate of GP73 of low-AFP HCC patients (40/50) compared to those of non-HCC patients (3/45) and healthy controls (1/100) (both P < 0.05). However, no obvious differences in the positive rates of AFP-L3 and GP73 were observed between non-HCC patients and healthy controls (both P > 0.05). ROC curves showed that the area under the curve (AUC) of AFP-L3 for the diagnosis of low-AFP HCC was 0.6994 (sensitivity [Sen] = 70.0 %, specificity [Spe] = 95.2 %, accuracy = 88.7 %), while the AUC of GP73 was 0.8411 (Sen = 80.0 %, Spe = 97.2 %, accuracy = 92.8 %). Compared with single detection, the combination of AFP-L3 and GP73 levels for the diagnosis of low-AFP HCC showed higher Sen (94.0 %), Spe (93.1 %), and better accuracy (93.3 %). Our findings provide empirical evidence that the combination of AFP-L3 and GP73 is a good diagnostic strategy for low-AFP HCC.

Agreement of Potassium, Sodium, Glucose, and Hemoglobin Measured by Blood Gas Analyzer With Dry Chemistry Analyzer and Complete Blood Count Analyzer: A Two-Center Retrospective Analysis.

Background: Blood gas analyzers (BGAs) and dry biochemistry analyzers for potassium and sodium are based on direct electrode methods, and both involve glucose oxidase for glucose detection. However, data are lacking regarding whether the results of the two assay systems can be used interchangeably. In addition, there remains controversy over the consistency between BGA-measured hemoglobin and complete blood count analyzer data. Here, we compared the consistency of sodium, potassium, glucose, and hemoglobin levels measured by BGA and dry chemistry and complete blood count analyzers. Methods: Data from two teaching hospitals, the Zhejiang Provincial People's Hospital (ZRY) and the Qianfoshan Hospital (QY), were retrospectively analyzed based on dry biochemistry and complete blood count analyzer results as the reference system (X) and BGA as the experimental system (Y). Plasma was used for biochemical analysis at the ZRY Hospital, and serum at the QY Hospital. Paired data from the respective hospitals were evaluated for consistency, and biases between methods were assessed by simple correlation, Passing-Bablok regression, and Bland-Altman analyses. Results: The correlations of potassium, sodium, glucose, and hemoglobin measured by BGA and dry biochemistry and complete blood count analyzers were high, at 0.9573, 0.8898, 0.9849, and 0.9883 for the ZRY Hospital and 0.9198, 0.8591, 0.9764, and 0.8666, respectively, for the QY Hospital. The results of Passing to Bablok regression analysis showed that the predicted biases at each medical decision level were within clinically acceptable levels for potassium, sodium, glucose, and hemoglobin at the ZRY Hospital. Only the predicted bias of glucose was below the clinically acceptable medical decision levels at the QY Hospital, while potassium, sodium, and hemoglobin were not. Compared with the reference system, the mean bias for BGA measurements at the ZRY Hospital was -0.08 mmol/L (95% confidence interval [CI] -0.091 to -0.069) for potassium, 1.2 mmol/L (95% CI 1.06 to 1.42) for sodium, 0.20 mmol/L (95% CI 0.167 to 0.228) for glucose, and -2.8 g/L for hemoglobin (95% CI -3.14 to -2.49). The mean bias for potassium, sodium, glucose, and hemoglobin at the QY Hospital were -0.46 mmol/L (95% CI -0.475 to -0.452), 3.7 mmol/L (95% CI 3.57 to 3.85), -0.36 mmol/L (95% CI -0.433 to -0.291), and -8.7 g/L (95% CI -9.40 to -8.05), respectively. Conclusion: BGA can be used interchangeably with plasma electrolyte results from dry biochemistry analyzers but does not show sufficient consistency with serum electrolyte results from dry biochemistry analyzers to allow data interchangeability. Good consistency was observed between BGA and plasma or serum glucose results from dry biochemistry analyzers. However, BGA-measured hemoglobin and hematocrit assay results should be treated with caution.

Effects of cAMP and ß-adrenergic receptor antagonists on the function of peripheral T helper lymphocytes in patients with heart failure.

OBJECTIVE: To observe the effects of cyclic adenosine monophosphate (cAMP) in peripheral lymphocytes on T helper 1 (TH1)/TH2 cytokine ratios and to investigate the potential impact and mechanism of ß-adrenergic receptor antagonists on immune function in patients with chronic heart failure (CHF). METHODS: Sixty-nine patients with New York Heart Association functional class II-IV CHF and a radionuclide left ventricular ejection fraction of less than 45% received carvedilol or metoprolol in a randomized fashion. Thirty healthy persons were studied as controls. Interferon (IFN)-γ and interleukin (IL)-10 in CD4+ T lymphocytes were quantified by three-color flow cytometry. cAMP levels in peripheral blood mononuclear cells were tested by radioimmunoassay at baseline and 6 months after treatment. RESULTS: The levels of lymphocyte cAMP in CHF patients were significantly lower than in normal controls (p < 0.01). The IFN-γ/IL-10 ratio was significantly higher in CHF patients (p < 0.01). The levels of cAMP, IFN-γ and IL-10 among CHF patients with different pathogenic factors displayed no significant differences (p > 0.05). The lymphocyte cAMP level was negatively correlated with the IFN-γ/IL-10 ratio (p < 0.01). After treatment with metoprolol and carvedilol, the IFN-γ/IL-10 ratio in the CHF patients was dramatically decreased (p < 0.01 for each drug) and lymphocyte cAMP was remarkably increased (p < 0.01 for each drug). CONCLUSION: These results suggest that the decrease of cAMP affects the TH1/TH2 phenotype in peripheral lymphocytes of CHF patients. ß-Blocking medications appear to have a beneficial effect on the TH1/TH2 balance and on the immune system through increasing production of cAMP, offering further evidence to support the use of ß-adrenergic receptor blockers to treat CHF.

Clinical laboratory evaluation of COVID-19.

COVID-19, caused by SARS-CoV-2, is a highly infectious disease, and clinical laboratory detection has played important roles in its diagnosis and in evaluating progression of the disease. Nucleic acid amplification testing or gene sequencing can serve as pathogenic evidence of COVID-19 diagnosing for clinically suspected cases, and dynamic monitoring of specific antibodies (IgM, IgA, and IgG) is an effective complement for false-negative detection of SARS-CoV-2 nucleic acid. Antigen tests to identify SARS-CoV-2 are recommended in the first week of infection, which is associated with high viral loads. Additionally, many clinical laboratory indicators are abnormal as the disease evolves. For example, from moderate to severe and critical cases, leukocytes, neutrophils, and the neutrophil-lymphocyte ratio increase; conversely, lymphocytes decrease progressively but are over activated. LDH, AST, ALT, CK, high-sensitivity troponin I, and urea also increase progressively, and increased D-dimer is an indicator of severe disease and an independent risk factor for death. Severe infection leads to aggravation of inflammation. Inflammatory biomarkers and cytokines, such as CRP, SAA, ferritin, IL-6, and TNF-α, increase gradually. High-risk COVID-19 patients with severe disease, such as the elderly and those with underlying diseases (cardiovascular disease, diabetes, chronic respiratory disease, hypertension, obesity, and cancer), should be monitored dynamically, which will be helpful as an early warning of serious diseases.

Alpha-fetoprotein-L3 and Golgi protein 73 may serve as candidate biomarkers for diagnosing alpha-fetoprotein-negative hepatocellular carcinoma.

Currently, there is no reliable biomarker for use in diagnosing alpha-fetoprotein (AFP)-negative hepatocellular carcinoma (HCC). Such a biomarker would aid in making an early diagnosis of AFP-negative HCC, ensuring the timely initiation of treatment. This study examined AFP-L3 and Golgi protein 73 (GP73) as candidate biomarkers for AFP-negative HCC. The affinity adsorption method and enzyme-linked immunoassays were separately used to determine serum levels of AFP-L3 and GP73 in 50 patients with AFP-negative HCC, 30 non-HCC patients, and 50 healthy subjects. Fifty percent of patients with AFP-negative HCC tested positive for AFP-L3, while 3.33% of non-HCC patients and 2.00% of healthy subjects were AFP-L3 positive. Patients with AFP-negative HCC had significantly higher serum levels of AFP-L3 compared to non-HCC patients and healthy individuals; however, there was no significant difference in the AFP-L3 levels of non-HCC patients and healthy subjects. Sixty-six percent of patients with AFP-negative HCC tested positive for GP73, while 10% of non-HCC patients and 0% of healthy subjects were GP73-positive. Patients with AFP-negative HCC had significantly higher serum levels of GP73 compared to non-HCC patients and healthy subjects, but there was no significant difference between the GP73 levels of non-HCC patients and healthy individuals. Moreover, 20 patients with AFP-negative HCC were both AFP-L3- and GP73-positive, while no non-HCC patients or healthy subjects tested positive for both markers. Either AFP-L3 or GP73 may be used as a biomarker for diagnosing AFP-negative HCC, while their combined use provides improved diagnostic accuracy and greater sensitivity.

Maxilla-nasion-mandible (MNM) angle: an indicator to assess fetal facial profile in first-trimester of pregnancy.

OBJECTIVE: The aim of this study was to observe whether there existed significant differences in the maxilla-nasion-mandible angle (MNM) between the first- and second-trimester of pregnancy, and to observe its predictive values for trisomy 18. METHODS: Two experienced ultrasonologists used 2D and 3D ultrasound imaging techniques to obtain the facial sagittal sections of fetuses in the first-trimester of pregnancy (crown-rump length 45-84 mm), respectively, so as to measure MNM. RESULTS: MNM could be measured in 91 % of normal fetuses, and the measurement differences by different operators in different groups were <1.1°; average MNM was 11.0°, and no significant change was observed in different gestational ages (P = 0.15). The average of MNMs in fetuses with trisomy 18 was 16.6°, which were all higher than the 95th percentile of normal measurement data. The sensitivity and specificity of increased MNM on the abnormal detection of trisomy 18 were 54.7 and 97.4 %, respectively. CONCLUSIONS: The feasibility and reproducibility of measuring MNM in early pregnancy were good. MNM had certain suggestive roles for aneusomic chromosomal abnormalities, especially for fetuses with trisomy 18.