Diagnostic Value of Combined Detection via Protein Induced by Vitamin K Absence or Antagonist II, Alpha-Fetoprotein, and D-Dimer in Hepatitis B Virus-Related Hepatocellular Carcinoma.

Purpose: We aimed to explore the clinical diagnostic value of combined detection via protein induced by vitamin K absence or antagonist II (PIVKA-II), alpha-fetoprotein (AFP), and D-dimer (D-D) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Materials and Methods: We analyzed PIVKA-II, AFP, and D-D levels in 291 subjects comprising liver cirrhosis (LC) patients (n = 143) and HCC patients (n = 148). Receiver operating characteristic (ROC) curves were used to analyze and compare the clinical diagnostic value of the three biomarkers for HBV-related HCC alone and in combination. Results: The levels of PIVKA-II, AFP, and D-D were positively correlated with tumor size in HCC patients. The levels of PIVKA-II and AFP in early-stage HCC, advanced HCC, HBV DNA+ HCC, and HBV DNA- HCC patients were higher than those in LC patients, while the levels of D-D were lower. The area under the curve for combined detection was greater than that for single-index detection in early-stage HCC, advanced HCC, HBV DNA+ HCC, and HBV DNA- HCC patients. Conclusion: D-D may be a useful biomarker for the diagnosis of HBV-related HCC. The combined detection of PIVKA-II, AFP, and D-D had better diagnostic value for different types of HCC than the detection of individual biomarkers.

Expression and Correlation of IgG4 and IL-21 in Collagen-Induced Arthritis Rats.

PURPOSE: We explored the expression levels of IgG4 and interleukin (IL)-21 in the serum and ankle joints of collagen-induced arthritis (CIA) rats at different disease stages. MATERIALS AND METHODS: Wistar rats were randomly divided into normal and model groups, and the latter group was administered bovine type II collagen to induce arthritis. Enzyme-linked immunosorbent assay was performed at 21, 28, 35, and 42 days to detect IgG4 and IL-21 in the serum, followed by histological and immunohistochemical analyses of IgG4 and IL-21r in the ankle joint of rats. RESULTS: The contents of IgG4 and IL-21 in the serum of the CIA model group were positively correlated and increased with disease progression. The expression of IgG4 and IL-21 receptors in the ankle joint of the CIA model group was significantly higher than that in the control group. These proteins were closely related to the pathological score. The serum IL-21 level in the model group was closely related to the level of IL-21 receptor in the ankle joint. CONCLUSION: IL-21 may promote the occurrence and development of rheumatoid arthritis by combining with IL-21r to regulate the content of IgG4.

Nucleocytoplasmic trafficking and turnover mechanisms of BRASSINAZOLE RESISTANT1 in Arabidopsis thaliana.

Regulation of the nucleocytoplasmic trafficking of signaling components, especially transcription factors, is a key step of signal transduction in response to extracellular stimuli. In the brassinosteroid (BR) signal transduction pathway, transcription factors from the BRASSINAZOLE RESISTANT1 (BZR1) family are essential in mediating BR-regulated gene expression. The subcellular localization and transcriptional activity of BZR1 are tightly regulated by reversible protein phosphorylation; however, the underlying mechanism is not well understood. Here, we provide evidence that both BZR1 phosphorylation and dephosphorylation occur in the nucleus and that BR-regulated nuclear localization of BZR1 is independent from its interaction with, or dephosphorylation by, protein phosphatase 2A. Using a photoconvertible fluorescent protein, Kaede, as a living tag to distinguish newly synthesized BZR1 from existing BZR1, we demonstrated that BR treatment recruits cytosolic BZR1 to the nucleus, which could explain the fast responses of plants to BR. Additionally, we obtained evidence for two types of protein turnover mechanisms that regulate BZR1 abundance in plant cells: a BR- and 26S proteosome-independent constitutive degradation mechanism and a BR-activated 26S proteosome-dependent proteolytic mechanism. Finally, treating plant cells with inhibitors of 26S proteosome induces the nuclear localization and dephosphorylation of BZR1, even in the absence of BR signaling. Based on these results, we propose a model to explain how BR signaling regulates the nucleocytoplasmic trafficking and reversible phosphorylation of BZR1.

Serum hepatitis B virus ribonucleic acid and its influencing factors in chronic hepatitis B.

BACKGROUND: Hepatitis B virus (HBV) remains one of the most serious and prevalent health problems in the world. OBJECTIVES: To determine the serum hepatitis B virus (HBV) RNA levels in patients with chronic hepatitis B (CHB) with low HBV DNA levels and analyze the influencing factors. MATERIAL AND METHODS: Seventy-two CHB patients with low HBV DNA levels were enrolled and divided into 2 groups according to hepatitis B e antigen (HBeAg) status; their age, sex, the incidence of HBV RNA level < lower limit of detection (LLD), and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), quantitative determination of HBsAg (qHBsAg), HBV DNA, and HBV RNA levels were compared. The factors influencing serum HBV RNA levels < LLD and the correlation between serum HBV RNA levels, and serum ALT, AST, qHBsAg and HBV DNA levels were analyzed. RESULTS: In HBeAg-positive patients, serum AST, qHBsAg and HBV RNA levels were higher, and serum HBV DNA levels and incidence of HBV RNA < LLD were lower than those in HBeAg-negative patients (p < 0.05). Multivariate linear regression analysis revealed that HBeAg is a factor that significantly influences serum HBV RNA levels in patients with CHB (p < 0.05). Multivariate logistic regression analysis indicated that HBeAg and qHBsAg are factors that influence serum HBV RNA levels < LLD in patients with CHB. In HBeAg-positive patients, serum HBV RNA levels were positively correlated with qHBsAg and HBeAg. CONCLUSIONS: The serum HBV RNA levels in CHB patients with low HBV DNA levels varied according to HBeAg status. The HBeAg is a factor that significantly influences serum HBV RNA levels in patients with CHB, while HBeAg and qHBsAg are factors that significantly influence serum HBV RNA levels < LLD in patients with CHB.

[Thromboelastography-based assessment of coagulation function in patients with chronic kidney disease and the risk factors of hypercoagulability].

OBJECTIVE: To assess the changes in the coagulation profiles of patients with chronic kidney disease (CKD) using thromboelastography (TEG) and identify the risk factors of hypercoagulation in CKD patients. METHODS: A total of 128 patients with CKD admitted in Hunan Provincial People's Hospital between August, 2018 and May, 2019 were recruited. The results of conventional coagulation test and TEG were compared between patients with CKD and 21 healthy control adults. The patients with CKD were divided into hypercoagulation group with a maximum amplitude (MA) > 68 mm (n=66) and non-hypercoagulation group (MA≤68 mm, n=62). The laboratory indicators were compared between the groups, and the factors affecting the hypercoagulable state in patients with CKD were analyzed. RESULTS: The levels of fibrinogen and D-Dimer increased significantly in patients with CKD at different stages as compared with the control subjects (P < 0.05). In the patients with CKD, the reaction time and K time decreased while MA, α-angle and coagulation index increased significantly in patients in stage 3-4 and those in stage 5 either with or without hemodialysis compared with the control group (P < 0.05). The estimated glomerular filtration rate (eGFR), percentage of patients with diabetes mellitus, history of stroke, percentage of neutrophils, neutrophil-lymphocyte ratio, red blood cell count, hemoglobin levels, platelet count, serum creatinine, serum cystatin-C, serum albumin, and lipoprotein (a) all differed significantly between hypercoagulation group and non-hypercoagulation group (P < 0.05). The eGFR, platelet count and hemoglobin levels were identified as independent factors affecting hypercoagulability in patients with CKD (P < 0.05). CONCLUSIONS: s The hypercoagulable state of patients with CKD worsens gradually with the disease progression, and eGFR, platelet count and hemoglobin levels are all risk factors for the hypercoagulable state in patients with CKD.

Lipid nanoparticles co-loaded with miRNA-22 and methotrexate for enhanced anti-inflammatory response in rheumatoid arthritis.

Present investigation was aimed at developing methotrexate (MTX) and miR-22 mimics-loaded lipid nanoparticles for the effective treatment of rheumatoid arthritis. The dual therapeutics loaded nanoparticles was prepared and subjected to in vitro and in vivo characterizations. The in vivo study was performed on adjuvant- induced arthritis model. The addition of IL-1ß significantly decreased the expression of miR-22 levels in negative control groups, whereas miR-22 mimics treated cells showed significantly higher miR-22 expression compared to both the NC groups. MTX+miR-22 showed significantly lower cell viability compared to that of free MTX indicating a synergistic anti-inflammatory in the MH7A cells. To be specific, MTX/miR-22-loaded lipid nanoparticles (MTmiR-NP) showed the significantly lower cell viability compared to any other group indicating the potential of lipid nanoparticles. Consistently, MTmiR-NP exhibited a significantly higher cell apoptosis (~50%) compared to any other tested group further reiterating the nanoparticle-based combinational therapeutics. MTmiR-NP exhibited the significant reduction in the paw thickness and significantly lower arthritic score compared to all other groups on all time points. Present study clearly highlights the potential of lipid nanoparticles-based synergistic combination of MTX and miR-22 in achieving higher therapeutic response in rheumatoid arthritis treatment.