Guocai Lv

Effect of miRNA‐10b in regulating cellular steatosis level by targeting PPAR‐α expression, a novel mechanism for the pathogenesis of NAFLD

Background and Aim:  Accumulating evidence supports the effects of miRNA in lipid metabolism, providing a potential linkage between certain miRNA and non‐alcoholic fatty liver disease (NAFLD). We aimed to investigate the miRNA expression pattern in a steatotic L02 cell model and explore the function of certain miRNA target pairs.

Association between red cell distribution width and acute pancreatitis: a cross-sectional study

Objective We investigated whether red cell distribution width (RDW) was associated with mortality in patients with acute pancreatitis (AP). Design A cross-sectional study. Setting Patients with AP were recruited in the emergency department and healthy individuals were recruited in healthcare centre in the First Affiliated Hospital of Zhejiang University. Participants A total of 106 patients with AP and 204 healthy individuals were enrolled. Primary and secondary outcome measures Haematology and biochemistry results of the first test after admission were collected. The significance of the differences in RDW values among healthy individuals, non-survivors of patients with AP, and survivors of patients with AP was determined using one-way analysis of variance. Patients with AP were divided into three groups according to RDW tertiles. All patients with AP were followed up for at least 3 months. Receiver-operating characteristic (ROC) curve analysis and Kaplan-Meier analysis were used to evaluate RDW values to predict mortality of patients with AP. Results The RDW values were non-survivors of patients with AP>healthy individuals>survivors of patients with AP. Patients with AP with the highest RDW tertiles had the lowest levels of Ca, total protein, albumin, haemoglobin, white and red blood cell count, but the highest mortality. The area under the ROC curve of RDW was 0.846 (95% CI 0.727 to 0.964, p<0.001). With a cut-off value of 14.2 for RDW, sensitivity and specificity of RDW to predict mortality were 75.0% and 89.8%, and Kaplan-Meier analysis showed an increase in probability of death with high RDW values. Conclusions There is significant association between RDW and mortality of patients with AP.

Dynamic analysis of CD127 expression on memory CD8 T cells from patients with chronic hepatitis B during telbivudine treatment

BackgroundAccumulating evidence supports the theory that expression of CD127 on CD8 T cells during the process of antiviral immune response indicates a subset of effect CD8 T cells that successfully develop into fully protective memory. CD8 T cells expression of CD127 may be used as a predictor to evaluate disease status in chronic viral infection. The aim of this study was to investigate the CD127 expression level on different subsets of CD8 T cell and explore the relationship between CD127 expression on CD8 memory T cells and serum hepatitis B virus (HBV) DNA and hepatitis B e antigen (HBeAg) levels in patients with chronic hepatitis B (CHB). We also aimed to investigate the CD127 expression pattern on CD8 memory T cells of CHB patients who were treated with Telbivudine.Methods/ResultsTwenty HBeAg-positive CHB patients were selected and treated with telbivudine 600 mg/day for 48 weeks. The memory CD8 T cells were characterized by expression of CD45RA and CD27 markers. CD127 expression on the CD8 T-cell surface was measured by four-colour flow cytometry. Our results showed that CD127 expression on memory CD8 T cells was reduced in CHB patients. There was a strong negative correlation between CD127 expression on memory CD8 T cells and serum HBV DNA and HBeAg levels in CHB patients. Moreover, successful antiviral therapy increased CD127 expression on CD8 memory T cells as well as on HBV-specific CD8 T cells in CHB patients.ConclusionThese results suggest that diminished CD127 expression on CD8 memory T cells of CHB patients is a potential mechanism explaining cellular immune function impairment in CHB infection, and that CD127 expression on CD8 memory T cells is a useful indicator for evaluating the effects of anti-HBV therapy.

The significance of serum xanthine oxidase and oxidation markers in acute paraquat poisoning in humans

OBJECTIVES Determine xanthine oxidase (XO) activity and oxidative-stress parameters in human acute paraquat poisoning. DESIGN AND METHODS Twnty-five patients and 26 healthy control participants were recruited. Serum XO, superoxide dismutase (SOD), Glutathione (GSH) and malondialdehyde (MDA) were determined by spectrophotometric methods. RESULTS XO activity and MDA levels were higher and SOD activity and GSH level were lower in the patients group. XO activity and MDA level were significantly higher, and the GSH level and SOD activity were lower in the paraquat poisoning fatality group. There was a significant negative correlation between the XO activity and both the SOD and GSH, while there was a significant positive correlation between XO activity and the MDA level in the patients group. CONCLUSIONS XO activity contributes to the development of oxidative injury in patients with paraquat poisoning. Serum XO activity could be used as a marker for prognosis in human acute paraquat intoxication.

Hepatocytes treated with HBV X protein as cytotoxic effectors kill primary hepatocytes by TNF-alpha-related apoptosis-induced ligand-mediated mechanism.

Objective: To investigate the effect of HBV X protein (HBX) on TNF-α-related apoptosis-induced ligand (TRAIL) expression in HepG2 cells, and observe death of primary hepatocytes induced by HBX-transfected HepG2 cells. Methods: Western blot was used to detect the TRAIL expression in HepG2 cells transfected with mammalian expression plasmid pSG5UTPL-HBX. The reverse transcription-PCR was used to observe TRAIL mRNA transcription stimulated by HBX protein, and chromium release assay was used to detect death of primary hepatocyte induced by HBX-transfected HepG2 cells. Results: HBX could increase TRAIL expression and mRNA transcription in HepG2 cells in a dose-dependent manner. The C-terminal truncated version of HBX (HBXD1) is responsible for inducing TRAIL expression in HepG2 cells. Chromium release assay results showed that HBX-transfected HepG2 cells kill primary human hepatocytes by a TRAIL-mediated mechanism. Neutralizing anti-TRAIL inhibits the HepG2 killing. Conclusion: HBX protein increases TRAIL expression in HepG2 cells which induced death of primary hepatocytes. HBX protein may play an important role in mechanisms of hepatic cell death and hepatic inflammation caused by HBV infection.

The significance of serum uric acid level in humans with acute paraquat poisoning.

Hyperuricemia is a strong and independent predictor of all-cause mortality in cardiovascular disease and has been found to play a role in diseases exacerbated by oxidative stress and inflammation. This study aimed to evaluate whether serum uric acid (UA) level is an indicator of outcome in patients with acute paraquat poisoning. A total of 205 subjects who had attempted suicide by oral ingestion of paraquat were admitted to the emergency room between January 2009 and June 2014. Initial serum UA level and other laboratory parameters were measured. A total of 66 patients died during the 30 days after admission, corresponding to a 32.2% cumulative incidence of mortality. UA levels were higher in non-survivors than survivors (P < 0.001) and 30-day mortality increased with increasing baseline serum UA level (P < 0.001). In a prediction analysis for 30-day mortality, the serum UA level had a cut-off concentration of 284 µmol/L in female patients and 352 µmol/L in male patients. Multivariate Cox proportional hazards regression analyses showed that white blood cell counts and UA were independent prognostic factors. In conclusion, we showed that serum UA may be an independent predictor of 30-day mortality in patients with paraquat poisoning.

The Significance of the Measurement of Serum Xanthine Oxidase and Oxidation Markers in Patients with Acute Organophosphorus Pesticide Poisoning

This study investigated whether xanthine oxidase (XO) plays an important role in the mechanism of toxicity of acute organophosphorus pesticide poisoning (AOPP). The serum activities of XO, superoxide dismutase (SOD), paraoxonase-1 (PON1), butyrylcholinesterase (BChE) and malondialdehyde (MDA) were compared in 49 patients with AOPP and 50 age- and gender-matched healthy controls. Serum XO and MDA activities were higher and the serum SOD, PON1 and BChE activities were lower in the AOPP patients compared with the controls. Pearson correlation analysis demonstrated a significant negative correlation between XO activity and the SOD, PON1 and BChE activities, but a significant positive correlation between XO activity and MDA. These results suggest that increased activity of XO and decreased antioxidant enzyme activity contribute to the development of oxidative injury in AOPP patients. Thus, effective antioxidant therapy may be a therapeutic option following AOPP.

Assessment of Serum Antioxidant Status in Patients with Silicosis

Prolonged exposure to silica dust causes an imbalance in the generation of free radicals and in the antioxidant system, thereby inducing oxidative stress. The antioxidant status of 113 silicosis patients and 116 control subjects without silicosis was examined. Serum superoxide dismutase (SOD) activity and serum levels of malondialdehyde (MDA) and glutathione (GSH) were significantly higher in silicosis patients than in controls. The GSH level in patients with stage I silicosis was higher than that in patients with other stages, but there was no difference in serum MDA level and SOD activity between disease stages. The GSH level of patients who worked with air drills was significantly lower than that of patients in other occupations, whereas the MDA level was significantly elevated in patients who used air drills. Serum SOD activity did not differ significantly according to the occupational group. It is concluded that the measurement of serum SOD, GSH and MDA levels could be beneficial in the clinical evaluation of serum antioxidant status in silicosis patients.

Association Between Urinary Alpha1-Microglobulin Levels and Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study

Background: We aimed to explore the association between urinary alpha1-microglobulin (A1M) levels and nonalcoholic fatty liver disease (NAFLD) in a Chinese population. Study: We performed a cross-sectional study among 2,215 Chinese who attended their annual health examination at First Affiliated Hospital, College of Medicine, Zhejiang University. Urinary A1M-creatinine ratio and other clinical and laboratory parameters were measured. Results: A total of 20.9% of subjects fulfilled the diagnostic criteria of NAFLD. NAFLD subjects had significantly higher urinary A1M-creatinine ratios. These levels were positively associated with NAFLD prevalence. The association between A1M-creatinine ratio and NAFLD was independent of hyperglycemia status. Stepwise regression showed that urinary A1M-creatinine ratio was significantly associated with the risk for NAFLD. Urinary A1M-creatinine ratio was an independent factor predicting advanced fibrosis (FIB-4 ≥1.3) in NAFLD patients. Conclusions: Our results showed a significant association between urinary A1M-creatinine ratio and NAFLD.

Study on the serum oxidative stress status in silicosis patients

To determine whether oxidative-stress damage play an important role in the mechanism of silicosis, the oxidative stress parameters were investigated in silicosis patients and controls group. 128 silicosis patients and 130 healthy controls were included. The serum superoxide dismutase (SOD) activity and the levels of malonyldialdehyde (MDA) and glutathione (GSH) were analyzed. The levels of GSH and MDA in silicosis patients were significantly higher than those of the controls group. SOD activity was higher in the silicosis group than that in the controls (p < 0.05) except for III stage. None of the 3 variables examined were associated with the age among both the controls and silicosis patients. The GSH level and SOD activity significantly declined over a prolonged disease period, while MDA levels remained largely unaffected by the disease duration. These results confirmed the role of oxidative stress in the mechanism of silicosis. Therefore, effective antioxidant therapy for inhibiting oxidative stress may be a therapeutic option in silicosis.