Histological Outcome of Fuzheng Huayu plus Entecavir Combination Therapy in Chronic Hepatitis B Patients with Significant Liver Fibrosis.

Background and Aims: To evaluate the efficacy of Fuzheng Huayu (FZHY), a Chinese herbal formula, plus entecavir (ETV) in regression of liver fibrosis in chronic hepatitis B (CHB) patients with significant fibrosis/cirrhosis. Methods: The current study was a two-center, randomized, double-blind and placebo-controlled pilot study. Fifty-two currently untreated chronic hepatitis B patients with Ishak fibrosis score ≥3 points were identified and 1:1 randomized into FZHY plus ETV combination and placebo plus ETV groups. The second liver biopsy was performed after 48-week treatment. Necroinflammatory improvement and regression of fibrosis were assessed. Fine changes in different collagen features in paired liver biopsies were evaluated by dual-photon microscopy for both groups. Results: Forty-nine patients completed the full course of treatment; forty-six of them underwent second liver biopsy (for which twenty-two were in the combination group and twenty-four were in the control group). Compared to those in the control group, patients in the combination group had significantly higher rate of fibrosis regression (82% vs. 54%) (p<0.05). Furthermore, the necroinflammatory improvement was greater in the combination group than in the control group (59% vs. 25%, p<0.05). Among the more than 80 collagen parameters in the dual-photon analysis, 5 decreased significantly in the combination group compared to the control group (p<0.05). However, no significant improvement was detected in either biochemical, virologic or serologic responses between these two groups at week 48. Conclusions: The combination therapy of FZHY plus ETV for 48 weeks resulted in a higher rate of necroinflammatory improvement and fibrosis regression than ETV alone in chronic hepatitis B patients with significant fibrosis/cirrhosis. The clinical trial number is ChiCTR-TRC-11001377.

Bacterial infection triggers and complicates acute-on-chronic liver failure in patients with hepatitis B virus-decompensated cirrhosis: A retrospective cohort study.

BACKGROUND: Reports on bacterial infection (BI) in decompensated cirrhosis (DC) is mainly from alcoholic cirrhosis. The role of BI as a trigger or complication of acute-on-chronic liver failure (ACLF) in patients with hepatitis B virus decompensated cirrhosis (HBV-DC) remains to be investigated. AIM: To investigate the impact of BI on the outcomes of the patients with HBV-DC admitted into the hospital with or without ACLF. METHODS: This retrospective study included patients with HBV-DC admitted to two tertiary centers in China. In-hospital overall survival, 90-d transplant-free survival, 5-year post-discharge survival, and cumulative incidence of ACLF were evaluated. Risk factors for death were analyzed considering liver transplantation as a competing event. RESULTS: A total of 1281 hospitalized HBV-DC patients were included; 284 had ACLF at admission. The overall prevalence of BI was 28.1%. The patients with BI had a significantly lower in-hospital survival and transplant-free 90-d survival than those without, in both the patients admitted with and without ACLF. The presence of BI significantly increased the risk of developing ACLF [sub-distribution hazard ratio (sHR) = 2.52, 95%CI: 1.75-3.61, P < 0.001] in the patients without ACLF. In the patients discharged alive, those who had an episode of BI had a significantly lower 5-year transplant-free survival. BI was an independent risk factor for death in the patients admitted without ACLF (sHR = 3.28, 95%CI: 1.93-5.57), while in ACLF admissions, the presence of pneumonia, but not other type of BI, independently increased the risk of death (sHR = 1.87, 95%CI: 1.24-2.82). CONCLUSION: BI triggers ACLF in patients with HBV-DC and significantly impairs short-term survival. HBV-DC patients should be monitored carefully for the development of BI, especially pneumonia, to avoid an adverse outcome.

Aclidinium inhibits proliferation and metastasis of ovarian cancer SKOV3 cells via downregulating PI3K/AKT/mTOR signaling pathway.

Aclidinium, a muscarinic antagonist, is generally used to treat the respiratory system diseases whereas it is not clear whether aclidinium has therapeutic effect in ovarian cancer (OC). The aim of this study was to investigate the impact of aclidinium on OC and its potential mechanism. CCK-8 was employed to test the potential effect of aclidinium on SKOV3 cell proliferation. Transwell migration and invasion assay was performed to assess the influence of aclidinium on SKOV3 cell metastasis and invasion. Furthermore, flow cytometry apoptotic analysis was used to evaluate the effect of aclidinium on cell apoptosis. Finally, western blotting was applied to determine the changes of key proteins in apoptosis and PI3K/AKT/mTOR signaling pathway induced by aclidinium. The study showed that aclidinium had antiproliferative activity on SKOV3 cells. Simultaneously, aclidinium could significantly inhibit the number of migrated and invaded SKOV3 cells and markedly increased the SKOV3 cell apoptosis rate. Mechanistically, the expression of PI3K/AKT/mTOR signaling pathway related proteins were significantly inhibited in aclidinium treated SKOV3 cells. Our findings proposed a clue for further OC studies in preclinical and clinical treatment and aclidinium may be useful for the treatment of OC in the future.

Correlation between circulating miR-122 and prognosis of chronic HBV-related liver failure.

OBJECTIVE: To assess the correlation between circulating microRNA (miR)-122 level and the prognosis of chronic hepatitis B-related liver failure (CHBLF). METHODS: Serum miR-122 from CHBLF patients (n = 6) and healthy controls (n = 6) was quantified using an Exiqon locked nucleic acid microarray. Quantitative real-time polymerase chain reaction was utilized to determine serum miR-122 expression in 102 patients with different liver diseases [CHBLF (n = 58), acute hepatitis B (n = 10), chronic hepatitis B (n = 22) and hepatitis B-related cirrhosis (n = 12)] and 23 healthy controls. The correlations between miR-122 and disease stages based on prothrombin activity (PTA) and model for end-stage liver disease (MELD) scores were further analyzed. RESULTS: Microarray showed that miR-122 was significantly upregulated among 148 significantly modified miRNAs in CHBLF patients. Serum level of miR-122 in CHBLF patients was significantly upregulated at early stage based on PTA or stages I-II based on MELD score. Interestingly, there was a significant correlation between the MELD score and circulating miR-122 level in patients with an MELD score of <30 (r = 0.521, P = 0.001). Moreover, serum level of miR-122 was significantly decreased at discharge compared with that at admission as shown in the same group of CHBLF patients (P < 0.05). CONCLUSIONS: Serum level of miR-122 is correlated with the severity of liver injury at an early stage. miR-122 may be a potential biomarker for both the diagnosis at an early stage of CHBLF and the prognosis for recovery.

Association of cholesterol with risk of pancreatic cancer: a meta-analysis.

AIM: To evaluate the effect of dietary cholesterol and serum total cholesterol (TC) on the risk of pancreatic cancer. METHODS: A literature search was performed up to June 2014 in PubMed, EMBASE, China National Knowledge Infrastructure and China Biology Medical literature database for relevant articles published in English or Chinese. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated with a random-effects model. RESULTS: We included 14 published articles with 439355 participants for dietary cholesterol, and 6 published articles with 1805697 participants for serum TC. For the highest vs lowest category of dietary cholesterol, the pooled RR (95%CI) of pancreatic cancer was 1.308 (1.097-1.559). After excluding two studies (RR > 3.0), the pooled RR (95%CI) was 1.204 (1.050-1.380). In subgroup analysis stratified by study design, the pooled RRs (95%CIs) were 1.523 (1.226-1.893) for case-control studies and 1.023 (0.871-1.200) for cohort studies. The association of dietary cholesterol with the risk of pancreatic cancer was significant for studies conducted in North America [1.275 (1.058-1.537)] and others [2.495 (1.565-3.977)], but not in Europe [1.149 (0.863-1.531)]. No significant association [1.003 (0.859-1.171)] was found between the risk of pancreatic cancer and serum TC. CONCLUSION: Dietary cholesterol may be associated with an increased risk of pancreatic cancer in worldwide populations, except for Europeans. The results need to be confirmed further.

[Clinical and pathological features in 138 cases of drug-induced liver injury].

OBJECTIVE: To explore the categories of drugs causing hepatotoxicity and analyze the clinical and histological features of the corresponding drug-induced liver injury (DILI), in order to gain insights into potential diagnostic factors for DILI. METHODS: A total of 138 DILI patients treated at our hospital from April 2008 to April 2010 were retrospectively analyzed. The responsible drug for each DILI case was recorded. The Roussel Uclaf Causality Assessment Method (RUCAM) had been used to diagnose DILI. Only cases that had scored as highly probable or probable (more than or equal to 6 points by RUCAM) were included in this study. The patients' general condition, clinical manifestations, and serum biochemical and immunological parameters were assessed. Sixty-six of the patients underwent liver biopsy, and were assessed for liver pathological changes. Clinical and laboratory test data were collected and used to classify the total 138 cases as hepatocellular injury, cholestatic, or mixed hepatocellular-cholestatic types. RESULTS: Within our patient population, the leading cause of DILI was Chinese herb medicine, accounting for 53.62% of cases. Antibiotics were implicated in 7.97% of cases, and dietary supplement in 6.52% of cases. Correlation between the clinical features and histological injury pattern was stronger at the time of biopsy (more than or equal to 3 days after laboratory results) (kappa = 0.63, P less than 0.05) than at the onset of DILI (kappa = 0.25, P less than 0.05). All modified hepatic activity index (HAI) necroinflammatory scores and fibrosis scores were more severe in the cholestatic and mixed injury types than in the hepatocellular injury type (P less than 0.01 and P less than 0.05, respectively). CONCLUSION: Chinese herbal medicine, dietary supplements and antibiotics were the main causes of DILI in our patient population. The clinical and histological features correlated well, especially at later stages of DILI. The degree of inflammation and fibrosis was significantly higher in cholestatic and mixed hepatocellular-cholestatic injury types than in the hepatocellular injury type. Assessment of both clinical and pathological features may represent a more accurate diagnostic method for DILI.

Anodic oxidation process for the degradation of 2, 4-dichlorophenol in aqueous solution and the enhancement of biodegradability.

Degradation of 2, 4-dichlorophenol (2, 4-DCP) in aqueous media by anodic oxidation using Ti-based oxide electrode has been studied. Additionally, the influence of anodic oxidation on the biodegradability of 2, 4-DCP solution was investigated. It was found that alkaline media was suitable for the anodic oxidation of 2, 4-DCP, while acidic media tended to cause more 2, 4-DCP volatizing. The poor degradation of 2, 4-DCP was ascribed to the direct anodic oxidation at lower anodic potential, while the indirect anodic oxidation was responsible for the better degradation at higher anodic potential with a high power consumption. The variation of COD and the characteristic of UV-vis spectra indicated that some organic intermediates were produced during the course of the degradation of 2, 4-DCP. The obvious inhibition of microbial activity was observed when 2, 4-DCP concentration was about 100 mg/L. The anodic oxidation process was able to enhance the biodegradability of 2, 4-DCP solution and this enhancement became greater with the extension of anodic oxidation treatment. This work suggests that the anodic oxidation with the Ti/IrO(2)/RuO(2)/TiO(2) electrode generally applied in chemical industry is a promising alternative for the pretreatment of the wastewaters containing chlorophenols.

[Removal of pentachlorophenol catalyzed by immobilized horseradish peroxidase].

The removal of PCP using HRP immobilized by Fe3O4 sorption-gelatin embedding-cross linkage method as catalyzer was studied. Reaction conditions including the reacting time, different buffer systems and pH value, PCP initial concentration, HRP dosage were discussed in detail compared with free HRP. The results indicate that the equilibrium time of PCP removal reaction catalyzed by immobilized HRP is about 30 min, which is as fast as free HRP. The optimal pH for PCP removal by immobilized HRP is between 4-6, the proper pH should be more extensive than using free HRP. The highest catalyzing removal percent is 41% at pH 5. Low concentration of immobilized HRP can remove PCP effectively. PCP removal quantity increases but the removal percent decreases with the increase of initial concentration of PCP. The catalyzing removal percent goes down from 39.68% to 24.4%. Immobilized HRP can remove PCP repetitively. The catalyzing removal percent is still above 39% at 0.05 U/mL dosage of HRP when using 7 times repeatedly.

Double fluorescence conversion in ultraviolet and visible region for some praseodymium complexes of aromatic carboxylates.

Four praseodymium complexes of aromatic carboxylates (benzoate, 4-tert-butylbenzoate, 2-benzoylbe-noate, and benzimidazole-5-carboxylate) have been synthesized and characterized, whose photophysical properties have been studied with ultraviolet spectra, phosphorescence spectra, and fluorescence spectra. The fluorescent emission spectra of all praseodymium complexes show two emission peaks under the excitation band of 245 nm at about 395 and 595 nm respectively, while one peak under 415 nm at about 595 nm, which attributed to be 1S0 --> 1I6 (395 nm) transition and the characteristic emission 1D2 --> 3H4 (595 nm) transition of Pr3+ ion. The 1S0 --> 1I6 transition can be ascribed as the transition of charge transfer state, and the 1D2 --> 3H4 can be further proved that there exists an antenna effect in the fluorescence of praseodymium with aromatic carboxylic acids. In conclusion, the praseodymium complexes systems can realize the double fluorescent conversion in both ultraviolet and visible region and can be further studied the application of this conversion.