Objective This study aimed to evaluate the links between CYP450 family genes in tumor tissues and hepatocellular carcinoma (HCC) outcomes. Methods Gene Expression Omnibus (GEO) databases GSE14520 and GSE36376 were used to identify differential expressed CYP450 genes between tumor and nontumor tissues and related to HCC clinicopathological features and survivals. Results Seven CYP450 genes including CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2E1, CYP3A4, and CYP4A11 were downregulated in tumor tissues, which were validated in both GSE14520 and GSE36376. HCC patients with CYP2A6 and CYP2C8 low levels in tumor tissues suffered from poorer overall survival (OS) compared to those with high CYP2A6 and CYP2C8 in GSE14520 profile (log ranks P = 0.01 and P = 0.006, respectively). In addition, HCC patients with lower CYP2A6 and CYP2C8 in tumors had worse recurrence-free survival (RFS) than those with higher CYP2A6 and CYP2C8 (log ranks P = 0.02 and P = 0.012, respectively). In GSE36376 validation dataset, HCC patients with lower CYP2A6 and CYP2C8 had worse OS and RFS than those with higher CYP2A6 and CYP2C8 (all P < 0.05), in line with results in GSE14520 dataset. Additionally, lower CYP2A6 and CYP2C8 are associated with advanced clinicopathological features including tumor staging, vascular invasion, intrahepatic metastasis, and high alpha fetoprotein (all P < 0.05). Conclusion Downregulation of CYP2A6 and CYP2C8 in tumor tissues links to poorer OS and RFS in HCC patients.

Background and Aim: Economic efficiency of the alternative antiviral therapies for chronic hepatitis B has not been systematically investigated and their quality remains unknown. The aim of the present study was to systematically overview economic evidence of antiviral therapies for chronic hepatitis B. Methods: We searched six databases and eight major journals supplemented with screening references of eligible studies. Full economic evaluations comparing alternative antiviral therapies in patients with chronic hepatitis B virus infection were included. Two investigators assessed the study quality and transferability, independently. Data were analyzed qualitatively with adjustment when appropriate. Results: Fourteen studies (six modeling vs eight trials and database analyses) were included. Quality was high in five studies, moderate in one US and five Chinese studies, and low in three Chinese studies. The major problems of quality are costing methods and analysis and the presentation of results. In Australia and Poland, lamivudine-preferred strategies dominated interferon (IFN)-a and its related strategy from the health-care sector

The effects of filler particle size and concentration on the rheological properties of hydroxyl terminated polydimethylsiloxane (HO-PDMS) filled with calcium carbonate (CaCO 3 ) were investigated by an advanced rheometric expansion system (ARES). The Casson model was used to describe the relationship between shear stress and shear rate for steady-state measurement. Micron-CaCO 3 could not afford the CaCO 3 /HO-PDMS suspensions obvious shear thinning behavior and a yield stress high enough, whereas nanoCaCO 3 could provide the suspensions with remarkable shear thinning behavior and high yield stress. Incorporation of nano-CaCO 3 into HO-PDMS resulted in the transformation of HO-PDMS from a mainly viscous material to a mainly elastic material. With increasing nano-CaCO 3 content, shear thinning behavior of nano-CaCO 3 /HO-PDMS suspensions became more obvious. Remarkable yield stress was observed in nano-CaCO 3 /HO-PDMS suspensions with high filler content, and increased with increasing nanoCaCO 3 content. The degree of thixotropy was quantitatively determined using a thixotropic loop method. It was found that nano-CaCO 3 favored more the buildup of filler network structure in the suspensions than micron-CaCO 3 at the same weight fraction. Furthermore, increasing nano-CaCO 3 content accelerated the establishment of filler network structure in the nano-CaCO 3 /HO-PDMS suspensions. An overshoot phenomenon was observed in the nano-CaCO 3 /HO-PDMS suspensions at high shear rates.

Somatostatin (Som), one of the most concentrated neuropeptides in the brain, is highly expressed in the olfactory bulb (OB). However, the temporal profile by which OB somatostatin-expressing (Som+) interneurons are produced and the molecular mechanisms controlling this profile are totally unknown. In the present study, we found that all the Som+ interneurons in the mouse external plexiform layer (EPL) and the rat glomerular layer (GL) express the transcription factor Sp8.Using the 5-bromo-2′-deoxyuridine (BrdU) birth dating method, combined with immunostaining, we showed that the generation of Som+ interneurons in the mouse and rat OB is confined to the later embryonic and earlier postnatal stages. Within the mouse OB, the production of Som+ interneurons is maximal during late embryogenesis and decreases after birth, whereas the generation of Som+ interneurons is low during embryogenesis and increases gradually after birth in the rat OB. Interestingly, genetic ablation of Sp8 by cre/loxP-based recombination severely reduces the number of Som+ interneurons in the EPL of the mouse OB. Taken together, these results suggest that Sp8 is required for the normal production of Som+ interneurons in the EPL of the mouse OB.

A variant in signal transducer and activator of transcription 4 (STAT4) was reported to correlate with the response of interferon-α (IFN-α) in a retrospective study in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B virus (CHB) patients. Here, we conducted a prospective study to analyze the effect of STAT4 genetic polymorphism on the response of pegylated interferon-α-2a (PegIFN-α-2a) in HBeAg-positive patients. A prospective, multicenter, open-label, parallel cohort study was performed. One hundred and fifty treatment-naïve and 156 nucleos(t)ide analog (NA)-experienced HBeAg-positive CHB patients were enrolled, respectively.All patients received PegIFN-α-2a treatment for 48 weeks and 24-week follow-up post PegIFN-α-2a treatment. Before treatment, STAT4 genetic polymorphism was determined by PCR and DNA sequencing. Serological markers, serum HBV DNA levels, and adverse events were collected at each visit. We observed a larger reduction of HBV DNA load and a significantly higher HBeAg seroconversion rate in the GT/TT group than in the GG group at week 72 (p = 0.002 and p = 0.023) in treatment-naïve patients. In NA-experienced patients, the HBeAg seroconversion rate in the GT/TT group was higher than that in the GG group at week 72 (p = 0.005). STAT4 rs7574865 gene polymorphism was the strongest independent predictor of HBeAg seroconversion in both paralleled cohorts. Also, patients in the GT/TT group had a higher hepatitis B surface antigen loss rate than in the GG group in the study. There was no significant difference in adverse events between GG and GT/TT groups. This prospective cohort study confirmed that STAT4 rs7574865 gene polymorphism is associated with HBeAg seroconversion and HBsAg loss irrespective of naïve and NA-experienced HBeAg-positive CHB patients treated with PegIFN-α-2a.