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Background and AimsThe Roadmap concept is a therapeutic framework in chronic hepatitis B for the intensification of nucleoside analogue monotherapy based on early virologic response. The efficacy and safety of this approach applied to telbivudine treatment has not been investigated.MethodsA multinational, phase IV, single-arm open-label study (ClinicalTrials.gov ID NCT00651209) was undertaken in HBeAg-positive, nucleoside-naive adult patients with chronic hepatitis B. Patients received telbivudine (600 mg once-daily) for 24 weeks, after which those with undetectable serum HBV DNA (<300 copies/mL) continued to receive telbivudine alone while those with detectable DNA received telbivudine plus tenofovir (300 mg once-daily). Outcomes were assessed at Week 52.Results105 patients commenced telbivudine monotherapy, of whom 100 were included in the efficacy analysis. Fifty-five (55%) had undetectable HBV DNA at Week 24 and continued telbivudine monotherapy; 45 (45%) received tenofovir intensification. At Week 52, the overall proportion of undetectable HBV DNA was 93% (93/100) by last-observation-carried-forward analysis (100% monotherapy group, 84% intensification group) and no virologic breakthroughs had occurred. ALT normalization occurred in 77% (87% monotherapy, 64% intensification), HBeAg clearance in 43% (65% monotherapy, 16% intensification), and HBeAg seroconversion in 39% (62% monotherapy, 11% intensification). Six patients had HBsAg clearance. Myalgia was more common in the monotherapy group (19% versus 7%). No decrease in the mean glomerular filtration rate occurred in either treatment group at Week 52.ConclusionsTelbivudine therapy with tenofovir intensification at Week 24, where indicated by the Roadmap strategy, appears effective and well tolerated for the treatment of chronic hepatitis B.Trial RegistrationClinicalTrials.gov NCT00651209

The fact that Th1 cytokines are increased while Th2 cytokines are decreased suggests that oxymatrine treatment triggers the change of immune response to hepatitis B infection in transgenic mice, which leads to improved HBV inhibitory activities. The study can help us better understand the mechanisms of the anti-HBV drug, oxymatrine, and how it has potential as an application in clinical chronic hepatitis B treatment.

Age-related macular degeneration (AMD), one of the most common causes of visual impairment, often occurrs in the elderly in developed countries. Oxidative stress, autophagy, and apoptosis of retinal pigment epithelial (RPE) cells play roles in the pathogenesis of AMD. In the current study, the protective effect of celastrol against hydrogen peroxide (H 2 O 2 )-induced oxidative stress and apoptosis was investigated using a human RPE cell line . H 2 O 2 inhibited ARPE-19 cells' survival and autophagy and induced their oxidative stress and apoptosis.Compared with the H 2 O 2 group, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay showed that celastrol increased ARPE-19 cells' survival in a dose-and time-dependent manner. Further, studies have suggested that celastrol has antioxidative stress and antiapoptosis effects in H 2 O 2 -treated ARPE-19 cells. Also, cell autophagy is activated by celastrol in H 2 O 2 -treated ARPE-19 cells. Reverse transcription polymerase chain reaction and Western blot showed that celastrol elevated the messenger RNA (mRNA) and protein expression of sirtuin 3 (SIRT3) in H 2 O 2 -induced ARPE-19 cells. Inhibition of the level of SIRT3 by SIRT3 small interfering RNA (siRNA) reversed the effects of celastrol on oxidative stress, autophagy, and apoptosis in H 2 O 2 -induced ARPE-19 cells. In conclusion, these observations suggest that celastrol activates the SIRT3 pathway in RPE cells and protects against H 2 O 2 -induced oxidative stress and apoptosis. K E Y W O R D S autophagy, celastrol, oxidative stress, retinal pigment epithelial cells, sirtuin 3 1 | INTRODUCTION Age-related macular degeneration (AMD) is a common cause of age-related irreversible vision loss among persons older than 50 years of age. It is common in the developed world. 1,2 Ample evidence suggests that retinal pigment epithelial (RPE) cell death and progressive degeneration result in age-related vision loss. 3 There are two stages of AMD progression: early and advanced stages. The primary early target of AMD is RPE cells. The aggregation of extracellular deposits between Bruch's membrane and RPE cells and the change of the pigmentation of the RPE cells are the key clinical features of AMD. 4 Various genetic and environmental risk factors are involved in RPE cell dysfunction in AMD, such as oxidative stress. 5 The elevation of oxidative stress leads to RPE cell apoptosis and hastens AMD onset. 6,7