We followed 145 men with chronic hepatitis B virus (HBV) hepatitis for 10 years to determine whether exposure to aflatoxin, or concomitant exposure to hepatitis C virus (HCV), or family history of hepatocellular carcinoma (HCC) increased the risk of developing HCC. We collected 8 monthly urine samples before beginning follow-up and pooled them to detect aflatoxin metabolite M1 (AFM1). AFM1 was detected in 78 (54%) of the subjects. The risk of HCC was increased 3.3-fold (with a 95% confidence interval of 1.2-8.7) in those with detectable AFM1 (above 3.6 ng/L). This relative risk was adjusted for age and for HCV status. Hepatocellular carcinoma (HCC) is the second most common cause of death from cancer in China, where the mortality rate was 18 per 100,000 person-years in 1990 through 1992. 1 Infection with hepatitis B virus (HBV) and exposure to aflatoxin are both important risk factors for HCC. Ross et al. 2 studied 18,244 men aged 45 to 64 who lived in Shanghai between 1986 and 1989. In a sample of 140 controls who were age-matched to HCC cases, it was found that 15 (11%) were hepatitis B surface antigen (HBsAg)-positive, and 53 (38%) had detectable urinary aflatoxin metabolites or DNAadducts. A later analysis of 50 HCC cases and 267 agematched controls from this study 3 showed that compared with men without HBsAg or urinary aflatoxin biomarkers, relative risks were 7.3 with 95% a confidence interval (2.2, 24) for those only with HBsAg, 3.4 (1.1, 10) for those only with aflatoxin biomarkers, and 59 (17, 212) for those with both. Based on such data, Ross et al. 2 and Qian et al. 3 suggested that reduction of exposure to aflatoxin might prevent a considerable fraction of the HCC in this population.The previous cohort represented the general male population of Shanghai. We chose instead to follow prospectively a representative group of 145 carriers of HBsAg with a history of chronic hepatitis. These men were being cared for at the Medical Oncology Department of the Qidong Liver Cancer Institute/Hospital, Qidong, Jiangsu Province, China. HCC rates are very high in Qidong. The purpose of the study was to determine whether exposure to aflatoxin increased the risk of HCC or of fatal cirrhosis over a 10-year period in patients with HBV hepatitis. A positive finding would suggest that measures to reduce exposure to aflatoxin might also be beneficial to men with chronic HBV hepatitis and could be evaluated in treatment protocols. Because we collected monthly urine samples for 8 months before beginning follow-up, we were able to pool the samples to obtain estimates of long-term average urinary aflatoxin M1 (AFM1) concentrations, and the assay could detect concentrations of AFM1 as low as 3.6 ng/L. These data also give information on the added risks of HCC in men with chronic HBV hepatitis from exposure to hepatitis C virus (HCV) and from a family history of HCC. PATIENTS AND METHODSPopulation-based sampling was used to obtain a representative study cohort. In an earlier study of the prevalence of HBV infection sponsored by...

Background: Treatment of large bone defects represents a major clinical problem worldwide. Suitable bone substitute materials are commonly required to achieve successful bone regeneration, and much effort has been spent to optimize their chemical compositions, 3D architecture and mechanical properties. However, material-immune system interactions are increasingly being recognized as a crucial factor influencing regeneration. Here, we envisioned an accurate and proactive immunomodulation strategy via delivery of IL-4 (key regulator of macrophage polarization) to promote bone substitute material-mediated regeneration.Methods: Four different IL-4 doses (0 ng, 10 ng, 50 ng and 100 ng) were delivered into rat large cranial bone defects at day 3 post-operation of decellularized bone matrix (DBM) material implantation, and the osteogenesis, angiogenesis and macrophage polarization were meticulously evaluated.Results: Micro-CT analysis showed that immunomodulation with 10 ng IL-4 significantly outperformed the other groups in terms of new bone formation (1.23-5.05 fold) and vascularization (1.29-6.08 fold), achieving successful defect bridging and good vascularization at 12 weeks. Histological analysis at 7 and 14 days showed that the 10 ng group generated the most preferable M1/M2 macrophage polarization profile, resulting in a pro-healing microenvironment with more IL-10 and less TNF-α secretion, a reduced apoptosis level in tissues around the materials, and enhanced mesenchymal stem cell migration and osteogenic differentiation. Moreover, in vitro studies revealed that M1 macrophages facilitated mesenchymal stem cell migration, while M2 macrophages significantly increased cell survival, proliferation and osteogenic differentiation, explaining the in vivo findings.Conclusions: Accurate immunomodulation via IL4 delivery significantly enhanced DBM-mediated osteogenesis and angiogenesis via the coordinated involvement of M1 and M2 macrophages, revealing the promise of this accurate and proactive immunomodulatory strategy for developing new bone substitute materials.

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Exploring high performance cathode materials is essential to realize the adoption of Li-ion batteries for application in electric vehicles and hybrid electric vehicles. FeF 3 , as a typical iron-based fluoride, has been attracting considerable interest due to both the high electromotive force value of 2.7 V and the high theoretical capacity of 237 mA h g À1 (1e À transfer). In this study, we report a facile lowtemperature solution phase approach for synthesis of uniform iron fluoride nanocrystals on reduced graphene sheets stably suspended in ethanol solution. The resulting hybrid of iron fluoride nanocrystals and graphene sheets showed high specific capacity and high rate performance for iron fluoride type cathode materials. High stable specific capacity of about 210 mA h g À1 at a current density of 0.2 C was achieved, which is much higher than that of LiFePO 4 cathode material. Notably, these iron fluoride/ nanocomposite cathode materials demonstrated superior rate capability, with discharge capacities of 176, 145 and 113 mA h g À1 at 1, 2 and 5 C, respectively.