Interleukin-22 , one of the cytokines secreted by T helper 17 (Th17) cells, was recently reported to be a novel inflammation driver through STAT3 signaling activation. We aimed to investigate the role of IL-22 expression in hepatocellular carcinoma (HCC). We demonstrated significant up-regulation of IL-22 in human HCC tumor infiltrated leukocytes (TILs) compared to peripheral lymphocytes. Moreover, IL-22 expression was significantly higher in Edmondson Grade III-IV HCC patients versus Grade I-II, confirmed by both real-time polymerase chain reaction and immunohistochemistry. Both IL-22 receptor a and IL-23 were highly expressed in HCC and adjacent cirrhotic tissues compared to normal controls. Enhanced tumor growth and metastasis was found in mice that underwent subrenal transplantation of MHCC-97H cells cotransplanted with IL-221 TILs cells. STAT3 phosphorylation and up-regulation of downstream genes Bcl-2, Bcl-XL, CyclinD1, and vascular endothelial growth factor (VEGF) promoted tumor growth and metastasis. In vitro studies confirmed the tumor-promoting and antiapoptotic effect of IL-22, as well as IL-6. In the mouse chronic hepatitis and HCC model, sustained and increased IL-22 expression and STAT3 activation were found in liver tissues. A linear correlation was demonstrated between IL-22 expression and hepatic complementary proliferation. An in vivo diethyl-nitrosamineinduced mouse HCC model verified that tumor formation was significantly decreased in IL-22 knockout mice. Conclusion: Excessive IL-22 can be found in the HCC microenvironment, leading to tumor growth, inhibition of apoptosis, and promotion of metastasis due to STAT3 activation. (HEPATOLOGY 2011;54:900-909) H epatocellular carcinoma (HCC) is the fifth most common malignancy worldwide, with a 5-year survival rate of 9%.1 It is the final outcome of nonresolvable chronic hepatitis and is a major concern in clinical epidemiologic research. Tumor and inflammation microenvironments are considered the major battlefield between tumor promotion and antitumor immunity; malignant transformation occurs when tumor promotion dominates the microenvironment. Therefore, the determinants of pro-or antitumor effects in the microenvironment have become central in cancer research.Tumor microenvironments that have a growth stimulation effect in malignancy include a large population of tumor cells, malignant transforming cells, immune cells, macrophages, etc. Moreover, much of the growth stimulating crosstalk between immune and malignant cells is mediated by cytokines that activate the oncogenic transcription factor STAT3, 2 a major intrinsic activator in cancer inflammation 3,4 and a regulator of the tumor microenvironment. STAT3 modulates many immunosuppressive and tumor-promoting genes by targeting myeloid derived suppressor cells (mDSCs) and tumor-associated macrophages.5-8 STAT3 also mediates T-regulatory cell expansion in tumors and is necessary for Th17 cell development, 9,10 which promotes tumor growth. 2,11,12 Moreover, cytokines, growth factors, and angiog...

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Abstract-The performance of the noncoherent differential chaos-shift-keying (DCSK) communication system over a multipath fading channel with delay spread is evaluated. Analytical expressions of the bit error rates are derived under the assumption of an independent Rayleigh fading two-ray channel model. Analytical and simulated results are presented and compared. The multipath performance of the DCSK system is also compared with that of the coherent CSK system as well as conventional generic waveform communication schemes.Index Terms-Chaos communications, delay spread, differential chaos shift keying (DCSK), multipath Rayleigh fading channel.

The early detection of hepatocellular carcinoma (HCC) presents a challenge because of the lack of specific biomarkers. Serum/ plasma microRNAs (miRNAs) can discriminate HCC patients from controls. We aimed to identify and evaluate HCC-associated plasma miRNAs originating from the liver as early biomarkers for detecting HCC. In this multicenter three-phase study, we first performed screening using both plasma (HCC before and after liver transplantation or liver hepatectomy) and tissue samples (HCC, para-carcinoma and cirrhotic tissues). Then, we evaluated the diagnostic potential of the miRNAs in two case-control studies (training and validation sets). Finally, we used two prospective cohorts to test the potential of the identified miRNAs for the early detection of HCC. During the screening phase, we identified ten miRNAs, eight of which (miR-20a-5p, miR-25-3p,