al groups. For example, the ALT level between p.DDR2.shRNA+ALD group and ALD group had no significant differences, which may be because an elevated ALT level is considered a consequence of hepatocyte damage, however, DDR2 correlated HSCs activation and collagen deposition, so we suspected that DDR2 could not directly reduce the injury from alcohol to hepatocytes, once the ALT level elevated which was (S)-(-)-Blebbistatin supplier induced by 2-week alcohol ingestion, it would not decline rapidly through DDR2 knockdown treatment. Alcohol is toxic to hepatocytes, causes inflammation in liver, and irritates the digestive system. As a result, gene-therapy group’s final weight had differences compared to normal group. Fourth, although intravenous 
injection of a large volume of plasmids can achieve effective localization mainly in the liver, we could not completely reverse the damage, perhaps because DDR2 could not be silenced completely, and many other cytokines participate in ALD. Meanwhile, our research mainly focused on the effect of gene therapy with ALD, but the side effects of DDR2 knockdown in other DDR2-expressing organs needs to be examined. Fifth, as the disease develops, the effect of DDR2 along with MMP2 may be more prominent in disrupting collagen than activating HSCs, so DDR2 may play different roles in the early stage of ALD and in the fibrosis stage of chronic liver disease, which has been demonstrated in a CCl4-induced liver fibrosis model. Indeed, MMP2 level is correlated with DDR2 level, and MMP2 has differential effects on HSCs being proliferative or apoptotic depending on its concentration. During the early stage of liver injury, although MMP2 is induced 26841170 by DDR2, MMP2 activity is still restrained by increased TIMP expression. Limited collagen degradation by MMP2 contributes to expanded HSC numbers, and MMP2 can induce HSC activation and proliferation. During the resolution of fibrosis, when TIMP expression DDR2 Knockdown Protects Early-Stage ALD decreases, unrestrained MMP2 degradation of the matrix might contribute to apoptosis of HSCs. So DDR2, via MMP2, plays an important and controversial role in different stages of ALD. In conclusion, we established a p.DDR2.shRNA knockdown plasmid for transfection into HSC-T6 cells and rats with ALD. Inhibition of DDR2 could inhibit HSC proliferation, induce HSC death, and ameliorate liver injury and collagen deposition in rats with early-stage ALD. As well, DDR2 was closely associated with MMP2 expression. DDR2 may play an important and controversial role in the pathogenesis of ALD along with MMP2. As a therapeutic target for managing early-stage ALD, DDR2 warrants further study. Acknowlegments We thank staff of the Key Laboratory of Cardiovascular Remodeling and Function Research and the Institute of Basic Medical Sciences for technical support. We thank Laura Smales for English editing. ~~ ~~: Lung cancer, the most 16873882 prevalent malignant cancer in the world, remains a serious threat to public health. Recently, a large number of studies have shown that an epidermoid growth factor receptor-tyrosine kinase inhibitor, Erlotinib, has significantly better efficacy and is better tolerated in advanced non-small cell lung cancer patients with a positive EGFR gene mutation. However, access to this drug is severely limited in China due to its high acquisition cost. Therefore, we decided to conduct a study to compare cost-effectiveness between erlotinib monotherapy and carboplatin-gemcitabine combination therapy in patients