Objective To explore the detection trend of vaginal intraepithelial neoplasia(VaIN)of lower genital tract from 2013 to 2015. Methods A retrospective analysis was undertaken of colposcopy-directed biopsy of cervical, vaginal and vulvar intraepithelial neoplasia lesions include cervical intraepithelial neoplasia (CIN), VaIN and vulvar intraepithelial neoplasia (VIN) in Obstetrics and Gynecology Hospital of Fudan University from January 2013 to December 2015. Results (1) Overall data of CIN, VaIN and VIN:a total of 16732 cases were diagnosed of lower genital intraepithelial neoplasia in 3 years, accounting for 23.20% (16732/72128) of total colposcopy-directed biopsy cases. Among them, CIN, VaIN and VIN accounted for 19.48%(14053/72128), 2.67%(1923/72128), 1.05%(756/72128) of total colposcopy-directed biopsy cases of the lower genital tract, 83.99%(14053/16732), 11.49%(1923/16732), 4.52%(756/16732) of total lower genital intraepithelial neoplasia, respectively. (2) Annual data of CIN, VaIN and VIN from 2013 to 2015. The annual proportion of CIN in all intraepithelial neoplasia of lower gential tract was basically stable, consisting of 86.02%(3955/4598),83.25%(4795/5760) and 83.20%(5303/6374), respectively. The annual proportion of VaIN was gradually increasing, consisting of 8.09% (372/4598), 12.45%(717/5760) and 13.08%(834/6374), respectively. The annual proportion of VIN was gradually decreasing, consisting of 5.89% (271/4598), 4.31% (248/5760) and 3.72% (237/6374), respectively. Conclusion The increasing detection of VaIN from 2013 to 2015 might correlate with the increasing attention to inspection of the entire vaginal wall.

OBJECTIVE To investigate the mechanism of glucose -6-phosphate dehydrogenase （G6PD）-induced sorafenib - resistance in hepatocarcinoma cell based on phoshorylated 3-kinase/protein kinase B （PI3K/Akt）signaling pathway . METHODS Cell lines including hepatocarcinoma cell Huh 7，sorafenib-resistant cell Huh 7-SR，G6PD overexpressed cell Huh 7-G6PD and its control cell Huh 7-CT，and compounds including G 6PD inhibitor （6-Aminonicotinamide，6AN）and sorafenib were used as objects or intervention drugs in these research . CCK8 assay was applied to evaluate cell viability . The protein levels of G 6PD and the phosphorylation levels of PI 3K/Akt signaling pathway were detected by Western blot . Flow cytometry was utilized to investigate cell apoptosis. RESULTS Compared with Huh 7 cells，the protein level of G 6PD was significantly increased in Huh 7-SR cells （P＜ 0.05）. The combination of 6AN and sorafenib reduced cell viability of Huh 7-SR cells （P＜0.01）. However，compared with Huh 7- CT，increased cell viability and decreased cell apoptosis rate were observed in Huh 7-G6PD cells while cells were treated with sorafenib（P＜0.01）. Mechanistically，the phosphorylation levels of PI 3K and Akt were significantly decreased in Huh 7-SR cells that were treated with 6AN（P＜0.05）. Moreover，under the condition of no drug intervention ，the phosphorylation levels of PI 3K and Akt were significantly elevated in Huh 7-G6PD cells when compared with Huh 7-CT（P＜0.01）. CONCLUSION G6PD could induce sorafenib -resistance in hepatocarcinoma cell by activating PI 3K/Akt signaling pathway .

OBJECTIVE To investigate the regulatory effect of autophagy on the resistance of human liver cancer cell Huh7 to lenvatinib. METHODS Using human liver cancer cell Huh7 as subject， the lenvatinib-resist cell model （Huh7-LR） was generated by the low-dose gradient method combined with long-term administration. The sensitivity of parental cell Huh7 and drug-resistant cell Huh7-LR to lenvatinib was detected by using CCK-8 assay and flow cytometry. Western blot assay and GFP-mCherry-LC3 plasmid transfection were performed to detect the expression levels of autophagic protein Beclin-1， autophagic adapter protein sequestosome 1 （p62）， microtubule-associated protein 1 light chain 3 （LC3） and autophagic level. Furthermore， an autophagy activation model was constructed by cell starvation， the protein expression of p62 and autophagy level were detected by using Western blot assay and GFP-mCherry-LC3 plasmid transfection， and the effect of autophagy activation on the sensitivity of Huh7-LR cells to lenvatinib was detected by flow cytometry. RESULTS Compared with parental cells， the drug resistance index of Huh7-LR cells was 6.2； protein expression of p62 was increased significantly， while apoptotic rate， protein expression of Beclin-1 and LC3Ⅱ/ LC3Ⅰ ratio were all reduced significantly （P＜0.05 or P＜0.01）； the level of autophagy was decreased to some extent. Autophagy activation could significantly increase the protein expression of p62 in Huh7-LR cells （P＜0.05） and autophagy level， and significantly increase its apoptotic rate （P＜0.05）. CONCLUSIONS Autophagy is involved in lenvatinib resistance， and activating autophagy can reverse the resistance of liver cancer cells to lenvatinib to some extent.