Objective: To investigate the effect of loss of function of lanosterol synthase( LSS) gene on intestinal function in a mouse model of non-alcoholic fatty liver disease( NAFLD) induced by a high-fat diet． Methods: LSS gene heterozygous knockout C57 mice ( LSS + / －) were established using the CRISRP / Cas9 system．After being fed a high-fat diet with 60% fat content for 6 months，the fat deposition in liver tissues was detected by HE and Oil red O staining，the morphological changes of small intestine tissue were detected by HE staining．The changes in total cholesterol content in intestinal tissue were detected by kits．The gastrointestinal motility function of mice was detected by phenol red paste．The intestinal permeability was detected by Evans blue staining，and the expression of LSS，tight junction protein ( Claudin) -1，Claudin-5，cluster of differentiation 36 ( CD36) ，and Niemann-Pick type C1-like 1 protein ( NPC1L1) proteins in small intestinal tissues were detected by Western blot． Results : The results of HE and Oil red O staining of liver tissues showed that liver fat deposition in LSS gene heterozygous knockout mice was lower than that in wild-type mice in the high-fat diet group．The total cholesterol content in intestinal tis- sue of LSS gene heterozygous knockout mice decreased ( P ＜0. 01) ，but no morphological differences were ob- served between the two groups of mice by HE staining of intestinal tissues．The gastrointestinal motility function of LSS gene heterozygous knockout mice did not show significant changes．The intestinal permeability of LSS gene het- erozygous knockout mice in the high-fat diet group decreased as detected by Evans blue ( P＜0. 05) ．The expres- sion levels of Claudin-5 protein in the intestinal tissue of LSS gene heterozygous knockout mice in the high-fat diet group increased ( P ＜0. 05 ) ，while the expression of LSS protein in the intestinal tissues of LSS heterozygous knockout mice decreased ( P ＜0. 05) ． Conclusion In the NAFLD model induced by a high-fat diet，LSS gene heterozygous knockout reduces liver fat deposition induced by a high-fat diet and improves intestinal barrier function by regulating cholesterol metabolism in intestinal tissues and up-regulating the expression of Claudin-5．

Objective    To explore whether surgery combined with adjuvant chemotherapy can bring survival benefits to patients with cervical and upper thoracic esophageal squamous cell carcinoma (ESCC). Methods    The clinical data of patients with cervical and upper thoracic ESCC who underwent R0 resection and neck anastomosis in our department from 2006 to 2010 were retrospectively analyzed. Patients received neoadjuvant therapy or adjuvant radiotherapy were excluded. The adjuvant chemotherapy group was given a combination of taxanes and platinum based chemotherapy after surgery; the surgery alone group did not receive adjuvant chemotherapy. The Kaplan-Meier method was used to analyze the survival difference between the adjuvant chemotherapy group and the surgery alone group. Results    A total of 181 patients were enrolled, including 141 (77.9%) males and 40 (22.1%) females, with an average age of 61.0±8.2 years (80 patients aged≤61 years, 101 patients aged>61 years). There were 70 (38.7%) patients of cervical ESCC, and 111 (61.3%) patients of upper thoracic ESCC. Eighty-seven (48.1%) patients underwent postoperative adjuvant chemotherapy, and 94 (51.9%) patients underwent surgery alone, and the basic clinical characteristics were well balanced between the two groups (P>0.05). The median survival time of patients in the adjuvant chemotherapy group and the surgery alone group was 31.93 months and 26.07 months, and the 5-year survival rate was 35.0% and 32.0%, respectively (P=0.227). There was no statistical difference in median survival time between the cervical ESCC and upper thoracic ESCC group (31.83 months vs. 29.76 months, P=0.763). For cervical ESCC patients, the median survival time was 45.07 months in the adjuvant chemotherapy group and 14.70 months in the surgery alone group (P=0.074). Further analysis showed that the median survival time of lymph node negative group was 32.53 months, and the lymph node positive group was 24.57 months (P=0.356). The median survival time was 30.43 months in the lymph-node positive group with adjuvant chemotherapy and 17.77 months in the lymph-node positive group with surgery alone. The survival curve showed a trend of difference, but the difference was not statistically significant (P=0.557). Conclusion    There is no statistical difference in the long-term survival of cervical and upper thoracic ESCC patients after R0 resection. Postoperative adjuvant chemotherapy may have survival benefits for patients with cervical ESCC and upper ESCC with postoperative positive lymph nodes, but the differences are not statistically significant in this setting.