Objective To explore the expressions of endoplasmic reticulum stress (ERs) related factors including inositol requiring enzyme-1α(IRE1αα),p-IRE1 α,c-jun N-terminal Kinase(JNK),and p-JNK in rats with non-alcoholic fatty liver disease,and to investigate the effect of intervention with glucagon-like peptide 1 (GLP-1) analogue.Methods Forty male Sprague-Dawley rats were divided into normal chow group(n =15) and high-fat diet group(n=25).After 12 weeks,5 rats of each group were used to assess the establishment of rat models with non-alcoholic fatty liver disease.Then the high-fat diet group rats were divided into high-fat diet group (HF,n =10) and GLP-1 group(HG,n=10) and treated with normal saline and GLP-1 analogue for4 weeks respectively.Body weight and biochemical markers in rats were measured.The expressions of IRE1α,p-IRE1α,JNK,and p-JNK were measured by Western blot.Results Compared with the NC group,the levels of body weight,plasma triglyceride (TG),total cholesterol (TC),low density lipoprotein-cholesterol (LDL-C),alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in HF group were significantly higher (all P ＜ 0.01),high density lipoprotein-cholesterol(HDL-C) was decreased(P＜0.01),and p-IRE1 α/IRE1 α and p-JNK/JNK were increased(P＜0.05 and P＜0.01).After GLP-1 treatment,body weight,plasma TG,TC,LDL-C,AST,ALT in HF group were significantly lowered(P＜0.05 or P＜0.01),HDL-C was increased(P＜0.01),p-IRE1 α/IRE1 α and p-JNK/JNK were decreased (P＜0.05 and P＜0.01).Conclusion GLP-1 analogue may improve hepatic steatosis via regulating ERs related IRE1 α-JNK signaling pathway.

Objective To explore the imaging features of breast cancer by CR mammography,in order to improve the diagnostic level. Methods The CR mamographic features of 37 patients with breast cancer confirmed surgically and pathologically were analysed retrospectively. Results In the 37 cases of breast cancer,the following abnormal signs were found in CR mammograms: mass(n=29),without mass(n=8),calcification(n=15),abnormal vascularity(n=7),inverted nipple(n=6),thickened skin(n=3),sign of tower's tine(n=3),sign of funnel(n=1),focal structural disorder and small focus of increased density(n=3). Conclusion The masses and calcificationsare the main radiological features in breast cancer,CR mammography may show the characteristics of breast cancer,it is one of the mosteffective means in diagnosis of breast cancer.

Objective To investigate the relationship between with or without non?alcoholic fatty liver disease(NAFLD) and diabetic retinopathy(DR) in type 2 diabetes mellitus(T2DM)?Methods Clinical and laboratorial data of 517 cases T2DM hospitalized patients were collected,and the patients were divided into two groups according to if the NAFLD was complicated or not?Group A was T2DM with NAFLD and group B was T2DM without NAFLD?The general information and the laboratorial checking results were Compared, then various index were used as the independent variable, DR was used as the dependent variable for Logistic regression analysis?Results (1)In the 517 cases of T2DM patients,the incorporative rate of the NAFLD was 65?7%(349/517)?(2)Compared with group B,the levels of body mass index(BMI),insulin resistance index (HOMA?IR),glutamyltransferase(GGT),alanine aminotransferase(ALT),aspartate aminotransferase(AST), triglyceride(TG),total cholesterol(TC),low?density lipoprotein cholesterol(LDL?C) and uric acid(UA) for group A were significantly increased, while the high?density lipoprotein cholesterol ( HDL?C ) level was significantly decreased?All the differences were statistically significant( P<0?05)?( 3) Logistic analysis showed that the duration of the extension,hypertension,the increasing level of NAFLD,LDL?C were the risk factors of DR?Even though excluded the influence of duration,high blood pressure and LDL?C level,NAFLD was still the risk factor for T2DM complicated by the DR( OR=2?176,95% CI ( 1?354,3?199) )?Conclusion NAFLD and DR are closely related, so early diagnosis and intervention of NAFLD may prevent the occurrence and development of DR.

Objective To discuss feasibility and therapeutic effect of the interventional management through biliary tract drainage with percutaneous transhepatic puncture technique for biliary tract stricture after orthotopic liver transplantation. Methods A retrospective review of the clinical and imaging materials of 292 postoperative orthotopic liver transplantation cases was made. Of these 292 cases, 30 patients suffered from biliary tract complications and treated with billiary balloon dilatation, bile drainage and biliary stenting techniques. Results After biliary balloon dilatation, 3 cases of biliary tract strictures and leaks, 3 cases of simple biliary anastomosis site strictures and 7 out of the 8 cases of multiple biliary tract strictures were cured. In one of the multiple biliary tract stricture patients, a hepatic hematoma after biliary balloon dilatation was found and a second liver transplantation was done. In the 14 cases of multiple biliary tract strictures accompanied with biliary sludge, balloon dilatation technique was repeatedly performed. In 12 of the 14 cases, the strictures were improved remarkably and jaundice was subsided; In one of 14 cases, biliary tract stenting procedure was performed, but liver re-transplatation was carried out because of stent obstruction by much sludge. In the remaining 1 of the 14 cases, because there was no improvement of the strictures and relief of jaundice was revealed after the repeated procedures, liver re-transplantation was finally done In 2 cases of strictures at the opening segment of the T tube, the procedure of percutaneous transhepatic puncture for bile drainage was managed. After the procedure, the strictures were alleviated and the jaundice relieved. Conclusion The interventional managements through percutaneous transhepatic puncture techniques were effective, convenient and minimally invasive for treating biliary tract strictures after orthotopic liver transplantation.

A set of primers amplified the VP1 gene of foot-and-mouth disease vims (FMDV) was designed and synthesized. A reverse transcription-polymerase chain reaction (RT-PCR) technique detected the RNA of FMDV was established after selecting the best purification method, reagents and reaction conditions. Samples of fresh milk, lymph node, spinal cord, vesicular skin, milk powder, cotton swab, mouse and meat in daughter-house were detected by RT-PCR, positive rates were41.4% (24/58), 13.33% (2/15), 20% (1/5), 100% (1/1), 100% (1/1), 37.5% (12/32), 100% (2/2) and 10% - 70%, respectively. However, positive rate of cockroach detected by RT-PCR was 0. The results showed that the established FMDV RT-PCR technique provided a more sensitive, specific and reliable method for diagnosis and epizootic study of the foot-and-mouth disease.

Objective Enzyme triggered multi unit colon targeting mini tablet of indomethacin were prepared,in order to improve the target treatment of colon disease.Methods Different proportion of enteric layer and chitosan layer were screened to optimize the prescription.The colon targeting mini tablets were prepared by direct compression method.The drug release properties were investigated in different release medium.Rats were used to investigate the distribution of tissue in vivo.The Beagle dogs were used to study the pharmacokinetics and bioavailability.Results The optimum chitosan layer prescription:coating liquid concentration was 2％,plasticizer three citric acid ethyl ester (TEC) was 15％,an anti sticking agent amount of talc was 30％,coating weight was 5％;Enteric layer prescription:coating liquid solid content was 20％,plasticizer content of TEC was 5％,anti sticking agent talc powder dosage was 40％,coating weight was 3％.The chitosan multi unit colon targeted preparation seldom released in rat stomach and small intestine,released slowly in colon.The pharmacokinetics parameters in Beagle dogs were:Cmax =(3.25 + 0.672) mg·L-1,tmax =(2.00 + 0.014) h,AUC(0.∞) =(10.2 +0.871) mg·L-1 ·h,MRT (0-∞) =(2.82 + 0.180) h,CL =(2.46 + 0.202) L·h-1 ·kg-1.The release time of mini tablets for colon targeted was significantly prolonged and preserved stable blood concentration.Conclusion The enzyme triggered multi unit colon targeting mini tablet of indomethacin showed good target to colon and sustained release effect,providing an important reference for the development of preparation of indomethacin for the treatment of colon disease.

Objective To study the changes of hippocampal caspase-3 and PSD-95 expression levels in the mice exposed to ketamine 30 mg/(kg·d)for three months. Methods Forty C57BL/6 mice were randomly divided into two groups,and the chronic ketamine addiction model was established by giving mice a three month course of daily intraperitoneal injections of ketamine. Immunohistochemical study and Western blot-ting were applied to observe the expression of caspase-3 and PSD-95 protein. Results There were more expression of caspase-3 and less of PSD-95 in ketamine group as detected by immuohistochemistry. Western blotting results showed caspase-3 active fragment level significantly increased com-pared to saline group,but PSD-95 protein level was decreased. Conclusion The increased level of caspase-3 protein and reduced expression of PSD-95 are observed after long-term ketamine administration. These findings may provide an evidence for the neurotoxicity in mouse hippocampus of chronic ketamine addition as a recreational drug.

Objective: To observe whether liraglutide protects HepG2 cells from lipotoxicity by affecting mitogen-activated protein kinase (MAPKs) pathway. Methods: HepG2 cells were induced with 400μmol/L palmitic acid, and cells were treated with a final concentration of 100 nmol/L liraglutide. In addition, JNK inhibitor (SP600125) and p38 MAPK inhibitor (SB203580) were added in advance, respectively. Apoptosis rate, malondialdehyde (MDA) content, and caspase3 activity were detected. Western blot was used to detect p38 mitogen-activated protein kinase (p38 MAPK), c-jun amino terminal kinase (JNK), cytochrome oxidase P450 2E1 (CYP2E1), glucose regulatory protein 78 (GRP78), activated caspase 3, B cell lymphoma associated Protein X (Bax), B cell lymphoma 2 (Bcl-2), and expression of C/EBP homologous protein (CHOP) protein. LSD or Dunnett’s T3 test were used to compare the mean of multiple samples. Results: Palmitic acid increased the phosphorylation of p38 MAPK and JNK in HepG2 cells (P< 0.05). Furthermore, it increased the expression of GRP78, CHOP, CYP2E1, MDA, Bax, caspase3 and apoptosis rate, but inhibited the expression of Bcl-2 (Pvalue < 0.05). SP600125 and SB203580 had inhibited oxidative stress and apoptosis induced by palmitic acid (including CYP2E1, MDA, Bax, Bcl-2, caspase3, CHOP) (P< 0.05). The phosphorylation level of p38 MAPK and JNK was reduced with liraglutide and the expression of apoptosis-related proteins (Bax, Bcl-2, caspase3, CHOP) (P< 0.05) was regulated. There was no significant difference in the effect of liraglutide on apoptotic proteins (Bax, Bcl-2, caspase-3, CHOP) (P> 0.05) after pretreatment with those two inhibitors. Conclusion Palmitic acid has strong lipotoxicity to HepG2 cells and induces apoptosis. Glucagon-like peptide-1 analogue, liraglutide may improve lipotoxicity of palmitic acid by mediating p38 MAPK and JNK pathways.

Humans ; Lung Neoplasms/surgery* ; Neoadjuvant Therapy ; Pneumonectomy ; Retrospective Studies ; Treatment Outcome ; Minimally Invasive Surgical Procedures

OBJECTIVETo investigate the effects of glucagon-like peptide-1 (GLP-1) on liver oxidative stress injury using a rat model of non-alcoholic fatty liver disease.

METHODSSixty male Sprague-Dawley rats were fed 12 weeks of either a diet of normal chow (NC), for use as controls (n =15) or high-fat chow (HF), for use as models (n =45).The NC rats were administered normal saline, while the HF rats were treated with either normal saline (NS), for use as untreated model controls (n =10), low-dose GLP-1 (LG, 50 mutg/kg; n =10), mid-dose GLP-1 (MG, 100 mutg/kg; n =10), or high-dose GLP-1 (HG, 200 mug/kg; n =10); all treatments lasted for 4 weeks.The rats' weight, levels of serum biochemical markers (triglycerides, total cholesterol, high-density lipoproteincholesterol, low-density lipoprotein-cholesterol, alanine arninotransferase, and aspartate aminotransferase), levels of superoxide dismutase (SOD) and malondialdehyde (MDA), and expression of CYP2E1 mRNA and protein in liver homogenates were measured.The F test, t-test, least significant difference test and Dunnett's T3 test were used for statistical analyses.

RESULTSCompared with the NC group, the rars in the NS group showed significantly lower SOD (165.81 ± 11.64 vs.192.89 ± 16.53 U/mg, P < 0.05), significantly higher MDA (7.30 ± 1.79 vs.3.10 ± 1.30 nmol/ mg, P < 0.05), and significantly higher expressions of CYP2E1 mRNA and protein (both P < 0.05).After GLP1 treatment, the rats in the LG, MG and HG groups showed increased levels of SOD (compared to the NS group; 171.44 ± 9.80 vs.177.66 ± 14.77 vs.186.17 ± 15.43 U/mg; only the HG group had P < 0.05), significantly decreased levels of MDA (compared to the NS group; 5.16 ± 1.45 vs.4.08 ± 1.22 vs.3.31 ± 1.14 nmol/mg; all P < 0.05], and decreased levels of CYP2E1 mRNA and protein expressions (CYP2E1 mRNA:only the HG group had P < 0.05; CYP2E1 protein: both the MG and HG groups had P < 0.05).

CONCLUSIONGLP-1 treatment can improve oxidative stress injury, suggesting its potential as a therapeutic agent for non-alcoholic fatty liver disease.

Animals ; Aspartate Aminotransferases ; Cytochrome P-450 CYP2E1 ; Glucagon-Like Peptide 1 ; metabolism ; Male ; Malondialdehyde ; Non-alcoholic Fatty Liver Disease ; metabolism ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; Triglycerides