This study investigated the effects of bile duct ligation(BDL)-induced liver injury on the function and expression of organic cation transporter 1/2(OCT1/2)at blood brain barrier(BBB)and their potential mechanisms.BDL rat model was constructed,and physiological and biochemical parameters,BBB integrity,cortical OCT1/2 protein expression and function,and plasma chenodeoxycholic acid(CDCA)level were then examined by kits,Western blot,and LC-MS.Physiological and biochemical parameters,plasma bile acid levels,and cortical OCT1/2 protein expression were determined in rats after ig administration of CDCA for 14 d.The results showed that serum aspartate aminotransferase(AST),alanine aminotransferase(ALT),and alkaline phosphatase(ALP)levels increased,plasma CDCA level increased,the brain-to-blood concentration ratio(Kp)of amantadine decreased,while cortical Claudin-5 and Occludin did not significantly change,OCT1 expression was downregulated,while OCT2 did not significantly change in BDL rats.Serum AST,ALT,and ALP levels did not significantly change,plasma CDCA level increased,cortical OCT1 expression was downregulated,and OCT2 did not significantly change in rats after ig administration of CDCA.This study suggests that downregulation of OCT1 function and expression at BBB of BDL rats is related to elevated CDCA in plasma.

Body is equipped with organic cation transporters (OCTs). These OCTs mediate drug transport and are also involved in some disease process. We aimed to investigate whether liver failure alters intestinal, hepatic and renal Oct expressions using bile duct ligation (BDL) rats. Pharmacokinetic analysis demonstrates that BDL decreases plasma metformin exposure, associated with decreased intestinal absorption and increased urinary excretion. Western blot shows that BDL significantly downregulates intestinal Oct2 and hepatic Oct1 but upregulates renal and hepatic Oct2. In vitro cell experiments show that chenodeoxycholic acid (CDCA), bilirubin and farnesoid X receptor (FXR) agonist GW4064 increase OCT2/Oct2 but decrease OCT1/Oct1, which are remarkably attenuated by glycine-β-muricholic acid and silencing FXR. Significantly lowered intestinal CDCA and increased plasma bilirubin levels contribute to different Octs regulation by BDL, which are confirmed using CDCA-treated and bilirubin-treated rats. A disease-based physiologically based pharmacokinetic model characterizing intestinal, hepatic and renal Octs was successfully developed to predict metformin pharmacokinetics in rats. In conclusion, BDL remarkably downregulates expressions of intestinal Oct2 and hepatic Oct1 protein while upregulates expressions of renal and hepatic Oct2 protein in rats, finally, decreasing plasma exposure and impairing hypoglycemic effects of metformin. BDL differently regulates Oct expressions via Fxr activation by CDCA and bilirubin.

OBJECTIVE: To analyze the differentially expressed genes (DEGs) between lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) with bioinformatics analysis and search for potential biomarkers for clinical diagnosis of nonsmall cell lung cancer (NSCLC). METHODS: The gene expression profiling datasets of LUAD and LUSC were acquired. The transcriptome differences between LUAD and LUSC were identified using R language processing and t-test analysis. The differential expressions of the genes were shown by Venn diagram. The DEGs identified by GEO2R were analyzed with DAVID and Ingenuity Pathway Analysis (IPA) to identify the signaling pathways and biomarkers that could be used for differential diagnosis of LUAD and LUSC. The TCGA data and the biomarker expression data from clinical lung cancer samples were used to verify the differential expressions of the Osteoarthritis pathway and LXR/RXR between LUAD and LUSC. We further examined the differential expressions of miR-181 and its two target genes, and , in 23 clinical specimens of lung squamous cell carcinoma and the paired adjacent tissues. RESULTS: GEO data analysis identified 851 DEGs (including 276 up-regulated and 575 down-regulated genes) in LUAD and 885 DEGs (including 406 up-regulated and 479 down-regulated genes) in LUSC. DAVID and IPA analysis revealed that leukocyte migration and inflammatory responses were more abundant in LUAD than in LUSC. Osteoarthritis pathway was inhibited in LUAD and activated in LUSC. IPA analysis showed that transcription factors (GATA4, RELA, YBX1, TP63 and MBD2), cytokines (WNT5A and IL1A) and microRNAs (miR-34a, miR-181b and miR-15a) differed significantly between LUAD and LUSC. miR-34a with IL-1A, miR-15a with YBX1, and miR-181b with WNT5A and MBD2 could serve as the paired microRNA and mRNA targets for differential diagnosis of NSCLC subtypes. Analysis of the clinical samples showed an increased expression of miR-181b-5p and the down-regulation of WNT5A, which could be used as molecular markers for the diagnosis of LUSC. CONCLUSIONS Through transcriptome analysis, we identified candidate genes, paired microRNAs and pathways for differentiating LUAD and LUSC, and they can provide novel differential diagnosis and therapeutic strategies for LUAD and LUSC.
Adenocarcinoma of Lung ; Carcinoma, Non-Small-Cell Lung ; Carcinoma, Squamous Cell ; Humans ; Lung Neoplasms ; MicroRNAs ; Y-Box-Binding Protein 1

Although lymph node metastasis (LNM) is one of the most important contributory factors to the overall survival of ICC patients,the role of lymph node dissection (LND)is still under research.Some researchers thought hepatectomy combined with extended lymphadenectomy is the standard surgical treatment for ICC.However,not all the clinical centers approved routine LND.Some centers have reported the use of selective LND and limited routine LND.This review will mainly concern lymph node metastasis and lymph node dissection.

Objective To study the influence of microvascular invasion (MVI) on progression-free survival (PFS) in patients with a solitary small hepatocellular carcinoma,and to analyze the risk factors of MVI.Methods 126 patients with a solitary small hepatocellular carcinoma who underwent liver resection at Tianjin Medical University Cancer Hospital from January 2010 to December 2012 were retrospectively studied.Their demographic and clinicopathological characteristics including age,gender,HBV infection,HCV infection,alcohol consumption,comorbidity,liver cirrhosis,ascites,tumor size,tumor differentiation,MVI,satellite lesion,AFP,CA19-9,ALT and TBil were analyzed.Results The 1-,2-and 3-year PFS rates of patients with a solitary small hepatocellular carcinoma were 81.0％,60.3％ and 47.3％ after surgical resection,respectively.Univariate analysis revealed that MVI,comorbidity,non-well-differentiated tumor,tumor size ＞4 cm were risk factors of PFS.Multivariate analysis demonstrated that only MVI and comorbidity were independent factors of PFS.MVI occurred in 43.7％ of the patients.The median PFS of patients without MVI was 45 months,and the 1-,2-and 3-year PFS rates of these patients were 91.5％,67.6％ and 56.0％,respectively.The median PFS of patients with MVI was 30 months,and the 1-,2-and 3-year PFS rates were 67.3％,50.9％ and 35.4％,respectively.On univariate analysis,AFP ＞ 100 μg/L,non-well-differentiated tumor and satellite lesions were significantly associated with MVI.On multivariate analysis only non-well-differentiated tumor was independently associated with MVI.Conclusions MVI was an important factor affecting PFS in patients with a solitary small hepatocellular carcinoma.AFP ＞ 100 μg/L,non-well-differentiated tumor and satellite lesions were risk factors of MVI.

AIM:To investigate the protective effect of N-acetylcysteine (NAC) on H9c2 cells from injuries induced by methylglyoxal (MG) and the potential mechanism.METHODS:H9c2 cells were divided into control group, MG treatment group, NAC +MG treatment group, SP600125 pretreatment +MG group, NAC group and SP600125 group.The viability of the H9c2 cells was measured by CCK-8 assay.The protein levels of p-JNK and t-JNK were tested by Western blot .The changes of intracellular reactive oxygen species ( ROS) were evaluated by 2′, 7′-dichlorofluorescein di-acetate (DCFH-DA) staining.Mitochondrial membrane potential (MMP) was measured by rhodamine 123 (Rh123) stai-ning.The morphological changes in apoptotic cardiomyocytes were detected by Hoechst 33258 staining.RESULTS: Du-ring 100~800 μmol/L concentration range , MG caused significantly reduced viability of the H 9c2 cells in a dose-depend-ent manner.NAC had a protective effect on H9c2 cells against the injuries induced by MG during 500~1 500μmol/L con-centration range through raising cell viability , inhibiting cellular oxidative stress and improving MMP ( P <0.01 ) . SP600125,an inhibitor of JNK, showed the protective effect similar to NAC on H9c2 cells against MG-induced injuries, in-cluding attenuating oxidative stress , improving MMP and suppressing apoptosis .CONCLUSION: N-acetylcysteine offers obvious protective effect on H9c2 cells against the injuries induced by methylglyoxal .The underlying mechanisms may be associated with decreasing the production of ROS , ameliorating MMP , inhibiting the activation of JNK and suppressing ap-optosis.

Objective To investigate the treatment and mechanism of aminoguanidine in retina of diabetic of rats .Methods To-tal 60 rats were divided into control group(n=20) ,diabetic group(n=20) and aminoguanidine treatment group(n=20)which would be treated by aminoguanidine for 14 days .Then the eye tissue of rats were took after 14 days administration for pathological obser-vation(HE staining) ,and the induced nitric oxide synthase(iNOS) ,endothelial nitric oxide synthase(eNOS) ,nerve type of nitric ox-ide synthase(nNOS) level and the expression of differences content and expression were investigated by ELISA ,Western blot and PT-PCR .Results HE staining showed that retinal tissue defects decreased and neuronal cells of rats in aminoguanidine treatment group were increased and significant (P<0 .05) compared rats in diabetic group .The iNOS content and expression of rats in amin-oguanidine treatment group were lower than diabetic group by ELISA ,Western blot and PT-PCR ,it was significantly difference (P<0 .05) and without significant difference between the normal group and diabetic group (P> 0 .05) .Compared with diabetes group ,iNOS ,eNOS ,nNOS protein expression in the rat retina in aminoguanidine treatment group were reduced (P< 0 .05) ,and without significant difference between the normal group and aminoguanidine treatment group (P>0 .05) .The iNOS mRNA expres-sion was lower than that of eNOS mRNA and nNOS mRNA in aminoguanidine treatment group .Conclusion Aminoguanidine can improve retinal tissue of diabetic rats with lesions ,the pathways may be selectively inhibit inducible nitric oxide synthase activity of iNOS .

Objective To assess the effect of case-based learning (CBL) in ophthalmology teaching.Methods Lecture based learning combined with CBL was applied in ophthalmology teaching for 19 undergraduates majored in clinical medicine of 2007 grade from Shanghai Jiao Tong University School of Medicine.Questionnaire survey was conducted for students after the course ended to understand their evaluation on CBL.Proportion of selected data was analyzed comparatively.Results 100％ (19/19) students believed that CBL was essential in ophthalmology teaching and rational at the end of course.84.2％ (16/19) students accounted that CBL could only be assistant teaching method.94.7％ (18/19) and 84.2％ (16/19) students considered that CBL was beneficial for cognition of eye diseases completely and clinical thinking formation.4-6 class hours for CBL were approved by 73.7％ (14/19) students.Conclusions CBL is essential in ophthalmology teaching and is accepted and supported by students,therefore it should be the main assistant teaching method.

Objective To observe the clinical effect of interferon on the treatment of virus keratitis. Meth-ods Review and analysis was made of 476 patients with virus keratitis who was treated with high concentration of an-ti-virus eyedrops and one million unit of α-2b interferon, the clinical safety and effect was evaluated. Result The total cure rate was 59. 1%, and the type from high to low is interstitial、endothelial、epithelial and the total cornea. The total recurrence rate is 23.5% ,and the type from high to low is epithelial,the total cornea,endothelial and inter-stitial. The incidence rate of the adverse effect is 10. 7%. Condusion Systemic administration of interferon has a direct anti-virus effect, and it can raise the cure rate of virus keratitis as well as decrease recurrencerate. One million unit of interferon has a high clinical safety and effect.

Objective To investigate the prognostic factors of gastrointestinal stromal tumors.Methods From Nov.1999 to Dec.2006,a total of 85 patients were diagnosed by postoperative pathology as gastrointestinal stromal tumors.The relationship between the prognosis of GIST and demographic factors、tumor location、operation style、preoperative metastasis、lymphadenectomy、grading of Fletcher were analyzed retrospectively.Results The 1 year、3 year and 5 year survival rate of these 85 patients were 94%,60%,57%respectively,Univariate analysis indicated that tumor location、operation style、grading of Fletcher and preoperative metastasis were significant predictors of survival(P<0.05),while demographics and lymphadenectomy were not statistically related with prognosis.Multivariate analysis showed that preoperative metastasis was the independent factor predicting the prognosis(P=0.020,β=4.226).Conclusion Radical surgical excision is still the therapy of choice for primary gastrointestinal stromal tumors.Preoperative metastasis is the independent factor predicting poor prognosis,therefore early diagnosis and treatment are very important for GIST.Fletcher grading is also a simple recalls to predict the prognosis of GIST.