Objective To clarify the protective effect of nrsodeoxycholic acid ( UDCA ) on endoplasmic reticulum stress-mediated apoptosis in pancreatic β-cell of streptozotocin ( STZ )-induced diabetic rats.Methods Rats( n =40) received a single injection STZ( 50 mg/kg) intra-peritoneally and formed a β-cell injury model.Weight-matched normal rats( the control group,n =10 ) were injected with the buffer alone.STZ-treated rats with persistent random blood glucose higher than 16.7 mmol/L for 1 week were considered as diabetic status( n=14 ),then divided randomly into STZ-induced diabetes mellitus ( DM ) group ( n =7 ) and UDCA-treated DM group ( n =7 ).UDCA (40 mg· kg- 1,d-1 ) was administered daily by intragastric intubations throughout the experimental period (30 d).During the entire experiment,blood glucose in all rats was assessed.By the end of the experiment,all rats were sacrificed with the pancreas removed and the blood sample collected immediately.Fasting insulin levels were assayed by radioimmunoassay.The morphological changes of pancreatic β-cells apoptosis were determined by TUNEL assay.RNA in pancreas was abstracted and microarray containing 89 pieces of apoptosis related genes was applied.The related gene expressions were detected by RT-PCR and Western blot.Results The concentration of blood glucose in diabetic rats was gradually decreased after UDCA treatment,but at the end of the experiment it was still higher than that in the normal control group.The treatment with UDCA raised the fasting insulin level in diabetic rats,but this concentration was significantly lower as compared to the control group.Based on TUNEL stained tissue sections,the percentage of β-cell apoptosis of UDCA-treated DM group was significantly lower than that of STZ-induced diabetic group(P＜0.05 ).Among 89 genes,42 genes up-regulated and 46 genes down-regulated in diabetic rats,some of which were ameliorated by UDCA treatment.The expressions of Caspase-3,Bax,Bip,and CHOP mRNA in pancreas of DM group were significantly up-regulated as compared with those in the control group ( P ＜ 0.05 ) ; while the expression of Bcl-2 mRNA was markedly down-regulated (P＜0.05 ).However,these parameters in the U DCA-treated animals showed a marked improvement.Conclusion Ursodeoxycholic acid seems to protect pancreatic β-cell from apoptosis in STZ-induced diabetes by attenuating the severity of endoplasmic reticulum stress.

Objective To assess the value of susceptibility-weighted imaging (SWI) in staging hepatic fibrosis (HF) in rabbits. Methods Sixty healthy rabbits were randomly divided into HF group (n=44), control group (n=16). Rabbits in the HF group and supplementary group were injected subcutaneously with 50%CCl4 oily solution to establish hepatic fibrosis model. On the basis of preliminary test, 8 rabbits in the HF group and 4 rabbits in the control group were selected randomly at the 4th, 5th, 6th, 10th week after CCL4 injection ,respectively , to undergo liver MR scan,including conventional axial T1WI, T2WI and axial SWI, DWI scan. All rabbits were sacrificed after MR scan and the tissue of liver were sampled for pathological test and hepatic fibrosis staging. Rabbits were classified into group F0, F1-2 and F3-4 based on pathological results. Liver signal intensity (SI), and liver-to-muscle SI ratio were measured on SWI images and ADC values were measured on DWI images correspondently. One-way ANOVA analysis was performed to compare difference in liver SI, liver-to-muscle SI ratio and ADC values among group F0 (no fibrosis), F1-2 (mild-moderate fibrosis) and F3-4 (severe fibrosis) . Spearman correlation analysis was performed to correlate pathological staging and liver SI, liver-to-muscle SI ratio and ADC values. Receiver operating characteristic (ROC) curve analysis was performed to compare the diagnostic performance of SWI and DWI for staging HF. Results Two and 5 rabbits in the HF group died at the 5th and the 6th week after CCL4 injection , respectively due to acute hepatic necrosis, hepatorrhexis and systemic failure. Seven rabbits in supplementary group were used as supplement. Of the 16 rabbits in the control group, 1 was excluded from the study due to liver fibrosis. Fifteen rabbits in group F0, sixteen rabbits in group F1-2 and sixteen rabbits in group F3-4 underwent MRI and were included into this study. Liver-to-muscle SI ratio in group F0, F1-2 and F3-4 were 0.973 ± 0.020, 0.880 ± 0.090 and 0.649 ± 0.140, respectively. Liver SI were 378 ± 45, 374 ± 19 and 317 ± 34. ADC values were (1.473 ± 0.320) × 10-3, (1.311 ± 0.310) × 10-3 and (0.942 ± 0.180) × 10-3mm2/s. There were statistically significant differences in liver SI, liver-to-muscle SI ratio and ADC values among group F0, F1-2 and F3-4 (F=46.571,15.803 and 15.317, P< 0.01). Liver-to-muscle SI ratio was highly negatively correlated with HF staging (r=-0.818,P<0.01), while liver SI and ADC values were moderately correlated with HF staging (r=-0.565,-0.630;P<0.01). Area under ROC curve (AUC) of liver-to-muscle SI ratio, liver SI and ADC value for differentiating hepatic fibrosis stage F0 and stage F1-4 were 0.916, 0.695 and 0.768, while the AUC for differentiating hepatic fibrosis stage F0-2 and stage F3-4 were 0.951, 0.904 and 0.900. Conclusion Liver-to-muscle SI ratio on SWI provide added diagnostic value and could be an useful parameter for staging hepatic fibrosis.

Objective To establish a rabbit model of facial skin lifting and to evaluate the skin lifting effects of absorbable soft tissue plastic belt, and to provide experimental basis for clinical application of this plastic belt.Methods 36 Japanese white rabbits were randomly divided into model control group (n=6) and plastic belt lifting group (n=30). The model control group received only facial skin resection surgery, while the plastic belt lifting group had facial skin resection and plastic belt implantation.The changes of rabbit general status, skin lifting effects, performance of plastic belt and pathological changes of subcutaneous tissue after implantation were determined during the 4 weeks after surgery. Results The rabbit skin wound was healed within 3-7 days after surgery without infection.Meanwhile, the plastic belts did not show shifting or rupture, and only whitening around the perforations was observed in the two groups.Compared with the model control group, the MA and MB distances in the plastic belt lifting group were significantly lower ( P<0.01 ) , while the biological tension of plastic belts in the facial skin lifting rabbit models was significantly increased with the extension of time after implantation (P<0.01), and the biological tension was 18.62 N at 4 weeks after transplantation. In addition, the tensile intensities of perforations and plate in the two groups were significantly reduced at 4 weeks postoperatively (P<0.01), the tensile intensity of perforations and plate in the two groups were maintained at 35.07 N and 53.31 N, respectively, and the perforations/plate tensile intensity ratio of the two groups remained unchanged during 4 weeks after transplantation ( P >0.05 ) .Moreover, the molecular weight ( Mw ) , peak molecular weight ( Mp ) , Z molecular weight (Mz) and viscosity were gradually decreased along with the time passing after implantation (P<0.01), and its dispersion Mz/Mw ratio was also gradually decreased from 2 weeks after implantation (P<0.01), and no obvious pathological changes were found after subcutaneous implantation of the plastic belts.Conclusions We have successfully established a facial skin lifting rabbit model, and the plastic belt can obviously lift the facial skin fascia system and keep intact more than 4 weeks in the body.Therefore, this plastic belt can be applied for anti-wrinkle facial soft tissue lifting against the skin damage caused by aging.

Objective The aim of this study was to compare the biochemical and virological characteristics among patients infected with hepatitis B virus (HBV) according to pathologic inflammation grade.Methods 428 patients with chronic HBV infection accept liver biopsy,liver function test,HBeAg detection and HBV DNA levels detection.They were studied and subdivided into four groups according to pathologic inflammation grade.The biochemical and virological characteristics were studied.Univariate analysis was performed with the SPSS 16.0.Results In different inflammation grading group,mean age and sex composition were no difference.Serum levels of ALT was highest in group G3 and lowet in group G0-1,there was statistically significant among groups (P =0.005) ;AST and TBil were all highest in group G4 and lowest in group G0-1,statistically significant also found among groups (P =0.000&0.004).Serum levels of ALB and PTA were all highest in group G0-1 and lowest in group G4,had statistically significant among groups (P =0.000&0.000).There was no difference of HBV DNA level and percentage of HBeAg (+) among four groups (P =0.565&0.065).Conclusions The serum AST,TBil,ALB and PTA were different and can partly reflect the inflammation degree of liver damage in patients with HBV infection.ALT and PTA can reflect the inflammation degree of G0-1,G2 and G3 ;AST,TBil,ALB and PTA reflect the G3 and G4.HBV DNA level and HBeAg status can not indicate the inflammation degree in HBV infection patients.

BACKGROUND AND OBJECTIVERecent studies indicated that Non-small cell lung cancer (NSCLC) patients with mutant K-RAS failed to benefit from adjuvant chemotherapy, and the cancer did not respond to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). These findings indicated that K-RAS gene status can be a biomarker to predict the sensitivity of EGFR TKIs. The aim of this study is to analyze K-RAS gene mutations with NSCLC patients in Cancer Center of Sun Yet-sen University.

METHODS52 fresh frozen tumor tissues were collected and K-RAS genes were amplified by PCR. Then PCR amplification fragments were sequenced and analyzed.

RESULTSSomatic mutations in the codon 12 of K-RAS gene in tumors were identified from 2 of 52 (3.8%) patients. There were no relationships among K-RAS gene mutations and gender, pathology, smoking, differentiation and stage.

CONCLUSIONThe frequency of K-RAS gene mutations with NSCLC in our center is very low and is similar to that in Asia patients, and is lower than that in Caucasian population.

Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; genetics ; Female ; Humans ; Lung Neoplasms ; genetics ; Male ; Middle Aged ; Mutation ; Proto-Oncogene Proteins ; genetics ; Proto-Oncogene Proteins p21(ras) ; ras Proteins ; genetics

A novel mucoadhesive microcapsule with drug-resin complex core loaded with berberine hydrochloride (BH) was developed and optimized. Drug-ion exchange resin (IER) complex was prepared by static method which stirring IER in drug solution at certain conditions. The influences of different IERs, different temperature, pH values and concentrations of drug solution on the drug loading were investigated. IER complex was coated by emulsion-solvent evaporation method. The coating fluid formulation was optimized using central composite design-response surface methodology, where the ratio between Carbopol 934 and IER (X1), the ratio between Eudragit and IER (X2) and the ratio between Eudragit RL and RS (X3) were taken as independent variables. Time of cumulative release 85% (Y1) and percentage of gastric retention (Y2) were taken as response variables. Drug loading achieved a high level and more drug available in the condition of IER (IRP 88), 37 degrees C, pH 5 and 1.0 mg x mL(-1) drug solution. When X1 = 0.75, X2 = 0.9, X3 = 0.6, the time of cumulative release reached 85% at 300 min, the highest percentage of gastric retention in the range of this experiment were procured.
Acrylates ; chemistry ; Animals ; Berberine ; administration & dosage ; pharmacokinetics ; Capsules ; Delayed-Action Preparations ; Drug Compounding ; methods ; Drug Delivery Systems ; Emulsions ; Gastric Mucosa ; metabolism ; Hydrogen-Ion Concentration ; Ion Exchange Resins ; chemistry ; Male ; Polymers ; chemistry ; Rats ; Rats, Sprague-Dawley ; Temperature

To increase the dissolution rate and extent of valsartan, valsartan nanosuspensions have been prepared. Controlled precipitation assisted with sonication is utilized to prepare valsartan nanosuspensions, the concentration of the drug, stabilizer and costablizer had a great effect on the stability of the preparation according to the pre-experiment. So the method of central composite design-response surface is used to optimize the prescription based on the above three factors and the particle size as the response value. The software Origin 8.0 is used to draw the view of the three-dimensional effects and 2D contour map, to get the optimal prescription area. Valsartan nanosuspensions were prepared. The mean diameter and zeta potential are about 216.6 nm and -57.7 mV, respectively. Compared with the microsuspensions and commercial preparation, the dissolution of valsartan nanosuspensions was faster and the bioavailability can be enhanced to some extent.
Angiotensin II Type 1 Receptor Blockers ; administration & dosage ; chemistry ; Biological Availability ; Chemical Precipitation ; Drug Stability ; Nanoparticles ; administration & dosage ; chemistry ; ultrastructure ; Particle Size ; Research Design ; Solubility ; Suspensions ; Ultrasonics ; methods ; Valsartan ; administration & dosage ; chemistry

OBJECTIVETo investigate the characteristic of cervical lymph node metastasis of hypopharyngeal carcinoma and its influence to the prognosis.

METHODSOne hundred and eight hypopharyngeal carcinoma patients who accepted treatments in the 1st Affiliated Hospital of China Medical University from 1985 to 2000 were reviewed retrospectively. All of them accepted surgical treatment without pre-operative chemotherapy or radiotherapy. Stage was made according to the standard of International Union Against Cancer (UICC) in 1992. Specimens of the patients were carefully examined to confirm the primary site of the tumor and the distribution of cervical lymph node metastasis. Pathological differentiations of the tumor were classified into high, middle and low category. Kaplan-Meier method was used to estimate the 3rd, 5th years survival.

RESULTSThe rates of lymph node metastasis of was 45.8% for patients with TI and T2 disease, 79.8% for those with T3 and T4, and 75.0% (81/108)for the whole patients(P < 0.05). Patients with pyriform sinus cancer occupied 92.6% (100/108) of all the cases. Cervical lymph node metastasis rate of pyriform sinus cancer and posterior pharyngeal wall cancer were 74. 0% and 87. 5% respectively (P > 0.05). Cervical lymph node metastasis rate of patients with the high, middle and low differentiation tumor were 72. 2% , 67.6% and 85.7% respectively (P > 0.05). The 3rd and 5th years survival rates of all patients were 67.53% and 29.87% respectively. The occurrence of cervical lymph node metastasis was 76.5% in the level II and III, and 8.6% in the level V and VI. CONCLUSIONS Cervical lymph node metastasis rate of hypopharyngeal carcinoma is high. Cervical lymph node metastasis was one of the most significant prognostic factors of hypopharyngeal carcinoma. With the increase of the cervical node metastasis, the 3rd and 5th years survival of the patients declined gradually.

Adult ; Aged ; Female ; Humans ; Hypopharyngeal Neoplasms ; diagnosis ; pathology ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Neck ; pathology ; Prognosis ; Survival Rate

OBJECTIVETo investigate whether hepatitis B virus (HBV) can induce the expression of the host-encoded cytokine interleukin-32 (IL-32) and its effects on host signaling mechanisms related to HBV pathogenesis.

METHODSA eukaryotic expression vector harboring an enhanced green fluorescent protein was constructed with HBV genomic sequences (pIRES2-HBV-EGFP) and transfected into HepG2 cells. In addition, the nuclear factor-kappa B (NF-kB) subunits, p50 and p65, were transfected respectively into HepG2 cells. In both cases, 48 hrs after transfection, IL-32 expression was determined at the mRNA and protein levels using real-time PCR and ELISA and western blot, respectively. The HepG2 cells transfected with pIRES2-HBV-EGFP were also treated with the NF-kB inhibitor SN50 at various concentrations, and the effects on IL-32 protein expression 48 hrs later were evaluated by western blot. Significance of between-group differences was assessed by the Student's t-test.

RESULTSTransfection with pIRES2-HBV-EGFP led to significantly higher IL-23 expression than transfection with empty vector (mRNA: 2.8-fold higher and protein: 4.5-fold higher; both P less than 0.05). Transfection of p50 and p65 proteins led to significantly higher IL-32 expression (both P less than 0.05), and NF-kB activation was found to be required for HBV-induced IL-32 expression.

CONCLUSIONIL-32 expression is induced by HBV in HepG2 cells. This host-encoded cytokine, and its downstream activation of NF-kB, may be involved in the pathogenesis of HBV, especially in the subsequent liver inflammation that accompanies HBV infection.

Genetic Vectors ; Hep G2 Cells ; metabolism ; Hepatitis B virus ; Host-Pathogen Interactions ; Humans ; Interleukins ; metabolism ; NF-kappa B p50 Subunit ; metabolism ; Transcription Factor RelA ; metabolism ; Transfection

OBJECTIVETo explore the relationship between the -344T/C polymorphism of aldosterone synthase (CYP11B2) gene and essential hypertension in Chinese Mongolian population.

METHODSBy cluster-sampling method, a total of 1575 Mongolian people in Tongliao city of Inner Mongolia were included in this study. And 417 subjects were normotension, 596 subjects were prehypertension and 562 subjects were essential hypertension. A survey was conducted to collect data by personal interview using a standard questionnaire, meanwhile fasting blood samples were drawn. Height, weight, waist circumference, blood pressure, blood-fat indexes and fasting plasma glucose were measured. The variant genotypes of CYP11B2 were identified by PCR assays. The relationship between the -344T/C polymorphism of CYP11B2 gene and essential hypertension were analyzed by multinomial logistic regression model.

RESULTSCrude prevalence of prehypertension among Mongolian people was 37.84% (596/1575) and hypertension was 35.68% (562/1575). The age-standardized prevalence of prehypertension was 38.57% and hypertension was 31.53%. The frequency of the T and C allele was 0.66 (481/728) and 0.34 (247/728) for normotension group, 0.69 (696/1042) and 0.33 (346/1042) for prehypertension group, 0.71 (706/998) and 0.29 (292/998) for hypertension group. The multiple logistic models showed CYP11B2 variant genotypes were associated with prehypertension (TT/CC, OR = 1.33, 95%CI: 0.87 - 2.01; TC/CC, OR = 1.74, 95%CI: 1.13 - 2.67; TC + TT/CC, OR = 1.49, 95%CI: 1.01 - 2.22); CYP11B2 variant genotypes were associated with hypertension (TT/CC, OR = 1.70, 95%CI: 1.07 - 2.70; TC/CC, OR = 1.59, 95%CI: 0.98 - 2.50; TC + TT/CC, OR = 1.66, 95%CI: 1.06 - 2.58).

CONCLUSIONCYP11B2 gene -344T/C polymorphism were associated with essential hypertension in Chinese Mongolian population.

Adult ; Alleles ; Asian Continental Ancestry Group ; genetics ; Blood Pressure ; genetics ; China ; epidemiology ; Cytochrome P-450 CYP11B2 ; genetics ; Female ; Gene Frequency ; Genotype ; Humans ; Hypertension ; epidemiology ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Young Adult