Objective： To discover HER2/neu tyrosine kinase inhibitor through computer-aided drug design approach. Methods： The three-dimensional(3D) structure of HER2/neu and EGFR tyrosine kinase domain was modeled using MODERLAR software. To search database and pick up candidate compounds based 3D structure of HER2/neu tyrosine kinase domain. Inhibition of HER2/neu tyrosine kinase phosphorylation by the compounds was detected using Western blot analysis. Inhibition of cell proliferation was determined by MTT assay. Results： The amino acid identity and similarity between HER2/neu and EGFR kinase domain, insulin receptor kinase domain, FGFR1 kinase domain, Src kinase domain were compared. The identity was 35％ -41％ and the similarity was 52％ -55％ . The 3D structure of HER2/neu and EGFR was obtained by MODERLAR software. Through searching, screening and optimization, the authors found that ST2325 had significantly inhibitory effect on HER2/neu tyrosine kinase phosphorylation with IC50 of 6.6 μ mol/L. The inhibition of HER2/neu phosphorylation was selective and reversible. ST2325 inhibited cell proliferation of HER2/neu-overexpressing MDA-MB-453m1 preferentially compared with EGFR-overexpressing MDA- MB-468, The IC50 values were 29.05 and 60.4 μ mol/L. Conclusion： ST2325 which was discovered through structure-based approach had notable inhibitory effect on HER2/neu tyrosine kinase.

OBJECTIVETo study the effect of chronic rapid eye movement sleep deprivation on energy metabolism, FT3, FT4 in serum.

METHODSRapid eye movement sleep deprivation of rats were deprived by flower pot, and then the energy metabolism were detected. The FT3, FT4 level in serum was determined by radioimmunoassay kit.

RESULTSRats after sleep deprivation displayed food intake increased from (75.06 +/- 25.37)g/(d x kg) to (122.30 +/- 20.43)g/(d x kg), body weight substantially decreased from (360.89 +/- 43.01) g to (295.97 +/- 37.95) g, body temperature from (37.62 +/- 1.12) degrees C up to the first (39.00 +/- 0.87) degrees C and then reduced to (37.72 +/- 0.84) degrees C, the basal metabolism rate increased significantly from (1.69 +/- 0.36) mlO2/(g x h) to (2.40 +/- 0.09) mlO2/(g x h), compared with the control group( P < 0.05). Sleep deprivation also resulted significantly lower serum thyroxine levels in comparison with the control, serum free triiodothyronine (FT3) level reduced from (3.38 +/- 0.88) pmol/L to (2.38 +/- 0.83) pmol/L, then free thyroxine(FT4) decreased from (14.62 +/- 3.62) pmol/L to (8.26 +/- 2.80) pmol/L (P < 0.05).

CONCLUSIONRapid eye movement sleep deprivation can change energy metabolism remarkable, as well as the alteration of FT3, FT4 levels in serum.

Animals ; Energy Metabolism ; physiology ; Male ; Rats ; Rats, Wistar ; Sleep Deprivation ; blood ; metabolism ; Sleep, REM ; physiology ; Thyroxine ; blood ; Time Factors ; Triiodothyronine ; analogs & derivatives ; blood

OBJECTIVETo prepare a glypican-3 (GPC3)-targeting hepatocellular carcinoma MR molecular probe and to evaluate its targeting specificity using HepG2 cells.

METHODSPoly(lactic-co-glycolic acid) (PLGA) nanoparticles were prepared by a double emulsion solvent evaporation method, and the surfaces were connected with anti-GPC3 mono-antibody and paramagnetic substance Gd3+. The physical properties of the probes were investigated using fluorescence microscopy, electron microscopy, Malvern particle size analysis, inductively coupled plasma atomic emission spectroscopy (ICP-AES) and 1.5T MR imaging. The specificity of the probes to target cultured HepG2 cells was determined by laser confocal microscopy. The signal characteristics, including signal-to-noise ratio (SNR), after co-incubation with HepG2 cells were analyzed by 1.5T MR imaging. Significance of differences between multiple groups (target group, non-target group, and control group) was assessed by one-way analysis of variance, and between two groups was assessed by the LSD-t test. A difference was considered to be statistically significant at P less than 0.05.

RESULTSThe GPC3-targeting hepatocellular carcinoma MR molecular probes were successfully prepared. The nanoparticles had a spherical shape, size of 495 +/- 17.5 nm, uniform size distribution, good dispersibility, no obvious aggregation, and could significantly increase the T1 signal. Using the ICP-AES measurement, 1 mol PLGA carried about 12 mol Gd3+, and as the Gd3+ concentration increased, the T1 signal increased. The prepared MR molecular probes could specifically target HepG2 cells, and could increase the T1 signal. The SNR value of the target group was 3.45 +/- 0.21, of the non-target group was 1.43 +/- 0.07, and of the control group was 1.12 +/- 0.03. The SNR value of the target group was significantly higher than that of the non-target group and the control group (P less than 0.05); there was no significant difference between the non-target group and the control group (P more than 0.05).

CONCLUSIONPLGA nanoparticles, anti-GPC3 mono-antibody and paramagnetic Gd3+ can be used to successfully prepare GPC3-targeting hepatocellular carcinoma MR molecular probes which are capable of specifically targeting HepG2 cells in vitro and being detected by 1.5T MR imaging. These MR molecular probes may represent a useful noninvasive imaging method for detecting early hepatocellular carcinoma in vivo.

OBJECTIVETo study the clinicopathologic features, differential diagnosis and pathogenesis of sclerosing angiomatoid nodular transformation of spleen.

METHODSTen cases of sclerosing angiomatoid nodular transformation of spleen were retrieved from the archival file. Histochemical and immunohistochemical (EnVision method) studies were performed. Ultrastructural findings were also available in one of them.

RESULTSSclerosing angiomatoid nodular transformation was characterized by micronodular appearance of vascular spaces lined by plump endothelial cells with interspersed ovoid spindle cells. Immunohistochemical study showed that the endothelial cells of vessels in the angiomatoid nodules had various expressions of immunologic phenotypes and could be mainly classified into 3 types: CD34(+)/CD31(+)/CD8⁻ endothelial cells of the capillaries, CD8(+)/CD31(+)/CD34⁻ lining cells of the sinusoids and CD31(+)/CD8⁻/CD34⁻ endothelial cells of the small veins. Collagen network and dilated lymphatic sinuses were evident under transmission electron microscope.

CONCLUSIONSSclerosing angiomatoid nodular transformation of spleen is a rare benign entity. It may represent a reactive condition and bears some relationship with splenic angioma. It needs to be distinguished from borderline or malignant vascular tumors of spleen.

Adult ; Antigens, CD34 ; metabolism ; CD8 Antigens ; metabolism ; Diagnosis, Differential ; Female ; Hemangioendothelioma ; metabolism ; pathology ; Hemangiosarcoma ; metabolism ; pathology ; Histiocytoma, Benign Fibrous ; metabolism ; pathology ; surgery ; ultrastructure ; Humans ; Male ; Microscopy, Electron ; Middle Aged ; Platelet Endothelial Cell Adhesion Molecule-1 ; metabolism ; Splenic Neoplasms ; metabolism ; pathology ; surgery ; ultrastructure

Objective To analyze the outcome of surveillance results on plague and to provide the evidences for the policy making in Longlin county Guangxi. Methods The epidemic data and the surveillance results of plague were analyzed and assessed with epidemiology methods in Longlin county Guangxi from 2000 to 2009, and the density of rodents, the rodents infected with flea, flea index and other indicators were calculated. Regional composition of the rats and fleas were analyzed. Results A totally of 4829 rats were captured and 4737 fleas were collected in the past 10 years, Rattus Flavipestus(81.92%,3956/4829) and Xenopsylla Cheopis (79.04%,3744/4737) were dominant species. The annual average density of rodents, the rodents infected with flea, index of flea were 3.30%(4829/146 206), 27.99%(1351/4827) and 0.98(4737/4827), respectively. A totally of 4792 rats were examined and 10 strains Yersinia Pestis were isolated. Indirect hemorrhagic assessed(IHA) was used to test the F1 antibody against plague in the blood serum of the rats and indicator animals, and 3 positive rats and 24 positive animals were found, respectively. Twenty seven natural villages in 3 towns had been involved in the plague. Conclusions The plague foci exists in Longlin county of Guangxi province. The plague foci in the areas have the same feature with the plague foci of Rattus Flavipectus. There is a potential risk for plague in this region, we should improve the quality of surveillance, increase indicator animals of the plague, and try to apply new surveillance method.

Objective To explore the current status of H.pylori infection in the natural population of Sanya City,analyze its influencing factors,and provide a reference basis for the prevention and control of H.pylori infection.Methods A total of 677 residents from four districts of Sanya City were selected by overall stratified random sampling method,and were subjected to urea 14C breath test and questionnaire survey to calculate the positive rate of H.pylori in the natural population and analyze the influencing factors of H.pylori infection.Results A total of 606 residents were included,and the number of H.pylori positive detections was 261,with a positive detection rate of 38.5％.Among them,different ethnicity,marital status,smoking,eating vegetables and fruits,and literacy level were associated with H.pylori infection(P＜0.05);gender,age,BMI,alcohol consumption,drinking water source,betel quid chewing,and the number of cohabitants were not significantly associated with H.pylori infection(P＞0.05).Family infection was an independent risk factor for H.pylori infection in the natural population of Sanya City,and Li ethnicity,frequent consumption of fruits and vegetables,and college and higher education level were independent protective factors for H.pylori infection in the natural population of Sanya City.Conclusion The rate of H.pylori infection in the natural population of Sanya City is lower than the national average.Consuming more fruits and vegetables and improving the awareness of hygiene protection are conducive to the prevention of H.pylori infection;and the promotion of the family and related members with the same examination and treatment is important to avoid aggregation of infection within the family.

OBJECTIVESTo examine whether or not vascular endothelial growth factor (VEGF) and its receptors were expressed in hepatocellular carcinoma cell lines with various metastatic potentialities.

METHODSReverse transcription-polymerase chain reaction (RT-PCR), enzyme linked immunosorbent assay (ELISA) and Western blot were employed to study the expressions of VEGFR-1, VEGFR-2, VEGF-A and VEGF-B in four hepatocellular carcinoma cell lines MHCC97-H, MHCC97-L, SMMC7721 and HepG-2 and one normal liver cell line L-02.

RESULTSThree hepatocellular carcinoma cell lines (MHCC97-H, MHCC97-L, SMMC7721) expressed VEGFR-1 mRNA and their proteins. The expression level of VEGFR-1 in MHCC97-H was higher than that in MHCC97-L (P less than 0.05) and the expression level of VEGFR-1 in MHCC97-L was higher than that in SMMC7721 (P less than 0.05). No expression of VEGFR-1 was found in HepG-2 or L-02. All four hepatocellular carcinoma cell lines and the L-02 cell line expressed VEGFR-2 mRNA and the protein, as well as the VEGFR-1 ligands VEGF-A and VEGF-B. The expression level of VEGFR-2 in all tested hepatocellular carcinoma cell lines and normal liver cell line L-02 showed no significant differences (P more than 0.05).

CONCLUSIONVEGFR-1 was expressed in 4 hepatocellular carcinoma cell lines with various metastatic potentialities. The expression levels appeared to be positively correlated with the potentialities of metastasis of the hepatocellular carcinoma cell lines. VEGFR-1 may relate to the invasiveness and metastatic potential of the hepatocellular carcinoma.

Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Humans ; Liver Neoplasms ; metabolism ; pathology ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neovascularization, Pathologic ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor Receptor-1 ; metabolism

OBJECTIVETo establish an animal model of prostate cancer (PCa) metastasis to the lung using PCa PR7 (PCa PC-3 cells stably expressing red fluorescent protein AsRed2) cell lines that can be monitored by in vivo fluorescence imaging technology.

METHODSMTT and Transwell assay were used to compare the abilities of proliferation, migration and invasion of PC-3 and PR7 cells. Twenty BALB/c nude mice were equally randomized to 4 groups to receive tail vein injection of PR7 cell suspension at the concentration of 1 x 107/ml (group A), 2.5 x 107/ml (group B), 5 x 107/ml (group C) and 2.5 x 107/ml followed by the same dose 1 week later (group D). PCa metastasis to the lung was then monitored by in vivo fluorescence imaging technology at the end of 2, 4, 6 and 8 weeks.

RESULTSThere were no statistically significant differences between PC-3 and PR7 cells in their abilities of proliferation, migration and invasion (P > 0.05). At the end of 4 weeks, lung metastasis was observed in 40% of the mice in group D, and at the end of 8 weeks, it was detected in 20% in group A, 60% in group B, 100% in group C, and 100% in group D, all confirmed by pathological examination.

CONCLUSIONThe animal model of PCa metastasis to the lung that can be monitored by in vivo fluorescence imaging technology was established successfully by tail vein injection of PR7 cells carrying red fluorescent protein.

Animals ; Cell Line, Tumor ; Disease Models, Animal ; Humans ; Luminescent Proteins ; Lung Neoplasms ; diagnosis ; secondary ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Optical Imaging ; Prostatic Neoplasms ; diagnosis ; pathology

OBJECTIVETo study the pathological and clinical features of nonalcoholic fatty liver disease (NAFLD).

METHODSGrades and stages of liver lesions in 41 patients with NAFLD were analyzed. The relationships between pathohistological features of the livers, serum biochemical parameters, ultrasound examination and other clinical data of the patients were studied.

RESULTSAmong the 41 patients with NAFLD (there were 21 with their liver fatty degeneration in grade 1, 15 in grade 2, and 5 in grade 3). There were 2 of grade 0, grade 1 had 25, grade 2 had 10, grade 3 had 3, and grade 4 had 1. Stage 0 of fibrosis was 20, stage 1 was 14, stage 2 was 4, stage 3 was 2, and stage 4 was 1. Degree of fatty degeneration was not positively associated with the body mass index (BMI) of the patients and the ultrasound findings in their livers. Grading of the inflammation was positively related to the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the blood and ultrasound findings in their livers, but negatively to the platelet counts. Staging of fibrosis of the livers was positively related to the blood ALT, AST, GGT, and ALP, and negatively to triglyceride levels and platelet counts.

CONCLUSIONSDegree of liver fatty degeneration was not associated with grades of inflammation and staging of fibrosis of the liver. BMI, ALT and AST level, platelet counts, and ultrasound grades of fatty liver were associated with the liver histopathological changes of NAFLD patients. Liver biopsy is the essential way to make a diagnosis of NAFLD.

Adolescent ; Adult ; Biopsy, Needle ; Fatty Liver ; diagnosis ; diagnostic imaging ; pathology ; Female ; Humans ; Liver ; diagnostic imaging ; pathology ; physiopathology ; Male ; Middle Aged ; Ultrasonography

OBJECTIVETo evaluate the occurrence and management of complications following minimally invasive percutaneous nephrolithotomy (MPCNL).

METHODSThe data of 4326 cases of MPCNL from January 2001 to February 2006 were reviewed, including 2451 male cases and 1875 female cases. Their age ranged from 4 to 82 years with a mean of 42 years. Of 4326 cases, 1221 cases had simple nephrolithiasis, 1735 staghorn nephrolithiasis, 386 upper ureterolithiasis, 90 serious stone street after extracorporeal shock wave lithotripsy, and 894 residual calculi after open surgery.

RESULTSAmong the 4326 cases of MPCNL, complications occurred in 445 cases (10.3%). Of the 445 cases, 20 had massive hemorrhage, 13 pleural injuries, 1 colonic perforation, 343 fever attacks (T > 38 degrees C), 13 septic shocks, 16 perinephric urinoma, 9 perinephric abscess, 26 renal perforating injuries, 1 guide wire misled into inferior vena cava, 3 died.

CONCLUSIONSMPCNL is a minimally invasive operation. However, serious complications would occur if the procedure were ignored. The improvement in the prevention and management of complications can promote the application of this procedure.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Kidney Calculi ; surgery ; Male ; Middle Aged ; Nephrostomy, Percutaneous ; adverse effects ; methods ; Postoperative Complications ; prevention & control ; therapy ; Ureteral Calculi ; surgery