OBJECTIVETo study the effect of ginsenoside Rb1 on GSKbeta/IDE signal transduction pathway and Abeta protein secretion in hippocampal neurons of high glucose-treated rats.

METHODHippocampal neurons of 24 h-old newly born SD rats were primarily cultured, inoculated in culture medium under different conditions, and then divided into the normal group, the high glucose group, the LiCl group and the Rb1 group. After being cultured for 72 h, the expressions of their phosphorylated GSK3beta, total GSK3beta and IDE protein were detected by Western blotting analysis. The mRNA expressions of GSK3beta and IDE were determined by RT-PCR. The ELISA assay was used to detect the secretion of Abeta protein in cell supernatant.

RESULTCompared with the normal group, the high glucose group showed increase in the p/tGSK3beta protein ratio and the secretion of Abeta protein and decrease in IDE protein and mRNA (P < 0.05). Compared with the high glucose group, both Rb1 and LiCl groups showed decrease in the p/tGSK3beta protein ratio and the expression of Abeta protein and increase in IDE protein and mRNA expression (P < 0.05). Compared with the LiCl group, the Rb1 group showed no significant difference in the expressions of p/tGSK3beta protein, IDE protein, mRNA and Abeta protein expression. In addition, the GSK3beta mRNA expression of the four groups had no significant difference.

CONCLUSIONGinsenoside Rb1 may reduce the secretion of Abeta protein in hippocampal neurons by reducing the phosphorylation of GSK3beta, down-regulating the ratio of pGSK3beta/GSK3beta and upregulating the expression of IDE.

Amyloid beta-Peptides ; genetics ; metabolism ; secretion ; Animals ; Dietary Carbohydrates ; adverse effects ; Gene Expression Regulation ; drug effects ; Ginsenosides ; pharmacology ; Glucose ; adverse effects ; Glycogen Synthase Kinase 3 ; genetics ; metabolism ; Glycogen Synthase Kinase 3 beta ; Hippocampus ; cytology ; Insulin ; metabolism ; Insulysin ; genetics ; metabolism ; Neurons ; cytology ; drug effects ; metabolism ; secretion ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects

AIM: To investigate the preoperative binocular visual function of intermittent exotropia and the rebuilding and recovery of the postoperative binocular visual function, and analyze the effect of binocular visual function on orthophoria after surgery.
METHODS:From January 2011 to January 2014, 47 basic intermittent exotropia patients caming for treatment were collected in the clinical data. The changes in their near stereopsis, binocular visual function, binocular fusion and distance stereopsis after operations were recorded in the form of data. The preoperative binocular vision and the postoperative rebuilding were analyzed and contrasted with each other. In addition, the effect on the postoperative maintaining of orthophoria due to the existence, recovery and rebuilding of binocular visual function were observed.
RESULTS:Intermittent exotropia patients got damage in different levels on their binocular visual functions, especially on distance stereopsis, which was the heaviest and earliest. After the operation, all functions were obviously recovered and reconstructed and the improvements were statistically significant compared against those before the operation (P<0. 01). Patients having binocular visual function or part of it before the operation had a higher ratio of orthophoria compared against the patients who had lost binocular visual function before the operation and the difference was statistically significant (P<0. 01). The recovery and reconstruction of the postoperative binocular visual function played an important role in maintaining the orthophoria.
CONCLUSION: The intermittent exotropia cause damage to the stereopsis which happened the earliest. Obvious recovery and reconstruction of binocular visual function can be observed after the surgery. A relatively good preoperative binocular visual function may lead to the increase in the ratio of orthophoria or cure the intermittent exotropia. Performing an operation when distance stereopsis is damaged can increase the success rate for the surgery and reduce the recurrence rate.

Adrenal Hyperplasia, Congenital ; complications ; metabolism ; Body Height ; Growth Disorders ; etiology ; Humans ; Risk Factors ; Steroid 21-Hydroxylase ; metabolism

Adult ; CD56 Antigen ; metabolism ; Combined Modality Therapy ; Diagnosis, Differential ; Humans ; Lymphoma, Extranodal NK-T-Cell ; metabolism ; pathology ; Lymphoma, Large B-Cell, Diffuse ; metabolism ; pathology ; therapy ; Lymphoma, Large-Cell, Anaplastic ; metabolism ; pathology ; Male ; Neprilysin ; metabolism ; Proto-Oncogene Proteins c-bcl-6 ; metabolism

Objective To evaluate the relationship between k -RAS mutation and the resistance to gefinitib treatment in patients with non -small -cell lung cancer (NSCLC).Methods 88 patients with NSCLC treated with gefinitib were analyzed respectively.The mutation of codon 12 and 13, located in exon1 and exon 2, was detected by PCR and DAN sequencing in the 88 NSCLC.The response between k -RAS mutation and the resistance to gefinitib treatment in patients with NSCLC was ana -lyzed.Results Fifteen patients were found mutated coden 12 /13, with an mutation frequency of 17.0% (15 /88).The objective response rate (ORR) was 22.7%(20 /88) with 4 cases of complete response and 16 cases of partial response, which indicating the ORR was much higher in patients with wild -type k -RAS gene than that in patients with mutated k -RAS genen (P <0.05).Conclusion NSCLC patients with mutated k -RAS gene can not benefit from EGFR -TIK treatment.

Adenoma ; genetics ; metabolism ; pathology ; surgery ; Adult ; Carcinoma, Papillary ; genetics ; metabolism ; pathology ; Diagnosis, Differential ; Exons ; Female ; Follow-Up Studies ; Humans ; Ki-67 Antigen ; metabolism ; Male ; Mutation ; Nuclear Proteins ; metabolism ; Proto-Oncogene Proteins B-raf ; genetics ; Thyroglobulin ; metabolism ; Thyroid Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Thyroid Nuclear Factor 1 ; Transcription Factors ; metabolism

OBJECTIVETo report the results of clinical characteristics, enzyme activity determination and mutation analysis of GLB1 gene in a Chinese patient with mucopolysaccharidosis (MPS) type IVB (Morquio B disease).

METHODA 14-year-old Chinese boy with MPS type IVB was firstly diagnosed by blood leucocytes galactosamine-6-sulfate sulfatase (GALNS) and β-galactosidase (GLB1) determination, who was characterized by short stature, multiplex skeletal abnormalities, difficulty in walking. PCR-sequencing analysis was applied to detect the mutations in GLB1 of the patient.

RESULTThe patient was characterized by dwarfism, pectus carinatum, kyphosis, normal intelligence, and no neurologic damage of spasms, linguistic capacity and so on. The patient had normal GALNS enzyme activity and very low GLB1 enzyme activity [5.03 nmol/(h·mg) vs. normal value 118 - 413 nmol/(h·mg) ] in leukocytes. A compound heterozygous missense mutations c.442C > T(p.R148C)/c.1454A > G(p.Y485C) in GLB1 gene were detected in this patient. The mutation p.Y485C is a novel variant. With the method of gene analysis of new variant, the mutation p.Y485C was considered to be a pathogenic mutation.

CONCLUSIONThe MPS IVB patient showed severe multiple skeletal deformities, normal intelligence, no neurologic damage and very low GLB1 enzyme activity, who carries compound heterozygous mutations p.R148C/p.Y485C. The mutation p.Y485C in GLB1 gene may be a novel pathologic mutation of MPS type IVB.

Adolescent ; Amino Acid Sequence ; Asian Continental Ancestry Group ; genetics ; Chondroitinsulfatases ; genetics ; metabolism ; DNA Mutational Analysis ; Humans ; Joints ; pathology ; Male ; Molecular Sequence Data ; Mucopolysaccharidosis IV ; enzymology ; genetics ; pathology ; Mutation, Missense ; Pedigree ; Polymerase Chain Reaction ; Radiography ; Spine ; diagnostic imaging ; pathology ; beta-Galactosidase ; genetics ; metabolism

OBJECTIVETo investigate the relationship between and underlying mechanistic pathway of clusterin (CLU) and chemo-resistance ofhepatocellular carcinoma (HCC) cells.

METHODSCLU protein expression in HCC cell lines (Hep3B, SMMC7721, PLC, and HepG2) and HepG2/ADM cells was quantified by western blotting. Four short-hairpin (sh)RNAs designed to block CLU-mRNA were generated, screened by RT-PCR, and transfected into the cells to determine effects of CLU on cell viability and apoptosis. Effects of CLU blockade on drug efflux pump activity were measured by flow cytometry.

RESULTSCLU was found to be over-expressed in HCC cell lines and HepG2/ADM cells. The four shRNAs inhibited CLU-mRNA as follows (vs. levels in untransfected cells): shRNA-1: 73.68% (q =23.011, P < 0.01), shRNA-2: 39.26% (q =11.991, P < 0.01), shRNA-3: 62.36% (q =19.392, P < 0.01), and shRNA-4: 55.35% (q =17.149, P < 0.01). shRNA-mediated depletion of CLU led to increased sensitivity to anti-cancer drugs and increased doxorubicin-induced apoptosis in HepG2/ADM cells, as evidenced by the apoptosis ratio of the shRNA-1 group of 39.28% vs. the apoptosis ratio of the untransfected control group of 4.92%. Silencing of CLU also decreased drug etflux pump activity, and the level of MDR1/P-gp expression was significantly reduced (shRNA-1 group vs.untransfected control group: q =14.604, P < 0.01).

CONCLUSIONCLU repression may enhance sensitivity of HCC cells to anti-cancers drugs and represents a potential molecular-target for reversal of multidrug-resistant HCC.

ATP Binding Cassette Transporter, Sub-Family B ; metabolism ; Antineoplastic Agents ; pharmacology ; Apoptosis ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Line, Tumor ; Cell Survival ; Clusterin ; genetics ; metabolism ; Down-Regulation ; Doxorubicin ; Drug Resistance, Neoplasm ; Humans ; Liver Neoplasms ; metabolism ; pathology ; RNA, Small Interfering ; genetics ; Transfection

OBJECTIVETo observe the correlation between brain-derived neurotrophic factor (BDNF) expression in the nerve system of diabetes mellitus (DM) rats and diabetic erectile dysfunction (ED).

METHODSDM rats were induced by injecting streptozotocin and erectile function test was done by injecting apomorphine (APO) at 1 month, 2 months, 3 months and 4 months. Then the brain, lumbosacral spinal cord, thoracic and lumbar sympathetic trunks, penis and prostate were taken from the diabetic and normal rats of the same age. The BDNF positive neurons and nerve fibers were shown by immunohistochemistry or fluorescence immunohistochemistry. The number and the grey density of BDNF positive cells and fibers were detected by image analysis.

RESULTSCompared with the control group, the erection frequency of the DM rats decreased at 2 months (P <0. 05) , and significantly at 3 and 4 months (P > 0.01) , and the BDNF positive neurons and nerve fibers in the cerebral cortex, lumbosacral spinal cord, thoracic and lumbar sympathetic trunks, penis and prostate of 1-month DM rats were reduced (P <0. 05). As time went on, BDNF declined progressively.

CONCLUSIONBDNF decreases in the central and peripheral nerve system in the early stage of diabetes mellitus, wich is closely correlated with diabetic ED.

Animals ; Brain-Derived Neurotrophic Factor ; biosynthesis ; Diabetes Mellitus, Experimental ; physiopathology ; Erectile Dysfunction ; physiopathology ; Male ; Nerve Tissue ; metabolism ; Rats ; Rats, Sprague-Dawley

Sixty healthy Sprague-Dawley male rats were used and divided randomly into control group (group C), cadmium loading group with medium dose (group M) and cadmium loading group with high dose (group H). Groups C, M and H were orally dosed daily with 0, 5 and 10 mg/kg of cadmium for over 6 weeks. Effects of cadmium loading on testis and endocrine function of reproduction in male rats were studied. The results showed that the zinc content decreased slightly in testis and plasma, and the cadmium concentration increased significantly in the testis of groups M and H; while the plasma levels of cadmium and zinc had no obvious difference as compared with those of group C; daily sperm production in the testis of group H decreased markedly during week 3 of cadmium loading, and was significantly lower in groups M and H as compared to that in group C during week 6; alkaline phosphatase (ALP) in group H and lactate dehydrogenase-X (LDH-X) in groups M and H were markedly lower compared to those of group C; plasma testosterone (T) level in both cadmium loading groups decreased and was low or significantly lower than that in group C; follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels had no apparent difference between the three groups. It is suggested that the gradual accumulation of cadmium in testis tissue induced by chronic cadmium loading results in changes in some enzyme activity, a decrease in sperm production, and defect of endocrine function activity in the testis.
Alkaline Phosphatase ; drug effects ; Animals ; Cadmium ; blood ; Cadmium Chloride ; administration & dosage ; toxicity ; Follicle Stimulating Hormone ; blood ; Isoenzymes ; drug effects ; L-Lactate Dehydrogenase ; drug effects ; Luteinizing Hormone ; blood ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reproduction ; drug effects ; Spermatogenesis ; drug effects ; Testis ; enzymology ; pathology ; Testosterone ; blood