AIM:To investigate the effect of insulin and gliclazide therapies on the liver fat accumulation in type 2 diabetic rats .METHODS:A high-fat diet plus low-dose streptozotocin was implemented to establish a type 2 dia-betic rat model, and the rats were randomly divided into diabetes mellitus (DM) group, diabetic rats treated with insulin ( INS) group, diabetic rats treated with gliclazide per os ( PO) group, and normal control ( NC) group.The diabetic rats in INS group and PO group were given insulin and gliclazide for 3 weeks, respectively.The changes of the liver fatty were evaluated with oil red O staining .Fasting plasma adiponectin concentration was measured by ELISA .The expression of adi-ponectin receptor 1 ( AdipoR1 ) was detected by real-time PCR.The protein levels of AMP-activated protein kinase (AMPK), phosphorylated AMPK on threonine 172 ( Thr172p-AMPK), sterol regulatory element-binding protein 1c (SREBP-1c), phosphorylated SREBP-1c on serine 372 (Ser372p-SREBP-1c), acetyl-CoA carboxylase (ACC), phospho-rylated ACC on serine79 (Ser79p-ACC) and immunoglobulin-binding protein (BiP) in the liver homogenate were deter-mined by Western blotting .RESULTS:Compared with the normal rats , in DM group, the presence of cytoplasmic lipid deposits was confirmed by oil red O staining .In INS group, these changes were significantly lower than those in DM group . Similar results were obtained in PO group .Insulin therapy significantly increased the plasma concentration of diponectin and liver tissue levels of AdipoR1 compared with DM group.At the same time, these 2 indicators returned to normal levels after gliclazide therapy .Thr172p-AMPK/AMPK, Ser372p-SREBP-1c/SREBP-1c and Ser79p-ACC/ACC expression ratios were significantly reduced in DM group compared with control values .The expression of BiP was increased on the contrary . After insulin therapy, Thr172p-AMPK/AMPK and Ser372p-SREBP-1c/SREBP-1c were significantly increased, and Ser79p-ACC/ACC and BiP returned to the normal levels .After gliclazide treatment, Thr172p-AMPK/AMPK and Ser372p-SREBP-1c/SREBP-1c returned to the normal levels , the expression ratio of Ser79p-ACC/ACC had no significant improve-ment compared with DM group , and the expression of BiP significantly declined .CONCLUSION: Both the insulin and gliclazide therapies reduce the lipid deposition in the liver of rats with type 2 diabetes by activating AMPK , but the extent and mechanism are not the same.In insulin therapy, AMPK restrains the expression of SREBP-1c directly, increases the phosphorylation of SREBP-1c, and affects SREBP-1c by inhibiting the endoplasmic reticulum stress .Gliclazide treatment, which has no effect on the lipid oxidation , reduces lipid deposition in the liver only through the phosphorylation of SREBP-1c and the suppression of the endoplasmic reticulum stress .

ovel GCK-E339K mutation might be linked to this MODY2 pedigree.

AIM:To investigate the effects of glucagon-like peptide-1 (GLP-1) receptor agonist exendin-4 on white adipose tissue (WAT) and the underlying mechanisms.METHODS:Male C57BL/6J mice (8 weeks) were chal-lenged by high-fat diet for 12 weeks, and were randomly divided into saline group and exendin-4 group.The mRNA expres-sion of sirtuin 1 (SIRT1), adipose triglyceride lipase (ATGL), TNF-αand adiponectin of WAT was detected by real-time PCR.3T3-L1 adipocytes or mouse embryonic fibroblasts cells were treated with exendin-4 for 24 h.The protein levels of SIRT1, ATGL and hormone-sensitive lipase (HSL) were determined by Western blot.RESULTS:Exendin-4 significantly decreased epididymal fat weight, fasting blood glucose and serum triglyceride levels ( P<0.05) , and reduced body weight and serum TNF-αlevel.The mRNA expression of SIRT1, ATGL and adiponectin in WAT was all significantly up-regulated by exendin-4, which were contrary to the down-regulation of TNF-αmRNA expression (P<0.05).Exendin-4 promoted the protein expression of SIRT1, ATGL, and HSL in 3T3-L1 adipocytes in a dose-dependent manner.Less lipid droplets with up-regulation of lipolytic protein expression were observed when combined with SIRT1 agonist treatment, which were suppressed by SIRT1 inhibitor.Deletion of SIRT1 led to larger adipocytes with more lipid droplets, and the effect of ex-endin-4 on the lipolysis disappeared when SIRT1 was deficient.CONCLUSION:Exendin-4 promotes lipolysis in WAT of obese mice via activation of SIRT1.

Objective To analyze the clinical speciality of invasive fungal infection(IFI)and provide doctors with clinical evidence for early anti-fungal therapy.Method One hundred and thirty-seven patients with 91 male and 46 female,who suffered from invasive fungal infection in ICU from January.1,2000 to June 30, 2006,were enrolled in this study.The age ranged from 17 to 82 years old.Out of 137 patients with IFI,the percentage of albicans candida,glabirate candida,tropicalis candida and parapsilosis candida were 47.4%, 26.3%,20.4% and 3.6%,reseparately.The sputum,urine,blood and other drainages were collected to perform the fungal examination after three days of admission every three days.Results Of 137 patients,42 of them were complicated with hemorrhage,53 patients with IFI developed candida anthema in the chest,abdomen and extremity.,49 patients suffering from IFI had organ dysfunction.The chest image revealed that infiltration caused by IFI especially occurred in apex of lung in some patients.The pathogen analysis displayed that albicans candidiasis easily developed candida anthema,glabirate candidiasis frequently resulted in organ dysfunction,and tropicalis candida led to hemorrhage in some organs.Conclusions The clinical specialty,of IFI caused by candida included hemorrhage,candida anthema,organ dysfunction,and infiltration in apex of lung.

Objective To investigate the expressions of human telomerase reverse transcriptase(hTERT) mRNA and protein in pheochromocytoma and paraganglioma and their significance as diagnostic markers in predicting the biological behaviour of these tumours.Methods Expression of hTERT mRNA was determined by in situ hybridization in 45 pheochromocytomas/paragangliomas(31 benign,7 suspected malignant and 7 malignant) and 9 normal adrenal medulla samples,hTERT protein was determined by immunohistoebemistry.Results hTERT mRNA was expressed in 5/7 malignant turnouts and 5/7 suspected malignant tumours as compared with 3/31 benign tumours(P

Objective To investigate the expression and clinical value of immunohistochemistry in endometrial stromal tumors.Methods Immunohistochemical technique(Envision method)was applied to de- tect the expression of CD_(10),SM-MHC,h-caldesmon,AE1/3,CD_(99),Ki-67,CD_(34),c-kit,ER and PR in 15 cases of endomertrial stromal sarcoma and 3 metastases.The clinical pathological data,including the histological characteristics,histochemical and immunohistochemical staining features,complication,differential diagnosis and prognosis of endometrial stromal tumours were analyzed.Results Among the 18 cases of endometrial stromal tumor,17 cases had shown positive for CD_(10),including 13 cases diffuse positive and 4 muitifocal,7 cases with smooth muscle differentiation,3 cases with epithelial differentiation,7 cases with sex-cord differ- entiation.13 cases of ER and 16 cases of PR were positive expression in endometrial stromal sarcoma.Ki-67 in range 36 %～78 %.Conclusion Endometrial stromal tumour can display multi-differentiation.They show various pathomorphological features,Smooth muscle and sex-coed differentiation,the most common types. CD_(10) can be expressed consistently in endometrial stromal tumors.CD_(10) with h-caldesmon and SM-MHC can be used to make differential diagnosis between the endometrial stromal tumors and cellular leiomy0ma.ER and PR should be routinely estimated and be a prognostic predictor for endometrial stromal sarcoma.

Baculoviridae ; genetics ; metabolism ; Phylogeny ; Viral Proteins ; chemistry ; classification ; genetics ; metabolism

Enterohemorrhagic Escherichia coli ; Escherichia coli Infections ; epidemiology ; Germany ; epidemiology ; Humans

To increase the in vivo half-life of human CNTF mutein AX15 (R13K), HSA-AX15 (R13K) fusion protein was constructed by the fusion of the C-terminus of HSA to the N-terminus of AX15 (R13K) via an 11 amino acids linker. HSA-AX15 (R13K) fusion protein was purified to homogeneity by cation exchange chromatography, reverse phase chromatography and gel filtration after expressed in pichia pastoris. TF-1 cell survival bioassay showed the biological activity of AX15 (R13K) was not affected by the fusion to HSA. It was demonstrated that tertian injection of 4.8 mg/kg HSA-AX15 (R13K) fusion protein could produce more potent anti-obesity effects on KM mice than daily injection of 1.6 mg/kg AX15 (R13K). The long-acting form of hCNTF variant has the potential to reduce discomfort by requiring fewer injections and to minimize the side-effects by decreasing the dosage and fluctuation of plasma concentration, and thus has superior clinical application.
Animals ; Ciliary Neurotrophic Factor ; genetics ; Humans ; Mice ; Mutant Proteins ; biosynthesis ; genetics ; Pichia ; genetics ; metabolism ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; isolation & purification ; Serum Albumin ; genetics

OBJECTIVETo investigate the influence of the time interval from the end of semen processing to artificial intrauterine in semination with husband's sperm (AIH-IUI) on the rate of clinical pregnancy.

METHODSThis study involved 191 AIH-IUI cycles with the same ovulation induction protocol. After Percoll density gradient centrifugation, we divided the sperm into four groups based on the incubation time: 0-19, 20-39, 40-59, and 60-80 min, and again into another four groups according to the total progressively motile sperm count (TPMC): (0-9), (10-20), (21-30), and > 30 x 10(6). We analyzed the correlation of the clinical pregnancy rate with the time interval from the end of sperm processing to AIH-IUI and with other influencing factors, such as maternal age, infertility duration, and semen quality.

RESULTSThe rate of clinical pregnancy was significantly higher in the 20-39 min group (18.3%) than in the 0-19, 40-59, and 60-80 min groups (12.7, 11.4 and 9.1%) (all P < 0.05). The (10-20) x 10(6) group achieved a remarkably higher pregnancy rate (16.7%) than the (0-9), (21-30), and > 30 x 10(6) groups (0, 11.4, and 8.3%) (all P < 0.05). Logistic multivariate analysis showed that the rate of clinical pregnancy was decreased with the increased age of the women (OR 0.89, 95% CI 0.83-0.94) but significantly elevated in the 20-39 min group (OR 2.11, 95% CI 1.34-3.13) and of (10-20) x 10(6) group (OR 2.06, 95% CI 1.32-3.46).

CONCLUSIONThe time interval from the end of sperm processing to AIH-IUI is a most significant factor influencing the rate of clinical pregnancy of AIH-IUI.

Centrifugation, Density Gradient ; Female ; Humans ; Infertility ; therapy ; Insemination, Artificial, Homologous ; statistics & numerical data ; Male ; Pregnancy ; Pregnancy Rate ; Semen ; Semen Analysis ; Sperm Count ; Spermatozoa ; Time Factors