Cardiomyopathy, Dilated ; pathology ; Cardiomyopathy, Hypertrophic ; pathology ; Diagnosis, Differential ; Fetal Diseases ; pathology ; Fetus ; Heart Neoplasms ; pathology ; Humans ; Myocardium ; pathology ; Ventricular Dysfunction, Left ; pathology

Humans ; Sinus of Valsalva ; Death, Sudden, Cardiac/etiology* ; Coronary Stenosis/complications*

BACKGROUND: The introduction of cyclosporin A (CsA) has greatly enhanced the early survival rate of kidney graft, but the long-term graft survival rate is still limited. Whether tacrolimus prevents chronic allograft nephropathy (CAN) and prolongs survival time is now becoming a hot spot in field of renal transplantation.OBJECTIVE: To investigate the feasibility and safety of converting CsA to tacrolimus (FK506) in preventing progression of CAN. DESIGN: Observation and controlled trial.SETTING: Department of Urological Organ Transplantation, Center of Organ Transplantation, the Second Xiangya Hospital, Central South University.PARTICIPANTS: A total of 73 patients who had received kidney transplantation at the Department of Urological Organ Transplantation, Center of Organ Transplantation, the Second Xiangya Hospital of Central South University from April 2001 to October 2005, and had been diagnosed as CAN by graft biopsy (42 male patients and 31 female patients; age ranged 19-69 years), were enrolled in the study approved by the ethics committee of this hospital after their written informed consents. CsA soft capsules (Hangzhou Zhongmei Huadong Pharmaceutical Limited Company or Huabei Pharmaceutical Limited Company); mycophenolate mofetil capsules (Shanghai Roche Pharmaceutical Limited Company); prednisone acetate tablets (Second Xiangya Hospital of Central South University); tacrolimus capsules (Fujisawa Pharmaceutical Limited Company).METHODS: Seventy-three patients voluntarily participated in CsA group (n =30) or FK506 group (n =43). The two groups were homogenous regarding patients' sex, age and general data (P > 0.05). Patients in the CsA group were continued on their initial immunosuppression protocol, which consisted of CsA, mycophenolate mofetil and prednisone acetate. In the FK506 group, CsA was stopped, and FK506 was started at a dose of 0.08-0.1 mg/(kg·d) 24 hours later, twice daily, administered 2 hours after breakfast and supper. Three days later, the blood trough concentration of FK506 was tested and adjusted to a target range of 5-8μg/L. FK506 dosage adjustment was based on the blood trough concentration, serum creatinine (SCr) and its side effects. All 73 patients were treated for 12 months. MAIN OUTCOME MEASURES: SCr, glomerular filtration rate (GFR), 24-hour urine protein excretion, serum total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL) and the toxic side effects of calcineurin inhibitors (incidences of tremor, hyperglycemia and hypertension) were monitored during a follow-up of over 12 months. RESULTS: A total of 73 patients were involved in the result analysis.①12 months after conversion, the level of SCr was statistically reduced and GFR levels were markedly elevated in the FK506 group compared with the CsA group (P < 0.01). TC, TG and LDL levels in the FK506 group were significantly lower than those in the CsA group (P < 0.01).②Compared with the CsA group, the incidence of tremor was obviously increased [30% (9/30), 5% (2/43), P < 0.01] and the incidence of hypertension was obviously decreased [56% (24/43), 83% (25/30), P < 0.05] in the FK506 group.CONCLUSION: Conversion from CsA to FK506 can postpone renal dysfunction, reduce proteinuria and improve hyperlipidemia. FK506 treatment is an effective therapy in slowing the progression of CAN.

A series of novel tetrahydrocarboline derivatives was designed and synthesized in order to discover more potent peroxisome proliferator-activated receptor (PPAR) alpha/gamma dual regulators. The structures of these compounds were confirmed by 1H NMR and HR-MS; their PPAR-regulating activities were evaluated in vitro. Compounds 6h, 6n, 6p and 6q exhibited more potent PPARalpha agonistic activities than the control drug WY14643, while compounds 60, 6g, 6i and 6q exhibited more potent PPARgamma agonistic activities than the control drug rosiglitazone. Compound 6q was discovered as a potent PPARalpha/gamma dual agonist and deserves further investigation.
Animals ; Carbolines ; chemical synthesis ; chemistry ; pharmacology ; Cells, Cultured ; Drug Design ; Hypoglycemic Agents ; chemical synthesis ; chemistry ; pharmacology ; Molecular Structure ; PPAR alpha ; agonists ; PPAR gamma ; agonists ; Peroxisome Proliferator-Activated Receptors ; agonists ; Pyrimidines ; metabolism ; Structure-Activity Relationship ; Thiazolidinediones ; metabolism ; Transfection

Objective To investigate whether recombinant human endostatin can create a time window of vascular normalization prior to vascular pruning to alleviate hypoxia in Lewis lung carcinoma in mice. Methods Kinetic changes in morphology of tumor vasculature in response to recombinant human endostatin were detected under a confocal microscope with immunofluorescent staining in Lewis lung carcinomas in mice. The hypoxic cell fraction of different time was assessed with immunohistochemical staining . Effects on tumor growth were monitored as indicated in the growth curve of tumors . Results Compared with the control group vascularity of the tumors was reduced over time by recombinant human endostatin treatment and significantly regressed for 9 days. During the treatment, pericyte coverage increased at day 3, increased markedly at day 5, and fell again at day 7. The vascular basement membrane was thin and closely associated with endothelial cells after recombinant human endostatin treatment, but appeared thickened, loosely associated with endothelial cells in control tumors. The decrease in hypoxic cell fraction at day 5 after treatment was also found. Tumor growth was not accelerated 5 days after recombinant human endostatin treatment. Conclusions Recombinant human endostatin can normalize tumor vasculature within day 3 to 7, leading to improved tumor oxygenation. The results provide important experimental basis for combining recombinant human endostatin with radiation therapy in human tumors.

Objective To investigate the expression and the possible clinical significance of serum Golgi protein(GP73)in infantile hepatitis syndrome(IHS)by different causes.Methods Totally 79 patients with IHS in Guangzhou Women and Children's Medical Center from February 2012 to December 2012 were enrolled in this study,including 15 cases with biliary atresia(BA)group,29 cases with infection(infection group),5 cases with neonatal intrahepatic cholestasis caused by citrin deficiency(NICCD group),and 30 cases with unknown etiology(idiopathic infantile hepatitis group).At the same time,30 healthy infants were enrolled as healthy control group.The serum levels of GP73 were determined by quantitative enzyme-linked immunosorbent assay(ELISA),and the children's liver function[alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),direct bilirubin(DBIL),alkaline phosphatase(ALP),γ-glutamyl trans-peptidase(γ-GT),total bile acid(TBA)and albumin(ALB)] were measured by turbidimetric inhibition immuno assay.Then,the corresponding data were statistically analyzed.Results Serum GP73 in BA group,infection group,NICCD group,idiopathic infantile hepatitis group and the healthy control group were(296.6±67.5)μg/L,(185.1±66.4)μg/L,(199.2±87.1)μg/L,(181.7±74.2)μg/L and(65.3±17.0)μg/L,respectively.Serum γ-GT levels in BA group,infection group,NICCD group,idiopathic infantile hepatitis group and healthy control group were(764.7±775.8)U/L,(448.2±352.7)U/L,(239.4±88.7)U/L,(283.3±377.2)U/L and(54.0±72.6)U/L,respectively.The levels of GP73 and γ-GT were significantly higher in infants with IHS,and the levels of GP73 and γ-GT in infants with BA were the highest(F=46.775,9.238,all P<0.05).There was a positive correlation between serum levels of GP73 and γ-GT(r=0.280,P<0.05),and there was no correlation between GP73 and ALT,AST,TBIL,DBIL,ALP,TBA,ALB(r=-0.061,-0.071,0.164,0.123,0.137,0.008,-0.047,respectively,all P>0.05).The receiver operating characteristic curve(ROC)constructed with GP73 showed a sensitivity of 80.0％and specificity of 82.8％with an area under the receiver(AUC)of 0.872 for diagnosis of BA,comparatively,a sensitivity of 66.7％and specificity of 71.9％were showed with a AUC of 0.731 when performed with γ-GT.Conclusions Serum GP73 concentration significantly increased in all liver disease groups,regardless of the etiology.Serum GP73 expression is significantly higher in infants with BA.Serum GP73 shows a superior sensitivity and specificity to γ-GT for diagnosis of BA,which might be useful for early diagnosis of BA and IHS with different causes.

ObjectiveTo observe production of vascular endothelial growth factor (VEGF) induced by granulocyte/macrophage colony-stimulating factor (GMCSF)via ERK nerve growth factor (NF)-κB singling pathway in human fibroblasts during wound healing and explore relating mechanism.MethodsHuman fibroblasts from the injured skin were used for this study and treated with GMCSF.RT-PCR was used for analyzing the protein and mRNA levels of VEGF and Western blotting was employed to determine the phosphorylation of ERK. The fibroblasts were pre-treated with ERK specific inhibitor PD98059 and further treated with GMCSF, then the fibroblasts and the supernatant were collected for detection of protein level of VEGF by means of Western blot. ERK signal pathway was inhibited to detect the activation of NF-κB by means of immunofluorescence staining. Furthermore, the nuclear and cytoplasmic extraction kit was used to separate the cytoplasm and nucleus and Western blot employed for observation of the NF-κB activation. ResultsThe mRNA level and protein level of VEGF were increased significantly with treatment with higher concentration of GMCSF in a dose-dependent manner. VEGF mRNA level was increased two hours after administration with GMCSF and reached peak at 4-6 hours. GMCSF could remarkably activate the ERK phosphorylation. Compared with GMCSF, the ERK specific inhibitor PD98059inhibited significantly the effect of GMCSF in inducing VEGF expression (P ＜ 0.05). Western blot and immunofluorescence staining analyses showed that the activation of NF-ΚB was inhibited with reduced production of VEGF after GMCSF treatment.Conclusion GMCSF up-regulates production of VEGF through activating NF-κB via ERK signal pathway in the human fibroblasts.

Objective To explore the role of default mode network (DMN) in the pathophysiology of depression and the correlations between the functional connectivity (FC) of DMN and the clinical characteristics of depression through the resting-state fMRI scan in depressed patients. Methods Sixteen medication-na?ve patients with major depressive disorder and 15 healthy controls were recruited and underwent the resting-state MRI scan. Hamiliton depression rating scale (HAMD) was used to evaluate patients’symptom. The FC of DMN and its correlations with clinical features of pa-tients were analyzed. Results Compared with healthy controls, the FC within DMN in depressed patients is disturbed. There were negative correlations between the left mPFC-left hippocampus FC and HAMD total scores (r=-0.569, P=0.021) and subscale scores for sluggishness (r=-0.498, P=0.050). The left mPFC-right hippocampus FC in patients was negatively correlated with HAMD scores (r=-0.508, P=0.045). There were negative correlations between FC in the hippo-campus and HAMD subscale scores for cognitive impairment (r=-0.509, P=0.044). Conclusions The results suggest that there is abnormal FC within DMN in drug-na?ve patients with depression during resting state and some abnormal altera-tions of FC may be correlated with the clinical characteristics in depression.

Objective To analyze the correlation of hypersensitive C-reactive protein(hs-CRP),homocysteine(Hcy) and D-dimer(D-D) with pathological change degree of coronary heart disease(CHD),and to investigate the diagnostic specificity and sensitivity of joint detection in CHD.Methods A total of 100 cases of CHD patients(experimental group) and 100 healthy subjects(control group) were enrolled,.Patients of the experimental group were divided into four groups on the basis of complications,including simple CHD group(32 cases),amalgamating hypertension group(46 cases),amalgamating diabetes group(9 cases),amalgamating hypertension diabetes group(13cases).The levels of hs-CRP,Hcy and D-D in the five groups were detected and analyzed.Results The levels of hs-CRP,Hcy and D-D in the experimental group were all higher than the control group(P<0.05).Logistic regression confirmed that three indexes were the independent risk factors for CHD.Each indicator has a certain clinical significance to the diagnosis and treatment of CHD but the value of Hcy could be better.Joint detection of hs-CRP and Hcy could be an ideal combination of detection,and the three joint detection might not be suitable for early diagnosis and treatment of CHD.The levels of hs-CRP and D-D in simple CHD group,amalgamating hypertension group,amalgamating hypertension diabetes group were all higher than amalgamating diabetes group(P<0.05).Conclusion hs-CRP,Hcy and D-D could be the independent risk factors of CHD,and joint detection might be with important clinical value for diagnosis of CHD.