Objective To observe the effect of MG132 on the expression of extracellular regulated kinase 1/2 (ERK1/2) and connective tissue growth factor (CTGF) in rat peritoneal mesothelial cells (RPMCs) induced by high glucose.Methods RPMCs were isolated,cultured and passaged by trypsin,then identified.The second generation of cultured RPMCs were used in the experiment.RPMCs were divided into normal control group,high glucose (1.5％,2.5％,4.25％) for 24 hours,high glucose (2.5％) for 0,12,24,48 hours,incubated with MG132 (0.5,1,2 μmol/L) for half an hour and then with high glucose (2.5％) for 24 hours.ERK1/2 protein was detected by Western blotting,and CTGF protein in supernatant was detected by ELISA.Results Compared with the control group,the expression of p-ERK1/2 was significantly increased in the groups stimulated by high glucose (P ＜0.01),reached the peak at 24th hour (P ＜ 0.01),and then the expression decreased at 48th hour,but still was higher than that in the normal control group (P ＜ 0.01).CTGF protein expression of RPMCs induced by high glucose increased,in time-and dose-dependent manner (P ＜ 0.05).MG132 could significantly decrease the expression of ERK1/2 and CTGF induced by high glucose (P＜0.05).Conclusions MG132 can decrease the expression of p-ERK1/2 and CTGF in RPMCs induced by high glucose.The ubiquitin proteasome pathway participates in the development of peritoneal fibrosis,and blocking the way may contribute to the prevention of peritoneal fibrosis.

Applications of network pharmacology are increasingly widespread and methods abound in the field of drug development and pharmacological research. In this study, we choose rosiglitazone compound as the object to predict the targets and to discuss the mechanism based on three kinds of prediction methods of network pharmacology. Comparison of the prediction result has identified that the three kinds of prediction methods had their own characteristics: targets and pathways predicted were not in accordance with each other. However, the calcium signaling pathway could be predicted in the three kinds of methods, which associated with diabetes and cognitive impairment caused by diabetes by bioinformatics analysis. The above conclusion indicates that the calcium signaling pathway is important in signal pathway regulation of rosiglitazone compound, which provides a clue to further explain the mechanism of the compound and also provides a reference for the selection and application of methods of network pharmacology in the actual research.
Calcium Signaling ; Cognitive Dysfunction ; Computational Biology ; Diabetes Mellitus ; Humans ; Pharmacology ; methods ; Thiazolidinediones ; pharmacology

ObjectiveTo evaluate the effects of cardiac resynchronization therapy (CRT) on improving left ventricle (LV) function and LV asynchrony in patients with dilated cardiomyopathy(DCM)using three-dimensional ultrasound speckle tracking imaging(3D-STI).MethodsTwenty one patients with DCM and 25 normal subjects were enrolled in this study.Parameters including LV mean longitudinal peak strain (MLS),LV mean circumferential peak strain (MCS),LV mean radial peak strain (MRS),LV ejection fraction(3D-LVEF),maximal temporal difference in area strain of LV 16 segments (A-MaxTs) and its standard deviation (A-Ts-SD) were investigated by 3D-STI.LV ejection fraction (ECT-LVEF) and LV phase angle width (LVW) were obtained by radionuclide ventriculography and phase image analysis.Results The indexes of MLS,MCS,MRS and 3D-LVEF were decreased and A-MaxTs,A-Ts-SD were prolonged in DCM group compared with those of control group.There was a slightly improvement in MRS and ECTLVEF 1 week after CRT,but other Parameters including MLS,MCS,A-MaxTs,A-Ts-SD and 3D-LVEF had no significant change.Compared with corresponding values before and 1 week after CRT,all parameters (MCS,MRS,A-MaxTs,A-Ts-SD,3D-LVEF and ECT-LVEF) were further improved 6 months after CRT.MLS,MCS,MRS and 3D-LVEF had good relationship with ECT-LVEF,and A-MaxTs,A-Ts-SD had good relationship with LVW in DCM group.Conclusions3D-STI is a simple and accurate method for evaluating effects of CRT on improving LV function and LV asynchrony in patients with DCM.

Objective To observe the effect of silibinin on the expression of integrin linked kinase (ILK),transforming growth factor β1 (TGF-β1) and α-smooth muscle actin (α-SMA) in rat peritoneal mesothelial cells (RPMCs) induced by high glucose.Methods RPMCs were isolated,cultured and passaged by trypsin,then identified.The second generation of cultured RPMCs were used in the experiment.RPMCs were divided into normal control group,high glucose(1.5％,2.5％,4.25％)for 24 hours,high glucose (2.5％) for 12,24,48,72 hours,high glucose (2.5％) for 24 hours after silibinin (5,10,20 mg/L) preincubate for 2 hours.ILK and α-SMA mRNA were detected by real-time PCR.ILK protein was detected by Western blotting.TGF-β1 protein in supernatants was detected by ELISA.Results Compared with the control group,the expresssion of ILK,TGF-β1 and α-SAM was significantly increased in groups stimulated by high glucose (all P ＜ 0.05).Silibinin could significantly decrease the expression of ILK,TGF-β1 and α-SMA induced by high glucose (all P ＜ 0.05).Conclusions High glucose can up-regulate the expression of ILK,TGF-β1 and α-SMA.Silibinin can reverse these changes.

Objective To investigate the features of malignancy in end-stage aristolochic acid nephropathy (AAN) patients undergoing renal replacement therapy in the First Affiliated Hospital of Wenhou Medical University.Methods One hundred and two patients diagnosed as end-stage AAN during 2004 to 2013 were enrolled in the study,and separately udergoing hemodialysis,peritoneal dialysis and renal transplantation,to study the features of the malignancy and its risk factors.Results (1) There were totally 42 AAN patients suffering from malignancy,and 39 of them had urinary cancer.Eight cases of urinary cancer had metastasis,and 11 cases of bladder cancer had repeated recurrences.Patients suffering from malignancy had an increased mortality compared to patients without malignancy (13/42 vs 7/60,P =0.022).(2) Thirteen malignacy cases were diagnosed before the end-stage of AAN,the rest cases appeared in 1-13 years[(4.62±3.31) years] after renal replacement.(3) A further logistic regression analysis of the 29 maligancy patients after renal replacement showed that,the dose of aristolochic acid (counted by Mutong) was the only risk factor of malignancy (P =0.091),compared with the dose of Mutong less than 60 g,the patients with an accumulated dose of Mutong more than 200 g had a 4.26 folds (95％CI 1.02,17.83)higher risk of malignancy.There was no statistic difference of the malignancy risk among different renal replacement therapies,which however might influence the pathogenic sites of the urinary cancer.The simple bladder cancer was the most common malignancy among the hemodialysis patients (72.72％),and the upper urinary tract cancer among the peritoneal dialysis patients (66.67％),while the complex of both were dominant among the renal transplantation patients(40.00％).Conclusions Among the end-stage of AAN patients undergoing renal replacement therapy in Wenzhou area,the incidence of urinary cancer is high,with a character of complex,multiple and repeated recurrences.The occurence of malignancy seems to be separated from the renal function,but turns out obviously dose-dependent.There was no statistical difference of cancer risk among hemodialysis,peritoneal dialysis,and renal transplantation,which may induce different pathogenic sites of the urinary cancer.

Objective To evaluate the effects of aerobic exercise of middle intensity on cognitive and motor functions of elderly people with Alzheimer's disease (AD).Methods Forty-eight patients with AD were studied.The subjects were randomly divided into a treatment group and a control group.The subjects in treatment group were treated with cycle ergometer exercise for 3 months.The control group accepted dementia education.All the patients performed the mini-mental state examination (MMSE) and Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog) at the beginning and after 3 months of treatment.Results Forty-one participants completed the whole treatment and observation program.After treatment,the scores of MMSE and ADAS-Cog improved significantly more in treatment group than those in control group (P ＜ 0.05).Conclusion Middle intensity of aerobic exercise can improve cognitive and motor function in patients with AD.

Objective To investigate the relationship between expression of Her-2 gene and the transfer number of axillary lymph node and its influence on prognosis.Methods A total of 351 cases with primary breast cancer from January 2008 to January 2011 were selected.The expression of Her-2 gene was detected by immunohistochemical method,and analyzed the relationship between it and the transfer number of axillary lymph node and its influence on prognosis.Results The expression of Her-2-,+,++ had no correlation with the transfer number of axillary lymph node (x2 =3.757,1.650,2.379,P ＞ 0.05),while the expression of Her-2 +++ had correlation with the transfer number of axillary lymph node (x2 =8.681,P ＜ 0.05).The 2 years survival rates in the expression of Her-2-,+,++,+++ were 77.01％ (201/261),85.00％ (34/40),29.17％(7/24),1 1.54％ (3/26),and which in the expression of Her-2--+ was significantly higher than that in the expression of Her-2 ++-+++ (x2 =61.605,P ＜ 0.01).The transfer number of axillary lymph node was 0 and 1-3,the 2 years survival rate in the expression of Her-2--+ was significantly higher than that in the expression of Her-2 ++-+++,and there was significant difference (x2 =61.605,14.747,P ＜ 0.05).The transfer number of axillary lymph node was 4-9 and ≥ 10,there was no significant difference in the 2 years survival rate between the expression of Her-2--+ and Her-2 ++-+++ (x2 =3.691,3.482,P ＞ 0.05).Conclusions The expression of Her-2-,+,++ has no correlation with axillary lymph node metastasis,and the 2 years survival rate in the expression of Her-2--+ is higher than that in the expression of Her-2 ++-+++,while Her-2-has no difference with Her-2 + in prognosis.While the transfer number of axillary lymph node ≤ 3,the expression of Her-2 gene may be an important prognostic factor.

Many somatic cell typos were obtained by in vitro differentiation or teratoma formation of human embryonic stem ceLls (hESCs). However, it is unclear whether specific cell types can be obtained from hESCs-derived teratoma. It was reported that many kinds of cells, including neural progetfitor/precursor cells (NPCs) and mesenchymal stem cells (MSCs) were isolated efficiently from the teratoma of hESCs through in vitro selection. The teratoma-derived NPCs and MSCs showed specific characteristics of molecular markers similar to the primary NPCs and MSCs. Moreover, these teratoma-induced NPCs and MSCs can be further induced to differentiate into neurons, astrocytes, or adipose and bone cells, reflecting their inherent multi-potencies. Given that teratoma normally contains a mixture of ectoderm, mesodenn, and endoderm lineage cells at different differentiation stage, it was suggested that hESCs-derived teratoma could be an alternative source to generate a variety of uncommitted progenitor cells or terminally differentiated somatic cells, which may be otherwise difficult to obtain through direct in vitro differentiation.

Objective To investigate the immunoregulatory effect and compare the different regula- tions of bone marrow mescnchymal stem cells(MSCs)derived from both lupus(NZBWF1/J)and normal(BALB/ c)mice on T lymphocytes in vitro.Methods MSCs from NZBWF1/J and BALB/c mice bone marrow were iso- lated and expanded,and identified by the surface phenotypes.CD3~+ T lymphocytes isolated by nylon wool columns were stimulated by phorbol myristate acetate(PMA)and co-cultured with or without the two strains of MSCs for 24 h.Intracellular eytokines of T cell,such as interferon(IFN)-?,interleukin(IL)-4,IL-12,IL-6, were analyzed by flow cytometry and quantification of transcription factors T-box expressed in T cells(T-bet) and GATA-binding protein 3(GATA-3)were detected by reverse transcriptase PCR(RT-PCR).T cell apop- tosis was assessed by flow cytometry using rhodamine123.Results The results showed that a decrease of CD3~+ T cell apoptosis was seen when NZBWF1/J MSCs or BALB/c MSCs were added to T cells stimulated by PMA(P＜0.05),and an increase of TH2 cytokines by NZBWF1/J MSCs and TH1 eytokines by BALB/c MSCs were observed in the CD3~+ T cells eo-cuhured with MSCs(P＜0.05).Conclusion It is suggested that the al- teration of T subsets caused by MSCs may interfere with the systemic lupus erythematosus(SLE)development and normal MSCs may be effective in the improvement of SLE.NZBWF1/J MSCs have defective immunoregula- tory function when compared with MSCs from healthy mouse strains.

Objective To assess any differences in brain activation during active,passive and imaginary movement of the hands using blood oxygen level-dependent functional magnetic resonance imaging (fMRI),and to provide references for the cortical reorganization in patients with brain injuries.Methods Twenty healthy,righthanded,adult volunteers were studied,fMRI was performed during active,passive and imaginary fist clutching.Whole brain analysis and group analysis were applied to get the voxels,the volume of activation,the peak t-score and its coordinates.Results Active and passive movement both produced significant activation in the contralateral sensorimotor cortex,the contralateral supplementary motor area and the ipsilateral cerebellum.The sensorimotor cortex was the most frequently and most strongly activated brain area.Imaginary movement produced significant bilateral activation in the supplementary motor area.Conclusions Active and passive movement induce similar brain activation patterns.This indicates that passive might replace active movement when observing activation of the brain's cortex during the rehabilitation of patients with hemiplegia.