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.

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.

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.

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

Animals ; Arsenic ; toxicity ; Comet Assay ; DNA Damage ; drug effects ; Lymphocytes ; drug effects ; metabolism ; Male ; Malondialdehyde ; metabolism ; Rats ; Rats, Wistar ; Tobacco Smoke Pollution ; adverse effects

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 compare preoperative planning parameters between non-coplanar and coplanar template-assisted radioactive seed implantation in the treatment of pancreatic cancers, in order to guide clinical application.Methods:Patients with pancreatic cancers who received external irradiation in the Peking University Third Hospital from Jan 2017 to May 2019 were selected.Their image information was imported into the brachytherapy planning system, and the non-coplanar plan and coplanar plan were designed individually.Each patient′s prescription dose was set to 110 Gy, and the activity of the radioactive seeds were 0.4 mCi(1 Ci=3.7×10 10Bq), respectively.For the two plans, the dose distribution was optimized and dosimetric parameters were compared, including the implantation needle number, the implanted seed number, the minimum prescription doses delivered to 90% and 100% of the target volume ( D90 and D100), mean percentages of volume receiving 100%, 150% and 200% of the prescription doses ( V100, V150 and V200), conformity index (CI), external index (EI), and homogeneity index (HI) of the target volume, as well as the doses of 2 cm 3 and 5 cm 3 ( D2 cm 3 and D5 cm 3) of the surrounding normal organs such as the small intestines, colon, duodenum, stomach, and spinal cord. Results:The implantation needle number in the coplanar plan was slightly higher than that in the non-coplanar plan, namely 18.63 vs. 16.45 ( t=-3.239, P <0.05). The implanted seed number was equivalent, namely 90.2 vs. 91.01, with no statistical difference ( P>0.05). There was no significant difference between D90, D100, V100, V150, V200, CI, EI, and HI in the target area of the two plans ( P>0.05). Meanwhile, there was no obvious difference in D2 cm 3 and D5 cm 3 of normal organs including the small intestines, colon, duodenum, stomach, and spinal cord ( P>0.05). Conclusions:With both the coplanar plan and the non-coplanar plan, the prescription doses can be achieved and meanwhile, there are very small differences in the doses of normal organs.Given that 3D-printing non-coplanar and coplanar templates have their own characteristics, it is necessary to choose them according to specific situations.

Objective To investigate the expression and relationship between Phosphatase and tension homolog deleted on chromosome ten (PTEN) and Alpha fetoprotein(AFP) in hepatocellular carcinoma. Methods PTEN and AFP expression was examined by immunohistochemical method. Results PTEN expression was significantly weaker in patients with tumor less than 5.0 cm and patients with CLIP score≥1 (P<0.05). The expression of PTEN and AFP was negatively correlated ( Rs=-0.422, P=0.043), serum AFP and tissue expression of AFP was positively correlated (Rs=0.380, P=0.042), but for individual expression was not consistent. Conclusions PTEN and AFP is respectively negative and positive adjustment factor of PI3K/AKT pathway. Tissue expression of AFP may be more significant, and may become the new targets for the treatment of hepatocellular carcinoma.

Aim To investigate the effects of dioscin ( Dio) on rat myocardial contractility. Methods Left ventricular contractile function was measured using the Langendorff non-recirculating mode of isolated rat heart perfusion. Effects of low, middle and high concentra-tion of Dio were investigated by measuring left ventricu-lar systolic pressure ( LVSP ) and left ventricular end diastolic pressure ( LVEDP) . Also, peak rates of rise/fall of left ventricular pressure ( ± dp/dtmax ) of isolated rat heart were calculated. Effects of Dio on intracellu-lar free calcium concentration in rat H9 c2 cells were measured by using the confocal microscopy. Mitochon-drial membrane potential was detected with multifunc-tional microplate reader. Results With 0. 1, 1 μmol · L-1 Dio, LVSP were significantly enhanced from (11. 55 ± 0. 52), (10. 53 ± 0. 28) kPa to (13. 08 ± 0. 72), (12. 53 ±0. 64) kPa(P<0. 01); +dp/dtmax were dramatically increased from ( 0. 38 ± 0. 10 ) , (0. 40 ± 0. 07) kPa·ms-1 to (0. 42 ± 0. 11), (0. 43 ± 0. 02) kPa·ms-1(P<0. 05). With the 10μmol· L-1 Dio, LVSP and + dp/dtmax were both decreased from (12. 13 ± 0. 33) kPa and (0. 42 ± 0. 04) kPa· ms-1 to ( 9. 46 ± 0. 77 ) kPa and ( 0. 24 ± 0. 04 ) kPa ·ms-1 (P <0. 01). With 0. 1, 1, 10 μmol·L-1 Dio, the relative fluorescence intensity of intracellular free calcium concentrations was increased significantly from (16. 62 ± 0. 89) to (21. 48 ± 0. 80), (25. 68 ± 0. 69) and (19. 84 ± 0. 66)(P <0. 01)respectively. 0. 1, 1μmol·L-1 Dio showed no significant effects on the mitochondrial membrane potential of rat H9 c2 cells, while with effects of 10 μmol·L-1 Dio, the ra-tio of JC-1 monomer and J-aggregates was changed from (1. 14 ± 0. 03) to (1. 35 ± 0. 06)(P<0. 01), indica-ting a decrease in the mitochondrial membrane poten-tial. Conclusion Low and middle concentrations of Dio show a positive inotropic effect on isolated rat heart, as the LVSP and + dp/dtmax are enhanced, which may concern with the increase of the intracellu-lar concentration of Ca2+. It will not cause the calcium overload while the intracellular concentration of Ca2+ is increased by low and middle concentration of Dio in the myocytes except high concentration of Dio.