Objective To explore the relationship between diethylhexylphthalate (DEHP) and peritoneal sclerosis and its possible mechanism. Methods Isolated human peritoneal mesothelial cells (HPMC) was cultured for five days in culture solution with varied doses of DEHP ７．７?of 10-6mol/L (A group), 5.4?１０－５mol/L (B group) and 2. 2?10-4 mol/L (C group) respectively. Culture solution without DEHP was as control. Total collagen synthesis and secretion was assayed by 3H-proline incorporation. ELISA method was used to detect the level of secreted fibronectin (FN) . The expression of FN mRNA , collagen ImRNA, collagen Ⅲ mRNA and TGF－?l mRNA was determined by RT-PCR. Results (1)HPMC expressed FN, laminin, collagen Ⅲ and TGF-?１. (2)DEHP stimulated FN and collagen expression with a higher level in C group compared with control(P

Objective To investigate the influence of a combination of Chinese herbs,Astragalus membranaceus var.mongholicus and A ngelica sinensis (A&A)on the production and elimination of reactive oxygen species (ROS)and the underlying mechanism during the process of renal interstitial fibrosis in the obstructive kidneys of rats with unilateral ureteral obstruction(uuo).Method Male Wistar rats were randomly divided into control,sham,UUO and UAA (UUO+A&A)groups.The rats in UAA group were administered with A&A(14 g/kg)by oral gavage once daily:the ones in sham and UUO group were given with equal volumes of water.Three days after setting up models,pathological injury of renal tissue was evaluated.Level of total antioxidant capacity(T-AOC)and activity of CuZn superoxide dismutase(CuZn-SOD)in renal homogenates were measured bv spectrophotometry.Expression of NADPH oxidase subunits p47-phox,p22-phox and nintrotyrosine was analyzed by Western blot. Results Severe interstitial inflammatory cells infiltration, mild tubular atrophy and interstitial fibrosis were found in UUO group, which were alleviated by A&A administration. Compared to sham group, T-AOC of UUO group was not significantly changed, but the expression of the nitrotyrosine, NADPH oxidase subunits p47-phox and p22-phox was increased significantly (P<0.05). After A&A administration, T-AOC level was increased (2.5±1.1 vs 1.5±0.5, P<0.05) and the expression of nitrotyrosine was decreased (P< 0.05) in UAA group compared with UUO group. Additionally, the expression of p47-phox was reduced at day 3 (P<0.05), accompanied with a reduced expression of p22-phox (P< 0.05). CuZn-SOD activity was not significantly changed among the groups. Conclusion The inhibition of A&A in NADPH oxidase subunits p47-phox and p22-phox, which is responsible for reduction of oxidative stress, is associated with the alleviation of renal fibrosis in obstructive rat kidney.

Objective To clarify whether the NADPH oxidases (NOXs) family contributed to the reactive oxygen species (ROS) production and subsequent interstitial fibrosis in unilateral ureter obstruction (UUO) rats.Methods Male Wistar rats were randomly divided into sham operation group (n =8),sham operation + apocynin treatment group (n =8),UUO operation group (n =8) and UUO operation+apocynin treatment group (n =8).Either vehicle or apocynin (100 mg/kg per day) were given by gavage for 7 days after surgery.Rats were sacrificed at 7th day.ELISA was used to detect the activity of superoxide dismutase (SOD) and catalase (CAT),and the level of 8-iso-prostaglandin F2alpha (8-isoPGF2α) in renal tissue.Western blotting was used to detect the protein expressions of NADPH oxidase subunit NOX2 and NOX4,α-smooth muscle actin(α-SMA),collagen Ⅰ (COL-Ⅰ) and the level of ERK1/ 2 phosphorylation (p-ERK1/2).Results UUO rats with vehicle displayed increased oxidative stress,as measured by renal tissue 8-iso-PGF2α,accompanied with increased renal expression of NADPH oxidases (NOX2,1.5-fold and NOX4,1.7-fold,respectively),compared with sham-operated rats (P ＜0.05).Furthermore,vehicle treated UUO rats showed increased renal COL-Ⅰ and α-SMA levels,compared with sham-operated rats (P ＜ 0.05).ERK1/2 was also activated as detected by p-ERK1/2 expression in UUO rats with vehicle (P ＜ 0.05).Apocynin treatment significantly decreased renal tissue 8-iso-PGF2α level and expressions of NOX2 (-28.7％) and NOX4 (-31.0％) in UUO rats,respectively,compared with vehicle treated rats (P ＜ 0.05).And significant decrease of COL-Ⅰ (-26.4％) and α-SMA expression (-80.0％) were also observed (P ＜ 0.05).The activation of ERK1/2 in UUO rats was greatly inhibited by apocynin treatment (P ＜ 0.01).Despite the pronounced dysregulation of pro-oxidative NOXs family,no compensatory increase of antioxidative enzyme activities occurred.Conclusion The NOXs family contributes largely to the production of ROS and subsequent interstitial fibrosis after ureter ligation,and inhibition of the NOXs family may be a choice for preventing interstitial fibrosis.

0.05).AA-I could induce the TGF-?1 secretion by HK-2 cells(18.26?5.98 ?g/L,vs.control,P

[ Objective ] To observe the therapeutic effect of acupoint thread-embedding therapy for chronic gastritis. [Methods] Seventy cases of chronic gastritis were randomized into group A ( n = 36, treated with acupoint thread-embedding therapy) and group B (n = 34, treated with acupuncture); the changes of electrogastrogram (ECG) and plasma contents of gastrin (Gas) and substance P (SP) were compared before and after treatment. [Results] The effective rate was 88.89% in group A and 76.47% in group B, the difference being significant ( P 0.05 ) while postprandial ECG frequency differed from that before treatment ( P 0.05). [Conclusion] Acupoint thread-embedding therapy exerts certain effect for the treatment of chronic gastritis; its therapeutic mechanism may be related to the regulation of gastrointestinal function by regulating gastrointestinal hormone levels and by increasing ECG amplitude and frequency.

Objective:To study the effects of different duty cycles [modulated by pulse repetition frequency(PRF)] of diagnostic ultrasound on enhancing blood perfusion in hypovascular tumors.Methods:Walker-256 tumor cells were injected subcutaneously into the inner thigh of 15 SD rats, and the rats were randomly divided into 3 groups according to PRF: group A(PRF=50 Hz), group B(PRF=1.0 kHz) and group C(PRF=2.0 kHz), with 5 rats in each group. The tumor-bearing rats in each group were treated with ultrasound combined with microbubbles for 10 minutes. Contrast-enhanced ultrasound was performed before treatment, immediately after treatment, and 4 hours after treatment, respectively, to compare the peak intensity(PI), area under curve(AUC), and tumor perfusion area in each group.Results:Immediately after treatment, PI and AUC values of group A and B increased compared with those before treatment (all P<0.05); 4 hours after treatment, PI and AUC values of group B continued to increase, superior to that immediately after treatment (all P<0.05), while PI and AUC values of group A and C were decreased compared with those immediately after treatment (all P>0.05). Immediately after treatment, the tumor blood perfusion area in group A and B increased significantly compared with that before treatment (all P<0.05); 4 hours after treatment, the tumor blood flow perfusion area of group B continued to increase, which was better than that immediately after treatment ( P<0.05), and the tumor blood perfusion areas of group A and C decreased compared with that immediately after treatment (all P>0.05). Conclusions:Low-intensity diagnostic ultrasound stimulated microbubble cavitation with PRF=1.0 kHz can enhance tumor blood flow significantly which can last for more than 4 hours.

Objective:Bioinformatics was used to analyze the gene expression profile of renal chromophobe cell carcinoma (RCCC) to find out the key genes of RCCC.Methods:Chromophobe renal cell carcinoma gene chip data GSE15641 and GSE11151 were downloaded from the GEO database. Using R software packages such as " Affy" and " limma" in R software to screen differentially expressed genes, combining with David and STRING online bioinformatics tools to analyze the regulatory network of differentially expressed genes and construct protein-protein interaction (PPI) network, the Hub gene was screened through the Cytohubba plug-in of Cytoscape software.Results:A total of 261 differentially expressed genes were screened, including 194 down-regulated genes and 67 up-regulated genes. Gene enrichment (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to explore their biological functions. In GO enrichment analysis, biological processes were mainly enriched in cell secretion, gluconeogenesis and cell proliferation regulation; in cell composition, they were mainly enriched in exosomes, plasma membranes and their components; in molecular function, they were mainly enriched in heparin binding; in KEGG pathway analysis, they were mainly enriched in metabolic pathway, antibody biosynthesis pathway and renin angiotensin system pathway. PPI network was constructed by using online bioinformatics tools. The top 10 Hub genes were screened by using cytohubba plug-in in Cytoscape software, which were pipecolic acid and sarcosine oxidase (PIPOX), hydroxyacid oxidase 2 (HAO2), kynurenine 3-monooxygenase (KMO), solute carrier family 2 member 2 (SLC2A2), formimidoyltransferase cyclodeaminase (FTCD), angiogenin (ANG), APOBEC1 complementation factor (A1CF), aldehyde dehydrogenase 8 family member A1 (ALDH8A1), vitamin D binding protein (GC), histidine rich glycoprotein (HRG).Conclusions:Bioinformatics analysis of differentially expressed genes in renal chromophobe cell carcinoma can effectively explore the interaction information of these differentially expressed genes, and provide new ideas for the treatment of renal chromophobe cell carcinoma.

Objective To investigate whether the activation of secretory prophospholipase A2 (sPLA2) plays the role in the pathophysiological mechanism of acute aristolochic acid nephropathy (AAN) in rats. Methods Wistar rats were randomly divided into two groups. Model group received decocted Aristolochia Manshuriensis Kom 30 g·kg-1d-1 by gavage for 7 days following tap water in same way for additional 7 days. Control group received only tap water by garage at parallel time. The renal pathological changes were observed at the 4th, 8th and 14th day. The injury of renal tubules and interstitium was observed under light microscope following a semi-quantity grade. The level of Scr was measured to evaluate glomerular function. Urinary N-acetyl-beta-glucosaminidase (NAG) was tested as renal tubular injury marker. The activity of sPLA2 in serum was detected by manifesting the color of thiols in the substrate. The protein expression of renal cortex and medulla COX-2 was analyzed by Western blot. The metabolic products of pretaglandins (PC, s) including 6-kcto-PGF1α and TXB2 in the plasma and urine were assayed by radioimmunoassay. The ratio of 6-keto-PGF1α/TXB2 was calculated. Results After Aristolochia administration, the tubulointerstitial injury and Scr increased in AA rats and reached the peak at the 8th day, the tubulointerstitial injury index(8.14±2.55 vs 1.50±0.71, P<0.05) and Scr[(0.24±0.10) vs (0.19±0.02) μmol/g, P<0.05] increased significantly in AA rats compared with control group. The activity of sPLA2 (μmol ·min-1·mg-1) in AA group elevated by 1.3-fold compared to control group at 8th day (133.15±17.05 vs 101.3±16.07, P<0.05), while theexpression of COX-2 in renal cortex increased (1.16±0.36 vs 0.69±0.28, P<0.05) with no change in renal medulla. Even though the levels of serum 6-keto-PGF1α and TXB2 did not change obviously in both AA and control group, but urinary levels of 6-keto-PGF1α and TXB2 increased by 2-fold and 3-fold in AA group compared to control group, respectively (all P<0.05), while the ratio of 6-keto-PGF1α/TXB2 decreased significantly (207.53±17.52 vs 296.64±51.31, P<0.05). All of above changes recovered to the control level at the 14th day except the tubulointerstitial injury index. Conclusion Serum sPLA2 is activated in the rots with acute kidney injury induced by aristolochic acid, which accompanied by up-regulated expression of COX-2 in renal cotex and increased the metabolic products of vasoconstrictive PG s in urine. These changes may participate the mechanism of renal peritubular ischemia in AAN.

To observe therapeutic effect of levosimendan on acute heart failure (AHF) and its impact on cardiac function ,levels of brain natriuretic peptide (BNP) ,high sensitive C reactive protein (hsCRP) ,tumor necro‐sis factor (TNF)‐α and interleukin (IL)‐6. Methods :A total of 148 AHF patients treated in our hospital from Jan 2016 to Jan 2018 were randomly and equally divided into dobutamine group and levosimendan group ,both groups re‐ceived corresponding medication based on routine treatment for 21d.Cardiac function ,levels of plasma BNP ,serum hsCRP ,TNF‐α and IL‐6 ,6min walking distance (6MWD) before and after treatment ,total effective rate and inci‐dence of adverse reactions were observed and compared between two groups .Results :Total effective rate of levosi‐mendan group was significantly higher than that of dobutamine group (83. 78% vs.68.92%) , P＝0.033. Compared with dobutamine group after treatment , there were significant rise in LVEF [ (49. 98 ± 3. 68 )% vs.(52.17 ± 3.82)%] ,stroke volume [SV ,(67. 52 ± 5. 79) ml vs.(69. 48 ± 5. 83) ml] and 6MWD [ (328.46 ± 31.62) m vs. (396.75 ± 31.89) m] ,and significant reductions in left ventricular end systolic dimension [ (54. 12 ± 8.64) mm vs. (51.31 ± 8.26) mm] ,left ventricular end diastolic dimension [(65.25 ± 8. 86) mm vs.(62.14 ± 8.57) mm] ,levels of plasma BNP [ (572.59 ± 89. 62) mg／ml vs .(351.78 ± 81. 41) mg／ml] ,serum TNF‐α [ (24. 68 ± 5.83) ng／L vs. (21.05 ± 5. 39) ng／L] ,IL‐6 [(21.36 ± 4. 51) ng／L vs.(18.29 ± 4.34) ng／L] and hsCRP [(4. 89 ± 2. 15) ng／L vs. (3. 06 ± 1.47) ng／L] in levosimendan group , P＜0. 05 or ＜0. 01. There was no significant difference in incidence rate of adverse reactions during treatment between two groups , P＝0.690. Conclusion :Compared with dobutamine , levosimendan possesses more significant therapeutic effect on AHF .It can more significantly improve cardiac func‐tion ,exercise capacity and reduce cytokine levels in these patients .

OBJECTIVE To study the mitochondrial toxicity effect of Radix Aconiti Lateralis Praepa?rata(Fuzi)on H9c2 cardiomyocytes. METHODS H9c2 cells were exposed to Fuzi decoction 6.25, 12.5,25,50 and 100 g·L-1 for 24 h. Fluorescence staining and CCK-8 assay were used to detect cell viability. H9c2 cells were exposed to Fuzi decoction 6.25,12.5 and 25 g · L-1 for 24 h,while the effect on mitochondrial membrane potential and reactive oxygen species(ROS)was detected by flow cytometry. The fluorescence molecular probe and laser scanning confocal microscope were used to observe the effect on Ca2+ in cells,Ca2+ and superoxide in mitochondria. The effect on ATP concentration in cells was detected via firefly luciferin and the expression of Pgc-1α,Bcl-2 and Bax mRNA evaluated by real-time PCR,while the expression of Pgc-1α protein was measured by Western blotting. RESULTS H9c2 cell viability was significantly inhibited by Fuzi decoction 12.5-100 g · L-1(P<0.05,P<0.01). The IC50 value was 47.4669 g · L-1,while the 95%confidence limit was 32.5997-69.1145 g · L-1. After treatment with Fuzi decoction 25 g · L-1 ,the fluorescence intensity of ROS in the normal control group increased from 204±67 to 454±78(P<0.05),that of mitochondrial superoxide increased from 5.4±1.8 to 26.8±8.5 (P<0.01),mitochondrial membrane potential decreased from 1.7±0.5 to 0.8±0.4(P<0.05),the fluores?cence intensity of intracellular Ca2+increased from 7.8±0.8 to 22.1±0.5(P<0.05)while that of mitochon?drial Ca2+decreased from 38.0±4.3 to 9.2±1.6(P<0.01),and intracellular ATP concentration decreased from (10.6 ± 0.4)μmol · g-1 to (5.3 ± 1.1)μmol · g-1 protein (P<0.05). qPCR and Western blotting test results showed that compared with the normal control group ,Pgc-1αand Bcl-2 mRNA relative expression level in Fuzi decoction 25 g·L-1 group was decreased from 1.00±0.10 and 1.00±0.10 to 0.09±0.06(P<0.01)and 0.43±0.06(P<0.01),respectively, while the relative expression of Bax mRNA was increased from 1.00 ± 0.03 to 1.17 ± 0.06 (P<0.05),and the expression of Pgc-1α protein was decreased from 0.906±0.034 to 0.541±0.003(P<0.01). CONCLUSION Fuzi has some mitochondrial toxicity to cardiomy?opathy. This effect arises from the combined action of different mechanisms. Mitochondrial toxicity of myocytes may account for the cardiac toxicity of Fuzi.