1.Antagonist of leukotriene B4 receptor 1 attenuates cisplatin induced acute kidney injury in mice and its associated mechanism
Bo DENG ; Yuli LIN ; Shuai MA ; Rui HE ; Feng DING
Chinese Journal of Nephrology 2015;31(5):345-350
Objective To investigate the effect of pretreatment with U75302,antagonist of leukotriene B4 receptor 1 (BLT1),on cisplatin induced acute kidney injury in mice and its immunoregulatory mechanism.Methods Healthy C57BL/6 mice were randomized into four subgroups:1.healthy control group;2.cisplatin group;3.U75302 control group;4.cisplatin + U75302 group,n=6.Group 2 and 4 received intraperitoneal injection of cisplatin (20 mg/kg) on day 0,group 3 and 4received intraperitoneal injection of U75302 (5 μg/mouse) on day 0 and day 2.Mice were sacrificed on the 3rd day and blood and kidney were collected.Renal function and histological changes were estimated,the infiltration of immune cells were determined by flow cytometry,the level of peroxidase (MPO) in kidney were determined by colorimetry,relative expression of TNF-α,IL-1β,CXCL1,CXCL2 were detected by Real-time PCR.Results Compared with healthy control group,levels of BUN,Scr were higher in cisplatin group with serious tubular structural damage.There were more neutrophils,macrophages,CD4+ T lymphocytes,CD8+ T lymphocytes in kidneys of cisplatin group,the level of MPO and relative expression of TNF-α,IL-1β,CXCL1,CXCL2 were also higher in cisplatin group.Compared with cisplatin group,lower BUN [(17.75±1.80) mmol/L vs (42.6±6.66) mmol/L,P <0.05],Scr were found in cisplatin+ U75302 group with less tubular structural damage.Meanwhile,U75302 reduced infiltration of neutrophils [(146±13)×103/g vs (296±66) ×103/g,P < 0.05],macrophages [(245± 13)× 103/g vs (420±78)× 103/g,P < 0.05] in the kidney.Levels of MPO [(1.756±0.283) U/g vs (3.308±0.577) U/g,P<0.05] and relative expression of TNF-α,IL-1β,CXCL1,CXCL2 were also lower.Conclusions BLT1 antagonist U75302 protects mice against AKI induced by cisplatin,and the mechanism is associated with reduced infiltration of inflammatory cells in kidney and the inhibition of kidney inflammation.
2.Roles of Tumor Infiltrating Dendritic Cells and T Lymphocytes in Tumor Immunity of EBV-associated Gastric Carcinoma
Lin XIAO ; Dan HE ; Yungang DING ; Zhiying FENG ; Chunkui SHAO
Journal of Sun Yat-sen University(Medical Sciences) 2010;31(2):253-257
[Objective]To explore the roles of TIDC(tumor infiltrating dendritic cell)and TIL-T(tumor infiltrating T lymphocyte)in tumor immunity of EBV-associated gastric carcinoma(EBVaGC)and their clinical significance.[Methods]TIDC and TIL-T in EBVaGC(n=49)and EBVnGC(EBV-negative gastric carcinoma)(n=20)were detected by immunohistochemistry method and then their subtypes and their relationships with clinical and pathological factors were analyzed.[Results]Mild infiltration was detected in 29 of 49(59.2%)EBVaGCs and 18 of 20(90%)EBVnGCs,while marked infiltration of TIDC was detected in 20 of 49(40.8%)EBVaGCs and 2 of 20(10%)EBVnGCs.And the difference between the two groups was significant (P=0.013).The number of TIL-T in EBVaGC was hisher than that in EBVnGC(P=0.017),and most of them were CTLs.The number of TIL-T was positively correlated with that of TIDC(r=0.386,n=49,P=0.006).The degree of TIL-T infiltration in EBVaGC had negative relationship with the lymph node metastasis(P<0.001),while TIDC had no relationship with the clinical features.[Conclusion]TIDC and TIL-T may play important roles in the tumor immunity of EBVaGC;TIDC may contribute to the TIL-T recruitment in EBVaGC.
3.A new strategy for Chinese medicine processing technologies: coupled with individuation processed and cybernetics.
Ding-kun ZHANG ; Ming YANG ; Xue HAN ; Jun-zhi LIN ; Jia-bo WANG ; Xiao-he XIAO
China Journal of Chinese Materia Medica 2015;40(16):3323-3326
The stable and controllable quality of decoction pieces is an important factor to ensure the efficacy of clinical medicine. Considering the dilemma that the existing standardization of processing mode cannot effectively eliminate the variability of quality raw ingredients, and ensure the stability between different batches, we first propose a new strategy for Chinese medicine processing technologies that coupled with individuation processed and cybernetics. In order to explain this thinking, an individual study case about different grades aconite is provided. We hope this strategy could better serve for clinical medicine, and promote the inheritance and innovation of Chinese medicine processing skills and theories.
Chemistry, Pharmaceutical
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methods
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standards
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Cybernetics
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standards
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Drug Therapy
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standards
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Drugs, Chinese Herbal
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chemistry
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standards
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toxicity
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Humans
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Quality Control
4.Exclusive gene mapping on a Chinese familial IgA nephropathy family
Shumei SHI ; Linghan GAO ; Xuezhi ZHAO ; Aiping ZHANG ; Yaohai DING ; Yanxia WANG ; Guoyin FENG ; Lin HE
Chinese Journal of Nephrology 2011;27(2):77-81
Objective To initially map the gene responsible for autosomal dominant familial IgA nephropathy of a Chinese family by exclusive the five loci that had been reported with linkage analysis.Methods The genetic pattern of the familial IgA nephropathy was identified and the genomic DNA was extracted from the blood samples collected from the family members.Short tandem repeat (STR) inside the loci that had been reported was selected,such as 2q36,3p23-24,4q26-31,6q22-23,17q12-22,and the data with two-point linkage analysis were performed.Results Autosomal dominant inheritance pattern was demonstrated in phenotypes of the family and there was no linkage relationship in the above five loci of chromosomes because the maximum two-point LOD score was 0.39 at D17S1868.Conclusion Following exclusion of the loci which had been reported,there are other new pathopoiesis loci of FIgAN and it reveals that FIgAN has the genetic heterogeneity according to initial result at the same time.
5.Comparative study on clinical and pathological changes of liver fibrosis with acoustic radiation force impulse elastography imaging
Senhao LIN ; Hong DING ; Lijuan MAO ; Wen SHEN ; Wenping WANG ; Beijian HUANG ; Deming HE
Chinese Journal of Ultrasonography 2012;21(10):855-858
Objective To evaluate the clinical values of acoustic radiation force impulse(ARFI) elastography for liver fibrosis on hepatopath patients.Methods ARFI elastography was prospectively performed on 99 patients prepared to undergo hepatic surgery to get a shear wave velocity(Vs) which was the representative of liver stiffness.The fibrosis stages,inflammation grades and steatosis grades were evaluated histologically after surgery.Values of Vs were compared with the histological results.Results Values of Vs with fibrosis stage 0-4 was (1.14 ± 0.22) m/s,(1.30 ± 0.22) m/s,(1.36 ± 0.38) m/s,(1.47 ± 0.37)m/s and (1.87 ± 0.08) m/s,respectively.A significant difference was observed among them (P <0.001).There was a certain correlation between Vs and fibrosis stage(r =0.541,P <0.001).Vs was a significant predictor of stage ≥3 fibrosis with an area under the ROC curve of 0.812,sensitivity 73.2% and specificity 81.4% when 1.40 m/s was the cutoff value (P < 0.001).Values of Vs with inflammation grade 0-3 was (1.17 ± 0.16)m/s,(1.43 ± 0.36) m/s,(1.59 ± 0.53) m/s and (1.89 ± 0.59) m/s,respectively,which were significantly different (P < 0.001).A certain correlation was observed between Vs and inflammation grade(r =0.383,P <0.001).Values of Vs with steatosis grade 0-4 was (1.61 ±0.42) m/s,(1.47±0.58) m/s,(1.56 ± 0.71)m/s,1.13 m/s and (0.94 ± 0.95) m/s.Obvious difference didn't exist between Vs and steatosis grade (P =0.286).Obvious correlation wasn't observed between them,either (r =-0.177,P =0.080).Conclusions ARFI elastography has a certain value for the evaluation of liver fibrosis,while inflammation grade may affect its performance.
6.Ramiprii in combination with irbesartan for treatment of chronic heart failure in patients with rheumatic heart disease
Ping DING ; Li LI ; Zhi-Yun XU ; Lin HAN ; Bin HE ;
Academic Journal of Second Military Medical University 1985;0(06):-
Objective:To investigate the effectiveness of irbesartan in combination with ramipril for treatment of chronic heart failure in patients with rheumatic heart disease(RHD).Methods:A total of 120 RHD patients with chronic heart failure were randomized into treatment group(n=60)and control group(n=60)after valve replacement.All patients received regular ramipril treatment(5 mg/d);treatment group were also given irbesartan(150 mg/d).The patients were followed up for 6 months.The indices of observation included cardiac function(NYHA Class),6-Minute Hall Walk distance,and echocardiographie parameters.Results:Six months later the cardiac function in the treatment group was obviously improved compared with the control group;the patients in the treatment group had significant increase in 6-Minute Hall-Walk distance and improvement in echocardiographic parameters(left ventricle end-systolic diameters,end-diastolic diameter,ejection fraction, fractional shortening,P
7.Nitric Oxide ameliorates ischemia-reperfusion injury after rat lung transplantation
Wenxin HE ; Ge-Ning JIANG ; Jia-An DING ; Ruobai LIN ; Mingqiang KANG ; Yong ZHU
Chinese Journal of Organ Transplantation 2005;0(10):-
Objective To investigate the effects of inhaled low dose nitric oxide(NO)on lung ischemia-reperfusion injury during flush and delayed 10 min after reperfusion.Methods Sixty health a- dult male Sprague-Dawley rats were randomly allocated to the control and the NO group.Before the donor lung was harvested,the right hilus was clipped for 5 min(clipping test),then blood sample was collected from carotid artery for arterial blood gas analysis as baseline.Lung transplantation was per- formed in a“cuff-like”vessel anastomosis technique.Dynamic compliance(Cdyn)and resistance of airway(Raw)were monitored before operation(baseline)and after 2-h reperfusion.The graft's gas exchange and oxygenation were assessed by“clipping test”after 2-h reperfusion.The lung graft was harvested for measuring wet/dry weight ratio(W/D),the activity of myeloperoxidase(MPO)and in- ducible nitric oxide synthase(iNOS),the content of malonyldialdehyde(MDA),and the expression of iNOS gene and protein.Results After 2-h reperfusion,compared to the control group,PaO_2/FiO_2, OI,and Qs/Qt were improved significantly in the NO group(277?91 vs.157?47,P<0.01;2.67?0.89 vs.4.72?1.48,P<0.01;21.1?4.57 vs.27.1?2.37,P<0.01,respectively).The activi- ties of MPO were significantly reduced in NO group(1.80?0.46 vs 3.08?0.65 U/g tissue,P<0.01).The content of MDA in the lung tissue of NO group was significantly higher than that of the control group(34.8?7.9 vs.20.0?11.2 nmol/mg protein,P<0.05).Inflammatory cell infiltration was also significantly reduced(P<0.05).The expression of iNOS gene and protein in the lung tissue of NO group was significantly lower than that of the control group.The activities of iNOS were also significantly reduced in NO group(10.6?10.2 vs 97.8?82.2 nmol?g~(-1)?min~(-1),P<0.05).The im- munohistochemical positive staining of iNOS was localized in the alveolar epithelial cells and the in- flammatory cells infiltrated in the alveolar spaces and mesenchymal tissue.But there were no signifi- cant differences between two groups in Cdyn,Raw and W/D ratio.Conclusion Inhaled low dose NO might mitigate the intrapulmonary shunt,prevent neutrophil sequestration,inhibit the expression of iNOS gene and protein in isograft,thereby ameliorate ischemia-reperfusion injury and improve the ox- ygenation of the graft.
8.Role of angiotensinⅡin the changes of MMP-9 and TIMP-1 mRNA expressions in high glucose-induced mesangial cells of rat
Hai-Yan LI ; Ying GUO ; He-Lin DING ; Zu-Zhi FU ;
Chinese Journal of Endocrinology and Metabolism 1985;0(02):-
High glucose stimulated angiotensinⅡ(ATⅡ) production in mesangial cells of rat.Both high glucose and ATⅡdecreased expressions of matrix metalloprotein-9 (MMP-9) mRNA and MMP-9/tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA ratio and increased TIMP-1 mRNA expression in mesangial cells of rat,which could be reversed by an ATⅡreceptor blocker,Saralasin.
9.Influence of albumin-activated renal proximal tubular epithelial cells on peritubular capillaries and its potential mechanism
Jing LIN ; Yani HE ; Huiming WANG ; Kailong LI ; Hanlu DING ; Haiying SHEN ; Jvrong YANG
Chinese Journal of Nephrology 2008;24(9):657-662
Objective To explore the influence of albumin-activated renal tubular epithelial cells (RTECs)on peritubular capillaries in co-culture system and its potential mechanism. Methods Endocytosis of TRITC labeled bovine scrum albumin (TRITC-BSA) by HKC was detected by laser scanning confocal fluorescence microscope. HKC or HKC transfected with cubilin (endocytic receptor of albumin) siRNA or pre-treated with rotenone was incubated with albumin(20 g/L) for 24 h respectively. Fluorescence probe technique and spectrometry were applied for determination of intracellular superoxide anion O2-and H2O2 in supematant. Then, the albumin-aetivated-HKC, pretreated-HKC with cubilin siRNA or rotenone, was cultured with HUVEC for 24 h in co-culture system respectively. HUVEC proliferation was determined by MTT and cellular apoptosis was analyzed by flow cytometry. Tabular morphogenesis of endothelial cells was examinedby microscopy. Results TRITC-BSA uptake was obviously lower in HKC transfected with cubilin siRNA. Intracellular generation of O2-and H2O2 in culture supernatant was increased in dose-and time-dependent manner after stimulating with albumin. The levels of O2-and H2O2 were suppressed by cubilin siRNA and rotenone. In co-culture system, albumin-activated-HKC induced endothelial cells apoptosis and inhibited their capillary tubular morphogenesis. Pretreatment of HKC with cubilin siRNA or rotenone could suppress endothelial cells apoptosis and promote capillary tubular morphogenesis. Conclusions There may be a crosstalk between RTECs and peritubular microvascular endothelial cells in renal proteinurie diseases. The generation of ROS by albumin-activated RTECs may play an important role in this process.
10.Temporal alteration of stone composition and onset age in the upper urinary tract: a cross-sectional study of 1 878 cases
Wei WANG ; Fengning MA ; Ruixian PENG ; Zhiyuan LIN ; Guowei SHI ; Qiang DING ; Jiayang HE
Chinese Journal of Urology 2015;36(8):620-623
Objective To investigate if distribution of stone composition and onset age in the upper urinary tract changed during the past 12 years in China.Methods There were 1 878 urolithiasis patients of the upper urinary tract in our hospital from 2003 to 2014 enrolled in present cross-sectional study.There were 1 300 male and 578 female patients with a median onset age of 46 (6-95) years.Stone composition was measured by infrared spectrophotometry.All the patients were divided into 3 groups according to the onset year:Year 2003-2006,Year 2007-2010 and Year 2011-2014.The distributions of stone types were compared among the 3 groups.Age and gender were included as potential confounders.Chi square test,P trend test,Kruskal-Wallis test and logistic regression were employed in the statistical analysis.Results Calcium oxalate was the most common type with a dominant proportion of 78.1% (1 466/1 878),while uric acid had a small proportion of 4.8% (91/1 878).The proportions of uric acid in the 3 groups were 2.7% (12/441),5.1% (39/758) and 5.9% (40/679),showing an increasing trend (P <0.05).Multivariate analysis showed that year group was independently correlated with the proportion of uric acid,with an OR of 1.385 (95% CI,1.027-1.867).From 2003 to 2014,the proportion of uric acid calculus increased by 0.42% (95% CI,0.25%-0.59%) annually.The median ages of disease onset were 43,46 and 49 years respectively in those three groups,also showing an increasing trend with time (P <0.01).Conclusion From 2003 to 2014,the proportion of uric acid and onset age in patients of upper urinary tract calculi were increased in the present cohort.