1.Effects of continuous venovenous hemodiafiltration on plasma LPS, IL-1β, IL-4, HMGB-1 in multiple organ dysfunction syndrome dogs
Hongyan LIU ; Lei YE ; Zenghua LIU ; Wenwen LV ; Jihong CHEN
Chinese Journal of Nephrology 2013;29(6):444-448
Objective To investigate the effects of continuous venovenous hemodiafiltration (CVVHDF) on plasma lipopolysaccharide (LPS),interleukin(IL) 1β,IL-4,high mobility group box 1 (HMGB-1) in multiple organ dysfunction syndrome (MODS) dogs,to explore the therapeutic mechnism of CVVHDF.Methods Dogs were subjected to hemorrhagic shock plus resuscitation and endotoxemia to establish MODS model,then they were randomly divided into 2 groups:CVVHDF group (n=6) and MODS group (n=6).After endotoxin injection completed,the CVVHDF group received CVVHDF treatment for 24 h; MODS group did not receive CVVHDF treatment.The LPS,IL-1β,IL-4,HMGB-1 levels in plasma and ultrafiltrate were measured at different time points(before operation,before intravenous infusion of endotoxin,0 h,3 h,6 h,9 h,12 h,18 h,24 h after intravenous infusion completion of endotoxin),then the sieving coefficient (SC) was calculated.Results Compared with MODS group,the LPS,IL-1β,IL-4,HMGB-1 levels in plasma were significantly decreased in the CVVHDF group at 9 h,12 h,18 h,24 h (P < 0.05).Some concentration of IL-1β,IL-4 and HMGB-1 was detected in the ultrafiltrate,the SC for IL-1β,IL-4 and HMGB-1 was 0.60±0.12,0.83±0.11,0.70±0.09 respectively,and LPS could not be detected in the ultrafiltrate,its SC was 0.After treatment,the damage level of lung and renal had been significantly reduced in CVVHDF group.Conclusion CVVHDF can effectively reduce the levels of pro-inflammatory mediator and anti-inflammatory cytokine related to MODS,cut off the vicious circle of cytokine network and reduce the damage level of organism in the treatment of MODS.
2.Effect of Lycium barbarum polysaccharide on atherosclerosis in mice by up-regulating adiponectin expression
Lei HU ; Ling DONG ; Lei QU ; Libin WANG ; Wenwen WU ; Haifang WANG
Drug Evaluation Research 2017;40(3):292-299
Objective To explore the effect of Lycium barbarum polysaccharide (LBP) on adiponectin (APN) expression and the mechanism of lowering blood-lipid and anti-inflammation in atherosclerotic (AS) mice.Methods C57BL/6J mice with normal feed were chosen as control group.Thirty-two ApoE-/-mice with high cholesterol diet were successfully established as AS models,and then the mice were randomly divided into model group and three LBP groups,which were feed with high,medium,and low dose of LBP.After feeding for four weeks,aortic blood and tissues were collected.Blood-lipid,inflammatory factors,endothelin-1 (ET-1),APN,AdipoR1,and AMPK pathway related protein expression were detected.Differentiated 3T3-L1 cells were divided into control group,LBP group,and LBP + BML-275 group.Triglyceride (TG),inflammatory factors,APN,AdipoR1,and AMPK pathway related protein expression was investigated.Results In mice,compared with the control group,typical AS pathomorphologic changes were found in aorta and the levels of TG,total cholesterol (TC),nitric oxide (NO),ET-1,interleukin-6 (IL-6),and tumor necrosis factor (TNF-α) in the model group were significantly increased,while the protein expression of HDL-C,APN,AdipoR1,PPARα,AMPKα,and p-AMPK-α and Acyl-CoA oxidase (ACO) mRNA expression was reduced.Compared with the model group,AS pathomorphologic state was obviously improved in aorta and the amount of TG,TC,NO,ET-1,IL-6,and TNF-α in LBP groups were markedly decreased,while the protein expression of HDL-C,APN,AdipoR1,PPARα,AMPKα,p-AMPKα,and ACO mRNA expression was up-regulated.These changes were all in a dose-dependent manner.In differentiated 3T3-L1 fat cells,compared with control group,LBP enhanced the expression of APN,AdipoR1,PPARα,AMPKα,p-AMPKα,and ACO,but decreased the amount of TG,IL-6,and TNF-α.Compared with LBP group,the levels of TG,IL-6 and TNF-α was notably increased in BML-275 group.Conclusion LBP up-regulates the expression of APN and AdipoR1,activates APN/AMPK pathway,plays a role in lowering blood-lipid and anti-inflammation,and thus relieves AS in mice.
3.Pathogenic role of Bcl-6/Blimp-1/IL-21 in primary Sj?gren′s syndrome
Chunqiao DUAN ; Wenwen YANG ; Lingyan LEI ; Huifang GUO ; Mingfeng ZHANG ; Lixia GAO ; Chao SUN
Chinese Journal of Immunology 2015;(3):384-388,392
Objective:To analyse the role of Bcl-6/Blimp-1/IL-21 in pathogenesis of primary Sj?gren′s syndrome(PSS),the relationship between Bcl-6/Blimp-1/IL-21 expression and labial gland biopsy grading.Methods:Immunohistochemical(IHC) method was used to detect the expression of Bcl-6/Blimp-1 in salivary gland between 30 cases pations with PSS in disease group and 11 cases patients with mucous cyst,lower lip trauma in control group,and the serum IL-21 levels between disease group of 40 cases patients with PSS and 30 cases healthy volunteers were measured by enzyme-linked immunosorbent assay( ELISA) ,relations among 15 patients with IL-21 expression levels with labial gland biopsy grading.Results:The expression levels of Bcl-6/Blimp-1/IL-21 in disease group were higher than control group;in disease group,with pathological grades increased,the expression levels of Bcl-6/Blimp-1/IL-21 were also raised.Conclusion:①Bcl-6/Blimp-1/IL-21 may participate in the pathogenesis of PSS;Bcl-6/Blimp-1/IL-21 is associated with infiltration lymphocytes of salivary gland.
4.Epidermal growth factor receptor involvement in cardiovascular remodeling in renovascular hypertensive rats
Mei FENG ; Wenhao TENG ; Wenwen JIANG ; Jizhou XIANG ; Hui LIU ; Lei YANG
Chinese Pharmacological Bulletin 2016;32(5):625-630,631
Aim To determine the possibilities and mechanisms of EGFR, a receptor protein tyrosine kinase associated with many important cellular processes re-sponsible for cardiovascular remodeling in renovascular hypertensive rats. Methods 2K1C hypertensive rats were used in the present study. Blood pressure was measured with the tail-cuff method. LVMI and his-topathological changes in the cardiovascular system were analysed. EGFR expressions of aorta and myocar-dium as well as phosphorylation levels of ERK in hy-pertensive rats were detected by immunohistochemistry and Western blot analysis, respectively. Results Sys-tolic blood pressure was markedly increased 2 weeks after 2K1C surgery. Cardiovascular remodeling induced by hypertension was confirmed by elevated LVMI, pro-liferation of collagen fibers in myocardial interstitium, histopathological changes in cardiovascular system and increased IMT of thoracic aorta 6 weeks after 2 K1 C surgery. Compared with sham rats, EGFR expression in the ventricular myocardium of 2 K1 C rats was signifi-cantly increased at 6 weeks ( P<0. 05 ) , and the EG-FR/GAPDH ratio was higher in 2 K1 C rats with higher systolic blood pressure ( P < 0. 05 ) . Phosphorylation level of ERK 1/2 was upregulated correspondingly in 2 K1 C rats ( P <0. 01 ) . Increased EGFR expression was also found in aortas of 2K1C rats, particularly in tunica intima and media. Conclusion EGFR and its down-stream kinases ERK 1/2 are involved in cardio-vascular remodeling in association with the severity of hypertension in renovascular hypertensive rats.
5.Metabonomics research of acute renal graft rejection patients based on UPLC-qTOF-MS system
Lei YE ; Jingjing ZHANG ; Hongyan LIU ; Zenghua LIU ; Wenwen LV ; Jihong CHEN
Chinese Journal of Nephrology 2013;29(12):902-907
Objective Plasma phospholipid metabolism analysis was employed to investigate plasma metabolic profile of acute renal graft rejection in order to find potential disease biomarkers and reveal its pathophysiological changes.Methods Selected 33 patients which did renal transplant in our hospital during 2009 to 2010,named preoperative group.14 patients were diagnosed as acute graft rejection,and 19 patients were non-acute graft rejection.Then use ultra performance liquid chromatography (UPLC) coupled with quadrupole time of flight mass spectrometry (qTOF-MS) to establish the metabolic fingerprint in those patients.The date was preprocessed with software Markerlynx,and analyzed with partial least squares discriminant analysis (PLS-DA),and data from conventional laboratory techniques were used for assessing renal function.Results In the plasma of renal transplant patients,seventeen biomarkers were discovered:creatinine,four sphingomyelins (SM),nine phosphatidylcholines (PC),three lysophosphatidylcholine (LPC).While the creatinine was increased,the others were reduced obviously.Conclutions UPLC-qTOF-MS based metabonomics can analyze the plasma phospholipid metabolism in patients with renal transplantation,reveal the law of phospholipids metabolic changes in the process of acute rejection.The levels of plasma phosphatidylcholine's esterlysis and fatty acids' β-oxidation are increased.The immunosuppressive therapy can reduce the activity of phospholipase,inhibit the level of plasma phosphatidylcholine's esterlysis and fatty acids' β-oxidation,which restraines the development of acute rejection after renal transplantation.Therefore it may be a promising new technology in diagnosing acute renal graft rejection after renal transplantation.
6.The quality of life of long-term stroke patients and related factors
Xia GAO ; Lei GAO ; Wenwen ZHANG ; Zhao MA ; Enquan YANG ; Guangle LI ; Zeng LI ; Xiling JIN
Chinese Journal of Physical Medicine and Rehabilitation 2011;33(11):839-842
Objective To investigate the quality of life(QOL)of patients with stroke and its related factors.Methods The QOL of eighty-two stroke survivors was assessed in terms of SF-36 scores,motor impairment (Fugl-Meyer),disability[Barthel index(BI)]and depression(HAMD)more than one year after their first episode.Their social demographic characteristics such as age,gender,education and income were recorded,as were the characteristics of their disease and any complications.Multiple regression analysis was used to analyse the related factors.Results The average age of the 82 subjects was 61.89 + 9.81 years(range,33-81).56 of them were male (68.2%).Scores on all items of the SF-36 for these subjects were lower than those of a normal population.Correlation analysis showed income,cost for medical care,regular exercise,movement function,ability in the activities of daily living,depression,hypertension and shoulder pain were significantly correlated with most of the SF-36 domain scores.Motor function,income and cost for medical care explained 34% of the variance in SF-36 scores.Motor function was the single most important factor.Conclusion The major factors affecting the QOL of stroke patients are motor function,level of income and cost for medical care.Paying more attention to rehabilitation treatment,taking regular exercise and more income could help improve the QOL of stroke survivors.
7.Relationship of platelet count with clinicopathological features and prognosis of patients with breast cancer
Pei XUN ; Lei HAN ; Chunqing SONG ; Wei HAO ; Ying ZHANG ; Hanhong LU ; Wenwen LI ; Jian LUO
Journal of Chinese Physician 2017;19(8):1176-1179
Objective To investigate relationship of platelet (PLT) count with clinicopathological features and prognosis of patients with breast cancer,and explore the susceptibility index to evaluate prognosis of patients with breast cancer.Methods A retrospective analysis of clinical data of 498 patients with breast cancer in January 1995 to December 2005 was carried out.PLT count was tested.Those patients were divided into group A (PLT < 150 × 109/L),group B[(150-250) × 109/L],and group C (PLT > 250 × 109/L) according to PLT count level.The relationship of platelet count with clinicopathological features was analyzed.Kaplan-Meier and Cox proportional hazards model were used for univariate analysis and multivariate analysis of PLT impact on survival time.Results There was positively correlated between PLT count and clinicopathological features (Pearson coefficient > 0,P < 0.05).There was negative correlated between PLT count and survival time (Pearson coefficient =-O.583,P < 0.05).The survival time of groups A,B and C were significantly different (P =0.018).Cox proportional hazards model multi-factor analysis showed that PLT count was an independent factors affecting survival time (OR =2.256,P < 0.05).Conclusions Patients with breast cancer associated with increased emphasis and PLT count.PLT count had negative correlation with survival time.PLT count could be a susceptible index to predict the prognosis of patients with breast cancer.
8.The changes of atrial muscle RAS and ACE2-Ang(1-7)-Mas axis in MODS dogs treated by CVVHDF and the mechanism
Wenwen LYU ; Jing YU ; Lei YE ; Hongyan LIU ; Zenghua LIU ; Jihong CHEN
Chinese Journal of Nephrology 2014;30(4):286-292
Objective To observe the members' dynamic change of renin-angiotensin system (RAS) and angiotensin converting enzyme 2(ACE2)-Ang(1-7)-Mas axis during the continuous venovenous hemodiafiltration (CVVHDF) treating the dogs with multiple organ dysfunction syndrome (MODS),and to investigate the efficacy mechanism on cardiac function.Methods Dogs were subjected to hemorrhagic shock plus resuscitation and endotoxemia to establish MODS model,then they were randomly divided into 2 groups:CVVHDF group (n=8) and MODS group (n=6).After endotoxin injection completion,the CVVHDF group received CVVHDF for 12 h,MODS group didn't.Radioimmunoassay,euzymelinked mmunosorbent assay (ELISA) were used to detect the content of renin,Ang Ⅰ,Ang Ⅱ,Ang (1-7).Real-time PCR was used to detect the expression of renin mRNA and ACE2 mRNA.Western blotting was used to detect the protein content of renin,Ang Ⅱ,ACE2 and Ang (1-7).Results (1) Organ function:Compared with the MODS group,the vital signs,heart,lung and renal function were significantly ameliorated in the CVVHDF group,the difference had statistical significance (P< 0.05).(2) RAS changes:To detect index from the level of organs,genetic and molecular in arterial tissue,the results displayed that the content of renin,Ang Ⅰ,Ang Ⅱ,the expression of renin mRNA,the protein content of renin,Ang Ⅱ in CVVHDF group were lower than that in MODS group,the difference had statistical significance (P < 0.01).(3)ACE2-Ang(1-7)-Mas axis's changes:Using the same methods above to detect corresponding indicators,the results displayed that the content of ACE2,Ang(1-7),the expression of ACE2 mRNA and the protein content of ACE2,Ang(1-7) in CVVHDF group were significantly improved than that in MODS group,the difference had statistical significance (P < 0.01).Conclusions In the process of CVVHDF treating MODS,the ACE2 -Ang(1-7)-Mas axis plays the role which antagonizes the RAS system,and to protect the cardiac function.This research may be important for MODS' clinical rescue.
9.Correlation analysis between KCNJ11 polymorphism and essential hypertension in Kazakh from Xinjiang
Lijie WANG ; Wenwen ZHANG ; Liang ZHANG ; Lei ZHAO ; Ketao MA ; Li LI ; Junqiang SI
The Journal of Practical Medicine 2016;32(6):894-896
Objective To explore the relationship between KCNJ11-E23K polymorphism and essential hypertension (EH) in Kazakh from Xinjiang. Methods PCR-RFLP method was used to test KCNJ11-E23K genotypes of Kazakh from Xinjiang,including 237 EH patients and 221 normotension (NT). Logistic regression analysis was used to analyze the risk factors associated with EH. Results The frequencies of KCNJ11-E23K genotype (EE and (EK + KK)) and allele (E and K) were 34.18%, 65.82%, 61.60% and 38.40%respectively in EH group. There was a significant difference between two groups (P < 0.05). Weight and EE genotype were risk factors affecting EH in Kazakh from Xinjiang. Individual who carried EE genotype and allele E were 2.501 and 1.388 times than (EK + KK) and allele K suffered from EH respectively. Conclusion KCNJ11-E23K polymorphism was associated with EH in Kazakh from Xinjiang.
10.The efficacy of traditional Chinese medicin in animal model of lung injury induced by paraquat: a Meta-analysis
Lei WANG ; Guangliang HONG ; Dong LI ; Xiao CHEN ; Wenwen HAN ; Zhongqiu LU
Chinese Critical Care Medicine 2014;26(6):399-404
Objective To systematically review the effect of traditional Chinese medicine (TCM) in an animal model of lung injury induced by paraquat (PQ),and to provide a theoretical basis for future clinical trials.Methods The Wanfang,CNKI,VIP,PubMed/MEDLINE,EMBASE database (from January 1979 to September 2012) were searched.All papers concerning TCM in animal model of lung injury induced by PQ were retrieved.Study selection and data extraction were performed on the basis of Cochrane systematic review methods.Weighted mean difference (WMD) and 95% confidence interval (95%CI) with random effects model was adopted to investigate the effect of TCM on lung injury induced by PQ.Results Eighteen papers involving 1 188 rats met our criteria.Meta-analysis showed that TCM could improve the lung coefficiency (WMD-0.07,95% CI-0.14 to-0.01,P=0.03),reduce lung wet/dry weight ratio (WMD-1.15,95%CI-2.03 to-0.27,P=0.01),increase the serum superoxide dismutase (SOD) activity (WMD 56.08,95%CI 23.46 to 88.70,P=0.000 8),improve plasma glutathione peroxidase (GSH-Px) level (WMD 26.64,95%CI 18.95 to 34.33,P<0.000 01),and lower serum malondialdehyde(MDA) level (WMD-0.65,95%CI-1.00 to-0.30,P=0.000 2),however there was no significant difference in the level of serum tumor necrosis factor-α (TNF-α) and hydroxyproline (HYP) level between TCM and controls (TNF-α:WMD-25.15,95%CI-54.87 to 4.57,P=0.10; HYP:WMD-0.11,95%CI-2.71 to 0.48,P=0.17).Conclusions These findings demonstrate the efficacy of TCM in animal models of lung injury induced by PQ.However taking account of heterogeneity,the efficacy should be interpreted with caution.