1.cAMP/PKA signal activation prevents chemical-induced podocyte injury
Kai WEI ; Xiaoying LI ; Zhaohui NI ; Hua TAO ; Leyi GU
Chinese Journal of Nephrology 2013;29(10):754-760
Objective To investigate the role of activated cylic AMP(cAMP) signaling in chemical-induced podocyte injury.Methods Eight-weeks-old male BalB/C mice were randomly divided into three groups:control group,Adriamycin (ADR) group and Forskolin+ADR group.ADR nephropathy models were established by tail intravenous injection,and part of them were injected Forskolin,an agonist of adenylate cyclase,intraperitoneally.Phosphorylation of cAMP response element binding protein (CREB) was detected by laser confocal microscopy,morphology of foot processes were determined with transmission electron microscope,and WT-1 expression in glomeruli were detected by immunohistochemistry.Conditionally immortalized podocytes were treated with puromycin aminonucleoside (PAN),Exchange protein directly activated by cAMP (Epac) agonist 8-pCPT-2-O-Me-cAMP (2Me),protein kinase A (PKA) antagonist H89 and its agonist pCPT-cAMP(pCPT).Western blot was used to detect the expression levels of Epac,caspase3 and cleaved caspase3.PKA activity was assayed using cAMP-dependent protein kinase detection system.Cell viability was determined by a cell count kit and podocyte apoptosis was estimated by TUNEL staining.Mitochondrial membrane potential was evaluated by JC-1 staining.Results (1)Compared with ADR group,the urine albumin decreased significantly (P < 0.05) among Forskolin + ADR group and the WT-1 positive cells per glomerulus increased obviously (P < 0.05).(2)PAN decreased podocyte number in a time-dependent manner (P < 0.05),pre-treatment with pCPT obviously inhibited PAN induced podocyte decrease (P <0.05),but H89 prevented the effect of pCPT in a dose-dependent manner (P < 0.05).(3)JC-1 staining showed that the percentage of podocyte with green fluorescence for control,PAN and pCPT+PAN group were (12.67±2.15)%,(31.35±4.60)% and (16.96 ± 2.51)% respectively (P < 0.05),and pretreatment with H89 inhibited the effect of pCPT (P < 0.05).(4) PAN promoted podocyte apoptosis and cleaved caspase3 expression (P < 0.05),and pretreatment with pCPT significantly prevented PAN-induced podocyte apoptosis and cleaved caspase3 expression (P < 0.05).Conclusions cAMP signaling activation ameliorated podocyte injury in ADR nice and PAN-induced podocyte apoptosis,and cAMP/ PKA pathway may mediate these processes.
2.Marrow mesenchymal stem cell transplantation in treatment of ischemic heart disease in rabbits
Guotao MA ; Hua REN ; Zhaohui ZHU ; Chaoji ZHANG
Basic & Clinical Medicine 2006;0(03):-
Objective To investigate the feasibility of treating ischemic heart disease with transplantation of marrow mesenchymal stem cells.Methods Marrow mesenchymal stem cells were collected from New Zealand rabbit's sternum and cultured.A myocardial infarction model was created by ligation of the distal left anterior descending artery in New Zealand rabbit.MSCs were injected into the region of myocardial infarction.The size of the myocardial infarction area was measured by PET and the cardiac function was assessed by measuring the pressure change of left ventricle(dp/dt).Results The size of the myocardial infarction area diminished and the cardiac function was improved after the transplantation of marrow mesenchymal stem cells.Conclusion Transplantation marrow mesenchymal stem cells may improve cardiac function of ischemic heart disease in animal model of New Zealand rabbit.
3.Effects of high mechanical index ultrasound of radiation microbubble on the colon cancer cell skeletal
Hua ZHONG ; Rui LI ; Yanli GUO ; Xing HUA ; Xiaohang ZHANG ; Yafang XUE ; Zhaohui CHEN
Chinese Journal of Ultrasonography 2011;20(11):996-999
Objective To Study the effects of high mechanical index ultrasound radiation microbubble on colon cancer cell skeletal.Methods Lovo cell were cultured in vitro,and this study was divided into control group,simple contrast agent group,microbubble plus ultrasound radiation group and simple ultrasound radiation group.Ultrasound contrast agent SonoVue and ultransound (frequency 1.5 MHz and MI 1.7) were used.Results In the control group,the microtubes were densest in dyeing silk,and extended to the edge of a cell.In the ultrasound and microbubble group,the microtubes were weaker and thin,the.network was mainly in the structure of the long axis.The cells arranged in a slight pigmentation to the density cell,to reach out many fine short hair,there were obviously a sense of silk and directional.In the microbubble and ultrasound group,Lovo cells streamed of the central significantly reduced,fluorescent lighting,with short hair.There was no difference in the ultrasound group and the microbubble group with microfilament and microtubule.Conclusions High mechanical index ultrasound radiation can changed into vacant,a trace of the assembly and distributed to the tumor cells are attacking,the transfer of restraining.
4.Effects of high mechanical index ultrasound contrast on the hepatic metastasis of cancer
Hua ZHONG ; Rui LI ; Yingxue HAO ; Yanli GUO ; Xing HUA ; Yafang XUE ; Zhaohui CHEN
Chinese Journal of Ultrasonography 2008;17(5):430-433
Objective To observe the effects of high mechanical index ultrasound contrast on hepatic metastasis of colorectal cancer. Methods Hepatic metastasis models were established by injecting Lovo cells into the spleen of SD rats.This study was divided into control group, microbubble plus ultrasound radiation group simple contrast agent group and simple ultrasound radiation group.Ultrasound contrast agent SonoVue(1 ml/kg) was injected via tail vein, high mechanical index ultrasound contrast (frequency 1.5 MHz,MI 1.7) was performed intermittently for 2 min.After 10 d,the animals were killed and the size and number of hepatic metastasis were compared.Histological pathology and its ultrastructure were observed.Results There were no significant differences between contral group,simple ultrasound radiation group and simple contrast agent group in metastatic rate ( P>0.05).There were no obvious differences between contral group, simple ultrasound radiation group and simple contrast agent group in cells'ultrastructure by transmission electron microscopy (TEM).The number and size of hepatic metastasis decreased obviously in microbabble plus ultrasound radiation group ( P<0.01 ), the mitochondrion was swelling and the gaps of endothelial cells were loose. Conclusions High mechanical index ultrasound contrast can inhibit the hepatic metastasis of colorectal cancer.
5.Preoperative diagnosis of hepatic angiomyolipomas using real-time contrast-enhanced ultrasound: comparison with contrast-enhanced helical CT
Rui LI ; Xiaohang ZHANG ; Hua ZHONG ; Xing HUA ; Yanli GUO ; Aimin GUO ; Zhaohui CHEN
Chinese Journal of Ultrasonography 2010;19(6):485-488
Objective To observe the perfusion pattern of hepatic angiomyolipomas using contrastenhanced ultrasound(CEUS) and compare diagnostic efficacy of contrast-enhanced ultrasound with contrastenhanced helical CT(CECT).Methods Nineteen patients with 21 resected and pathologically proven hepatic angiomyolipomas were included in this study.Low mechanical index (mechanical index less than 0.2) realtime CEUS was performed in nineteen patients (5 patients with pulse inversion harmonic, 14 patients with contrast pulse sequencing, CPS) after 2.4ml bolus injection of contrast agent SonoVue.CECT was performed using 16-slice helical CT and contrast agent Ultravist.The diagnostic performance was calculated by considering histologic results as the reference standards.Results Fifteen tumors were correctly diagnosed as hepatic angiomyolipomas,4 tumors were misdiagnosed (including 1 hepatocellular carcinoma,2hepatic adenomas, 1 hemangioma) and 2 tumors were characterized as benign lesions by CEUS.Eight tumors were correctly diagnosed as hepatic angiomyolipomas, 13 tumors were misdiagnosed (including 7hepatocellular carcinoma, 1 liposarcoma, 2 lipomas, 1 hepatic adenomas, 2 hemangiomas) by CECT.The preoperative diagnostic accuracy was 71.4% for CEUS and 38.1 % for CECT(P<0.05 ).Conclusions CEUS can demonstrate typical imaging characteristics of most hepatic angiomyolipomas, and has higher diagnostic performance than CECT in characterization of hepatic angiomyotipomas.
6.Values of high resolution manometry in the diagnosis of hiatal hernia
Feng JI ; Zhonggao WANG ; Zhen LI ; Xiang GAO ; Chengchao ZHANG ; Zhitong LI ; Zhaohui HUA
Chinese Journal of General Surgery 2013;(6):427-430
Objective To evaluate high resolution manometry in the diagnosis of hiatal hernia.Methods Clinical data were reviewed on 20 patients suffering from gastroesophageal reflux who had laparoscopic Toupet fundoplication for preoperative tentative diagnosis of hiatal hernia.Preoperative diagnosis of hiatal hernia was made collectively by endoscopy,X-ray examination,24 hour esophageal pH monitoring and high resolution manometry before surgery.Results Preoperative diagnosis of hiatal hernia was made in 3 patients by X-ray examination,in 9 patients by high resolution manometry.11 patients were finally diagnosed with hiatat hernia intraoperatively.X ray was consistent with intraoperative diagnosis in 27% cases.Intraoperative and endoscopic diagnoses were 55%.High resolution manometry and intraoperative diagnoses were consistent in 82%.Lower esophageal sphincter length was (1.92 ± 0.38) cm in hiatal hernia group and (2.10 ± 0.92) cm in non-hiatal hernia group (t =0.60,P > 0.05),lower esophageal sphincter pressure (respiratory min) was (0.64 ±0.55) kPa in hiatal hernia group and (1.31 ± 1.07) kPa in nonhiatal hernia group(t =1.80,P > 0.05),and lower esophageal sphincter pressure (respiratory mean) was (1.43 ±0.92) kPa in hiatal hernia group and (2.57 ± 1.33) kPa in non-hiatal hernia group(t =2.26,P <0.05).The reflux parameters,including the percent total time pH < 4,and DeMeester score,were significantly greater in hiatal hernia group than in non-hiatal hernia group (all P < 0.05).Conclusions Hiatal hernia patients are with poor esophageal antireflux competency and severe reflux.High resolution manometry is more valuable in the diagnosis of hiatal hernia than endoscopy or X-ray examination.
7.Staging bilateral CEA perioperative management of blood pressure
Birun HUANG ; Zhen LI ; Zhaohui HUA ; Ke MA ; Hui CAO ; Linfeng ZHANG ; Zhonggao WANG
Journal of Chinese Physician 2016;18(11):1619-1621,1625
Objective To evaluate the perioperative management of blood pressure in patients with bilateral carotid artery severe stenosis underwent staging carotid endarterectomy (CEA).Methods This retrospective study included 31 patients with bilateral carotid stenosis who underwent bilateral revascularizations in our department from April 2012 to November 2015.Patients were recorded with general information,and the changes of blood pressure in preoperative,intraoperative and postoperative were observed,respectively.Regulation and control of blood pressure were performed according to individual patient's condition.Results Thirty one patients underwent a total of 62 consecutive procedures successfully.Postoperative symptoms disappeared or significantly reduced.Twenty three cases (74.2%) had high perfusion symptoms in the ipsilateral CEA,and 5 cases (16.1%) with high perfusion syndrome in the contralateral surgery.Patients were improved after strict control of blood pressure and dehydration reduced intracranial pressure.The high peffusion symptoms in patients were significantly improved or disappeared after 1 week.Doppler ultrasound was used to evaluate the carotid artery before discharge.Conclusions For patients with bilateral carotid stenosis,staging purposes CEA is safe and effective.However,perioperative blood pressure management is very important.Individual control of blood pressure can significantly reduce the risk of postoperative high perfusion and cerebral infarction.Blood pressure control is recommended after 1 week in about 85% of preoperative blood pressure.
8.Retrospective dose estimation for individuals exposed to accidental exposure in uterus with fluorescence in situ hybridization
Xue LU ; Hua ZHAO ; Li LIANG ; Shulan ZHANG ; Zhaohui ZHANG ; Deqing CHEN ; Liwen MA ; Tingzhen JIA ; Qingjie LIU
Chinese Journal of Radiological Medicine and Protection 2010;30(5):513-515
Objective To reconstruct the absorbed dose for the individual who was accidentally exposed in uterus 16 years ago.Methods Peripheral blood samples were taken from the victim and her mother.The dicentric and centric ring chromosome aberrations were analyzed with conventional method,the micronucleus was observed with cytokinesis-block micronucleus method,and fluorescence in situ hybridization (FISH) with chromosomes 1,2 and 4 painting probes were used for translocation detection.Dose was estimated according to the standard dose-response curves previously established.Results No unstable chromosome aberrations and normal micronucleus frequencies were observed in two persons 16years after the accident.Against the established dose-response curves with FISH,the doses to the mother and her daughter were 0.76 Gy (95% GI 0.41-1.00 Gy) and 0.61 Gy (95% CI 0.44-0.86 Gy),respectively.Because the biological dose estimated for the mother 1 month after the accident was 2.30 Gy (95% CI 2.07-2.50 Gy),the dose correction factor was 3.03 for dose estimation 16 years later.The estimated dose in uterus to the victim was 1.85 Gy (95% CI 1.33-2.61 Gy).Conclusions The estimated dose to the individual accidentally exposed in uterus 16 years ago can be obtained according to the dose correction factor of the mother with FISH method.
9.Association between non-dipping circadian blood pressure rhythm and left ventricular hypertrophy in chronic kidney disease patients
Xiajing CHE ; Zhaohui NI ; Weiming ZHANG ; Minfang ZHANG ; Leyi GU ; Yucheng YAN ; Hua YING ; Chunhua HU ; Jiaqi QIAN
Chinese Journal of Nephrology 2009;25(9):663-667
Objective To clarify the association between non-dipping circadian blood pressure (BP) rhythm and left ventrieular hypertrophy (LVH) in chronic kidney disease (CKD) patients. Methods A total of 257 CKD patients of stage 1 to 5 were enrolled in the study. The parameters of BP and circadian rhythm were measured by ambulatory BP monitoring (ABPM) and the cardiac structure was examined by echocardiography. The association between circadian BP rhythm and echocardiographic parameters was studied. Results The prevalence of abnormal circadian BP rhythm (non-dipping rhythm) was quite high (75.4%) in CKD patients and increased with the deterioration of renal function. Even if in the normal BP group, the prevalence of non-dipping rhythm was 71.3%. The change of cardiac structure such as LVH in non-dipping patients was more obvious than the dipping patients. The left ventrieular mass index (LVMI) was positively correlated with BP, non-dipping rhythm. Multiple regression analysis showed that 24 h-SBP (β=0.417, P<0.01), triglyceride (TG) (β=-0.132, P=O.007), Hb (β=-0.394, P=0.016) and gender(β=0.158, P=0.039) were independent risk factors of LVMI. Conclusions The prevalence of non-dipping rhythm is quite high in CKD patients and increases with the deterioration of renal function. The change of cardiac structure such as LVH is obvious in CKD patients, especially in non-dipping group. The non-dipping rhythm is related with LVMI.
10. Surgical and comprehensive treatment for intrahepatic cholangiocarcinoma patients from the perspective of tumor heterogeneity
Chinese Journal of Surgery 2018;56(5):328-331
Intrahepatic cholangiocarcinoma(ICC) is generally found late along with extremely poor prognosis and lack of effective and standardized treatment. Tremendous heterogeneities exist in onset factors, geographic distribution, clinical manifestation, and biological characteristics of ICC patients. However, the relevant causes and mechanisms have not been clearly illustrated. Recent studies indicate that the diverse celluar origins of ICC, including liver cells, bile duct epithelial cells, glandular cells around the duct, and liver stem cells, etc. Besides, the tumorigenesis, progression and metastasis of ICC are closed related to metabolism such as glucose, lipid metabolism. It can be inferred that the varieties of biological characteristics and clinical manifestation of ICC patients are possibly closely linked with heterogeneous cellular origins, multiple metabolic mechanisms or pathways. Therefore, it′s necessary to conduct research with regard to the connection between cellular origins, cell metabolism and clinical manifestation, biological characteristics, and make further classifications. Based on the accurate classification, surgeons can exert corresponding surgical and comprehensive treatment strategies on ICC patients, attaining the goal of individualized and standardized treatment, ultimately, improving prognosis and prolonging survival time.