Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent inherited kidney disease,its prevalence ranges from 1 in 1 000 to 1 in 400.Two genes responsible for ADPKD, PKD 1 and PKD 2,were cloned in 1994 and 1996 respectively. Many researches have been done and great progress has been made on ADPKD.Current hot issues in this area included the structures and functions of polycystin 1 and polycystin 2,the role of cilia on polycystic kidney disease(PKD),the relationship between polycystins and the vascular abnormalities,the image evaluation of PKD,the effects of blocking RAS on slowing down the PKD progression and the treatment prospects for ADPKD. This paper focused on some issues and their implications for the diagnosis and treatment of PKD.

Objective: To study the influence of recombinant human hepatocyte growth factor (rhHGF) on proliferation and extracellular matrix synthesis of autosomal dominant polycystic kidney disease (ADPKD) cyst lining epithelial cells in vitro . Methods: The effects of different concentration rhHGF (0.5,1,2.5,5 ng/ml)in 48 h and the optimal concentration rhHGF of different time (24,48,72 h ) on proliferation of ADPKD cyst lining epithelial cell lines were observed by the incorporation of 3H TdR, and synthesis of collagen and laminin were respectively observed by the incorporation of 3H proline and radioimmunoassay. Results: rhHGF stimulated the proliferation of ADPKD cyst lining epithelial cells and synthesis of collagen and laminin,the optimal concentration and time of rhHGF were 1 ng/ml and 48 h. Conclusion: rhHGF can significantly stimulate ADPKD cyst lining epithelial cells proliferation and extracellular matrix synthesis in vitro . [

Objective: To study the effect of N (4 hydroxyphenyl) retinamide (4 HPR) on apoptosis of cyst lining epithelial cells in autosomal dominant polycystic kidney disease (ADPKD).Methods: The proliferation of ADPKD cyst lining epithelial cells was detected by MTT assay after stimulated by 1,2.5,5 and 10 ?mol/L 4 HPR for 24,48,72 and 96 h respectively.The effect of 4 HPR on the survival rate of cells stimulated by HGF was analyzed with trypan blue staining.The effect of 4 HPR on the apoptotic rate of cyst lining epithelial cells stimulated by HGF was detected with DNA laddering and cell staining with fluorescent dye Hoechst 33342.The expression of HGF and c Myc protein was examined by immunohistochemical staining and semi quantitative analysis in cyst lining epithelial cells stimulated by 4 HPR.Results: Compared with control group,4 HPR inhibited the proliferation of ADPKD cyst lining epithelial cells in a dose and time dependent manner.The most remarkable inhibition effect was observed by 5 or 10 ?mol/L 4 HPR for 96 h ( P

Objective:To study the effects of recombinant human hepatocyte growth factor (rhHGF) on the synthesis of extracellular matrix (ECM) and matrix metalloproteinases and tissue inhibitor of metalloproteinases in autosomal dominant polycystic kidney disease (ADPKD) cyst lining epithelial cells.Methods:The synthesis of laminin (LN) and aminoterminal propeptide of type Ⅲ procollagen (PⅢNP) in ADPKD cyst lining epithelial cells stimulated by rhHGF was examined with radioimmunoassay.The synthesis of type Ⅳ collagen (ColⅣ) was analyzed with ELISA.The mRNA expression of transforming growth factor ? 1 (TGF? 1),matrix metalloproteinases 2 (MMP 2),tissue inhibitor of metalloproteinases 1 (TIMP 1) and TIMP 2 in rhHGF stimulated cyst lining epithelial cells were detected by RT PCR.MMP 2 protein expression was examined with Western blotting and MMP 2 activity was analyzed by gelatin zymography in supernatant of cyst lining epithelial cells stimulated by rhHGF.Results:In rhHGF group and rhHGF+ anti TGF? 1 antibody group,the synthesis of LN and ColⅣ were markedly increased.There was no significant difference in the synthesis of LN and ColⅣ between the 2 groups.Among control group,rhHGF group,rhHGF+ anti HGF antibody group and rhHGF+ anti TGF? 1 antibody group,no significant difference in the synthesis of PⅢNP was found.No significant difference was found in the expression level of TGF? 1 mRNA in cyst lining epithelial cells among control group,rhHGF group and rhHGF+anti HGF antibody group.Compared with control group,MMP 2 mRNA expression in ADPKD cyst lining epithelial cells was significantly increased and TIMP 1 mRNA and TIMP 2 mRNA expression were significantly decreased in rhHGF group.Furthermore,MMP 2 protein expression and MMP 2 activity in supernatant of cyst lining epithelial cells also greatly increased.Conclusion:HGF stimulates the synthesis of LN and ColⅣ.HGF up regulates MMP 2 expression while HGF down regulates TIMP 1 and TIMP 2 expression in ADPKD cyst lining epithelial cells.All these changes may involve in the initiation and progression of ADPKD cysts.

Objective To study the expression of extracellular matrix and polycystin-1 in ADPKD and their relation to cyst formation. Methods The expression of polycystin-1, fibronectin, laminin, type Ⅰ collagen, and type Ⅳ collagen were analysed in the normal kidney, fetal kidney and polycystic renal tissue by using immunohistochemical technique. Results The expression Of fibronectin, laminin, type Ⅰ collagen, and type Ⅳ collagen increased in polycystic renal tissue compared with normal kidney. The basement membrane lining cysts was markedly thickened. Type Ⅰ collagen was detected in the interstitium between cysts. Laminin, fibronectin and type Ⅳ collagen were localized in cyst basement membrane. The expression of polycystin-1 increased in polycystic renal tissue. The expression of extracellular matrix had significant correlation with the expression of polycystin-1. Conclusion The abnormal expressions of extracellular matrix and polycystin-1 exist in ADPKD. Abnormal expression of polycystin-1 may result in the alterations of extracellular matrix that is related to cyst formation.

Objective To explore the autocrine mechanism of hepatocyte growth factor (HGF) and its receptor c-MET distribution in autosomal dominant polycystic kidney disease (ADPKD) cyst-lining epithelial cells. Methods The concentration of HGF was examined with ELISA in ADPKD patients' cystic fluid, serum and cultured media of cyst-lining epithelial cells. The expression of HGF and c-MET mRNA and protein in cyst-lining epithelial cells was detected by RT-PCR, in-situ hybridization, Western blotting, immunohistochemical analysis and computer image analysis. Results The concentration of HGF in ADPKD non-dialyzed patients'cystic fluid was much higher than that in ADPKD patients' serum [(8. 61?0. 07)ng/ml vs (0.26?0.05) ng/ml, P

Objective To investigate the significance of HLA haploidentical peripheral blood stem cell transplantation for the treatment of intestinal form of acute radiation sickness. Methods Patient “A” from Shandong province suffered from a 60 Co radiation accident with a dose of 20-25Gy, and was diagnosed as intestinal form of acute radiation sickness. On the 3rd day after irradiation, total environmental protection (TEP), antibiotics treatment and emergency HLA zygosity with his elder sister were done, and HLA haploidentical peripheral blood stem cell transplantation was performed with a preconditioning regimen of “CTX+ATG+Flu”. The regimen for protecting from GVHD was “CsA/FK506+MMF+CD25+MSC”. Results WBC began to increase on the 17th day after treatment, and WBC recovered to 5.1?109/L on the 19th day, platelet to over 30?109/L, and RCT to normal. Bone marrow image showed hematopoietic recovery of the three cell lineages. Continuously detection of the implantation ratio of donor's cells by STR-PCR, sexual chromosome analysis and HLA zygosity showed stable complete donor-derived chimera. No GVHD was observed. On the 19th days after treatment, chest X-ray films and CT suggested that a mixed bacterial and fungous infection existed in the patient's lungs. The severest skin damage occurred on the 25th day which occupied 14% of whole body surface. The functions of lung, kidney and heart were damaged sequentially. The patient died of multiple organ failure (MOF) 33 days after admission. Conclusion It is the first time to report a successful HLA haploidentical peripheral blood stem cell transplantation for the treatment of intestinal form of acute radiation sickness in China. A successful transplantation might be a key for prolonging the survival period of such a patient.

Objective To report the diagnosis and treatment of an extremely severe bone marrow form of acute radiation sickness complicated with disseminated Trichosporon Asahii in Jining,Shandong province, China.Methods An extremely severe bone marrow form of acute radiation sickness was transfered to our hospital 3 days after the accident on October 24,2004.The patient was performed allogeneic stem cell transplantion from his brother and soon acquired hematogenesis recovery, however, refractory disseminated Trichosporonosis(mainly lung) then occured in the patient.after the hemato-reconstitusion,and gradually aggravate.Result Strong support treatment and high dosage combination of drug therapy were used to combat fungi ,the accumulative dose of Ampghotec (amphotericin B) was 2965mg, the accumulative dose of itraconazole was 4000mg, and the accumulative dose of Caspofungin(concidas) was 3020mg. The refractory disseminated Trichosporon Asahii was once partially controlled, but the radiation injury and infection were still becoming worse even after many kinds of antiinfection drugs, the patient then died of multiple organ failure on d75 after the accident. Conclution The combination of Ampghotec with Caspofungin and Itraconazole in the treatment of disseminated Trichosporon Asahii was effective, no related toxicity occured, which has not been reported before. However, with continuously injury of radiation, we couldn’t cure the Trichosporonosis thoroughly, and the patient finally died of multiple organs failure related with radiation and infection.According to the clinical treatment of the patient, we also acquired the experience that when we resolve the hematogenesis, to promote the immunologic reconstitution and the tissue damage repair, control the whole body radiation damage and infection will be the key point for this kind of patient to survive.

Objective To observe the changes of serum high-sensitivity C-reactive protein (hs-CRP) in 2 patients diagnosed as acute radiation sickness, and to evaluate its clinical significance. Methods Two victims from Shandong province, China were accidentally received a 60 Co irradiation from a dropped 60 Co source in 2004. They were exposed to more than 20Gy (patient A) and 9Gy (patient B) of X-ray irradiation respectively. The patient A was diagnosed as extremely severe bone marrow form of acute radiation sickness (ARS), and patient B was diagnosed as having developed intestinal form of ARS. The two patients successfully got HLA-haploidentical (patient A) and HLA-identical (patient B) peripheral blood stem cell transplantation, and their hematopoiesis recovered, but they cached serious bacterial infection in whole clinical course. Hs-CRP was quantitatively detected by automatically immunoturbidimetric assay. Result The serum level of hs-CRP in the two patients elevated quickly when they suffered from serious bacterial infection, and declined markedly when the infection was controlled effectively. The serum level of hs-CRP also increased slightly when the patients suffered from severe damage on organs or skin function. There existed 3 peak values of hs-CRP level in patient A when kept in the hospital, with a highest value of 188.8mg/L; there existed 4 peak values of hs-CRP level in patient B when kept in the hospital, with the highest value of 377.2mg/L. Conclusion The present results suggested that hs-CRP may be a good indicator to acute radiation sickness complicated with serious bacterial infection, for the hs-CRP levels may fluctuate following the bacterial infection and effectively controlling.

Objective To investigate the effect of over-expressed Cyr61 on the expression of extracellular matrix of human renal tubular epithelial cells(HKC), and explore the role of Cyr61 in the pathogenesis and development of autosomal dominant polycystic kidney disease(ADPKD). Methods Cyr61 gene cDNA was amplified by RT-PCR. A recombinant plasmid pcDNA3.1+ Cyr61 was constructed by cloning Cyr61 gene into pcDNA3.1. HKC cells were transfected with wild-type Cyr61 plasmid vector (pcDNA3.1+Cyr61). Then the fusion of Cyr61 gene and expression of its protein were detected by RT-PCR and Western blot. The mRNA expression of Cyr61, collagen Ⅰ, collagen Ⅳ, and laminin were determined in four groups (the untransfected cells, pcDNA3.1 transfected cells, pcDNA3.1+Cyr61 -transfected cells and cyst-lining epithelial cells) by fluorescence quantum PCR. Results The amount of Cyr61 protein in Cyr61-transfected cells and cyst-lining epithelial cells were much greater than the control. The mRNA expression of Cyr61, collagen Ⅰ, collagen Ⅳ and laminin in Cyr61-transfected cells were all amplified significantly, and the level of collagen Ⅳwas much higher than collagen I(P