Collagen Type IV ; genetics ; Female ; Fetal Development ; Humans ; Nephritis, Hereditary ; diagnosis ; genetics ; Pregnancy ; Prenatal Diagnosis ; methods

Humans ; Molecular Biology ; Nephrotic Syndrome ; genetics

Background and purpose:TGF-?/EGFR autocrine loop is markedly activated in wide malignant tumor. It is closely correlated with the tumorigenesis and development of different cancers. Our study is to investigate the biological behavior and signaling molecule changes in TGF- induced ovarian cancer cell line Caov-3, and to study the effect and molecular mechanism of the activation of TGF- /EGFR autocrine loop in ovarian cancer.Methods:The tetrazolium-based colorimetry assay was used to evaluate the cell growth treated by TGF-?. The vitro invasion assay was used to examine the invasiveness of Caov-3 treated by TGF-?.Expression of EGFR、 ERK1/2、PI3K、AKT、P70S6K were determined by western blotting.Results:Exogenous TGF-? enhanced significantly the proliferation and invasiveness of Caov-3 cells. The proliferation rate of Caov-3 was in a dose-dependent manner to TGF-? within the concentration of 0.5~25ng/ml.Exogenous TGF-? up-regulated the expression of EGFR、PI3K、AKT、P70S6K but not ERK1/2.Conclusions:The activation of TGF-?/EGFR autocrine loop could promote the growth,invasion and metastasis of ovarian cancer through PI3K/AKT/P70S6K signaling survival pathway.

Objective To explore the correlation between phenotypes in female with X-linked Alport syndrome(XLAS) and X-inactivation of different tissues.Methods Thirty-six female diagnosed as XLAS were studied,and proteinuria was taken as a marker of the severity of clinical phenotypes.X-inactivation patterns were analyzed in peripheral blood cells of 36 XLAS female and in skin fibroblasts of 12 XLAS female.The X-inactivation analysis was performed by using Hpa Ⅱ predigestion of DNA followed by polymerase chain reaction(PCR) of the highly polymorphic CAG repeat of the androgen receptor gene.Results The average X-inactivation levels of the mutant allele decreased while the degree of proteinuria increased,so there was a negative correlation between the degree of proteinuria and the X-inactivation ratios of the mutant allele in blood cells(r=-0.543,P=0.002).However,there was no correlation between the degree of proteinuria and the X-inactivation ratios of the mutant allele in skin fibroblasts(r=-0.131,P=0.701).Conclusions X-inactivation ratios might explain partially the diverse phenotypes in XLAS female patients,which suggested that the prognosis of XLAS female might be predicted via analysis of the X-inactivation in peripheral blood cells.

Deflazacort (DFZ, a prodrug) is well absorbed and rapidly metabolized into the active metabolite 21-hydroxydeflazacort (21-OH DFZ) after oral administration. The aim of this study is to evaluate the pharmacokinetic properties of 21-OH DFZ in healthy Chinese volunteers after a single and multiple oral administration of DFZ tablets under fed condition. Twelve volunteers (six males and six females) were administered a single dose of 6 mg or 12 mg or 24 mg of DFZ in three different periods separately, according to the 3 x 3 Latin square design. Between each administration period there was a washout period of one week. The multiple-dose study of 12 mg dose DFZ per day for 7 consecutive days was started after a 1 w washout period when the single-dose study completed. The pharmacokinetic parameters of 21-OH DFZ after the single oral administration of 6 mg, 12 mg and 24 mg DFZ tablets were as follows: (37.7 +/- 11.6), (61.5 +/- 17.7) and (123 +/- 23) ng x mL(-1) for C(max); (1.90 +/- 0.32), (1.96 +/- 0.27) and (2.13 +/- 0.34) h for t1/2; (96.6 +/- 25.9), (190 +/- 44) and (422 +/- 107) ng x h x mL(-1) for AUC(0-14 h), respectively. After the multiple dose administration, the mean plasma concentration at steady-state C(av) was (7.00 +/- 1.66) ng x mL(-1) and the degree of plasma concentration fluctuation DF was 7.7 +/- 1.2. The results showed that the pharmacokinetic characteristics of 21-OH DFZ in healthy Chinese volunteers were linear over the dose range of 6 to 24 mg. No significant gender differences were found in the pharmacokinetics of 21-OH DFZ in healthy Chinese volunteers. After the multiple dose administration of 12 mg DFZ for 7 d, no accumulation of 21-OH DFZ in healthy Chinese volunteers was observed.

Deflazacort (DFZ, a prodrug) is well absorbed and rapidly metabolized into the active metabolite 21-hydroxydeflazacort (21-OH DFZ) after oral administration. The aim of this study is to evaluate the pharmacokinetic properties of 21-OH DFZ in healthy Chinese volunteers after a single and multiple oral administration of DFZ tablets under fed condition. Twelve volunteers (six males and six females) were administered a single dose of 6 mg or 12 mg or 24 mg of DFZ in three different periods separately, according to the 3 x 3 Latin square design. Between each administration period there was a washout period of one week. The multiple-dose study of 12 mg dose DFZ per day for 7 consecutive days was started after a 1 w washout period when the single-dose study completed. The pharmacokinetic parameters of 21-OH DFZ after the single oral administration of 6 mg, 12 mg and 24 mg DFZ tablets were as follows: (37.7 +/- 11.6), (61.5 +/- 17.7) and (123 +/- 23) ng x mL(-1) for C(max); (1.90 +/- 0.32), (1.96 +/- 0.27) and (2.13 +/- 0.34) h for t1/2; (96.6 +/- 25.9), (190 +/- 44) and (422 +/- 107) ng x h x mL(-1) for AUC(0-14 h), respectively. After the multiple dose administration, the mean plasma concentration at steady-state C(av) was (7.00 +/- 1.66) ng x mL(-1) and the degree of plasma concentration fluctuation DF was 7.7 +/- 1.2. The results showed that the pharmacokinetic characteristics of 21-OH DFZ in healthy Chinese volunteers were linear over the dose range of 6 to 24 mg. No significant gender differences were found in the pharmacokinetics of 21-OH DFZ in healthy Chinese volunteers. After the multiple dose administration of 12 mg DFZ for 7 d, no accumulation of 21-OH DFZ in healthy Chinese volunteers was observed.
Administration, Oral ; Area Under Curve ; Asian Continental Ancestry Group ; Female ; Healthy Volunteers ; Humans ; Male ; Pregnenediones ; pharmacokinetics ; Tablets

Objective To investigate the viability of analysis of hemodynamic changes with color Doppler flow imaging in the prediction of acute rejection in transplanted liver.Methods Sixty-eight patients enrolled in the study were categorized into three groups:transplanted liver without acute rejection [rejection activity index(RAI) 0-3,n =24],transplanted liver with mild acute rejection (RAI 4-5,n =23),transplanted liver with moderate and severe acute rejection (RAI 6-9,n =21).All the patients were confirmed by pathology.The color Doppler flow imaging were performed in all the patients within 24 hours and 1 week after biopsy.Results In transplanted liver with moderate and severe acute rejection,the peak systolic velocity of portal vein (PV-PSV) was (31.4 ± 14.1)cm/s,significantly lower than that in transplanted liver without acute rejection,which was (45.1 ± 17.7)cm/s (P ＜0.05).A week later after steroid therapy,the PV-PSV in transplanted liver with moderate and severe rejection was increased to (46.7 ± 21.8)cm/s(P ＜0.05).Patients with acute rejection were associated with the decrease of the PVPSV (P ＜0.05).Conclusions The decrease of PV-PSV may have some clinical value in evaluation the acute rejection in transplanted liver.

Objective To explore the diagnostic value of virtual touch tissue quantification (VTQ) for the assessment of liver fibrosis in patients with chronic hepatitis B.Methods VTQ was prospectively performed in 181 patients with chronic hepatitis B and a shear wave velocity (Vs) indirectly reflecting liver stiffness was obtained for each patient.With the gold standards of fibrotic stages and inflammation grades,the relationship between Vs,fibrotic stages and inflammation grades was evaluated.Results A relatively high correlation existed between Vs and liver fibrotic stages (r ＝ 0.812,P ＜ 0.001).Significant differences existed among groups with different fibrotic stages except for groups SO vs.S1 and S1 vs.S2 (P ＜ 0.05).The areas under the ROC curve were 0.971,0.96l,0.969 and 0.908 for Vs predicting S≥S1,S≥S2,S≥S3 and S =S4 fibrosis respectively.Moderate correlation existed between Vs and inflammation grades (r =0.476,P =0.000).Conclusion Capable of staging liver fibrosis and preliminarily grading inflammation,VTQ is helpful for the early diagnosis of liver fibrosis and assessment of therapeutic follow-up and prognosis in patients with chronic hepatitis B.

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.

Objective To evaluate the feasibility of virtual touch tissues quantification (VTQ) technique in the assessment of liver fibrosis and to find the suitable measuring position of VTQ. Methods Liver stiffness was measured with Acuson S2000 ultrasound system in totally 533 subjects including healthy people ( n = 302), patients with hepatitis B virus(HBV) ( n = 191) and patients with fatty liver ( n =40). Each subject received VTQ measurements in four parts (superficial and deep parts of right lobe, and superficial and deep parts of left lobe) and every part was measured five times to get five values. The reproducibility of different part of VTQ was analyzed with intraclass correlation coefficient (ICC). Results The achievement rate was high in both right and left lobes,especially in right lobe. The lowest rate was from the deep part of left lobe. Except deep part of left hepatic lobe in fatty liver,all parts of liver in all groups of patients were with ICC higher than 0. 75. In deep part of right lobe, VTQ values were (1.12 ± 0. 19)m/s in control group subjects, (1.83 ± 0. 62)m/s in patients with hepatitis B virus and (1.05 ± 0. 25)m/s in patients with fatty liver. There was significant difference of VTQ value between control group and patients with HBV ( P = 0.000), also between patients with HBV and patients with fatty liver ( P = 0.000). Conclusions It is stable to measure liver stiffness with VTQ technique, which is a new method to evaluate liver stiffness noninvasively. Right hepatic lobe is the most suitable position to be measured.