As a mature tool for estimating tissue dosimetry,physiologically based pharmacokinetic (PBPK) models are being used to simulate the process from an external chemical exposure to an internal exposure at a target site,for supporting quantitative predictions of risks to human health. This paper reviewed these models from three aspects: the general steps of model construction,the criteria of model evaluation,the use of model in risk assessment and taking xylene as an example particularly described the third aspect.

Objective To investigate the effect of propofol on human renal tubule epithelial cell (HK-2 cells) fibrosis induced by ATP depletion/recovery and the role of transforming growth factor β activated kinase 1 (TAK1) in it.Methods HK-2 cells were seeded in 96-well plates,and randomly divided into 4 groups (n =36 each) using a random number table:control group (group C),ATP depletion/recovery group (group D/R),propofol group (group P),and TAK1 over-expression group (group T).HK-2 cells were exposed to antimycin A for 1 h and then returned to normal culture medium to establish the model of ATP depletion/recovery-induced injury.At 1 h before ATP depletion,the cells were incubated for 1 h in the DMEM liquid culture medium containing propofol with the final concentration of 20 μmol/L in group P,and the cells were incubated for 1 h in the DMEM liquid culture medium containing propofol with the final concentration of 20 μmol/L and TAK1 with the titer of 2× 107 TU/ml in group T,and the other treatments were similar to those previously described in group D/R.At 12 h after ATP recovery,the cell viability was evaluated by methyl thiazolyl tetrazolium assay,and cell apoptosis was detected using TUNEL and scored.The expression of TAK1 was detected using Western blot at 12,24 and 48 h after ATP recovery.The expression of α-smooth muscle actin (αSMA),fibronectin (FN),and collagen protein 1 (COL1) was measured at 48 h after ATP recovery.Results Compared with group C,the cell viability was significantly decreased,the apoptosis score was increased,and the expression of TAK1,COL1,αSMA and FN was up-regulated after ATP recovery in D/R,P and T groups (P＜0.05).Compared with group D/R,the cell viability was significantly increased,the apoptosis score was decreased,and the expression of TAK1,COL1,αSMA and FN was down-regulated after ATP recovery in P and T groups (P＜0.05).Compared with group P,the cell viability was significantly decreased,the apoptosis score was increased,and the expression of TAK1,COL1,αSMA and FN was up-regulated after ATP recovery in group T (P＜ 0.05).Conclusion Propofol can reduce HK-2 cell fibrosis induced by ATP depletion/recovery,and the mechanism may be related to down-regulation of TAK1 expression.

Physical ablation is a new kind of tumor treatment which directly acts on local solid tumors to eradicate or destroy tumor tissues by use of various advanced physical techniques. Physical ablation can be classified by physical characteristics as thermal ablate therapy (TAT), cryoablation and electrical ablation. Recent studies and technical trend of these three physical ablation treatments are reviewed in this paper.
Animals ; Catheter Ablation ; methods ; Cryosurgery ; Humans ; Hyperthermia, Induced ; Neoplasms ; surgery ; therapy ; Salvage Therapy

Objective To investigate the effects of sevoflurane on HIF-1α/epithelial mesenchymal transition (EMT)pathway activity and invasion of lung cancer in rats undergoing one lung ventilation (OLV). Methods Lung cancer model of SD rats was established. Rats were randomly divided into 4 groups:group control(group C), group two lungs ventilation(TLV)(group T),group one lungs ventilation(group O),and group sevoflurane +one lungs ventilation(group SO). Two lung ventilation was performed after endotracheal intubation for 2.5 h in group T. OLV was performed after endotracheal intubation for 2 h in group O and SO. The end-expiratory concentration of sevoflurane of rats in group SO was maintained 2.6% during OLV period. Left lung cancer tissues were harvested at 0.5 h of TLV. The protein levels of HIF-1α,Vimentin and Fibronectin in lung cancer were determined by Western blot. The mRNA levels of MMP-2 and MMP-9 in lung cancer were evaluated by RT-PCR. Results The expres-sions of HIF-1α,Vimentin,Fibronectin,MMP-2,and MMP-9 in group O and group SO were significantly higher than those in group C and group T(P<0.05). The expressions of HIF-1α,Vimentin,Fibronectin,MMP-2,and MMP-9 were decreased significantly in group SO as compared with group O(P<0.05). Conclusion Sevoflurane inhibits the elevation of HIF-1α/EMT pathway activity and invasion ability induced by OLV.

Objective To observe the effect of intrathecal injection of TRESK overexpression adenoviruson phosphorylation of JNK and apoptosis of neurons in neuropathic pain rats.Methods Seventy-two male SD rats were randomly divided into six groups:groups C,S,NP,T,V,and NS,12 for each group.SNI was administrated to rats in groups NP,T,V and NS.TRESK adenovirus and negative virus were intrathecally injected after use of SNI in groups T and V,while equal volume of NS was injected to rats in group NS.MWT and TWL were measured at 1 day before operation(baseline,BL)and at 1,3,7 and 14 days after operation (days 1,3,7,and 14).Six rats in each group were sacrificed at D7 to determinate the expression of TRESK protein of DRG.The other rats were sacrificed at D14 to determinate neural apoptosis and the expressions of caspase3 and p-JNK of DRG.Results As compared with groups C,S and T,the expression of TRESK protein was significantly decreased at D7 in groups NP,NS and V (P＜0.05).Compared with groups C and S,MWT was significantly decreased at days 1,3,7 and 14 (P＜0.05),phosphorylation of JNK in DRG was significantly increased at D14 (P＜0.05),neuronal apoptosis rate and expressions of Caspase3 of DRG were significantly increased at D14 (P＜0.05) in groups NP,T,NS and V.Compared with groups NP,V and NS,MWT was significantly increased at time points of days 1,3,7 and 14 in group T (P＜0.05),phosphorylation of JNK of in DRG was significantly decreased at D14 in group T (P＜0.05),neuronal apoptosis rate and expression of Caspase3 of DRG were significantly decreased at D14 in group T (P＜0.05).Intrathecal injection ofpAd/CMV/VS-DEST-TRESK obviously reduced mechanical hyperalgesia,upregulated TRESK expression,and lowered JNK phosphorylation and NP in SNI rat.Conclusions Intrathecal injection of TRESK over expression adenovirus relieves NP via inhibiting JNK activation and neuronal apoptosis.