Human protein tyrosine kinases play an essential role in carcinogenesis and have been recognized as promising drug targets. By the end of 2012, eight small molecule tyrosine kinase inhibitors (TKIs) have been approved by State Food and Drug Administration of China for cancer treatment. In this paper, the pharmacokinetic characteristics (absorption, distribution, metabolism and excretion) and drug-drug interactions of the approved TKIs are reviewed. Overall, these TKIs reach their peak plasma concentrations relatively fast; are extensively distributed and highly protein bound (> 90%); are primarily metabolized by CYP3A4; most are heavily influenced by CYP3A4 inhibitors or inducers except for sorafenib; are mainly excreted with feces and only a minor fraction is eliminated with the urine; and are substrate of the efflux transporters ABCB1 (P-gp) and ABCG2 (BCRP). Additionally, many of the TKIs can inhibit some CYP450 enzymes, UGT enzymes, and transporters. Gefitinib, erlotinib, dasatinib, and sunitinib are metabolized to form reactive metabolites capable of covalently binding to biomolecules.

Objective To observe the clinical efficacy of rigid gaspermeable contact lens (RGPCL) for correcting keratoconus and analyze the predictors for the base curve of RGPCL.Methods Data of 86 patients (143 eyes) with keratoconus fitted with RGPCL were retrospectively analyzed.All eyes were divided into the mild (n =18 eyes),moderate (n =73 eyes),advanced (n =34 eyes) and severe group (n =18 eyes).After evaluating the lens fitting,best corrected visual acuity of eyes wearing spectacle lenses and RGPCL among the 4 groups was statistically compared.And the correlation between the fitting guidance index and HL-K RGPCL base curve in each group was analyzed according to keratometry.Results All patients wearing RGPCL gained significantly better corrected vision in the mild (t =-3.336,P =0.004),moderate (t =-11.213,P ＜0.001),advanced (t =-13.959,P ＜0.001) and severe groups(t =-11.047,P ＜0.001) than those with spectacles.Equivalent spherical degree of spectacle lenses was lower than the diopter of HL-K RGPCL in the moderate (P =0.043) and severe group (P =0.006).The mean base curve of RGPCL was (50.52 ±5.64) diopter,and it was correlated with corneal curvature parameters.In mild group,the RGPCL base curve was correlated with the steep keratometry (P ＜ 0.001).The average K and relative steep K of 0.2 mm (Rm-0.2) were highly correlated with RGPCL base curve in moderate group (r =0.798,P ＜ 0.001;r =0.798,P ＜ 0.001),in advanced group (r =0.745,P ＜ 0.001;r =0.745,P ＜ 0.001) and in severe group (r =0.616,P =0.007;r =0.617,P =0.006).Conclusion Patients with keratoconus wearing HL-K RGPCL can obtain ideal corrected vision.Determination of RGPCL base curve by adjusting the corresponding indicators is conducive to improving the long-term wearing safety of the lens and enhancing the efficiency of lens fitting.

Obiective: To compare the tissue biocompatibility of domestically manufactured NiTi alloy before and after thermal surface oxidation under 3 different temperatures. Methods: Domestically manufactured NiTi alloy was oxidized in air (group A) and subjected to 30 min heat treatment at 400°C (group B),500°C, (group C),and 600°C (group D) to form different protective oxide surface layers in presence of argon (607.95 kPa). Wire samples from A, B, C and D groups were subcutaneously implanted in guinea pigs. Guinea pigs received 317L stainless steel transplantation(group E) and sham-operation group (F) were taken as control. The order of inflammatory cell infiltration and tissue hyperplasia around implanted materials were observed 1, 2, 4, and 8 weeks after implantation. Results: The peak time of inflammatory cell infiltration and fibrous hyperplasia were at the first and fourth week after implantation. The inflammatory cell infiltration and fibrous hyperplasia were both slight and all met the GB/T 16886. 6-1997 in vivo implantation standard. The order of inflammatory cell infiltration and thickness of capsule walls from low to high was F

Blood Pressure ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Hypertension ; drug therapy ; Inflammation

Actins ; metabolism ; Adult ; Carcinosarcoma ; diagnostic imaging ; metabolism ; pathology ; surgery ; Hepatectomy ; methods ; Humans ; Liver Neoplasms ; diagnostic imaging ; metabolism ; pathology ; surgery ; Male ; Tomography, X-Ray Computed ; Vimentin ; metabolism

Heart Valve Diseases ; therapy ; Heart Valve Prosthesis Implantation ; methods ; Humans

Adenoma, Pleomorphic ; Adult ; Female ; Humans ; Nose Neoplasms

Animals ; Atherosclerosis ; prevention & control ; Biflavonoids ; pharmacology ; Catechin ; pharmacology ; Grape Seed Extract ; pharmacology ; Humans ; Proanthocyanidins ; pharmacology

The hypothesis that tumor comes from stem cells has been demonstrated in various human tumors.Cancer is not only a genetic disease but also a stem cell disease. It is a key to regeneration, mutations and recurrence of tumors that gene mutations affect stem cells, and then stem cells mutate to cancer stem cells. In an effort to review the evidence that liver cancer stem cells exist, two fundamental questions must be addressed. First, do hepatocellular carcinomas(HCC)arise from liver stem cells? Second, do HCCs contain cells that possess properties of cancer stem cells?More recently, there is a hypothesis that HCC arise from maturation arrest of liver stem cells. Analysis of the cells in HCC supports the presence of cells with stem-cell properties(ie, immortality, transplantability, and resistance to therapy). However, definitive markers for these putative cancer stem cells have not yet been found and a liver cancer stem cell has not been isolated.

Objective To evaluate the effect of a bioartificial liver (BAL) system for treatment of acute liver failure (ALF) in canines and its relationship to serum endotoxin. Methods ALF was induced by end-side portocaval shunt combined with common bile duct ligation and transection. Ten ALF canines were distributed to BAL group (n=5), or to a control group (n=5). Each BAL circulation lasted 5h. Serum endotoxin, alanine aminotransferase (ALT) and total bilirubin (TB) before establishment of ALF model, pre-circulation and post-circulation were determined. Results Serum endotoxin level was 0.284 EU/ml, 0.526 EU/ml and 0.416 EU/ml before establishment of ALF model, and pre-circulation and post-circulation in BAL group, respectively. The serum endotoxin level in BAL group increased pre-circulation (P