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

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

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

Objective To investigate the clinical significance of dynamic change of serum IL‐17A/IL‐23 in131 I treatment of Graves hyperthyroidism by dynamically detecting the serum IL‐23/Th17 axis related factor levels before and after 131 I treatment of Graves hyperthyroidism .Methods 30 untreated inpatients with Graves disease(GD) in our hospital were selected as the T0 group , those treated by 1- ,3- ,6-month 131 I treatment were taken as the group T1 ,T3 and T6 .Contemporeneous 30 individuals under‐going healthy physical examination were selected as the normal control (NC) group .The various groups had no statistical differences in the aspects of the age ,gender and disease course ,and had the comparability (P>0 .05) .Serum concentration of IL‐17A and IL‐23 was measured by the enzyme‐linked immunosorbent assay (ELISA) technique .FT3 ,FT4 and TSH were detected by combing with clinic .Results The levels of serum IL‐17A and IL‐23 before131I treatment were significantly higher than those in the NC group(P<0 .05);with the treatment proceeding ,which at ,1 ,3 ,6 months were gradually decreased ,the differences were statistically signifi‐cant but(P<0 .05);after 6 -month 131 I treatment in the GD patients ,the effects of IL‐17A and IL‐23 double negative in the T6 group were better than those of single negative ,and better than those of double positive ,the differences were statistically (Fisher value=13 .273 ,P<0 .05) .Conclusion Dynamically monitoring the serum IL‐23/Th17 axis related factor levels has the significance for guiding treatment ,judging the curative effect and predicting recurrence .

In this paper, the application of 霤/OS-II, one of the real-time oper ation systems (RTOS), to ECG tele-monitoring system based on mobile communicatio n is introduced. The system is composed of monitoring terminals and a monitoring center. The terminals have functions such as ECG data acquisition and storage, real-time data analysis, keyboard input, LCD display, system monitor and automat ic transmission of abnormal ECG data to the monitoring center through mobile com munication network. Because these functions are not executed simultaneously, mul ti-task management is adopted instead of single task management. In Rabbit2000 m ain controller, 霤/OS-II is applied to multi-task management.

Objective To evaluate the efficacy and safety of holmium laser lithotripsy for ureteral stones. Methods A total of 238 patients with ureteral stones (upper segment, 60 patients; middle segment, 93; lower segment, 85) received the holmium laser lithotripsy under a semi-rigid ureteropyeloscope. Results Stones were successfully fragmented on one session in 97.1% of patients (231/238). The success rate was 91.7% in patients with stones in the upper ureteral segment (55/60) and 98.9% in patients with stones in the!mid-lower ureteral segment (176/178). Five patients with bilateral ureteral stones associated with acute renal failure and anuria returned to normal rapidly. No complications such as perforation or severe trauma were encountered during the operation. The postoperative hospital stay of the 231 patients was 1~2 days (mean, 1.3 days). Follow-up for 0.5~12 months (mean, 4.1 months) revealed a stone-free rate of 98.7% (228/231). No stricture of the ureter was found. Conclusions Holmium: YAG laser lithotripsy is effective, mini-invasive and safe. It is indicated as the first choice in the treatment of ureteral stones, especially stones located in the mid-lower ureteral segment.

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

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