Dysfunction in tyrosine kinase activity disrupts the nor-mal control of cellular phosphorylation signaling pathways,which plays a vital role in genesis and development of various tumors, and makes tyrosine kinases a class of targets of many anti-tumor drugs. Currently most approved tyrosine kinase inhibitors ( TKIs) are based on irreversible binding mechanisms, making them poorly selective, not potent or sustained enough regarding pharmacological effects and prone to triggering resistance. In the past decade, much progress has been made in the development of
a new class of TKIs which irreversibly inhibit their target proteins via the formation of covalent bonds, overcoming the drawbacks of irreversible TKIs. Several irreversible TKIs have entered markets or clinical research phases. This review is to summarize the structural, pharmacological and medicinal chemical properties of investigational and marketed irreversible TKIs as well as their re-cent developments.

Monoclonal antibody ( mAb ) represents a class of therapeutics experienced dramatic development over the past 30 years. Because of the tremendous differences in physicochemical and biological properties between mAbs and small molecules, the mAb therapeutics significantly differ from the chemical drugs in pharmacokinetic characteristics and underlying mechanisms. Full understanding of those characteristics and mechanisms may efficiently guide the screening and development of mAb medi-cines, and would well support their safety evaluation and clinical dosage regimen designing. This review is to summarize pharma-cokinetics and underlying mechanisms of mAbs from the aspects of absorption, distribution and elimination, as well as the ap-proaches for prediction of mAb pharmacokinetics in humans.

Objective To investigate the role of the percentage of the total cross-sectional area of small pulmonary vessels for the lung area (%CSA) from multi-slice CT (MSCT) in evaluating the severity of chronic obstructive pulmonary disease (COPD). Methods One hundred and sixty-six COPD patients and 166 normal subjects underwent chest MSCT scans and all data were analyzed retrospectively. COPD patients underwent pulmonary function tests (PFT), including forced expiratory volume in one second (FEV1%) and FEV1/forced vital capacity (FEV1/FVC), and were classified into mild (n=32), moderate (n=65), severe (n=69) groups according to pulmonary function results, respectively. The%CSA less than 5 mm2 and 5—10 mm2 for the lung area (%CSA<5 and %CSA5-10) of small pulmonary vessels were measured with Image J image-processing program. Comparison of%CSA<5 and%CSA5-10 between the COPD and control groups was perfomred using t test, and the comparison between the 3 COPD subgroups and control group were carried out using ANOVA test. The correlation between %CSA and PFT was evaluated by the Spearman rank correlation test. The sensitivity and specificity of %CSA to diagnose COPD and the best cutoff were calculated from areas under the ROC curves. Results %CSA<5 of COPD patients and control group were (0.56 ± 0.19)%and (0.82 ± 0.15)%(t=12.80, P<0.001), respectively.%CSA5-10 of the two groups were (0.19 ± 0.09)%and (0.33 ± 0.16)%(t=8.93,P<0.001), respectively. The AUC values of%CSA<5 and%CSA5-10 were 0.866 and 0.790, respectively. When the cut-off values of%CSA<5 and%CSA5-10 were 0.65%and 0.24%, the sensitivities and specificities were 88%and 71%, 76%and 81%, respectively. The mean values of%CSA<5 in mild, moderate and severe groups were (0.67±0.20)%, (0.61±0.16)%and (0.44±0.14)%, respectively (P<0.05). The mean values of %CSA5-10 in the three groups were (0.19 ± 0.06)%, (0.19 ± 0.10)% and (0.20 ± 0.08)%, respectively.%CSA5-10 in the three groups were of no significant difference (P>0.05). FEV1%and FEV1/FVC in COPD patients were (60.38±15.52)%and 57.95±22.27.%CSA<5 in COPD patients correlated positively with both FEV1%and FEV1/FVC (r=0.609 and 0.721, P<0.01, respectively).%CSA5-10 in COPD patients correlated positively with both FEV1%and FEV1/FVC (r=0.271 and 0.288, P<0.01, respectively). Conclusion The measurement of%CSA<5 and%CSA5-10 in MSCT images correlated with PFTs and%CSA<5, which may play an important role in evaluating the severity of COPD.

Antibody-drug conjugate (ADC) is a new class of therapeutics composed of a monoclonal antibody and small cytotoxin moieties conjugated through a chemical linker. ADC molecules bind to the target antigens expressed on the tumor cell surfaces guided by the monoclonal antibody component. The binding ADC molecules can be internalized and subsequently the toxin moieties can be released within the tumor cells via chemical and/or enzymatic reactions to kill the target cells. The conjugation combines the merits of both components, i.e., the high target specificity of the monoclonal antibody and the highly potent cell killing activity of the cytotoxin moieties. However, such complexities make the pharmacokinetic and metabolic studies of ADCs highly challenging. The major challenges should include characterization of absorption, distribution, metabolism and excretion, investigation of underlying mechanisms, assessment of pharmacokinetic- pharmacodynamic relationship, and analytical method development of ADC drugs. This review will discuss common pharmacokinetic issues and considerations, as well as tools and strategies that can be utilized to characterize the pharmacokinetic and metabolic properties of ADCs.

Objective To investigate the hepatic hemodynamic characteristics of cirrhotic patients with splenectomy using iodine map of dual-source computed tomography(DSCT).Methods Twenty-four cirrhotic patients with splenectomy were selected as a study group,41 cirrhotic patients without splenectomy as a cirrhosis group and other 32 patients with normal liver as a control group.The iodine concentration(IC)in hepatic arterial and venous phases was measured on the iodine map,and the arterial iodine fraction(AIF)and portal venous iodine concentration(PVIC)were calculated.Receiver operating characteristic(ROC)curves were plotted and the area under the curve(AUC)was recorded to evaluate the diagnostic efficacy of each parameter using the DeLong test.Results IC in arterial phase and AIF were significantly higher,and IC in venous phase and PVIC were significantly lower in study group(P<0.05).The AUC values of the four parameters between study group and cirrhosis group were 0.735,0.992,0.943,and 0.994,respectively.Conclusion DSCT iodine map is helpful for clinical quantitative assessment of hepatic hemodynamic characteristics in cirrhotic patients with splenectomy,and the PVIC has optimal independent diagnostic performance.