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.

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.

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.

The disease risk prediction model is the basis of precision prevention and an essential reference for clinical treatment decisions. The development of risk prediction models requires the support of a large amount of high-quality data. A large population cohort study is an important basis for this study. The United Kingdom Biobank (UKB), as a mega-population cohort and biobank, has played an essential role in the exploration of disease etiology and research related to disease prevention and control, with its rich baseline and follow-up data and concepts and mechanisms shared globally. This study followed PRISMA guidelines and included 210 articles with corresponding authors from 18 countries, of which 58 (27.62%) were from the UKB. A total of 491 disease risk prediction models were extracted for cancer, cardiovascular and cerebrovascular diseases, endocrine and metabolic diseases, respiratory diseases, and other diseases and their subgroups, of which 132 were developed by UKB without validation, 183 were developed by UKB with internal validation, 17 were developed by UKB with external validation, and 159 were developed by external development with UKB validation. A total of 188 models used only macro variables (38.29%), and 303 models combined macro and micro variables (61.71%). Model construction methods included survival outcome models, logistic regression, and machine learning. Survival outcome models were dominated by Cox proportional risk regression models and a few models considering competitive risk, accelerated failure models, or different baseline risk functions. Machine learning models included random forest, XGBoost, CatBoost, support vector machine, convolutional neural network, and other methods. The UKB is an essential resource for multiple disease risk prediction modeling studies.

Objective:To explore the consistency of peripheral whole blood and venous serum procalcitonin (PCT) levels, and the value of peripheral whole blood PCT in evaluating pediatric bacterial infection.Methods:This multicenter cross-sectional parallel control study was conducted in 11 children′s hospital. All the 1 898 patients older than 28 days admitted to these hospitals from March 2018 to February 2019 had their peripheral whole blood and venous serum PCT detected simultaneously with unified equipment, reagent and method. According to the venous serum PCT level, the patients were stratified to subgroups. Analysis of variance and chi-square test were used to compare the demographic characteristics among groups. And the correlation between the peripheral blood and venous serum PCT level was investigated by quantitative Pearson correlation analysis.The PCT resultes were also converted into ranked data to further test the consistency between the two sampling methods by Spearman′s rank correlation test. Furthermore, the ranked data were converted into binary data to evaluate the consistency and investigate the best cut-off of peripheral blood PCT level in predicting bacterial infection.Results:A total of 1 898 valid samples were included (1 098 males, 800 females),age 27.4(12.2,56.7) months. There was a good correlation between PCT values of peripheral whole blood and venous serum ( r=0.97 , P<0.01). The linear regression equation was PCT?venous serum=0.135+0.929×PCT peripheral whole blood. However, when stratified to 5 levels, PCT results showed diverse and unsatisfied consistency between the two sampling methods ( r=0.51-0.92, all P<0.01). But after PCT was converted to ordinal categorical variables, the stratified analysis showed that the coincidence rate of the measured values by the two sampling methods in each boundary area was 84.9%-97.1%. The dichotomous variables also showed a good consistency (coincidence rate 96.8%-99.3%, Youden index 0.82-0.89). According to the severity of disease, the serum PCT value was classified into 4 intervals（<0.5、0.5-<2.0、2.0-<10.0、≥10.0 μg/L）, and the peripheral blood PCT value also showed a good predictive value (AUC value was 0.991 2-0.997 9). The optimal cut points of peripheral whole blood PCT value 0.5、1.0、2.0、10.0 μg/L corresponding to venous serum PCT values were 0.395, 0.595, 1.175 and 3.545 μg/L, respectively. Conclusions:There is a good correlation between peripheral whole blood PCT value and the venous serum PCT value, which means that the peripheral whole blood PCT could facilitate the identification of infection and clinical severity. Besides, the sampling of peripheral whole blood is simple and easy to repeat.