The traditional approaches of pharmacokinetics (PK) focused on the dynamic changing process of single or several effective components of drugs in vivo,which was noted as limitations for the complexity studies on PK of multicomponent herbal medicine featuring multi-component,multi-target and multi-effect.It was turned into a bottleneck in the modernization process of traditional Chinese medicine,which could have made misunderstanding of pharmacological and toxicological knowledge of Chinese herbal medicine and its combination drugs.Owing to the advanced high-throughput platforms and various big data mining technology,metabolomics was capable for simultaneously detecting and depicting the variations of hundreds or even thousands of small molecules offering new opportunities for the PK studies on some complicated components.This review summarized recent PK studies over multicomponent drugs and chiefly introduced two remarkable applications to metabolomics in pharmacokinetics research,Chinmedomics and Poly-PK,integrating the theories of both metabolomics and traditional PK.The challenges and strengths of the two new strategies were also expounded.

AIM:To study the effect of Hand2 (one of basic helix-loop-helix proteins’ transcription factors) expression on the development of the cardiac tissues in the fetal rats from gestational diabetes mellitus ( GDM) parents, and to investigate the potential pathogenesis of GDM-induced congenital cardiac defects in rats.METHODS: The adult Spra-gue-Dawley female rats were randomly divided into blank control group (n=24), GDM group (n=30), negative control group ( n=30) and insulin intervened group ( n=30) .The GDM model was established by intraperitoneal injection of 2%streptozotocin (STZ, 40 mg/kg body weight) to the pregnant rats on the successive day.The rats in insulin intervened group were injected with intermediate-acting insulin in order to keep the fasting blood glucose in the normal range.The rats in negative control group were injected with citric acid-sodium citrate buffer solution in the same position.Blood glucose and body weight were examined every day 72 h after STZ injection.On E12, E15 and E19, the rats were anesthetized and the embryonic cardiac tissues were collected after caesarean section.The histopathological changes of the cardiac tissues were observed under microscope with HE staining.The expression of Hand2 was analyzed by the method of immunohisto-chemistry.The expression of Hand2 in the cardiac tissues at mRNA and protein levels was determined by real-time fluores-cence quantitative PCR and Western blotting.RESULTS:During the development of embryonic heart, the protein expres-sion of Hand2 in the cardiac tissues was showed dynamic changes.Observed on E12, obviously increased on E15, and at the highest level on E19.Compared with the other 3 groups, the protein and mRNA expression of Hand2 in GDM group was decreased at the time points of E12 and E15.CONCLUSION:The morbidity of fetal cardiac malformation is significantly increased in GDM group, suggesting that Hand2 may be involved in the development of cardiac malformation in GDM.

Objective To express and purify the human scFv antibody,SA3,against the hepatoma fused to enhanced green fluorecsent protein,and to observe the targeted capacity of fusion protein EGFP-SA3 in vivo.Methods SA3 and EGFP genes were cloned into plasmid pET-25b( + )to construct the recombinant plasmid EGFP-SA3/pET-25b ( + ),followed by DNA sequencing.Then it was transformed into E.coli BL21 ( DE3 ) and induced for fusion expression of EGFP-SA3with IPTG.The expressed fusion protein EGFP-SA3 was purified and detected with SDS-PAGE.HepG2 cells were incubated with the fusion protein EGFP-SA3 in vitro,and the binding bioactivity was observed under the fluorecsent microscope.Further more,we injected the EGFP-SA3 by caudal vein into nude mice planted by hepatoma and observed the whole body fluorescence image of EGFP.Results SA3 and EGFP genes were successfully cloned into pET-25b( + ),which was confirmed by restriction enzyme Nco I-Xho I or Nco I-Eco RI.A band migrated at the position 750 bp,same to EGFP gene,emerged when recombinant plasmid was digested by restriction enzyme Nco I-Eco RI.Similarly,a band,about 1 500 bp,emerged when digested by Nco I-Xho I.The open-reading frame was confirmed by DNA sequencing.Fusion protein EGFP-SA3 was expressed as inclusion body.After purification and refolding,the result of immunofluorecsence detection verified that EGFP-SA3could specifically bind to HepG2 cells and maximum tumor penetration was at 24 h after the injection.Conclusion The purified fusion protein EGFP-SA3 has strong binding capacity to HepG2cells,indicating the scFv SA3 has a potential value as a targeting molecule for diagnosis and targeted therapy for liver cancer.

Cancer-related fatigue (CRF) belongs to the category of "consumptive disease" in TCM, and its occurrence is based on "internal deficiency" of the body causing by the tumor. Its nature is intermingled deficiency and excess. Its pathogenesis is the deficiency of qi, blood, yin and yang and zang-fu viscera dysfunction caused by disorders of "rise and fall of middle qi" and kidney origin depletion. The theory of "treating overstrain syndrome with warming methods" originates from Huang Di Nei Jing, which proposes that warming methods are the basic methods of treating consumptive disease. Therefore, starting from the cause and pathogenesis of CRF, this article sorted out the theoretical origin of "treating overstrain syndrome with warming methods", and discussed the clinical application of warming methods for the treatment of CRF combining with modern clinical research, with the purpose to provide references for clinical practice.

Objective:To construct a prediction model of inadvertent perioperative hypothermia in patients under general anesthesia , and to apply to clinic to verify its performance.Methods:The data of 19 068 surgical patients in a Grade Ⅲ Class A hospital in Zhejiang Province from January 2016 to September 2020 were included. The model was constructed by using artificial intelligence technology based on deep learning, and the prediction effect of the model was tested by using the area under the subject operating characteristic curve and decision curve. Totally 2 157 surgical patients were included from October 2020 to March 2021 to test the prediction accuracy of the model.Results:The incidence of hypothermia was 13.89% (2 649/19 068) in the modeling group and 14.18% (306/2 157) in the validation group. The area under the subject operating characteristic curve of the prediction model was 0.724 (95% CI: 0.707-0.741), the sensitivity was 0.516, the specificity was 0.823, the cut-off value was 0.175, and the accuracy of practical application was 79.54%. Conclusions:This model can stably predict the incidence of perioperative inadvertent hypothermia in patients under general anesthesia, and provide reference for clinical prevention of inadvertent perioperative hypothermia.