This article emphasizes the importance of medical communication and expounds how to strenthen medical communication by some principles and methods,like paying attention to and lov-ing patients,listenning carefully,explaining patiently and confidently,learning modestly and so on.

Objective To evaluate the effectiveness and safety of gefitinib retreatment beyond progression(GRBP)in non-small cell lung cancer(NSCLC)patients with rare EGFR mutations.Methods We retrospectively analyzed six rare-EGFR-mutation NSCLC patients from Jan 2011 to Dec 2015.Those patients had previous disease control and then disease progression according to Response Evaluation Criteria in Solid Tumors version 1.1(RECIST v1.1)after taking oral gefitinib 250 mg once a day.After that,continuing gefitinib was decided by clinicians′ experience at the same treatment option.The primary endpoints were response rate(RR),overall survival(OS),the first and second progression-free survival(PFS-1 and PFS-2).Safety was assessed according to the NCI-CTCAE version 4.0.Results After initial treatment of gefitinib,4 patients achieved partial response(PR)and 2 patients showed stable disease(SD),with RR being 66.7％.The median PFS-1 and PFS-2 were 10 months(95％CI 6.6-13.4)and 9 months(95％CI 6.9-11.1),respectively.The median OS time was 28 months(95％CI 10.4-45.6).The most common treatment-related adverse events were fatigue,diarrhea,rash,itching and elevated transaminases.Conclusion In our study,gefitinib retreatment beyond disease progression is effective with a manageable tolerability profile.

Objective To investigate the possible function of integrin-linked kinase (ILK)/protein kinase B (PKB/Akt) signaling in repair of neonatal rat hypoxia-ischemia brain damage (HIBD). Methods Postnatal day 10 SD rats were randomly divided into hypoxia ischemia (HI) group and sham control group. Rat brains were collected at 0 h, 4 h, 6 h, 12 h, 24 h, 48 h and 72 h after hypoxia ischemia damage. Immunolfuorescence staining was used to observe the distribution and expression of ILK. Western blot was used to detect the expression of ILK, Akt, phosphorylated Akt (p-Akt) and vascular endothelial growth factor (VEGF). Lentiviral vectors expressing ILK shRNA were constructed to inhibit the expression of ILK in neonatal rats. After intracerebroventricular injections of LV-ILK shRNA lentivirus and LV-control respectively, HIBD model was established. Rat brains were collected at 4 h and 24 h after HIBD. Western blot was used to detect the expression of ILK, p-Akt, and VEGF. TdT-mediated dUTP-biotin nick end labeling (TUNEL) staining was used to detect cell apoptosis. Results Immunolfuorescence staining showed that ILK was widely distributed in cortex and hippocampus both in HI group and sham control group. ILK located at cell membrane and cytoplasm. Western blot results demonstrated that ILK protein increased after HI, with a peak at 24 h, and maintained higher level than those in sham control group. The p-Akt protein signiifcantly increased at 4 h after HI, and signiifcantly decreased in the following 24 h, and then increased again, with a peak at 48 h, but the level of p-Akt protein was higher than that of sham control group. The VEGF protein increased at 4 h after HI, with a peak at 12 h, higher than that of sham control group. The expression of Akt protein showed no signiifcant difference between HI group and sham control group. Lentiviral vectors containing RNAi targeting ILK was applied successfully in vivo. At 4 h and 24 h after HIBD model, the expression of ILK, p-Akt, and VEGF proteins in right side brain received LV-ILK shRNA signiifcantly decreased compared with those of right side brain received LV-control at the same time point. And cell apoptosis signiifcantly increased in LV-ILK shRNA group. Conclusions The expression of ILK, p-Akt, VEGF proteins increased after HI. By inhibiting the expression of ILK, the expression of p-Akt and VEGF proteins can be reduced, and cell apoptosis could increase in newborn rats after HIBD. The results suggest that ILK may induce the expression of VEGF through activating the PI3K/Akt signaling pathway, and promote cell survival and angiogenesis after HIBD.

Bladder cancer remains the 10th most common cancer worldwide. In recent years, metformin has been found to have potential anti-bladder cancer activ-ity while high concentration of IC50 at millimolar level is needed, which could not be reached by regular oral administration route. Thus, higher efficient agent is urgently demanded for clinically treating bladder cancer. Here, by conjugating artesunate to metformin, a novel artesunate-metformin dimer triazine derivative AM2 was designed and synthesized. The inhibitory effect of AM2 on bladder cancer cell line T24 and the mechanism underlying was determined. Anti-tumor activity of AM2 was assessed by MTT, cloning formation and wound healing assays. Decreasing effect of AM2 on lipogenesis was determined by oil red O staining. The protein expressions of Clusterin, SREBP1 and FASN in T24 cells were evaluated by Western blotting. The results show that AM2 significantly inhibited cell proliferation and migration at micromolar level, much higher than parental metformin. AM2 reduced lipogenesis and down-regulated the expressions of Clusterin, SREBP1 and FASN. These results suggest that AM2 inhibits the growth of bladder cancer cells T24 by inhibiting cellular lipogenesis associated with the Clusterin/SREBP1/FASN signaling pathway.

Zidovudine (AZT), the first drug approved by the US Food and Drug Administration for the treatment of human immunodeficiency virus (HIV) infection, is metabolized in the host cells to 5'-AZT triphosphate (AZT-TP) which inhibits HIV reverse transcriptase. As the pharmacokinetics of AZT and its phosphorylated metabolites in human peripheral blood mononuclear cells (hPBMCs) is limited, the aim of this study was to determine the pharmacokinetic parameters of AZT and its phosphorylated metabolites in hPBMCs from 12 healthy Chinese male subjects after a single oral dose of 600 mg of AZT. Blood samples were collected prior to drug administration, then at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8 and 10 h after drug administration. Mononuclear cells collected by Ficoll-Hypaque density gradient centrifugation were used for determination of AZT and metabolites [AZT monophosphate (AZT-MP), AZT diphosphate (AZT-DP) and AZT-TP] and the plasma was used to evaluate the pharmacokinetics of AZT. Plasma concentration of AZT peaked within 0.583 h and intracellular concentrations of AZT, AZT-MP, AZT-DP and AZT-TP peaked within 1.083, 1.500, 1.417 and 1.583 h, respectively. AZT in plasma was eliminated rapidly with t 1/2 of 2.022 h, and AZT-MP, AZT-DP and AZT-TP were eliminated with t 1/2 of 13.428, 8.285 and 4.240 h, respectively. The plasma concentration of the phosphorylated metabolites was not quantifiable.

Biological sample pretreatment is an important step in biological sample analysis. Due to the diversity of biological matrices, the analysis of target substances in these samples presents significant challenges to sample processing. To meet these emerging demands on biopharmaceutical analysis, this paper summarizes several new techniques of on-line biological sample processing: solid phase extraction, solid phase micro-extraction, column switching, limited intake filler, molecularly imprinted solid phase extraction, tubular column, and micro-dialysis. We describe new developments, principles, and characteristics of these techniques, and the application of liquid chromatography-mass spectrometry (LC-MS) in biopharmaceutical analysis with these new techniques in on-line biological sample processing.

The aim of this study was to apply the reference-scaled average bioequivalence (RSABE) approach to evaluate the bioequivalence of 2 formulations of agomelatine, and to investigate the pharmacokinetic properties of agomelatine in Chinese healthy male subjects. This was performed in a single-dose, randomized-sequence, open-label, four-way crossover study with a one-day washout period between doses. Healthy Chinese males were randomly assigned to receive 25 mg of either the test or reference formulation. The formulations were considered bioequivalent if 90% confidence intervals (CIs) for the log-transformed ratios and ratio of geometric means (GMR) of AUC and C max of agomelatine were within the predetermined bioequivalence range based on RSABE method. Results showed that both of the 90% CIs for the log-transformed ratios of AUC and C max of 7-desmethyl-agomelatine and 3-hydroxy-agomelatine were within the predetermined bioequivalence range. The 90% CIs for natural log-transformed ratios of C max, AUC0-t and AUC0-∞ of agomelatine (104.42-139.86, 101.33-123.83 and 97.90-117.94) were within the RSABE acceptance limits, and 3-hydroxy-agomelatine (105.55-123.03, 101.95-109.10 and 101.72-108.70) and 7-desmethyl-agomelatine (104.50-125.23, 102.36-111.50 and 101.62-110.64) were within the FDA bioequivalence definition intervals (0.80-1.25 for AUC and 0.75-1.33 for C max). The RSABE approach was successful in evaluating the bioequivalence of these two formulations.