Pharmacological perturbation studies based on protein-level signatures are fundamental for drug dis-covery.In the present study,we used a mass spectrometry(MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds.The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells.Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol,as well as the noncanonical targets of clinically approved tamoxifen,lovastatin,and their derivatives.Furthermore,the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints.This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine.

Objective:To develope a titanium specimen with good osteogenic activity through fabrication of a composite hydroxyapatite coating on ordered micro-/nanotextured titanium surface.Methods:An ordered micro-/nanotextured structure was prepared on the surface of titanium (the control), and then hydroxyapatite was deposited on the as-prepared ordered micro-/nanotextured structure by alternative loop immersion method. The ordered micro-/nanotextured structures before and after hydroxyapatite deposition were denoted as HA and MN, respectively. Surface morphology was observed using a scanning electron microscope. Bone marrow mesenchymal stem cells (BMMSC) were seeded on the surface of three different materials. Cell morphology was observed with a scanning electron microscope. Cell adhesion and cell proliferation were evaluated using 4', 6-diamidino-2-phenylindole staining and cell counting kit-8 assay, respectively. Extracellular matrix mineralization and the expression levels of osteogenesis-related genes were evaluated by alizarin red staining and real-time quantitative PCR, respectively. Each group has three samples in every experiment.Results:After alternative loop immersing, the MN's original microholes (20 μm in diameter) were retained, and the uniform petal-like hydroxyapatite was deposited on the MN's original titania nanotubes (70 nm in diameter). Compared with the control, BMMSC on MN and HA elongated further and intersected along the micron structure with noticeable pseudopodia and pseudoplates, and the trend was more pronounced especially on HA. The number of early adherent cells on HA was remarkably larger than that on the control and MN at each time point ( P<0.05). On day 1, the A value of cell proliferation on HA was significantly higher than that on the control and MN ( P<0.05). The A value of cell proliferation on HA was significantly lower than that on the control and MN on day 3 ( P<0.05). On day 7, the A value of cell proliferation on HA was significantly lower than that on MN ( P<0.05), but there was no statistically significant difference in the A value of cell proliferation between HA and the control on day 7 ( P>0.05). The Avalue of extracellular matrix mineralization on HA (0.607±0.011) was significantly higher than that on the control and MN (0.268±0.025 and 0.522±0.022, respectively) ( t=-0.25, P<0.001; t=-0.34, P<0.001). The expression levels of bone related genes on HA were significantly higher than those on the control and MN ( P<0.05). Conclusions:HA could promote the BMMSC adhesion and osteogenic differentiation, support BMMSC proliferation, and demonstrate good osteogenic activity.

Objective:To introduce the health insurance fund supervision model in Japan,compare the current situation of health insurance fund supervision in China,learn from experiences,and propose suggestions for improvement.Methods:By combining cases and regulatory effects,it introduces Japan's"guidance-inspection"based health insurance fund supervision model.Results:Japan's"guidance-inspection"based health insurance fund supervision model is relatively effective.Compared with China,it has a higher level of organizational hierarchy,focuses on education in its supervisory approach,clarifies the direction of patients'self-paid expences,and has a well-developed dual-way communication mechanism.Conclusion:China should establish a comprehensive health insurance fund supervision pathway,clearly define the resolution pathway for self-paid expenses caused by violations,and improve the mechanisms for negotiation and dispute resolution during the process.

Objective:To introduce the health insurance fund supervision model in Japan,compare the current situation of health insurance fund supervision in China,learn from experiences,and propose suggestions for improvement.Methods:By combining cases and regulatory effects,it introduces Japan's"guidance-inspection"based health insurance fund supervision model.Results:Japan's"guidance-inspection"based health insurance fund supervision model is relatively effective.Compared with China,it has a higher level of organizational hierarchy,focuses on education in its supervisory approach,clarifies the direction of patients'self-paid expences,and has a well-developed dual-way communication mechanism.Conclusion:China should establish a comprehensive health insurance fund supervision pathway,clearly define the resolution pathway for self-paid expenses caused by violations,and improve the mechanisms for negotiation and dispute resolution during the process.

Objective:To introduce the health insurance fund supervision model in Japan,compare the current situation of health insurance fund supervision in China,learn from experiences,and propose suggestions for improvement.Methods:By combining cases and regulatory effects,it introduces Japan's"guidance-inspection"based health insurance fund supervision model.Results:Japan's"guidance-inspection"based health insurance fund supervision model is relatively effective.Compared with China,it has a higher level of organizational hierarchy,focuses on education in its supervisory approach,clarifies the direction of patients'self-paid expences,and has a well-developed dual-way communication mechanism.Conclusion:China should establish a comprehensive health insurance fund supervision pathway,clearly define the resolution pathway for self-paid expenses caused by violations,and improve the mechanisms for negotiation and dispute resolution during the process.

Objective:To introduce the health insurance fund supervision model in Japan,compare the current situation of health insurance fund supervision in China,learn from experiences,and propose suggestions for improvement.Methods:By combining cases and regulatory effects,it introduces Japan's"guidance-inspection"based health insurance fund supervision model.Results:Japan's"guidance-inspection"based health insurance fund supervision model is relatively effective.Compared with China,it has a higher level of organizational hierarchy,focuses on education in its supervisory approach,clarifies the direction of patients'self-paid expences,and has a well-developed dual-way communication mechanism.Conclusion:China should establish a comprehensive health insurance fund supervision pathway,clearly define the resolution pathway for self-paid expenses caused by violations,and improve the mechanisms for negotiation and dispute resolution during the process.

Objective:To introduce the health insurance fund supervision model in Japan,compare the current situation of health insurance fund supervision in China,learn from experiences,and propose suggestions for improvement.Methods:By combining cases and regulatory effects,it introduces Japan's"guidance-inspection"based health insurance fund supervision model.Results:Japan's"guidance-inspection"based health insurance fund supervision model is relatively effective.Compared with China,it has a higher level of organizational hierarchy,focuses on education in its supervisory approach,clarifies the direction of patients'self-paid expences,and has a well-developed dual-way communication mechanism.Conclusion:China should establish a comprehensive health insurance fund supervision pathway,clearly define the resolution pathway for self-paid expenses caused by violations,and improve the mechanisms for negotiation and dispute resolution during the process.

Objective:To introduce the health insurance fund supervision model in Japan,compare the current situation of health insurance fund supervision in China,learn from experiences,and propose suggestions for improvement.Methods:By combining cases and regulatory effects,it introduces Japan's"guidance-inspection"based health insurance fund supervision model.Results:Japan's"guidance-inspection"based health insurance fund supervision model is relatively effective.Compared with China,it has a higher level of organizational hierarchy,focuses on education in its supervisory approach,clarifies the direction of patients'self-paid expences,and has a well-developed dual-way communication mechanism.Conclusion:China should establish a comprehensive health insurance fund supervision pathway,clearly define the resolution pathway for self-paid expenses caused by violations,and improve the mechanisms for negotiation and dispute resolution during the process.

Objective:To introduce the health insurance fund supervision model in Japan,compare the current situation of health insurance fund supervision in China,learn from experiences,and propose suggestions for improvement.Methods:By combining cases and regulatory effects,it introduces Japan's"guidance-inspection"based health insurance fund supervision model.Results:Japan's"guidance-inspection"based health insurance fund supervision model is relatively effective.Compared with China,it has a higher level of organizational hierarchy,focuses on education in its supervisory approach,clarifies the direction of patients'self-paid expences,and has a well-developed dual-way communication mechanism.Conclusion:China should establish a comprehensive health insurance fund supervision pathway,clearly define the resolution pathway for self-paid expenses caused by violations,and improve the mechanisms for negotiation and dispute resolution during the process.

Objective·To investigate the relation between urinary excretion of protein-bound uremic toxins(PBUTs)and upper urinary tract calculus.Methods·Residents aged 18?80 years in the community of Haitou,Danzhou city in Hainan Province were recruited.Basic information and diet for the last 3 d of the subjects were recorded.Their fasting sera and 24-hour urine samples were collected,and they also underwent ultrasound examination of kidneys and ureters.The subjects with upper urinary calculi detected by ultrasound or a clear history of upper urinary calculi were selected as the calculus group,and the others as the non-calculus group.The biochemical indicators related to the formation of calculus in blood and urine were detected,and the levels of PBUTs,including indoxyl sufate(IS),indole-3-acetic acid(IAA),and p-cresol sulfate(PCS)in blood and urine,as well as oxalic acid and citric acid in urine were detected by high-performance liquid chromatography.The related factors of upper urinary tract calculus formation were analyzed by multivariate Logistic regression.The correlations of urine PBUTs with urine uric acid,oxalic acid,and citric acid were analyzed by Spearman correlation test.Results·A total of 117 participants were screened out with 54 people in the calculus group and 63 people in the non-calculus group.There were no significant differences between the two groups in terms of gender,age,serum indicators,and prevalence of complications such as hypertension,diabetes,and hyperuricemia/gout.The 24-hour urine pH,calcium,uric acid,and chlorine in the calculus group were significantly higher than those in the non-calculus group(all P<0.05),while IS was significantly lower than that in the non-calculus group(P<0.05).Multivariate Logistic regression analysis showed that urinary IS(OR=0.929,95%CI 0.875?0.986,P=0.016)was related to the calculus formation independently,in addition to urinary calcium.The Spearman correlation analysis results showed that the levels of IAA(r=0.420,P=0.000)and PCS(r=0.307,P=0.001)in 24-hour urine were positively correlated with oxalic acid,PCS was positively correlated with uric acid(r=0.297,P=0.002),and IS was positively correlated with citric acid(r=0.289,P=0.002).Conclusion·In the population,a decrease in urinary excretion of IS may be an independent risk factor for the formation of upper urinary tract calculus,and PBUTs levels are correlated with levels of uric acid,oxalic acid,and citric acid.