OBJECTIVE To investigate the effects of multiple doses of Shugan jieyu capsules on the pharmacokinetics of voriconazole， rivaroxaban and apixaban in rats. METHODS Male SD rats were randomly divided into voriconazole group （30 mg/kg）， rivaroxaban group （2 mg/kg）， apixaban group （0.5 mg/kg）， Shugan jieyu capsules+voriconazole group （145 mg/kg+30 mg/kg）， Shugan jieyu capsules+rivaroxaban group （145 mg/kg+2 mg/kg）， Shugan jieyu capsules+apixaban group （145 mg/kg+0.5 mg/kg）， with 6 rats in each group. After the rats in each group were consecutively administered solvent （0.5% sodium carboxymethyl cellulose solution） or Shugan jieyu capsules by intragastric gavage for 8 days， they were respectively given voriconazole， rivaroxaban and apixaban solution by intragastric gavage on the 8th day. Blood samples were then collected at different time points （in voriconazole group， rivaroxaban group and corresponding drug combination groups， blood was collected before administration and at 0.17， 0.34， 0.5， 0.75， 1， 1.5， 2， 3， 4， 5， 6， 8， 10 and 12 hours post-administration； in apixaban group and corresponding drug combination group， blood was collected before administration and at 0.08， 0.17， 0.25， 0.34， 0.5， 0.75， 1， 3， 5， 7， 10 and 12 hours post-administration）. Ultra-high performance liquid chromatography-tandem mass spectrometry method was employed to determine the mass concentrations of voriconazole， rivaroxaban and apixaban in rat plasma. The main pharmacokinetic parameters of these drugs were calculated using a non-compartmental model， and the comparisons were made between groups. RESULTS Compared with single drug group， after multiple administrations of Shugan jieyu capsules， AUC0－t， AUC0－∞ and cmax of voriconazole were significantly decreased， while CLz/F was significantly increased， and tmax was also significantly prolonged （P＜0.05）. For rivaroxaban and apixaban， their tmax values were both significantly prolonged （P＜0.05）. However， there were no statistically significant differences in the other pharmacokinetic parameters between the two groups （P＞0.05）. CONCLUSIONS The combination of Shugan jieyu capsules can decrease the exposure， increase the clearance， and delay the peak concentration of oral voriconazole. However， it does not affect the exposure levels of rivaroxaban and apixaban， but it does delay the time to reach peak concentration for both drugs.

In non-small cell lung cancer(NSCLC),as an improtant oncogenic driver gene,epidermal growth factor receptor exon 20 insertion(EGFR ex20ins)has a unique protein structure and is primarily drug-resistant to tradi-tional EGFR-tyrosine kinase inhibitors(EGFR-TKIs).In recent years,exploration of targeted therapy for EGFR ex20ins has never stopped.Firstly Mobocertinib and Amivantamab obtained approval from U.S.Food and Drug Administration(FDA)for EGFR ex20ins mutant NSCLC patients,then other drugs,such as Sunvozertinib,made breakthroughs and combination therapies also obtained gains.Multi-pronged measures are hopeful to overcome EGFR ex20ins drug resistance.As men-tioned above,it's definitely important to gain deeper understanding of molecular mechanism of EGFR ex20ins and assess ef-fect and difference between novel drugs.This review is devoted to make a summary about newest achievement so to provide valuable reference about precise therapy for patients with EGFR ex20ins.

Objective:To explore the influence of outpatient co-ordination on the purchase of commercial medical insurance in China,enrich the research perspective of outpatient co-ordination.Methods:Based on the data of China Health and Retirement Longitudinal Study from 2011 to 2020,past outpatient co-ordination policies in pilot cities and the Digital Inclusive Finance insurance index,using staggered DID to empirically test the impact of outpatient co-ordination on employees'commercial medical insurance purchase.Results:Outpatient co-payment increases workers'willingness to purchase commercial health insurance,which increases by about 4％;heterogeneity analysis finds outpatient co-payment primarily affects individuals'commercial insurance purchasing behavior and that the extent of the effect is related to workers'age,health status,and the outpatient co-payment coverage model of the affiliation.Conclusion:Improving the outpatient co-payment guarantee mechanism at the national level and promoting the effective connection between basic medical insurance and commercial medical insurance.

Objective:To explore the influence of outpatient co-ordination on the purchase of commercial medical insurance in China,enrich the research perspective of outpatient co-ordination.Methods:Based on the data of China Health and Retirement Longitudinal Study from 2011 to 2020,past outpatient co-ordination policies in pilot cities and the Digital Inclusive Finance insurance index,using staggered DID to empirically test the impact of outpatient co-ordination on employees'commercial medical insurance purchase.Results:Outpatient co-payment increases workers'willingness to purchase commercial health insurance,which increases by about 4％;heterogeneity analysis finds outpatient co-payment primarily affects individuals'commercial insurance purchasing behavior and that the extent of the effect is related to workers'age,health status,and the outpatient co-payment coverage model of the affiliation.Conclusion:Improving the outpatient co-payment guarantee mechanism at the national level and promoting the effective connection between basic medical insurance and commercial medical insurance.

Objective:To explore the influence of outpatient co-ordination on the purchase of commercial medical insurance in China,enrich the research perspective of outpatient co-ordination.Methods:Based on the data of China Health and Retirement Longitudinal Study from 2011 to 2020,past outpatient co-ordination policies in pilot cities and the Digital Inclusive Finance insurance index,using staggered DID to empirically test the impact of outpatient co-ordination on employees'commercial medical insurance purchase.Results:Outpatient co-payment increases workers'willingness to purchase commercial health insurance,which increases by about 4％;heterogeneity analysis finds outpatient co-payment primarily affects individuals'commercial insurance purchasing behavior and that the extent of the effect is related to workers'age,health status,and the outpatient co-payment coverage model of the affiliation.Conclusion:Improving the outpatient co-payment guarantee mechanism at the national level and promoting the effective connection between basic medical insurance and commercial medical insurance.

Objective:To explore the influence of outpatient co-ordination on the purchase of commercial medical insurance in China,enrich the research perspective of outpatient co-ordination.Methods:Based on the data of China Health and Retirement Longitudinal Study from 2011 to 2020,past outpatient co-ordination policies in pilot cities and the Digital Inclusive Finance insurance index,using staggered DID to empirically test the impact of outpatient co-ordination on employees'commercial medical insurance purchase.Results:Outpatient co-payment increases workers'willingness to purchase commercial health insurance,which increases by about 4％;heterogeneity analysis finds outpatient co-payment primarily affects individuals'commercial insurance purchasing behavior and that the extent of the effect is related to workers'age,health status,and the outpatient co-payment coverage model of the affiliation.Conclusion:Improving the outpatient co-payment guarantee mechanism at the national level and promoting the effective connection between basic medical insurance and commercial medical insurance.

Objective:To explore the influence of outpatient co-ordination on the purchase of commercial medical insurance in China,enrich the research perspective of outpatient co-ordination.Methods:Based on the data of China Health and Retirement Longitudinal Study from 2011 to 2020,past outpatient co-ordination policies in pilot cities and the Digital Inclusive Finance insurance index,using staggered DID to empirically test the impact of outpatient co-ordination on employees'commercial medical insurance purchase.Results:Outpatient co-payment increases workers'willingness to purchase commercial health insurance,which increases by about 4％;heterogeneity analysis finds outpatient co-payment primarily affects individuals'commercial insurance purchasing behavior and that the extent of the effect is related to workers'age,health status,and the outpatient co-payment coverage model of the affiliation.Conclusion:Improving the outpatient co-payment guarantee mechanism at the national level and promoting the effective connection between basic medical insurance and commercial medical insurance.

Objective:To explore the influence of outpatient co-ordination on the purchase of commercial medical insurance in China,enrich the research perspective of outpatient co-ordination.Methods:Based on the data of China Health and Retirement Longitudinal Study from 2011 to 2020,past outpatient co-ordination policies in pilot cities and the Digital Inclusive Finance insurance index,using staggered DID to empirically test the impact of outpatient co-ordination on employees'commercial medical insurance purchase.Results:Outpatient co-payment increases workers'willingness to purchase commercial health insurance,which increases by about 4％;heterogeneity analysis finds outpatient co-payment primarily affects individuals'commercial insurance purchasing behavior and that the extent of the effect is related to workers'age,health status,and the outpatient co-payment coverage model of the affiliation.Conclusion:Improving the outpatient co-payment guarantee mechanism at the national level and promoting the effective connection between basic medical insurance and commercial medical insurance.

Objective:To explore the influence of outpatient co-ordination on the purchase of commercial medical insurance in China,enrich the research perspective of outpatient co-ordination.Methods:Based on the data of China Health and Retirement Longitudinal Study from 2011 to 2020,past outpatient co-ordination policies in pilot cities and the Digital Inclusive Finance insurance index,using staggered DID to empirically test the impact of outpatient co-ordination on employees'commercial medical insurance purchase.Results:Outpatient co-payment increases workers'willingness to purchase commercial health insurance,which increases by about 4％;heterogeneity analysis finds outpatient co-payment primarily affects individuals'commercial insurance purchasing behavior and that the extent of the effect is related to workers'age,health status,and the outpatient co-payment coverage model of the affiliation.Conclusion:Improving the outpatient co-payment guarantee mechanism at the national level and promoting the effective connection between basic medical insurance and commercial medical insurance.

Objective:To explore the influence of outpatient co-ordination on the purchase of commercial medical insurance in China,enrich the research perspective of outpatient co-ordination.Methods:Based on the data of China Health and Retirement Longitudinal Study from 2011 to 2020,past outpatient co-ordination policies in pilot cities and the Digital Inclusive Finance insurance index,using staggered DID to empirically test the impact of outpatient co-ordination on employees'commercial medical insurance purchase.Results:Outpatient co-payment increases workers'willingness to purchase commercial health insurance,which increases by about 4％;heterogeneity analysis finds outpatient co-payment primarily affects individuals'commercial insurance purchasing behavior and that the extent of the effect is related to workers'age,health status,and the outpatient co-payment coverage model of the affiliation.Conclusion:Improving the outpatient co-payment guarantee mechanism at the national level and promoting the effective connection between basic medical insurance and commercial medical insurance.