Objective To optimize the purification process of freeze-dried attenuated live hepatitis A vaccine to improve vaccine quality and safety.Methods The extraction times(six times) and centrifugal forces(2 990, 4 070, 5 316, 6 728 × g)of hepatitis A virus(HAV) harvests were optimized, and the virus titers were detected under different extraction times and centrifugal forces. The extracted solution was homogenized and the trichloromethane residue was measured pre-ultrafiltration. The trichloromethane residue, protein content, virus titer and virus content below the membrane were detected after ultrafiltration concentration with a 300 KD molecular weight cutoff(MWCO) membrane. The bulk solutions were prepared by two processes, sampled, and detected for the virus titer, protein content and trichloromethane residue.Results With the increase of extraction times, the virus titer of the supernatant showed a decreasing trend. The average virus titers of the supernatant in the first four extractions exceeded 7. 00 lgCCID_(50)/mL, while the fifth and sixth extractions fell below this threshold. The extraction times of virus harvest were selected as four times. The average virus titers of the bulk solutions prepared under different centrifugation conditions in the four groups ranged from 8. 11 to 8. 39 lgCCID_(50)/mL with no statistically significant difference(F = 1. 319, P = 0. 334). Using 300 KD membrane for ultrafiltration concentration, the virus detection below the membrane was negative. The trichloromethane residues decreased significantly(t = 4. 975, P = 0. 037),and the virus titers and protein contents in bulk solutions were all within the qualification criteria. There was no significant difference in virus titers and trichloromethane residues between the original and optimized processes(t =-0. 970 and 2. 306,P = 0. 369 and 0. 082, respectively), but the trichloromethane residue of the optimized process was lower than that of the original process. The protein levels of bulk solutions prepared by the two processes were stable, well below the internal control standards.Conclusion The purification process of the freeze-dried attenuated live hepatitis A vaccine was successfully optimized, further improving the quality of the vaccine.

Objective To compare the efficacy and safety of osimertinib and aumolertinib in the treatment of advanced non-small cell lung carcinoma(NSCLC)with epidermal growth factor receptor(EGFR)mutation.Methods A total of 139 patients with EGFR-mutated advanced NSCLC treated in the First People's Hospital of Yunnan Province from January,2019 to December,2022 were retrospectively collected.After screening by that row of criteria,104 patients were included in this study.According to the treatment drugs,they were divided into osimertinib group and aumolertinib group,with 52 cases in each group.The osimertinib group received osimertinib mesylate tablets 80 mg once daily,and the aumolertinib group received aumolertinib mesylate tablets 110 mg once daily.The disease control rate(DCR),objective remission rate(ORR)and progression-free survival(PFS)of the two groups were observed.PFS and overall survival(OS)were evaluated.The Cox regression model was used to analyze the key factors affecting patient survival.Results The ORR of aumolertinib group was significantly higher than that of osimertinib group.The median progression-free survival(mPFS)of aumolertinib group was significantly longer than that of osimertinib group(P=0.045).Cox regression model showed that clinical stage Ⅲ(HR=2.25,95%Cl 1.28～3.95,P=0.005),no brain metastasis(HR=0.59,95%Cl 0.35～0.98,P=0.040),third generation TKI type aumolertinib(HR=1.82,95%CI 1.15～2.87,P=0.011).Conclusion Aumolertinib and osimertinib have similar clinical efficacy in the treatment of advanced NSCLC patients with EGFR mutation.However,in terms of long-term efficacy,aumolertinib has significantly better median PFS and overall OS,and higher safety than osimertinib.