Purpose: We aimed to evaluate whether the addition of pemetrexed is effective in improving progression-free survival (PFS) in epidermal growth factor receptor (EGFR)–mutated patients with or without concomitant alterations. Materials and Methods: This multicenter clinical trial was conducted in China from June 15, 2018, to May 31, 2019. A total of 92 non–small cell lung cancer (NSCLC) patients harboring EGFR-sensitive mutations were included and divided into concomitant and non-concomitant groups. Patients in each group were randomly treated with EGFR–tyrosine kinase inhibitor (TKI) monotherapy or EGFR-TKI combined with pemetrexed in a ratio of 1:1. PFS was recorded as the primary endpoint. Results: The overall median PFS of this cohort was 10.1 months. There were no significant differences in PFS between patients with and without concomitant and between patients received TKI monotherapy and TKI combined with pemetrexed (p=0.210 and p=0.085, respectively). Stratification analysis indicated that patients received TKI monotherapy had a significantly longer PFS in non-concomitant group than that in concomitant group (p=0.002). In concomitant group, patients received TKI combined with pemetrexed had a significantly longer PFS than patients received TKI monotherapy (p=0.013). Molecular dynamic analysis showed rapidly emerging EGFR T790M in patients received TKI monotherapy. EGFR mutation abundance decreased in patients received TKI combined chemotherapy, which supports better efficacy for a TKI combined chemotherapy as compared to TKI monotherapy. A good correlation between therapeutic efficacy and a change in circulating tumor DNA (ctDNA) status was found in 66% of patients, supporting the guiding role of ctDNA minimal residual disease (MRD) in NSCLC treatment. Conclusion EGFR-TKI monotherapy is applicable to EGFR-sensitive patients without concomitant alterations, while a TKI combined chemotherapy is applicable to EGFR-sensitive patients with concomitant alterations. CtDNA MRD may be a potential biomarker for predicting therapeutic efficacy.

Objective:To explore whether life satisfaction has a mediating effect between child neglect and middle school student’ problematic mobile phone use.Methods:Totally 1 692 middle school students from four middle schools of Xiamen in June 2020 were selected by cluster stratified sampling.The self-rating questionnaire for adolescent problematic mobile phone use (SQAPMPU), child neglect scale (CNS) and quality of life scale for children and adolescents (QLSCA) were used for the survey. SPSS 23.0 software was used for descriptive statistics, correlation analysis, regression analysis and the mediating effect analysis.Results:The scores of CNS, QLSCA and SQAPMPU were (24.45±14.28), (134.44±19.34), (23.20±8.94)respectively.And the detection rate of problematic mobile phone use was 23.6%. There were significant differences in the scores of SQAPMPU scale in different grades, father's education degrees, mother's education degrees and monthly pocket money(all P<0.05). In SQAPMPU, high school students scored significantly higher than junior school students( t=-2.403, P=0.016), adolescents with undergrate education of their father and mother scored the lowest( F=3.411, P=0.017; F=2.729, P=0.043), adolescents with monthly pocket money of "500-1 000" and "1 000-2 000" scored significantly higher than those with monthly pocket money of "under 500". The total scores and sub scores of child neglect were significantly positively correlated with the total scores and sub scores of problematic mobile phone use ( r=0.177-0.360, all P<0.05). The total scores and sub scores of life satisfaction were significantly negative correlated with the total scores and sub scores of problematic mobile phone use ( r==-0.508--0.250, all P<0.05). Child neglect had a positive predictive effect on problematic mobile phone use ( t=15.598, R2=0.130, P<0.05), but had a negative predictive effect on life satisfaction ( t=-27.798, R2=0.321, P<0.05). There were the part intermediary role of life satisfaction between child neglect and problematic mobile phone use( t=-13.937, R2=0.222, P<0.05), and the mediating effect accounted for 58.29% of the total effect. Conclusion:The neglected experience in childhood of adolescents not only can directly affect problematic mobile phone use, but also can affect the problematic mobile phone use by affecting life satisfaction.