GARNL3 identified as a crucial target for overcoming temozolomide resistance in EGFRvIII-positive glioblastoma.

OBJECT: Amplification of the epidermal growth factor receptor (EGFR) and its active mutant type III (EGFRvIII), frequently occurr in glioblastoma (GBM), contributing to chemotherapy and radiation resistance in GBM. Elucidating the underlying molecular mechanism of temozolomide (TMZ) resistance in EGFRvIII GBM could offer valuable insights for cancer treatment. METHODS: To elucidate the molecular mechanisms underlying EGFRvIII-mediated resistance to TMZ in GBM, we conducted a comprehensive analysis using Gene Expression Omnibus and The cancer genome atlas (TCGA) databases. Initially, we identified common significantly differentially expressed genes (DEGs) and prioritized those correlating significantly with patient prognosis as potential downstream targets of EGFRvIII and candidates for drug resistance. Additionally, we analyzed transcription factor expression changes and their correlation with candidate genes to elucidate transcriptional regulatory mechanisms. Using estimate method and databases such as Tumor IMmune Estimation Resource (TIMER) and CellMarker, we assessed immune cell infiltration in TMZ-resistant GBM and its relationship with candidate gene expression. In this study, we examined the expression differences of candidate genes in GBM cell lines following EGFRvIII intervention and in TMZ-resistant GBM cell lines. This preliminary investigation aimed to verify the regulatory impact of EGFRvIII on candidate targets and its potential involvement in TMZ resistance in GBM. RESULTS: Notably, GTPase Activating Rap/RanGAP Domain Like 3 (GARNL3) emerged as a key DEG associated with TMZ resistance and poor prognosis, with reduced expression correlating with altered immune cell profiles. Transcription factor analysis suggested Epiregulin (EREG) as a putative upstream regulator of GARNL3, linking it to EGFRvIII-mediated TMZ resistance. In vitro experiments confirmed EGFRvIII-mediated downregulation of GARNL3 and decreased TMZ sensitivity in GBM cell lines, further supported by reduced GARNL3 levels in TMZ-resistant GBM cells. CONCLUSION: GARNL3 downregulation in EGFRvIII-positive and TMZ-resistant GBM implicates its role in TMZ resistance, suggesting modulation of EREG/GARNL3 signaling as a potential therapeutic strategy.

[Study on the relationship between smoking behavior and other unhealthy behaviors among middle school students in 4 cities of China].

OBJECTIVE: To explore the situation of smoking behavior among the students of middle school in Beijing, Hangzhou, Wuhan and Urumchi and to analyze the relationship between smoking behavior and several unhealthy behaviors together with psychological troubles to provide evidence in developing an early intervention plan. METHODS: The National Health Education Institute (NHEI) of Chinese Center for Disease Control and Prevention (CDC) provided relevant data on all middle schools in the 4 cities and then U.S. CDC randomly sampled 100 common middle schools from them with a special sampling process. The core questionnaire developed by the experts from WHO and other countries was used in the survey among 9015 sampled students. RESULTS: Among all the sampled students, 29.4% of them had ever attempted cigarettes smoking while 6.6% of them tried tobacco in the 30 days before survey, 27.0% of the students with smoking behavior began smoking at the age of 9 or younger, 31.8% had learned how to refuse smoking from school education. The students with smoking behavior were more likely to drink alcohol, use drugs, bully others, be injured, miss classes, and have some psychological troubles than those without smoking behavior. CONCLUSION: There were increasing trends noticed on the incidence of attempt and smoking cigarettes. Smoking was closely related to other unhealthy behaviors and psychological troubles. Comprehensive education activities on "no-smoking" should be implemented as early as possible among adolescents, as well as to promote training on life skills.

[The relationship between test anxiety and personality, self-esteem in grade one senior high students].

OBJECTIVE: To explore the relationship between test anxiety and personality, self-esteem in grade one senior high school students. METHODS: Totally 538 senior high school students of grade one were investigated by Test Anxiety Scale (TAS), Eysenck Personality Questionnaire (EPQ) and Self-Esteem Scale (SES) in a Senior High School in Shandong Province. RESULTS: The prevalence of test anxiety among all the surveyed students was rated 65.2%. The Psychoticism (P) (51.60 +/- 9.66) or Neuroticism (N) (51.57 +/- 10.75) factor score of EPQ in students with test anxiety was significantly higher than that in students without test anxiety (48.07 +/- 8.62, 45.65 +/- 10.14) (P < 0.001), while the Extroversion or Introversion (E) score (50.76 +/- 11.09) was on the contrary (53.68 +/- 11.60) (P < 0.01). The total score of TAS was significantly positively related to the P (r = 0.14) and N (r = 0.36) factor score and significantly negatively related to the E factor score of EPQ (r = -0.15) (P < 0.001). The prevalence of test anxiety in introversive students (72.3%) was higher than that in extroversive students (53.2%) (P < 0.05), and that in students with unstable emotion (81.4%) and in students with apparent psychoticism (84.1%) were also higher than that in those with stable emotion (41.0%) and in those without psychoticism (57.7%) (P < 0.01). The total score of SES in students with test anxiety (29.12 +/- 4.41) was significantly lower than that in students without test anxiety (30.29 +/- 4.25) (P < 0.01). The total score of TAS was significantly negatively related to the total score of SES (r = -0.23) (P < 0.001). CONCLUSION: Test anxiety should be related to the personality and self-esteem, and the prevalence of test anxiety in introversive, unstable emotional, apparent psychoticism or low self-esteem students should be higher.