Predictive Value of EGFR Mutation Status for First-Line Tyrosine Kinase Inhibitor Treatment in Patients with Advanced Lung Cancer.

Objective: This study aims to investigate and analyze the correlation between EGFR-TKI first-line therapy and EGFR mutation status in patients with advanced lung cancer. Methods: We selected 60 patients with advanced lung cancer and EGFR mutations (diagnosed as stage IIIb or IV) from our hospital between January 2019 and November 2022. Each patient underwent an EGFR mutation test and was categorized into two groups based on their mutation status: 28 patients with exon 21 mutations and 32 with exon 19 deletions. After three months of therapy, we assessed treatment efficacy and adverse reactions. Results: Our data revealed that in the EGFR exon 21 mutation group, the objective response rate (ORR) and disease control rate (DCR) were 57.14% and 60.71%, respectively. In the EGFR exon 19 deletion group, the ORR and DCR were 68.75% and 84.38%, respectively. There were significant differences in DCR and ORR between the two EGFR mutation states, with statistical significance (P < .05). The progression-free survival (PFS) in the EGFR exon 21 mutant group was 8.4 months after third-generation EGFR-TKI treatment, while the EGFR exon 19 deletion group had a PFS of 12.7 months after the same treatment, with a statistically significant difference (P < .05). Cox regression analysis showed that female patients with no smoking history and an adenocarcinoma pathological type had significantly better PFS after treatment compared to male patients with a smoking history and squamous cell carcinoma type, with statistical significance (P < .05). Age and clinical stage did not significantly impact PFS after third-generation EGFR-TKI treatment (P > .05). Adverse reaction incidences, such as nausea, fatigue, diarrhea, vomiting, and rash, did not significantly differ in either the EGFR exon 21 mutation group or the EGFR exon 19 deletion group (P > .05). Conclusion: The status of EGFR mutations serves as a predictive factor for PFS, DCR, and ORR in lung cancer patients undergoing EGFR-TKI first-line therapy. This status can be a valuable predictive indicator of lung cancer treatment efficacy, with potential applications in clinical practice.

Dexmedetomidine decreases the 50% effective dose (ED50) of intravenous propofol required to prevent tracheal intubation response in Beagles.

OBJECTIVE: To determine the 50% effective dose (ED50) of intravenous propofol required for successfully preventing tracheal intubation response in Beagles co-induced with dexmedetomidine. ANIMALS: 36 adult male Beagles. PROCEDURES: The dogs were randomly assigned to either group D1, group D2, or group C (received 1 µg/kg, 2 µg/kg dexmedetomidine intravenously, or the same amount of normal saline as dexmedetomidine, 10 mL). The first dog in each group received 6 mg/kg of propofol for induction. The pump speed of propofol was 600 mL/h. The dosage varied with increments or decrements of 0.5 mg/kg based on the Dixon up-and-down method. The duration of eye-opening after propofol administration was recorded. Changes in heart rate (HR) and respiratory rate (RR) were recorded at 5 timepoints: after entering the operation room and prior to propofol administration (T1), 1 and 3 min after propofol administration (T2 and T3), 3 and 5 min after intubation (T4 and T5). RESULTS: The required ED50 of propofol that prevented tracheal intubation response in D1, D2, and C groups were 6.4 mg/kg (95% CI, 6.1 to 6.7 mg/kg), 5.8 mg/kg (95% CI, 5.67 to 6 mg/kg), and 8.3 mg/kg (95% CI, 8 to 8.5 mg/kg), respectively. The recovery time of group D2 was significantly longer than that of groups D1 and C (P < .05). The differences in HR among the 3 groups were significant from T2 up to T5 timepoint (P < .05). The differences in RR among the 3 groups were significant at T2 and T3 timepoints (P < .05). CLINICAL RELEVANCE: Dexmedetomidine pre-injection reduces the amount of propofol required for endotracheal intubation response in Beagles, thereby reducing the respiratory inhibition induced by propofol.

Identification of m6A methyltransferase-related genes predicts prognosis and immune infiltrates in head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) accounts for 90% of head and neck malignant tumors. As the early symptoms of HNSCC are not obvious, and it is prone to recurrence and metastasis, making the overall survival (OS) rate of patients very low. Existing studies have shown m6A methylation plays a crucial role in various cancers, but it is rarely studied in HNSCC. This study aimed to explore the expression of m6A methylation-related genes in HNSCC and its correlation with prognosis, and to explore its relationship with immune infiltration. METHODS: The gene expression data of HNSCC patient tumor samples (tumor =510) and adjacent normal tissue samples (normal =50) were extracted from The Cancer Genome Atlas (TCGA) database, and the expression characteristics of m6A regulatory factors were described. Kaplan-Meier survival analysis was used to analyze the relationship between m6A regulatory factors and OS and disease-specific survival (DSS). Least absolute shrinkage and selection operator (LASSO) regression was used to construct the m6A regulatory factor-HNSCC risk prediction model. In addition, the relationship between m6A methylation-related genes and tumor immune infiltration were discussed. RESULTS: The differential expression of 20 genes were identified by TCGA, and 18 genes (IGF2BP2, IGF2BP1, IGF2BP3, VIRMA, YTHDF1, YTHDF2, YTHDF3, ZC3H13, METTL14, ALKBH5, METTL3, RBMX, WTAP, YTHDC1, FTO, HNRNPC, HNRNPA2B1, and RBM15) were overexpressed in HNSCC. The survival rate of different gene expression levels was different. The high expression of YTHDC1 and YTHDC2 indicated better OS. Furthermore, for DSS, increased expression of YTHDC2 was also correlated with better clinical outcomes (P<0.05). At the same time, we drew a 3-gene risk score model in the TCGA-HNSCC cohort, and the survival curve showed compared with low-risk patients, high-risk patients had significantly worse OS (P<0.05). Gene enrichment analysis showed EPITHELIAL_MESENCHYMAL_TRANSITIO, MTORC1_SIGNALING, MYC_TARGETS_V1, MYC_TARGETS_V2, MYOGENESIS pathways, high TP53 mutations, and suppressive immunity were related to the high-risk group. The low-risk group was related to ALLOGRAFT_REJECTION, COMPLEMENT, IL6_JAK_STAT3_SIGNALING, INTERFERON_ALPHA_RESPONSE, INTERFERON_GAMMA_RESPONSE pathways, low TP53 mutations, and active immunity. CONCLUSIONS: The m6A methyltransferase-related genes can predict the prognosis of HNSCC and are related to immune infiltration.

Circular RNA_LARP4 Sponges miR-1323 and Hampers Progression of Esophageal Squamous Cell Carcinoma Through Modulating PTEN/PI3K/AKT Pathway.

BACKGROUND: Emerged as important regulators in cancer progression, circular RNAs have been tested to participate in diverse biological processes. Former studies have suggested that circular RNA_LARP4 (circLARP4) exerts indispensable function on the development of different cancers such as gastric cancer and ovarian cancer. Nonetheless, the specific role of circLARP4 has not been discovered in ESCC. AIMS: The aim of this study is to explore the biological function and regulatory mechanism of circLARP4 in ESCC. METHODS: CircLARP4, miR-1323, and PTEN expression levels were quantified by RT-qPCR. CCK-8, EdU, caspase-3 activity, wound healing, transwell, and western blot assays were chosen to assess ESCC cell growth. Luciferase reporter, RIP, and RNA pull-down assays were performed to examine the interaction between miR-1323 and circLARP4 (or PTEN). RESULTS: CircLARP4 expression was observably downregulated in ESCC cell lines, and overexpressed circLARP4 restrained cell proliferation and migration whereas boosted cell apoptosis in ESCC. Molecular mechanism experiments revealed that circLARP4 could act as a sponge for miR-1323 and negatively modulated miR-1323 expression in ESCC. Interestingly, the repression of miR-1323 was correlated with inhibitive cell proliferation, migration, and promotive apoptosis. Besides, miR-1323 bound with PTEN, and PTEN expression was negatively regulated by miR-1323 whereas positively regulated by circLARP4 in ESCC. Moreover, rescue assays testified that miR-1323 overexpression or PTEN deficiency could countervail the function of circLARP4 overexpression on ESCC progression. More importantly, circLARP4 played an inhibitory role in PI3K/AKT pathway. CONCLUSIONS: CircLARP4 sponges miR-1323 and hampers tumorigenesis of ESCC through modulating PTEN/PI3K/AKT pathway.

Analytical Expression for the NO Concentration Profile Following NONOate Decomposition in the Presence of Oxygen.

We have derived an analytical expression for the time dependent NO concentration from NONOate donors in the presence of oxygen for the process of NO release from NO donors following autoxidation. This analytical solution incorporates the kinetics of the releases with the autoxidation and is used to fit the simulated NO concentration profile to the experimental data. This allows one to determine the NO release rate constant, k 1, the NO release stoichiometric coefficient, v NO, and the NO autoxidation reaction rate constant, k 2. This analytical solution also allows us to predict the real NO concentration released from NO donors under aerobic conditions, while v NO is reportedly two under aerobic conditions, it falls to lower values in the presence of oxygen.