BACKGROUND: Double-stranded RNA-specific adenosine deaminase 1 (ADAR1) binds to double-stranded RNA and catalyzes the deamination of adenosine (A) to inosine (I). The functional mechanism of ADAR1 in non-small cell lung cancer (NSCLC) remains incompletely understood. This study aimed to investigate the prognostic significance of ADAR1 in NSCLC and to elucidate its potential role in regulating tumor cell proliferation and migration. METHODS: Data from The Cancer Genome Atlas (TCGA) and cBioPortal were analyzed to assess the correlation between high ADAR1 expression and clinicopathological features as well as prognosis in lung cancer. We performed Western blot (WB), cell proliferation assays, Transwell invasion/migration assays, and nude mouse xenograft modeling to examine the phenotypic changes and molecular mechanisms induced by ADAR1 knockdown. Furthermore, the ADAR1 p150 overexpression model was utilized to validate the proposed mechanism. RESULTS: ADAR1 expression was significantly elevated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues compared with adjacent non-tumor tissues (LUAD: P=3.70×10-15, LUSC: P=0.016). High ADAR1 expression was associated with poor prognosis (LUAD: P=2.03×10-2, LUSC: P=2.81×10-2) and distant metastasis (P=0.003). Gene Set Enrichment Analysis (GSEA) indicated that elevated ADAR1 was associated with mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway activation, matrix metalloproteinase-9 (MMP-9) expression, and cell adhesion. ADAR1 and MMP-9 levels showed a strongly positive correlation (P=6.45×10-34) in 10 lung cancer cell lines, highest in H1581. Knockdown of ADAR1 in H1581 cells induced a rounded cellular morphology with reduced pseudopodia. Concomitantly, it suppressed cell proliferation, invasion, migration, and in vivo tumorigenesis. It also suppressed ERK phosphorylation and downregulated cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog (c-FOS), MMP-9, N-cadherin, and Vimentin. Conversely, ADAR1 p150 overexpression in PC9 cells enhanced ERK phosphorylation and increased c-FOS and MMP-9 expression. CONCLUSIONS High ADAR1 expression is closely associated with poor prognosis and distant metastasis in NSCLC patients. Mechanistically, ADAR1 may promote proliferation, invasion, migration, and tumorigenesis in lung cancer cells via the ERK/c-FOS/MMP-9 axis.
Humans ; Lung Neoplasms/physiopathology* ; Adenosine Deaminase/genetics* ; Matrix Metalloproteinase 9/genetics* ; Cell Proliferation ; Carcinoma, Non-Small-Cell Lung/physiopathology* ; Cell Movement ; Animals ; Mice ; RNA-Binding Proteins/genetics* ; Female ; Male ; Cell Line, Tumor ; Proto-Oncogene Proteins c-fos/genetics* ; Middle Aged ; MAP Kinase Signaling System ; Gene Expression Regulation, Neoplastic ; Mice, Nude ; Extracellular Signal-Regulated MAP Kinases/genetics*

General anesthesia, pivotal for surgical procedures, requires precise depth monitoring to mitigate risks ranging from intraoperative awareness to postoperative cognitive impairments. Traditional assessment methods, relying on physiological indicators or behavioral responses, fall short of accurately capturing the nuanced states of unconsciousness. This study introduces a machine learning-based approach to decode anesthesia depth, leveraging EEG data across different anesthesia states induced by propofol and esketamine in rats. Our findings demonstrate the model's robust predictive accuracy, underscored by a novel intra-subject dataset partitioning and a 5-fold cross-validation method. The research diverges from conventional monitoring by utilizing anesthetic infusion rates as objective indicators of anesthesia states, highlighting distinct EEG patterns and enhancing prediction accuracy. Moreover, the model's ability to generalize across individuals suggests its potential for broad clinical application, distinguishing between anesthetic agents and their depths. Despite relying on rat EEG data, which poses questions about real-world applicability, our approach marks a significant advance in anesthesia monitoring.
Animals ; Machine Learning ; Electroencephalography/methods* ; Ketamine/administration & dosage* ; Rats ; Male ; Propofol/administration & dosage* ; Rats, Sprague-Dawley ; Anesthesia, General/methods* ; Brain/physiology* ; Intraoperative Neurophysiological Monitoring/methods*

BACKGROUND: The switch/sucrose nonfermentable chromatin-remodeling (SWI/SNF) complex is a pivotal chromatin remodeling complex, and the genomic alterations (GAs) of the SWI/SNF complex are observed in several cancer types, correlating with multiple biological features of tumor cells. However, their role in liver metastasis of non-small cell lung cancer (NSCLC) remains unclear. Our study aims to investigate the role and potential mechanisms underlying NSCLC liver metastasis induced by the GAs of SWI/SNF complex. METHODS: The GAs of SWI/SNF complex in NSCLC cell lines (H1299, H23 and H460) were identified by whole-exome sequencing (WES). ARID1A knockout H1299 cell was constructed with the CRISPR/Cas9 technology. The mouse model of liver metastasis from NSCLC was established to simulate lung cancer liver metastasis and observe the metastasis rate under different gene mutation conditions. RNA sequencing and Western blot were conducted for differential gene expression analysis. Immunohistochemistry (IHC) analysis was used to assess protein expression levels of SWI/SNF-regulated target molecules in mouse liver metastases. RESULTS: WES analysis revealed intracellular gene mutations. The animal experiments demonstrated a correlation between the GAs of SWI/SNF complex and a higher liver metastasis rate in immunodeficient mice. Transcriptome sequencing and Western blot analysis showed upregulated expression of ALDH1A1 and APOBEC3B in SWI/SNF-mut cells, particularly in ARID1A-deficient H460 and H1299 sgARID1A cells. IHC staining of mouse liver metastases further demonstrated elevated expression of ALDH1A1 in the H460 and H1299 sgARID1A group. CONCLUSIONS This study underscores the critical role of the GAs of SWI/SNF complex, such as ARID1A and SMARCA4, in promoting liver metastasis of lung cancer cells. The GAs of SWI/SNF complex may promote liver-specific metastasis by upregulating ALDH1A1 and APOBEC3B expression, providing novel insights into the molecular mechanisms underlying lung cancer liver metastasis.
Animals ; Mice ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Liver Neoplasms/genetics*

Background and objective Uridine-diphosphoglucuronosyl transferase 1A1 (UGT1A1),UGT1A1 *28 polymorphism can reduce UGT1A1 enzymatic activity,which may lead to severe toxicities in patients who receive irinotecan.This study tries to build a fragment analysis method to detect UGT1A1 *28 polymorphism.Methods A total of 286 blood specimens from the lung cancer patients who were hospitalized in Guangdong General Hospital between April 2014 to May 2015 were detected UGT1A1*28 polymorphism by fragment analysis method.Results Comparing with Sanger sequencing,precision and accuracy of the fragment analysis method were 100％.Of the 286 patients,236 (82.5％ harbored TA6/6 genotype,48 (16.8％) TA 6/7 genotype and 2 (0.7％) TA7/7 genotype.Conclusion Our data suggest hat the fragment analysis method is robust for detecting UGT1A1 *28 polymorphism in clinical practice.It's simple,time-saving,and easy-to-carry.

OBJECTIVE: To evaluate the safety of the circular round window and discus anatomic landmarks of posterior wall of internal auditory canal by investigating the microscopic anatomy of internal auditory canal area of the retrosigmold approach, which can provide the anatomical basis for acoustic neutrinomas surgery. METHOD: Fifteen adult cadaver heads (30 sides) fixed with formalin were used in the study. The retrosigmold approach operations were imitated to dissect the blood vessels and nerves in internal auditory canal area by opening round bony window and removing posterior wall of internal auditory canal. RESULT: Fifteen specimens of 30 sides circular bone window were opened without injury with transverse sinus and sigmoid sinus. The vertical distance between the highest point of bone window margo superior and the lowest point of transverse sinus margo inferior was (4.02 ± 0.32) mm. The vertical distance from the most anterior point of bone window leading edge to the most posterior point of sigmoid sinus trailing edge was (6.31 ± 0.43) mm. The internal auditory canal tubercle located in the anterior superior position of internal auditory canal. The vertical distance from the highest point of internal auditory canal tubercle to the upper margin of internal auditory canal was (2.31 ± 0.32) mm. To expose the whole internal auditory canal, the length and width of the internal auditory canal posterior wall removal was (7.29 ± 0.32) mm, (4.12 ± 0.29) mm. Within this removal range, no case of cochlea, semicircular canal or venous was injured in 30 specimens. CONCLUSION The method of opening round window through retrosigmold approach is simple, practial and convenient. With little variation and easiness of location, the sinternal auditory canal tubercle can be used in the identification of the internal auditory canal. When exposing the whole internal auditory canal, the removal scope of the posterior wall should be paid more attention to, in order to avoid the damage of cochlea, semicircular canal and jugular bulb.
Adult ; Cranial Sinuses ; Ear Canal ; Ear, Inner ; Humans ; Round Window, Ear ; anatomy & histology ; Semicircular Canals ; anatomy & histology ; Temporal Bone

Objective To explore the clinical value of spiral CT airway measurements on awake patients under OSAHS discussed. Methods The upper airway of 104 patients with OSAHS diagnosed with polysomnography (PSG) and 25 nor-mal controls were examined and compared. The cross-sectional areas, diameters, and the thickness of the pharyngeal wall of retropalate, lingua regions planes were scanned by MSCT scan in the waking state. Results The cross-section areas of upper airway of OSAHS were significantly smaller than those of the control group, the difference was significant (P<0.05). The cross-section areas decreased and the thickness of pharyngeal walls increased with the increase of severity of OSAHS. Conclusion Patients with OSAHS has upper airway anatomic strictures. MSCT scan can effectively localize the obstructed site and degree of upper airway accurately.

Summary: The aim of present study was to evaluate the feasibility and efficiency of enhanced green fluorescent protein (EGFP) gene delivery to myocardium in vivo by ultrasound targeted microbubble destruction (UTMD) and polyethylenimine (PEI). SonoVue/DNA and PEI/DNA/SonoVue complexes were prepared. Gel electrophoresis analysis was performed to determine the structural integrity of plasmid DNA or PEI/DNA after UTMD. Solutions of plasmid DNA, SonoVue/DNA, PEI/DNA complexes or PEI/DNA/SonoVue complexes were respectively transduced into BALB/c mice hearts by means of transthoracic ultrasound irradiation. Mice undergoing PBS injection, plasmid injection or PEI/DNA complexes injection without ultrasound irradiation served as controls. Gene expression in myocardium was detected 4 days after treatment. Cryosections and histological examinations were conducted. Electrophoresis gel assay showed no damage to DNA or PEI/DNA complexes after UTMD. When the heart was not exposed to ultrasound, the expression of EGFP was observed in the subendocardial myocardium obviously. The strongest expression was detected in the anterior wall of the left ventricle when the heart was exposed to ultrasound alone. Injection of PEI/DNA complexes and UTMD resulted in the highest transfection efficiency and the distributional difference of EGFP was not obvious. No tissue damage was seen histologically. In conclusion, a combination of UTMD and PEI was highly effective in transfecting mice hearts without causing any apparently adverse effect. It provides an alternative to current clinical gene therapy and opens a new concept of non-viral gene delivery for the treatment of cardiac disease.