1.Spatiotemporal Electrical Impedance Tomography for Speech Respiratory Assessment in Cleft Palate: an Interpretable Machine Learning Study
Yang WU ; Xiao-Jing ZHANG ; Hao YU ; Cheng-Hui JIANG ; Bo SUN ; Jia-Feng YAO
Progress in Biochemistry and Biophysics 2026;53(2):485-500
ObjectiveCleft palate (CP) is a common congenital deformity often associated with velopharyngeal insufficiency (VPI), which disrupts the physiological coupling between respiration and speech. Conventional clinical assessments, such as nasometry and spirometry, provide limited static data and fail to visualize the dynamic spatiotemporal distribution of lung ventilation during phonation. This study introduces spatiotemporal electrical impedance tomography (ST-EIT) to evaluate speech-respiratory functional features in CP patients compared to normal controls (NC). The aim is to characterize multi-domain respiratory patterns and to validate an interpretable machine learning framework for providing objective, quantitative evidence for clinical assessment. MethodsSeventy-five participants were enrolled in this study, comprising 37 patients with surgically repaired CP and 38 healthy volunteers matched for age, gender, and body mass index (BMI). All subjects performed standardized sustained phonation tasks while undergoing synchronous monitoring with a 16-electrode EIT system and a pneumotachograph. A comprehensive feature engineering pipeline was developed to extract physiological parameters across 3 complementary domains. (1) Temporal domain: including inspiratory/expiratory phase duration (tPhase), time constants (Tau), and inspiratory-to-expiratory time ratios (TI/TE); (2) airflow domain: comprising mean flow, peak flow, and instantaneous flow at 25%, 50%, and 75% of tidal volume; and (3) spatial domain: quantifying global and regional tidal impedance variation (TIV), global inhomogeneity (GI), and center of ventilation (CoV). Extreme Gradient Boosting (XGBoost) classifiers were trained using 5 distinct data sources (Spirometry, Nasometry, Inspiratory-EIT, Expiratory-EIT, and fused ST-EIT). Model performance was rigorously evaluated via stratified 5-fold cross-validation, and Shapley additive explanations (SHAP) were employed to quantify global and local feature contributions. ResultsThe CP group exhibited a distinct respiratory phenotype compared to controls. In the temporal domain, CP patients showed significantly shorter inspiratory (1.60 s vs.1.85 s, P<0.001) and expiratory phase durations (2.45 s vs. 3.95 s, P<0.001), indicating a rapid, shallow breathing rhythm. In the airflow domain, while inspiratory flows were comparable, the CP group demonstrated significantly elevated mean and peak flows during the expiratory phase (P<0.001), reflecting compensatory respiratory effort. Spatially, CP patients presented significant ventilation redistribution, characterized by higher regional TIV in the right-anterior (ROI1) and left-posterior (ROI4) quadrants, but lower TIV in the left-anterior (ROI2) quadrant. In terms of diagnostic accuracy, the multi-modal ST-EIT model achieved the highest performance (AUC: 0.915±0.012, Accuracy: 0.843±0.019, F1-score: 0.872±0.017), substantially outperforming models based on spirometry (AUC: 0.721) or nasometry (AUC: 0.625) alone. Interpretability analysis revealed that spatial domain features were the most critical, contributing 53.4% to the model’s decision-making, followed by temporal (25.0%) and airflow (21.6%) features. ConclusionST-EIT successfully captures the temporal, airflow, and spatial deviations in CP speech respiration that are undetectable by conventional methods—specifically, rapid phase transitions, hyperdynamic expiratory airflow, and regional ventilation heterogeneity. This study validates ST-EIT as a robust, non-invasive, and radiation-free tool for characterizing speech-respiratory dysfunction, offering high clinical value for bedside screening, rehabilitation planning, and longitudinal monitoring of patients with cleft palate.
2.Spatiotemporal Electrical Impedance Tomography for Speech Respiratory Assessment in Cleft Palate: an Interpretable Machine Learning Study
Yang WU ; Xiao-Jing ZHANG ; Hao YU ; Cheng-Hui JIANG ; Bo SUN ; Jia-Feng YAO
Progress in Biochemistry and Biophysics 2026;53(2):485-500
ObjectiveCleft palate (CP) is a common congenital deformity often associated with velopharyngeal insufficiency (VPI), which disrupts the physiological coupling between respiration and speech. Conventional clinical assessments, such as nasometry and spirometry, provide limited static data and fail to visualize the dynamic spatiotemporal distribution of lung ventilation during phonation. This study introduces spatiotemporal electrical impedance tomography (ST-EIT) to evaluate speech-respiratory functional features in CP patients compared to normal controls (NC). The aim is to characterize multi-domain respiratory patterns and to validate an interpretable machine learning framework for providing objective, quantitative evidence for clinical assessment. MethodsSeventy-five participants were enrolled in this study, comprising 37 patients with surgically repaired CP and 38 healthy volunteers matched for age, gender, and body mass index (BMI). All subjects performed standardized sustained phonation tasks while undergoing synchronous monitoring with a 16-electrode EIT system and a pneumotachograph. A comprehensive feature engineering pipeline was developed to extract physiological parameters across 3 complementary domains. (1) Temporal domain: including inspiratory/expiratory phase duration (tPhase), time constants (Tau), and inspiratory-to-expiratory time ratios (TI/TE); (2) airflow domain: comprising mean flow, peak flow, and instantaneous flow at 25%, 50%, and 75% of tidal volume; and (3) spatial domain: quantifying global and regional tidal impedance variation (TIV), global inhomogeneity (GI), and center of ventilation (CoV). Extreme Gradient Boosting (XGBoost) classifiers were trained using 5 distinct data sources (Spirometry, Nasometry, Inspiratory-EIT, Expiratory-EIT, and fused ST-EIT). Model performance was rigorously evaluated via stratified 5-fold cross-validation, and Shapley additive explanations (SHAP) were employed to quantify global and local feature contributions. ResultsThe CP group exhibited a distinct respiratory phenotype compared to controls. In the temporal domain, CP patients showed significantly shorter inspiratory (1.60 s vs.1.85 s, P<0.001) and expiratory phase durations (2.45 s vs. 3.95 s, P<0.001), indicating a rapid, shallow breathing rhythm. In the airflow domain, while inspiratory flows were comparable, the CP group demonstrated significantly elevated mean and peak flows during the expiratory phase (P<0.001), reflecting compensatory respiratory effort. Spatially, CP patients presented significant ventilation redistribution, characterized by higher regional TIV in the right-anterior (ROI1) and left-posterior (ROI4) quadrants, but lower TIV in the left-anterior (ROI2) quadrant. In terms of diagnostic accuracy, the multi-modal ST-EIT model achieved the highest performance (AUC: 0.915±0.012, Accuracy: 0.843±0.019, F1-score: 0.872±0.017), substantially outperforming models based on spirometry (AUC: 0.721) or nasometry (AUC: 0.625) alone. Interpretability analysis revealed that spatial domain features were the most critical, contributing 53.4% to the model’s decision-making, followed by temporal (25.0%) and airflow (21.6%) features. ConclusionST-EIT successfully captures the temporal, airflow, and spatial deviations in CP speech respiration that are undetectable by conventional methods—specifically, rapid phase transitions, hyperdynamic expiratory airflow, and regional ventilation heterogeneity. This study validates ST-EIT as a robust, non-invasive, and radiation-free tool for characterizing speech-respiratory dysfunction, offering high clinical value for bedside screening, rehabilitation planning, and longitudinal monitoring of patients with cleft palate.
3.Characterization and Application of Moisture Absorption Kinetics of Traditional Chinese Medicines Based on Double Exponential Model:A Review
Yanting YU ; Lei XIONG ; Yan HE ; Wei LIU ; Jing YANG ; Yao ZHANG ; Jiali CHEN ; Xiaojian LUO ; Xiaoyong RAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):340-346
Hygroscopicity research has long been a key focus and hot topic in Chinese materia medica(CMM). Elucidating hygroscopic mechanisms plays a vital role in formulation design, process optimization, and storage condition selection. Hygroscopic models serve as essential tools for characterizing CMM hygroscopic mechanisms, with various types available. The double exponential model is a kinetic mathematical model constructed based on the law of conservation of energy and Fick's first law of diffusion, tailored to the physical properties of CMM extracts. In recent years, this model has been extensively applied to simulate the dynamic moisture absorption behavior of CMM extracts and solid dosage forms under varying humidity conditions. It has revealed the correlation between moisture absorption kinetic parameters and material properties, offering a new perspective for characterizing the moisture uptake behavior of CMM. This paper systematically reviews the application progress of this model in the field of CMM, analyzes its advantages, disadvantages, and challenges in this domain, and explores its potential application trends in other fields. It aims to provide references for elucidating the moisture absorption mechanisms of CMM and researching moisture-proofing technologies, while also offering insights for its broader application in food and polymer materials.
4.Analysis of related factors for the comorbidity of allergic rhinitis and obesity among primary and secondary school students in Inner Mongolia
Chinese Journal of School Health 2026;47(1):27-31
Objective:
To investigate the factors influencing the co-prevalence of allergic rhinitis and obesity among primary and secondary school students in Inner Mongolia, so as to provide a data foundation and theoretical basis for developing targeted intervention measures.
Methods:
In September and October 2024, a stratified cluster random sampling method was employed to select 139 102 students from 539 schools across 12 leagues/cities and 103 banners/counties in Inner Mongolia Autonomous Region. Participants who were diagnosed with allergic rhinitis by a doctor at least once within one year and had a body mass index ≥ 28 kg/m 2 were considered to have comorbid conditions.
Results:
The coprevalence rate of allergic rhinitis and obesity among primary and secondary school students in Inner Mongolia was 6.4% (8 931 cases). Lasso-Logistic regression revealed that nonboarding status, higher maternal education, consuming high protein foods ≥1 time daily, occasionally or never eating breakfast, engaging in moderate to vigorous physical activity for ≥60 minutes on fewer than half of holidays, and having been exposed to second hand smoke in person within the past seven days were associated with higher odds ratios for co-prevalence of allergic rhinitis and obesity( OR = 1.23 , 1.22-1.63, 1.20, 1.19, 1.38, 1.35); being female, higher grade level, residence in flag/county/district areas, non only child status, never having consumed a full glass of alcohol, non hypertensive status, and households without pets were associated with lower co-prevalence risks ( OR =0.65, 0.67-0.77, 0.81, 0.87, 0.73, 0.41, 0.68) (all P <0.05). The ROC curve indicated an area under the curve of 0.64 for the predictive model, demonstrating satisfactory discriminatory ability. The calibration curve showed consistency between predicted and actual occurrence probabilities.
Conclusions
The co-prevalence of allergic rhinitis and obesity among primary and secondary school students in Inner Mongolia is closely associated with demographic characteristics, dietary behaviours, and lifestyle habits. Future prevention and control strategies should prioritize these factors to implement targeted interventions.
5.Study on the compatibility stability of 16 commonly used intravenous antibiotics in ICU
Liting ZHANG ; Haotian YANG ; Siqi YU ; Liju FAN ; Jing AN
China Pharmacy 2026;37(4):468-475
OBJECTIVE To systematically analyze the compatibility stability of commonly used intravenous antibiotics in the intensive care unit (ICU), and to provide evidence-based support for rational clinical drug use. METHODS Medication data from the ICU of Hebei General Hospital between January and December 2024 were extracted from the Prescription Automatic Screening System. Commonly used intravenous antibiotics and other intravenous drugs in the ICU were selected through consultations with critical care and pharmacy experts in Hebei province, drug package inserts and compatibility information retrieved from Micromedex, Trissel’s Injectable Drug Handbook and PubMed. The physicochemical stability of drug combinations was analyzed. In addition, Cytoscape 3.10.2 software was used to construct a drug compatibility network for identifying high-risk drugs. RESULTS &CONCLUSIONS A total of 904 pairwise drug combinations involving 16 antibacterial agents and 65 intravenous drugs were collected. Among them, 549 combinations (60.7%) were compatible, 88 combinations (9.7%) were incompatible, 82 combinations (9.1%) had conflicting evidence, and 185 combinations (20.5%) lacked valid data support. High-risk combination drugs primarily involved Amphotericin B for injection, Ceftazidime for injection, Imipenem-cilastatin for injection, Ceftriaxone sodium for injection, Vancomycin hydrochloride for injection, etc. The main risk factors for drug-drug incompatibility included drug concentration, temperature, mixing rate, pH, and chemical structure. In clinical practice, drugs and diluents should be selected rationally based on specific compatibility data, and research and monitoring of drug compatibility should be further strengthened.
6.Investigation of Effect of Different Drying Conditions on Appearance Characteristics and Internal Indicators of Pinelliae Rhizoma Based on Standardization
Suqing LIU ; Xueli ZHANG ; Jing ZHANG ; Cong YANG ; Changfu YANG ; Jun YU ; Bingpeng ZHENG ; Huiwu LI ; Yanhua JIANG ; Chang LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):208-215
ObjectiveTo explore the effect of different drying conditions on the appearance and intrinsic quality indicators of Pinelliae Rhizoma for screening suitable drying conditions, so as to provide reference for its standardized production and quality evaluation. MethodsDifferent dried samples of Pinelliae Rhizoma were prepared by lime-assisted sweating method and intermittent drying method. Visual analysis was employed to measure the color brightness values(L*) of the surface, cross-section and powder of the samples, texture analyzer was used to determine the hardness of the samples under different drying conditions. The total starch content was calculated by measuring the contents of amylose and amylopectin in the samples with ultraviolet-visible spectroscopy. High performance liquid chromatography(HPLC) was used to determine the contents of seven nucleoside components(uracil, hypoxanthine, uridine, inosine, guanosine, β-thymidine and adenosine) in the samples. Pearson correlation analysis was conducted to explore the correlation between the external characteristics and intrinsic indicators of the different dried samples. Principal component analysis(PCA) was used to comprehensively rank the data of various indicators, and partial least squares-discriminant analysis(PLS-DA) was used to screen differential components with variable importance in the projection(VIP) value>1. Furthermore, the difference between the optimal drying condition for Pinelliae Rhizoma and the traditional sun-drying method was explored by independent samples t-test. ResultsWith the increase of temperature, the color of the intermittently dried samples gradually deepened, while their hardness gradually decreased. Concurrently, the contents of extract, total starch, uridine and adenosine exhibited an upward trend, whereas the contents of uracil, hypoxanthine and inosine displayed a downward trajectory. Compared with the intermittent drying group, the content of extract in the samples subjected to lime-assisted sweating increased. With the increase of lime dose, the hardness and the total content of nucleoside components in the samples showed a downward trend, while the total starch content showed an upward trend. Correlation analysis showed that the comprehensive score of L* was negatively correlated with the contents of uracil, hypoxanthine and inosine, and positively correlated with the contents of uridine, guanosine and adenosine. Hardness was negatively correlated with adenosine content, and positively correlated with the contents of inosine, uracil and hypoxanthine. Through comprehensive consideration and comprehensive score of principal components, the method of 5% lime-mixed sweating for 6 days emerged as the top-ranking approach. Except for the extract, the results of independent samples t-test showed that there was no significant difference between the 5% lime-mixed sweating for 6 days and the traditional sun-drying in terms of other content indicators. ConclusionThe whiteness and firmness of Pinelliae Rhizoma exhibit significant correlations with its chemical composition, while uridine, uracil, guanosine, adenosine and inosine are the key constituents responsible for the quality difference of Pinelliae Rhizoma under different drying conditions. The lime-assisted sweating method optimized in this study can be proposed as a viable alternative to the traditional sun-drying method. This method not only ensures the quality of the medicinal material but also effectively reduces the drying time and prevents mold contamination, which provides a valuable reference for the standardization of drying conditions and the establishment of quality evaluation criteria for Pinelliae Rhizoma.
7.Prevalence trends of elevated blood pressure and its association with nutritional status among primary and secondary school students in Inner Mongolia
Chinese Journal of School Health 2025;46(9):1342-1345
Objective:
To analyze the prevalence trends of different types of elevated blood pressure and their association with nutritional status among primary and secondary school students in Inner Mongolia from 2019 to 2024, providing references for targeted prevention strategies.
Methods:
From September 2019 to 2024, a stratified random cluster sampling method was used to select 12 primary and secondary schools from each league city in Inner Mongolia Autonomous Region. A total of 177 108, 137 758, 190 182, 180 084 , 188 056, 180 351 primary and secondary school students (excluding grades one to three of primary school) were included for physical examination. The correlation between their nutritional status and high blood pressure was analyzed based on the basic situation of 129 821 primary and secondary school students who completed a questionnaire survey at the same time in 2024. Statistical analysis was conducted using a Chi-square test and multiple Logistic regression model.
Results:
From 2019 to 2024, the detection rates of elevated blood pressure were 13.60%, 13.68%, 17.60%, 17.24%, 14.77% and 15.96%, respectively. The rates for isolated systolic hypertension were 4.24%, 5.83%, 7.26%, 7.19%, 6.24% and 6.93%; isolated diastolic hypertension rates were 6.38%, 4.99%, 6.23 %, 6.41%, 5.39% and 5.66%; and combined systolic and diastolic hypertension rates were 2.97%, 2.86%, 4.11%, 3.65%, 3.14 % and 3.36%. Multivariate Logistic regression analysis showed that girls, junior high school, senior high school, overweight, and obesity were positively associated with elevated blood pressure risk ( OR =1.27, 1.25, 1.32, 1.66, 3.07, all P <0.05); conversely, county residence, Mongolian ethnicity, and other ethnicities showed negative associations ( OR =0.90, 0.93, 0.90, all P <0.05).
Conclusions
Overweight and obesity among children and adolescents are closely related to various types of elevated blood pressure. Prevention strategies should prioritize effectively controlling weight issues among children and adolescents, thereby effectively reducing the incidence of elevated blood pressure.
8.Clinical Efficacy of Xiaoji Hufei Formula in Protecting Children with Close Contact Exposure to Influenza: A Multicenter,Prospective, Non-randomized, Parallel, Controlled Trial
Jing WANG ; Jianping LIU ; Tiegang LIU ; Hong WANG ; Yingxin FU ; Jing LI ; Huaqing TAN ; Yingqi XU ; Yanan MA ; Wei WANG ; Jia WANG ; Haipeng CHEN ; Yuanshuo TIAN ; Yang WANG ; Chen BAI ; Zhendong WANG ; Qianqian LI ; He YU ; Xueyan MA ; Fei DONG ; Liqun WU ; Xiaohong GU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):223-230
ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza, and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter, prospective, non-randomized, parallel, controlled trial was conducted from October 2021 to May 2022 in five hospitals, including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness (ILI) cases were collected, and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention, they were assigned to the observation group (108 cases) or the control group (108 cases). Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine (TCM) symptom score scale for influenza, influenza-related emergency (outpatient) visit rate, influenza hospitalization rate, and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled, with 108 in the observation group and 108 in the control group. Primary outcomes: (1) Incidence of ILI: The incidence was 12.0% (13/108) in the observation group and 23.1% (25/108) in the control group, with the observation group showing a significantly lower incidence (χ2=4.6, P<0.05). (2) Influenza confirmation rate: 3.7% (4/108) in the observation group and 4.6% (5/108) in the control group, with no statistically significant difference. Secondary outcomes: (1) TCM symptom score scale: after onset, nasal congestion and runny nose scores differed significantly between the two groups (P<0.05), while other symptoms such as fever, sore throat, and cough showed no significant differences. (2) Influenza-related emergency (outpatient) visit rate: 84.6% (11 cases) in the observation group and 96.0% (24 cases) in the control group, with no significant difference. (3) Time to onset after exposure: The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group, with a statistically significant difference (P<0.05). ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions, Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.
9.Clinical Efficacy of Xiaoji Hufei Formula in Protecting Children with Close Contact Exposure to Influenza: A Multicenter,Prospective, Non-randomized, Parallel, Controlled Trial
Jing WANG ; Jianping LIU ; Tiegang LIU ; Hong WANG ; Yingxin FU ; Jing LI ; Huaqing TAN ; Yingqi XU ; Yanan MA ; Wei WANG ; Jia WANG ; Haipeng CHEN ; Yuanshuo TIAN ; Yang WANG ; Chen BAI ; Zhendong WANG ; Qianqian LI ; He YU ; Xueyan MA ; Fei DONG ; Liqun WU ; Xiaohong GU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):223-230
ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza, and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter, prospective, non-randomized, parallel, controlled trial was conducted from October 2021 to May 2022 in five hospitals, including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness (ILI) cases were collected, and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention, they were assigned to the observation group (108 cases) or the control group (108 cases). Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine (TCM) symptom score scale for influenza, influenza-related emergency (outpatient) visit rate, influenza hospitalization rate, and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled, with 108 in the observation group and 108 in the control group. Primary outcomes: (1) Incidence of ILI: The incidence was 12.0% (13/108) in the observation group and 23.1% (25/108) in the control group, with the observation group showing a significantly lower incidence (χ2=4.6, P<0.05). (2) Influenza confirmation rate: 3.7% (4/108) in the observation group and 4.6% (5/108) in the control group, with no statistically significant difference. Secondary outcomes: (1) TCM symptom score scale: after onset, nasal congestion and runny nose scores differed significantly between the two groups (P<0.05), while other symptoms such as fever, sore throat, and cough showed no significant differences. (2) Influenza-related emergency (outpatient) visit rate: 84.6% (11 cases) in the observation group and 96.0% (24 cases) in the control group, with no significant difference. (3) Time to onset after exposure: The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group, with a statistically significant difference (P<0.05). ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions, Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.
10.Precision therapy targeting CAMK2 to overcome resistance to EGFR inhibitors in FAT1 -mutated oral squamous cell carcinoma.
Yumeng LIN ; Yibo HUANG ; Bowen YANG ; You ZHANG ; Ning JI ; Jing LI ; Yu ZHOU ; Ying-Qiang SHEN ; Qianming CHEN
Chinese Medical Journal 2025;138(15):1853-1865
BACKGROUND:
Oral squamous cell carcinoma (OSCC) is a prevalent type of cancer with a high mortality rate in its late stages. One of the major challenges in OSCC treatment is the resistance to epidermal growth factor receptor (EGFR) inhibitors. Therefore, it is imperative to elucidate the mechanism underlying drug resistance and develop appropriate precision therapy strategies to enhance clinical efficacy.
METHODS:
To evaluate the efficacy of the combination of the Ca 2+ /calmodulin-dependent protein kinase II (CAMK2) inhibitor KN93 and EGFR inhibitors, we performed in vitro and in vivo experiments using two FAT atypical cadherin 1 ( FAT1 )-deficient (SCC9 and SCC25) and two FAT1 wild-type (SCC47 and HN12) OSCC cell lines. We assessed the effects of EGFR inhibitors (afatinib or cetuximab), KN93, or their combination on the malignant phenotype of OSCC in vivo and in vitro . The alterations in protein expression levels of members of the EGFR signaling pathway and SRY-box transcription factor 2 (SOX2) were analyzed. Changes in the yes-associated protein 1 (YAP1) protein were characterized. Moreover, we analyzed mitochondrial dysfunction. Besides, the effects of combination therapy on mitochondrial dynamics were also evaluated.
RESULTS:
OSCC with FAT1 mutations exhibited resistance to EGFR inhibitors treatment. The combination of KN93 and EGFR inhibitors significantly inhibited the proliferation, survival, and migration of FAT1 -mutated OSCC cells and suppressed tumor growth in vivo . Mechanistically, combination therapy enhanced the therapeutic sensitivity of FAT1 -mutated OSCC cells to EGFR inhibitors by modulating the EGFR pathway and downregulated tumor stemness-related proteins. Furthermore, combination therapy induced reactive oxygen species (ROS)-mediated mitochondrial dysfunction and disrupted mitochondrial dynamics, ultimately resulting in tumor suppression.
CONCLUSION
Combination therapy with EGFR inhibitors and KN93 could be a novel precision therapeutic strategy and a potential clinical solution for EGFR-resistant OSCC patients with FAT1 mutations.
Humans
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ErbB Receptors/metabolism*
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Mouth Neoplasms/metabolism*
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Cell Line, Tumor
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Animals
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Drug Resistance, Neoplasm/genetics*
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Cadherins/metabolism*
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Carcinoma, Squamous Cell/metabolism*
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Mice
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Mutation/genetics*
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Mice, Nude
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Protein Kinase Inhibitors/therapeutic use*
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Cetuximab/pharmacology*
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Afatinib/therapeutic use*
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Cell Proliferation/drug effects*
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Signal Transduction/drug effects*


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