1.Gene Expression Alteration by Non-thermal Plasma-Activated Media Treatment in Radioresistant Head and Neck Squamous Cell Carcinoma
Sicong ZHENG ; Yudan PIAO ; Seung-Nam JUNG ; Chan OH ; Mi Ae LIM ; QuocKhanh NGUYEN ; Shan SHEN ; Se-Hee PARK ; Shengzhe CUI ; Shuyu PIAO ; Young Il KIM ; Ji Won KIM ; Ho-Ryun WON ; Jae Won CHANG ; Yujuan SHAN ; Lihua LIU ; Bon Seok KOO
Clinical and Experimental Otorhinolaryngology 2025;18(1):73-87
Objectives:
. Head and neck squamous cell carcinoma (HNSCC) exhibits high recurrence rates, particularly in cases of radioresistant HNSCC (RR-HNSCC). Non-thermal plasma (NTP) therapy effectively suppresses the progression of HNSCC. However, the therapeutic mechanisms of NTP therapy in treating RR-HNSCC are not well understood. In this study, we explored the regulatory role of NTP in the RR-HNSCC signaling pathway and identified its signature genes.
Methods:
. After constructing two RR-HNSCC cell lines, we prepared cell lysates from cells treated or not treated with NTP-activated media (NTPAM) and performed RNA sequencing to determine their mRNA expression profiles. Based on the RNA sequencing results, we identified differentially expressed genes (DEGs), followed by a bioinformatics analysis to identify candidate molecules potentially associated with NTPAM therapy for RR-HNSCC.
Results:
. NTPAM reduced RR-HNSCC cell viability in vitro. RNA sequencing results indicated that NTPAM treatment activated the reactive oxygen species (ROS) pathway and induced ferroptosis in RR-HNSCC cell lines. Among the 1,924 genes correlated with radiation treatment, eight showed statistical significance in both the cell lines and The Cancer Genome Atlas (TCGA) cohort. Only five genes—ABCC3, DUSP16, PDGFB, RAF1, and THBS1—showed consistent results between the NTPAM data sequencing and TCGA data. LASSO regression analysis revealed that five genes were associated with cancer prognosis, with a hazard ratio of 2.26. In RR-HNSCC cells, NTPAM affected DUSP16, PDGFB, and THBS1 as activated markers within 6 hours, and this effect persisted for 12 hours. Furthermore, enrichment analysis indicated that these three DEGs were associated with the extracellular matrix, transforming growth factor-beta, phosphoinositide 3-kinase/protein kinase B, and mesenchymal-epithelial transition factor pathways.
Conclusion
. NTPAM therapy exerts cytotoxic effects in RR-HNSCC cell lines by inducing specific ROS-mediated ferroptosis. DUSP16, PDGFB, and THBS1 were identified as crucial targets for reversing the radiation resistance induced by NTPAM therapy, providing insights into the mechanisms and clinical applications of NTPAM treatment in RR-HNSCC.
2.Gene Expression Alteration by Non-thermal Plasma-Activated Media Treatment in Radioresistant Head and Neck Squamous Cell Carcinoma
Sicong ZHENG ; Yudan PIAO ; Seung-Nam JUNG ; Chan OH ; Mi Ae LIM ; QuocKhanh NGUYEN ; Shan SHEN ; Se-Hee PARK ; Shengzhe CUI ; Shuyu PIAO ; Young Il KIM ; Ji Won KIM ; Ho-Ryun WON ; Jae Won CHANG ; Yujuan SHAN ; Lihua LIU ; Bon Seok KOO
Clinical and Experimental Otorhinolaryngology 2025;18(1):73-87
Objectives:
. Head and neck squamous cell carcinoma (HNSCC) exhibits high recurrence rates, particularly in cases of radioresistant HNSCC (RR-HNSCC). Non-thermal plasma (NTP) therapy effectively suppresses the progression of HNSCC. However, the therapeutic mechanisms of NTP therapy in treating RR-HNSCC are not well understood. In this study, we explored the regulatory role of NTP in the RR-HNSCC signaling pathway and identified its signature genes.
Methods:
. After constructing two RR-HNSCC cell lines, we prepared cell lysates from cells treated or not treated with NTP-activated media (NTPAM) and performed RNA sequencing to determine their mRNA expression profiles. Based on the RNA sequencing results, we identified differentially expressed genes (DEGs), followed by a bioinformatics analysis to identify candidate molecules potentially associated with NTPAM therapy for RR-HNSCC.
Results:
. NTPAM reduced RR-HNSCC cell viability in vitro. RNA sequencing results indicated that NTPAM treatment activated the reactive oxygen species (ROS) pathway and induced ferroptosis in RR-HNSCC cell lines. Among the 1,924 genes correlated with radiation treatment, eight showed statistical significance in both the cell lines and The Cancer Genome Atlas (TCGA) cohort. Only five genes—ABCC3, DUSP16, PDGFB, RAF1, and THBS1—showed consistent results between the NTPAM data sequencing and TCGA data. LASSO regression analysis revealed that five genes were associated with cancer prognosis, with a hazard ratio of 2.26. In RR-HNSCC cells, NTPAM affected DUSP16, PDGFB, and THBS1 as activated markers within 6 hours, and this effect persisted for 12 hours. Furthermore, enrichment analysis indicated that these three DEGs were associated with the extracellular matrix, transforming growth factor-beta, phosphoinositide 3-kinase/protein kinase B, and mesenchymal-epithelial transition factor pathways.
Conclusion
. NTPAM therapy exerts cytotoxic effects in RR-HNSCC cell lines by inducing specific ROS-mediated ferroptosis. DUSP16, PDGFB, and THBS1 were identified as crucial targets for reversing the radiation resistance induced by NTPAM therapy, providing insights into the mechanisms and clinical applications of NTPAM treatment in RR-HNSCC.
3.Gene Expression Alteration by Non-thermal Plasma-Activated Media Treatment in Radioresistant Head and Neck Squamous Cell Carcinoma
Sicong ZHENG ; Yudan PIAO ; Seung-Nam JUNG ; Chan OH ; Mi Ae LIM ; QuocKhanh NGUYEN ; Shan SHEN ; Se-Hee PARK ; Shengzhe CUI ; Shuyu PIAO ; Young Il KIM ; Ji Won KIM ; Ho-Ryun WON ; Jae Won CHANG ; Yujuan SHAN ; Lihua LIU ; Bon Seok KOO
Clinical and Experimental Otorhinolaryngology 2025;18(1):73-87
Objectives:
. Head and neck squamous cell carcinoma (HNSCC) exhibits high recurrence rates, particularly in cases of radioresistant HNSCC (RR-HNSCC). Non-thermal plasma (NTP) therapy effectively suppresses the progression of HNSCC. However, the therapeutic mechanisms of NTP therapy in treating RR-HNSCC are not well understood. In this study, we explored the regulatory role of NTP in the RR-HNSCC signaling pathway and identified its signature genes.
Methods:
. After constructing two RR-HNSCC cell lines, we prepared cell lysates from cells treated or not treated with NTP-activated media (NTPAM) and performed RNA sequencing to determine their mRNA expression profiles. Based on the RNA sequencing results, we identified differentially expressed genes (DEGs), followed by a bioinformatics analysis to identify candidate molecules potentially associated with NTPAM therapy for RR-HNSCC.
Results:
. NTPAM reduced RR-HNSCC cell viability in vitro. RNA sequencing results indicated that NTPAM treatment activated the reactive oxygen species (ROS) pathway and induced ferroptosis in RR-HNSCC cell lines. Among the 1,924 genes correlated with radiation treatment, eight showed statistical significance in both the cell lines and The Cancer Genome Atlas (TCGA) cohort. Only five genes—ABCC3, DUSP16, PDGFB, RAF1, and THBS1—showed consistent results between the NTPAM data sequencing and TCGA data. LASSO regression analysis revealed that five genes were associated with cancer prognosis, with a hazard ratio of 2.26. In RR-HNSCC cells, NTPAM affected DUSP16, PDGFB, and THBS1 as activated markers within 6 hours, and this effect persisted for 12 hours. Furthermore, enrichment analysis indicated that these three DEGs were associated with the extracellular matrix, transforming growth factor-beta, phosphoinositide 3-kinase/protein kinase B, and mesenchymal-epithelial transition factor pathways.
Conclusion
. NTPAM therapy exerts cytotoxic effects in RR-HNSCC cell lines by inducing specific ROS-mediated ferroptosis. DUSP16, PDGFB, and THBS1 were identified as crucial targets for reversing the radiation resistance induced by NTPAM therapy, providing insights into the mechanisms and clinical applications of NTPAM treatment in RR-HNSCC.
4.Influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis
Danqing XU ; Huan MU ; Yingyuan ZHANG ; Lixian CHANG ; Yuanzhen WANG ; Weikun LI ; Zhijian DONG ; Lihua ZHANG ; Yijing CHENG ; Li LIU
Journal of Clinical Hepatology 2025;41(2):269-276
ObjectiveTo investigate the influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis, and to establish a predictive model. MethodsA total of 217 patients who were diagnosed with decompensated hepatitis C cirrhosis and were admitted to The Third People’s Hospital of Kunming l from January, 2019 to December, 2022 were enrolled, among whom 63 patients who were readmitted within at least 1 year and had no portal hypertension-related complications were enrolled as recompensation group, and 154 patients without recompensation were enrolled as control group. Related clinical data were collected, and univariate and multivariate analyses were performed for the factors that may affect the occurrence of recompensation. The independent-samples t test was used for comparison of normally distributed measurement data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed measurement data between two groups; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. A binary Logistic regression analysis was used to investigate the influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis, and the receiver operating characteristic (ROC) curve was used to assess the predictive performance of the model. ResultsAmong the 217 patients with decompensated hepatitis C cirrhosis, 63 (29.03%) had recompensation. There were significant differences between the recompensation group and the control group in HIV history (χ2=4.566, P=0.034), history of partial splenic embolism (χ2=6.687, P=0.014), Child-Pugh classification (χ2=11.978, P=0.003), grade of ascites (χ2=14.229, P<0.001), albumin (t=4.063, P<0.001), prealbumin (Z=-3.077, P=0.002), high-density lipoprotein (t=2.854, P=0.011), high-sensitivity C-reactive protein (Z=-2.447, P=0.014), prothrombin time (Z=-2.441, P=0.015), carcinoembryonic antigen (Z=-2.113, P=0.035), alpha-fetoprotein (AFP) (Z=-2.063, P=0.039), CA125 (Z=-2.270, P=0.023), TT3 (Z=-3.304, P<0.001), TT4 (Z=-2.221, P=0.026), CD45+ (Z=-2.278, P=0.023), interleukin-5 (Z=-2.845, P=0.004), tumor necrosis factor-α (Z=-2.176, P=0.030), and portal vein width (Z=-5.283, P=0.005). The multivariate analysis showed that history of partial splenic embolism (odds ratio [OR]=3.064, P=0.049), HIV history (OR=0.195, P=0.027), a small amount of ascites (OR=3.390, P=0.017), AFP (OR=1.003, P=0.004), and portal vein width (OR=0.600, P<0.001) were independent influencing factors for the occurrence of recompensation in patients with decompensated hepatitis C cirrhosis. The ROC curve analysis showed that HIV history, grade of ascites, history of partial splenic embolism, AFP, portal vein width, and the combined predictive model of these indices had an area under the ROC curve of 0.556, 0.641, 0.560, 0.589, 0.745, and 0.817, respectively. ConclusionFor patients with decompensated hepatitis C cirrhosis, those with a history of partial splenic embolism, a small amount of ascites, and an increase in AFP level are more likely to experience recompensation, while those with a history of HIV and an increase in portal vein width are less likely to experience recompensation.
5.Research Progress of Cellular Mechanosensors Mediating Cancer Pain
Chang LIU ; Haiyan LI ; Lihua HANG
Journal of Medical Biomechanics 2025;40(4):1040-1049
Cellular mechanical transduction is the process by which cells perceive mechanical signals and transform them into chemical ones.Crucial cellular mechanosensors include PIEZO,TRPV4,and integrins.These sensors can modulate specific pathophysiological processes,such as fibrosis,tumor development,as well as cell proliferation,differentiation,and movement.Recent researches indicate that PIEZO,TRPV4,and integrins play an important role in various types of cancer pain,such as bone cancer pain,by detecting mechanical stimuli,which subsequently activate internal signaling pathways.This review summarizes advancements of PIEZO,TRPV4,and interegrins in cancer pain researches,aiming to lay a foundation for developing new therapeutic drugs that target cellular mechanical transduction for treating cancer pain.
6.Development and Initial Use of a New Inflammatory Bowel Disease Clinical Database Integrating Both Eastern and Western Clinical Characteristics
Jingshuang YAN ; Rongrong REN ; Ruqi CHANG ; Wanyue DAN ; Xiaohan ZHANG ; Fei PAN ; Bin YAN ; Hongzhe LEE ; Ni JOSIE ; Gang SUN ; Lihua PENG ; Wu Gary D. ; Yunsheng YANG
Chronic Diseases and Translational Medicine 2025;11(2):130-139
Background::The increasing incidence of inflammatory bowel disease (IBD) presents significant medical and societal challenges. A well-designed IBD database is crucial for both epidemiological studies and clinical management. However, inconsistencies between regional databases hinder cross-institutional and international research, especially between Eastern and Western societies.Methods::We developed a new IBD database, the 301 IBD database, integrating the IBD clinical characteristics from the Penn IBD database (USA) and the latest IBD guidelines and consensus and clinical practices of the Chinese PLA General Hospital (PLAGH). We applied this database to analyze clinical data of IBD inpatients at PLAGH from 2008 to 2023.Results::The 301 IBD database contains 490 items in 6 sections including demographic characteristics, personal history, clinical phenotype, disease activity, laboratory tests and examinations, and treatment. Features of the 301 IBD database include inpatient focus, biochemical indicators and opportunistic infection focus, and more about ulcerative colitis (UC)-associated complications. Single-center analysis revealed an increasing hospitalization trend, from 2.35% in 2008 to 3.94% in 2023. We found that the clinical characteristics of our UC inpatients are predominantly male (62.5%), extensive lesions (55.1%), low usage of biologics (4.1%), and a high incidence of UC-CRC (3.0%). The clinical characteristics of CD inpatients included male predominance (68.39%), early onset age (35.43 ± 14.75-year-old), and high rate of surgery (25.81%).Conclusion::The 301 IBD database, integrating Eastern and Western clinical data, provides a valuable tool for IBD clinical research. Future international, multicenter collaborations are expected to further enhance its utility.
7.The relationship between the serum levels of vascular endothelial growth factor, matrix metalloproteinase-9, S100 calcium binding protein with glycolipid metabolism, pregnancy outcome in pregnant women with gestational diabetes
Lizhen CHEN ; Lihua CHANG ; Fei LI ; Fenxia LI ; Yanli ZHENG ; Rongrong XU
Chinese Journal of Postgraduates of Medicine 2025;48(7):608-614
Objective:To investigate the relationship between the serum levels of vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), S100 calcium binding protein B (S100B) with glycolipid metabolism, pregnancy outcome in pregnant women with gestational diabetes.Methods:The clinical data of 153 pregnant women with gestational diabetes (research group) and 153 healthy pregnant women (control group) in the Second Affiliated Hospital of Xi ′an Medical University from January 2020 to October 2023 were retrospectively analyzed. The serum levels of VEGF, MMP-9 and S100B were measured by enzyme linked immunosorbent assay, and the fasting blood glucose, triglyceride, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting insulin and glycated hemoglobin were measured, and the homeostasis model assessment insulin resistance index (HOMA-IR) was calculated. The adverse outcomes of pregnant women with gestational diabetes were recorded. Pearson method was used to analyze the correlation between glycolipid metabolism indexes and VEGF, MMP-9, S100B in pregnant women with gestational diabetes. Multivariate Logistic regression was used to analyze the independent risk factors of adverse pregnancy outcome in pregnant women with gestational diabetes. Receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of VEGF, MMP-9 and S100B on adverse pregnancy outcome in pregnant women with gestational diabetes. Results:The fasting blood glucose, fasting insulin, glycated hemoglobin, HOMA-IR, triglyceride, total cholesterol, LDL-C, VEGF, MMP-9 and S100B in research group were significantly higher than those in control group: (9.42 ± 0.65) mmol/L vs. (4.13 ± 0.46) mmol/L, (16.58 ± 2.37) mU/L vs. (13.41 ± 2.05) mU/L, (7.28 ± 0.46)% vs. (4.35 ± 0.39)%, 4.83 ± 0.42 vs. 2.71 ± 0.37, (3.41 ± 0.67) mmol/L vs. (2.85 ± 0.63) mmol/L, (5.54 ± 1.56) mmol/L vs. (5.12 ± 1.50) mmol/L, (3.14 ± 0.97) mmol/L vs. (2.86 ± 0.93) mmol/L, (184.02 ± 30.25) ng/L vs. (156.33 ± 26.41) ng/L, (45.78 ± 7.56) μg/L vs. (29.36 ± 5.03) μg/L and (117.51 ± 25.12) ng/L vs. (89.74 ± 22.46) ng/L, the HDL-C was significantly lower than that in control group: (1.34 ± 0.27) mmol/L vs. (1.42 ± 0.30) mmol/L, and there were statistical differences ( P<0.01 or <0.05). Pearson correlation analysis result showed that VEGF, MMP-9, S100B in pregnant women with gestational diabetes were positively correlated with fasting blood glucose, fasting insulin, glycated hemoglobin, HOMA-IR, triglyceride, total cholesterol and LDL-C ( P<0.01), negatively correlated with HDL-C ( P<0.01). Among 153 pregnant women with gestational diabetes, 49 had adverse pregnancy outcome, and 104 had good pregnancy outcome. The VEGF, MMP-9 and S100B in pregnant women with adverse pregnancy outcome were significantly higher than those in pregnant women with good pregnancy outcome: (212.75 ± 28.63) ng/L vs. (170.49 ± 26.58) ng/L, (52.37 ± 7.14) μg/L vs. (42.68 ± 6.35) μg/L and (136.83 ± 23.62) ng/L vs. (108.41 ± 21.35) ng/L, and there were statistical differences ( P<0.01). Multivariate Logistic regression analysis result showed that VEGF, MMP-9 and S100B were independent risk factors for adverse pregnancy outcome in pregnant women with gestational diabetes ( OR = 7.013, 5.382 and 6.129; 95% CI 5.206 to 9.447, 3.449 to 8.398 and 3.520 to 10.673; P<0.01). ROC curve analysis result showed that the area under the curve of VEGF, MMP-9 combined S100B in predicting adverse pregnancy outcome in pregnant women with gestational diabetes was significantly larger than that of VEGF, MMP-9 and S100B alone (0.945 vs. 0.863, 0.847 and 0.801; P<0.05 or <0.01), with sensitivity of 89.80% and specificity of 91.30%. Conclusions:The high serum levels of VEGF, MMP-9 and S100B are associated with abnormal glycolipid metabolism and adverse pregnancy outcome in pregnant women with gestational diabetes, and the combination of the three indexes has a high predictive value for adverse pregnancy outcome.
8.Principles and Methods of Using Metering Unit in National Technical Specification of Medical Service Items(Version 2023)
Jingjing LANG ; Jinming KONG ; Lihua YU ; Huanhuan CHANG ; Xingyu YANG ; Hailong ZHOU ; Qin JIANG
Chinese Health Economics 2025;44(7):10-12,15
Metering unit is important component of medical service items and also serve as significant bases for scientifically estimating the costs of medical services.National Technical Specification of Medical Service Items(2023 Edition)has set up elements such as"metering unit"and"adjustment coefficient for resource consumption in special circumstances",which clearly stipulate the metering units of each medical service item and the multiples for discretionary increases or decreases in the overall resource consumption when special circumstances occur.These two elements are important references for the cost accounting in medical institutions.The project team has elaborated on the definitions,establishment principles and special circumstances of these two types of elements,namely"metering units"and"adjustment coefficient for resource consumption in special circumstances",providing references for the application of relevant governments and healthcare institutions.
9.Setting up and Use of Relative Value Scale of Human Resource Consumption in the National Technical Specification of Medical Service Items(Version 2023)
Hailong ZHOU ; Qin JIANG ; Huanhuan CHANG ; Lihua YU
Chinese Health Economics 2025;44(7):13-15
The relative value of human resource consumption is a relative value scale of the workload and difficulty of medical personnel needed to provide medical service items.Based on"basic human resource consumption and time consumption","technical difficulty"and"risk level"of the medical service items,it is comprehensively calculated by"relative value indicator standardization","relative value indicator weight setting","relative value indicator calculation model construction",and"relative value indicator expert verification".By formulating the relative value of human resource consumption,it could be used in rationalizing the relative value scale of medical service items,promoting cost accounting in hospitals,and establishing a scientific and reasonable performance evaluation system as technical tools.
10.The Rationale and Implementation of the Financial Classification of Medical Service Items
Xingyu YANG ; Lihua YU ; Huanhuan CHANG ; Jingjing LANG ; Qin JIANG
Chinese Health Economics 2025;44(7):16-18
As an important indicator to assess the revenue structure of hospitals,healthcare service revenue can truly reflect the labor value of medical personnel.A unified financial classification is the premise of accurate calculation of revenue structure.Meeting the needs of financial management of medical institutions through mapping with current healthcare service items in various regions,Financial Classification of Medical Service Items has unified the financial classification from the aspects of bill classification,accounting subject and expense classification in medical record.

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