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.

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.

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.

Objective:To explore the mechanism of Coicis Semen in treating non -small cell lung cancer combined with network pharmacology and in vitro cell experiment.Methods:The components and potential targets of Coicis Semen were obtained from TCMSP, and NSCLC related targets were collected from Genecards and Drugbank. They were intersected to get common targets. An intersection target PPI network was constructed using STRING database. GO function and KEGG pathway enrichment analysis were performed using DAVID database. A "disease-drug component-target" network was constructed using Cytoscape 3.8.0. The CCK-8 method was used to screen the concentration of Coicis Semen, and the cells were randomly divided into control group, Coicis Semen low-concentration group (0.125 mg/ml), Coicis Semen high-concentration group (0.25 mg/ml), Coicis Semen low concentration+FoxO1 inhibitor group, and FoxO1 inhibitor group (50 μmol/L) using a random number table. Cell proliferation ability was determined using CCK-8 method, and cell migration and invasion ability were detected using cell scratch assay and Transwell cell invasion assay. Western blot was used to detect the expression of FoxO1, cofilin-1, and p-cofilin-1 proteins.Results:A total of 9 active components and 246 targets were screened from Coicis Semen, 1 074 targets related to non-small cell lung cancer, and 11 intersecting targets were identified. The key targets of Coicis Semen in the treatment of non-small cell lung cancer were MAPK1, MAPK8, MAPK14, CDK2, INSR, AR, FGFR2, PGR, DHFR, and PLAU; GO functional enrichment analysis showed that Coicis Semen had an impact on the cellular, molecular, and biological functions of A549 cells; KEGG pathway enrichment analysis showed that the pathways of Coicis Semen in treating non-small cell lung cancer mainly focus on FoxO pathway, MAPK pathway, prostate cancer pathway, Ras pathway, etc. Compared with the control group, the proliferation rate, migration rate, and invasion number of A549 cells in the low and high concentration groups of Coicis Semen decreased ( P<0.05), p-cofilin-1 expression decreased ( P<0.05), and FoxO1 expression increased ( P<0.05). Conclusion:Coicis Semen can treat non-small cell lung cancer by regulating MAPK1, MAPK8, and MAPK14 targets, and acting on pathways such as the FoxO and MAPK pathways.

Objective To conduct a scoping review of studies related to gamified physical activity interventions for pediatric cancer patients,and to extract the gamification elements and application effects within physical activity intervention programs.Methods A computer-assisted search was conducted in CNKI,Wanfang Data,VIP Database,China Biology Medicine disc,Cochrane Library,PubMed,Embase,and Web of Science for studies on gamified physical activity interventions in pediatric cancer patients,with a search period from database inception to December 31,2023.The included literature was screened,summarized,and analyzed.Results A total of 18 articles were included,including 9 randomized controlled trials,4 quasi-experimental studies,and 5 mixed-method studies.The gamified intervention programs for physical activity in children with cancer integrated 7 gamification elements,including goal setting,capacity to overcome challenges,providing feedback on performance,reinforcement,progress monitoring,social connectivity,and fun and playfulness.The types of physical activity in the intervention programs included aerobic exercise,balance training,strength training,endurance training,etc.The intensity of the activities was mainly low to moderate;the duration was mostly 30～60 minutes per session;the intervention duration ranged from 5 weeks to 1 year.Numerous research findings indicate that gamified physical activity interventions for children with cancer can help improve physical function,quality of life,and fatigue levels.However,there is signi-ficant controversy regarding their impact on improving physical activity levels.Conclusion The gamified inter-vention for physical activity in children with cancer was safe and feasible.It is recommended that in the future,personalized and phased gamified intervention programs should be developed to evaluate the intervention effects.

Objective To conduct a scoping review of studies related to gamified physical activity interventions for pediatric cancer patients,and to extract the gamification elements and application effects within physical activity intervention programs.Methods A computer-assisted search was conducted in CNKI,Wanfang Data,VIP Database,China Biology Medicine disc,Cochrane Library,PubMed,Embase,and Web of Science for studies on gamified physical activity interventions in pediatric cancer patients,with a search period from database inception to December 31,2023.The included literature was screened,summarized,and analyzed.Results A total of 18 articles were included,including 9 randomized controlled trials,4 quasi-experimental studies,and 5 mixed-method studies.The gamified intervention programs for physical activity in children with cancer integrated 7 gamification elements,including goal setting,capacity to overcome challenges,providing feedback on performance,reinforcement,progress monitoring,social connectivity,and fun and playfulness.The types of physical activity in the intervention programs included aerobic exercise,balance training,strength training,endurance training,etc.The intensity of the activities was mainly low to moderate;the duration was mostly 30～60 minutes per session;the intervention duration ranged from 5 weeks to 1 year.Numerous research findings indicate that gamified physical activity interventions for children with cancer can help improve physical function,quality of life,and fatigue levels.However,there is signi-ficant controversy regarding their impact on improving physical activity levels.Conclusion The gamified inter-vention for physical activity in children with cancer was safe and feasible.It is recommended that in the future,personalized and phased gamified intervention programs should be developed to evaluate the intervention effects.

Objective To explore the value of CT radiomics combined with clinical data and CT features for predicting TNM stage of thymic epithelial tumor(TET).Methods Data of 216 single TET patients confirmed by surgical pathology were retrospectively analyzed.Totally 151 cases with TNM stage Ⅰ TET were divided into early group,while 27 with TNM stage Ⅲ and 38 with TNM stage Ⅳ TET were divided into late group(n=65).Univariate analysis was used to analyze clinical data and chest CT manifestations.Based on non-contrast-enhanced CT(NECT)and contrast-enhanced CT(CECT),the best radiomics features were extracted and screened to establish radiomics models(RMNECT,RMCECT)for predicting TNM stage of TET.RMNECT-clinic,RMCECT-clinic,RMNECT-clinic-CT and RMCECT-clinic-CT were constructed based on combination of clinical and CT features being significantly different between groups,respectively.The patients were divided into training set(n=151)and validation set(n=65)at the ratio of 7∶3.The above models were trained in the training set using repeated 5-fold cross validation method,and their efficacy were verified in the validation set.Results Significant differences of clinical symptoms and CT manifestations including fat infiltration around the lesion,mediastinal lymph node enlargement and pleural effusion were found between groups(all P＜0.05).Based on NECT and CECT,2 and 9 best radiomics features were selected to construct the corresponding models.In validation set,the area under the curve(AUC)of RMNECT-clinic-CT for predicting TNM stage of TET(0.864)was higher than that of RMNECT and RMNECT-clinic(AUC=0.634,0.721,Z=3.081,2.937,P=0.002,0.003),while AUC of RMCECT-clinic-CT(0.920)was also higher than that of RMCECT and RMCECT-clinic(AUC=0.689,0.751,Z=2.698,2.390,P=0.007,0.017).Conclusion CT radiomics combined with clinical data and CT features could effectively predict TNM stage of TET.

Objective:To compare the surgical efficacy of pericardial soft ring tricuspid valvuloplasty with DeVega and artificial valvuloplasty.Methods:227 patients undergoing tricuspid valvuloplasty due to rheumatic heart disease complicated with functional tricuspid valve insufficiency were retrospectively analyzed and divided into 3 groups according to tricuspid valvuloplasty dynamic cohort(pericardial ring group, 89 cases; the artificial flap ring group, 61 cases, and the DeVega group, 77 cases) were matched 1∶1 for propensity score(match A: pericardial ring group and artificial flap ring group; match B: pericardial ring group and DeVega group), the successful matching was included in follow-up and data collection, and cases with incomplete case data during follow-up were removed from the study cohort in pairs according to matching conditions. The results of follow-up 1 month, 6 months and 24 months after surgery were compared.Results:1 month after operation: the tricuspid valve regurgitant in all groups was significantly reduced or even disappeared compared with that before operation, and the right atrium and right ventricle were also smaller than that before operation, with statistical significance( P<0.05). 6 months after surgery: There was no statistical significance in the area of tricuspid regurgitation and right atrial/indoor diameter between all groups compared with the results one month after surgery( P>0.05), and there was no statistical significance in the recurrence rate of tricuspid regurgitation between all groups( P>0.05). 24 months after surgery: There were no significant differences in the recurrence rate of tricuspid regurgitation, area of tricuspid regurgitation and right atrial/indoor diameter between the two groups in matching A( P>0.05). There was no statistical significance in the right atrial/indoor diameter between the matched pericardial ring group and the Devega group, but the tricuspid valve regurgentation area of the Devega group at 24 months after surgery was higher than that of the Devega group at 1 month after surgery, and the difference was statistically significant( P<0.05). The regurgitation area and recurrence rate of tricuspid valve were significantly higher than those of pericardium-TVP group( P<0.05). Conclusion:Pericardial soft ring tricuspid valvuloplasty can effectively correct functional tricuspid valvuloplasty and reverse right heart remodeling, which is an effective tricuspid valvuloplasty.

ObjectiveTo elucidate the pharmacodynamic substances responsible for the anti-inflammatory and analgesic effects of Cyperi Rhizoma by structure-activity omics. MethodOn the basis of the previous in vitro efficacy study by our research group， this study explored the in vivo efficacy of the flavonoids in Cyperi Rhizoma. The flavonoids in Cyperi Rhizoma and their targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， PharmMapper， Swiss TargetPrediction， and available articles. The targets of the anti-inflammatory and analgesic effects were collected from DisGeNET and Online Mendelian Inheritance in Man （OMIM）. The common targets shared by flavonoids and the effects were selected as the direct targets of flavonoids endowing Cyperi Rhizoma with anti-inflammatory and analgesic effects， and protein-protein interaction （PPI） network of the core targets was constructed. The method of structure-activity omics was employed to correlate the structure and efficacy of one or more classes of chemical components in Cyperi Rhizoma with the targets as a bridge. The components were classified according to structure. Molecular docking of components to core targets was carried out via SYBYL-X 2.1.1， PyMol， and Discovery Studio 4.5 visualizer. Two targets with the highest binding affinity were selected to explore the relationship between compound structures and targets. ResultThe flavonoids in Cyperi Rhizoma exerted anti-inflammatory and analgesic effects on the mouse model of pain induced by formaldehyde. Eighteen components and 115 direct targets were screened out， and the core targets with high activities were protein kinase B1 （Akt1）， interleukin-1β （IL-1β）， cellular tumor antigen p53 （TP53）， prostaglandin-endoperoxide synthase 2 （PTGS2）， and matrix metalloproteinase-9 （MMP-9）. According to the structures， the flavonoids in Cyperi Rhizoma were classified into bioflavonoids， flavonols， flavones， and flavanes. The molecular docking results showed that flavonoids of Cyperi Rhizoma had the highest binding affinity to TP53 and PTGS2. The results of structure-activity omics showed that bioflavonoids represented the best binding structure to the targets， while their polyhydroxyl etherification resulted in a significant decrease in the binding affinity to PTGS2. Glycosides had higher binding affinity to PTGS2. The introduction of the long-chain hydrocarbon group to the A ring of flavonols facilitated the binding to TP53， while the change of B ring substituents was not the main factor affecting the binding affinity. The 3，4-dihydroxyl flavane outperformed 3-hydroxyl flavane in the binding to TP53， while the two compounds showed similar binding affinity to PTGS2. ConclusionThe method of structure-activity omics was used to analyze the material basis for the anti-inflammatory and analgesic effects of flavonoids in Cyperi Rhizoma. Structure-activity omics provides new ideas for revealing the pharmacodynamic substances of traditional Chinese medicine.

ObjectiveTo reveal the pharmacodynamic substances for the anti-inflammatory and analgesic effects of Glycyrrhizae Radix et Rhizoma by structure-activity omics. MethodOn the basis of the previous study about the screening of active components in vitro， this study explored the effects of flavonoids in Glycyrrhizae Radix et Rhizoma in vivo. The flavonoids in Glycyrrhizae Radix et Rhizoma and their direct targets for the anti-inflammatory and analgesic effects were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， PharmMapper， Swiss TargetPrediction， DisGeNET， and Online Mendelian Inheritance in Man （OMIM）. STRING and Cytoscape 3.7.2 were employed to establish the protein-protein interaction （PPI） network of key targets. Molecular docking was performed to simulate the binding of five targets with high degrees to flavonoids in Glycyrrhizae Radix et Rhizoma， on the basis of which the key core targets were selected. The targets were used as a bridge to correlate the structures and effects of one or more classes of chemical components in Glycyrrhizae Radix et Rhizoma. According to the binding affinity between flavonoids with different structures in Glycyrrhizae Radix et Rhizoma and targets， the relationships between compound structures and core targets were discussed. ResultThe flavonoids in Glycyrrhizae Radix et Rhizoma reduced the content of prostaglandin E₂ （PGE₂） in the rat model of pain induced by formalin， demonstrating definite anti-inflammatory and analgesic effects. Sixty active compounds （flavonoids） with anti-inflammatory and analgesic effects of Glycyrrhizae Radix et Rhizoma were obtained. With the total score as the standard， prostaglandin-endoperoxide synthase 2 （PTGS2） and mitogen-activated protein kinase 3 （MAPK3） were selected as the key core targets of Glycyrrhizae Radix et Rhizoma for the anti-inflammatory and analgesic effects. Except that flavones showed selectivity of binding to MAPK3， the other flavonoids of Glycyrrhizae Radix et Rhizoma showed strong binding to PTGS2 and MAPK3， and the structures containing glycoside fragments showed stronger binding affinity to the targets. The introduction of chain olefins in the ring of chalcones facilitated the binding to the targets. The isopentenyl fragment in flavonols may cause the difference in binding affinity. The parallel combination of a ring into pyran ring in flavanes was not conducive to the binding to the target. The electric charge， liposolubility， and steric hindrance of the substituent group on the B ring of isoflavones directly affected the binding affinity. ConclusionThis study adopts structure-activity omics to analyze the material basis for the anti-inflammatory and analgesic effects of Glycyrrhizae Radix et Rhizoma. Structure-activity omics provides new ideas and methods for predicting the pharmacodynamic substances of traditional Chinese medicine.