ObjectiveTo investigate the molecular mechanisms by which salvianolic acid B （SalB） inhibits epithelial-mesenchymal transition （EMT） in non-small cell lung cancer （NSCLC） by downregulating phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazole succinocarboxamide synthetase （PAICS） expression. MethodsNSCLC A549 cells and normal bronchial epithelial cells （bronchial epithelium transformed with Ad12-SV40 2B， BEAS-2B） were used as models. Cell viability was assessed using the cell counting kit-8 （CCK-8） assay after treatment with SalB （0， 50， 100， 200， 300， 400， 500 μmol·L^-1 for 24 or 48 h to determine effective and safe intervention concentrations. Cell proliferation， cell cycle distribution， and apoptosis were evaluated by 5-ethynyl-2′-deoxyuridine （EdU） staining and flow cytometry， respectively. Wound healing and Transwell invasion assays were performed to assess cell migration and invasion. RNA sequencing combined with bioinformatic analysis was conducted to identify differentially expressed genes and functional enrichment. Molecular docking was used to predict the binding ability between SalB and PAICS， and the cellular thermal shift assay （CETSA） was performed to evaluate the effect of SalB on the thermal stability of the PAICS protein. Western blot （WB） was used to detect the effects of SalB on PAICS and EMT-related proteins （E-cadherin， N-cadherin， Vimentin， Snail， and Slug）. A functional rescue assay was conducted by PAICS overexpression via plasmid transfection. ResultsCompared with the control group， SalB inhibited A549 cell viability in a dose-dependent manner （P<0.05）， and the effective concentrations （≤300 μmol·L^-1） showed no significant cytotoxicity in BEAS-2B cells. Within this concentration range， SalB significantly inhibited A549 cell proliferation， migration， and invasion， and induced G₀/G₁ phase arrest and apoptosis （P<0.05）. Transcriptomic analysis showed that SalB significantly downregulated PAICS expression， and its functions were enriched in cell proliferation and EMT. Bioinformatic analysis indicated that PAICS is highly expressed in lung adenocarcinoma and is associated with poor prognosis （P<0.01）. Molecular docking showed that SalB has strong binding ability to PAICS （binding energy -9.1 kcal·mol^-1. CETSA results showed that SalB significantly increased the thermal stability of the PAICS protein （P<0.05）. WB results showed that， compared with the control group， SalB dose-dependently downregulated PAICS expression， upregulated E-cadherin， and downregulated N-cadherin， Vimentin， Snail， and Slug （P<0.05）. Functional rescue experiments showed that， compared with the empty vector group， PAICS overexpression significantly enhanced A549 cell proliferation， migration， and invasion， promoted cell cycle progression， and inhibited apoptosis （P<0.05）. Meanwhile， compared with the empty vector + SalB-H group， PAICS overexpression partially reversed the inhibitory effects of SalB on malignant phenotypes and EMT-related proteins （N-cadherin， Vimentin， Snail， and Slug）， and downregulated E-cadherin expression （P<0.05，P<0.01）， indicating that PAICS is a key functional target mediating the antitumor effects of SalB. ConclusionSalB effectively inhibits EMT progression and cell cycle progression in A549 cells by downregulating PAICS expression， thereby exerting anti-NSCLC effects. This study not only reveals that PAICS is a key functional target through which SalB regulates EMT， but also provides experimental evidence supporting SalB as a potential candidate drug for inhibiting NSCLC metastasis.

ObjectiveTo investigate the mechanisms by which eupatilin （Eup） inhibits proliferation， invasion， and metastasis of non-small cell lung cancer （NSCLC） through the enhancer of zeste homolog 2/histone H3 lysine 27 trimethylation （EZH2/H3K27me3） signaling pathway. MethodsIn vivo， a subcutaneous xenograft tumor model was established in nude mice using H1299 cells to evaluate the anti-NSCLC effects of Eup. Immunohistochemistry （IHC-P） was used to detect the expression of proliferation- and invasion/metastasis-related proteins， including proliferating cell nuclear antigen （PCNA）， matrix metalloproteinase-2 （MMP-2）， matrix metalloproteinase-9 （MMP-9）， and vascular endothelial growth factor A （VEGFA）. In vitro， cell counting kit-8 （CCK-8） assays were performed to determine the viability of H1299 cells treated with different concentrations of Eup （0-200 μmol·L^-1） and to select appropriate concentrations. Colony formation and 5-ethynyl-2′-deoxyuridine （EdU） assays were used to evaluate cell proliferation. Wound healing and invasion assays were conducted to assess cell migration and invasion. Human umbilical vein endothelial cell （HUVEC） angiogenesis assays were used to evaluate the effects of Eup on angiogenesis. Transcriptomic analysis was performed to identify the targets of Eup in H1299 cells and to explore its major functions. Molecular docking and molecular dynamics simulations were conducted to predict the binding affinity and interaction stability between Eup and its target proteins. Western blot was used to detect the effects of Eup on the expression levels of EZH2/H3K27me3 pathway-related proteins and proliferation- and invasion/metastasis-related proteins， including PCNA， MMP-2， MMP-9， and VEGFA. ResultsIn the subcutaneous xenograft model， compared with the model group， Eup treatment dose-dependently inhibited the growth of H1299 xenograft tumors， and the tumor inhibition rate was significantly increased （P<0.05）. IHC-P results showed that， compared with the model group， high-dose Eup significantly reduced the expression levels of PCNA， MMP-2， MMP-9， and VEGFA in vivo （P<0.05）. In vitro， compared with the control group， Eup inhibited the proliferation， invasion， and metastasis of NSCLC cells in a concentration-dependent manner. Transcriptomic analysis further showed that， compared with the control group， Eup significantly downregulated EZH2 expression， and its functional effects were associated with inhibition of tumor metastasis. Molecular docking and molecular dynamics simulations indicated that Eup exhibited strong binding affinity with EZH2 and stable interactions. Western blot results demonstrated that， compared with the model group， Eup significantly inhibited， in a dose-dependent manner， the expression levels of EZH2， H3K27me3， and proliferation- and invasion/metastasis-related proteins （PCNA， MMP-2， MMP-9， and VEGFA） in both in vivo and in vitro experiments （P<0.05）. In vitro， compared with the control group， overexpression of EZH2 via plasmid transfection partially reversed the inhibitory effects of Eup on the expression of key proteins involved in proliferation and invasion/metastasis in H1299 cells. ConclusionEup effectively inhibits the proliferation， migration， and invasion of H1299 cells both in vivo and in vitro. The underlying mechanism may be related to inhibition of the EZH2/H3K27me3 signaling pathway and downregulation of proliferation- and invasion/metastasis-related proteins， including PCNA， MMP-2， MMP-9， and VEGFA. Eup may serve as a potential therapeutic agent for suppressing proliferation and invasion/metastasis in NSCLC.

ObjectiveTo investigate the molecular mechanisms by which salvianolic acid B （SalB） inhibits epithelial-mesenchymal transition （EMT） in non-small cell lung cancer （NSCLC） by downregulating phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazole succinocarboxamide synthetase （PAICS） expression. MethodsNSCLC A549 cells and normal bronchial epithelial cells （bronchial epithelium transformed with Ad12-SV40 2B， BEAS-2B） were used as models. Cell viability was assessed using the cell counting kit-8 （CCK-8） assay after treatment with SalB （0， 50， 100， 200， 300， 400， 500 μmol·L^-1 for 24 or 48 h to determine effective and safe intervention concentrations. Cell proliferation， cell cycle distribution， and apoptosis were evaluated by 5-ethynyl-2′-deoxyuridine （EdU） staining and flow cytometry， respectively. Wound healing and Transwell invasion assays were performed to assess cell migration and invasion. RNA sequencing combined with bioinformatic analysis was conducted to identify differentially expressed genes and functional enrichment. Molecular docking was used to predict the binding ability between SalB and PAICS， and the cellular thermal shift assay （CETSA） was performed to evaluate the effect of SalB on the thermal stability of the PAICS protein. Western blot （WB） was used to detect the effects of SalB on PAICS and EMT-related proteins （E-cadherin， N-cadherin， Vimentin， Snail， and Slug）. A functional rescue assay was conducted by PAICS overexpression via plasmid transfection. ResultsCompared with the control group， SalB inhibited A549 cell viability in a dose-dependent manner （P<0.05）， and the effective concentrations （≤300 μmol·L^-1） showed no significant cytotoxicity in BEAS-2B cells. Within this concentration range， SalB significantly inhibited A549 cell proliferation， migration， and invasion， and induced G₀/G₁ phase arrest and apoptosis （P<0.05）. Transcriptomic analysis showed that SalB significantly downregulated PAICS expression， and its functions were enriched in cell proliferation and EMT. Bioinformatic analysis indicated that PAICS is highly expressed in lung adenocarcinoma and is associated with poor prognosis （P<0.01）. Molecular docking showed that SalB has strong binding ability to PAICS （binding energy -9.1 kcal·mol^-1. CETSA results showed that SalB significantly increased the thermal stability of the PAICS protein （P<0.05）. WB results showed that， compared with the control group， SalB dose-dependently downregulated PAICS expression， upregulated E-cadherin， and downregulated N-cadherin， Vimentin， Snail， and Slug （P<0.05）. Functional rescue experiments showed that， compared with the empty vector group， PAICS overexpression significantly enhanced A549 cell proliferation， migration， and invasion， promoted cell cycle progression， and inhibited apoptosis （P<0.05）. Meanwhile， compared with the empty vector + SalB-H group， PAICS overexpression partially reversed the inhibitory effects of SalB on malignant phenotypes and EMT-related proteins （N-cadherin， Vimentin， Snail， and Slug）， and downregulated E-cadherin expression （P<0.05，P<0.01）， indicating that PAICS is a key functional target mediating the antitumor effects of SalB. ConclusionSalB effectively inhibits EMT progression and cell cycle progression in A549 cells by downregulating PAICS expression， thereby exerting anti-NSCLC effects. This study not only reveals that PAICS is a key functional target through which SalB regulates EMT， but also provides experimental evidence supporting SalB as a potential candidate drug for inhibiting NSCLC metastasis.

ObjectiveTo investigate the mechanisms by which eupatilin （Eup） inhibits proliferation， invasion， and metastasis of non-small cell lung cancer （NSCLC） through the enhancer of zeste homolog 2/histone H3 lysine 27 trimethylation （EZH2/H3K27me3） signaling pathway. MethodsIn vivo， a subcutaneous xenograft tumor model was established in nude mice using H1299 cells to evaluate the anti-NSCLC effects of Eup. Immunohistochemistry （IHC-P） was used to detect the expression of proliferation- and invasion/metastasis-related proteins， including proliferating cell nuclear antigen （PCNA）， matrix metalloproteinase-2 （MMP-2）， matrix metalloproteinase-9 （MMP-9）， and vascular endothelial growth factor A （VEGFA）. In vitro， cell counting kit-8 （CCK-8） assays were performed to determine the viability of H1299 cells treated with different concentrations of Eup （0-200 μmol·L^-1） and to select appropriate concentrations. Colony formation and 5-ethynyl-2′-deoxyuridine （EdU） assays were used to evaluate cell proliferation. Wound healing and invasion assays were conducted to assess cell migration and invasion. Human umbilical vein endothelial cell （HUVEC） angiogenesis assays were used to evaluate the effects of Eup on angiogenesis. Transcriptomic analysis was performed to identify the targets of Eup in H1299 cells and to explore its major functions. Molecular docking and molecular dynamics simulations were conducted to predict the binding affinity and interaction stability between Eup and its target proteins. Western blot was used to detect the effects of Eup on the expression levels of EZH2/H3K27me3 pathway-related proteins and proliferation- and invasion/metastasis-related proteins， including PCNA， MMP-2， MMP-9， and VEGFA. ResultsIn the subcutaneous xenograft model， compared with the model group， Eup treatment dose-dependently inhibited the growth of H1299 xenograft tumors， and the tumor inhibition rate was significantly increased （P<0.05）. IHC-P results showed that， compared with the model group， high-dose Eup significantly reduced the expression levels of PCNA， MMP-2， MMP-9， and VEGFA in vivo （P<0.05）. In vitro， compared with the control group， Eup inhibited the proliferation， invasion， and metastasis of NSCLC cells in a concentration-dependent manner. Transcriptomic analysis further showed that， compared with the control group， Eup significantly downregulated EZH2 expression， and its functional effects were associated with inhibition of tumor metastasis. Molecular docking and molecular dynamics simulations indicated that Eup exhibited strong binding affinity with EZH2 and stable interactions. Western blot results demonstrated that， compared with the model group， Eup significantly inhibited， in a dose-dependent manner， the expression levels of EZH2， H3K27me3， and proliferation- and invasion/metastasis-related proteins （PCNA， MMP-2， MMP-9， and VEGFA） in both in vivo and in vitro experiments （P<0.05）. In vitro， compared with the control group， overexpression of EZH2 via plasmid transfection partially reversed the inhibitory effects of Eup on the expression of key proteins involved in proliferation and invasion/metastasis in H1299 cells. ConclusionEup effectively inhibits the proliferation， migration， and invasion of H1299 cells both in vivo and in vitro. The underlying mechanism may be related to inhibition of the EZH2/H3K27me3 signaling pathway and downregulation of proliferation- and invasion/metastasis-related proteins， including PCNA， MMP-2， MMP-9， and VEGFA. Eup may serve as a potential therapeutic agent for suppressing proliferation and invasion/metastasis in NSCLC.

BackgroundStudents in secondary vocational health school are at the age of puberty and prone to depressive symptoms. Peer victimization and social media addiction are found to be crucial in influencing the development of depression， and positive mental health has been proven to alleviate depressive symptoms， whereas there remains a striking lack of research on the mediating role of positive mental health and social media addiction in the relationship between peer victimization and depressive symptoms among secondary vocational health school students. ObjectiveTo explore the relationship between peer victimization and depressive symptoms and investigate the mediating role of positive mental health and social media addiction， so as to provide references for the prevention of depression among secondary vocational health school students. MethodsFrom October to December 2020， a cluster sampling framework was utilized to recruit 7 307 students from a secondary vocational health school in Luzhou City， Sichuan Province. Assessments were performed using Multidimensional Peer Victimization Scale （MPVS）， Warwick-Edinburgh Mental Well-being Scale （WEMWBS）， Bergen Social Media Addiction Scale （BSMAS） and Patient Health Questionnaire Depression Scale-9 item （PHQ-9）. Spearman correlation analysis was calculated to determine correlations between scores of scales， Process 4.0 was employed to test the mediation effect， and the bias-corrected Bootstrap procedure was used to test the significance of the mediation effect. ResultsA total of 7 044 （96.40%） valid questionnaires were collected. And 4 391（62.34%）students were found to have depressive symptoms. Correlation analysis revealed that PHQ-9 score was positively correlated with BSMAS score and MPVS score （r=0.404， 0.506， P<0.01）. WEMWBS score was negatively correlated with PHQ-9 score， BSMAS score and MPVS score （r=-0.587， -0.259， -0.358， P<0.01）. BSMAS score was positively correlated with MPVS score （r=0.328， P<0.01）. Positive mental health played a mediating role in the relationship between peer victimization and depressive symptoms， with an indirect effect value of 0.130 （95% CI： 0.119~0.141）， accounting for 30.81% of the total effect. Social media addiction also mediated the relationship between peer victimization and depressive symptoms， with an indirect effect value of 0.052 （95% CI： 0.045~0.059）， accounting for 12.34% of the total effect. Positive mental health and social media addiction exhibited a chained mediation effect on the relationship between peer victimization and depressive symptoms， with an indirect effect value of 0.012 （95% CI： 0.010~0.014） and accounting for 2.84% of the total effect. ConclusionPeer victimization can affect the presence of depressive symptoms among secondary vocational health school students both directly and indirectly through either separate or chained mediation of positive mental health and social media addiction.

Sensorineural hearing loss (SNHL), the most commonly-occurring form of hearing loss, is caused mainly by injury to or the loss of hair cells and spiral ganglion neurons in the cochlea. Numerous environmental and physiological factors have been shown to cause acquired SNHL, such as ototoxic drugs, noise exposure, aging, infections, and diseases. Several programmed cell death (PCD) pathways have been reported to be involved in SNHL, especially some novel PCD pathways that have only recently been reported, such as ferroptosis, necroptosis, and pyroptosis. Here we summarize these PCD pathways and their roles and mechanisms in SNHL, aiming to provide new insights and potential therapeutic strategies for SNHL by targeting these PCD pathways.
Humans ; Hearing Loss, Sensorineural/metabolism* ; Necroptosis/drug effects* ; Pyroptosis/drug effects* ; Ferroptosis/drug effects* ; Animals

Picky eating is a term used to describe children's eating behavior and food preferences，characterized by their preference for and avoidance of certain foods or food groups. These behaviors can have long-term consequences related to nutrition and health. It should be addressed as early as possible to improve the development of picky eating in children. Therefore，it is important to understand children's picky eating deeply in order to design appropriate intervention strategies to successfully mitigate picky eating. Based on domestic and foreign research，this paper summarizes the related factors of children's picky eating，the influence of picky eating on children，the characteristics and influencing factors of picky eating，and the intervention measures and effects of picky eating，and puts forward the prevention and improvement direction of children's picky eating in the future.

Objective To observe the clinical efficacy of Si-hour"Supplementing Yang and Unblocking Collaterals"Electroacupuncture Therapy based on the midnight-midday ebb-flow theory in treating hemiplegia caused by ischemic stroke.Methods A total of 160 patients diagnosed with ischemic stroke hemiplegia who were treated in the wards and outpatient departments of Huaian Hospital of Traditional Chinese Medicine between January 2023 and June 2024 were selected as study subjects.Patients were randomly divided into an observation group and a control group using a random number table,with 80 cases in each group.Both groups received conventional internal medicine rehabilitation treatment.The control group received conventional acupuncture therapy,while the observation group received Si-hour"Supplementing Yang and Unblocking Collaterals"Electroacupuncture Therapy based on the midnight-midday ebb-flow theory.Treatment was administered for 2 weeks per course,with a total of 3 courses.After completion of treatment,clinical efficacy was evaluated by observing changes in traditional Chinese medicine(TCM)syndrome scores,simplified Fugl-Meyer Assessment(FMA)scores,modified Barthel Index(MBI)scores,fractional anisotropy(FA)values in the cerebral peduncle and posterior limb of internal capsule regions,modified Edinburgh-Scandinavian Stroke Scale(MESSS)scores,as well as plasma viscosity,hematocrit(HCT),and fibrinogen(FIB)levels before and after treatment in both groups.Results(1)The total effective rate was 86.25％(69/80)in the observation group and 70.00％(56/80)in the control group.The efficacy of the observation group was significantly superior to that of the control group,with a statistically significant difference(P＜0.05).(2)After treatment,TCM syndrome scores were significantly improved in both groups(P＜0.05),and the improvement in the observation group was significantly greater than that in the control group,with a statistically significant difference(P＜0.05).(3)After treatment,FMA and MBI scores were significantly improved in both groups(P＜0.05),and the improvement in the observation group was significantly greater than that in the control group,with a statistically significant difference(P＜0.05).(4)After treatment,FA values in the cerebral peduncle and posterior limb of internal capsule regions,as well as MESSS scores,were significantly improved in both groups(P＜0.05),and the improvement in the observation group was significantly greater than that in the control group,with a statistically significant difference(P＜0.05).(5)After treatment,plasma viscosity,HCT,and FIB levels were significantly improved in both groups(P＜0.05),and the improvement in the observation group was significantly greater than that in the control group,with a statistically significant difference(P＜0.05).Conclusion Si-hour"Supplementing Yang and Unblocking Collaterals"Electroacupuncture Therapy based on the midnight-midday ebb-flow theory significantly improves limb motor function,enhances neural conduction,and optimizes hemorheological parameters in patients with hemiplegia caused by ischemic stroke,demonstrating notable clinical efficacy.

Objective To summarize the whole process comprehensive management experience in transfemoral aortic valve replacement(TF-TAVR)using self-expanding valve in 79 patients with pure native aortic valve regurgitation(PNAR).Methods The nursing team adopted a multi-team collaboration approach.Preoperative nursing assessment and full preparation,enhanced psychological support,and sleep management were carefully carried out;during the operation,nurses well cooperated with doctor,implemented predictive care and intervention for possible complications;and after surgery the hemodynamics and respiratory functions were closely monitored to promptly detect and manage the complications,and to implement the infection prevention cluster management process and discharge preparation services.Besides,the comprehensive management measures throughout the entire process,the occurrence of complications and corresponding nursing responses,as well as the six-minute walk test before and after the operation were recorded.The Discharge Readiness Scale was used to evaluate the implementation of patient discharge readiness services so as to check the implementation effect of the comprehensive whole process management measures.Results Through the implementation of comprehensive whole process management measures,the surgery-related ventricular fibrillation and cardiac arrest obtained accurate and timely treatment,no newly-developed complications such as deep vein thrombosis of lower limbs occurred.Through the implementation of infection cluster nursing measures,the incidence of pulmonary infection in patients decreased from 52.00％in the early stage of carrying out the management measures to 9.26％.Through the implementation of discharge preparation services and continuous quality improvement,the left ventricular ejection fraction(LVEF)value in 64 patients receiving successful TAVR increased from(44.06±5.51)％to(54.67±5.20)％,and the difference was statistically significant(t=19.634,P＜0.001).On the day of discharge,the six-minute walk test distance increased from preoperative(131.39±39.36)meters to postoperative(180.77±29.72)meters,and the difference was statistically significant(t=10.898,P＜0.001).The average self-assessment score of discharge readiness of patients was(7.33±1.41)points.All patients were well recovered when discharged from hospital.Conclusion According to the different surgical key points and the difficult problems,full and effective implementation of comprehensive whole process management measures can ensure that the PNAR patients are able to smoothly pass through the perioperative period and obtain a satisfactory recovery after receiving TF-TAVR.