Lung cancer is the leading cause of cancer-related deaths worldwide， and tumor metastasis is a key factor contributing to the mortality of most lung cancer patients. Aberrant activation of epithelial-mesenchymal transition （EMT） is a major driver of lung cancer progression and metastasis. EMT is characterized by the loss of apical-basal polarity and intercellular adhesion in highly differentiated， polarized， and organized epithelial cells， which acquire motility， migratory potential， and invasive properties. During this process， cells undergo cytoskeletal remodeling and transform into a mesenchymal phenotype， accompanied by associated changes in cellular markers. The EMT process is highly complex and is tightly regulated by intricate networks involving multiple transcription factors， post-translational controls， epigenetic modifications， and non-coding RNAs. Therefore， therapies targeting the mechanisms of malignant transformation and their associated pathways in lung cancer are of significant clinical importance. In recent years， EMT has attracted increasing attention as a potential target for cancer therapy. Chinese medicine， with its characteristics of multi-target action， low side effects， and good therapeutic efficacy， has demonstrated an important role in anticancer treatment. A series of studies have investigated the role of Chinese medicine in inhibiting EMT in lung cancer. Active ingredients of Chinese medicine， including flavonoids， glycosides， phenols， terpenoids， saccharides， and alkaloids， as well as Chinese medicine compound formulas， have shown significant regulatory effects on EMT. Their mechanisms mainly involve multiple pathways， targets， and links， including signaling pathways， exosomes， microRNAs （miRNAs）， and the tumor-associated immune microenvironment. This article summarizes the mechanisms by which EMT promotes malignant tumor progression and reviews the current research on how Chinese medicine active ingredients， monomers， and compound formulas inhibit EMT and suppress lung cancer cell migration and invasion. This study is expected to provide comprehensive theoretical information for basic and translational research on lung cancer.

OBJECTIVES: To explore the mechanism by which Pulsatilla saponin D (PSD) inhibits invasion and metastasis of triple-negative breast cancer (TNBC). METHODS: The public databases were used to identify the potential targets of PSD and the invasion and metastasis targets of TNBC to obtain the intersection targets between PSD and TNBC. The "PSD-target-disease" interaction network was constructed and protein-protein interaction (PPI) analysis was performed to obtain the core targets, which were analyzed for KEGG pathway and GO functional enrichment. Molecular docking study of the core targets and PSD was performed, and the therapeutic effect and mechanism of PSD were verified using Transwell assay and Western blotting in cultured TNBC cells. RESULTS: Network pharmacology analysis identified a total of 285 potential PSD targets and 26 drug-disease intersection core targets. GO analysis yielded 175 entries related to the binding of biomolecules (protein, DNA and RNA), enzyme activities, and regulation of gene transcription. KEGG analysis yielded 46 entries involving pathways in cancer, chemical carcinogenesis-receptor activation, microRNAs in cancer, chemical carcinogenesis-reactive oxygen species, PD-L1 expression and PD-1 checkpoint pathway in cancer. Molecular docking showed high binding affinities of PSD to MTOR, HDAC2, ABL1, CDK1, TLR4, TERT, PIK3R1, NFE2L2 and PTPN1. In cultured TNBC cells, treatment with PSD significantly inhibited cell invasion and migration and lowered the expressions of MMP2, MMP9, N-cadherin and the core proteins p-mTOR, ABL1, TERT, PTPN1, HDAC2, PIK3R1, CDK1, TLR4 as well as NFE2L2 expressionin the cell nuclei. CONCLUSIONS The inhibitory effects of PSD on TNBC invasion and metastasis are mediated by multiple targets and pathways.
Humans ; Triple Negative Breast Neoplasms/metabolism* ; Saponins/pharmacology* ; Pulsatilla/chemistry* ; Female ; Molecular Docking Simulation ; Cell Line, Tumor ; Neoplasm Invasiveness ; Protein Interaction Maps ; Neoplasm Metastasis ; Signal Transduction/drug effects* ; Cell Movement/drug effects*

Objective To explore the mechanism by which Pulsatilla saponin D(PSD)inhibits invasion and metastasis of triple-negative breast cancer(TNBC).Methods The public databases were used to identify the potential targets of PSD and the invasion and metastasis targets of TNBC to obtain the intersection targets between PSD and TNBC.The"PSD-target-disease"interaction network was constructed and protein-protein interaction(PPI)analysis was performed to obtain the core targets,which were analyzed for KEGG pathway and GO functional enrichment.Molecular docking study of the core targets and PSD was performed,and the therapeutic effect and mechanism of PSD were verified using Transwell assay and Western blotting in cultured TNBC cells.Results Network pharmacology analysis identified a total of 285 potential PSD targets and 26 drug-disease intersection core targets.GO analysis yielded 175 entries related to the binding of biomolecules(protein,DNA and RNA),enzyme activities,and regulation of gene transcription.KEGG analysis yielded 46 entries involving pathways in cancer,chemical carcinogenesis-receptor activation,microRNAs in cancer,chemical carcinogenesis-reactive oxygen species,PD-L1 expression and PD-1 checkpoint pathway in cancer.Molecular docking showed high binding affinities of PSD to MTOR,HDAC2,ABL1,CDK1,TLR4,TERT,PIK3R1,NFE2L2 and PTPN1.In cultured TNBC cells,treatment with PSD significantly inhibited cell invasion and migration and lowered the expressions of MMP2,MMP9,N-cadherin and the core proteins p-mTOR,ABL1,TERT,PTPN1,HDAC2,PIK3R1,CDK1,TLR4 as well as NFE2L2 expressionin the cell nuclei.Conclusion The inhibitory effects of PSD on TNBC invasion and metastasis are mediated by multiple targets and pathways.

Objective:To investigate the relationship between plasma fluoride content, daily calcium intake and blood cell parameters in children and adolescents.Methods:This study was based on the National Health and Nutrition Examination Survey (NHANES) database of the United States from 2013 to 2016, with 3 684 children and adolescents aged 6 - 19 as the research subjects. Information on plasma fluoride content, daily calcium intake and blood cell parameters from the database were collected. Non-linear relationships between plasma fluoride content, daily calcium intake and blood cell parameters were analyzed using restricted cubic splines. If there was a non-linear relationship, the optimal inflection point was calculated using threshold/saturation effect analysis method. Subsequently, multiple linear regression models were used to analyze the associations among the three, and the modification effect of daily calcium intake (binary classification, stratified by median daily calcium intake) on the association between plasma fluoride content and blood cell parameters was analyzed.Results:There was no non-linear relationship between plasma fluoride content and white blood cell count, hemoglobin content and platelet count ( Pnon-linear > 0.05), but there was a non-linear relationship between plasma fluoride content and erythrocyte count and hematocrit ( Pnon-linear < 0.001). After adjusting for confounding factors, the optimal inflection points of the effects of plasma fluoride content on erythrocyte count and hematocrit were 0.54 and 0.31 μmol/L, respectively. There was no non-linear relationship between daily calcium intake and blood cell parameters ( Pnon-linear > 0.05). After adjusting for confounding factors, for every 1 μmol/L increase in plasma fluoride content, the white blood cell count increased by 0.49 × 10 9/L ( P = 0.009). There was a saturation effect in the association between plasma fluoride content, erythrocyte count and hematocrit: when plasma fluoride content was < 0.54 μmol/L, the erythrocyte count decreased by 0.46 × 10 12/L for every 1 μmol/L increase ( P < 0.001). When plasma fluoride content was < 0.31 μmol/L, the hematocrit decreased by 6.29% for every 1 μmol/L increase ( P = 0.006). The above associations were not statistically significant when plasma fluoride content was higher than the optimal inflection points ( P > 0.05). After stratification according to the median daily calcium intake, in the low-calcium group (daily calcium intake < 0.87 g), for every 1 μmol/L increase in plasma fluoride content, the white blood cell count increased by 0.77 × 10 9/L ( P = 0.001). When plasma fluoride content was < 0.54 μmol/L, the erythrocyte count decreased by 0.41 × 10 12/L for every 1 μmol/L increase ( P = 0.002). When plasma fluoride content was ≥0.54 μmol/L, erythrocyte count decreased by 0.47 × 10 12/L for every 1 μmol/L increase ( P < 0.001). When the plasma fluoride content was < 0.31 μmol/L, the hematocrit decreased by 8.29% for every 1 μmol/L increase ( P = 0.011). The above associations were not statistically significant in the high-calcium group (daily calcium intake ≥0.87 g, P > 0.05). There was an interaction of daily calcium intake and plasma fluoride content on platelet count ( Pinteraction = 0.070), as demonstrated by an increase in platelet count of 12.68 × 10 9/L ( P = 0.013) in the low-calcium group and a decrease in platelet count of 9.05 × 10 9/L ( P = 0.035) in the high-calcium group for every 1 μmol/L increase in plasma fluoride content. Conclusions:The blood cell parameters of children and adolescents are closely related to plasma fluoride content, but not directly related to daily calcium intake. However, the correlation between plasma fluoride content and blood cell parameters varies among different calcium intake populations, and daily calcium intake can modify the association between plasma fluoride content and platelet count.

Objective To explore the mediating effect of facial emotion recognition on prosocial behavior of medical students in mask-obscured scenes.Methods Fifty-three medical students from a medical university in Chongqing were enrolled from July to September 2023 to complete the facial emotion recognition task,the dictator gaming task and the state empathy test.Spearman correlation analysis was used to examine the correlation between mask wearing and state empathy,trait empathy and prosocial behaviours,and the PROCESS procedure was used to test the mediation of state empathy and the moderating effect of mask wearing or not.Results ①mask wearing,state empathy and prosocial behaviour were significantly correlated(P＜0.01);② State empathy exerted mediated effect between facial emotion recognition and prosocial behavior,with the largest effect size(47％)for the relative mediating effect of sadness;③The interaction terms of facial emotion recognition and mask wearing had a significant effect on state empathy(P＜0.05).Conclusion Facial emotion recognition can influence prosocial behavior directly and also exert indirect effect on prosocial behavior through state empathy.Compared to the condition without mask wearing,mask wearing can significantly facilitate the effect of happy,sad and neutral emotions on state empathy.

Objective To develop a group psychological training program to cultivate a sense of meaning in life for retired soldiers during the transitional period,and to explore the efficacy of the training.Methods A psychological training program for retired soldiers during the transitional period was developed based on Delphi method.A total of 64 retired soldiers who participated in a retirement training in transitional period were subjected through cluster sampling in a certain city in Shandong province and assigned into a training group(n=31)and a control group(n=33).The training group attended group psychological training based on the developed training program(twice a week,1.5～2 h each time,for 4 weeks),and the control group received routine adaptive training for retirement.Purpose in Life(PIL)Test,Chinese Perceived Stress Scale(CPSS)and Social Adaptability Scale(SAS)were used to survey the participants before(T1),and at the end of(T2)and 1 month after the training(T3).Results ① The results of 2 rounds of expert consultation showed that the coefficient of authority(Cr)was 0.89,and the Kendall's coefficient(ω)of the 2 rounds was 0.134 and 0.204,respectively(P＜0.001),with a coefficient of variation ranging from 0.05 to 0.14.The prepared group psychological training program consisted of 3 first-level indexes,6 second-level indexes,and 24 third-level indexes.② The results of the interaction between group and time after training showed that the training group had significantly higher total score and score of each dimension in sense of meaning in life,and increased total score of social adaptability,but lower total score of perceived stress when compared with the control group(all P＜0.001).③ The results of group main effect after training indicated that obviously higher total score and score of each dimension in sense of meaning in life(P＜0.01),elevated total score of social adaptability(P＜0.01),and reduced total score of perceived stress(P＜0.001)were observed in the training group than the control group.④ The results of the post-training time main effect revealed that the training group had notably higher total score and score of each dimension in sense of meaning in life(P＜0.05),increased total score of social adaptability(P＜0.001),and decreased total score of perceived stress(P＜0.001)when compared with the control group.Conclusion Our developed group psychological training can significantly improve the sense of meaning in life,reduce perceived stress and improve their social adaptation ability for retired soldiers during the transitional period.

Objective To investigate the value of multiparametric magnetic resonance imaging(MRI)texture analysis based on T2 weighted image(T2WI),diffusion weighted imaging(DWI),and dynamic contrast enhanced-MRI(DCE-MRI)in predicting the axillary lymph node status of small-sized invasive ductal carcinoma(IDC)of the breast.Methods A retrospective analysis was conducted on the medical records of 139 patients with newly diagnosed IDC,who were treated at Taizhou Central Hospital from January 2018 to June 2023.Based on the postoperative pathological results,the patients were divided into two groups:85 cases without axillary lymph node metastasis and 54 cases with axillary lymph node metastasis.All patients underwent preoperative MRI examination,including sequences such as T2WI,DWI,and DCE-MRI.After delineating the region of interest(ROI)on the slice with the largest tumor diameter in each sequence,texture analysis was performed using Firevoxel software,which yielded five major parameters,including mean,standard deviation,skewness,kurtosis,and entropy.Univariate analysis was employed to evaluate the effectiveness of each parameter in distinguishing the axillary lymph node status.Variables that showed significant results in the univariate analysis were then included in binary Logistic regression analysis to explore the relationship between these parameters and lymph node metastasis status.Receiver operating characteristic(ROC)curves were plotted,and the area under the curve(AUC)was calculated.Results Significant differences were observed between the two groups in the entropy and mean values of the ROI delineated on the DCE-MRI sequence,as well as the skewness of the T2WI(P<0.001).Among these texture parameters,the entropy of the DCE-MRI sequence showed the highest AUC value of 0.719 in the univariate analysis.Multivariate analysis of the selected parameters yielded an optimal diagnostic model,with an AUC of 0.769 in differentiating lymph node metastasis from non-metastasis.Conclusion Texture analysis of small-sized breast cancer based on multiparametric MRI can effectively predict the preoperative axillary lymph node status of breast cancer.

Objective To investigate the diagnostic value of biparametric magnetic resonance imaging(bpMRI)radiomics combined with prostate-specific antigen density(PSAD)in predicting low-grade and high-grade prostate carcinoma(PCa).Methods The clinical and imaging data of patients with PCa confirmed by pathology in Taizhou Central Hospital from June 2018 to October 2022 were retrospectively analyzed.According to Gleason grade group(GGG),GGG≤2 was defined as low-grade PCa,and GGG＞2 was defined as high-grade PCa.PCa patients with different grades were randomly divided into training group and test group according to a ratio of 7∶3.Radiomics features were extracted based on T2 weighted imaging(T2WI)and apparent diffusion coefficient(ADC)sequences.Feature selection and dimensionality reduction were carried out using maximum relevance minimum redundancy,least absolute shrinkage and selection operator,and 5-fold cross validation was performed to retain the best radiomics features.Receiver operating characteristic(ROC)curve and Delong's test were used to evaluate the performance of each model.Decision curve analysis(DCA)was used to evaluate the clinical utility of the model.Results Among all the models,T2WI-ADC-PSAD combined model had the best diagnostic efficiency,the area under the curve(AUC)in training group and test group were 0.882,0.772,respectively.Delong's test showed that in training group,there was no significant difference in AUC between T2WI-ADC-PSAD model and T2WI model(P＞0.05),but there were significant differences between T2WI-ADC-PSAD model and other models(P＜0.05).In test group there were no significant differences in AUC between T2WI-ADC-PSAD model and other models(P＞0.05).The DCA showed that the T2WI-ADC-PSAD model provided a higher net benefit for clinical decision-making when the threshold probability was less than 97％.Conclusion BpMRI radiomics combined with PSAD can improve the diagnostic efficiency of low-grade and high-grade PCa,and guide the treatment decision of patients.

Objective:To screen differentially expressed circular RNA (circRNA) in rat articular chondrocyte injury induced by T-2 toxin, and explore the mechanism of cartilage injury.Methods:Twenty-four SD rats (males, body weight 60 - 80 g) were randomly divided into T-2 toxin group (administrated T-2 toxin 100 ng·g -1·d -1 by gavage) and control group (administrated equal amounts of deionized water by gavage) using a random number table method, 12 rats in each group. After 4 weeks of intervention, the articular cartilage was collected for transcriptome sequencing. Deseq2 software [ P < 0.05 and |log 2(fold change)| > 1, fold change was the multiple of differential expression] was used to identify differentially expressed circRNA. Based on the competing endogenous RNAs (ceRNA) hypothesis, the miRanda software was used to predict the microRNA (miRNA, miR) binding sites of differentially expressed circRNA, and Cytoscape 3.10.0 software was used to plot the circRNA-miRNA interaction network. MiRWalk 3.0, MiRDB, and miRTarBase softwares were used to predict downstream target genes, and Cytoscape 3.10.0 software was used to map the circRNA-miRNA-mRNA interaction network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the biological functions and enrichment pathways of target genes. Results:A total of 19 differentially expressed circRNAs were screened (including 10 upregulated and 9 downregulated). A total of 1 320 miRNAs binding sites and 16 target genes were predicted. Target gene enrichment analysis revealed significant enrichment of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signaling pathway ( P < 0.05). Tumour necrosis factor receptor-associated factor 6 (Traf6) and interleukin-1 receptor-associated kinase 1 (Irak1) were enriched in the MAPK and NF-κB signaling pathways, with corresponding miRNA and circRNA of miR-146a-5p and chr2: 94716330|94720889. Conclusion:Nineteen differentially expressed circRNAs in rat articular chondrocyte injury are successfully screened, and chr2: 94716330|94720889 may regulate the MAPK and NF-κB signaling pathways through the miR-146a-5p/Traf6/Irak1 axis, inducing articular chondrocyte injury.

Objective:To study the relationship between fluoride exposure and adrenocorticotropic hormone (ACTH)/cortisol (CORT) in rural children in eastern Henan, and to reveal the modifying effect of brain-derived neurotrophic factor (BDNF) gene polymorphism.Methods:A total of 463 children aged 7 - 12 (245 boys and 218 girls) from 4 primary schools in Tongxu County, Henan Province were recruited by a cluster sampling method for questionnaire survey, physical examination, and collection of morning urine and fasting venous blood. The concentrations of urinary fluoride and creatinine were determined by a fluoride ion selective electrode method and picric acid method, respectively. Serum ACTH and CORT levels were determined with a fully automated biochemical analyzer, and the genotyping of BDNF gene loci of single nucleotide polymorphism was conducted by a customized 48-Plex SNPscan TM reagent kit. Besides, the relationships between urinary fluoride concentrations and serum ACTH/CORT levels in children were analyzed by multiple linear regression models. The interaction term between urinary fluoride concentration and BDNF gene polymorphism was established, and the interaction between unit point gene polymorphism and environment on serum ACTH or CORT levels of children was analyzed by multiple linear regression. Results:For every 1 mg/L increase in urinary fluoride concentration, serum ACTH level in girls increased by 1.98 pg/ml [95% confidence interval ( CI): 0.71, 3.24; P = 0.002], while serum CORT level in boys decreased by 37.48 ng/ml (95% CI: - 63.99, - 10.97; P = 0.006). Regardless of stratified analysis, the urinary fluoride concentration of individuals carrying the TA genotype at the rs6484320 locus was positively correlated with serum ACTH level (β > 0, P < 0.05); in addition, there was a positive correlation between urinary fluoride concentration and serum ACTH level in the total population and boys carrying the CC genotype of rs7103873 locus (β > 0, P < 0.05); and the serum ACTH and CORT levels in girls carrying the AA genotype of rs12291186 locus were positively correlated with urinary fluoride concentration (β > 0, P < 0.05). The interaction analysis showed that there was an interaction between urinary fluoride concentrations and rs6484320/rs7103873 loci polymorphisms on serum ACTH level in the total population and boys ( Pinteraction < 0.1), as well as urinary fluoride concentrations and rs12291186 locus polymorphism on serum CORT level in girls ( Pinteraction = 0.035). Conclusions:Urinary fluoride concentration is associated with increased serum ACTH level in girls and decreased serum CORT level in boys. BDNF gene polymorphism can modify the association between fluoride exposure and serum ACTH or CORT levels in children, and the modification effect varies by gender.