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.

Objective To analyze the global burden of disease and cross-national imbalances of tracheal,bronchial and lung cancer from 1990-2021 and to further predict changes up to 2040.Methods Age-standardised incidence rate(ASIR),prevalence rate(ASPR),mortality rate(ASMR),disability-adjusted life years rate(ASDR)and 95%confidence interval(95%UI)were extracted from GHDx.The official data platform of the institute for health metrics and evaluation(IHME)and the source of data were the Global Burden of Disease Study 2021(GBD 2021)for global burden of disease of trachea,bronchus and lung cancer.The estimated annual percentage change(EAPC)was calculated to describe the prevalence at global,regional and national levels,to understand the differences in diseases at different gender,age and socio-demographic index(SDI)levels,and to explore the overall situation through cluster analysis,cross-country health inequality analysis and to predict the future prevalence up to 2040 through Nordpred model.Results Globally,the ASIR for tracheal,bronchial and lung cancer fluctuated slightly from 1990 to 2009,and began to decline rapidly after 2009,with an ASIR of 26.42/100 000 in 2021.ASPR showed an increasing and then decreasing trend,reaching a peak in 2011,with a peak of 37.28/100 000 in 2021,while the ASMR and the ASDR showed a general decreasing trend.Tracheal,bronchial and lung cancer diseases showed the highest disease burden in men,those aged 65-74 and in countries and regions with high SDI.ASDR burden showed significant inequalities globally,with a significant positive correlation between ASDR and SDI,mainly concentrated in countries and regions with high SDI,and the unequal burden of ASDR for tracheal,bronchial and lung cancer decreases over time.Predictive analyses found that the number of new cases,current cases,deaths and disability-adjusted life years(DALY)for tracheal,bronchial and lung cancer were expected to increase through 2040,whereas ASIR,ASPR,ASMR and ASDR were projected to decrease each year.Conclusion The overall burden of tracheal,bronchial and lung cancer has declined globally from 1990 to 2021,but with demographic and regional differences.The actual number of cases will continue to climb in the future,despite the continuing decline in age-specified rates,and disease prevention and control will need to focus on growth trends and equity in resource allocation.

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 compare TyG index between the patients with CHF and ADHF to eluci-date the metabolic difference between these two stages.Methods A total of 1156 HF patients ad-mitted in Taizhou People's Hospital between January 2020 and December 2022 were enrolled,and according to 2021 ESC Guidelines for Diagnosis and Treatment of Acute and Chronic Heart Fail-ure,they were divided into CHF group(365 cases)and ADHF group(791 cases).The clinical da-ta,results of laboratory tests,and cardiovascular history were collected,and TyG index was calcu-lated.All-cause death outcome was observed in ADHF patients during a follow-up of 1 year.Results The TyG index was significantly lower in the ADHF group than the CHF group[8.27(7.99,8.62)vs 8.35(8.04,8.75),P=0.001].In the ADHF group,the TyG index was positively correlated with SBP,DBP,TC,TG,LDL-C,FPG,HbA1c,BMI,and LVEF,and negatively with age(P＜0.01).In the CHF group,the index was positively correlated with DBP,TC,TG,LDL-C,FPG,BMI,and HbA1c,and negatively with age(P＜0.05,P＜0.01).Both univariate and multiva-riate logistic regression analyses indicated that the TyG index was a protective factor for ADHF(OR=0.647,95％CI:0.503～0.832,P=0.001;OR=0.694,95％CI:0.536～0.898,P=0.005).Multivariate logistic regression analysis showed that the index in ADHF patients was a protective factor for one-year all-cause mortality(OR=0.483,95％CI:0.254-0.916;P=0.026).Conclusion TyG index might be regarded as an important marker for assessing the metabolic status in HF patients and predicting the prognosis in ADHF patients.

Objective To analyze the global burden of disease and cross-national imbalances of tracheal,bronchial and lung cancer from 1990-2021 and to further predict changes up to 2040.Methods Age-standardised incidence rate(ASIR),prevalence rate(ASPR),mortality rate(ASMR),disability-adjusted life years rate(ASDR)and 95%confidence interval(95%UI)were extracted from GHDx.The official data platform of the institute for health metrics and evaluation(IHME)and the source of data were the Global Burden of Disease Study 2021(GBD 2021)for global burden of disease of trachea,bronchus and lung cancer.The estimated annual percentage change(EAPC)was calculated to describe the prevalence at global,regional and national levels,to understand the differences in diseases at different gender,age and socio-demographic index(SDI)levels,and to explore the overall situation through cluster analysis,cross-country health inequality analysis and to predict the future prevalence up to 2040 through Nordpred model.Results Globally,the ASIR for tracheal,bronchial and lung cancer fluctuated slightly from 1990 to 2009,and began to decline rapidly after 2009,with an ASIR of 26.42/100 000 in 2021.ASPR showed an increasing and then decreasing trend,reaching a peak in 2011,with a peak of 37.28/100 000 in 2021,while the ASMR and the ASDR showed a general decreasing trend.Tracheal,bronchial and lung cancer diseases showed the highest disease burden in men,those aged 65-74 and in countries and regions with high SDI.ASDR burden showed significant inequalities globally,with a significant positive correlation between ASDR and SDI,mainly concentrated in countries and regions with high SDI,and the unequal burden of ASDR for tracheal,bronchial and lung cancer decreases over time.Predictive analyses found that the number of new cases,current cases,deaths and disability-adjusted life years(DALY)for tracheal,bronchial and lung cancer were expected to increase through 2040,whereas ASIR,ASPR,ASMR and ASDR were projected to decrease each year.Conclusion The overall burden of tracheal,bronchial and lung cancer has declined globally from 1990 to 2021,but with demographic and regional differences.The actual number of cases will continue to climb in the future,despite the continuing decline in age-specified rates,and disease prevention and control will need to focus on growth trends and equity in resource allocation.

Objective To compare TyG index between the patients with CHF and ADHF to eluci-date the metabolic difference between these two stages.Methods A total of 1156 HF patients ad-mitted in Taizhou People's Hospital between January 2020 and December 2022 were enrolled,and according to 2021 ESC Guidelines for Diagnosis and Treatment of Acute and Chronic Heart Fail-ure,they were divided into CHF group(365 cases)and ADHF group(791 cases).The clinical da-ta,results of laboratory tests,and cardiovascular history were collected,and TyG index was calcu-lated.All-cause death outcome was observed in ADHF patients during a follow-up of 1 year.Results The TyG index was significantly lower in the ADHF group than the CHF group[8.27(7.99,8.62)vs 8.35(8.04,8.75),P=0.001].In the ADHF group,the TyG index was positively correlated with SBP,DBP,TC,TG,LDL-C,FPG,HbA1c,BMI,and LVEF,and negatively with age(P＜0.01).In the CHF group,the index was positively correlated with DBP,TC,TG,LDL-C,FPG,BMI,and HbA1c,and negatively with age(P＜0.05,P＜0.01).Both univariate and multiva-riate logistic regression analyses indicated that the TyG index was a protective factor for ADHF(OR=0.647,95％CI:0.503～0.832,P=0.001;OR=0.694,95％CI:0.536～0.898,P=0.005).Multivariate logistic regression analysis showed that the index in ADHF patients was a protective factor for one-year all-cause mortality(OR=0.483,95％CI:0.254-0.916;P=0.026).Conclusion TyG index might be regarded as an important marker for assessing the metabolic status in HF patients and predicting the prognosis in ADHF patients.

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 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-75 G/A single-nucleotide polymorphism in the promoter region of apolipoprotein A1 gene(apoA1)and its association with gestational diabetes mellitus(GDM)in pregnant women and to provide references for the exploration in the molecular genetic basis of GDM.Methods A total of 626 GDM patients and 1022 normal pregnant women,ie,the controls,were included in the study.The genotyping of apoA1-75 G/A polymorphism was performed by polymerase chain reaction and restriction fragment length polymorphism(PCR-RFLP)analysis.Total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),and glucose(Glu)were measured by enzymatic methods.Plasma insulin(INS)was measured by chemiluminescence immunoassay.The protein levels of apoA1 and apoB were measured by the turbidimetric immunoassay.Results Allele frequencies of G and A were 0.718 and 0.282 in the GDM group and 0.713 and 0.287 in the control group,respectively.Distribution of the genotype frequencies was found to be in Hardy-Weinberg equilibrium in both the GDM and control groups.There was no significant difference in the frequencies of alleles G and A and the genotypes of apoA1-75 G/A polymorphism between the GDM and the control group(P>0.05).In the GDM group,the carriers with the genotype AA were associated with significantly higher levels of TC,HDL-C,and apoA1 than those with genotypes GG and GA did(all P<0.05).After the GDM patients were divided into obese and non-obese subgroups,the genotype-related apoA1 variation was observed only in obese patients,while the genotype-related TC and HDL-C variations were evident in non-obese patients(P<0.05).In the control group,carriers of genotypes AA and GA had higher systolic blood pressure(SBP)and HDL-C than the carriers of genotype GG did(all P<0.05).Carriers of genotypes AA had significantly lower Glu levels than carriers of genotypes GG and GA did(P<0.05).The control subjects were further divided into subgroups according to their body mass index(BMI).Analysis of the subgroups showed that AA carriers were associated with higher SBP levels in the obese control women only,while lower Glu levels were evident in both obese and non-obese control women.Conclusion These results suggest that-75 G/A polymorphism in the apoA1 gene is not associated with GDM.However,the genetic variation is closed associated with the plasma apoA1,HDL-C,and TC levels in GDM patients and plasma HDL-C,Glu,and SBP levels in the control subjects.The apoA1 variant-associated lipids and SBP variation is BMI dependent in both groups.