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.

Background/Aims: Dysregulated cholesterol metabolism is a hallmark of hepatocellular carcinoma (HCC) that drives tumor initiation and progression. However, clinical targeting of cholesterol metabolism has yielded limited benefits due to stringent feedback in tumor cells. Identifying a central mediator capable of restoring cholesterol homeostasis within the cell’s intrinsically fine-tuned regulatory framework is urgently needed. Methods: We integrated a proteomic dataset from patients with cholesterol-dysregulated HCC into a global cholesterol metabolic regulatory network to identify potential therapeutic targets for disrupted cholesterol homeostasis. The prognostic significance of the candidate targets was further validated in an independent cohort through immunohistochemistry. Functional and mechanistic studies were conducted in vitro using HCC cell lines and in vivo using mouse models. The pharmacological efficacy of the candidate agent was evaluated in both subcutaneous and orthotopic HCC mouse models. Results: ER lipid raft-associated 1 (ERLIN1), a pivotal regulator of cholesterol metabolism reprogramming, was identified as an independent favorable prognostic indicator in HCC. ERLIN1 constrains HCC progression both in vitro and in vivo by stabilizing the INSIG1–SCAP–SREBP2 axis and maintaining the metabolic balance of intracellular cholesterol. Under hypoxia, impaired factor-inhibiting hypoxia-1-dependent hydroxylation of ASB11 at asparagine residues 90 and 92 enhances ASB11-mediated ERLIN1 degradation. Pharmacological targeting of this axis using zoledronic acid (ZoA) attenuated HCC progression by weakening the ASB11–ERLIN1 interaction and restoring cholesterol homeostasis. Conclusions ERLIN1 represents a druggable metabolic vulnerability in cholesterol-dysregulated HCC. Targeting the ASB11–ERLIN1 axis with the clinically approved ZoA reestablishes cholesterol homeostasis and offers a promising therapeutic strategy to overcome the current limitations of cholesterol-targeted HCC therapies.

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 investigate the establishment and evaluation of an idiopathic pulmonary fibrosis(IPF)mouse model induced by the intratracheal infusion of bleomycin(BLM)of different concentrations.Methods Male C57BL/6J mice were randomly divided into a control group,Model-L group(1.5 mg/kg,BLM),Model-M group(2.5 mg/kg,BLM),and Model-H group(3.5 mg/kg,BLM).An IPF mouse model was constructed by one-time intratracheal infusion of BLM.The general status,body mass,survival rate,and lung coefficient of mice in different groups were compared.Pathological changes in lung tissue,the hydroxyproline content,fibrosis markers and inflammatory factor levels were observed.Results Compared with the control group,the survival rate decreased and body weight showed a downward trend in the low-,medium-,and high-dose model groups,with significant increases in lung coefficients.Inflammatory infiltration(P＜0.01)and collagen deposition(P＜0.0001)were observed in the lung tissues of all model groups.Hydroxyproline levels in lung tissue and serum were significantly elevated(P＜0.05).The mRNA levels of fibrosis markers α-Sma,Fn1,and Col1a1 were upregulated(P＜0.001),with significant increases in corresponding protein expression(P＜0.05).The mRNA expression of the inflammatory factor Tgfb1 also increased(P＜0.0001).Conclusion 1.5,2.5 and 3.5 mg/kg BLM can induce an IPF model in C57BL/6J mice.Based on the results observed for survival rate,body mass,lung coefficient changes,lung tissue gross and pathological changes,and fibrosis-related biomarkers,2.5 mg/kg BLM is the optimal concentration for inducing an IPF mouse model.

Phospholipid pharmaceutical excipients are primarily composed of a glycerol backbone,fatty acid chains,and phosphate groups.Due to their amphiphilic structure and unique physicochemical properties,they are commonly used as emulsifiers and carrier materials in pharmaceutical formulations.The pharmacopoeias of various countries have included phospholipid based pharmaceutical excipients and specified the testing methods and limits for their critical quality attributes.This article focuses on the current inclusion status,characteristic indicators,component content determination indicators,and functionality-related indicators determination methods and limits of phospholipid pharmaceutical excipients of various countries,in order to provide references and a basis for the rational applicatione of phospholipid pharmaceutical excipients.

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.

BACKGROUND:Mitophagy is closely associated with the development of idiopathic pulmonary fibrosis,but its mechanism remains unclear.OBJECTIVE:To investigate the biological mechanism of mitophagy in idiopathic pulmonary fibrosis and provide ideas for the risk prediction of idiopathic pulmonary fibrosis and subtype differentiation.METHODS:The mitophagy-related genes in idiopathic pulmonary fibrosis were obtained through GEO and Reactome Pathway databases.The mitophagy-related characteristic genes in idiopathic pulmonary fibrosis were screened based on intergroup differences and random forest model.GO functional enrichment analysis and KEGG,Reactome with WIKI pathway enrichment analyses were performed by g:Profiler database.Mitophagy subtypes in idiopathic pulmonary fibrosis were distinguished by consensus clustering method and immune infiltration analysis was performed.The mitophagy-related key gene was screened.Finally,the predictive value of mitophagy-related key gene for the risk of idiopathic pulmonary fibrosis was quantified by alignment diagram and the correlation between mitophagy-related key gene and clinical characteristics of idiopathic pulmonary fibrosis was explored.RESULTS AND CONCLUSION:(1)A total of 13 genes related to mitophagy in idiopathic pulmonary fibrosis were identified and 5 characteristic genes were screened,containing PINK1,RPS27A,SRC,HIF1A,and CDH6.(2)GO analysis was mainly involved in ubiquitin protein ligase binding,and cellular response to hypoxia.Pathway enrichment analysis was mainly involved in PINK1-PRKN mediated mitophagy,NOTCH signaling pathway,signaling by EGFR and angiogenesis.(3)HIF1A had significant expression differences between subtypes,which might serve as a key gene for the differentiation of mitophagy subtypes of idiopathic pulmonary fibrosis.(4)Immune infiltration analysis suggested that myeloid-derived suppressor cell,neutrophil and type 1 T helper cell might have infiltration differences between subtypes,while HIF1A was positively correlated with multiple immune cells.(5)Alignment diagram suggested that the risk of idiopathic pulmonary fibrosis might be predicted by the expression level of HIF1A.(6)Clinical characteristics analysis indicated patients with high expression of HIF1A might have poorer lung function and more severe fibrosis.It is concluded that PINK1,RPS27A,SRC,HIF1A,and CDH6 may influence the development of idiopathic pulmonary fibrosis through mitophagy,in which HIF1A may serve as a key gene for risk prediction with clinical subtype differentiation and HIF1A is strongly associated with the lung function of patients.

Objective:The purpose of this study was to develop a dynamic prediction model for patients with gastric signet ring cell cancer (GSRCC)following laparoscopic radical gastrectomy in order to improve the precision and usefulness of prognoses prediction for overall survival and disease-free survival.Methods:From 2011 to 2018, 914 National Cancer Center patients participated in the study. To find independent prognostic indicators and create a prognostic nomogram model, univariate and multivariate regression analyses were performed. Calibration curves, receiver operating characteristic curves, and consistency indices were used to assess the model's performance. To make clinical application more convenient, two web-based prediction tools were created.Results:A training set of 639 cases and a validation set of 275 instances were randomly selected from among the patients. Important predictive variables such as age, tumor size, location, pN and pT staging, and postoperative chemotherapy were all incorporated in the model (all P<0.05). The model's consistency index and area under the receiver operating characteristic curves were both higher than 0.7, and the calibration curves demonstrated a good fit between the expected and actual values, indicating high accuracy and consistency in postoperative survival prediction for patients with gastric signet ring cell carcinoma. Conclusion:We successfully developed two dynamic prediction models in this study, which improved its clinical practicability using web-based tools and is anticipated to be crucial to clinical practice going forward.

Objective:To identify factors associated with depressive symptoms in maintenance hemodialysis patients and to examine the relationship between these symptoms and mortality.Methods:Between January and December 2019, patients who received maintenance hemodialysis in the Blood Purification Center of the Second Affiliated Hospital of Nanjing Medical University were enrolled in a prospective cohort study. Depressive symptoms were assessed using the internationally validated patient health questionnaire-8 (PHQ-8). Sleep quality and anxiety were measured with the Pittsburgh sleep quality index (PSQI) and the generalized anxiety disorder-7 (GAD-7) scale, respectively. Follow-up continued until December 31, 2022, with all-cause mortality as the primary outcome. Ordinal logistic regression was used to identify independent predictors of depression severity. Cox proportional hazards models evaluated the association between depressive symptoms and mortality.Results:A total of 532 maintenance hemodialysis (MHD) patients completed the study. Among them, 177 (33.3%) exhibited depressive symptoms. Compared with patients without depression, those with mild or moderate-to-severe depression were older [median age: 58 (50, 66) vs. 60 (55, 65) vs. 55 (46, 64)], more likely to smoke [35.9% (51/142) vs. 40.0% (14/35) vs.26.2% (93/355)], had poorer sleep quality [PSQI: 9 (6, 13) vs. 12 (9, 17) vs. 5 (3, 9)], and higher anxiety levels [GAD-7: 1 (0, 3) vs. 3 (1, 6) vs. 0 (0, 1)], the differences among the three groups were statistically significant (all P<0.05). Ordinal logistic regression identified smoking status, history of diabetes or cardiovascular disease, hemoglobin level, PSQI score, and GAD-7 score as independent predictors of depression severity ( OR=1.60, 1.80, 1.81, 0.98, 3.67, 8.67; all P<0.05). After a median follow-up of 40 (35, 44) months, 109 patients died, including 66 (60.6%) from cardio-cerebrovascular causes and 24 (22.0%) from infections. Kaplan-Meier analysis revealed significantly lower cumulative survival in the depression group compared to the non-depression group ( P<0.001). Cox regression analysis demonstrated that depressive symptoms remained independently associated with all-cause mortality after adjusting for confounders ( HR=1.06, 95% CI 1.00-1.13, P=0.048), with an even stronger association observed for patients with PHQ-8 scores≥2.9 ( HR=1.10, 95% CI 1.03-1.16, P=0.005). However, the associations between depression and cardio-cerebrovascular mortality ( P=0.111) or infection-related mortality ( P=0.509) were not statistically significant. Conclusions:Depressive symptoms are prevalent among maintenance hemodialysis patients and are independently associated with increased all-cause mortality. Smoking, comorbid diabetes or cardiovascular disease, low hemoglobin level, poor sleep quality, and anxiety are risk factors contributing to depression. Maintenance hemodialysis patients with PHQ-8 scores≥3 should be considered at heightened risk for mortality.

Phospholipid pharmaceutical excipients are primarily composed of a glycerol backbone,fatty acid chains,and phosphate groups.Due to their amphiphilic structure and unique physicochemical properties,they are commonly used as emulsifiers and carrier materials in pharmaceutical formulations.The pharmacopoeias of various countries have included phospholipid based pharmaceutical excipients and specified the testing methods and limits for their critical quality attributes.This article focuses on the current inclusion status,characteristic indicators,component content determination indicators,and functionality-related indicators determination methods and limits of phospholipid pharmaceutical excipients of various countries,in order to provide references and a basis for the rational applicatione of phospholipid pharmaceutical excipients.