Cuproptosis, recently defined as a unique form of cell death distinct from programmed cell death, is triggered by copper overload within mitochondria. Genes associated with cuproptosis have been found to correlate with tumorigenesis and tumor progression, making the targeting of cuproptosis pathways a promising direction for anti-tumor therapies. Copper ion carriers can transport copper ions into cells, inducing cuproptosis and laying the foundation for its application in cancer treatment. This article elaborates on the homeostasis of copper and the mechanisms related to cuproptosis, further clarifying the relationship between cuproptosis and lung cancer treatment targets. This review aims to summarize current progress in research related to cuproptosis and lung cancer, providing new theories and bases for the clinical treatment of lung cancer.

ObjectiveTo investigate the effect of SU056， an azo-podophyllotoxin derivative， on carbon tetrachloride （CCl₄）-induced liver fibrosis in mice and related mechanisms of action. MethodsA total of 12 mice were randomly divided into control group， model group （CCl₄+normal saline）， and treatment group （CCl₄+SU056）， with 4 mice in each group. Mice were given intraperitoneal injection of CCl₄ to establish a model of liver fibrosis， and during the middle stage of modeling， the mice in the treatment group were given daily intraperitoneal injection of SU056. Liver histopathological injury， collagen deposition， and liver function were assessed based on HE staining， Masson staining， Sirius Red staining， the content of hydroxyproline in liver tissue， and the serum levels of alanine aminotransferase and aspartate aminotransferase， and immunofluorescence assay was used to measure the expression levels of smooth muscle actin α （α-SMA）， collagen type Ⅰ， and Y-box binding protein 1 （YB1）. The human hepatic stellate cell （HSC） line LX-2 and primary mouse HSC were used， and CCK-8 assay was used to measure cell proliferation； Transwell assay was used to observe cell migration； quantitative reverse transcription-polymerase chain reaction and Western Blot were used to measure the expression levels of collagen type Ⅰ， collagen type Ⅲ， YB1， phosphorylated mammalian target of rapamycin （mTOR）， and phosphorylated S6K， so as to validate the function of the YB1/mTOR signaling axis. The one-way or two-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsIn the mouse model of liver fibrosis induced by CCl₄， compared with the model group， the treatment group had significant alleviation of inflammatory cell infiltration， collagen deposition， and pseudolobule formation in liver tissue and significant reductions in the serum levels of alanine aminotransferase and aspartate aminotransferase and the content of hydroxyproline in liver tissue （all P<0.01）. Immunofluorescence assay showed that SU056 significantly inhibited the abnormal high expression of α-SMA， collagen type I， and YB1 in liver tissue （all P<0.01）. In vitro experiments showed that SU056 inhibited the transforming growth factor-β1-induced proliferation of LX-2 cells （P<0.01）， the migration of LX-2 cells （P<0.05）， and the transcriptional up-regulation of collagen type Ⅰ and collagen type Ⅲ （all P<0.05） in a dose-dependent manner， and SU056 could inhibit the spontaneous activation of primary HSC in vitro. Mechanistic studies revealed that transforming growth factor-β1 simultaneously upregulated the expression levels of YB1， phosphorylated mTOR， and phosphorylated S6K in LX-2 cells， and treatment with SU056 （10 and 20 µmol/L） could downregulate the protein expression levels of collagen type I， YB1， phosphorylated mTOR， and phosphorylated S6K. Specific knockdown of YB1 or administration of the mTOR inhibitor rapamycin exerted a similar effect as SU056. SU056 also inhibited the co-upregulation of α-SMA and phosphorylated mTOR in liver tissue of model mice （P<0.01）. ConclusionSU056 can effectively inhibit HSC activation， proliferation， migration， and extracellular matrix production both in vivo and in vitro and thus delay the progression of liver fibrosis， by disrupting the YB1/mTOR positive feedback signaling axis.

Objective To examine the impact of climate, land use and their interaction effect on the population density of Oncomelania hupensis. Methods O. hupensis snail surveillance data in Yunnan Province from 2013 to 2022 were obtained from the National Information System for Parasitic Diseases Prevention and Control of Chinese Information System for Disease Control and Prevention, and the density of living snails was calculated in each county-level administrative district. Climate data were obtained from the China Meteorological Forcing Dataset version 2.0, and land use data were captured from the China Land Cover Dataset. The raster climate data and land use data were clipped to the administrative border of Yunnan Province in the R package version 4.5, and the climate data were resampled to a spatial resolution of 30 m × 30 m consistent with the land use data using bilinear interpolation. Annual meteorological indicators were extracted from each county-level schistosomiasis surveillance administrative area in Yunnan Province from 2013 to 2022, including average temperature, maximum temperature, minimum temperature, temperature difference, average precipitation rate, maximum precipitation rate, minimum precipitation rate, downward shortwave radiation flux, downward longwave radiation flux, air pressure, wind speed, specific humidity and relative humidity. Annual land use structure and landscape pattern index in each county-level schistosomiasis surveillance administrative area in Yunnan Province from 2013 to 2022 were extracted and calculated, including the proportion of areas occupied by each type of land use, patch density, largest patch index, landscape separation index, landscape fragmentation index, landscape segmentation index, contagion index, patch cohesion index, edge density, and shape index. Land use entropy index was introduced to represent the degree of habitat fragmentation and ecological niche breadth. The density of living snails and environmental factors were subjected to rank correlation analysis, and variables with no statistically significant correlation (P>0.1) were excluded. Then, a correlation coefficient matrix was constructed, and |r_s| of 0.85 and greater was defined as the threshold of high collinearity. For highly correlated variables in each group, indicators with a more biological explanatory power or a better statistical efficiency were retained. A generalized additive model (GAM) was constructed with O. hupensis snail density as a response variable and screened environmental variables as independent variables, and the model performance was evaluated using the variance explained. Results The area occupied by O. hupensis snail habitats was 1 056 to 1 680 hm² in Yunnan Province from 2013 to 2022, appearing an overall tendency towards a decline; however, the density of living snails appeared a tendency towards a slight rise. Based on the correlation coefficient matrix, 14 core explanatory variables were retained, including farmland, water bodies, bare land, impervious surface, landscape separation index, landscape fragmentation index, edge density, shape index, land use entropy index, downward longwave radiation flux, downward shortwave radiation flux, maximum temperature, minimum precipitation rate and specific humidity. Two types of GAM were constructed, including the main-effects model without interaction terms and the interaction model with interaction terms. The corrected Akaike information criterion (AICc) of the optimal main-effects model was −285.223, and the core variables included bare land, impervious surface, landscape separation index, edge density, shape index, land use entropy index and downward shortwave radiation flux. Following introduction of second-order interaction terms, the AICc value of the optimal interaction model was −345.526, and the significant interaction combinations included: farmland × impervious surface, farmland × landscape separation index, farmland × shape index, farmland × land use entropy index, impervious surface × landscape separation index, impervious surface × edge density, and shape index × downward shortwave radiation flux. The proportion of the main-effects model explaining the variation of O. hupensis snail density was 39.8%, and the explanatory power of GAM increased to 79.0% following introduction of interaction terms. Conclusion Landscape separation index, edge density, shape index and other landscape pattern indicators pose significant impacts on the intensity and direction of changes in O. hupensis snail density in Yunnan Province.

Objective: To assess the current status of knowledge, attitude, and practice (KAP) regarding health protection against air pollution among primary school students in China, and to analyze the impacts of fine particulate matter (PM 2.5 ) exposure, family, and individual factors on KAP levels, so as to provide empirical basis for implementing targeted interventions. Methods: Using stratified cluster random sampling method, a questionnaire survey was conducted among 19 297 primary school students from third to fifth grade across 30 provinces (autonomous regions and municipalities directly under the central government) in China in 2024. The questionnaire was developed based on the Technical Guidelines for the Assessment of Civic Environmental and Health Literacy (Trial), and encompasses three dimensions:knowledge, attitude, and practice. Spearman correlation analysis, Chi-square test, multivariate Logistic regression, and Bootstrap mediation effect test was applied for data analysis. Results: The overall mean KAP score for health protection against air pollution among primary school students was (79.73±13.53), with an adequacy rate of 80.47% ( n =15 528). The dimension scores for knowledge, attitude, and practice were (41.34±8.01, 16.43± 2.61 ), and (21.97±5.71), respectively. Knowledge was positively correlated with attitude and practice, and attitude was positively correlated with practice ( r =0.51, 0.35, 0.32, all P <0.01). Multivariate Logistic regression showed that the northeast region ( OR =2.36, 95% CI =2.02-2.75), having parents with a bachelor s degree or higher ( OR =4.76, 95% CI =2.71-8.37), living with both parents ( OR =1.33, 95% CI =1.15-1.55), being in the fifth grade ( OR =1.22, 95% CI =1.11-1.33), outdoor PM 2.5 level exceeding standard limits at the survey site ( OR =1.25, 95% CI =1.16-1.34), history of allergy ( OR =1.47, 95% CI =1.31-1.64), and wearing masks during heavily polluted weather ( OR =1.19, 95% CI =1.07-1.31) were promoting factors for KAP adequacy rate (all P <0.05). Conversely, obesity was a detrimental factor ( OR =0.78, 95% CI =0.69-0.88, all P <0.05). Conclusions Primary school students in China exhibit a favorable KAP level regarding health protection against air pollution, though regional, familial, and individual disparities persist. Exposure to PM 2.5 levels exceeding standard limits exerts a direct positive effect on enhancing health protection literacy. Future efforts should focus on the western region, families with lower educational attainment children to implement tailored, stratified interventions.

The study was conducted to investigate the mechanism of Xinyang Tablets( XYP) in modulating the fat mass and obesity-associated protein(FTO)/N6-methyladenosine(m6A) signaling pathway to ameliorate ventricular remodeling in heart failure(HF). A mouse model of HF was established by transverse aortic constriction(TAC). Mice were randomized into sham, model, XYP(low, medium, and high doses), and positive control( perindopril) groups(n= 10). From day 3 post-surgery, mice were administrated with corresponding drugs by gavage for 6 consecutive weeks. Following the treatment, echocardiography was employed to evaluate the cardiac function, and RT-qPCR was employed to determine the relative m RNA levels of key markers, including atrial natriuretic peptide( ANP), B-type natriuretic peptide( BNP), β-myosin heavy chain(β-MHC), collagen type I alpha chain(Col1α), collagen type Ⅲ alpha chain(Col3α), alpha smooth muscle actin(α-SMA), and FTO. The cardiac tissue was stained with Masson's trichrome and wheat germ agglutinin(WGA) to reveal the pathological changes. Immunohistochemistry was employed to detect the expression levels of Col1α, Col3α, α-SMA, and FTO in the myocardial tissue. The m6A modification level in the myocardial tissue was measured by the m6A assay kit. An H9c2 cell model of cardiomyocyte injury was induced by angiotensin Ⅱ(AngⅡ), and small interfering RNA(siRNA) was employed to knock down FTO expression. RT-qPCR was conducted to assess the relative m RNA levels of FTO and other genes associated with cardiac remodeling. The m6A modification level was measured by the m6A assay kit, and Western blot was employed to determine the phosphorylated phosphatidylinositol 3-kinase(p-PI3K)/phosphatidylinositol 3-kinase(PI3K) and phosphorylated serine/threonine kinase(p-Akt)/serine/threonine kinase(Akt) ratios in cardiomyocytes. The results of animal experiments showed that the XYP treatment significantly improved the cardiac function, reduced fibrosis, up-regulated the m RNA and protein levels of FTO, and lowered the m6A modification level compared with the model group. The results of cell experiments showed that the XYP-containing serum markedly up-regulated the m RNA level of FTO while decreasing the m6A modification level and the p-PI3K/PI3K and p-Akt/Akt ratios in cardiomyocytes. Furthermore, FTO knockdown reversed the protective effects of XYP-containing serum on Ang Ⅱ-induced cardiomyocyte hypertrophy. In conclusion, XYP may ameliorate ventricular remodeling by regulating the FTO/m6A axis, thereby inhibiting the activation of the PI3K/Akt signaling pathway.
Animals ; Ventricular Remodeling/drug effects* ; Heart Failure/physiopathology* ; Signal Transduction/drug effects* ; Mice ; Male ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred C57BL ; Humans ; Adenosine/analogs & derivatives* ; Myocytes, Cardiac/metabolism* ; Disease Models, Animal

This study investigates the effect and underlying mechanism of Guizhi Tongluo Tablets(GZTL) in treating atherosclerosis(AS) in a mouse model. Apolipoprotein E-knockout(ApoE~(-/-)) mice were randomly assigned to the following groups: model, high-, medium-, and low-dose GZTL, and atorvastatin(ATV), and age-matched C57BL/6J mice were selected as the control group. ApoE~(-/-) mice in other groups except the control group were fed with a high-fat diet for the modeling of AS and administrated with corresponding drugs via gavage for 8 weeks. General conditions, signs of blood stasis, and body mass of mice were monitored. Aortic plaques and their stability were assessed by hematoxylin-eosin, Masson, and oil red O staining. Serum levels of total cholesterol(TC), triglycerides(TG), and low-density lipoprotein cholesterol(LDL-C) were measured by biochemical assays, and those of interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6) were determined via enzyme-linked immunosorbent assay. Apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL). Single-cell RNA sequencing(scRNA-seq) was employed to analyze the differential expression of CD72hi macrophages(CD72hi-Mφ) in the aortas of AS patients and mice. The immunofluorescence assay was employed to visualize CD72hi-Mφ expression in mouse aortic plaques, and real-time fluorescence quantitative PCR was utilized to determine the mRNA levels of IL-1β, TNF-α, and IL-6 in the aorta. The results demonstrated that compared with the control group, the model group exhibited significant increases in body mass, aortic plaque area proportion, necrotic core area proportion, and lipid deposition, a notable decrease in collagen fiber content, and an increase in apoptosis. Additionally, the model group showcased elevated serum levels of TC, TG, LDL-C, IL-1β, TNF-α, and IL-6, alongside marked upregulations in the mRNA levels of IL-1β, TNF-α, and IL-6 in the aorta. In comparison with the model group, the GZTL groups and the ATV group showed a reduction in body mass, and the medium-and high-dose GZTL groups and the ATV group demonstrated reductions in aortic plaque area proportion, necrotic core area proportion, and lipid deposition, an increase in collagen fiber content, and a decrease in apoptosis. Furthermore, the treatment goups showcased lowered serum levels of TC, TG, LDL-C, IL-1β, TNF-α, and IL-6. The data of scRNA-seq revealed significantly elevated CD72hi-Mφ signaling in carotid plaques of AS patients compared with that in the normal arterial tissue. Animal experiments confirmed that CD72hi-Mφ expression, along with several pro-inflammatory cytokines, was significantly upregulated in the aortas of AS mice, which were downregulated by GZTL treatment. In conclusion, GZTL may alleviate AS by inhibiting CD72hi-Mφ activity.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Atherosclerosis/immunology* ; Mice ; Mice, Inbred C57BL ; Macrophages/immunology* ; Male ; Humans ; Apolipoproteins E/genetics* ; Tablets ; Tumor Necrosis Factor-alpha/genetics* ; Apoptosis/drug effects* ; Interleukin-1beta/genetics* ; Interleukin-6/genetics* ; Disease Models, Animal ; Mice, Knockout

Based on latent structure model and association rule analysis, this study investigates the prescription patterns used by professor YANG Zhong-qi in treating hypertension with traditional Chinese medicine(TCM) and infers the associated TCM syndromes, providing a reference for clinical syndrome differentiation and treatment. The observation window spanned from January 8, 2013, to June 26, 2024, during which qualified herbal decoction prescriptions meeting efficacy criteria were extracted from the outpatient medical record system of the First Affiliated Hospital of Guangzhou University of Chinese Medicine and compiled into a standardized database. Statistical analysis of high-frequency herbs included frequency counts and herbal property-channel tropism analysis. Latent structure modeling and association rule analysis were performed using R 4.3.2 and Lantern 5.0 software to identify core herbal combinations and infer TCM syndrome patterns. A total of 2 436 TCM prescriptions were included in the study, involving 263 drugs with a cumulative frequency of 29 783. High-frequency herbs comprised Uncariae Ramulus cum Uncis, Poria, Glycyrrhizae Radix et Rhizoma, Puerariae Lobatae Radix, and Alismatis Rhizoma, predominantly categorized as deficiency-tonifying, heat-clearing, and blood-activating and stasis-resolving herbs. Latent structure analysis identified 18 latent variables, 74 latent classes, 5 comprehensive clustering models, and 15 core herbal combinations, suggesting that the core syndrome clusters include liver Yang hyperactivity pattern, Yin deficiency with Yang hyperactivity pattern, phlegm-stasis intermingling pattern, and liver-kidney insufficiency pattern. Association rule analysis revealed 22 robust association rules. RESULTS:: indicate that hypertension manifests as a deficiency-rooted excess manifestation, significantly associated with functional dysregulation of the liver, lung, spleen-stomach, heart, and kidney. Key pathogenic mechanisms involve liver Yang hyperactivity, phlegm-stasis interaction, and liver-kidney insufficiency. Therapeutic strategies should prioritize liver-calming, spleen-fortifying, and deficiency-tonifying principles, supplemented by dynamic regulation of Qi-blood and Yin-Yang balance according to syndrome evolution, alongside pathogen-eliminating methods such as phlegm-resolving and stasis-dispelling. Synergistic interventions like mind-tranquilizing therapies should be tailored to individual conditions.
Hypertension/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Drug Prescriptions ; Latent Class Analysis

OBJECTIVE: To screen out the key metabolites related to diabetic foot (DF) by integrating genome-wide association studies (GWAS) and metabolome genome-wide association studies (mGWAS). METHODS: The literature databases such as PubMed and China national knowledge infrastructure(CNKI), as well as genomics databases such as PAN UKBB, FinnGen, and IEU Open GWAS were systematically retrieved from database estobilishment to November 2024 on DF-related single nucleotide polymorphisms and genome-wide association studies. DF-single nucleotide polymorphism-metabolite network was constructed by mGWAS package and mGWAS-Explorer platform. The causal relationship between key factors was evaluated by two-sample Mendelian randomization. The genetic correlation between DF and 575 metabolites (source:IEU Open GWAS) was evaluated by linkage disequilibrium score regression. In vitro experiments were conducted to induce injury of human umbilical vein endothelial cells with 30 mM glucose and intervene with 20 μM γ-tocopherol. Changes in cell migration, scratch healing and tube formation function were detected. RESULTS: Twenty-senen literatures on single nucleotide polymorphism literatures and 3 studies on GWAS were included. Genetic analysis results showed DF-related single nucleotide polymorphisms were enriched in vascular endothelial dysfunction-related pathways (such as fluid shear stress and atherosclerosis). The results of metabolic network analysis screened out 19 associated metabolites, among which 12 such as γ -tocopherol and pyruvate had significant genetic correlations with DF. Mendelian randomization suggested matrix metalloproteinase-9(MMP-9) might be a potential driver of DF (β=0.658, P=0.063 8), and the occurrence of DF could reduce the level of high-density lipoprotein (β=-0.002, P=0.015 2). The results of in vitro experiments confirmed that γ -tocopherol could improve endothelial dysfunction induced by high glucose, specifically manifested as an increase in the number of cell migrations, improvement in the scratch healing rate, and recovery of tubule formation ability (P<0.05). CONCLUSION DF has a genetic basis centered on vascular endothelial dysfunction, and its occurrence can lead to further metabolic disorders. The key single nucleotide polymorphism loci integrated provided molecular markers for the risk stratification of foot ulcers in diabetic patients. In addition, γ -tocopherol has demonstrated clinical application potential as a therapeutic drug for DF by significantly improving the function of vascular endothelial cells in a high-glucose environment.
Humans ; Diabetic Foot/drug therapy* ; Polymorphism, Single Nucleotide ; Genome-Wide Association Study ; Genomics ; Metabolomics ; Metabolome

Male factors contribute to 50% of infertility cases, with 20%-30% of cases being solely attributed to male infertility. Helicase for meiosis 1 ( HFM1 ) plays a crucial role in ensuring proper crossover formation and synapsis of homologous chromosomes during meiosis, an essential process in gametogenesis. HFM1 gene mutations are associated with male infertility, particularly in cases of non-obstructive azoospermia and severe oligozoospermia. However, the effects of intracytoplasmic sperm injection (ICSI) in HFM1 -related infertility cases remain inadequately explored. This study identified novel biallelic HFM1 variants through whole-exome sequencing (WES) in a Chinese patient with severe oligozoospermia, which was confirmed by Sanger sequencing. The pathogenicity of these variants was assessed using real-time quantitative polymerase chain reaction (RT-qPCR) and immunoblotting, which revealed a significant reduction in HFM1 mRNA and protein levels in spermatozoa compared to those in a healthy control. Transmission electron microscopy revealed morphological abnormalities in sperm cells, including defects in the head and flagellum. Despite these abnormalities, ICSI treatment resulted in a favorable fertility outcome for the patient, indicating that assisted reproductive techniques (ART) can be effective in managing HFM1 -related male infertility. These findings offer valuable insights into the management of such cases.
Humans ; Male ; Sperm Injections, Intracytoplasmic ; Oligospermia/therapy* ; Adult ; Spermatozoa/ultrastructure* ; Exome Sequencing ; Mutation