The pathogenesis of neurodegenerative diseases (NDDs) is fundamentally linked to complex and profound alterations in metabolic networks within the brain, which exhibit marked spatial heterogeneity. While conventional bulk metabolomics is powerful for detecting global metabolic shifts, it inherently lacks spatial resolution. This methodological limitation hampers the ability to interrogate critical metabolic dysregulation within discrete anatomical brain regions and specific cellular microenvironments, thereby constraining a deeper understanding of the core pathological mechanisms that initiate and drive NDDs. To address this critical gap, spatial metabolomics, with mass spectrometry imaging (MSI) at its core, has emerged as a transformative approach. It uniquely overcomes the limitations of bulk methods by enabling high-resolution, simultaneous detection and precise localization of hundreds to thousands of endogenous molecules—including primary metabolites, complex lipids, neurotransmitters, neuropeptides, and essential metal ions—directly in situ from tissue sections. This powerful capability offers an unprecedented spatial perspective for investigating the intricate and heterogeneous chemical landscape of NDD pathology, opening new avenues for discovery. Accordingly, this review provides a comprehensive overview of the field, beginning with a discussion of the technical features, optimal application scenarios, and current limitations of major MSI platforms. These include the widely adopted matrix-assisted laser desorption/ionization (MALDI)-MSI, the ultra-high-resolution technique of secondary ion mass spectrometry (SIMS)-MSI, and the ambient ionization method of desorption electrospray ionization (DESI)-MSI, along with other emerging technologies. We then highlight the pivotal applications of spatial metabolomics in NDD research, particularly its role in elucidating the profound chemical heterogeneity within distinct pathological microenvironments. These applications include mapping unique molecular signatures around amyloid β‑protein (Aβ) plaques, uncovering the metabolic consequences of neurofibrillary tangles composed of hyperphosphorylated tau protein, and characterizing the lipid and metabolite composition of Lewy bodies. Moreover, we examine how spatial metabolomics contributes to constructing detailed metabolic vulnerability maps across the brain, shedding light on the biochemical factors that render certain neuronal populations and anatomical regions selectively susceptible to degeneration while others remain resilient. Looking beyond current applications, we explore the immense potential of integrating spatial metabolomics with other advanced research methodologies. This includes its combination with three-dimensional brain organoid models to recapitulate disease-relevant metabolic processes, its linkage with multi-organ axis studies to investigate how systemic metabolic health influences neurodegeneration, and its convergence with single-cell and subcellular analyses to achieve unprecedented molecular resolution. In conclusion, this review not only summarizes the current state and critical role of spatial metabolomics in NDD research but also offers a forward-looking perspective on its transformative potential. We envision its continued impact in advancing our fundamental understanding of NDDs and accelerating translation into clinical practice—from the discovery of novel biomarkers for early diagnosis to the development of high-throughput drug screening platforms and the realization of precision medicine for individuals affected by these devastating disorders.

This study aims to investigate the potential effect of the water extract of fresh Rehmanniae Radix on hypercholesterolemia in mice that was induced by a high-fat and high-cholesterol diet and explore its possible mechanism from bile acid reabsorption. Male C57BL/6 mice were randomly assigned into the following groups: control, model, low-and high-dose(4 and 8 g·kg~(-1), respectively) fresh Rehmanniae Radix, and positive drug(simvastatin, 0.05 g·kg~(-1)). Other groups except the control group were fed with a high-fat and high-cholesterol diet for 6 consecutive weeks to induce hypercholesterolemia. From the 6th week, mice were administrated with corresponding drugs daily via gavage for additional 6 weeks, while continuing to be fed with a high-fat and high-cholesterol diet. Serum levels of total cholesterol(TC), triglycerides(TG), low density lipoprotein-cholesterol(LDL-c), high density lipoprotein-cholesterol(HDL-c), and total bile acid(TBA), as well as liver TC and TG levels and fecal TBA level, were determined by commercial assay kits. Hematoxylin-eosin(HE) staining, oil red O staining, and transmission electron microscopy were performed to observe the pathological changes in the liver. Three livers samples were randomly selected from each of the control, model, and high-dose fresh Rehmanniae Radix groups for high-throughput transcriptome sequencing. Differentially expressed genes were mined and KEGG pathway enrichment analysis was performed to predict the key pathways and target genes of the water extract of fresh Rehmanniae Radix in the treatment of hypercholesterolemia. RT-qPCR was employed to measure the mRNA levels of cholesterol 7α-hydroxylase(CYP7A1) and cholesterol 27α-hydroxylase(CYP27A1) in the liver. Western blot was employed to determine the protein levels of CYP7A1 and CYP27A1 in the liver as well as farnesoid X receptor(FXR), apical sodium-dependent bile acid transporter(ASBT), and ileum bile acid-binding protein(I-BABP) in the ileum. The results showed that the water extract of fresh Rehmanniae Radix significantly lowered the levels of TC and TG in the serum and liver, as well as the level of LDL-c in the serum. Conversely, it elevated the level of HDL-c in the serum and TBA in feces. No significant difference was observed in the level of TBA in the serum among groups. HE staining, oil red O staining, and transmission electron microscopy showed that the water extract reduced the accumulation of lipid droplets in the liver. Further mechanism studies revealed that the water extract of fresh Rehmanniae Radix significantly down-regulated the protein levels of FXR and bile acid reabsorption-related proteins ASBT and I-BABP. Additionally, it enhanced CYP7A1 and CYP27A1, the key enzymes involved in bile acid synthesis. Therefore, it is hypothesized that the water extract of fresh Rehmanniae Radix may exert an anti-hypercholesterolemic effect by regulating FXR/ASBT/I-BABP signaling, inhibiting bile acid reabsorption, and increasing bile acid excretion, thus facilitating the conversion of cholesterol to bile acids.
Animals ; Male ; Bile Acids and Salts/metabolism* ; Mice, Inbred C57BL ; Mice ; Diet, High-Fat/adverse effects* ; Cholesterol/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Hypercholesterolemia/genetics* ; Receptors, Cytoplasmic and Nuclear/genetics* ; Rehmannia/chemistry* ; Liver/drug effects* ; Humans ; Cholesterol 7-alpha-Hydroxylase/genetics* ; Plant Extracts

OBJECTIVE: Although dietary preferences influence chronic diseases, few studies have linked dietary preferences to mortality risk, particularly in large cohorts. To investigate the relationship between dietary preferences and mortality risk (all-cause, cancer, and cardiovascular disease [CVD]) in a large adult cohort. METHODS: A cohort of 1,160,312 adults (mean age 62.48 ± 9.55) from the Shenzhen Healthcare Big Data Cohort (SHBDC) was analyzed. Hazard ratios ( HRs) for mortality were estimated using the Cox proportional hazards model. RESULTS: The study identified 12,308 all-cause deaths, of which 3,865 (31.4%) were cancer-related and 3,576 (29.1%) were attributed to CVD. Compared with a mixed diet of meat and vegetables, a mainly meat-based diet (hazard ratio [ HR] = 1.13; 95% confidence interval [ CI]: 1.02, 1.27) associated with a higher risk of all-cause mortality, while mainly vegetarian ( HR = 0.87; 95% CI: 0.78, 0.97) was linked to a reduced risk. Furthermore, there was a stronger correlation between mortality risk and dietary preference in the > 65 age range. CONCLUSION A meat-based diet was associated with an increased risk of all-cause mortality, whereas a mainly vegetarian diet was linked to a reduced risk.
Humans ; China/epidemiology* ; Middle Aged ; Male ; Female ; Prospective Studies ; Aged ; Cardiovascular Diseases/mortality* ; Diet/statistics & numerical data* ; Neoplasms/mortality* ; Adult ; Cause of Death ; Food Preferences ; Proportional Hazards Models ; Mortality ; Cohort Studies

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Objective To analyze the drug resistance and serotype of Group B Streptococcus(GBS)isolated from pediatric patients,provide reference for the prevention and treatment of GBS infection as well as vaccine develop-ment in children.Methods 163 non-repetitive GBS strains detected at Beijing Children's Hospital of Capital Medi-cal University from January 1,2016 to December 31,2023 were collected.Strains were conducted resistance analy-sis and serotype testing.Results Among the 163 GBS strains,121 and 42 were invasive and non-invasive infection isolates,respectively.No strains were found to be resistant to penicillin,ceftriaxone,cefepime,linezolid,and van-comycin,and resistance rates to erythromycin,clindamycin,and levofloxacin were 91.4％,90.8％,and 53.4％,re-spectively.Non-invasive infection isolates had a higher resistance rate to levofloxacin than invasive infection isolates.The distribution of bacterial serotypes from high to low was as follows:type Ⅰb(n=75,46.0％),type Ⅲ(n=65,39.9％),type Ⅴ(n=13,8.0％),type Ⅰa(n=6,3.7％),type Ⅱ(n=2,1.2％),type Ⅳ and Ⅵ(n=1,0.6％,each).There was a statistically significant difference in the distribution of serotypes between invasive and non-invasive infection isolates(P＜0.05).Serotype distributions of erythromycin-and clindamycin-resistant GBS strains were both statistically different between two groups(both P＜0.05),while serotype distribution of levoflo-xacin-resistant GBS strains was not statistically different between two groups(P＞0.05).Conclusion GBS strains in children in Beijing have high resistance rates to erythromycin and clindamycin,with serotypes Ⅰb and Ⅲ being more frequent.Serotypes with high prevalence have higher resistance.Continuously monitoring on the epidemiology of GBS infection is crucial for the clinical prevention and treatment of GBS infection in children as well as the devel-opment of vaccines.

Diabetes mellitus is a metabolic disease with high incidence and many complications,among which type 2 diabetes mellitus(T2DM)accounts for a large proportion.Current studies have shown that T2DM is accompanied by damage of liver,kidney,and other organs and its complications seriously en-danger human health.Ferroptosis generates many Reactive Oxygen Species(ROS)through the Fenton reaction,and the accumulation of ROS activates Hypoxia Inducible Factor-1(HIF-1α).As a result,the level of vascular endothelial growth factor(VEGF)is increased.Ferrostatin-1(Fer-1),a ferroptosis in-hibitor,has strong antioxidant capacity.Therefore,based on the hypoxia-inducible factor-1α/vascular endothelial growth factor(HIF-1α/VEGF)signaling pathway,we explored the therapeutic effect of Fer-1 on the liver and kidney tissues of diabetic mice.db/db mice(21～22 weeks old)were used as the model of diabetes mellitus.Ferroptosis inhibitor Fer-1 was used as the intervention drug.db/m mice served as the blank control group,and body weight and blood glucose were measured for 4 weeks.Food intake and water intake were recorded in each group.The levels of Alanine aminotransferase(ALT)and Aspartate aminotransferase(AST)in the serum were measured.ROS and Glutathione(GSH)activity in liver and kidney tissues and urinary protein content were measured.Liver and kidney tissue sections were stained with Hematoxylin-Eosin(HE),and the pathological morphology was observed under a light microscope.The protein levels of HIF-1α,VEGF,and glutathione peroxidase 4(GPX4)in liver and kidney tissues were detected by Western blot.In db/db mice,Fer-1(1 mg·kg-1,ig)could significantly reduce the a-mount of food and water intake,the levels of ALT and AST in serum,the ROS production in liver and kidney tissues,and the level of urine protein,but significantly increase the activity of GSH,thus improve the pathological conditions of liver and kidney.Fer-1 also significantly inhibited HIF-1α and VEGF pro-tein indexes and increased GPX4 protein levels in liver and kidney tissues.Although Fer-1 can not change the body weight and reduce blood glucose in diabetic mice,it can play a therapeutic role in the liver and kidney tissues of diabetic mice in the middle and late stages,and its mechanism may be related to HIF-1α/VEGF and GPX4.

Objective:To improve the aqueous solubility, biocompatibility, fluorescence, and sonosensitivity of curcumin, this study aims to transform curcumin into curcumin-derived carbon dots (Cur-CDs) to enhance the efficacy of sonodynamic therapy (SDT) of atherosclerosis (AS).Methods:Cur-CDs were synthesized via a hydrothermal method. The morphology was characterized by transmission electron microscopy, while Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy were applied to analyze the chemical composition and surface functional groups. Optical properties were examined by UV-visible spectrophotometry and fluorescence spectroscopy. Cell proliferation and viability assay and a hemolysis experiment were performed to assess biocompatibility. The sonosensitivity of Cur-CDs was determined by the measurement of reactive oxygen species (ROS) produced by Cur-CDs.To verify the effect of Cur-CDs-mediated SDT on macrophage phenotype, the M1 and M2 macrophage marker genes were detected via real-time fluorescence quantitative polymerase chain reaction. The ability of Cur-CDs in plaque detection was assessed through in vivo fluorescence imaging and ex vivo aortic fluorescence imaging. Atherosclerotic plaque mice were divided into five groups: control group, curcumin group, Cur-CDs group, curcumin + low-intensity pulsed ultrasound (LIPUS) group, and Cur-CDs+ LPIUS group. Aortic Oil red O staining and blood lipid level measurements were conducted to evaluate the therapeutic efficacy of SDT on the plaques.Results:Cur-CDs exhibited a spherical morphology and a distinct lattice structure with the diameter of (1.87±0.35)nm. The aqueous solubility of Cur-CDs was about 10 5 times that of curcumin because of their abundant oxygen-containing hydrophilic functional groups.Cur-CDs at concentrations up to 500 mg/L had no significant impact on cell proliferation and viability, with a negligible hemolysis rate of <1%, indicating good biocompatibility of Cur-CDs. Cur-CDs exhibited a stable and excellent fluorescence with the maximum excitation and emission wavelengths of 420 nm and 530 nm, respectively. Cur-CDs had the potential to be used for plaque fluorescence imaging, with the fluorescence intensity at the plaque being significantly greater than that of curcumin( P<0.01). It was observed that Cur-CDs activated by LIPUS were capable of producing ROS, including 1O 2, ·OH, and ·O 2-, with the total amount of ROS exceeding that of curcumin( P<0.05). Cur-CDs-mediated SDT facilitated the transformation of macrophage phenotype from M1 to M2, with a more pronounced effect than that observed with curcumin-mediated SDT. Oil red O staining revealed the most significant reduction in plaque area and lipid content in the Cur-CDs+ LIPUS group, which was about three times greater than that in the curcumin+ LIPUS group, confirming the excellent efficacy of Cur-CDs-mediated SDT on plaques. Conclusions:The successfully prepared Cur-CDs exhibit superior aqueous solubility, biocompatibility, fluorescence, and sonosensitivity than curcumin, contributing to the significant improvement in sonodynamic efficacy on plaques.

Objective To investigate the effects of Erhuang Quzhi Granules combined with Silibinin Capsules on fatty liver index,inflammatory factors and autophagy-related gene levels in patients with nonalcoholic fatty liver disease(NAFLD).Methods A total of 126 patients with NAFLD of phlegm blended with blood stasis type were randomly divided into control group and observation group,with 63 cases in each group.The control group was treated with oral use of Silibinin Capsules,and the observation group was treated with oral use of Erhuang Quzhi Granules on the basis of treatment for the control group.The course of treatment lasted for 3 months.Before and after treatment,the two groups were observed in the changes of fatty liver index,and the levels of inflammatory factors of interleukin 6(IL-6)and tumor necrosis factor alpha(TNF-α),liver function and blood lipid indicators of alanine aminotransferase(ALT),aspartate aminotransferase(AST),γ-glutamyl transpeptidase(GGT),total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C),and autophagy-related genes of autophagy-related gene 7(ATG7)and myosin-like BCL2 binding protein(Beclin 1).After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After 3 months of treatment,the total effective rate of the observation group was 90.48％(57/63),and that of the control group was 71.43％(45/63).The intergroup comparison(tested by chi-square test)showed that the efficacy of the observation group was significantly superior to that of the control group(P＜0.01).(2)After treatment,the fatty liver index of the two groups was significantly decreased compared with that before treatment(P＜0.05),and the decrease of fatty liver index in the observation group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the serum levels of inflammatory factors of IL-6 and TNF-α in the two groups were significantly lower than those before treatment(P＜0.05),and the decrease of serum IL-6 and TNF-α levels in the observation group was significantly superior to that in the control group(P＜0.05).(4)AAfter treatment,the serum levels of liver function indicators of ALT,AST and GGT in the two groups were significantly lower than those before treatment(P＜0.05),and the decrease of serum ALT,AST and GGT levels in the observation group was significantly superior to that in the control group(P＜0.05).(5)After treatment,the serum levels of blood lipids of TG,TC and LDL-C in the two groups were significantly lower than those before treatment(P＜0.05),and the serum HDL-C level was significantly higher than that before treatment(P＜0.05).The decrease of serum TG,TC and LDL-C levels and the increase of serum HDL-C level in the observation group were significantly superior to those in the control group(P＜0.05).(6)After treatment,the serum levels of autophagy-related genes of ATG7 and Beclin 1 in the two groups were significantly higher than those before treatment(P＜0.05),and the increase of serum ATG7 and Beclin 1 levels in the observation group was significantly superior to that in the control group(P＜0.05).(7)During the medication,no liver or kidney function damage or serious adverse reactions were found in the two groups.Conclusion Erhuang Quzhi Granules combined with Silibinin Capsules are effective for the treatment of NAFLD patients with phlegm blended with blood stasis type,which is helpful to relieve the symptoms of fatty liver,reduce the levels of inflammatory factors,improve liver function and blood lipid levels,and regulate the expression of autophagy-related genes.

Objective To investigate the effects of total flavones from Oxytropis falcata Bunge on hepatic fibrosis(HF)induced by carbon tetrachloride and liver transforming growth factor(TGF-β)/Smad signaling pathway.Methods Forty-eight male rats were randomly divided into normal group(intraperitoneal injection of peanut oil,intragastric administration of 0.9％NaCl),model group(intraperitoneal injection of 40％CC14 peanut oil solution induced HF model,intragastric administration of 0.9％NaCl),positive control group(modeling,intragastric administration of 0.2 mg·kg-1 of colchicine),experimental-L,-M,-H groups(modeling,intragastric administration of 100,200 and 400 mg·kg-1 of total flavonoid extract of Oxytropis falcata Bunge),8 individuals in each group,for 4 consecutive weeks.The histopathological changes were observed by hematoxylin-eosin and Masson staining.Serum liver function and liver fibrosis were measured;erum inflammatory factors were detected;fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to determine gene expression in liver.Results The pathological injury of liver tissue in the model group was serious,and a large number of inflammatory factors and collagen fibers were accumulated,while the rest of the treatment groups had different degrees of remission.In normal group,model group,positive control group,experimental-L,-M,-H groups,glutamic-pyruvic transaminase levels were(49.28±12.44),(5 885.42±948.37),(4 454.60±489.27),(4 650.47±843.53),(3 761.75±887.30)and(3 544.90±1 066.75)μg·L-1;glutamic-oxaloacetic transaminase levels were(186.90±46.89),(5 936.23±793.81),(3 971.37±780.28),(4 360.30±863.35),(3 943.10±439.47)and(3 971.38±631.08)μg·L-1;hyaluronic acid levels were(45.08±17.16),(104.32±36.06),(66.83±20.09),(70.30±21.07),(60.00±9.68)and(59.02±10.73)μg·L-1;laminin levels were(23.13±3.89),(60.85±13.66),(35.67±9.92),(39.98±9.39),(36.55±12.21)and(34.68±24.83)μg·L-1;type Ⅲ procollagen level were(24.98±5.34),(82.58±30.14),(40.70±16.14),(51.08±23.21),(43.60±12.48)and(44.20±11.66)p±g·L-1;interleukin(IL)-1β levels were(37.63±1.24),(46.10±3.23),(39.22±2.36),(41.33±0.93),(40.25±2.04)and(39.18±2.23)pg·mL-1;tumor necrosis factor-α levels were(314.58±20.56),(383.71±16.97),(349.00±7.93),(348.88±25.11),(325.75±27.84)and(335.07±21.33)pg·mL-1;TGF-β1 mRNA expression of relative quantity respectively were 1.00±0.00,60.99±15.70,9.61±1.59,7.37±1.09,6.41±0.64,6.87±1.09;Smad7 mRNA relative expression were 1.00±0.00,0.34±0.05,0.21±0.03,0.35±0.02,0.38±0.02,0.42±0.03.The above indexes in the model group were compared with the normal group,and the above indexes in the experimental-M,-H groups were compared with the model group,and the differences were statistically significant(P＜0.05,P＜0.01,P＜0.001).Conclusion Total flavonoids of Oxytropis falcata Bunge have protective effects on CC14-induced liver fibrosis in rats,and the mechanism may be related to the regulation of TGF-β/Smad pathway.

Smoking is the leading preventable risk factor for disease and death worldwide. Tobacco and its smoke contain a complex mix of over 9 500 chemical substances, including oxidative gases, heavy metals, and 83 known carcinogens. Long-term smoking is a significant risk factor for respiratory diseases such as acute lung injury, emphysema, and pulmonary fibrosis. Damage to alveolar epithelial cells (AECs) is a common pathological feature in these smoking-related lung diseases. AECs, which line the surface of the alveoli, play a crucial role in preventing overexpansion or collapse, secreting cell factors and surfactants, containing abundant mitochondria, and being essential for lung tissue maturation, gas exchange, metabolism, and repair after damage. Damage to these cells can lead to pulmonary edema and alveolar collapse. Cigarette smoke (CS) can disrupt alveolar epithelial cell function through various pathways, resulting in cell death, tissue damage, and the development of lung diseases.This review summarizes recent research on the damage caused by CS to AECs, showing that CS can promote cell death and damage through induction of oxidative stress, autophagy, endoplasmic reticulum stress, mitochondrial dysfunction, inflammation, and epithelial-mesenchymal transition. It also affects the proliferative function of alveolar type II epithelial cells. The review highlights that CS-induced oxidative stress is a key factor in causing various types of damage, with TRP ion channels serving as important triggers. Inhibiting CS-induced oxidative damage can significantly prevent cell death and subsequent diseases such as pulmonary emphysema. The activation of the same pathway induced by CS can lead to different types of cell damage, potentially encouraging the development of different diseases. CS can either directly induce or indirectly promote cell inflammation through endoplasmic reticulum stress, mitochondrial dysfunction, and senescence. There are interconnected relationships between these mechanisms, and SIRT1 is an important protein in preventing CS-induced AECs damage. Increasing SIRT1 activity can alleviate CS-induced autophagy, endoplasmic reticulum stress, and senescence in various cell damages; its substrate NAD⁺ is already used clinically, and its effectiveness in COPD treatment deserves further exploration. The impact of CS on cells varies based on concentration: lower concentrations stimulate stress responses or apoptosis, while higher concentrations lead to apoptosis or necrosis through various mechanisms, ultimately impairing lung epithelial function. When external stimuli exceed the cells’ self-healing capacity, they can cause damage to cells, lung epithelial barriers, and alveoli, promoting the development of related lung diseases. Key proteins that play a protective role may serve as potential targets to mitigate cell damage.This review provides insights into the various mechanisms through which CS induces damage to AECs, covering important transcription factors, DNA repair proteins, and membrane channel proteins, paving the way for the study of new mechanisms and pathways. However, there are still unanswered questions, such as the need for further exploration of the upstream pathways of CS-induced autophagy in AECs and the intrinsic mechanisms of CS in enhancing the stem cell properties of AECs and its relationship to the occurrence of lung cancer.It is expected that this article will provide a theoretical basis for future research on the mechanisms of lung epithelial cell damage caused by CS or its individual components and inspire clinical strategies for the prevention and treatment of smoking-related lung diseases.