Oxidative stress is a pivotal factor in the onset and progression of diabetic kidney disease （DKD）， and it plays an essential role in the prevention and treatment of DKD. The "Gaozhuo" pathogenesis posits that DKD is characterized by the invasion of Gaozhuo and damage to the kidney collaterals， with the underlying cause being the insufficiency of spleen Qi and the internal formation of Gaozhuo， which provides valuable guidance on oxidative stress. The insufficiency of spleen Qi and the internal formation of Gaozhuo represent a dynamic， evolving process. Gaozhuo invades the kidney collaterals， impairs kidney Qi， and progressively leads to the congealing and stagnation of Gaozhuo and blood， ultimately resulting in the failure of both the spleen and kidneys. The damage caused by Gaozhuo to the kidney collaterals and kidney Qi is analogous to the organ and functional damage of the kidneys induced by excessive reactive oxygen species and oxidative stress. Damage to the kidney collaterals means organic injuries to the glomeruli， renal tubules， and renal interstitium， and the depletion of kidney Qi refers to damage to glomerular filtration and renal tubular reabsorption. The congealing and stagnation of Gaozhuo and blood in the kidney collaterals is similar to oxidative stress-induced thickening of the glomerular basement membrane and fibrosis. The interaction between spleen and kidney Qi deficiency and the congealing and stagnation of Gaozhuo and blood creates a vicious cycle that exacerbates the condition， ultimately evolving into the failure of both the spleen and kidneys. The failure of the spleen and kidneys is analogous to renal failure， and its extreme manifestation is end-stage renal disease and uremia. The treatment of oxidative stress in DKD with traditional Chinese medicine （TCM） is based on the principles of strengthening the spleen and tonifying the kidneys， and dispelling turbidity and removing blood stasis. According to the syndrome type， it is recommended to use methods such as strengthening the spleen and tonifying Qi while dispelling dampness and removing turbidity， strengthening the spleen and tonifying the kidneys while dispelling dampness and removing turbidity， strengthening the spleen and tonifying the kidneys while dispelling turbidity and removing blood stasis， or consolidating the spleen and kidneys while clearing away turbidity and blood stasis.

Dabuyuanjian is one of the classic famous formulas in the Catalog of Ancient Classic Famous Formulas （Second Batch）-Medicine of Han Ethnic Group. It consists of Ginseng Radix et Rhizoma， Dioscoreae Rhizoma， Rehmanniae Radix Praeparata， Eucommiae Cortex， Angelicae Sinensis Radix， Corni Fructus， Lycii Fructus， and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle， and is used to treat the symptoms of men and women who have a great loss of Qi and blood and a critical and dramatic loss of spiritual guardianship. This study reviewed the ancient and modern literature， and used literature tracing and bibliometrics methods to mine the key information of the historical origin， formula name， drug composition， compatibility， drug dosage， original plants and processing of drugs， decocting method， and clinical application of Dabuyuanjian. The results showed that Dabuyuanjian was first recorded in the Jing Yue's Collected Works （Jing Yue Quan Shu）， with the dosage mainly following the original formula. According to the dosage in the Ming and Qing dynasties， the formula is composed of 5.60 g （for mild cases）/39.17 g （for severe cases） Ginseng Radix et Rhizoma， 7.46 g Dioscoreae Rhizoma， 9.32 g （for mild cases）/ 93.25 g （for severe cases） Rehmanniae Radix Praeparata， 7.46 g Eucommiae Cortex， 9.32 g Angelicae Sinensis Radix， 3.73 g Corni Fructus， 9.32 g Lycii Fructus， and 5.60 g Glycyrrhizae Radix et Rhizoma Praeparata cum Melle. Regarding the original plants of drugs， Ginseng Radix et Rhizoma is produced from the dried roots and rhizomes of Panax ginseng， Dioscoreae Rhizoma from stir-fried dried rhizomes of Dioscorea opposita， Rehmanniae Radix Praeparata from steamed dried roots of Rehmannia glutinosa， Eucommiae Cortex from the dried bark of Eucommia ulmoides， Angelicae Sinensis Radix from the dried roots of Angelica sinensis， Corni Fructus from the dried mature fruit flesh of Cornus officinalis， Lycii Fructus from the dried mature fruits of Lycium barbarum， and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle from the honey-processed dried roots and rhizomes of Glycyrrhiza uralensis. These medicinal materials are decocted in 400 mL water to reach a volume of 140 mL， and the decoction should be taken 1 h after meals， 2-3 doses per day. Dabuyuanjian has a wide range of clinical applications， including gynecological and obstetrical diseases， deficiency， baffling and panic， consumptive thirst， and blood， ear， nose， and throat diseases. In modern clinical practice， it is mainly used for diseases of the nervous system， gynecology， urinary system， cardiovascular system， digestive system， musculoskeletal system， connective tissue， immune system， blood， and men. Through the review of ancient and modern literature， this study sorted out the historical evolution and mined the key information of Dabuyuanjian， aiming to provide a theoretical reference for safe and effective clinical application and subsequent research and development of this formula.

Chronic pain is a complex condition shaped by long-standing alterations in both physiological and psychological processes. Rather than representing a simple continuation of acute nociceptive signaling, chronic pain is increasingly understood as the outcome of progressive dysregulation within distributed neural systems that govern sensation, affect, motivation, and cognitive control. Neuroimaging and electrophysiological studies indicate that this state is accompanied by extensive plastic changes in deep brain structures and large-scale networks. Beyond well-described central sensitization processes, chronic pain is characterized by disrupted oscillatory rhythms and altered connectivity within large-scale brain networks, including thalamo-cortical circuits and prefrontal-limbic-reward networks. These findings support a conceptual shift from viewing chronic pain as a focal, lesion-driven phenomenon toward recognizing it as a disorder of distributed network pathology. Pharmacological treatments remain central to clinical practice, yet their long-term efficacy is often limited and frequently accompanied by substantial side effects. The ongoing concerns about opioid-related risks and the inadequate therapeutic response in a subset of patients highlight the need for safe, non-pharmacological approaches that can address not only pain but also comorbid disturbances in mood, sleep, and social functioning. Neuromodulation provides a promising path toward mechanism-based and non-pharmacological management of chronic pain by employing physical or chemical stimulation to alter the excitability and synchrony of specific neural populations within central, peripheral, and autonomic systems. While invasive deep brain stimulation demonstrates that targeting deep brain structures can be effective, its clinical application is restricted by surgical risks and cost, highlighting the importance of non-invasive techniques capable of reaching deep targets. Current non-invasive approaches, such as transcranial electric stimulation, are constrained by limited penetration depth and insufficient spatial precision. These limitations hinder reliable engagement of deep regions implicated in pain, including the thalamus and nucleus accumbens, and tend to produce broad, non-specific modulation of cross-network oscillatory activity. Temporal interference (TI) stimulation has emerged as a means of overcoming these obstacles. By delivering interacting high-frequency currents that generate a low-frequency envelope within the head, TI enables focal stimulation of deep targets while minimizing superficial current delivery. Recent multiscale modeling and animal studies indicate that TI exploits the nonlinear rectification properties of neuronal membranes in response to high-frequency carriers, as well as their phase-locked responses to low-frequency envelopes, to generate “peak-focused” electric fields in deep regions under relatively low superficial current loads. Moreover, TI appears to exhibit potential advantages in terms of cell-type selectivity and rhythm-specific engagement, including differential responses across neuronal subtypes and distinct coupling to θ-, β-, and γ-band oscillations. These features suggest a promising avenue for correcting abnormal rhythms and network dynamics that contribute to chronic pain. This review summarizes current knowledge of the neural mechanisms underlying chronic pain and recent advances in TI research. It examines functional disturbances across key pain-related regions and networks, outlines the principles and technical characteristics of TI, and discusses potential deep-brain targets and stimulation strategies relevant to chronic pain. Evidence to date indicates that TI, with its non-invasiveness, tolerability, and capacity for precise deep brain modulation, holds great promise for the management of treatment-resistant chronic pain and may evolve into a new generation of precise and efficient non-pharmacological analgesic strategies.

Chronic pain is a complex condition shaped by long-standing alterations in both physiological and psychological processes. Rather than representing a simple continuation of acute nociceptive signaling, chronic pain is increasingly understood as the outcome of progressive dysregulation within distributed neural systems that govern sensation, affect, motivation, and cognitive control. Neuroimaging and electrophysiological studies indicate that this state is accompanied by extensive plastic changes in deep brain structures and large-scale networks. Beyond well-described central sensitization processes, chronic pain is characterized by disrupted oscillatory rhythms and altered connectivity within large-scale brain networks, including thalamo-cortical circuits and prefrontal-limbic-reward networks. These findings support a conceptual shift from viewing chronic pain as a focal, lesion-driven phenomenon toward recognizing it as a disorder of distributed network pathology. Pharmacological treatments remain central to clinical practice, yet their long-term efficacy is often limited and frequently accompanied by substantial side effects. The ongoing concerns about opioid-related risks and the inadequate therapeutic response in a subset of patients highlight the need for safe, non-pharmacological approaches that can address not only pain but also comorbid disturbances in mood, sleep, and social functioning. Neuromodulation provides a promising path toward mechanism-based and non-pharmacological management of chronic pain by employing physical or chemical stimulation to alter the excitability and synchrony of specific neural populations within central, peripheral, and autonomic systems. While invasive deep brain stimulation demonstrates that targeting deep brain structures can be effective, its clinical application is restricted by surgical risks and cost, highlighting the importance of non-invasive techniques capable of reaching deep targets. Current non-invasive approaches, such as transcranial electric stimulation, are constrained by limited penetration depth and insufficient spatial precision. These limitations hinder reliable engagement of deep regions implicated in pain, including the thalamus and nucleus accumbens, and tend to produce broad, non-specific modulation of cross-network oscillatory activity. Temporal interference (TI) stimulation has emerged as a means of overcoming these obstacles. By delivering interacting high-frequency currents that generate a low-frequency envelope within the head, TI enables focal stimulation of deep targets while minimizing superficial current delivery. Recent multiscale modeling and animal studies indicate that TI exploits the nonlinear rectification properties of neuronal membranes in response to high-frequency carriers, as well as their phase-locked responses to low-frequency envelopes, to generate “peak-focused” electric fields in deep regions under relatively low superficial current loads. Moreover, TI appears to exhibit potential advantages in terms of cell-type selectivity and rhythm-specific engagement, including differential responses across neuronal subtypes and distinct coupling to θ-, β-, and γ-band oscillations. These features suggest a promising avenue for correcting abnormal rhythms and network dynamics that contribute to chronic pain. This review summarizes current knowledge of the neural mechanisms underlying chronic pain and recent advances in TI research. It examines functional disturbances across key pain-related regions and networks, outlines the principles and technical characteristics of TI, and discusses potential deep-brain targets and stimulation strategies relevant to chronic pain. Evidence to date indicates that TI, with its non-invasiveness, tolerability, and capacity for precise deep brain modulation, holds great promise for the management of treatment-resistant chronic pain and may evolve into a new generation of precise and efficient non-pharmacological analgesic strategies.

ObjectiveThe exacerbating trend of global population aging poses profound socioeconomic and public health challenges, making the comprehensive elucidation of biological aging mechanisms and the discovery of effective anti-aging interventions an urgent priority in the life sciences. Based on our previous serum metabolomics findings that dimethylglycine, an intermediate metabolite of amino acid metabolism naturally present in the human body, was significantly enriched in the serum of longevity families, this study aimed to systematically investigate the anti-aging effects of dimethylglycine both in living organisms and in controlled laboratory environments, and to preliminarily elucidate its underlying molecular mechanisms. While existing literature indicates that dimethylglycine possesses antioxidant and immunomodulatory properties, its direct anti-aging efficacy and the specific molecular pathways through which it operates remain largely unexplored. MethodsTo comprehensively evaluate the anti-aging properties of dimethylglycine, we utilized replicative senescent human embryonic lung fibroblasts, specifically the WI-38 cell line, as an experimental model in a controlled laboratory environment. Cell viability and safety were thoroughly assessed using Cell Counting Kit-8 and lactate dehydrogenase release assays across various concentrations of dimethylglycine. The impact of dimethylglycine on cellular senescence phenotypes, oxidative stress, and proliferative capacity was evaluated via senescence-associated beta-galactosidase staining, reactive oxygen species fluorescence detection, and 5-ethynyl-2'-deoxyuridine incorporation assays. Furthermore, the molecular alterations of senescence-associated secretory phenotype factors and core senescence signaling pathways were quantified using quantitative reverse transcription polymerase chain reaction for the messenger RNA levels of interleukin-6, interleukin-8, p21, and matrix metalloproteinase-1, and enzyme-linked immunosorbent assay for the measurement of p16 and p21 protein expression levels. For the living organism model, the wild-type nematode Caenorhabditis elegans was used to evaluate systemic physiological effects. We conducted a comprehensive lifespan analysis at 20°C, heat stress resistance survival assays at 35℃, senescence-associated beta-galactosidase staining, lipofuscin accumulation tracking, intracellular reactive oxygen species measurement, and Oil Red O staining to ascertain systemic lipid accumulation. Additionally, network pharmacology bioinformatics tools, including PharmMapper and STRING databases, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were utilized to predict target pathways, alongside highly detailed molecular docking simulations utilizing SwissDock and Protein-Ligand Interaction Profiler to examine interactions with the cytochrome P450 family 2 subfamily C member 9 protein. ResultsThe experimental outcomes robustly demonstrate the potent anti-aging capabilities of dimethylglycine. At the cellular level, toxicity analyses firmly confirmed that dimethylglycine is highly safe; continuous treatment with 50 mol/L and 70 mol/L of dimethylglycine for 5 d did not induce any cellular membrane damage or cytotoxicity, but rather actively promoted cellular proliferation. Utilizing the optimal standardized concentration of 50 mol/L, dimethylglycine treatment significantly ameliorated senescent phenotypic markers in human embryonic lung fibroblasts, which was evidenced by a drastic and highly significant reduction in the senescence-associated beta-galactosidase positive cell percentage (P<0.000 1) and intracellular reactive oxygen species levels (P<0.000 1), alongside a marked increase in the 5-ethynyl-2'-deoxyuridine-positive proliferation rate (P=0.003 5). On a molecular expression scale, dimethylglycine significantly downregulated the messenger RNA expression of multiple core senescence-associated secretory phenotype inflammatory factors, including interleukin-6, interleukin-8, p21, and matrix metalloproteinase-1. Concurrently, it effectively suppressed the protein expression of critical cell cycle arrest markers, diminishing p16 protein levels by 57.3% (P=0.000 4) and p21 protein levels by 27.2% (P=0.000 7). In the nematode Caenorhabditis elegans animal model, dimethylglycine significantly extended the mean lifespan from 20.402 d to an impressive 23.066 d (P<0.000 1) and notably enhanced overall survival rates under severe heat stress environmental conditions (P=0.017). Furthermore, systemic dimethylglycine intervention significantly mitigated age-related physiological decline by decreasing bodily lipofuscin accumulation (P<0.000 1), significantly reducing senescence-associated beta-galactosidase activity, lowering systemic reactive oxygen species fluorescence (P=0.008), and effectively alleviating overall fat accumulation (P<0.000 1). Mechanistically, extensive network pharmacology and Kyoto Encyclopedia of Genes and Genomes analyses strongly revealed that the potential targets of dimethylglycine are significantly enriched in fundamental drug metabolism and oxidative stress response pathways. Precision molecular docking simulations conclusively demonstrated that dimethylglycine forms highly stable structural interactions with the cytochrome P450 family 2 subfamily C member 9 protein, specifically highlighting the definitive formation of 5 stable hydrogen bonds involving serine 365, leucine 366, and serine 429 residues, as well as two critical salt bridge formations with arginine 97 and histidine 368 residues. It is additionally predicted to interact favorably with glutathione S-transferase family proteins. ConclusionDimethylglycine exhibits a profoundly significant and multifaceted anti-aging activity at both the cellular and entire living animal levels. By powerfully alleviating oxidative stress, heavily suppressing the core p16 and p21-dependent cellular senescence signaling pathways, and substantially mitigating the detrimental senescence-associated secretory phenotype, dimethylglycine effectively delays fundamental cellular senescence processes and drastically extends whole-organism lifespan. The biological mechanisms driving these robust protective effects are highly likely closely associated with its direct stable interactions with crucial metabolic and detoxifying enzyme systems, such as cytochrome P450 family 2 subfamily C member 9 and glutathione S-transferase family proteins, thereby systemically improving metabolic dysregulation and restoring critical redox homeostasis. This comprehensive study provides highly solid experimental evidence supporting dimethylglycine as a highly potent and safe potential anti-aging intervention agent, while simultaneously offering a clear molecular mechanistic explanation for the previously documented high abundance of dimethylglycine observed within exceptionally long-lived human populations.

OBJECTIVE To investigate the effects of ω-3 polyunsaturated fatty acid （ω-3PUFA） combined with clomiphene on clinical efficacy， pregnancy and safety in patients with polycystic ovary syndrome （PCOS）. METHODS A retrospective analysis was performed on the clinical data of 112 PCOS patients who received treatment in Dept. of Obstetrics and Gynecology of Hunan Prevention and Treatment Institute for Occupational Diseases from January 2022 to December 2023. According to the different treatment regimens， the patients were divided into single-drug group （60 cases） and drug-combination group （52 cases）. Single-drug group was given clomiphene orally， and drug-combination group was given clomiphene+ω-3PUFA. Clinical efficacy， pregnancy status and the occurrence of adverse drug reaction （ADR） as well as ovarian function and oxidative stress indexes before and after treatment were compared between 2 groups. RESULTS The overall response rate （90.38% vs. 71.67%）， ovulation rate （84.62% vs. 61.67%）， and pregnancy rate （51.92% vs. 26.67%） were all markedly higher in drug combination group than single drug group （ P ＜0.05）. Before treatment， there was no statistical significance in ovarian function and oxidative stress indexes between 2 groups （ P ＞0.05）. Compared with before treatment， serum anti-Müllerian hormone levels， inhibin B concentr ations， and the number of cystic follicles in 2 groups were decreased significantly after 12 weeks of treatment （ P ＜0.05）. The endometrial thickness increased significantly （ P ＜0.05）， while the serum levels of malondialdehyde and advanced oxidation protein products decreased significantly （ P ＜0.05）； the activities of serum superoxide dismutase and glutathione peroxidase increased significantly （ P ＜0.05）； the improvement of drug combination group was significantly better than single drug group （ P ＜0.05）. The ovarian volumes in both groups were significantly smaller after treatment compared to before treatment （ P ＜0.05）， but there was no statistically significant difference between the two groups （ P ＞0.05）. There was no significant difference in the overall incidence of ADR between the two groups during the treatment （ P ＞0.05）. CONCLUSIONS The combination of ω-3PUFA and clomiphene has a definite therapeutic effect on PCOS， which can effectively reduce the body’s oxidative stress response， improve ovarian function， and increase ovulation and pregnancy rates.

ObjectiveTo provide a reference for the rational clinical use of cold Chinese medicines by sorting and analyzing their properties， flavors， meridian tropism， primary therapeutic indications， methods of administration， dosages， and precautions as recorded in the 2020 edition of Pharmacopoeia of the People's Republic of China （Chinese Pharmacopoeia）. MethodsCold Chinese medicines for internal and external use included in the 2020 edition of Chinese Pharmacopoeia were entered one by one， and their efficacy， properties， flavors， meridian tropism， methods of administration， dosages， and usage precautions were statistically classified and summarized to guide clinical medication use. ResultsA total of 259 cold Chinese medicines for internal use were included and categorized into 18 efficacy groups， mainly comprising heat-clearing drugs， water-excreting and dampness-draining drugs， and phlegm-resolving， cough- and asthma-relieving drugs. Their predominant flavors were bitter， sweet， and pungent， and they primarily entered the liver， lung， and stomach meridians. The main methods of administration included decocting first， grinding into powder for oral use， or preparing into pills or powders， with most dosages ranging from 9 to 15 g. A total of 83 cold Chinese medicines for external use were included， involving 16 efficacy categories. Their main flavors were bitter， sweet， and pungent， primarily entering the liver， lung， and large intestine meridians. The main external application methods were grinding into powder for topical use or preparing decoctions for fumigation and washing， with most dosages ranging from 9 to 15 g. Whether for internal or external use， cold Chinese medicines should be used with caution or contraindicated in pregnant women. ConclusionThe cold Chinese medicines included in the 2020 edition of the Chinese Pharmacopoeia are mainly suitable for patients with carbuncles， swellings， and coughs. However， in clinical practice， it is necessary to strictly follow the principles of syndrome differentiation and treatment， pay attention to administration methods and dosages， and use cold medicines rationally and effectively to improve clinical efficacy.

OBJECTIVE To study the improvement effect and mechanism of Dendrobium officinale on skin damage in mice with xeroderma. METHODS The mice were randomly divided into control group， model group， and D. officinale group， with 5 mice in each group. Except for the control group （which only underwent shaving treatment）， the mice in all other groups were induced to develop a xeroderma model using an acetone-ether mixture for five consecutive days. The mice in D. officinale group were treated with 200 μL of D. officinale suspension （0.2 mg/mL） two hours after the first modeling each day. Mice in the control group and the model group were applied with an equal volume of pure water； once a day， until the end of the modeling process. After last medication， skin lesions and pathological morphology of the mice were observed. Immunofluorescence was used to detect the expressions of Filaggrin， Loricrin and Ki67 proteins in skin tissue of the mice. The core pathways through which D. officinale improves skin damage in xeroderma were screened using 16S rRNA sequencing combined with gene ontology and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses， and subsequent validation was conducted. RESULTS Compared with the control group， the mice in the model group exhibited obvious scratching behavior， with a large amount of scale on the skin， excessive epidermal keratinization， and thickened stratum spinosum. The skin scale score， epidermal thickness， and the expression levels of Ki67， Filaggrin， and Loricrin proteins in the skin tissue were significantly increased/elevated （ P ＜0.05）. Compared with model group， the mice in the D. officinale group exhibited reduced scratching behavior and scaling， along with a mitigated degree of skin keratinization. The aforementioned quantitative indicators were significantly decreased/reduced （ P ＜0.05）. The results of core pathway screening revealed that the KEGG pathways involving differentially expressed genes included signaling pathways such as interleukin-17 （IL-17） and tumor necrosis factor （TNF）. Further validation experim ents found that after intervention with D. officinale ， mRNA expression of downstream effector molecules CCN1， Hbegf， Tnfrsf12a， and Thbs1 genes in skin tissues were all significantly reduced （ P ＜0.05）. CONCLUSIONS D. officinale can repair skin damage in mice with xeroderma， and its mechanism of action is related to restoring the balance of proliferation and differentiation in keratinocytes and down-regulating the mRNA expressions of CCN1， Hbegf， Tnfrsf12a， and Thbs1.

ObjectiveTo investigate the molecular mechanisms by which salvianolic acid B （SalB） inhibits epithelial-mesenchymal transition （EMT） in non-small cell lung cancer （NSCLC） by downregulating phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazole succinocarboxamide synthetase （PAICS） expression. MethodsNSCLC A549 cells and normal bronchial epithelial cells （bronchial epithelium transformed with Ad12-SV40 2B， BEAS-2B） were used as models. Cell viability was assessed using the cell counting kit-8 （CCK-8） assay after treatment with SalB （0， 50， 100， 200， 300， 400， 500 μmol·L^-1 for 24 or 48 h to determine effective and safe intervention concentrations. Cell proliferation， cell cycle distribution， and apoptosis were evaluated by 5-ethynyl-2′-deoxyuridine （EdU） staining and flow cytometry， respectively. Wound healing and Transwell invasion assays were performed to assess cell migration and invasion. RNA sequencing combined with bioinformatic analysis was conducted to identify differentially expressed genes and functional enrichment. Molecular docking was used to predict the binding ability between SalB and PAICS， and the cellular thermal shift assay （CETSA） was performed to evaluate the effect of SalB on the thermal stability of the PAICS protein. Western blot （WB） was used to detect the effects of SalB on PAICS and EMT-related proteins （E-cadherin， N-cadherin， Vimentin， Snail， and Slug）. A functional rescue assay was conducted by PAICS overexpression via plasmid transfection. ResultsCompared with the control group， SalB inhibited A549 cell viability in a dose-dependent manner （P<0.05）， and the effective concentrations （≤300 μmol·L^-1） showed no significant cytotoxicity in BEAS-2B cells. Within this concentration range， SalB significantly inhibited A549 cell proliferation， migration， and invasion， and induced G₀/G₁ phase arrest and apoptosis （P<0.05）. Transcriptomic analysis showed that SalB significantly downregulated PAICS expression， and its functions were enriched in cell proliferation and EMT. Bioinformatic analysis indicated that PAICS is highly expressed in lung adenocarcinoma and is associated with poor prognosis （P<0.01）. Molecular docking showed that SalB has strong binding ability to PAICS （binding energy -9.1 kcal·mol^-1. CETSA results showed that SalB significantly increased the thermal stability of the PAICS protein （P<0.05）. WB results showed that， compared with the control group， SalB dose-dependently downregulated PAICS expression， upregulated E-cadherin， and downregulated N-cadherin， Vimentin， Snail， and Slug （P<0.05）. Functional rescue experiments showed that， compared with the empty vector group， PAICS overexpression significantly enhanced A549 cell proliferation， migration， and invasion， promoted cell cycle progression， and inhibited apoptosis （P<0.05）. Meanwhile， compared with the empty vector + SalB-H group， PAICS overexpression partially reversed the inhibitory effects of SalB on malignant phenotypes and EMT-related proteins （N-cadherin， Vimentin， Snail， and Slug）， and downregulated E-cadherin expression （P<0.05，P<0.01）， indicating that PAICS is a key functional target mediating the antitumor effects of SalB. ConclusionSalB effectively inhibits EMT progression and cell cycle progression in A549 cells by downregulating PAICS expression， thereby exerting anti-NSCLC effects. This study not only reveals that PAICS is a key functional target through which SalB regulates EMT， but also provides experimental evidence supporting SalB as a potential candidate drug for inhibiting NSCLC metastasis.

ObjectiveTo investigate the inhibitory effects of curcumol （Cur） on the proliferation and metastasis of non-small cell lung cancer （NSCLC） cells and to explore the underlying mechanisms. MethodsIn vivo， a subcutaneous tumor xenograft model was established to evaluate the antiproliferative effect of Cur. In vitro， the cell counting kit-8 （CCK-8） assay was used to assess the effects of Cur at concentrations of 0， 60， 120， 240， 360， 480， 600， 720， 840， 960 μmol·L^-1 on the viability of NCI-A549 and NCI-H23 cells， and to evaluate its inhibitory effect on the proliferation of human bronchial epithelial BEAS-2B cells. Wound healing and Transwell migration assays were conducted to assess changes in cell migratory capacity following Cur treatment. Immunohistochemistry （IHC-P） was used to investigate the regulatory effect of Cur on the Janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3） signaling pathway in tumor tissues. Western blot was performed to determine the protein expression levels of phosphorylated JAK2 （p-JAK2）， phosphorylated STAT3 （p-STAT3）， proliferating cell nuclear antigen （PCNA）， matrix metalloproteinase-2 （MMP-2）， matrix metalloproteinase-9 （MMP-9）， and vascular endothelial growth factor A （VEGFA） in tumor tissues and cells. To further verify the role of the JAK2/STAT3 signaling pathway in the pharmacological effects of Cur， rescue experiments were performed using the pathway agonist colivelin. ResultsIn vivo experiments showed that， compared with the model group， the tumor volumes of subcutaneous xenografts in nude mice in both low- and high-dose Cur groups were significantly reduced （P<0.05）， and the tumor inhibition rates were significantly increased （P<0.05）. The inhibitory effect in the high-dose group was comparable to that of the cisplatin group， and the body weight of mice in the Cur groups remained stable throughout the experiment. In vitro， compared with the control group， Cur at concentrations of 120 and 240 μmol·L^-1 inhibited the proliferation of NCI-A549 and NCI-H23 cells in a concentration-dependent manner （P<0.05）， with a significant inhibitory effect observed at 360 μmol·L^-1 （P<0.01）， while no significant effect on the viability of BEAS-2B cells was observed. Migration assays demonstrated that， compared with the control group， Cur treatment significantly reduced the migration rates of both cell lines in a concentration-dependent manner （P<0.05）， with an inhibitory effect at 360 μmol·L^-1 comparable to that of the cisplatin group. Mechanistic validation showed that， compared with the control group， the protein expression levels of p-JAK2 and p-STAT3 in tumor tissues and cells were significantly downregulated in the Cur groups （P<0.01）， and the expression levels of downstream proteins PCNA， MMP-2， MMP-9， and VEGFA were also significantly decreased with increasing Cur concentration （P<0.05）. In the rescue experiments， compared with the control group， colivelin pretreatment increased cell proliferation and migration rates （P<0.05） and upregulated the expression of related proteins （P<0.05）. Compared with the Cur group， the colivelin+Cur group showed significantly increased proliferation and migration rates （P<0.05）， along with significantly upregulated protein expression levels （P<0.05）. ConclusionCur can significantly inhibit the proliferation and metastasis of NSCLC both in vivo and in vitro， and its mechanism of action is closely associated with the inhibition of JAK2/STAT3 signaling pathway activation.