Obesity， a global chronic disease， is associated with adipose tissue dysfunction， which is one of the contributing factors to obesity. The cyclic adenosine monophosphate （cAMP） signaling pathway， a key regulator of lipid metabolism， plays a pivotal role in obesity development. Various of traditional Chinese medicine monomers， such as flavonoids， lignans， phenols， and terpenoids， as well as traditional Chinese medicine compound formulas like Xiaoyao powder， Shengmai powder， and Zexie decoction， can maintain energy homeostasis， balance adipose tissue function， regulate glucose metabolism， improve insulin resistance， and suppress inflammatory responses through cAMP signaling pathway regulation， thereby intervening in lipid metabolism for obesity treatment. Although a substantial amount of basic research has preliminarily elucidated the potential mechanisms by which traditional Chinese medicine intervenes in obesity through the cAMP signaling pathway， clinical translational research remains inadequate. There is an urgent need for large-sample， high-quality randomized controlled trials to validate these findings.

Plasminogen activator is a kind of enzyme that plays a key role in the process of physiological hemostasis and thrombolysis. Its main function is to convert plasminogen into active plasmin, thereby initiating the dissolution of fibrin and maintaining blood mobility. This article discusses the safety of plasminogen activator in the intraocular application, elaborates on the types, structure, physiological function and mechanism of action of plasminogen activator in the eye. The analysis addresses the ocular tissue damage and systemic adverse reactions that may be caused by the application of plasminogen activator in the eye, and the risks and countermeasures combined with relevant research examples, aiming to provide reference for the safe application of plasminogen activator in clinical practice.

BackgroundPatients with chronic schizophrenia often suffer from cognitive impairment. Traditional cognitive rehabilitation training has problems such as a single form and poor compliance， making it urgent to develop new cognitive intervention methods. ObjectiveTo explore the intervention effect of smartphone games on the cognitive function of patients with chronic schizophrenia， and to analyze the differences in cognitive function improvement between patients of different genders， in order to provide references for the cognitive function intervention of these patients. MethodsThis study was a prospective cohort study. A total of 30 patients who were hospitalized in the Psychiatry Department of Chaohu Hospital Affiliated to Anhui Medical University from March to October 2021， met the diagnostic criteria for schizophrenia as defined in the International Classification of Diseases， tenth edition （ICD-10）， and had a disease duration of above 5 years， were selected as the research subjects. All patients received smartphone game intervention for 12 weeks， 5 times a week， each session lasting 1 hour， in addition to conventional antipsychotic drug treatment. At the baseline and at 3， 6， 9， and 12 weeks of the intervention， the cognitive function was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status （RBANS）， the Positive and Negative Syndrome Scale （PANSS） was used to assess mental symptoms， and the Problematic Mobile Gaming Questionnaire （PMGQ） was used to assess addiction symptoms. ResultsA total of 26 patients （86.67%） completed the study， including 13 females and 13 males. The time effects， group effects， and interaction effect between time and group for the immediate memory factor score of RBANS in the female group and the male group were all statistically significant （F=36.682， 5.712， 3.090， P<0.05 or 0.01）， and the time effects and group effects for the verbal and delayed memory factors as well as the total score in both groups were also statistically significant （F=3.841， 6.149， 15.372， P<0.05 or 0.01）. The time effects and group effects of the total score of PANSS in both groups had no statistical significance （F=2.041， 0.623， P>0.05 for both）， and the interaction effect between time and group was statistically significant （F=5.728， P<0.01）. The time effects， group effects， and interaction effect of the total score of PMGQ in both groups were all without statistical significance （F=2.672， 0.166， 0.642， P>0.05 for both）. ConclusionSmartphone game intervention may help improve the cognitive function of patients with chronic schizophrenia （especially immediate memory， verbal function， and delayed memory）， and the benefits are greater for female patients. The smartphone game intervention did not induce game addiction， but no significant improvement in psychotic symptoms was observed. ［Funded by Excellent Young Talents Support Program of Anhui Provincial Department of Education （number， gxyqZD2022022）； www.chictr.org.cn number， ChiCTR2100044113］

OBJECTIVE To investigate the influence of CYP2C19 gene polymorphism on platelet function and inflammatory cytokines in elderly patients with ischemic stroke， and to analyze potential factors associated with poor prognosis. METHODS A retrospective study was conducted on elderly patients with ischemic stroke admitted to our hospital from June 2024 to June 2025， wh o underwent CYP2C19 genotype testing and received antiplatelet therapy with clopidogrel. The levels of platelet function indicators and inflammatory cytokines before and after treatment were compared among patients with different metabolic phenotypes. Based on the prognosis at 6 months post-treatment， patients were divided into poor prognosis group and good prognosis group. Univariate analysis was performed on general data， metabolic phenotype， the levels of platelet function indicators and inflammatory cytokines. Variables with P ＜0.05 and the levels of inflammatory cytokines before treatment were included in a multivariate Logistic regression analysis to identify independent risk factors for poor prognosis. Multiple linear regression was used to further analyze the relationship between metabolic phenotypes and inflammatory cytokines. RESULTS A total of 448 elderly patients with ischemic stroke were included； among them， 162 cases were normal metabolic phenotype， 218 were intermediate metabolic phenotype， and 68 were poor metabolic phenotype. No rapid or ultrarapid metabolic phenotypes were observed. After treatment， platelet aggregation rate， the levels of P-selectin and platelet activated complex-1 （PAC-1）， high-sensitivity C-reactive Protein （hs-CRP）， interleukin-1β （IL-1β）， IL-6 and tumor necrosis factor-α （TNF-α） in the normal metabolic phenotype group， intermediate metabolic phenotype group， and poor metabolic phenotype group （except for platelet aggregation rate， and the levels of P-selectin and PAC-1 in the poor metabolic phenotype group） were significantly lower than those before treatment in the same group. Moreover， the above indicators in the normal metabolic phenotype group were significantly lower than those in the intermediate and poor metabolic phenotype groups at the corresponding time， and the levels of platelet function indicators in the intermediate metabolic phenotype group were significantly lower than those in the poor metabol ic phenotype group at the corresponding time （ P ＜0.05）. Univariate and multivariate Logistic regression analyses showed that combined with hypertension， combined with diabetes mellitus， and intermediate or poor metabolic genotypes were independent risk factors for poor prognosis in elderly patients with ischemic stroke （ P ＜0.05）. Multiple linear regression analysis showed that serum levels of hs-CRP， IL-1β， IL-6 and TNF-α before treatment were significantly higher in patients with intermediate and poor metabolic genotypes compared to those with normal metabolic genotype （ P ＜0.05）， with a greater magnitude of increase in inflammatory cytokines observed in the patients with poor metabolic genotype. CONCLUSIONS The elderly ischemic stroke patients with CYP2C19 intermediate and poor metabolic genotypes have poor inhibition effect on platelet and higher levels of inflammatory cytokines than normal metabolic genotype； CYP2C19 gene polymorphism， and in combination with hypertension and diabetes， can be used as independent predictors of poor prognosis.

Objective To analyze the epidemiological characteristics and spatial-temporal clustering trend of scarlet fever in Nantong from 2009 to 2023, and to provide a scientific basis for scarlet fever prevention and control. Methods The incidence data of scarlet fever in Nantong from 2009 to 2023 were analyzed. Descriptive analysis, seasonal index method and Joinpoint 5.2.0 software were used to analyze epidemiological characteristics. Spatial-temporal clustering was assessed with SaTScan 10.2.5 software. Results The average annual incidence of scarlet fever in Nantong from 2009 to 2023 was 6.54/100 000. The overall morbidity rate of scarlet fever in Nantong had an increasing trend from 2009 to 2019 with an average annual percentage change of 14.55% (t=3.36，P<0.05). The cases mainly occurred during late spring to early summer and late autumn to early winter. Students, preschool children and scattered children were the main scarlet fever population. The average annual incidence of males was significantly higher than that of females (χ²=7.00, P<0.05). Rugao City, Chongchuan District and Tongzhou District were identified as high-incidence areas, accounting for 76.51% of all reported cases. Spatial-temporal scan analysis indicated that Rugao City and Chongchuan District were primary cluster areas, spanning from 2015 to 2021 (RR=3.77, LLR=1 308.07, P<0.05). Conclusion The number of reported cases of scarlet fever in Nantong City from 2009 to 2023 shows epidemic and spatial clustering, mainly concentrated in the central urban area and adjacent counties (cities). It is necessary to strengthen health education and disease surveillance in high-incidence areas, as well as in key institutions and key populations before epidemic peaks.

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 mechanisms by which eupatilin （Eup） inhibits proliferation， invasion， and metastasis of non-small cell lung cancer （NSCLC） through the enhancer of zeste homolog 2/histone H3 lysine 27 trimethylation （EZH2/H3K27me3） signaling pathway. MethodsIn vivo， a subcutaneous xenograft tumor model was established in nude mice using H1299 cells to evaluate the anti-NSCLC effects of Eup. Immunohistochemistry （IHC-P） was used to detect the expression of proliferation- and invasion/metastasis-related proteins， including proliferating cell nuclear antigen （PCNA）， matrix metalloproteinase-2 （MMP-2）， matrix metalloproteinase-9 （MMP-9）， and vascular endothelial growth factor A （VEGFA）. In vitro， cell counting kit-8 （CCK-8） assays were performed to determine the viability of H1299 cells treated with different concentrations of Eup （0-200 μmol·L^-1） and to select appropriate concentrations. Colony formation and 5-ethynyl-2′-deoxyuridine （EdU） assays were used to evaluate cell proliferation. Wound healing and invasion assays were conducted to assess cell migration and invasion. Human umbilical vein endothelial cell （HUVEC） angiogenesis assays were used to evaluate the effects of Eup on angiogenesis. Transcriptomic analysis was performed to identify the targets of Eup in H1299 cells and to explore its major functions. Molecular docking and molecular dynamics simulations were conducted to predict the binding affinity and interaction stability between Eup and its target proteins. Western blot was used to detect the effects of Eup on the expression levels of EZH2/H3K27me3 pathway-related proteins and proliferation- and invasion/metastasis-related proteins， including PCNA， MMP-2， MMP-9， and VEGFA. ResultsIn the subcutaneous xenograft model， compared with the model group， Eup treatment dose-dependently inhibited the growth of H1299 xenograft tumors， and the tumor inhibition rate was significantly increased （P<0.05）. IHC-P results showed that， compared with the model group， high-dose Eup significantly reduced the expression levels of PCNA， MMP-2， MMP-9， and VEGFA in vivo （P<0.05）. In vitro， compared with the control group， Eup inhibited the proliferation， invasion， and metastasis of NSCLC cells in a concentration-dependent manner. Transcriptomic analysis further showed that， compared with the control group， Eup significantly downregulated EZH2 expression， and its functional effects were associated with inhibition of tumor metastasis. Molecular docking and molecular dynamics simulations indicated that Eup exhibited strong binding affinity with EZH2 and stable interactions. Western blot results demonstrated that， compared with the model group， Eup significantly inhibited， in a dose-dependent manner， the expression levels of EZH2， H3K27me3， and proliferation- and invasion/metastasis-related proteins （PCNA， MMP-2， MMP-9， and VEGFA） in both in vivo and in vitro experiments （P<0.05）. In vitro， compared with the control group， overexpression of EZH2 via plasmid transfection partially reversed the inhibitory effects of Eup on the expression of key proteins involved in proliferation and invasion/metastasis in H1299 cells. ConclusionEup effectively inhibits the proliferation， migration， and invasion of H1299 cells both in vivo and in vitro. The underlying mechanism may be related to inhibition of the EZH2/H3K27me3 signaling pathway and downregulation of proliferation- and invasion/metastasis-related proteins， including PCNA， MMP-2， MMP-9， and VEGFA. Eup may serve as a potential therapeutic agent for suppressing proliferation and invasion/metastasis in NSCLC.

Lung cancer， particularly non-small cell lung cancer （NSCLC）， is the malignant tumor with the highest incidence and mortality in China and worldwide. In 2022， the global number of deaths reached 1.8 million， accounting for 18.7% of all cancer-related deaths， seriously threatening human health and life， and posing a severe challenge for prevention and treatment. Although treatment strategies for lung cancer have been continuously enriched in recent years， and progress has been made in targeted therapy and immunotherapy， long-term survival benefits remain limited due to primary or acquired drug resistance， low immune responsiveness， and chemotherapy-related toxicities. Therefore， there is an urgent need to explore safe and effective adjunctive therapeutic strategies. Traditional Chinese medicine （TCM）， with its advantages of holistic regulation and individualized syndrome differentiation， has played an increasingly prominent role in comprehensive cancer treatment. TCM holds that "Yang deficiency leads to accumulation" is a key pathogenesis of tumors. Based on the theory that "Yang transforms Qi， while Yin forms substance"， deficiency of Yang Qi results in impaired warming and transformation functions， leading to internal accumulation of Yin-cold. This is closely related to dysregulation of the immune microenvironment， "cold tumor" characteristics， and dysfunction of the neuroendocrine system in modern medicine. Accordingly， the therapeutic strategy of "warming Yang， supporting healthy Qi， and combating cancer" has gained increasing attention. In recent years， commonly used Yang-warming Chinese herbs， including Aconiti Lateralis Radix Praeparata， Zingiberis Rhizoma， Cinnamomi Cortex， Epimedii Folium， and Psoraleae Fructus， as well as their active constituents， have achieved notable progress in anti-lung cancer research by regulating multiple signaling pathways， inducing apoptosis， inhibiting metastasis， and reversing drug resistance. In addition， Yang-warming formulae such as Sini Tang and Yanghe Tang have shown promising effects in alleviating myelosuppression， improving cancer-related fatigue， managing malignant pleural effusion， and relieving cancer pain. These therapies exhibit toxicity-reducing and efficacy-enhancing effects， significantly improving patients' quality of life and survival benefits. To systematically summarize the roles and mechanisms of Yang-warming Chinese herbal medicines and compound formulae in lung cancer， this paper provides a comprehensive review of recent advances， aiming to offer insights for the clinical practice of TCM in the prevention and treatment of lung cancer.

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 mechanisms by which eupatilin （Eup） inhibits proliferation， invasion， and metastasis of non-small cell lung cancer （NSCLC） through the enhancer of zeste homolog 2/histone H3 lysine 27 trimethylation （EZH2/H3K27me3） signaling pathway. MethodsIn vivo， a subcutaneous xenograft tumor model was established in nude mice using H1299 cells to evaluate the anti-NSCLC effects of Eup. Immunohistochemistry （IHC-P） was used to detect the expression of proliferation- and invasion/metastasis-related proteins， including proliferating cell nuclear antigen （PCNA）， matrix metalloproteinase-2 （MMP-2）， matrix metalloproteinase-9 （MMP-9）， and vascular endothelial growth factor A （VEGFA）. In vitro， cell counting kit-8 （CCK-8） assays were performed to determine the viability of H1299 cells treated with different concentrations of Eup （0-200 μmol·L^-1） and to select appropriate concentrations. Colony formation and 5-ethynyl-2′-deoxyuridine （EdU） assays were used to evaluate cell proliferation. Wound healing and invasion assays were conducted to assess cell migration and invasion. Human umbilical vein endothelial cell （HUVEC） angiogenesis assays were used to evaluate the effects of Eup on angiogenesis. Transcriptomic analysis was performed to identify the targets of Eup in H1299 cells and to explore its major functions. Molecular docking and molecular dynamics simulations were conducted to predict the binding affinity and interaction stability between Eup and its target proteins. Western blot was used to detect the effects of Eup on the expression levels of EZH2/H3K27me3 pathway-related proteins and proliferation- and invasion/metastasis-related proteins， including PCNA， MMP-2， MMP-9， and VEGFA. ResultsIn the subcutaneous xenograft model， compared with the model group， Eup treatment dose-dependently inhibited the growth of H1299 xenograft tumors， and the tumor inhibition rate was significantly increased （P<0.05）. IHC-P results showed that， compared with the model group， high-dose Eup significantly reduced the expression levels of PCNA， MMP-2， MMP-9， and VEGFA in vivo （P<0.05）. In vitro， compared with the control group， Eup inhibited the proliferation， invasion， and metastasis of NSCLC cells in a concentration-dependent manner. Transcriptomic analysis further showed that， compared with the control group， Eup significantly downregulated EZH2 expression， and its functional effects were associated with inhibition of tumor metastasis. Molecular docking and molecular dynamics simulations indicated that Eup exhibited strong binding affinity with EZH2 and stable interactions. Western blot results demonstrated that， compared with the model group， Eup significantly inhibited， in a dose-dependent manner， the expression levels of EZH2， H3K27me3， and proliferation- and invasion/metastasis-related proteins （PCNA， MMP-2， MMP-9， and VEGFA） in both in vivo and in vitro experiments （P<0.05）. In vitro， compared with the control group， overexpression of EZH2 via plasmid transfection partially reversed the inhibitory effects of Eup on the expression of key proteins involved in proliferation and invasion/metastasis in H1299 cells. ConclusionEup effectively inhibits the proliferation， migration， and invasion of H1299 cells both in vivo and in vitro. The underlying mechanism may be related to inhibition of the EZH2/H3K27me3 signaling pathway and downregulation of proliferation- and invasion/metastasis-related proteins， including PCNA， MMP-2， MMP-9， and VEGFA. Eup may serve as a potential therapeutic agent for suppressing proliferation and invasion/metastasis in NSCLC.