OBJECTIVE To investigate the effect and mechanism of morin on alveolar bone resorption in periodontitis mice based on the silent information regulator 1 （SIRT1）/peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α）/nuclear factor-erythroid 2-related factor 2 （Nrf2） pathway. METHODS The mice were randomly divided into control group， model group， morin group （40 mg/kg）， SRT1720 （SIRT1 activator） group （5 mg/kg）， and morin+EX527 （SIRT1 inhibitor） group （40 mg/kg morin+7.5 mg/kg EX527）， with 18 mice in each group. Except for control group， mice in other groups were subjected to silk ligation to establish periodontitis model. After successful modeling， mice in each group were treated with corresponding medicinal solutions or normal saline intragastrically or intraperitoneally， once a day， for two consecutive weeks. After the last medication， serum levels of tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， IL-6 and IL-10 were measured. The distance between the cementoenamel junction and alveolar bone crest was determined， and bone volume fraction and bone mineral density were calculated. Pathological changes of periodontal tissue were observed， and the number of osteoclasts was measured. mRNA expressions of receptor activator of nuclear factor-κB ligand （RANKL） and osteoprotegerin （OPG） in periodontal tissue， the levels of malondialdehyde （MDA） and superoxide dismutase （SOD） as well as protein expressions of SIRT1， PGC-1α， and Nrf2 were determined. RESULTS Compared with model group， the alveolar bone resorption and inflammatory cell infiltration in the periodontal tissues of mice were improved in morin group and SRT1720 group. The serum levels of TNF-α， IL-1β and IL-6， the distance between cementoenamel junction and alveolar bone crest， the number of osteoclasts in periodontal tissue， RANKL mRNA expression and the MDA level were decreased， shortened and reduced significantly （ P ＜0.05）； however， serum level of IL-10， bone volume fraction and bone mineral density， OPG mRNA expression in periodontal tissue， SOD level and protein expressions of SIRT1， PGC-1α and Nrf2 were increased significantly （ P ＜0.05）. Compared with morin group， the above pathological changes were significantly aggravated in the morin+EX527 group； and the levels of quantitative indicators were markedly reversed （ P ＜0.05）. CONCLUSIONS Morin may inhibit alveolar bone resorption in periodontitis mice by activating the SIRT1/PGC-1α/Nrf2 pathway to reduce inflammatory reaction and oxidative stress.

Objective To explore the safety of Yttrium-90 resin microsphere selective internal radiation therapy (⁹⁰Y-SIRT) on malignant liver tumors. Methods A retrospective analysis was conducted on 64 patients with malignant liver tumors who underwent ⁹⁰Y-SIRT from February 2023 to November 2024 at Weifang People’s Hospital. The clinical characteristics of the patients and the occurrence of adverse reactions after treatment were analyzed to assess the safety of ⁹⁰Y-SIRT. Results Among the 64 patients, there were 52 males (81.25%) and 12 females (18.75%); the average age was (56.29±11.08) years. Seven patients (10.94%) had tumors with maximum diameter of less than 5 cm, 38 patients (59.38%) had tumors with maximum diameter of 5-10 cm, and 19 patients (29.68%) had tumors with maximum diameter of greater than 10 cm. There were 47 cases (73.44%) of solitary lesions and 17 cases (26.56%) of multiple lesions; 53 cases (82.81%) were primary liver cancers and 11 cases (17.19%) were metastatic liver cancers. Of the 64 patients, 63 successfully completed the Technetium-99m macroaggregated albumin (^99mTc-MAA) perfusion test and received the ⁹⁰Y-SIRT; one patient received ⁹⁰Y-SIRT after the second ^99mTc-MAA perfusion test due to a work error. The most common adverse reactions included grade 1 alanine aminotransferase (ALT) elevation in 26 cases (40.62%) and grade 2 in 2 cases (9.37%), grade 1 aspartate aminotransferase (AST) elevation in 27 cases (42.18%) and grade 2 in 7 cases (10.93%); grade 1 nausea in 17 cases (26.56%) and grade 2 in 6 cases (9.37%); grade 1 abdominal pain in 12 cases (18.75%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%); grade 1 vomiting in 11 cases (17.18%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%). Conclusion The adverse reactions of ⁹⁰Y-SIRT for treating malignant liver tumors are mild, indicating good safety.

ObjectiveTo explore the mechanism of the anti-cancer compound formula Feiyanning in inhibiting epithelial-mesenchymal transition （EMT） and invasion and metastasis of non-small cell lung cancer （NSCLC）. MethodsCell proliferation and activity were assessed using the cell counting kit-8（CCK-8） assay to evaluate the effect of Feiyanning on the proliferation of A549 and H1299 cells. Wound healing and Transwell assays were conducted to examine Feiyanning's impact on the metastasis of A549 and H1299 cells. The effects of Feiyanning on EMT and the transforming growth factor-β₁ （TGF-β₁）/Smad signaling pathway proteins in A549 and H1299 cells were detected by Western blot. Exogenous TGF-β₁ was used to induce EMT in A549 and H1299 cells. The effects of Feiyanning on TGF-β₁-induced NSCLC cell metastasis， EMT， and the TGF-β₁/Smad pathway proteins were assessed by wound healing assay， Transwell assay， and Western blot. In vivo， an A549 lung metastasis model was established via tail vein injection in nude mice. A total of 28 SPF male nude mice were randomly divided into four groups： Model （NC） group， Feiyanning low-dose （FYN1） group， Feiyanning high-dose （FYN2） group， and the positive control group （TGF-β receptor kinase inhibitor SB431542 group）. The corresponding interventions were performed. After 40 days， the mice were euthanized， and lung metastases were analyzed. The expression of E-cadherin， N-cadherin， p-Smad2， and p-Smad3 in each group was detected by immunohistochemistry （IHC）. ResultsAfter Feiyanning intervention， compared to the blank group， Feiyanning inhibited the proliferation of A549 and H1299 cells in a concentration-dependent manner （P<0.01）. The metastasis ability of Feiyanning-treated cells was significantly decreased compared to the blank group （P<0.01）. The expression of EMT marker proteins N-cadherin and zinc finger transcription factors （Zeb1， Snail， Slug） was significantly reduced in the Feiyanning groups compared to the blank group （P<0.05， P<0.01）. The expression of p-Smad2/3， Smad2/3， TβRI， and TβRⅡ， key proteins in the TGF-β₁/Smad signaling pathway， was also significantly decreased （P<0.01）. In the TGF-β₁-induced EMT model， compared to the TGF-β₁ group， the cell metastasis ability in the Feiyanning groups was reduced （P<0.01）， and the expression levels of N-cadherin， Zeb1， Snail， and Slug were significantly lower （P<0.01）. The expression levels of p-Smad2/3， Smad2/3， TβRI， and TβRⅡ were also significantly reduced （P<0.01）. In vivo results showed that compared to the model group， the number of lung metastases in the FYN1， FYN2， and SB431542 groups was reduced （P<0.01）， and the range of cell infiltration was narrowed. Immunohistochemical results showed that compared to the model group， the expression of E-cadherin in the FYN1， FYN2， and SB431542 groups was increased （P<0.01）， the expression of N-cadherin decreased （P<0.05， P<0.01）， and the expression of p-Smad2 and p-Smad3， key proteins of the TGF-β₁/Smad pathway， was reduced （P<0.01）. ConclusionFeiyanning inhibits the invasion and metastasis of NSCLC cells and EMT. The mechanism is related to the inhibition of TGF-β₁/Smad signaling pathway.

ObjectiveTo explore the mechanism of the anti-cancer compound formula Feiyanning in inhibiting epithelial-mesenchymal transition （EMT） and invasion and metastasis of non-small cell lung cancer （NSCLC）. MethodsCell proliferation and activity were assessed using the cell counting kit-8（CCK-8） assay to evaluate the effect of Feiyanning on the proliferation of A549 and H1299 cells. Wound healing and Transwell assays were conducted to examine Feiyanning's impact on the metastasis of A549 and H1299 cells. The effects of Feiyanning on EMT and the transforming growth factor-β₁ （TGF-β₁）/Smad signaling pathway proteins in A549 and H1299 cells were detected by Western blot. Exogenous TGF-β₁ was used to induce EMT in A549 and H1299 cells. The effects of Feiyanning on TGF-β₁-induced NSCLC cell metastasis， EMT， and the TGF-β₁/Smad pathway proteins were assessed by wound healing assay， Transwell assay， and Western blot. In vivo， an A549 lung metastasis model was established via tail vein injection in nude mice. A total of 28 SPF male nude mice were randomly divided into four groups： Model （NC） group， Feiyanning low-dose （FYN1） group， Feiyanning high-dose （FYN2） group， and the positive control group （TGF-β receptor kinase inhibitor SB431542 group）. The corresponding interventions were performed. After 40 days， the mice were euthanized， and lung metastases were analyzed. The expression of E-cadherin， N-cadherin， p-Smad2， and p-Smad3 in each group was detected by immunohistochemistry （IHC）. ResultsAfter Feiyanning intervention， compared to the blank group， Feiyanning inhibited the proliferation of A549 and H1299 cells in a concentration-dependent manner （P<0.01）. The metastasis ability of Feiyanning-treated cells was significantly decreased compared to the blank group （P<0.01）. The expression of EMT marker proteins N-cadherin and zinc finger transcription factors （Zeb1， Snail， Slug） was significantly reduced in the Feiyanning groups compared to the blank group （P<0.05， P<0.01）. The expression of p-Smad2/3， Smad2/3， TβRI， and TβRⅡ， key proteins in the TGF-β₁/Smad signaling pathway， was also significantly decreased （P<0.01）. In the TGF-β₁-induced EMT model， compared to the TGF-β₁ group， the cell metastasis ability in the Feiyanning groups was reduced （P<0.01）， and the expression levels of N-cadherin， Zeb1， Snail， and Slug were significantly lower （P<0.01）. The expression levels of p-Smad2/3， Smad2/3， TβRI， and TβRⅡ were also significantly reduced （P<0.01）. In vivo results showed that compared to the model group， the number of lung metastases in the FYN1， FYN2， and SB431542 groups was reduced （P<0.01）， and the range of cell infiltration was narrowed. Immunohistochemical results showed that compared to the model group， the expression of E-cadherin in the FYN1， FYN2， and SB431542 groups was increased （P<0.01）， the expression of N-cadherin decreased （P<0.05， P<0.01）， and the expression of p-Smad2 and p-Smad3， key proteins of the TGF-β₁/Smad pathway， was reduced （P<0.01）. ConclusionFeiyanning inhibits the invasion and metastasis of NSCLC cells and EMT. The mechanism is related to the inhibition of TGF-β₁/Smad signaling pathway.

OBJECTIVES: The application of photodynamic therapy in solid tumors has attracted increasing attention in recent years, and the efficiency of photosensitizers is a crucial determinant of therapeutic efficacy. This study aims to evaluate the cytotoxic effects of a novel photosensitizer, PEG-MTPABZ-PyC, in photodynamic therapy against gastric cancer cells. METHODS: Gastric cancer MKN45 cells were treated with PEG-MTPABZ-PyC. A high-content live-cell imaging system was used to assess the cellular uptake kinetics and subcellular localization of the photosensitizer. The cytotoxic effects of PEG-MTPABZ-PyC-mediated photodynamic therapy were examined using the cell counting kit-8 (CCK-8) assay and flow cytometry, while the intrinsic cytotoxicity of the photosensitizer alone was verified by the CCK-8 assay. Intracellular reactive oxygen species (ROS) generation after photodynamic therapy was detected using 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA). RESULTS: PEG-MTPABZ-PyC alone exhibited no cytotoxicity toward MKN45 cells, indicating excellent cytocompatibility. The compound efficiently entered cells within 6 hours and localized predominantly in lysosomes. Upon light irradiation, PEG-MTPABZ-PyC-mediated photodynamic therapy induced significant cytotoxicity compared with the control group (P<0.05) and generated abundant intracellular ROS. CONCLUSIONS The novel photosensitizer PEG-MTPABZ-PyC demonstrates potent photodynamic cytotoxicity against gastric cancer cells, showing promising potential for further development in gastric cancer photodynamic therapy.
Humans ; Stomach Neoplasms/drug therapy* ; Photochemotherapy/methods* ; Photosensitizing Agents/pharmacology* ; Cell Line, Tumor ; Polyethylene Glycols/chemistry* ; Reactive Oxygen Species/metabolism* ; Mesoporphyrins/pharmacology*

Traditional Chinese medicine (TCM) represents a paradigmatic approach to personalized medicine, developed through the systematic accumulation and refinement of clinical empirical data over more than 2000 years, and now encompasses large-scale electronic medical records (EMR) and experimental molecular data. Artificial intelligence (AI) has demonstrated its utility in medicine through the development of various expert systems (e.g., MYCIN) since the 1970s. With the emergence of deep learning and large language models (LLMs), AI's potential in medicine shows considerable promise. Consequently, the integration of AI and TCM from both clinical and scientific perspectives presents a fundamental and promising research direction. This survey provides an insightful overview of TCM AI research, summarizing related research tasks from three perspectives: systems-level biological mechanism elucidation, real-world clinical evidence inference, and personalized clinical decision support. The review highlights representative AI methodologies alongside their applications in both TCM scientific inquiry and clinical practice. To critically assess the current state of the field, this work identifies major challenges and opportunities that constrain the development of robust research capabilities-particularly in the mechanistic understanding of TCM syndromes and herbal formulations, novel drug discovery, and the delivery of high-quality, patient-centered clinical care. The findings underscore that future advancements in AI-driven TCM research will rely on the development of high-quality, large-scale data repositories; the construction of comprehensive and domain-specific knowledge graphs (KGs); deeper insights into the biological mechanisms underpinning clinical efficacy; rigorous causal inference frameworks; and intelligent, personalized decision support systems.
Medicine, Chinese Traditional/methods* ; Artificial Intelligence ; Humans ; Precision Medicine ; Decision Support Systems, Clinical

Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC₅₀ = 0.049 μmol/L, huBuChE IC₅₀ = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.

OBJECTIVES: To explore the correlation of ELFN1 expression level with prognosis of colorectal cancer and its regulatory role in colorectal cancer cell proliferation and metastasis. METHODS: We analyzed the expression levels of ELFN1 across 33 cancer types using publicly available databases and identified differential genes related to ELFN1 in colorectal cancer. Gene function annotation and enrichment analysis were used to identify the involved signaling pathways. Logistic analysis, Kaplan-Meier analysis and Cox regression analysis were performed to evaluate the correlation between ELFN1 expression and clinicopathological parameters and survival of colorectal cancer patients. qPCR and Western blotting were used to validate the expression levels of ELFN1 in different colorectal cancer cell lines and tissues, and Transwell and EDU experiments were carried out to assess the effect of ELFN1 knockdown on biological behaviors of SW480 cells. RESULTS: ELFN1 was highly expressed in 14 cancers, and its expression was significantly higher in colon cancer tissues than in adjacent tissues. A high expression of ELFN1 mRNA was associated with a poorer overall survival of colorectal cancer patients. Cox regression analysis indicated that ELFN1 expression was an independent prognostic factor for overall survival of the patients. ELFN1 was significantly enriched in tumor metastasis and proliferation and participated in several tumor signaling pathways. The colon cancer cell lines showed significantly higher expression levels of ELFN1 than normal cells, ELFN1 knockdown obviously inhibited proliferation and migration of SW480 cells in vitro. CONCLUSIONS ELFN1 is overexpressed in colorectal cancer and is associated with poor clinical prognosis of the patients. A high ELFN1 expression is associated with malignant phenotypes of colorectal cancer and promotes cancer cell proliferation and metastasis, suggesting its potential as a prognostic biomarker for colorectal cancer.
Humans ; Colorectal Neoplasms/diagnosis* ; Cell Proliferation ; Prognosis ; Cell Line, Tumor ; Biomarkers, Tumor/metabolism* ; Neoplasm Metastasis ; Gene Expression Regulation, Neoplastic ; Nerve Tissue Proteins/metabolism* ; Female ; Male

Objective To investigate the relationship between the mean platelet volume(MPV)to platelet count(PLT)ratio(MPV/PLT),blood urea nitrogen(BUN)to lipoprotein a[Lp(a)]ratio[BUN/Lp(a)]and the prognosis of patients with acute exacerbation of chronic obstructive pulmonary disease(COPD).Methods A total of 106 patients with acute exacerbation of COPD admitted to the hospital from January 2021 to January 2024 were selected as the research objects.According to the prognosis,they were divided into sur-vival group(72 cases)and death group(34 cases).The results of routine laboratory tests,blood lipid and lipo-protein levels were compared between the two groups.Multivariate Logistic regression was used to analyze the influencing factors of death in patients with acute exacerbation of COPD.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of MPV/PLT and BUN/Lp(a)for the prognosis of pa-tients with acute exacerbation of COPD.Results Compared with the survival group,the invasive ventilation rate,acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score,C reactive protein(CRP),white blood cell count(WBC),MPV,BUN,MPV/PLT and BUN/Lp(a)were significantly increased in the death group(P＜0.05).The non-invasive ventilation rate,lymphocyte count,PLT and Lp(a)levels were signifi-cantly decreased(P＜0.05).Multivariate Logistic regression analysis showed that APACHE Ⅱ score,CRP,WBC,lymphocyte count,MPV,PLT,MPV/PLT,BUN,Lp(a)and BUN/Lp(a)were the influencing factors of death in patients with acute exacerbation of COPD(P＜0.05).ROC curve results showed that the sensitivity and specificity of MPV/PLT combined with BUN/Lp(a)for predicting the prognosis of patients with acute exacerbation of COPD were 88.2％and 84.7％,respectively,and the area under curve was 0.887.Conclusion MPV/PLT and BUN/Lp(a)are closely related to the prognosis of patients with acute exacerbation of COPD.The combination of MPV/PLT and BUN/Lp(a)has a high predictive value for the prognosis of patients.