ObjectiveTo observe the effects of Yifei Tongluo prescription on the NOD-like receptor protein 3 （NLRP3）/Caspase-1/gasdermin D （GSDMD） pathway and epithelial-mesenchymal transition （EMT） in rats with pulmonary fibrosis. MethodsTracheal instillation of bleomycin was conducted to establish a rat model of pulmonary fibrosis. Thirty Sprague-Dawley （SD） rats were randomly divided into a blank group， a model group， a prednisone acetate group （1.17 mg·kg^-1）， and low- and high-dose Yifei Tongluo prescription groups （10.62 and 21.24 g·kg^-1， respectively）. Administration started on the 7th day after modeling， once a day for 28 consecutive days. The lung coefficient of each group was calculated. The pathological changes of lung tissues in each group were observed by hematoxylin-eosin （HE） staining and Masson staining. The expression of α-smooth muscle actin （α-SMA） and vimentin in rat lung tissues was detected by immunohistochemistry. The expression of NLRP3 inflammasome， E-cadherin （E-cad）， and typeⅠ collagen （ColⅠ） in lung tissues was detected by immunofluorescence. The content of hydroxyproline （HYP）， tumor necrosis factor （TNF）-α， interleukin （IL）-18， and IL-1β in rat serum was detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression levels of NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， IL-1β， and transforming growth factor （TGF）-β₁ in rat lung tissues were determined by real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of NLRP3， GSDMD， ASC， and Caspase-1 in rat lung tissues were determined by Western blot. ResultsCompared with the blank group， the model group exhibited a significantly increased lung coefficient （P<0.01） and significantly increased range of pulmonary interstitial inflammation and collagen deposition. In addition， the levels of α-SMA， Vimentin， E-cad， and ColⅠ in lung tissues were significantly increased （P<0.01）. The levels of fibrosis- and inflammation-related factors HYP， TNF-α， IL-18， and IL-1β in serum were significantly upregulated （P<0.01）. The levels of factors related to the activation of NLRP3 inflammasome in lung tissues， including NLRP3， GSDMD， ASC， Caspase-1， IL-1β， and TGF-β₁， were significantly upregulated （P<0.01）. Compared with the model group， the Yifei Tongluo prescription groups showed improved lung coefficients. Additionally， the extent of lung inflammation and collagen deposition was significantly reduced. The expression of α-SMA， Vimentin， E-cad， and ColⅠ in lung tissue was significantly decreased （P<0.01）. The levels of HYP， TNF-α， IL-18， and IL-1β in serum were significantly reduced （P<0.01）. The expression levels of NLRP3， GSDMD， ASC， Caspase-1， IL-1β， and TGF-β₁ in lung tissue were also significantly decreased （P<0.01）. ConclusionYifei Tongluo prescription can regulate the NLRP3/Caspase-1/GSDMD pathway， down-regulate release of pro-inflammatory and pro-fibrotic cytokines， alleviate NLRP3 inflammasome-mediated pyroptosis and EMT， and thereby improve pulmonary fibrosis in rats.

OBJECTIVE To investigate the effects and mechanism of the Yishen paidu formula on renal fibrosis in rats with chronic renal failure （CRF） through the reactive oxygen species （ROS）/thioredoxin-interacting protein （TXNIP）/NOD-like receptor thermal protein domain associated protein 3 （NLRP3） pathway. METHODS Rats were randomly divided into control group， model group， Yishen paidu formula low-dose （Yishen paidu formula-L） group， Yishen paidu formula high-dose （Yishen paidu formula- H） group， Yishen paidu formula-H+pcDNA-NC group， and Yishen paidu formula-H+ pcDNA-TXNIP group， with 10 rats in each group. Except for control group， all other rats were fed a diet containing 0.5% adenine to establish a CRF model； the rats were then administered corresponding drugs or normal saline intragastrically or via tail vein， once daily， for 8 consecutive weeks. After the last administration， the levels of serum creatinine （Scr）， blood urea nitrogen （BUN）， ROS， superoxide dismutase （SOD）， malondialdehyde （MDA）， tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， and IL-1β were measured in each group. Pathological changes in renal tissue were observed， and the protein expression levels of Collagen Ⅲ， α-smooth muscle actin （α-SMA）， transforming growth factor-β1 （TGF-β1）， TXNIP and NLRP3 in renal tissue were detected. RESULTS Compared with model group， the renal histopathological damage and fibrosis of rats in Yishen paidu formula-L group and Yishen paidu formula-H group were significantly alleviated. The levels of Scr， BUN， ROS， MDA， TNF- α， IL-6 and IL-1β， and the protein expressions of Collagen Ⅲ， α-SMA， TGF-β1， TXNIP and NLRP3 were significantly decreased， while SOD levels were significantly increased （P＜0.05）. Moreover， the changes were more pronounced in the Yishen paidu formula-H group （P＜0.05）. Compared with Yishen paidu formula-H+pcDNA-NC group， above indexes of rats in Yishen paidu formula-H+pcDNA-TXNIP group were reversed significantly （P＜0.05）. CONCLUSIONS Yishen paidu formula can inhibit renal fibrosis in CRF rats by suppressing the ROS/TXNIP/NLRP3 pathway.

OBJECTIVE To explore the mechanism of Chaiqi yigan granules （CQYG） against liver cancer through the ferroptosis pathway. METHODS Network pharmacology combined with ferroptosis-related database was used to screen key targets and main effective components of CQYG against liver cancer via regulating ferroptosis； molecular docking technology was employed to analyze the binding ability of main active components to key targets. Human liver Huh-7 cells were divided into blank serum control （CON） group， CQYG drug-containing serum （CQYGKL） group， ferroptosis inducer （RSL3） group， mammalian target of rapamycin complex 1 （mTORC1） inhibitor （RMC-5552） group， mTORC1 agonist （CCT007093） group， and CCT007093+CQYGKL group. The levels of Fe 2+ ， malondialdehyde （MDA）， and glutathione （GSH） in the cells were detected in the former three groups； mRNA expressions of mammalian target of rapamycin （mTOR）， sterol regulatory element-binding protein 1 （SREBP1）， and stearoyl-CoA desaturase 1 （SCD1）， protein expressions of SREBP1 and SCD1 as well as phosphorylation levels of mTOR and ribosomal S6 kinase （S6K） proteins were detected in all groups. RESULTS Key targets of CQYG for anti-liver cancer through the ferroptosis pathway were mTOR， SREBP1， SCD1，etc. The main active components included quercetin， tanshinone Ⅱ A ， baicalein， etc. The binding energies of main active components to key targets were all less than －5 kJ/mol. Compared with CON group， the levels of Fe 2+ and MDA in the cells in CQYGKL group and RSL3 group were significantly increased， while the levels of GSH were significantly decreased （ P ＜0.05）. mRNA expressions of mTOR， SREBP1 and SCD1， protein expressions of SREBP1 and SCD1， as well as the phosphorylation levels of mTOR and S6K proteins were significantly decreased in the CQYGKL group， RSL3 group， and RMC-5552 group， whereas all the above indicators were significantly increased in the CCT007093 group （ P ＜0.05）. Compared with CCT007093 group， the changes in all the above indicators were significantly suppressed in the CCT007093+CQYGKL group （ P ＜0.05）. CONCLUSIONS CQYG may induce ferroptosis by inhibiting mTORC1/SREBP1/SCD1 axis， thereby exerting anti-liver cancer effects.

ObjectiveHyperlipidemia （HLP） is a chronic metabolic disease characterized by abnormal lipid metabolism and is one of the important risk factors for the occurrence of cardiovascular and cerebrovascular diseases. Its incidence has increased year by year， showing a trend toward younger onset. The overall prevalence of HLP among adults in China is as high as 40.40%. Although existing animal models provide important tools for research on the mechanisms of HLP， they generally show insufficient clinical concordance and lack the combined disease-syndrome characteristics of traditional Chinese medicine （TCM） and Western medicine. This article systematically reviews the research progress of HLP animal models， integrates the clinicopathological characteristics of TCM and Western medicine， and proposes new model construction strategies， aiming to provide an experimental basis for accurately analyzing the pathogenesis of HLP and developing integrated TCM-Western medicine therapies. MethodsBased on literature included in PubMed， CNKI， and Wanfang databases over the past 30 years， the construction methods and evaluation systems of HLP animal models were systematically retrieved and summarized. The concordance of existing animal models was calculated according to the new animal model evaluation method proposed by Professor MIAO Mingsan. ResultsAmong existing Western medicine modeling approaches， genetically modified models showed the highest concordance （72%）， followed by dietary induction （66%） and chemical drug induction （60%）. The dietary induction method is the most widely used in practice because of its simple operation and mature technology. Existing TCM modeling approaches are classified into three types， i.e.， spleen deficiency type， phlegm syndrome type， and liver-kidney yin deficiency type. Among them， the phlegm syndrome type shows a high degree of concordance. However， all three types have the problem of non-objective evaluation indicators and insufficient application of tongue and pulse assessment. ConclusionThe construction of existing HLP disease-syndrome combined animal models is still mainly based on Western medicine modeling methods and lacks adequate reflection of TCM syndromes. In the future， HLP animal models that conform to the clinical disease-syndrome characteristics of both TCM and Western medicine may be constructed through multifactor composite modeling strategies， intelligent tongue image analysis via robot learning， objective pulse detection， the establishment of objective evaluation systems for TCM syndromes through big data computing， and the application of cutting-edge technologies.

BACKGROUND:Several observational studies have found a close relationship between thyroid function levels and sarcopenia,but the causal relationship between thyroid function levels and the onset of sarcopenia is not yet clear. OBJECTIVE:To investigate the causal relationship between thyroid function levels and sarcopenia using a two sample Mendelian randomization method. METHODS:A two sample Mendelian randomization analysis was conducted using genome-wide association study data on thyrotropin,free triiodothyronine,free tetraiodothyronine,subclinical hyperthyroidism,subclinical hypothyroidism,and four related phenotypes of sarcopenia-lefthand grip strength,right hand grip strength,limb lean mass,and gait speed.The inverse-variance weighted method,weighted median method,simple mode method,weighted median estimator method,and MR Egger regression method were used as analysis methods,while heterogeneity test,pleiotropy test,MR-PRESSO,leave-one-out method,funnel plot and other methods were used for sensitivity analysis. RESULTS AND CONCLUSION:Elevated levels of thyroid-stimulating hormone increased left-(β=0.02,SE=0.01,P=0.01)and right-handed grip strength(β=0.02,SE=0.01,P=0.01),an increase in free triiodothyronine decreased left-(β=-0.06,SE=0.02,P=9.5×10-5)and right-handed grip strength(β=-0.07,SE=0.02,P=9.3×10-5),and subclinical hyperthyroidism decreased gait speed(β=-4.4×10-3,SE=1.7×10-3,P=0.01).The sensitivity analysis results were basically consistent with the main analysis results.To conclude,an increase in thyroid-stimulating hormone is a protective factor for sarcopenia,and elevation of free triiodothyronine and subclinical hyperthyroidism may increase the risk of sarcopenia.

Research in photodynamic therapy (PDT) primarily focuses on enhancing light penetration depth, improving oxygen supply, and optimizing photosensitizer delivery. Notably, the delivery efficiency of the photosensitizer is crucial for therapeutic efficacy. Carboxyl-substituted phthalocyanines, as important photosensitizing molecules, possess unique chemical modification sites that enable direct targeted delivery or integration into diverse delivery systems. Their synthesis predominantly employs mixed- or cross-condensation, selective synthesis, and axial modification strategies to introduce carboxyl groups. However, their inherent hydrophobicity significantly hinders effective delivery. To address this limitation, modifications with peptides or quaternary ammonium salt derivatives may facilitate precise delivery to tumor cells and pathogens. With advances in nanotechnology, carboxyl-substituted phthalocyanines can serve as key photosensitizer modules, effectively integrated into nanomaterials such as biomacromolecules, inorganic metals, and polymers for both active and passive delivery. Recently, researchers have exploited the π-π stacking and other intermolecular forces among carboxyl-substituted phthalocyanine molecules to drive their self-assembly into nano-micelles, enabling carrier-free delivery or co-delivery with other therapeutic agents for synergistic effects. This review systematically outlines the synthesis strategies for carboxyl-substituted phthalo-cyanines. Taking mono-carboxyl-substituted zinc phthalocyanine as a model molecule, the performance of three delivery modalities were compared: single-molecule targeted delivery, nanocarrier-encapsulated delivery, and carrier-free self-assembled delivery, in terms of PDT efficacy, biocompatibility, and imaging-guided tracing capabilities, to provide a systematic technical framework for the rational design of novel modular photosensitizers and to advance the clinical translation of PDT in precision oncology and anti-infective therapy.
Photochemotherapy/methods* ; Indoles/administration & dosage* ; Isoindoles ; Photosensitizing Agents/administration & dosage* ; Drug Delivery Systems ; Humans

Lung cancer, particularly non-small cell lung cancer (NSCLC), is a leading cause of cancer-related mortality worldwide. In recent years, metabolomics has emerged as a key systems biology approach for analyzing small-molecule metabolites in cells, tissues and organisms. It provides new strategies for early diagnosis and metabolic profiling. Additionally, metabolomics plays a crucial role in studying resistance mechanisms in lung cancer. Tumor cell metabolic reprogramming is a key driving factor in the initiation and progression of lung cancer. Metabolomics studies have revealed how lung cancer cells regulate critical pathways such as energy metabolism, lipid metabolism, and amino acid metabolism to adapt to the demands of rapid proliferation and invasive metastasis. This review summarizes the latest advances in metabolomics research in lung cancer, focusing on the characteristics of metabolic reprogramming, the identification of potential metabolic biomarkers, and the prospects of metabolomics in early diagnosis and the elucidation of resistance mechanisms in lung cancer.
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Humans ; Metabolomics/methods* ; Lung Neoplasms/pathology* ; Animals ; Biomarkers, Tumor/metabolism*

OBJECTIVE: To explore the effects of two methods of smear layer removal on the surface properties of dentin. METHODS: Sixty extracted sound third molars were collected in this study, and were prepared as uniform dentin specimens with smear layer. All specimens were randomly divided into three groups: Control group, ultrasonic treatment (UT) group and etched treatment (ET) group. Scanning electron microscope (SEM) were used to observe the surface micromorphology of all three groups. Then, the surface elements, mineral phases and functional groups were analyzed by energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD) and flourier transformed infrared spectrometer (FTIR) respectively. The mechanical properties, hydrophilicity and biocompatibility were also further evaluated. RESULTS: It was revealed that dentin tubules of UT and ET groups were exposed, but lots of dentin debris piled up on the surface of the control one which covered up dentin tubules on the surface. The EDX results should that the weaker peak value of calcium and phosphorus in ET group than control and UT groups. Characteristic peaks of hydroxyapatite could be seen by XRD in all of the three groups, but lower distinctive peaks of amide Ⅰ, Ⅱ and Ⅲ bands of collagen of the dentin surface in control group than in ET and UT groups. The microhardness results showed that ET group was lower than control and UT groups, the difference was significant (P < 0.05). Better hydrophilicity of ET group was investigated (P < 0.05) than control group and UT group. Cells could be observed to adhere normally to dentin surface of each group which meant that all of the three groups had good biocompatibility. CONCLUSION Both UT and ET could effectively remove the smear layer on the surface of dentin and had no adverse effect of the dentin micromorphology and biocompatibility. The ultrasonic removal of the smear layer did not influence the mineral structure, hydrophilicity and mechanical properties of dentin surface. Although ET can effectively improve the hydrophilicity of dentin but decreased mechanical properties and the content of calcium and phosphorus.
Dentin/ultrastructure* ; Humans ; Surface Properties ; Smear Layer ; Molar, Third ; Microscopy, Electron, Scanning ; Dental Etching/methods*

BACKGROUND:Inflammation affects the osteogenic differentiation of periodontal ligament stem cells,and the osteogenic ability and autophagy level of periodontal ligament stem cells are closely related.However,there are no relevant reports on whether inflammation affects the osteogenic ability and autophagy level of periodontal ligament stem cells at different stages of osteogenic differentiation. OBJECTIVE:To explore alkaline phosphatase expression and autophagy periodontal ligament stem cells levels in periodontitis and normal conditions. METHODS:Periodontal ligament stem cells from normal and periodontitis patients were isolated and cultured,and underwent Vimentin,pan-CK,and Stro-1 fluorescence staining.At 3,7,and 14 days of osteogenic differentiation,western blot assay was used to detect the protein expression levels of alkaline phosphatase,LC3B,Beclin1,and ATG5 in normal and inflammatory periodontal ligament stem cells.The mRNA expression levels of alkaline phosphatase,bone sialoprotein,osteocalcin,Runx2,LC3B,Beclin1,and ATG5 were detected by real-time PCR. RESULTS AND CONCLUSION:(1)Stro-1 was positive,Vimentin was positive,and pan CK was negative in periodontal ligament stem cells.(2)At 3,7,and 14 days after osteogenic differentiation,compared with normal periodontal ligament stem cells,the mineralization nodules formed by periodontal ligament stem cells from inflammatory sources were significantly reduced(P<0.01);the expression of alkaline phosphatase protein and mRNA was significantly lower(P<0.05);the mRNA expression levels of bone sialoprotein,osteocalcin,and Runx2 were significantly decreased(P<0.05).(3)At 7 and 14 days after osteogenic differentiation,compared with normal periodontal ligament stem cells,the expression levels of ATG5,LC3B,and Beclin1 proteins and mRNA of periodontal ligament stem cells were downregulated(P<0.05).These findings suggest that inflammation reduces the activity of periodontal ligament stem cells in mineralizing nodule formation and the expression of alkaline phosphatase and weakens the autophagy potential of periodontal ligament stem cells at 7 and 14 days after osteogenic differentiation.

In recent years, the research on the microbial community within cancer has gradually attracted attention. The microbiota within the tumor affects the immune regulation of liver cancer and may promote the progression of liver cancer through inflammatory responses, metabolic regulation, etc. This article explores the sources and distribution characteristics of microorganisms in liver cancer, their potential mechanism of action in the occurrence and development of liver cancer, and evaluates the application prospects of intratumoral microorganisms in the early diagnosis, treatment response prediction and personalized treatment of liver cancer, especially their potential value in targeted therapy, providing new ideas for microbial intervention in future precision medicine.