[This corrects the article DOI: 10.1016/j.apsb.2018.08.009.].

OBJECTIVES: To explore the therapeutic mechanism of compound Centella asiatica formula (CCA) for alleviating Schistosoma japonicum (Sj)-induced liver fibrosis in mice. METHODS: The active components and targets of CCA were identified using the TCMSP database with cross-analysis of Sj-related liver fibrosis targets. A "drug-component-target-pathway-disease" network was constructed using Cytoscape 3.9.1. Functional enrichment analysis (GO/KEGG) was performed using DAVID. Molecular docking study was carried out to validate interactions between the core targets and the key compounds. For experimental validation of the results, 36 mice were divided into control group, Sj-infected model group, and CCA-treated groups. In the latter two groups, liver fibrosis was induced via abdominal infection with Sj cercariae for 8 weeks, followed by 8 weeks of daily treatment with CCA decoction or saline. Hepatic pathology of the mice was assessedwith HE and Masson staining, and hepatic expressions of collagen-I and collagen-III were detected using immunohistochemistry; serum IL-6 and TNF-α levels were determined with ELISA. Hepatic expressions of TLR4 and MyD88 proteins were analyzed with Western blotting. RESULTS: We identified a total of 107 bioactive CCA components and 791 targets, including 37 intersection targets linked to Sj-induced fibrosis. The core targets included TNF, TP53, JUN, MMP9, and CXCL8, involving the IL-17 signaling, lipid metabolism, TLR4/MyD88 axis, and cancer pathways. Molecular docking study confirmed strong binding affinity between quercetin (a primary CCA component) and TNF/TP53/JUN/MMP9. In Sj-infected mouse models, CCA treatment significantly attenuated hepatic inflammatory cell infiltration, reduced collagen-I and collagen-III deposition, improved tissue architecture, reduced serum IL-6 and TNF-α levels, and downregulated TLR4 and MyD88 expressions in the liver. CONCLUSIONS CCA mitigates Sj-induced liver fibrosis by targeting TNF, TP53, JUN, and MMP9 to modulate the TLR4/MyD88 pathway, thereby suppressing pro-inflammatory cytokine release, inhibiting hepatic stellate cell activation, reducing collagen deposition, and preventing granuloma formation in the liver.
Animals ; Toll-Like Receptor 4/metabolism* ; Mice ; Myeloid Differentiation Factor 88/metabolism* ; Schistosoma japonicum ; Liver Cirrhosis/parasitology* ; Schistosomiasis japonica ; Signal Transduction ; Molecular Docking Simulation ; Inflammation ; Centella/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Tumor Necrosis Factor-alpha/metabolism*

Tumor cell-intrinsic programmed death-ligand 1 (PD-L1) signals mediate tumor initiation, progression and metastasis, but their effects in ameloblastoma (AM) have not been reported. In this comprehensive study, we observed marked upregulation of PD-L1 in AM tissues and revealed the robust correlation between elevated PD-L1 expression and increased tumor growth and recurrence rates. Notably, we found that PD-L1 overexpression markedly increased self-renewal capacity and promoted tumorigenic processes and invasion in hTERT⁺-AM cells, whereas genetic ablation of PD-L1 exerted opposing inhibitory effects. By performing high-resolution single-cell profiling and thorough immunohistochemical analyses in AM patients, we delineated the intricate cellular landscape and elucidated the mechanisms underlying the aggressive phenotype and unfavorable prognosis of these tumors. Our findings revealed that hTERT⁺-AM cells with upregulated PD-L1 expression exhibit increased proliferative potential and stem-like attributes and undergo partial epithelial‒mesenchymal transition. This phenotypic shift is induced by the activation of the PI3K-AKT-mTOR signaling axis; thus, this study revealed a crucial regulatory mechanism that fuels tumor growth and recurrence. Importantly, targeted inhibition of the PD-L1-PI3K-AKT-mTOR signaling axis significantly suppressed the growth of AM patient-derived tumor organoids, highlighting the potential of PD-L1 blockade as a promising therapeutic approach for AM.
Ameloblastoma/metabolism* ; Humans ; B7-H1 Antigen/metabolism* ; Neoplasm Recurrence, Local/pathology* ; Signal Transduction ; Cell Proliferation ; Up-Regulation ; TOR Serine-Threonine Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Telomerase/metabolism* ; Jaw Neoplasms/metabolism* ; Epithelial-Mesenchymal Transition ; Animals ; Cell Line, Tumor ; Female ; Male

Objective:To investigate the relationship among iron content, volume and drainage venous oxygen saturation (SvO 2) in deep gray matter nuclei of healthy people using quantitative susceptibility mapping (QSM). Methods:The study was a cross-sectional study. A total of 126 healthy volunteers were prospectively enrolled in the community in Tianjin from June 2019 to December 2023, and 57 males and 69 females, aged 48±15 years. All healthy volunteers underwent MRI examinations to get STrategically Acquired Gradient Echo images, then it was post-processed to obtain T 1 weighted enhanced images, QSM maps and the maximum intensity projection images. In QSM maps, caudate nucleus (CN), putamen (PUT), globus pallidus (GP), thalamus (THU), subthalamic nucleus (STN), substantia nigra (SN) and red nucleus (RN) were semi-automatically segmented to calculate the iron content and volume using SPIN software. Four bilateral deep cerebral veins regions of interest, including septum pellucidum veins, thalamostriate veins, internal cerebral veins and basilar veins, were manually delineated on the maximum intensity projection images of QSM to obtain venous magnetic sensitivity. The venous magnetic sensitivity was calculated as SvO 2. To observe the age-related trend of SvO 2, iron content and volume, the partial correlation analysis was conducted. The relationships between iron content, volume and SvO 2 were explored using the partial correlation analysis. To explore the potential effects of SvO 2 between iron content and volume in deep gray matter, the mediation analysis was utilized. Results:The relationships between the SvO 2 of thalamostriate veins ( r=0.23, P=0.018), basilar veins ( r=0.27, P=0.004) and age were positive. The relationships between the SvO 2 of internal cerebral veins and the iron contents of CN ( r=?0.25, P=0.042) and PUT ( r=?0.33, P<0.001) were negative. The relationships between the SvO 2 of basilar veins and the iron contents of STN ( r=?0.25, P=0.042) and SN ( r=?0.24, P=0.045) were negative. The relationships between iron content and volume including CN ( r=0.46, P<0.001), PUT ( r=0.20, P=0.027), GP ( r=0.76, P<0.001), STN ( r=0.87, P<0.001), SN ( r=0.90, P<0.001), RN ( r=0.79, P<0.001) were positive. The mediation analysis showed that the SvO 2 of internal cerebral veins indirectly mediated the relationship between iron content and volume of CN, PUT, GP and THU. Conclusions:The process of iron deposition required the participation of oxygen in deep gray matter nuclei. Volume shows positive correlation with iron content in deep gray matter nuclei, with individual variations. The SvO 2 of internal cerebral veins mediate the relationship between iron content and volume of deep gray matter nuclei.

Objective:To investigate the influence of prealbumin on cerebral infarction severity, hemorrhage transformation and 1-year prognosis.Methods:A retrospective study was conducted to select 752 patients with cerebral infarction who were treated in Beijing Tiantan Hospital,Capital Medical University from December 2018 to December 2019 as the study objects. Personal information and laboratory indicators of the patients were collected including prealbumin, hemoglobin, white blood cell count, etc.Patients were divided into group B1 (<238 mg/L) and group B2 (≥238 mg/L) based on median prealbumin. By inquiry patient's case, NIHSS score (<16 was classified as mild, ≥16 as moderate and severe)and cerebral infarction volume (<20 cm 3 as small infarct, >20 cm 3 as large infarct) were recorded to evaluate the severity of the disease, and whether hemorrhage transformation occurred during hospitalization was recorded. Patients were followed up 1 year after discharge, and prognostic information of patients was recorded, including neurological function recovery (mRS score <3 was classified as good recovery, ≥3 as poor recovery),all-cause case fatality rate, and recurrence of cardio-cerebrovascular events. Normally distributed measurement data were expressed as xˉ±s, non-normally distributed measurement data were expressed as median and quartiles[ M( Q1, Q3)], categorical variable were expressed as ratio and percent(%). Comparison between groups of measurement data were performed by independent sample t test and Mann-Whitney U test. Chi-square test were used on comparison between groups of categorical variable. Single-factor comparison, Spearman correlation analysis and multiple Logistic regression were used to analyze the correlation between prealbumin and other laboratory indicators, cerebral infarction severity, hemorrhage transformation and 1-year prognosis, respectively. Results:The NIHSS score and infarct volume of patients in group B1 were 5(2,10) and 3.18(0.72,18.00) cm 3, and those in group B2 were 3(2,7) and 2.0(0.5,10.0) cm 3, respectively, which were higher in group B1 than in group B2, the differences were statistically significant ( Z=3.85, P<0.001, Z=2.81, P=0.005). The proportion of mRS Score ≥3 in group B1 was 28.8%(107/371), and the all-cause case fatality rate was 7.5%(28/371), both higher than 20.5%(78/381) and 3.1%(12/381) in group B2, with statistical significance ( χ2=7.10, P=0.008, χ2=7.22, P=0.007). Hemorrhage transformation and recurrence of cardio-cerebrovascular events were 13.5%(50/371) and 11.6%(43/371) in group B1 and 9.2% (35/381) and 8.7%(33/381) in group B2, respectively, with no significant difference between the two groups ( χ2=3.45, P=0.063, χ2=1.78, P=0.183). Multivariate logistic regression analysis showed that, after adjusted for potential confounding factors, prealbumin was protective factor of NIHSS ( OR and 95% CI: 0.990(0.984-0.997), P=0.035), poor neurological recovery(mRS≥3) ( OR and 95% CI:0.992(0.988-0.997), P<0.001) and all-cause case fatality rate ( OR and 95% CI:0.991(0.983-0.999), while prealbumin had no significant influence on cardiocerebrovascular recurrence events ( OR and 95% CI: 0.999(0.993-1.005), P=0.729). Conclusion:Prealbumin is significantly associated with the severity of cerebral infarction and poor prognosis 1 year after discharge, and low prealbumin was an independent risk factor for NIHSS score(≥16), poor neurological recovery (mRS≥3) and all-cause case fatality rate.

Objectives:To explore the effects of infarct volume, infarct type, inflammation, and coagulation indicators on hemorrhagic transformation in patients with acute cerebral infarction.Methods:711 patients with cerebral infarction admitted to Beijing Tiantan Hospital were retrospectively included as the study objects from December 2018 to December 2019 [535 males and 176 females, age 22-95 years, mean age (59.6±12.1) years]. Clinical data, laboratory indicators such as inflammation and coagulation function of patients were collected, and information such as location, volume and type of infarction were recorded. The patients were divided into hemorrhage transformation group and non-hemorrhage transformation group according to whether hemorrhage transformation occurred during hospitalization. Normally distributed measurement data were expressed as xˉ± s, non-normally distributed measurement data were expressed as median and quartiles [ M( Q1, Q3)], categorical variable were expressed as ratio and percent (%). Comparison between groups of measurement data were performed by independent sample t test and Mann-Whitney U test. χ2 test were used on comparison between groups of categorical variable. Univariate comparison and multivariate Logistic regression were used to analyze the correlation between hemorrhage transformation and infarct volume, infarction type and laboratory indicators, respectively, to explore the risk factors of hemorrhage transformation. ROC curve analysis was used to evaluate the diagnostic value of indicators. Results:The rates of coronary heart disease and atrial fibrillation history in the hemorrhage transformation group were 23.5% (20/85) and 22.4% (19/85), respectively, which were significantly higher than those in the non-hemorrhage transformation group (13.9% (87/626) and 5.8% (36/626), respectively), and the difference between the two groups was statistically significant ( χ2=5.43, χ2=28.90, P=0.020, P<0.001, respectively). The NIHSS score [10(4,17) points] and infarct volume [46.50 (14.21,118.42) mL] in the hemorrhage transformation group were significantly higher than those in the non-hemorrhage transformation group [4(2,7) points, 2.00(0.51,8.94) mL]. The difference between the two groups was statistically significant ( Z values were 6.69 and 10.69, respectively, P<0.001). The results of multivariate Logistic regression analysis showed that atrial fibrillation (OR=2.604, 95% CI: 1.186-5.716, P=0.107), infarct volume (OR=1.009, 95% CI: 1.004-1.015, P=0.001), infarct type of Chinese ischemic stroke subclassfication (OR=1.371, 95% CI: 1.085-1.731, P=0.008) and neutrophil/lymphocyte ratio (OR=1.047, 95% CI: 1.006-1.090, P=0.023) were independent risk factors for hemorrhage transformation. ROC curve analysis showed that the area under curve (AUC) of infarct volume and neutrophil/lymphocyte ratio were 0.861 (0.821-0.901) and 0.684 (0.626-0.741), respectively, which were effective in predicting hemorrhage transformation after cerebral infarction. The prediction of infarct volume was more efficient. Conclusion:History of atrial fibrillation, classification of cardioembolic stroke, infarct volume, and neutrophil/lymphocyte ratio are all risk factors for hemorrhagic transformation after acute cerebral infarction.

BACKGROUND:Leonurine has many biological activities such as improving microcirculation,anti-oxidation,anti-apoptosis,scavenging free radicals,anti-inflammation,and anti-fibrosis,and can promote osteogenic differentiation of bone marrow mesenchymal stem cells,which has the potential to be applied in the treatment of periodontitis. OBJECTIVE:To explore the anti-inflammatory and osteogenic effects of leonurine loading into chitosan/sodium glycerophosphate/sodium alginate hydrogel. METHODS:(1)Chitosan/sodium glycerophosphate/sodium alginate hydrogel(blank hydrogel)and chitosan/sodium glycerophosphate/sodium alginate/leonurus alkali hydrogel were prepared respectively.RAW 264.7 and MC3T3-E1 cells were inoculated with the two kinds of hydrogel.The cytotoxicity of hydrogels was detected by CCK-8 assay and live/dead cell staining.(2)RAW 264.7 cells were cultured in five groups.The blank group was cultured for 24 hours routinely.The lipopolysaccharide group was treated with lipopolysaccharide.The simple hydrogel group was treated with lipopolysaccharide and blank hydrogel.The drug-loaded hydrogel group was treated with lipopolysaccharide and drug-loaded hydrogel.The inhibitor group was treated with lippolysaccharide,drug-loaded hydrogel,and PI3K inhibitor LY294002.24 hours later,mRNA expression of inflammation-related factors was detected by qRT-PCR.Western blot assay was utilized to detect the protein expression of inflammation-related factors and PI3K/AKT signaling pathway.(3)MC3T3-E1 cells were inoculated in four groups.The blank group was cultured without any material.The simple hydrogel group was treated with blank hydrogel.The drug-loaded hydrogel group was treated with drug-loaded hydrogel.The inhibitor group was treated with drug-loaded hydrogel and PI3K inhibitor LY294002 for 7 days.Alkaline phosphatase staining was performed.mRNA expression levels of osteogenic factors were detected by qRT-PCR.The protein expression levels of the PI3K/AKT signaling pathway were detected by western blot assay. RESULTS AND CONCLUSION:(1)The results of CCK-8 assay and live/dead cell staining showed that the two kinds of hydrogels had no cytotoxic effect and had good cytocompatibility.(2)Compared with the blank group,the mRNA and protein expression levels of interleukin 6,tumor necrosis factor α,and interleukin 1β were significantly increased(P<0.05),and the protein expression levels of p-AKT,p-PI3K,p-p65,and p-IκBα were significantly increased in the lipopolysaccharide group(P<0.05).Compared with lipopolysaccharide group,mRNA and protein expression levels of the above indexes were decreased in drug-loaded hydrogel group(P<0.05).Compared with the drug-loaded hydrogel group,the mRNA and protein expression levels of the above indexes were decreased in the inhibitor group(P<0.05).(3)The activity of alkaline phosphatase in drug-loaded hydrogel group was higher than that in the blank group,simple hydrogel group,and inhibitor group(P<0.05).Compared with blank group,the mRNA expression levels of alkaline phosphatase,Runx2,osteocalcin,and type I collagen were increased(P<0.05),and the protein expression levels of p-AKT and p-PI3K were increased in the simple hydrogel group(P<0.05).Compared with the simple hydrogel group,the mRNA and protein expression levels of the above indexes were increased in the drug-loaded hydrogel group(P<0.05).Compared with the drug-loaded hydrogel group,the mRNA and protein expression levels of the above indexes were decreased in the inhibitor group(P<0.05).(4)These findings conclude that chitosan/sodium glycerophosphate/sodium alginate/leonurine hydrogel has anti-inflammatory and osteogenic effects,which may be related to the regulation of PI3K/AKT signaling pathway.

ObjectiveA qualitative analysis method was established for the composition of Astragali Radix（AR） before and after rice stir-frying. On the basis of systematic characterization of the chemical compositions in AR and stir-fried AR with rice（ARR）， the structures of their major compounds were deduced and identified， and the differential compositions between them were analyzed. MethodsUltra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was used to detect the samples of AR and ARR in positive and negative ion modes， respectively. The compounds were analyzed and identified through self-constructed databases， literature， and reference standards， etc. And the data were analyzed by chemometrics， in order to screen for the differential components between AR and ARR. ResultsA total of 123 compounds were identified in AR and ARR， including 41 flavonoids， 19 terpenoids， 26 organic acids， 8 amino acids， 5 nucleotides， 5 carbohydrates and 19 other compounds. Among them， there were 95 common components in both， 18 unique components in AR， and 10 unique components in ARR. Principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） results both showed that there were significant differences in the chemical constituents of AR before and after rice stir-frying， and a total of 26 constituents with differences in the content were screened out， including L-canavanine， L-pyroglutamic acid， L-phenylalanine， cis-caffeic acid， and malonylastragaloside Ⅰ. Among them， 19 constituents of ARR were down-regulated and 7 constituents were up-regulated by comparing with AR. ConclusionThis study clarifies that the chemical composition of AR and ARR is mainly composed of flavonoids， terpenoids， and organic acids， and analyzes the components with significant differences in content between the two in combination with chemometrics， and the differential components are dominated by amino acids， organic acids and terpenoids， which can provide reference for the subsequent quality control and material basis research.

Inflammatory bowel disease (IBD) is a chronic, relapsing intestinal disorder driven by multiple factors including genetics, immunity, and environment, and is clinically classified into ulcerative colitis and Crohn's disease. Currently, mice and zebrafish are the primary experimental animals used in IBD research, among which zebrafish have emerged as an ideal model due to their unique advantages. Compared with rodent models, zebrafish serve as an effective and convenient model, offering advantages such as a short life cycle, robust reproductive capacity, small size, and transparent embryos. These characteristics make zebrafish highly suitable for dynamic tracking of continuous pathological progression and high-throughput drug screening. Zebrafish share over 70% genetic homology with humans, and their intestinal cellular composition and ontogeny closely resemble those of humans. Moreover, the structure and characteristics of their gut microbiota are similar to the human intestinal microbiome, providing a solid foundation for studying the relationship between gut microbiota and IBD. With advances in biotechnology, zebrafish IBD models generated by chemical induction or genetic engineering can accurately simulate the core pathological features of human IBD, such as intestinal wall thickening, inflammatory cell infiltration, and elevated expression of pro-inflammatory factors. These models have played a significant role in revealing the pathogenesis of IBD as well as the development of targeted therapeutic drugs. This article first outlines the intestinal characteristics of zebrafish and features of zebrafish IBD models, then provides an in-depth analysis of their application in IBD pathogenesis research from multiple aspects, including genetics, immunity, environment and diet, and infection. It also reviews research progress on the application of zebrafish in the development of anti-inflammatory drugs, probiotics, and traditional Chinese medicine therapies, aiming to provide researchers with references for the rational use of zebrafish models at all stages of preclinical research, to advance fundamental IBD research and accelerate breakthroughs in this field.

Large language models (LLMs) such as ChatGPT, Claude, Llama, and Qwen are emerging as transformative technologies for the diagnosis and treatment of various diseases. With their exceptional long-context reasoning capabilities, LLMs are proficient in clinically relevant tasks, particularly in medical text analysis and interactive dialogue. They can enhance diagnostic accuracy by processing vast amounts of patient data and medical literature and have demonstrated their utility in diagnosing common diseases and facilitating the identification of rare diseases by recognizing subtle patterns in symptoms and test results. Building on their image-recognition abilities, multimodal LLMs (MLLMs) show promising potential for diagnosis based on radiography, chest computed tomography (CT), electrocardiography (ECG), and common pathological images. These models can also assist in treatment planning by suggesting evidence-based interventions and improving clinical decision support systems through integrated analysis of patient records. Despite these promising developments, significant challenges persist regarding the use of LLMs in medicine, including concerns regarding algorithmic bias, the potential for hallucinations, and the need for rigorous clinical validation. Ethical considerations also underscore the importance of maintaining the function of supervision in clinical practice. This paper highlights the rapid advancements in research on the diagnostic and therapeutic applications of LLMs across different medical disciplines and emphasizes the importance of policymaking, ethical supervision, and multidisciplinary collaboration in promoting more effective and safer clinical applications of LLMs. Future directions include the integration of proprietary clinical knowledge, the investigation of open-source and customized models, and the evaluation of real-time effects in clinical diagnosis and treatment practices.
Humans ; Large Language Models ; Tomography, X-Ray Computed