High-performance liquid chromatography(HPLC) was used to determine the content of three major components in Citri Reticulatae Semen(CRS), including limonin, nomilin, and obacunone. The chromaticity of the CRS sample during salt processing and stir-frying was measured using a color difference meter. Next, the relationship between the color and content of the salt-processed CRS sample was investigated through correlation analysis. By integrating the oil bath technique for processing simulation with HPLC, the changes in the relative content of nomilin and its transformation products were analyzed, with its structural transformation pattern during processing identified. Additionally, RAW264.7 cells were induced with lipopolysaccharides(LPSs) to establish an inflammatory model, and the anti-inflammatory activity of nomilin and its transformation product, namely obacunone was evaluated. The results indicated that as processing progressed, E~*ab and L~* values showed a downward trend; a~* values exhibited a slow increase over a certain period, followed by no significant changes, and b~* values remained stable with no significant changes over a certain period and then started to decrease. The limonin content remained barely unchanged; the nomilin content decreased, and the obacunone increased significantly. The changing trends in content and color parameters during salt-processing and stir-frying were basically consistent. The content of nomilin and obacunone was significantly correlated with the colorimetric values(L~*, a~*, b~*, and E~*ab), while limonin content showed no significant correlation with these values. By analyzing HPLC patterns of nomylin at different heating temperatures and time, it was found that under conditions of 200-250 ℃ for heating of 5-60 min, the content of nomilin significantly decreased, while the obacunone content increased pronouncedly. The in vitro anti-inflammatory activity results indicated that compared to the model group, the group with a high concentration of nomilin and the groups with varying concentrations of obacunone showed significantly reduced release of nitric oxide(NO)(P<0.01). When both were at the same concentration, obacunone showed better performance in inhibiting NO release. In this study, the obvious correlation between the color and content of major components during the processing of CRS samples was identified, and the dynamic patterns of quality change in CRS samples during processing were revealed. Additionally, the study revealed and confirmed the transformation of nomilin into obacunone during processing, with the in vitro anti-inflammatory activity of obacunone significantly greater than that of nomilin. These findings provided a scientific basis for CRS processing optimization, tablet quality control, and its clinical application.
Mice ; Animals ; Drugs, Chinese Herbal/pharmacology* ; RAW 264.7 Cells ; Limonins/chemistry* ; Chromatography, High Pressure Liquid ; Citrus/chemistry* ; Color ; Benzoxepins/chemistry* ; Anti-Inflammatory Agents/chemistry*

Acute lung injury(ALI) is a critical clinical condition primarily characterized by refractory hypoxemia and infiltration of inflammatory cells in lung tissue, which can progress into a more severe form known as acute respiratory distress syndrome(ARDS). Immune cells and inflammatory cytokines play important roles in the progression of the disease. Due to its unclear pathogenesis and the lack of effective clinical treatments, ALI is associated with a high mortality rate and severely affects patients' quality of life, making the search for effective therapeutic agents particularly urgent. Ginseng Radix et Rhizoma, the dried root of the perennial herb Panax ginseng from the Araliaceae family, contains active ingredients such as saponins and polysaccharides, which possess various pharmacological effects including anti-tumor activity, immune regulation, and metabolic modulation. In recent years, studies have shown that ginsenosides exhibit notable effects in reducing inflammation, ameliorating epithelial and endothelial cell injury, and providing anticoagulant action, indicating their comprehensive role in alleviating lung injury. This review summarizes the pathogenesis of ALI and the molecular mechanisms through which ginsenosides act at different stages of ALI development. The aim is to provide a scientific reference for the development of ginsenoside-based drugs targeting ALI, as well as a theoretical basis for the clinical application of Ginseng Radix et Rhizoma in the treatment of ALI.
Ginsenosides/pharmacology* ; Humans ; Acute Lung Injury/immunology* ; Animals ; Panax/chemistry* ; Drugs, Chinese Herbal

Fritillariae Cirrhosae Bulbus is the dried bulb of perennial herbaceous plants in the Fritillaria genus(Liliaceae family) and is a representative traditional Chinese medicinal material with distinctive regional characteristics. Clinically, it is widely used in the treatment of dry cough, bronchial asthma, and other respiratory diseases, possessing significant medicinal and economic value and being highly esteemed in TCM. Currently, Fritillariae Cirrhosae Bulbus primarily relies on wild harvesting. However, due to excessive collection, its wild resources have drastically declined, and all source species have been classified as category Ⅱ in the List of National Key Protected Wild Plants, exacerbating the supply-demand imbalance in the market. To mitigate this issue, large-scale cultivation through the domestication of wild Fritillariae Cirrhosae Bulbus has become an inevitable trend. However, its strict environmental requirements, low propagation efficiency, high seedling mortality, and immature cultivation techniques have severely hindered industrialization. This study investigates the domestication process of Fritillariae Cirrhosae Bulbus, focusing on seed propagation, seedling cultivation, and medicinal material production. It also reviews the species and distribution of wild resources, their endangered status, market supply-demand dynamics, and the historical and current development of domestication. The findings indicate that enhancing propagation efficiency, optimizing cultivation models, and distinguishing between seed propagation and medicinal material production are key measures to accelerate the industrialization of domesticated Fritillariae Cirrhosae Bulbus. This research aims to promote the industrialization of Fritillariae Cirrhosae Bulbus domestication and provide a reference model for the conservation and sustainable utilization of rare and endangered medicinal plant resources.
Fritillaria/chemistry* ; Endangered Species ; Plants, Medicinal/growth & development* ; Drugs, Chinese Herbal/economics* ; China

OBJECTIVE: Astragali Radix (AR, Huangqi in Chinese) has been utilized generally as a bulk drug for the treatment of chronic atrophic gastritis (CAG) in China. The efficacy of wild-simulated AR (WAR) and transplanted AR (TAR) commercially available is unclear. This study aimed to further clarify the therapeutic action of WAR and TAR to treat CAG rats based on endogenous-xenobiotics metabolism. METHODS: Ultra-high performance liquid chromatography coupled with quadrupole-time of flight mass spectrometer (UHPLC-Q-TOF/MS) based metabolomics had been used to analyze the cecal contents metabolic features and metabolic process differences of two ARs in the treatment of CAG. RESULTS: Apparent pharmacodynamic indicator examination revealed that the WAR group had a more substantial curative effect. Metabolomics studies revealed that seven endogenous metabolites were significant differences in two ARs. Furthermore, following treatment, 77 and 65 xenobiotics metabolites were identified in the WAR and TAR groups, respectively. Finally, the most critical riboflavin metabolic route in the formation of CAG was chosen for molecular docking with the relevant exogenous components, and WAR scored higher than TAR. CONCLUSION In this work, we analyzed the efficacy differences of AR from diverse cultivation forms by combining metabolomics and medicinal chemistry technologies, and it gave a fresh perspective for TCM efficacy evaluation and quality control research.

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Metabolomics covers a wide range of applications in life sciences, biomedicine, and phytology. Data acquisition (to achieve high coverage and efficiency) and analysis (to pursue good classification) are two key segments involved in metabolomics workflows. Various chemometric approaches utilizing either pattern recognition or machine learning have been employed to separate different groups. However, insufficient feature extraction, inappropriate feature selection, overfitting, or underfitting lead to an insufficient capacity to discriminate plants that are often easily confused. Using two ginseng varieties, namely Panax japonicus (PJ) and Panax japonicus var. major (PJvm), containing the similar ginsenosides, we integrated pseudo-targeted metabolomics and deep neural network (DNN) modeling to achieve accurate species differentiation. A pseudo-targeted metabolomics approach was optimized through data acquisition mode, ion pairs generation, comparison between multiple reaction monitoring (MRM) and scheduled MRM (sMRM), and chromatographic elution gradient. In total, 1980 ion pairs were monitored within 23 min, allowing for the most comprehensive ginseng metabolome analysis. The established DNN model demonstrated excellent classification performance (in terms of accuracy, precision, recall, F1 score, area under the curve, and receiver operating characteristic (ROC)) using the entire metabolome data and feature-selection dataset, exhibiting superior advantages over random forest (RF), support vector machine (SVM), extreme gradient boosting (XGBoost), and multilayer perceptron (MLP). Moreover, DNNs were advantageous for automated feature learning, nonlinear modeling, adaptability, and generalization. This study confirmed practicality of the established strategy for efficient metabolomics data analysis and reliable classification performance even when using small-volume samples. This established approach holds promise for plant metabolomics and is not limited to ginseng.

The incomplete degradation of tumour cells by macrophages (Mϕ) is a contributing factor to tumour progression and metastasis, and the degradation function of Mϕ is mediated through phagosomes and lysosomes. In our preliminary experiments, we found that overactivation of NADPH oxidase 2 (NOX2) reduced the ability of Mϕ to degrade engulfed tumour cells. Above this, we screened out liquiritin from Glycyrrhiza uralensis Fisch, which can significantly inhibit NOX2 activity and inhibit tumours, to elucidate that suppressing NOX2 can enhance the ability of Mϕ to degrade tumour cells. We found that the tumour environment could activate the NOX2 activity in Mϕ phagosomes, causing Mϕ to produce excessive reactive oxygen species (ROS), thus prohibiting the formation of phagolysosomes before degradation. Conversely, inhibiting NOX2 in Mϕ by liquiritin can reduce ROS and promote phagosome-lysosome fusion, therefore improving the enzymatic degradation of tumour cells after phagocytosis, and subsequently promote T cell activity by presenting antigens. We further confirmed that liquiritin down-regulated the expression of the NOX2 specific membrane component protein gp91 phox, blocking its binding to the NOX2 cytoplasmic component proteins p67 phox and p47 phox, thereby inhibiting the activity of NOX2. This study elucidates the specific mechanism by which Mϕ cannot degrade tumour cells after phagocytosis, and indicates that liquiritin can promote the ability of Mϕ to degrade tumour cells by suppressing NOX2.

ObjectiveTo explore the effect of a novel initiation model on initiating behavioral requests in children with autism spectrum disorder (ASD). MethodsFrom November to December, 2022, 44 children with ASD were selected from Jiaxing Sunlight Rehabilitation Kindergarten, and divided into prelinguistic group (n = 23) and linguistic group (n = 21) according to the language function. The initiation-requested skills, and types and frequency of initiation-requested behaviors were observed under the novel initiation model and the conventional initiation model. ResultsBoth the groups scored higher in the novel initiation model than in the conventional initiation model for initiation-requested skills (|t| > 2.794, P < 0.05) and types of initiation-requested behaviors (|t| > 3.697, P < 0.01), and it increased for the frequency of the use of two- and three-behavioral initiation of requests (χ² > 7.986, P < 0.05). ConclusionThe novel initiation model can improve initiation request skills in children with ASD.

BACKGROUND:Ossification of the ligamentum flavum was previously considered to be rare in the population.As research has progressed,its incidence rate is increasing gradually,which has aroused the interest of a large number of researchers. OBJECTIVE:To visualize and analyze the research results on ossification of the ligamentum flavum from the Web of Science Core Collection since 1999 using bibliometric methods,and to review the research history of ossification of the ligamentum flavum,highlighting important literature,summarizing research hotspots,and providing ideas for researchers to find research directions. METHODS:Using the Web of Science Core Collection as the data source,relevant papers on ossification of the ligamentum flavum were searched and screened.VOSviewer 1.6.19 and CiteSpace 6.2.R6 were used to conduct the visual analysis of annual publication volume,research countries,institutions,citations,journals,authors,and keywords. RESULTS AND CONCLUSION:(1)A total of 347 papers were included.Since 1999,the number of published papers has increased in a spiral pattern.China's research started later than Japan's,but the number of publications has come up later,with Peking University being the institution with the most publications,and Prof.Chen Zhongqiang from Peking University being the scholar with the most publications.(2)Five of the 10 most frequently cited publications were related to the surgical treatment of the disease.(3)Excluding keywords directly related to the research topic and synthetically analyzing frequencies and betweenness centralities of key words,terms such as"thoracic myelopathy,""dural ossification,""minimally invasive surgery,"and"ossification of the posterior longitudinal ligament"occupied a central position in this field.(4)Keywords clustering analysis showed that clinical manifestations and surgical treatment of ossification of the ligamentum flavum accounted for a large proportion of study.(5)The timeline and burst analysis of keywords revealed that"minimally invasive surgery"appeared as a keyword around 2015,with the highest burst strength and the latest burst start time,and began to receive extensive attention from researchers in 2019.The burst of the keyword"dural ossification"has not yet ended.(6)Surgical treatment for ossification of the ligamentum flavum has been at the forefront of research.Development and research of minimally invasive surgery and research on dural ossification secondary to ossification of the ligamentum flavum are both current research hotspots and possible future research trends.

Objective: To investigate the epidemiological characteristics of human brucellosis in Jiande City, Zhejiang Province from 2005 to 2024, so as to provide the evidence for strengthening the prevention and control of brucellosis. Methods: Data on brucellosis cases and surveillance in Jiande City from 2005 to 2024 were collected through the Chinese Disease Prevention and Control Information System, the annual brucellosis surveillance reports from the Jiande Center for Disease Control and Prevention, and the annual summaries of brucellosis prevention and control efforts. The epidemiological characteristics of human brucellosis were analyzed using a descriptive epidemiological method. Results: A total of 1 125 individuals were monitored in Jiande City from 2005 to 2024, with 18 seropositive cases identified and the seropositivity rate of 1.60%. The average annual seropositivity rate from 2015 to 2024 was 3.35%, which was significantly higher than that of 0.57% from 2005 to 2014 (P<0.05). There were 10 confirmed brucellosis cases and 8 asymptomatic infections, with no reported deaths. The peak incidence occurred between March and August. Among the 16 towns (streets) in Jiande City, 8 reported brucellosis cases. Of the brucellosis cases, 14 were male and 4 were female, with a male-to-female ratio of 3.5∶1. The majority of cases (13 cases) were aged between 40 and 60 years. Occupational exposure was identified in 16 cases, all of whom were infected through direct hand contact with the excreta, secretions, or animal products of infected sheep or cattle. The primary source of infection was sheep, followed by cattle. Five strains of Brucella were isolated and cultured, all identified as Brucella melitensis biovar 3. Conclusions The brucellosis epidemic in Jiande City remained at a sporadic and low prevalence level from 2005 to 2024, with an increasing trend observed from 2015 to 2024. Male occupational groups aged 40 to 60 years were the key population for brucellosis prevention and control, and sheep were the primary source of infection.