OBJECTIVE To compare the anti-hepatitis mechanisms of Abrus pulchellus subsp. cantoniensis （Hance） Verdc. （AC） and Abrus pulchellus subsp. mollis（Hance） Verdc. （AM）. METHODS SD rats were randomly divided into blank group， AC- treated group， and AM-treated group， with each group consisting of 10 rats. The rats’ orbital venous blood was collected at 5， 15， 30 minutes， and 1， 1.5， 2， 4， 6， 8， 12 hours after gavage administration of 24 g/kg of the corresponding drug （calculated by crude drug） or water， respectively. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry technology was utilized to identify the prototype components present in the serum. The network pharmacology method was adopted to predict the anti-hepatitis active components， key targets， and signaling pathways of AC and AM. Additionally， molecular docking technology was utilized to verify the binding activity of the core active components with key targets. RESULTS A total of 35 prototype components migrating to the blood of AC and AM were identified in the serum of administered rats， among which 24 were common components. The active components in AC， such as acetylanguidine， physcion， soyasaponin A3 and soyasaponin Ⅰ， as well as those in AM， including vicenin 3， acetylanguidine，soyasaponin Ⅰ and schaftoside， all acted on key targets such as steroid receptor coactivator， phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit alpha， epidermal growth factor receptor （EGFR）， and protein kinase B1（Akt1）. These components modulated pathways in cancer， EGFR tyrosine kinase inhibitor resistance， and the phosphoinositide 3-kinase （PI3K） -Akt pathway， thereby exerting anti-hepatitis effects. Furthermore， the binding energies between these active components and their key targets were all less than －5 kJ/mol. CONCLUSIONS There are differences in the active components of AC and AM against hepatitis， but their mechanisms of action are similar. Both may exert their anti-hepatitis effects through pathways in cancer， EGFR tyrosine kinase inhibitor resistance， and the PI3K-Akt pathway.

Stem-leaf saponins from Panax notoginseng (SLSP) comprise numerous PPD-type saponins with diverse pharmacological properties; however, their role in Parkinson's disease (PD), characterized by microglia-mediated neuroinflammation, remains unclear. This study evaluated the effects of SLSP on suppressing microglia-driven neuroinflammation in experimental PD models, including the 1-methyl-4-phenylpyridinium (MPTP)-induced mouse model and lipopolysaccharide (LPS)-stimulated BV-2 microglia. Our findings revealed that SLSP mitigated behavioral impairments and excessive microglial activation in models of PD, including MPTP-treated mice. Additionally, SLSP inhibited the upregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) and attenuated the phosphorylation of PI3K, protein kinase B (AKT), nuclear factor-κB (NFκB), and inhibitor of NFκB protein α (IκBα) both in vivo and in vitro. Moreover, SLSP suppressed the production of inflammatory markers such as interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α) in LPS-stimulated BV-2 cells. Notably, the P2Y2R agonist partially reversed the inhibitory effects of SLSP in LPS-treated BV-2 cells. These results suggest that SLSP inhibit microglia-mediated neuroinflammation in experimental PD models, likely through the P2Y2R/PI3K/AKT/NFκB signaling pathway. These novel findings indicate that SLSP may offer therapeutic potential for PD by attenuating microglia-mediated neuroinflammation.
Animals ; Panax notoginseng/chemistry* ; Saponins/pharmacology* ; Microglia/immunology* ; Mice ; NF-kappa B/immunology* ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/immunology* ; Phosphatidylinositol 3-Kinases/genetics* ; Male ; Parkinson Disease/immunology* ; Mice, Inbred C57BL ; Disease Models, Animal ; Plant Leaves/chemistry* ; Neuroinflammatory Diseases/drug therapy* ; Humans

Aconitum (Ranunculaceae) has a long-standing history in traditional Chinese medicine (TCM), where it has been widely used to treat conditions such as rheumatoid arthritis (RA), myocardial infarction, and heart failure. However, the potency of Aconitum alkaloids, the primary active components of Aconitum, also confers substantial toxicity. Therefore, assessing the efficacy and toxicity of these Aconitum alkaloids is crucial for ensuring clinical effectiveness and safety. Metabolomics, a quantitative method for analyzing low-molecular-weight metabolites involved in metabolic pathways, provides a comprehensive view of the metabolic state across multiple systems in vivo. This approach has become a vital investigative tool for facilitating the evaluation of their efficacy and toxicity, identifying potential sensitive biomarkers, and offering a promising avenue for elucidating the pharmacological and toxicological mechanisms underlying TCM. This review focuses on the applications of metabolomics in pharmacological and toxicological studies of Aconitum alkaloids in recent years and highlights the significant role of metabolomics in exploring compatibility detoxification and the mechanisms of TCM processing, aiming to identify more viable methods for characterizing toxic medicinal plants.
Aconitum/metabolism* ; Metabolomics/methods* ; Alkaloids/metabolism* ; Humans ; Animals ; Drugs, Chinese Herbal/pharmacology* ; Medicine, Chinese Traditional

ObjectiveTo study the effect and mechanism of Curculiginis Rhizoma in ameliorating kidney-Yang deficiency in castrated rats. MethodThe targets of Curculiginis Rhizoma and male reproductive diseases due to kidney-Yang deficiency were screened from relevant databases by network pharmacology， and key targets were screened out according to topological eigenvalues. After that， gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses were performed to obtain the pathways of Curculiginis Rhizoma in treating kidney-Yang deficiency. The rat model of kidney-Yang deficiency was established by castration. The rats were assigned into model， testosterone propinate （2 mg·kg^-1）， and low-， medium-， high-dose （0.14， 0.28， 0.56 g·kg^-1， respectively） Curculiginis Rhizoma groups. Another 8 healthy male rats with first incising and then suturing were used as the sham group. The rats were administrated with corresponding agents by gavage once a day for 6 consecutive weeks. During the experiment， the general conditions of rats in each group were observed， and their body mass was recorded. At the end of the experiment， the indexes of accessory sex organs were calculated， and the pathological changes of the seminal vesicle glands and prostate glands were observed by hematoxylin-eosin （HE） staining. The serum levels of luteinizing hormone （LH）， follicle-stimulating hormone （FSH）， testosterone （T）， and interleukin-6 （IL-6） were determined by enzyme-linked immunosorbent assay. The results of the network pharmacological prediction were verified by animal experiments， and the expression levels of related genes and proteins were determined by real-time polymerase chain reaction and Western blot， respectively. ResultThe biological functions enriched mainly involved four overexpression modules including regulation of cell responses to various stimuli， metabolic responses， regulation of intracellular signal transduction， and regulation of reproduction. Phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway was a significantly enriched pathway for the core target and also a pathway with the highest enrichment factor in the biological process of regulating cell responses to stimuli. The results of animal experiments showed that compared with the model group， low-dose Curculiginis Rhizoma group increased the body weight gain （P<0.05）. In addition， high-dose Curculiginis Rhizoma group increased the seminal vesicle gland index and epididymis index （P<0.05）. The administration with Curculiginis Rhizoma ameliorate epithelial cell hyperplasia of the seminal vesicle glands， did not attenuate the vacuolar degeneration， mitigated the enlarged vesicular lumen of the prostate gland， changing of epithelial cells of the glands from flattened to cubic and columnar shapes， and cellular disarrangement， and reduced the mesenchymal stroma thickness. Compared with the model group， all the intervention measures elevated the levels of FSH， LH， T， and IL-6 （P<0.05， P<0.01） and up-regulated the mRNA and protein levels of PI3K and the mRNA levels of Akt in the epididymis tissue （P<0.05）. ConclusionCurculiginis Rhizoma can alleviate the T level reduction and accessory sex organ atrophy in castrated rats by regulating the PI3K/Akt signaling pathway.

Objective To estimate the flexion and extension torques of the hip,knee,and ankle joints during straight-line walking using depth cameras and neural networks.Methods Gait information was collected from 20 individuals using an optical motion capture system,force plates,and an Azure Kinect depth camera.The subjects were asked to walk straight at their preferred speed while stepping on the force plates.The joint torques were obtained using visual 3D simulation as a reference value,and an artificial neural network(ANN)and long short-term memory(LSTM)network were trained to estimate the joint torques.Results The relative root mean square errors(rRMSEs)of the ANN model for estimating the joint torques of hip,knee,and ankle were 15.87％-17.32％,18.36％-25.34％,and 14.11％-16.82％,respectively,and the correlation coefficients were 0.81-0.85,0.69-0.74 and 0.76-0.82,respectively.The LSTM model had a better estimation effect,with rRMSEs of 8.53％-12.18％,14.32％-18.78％,and 6.51％-11.83％,and correlation coefficients of 0.89-0.95,0.85-0.91 and 0.90-0.97,respectively.Conclusions This study confirms the feasibility of using a depth camera and neural network for noncontact estimation of lower limb joint torques,and LSTM has a better performance.Compared with existing studies,the joint torque estimation results have better accuracy,and the potential application scenarios include telemedicine,personalized rehabilitation program development,and orthosis-assisted design.

Objective:To understand the current state of ethical competence levels of nurses and analyse the factors that influence them, in order to inform the development of targeted training programmes.Methods:This study adopted a cross-sectional survey method and used convenience sampling to select 825 clinical nurses from Tianjin Chest Hospital as the survey objects from July to August, 2023, and a questionnaire survey was conducted using the General Information Questionnaire, the Ethical Competence Scale, Ethical Competence Support Scale, and Ethical Safety Scale.Results:A total of 818 valid questionnaires were retracted. Among the 818 nurses, 48 were males and 770 were females, the age was (33.19 ± 7.40) years. The total score of nurses ′ Ethical Competence, Ethical Competence Support and Ethical Safety were (118.08 ± 19.96), (215.07 ± 32.02), (48.93 ± 7.55) points, all of which were at a high level. The total score of nurses ′ ethical competence were positively correlated with ethical competence support and ethical safety ( r=0.856, 0.830, both P<0.01); multivariate linear regression analysis showed that the department, the level of ethical competence support, and the level of ethical safety were the influencing factors of the level of ethical competence ( t=5.19, 12.35, 3.88, all P<0.01). Conclusions:Nurses ′ ethical competence, ethical competence support, and ethical safety were at a high level, and the department, the level of ethical competence support, and the level of ethical safety were the factors influencing the level of ethical competence. Nursing managers can provide more ethical education and address ethical issues in multiprofessional discussions, strengthen organizational and personal support for nurses ′ ethical competence, improve nurses ′ ethical safety, and help them implement good ethical care.

Objective To investigate the relationship between the expression of Krüppel-like factor 5(KLF5)and lysine demethylase 2A(KDM2A)in cancer tissues of patients with oral cancer and clinicopatho-logical characteristics and prognosis.Methods Cancer tissues of 80 patients with oral cancer who underwent surgical treatment in the Zigong First People's Hospital from January 2015 to January 2018 were retrospec-tively collected as research objects,and normal adjacent tissues were selected as controls.The expression of KLF5 and KDM2A in cancer tissues and adjacent tissues of patients with oral cancer was detected by immuno-histochemical staining,and the correlation between KLF5 and KDM2A in cancer tissues was analyzed by Spearman correlation.Clinicopathological features of patients with oral cancer were collected,and the relation-ship between the expression of KLF5 and KDM2A in cancer tissues and clinicopathological features of patients was analyzed,as well as the prognostic factors of patients with oral cancer were analyzed by multivariate Cox regression.Kaplan-Meier method was used to analyze the relationship between the expression of KLF5 and KDM2A and the prognosis of patients with oral cancer.Results The high expression rates of KDM2A and KLF5 in oral cancer tissues were significantly higher than those in adjacent tissues,and the difference was sta-tistically significant(P＜0.05).Spearman correlation analysis showed that there was a positive correlation be-tween KLF5 and KDM2A expression in oral cancer patients(r=0.375,P＜0.05).The expressions of KLF5 and KDM2A in patients with oral cancer were correlated with TNM stage,clinical stage,lymph node metasta-sis,local invasion and differentiation degree(P＜0.05).Multivariate Cox regression analysis showed that the expression level of KLF5 and KDM2A,TNM stage,lymph node metastasis,local invasion and differentiation degree were independent risk factors for poor prognosis in patients with oral cancer(P＜0.05).The 5-year survival rates of patients with high expression of KLF5 and KDM2A in cancer tissues[38.88％(21/54),42.37％(25/59)]were lower than those of patients with low expression of KLF5 and KDM2A in cancer tis-sues[65.38％(17/26),61.90％(13/21)],the difference was statistically significant(x2=6.554,4.046,P＜0.05).Conclusion The expression of KLF5 and KDM2A in cancer tissues of patients with oral cancer is high and affects the prognosis of patients.

Irinotecan (CPT11) chemotherapy-induced diarrhea affects a substantial cancer population due to β-glucuronidase (Gus) converting 10-O-glucuronyl-7-ethyl-10-hydroxycamptothecin (SN38G) to toxic 7-ethyl-10-hydroxycamptothecin (SN38). Existing interventions primarily address inflammation and Gus enzyme inhibition, neglecting epithelial repair and Gus-expressing bacteria. Herein, we discovered that dehydrodiisoeugenol (DDIE), isolated from nutmeg, alleviates CPT11-induced intestinal mucositis alongside a synergistic antitumor effect with CPT11 by improving weight loss, colon shortening, epithelial barrier dysfunction, goblet cells and intestinal stem cells (ISCs) loss, and wound-healing. The anti-mucositis effect of DDIE is gut microbiota-dependent. Analysis of microbiome profiling data from clinical patients and CPT11-induced mucositis mice reveals a strong correlation between CPT11 chemotoxicity and Gus-expressing bacteria, particularly Enterococcus faecalis (E. faecalis). DDIE counters CPT11-induced augmentation of E. faecalis, leading to decreased intestinal Gus and SN38 levels. The Partial Least Squares Path Model (PLS-PM) algorithm initially links E. faecalis to dysregulated epithelial renovation. This is further validated in a 3D intestinal organoid model, in which both SN38 and E. faecalis hinder the formation and differentiation of organoids. Interestingly, colonization of E. faecalis exacerbates CPT11-induced mucositis and disturbs epithelial differentiation. Our study unveils a microbiota-driven, epithelial reconstruction-mediated action of DDIE against mucositis, proposing the 'Gus bacteria-host-irinotecan axis' as a promising target for mitigating CPT11 chemotoxicity.

Shengmai formula,composed of Ginseng Radix et Rhizoma,Ophiopogon Radix and Schisandrae Chinensis Fructus,is a classic and famous formula.It is a representative formula for"supplementing qi,nourishing yin,and generating fluid"in Traditional Chinese Medicine theory.To date,a wide range of Shengmai formulae have been developed according to different medical applications,but the quality evaluation standards are at a relatively low level,and most of them only specify the individual components of a single herb,making it difficult to ensure clinical efficacy and safety.At the same time,the physical and chemical identification methods of Shengmai formula have been constantly updated,allowing for greater progress in research on its main chemical components such as saponins,lignans and flavonoids.However,there is little systematic summarization of the chemical components and analytical methods.Based on the existing references,we systematically summarized ginsenosides,ophiopogonins,schisandra lignans,homoisoflavonoids and some other compounds in this paper,as well as the quality standards of Shengmai formulae and their analytical methods in order to aid clinical research and formulation manufacture.

Bile acids(BAs)are synthesized by the liver from cholesterol through several complementary pathways and aberrant cholesterol metabolism plays pivotal roles in the pathogeneses of cholesterol gallbladder polyps(CGP)and cholesterol gallstones(CGS).To date,there is neither systematic study on BAs profile of CGP or CGS,nor the relationship between them.To explore the metabolomics profile of plasma BAs in healthy volunteers,CGP and CGS patients,an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method was developed and validated for simultaneous determination of 42 free and conjugated BAs in human plasma.The developed method was sensitive and reproducible to be applied for the quantification of BAs in the investigation of plasma samples.The results show that,compared to healthy volunteers,CGP and CGS were both characterized by the significant decrease in plasma BAs pool size,furthermore CGP and CGS shared aberrant BAs metabolic characteristics.Cheno-deoxycholic acid,glycochenodeoxycholic acid,λ-muricholic acid,deoxycholic acid,and 7-ketolithocholic acid were shared potential markers of these two cholesterol gallbladder diseases.Subsequent analysis showed that clinical characteristics including cysteine,ornithine and body mass index might be closely related to metabolisms of certain BA modules.This work provides metabolomic information for the study of gallbladder diseases and analytical methodologies for clinical target analysis and efficacy evaluation related to BAs in medical institutions.