ObjectiveThis study aims to explore the neurotoxicity mechanism of Dictamni Cortex by integrating network toxicology and metabolomics techniques. MethodsThe neurotoxicity targets induced by Dictamni Cortex were screened by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Traditional Chinese Medicine Information Database （TCM-ID）， and Comparative Toxicogenomics Database （CTD）. The target predictions of the components were performed by the Swiss Target Prediction tool. Neurotoxicity-related targets were collected from the Pharmacophore Mapping and Potential Target Identification Platform （PharmMapper）， GeneCards Human Gene Database （GeneCards）， DisGeNET Disease Gene Network （DisGeNET）， and Online Mendelian Inheritance in Man （OMIM）， and the intersection targets were identified. Protein-protein interaction （PPI） analysis， Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis， and Gene Ontology （GO） enrichment analysis were conducted. A "drug-compound-toxicity target-pathway" network was constructed via Cytoscape software to display the core regulatory network. Based on the prediction results， the neurotoxicity mechanism of Dictamni Cortex in mice was verified by using hematoxylin-eosin （HE） staining， Nissl staining， enzyme-linked immunosorbent assay （ELISA）， quantitative real-time fluorescence polymerase chain reaction （Real-time PCR）， and Western blot. The effects of Dictamni Cortex on the metabolic profile of mouse brain tissue were further explored by non-targeted metabolomics. ResultsNetwork toxicology screening identified 13 compounds and 175 targets in Dictamni Cortex that were related to neurotoxicity. PPI network analysis revealed that serine/threonine-protein kinase （Akt1） and tumor protein 53 （TP53） were the core targets. Additionally， GO/KEGG enrichment analysis indicated that Dictamni Cortex may regulate the phosphatidylinositol 3-kinase （PI3K）/Akt pathway and affect oxidative stress and cell apoptosis， thereby inducing neural damage. The "Dictamni Cortex-compound-toxicity target-pathway-neural damage" network showed that dictamnine， phellodendrine， and fraxinellone may be the toxic compounds. Animal experiments showed that compared with those in the blank group， the hippocampal neurons in the brain tissue of mice treated with Dictamni Cortex were damaged. The level of superoxide dismutase （SOD） and acetylcholine （ACh） in the brain tissue was significantly reduced， while the content of malondialdehyde （MDA） was significantly increased. The level of Akt1 and p-Akt1 mRNAs and proteins in the brain tissue was significantly decreased， while the level of TP53 was significantly increased. Non-targeted metabolomics results showed that Dictamni Cortex could disrupt the level of 40 metabolites in mouse brain tissue， thereby regulating the homeostasis of 13 metabolism pathways， including phenylalanine， glycerophospholipid， and retinol. Combined analysis revealed that Akt1， p-Akt1， and TP53 were significantly correlated with phenylalanine， glycerophospholipid， and retinol metabolites. This suggested that Dictamni Cortex induced neurotoxicity in mice by regulating Akt1， p-Akt1， and TP53 and further modulating the phenylalanine， glycerophospholipid， and retinol metabolism pathways. ConclusionDictamni Cortex can induce neurotoxicity in mice， and its potential mechanism may be closely related to the activation of oxidative stress， inhibition of the PI3K/Akt signaling pathway， and regulation of phenylalanine， glycerophospholipid， and retinol metabolism pathways.

ObjectiveThis study aims to investigate the effect of Dictamni Cortex on intestinal barrier damage in rats and its mechanism by untargeted metabolomics and targeted metabolomics for short-chain fatty acids （SCFAs）. MethodsRats were randomly divided into a control group， a high-dose group of Dictamni Cortex （8.1 g·kg^-1）， a medium-dose group （2.7 g·kg^-1）， and a low-dose group （0.9 g·kg^-1）. Except for the control group， the other groups were administered different doses of Dictamni Cortex by gavage for eight consecutive weeks. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in the ileal tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to detect the level of cytokines， including tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β）， in the ileal tissue of rats. Quantitative real-time fluorescence polymerase chain reaction （Real-time PCR） technology was used to detect the expression level of tight junction proteins， including zonula occludens-1 （ZO-1）， Occludin， and Claudin-1 mRNAs， in the ileal tissue of rats to preliminarily explore the effects of Dictamni Cortex on intestinal damage. The dose with the most significant toxic phenotype was selected to further reveal the effects of Dictamni Cortex on the metabolic profile of ileal tissue in rats by non-targeted metabolomics combined with targeted metabolomics for SCFAs. ResultsCompared with the control group， all doses of Dictamni Cortex induced varying degrees of pathological damage in the ileum， increased TNF-α （P<0.01）， IL-6 （P<0.01）， and IL-1β （P<0.01） levels in the ileal tissue， and decreased the expression level of ZO-1 （P<0.05， P<0.01）， Occludin （P<0.01）， and Claudin-1 （P<0.05） in the ileal tissue， with the high-dose group showing the most significant toxic phenotypes. The damage mechanisms of the high-dose group of Dictamni Cortex on the ileal tissue were further explored by integrating non-targeted metabolomics and targeted metabolomics for SCFAs. The non-targeted metabolomics results showed that 21 differential metabolites were identified in the control group and the high-dose group. Compared with that in the control group， after Dictamni Cortex intervention， the level of 14 metabolites was significantly increased （P<0.05， P<0.01）， and the level of seven metabolites was significantly decreased （P<0.05， P<0.01） in the ileal contents. These metabolites collectively acted on 10 related metabolic pathways， including glycerophospholipids and primary bile acid biosynthesis. The quantitative data of targeted metabolomics for SCFAs showed that Dictamni Cortex intervention disrupted the level of propionic acid， butyric acid， acetic acid， caproic acid， isobutyric acid， isovaleric acid， valeric acid， and isocaproic acid in the ileal contents of rats. Compared with those in the control group， the level of isobutyric acid， isovaleric acid， and valeric acid were significantly increased， while the level of propionic acid， butyric acid， and acetic acid were significantly decreased in the ileal contents of rats after Dictamni Cortex intervention （P<0.05， P<0.01）. ConclusionDictamni Cortex can induce intestinal damage by regulating glycerophospholipid metabolism， primary bile acid biosynthesis， and metabolic pathways for SCFAs.

Objective To explore the research hotspots and development trends of Ziziphi Spinosae Semen in the past 20 years,and to provide reference for related research.Methods Literatures on Ziziphi Spinosae Semen were searched from January 1,2000 to December 31,2022 in CNKI,Web of Science Core Collection Database.VOS viewer software was used to visually analyze the citation frequency,research institutions and keyword hotspots of English literatures.CiteSpace software was used to visually analyze research institutions,authors,emergence keywords and keyword overlap time of Chinese literatures,and Microsoft Excel 2021 software was used to analyze of annual publication trends and publication volume of Chinese and English literatures,and download frequency of Chinese literatures.Results A total of 4 872 Chinese and 128 English literatures were included,with an overall upward trend in the number of annual publications.The research institutions with the highest number of publications in Chinese and English were Shandong University of Traditional Chinese Medicine and Tianjin University of Commerce,and the authors with the highest number of publications were DU Chenhui and XIE Junbo,respectively.The most frequent keywords in Chinese literatures were"Ziziphi Spinosae Semen","composed"and"application of compound therapy",and in English literatures were"performance","oxidative stress".Conclusion From 2000 to 2022,the research hotspots of Ziziphi Spinosae Semen mainly focused on the chemical composition,pharmacological effects and clinical application analysis,compatibility research,formulation and preparation.Quality control and evaluation of Ziziphi Spinosae Semen,and the research on the mechanism of preventing and treating insomnia with Ziziphi Spinosae Semen may become future research directions.

Objective:To disclose phylogenetic and antigenic characteristics of hemagglutinin (HA) gene of influenza B virus (Victoria) (BV) in the 2023-2024 influenza surveillance season in Beijing, and understand the matching with influenza vaccine component strain.Methods:Pharyngeal swab specimens from influenza like-illness (ILI) in the 2023-2024 influenza surveillance season were collected from surveillance network labs in Beijing and BV strains were isolated through MDCK or chicken embryo culture. After extracting nucleic acid, HA gene was amplified and sequenced. The nucleotide and amino acid sequence identity were conducted and the maximum likelihood method in Mega 5.0 software was used to construct the phylogenetic tree of HA gene. N-glycosylation sites of HA were performed online. Furthermore, three-dimensional structure of HA was available from SWISS-MODEL homologous modeling. Hemagglutination inhibition (HI) tests were performed to analyze antigenic characteristics of HA of BV strains.Results:Fifty-four BV strains were randomly selected to be analyzed further. Compared with the HA gene of this influenza season vaccine strain (B/Austria/1359417/2021), there are three amino acid mutations among all BV strains, two of which are located in two different antigenic determinants. Furthermore, the phylogenetic tree analysis revealed that only one subgroup of 1A.3a.2 was circulating simultaneously. All BV strains are located in Clade 1A.3a.2 subgroup, and in the same subgroup with that of the vaccine component BV strain in 2023-2024. All BV strains have the same glycosylation sites as that of the vaccine component BV strain in 2023-2024. Antigenic analysis showed that all BV strains were antigenically similar with its vaccine strain.Conclusions:In the 2023-2024 influenza surveillance season, the prevalent BV strains in the population in Beijing city are located in Clade 1A. 3a. 2 subgroup. The antigen matching between BV epidemic strains and vaccine BV components is relatively high during this surveillance season.

Objective:To compare the clinical efficacy of camrelizumab and sintilimab in the treatment of advanced non-small cell lung cancer (NSCLC) , and to explore its impact on tumor marker levels and immune function index, as well as to perform safety analysis.Methods:A total of 87 patients with advanced NSCLC who were treated in Hai'an People's Hospital of Jiangsu Province from May 2019 to May 2021 were selected as the research objects. According to the treatment scheme, the patients were divided into camrelizumab group ( n=41) and sintilimab group ( n=46) . The clinical efficacy, prognosis, tumor marker levels, immune function index and immune related adverse reactions of the two groups were compared. Results:There were no statistically significant differences in objective response rate [48.78% (20/41) vs. 39.13% (18/46) , χ2=0.82, P=0.365] or disease control rate [78.05% (32/41) vs. 71.74% (33/46) , χ2=0.46, P=0.499] in both camrelizumab and sintilimab group. The median progression-free survival (PFS) in the camrelizumab group was 9.1 months, and the median overall survival (OS) was 15.4 months. The median PFS in the sintilimab group was 9.7 months, and the median OS was 15.7 months. There were no statistically significant differences in median PFS and median OS between the two groups ( χ2=0.18, P=0.633; χ2=0.15, P=0.697) . Before treatment, there were no statistically significant differences in carcinoembryonic antigen (CEA) [ (47.68±8.12) ng/ml vs. (49.03±8.70) ng/ml, t=0.75, P=0.458], cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) [ (18.06±3.41) ng/ml vs. (17.25±3.78) ng/ml, t=1.05, P=0.299], and carbohydrate antigen 125 (CA125) [ (72.26±21.06) U/ml vs. (74.03±22.10) U/ml, t=0.38, P=0.704] levels between the camrelizumab group and sintilimab group. After treatment, there were no statistically significant differences in CEA [ (28.11±7.68) ng/ml vs. (27.63±5.71) ng/ml, t=0.33, P=0.740], CYFRA21-1 [ (9.29±1.88) ng/ml vs. (9.06±1.80) ng/ml, t=0.15, P=0.814], and CA125 [ (61.39±21.22) U/ml vs. (60.51±11.03) U/ml, t=0.25, P=0.806] levels between the two groups, but CEA, CYFRA21-1, and CA125 levels decreased after treatment compared with those before treatment in both groups (all P<0.05) . Before treatment, there were no statistically significant differences in T cells CD4 + [ (41.15±3.24) % vs. (41.17±2.90) %, t=0.03, P=0.976], CD8 + [ (68.82±3.94) % vs. (70.06±4.08) %, t=1.44, P=0.154], and CD4 +/CD8 + (1.88±0.33 vs. 1.76±0.25, t=1.92, P=0.058) between the two groups. After treatment, there were no statistically significant differences in T cells CD4 + [ (47.08±3.22) % vs. (48.53±5.07) %, t=1.57, P=0.120], CD8 + [ (61.22±1.67) % vs. (61.45±1.66) %, t=0.64, P=0.522], and CD4 +/CD8 + (2.31±0.17 vs. 2.36±0.12, t=1.60, P=0.114) between the two groups, while T cells CD8 + was lower than that before treatment, and CD4 + as well as CD4 +/CD8 + were higher than those before treatment in both groups (all P<0.05) . The overall incidence of adverse reactions in the sintilimab group [10.87% (5/46) ] was lower than that in the camrelizumab group [31.71% (13/41) ], and with a statistically significance ( χ2=5.74, P=0.016) . Conclusion:The clinical efficacy of camrelizumab and sintilimab in NSCLC patients is basically the same, the impacts of which on tumor markers and immune function are comparable, but the safety of sintilimab is better than that of camrelizumab.

The update of multi-omics technology is a key means to promote the rapid development of accurate health model in the whole life cycle.It can formulate dynamic and accurate nursing measures and provide massive data information from the perspective of nursing biology of health and disease.At present,clinical nursing research faces many challenges such as insufficient application and transformation ability of multi-omics technology.This paper introduces the multi-omics technology,reviews the application status of multi-omics technology in cancer nursing,maternal and child nursing,chronic metabolic disease nursing and symptom management,and puts forward the cross integration and prospect of multi-omics technology and nursing research,so as to strengthen the information mining ability of nurses at different levels of health and disease,and provide an important basis for accelerating the clinical transformation of precision nursing.

With the intensification of the global population aging trend, the problem of obesity in the elderly has become increasingly prominent, which is closely related to the increase of the risk of various diseases and mortality.However, there are still many challenges in dealing with this problem.First, body mass index, waist circumference and waist-to-hip ratio, which are widely used for weight assessment, have certain limitations.Secondly, the screening and management of weight-related complications should be strengthened, and management concepts should be established to improve physical function and enhance health outcomes.At the same time, attention should be paid to the management of body composition, especially the monitoring and management of sarcopenia and sarcopenic obesity, which are common in the elderly.In the management of obesity in the elderly, it is necessary to consider the overall health status of patients, living habits and other factors, and formulate lifestyle intervention measures in line with their physiological characteristics.If lifestyle interventions do not work well, the drug regimen should consider the combined effects of cardiovascular, renal, and metabolic syndrome.With the continuous advancement of artificial intelligence technology, weight management in the elderly is expected to improve health outcomes by building risk prediction models through machine learning and enabling precise personalized treatment.This will provide a new strategy and method for solving the problem of obesity in the elderly.

Objective To investigate the inhibitory effect of epigallocatechin gallate(EGCG)on oxidative damage to the retina in a rat model of dry age-related macular degeneration(AMD)induced by sodium iodate.Methods A total of 36 male specific pathogen-free Sprague-Dawley rats were randomly divided into the blank control group,sodium iodate group and sodium iodate+EGCG group,with 12 rats in each group.Rats in the sodium iodate group and the sodium io-date+EGCG group were given 50 mg-kg·1 sodium iodate by tail vein injection by weight to build dry AMD models,while rats in the blank control group were administered with an equal volume of normal saline.Following the modeling proce-dure,rats in the sodium iodate+EGCG group received an intravitreal injection of 4 μL EGCG(0.5 g·L-1)into their right eyes,while the right eyes of rats in both the blank control and sodium iodate groups were treated with the same volume of normal saline.After 21 days,the rats were sacrificed,and ocular samples were collected for detection.Histopathological changes of the retinal tissues in each group were examined using hematoxylin and eosin(HE)staining.Additionally,the levels of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and malondialdehyde(MDA)in the retinal tis-sues were quantified.Western blot analysis was conducted to assess the protein expression levels of nuclear factor ery-throid-2-related factor 2(Nrf2),NADPH quinone oxidoreductase 1(NQO1),and heme oxygenase-1(HO-1)in the retinas.Furthermore,real-time quantitative polymerase chain reaction was performed to evaluate the relative messenger ribonucleic acid(mRNA)expression levels of Nrf2,NQO1 and HO-1 in the retinas of the rats.Results HE staining revealed that,in comparison to the blank control group,the entire retinal layer in the sodium iodate group exhibited injury,characterized by noticeable injury of the retinal pigment epithelial cells and disordered outer nuclear layer with wavy transformation.The so-dium iodate+EGCG group demonstrated ameliorated retinal injury across all layers compared to the sodium iodate group.Compared to the blank control group,the levels of SOD and GSH-Px were significantly reduced(both P＜0.01),while the level of MDA was significantly elevated(P＜0.01)in the sodium iodate group.Compared with the sodium iodate group,the sodium iodate+EGCG group showed a significant increase in the levels of SOD and GSH-Px(both P＜0.01),along-side a substantial decrease in the content of MDA(P＜0.01).Western blot analyses demonstrated that compared with the blank control group,the protein expression levels of Nrf2,NQO1 and HO-1 were significantly elevated in the sodium iodate group(all P＜0.01);compared with the sodium iodate group,the sodium iodate+EGCG group exhibited relatively higher protein expression levels of Nrf2,NQO1 and HO-1(all P＜0.05).The results from real-time quantitative polymerase chain reaction indicated that the relative mRNA expression levels of Nrf2,NQO1 and HO-1 in the retinas of rats in the sodium io-date group were significantly greater than those in the blank control group(all P＜0.05);compared with the sodium iodate group,the sodium iodate+EGCG group showed a significant increase in the relative mRNA expression levels of Nrf2,NQO1 and HO-1(all P＜0.05).Conclusion EGCG can improve the capacity to scavenge oxygen free radicals by promo-ting the upregulation of Nrf2 expression.This activation subsequently enhances the expression of downstream products such as NQO1 and HO-1,leading to increased levels of SOD and GSH-Px while simultaneously reducing the MDA level.Consequently,this process inhibits oxidative damage to the retina in rats with dry AMD induced by sodium iodate.

Objective To explore the mechanism of acute liver injury induced by Cortex dictamni through network pharmacology and in vivo experiment in animal.Methods The chemical constituents and targets of Cortex dictamni were retrieved from TCMSP,TCMIP and SwissTargetPrediction databases,and the related targets of liver injury diseases were identified through GeneCards and CTD databases.The protein interaction network of the intersection targets was analyzed by STRING database and the core targets were selected.The GO function and KEGG pathway enrichment analysis were completed by DAVID database,and the multi-level association network diagram of"drug-component-target"was constructed by Cytoscape software.In the animal study,Cortex dictamni was administered to mice at a dosage of 92.7 g/(kg·d)via intragastric administration,and the biological samples were collected after 7 days.The pathological changes of liver were observed by hematoxylin-eosin(HE),Masson and Oil Red O staining.The expression levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),and lactate dehydrogenase(LDH)in serum,as well as malondialdehyde(MDA),superoxide dismutase(SOD),tumor necrosis factor-α(TNF-α),and interleukin(IL)-1β in liver tissues,were quantified using enzyme-linked immunosorbent assay(ELISA).The expressions of protein kinase B1(AKT1),IL-6,TNF-α,tumor protein p53(TP53),cystatin 3(CASP3),and IL-1β mRNA in liver tissues were determined using real-time quantitative reverse transcription PCR(qRT-PCR).Molecular docking was employed to verify the binding affinity of potentially toxic components to their respective targets.Results A total of 14 chemical constituents,244 predicted targets and 202 intersection targets with liver injury were obtained.The GO biological process analysis mainly involved positive regulation of gene expression,negative regulation of apoptosis process.KEGG pathway enrichment analysis mainly included cancer pathway and PI3K-Akt,TNF,IL-17 signaling pathways.The pathological sections revealed severe hemorrhage,a considerable amount of hepatocyte necrosis,nuclear fragmentation or dissolution in the liver tissues of mouse with HE staining after the administration of Cortex dictamni.Masson staining showed evident fibrosis in the liver tissues,while Oil Red O staining indicated a substantial production of lipid droplets.Compared with the control group,the ELISA results demonstrated a significant increase in serum AST,ALT,ALP,LDH levels,as well as hepatic MDA,TNF-α,and IL-1β levels(P<0.05),and a decrease in hepatic SOD levels(P<0.05)in the treated group.The qRT-PCR results indicated a significant elevation in the expression levels of relevant mRNAs in the liver tissues of the treated mice(P<0.05).Molecular docking showed that the potentially toxic components of obacunone,dictamnine and fraxinellon had good binding affinity to AKT1,IL-6,TNF-α,TP53,CASP3 and IL-1β.Conclusion Obacunone,dictamnine,fraxinellon,and limonin might be the potential toxic components of acute liver injury induced by Cortex dictamni in mice.Cortex dictamni could act on the liver by changing the expressions of AKT1,IL-6,TNF-α,TP53,CASP3,IL-1β and other proteins,affecting energy metabolism,cell differentiation,inflammation,oxidative stress and immunity,leading to liver injury.

Ziziphi spinosae semen mainly contains contents of saponins,flavonoids,alkaloids and aliphatic acids.Meanwhile,it has a variety of activities such as sedative-hypnotic,anti-anxiety,anti-depression,nerve protection,cardiovascular and cerebrovascular protection,liver protection,and antioxidant,which is widely used in medicine,food,health food and other fields.The chemical constituents,pharmacological action and clinical application of Ziziphi spinosae semen were systematically summarized in this paper by reviewing the literature,in order to provide theoretical guidance for the sustainable development of the resources and the rational use of Ziziphi spinosae semen.