ObjectiveTo investigate the mechanism by which Simiao Wan improve intestinal uric acid excretion in hyperuricemic （HUA） rats by inhibiting ferroptosis via the solute carrier family 7 member 11/glutathione peroxidase 4 （SLC7A11/GPX4） signaling pathway. MethodsForty-eight male SD rats were randomly assigned to a normal group， a model group， a low-dose Simiao Wan group （282.6 mg·kg^-1）， a high-dose Simiao Wan group （565.2 mg·kg^-1）， an etoricoxib group （5.4 mg·kg^-1）， and a ferroptosis inhibitor （Fer-1） group （2 mg·kg^-1）. Except for the normal group， rats in all other groups were intraperitoneally injected with potassium oxonate （100 mg·kg^-1） combined with intragastric administration of hypoxanthine （500 mg·kg^-1） to establish the HUA rat model. After 21 days， rats in each administration group received the corresponding dose of drug by gavage， rats in the Fer-1 group received intraperitoneal injection of Fer-1， and rats in the normal and model groups were given an equal volume of normal saline by gavage. After sampling， serum levels of uric acid （SUA）， creatinine （Cr）， and blood urea nitrogen （BUN） were measured using biochemical assays. The content of ferrous ion （Fe²⁺）， reduced glutathione （GSH）， and malondialdehyde （MDA）， as well as superoxide dismutase （SOD） activity in ileal tissues were determined. Hematoxylin and eosin （HE） staining was performed to observe the histopathological changes in the ileum， and transmission electron microscopy was used to observe mitochondrial alterations in the ileal tissue. Immunohistochemistry （IHC） and Western blot were used to detect the protein expression levels of GPX4， ferritin heavy chain 1 （FTH1）， acyl-CoA synthetase long-chain family member 4 （ACSL4）， SLC7A11， and ATP-binding cassette transporter G2 （ABCG2） in ileal tissue. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to determine the mRNA expression of GPX4， FTH1， ACSL4， SLC7A11， and ABCG2 in the ileal tissue. ResultsCompared with the normal group， the model group exhibited significantly elevated serum UA， Cr， and BUN levels （P<0.01）， significantly increased content of MDA and Fe²⁺ in ileal tissue， and significantly decreased GSH content and SOD activity （P<0.01）. HE staining showed extensive shedding of the ileal villous epithelium， disrupted and disorganized villous structure， and incomplete local tissue architecture. Transmission electron microscopy revealed reduced mitochondrial volume， decreased or even vanished cristae， indicating ultrastructural features characteristic of ferroptosis. Molecular and immunohistochemical results demonstrated that the protein and mRNA expression levels of GPX4， FTH1， SLC7A11， and ABCG2 were significantly downregulated， whereas those of ACSL4 were significantly upregulated （P<0.05， P<0.01）. Compared with the model group， after intervention with Simiao Wan， the serum UA， Cr， and BUN levels significantly decreased in all dose groups （P<0.05，P<0.01）， the MDA and Fe²⁺ content in ileal tissues were significantly reduced （P<0.01）， and the GSH content and SOD activity significantly increased （P<0.01）. HE staining showed that the shedding of ileal villous epithelium was markedly alleviated， the villous structure became relatively intact and regularly arranged， and local tissue damage was obviously improved. Transmission electron microscopy showed attenuated mitochondrial damage， improvement in mitochondrial shrinkage， and partial restoration of mitochondrial cristae. Molecular and immunohistochemical results showed that Simiao Wan upregulated GPX4， FTH1， SLC7A11， and ABCG2， and downregulated ACSL4 in a dose-dependent manner. In the high‑dose group， all indices improved significantly （P<0.05，P<0.01）， whereas in the low‑dose group， only improving trends were observed for FTH1， SLC7A11 mRNA， and ABCG2 protein. ConclusionSimiao Wan may inhibit ferroptosis of ileal epithelial cells by regulating the SLC7A11/GPX4 signaling pathway， and upregulate the expression of the uric acid transporter ABCG2， thereby promoting intestinal uric acid excretion and improving HUA.

ObjectiveChemotherapy is one of the important therapeutic approaches for cancer treatment. However, the emergence of multidrug resistance and side effects significantly limit its application. To address these challenges, chemotherapy is often combined with other drugs or therapies. Among the 13 human fucosyltransferases (FUTs) identified, FUT8 (alpha-(1,6)-fucosyltransferase) is the only enzyme responsible for core fucosylation. Core fucosylation plays an important role in cancer occurrence, metastasis and chemotherapy resistance, making the suppression of FUT8 a potential strategy for reversing multidrug resistance. This study aims to evaluate the feasibility of combining the small molecule FUT8 inhibitor 2FF (2-deoxy-2-fluoro-L-fucose) with the clinical chemotherapeutic drug doxorubicin (DOX) for treating malignant tumors. MethodsThe human hepatocellular carcinoma cell line HepG2 and mouse colon cancer cell line CT26 cells were treated with 2FF, DOX or their combination and core fucosylation levels were assessed using Lectin blot. HepG2 and CT26 cells were exposed to 50 μmol/L 2FF for 72 h, followed by treatment with a gradient concentration of DOX for 24 h. Cell viability and IC₅₀ values were determined via the CCK-8 assay. Transwell invasion assays were conducted to evaluate the combined effect of 2FF and DOX on the invasion ability of HepG2 cells. Flow cytometry was performed to analyze the impact of 2FF, DOX and their combination on membrane PD-L1 expression of HepG2 cells. To assess the in vivo effect, 6- to 8-week-old female BALB/c mice (20-25 g), were subcutaneously injected with 1×10⁶ CT26 cells into the right axilla (four groups, six mice in each group). After the average tumor volume reached 100 mm³, mice were treated with DOX, 2FF, their combination, or saline (mock group) every other day. DOX was administrated intraperitoneally (2 mg/kg), 2FF intravenously (5 mg/kg), and the combination group, received the both treatment. Tumor size was measured every other day using a vernier caliper. ResultsThis study demonstrated that DOX upregulates the core fucosylation levels in HepG2 and CT26 cells,while 2FF effectively inhibits this DOX-induced effect. Furthermone, 2FF enhanced the sensitivity of HepG2 and CT26 cells to DOX. The combination of 2FF and DOX synergistically inhibited the invasion ability of HepG2 cells, and enhanced the anti-tumor efficacy of CT26 subcutaneous tumor model in BALB/c mice. However the combination treatment led to weight loss in mice. In addition, DOX increased the cell surface PD-L1 expression in HepG2 cells, which was effectively suppressed by 2FF. ConclusionThe FUT8 inhibitor 2FF effectively suppresses DOX-induced upregulation of core fucosylation and PD-L1 levels in tumor cells, and 2FF synergistically enhances the anticancer efficacy of DOX.

Objective:To investigate the nutritional risk status of children in PICU and analyze its influencing factors.Methods:From July 2021 to February 2023,all children aged 1 to 18 years admitted to PICU of Beijing Children's Hospital were investigated by using the pediatric Yorkhill Malnutrition Scoring tool(PYMS)and the clinical data questionnaire.Results:A total of 492 children in PICU were enrolled.The first nutritional risk screening results showed that there were 32 cases of no/low nutritional risk(6.5%),76 cases of medium risk(15.4%),and 384 cases of high risk(78.1%).The incidence of medium/high nutritional risk was as high as 93.5%.The PYMS score of nutritional risk in PICU was(2.61±1.42).The results of multiple linear regression analysis showed that weight,fever time before admission,white blood cells,body mass index,primary diagnosis,father's education,and diet before illness were the main influencing factors of nutritional risk of children in PICU(P<0.05).Conclusion:Children in PICU are in a state of high nutritional risk.It is suggested that children in PICU should carry out nutritional screening in a standardized manner,identify children with high nutritional risk and its influencing factors early.To actively conduct nutritional assessment and nutritional intervention could improve the clinical outcome of children in PICU.

Objective To propose a multiple regression-variational auto-encoders(MR-VAE)model to realize precise and non-invasive prediction of intra-abdominal pressure(IAP)in critically ill patients.Methods At first,a dataset was constructed by retrospectively analysing baseline characteristics and clinical indicators of 100 critically ill patients admitted to the Intensive Care Unit of Daping Hospital of Army Medical University between 30 August 2019 and 30 March 2021.Then,a MR-VAE prediction model was developed by integrating a feedforward neural network for supervised regression onto a variational autoencoder(VAE)framework and incorporating multiple regression strategies to mitigate feature interference.Finally,the MR-VAE model had its performance evaluated by its comparison with five classical models including support vector machines(SVM),convolutional neural networks(CNN),Scikit-learn integrated model(SIM),multi-layer perceptron(MLP)and K-nearest neighbors(KNN),and its prediction accuracy verified by testing the data of 10 randomly selected patients.Results The MR-VAE model behaved the best when compared with the five classical models,with a mean squared error(MSE)of 0.207,a root mean square error(RMSE)of 0.454,a mean absolute error(MAE)of 0.361,a median absolute deviation(MAD)of 0.243,an explained variance score(EVS)of 0.814 and a R2of 0.823,which also outperformed the five models in fitting performance,convergence and final loss.In random sample testing,the MR-VAE model exhibited high consistency between predicted and actual values.Conclusion The MR-VAE model proposed can accurately predict IAP,which has great potential in reducing the repeated measurements of IAP in critically ill patients and providing new ideas for the early diagnosis and treatment of IAH.

AIM To study the chemical constituents from ethyl acetate fraction of Balanophora harlandii Hook.f.and their tyrosinase inhibitory activity.METHODS Separation and purification were performed using silica gel,MCI,ODS,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The monophenolase inhibitory activity was determined by the tyrosinase-catalyzed oxidation of L-tyrosine.RESULTS Twenty-four compounds were isolated and identified as sesamin(1),methyl caffeate(2),quercetin(3),5,7-dihydroxychromanone(4),methyl 3,4-dihydroxybenzoate(5),esculetin(6),kaempferol(7),naringenin(8),pyrogallic acid(9),pinosylvin(10),methyl propionate(11),caffeic acid(12),saccharinol(13),ferulic acid(14),trans-p-hydroxycinnamic acid(15),cinnamic acid(16),vanillic acid(17),vanillin(18),4-hydroxyacetophenone(19),4-hydroxybenzaldehyde(20),apigenin(21),(-)-isolariciresinol(22),(-)-secoisolariciresinol(23)and meso-2,3-di(3′,4′-methylenedioxybenzyl)butane-1,4-diol(24).The IC50 values of compounds 3,5,7,8,19,and 20 ranged from(0.246 5±0.028 3)to(1.278 2±0.021 3)mmol/L.CONCLUSION Compounds 1-9、11、15、17-21、24 are isolated from this plant for the first time,and 1,6,9,17-19,24 are first isolated from genus Balanophora.Compounds 3、5、7、8、19 and 20 have tyrosinase inhibitory activity.

Objective To explore CT manifestations of perivascular epithelioid cell tumor(PEComa)of liver and kidney.Methods Totally 18 hepatic PEComa and 5 renal PEComa confirmed by surgical pathology were retrospectively enrolled,and the preoperative CT manifestations were explored.Results Single lesion of liver or kidney was found in all 23 cases,and the main CT manifestations included low or slightly low density lesion(23/23,100％),with irregular morphology(16/23,69.57％),clear boundaries(17/23,73.91％),non-envelope(21/23,91.30％)and enhancement after administration of contrast agents(21/23,91.30％).Among 18 cases of liver PEComa,most lesions(13/18,72.22％)presented as uniform density,while some(5/18,27.88％)presented as non-uniform density lesions often contained with fat components(5/5,100％)and thickened blood vessels(4/5,80.00％)but rare hemorrhagic necrosis(1/5,20.00％)nor calcification(0/5,0).Fast in and fast out of contrast agents were observed in 16(16/18,88.89％)lesions.Uneven density and internal fat components were found in all 5(5/5,100％)renal PEComa,which rarely with hemorrhagic necrosis(1/5,20.00％),blood vessels orientation(1/5,20.00％)and calcification(0/5,0).After enhancement,fast in and fast out,progressive enhancement and non-enhancement was observed in 2(2/5,40.00％),1(1/5,20.00％)and 2(2/5,40.00％)cases,respectively.Conclusion CT manifestations of PEComa in liver and kidney had certain characteristics.

Objective To propose a multiple regression-variational auto-encoders(MR-VAE)model to realize precise and non-invasive prediction of intra-abdominal pressure(IAP)in critically ill patients.Methods At first,a dataset was constructed by retrospectively analysing baseline characteristics and clinical indicators of 100 critically ill patients admitted to the Intensive Care Unit of Daping Hospital of Army Medical University between 30 August 2019 and 30 March 2021.Then,a MR-VAE prediction model was developed by integrating a feedforward neural network for supervised regression onto a variational autoencoder(VAE)framework and incorporating multiple regression strategies to mitigate feature interference.Finally,the MR-VAE model had its performance evaluated by its comparison with five classical models including support vector machines(SVM),convolutional neural networks(CNN),Scikit-learn integrated model(SIM),multi-layer perceptron(MLP)and K-nearest neighbors(KNN),and its prediction accuracy verified by testing the data of 10 randomly selected patients.Results The MR-VAE model behaved the best when compared with the five classical models,with a mean squared error(MSE)of 0.207,a root mean square error(RMSE)of 0.454,a mean absolute error(MAE)of 0.361,a median absolute deviation(MAD)of 0.243,an explained variance score(EVS)of 0.814 and a R2of 0.823,which also outperformed the five models in fitting performance,convergence and final loss.In random sample testing,the MR-VAE model exhibited high consistency between predicted and actual values.Conclusion The MR-VAE model proposed can accurately predict IAP,which has great potential in reducing the repeated measurements of IAP in critically ill patients and providing new ideas for the early diagnosis and treatment of IAH.

Objective To explore CT manifestations of perivascular epithelioid cell tumor(PEComa)of liver and kidney.Methods Totally 18 hepatic PEComa and 5 renal PEComa confirmed by surgical pathology were retrospectively enrolled,and the preoperative CT manifestations were explored.Results Single lesion of liver or kidney was found in all 23 cases,and the main CT manifestations included low or slightly low density lesion(23/23,100％),with irregular morphology(16/23,69.57％),clear boundaries(17/23,73.91％),non-envelope(21/23,91.30％)and enhancement after administration of contrast agents(21/23,91.30％).Among 18 cases of liver PEComa,most lesions(13/18,72.22％)presented as uniform density,while some(5/18,27.88％)presented as non-uniform density lesions often contained with fat components(5/5,100％)and thickened blood vessels(4/5,80.00％)but rare hemorrhagic necrosis(1/5,20.00％)nor calcification(0/5,0).Fast in and fast out of contrast agents were observed in 16(16/18,88.89％)lesions.Uneven density and internal fat components were found in all 5(5/5,100％)renal PEComa,which rarely with hemorrhagic necrosis(1/5,20.00％),blood vessels orientation(1/5,20.00％)and calcification(0/5,0).After enhancement,fast in and fast out,progressive enhancement and non-enhancement was observed in 2(2/5,40.00％),1(1/5,20.00％)and 2(2/5,40.00％)cases,respectively.Conclusion CT manifestations of PEComa in liver and kidney had certain characteristics.

Objective To explore the mechanism of matrine in the treatment of uveal melanoma by network pharmacology,and the related results were verified by molecular docking and cell experiments.Methods The potential targets of matrine were obtained from Swiss Target Prediction,SuperPred and TCMSP databases.The targets related to uveal melanoma were obtained from GeneCards,OMIM,CTD and DrugBank databases.Protein-protein interaction(PPI)network was established to screen core targets.Gene ontology(GO)enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)signal pathway analysis were carried out for potential targets.The interaction between matrine and core targets was evaluated by molecular docking technique.The effects of different concentrations of matrine(0.25 g/L,0.50 g/L,1.00 g/L,2.00 g/L)on the proliferation of uveal melanoma cells were evaluated based on CCK-8 method.Western blot was used to verify the regulatory effects of different concentrations of matrine(0.25 g/L,0.50 g/L,1.00 g/L,2.00 g/L)on PI3K-Akt signaling pathway.Results A total of 208 potential targets of matrine were identified,and 5 453 targets related to uveal melanoma were obtained.The topological analysis of PPI network revealed 8 core targets,namely interleukin-6(IL-6),tumor necrosis factor(TNF),myelocytomatosis proteins(MYC),signal transducer and activator of transcription 3(STAT3),caspase-3(CASP3),heat shock protein 90AB1(HSP90AB1),mammalian target of rapamycin(mTOR),and matrix metalloproteinase 9(MMP9).GO enrichment analysis showed that biological processes(BP)mainly included inflammatory response,protein phosphorylation and response to exogenous stimuli;cell components(CC)mainly included plasma membrane,cell surface and cytoplasm;molecular function(MF)mainly included the same protein binding,ATP binding and kinase activity.The enrichment analysis of KEGG pathway showed that the effect of matrine was mediated by viral carcinogenesis,cancer pathway,TNF signaling pathway and PI3K-Akt signaling pathway.Molecular docking showed that matrine had good binding ability with the selected core targets.The results of cell experiments showed that matrine at concentrations of 0.50 g/L,1.00 g/L and 2.00 g/L could inhibit the proliferation of MuM2B cells,and the cell survival rate gradually decreased with the increase of concentration.Matrine at concentrations of 0.50 g/L,1.00 g/L and 2.00 g/L could down-regulate the protein expression levels of p-PI3K and p-Akt,and the protein expression levels of p-PI3K and p-Akt gradually decreased with the increase of concentration.Conclusion Matrine acts on tar-gets such as IL-6,TNF,MYC,STAT3,CASP3,HSP90AB1,mTOR,MMP9,and exerts therapeutic effects on uveal melanoma by viral carcinogenesis,cancer pathway,TNF signaling pathway and PI3K-Akt signaling pathway,etc.

Combined seawater Hf and Nd isotope compositions have been applied as reliable tracers of water mass mixing and weathering input changes.The establishment of standardized synchronous extraction methods for Fe-Mn oxyhydroxide in sediments,which serve as effective carriers for isotopic signals of ancient seawater,is a prerequisite and key for paleoceanography research.The research material of this study was the surface sediments of the Western Arctic Ocean obtained from China's 7th Arctic Scientific Expedition,and a reliable simultaneous Nd-Hf isotope extraction method in Fe-Mn oxyhydroxide fraction was established through systematic optimization of pretreatment procedures and key extraction parameters.This research focused on analyzing the effects of pretreatment(Milli-Q water pre-wash)and key extraction parameters(leaching time,solution/solid ratios,concentration of EDTA-2Na,and concentration of mixed solution of hydroxyamine hydrochloride(HH)and acetic acid(HAc))on element extraction efficiency and isotopic composition.The experimental results indicated that the Milli-Q water pre-wash was not necessary,Fe-Mn oxyhydroxide extraction could be directly performed.Nd extraction amount in Fe-Mn oxyhydroxide fraction was not sensitive to changes in extraction conditions,while the Hf extraction amount was significantly affected by leaching time,solution/solid ratios and concentration of EDTA-2Na.The optimal conditions for synchronously extracting Nd-Hf isotopes were as follows:adding 20 mL of a mixed solution of 0.005 mol/L HH+1.5%HAc+0.03 mol/L EDTA-2Na per gram of sample,and reaction at room temperature for 3 h under shaking.Through systematic verification of 87Sr/86Sr ratio,εNd value,εHf value,Al/Nd ratio and Al/Hf ratio,it was confirmed that this method could effectively avoid interferences from residual components and accurately obtain Nd-Hf isotope signals of ancient seawater preserved in sediments.The standardized method established in this work provided reliable technical support for reconstructing water mass mixing between the Arctic,North Atlantic,and North Pacific Oceans and riverine input histories.It also provided important reference for the extraction methods of Nd and Hf isotopes from marine sources in sediments from other sea areas around the world.