OBJECTIVE To investigate the ameliorative effect and potential mechanism of imperatorin （IMP） on doxorubicin （DOX） resistance in breast cancer. METHODS The effects of maximum non-toxic concentration （100 μg/mL） of IMP combined with different concentrations of DOX （12.5， 25， 50， 75， 100 μg/mL） on the proliferation of MCF-7/DOX cells were determined by MTT method. MCF-7/DOX cells were divided into blank control group （1‰ dimethyl sulfoxide）， DOX group （50 μg/mL）， IMP+DOX group （100 μg/mL IMP+50 μg/mL DOX） and IMP group （100 μg/mL）. mRNA and protein expressions of multidrug resistance protein 1 （MDR1） and multidrug resistance-associated protein 1 in each group were measured. The relevant pathways and targets involved in the improvement of DOX resistance in breast cancer cells by IMP were screened and validated by using transcriptome sequencing technology， along with gene ontology （GO） enrichment analyses and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. RESULTS Compared with DOX alone， the combination of IMP and DOX reduced the half inhibitory concentration of DOX on MCF-7/DOX cells from 81.965 μg/mL to 43.170 μg/mL， the reverse fold was 1.90， and the mRNA expression of MDR1 was significantly down-regulated （P＜0.05）. The results of GO enrichment analyses and KEGG pathway enrichment analyses indicated that the reversal of DOX resistance in breast cancer by IMP was mainly associated with the regulation of biological processes such as detoxification， multiple biological processes， and cell killing. The main pathway involved was the p53 signaling pathway， and the key targets mainly included constitutively photomorphogenic protein 1 （COP1）， cyclin E1 （CCNE1）， growth arrest and DNA damage-inducible protein 45A E-mail：tangxilan1983@163.com （GADD45A） and GADD45B. The results of the verification experiments showed that compared with DOX group， there was a trend of up-regulation of COP1 mRNA， and significant down- regulation of CCNE1， GADD45A， and GADD45B mRNA expression in IMP+DOX group （P＜0.05）. CONCLUSIONS The effect of IMP in ameliorating DOX resistance in breast cancer is related to its regulation of COP1， CCNE1， GADD45A and GADD45B targets in the p53 signaling pathway.

ObjectiveTo explore the role and mechanism of Hei Xiaoyaosan in regulating the protein kinase B （Akt）/glycogen synthase kinase-3β （GSK-3β）/nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway in cascade modulation of oxidative stress and apoptosis for preventing and treating Alzheimer's disease （AD）. MethodsNinety male SD rats of 4 months old were randomly assigned into a control group （n=10）， a sham group （with injection of 1 μL normal saline into bilateral hippocampi， n=10）， and a modeling group （with injection of 1 μL beta-amyloid 1-42 solution into bilateral hippocampi to induce AD， n=70）. One week after modeling， 50 successfully modeled rats were selected and randomly allocated into model， donepezil hydrochloride （0.45 mg·kg^-1）， and high-， medium-， and low-dose （15.30， 7.65， 3.82 g·kg^-1， respectively） Hei Xiaoyaosan groups. The rats were administrated with corresponding drugs once daily for six consecutive weeks. The Morris water maze was used to assess the learning and memory abilities of rats. Hematoxylin-eosin （HE） staining was performed to reveal hippocampal morphological changes in AD rats. Apoptosis in the hippocampal CA3 region was detected by terminal-deoxynucleotidyl transferase-mediated Nick end labeling. Immunofluorescence was used to visualize the expression of neuronal nuclear antigen （NeuN） in the CA1 region. Additionally， enzyme-linked immunosorbent assay was performed to assess the activities of glutathione peroxidase （GSH-Px）， glutathione-S-transferase （GST）， and catalase （CAT） in the hippocampus. Real-time PCR was conducted to measure the mRNA levels of Akt， GSK-3β， Nrf2， and HO-1， while Western blot was employed to determine the protein levels of phosphorylated Akt （p-Akt）/Akt， phosphorylated GSK-3β （p-GSK-3β）/GSK-3β， Nrf2， and HO-1. ResultsCompared with the control group， the model group on day 5 showed an increase in total swimming distance （P<0.01）， a reduction in the percentage of time spent in the target quadrant （P<0.01）， reduced and disarranged neurons， nuclear condensation， varying degrees of cellular damage， increased apoptosis of hippocampal neurons （P<0.01）， decreased NeuN content （P<0.01）， weakend activities of GSH-Px， GST， and CAT （P<0.01）， and down-regulated mRNA levels of Nrf2 and HO-1 （P<0.01） and protein levels of p-Akt/Akt， p-GSK-3β/GSK-3β， Nrf2， and HO-1 （P<0.01） in the hippocampus. Compared with the model group， donepezil hydrochloride and high， medium， and low doses of Hei Xiaoyaosan shortened the total swimming distance on day 5 （P<0.05， P<0.01）， increased the percentage of time spent in the target quadrant （P<0.05， P<0.01）， improved the arrangement and morphology of neurons， reduced nuclear condensation and the apoptosis rate of hippocampal neurons （P<0.01）， increased the NeuN content （P<0.01）， enhanced the activities of GSH-Px， GST， and CAT （P<0.05， P<0.01）， and up-regulated the mRNA levels of Nrf2 and HO-1 （P<0.05， P<0.01） and the protein levels of p-Akt/Akt， p-GSK-3β/GSK-3β， Nrf2， and HO-1 （P<0.05， P<0.01） in the hippocampus. ConclusionHei Xiaoyaosan can regulate the Akt/GSK-3β/Nrf2/HO-1 pathway to enhance the antioxidant stress capacity and inhibit neuron apoptosis to exert the neuroprotective effect， thereby ameliorating the cognitive dysfunction and pathological damage in AD rats.

ObjectiveTo explore the mechanism of Hei Xiaoyaosan in improving the cognitive function in Alzheimer's disease （AD） from cell apoptosis mediated by the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/nuclear factor kappa B （NF-κB） signaling pathway. MethodsFour-month-old SD male rats were randomly assigned into a blank group， a sham group， a model group， a donepezil hydrochloride （0.45 mg·kg^-1） group， and high-， medium-， and low-dose （15.30， 7.65， and 3.82 g·kg^-1， respectively） Hei Xiaoyaosan groups， with 10 rats in each group. The sham group received bilateral hippocampal injection of 1 μL normal saline， while the other groups received bilateral hippocampal injection of 1 μL beta-amyloid 1-42 （Aβ_1-42） solution for the modeling of AD. Rats were administrated with corresponding agents once a day for 42 consecutive days. The Morris water maze test was carried out to assess the learning and memory abilities of rats. Hematoxylin-eosin staining was employed to observe pathological changes in the hippocampus of rats. Enzyme-linked immunosorbent assay was employed to measure the levels of cysteinyl aspartate-specific proteinase-3 （Caspase-3）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. Western blot was employed to determine the protein levels of PI3K， Akt， and NF-κB. A cell model of AD was established by co-culturing Aβ_1-42 and PC12 cells in vitro. Cell viability and apoptosis were detected by the cell-counting kit 8 （CCK-8） assay and flow cytometry （FC）， respectively. ResultsAnimal experiments showed that compared with the blank group， the model group had a prolonged escape latency （P<0.01）， a reduced number of crossing platforms （P<0.01）， disarrangement and a reduced number of hippocampal neurons， up-regulated expression of Bax and Caspase-3， down-regulated expression of Bcl-2 （P<0.01）， decreased p-PI3K/PI3K and p-Akt/Akt levels， and an increased p-NF-κB/NF-κB level （P<0.01）. Compared with the model group， donepezil hydrochloride and high- and medium-dose Hei Xiaoyaosan shortened the escape latency and increased the number of crossing platforms （P<0.05， P<0.01）， improved the arrangement and increased the number of hippocampal neurons， down-regulated the expression levels of Bax and Caspase-3， up-reguated the expression level of Bcl-2 （P<0.05， P<0.01）， increased the p-PI3K/PI3K and p-Akt/Akt levels （P<0.05， P<0.01）， and reduced the p-NF-κB/NF-κB level （P<0.05， P<0.01）. Cell experiments showed that compared with the blank group， the model group exhibited an increased apoptosis rate （P<0.01）. Compared with the model group， the serum containing Hei Xiaoyaosan at various doses improved the cell viability （P<0.01）， and the serum containing Hei Xiaoyaosan at the high dose decreased the cell apoptosis （P<0.01）. ConclusionHei Xiaoyaosan may improve the learning and memory abilities of AD model rats by regulating cell apoptosis， while increasing the vitality and reducing the apoptosis rate of AD model cells via the PI3K/Akt/NF-κB signaling pathway.

ObjectiveTo investigate the effects of Hei Xiaoyaosan on cognitive impairment and the histone deacetylase sirtuin-1 （SIRT1）/tumor suppressor p53/solute carrier family 7 member 11 （SLC7A11） signaling pathway in the rat model of Alzheimer's disease （AD）. MethodsA total of 90 16-week-old SPF-grade SD male rats were randomly assigned in a blank group （n=10）， a sham group （n=10， with injection of 1 μL normal saline into the bilateral hippocampi）， and an AD modeling group （n=70， with injection of 1 μL β amyloid 1-42 solution into the bilateral hippocampi）. According to the random number table method， fifty successfully modeled rats were assigned into model， donepezil hydrochloride （0.45 mg·kg^-1）， and high-， medium-， and low-dose （15.30， 7.65， and 3.82 g·kg^-1， respectively） Hei Xiaoyaosan groups， and they were administrated with corresponding agents via gavage once a day for 42 consecutive days. Morris water maze test was carried out to examine the cognitive function of rats. Nissl staining was employed to observe the morphology of hippocampal neurons in each group， and Prussian blue staining was used to detect iron deposition in the hippocampal tissue. Biochemical kits were used to measure the levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， and iron ion （Fe²⁺） in the hippocampal tissue. Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were employed to determine the protein and mRNA levels， respectively， of SIRT1， p53， SLC7A11， glutathione peroxidase 4 （GPX4）， and acyl-CoA synthetase long-chain family member 4 （ACSL4） in the hippocampus. ResultsCompared with the blank group， the model group showed reductions in target quadrant movement distance （P<0.01） and target quadrant residence time （P<0.05）， disarrangement of hippocampal neurons， increased ferroptosis deposition in the hippocampus， a lowered level of SOD， risen levels of MDA and Fe²⁺ （P<0.05， P<0.01）， down-regulated protein and mRNA levels of SIRT1， SLC7A11， and GPX4 （P<0.05， P<0.01）， up-regulated protein and mRNA levels of p53 and ACSL4 （P<0.01）， and aggravated pathological process of AD. Compared with the model group， donepezil hydrochloride extended the target quadrant residence time and the target quadrant movement distance （P<0.05， P<0.01）. High- and medium- doses of Hei Xiaoyaosan extended the target quadrant residence time and the target quadrant movement distance （P<0.05， P<0.01）， improved the neuron arrangement and reduced the ferroptosis deposition in the hippocampus， elevated the SOD level， lowered the MDA and Fe²⁺ levels （P<0.05， P<0.01）， up-regulated the protein and mRNA levels of SIRT1， SLC7A11， and GPX4 （P<0.01， P<0.05）， and down-regulated the protein and mRNA levels of p53 and ACSL4 （P<0.05， P<0.01）. ConclusionHei Xiaoyaosan can regulate the SIRT1/p53/SLC7A11 signaling pathway to mitigate oxidative stress and inhibit ferroptosis， thereby ameliorating the cognitive dysfunction in AD rats.

ObjectiveTo investigate the preventive effect and mechanism of Dendrobium officinale （DO） on non-alcoholic fatty liver disease （NAFLD） by network pharmacology and animal experiments. MethodsDO components in blood after administration were identified and analyzed using ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-QE-HF-MS/MS）. Network pharmacology and molecular docking methods were employed to obtain active ingredients and potential targets of DO for NAFLD control. High-fat feeds were used to replicate the NAFLD rat model. Biochemical kits were used for detecting the expression levels of blood lipids， hepatic lipids， and liver functions of rats. Hematoxylin-eosin （HE） staining and oil red O staining were employed to observe pathological changes in rat liver， and real-time fluorescence quantitative PCR （Real-time PCR） assay was performed to validate potential targets obtained from the network pharmacology analysis. ResultsA total of 13 DO components were identified in blood， including berberine， dihydrosanguinarine， and oxypeucedanin. A total of 14 potential targets were screened through network pharmacology， including Forkhead box protein O1 （FoxO1）， epidermal growth factor receptor （EGFR）， and insulin-like growth factor 1 （IGF-1R）， involving pathways such as the advanced glycation end product （AGE）/receptor for AGE （RAGE） signaling pathway， blood lipids and atherosclerosis， insulin resistance， and FoxO signaling. The results of animal experiments showed that the NAFLD rat model was successfully replicated. After the preventive treatment with DO for NAFLD rats， the indexes of blood lipids， hepatic lipids， and liver function were normalized； lipid deposition and lesions in the liver were significantly improved； the expression level of FoxO1 mRNA in the liver was significantly reduced （P<0.05）， and the mRNA expression levels of phosphatidylinositide 3-kinases （PI3K）， protein kinase B （Akt）， EGFR， and IGF-1R were significantly increased （P<0.05）. ConclusionDO has a preventive effect on NAFLD rats， and the mechanism of action may be related to the modulation of IGF1R and EGFR targets and activation of the PI3K/Akt/FoxO1 signaling pathway.

OBJECTIVE To study the effects of enteral immune microecological nutrition combined with ω-3 fish oil fat emulsion on postoperative recovery， immune function， liver function and inflammation level in patients with hepatocellular carcinoma resection， as well as the safety of the medication. METHODS A total of 106 patients with hepatocellular carcinoma admitted to our Hospital from June 2020 to December 2023 were selected and divided into control group and study group according to the random number table method， with 53 cases in each group. After undergoing hepatocellular carcinoma resection， control group was given Intacted protein enteral nutrition solution+Enhanced enteral immune microecological nutrition， and the study group was given ω-3 fish oil fat emulsion injection based on the control group. The clinical indicators （postoperative exhaust time， defecation time， postoperative ambulation， and hospital stay）， liver function indicators [alanine transaminase （ALT）， lactate dehydrogenase （LDH）， aspartate transaminase （AST）]， immune function indexes （CD3+ ， CD4+ ， CD8+ ， CD4+/CD8+）， inflammatory factor indexes [tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， IL-6， IL-8]， and indicators of intestinal mucosal barrier [D-lactic acid， intestinal fatty acid binding protein （I-FABP）] were compared between 2 groups， and the occurrence of ADR was recorded. RESULTS Compared with the control group， the postoperative exhaust time， postoperative defecation time， and hospital stay of the study group were shortened significantly， and postoperative ambulation increased significantly （P＜0.05）. After treatment， ALT， LDH， AST， CD8+， inflammatory factors， D-lactic acid and I-FABP of 2 groups were significantly lower than before treatment， and the study group was significantly lower than the control group （P＜0.05）； CD4+， CD3+， and CD4+/CD8+ of two groups were significantly higher than before treatment， and the study group was significantly higher than the control group （P＜0.05）. There was no significant difference in the incidence of ADR between 2 groups （P＞0.05）. CONCLUSIONS Enteral immune microecological nutrition combined with ω-3 fish oil fat emulsion injection can shorten the recovery time of patients after hepatocellular carcinoma resection， improve immune function， reduce inflammatory response， and improve liver function with good safety.

Intelligent algorithms， as the core element of artificial intelligence （AI）， have played an irreplaceable and key role in fields such as medical AI-assisted diagnosis and treatment. Meanwhile， they have also presented new features such as the complexity of interdisciplinary integration， the conflict of ethical convergence in science and technology， the duality of risks and benefits coexistence， and the concealment of algorithm black box calculations. These features lead to numerous ethical challenges， such as algorithm bias， data security， and difficulty in tracing responsibility. Therefore， it is urgent to break through these challenges by establishing a micro-ethical institutional system for intelligent medical algorithms， setting up an ethical supervision mechanism for the operation of intelligent medical algorithms， improving ethical norms for data security protection of intelligent medical algorithms， and strengthening ethical standards for the identification of the main responsibility of intelligent medical algorithms.

The discussion on the connotation of children’s subjectivity is not only a response to the lack of children’s subjectivity at the current stage of health management, but also a reference for children’s medical science popularization. Based on the perspective of social critical theory, this study used empirical research methods to review the "Dream Medical College" project of Children’s Hospital of Fudan University. The current situation and influencing factors of health management experience of 1 520 children participating in the "Dream Medical College" project were analyzed. The study showed that 96.35% of 1 316 subjects had diagnosis and treatment experience in specialized hospitals, and the overall negative emotional performance was at a low level (0~12 points). There was significant correlation between diagnosis and treatment, invasive experience and children’s emotional performance (P<0.05). The study revealed that the diagnosis and treatment field is the main practice place of children’s health management, while the subjective of children with different diagnosis and experience perform significantly different. Children over 4 years old have better language anxiety than physical anxiety when receiving diagnosis and treatment. Although medical science popularization is an important practical form of children’s health management, it lacks the science popularization content of invasive diagnosis and treatment and emotional management, and creative popular science form is more suitable for children with long-term and frequent diagnosis and treatment experience.

Objective:To investigate the incidence and risk factors of deep vein thrombosis(DVT)in patients with rheumatoid arthritis(RA).Methods:The clinical data of RA patients who were hospi-talized in the Department of Rheumatology and Immunology of Aerospace Center Hospital from May 2015 to September 2021 was retrospectively analyzed,including demographic characteristics,concomitant diseases,laboratory examinations(blood routine,biochemistry,coagulation,inflammatory markers,rheumatoid factor,antiphospholipid antibodies and lupus anticoagulant,etc.)and treatment regimens.The patients were compared according to the presence or absence of DVT,and the t test,Mann-Whitney U test or Chi-square test were applied to screen for relevant factors for DVT,followed by Logistic regres-sion analysis to determine risk factors for DVT in patients with RA.Results:The incidence of DVT in the RA patients was 9.6％(31/322);the median age of RA in DVT group was significantly older than that in non-DVT group[64(54,71)years vs.50(25,75)years,P＜0.001];the level of disease activity score using 28 joints(DAS28)-erythrocyte sedimentation rate(ESR)in DVT group was higher than that in non-DVT group[5.2(4.5,6.7)vs.4.5(4.5,5.0),P＜0.001];the incidence of hypertension,chronic kidney disease,fracture or surgery history within 3 months,and varicose veins of the lower ex-tremities in DVT group was higher than that in non-DVT group(P＜0.001).The levels of hemoglobin and albumin in DVT group were significantly lower than that in non-DVT group(P=0.009,P=0.004),while the D-dimer level and rheumatoid factor positive rate in DVT group were significantly higher than that in non-DVT group(P＜0.001).The use rate of glucocorticoid in DVT group was higher than that in non-DVT group(P=0.009).Logistic regression analysis showed that the age(OR=1.093,P＜0.001),chronic kidney disease(OR=7.955,P=0.005),fracture or surgery history with-in 3 months(OR=34.658,P=0.002),DAS28-ESR(OR=1.475,P=0.009),and the use of glu-cocorticoid(OR=5.916,P=0.003)were independent risk factors for DVT in RA patients.Conclu-sion:The incidence of DVT in hospitalized RA patients was significantly increased,in addition to tradi-tional factors,such as age and chronic kidney disease,increased DAS28-ESR level and the use of glu-cocorticoid were also independent risk factors for DVT.

Objective:To investigate the inhibitory effect of lycium barbarum polysaccharide(LBP)on apoptosis of Schwann cells(SCs)and its related mechanisms.Methods:The autophagy model was prepared by starvation treatment of RSC96 cells for 12 h,and the expressions of autophagy related proteins LC3 and p62 were detected by Western Blot.Cell Counting Kit-8(CCK-8)kits were used to detect the optimal concentration of LBP.RSC96 cells were randomly divided into Control group,Starvation group and Starvation+LBP group.The expressions of autophagy associated pro-teins(LC3,p62)and myelin associated proteins(p75NTR,PMP22,S100β)were detected by Western Blot or immu-nofluorescence staining.Annexin V/PI fluorescence staining was used to detect apoptosis of the cells.The cell cycle was analyzed by flow cytometry.Western Blot analysis of phosphorylation levels of pathway proteins Erk1/2 and Akt.Results:CCK8 results showed that the viability of damaged RSC96 cells was the best when LBP was 300 μg/ml.Com-pared with Control group,LC3-Ⅱ/LC3-I levels in Starvation group were significantly increased(P＜0.05).Compared with Starvation group,the proportion of apoptotic and necrotic cells in Starvation+LBP group was significantly de-creased,and the proportion of cells in S and G2/M stages was increased.The expression levels of LC3-Ⅱ,p75NTR,PMP22 and S100β were increased,while the expression levels of autophagy substrate protein p62 were decreased.In-creased expression of pathway protein p-Erk1/2(P＜0.05),while the expression of p-Akt protein decreased slightly.Conclusion:LBP can inhibit the apoptosis of SCs and promote the expression of myelin-related proteins by enhancing autophagy,which is related to the activation of Erk1/2 and/or the inhibition of Akt.