In order to explore the possible role and molecular mechanism of the combined action of leech and bear bile in liver and gallbladder diseases, this study first used network pharmacology methods to screen the components and targets of leech and bear bile, as well as the related target genes of liver and gallbladder diseases. The selected key genes were subjected to interaction network and GO/KEGG enrichment analysis. Then, using sodium oleate induced HepG2 cell lipid deposition model and DL-ethionine induced mouse fatty liver model, the activity of leech and bear bile alone and in combination in reducing liver fat was evaluated in vitro and in vivo, and the expression of key pathway related proteins suggested by network pharmacology was detected by Western blot. The results of network pharmacology analysis showed that the active ingredients of leech and bear bile have 295 intersecting targets with liver and gallbladder related diseases, involving more than 200 signaling pathways, including the PI3K/Akt signaling pathway and phospholipase D signaling pathway closely related to glucose and lipid metabolism. The results of in vitro validation experiments showed that both leech and bear bile, alone and in combination, can significantly inhibit the lipid deposition induced by sodium oleate in human liver cells, reduce the triacylglycerol level in cell culture supernatant, and inhibit the lipid content in liver cells. The observation results of Nile red staining confocal microscopy showed that the combination of leech and bear bile had better activity in reducing lipid deposition in liver cells compared to using them alone. In a mouse fatty liver model, the combination of leech and bear bile can better reduce elevated organ indices, blood lipids, and liver lipid levels, as well as lower the levels of serum liver injury biomarkers. The animals used in this experiment and related disposal meet the requirements of animal welfare. Before the experiment, it was reviewed and approved by IACUC, Institute of Materia Medica, Chinese Academy of Medical Sciences. The Western blot experiment results showed that the combination of leech and bear bile can significantly upregulate the expression levels of p-PI3K and p-Akt proteins, and increase the p-PI3K/PI3K and p-Akt/Akt ratios, which is consistent with the predicted results of network pharmacology. The combination of leech and bear bile has great potential for treating fatty liver disease, and activating the PI3K/Akt pathway may be one of the important mechanisms for reducing lipid deposition in liver cells.

Ferroptosis, a programmed cell death modality discovered and defined in the last decade, is primarily induced by iron-dependent lipid peroxidation. At present, it has been found that ferroptosis is involved in various physiological functions such as immune regulation, growth and development, aging, and tumor suppression. Especially its role in tumor biology has attracted extensive attention and research. Breast cancer is one of the most common female tumors, characterized by high heterogeneity and complex genetic background. Triple negative breast cancer (TNBC) is a special type of breast cancer, which lacks conventional breast cancer treatment targets and is prone to drug resistance to existing chemotherapy drugs and has a low cure rate after progression and metastasis. There is an urgent need to find new targets or develop new drugs. With the increase of studies on promoting ferroptosis in breast cancer, it has gradually attracted attention as a treatment strategy for breast cancer. Some studies have found that certain compounds and natural products can act on TNBC, promote their ferroptosis, inhibit cancer cells proliferation, enhance sensitivity to radiotherapy, and improve resistance to chemotherapy drugs. To promote the study of ferroptosis in TNBC, this article summarized and reviewed the compounds and natural products that induce ferroptosis in TNBC and their mechanisms of action. We started with the exploration of the pathways of ferroptosis, with particular attention to the System X_c^--cystine-GPX4 pathway and iron metabolism. Then, a series of compounds, including sulfasalazine (SAS), metformin, and statins, were described in terms of how they interact with cells to deplete glutathione (GSH), thereby inhibiting the activity of glutathione peroxidase 4 (GPX4) and preventing the production of lipid peroxidases. The disruption of the cellular defense against oxidative stress ultimately results in the death of TNBC cells. We have also our focus to the realm of natural products, exploring the therapeutic potential of traditional Chinese medicine extracts for TNBC. These herbal extracts exhibit multi-target effects and good safety, and have shown promising capabilities in inducing ferroptosis in TNBC cells. We believe that further exploration and characterization of these natural compounds could lead to the development of a new generation of cancer therapeutics. In addition to traditional chemotherapy, we discussed the role of drug delivery systems in enhancing the efficacy and reducing the toxicity of ferroptosis inducers. Nanoparticles such as exosomes and metal-organic frameworks (MOFs) can improve the solubility and bioavailability of these compounds, thereby expanding their therapeutic potential while minimizing systemic side effects. Although preclinical data on ferroptosis inducers are relatively robust, their translation into clinical practice remains in its early stages. We also emphasize the urgent need for more in-depth and comprehensive research to understand the complex mechanisms of ferroptosis in TNBC. This is crucial for the rational design and development of clinical trials, as well as for leveraging ferroptosis to improve patient outcomes. Hoping the above summarize and review could provide references for the research and development of lead compounds for the treatment for TNBC.

OBJECTIVE To explore the effects of prescription pre-review system on rational drug use and off-label drug use management in outpatient and emergency department. METHODS A retrospective analysis was conducted on outpatient and emergency department prescription data from three phases in our hospital： January to May 2023 （silent review phase， control group）， June to October 2023 （systematic automatic review phase， intervention group 1）， and November 2023 to March 2024 （phase combining systematic automatic review with centralized feedback from pharmacists to physicians regarding irrational prescriptions， intervention group 2）. These phases followed the implementation of our hospital’s pre-prescription review software. Statistical analysis of the prompt rate of alert， rate of irrational prescriptions， registered the off-label drug use rate and false positive irrationality prescription rate were conducted. Meanwhile， the composition of irrational prescriptions was analyzed， and evidence- based evaluation of the off-label drug use proposed by clinicians was also conducted. RESULTS Compared with control group， the prompt rate of alert and the rate of irrational prescriptions in intervention group 1 were all decreased significantly after receiving pop-up notification， with statistically significant differences （P＜0.05）. With the help of system warning and the pharmacists feedback， the prompt rate of alert and the rate of irrational prescriptions declined further in the intervention group 2， but there was no statistically significant difference when compared with intervention group 1 （P＞0.05）. The main type of irrational drug use was improper administration routes. When comparing intervention group 1 with the control group， as well as intervention group 2 with intervention group 1， a significant decrease in the rate of improper administration routes was observed， with statistically significant differences （P＜0.05）. Compared with control group， there was no significant difference in the registered off-label drug use rate of intervention group 1 and intervention group 2 （P＞0.05）. The doctor’s awareness of off-label drug use registration increased due to the real-time alerts from the pre-prescription review software， along with the pharmacists’ regular summarization and feedback. Total 13 items registrations of off-label drug use were proposed by clinicians from June 2023 to March 2024， all of which were supported by evidence of varying levels； among them， 3 items received FDA approval， 4 items were included in the Micromedex database， and the remaining 6 items were supported by evidence from system reviews or randomized controlled trials. CONCLUSIONS Prescription pre-review system can improve the level of rational drug use and assist in the standardized management of off-label drug use.

ObjectiveRepetitive transcranial magnetic stimulation (rTMS) has demonstrated efficacy in enhancing neurocognitive performance in Alzheimer’s disease (AD), but the neurobiological mechanisms linking synaptic pathology, neural oscillatory dynamics, and brain network reorganization remain unclear. This investigation seeks to systematically evaluate the therapeutic potential of rTMS as a non-invasive neuromodulatory intervention through a multimodal framework integrating clinical assessments, molecular profiling, and neurophysiological monitoring. MethodsIn this prospective double-blind trial, 12 AD patients underwent a 14-day protocol of 20 Hz rTMS, with comprehensive multimodal assessments performed pre- and post-intervention. Cognitive functioning was quantified using the mini-mental state examination (MMSE) and Montreal cognitive assessment (MOCA), while daily living capacities and neuropsychiatric profiles were respectively evaluated through the activities of daily living (ADL) scale and combined neuropsychiatric inventory (NPI)-Hamilton depression rating scale (HAMD). Peripheral blood biomarkers, specifically Aβ1-40 and phosphorylated tau (p-tau181), were analyzed to investigate the effects of rTMS on molecular metabolism. Spectral power analysis was employed to investigate rTMS-induced modulations of neural rhythms in AD patients, while brain network analyses incorporating topological properties were conducted to examine stimulus-driven network reorganization. Furthermore, systematic assessment of correlations between cognitive scale scores, blood biomarkers, and network characteristics was performed to elucidate cross-modal therapeutic associations. ResultsClinically, MMSE and MOCA scores improved significantly (P<0.05). Biomarker showed that Aβ1-40 level increased (P<0.05), contrasting with p-tau181 reduction. Moreover, the levels of Aβ1-40 were positively correlated with MMSE and MOCA scores. Post-intervention analyses revealed significant modulations in oscillatory power, characterized by pronounced reductions in delta (P<0.05) and theta bands (P<0.05), while concurrent enhancements were observed in alpha, beta, and gamma band activities (all P<0.05). Network analysis revealed frequency-specific reorganization: clustering coefficients were significantly decreased in delta, theta, and alpha bands (P<0.05), while global efficiency improvement was exclusively detected in the delta band (P<0.05). The alpha band demonstrated concurrent increases in average nodal degree (P<0.05) and characteristic path length reduction (P<0.05). Further research findings indicate that the changes in the clinical scale HAMD scores before and after rTMS stimulation are negatively correlated with the changes in the blood biomarkers Aβ1-40 and p-tau181. Additionally, the changes in the clinical scales MMSE and MoCA scores were negatively correlated with the changes in the node degree of the alpha frequency band and negatively correlated with the clustering coefficient of the delta frequency band. However, the changes in MMSE scores are positively correlated with the changes in global efficiency of both the delta and alpha frequency bands. Conclusion20 Hz rTMS targeting dorsolateral prefrontal cortex (DLPFC) significantly improves cognitive function and enhances the metabolic clearance of β-amyloid and tau proteins in AD patients. This neurotherapeutic effect is mechanistically associated with rTMS-mediated frequency-selective neuromodulation, which enhances the connectivity of oscillatory networks through improved neuronal synchronization and optimized topological organization of functional brain networks. These findings not only support the efficacy of rTMS as an adjunctive therapy for AD but also underscore the importance of employing multiple assessment methods—including clinical scales, blood biomarkers, and EEG——in understanding and monitoring the progression of AD. This research provides a significant theoretical foundation and empirical evidence for further exploration of rTMS applications in AD treatment.

OBJECTIVE To investigate the effects of echinacoside （ECH） on renal injury in uremia （URE） rats and its mechanism. METHODS URE model of the rat was established by 5/6 nephrectomy. Successfully modeled rats were grouped into uremia group （URE group）， ECH low-dose [10 mg/（kg·d）] group， ECH medium-dose [20 mg/（kg·d）] group， ECH high-dose [40 mg/（kg·d）] group， ECH high-dose+anisomycin [p38 mitogen-activated protein kinase （p38 MAPK） pathway activator] group [ECH-H+Ani group， 40 mg/（kg·d） ECH +2 mg/（kg·d） anisomycin]， with a sham operation group， 12 mice in each group. Each drug group was given corresponding ECH intragastrically， while ECH-H+Ani group was further injected with anisomycin via the tail vein， once a day， for 8 consecutive weeks. The serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， IL-6， blood urea nitrogen （BUN）， β2-microglobulin （β2-MG）， serum creatinine （Scr）， neutrophil gelatinase-associated lipocalin （NGAL）， kidney injury molecule-1 （KIM-1）， cystatin C （Cys-C） and 24 h urine protein （24 h UP） as well as the levels of malondialdehyde （MDA） and superoxide dismutase （SOD） activity in renal tissue were all detected； pathological changes of renal tissue were observed； the rate of positive expression of α-smooth muscle protein （α-SMA） and E-cadherin， and the phosphorylation of p38 MAPK and nuclear factor-κB （NF-κB） p65 were determined in renal tissue of rats. RESULTS Compared with URE group， glomerular swelling， damage and necrosis of renal tubular epithelial cells and inflammatory cell infiltration were relieved significantly in ECH groups. The renal injury score， levels of TNF-α， IL-1β， IL-6， BUN， Scr， β2-MG， 24 h UP， NGAL， KIM- 1， Cys-C and MDA， the positive expression rate of α-SMA in renal tissue， the phosphorylation of p38 MAPK and NF-κB p65 were decreased in dose-dependent manner， while SOD activity and the positive expression rate of E-cadherin were obviously increased in dose-dependent manner （P＜0.05）. Anisomycin significantly attenuated the improvement effect of high-dose ECH on renal injury in URE rats （P＜0.05）. CONCLUSIONS ECH may inhibit inflammation and oxidative stress， enhance renal function， and improve renal injury in uremic rats by inhibiting the activation of p38 MAPK/NF-κB signaling pathway.

Objective To investigate the impact of emodin(EM)on vascular endothelial cell injury in rats with diabetes macroangiopathy by regulating hypoxia inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)signaling pathway.Methods SD rats were divided into blank group and modeling group,the rats in the modeling group were fed with high fat and high sugar combined with N-nitro-L-arginine methyl ester to build the diabetes macroangiopathy model,and the blank group was fed with ordinary diet.The vascular endothelial cells successfully isolated from the thoracic aorta of rats in blank group and modeling group were named control group and model group,respectively.The vascular endothelial cells in the modeling group were divided into model group,dimethyloxallyl glycine(DMOG)group(10 μmol·L-1DMOG),combined group(80 mg·L-1EM+10 μmol·L-1 DMOG)and experimental-L,-M,-H groups(20,40,80 mg·L-1 EM).The apoptosis of rat vascular endothelial cells was detected by flow cytometry;Western blot was applied to detect the expression of HIF-1αand VEGF proteins in rat vascular endothelial cells.Results The apoptosis rates of vascular endothelial cells in experimental-M,-H groups,DMOG group,combined group,model group and control group were(10.18±0.36)％,(6.28±0.20)％,(24.96±1.18)％,(12.36±0.49)％,(18.76±0.68)％and(4.59±0.26)％;HIF-1α protein levels were 0.96±0.07,0.78±0.06,2.03±0.12,1.05±0.13,1.58±0.12 and 0.69±0.05;VEGF protein levels were 0.59±0.05,0.23±0.02,0.98±0.06,0.63±0.04,0.86±0.07 and 0.11±0.01.The above indexes in the model group were compared with the control,DMOG,experimental-M and experimental-H groups,and the above indexes in the combined group were compared with the experimental-H group,and the differences were statistically significant(all P＜0.05).Conclusion EM may inhibit HIF-1α/VEGF pathway to improve vascular endothelial cell injury in rats with diabetes macroangiopathy.

Nowadays,with the continuous deepening and development of vocational education teaching reform,medical higher vocational education always takes moral education as the fundamental task.As an independent type of education,vocational education should always deepen the integration of industry and education and the integration of science and education.Through the teaching research of"problem chain+course ideological and political case",this study innovates the coordinated education team of drug nursing curriculum,the collaborative education method and the collaborative education evaluation,and improves the teaching effect.

Objective To observe the protective effect of polyene phosphatidylcholine on palmitic acid-induced lipotoxicity in hepatocytes and explore the possible mechanism.Methods HepG2 cells were continuously stimulated with 0.4 mmol·L-1palmitic acid filtrate for 24 h at logarithmic growth stage,and 0,0.5,1.0 and 2.0 mg·mL-1 polyene phosphatidylcholine solution were added at the same time,which were set as model group and experimental-L,-M,-H groups,respectively.Cells without any treatment were taken as control group.Methyl thiazolyl tetrazolium method was used to detect cell viability.Enzyme-linked immunosorbent assay was used to detect the content of triglyceride(TG)in cells.Probe method was used to detect mitochondrial function.Western blotting was used to detect the protein expression of protein kinase B(AKT)and forkhead box transcription factor O1(FoxO1).Results The cell viability rates of the experimental-M,-H groups,model group and control group were(74.31±8.69)％,(78.13±9.34)％,(63.67±7.40)％and(82.47±12.30)％;the cellular TG contents were(11.45±3.06),(8.34±2.05),(17.63±5.12)and(5.12±1.32)mg·g-1 protein;the mitochondrial reactive oxygen species production levels were(0.47±0.06),(0.39±0.05),(0.62±0.09)and(0.31±0.05)U·mg-1 protein;the cellular expression levels of FoxO1 protein were 0.27±0.05,0.22±0.03,0.41±0.08 and 0.07±0.02;the p-AKT/AKT ratios were 0.23±0.07,0.34±0.06,0.09±0.01 and 0.38±0.05,respectively.The differences of the above indicators were statistically significant among the experimental-M,-H groups and model group(all P＜0.05).Conclusion Polyene phosphatidylcholine can reduce palmitic acid-induced lipotoxicity in hepatocytes,improve hepatocyte viability and mitochondrial function,and its mechanism may be related to the regulation of AKT/FoxO1 signaling pathway activity.

ObjectiveTo investigate the therapeutic effect of ganoderic acid A （GA-A） on a mouse model of concanavalin A （ConA）-induced autoimmune hepatitis （AIH）. MethodsA total of 35 mice were randomly divided into control group （NC group）， model group （ConA group）， and low-， middle-， and high-dose GA-A treatment groups （GA-A-L， GA-A-M， and GA-A-H groups， respectively）， with 7 mice in each group. ConA was injected via the caudal vein of mice to establish a classic mouse model of AIH， and different doses of GA-A were administered via intraperitoneal injection 1 hour later for treatment. Proteomic techniques were used to investigate the protective mechanism of GA-A on hepatocytes， and HL-60 cells were differentiated into dHL-60 neutrophils by all-trans retinoic acid in vitro to validate the mechanism of action of GA-A. Related indicators were measured， including inflammatory markers （the activities of serum alanine aminotransferase ［ALT］ and aspartate aminotransferase ［AST］， HE staining， and inflammation-related genes）， apoptosis markers （TUNEL staining）， neutrophils， and neutrophil extracellular trap （NET） markers （myeloperoxidase ［MPO］， citrullinated histone H3 ［CitH3］， Ly6G， and free double-stranded DNA ［dsDNA］）， and p38 phosphorylation markers. The independent samples t-test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the NC group， the ConA group had significant increases in the serum levels of ALT and AST （both P<0.001）， and compared with the ConA group， GA-A treatment significantly reduced the levels of ALT and AST （both P<0.01）. HE staining showed that the mice in the ConA group had significant liver necrosis， while GA-A treatment significantly reduced the area of liver necrosis and the number of TUNEL-positive cells （both P<0.05）. Compared with the ConA group， the GA-A group had significant reductions in the expression levels of the inflammatory factors interleukin-6， tumor necrosis factor-α， and interferon gamma in serum and liver tissue （all P<0.05）. The proteomic analysis showed that GA-A alleviated ConA-induced acute immune liver injury by inhibiting the release of NET and the p38 MAPK pathway. Immunofluorescent staining of mouse liver tissue showed that compared with the ConA group， the GA-A group had significant reductions in the number of MPO-positive neutrophils and the number of cells with positive Ly6G and CitH3 （all P<0.01）. Western Blot and dsDNA testing showed that GA-A significantly inhibited the levels of the NET markers dsDNA and CitH3 and the level of p38 phosphorylation in liver tissue and dHL-60 cells （all P<0.05）. ConclusionGA-A alleviates liver inflammatory response and hepatocyte death by inhibiting the p38 MAPK pathway and the release of NET， thereby alleviating ConA-induced acute immune liver injury. This study provides a theoretical basis for the use of GA-A to treat immune liver injury by regulating neutrophil function.

Objective: To assess the efficacy and safety of combining traditional Chinese medicine (TCM), specifically Chinese herbal medicine (CHM), with Western medicine (WM), compared to WM alone to treat breast cancer endocrine therapy-related osteoporosis (BCET-OP) by meta-analysis. Methods: Thirty-eight randomized controlled trials involving 2170 participants were analyzed. Eight databases were searched for articles published between inception and December 2023. Quality assessment was performed using the Risk of Bias 2 tool. Results: Significant increases were observed in the TCM-WM group in lumbar vertebrae bone mineral density (BMD) (P < .001, mean difference (MD) = 0.07, 95% confidence interval (CI): 0.06 to 0.08), lumbar vertebrae T-score (P = .0005, MD = 0.21, 95%CI: 0.09 to 0.33) and collum femoris BMD (P = .01, MD = 0.10, 95%CI: 0.02 to 0.19). No significant difference was observed between the groups in the collum femoris T-score and estradiol levels. Bone gla-protein levels were significantly increased in the TCM-WM group (P = .0002, MD = 0.52, 95%CI: 0.25 to 0.79). Beta-CrossLaps decreased significantly in the TCM-WM group (P = .0008, MD = −0.10, 95%CI: −0.16 to −0.04). No significant difference was observed between the TCM-WM and WM groups in alkaline phosphatase, in procollagen type I N-terminal propeptide, and in the Kupperman index. The visual analog score (VAS) was decreased in the TCM-WM group compared to the WM group (P < .001, MD = −1.40, 95%CI: −1.94 to −0.87). No significant difference in adverse events was observed between the two groups. Conclusion Combining CHM with WM in patients with BCET-OP significantly improved BMD, T-score, and certain bone turnover markers and reduced the VAS score, indicating potential benefits for bone health and related pain. Adverse event analysis revealed no differences between the groups, supporting the feasibility of the combination therapy. However, further research, particularly in diverse populations, is required.