Objective: To systematically elucidate the molecular mechanisms and core targets underlying the anti-hepatocellular carcinoma (HCC) effects of icariin through integrated network pharmacology and experimental validation. Methods: Potential targets of icariin were screened using the PubChem database and SwissTargetPrediction platform, followed by intersection analysis with HCC-related genes from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to characterize the biological functions of candidate targets. Key genes were identified using the random survival forest algorithm, and their associations with the tumor microenvironment were evaluated through immune infiltration analysis. Molecular docking was employed to predict the binding affinity between icariin and its core targets, which was subsequently validated by in vitro enzyme inhibition assays. Functional targets were determined through overexpression experiments in HepG2 cells, and mechanistic investigations were conducted using Western blot and co-immunoprecipitation techniques. In vivo anti-tumor efficacy was evaluated using a subcutaneous HepG2 xenograft mouse model by monitoring tumor volume progression and endpoint tumor weight, and the impact of polo-like kinase 1 (PLK1) overexpression on icariin-mediated tumor growth inhibition was assessed. Results: Network pharmacology analysis identified 36 common targets between icariin and HCC, which were primarily enriched in hypoxia-inducible factor-1 (HIF-1), phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), and forkhead box O (FoxO) signaling pathways. Among these, PLK1, ATP binding cassette subfamily C member 1 (ABCC1), and matrix metallopeptidase 3 (MMP3) were identified as key genes, with their high expression significantly associated with poor patient prognosis (P < 0.0001, P = 0.004, and P = 0.03, respectively). Immune infiltration analysis revealed significant correlations between these three genes and various immune cell types, suggesting their involvement in modulating the tumor immune microenvironment. Molecular docking predicted stable binding between icariin and these targets, and in vitro enzymatic assays confirmed that icariin (20 µmol/L) exhibited the highest inhibitory rate against PLK1 (49.67% ± 4.19%), significantly greater than that against ABCC1 (24.33% ± 3.40%) and MMP3 (38.00% ± 3.06%). Functional validation demonstrated that PLK1 overexpression reversed icariin-mediated inhibition of HepG2 cell proliferation (P < 0.05), whereas ABCC1 or MMP3 overexpression showed no such effect, indicating PLK1 as the primary functional target of icariin. Mechanistic studies revealed that icariin specifically reduced PLK1 phosphorylation levels and disrupted its interaction with forkhead box M1 (FoxM1). In vivo experiments confirmed that PLK1 overexpression significantly attenuated icariin-induced suppression of tumor growth in xenograft mice (P < 0.001). Conclusion PLK1 is a critical target mediating the anti-HCC effects of icariin through inhibition of the PLK1-FoxM1 axis, providing a mechanistic basis for the clinical development of icariin as an HCC therapeutic agent.

Objective:To investigate the protective effect of myrislignan（MRL）on concanavalin A（Con A）-induced autoimmune hepatitis（AIH）.Methods:C57BL/6J mice were divided into the following groups using a random number table，with five mice in each group：control group，MRL group，model group（Con A group），and MRL pretreatment group（MRL+Con A group）. MRL was injected intraperitoneally at a dose of 30 μg/g；3 h after pretreatment，Con A（18 μg/g）was administrated by intravenous injection；mouse livers and serum samples were collected 12 h after injection for measuring serum transaminase levels and liver cell apoptosis. The mRNA and protein expression levels of IL-6，IL-12，and TNF-α were measured using qRT-PCR and ELISA. Flow cytometry was performed to detect the proportion and activation status of macrophages in liver tissues. Bone marrow-derived macrophages（BMDMs）were isolated and induced in vitro to analyze the regulatory effect of MRL on macrophages. One-way analysis of variance was used to compare the differences in various indicators among groups. Results:Compared with the Con A group，MRL（30 μg/g）pretreatment significantly reduced alanine aminotransferase（ P<0.05）and aspartate transaminase（ P<0.01）levels，attenuated liver oxidative stress（increased superoxide dismutase activity，while decreased levels of malondialdehyde and myeloperoxidase；all P<0.05），and suppressed hepatocyte apoptosis（ P<0.01）. Both in vivo and in vitro experiments confirmed that MRL（30 μg/g）could reduce the proportion of M1 macrophages（ in vivo： P<0.05； in vitro：all P<0.001）and inhibit macrophage activation（ in vivo： P<0.01； in vitro：all P<0.05）. Conclusion:MRL effectively prevents Con A-induced autoimmune hepatitis by inhibiting liver cell apoptosis，attenuating liver oxidative stress，suppressing M1 macrophage polarization，and reducing inflammatory cytokine expression.

Objective:To investigate the effects and mechanisms of subchronic exposure to pyrethrin on the mice nervous system.Methods:Twenty-four male mice were randomly divided into a control group,low-,medium-,and high-dose groups,and were exposed continuously for 28 days.The control group received corn oil.The general condi-tion of the mice was observed,and the body weight and brain organ coefficient were measured.Neurobehavioral tests were conducted after the exposure period.The histopathological changes of the hippocampus in mice were observed by HE and nissl staining.The activities of lactate dehydrogenase(LDH),superoxide dismutase(SOD),catalase(CAT)and the contents of malondialdehyde(MDA),glutathione(GSH),acetylcholine(ACh)and glutamate(Glu)in brain tissue of mice were detected by biochemical kit.The Western blot was employed to measure the expression levels of kelch-like ech-associated protein 1(Keap1),nuclearfactorerythroid2-relatedfactor2(Nrf2),and heme oxygenase 1(HO-1)in brain tissue of mice.Results:Compared with the control group,the body weight of the mice in the high-dose group decreased,the brain organ coefficient increased,and the neurological function test showed that the mice had reduced autonomic activity,delayed nerve reflex,and impaired sensory and motor function.Histopathology showed that the hippocampal neurons in the middle-and high-dose groups presented with pyknosis,vacuolization,and disordered arrangement of the CA3 area.Biochemical analysis indicated that in the brain tissue of mice,the activity of LDH and the content of MDA were increased in the medium-and high-dose groups,while the activity of CAT and the content of GSH were decreased.The content of Glu was increased and the content of ACh was decreased.The activity of SOD was reduced in the low-,medium-,and high-dose groups.Western blot analysis showed that the expression of HO-1 and Nrf2 protein in the brain tissue of mice in the middle-and high-dose groups was down-regulated,while the expression of Keap1 protein in the high-dose group was up-regulated.Conclusion:Pyrethrin may cause damage to the nervous system by affecting the Keap1/Nrf2/HO-1 signaling pathway and neurotransmitter levels.

Objective To investigate the correlation between maternal serum folic acid(FA),monocyte chemoattractant protein-1(MCP-1),progesterone-induced blocking factor(PIBF)levels and embryonic development cessation in early pregnancy.Methods From December 2021 to December 2023,98 pregnant women with embryonic development cessation in early pregnancy admitted to the Second Hospital of Jingzhou were regarded as the cessation group,and 50 normal early pregnancy pregnant women who underwent pregnancy examinations during the same period were as the control group.General clinical data was collected and analyzed.Enzyme-linked immunosorbent assay(ELISA)was applied to detect serum levels of FA,MCP-1 and PIBF.Multivariate logistic regression was applied to analyze the influencing factors of early pregnancy embryo cessation of development.Receiver operating characteristic(ROC)curve was plotted to analyze the predictive value of serum FA,MCP-1,and PIBF for early embryonic development cessation in pregnancy.Pearson method was applied to analyze the correlation between serum FA,MCP-1,PIBF,progesterone(PROG),estradiol(E2)and β-human chorionic gonadotropin(β-HCG).Results Compared with the control group,the serum FA(9.51±1.21 nmol/L vs 11.32±1.56 nmol/L)and PIBF(295.46±30.22 ng/ml vs 342.14±36.97 ng/ml)levels in the cessation group were greatly reduced,while the serum MCP-1(1.02±0.15 mg/ml vs 0.82±0.11 mg/ml)level was greatly increased,and the differences were statistically significant(t=7.785,8.347,8.229,all P＜0.001).There were great statistical differences in the history of embryonic development cessation(75.64%vs 25.36%),PROG(13.32±1.81 ng/ml vs 23.65±2.74 ng/ml),E2(221.34±25.69 pmol/L vs 298.65±31.64 pmol/L),and β-HCG levels(5 323.62±536.85U/L vs 8 562.31±924.55 U/L)between the two groups(t/χ2=6.548～27.428,all P<0.05).Pregnant women's history of embryonic development cessation and elevated level of MCP-1 were risk factors for embryonic development cessation in early pregnancy(Wald χ2=4.239,4.613,all P<0.05),while elevated levels of β-HCG,FA and PIBF were protective factors for embryonic development cessation in early pregnancy(Wald χ2=4.476,4.423,5.974,all P<0.05).The AUC of FA,MCP-1,PIBF,and their combination in predicting early embryonic development cessation in pregnancy was 0.811,0.805,0.816 and 0.908,respectively.The combined prediction was greatly better than that of individual diagnosis of FA MCP-1,and PIBF(Z=2.749,2.381,1.993,all P<0.05).FA and PIBF were positively correlated with PROG,E2 and β-HCG(r=0.433～0.512,all P<0.05),while MCP-1 was negatively correlated with PROG,E2 and β-HCG(r=-0.432,-0.487,-0.458,all P<0.05).Conclusion The serum levels of FA and PIBF in pregnant women with embryonic development cessation in early pregnancy decrease,while the level of MCP-1 increases.These three factors are all influencing factors for embryonic development cessation in pregnant women,and have certain auxiliary predictive value for embryonic development cessation in early pregnancy.

Objective:To investigate the effects and mechanisms of subchronic exposure to pyrethrin on the mice nervous system.Methods:Twenty-four male mice were randomly divided into a control group,low-,medium-,and high-dose groups,and were exposed continuously for 28 days.The control group received corn oil.The general condi-tion of the mice was observed,and the body weight and brain organ coefficient were measured.Neurobehavioral tests were conducted after the exposure period.The histopathological changes of the hippocampus in mice were observed by HE and nissl staining.The activities of lactate dehydrogenase(LDH),superoxide dismutase(SOD),catalase(CAT)and the contents of malondialdehyde(MDA),glutathione(GSH),acetylcholine(ACh)and glutamate(Glu)in brain tissue of mice were detected by biochemical kit.The Western blot was employed to measure the expression levels of kelch-like ech-associated protein 1(Keap1),nuclearfactorerythroid2-relatedfactor2(Nrf2),and heme oxygenase 1(HO-1)in brain tissue of mice.Results:Compared with the control group,the body weight of the mice in the high-dose group decreased,the brain organ coefficient increased,and the neurological function test showed that the mice had reduced autonomic activity,delayed nerve reflex,and impaired sensory and motor function.Histopathology showed that the hippocampal neurons in the middle-and high-dose groups presented with pyknosis,vacuolization,and disordered arrangement of the CA3 area.Biochemical analysis indicated that in the brain tissue of mice,the activity of LDH and the content of MDA were increased in the medium-and high-dose groups,while the activity of CAT and the content of GSH were decreased.The content of Glu was increased and the content of ACh was decreased.The activity of SOD was reduced in the low-,medium-,and high-dose groups.Western blot analysis showed that the expression of HO-1 and Nrf2 protein in the brain tissue of mice in the middle-and high-dose groups was down-regulated,while the expression of Keap1 protein in the high-dose group was up-regulated.Conclusion:Pyrethrin may cause damage to the nervous system by affecting the Keap1/Nrf2/HO-1 signaling pathway and neurotransmitter levels.

Objective To investigate the correlation between maternal serum folic acid(FA),monocyte chemoattractant protein-1(MCP-1),progesterone-induced blocking factor(PIBF)levels and embryonic development cessation in early pregnancy.Methods From December 2021 to December 2023,98 pregnant women with embryonic development cessation in early pregnancy admitted to the Second Hospital of Jingzhou were regarded as the cessation group,and 50 normal early pregnancy pregnant women who underwent pregnancy examinations during the same period were as the control group.General clinical data was collected and analyzed.Enzyme-linked immunosorbent assay(ELISA)was applied to detect serum levels of FA,MCP-1 and PIBF.Multivariate logistic regression was applied to analyze the influencing factors of early pregnancy embryo cessation of development.Receiver operating characteristic(ROC)curve was plotted to analyze the predictive value of serum FA,MCP-1,and PIBF for early embryonic development cessation in pregnancy.Pearson method was applied to analyze the correlation between serum FA,MCP-1,PIBF,progesterone(PROG),estradiol(E2)and β-human chorionic gonadotropin(β-HCG).Results Compared with the control group,the serum FA(9.51±1.21 nmol/L vs 11.32±1.56 nmol/L)and PIBF(295.46±30.22 ng/ml vs 342.14±36.97 ng/ml)levels in the cessation group were greatly reduced,while the serum MCP-1(1.02±0.15 mg/ml vs 0.82±0.11 mg/ml)level was greatly increased,and the differences were statistically significant(t=7.785,8.347,8.229,all P＜0.001).There were great statistical differences in the history of embryonic development cessation(75.64%vs 25.36%),PROG(13.32±1.81 ng/ml vs 23.65±2.74 ng/ml),E2(221.34±25.69 pmol/L vs 298.65±31.64 pmol/L),and β-HCG levels(5 323.62±536.85U/L vs 8 562.31±924.55 U/L)between the two groups(t/χ2=6.548～27.428,all P<0.05).Pregnant women's history of embryonic development cessation and elevated level of MCP-1 were risk factors for embryonic development cessation in early pregnancy(Wald χ2=4.239,4.613,all P<0.05),while elevated levels of β-HCG,FA and PIBF were protective factors for embryonic development cessation in early pregnancy(Wald χ2=4.476,4.423,5.974,all P<0.05).The AUC of FA,MCP-1,PIBF,and their combination in predicting early embryonic development cessation in pregnancy was 0.811,0.805,0.816 and 0.908,respectively.The combined prediction was greatly better than that of individual diagnosis of FA MCP-1,and PIBF(Z=2.749,2.381,1.993,all P<0.05).FA and PIBF were positively correlated with PROG,E2 and β-HCG(r=0.433～0.512,all P<0.05),while MCP-1 was negatively correlated with PROG,E2 and β-HCG(r=-0.432,-0.487,-0.458,all P<0.05).Conclusion The serum levels of FA and PIBF in pregnant women with embryonic development cessation in early pregnancy decrease,while the level of MCP-1 increases.These three factors are all influencing factors for embryonic development cessation in pregnant women,and have certain auxiliary predictive value for embryonic development cessation in early pregnancy.

OBJECTIVE To retrospectively analyze the drug resistance characteristics of the patients with multidrug-resistant organisms(MDROs)infections who were hospitalized from 2022 to 2023 and observe the effect of multi-disciplinary teamwork(MDT)mode so as to provide scientific bases for prevention and control of MDROs infec-tions and hospital-associated infections.METHODS A total of 639 patients with MDROs infection who were hospi-talized in Jianyang People's Hospital from Jan.2022 to Dec.2023 were recruited as the research subjects.The clinical data were collected from the patients,the drug resistance characteristics of bacteria were analyzed.The effects of MDT and pharmacological supervision on treatment of the patients with MDROs infection were observed and compared.RESULTS The methicillin-resistant Staphylococcus aureus(MRSA)(359 strains,56.18％)was dominant among the pathogens isolated from the 639 patients with MDROs infections,followed by the carbapen-em-resistant Klebsiella pneumoniae(CRKP)(96 strains,15.02％)and carbapenem-resistant Acinetobacter bau-mannii(82 strains,12.83％).Of the patients with MDROs infection,150(23.47％)were from critical care medicine department,94(14.71％)from pediatrics department,and 82(12.83％)from general surgery de-partment.The result of drug susceptibility test showed that the S.aureus strains were susceptible to linezolid,daptomycin,vancomycin and tigecycline;most of the gram-negative bacteria were susceptible to carbapenems,while the A.baumannii strains were highly resistant to the commonly used antibiotics.The total isolation rate of MDROs and the case-time infection rate of MDROs infections were 14.32％and 0.05％,respectively,after MDT and pharmacological supervision were carried out,lower than those before carried out;the effective treatment rate of the patients with MDROs was 76.47％after MDT and pharmacological supervision were carried out,higher than that before they were carried out,and there were significant differences(all P＜0.05).CONCLUSION MDT and pharmacological supervision may improve the curative effect of the patients with MDROs infection and reduce the isolation rate of MDROs as well as the incidence of hospital-associated infections.

OBJECTIVE To retrospectively analyze the drug resistance characteristics of the patients with multidrug-resistant organisms(MDROs)infections who were hospitalized from 2022 to 2023 and observe the effect of multi-disciplinary teamwork(MDT)mode so as to provide scientific bases for prevention and control of MDROs infec-tions and hospital-associated infections.METHODS A total of 639 patients with MDROs infection who were hospi-talized in Jianyang People's Hospital from Jan.2022 to Dec.2023 were recruited as the research subjects.The clinical data were collected from the patients,the drug resistance characteristics of bacteria were analyzed.The effects of MDT and pharmacological supervision on treatment of the patients with MDROs infection were observed and compared.RESULTS The methicillin-resistant Staphylococcus aureus(MRSA)(359 strains,56.18％)was dominant among the pathogens isolated from the 639 patients with MDROs infections,followed by the carbapen-em-resistant Klebsiella pneumoniae(CRKP)(96 strains,15.02％)and carbapenem-resistant Acinetobacter bau-mannii(82 strains,12.83％).Of the patients with MDROs infection,150(23.47％)were from critical care medicine department,94(14.71％)from pediatrics department,and 82(12.83％)from general surgery de-partment.The result of drug susceptibility test showed that the S.aureus strains were susceptible to linezolid,daptomycin,vancomycin and tigecycline;most of the gram-negative bacteria were susceptible to carbapenems,while the A.baumannii strains were highly resistant to the commonly used antibiotics.The total isolation rate of MDROs and the case-time infection rate of MDROs infections were 14.32％and 0.05％,respectively,after MDT and pharmacological supervision were carried out,lower than those before carried out;the effective treatment rate of the patients with MDROs was 76.47％after MDT and pharmacological supervision were carried out,higher than that before they were carried out,and there were significant differences(all P＜0.05).CONCLUSION MDT and pharmacological supervision may improve the curative effect of the patients with MDROs infection and reduce the isolation rate of MDROs as well as the incidence of hospital-associated infections.

Objective:To investigate the protective effect of myrislignan（MRL）on concanavalin A（Con A）-induced autoimmune hepatitis（AIH）.Methods:C57BL/6J mice were divided into the following groups using a random number table，with five mice in each group：control group，MRL group，model group（Con A group），and MRL pretreatment group（MRL+Con A group）. MRL was injected intraperitoneally at a dose of 30 μg/g；3 h after pretreatment，Con A（18 μg/g）was administrated by intravenous injection；mouse livers and serum samples were collected 12 h after injection for measuring serum transaminase levels and liver cell apoptosis. The mRNA and protein expression levels of IL-6，IL-12，and TNF-α were measured using qRT-PCR and ELISA. Flow cytometry was performed to detect the proportion and activation status of macrophages in liver tissues. Bone marrow-derived macrophages（BMDMs）were isolated and induced in vitro to analyze the regulatory effect of MRL on macrophages. One-way analysis of variance was used to compare the differences in various indicators among groups. Results:Compared with the Con A group，MRL（30 μg/g）pretreatment significantly reduced alanine aminotransferase（ P<0.05）and aspartate transaminase（ P<0.01）levels，attenuated liver oxidative stress（increased superoxide dismutase activity，while decreased levels of malondialdehyde and myeloperoxidase；all P<0.05），and suppressed hepatocyte apoptosis（ P<0.01）. Both in vivo and in vitro experiments confirmed that MRL（30 μg/g）could reduce the proportion of M1 macrophages（ in vivo： P<0.05； in vitro：all P<0.001）and inhibit macrophage activation（ in vivo： P<0.01； in vitro：all P<0.05）. Conclusion:MRL effectively prevents Con A-induced autoimmune hepatitis by inhibiting liver cell apoptosis，attenuating liver oxidative stress，suppressing M1 macrophage polarization，and reducing inflammatory cytokine expression.

Corilagin is one of major bioactive compounds in many Chinese medical plants,which has been demonstrated to exhibit multiple pharmacological activities.Hepatoprotective effects of corilagin have been reported in some liver diseases,such as hepatitis,liver fibrosis and hepatic carcinoma.Therefore,corilagin has shown broad prospects in treatment of liver diseases.However,problems exposed in application process prompted researchers to further explore potential role of corilagin.Research progress of the role and mechanism of corilagin in hepatitis,liver fibrosis and hepatic carcinoma are summarized to provide reference for subsequent studies.