Objective To investigate the effect of drug-eluting bead DACE(DEB-TACE)combined with systemic treatment for hepatocellular carcinoma(HCC)in different locations.Methods A total of 204 HCC patients who underwent DEB-TACE combined with systemic therapy(targeted and immunotherapy)were retrospectively collected.According to the anatomical location of HCC,86 cases with lesions located at the main trunk of portal vein(PV)or within 1 cm of the first PV branch were classified into central type group,while 118 cases with lesions located at the other areas were classified as peripheral type group.Follow-up was regularly performed after DEB-TACE until August,2024.The objective response rate(ORR)and disease control rate(DCR)at 1,3,6 and 12 months after DEB-TACE,also patients'progression-free survival(PFS)and overall survival(OS)were compared between groups.Results All patients were followed up for a median of 32.6 months,during which 164 cases died.Significant differences of ORR at 1 and 3 months after DEB-TACE(77.91％[67/86]vs.89.83％[106/118],34.88％[30/86]vs.54.24％[64/118])and DCR at 3 and 6 months after DEB-TACE(51.16％[44/86]vs.66.95％[79/118],34.88％[30/86]vs.50.00％[59/118])were found between groups(all P＜0.05).Patients'PFS(30.18[9.12,48.54]months)and OS(37.36[17.79,56.68])in peripheral type group were better than those in central type group(20.11[11.35,28.87]months and 23.24[3.11,43.47]months,x2=3.971,4.162,P=0.048,0.041).Conclusion The effect of DEB-TACE combined with systemic treatment for peripheral type HCC was better than for central type HCC.

Aim To predict the mechanism of action of ginsenoside Rg1(G-Rg1)paired with hirudin in the treatment of myocardial fibrosis in acute myocardial in-farction(AMI)based on the network pharmacology ap-proach,and to validate it by in vivo and in vitro experi-ments.Methods The corresponding targets of G-Rg1 and Hirudin were collected using SwissTargetPredic-tion,TargetNet,ETCM and ChEMBL databases,and the targets related to AMI and myocardial fibrosis were collected using GeneCards,OMIM and DisGeNET da-tabases.The drug-disease intersection targets were subjected to protein-protein interaction network(PPI)network analysis,gene ontology(GO)functional en-richment analysis and kyoto encyclopedia of genomes(KEGG)pathway enrichment analysis.Key targets and pathways were validated using an AMI mouse mod-el induced by ligation of the anterior descending branch of the left coronary artery in mice versus a hypoxia-in-duced injury model of human cardiac microvascular en-dothelial cells(HCMECs).Results G-Rg1 paired with hirudin had 229 drug targets,816 AMI and myo-cardial fibrosis disease targets,and 65 intersecting tar-gets.PPI analysis showed that tumor necrosis factor(TNF),interleukin-1[3(IL-1 β),transforming growth factor beta-1(TGF-β1),nuclear factor kappa-B(NF-κB),and interleukin-6(IL-6)might be the core tar-gets of G-Rg1 paired with Hirudin in the treatment of post-MI myocardial fibrosis;KEGG was enriched for a total of 141 pathways involving endocrine and metabo-lism,inflammation,and immunity,mainly TNF signa-ling pathway,PI3K/Akt signaling pathway and TGF-βsignaling pathway.In vivo experiments confirmed that G-Rg1 paired with hirudin attenuated myocardial fibro-sis after AMI in mice,and down-regulated the expres-sion of TNF-α,IL-1β,NF-κB,TGF-β1,and Smad2/3 proteins in myocardial tissues.In vitro experiments confirmed that G-Rg1 paired with Hirudin inhibited cellular NF-κB/TGF-β1 pathway,reduced hypoxia-in-duced cellular TNF-α and IL-1β expression,and su-perimposed NF-κB inhibitor significantly reduced IL-1 β expression and attenuated cellular inflammatory re-sponse.Conclusions G-Rg1 with Hirudin treats post-MI myocardial fibrosis by regulating TNF-α,IL-1 β and other targets and NF-KB/TGF-β1 pathway,reflecting its multi-pathway and multi-target action characteris-tics,and providing a pharmacological basis for the treatment of post-MI myocardial fibrosis with G-Rg1 with Hirudin.

Objective:To explore the effect of multiple modified process management intervention on cardiac func-tion,psychological state,stress level,sleep quality and adverse events in patients with severe coronary atherosclerot-ic heart disease(CHD).Methods:This randomized controlled study enrolled 130 severe CHD patients who were treated in Affiliated Beijing Shijitan Hospital of Capital Medical University between January 2020 and May 2023.Patients were randomly divided into control group(n=65)and intervention group(n=65).Patients in the control group were treated with routine management intervention,while those in the intervention group were given addi-tional multiple modified process management interventions.Both groups were intervened for 4 weeks.Cardiac func-tion,levels of norepinephrine(NE)and cortisol(COR),scores of Self-rating Anxiety Scale(SAS),Self-rating Depression Scale(SDS),General Comfort Questionnaire(GCQ),Pittsburgh Sleep Quality Index(PSQI),and the incidence of adverse events during intervention were compared between the two groups.Results:Compared to those in control group after intervention,patients in intervention group had significant higher left ventricular ejection fraction(LVEF)[(57.81±2.15)％vs.(50.11±2.99)％]and GCQ score[(95.88±5.37)points vs.(75.81±6.67)points](P＜0.001 all),and significant lower left ventricular end-diastolic volume(LVEDV)[(109.81±5.37)ml vs.(129.26±5.17)ml],left ventricular end-systolic volume(LVESV)[(50.85±3.08)ml vs.(66.02±3.77)ml],levels of NE[(61.56±5.49)pg/ml vs.(69.86±5.03)pg/ml],COR[(85.63±5.19)ng/ml vs.(92.28±6.57)ng/ml],scores of SAS[(30.06±5.19)points vs.(49.51±5.85)points],SDS[(31.86±4.51)points vs.(40.00±5.10)points]and PSQI[(8.72±1.58)points vs.(13.89±2.40)points],and incidence of ad-verse events(4.69％vs.23.44％)(P＜0.01 all).Conclusion:The multiple modified process management interven-tion may improve the cardiac function,adverse psychological state,stress level,sleep quality and reduce the inci-dence of adverse events in patients with severe CHD.

Objective:To explore the effect of multiple modified process management intervention on cardiac func-tion,psychological state,stress level,sleep quality and adverse events in patients with severe coronary atherosclerot-ic heart disease(CHD).Methods:This randomized controlled study enrolled 130 severe CHD patients who were treated in Affiliated Beijing Shijitan Hospital of Capital Medical University between January 2020 and May 2023.Patients were randomly divided into control group(n=65)and intervention group(n=65).Patients in the control group were treated with routine management intervention,while those in the intervention group were given addi-tional multiple modified process management interventions.Both groups were intervened for 4 weeks.Cardiac func-tion,levels of norepinephrine(NE)and cortisol(COR),scores of Self-rating Anxiety Scale(SAS),Self-rating Depression Scale(SDS),General Comfort Questionnaire(GCQ),Pittsburgh Sleep Quality Index(PSQI),and the incidence of adverse events during intervention were compared between the two groups.Results:Compared to those in control group after intervention,patients in intervention group had significant higher left ventricular ejection fraction(LVEF)[(57.81±2.15)％vs.(50.11±2.99)％]and GCQ score[(95.88±5.37)points vs.(75.81±6.67)points](P＜0.001 all),and significant lower left ventricular end-diastolic volume(LVEDV)[(109.81±5.37)ml vs.(129.26±5.17)ml],left ventricular end-systolic volume(LVESV)[(50.85±3.08)ml vs.(66.02±3.77)ml],levels of NE[(61.56±5.49)pg/ml vs.(69.86±5.03)pg/ml],COR[(85.63±5.19)ng/ml vs.(92.28±6.57)ng/ml],scores of SAS[(30.06±5.19)points vs.(49.51±5.85)points],SDS[(31.86±4.51)points vs.(40.00±5.10)points]and PSQI[(8.72±1.58)points vs.(13.89±2.40)points],and incidence of ad-verse events(4.69％vs.23.44％)(P＜0.01 all).Conclusion:The multiple modified process management interven-tion may improve the cardiac function,adverse psychological state,stress level,sleep quality and reduce the inci-dence of adverse events in patients with severe CHD.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Objective:To investigate the outcomes of natural cycle (NC) and modified natural cycle (MNC) assisted reproductive technology (ART) in patients with diminished ovarian reserve (DOR), and to provide a scientific basis for individualized treatment strategies for DOR patients.Methods:A retrospective cohort analysis was performed on the clinical data of DOR patients who underwent ART at the Center for Reproductive Medicine of the Department of Obstetrics and Gynecology, Peking University Third Hospital from January 1, 2015 to December 31, 2023. Patients were divided into the NC group ( n=801) and the MNC group ( n=385) based on their treatment protocol. The primary outcomes were cycle cancellation rate and oocyte retrieval rate. Secondary outcomes included clinical pregnancy rate and live birth rate per fresh embryo transfer cycle and frozen-thawed embryo transfer cycle, cumulative pregnancy rate and cumulative live birth rate per started cycle and per transfer cycle, as well as laboratory parameters such as the number of retrieved oocytes, the number of two pronuclei (2PN) fertilized oocytes, the number of transferable embryos, and transferable embryo formation rate. Further, multivariate logistic regression was used to analyze the impact of the treatment protocol on pregnancy and live birth outcomes. Results:There were no statistically significant differences between the NC and MNC groups in terms of general characteristics such as age, body mass index, and baseline hormone levels (all P>0.05). The cycle cancellation rate was significantly higher in the NC group [19.10% (153/801)] than in the MNC group [10.65% (41/385), P<0.001], and the oocyte retrieval rate was significantly lower in the NC group [66.31% (431/650)] than in the MNC group [74.86% (259/346), P=0.005]. The number of retrieved oocytes [1 (0,1)], the number of 2PN fertilized oocytes [1 (0,1)], and the number of transferable embryos [0 (0, 1)] were also significantly lower in the NC group than in the MNC group [1 (1, 2), P<0.001; 1 (1, 1), P<0.001; 0 (0, 1), P<0.001]. However, there were no statistically significant differences in 2PN fertilization rate and transferable embryo formation rate between the NC and MNC groups (all P>0.05). In both fresh embryo transfer cycles and frozen-thawed embryo transfer cycles, there were no statistically significant differences in clinical pregnancy rate and live birth rate between the NC and MNC groups (all P>0.05). The cumulative pregnancy rate per started cycle and transfer cycle, the cumulative live birth rate per started cycle and per transfer cycle were also not significantly different between the NC and MNC groups (all P>0.05). Multivariate logistic analysis showed no significant association between NC and clinical pregnancy or live birth compared with MNC. Conclusion:While MNC to some extent reduced the cycle cancellation rate and improved oocyte retrieval rates compared with NC, it did not ultimately improve pregnancy outcomes in DOR patients.

Objective:To analyze the influencing factors of postoperative intestinal adhesion in patients undergoing laparoscopic cholecystectomy(LC),and to construct a nomogram prediction model based on this.Methods:A total of 265 patients who underwent LC in our hospital from November 2021 to March 2025 were retrospectively selected and randomly divided into a training set(185 cases)and a validation set(80 cases)according to the ratio of 7∶3.According to the presence or absence of postoperative intestinal adhesion,185 patients in the training set were divided into occur-rence group(28 cases)and non-occurrence group(157 cases).In the validation set,13 cases occurred and 67 cases did not occur.The clinical data of patients were collected to analyze the influencing factors of postoperative intestinal adhe-sion,and a nomogram model was constructed based on this.The receiver operating characteristic(ROC)curve was used to analyze the predictive efficacy of the prediction model on the risk of postoperative intestinal adhesion.Decision curve analysis(DCA)was used to analyze the clinical benefit of the prediction model.Result:The proportion of patients aged≥65 years,complicated with diabetes,indwelling drainage tube,residual abdominal infection,and WBC level in the occurrence group were higher than those in the non-occurrence group(P<0.05).Logistic regression analysis showed that age(OR=3.025,95%CI:1.453-6.296),diabetes(OR=3.836,95%CI:1.557-9.450),indwelling drainage tube(OR=5.312,95%CI:1.898-14.864)and residual abdominal infection(OR=6.174,95%CI:2.914-13.079)were independent influencing factors for postoperative intestinal adhesion(P<0.05).The corresponding risk rate of the nomogram model based on Logistic results ranged from 0.10 to 0.80,and the C-index was 0.842(95%CI:0.765-0.919).The calibration curve of predicting postoperative intestinal adhesion was close to the ideal curve(P>0.05).The ROC of the training set showed that the sensitivity and specificity of the model in predicting postoperative intestinal adhesion were 85.70%and 88.50%,respectively,and the area under the curve(AUC)was 0.882(P<0.05).In the validation set,the sensitivity,speci-ficity and AUC of ROC curve were 81.30%,84.10%and 0.860(P<0.05),respectively.DCA curve showed that the pre-diction model could obtain the maximum clinical benefit at the threshold probability of 0-0.23.Conclusion:The pre-diction model based on age,diabetes,indwelling drainage tube and residual abdominal infection has a good predictive value for the risk of intestinal adhesion after LC.

Objective To investigate the effect of drug-eluting bead DACE(DEB-TACE)combined with systemic treatment for hepatocellular carcinoma(HCC)in different locations.Methods A total of 204 HCC patients who underwent DEB-TACE combined with systemic therapy(targeted and immunotherapy)were retrospectively collected.According to the anatomical location of HCC,86 cases with lesions located at the main trunk of portal vein(PV)or within 1 cm of the first PV branch were classified into central type group,while 118 cases with lesions located at the other areas were classified as peripheral type group.Follow-up was regularly performed after DEB-TACE until August,2024.The objective response rate(ORR)and disease control rate(DCR)at 1,3,6 and 12 months after DEB-TACE,also patients'progression-free survival(PFS)and overall survival(OS)were compared between groups.Results All patients were followed up for a median of 32.6 months,during which 164 cases died.Significant differences of ORR at 1 and 3 months after DEB-TACE(77.91％[67/86]vs.89.83％[106/118],34.88％[30/86]vs.54.24％[64/118])and DCR at 3 and 6 months after DEB-TACE(51.16％[44/86]vs.66.95％[79/118],34.88％[30/86]vs.50.00％[59/118])were found between groups(all P＜0.05).Patients'PFS(30.18[9.12,48.54]months)and OS(37.36[17.79,56.68])in peripheral type group were better than those in central type group(20.11[11.35,28.87]months and 23.24[3.11,43.47]months,x2=3.971,4.162,P=0.048,0.041).Conclusion The effect of DEB-TACE combined with systemic treatment for peripheral type HCC was better than for central type HCC.

Aim To predict the mechanism of action of ginsenoside Rg1(G-Rg1)paired with hirudin in the treatment of myocardial fibrosis in acute myocardial in-farction(AMI)based on the network pharmacology ap-proach,and to validate it by in vivo and in vitro experi-ments.Methods The corresponding targets of G-Rg1 and Hirudin were collected using SwissTargetPredic-tion,TargetNet,ETCM and ChEMBL databases,and the targets related to AMI and myocardial fibrosis were collected using GeneCards,OMIM and DisGeNET da-tabases.The drug-disease intersection targets were subjected to protein-protein interaction network(PPI)network analysis,gene ontology(GO)functional en-richment analysis and kyoto encyclopedia of genomes(KEGG)pathway enrichment analysis.Key targets and pathways were validated using an AMI mouse mod-el induced by ligation of the anterior descending branch of the left coronary artery in mice versus a hypoxia-in-duced injury model of human cardiac microvascular en-dothelial cells(HCMECs).Results G-Rg1 paired with hirudin had 229 drug targets,816 AMI and myo-cardial fibrosis disease targets,and 65 intersecting tar-gets.PPI analysis showed that tumor necrosis factor(TNF),interleukin-1[3(IL-1 β),transforming growth factor beta-1(TGF-β1),nuclear factor kappa-B(NF-κB),and interleukin-6(IL-6)might be the core tar-gets of G-Rg1 paired with Hirudin in the treatment of post-MI myocardial fibrosis;KEGG was enriched for a total of 141 pathways involving endocrine and metabo-lism,inflammation,and immunity,mainly TNF signa-ling pathway,PI3K/Akt signaling pathway and TGF-βsignaling pathway.In vivo experiments confirmed that G-Rg1 paired with hirudin attenuated myocardial fibro-sis after AMI in mice,and down-regulated the expres-sion of TNF-α,IL-1β,NF-κB,TGF-β1,and Smad2/3 proteins in myocardial tissues.In vitro experiments confirmed that G-Rg1 paired with Hirudin inhibited cellular NF-κB/TGF-β1 pathway,reduced hypoxia-in-duced cellular TNF-α and IL-1β expression,and su-perimposed NF-κB inhibitor significantly reduced IL-1 β expression and attenuated cellular inflammatory re-sponse.Conclusions G-Rg1 with Hirudin treats post-MI myocardial fibrosis by regulating TNF-α,IL-1 β and other targets and NF-KB/TGF-β1 pathway,reflecting its multi-pathway and multi-target action characteris-tics,and providing a pharmacological basis for the treatment of post-MI myocardial fibrosis with G-Rg1 with Hirudin.