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.

Objective To investigate the predictive value of pre-transfer serum fibroblast growth factor 21(FGF-21),anti-Müllerian hormone(AMH),and neuropilin-1(NRP-1)for early pregnancy loss at 6 weeks following in vitro fertilization-embryo transfer(IVF-ET),and to establish an early predictive model based on serum biochemical markers.Methods This prospective study consecutively enrolled 322 women who achieved clinical pregnancy after IVF-ET at our center between September 2022 and September 2024.Participants were randomly divided into a modeling cohort(n=225)and a validation cohort(n=97)at a 7:3 ratio.According to ultrasound findings at 6 weeks of gestation,patients in the modeling cohort were classified into an early pregnancy loss group(n=59)and an ongoing pregnancy group(n=166).Baseline clinical characteristics and pre-transfer serum levels of FGF-21,AMH,and NRP-1 were collected.Multivariate logistic regression was applied to identify inde-pendent risk factors for early pregnancy loss and to construct a predictive model.Model discrimination,calibra-tion,and stability were evaluated using receiver operating characteristic(ROC)curves,the Hosmer-Lemeshow goodness-of-fit test,and bootstrap resampling in both cohorts.Results Univariate analysis revealed that the FSH/LH ratio,antral follicle count,and number of retrieved oocytes were significantly associated with early pregnancy loss(P<0.001).Compared with the ongoing pregnancy group,women with early loss showed significantly elevated pre-transfer serum FGF-21 levels,whereas AMH and NRP-1 levels were markedly reduced(P<0.001).Multivariate logistic regression demonstrated that an FSH/LH ratio<1.8(OR=1.629,P=0.002)and higher FGF-21 levels(OR=1.338,P=0.002)were independent risk factors,while higher AMH(OR=0.741,P=0.010)and NRP-1 levels(OR=0.874,P=0.007)were protective.Stratified analysis indicated that among patients with FSH/LH≥1.8,FGF-21 levels were significantly higher and AMH and NRP-1 levels significantly lower(all P<0.001).Interaction analysis further suggested that the FSH/LH ratio significantly modified the associations between these biomarkers and pregnancy loss risk(P for interaction<0.05).Specifically,in the higher FSH/LH subgroup,the risk effect of FGF-21 was amplified,while the protective effects of AMH and NRP-1 were more pronounced.The combined predictive model achieved C-indices of 0.869(95%CI:0.826～0.926)in the modeling cohort and 0.835(95%CI:0.811～0.907)in the validation cohort.Its AUC for predicting early pregnancy loss was 0.934 in the modeling co-hort and 0.909 in the validation cohort,both significantly outperforming individual markers(AUCs:FGF-21=0.867,AMH=0.881,NRP-1=0.853;Z=2.024,1.831;P<0.001).Decision curve analysis showed that the model provided consistent net clinical benefit across threshold probabilities of 0.1～0.4,underscoring its clinical utility.Conclusions Elevated pre-transfer serum FGF-21 and reduced AMH and NRP-1 levels are strongly associ-ated with early pregnancy loss at 6 weeks after IVF-ET.The predictive model developed in this study demonstrates robust accuracy and stability,offering substantial clinical application value for early risk stratification.

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.

Insomnia is often comorbid with anxiety and/or depression.Identifying biomarkers for this comorbidity is crucial for precise diagnosis,elucidating the underlying pathological mechanisms,and developing personalized treatment strategies.Current research has preliminarily revealed a series of potential biomarkers for insomnia comorbid with anxiety and/or depression.Elevated peripheral pro-inflammatory factors(e.g.,interleukin-6),and decreased peripheral brain-derived neurotrophic factor,and monoamine neurotransmitters(e.g.,5-hydroxytryptamine)may indicate the presence of a comorbid state.However,studies focusing on this comorbidity remain relatively limited.In the future,it will be necessary to systematically explore and verify the clinical application value of potential biomarkers through measures such as expanding sample size,strengthening longitudinal design,and expanding the categories of biomarkers.This will provide a more solid theoretical foundation for the early diagnosis and personalized treatment of insomnia comorbid with anxiety and/or depression.

Objective To investigate the association between the TyG index,its modified variants,and the risk of developing colorectal cancer(CRC).Methods This study included a total of 93,177 participants from the 2006 Kailuan Group health examination cohort.Participants were categorized into four quartiles(Q1-Q4)according to their TyG and modified TyG indices.Follow-up began at the baseline examination,with incident CRC as the primary outcome.Participants were censored at the time of CRC diagnosis,death,or the end of the study,whichever occurred first.The dose-response relationship between TyG and its modified indices and the risk of CRC was evalu-ated using restricted cubic splines(RCS)in conjunction with Cox proportional hazards regression models,yielding hazard ratios(HRs)and 95%confidence intervals(CIs).To compare the strength of associations between TyG and its modified versions(TyG-BMI,TyG-WC,TyG-WHR,TyG-WHtR,TyG-WWI)and CRC risk,HRs for CRC per one standard deviation increase in each index were calculated and compared.Results Both the TyG index and its modified variants demonstrated a significant dose-response relationship with the risk of CRC incidence.Specifically,for the TyG index,each 1-standard deviation(SD)increase was associated with a 1.17-fold(95%CI:1.09～1.27)higher risk of CRC.Compared with the first quartile(Q1),the third quartile(Q3)and fourth quartile(Q4)exhibited a 1.25-fold(95%CI:1.01～1.55)and 1.26-fold(95%CI:1.01～1.57)increased risk,respectively.For TyG-BMI,each 1-SD increase was linked to a 1.20-fold(95%CI:1.07～1.35)elevated CRC risk.Compared with Q1,Q3 and Q4 showed a 1.32-fold(95%CI:1.06～1.64)and 1.51-fold(95%CI:1.21～1.88)increase,respectively.Regarding TyG-WC,each 1-SD increment was associated with a 1.22-fold(95%CI:1.13～1.32)higher CRC risk,with Q3 and Q4 showing a 1.35-fold(95%CI:1.08～1.70)and 1.56-fold(95%CI:1.24～1.96)increased risk compared to Q1.For TyG-WHtR,each 1-SD increase was associated with a 1.24-fold(95%CI:1.08-1.42)higher CRC risk.Compared with Q1,Q2,Q3,and Q4 demonstrated a 1.31-fold(95%CI:1.03～1.66),1.55-fold(95%CI:1.23～1.95),and 1.60-fold(95%CI:1.27～2.02)increase,respectively.In the case of TyG-WHR,each 1-SD increase was associated with a 1.19-fold(95%CI:1.10～1.29)higher CRC risk,with Q4 showing a 1.42-fold(95%CI:1.14～1.77)increased risk compared to Q1.Finally,for TyG-WWI,each 1-SD increase was associated with a 1.22-fold(95%CI:1.13～1.32)elevated CRC risk,with both Q3 and Q4 showing a 1.58-fold increase(Q3:95%CI:1.26～1.98;Q4:95%CI:1.25～1.99).Stratified analyses by sex and age consistently revealed significant associations between the TyG index and its modified variants and CRC risk.Furthermore,these indices were independently associated with the incidence of both colon cancer and rectal cancer.Conclusions(1)Elevated levels of the TyG index and its modified variants are independent risk factors for CRC.(2)Both the TyG index and its modified forms demonstrate a significant dose-response association with the incidence of CRC.(3)Among the modified TyG indices,TyG-WWI,TyG-WHtR,TyG-BMI,TyG-WC,and TyG-WHR showed stronger correlations with CRC risk compared to the original TyG index.

Objective To investigate effects of Cordyceps sinensis(CS)on high glucose(HG)induced podocyte injury by regulating the adenylate activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)signaling pathway.Methods Mouse podocytes were cultured in vitro and divided into the normal glucose(NG)group,the HG group,the HG+CS group,the HG+CS+autophagy inhibitor(HG+CS+3MA)group and the HG+CS+AMPK inhibitor(HG+CS+Compound C)group.Podocyte viability was detected by CCK-8 method.Western blot assay was used to detect the expression levels of podocyte marker proteins podocin and nephrin,autophagy-related proteins Beclin-1 and P62,and pathway related proteins p-AMPK and p-mTOR.Results Compared with the NG group,the cell viability of podocytes decreased,the expression levels of podocin,nephrin,Beclin-1 and p-AMPK protein were decreased,and the expression levels of P62 and p-mTOR protein were increased in the HG group(P＜0.05).Compared with the HG group,the cell viability of podocytes was increased,the expression levels of podocin,nephrin,Beclin-1 and p-AMPK protein were significantly increased(P＜0.05),and the expression levels of P62 and p-mTOR protein were decreased in the HG+CS group(P＜0.05).Compared with the HG+CS group,the cell viability decreased in the HG+CS+3MA group and the HG+CS+Compound C group(P＜0.05).Compared with the HG+CS group,the HG+CS+3MA group and the HG+CS+Compound C group showed decreased expression levels of podocin,nephrin and Beclin-1 protein,and increased expression of P62 protein(P＜0.05).Compared with the HG+CS group,the expression of p-AMPK protein decreased and the expression of p-mTOR protein increased in the HG+CS+Compound C group(P＜0.05).Conclusion Cordyceps sinensis may play a protective role in diabetic nephropathy by up-regulating AMPK/mTOR signaling pathway to induce podocyte autophagy,alleviate high glucose induced podocyte injury and apoptosis.

Objective To investigate the predictive value of pre-transfer serum fibroblast growth factor 21(FGF-21),anti-Müllerian hormone(AMH),and neuropilin-1(NRP-1)for early pregnancy loss at 6 weeks following in vitro fertilization-embryo transfer(IVF-ET),and to establish an early predictive model based on serum biochemical markers.Methods This prospective study consecutively enrolled 322 women who achieved clinical pregnancy after IVF-ET at our center between September 2022 and September 2024.Participants were randomly divided into a modeling cohort(n=225)and a validation cohort(n=97)at a 7:3 ratio.According to ultrasound findings at 6 weeks of gestation,patients in the modeling cohort were classified into an early pregnancy loss group(n=59)and an ongoing pregnancy group(n=166).Baseline clinical characteristics and pre-transfer serum levels of FGF-21,AMH,and NRP-1 were collected.Multivariate logistic regression was applied to identify inde-pendent risk factors for early pregnancy loss and to construct a predictive model.Model discrimination,calibra-tion,and stability were evaluated using receiver operating characteristic(ROC)curves,the Hosmer-Lemeshow goodness-of-fit test,and bootstrap resampling in both cohorts.Results Univariate analysis revealed that the FSH/LH ratio,antral follicle count,and number of retrieved oocytes were significantly associated with early pregnancy loss(P<0.001).Compared with the ongoing pregnancy group,women with early loss showed significantly elevated pre-transfer serum FGF-21 levels,whereas AMH and NRP-1 levels were markedly reduced(P<0.001).Multivariate logistic regression demonstrated that an FSH/LH ratio<1.8(OR=1.629,P=0.002)and higher FGF-21 levels(OR=1.338,P=0.002)were independent risk factors,while higher AMH(OR=0.741,P=0.010)and NRP-1 levels(OR=0.874,P=0.007)were protective.Stratified analysis indicated that among patients with FSH/LH≥1.8,FGF-21 levels were significantly higher and AMH and NRP-1 levels significantly lower(all P<0.001).Interaction analysis further suggested that the FSH/LH ratio significantly modified the associations between these biomarkers and pregnancy loss risk(P for interaction<0.05).Specifically,in the higher FSH/LH subgroup,the risk effect of FGF-21 was amplified,while the protective effects of AMH and NRP-1 were more pronounced.The combined predictive model achieved C-indices of 0.869(95%CI:0.826～0.926)in the modeling cohort and 0.835(95%CI:0.811～0.907)in the validation cohort.Its AUC for predicting early pregnancy loss was 0.934 in the modeling co-hort and 0.909 in the validation cohort,both significantly outperforming individual markers(AUCs:FGF-21=0.867,AMH=0.881,NRP-1=0.853;Z=2.024,1.831;P<0.001).Decision curve analysis showed that the model provided consistent net clinical benefit across threshold probabilities of 0.1～0.4,underscoring its clinical utility.Conclusions Elevated pre-transfer serum FGF-21 and reduced AMH and NRP-1 levels are strongly associ-ated with early pregnancy loss at 6 weeks after IVF-ET.The predictive model developed in this study demonstrates robust accuracy and stability,offering substantial clinical application value for early risk stratification.

Objective To investigate the factors influencing the efficacy of intravesical Bacille Calmette-Guérin(BCG)instillation after transurethral resection of bladder tumor(TURBT)in patients with intermediate-and high-risk non-muscle invasive bladder cancer(NMIBC),and to construct a prediction model for recurrence after BCG treatment.Methods A retrospective cohort study was conducted on the subjected patients diagnosed with intermediate-and high-risk NMIBC undergoing TURBT followed by standard BCG instillation.The 110 patients treated in Department of Urology of Army Medical Center of PLA from January 2018 to December 2023 were assigned into a training set,while the 52 patients treated at Department of Urology of General Hospital of Central Theater Command from January 2015 to December 2020 were into an external validation set.A total of 17 variables were included and analyzed.Univariate and multivariate Cox regression analyses were performed to identify factors associated with recurrence after BCG instillation,and nomograms were plotted to predict 1-year,3-year,and 5-year recurrence-free survival(RFS).Calibration curve,decision curve analysis(DCA),and receiver operating characteristic(ROC)curve analysis were conducted for internal and external validation to evaluate the predictive performance and clinical utility of the model.Results In the training set,26 patients(23.64%)experienced recurrence during the follow-up period,with a median RFS of 32.00(18.00～50.50)months.Univariate Cox regression analysis suggested that platelet count,eosinophil to lymphocyte ratio(ELR),neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),systemic immune inflammation(SII)index,and neutrophil-monocyte to lymphocyte ratio(NMLR),pathological T1 stage(pT1)tumor and hemoglobin,albumin,lymphocyte,and platelet(HALP)score were potential factors influencing recurrence after BCG instillation.Multivariate Cox regression analysis identified high HALP score(HR=0.185,95%CI:0.046～0.736,P=0.017)as an independent protective factor,while high ELR(HR=3.599,95%CI:1.505～8.608,P=0.004)and pT1 stage(HR=3.240,95%CI:1.191～8.818,P=0.021)were independent risk factors for recurrence.Based on this,a nomogram prediction model was constructed.The calibration curves demonstrated good agreement between predicted and actual 1-,3-,and 5-year recurrence risks.Decision curve analysis indicated clinical utility across a wide threshold probability range.In the training set,the model showed strong predictive performance for 1-(AUC=0.842),3-(AUC=0.847),and 5-year(AUC=0.887)recurrence risks,which was further validated in the external cohort.Conclusion Higher HALP score prior to BCG instillation therapy is a protective factor against tumor recurrence,while higher ELR and pT1 stage are risk factors.Our nomogram prediction model based on HALP score,ELR and pathological T stage,can identify individuals at high risk of recurrence after BCG instillation therapy.

Insomnia is often comorbid with anxiety and/or depression.Identifying biomarkers for this comorbidity is crucial for precise diagnosis,elucidating the underlying pathological mechanisms,and developing personalized treatment strategies.Current research has preliminarily revealed a series of potential biomarkers for insomnia comorbid with anxiety and/or depression.Elevated peripheral pro-inflammatory factors(e.g.,interleukin-6),and decreased peripheral brain-derived neurotrophic factor,and monoamine neurotransmitters(e.g.,5-hydroxytryptamine)may indicate the presence of a comorbid state.However,studies focusing on this comorbidity remain relatively limited.In the future,it will be necessary to systematically explore and verify the clinical application value of potential biomarkers through measures such as expanding sample size,strengthening longitudinal design,and expanding the categories of biomarkers.This will provide a more solid theoretical foundation for the early diagnosis and personalized treatment of insomnia comorbid with anxiety and/or depression.

Objective To investigate effects of Cordyceps sinensis(CS)on high glucose(HG)induced podocyte injury by regulating the adenylate activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)signaling pathway.Methods Mouse podocytes were cultured in vitro and divided into the normal glucose(NG)group,the HG group,the HG+CS group,the HG+CS+autophagy inhibitor(HG+CS+3MA)group and the HG+CS+AMPK inhibitor(HG+CS+Compound C)group.Podocyte viability was detected by CCK-8 method.Western blot assay was used to detect the expression levels of podocyte marker proteins podocin and nephrin,autophagy-related proteins Beclin-1 and P62,and pathway related proteins p-AMPK and p-mTOR.Results Compared with the NG group,the cell viability of podocytes decreased,the expression levels of podocin,nephrin,Beclin-1 and p-AMPK protein were decreased,and the expression levels of P62 and p-mTOR protein were increased in the HG group(P＜0.05).Compared with the HG group,the cell viability of podocytes was increased,the expression levels of podocin,nephrin,Beclin-1 and p-AMPK protein were significantly increased(P＜0.05),and the expression levels of P62 and p-mTOR protein were decreased in the HG+CS group(P＜0.05).Compared with the HG+CS group,the cell viability decreased in the HG+CS+3MA group and the HG+CS+Compound C group(P＜0.05).Compared with the HG+CS group,the HG+CS+3MA group and the HG+CS+Compound C group showed decreased expression levels of podocin,nephrin and Beclin-1 protein,and increased expression of P62 protein(P＜0.05).Compared with the HG+CS group,the expression of p-AMPK protein decreased and the expression of p-mTOR protein increased in the HG+CS+Compound C group(P＜0.05).Conclusion Cordyceps sinensis may play a protective role in diabetic nephropathy by up-regulating AMPK/mTOR signaling pathway to induce podocyte autophagy,alleviate high glucose induced podocyte injury and apoptosis.