ObjectiveTo explore the mechanism of ventricular remodeling mediated by the p38 mitogen-activated protein kinase （MAPK）/nuclear factor kappa B （NF-κB） signaling pathway in the rat model of chronic heart failure （CHF） with heart-blood stasis syndrome， as well as the intervention effect of Danhong injection. MethodsIn vivo experiment： SPF-grade male SD rats were assigned via the random number table method into 4 groups： Sham operation， model， captopril （8.8 mg·kg^-1）， and Danhong injection （6.0 mL·kg^-1）. The model of CHF with heart-blood stasis syndrome was established by abdominal aortic constriction， and the sham operation group only underwent laparotomy without constriction. All the groups were treated continuously for 15 days. The tongue color of rats was observed. Echocardiography， hemorheology， heart mass index （HMI）， and left ventricular mass index （LVMI） were measured. Hematoxylin-eosin （HE） staining and Masson staining were performed to observe the pathological and fibrotic changes of the myocardial tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to quantify the levels of N-terminal pro-B-type natriuretic peptide （NT-proBNP）， interleukin-6 （IL-6）， angiotensin Ⅱ （AngⅡ）， tumor necrosis factor-α （TNF-α）， and Creactive protein （CRP） in the serum， as well as the levels of matrix metalloproteinase-2 （MMP-2） and matrix metalloproteinase-9 （MMP-9） in the myocardial tissue. Western blot was used to quantify the protein levels of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 in the myocardial tissue. In vitro experiment： H9C2 cardiomyocytes were treated with 1×10^-6 mol·L^-1 AngⅡ to establish a model of myocardial hypertrophy. H9C2 cardiomyocytes were allocated into normal， model， inhibitor + Danhong injection， Danhong injection （20 mL·L^-1）， and inhibitor （SB203580， 5 μmol·L^-1） groups. CCK-8 assay was used to detect the viability of H9C2 cardiomyocytes. Rhodamine-labeled phalloidin staining was used to reveal the area of cardiomyocytes. Real-time PCR was performed to determine the mRNA levels of atrial natriuretic peptide （ANP） and brain natriuretic peptide （BNP）. Western blot was used to assess the protein levels of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65. ResultsIn vivo experiment： Compared with the sham operation group， the model group showed purplish-dark tongue with decreased R， G， B values of the tongue surface （P<0.01）， increased whole blood viscosity （at low， medium， and high shear rates） （P<0.01）， decreased left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （P<0.01）， increased left ventricular end-diastolic diameter （LVIDd）， left ventricular end-systolic diameter （LVIDs）， and left ventricular posterior wall thickness at end-diastole （LVPWd） （P<0.01）， raised LVMI and HMI （P<0.01）， and elevated levels of NT-proBNP， TNF-α， IL-6， and CRP in the serum and MMP-2 and MMP-9 in the myocardial tissue （P<0.01）. The HE and Masson staining of the myocardial tissue showed compensatory myocardial hypertrophy， fibrosis， and massive inflammatory cell infiltration in the model group. Additionally， the model group presented up-regulated protein levels of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 in the myocardial tissue （P<0.01）. Compared with the model group， each administration group showed increased R， G， B values of the tongue surface （P<0.05， P<0.01）， decreased whole blood viscosity （at low， medium， and high shear rates） （P<0.05， P<0.01）， increased LVEF and LVFS （P<0.01）， decreased LVIDd， LVIDs， and LVPWd （P<0.05， P<0.01）， declined LVMI and HMI （P<0.05， P<0.01）， and lowered levels of NT-proBNP， TNF-α， IL-6， and CRP in the serum and MMP-2 and MMP-9 in the myocardial tissue （P<0.01）. HE and Masson staining showed alleviated compensatory myocardial hypertrophy， reduced fibrosis， and decreased expression of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 in the myocardial tissue （P<0.01）. In vitro experiment： When the concentration of Danhong injection reached 20 mL·L^-1， the survival rate of H9C2 cardiomyocytes was the highest （P<0.01）. Compared with the normal group， the model group showed up-regulated mRNA levels of ANP and BNP （P<0.01）， increased relative cell surface area （P<0.01）， and raised protein levels of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 （P<0.01）. Compared with the model group， each administration group showed down-regulated mRNA levels of ANP and BNP （P<0.01）， reduced relative cell surface area （P<0.05， P<0.01）， and down-regulated protein levels of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 （P<0.05， P<0.01）. ConclusionDanhong injection can regulate ventricular remodeling through the p38 MAPK/NF-κB pathway， thereby exerting a protective effect on the rat model of CHF with heart-blood stasis syndrome.

Pancreatic cancer is characterized by occult clinical manifestations and high malignancy， and conventional imaging examinations and carbohydrate antigen 19-9 lack sufficient sensitivity and specificity for detecting early-stage pancreatic cancer lesions. Difficulty in early diagnosis severely restricts the long-term survival of pancreatic cancer patients. Liquid biopsy targets the biomarkers in body fluid samples， including circulating tumor cells， circulating tumor DNA， circulating tumor microRNA， and extracellular vesicles， showing the advantages of noninvasiveness and continuous monitoring. This review systematically summarizes the latest advances in liquid biopsy for the early screening and diagnosis， recurrence prediction， and prognostic assessment of pancreatic cancer， aiming to provide new insights and references for precision screening of high-risk populations and the clinical translation of liquid biopsy.

ObjectiveTo compare the performance of different automatic evaluation methods for detecting pattern hallucinations generated by large language models （LLMs） in traditional Chinese medicine （TCM） syndrome differentiation and to identify a strategy with higher overall discriminative performance against expert manual judgment. MethodsA standardized TCM syndrome-differentiation dataset containing 598 cases was constructed from case reports published in Chinese core journals indexed by Peking University Core Journals or Chinese Science Citation Database. Each of the 598 cases was submitted to five Chinese LLMs， with each model generating one syndrome-pattern output per case， yielding 2990 outputs in total. The 598 outputs generated by Qwen3-Next-80B-A3B-Thinking were independently annotated for syndrome-pattern hallucinations by two licensed TCM physicians with intermediate or higher professional titles. Disagreements were adjudicated by a third licensed TCM physician with a senior associate professional title and more than 10 years of clinical experience. The resulting consensus annotations served as the reference labels for training and validating the automated evaluation method. Based on these reference labels， three categories of automated evaluation methods were developed and compared following a progressive strategy from text-level semantic similarity， to syndrome-element structural consistency， and finally multi-feature fusion. Method A employed sentence-embedding models based on semantic similarity between pattern texts. Method B adopted a rule-based threshold method using weighted Jaccard coefficients of disease-location and disease-nature syndrome elements. Method C utilized a machine-learning classifier integrating syndrome-element matching scores， missing and redundant syndrome-element counts， and multiple semantic-similarity features. Five-fold cross-validation was used to evaluate the discriminative performance of each method against manual judgment. The optimal method was then applied to uniformly assess the pattern hallucination rates of five LLMs. ResultsIn method A， text2vec-large-chinese showed best overall performance， with an area under the receiver operating characteristic curve （AUROC）， area under the precision-recall curve （PR-AUC）， F1-score， sensitivity， and specificity of 0.849， 0.884， 0.794， 0.801， and 0.691， respectively. In method B， the corresponding metrics of the rule-based syndrome-element Jaccard threshold method were 0.848， 0.851， 0.817， 0.845， and 0.684， respectively； those of the LLM-based syndrome-element Jaccard method were 0.872， 0.906， 0.795， 0.764， and 0.780， respectively. In method C， the multilayer perceptron （MLP） classifier showed the best overall performance， with AUROC， PR-AUC， F1-score， sensitivity， and specificity of 0.933， 0.951， 0.871， 0.857， and 0.846， respectively. Under the unified evaluation framework combining DeepSeek-R1 syndrome-element extraction and MLP classifier， the estimated pattern hallucination rates of the five LLMs ranged from 56.0% to 77.4%. ConclusionAmong the three automatic evaluation methods， Method C integrating syndrome-element discrepancy features and text semantic features using an MLP classifier showed the highest overall discriminative performance against manual judgment， and is more suitable for evaluating syndrome hallucinations in LLM-based TCM syndrome differentiation tasks.

ObjectiveTo investigate whether Carthamus tinctorius L.-derived nanovesicles （CDNVs） can alleviate angiotensin Ⅱ （ANGⅡ）-induced cardiomyocyte （H9C2） hypertrophy by inhibiting the NF-κB signaling pathway and to elucidate the underlying molecular mechanisms. MethodsCDNVs were isolated and purified by ultracentrifugation combined with sucrose density gradient centrifugation， and their morphology and particle size distribution were identified by transmission electron microscopy and nanoparticle tracking analysis. Rat H9C2 cardiomyocytes were cultured in vitro and randomly divided into the normal control group （NC）， ANGⅡ （1.0 μmol/L） group， ANGⅡ+CDNVs group， and ANGⅡ+CDNVs+NF-κB activator 1 group. After 24 h of intervention， cell viability was detected by the CCK-8 assay， the expression of myocardial hypertrophy-related genes （ANP， BNP） was determined by qPCR， the relative cell area was measured by phalloidin staining， the expression of hypertrophy marker proteins and NF-κB pathway proteins （P-p65/p65， P-IκBα/IκBα） was examined by Western blot， and nuclear translocation of p65 was observed by immunofluorescence. Subsequently， NF-κB signaling pathway agonist activator 1 was added， and the expression of myocardial hypertrophy marker proteins and NF-κB pathway proteins was detected. ResultsCDNVs exhibited a typical round-like vesicle structure with an average particle size of 140.4 nm， which was consistent with the morphological characteristics of exosomes. ANGⅡ at concentrations of 0.1-1.0 μmol/L had no significant effect on cardiomyocyte viability. Compared with the NC group， ANGⅡ significantly upregulated the gene expression of ANP and BNP， increased the relative surface area of cardiomyocytes， elevated the levels of myocardial hypertrophy marker proteins and NF‑κB pathway proteins， and promoted the nuclear translocation of p65 （P<0.05）. Following treatment with CDNVs， all the above indicators were markedly reduced in comparison with the ANGⅡ group （all P<0.05）. However， all these experimental results were reversed after the addition of an NF‑κB agonist. ConclusionCDNVs alleviate ANGⅡ-induced H9C2 cell hypertrophy by inhibiting the NF-κB signaling pathway.

Objective To explore the mechanism of Shuangshu Decoction(SSD)for inhibiting growth of gastric cancer xenografts in nude mice.Methods Network pharmacology analysis was conducted to identify the common targets of SSD and gastric cancer cell ferroptosis,and bioinformatics analysis and molecular docking were used to validate the core targets.In the cell experiment,AGS cells were treated with SSD-medicated serum,Fer-1(a ferroptosis inhibitor),or both,and the changes in cell viability,ferroptosis markers(ROS,Fe2+and GSH),expressions of P53,SLC7A11 and GPX4,and mitochondrial morphology were examined.In a nude mouse model bearing gastric cancer xenografts,the effects of gavage with SSD,intraperitoneal injection of Fer-1,or their combination on tumor volume/weight,histopathology,and expressions of P53,SLC7A11 and GPX4 levels were evaluated.Results The active components in SSD(quercetin and wogonin)showed strong binding affinities to P53.In AGS cells,SSD treatment dose-dependently inhibited cell proliferation,increased ROS and Fe2+levels,upregulated P53 expression,and downregulated the expressions of SLC7A11 and GPX4,but these effects were effectively attenuated by Fer-1 treatment.SSD also induced mitochondrial shrinkage and increased the membrane density,which were alleviated by Fer-1.In the tumor-bearing mouse models,gavage with SSD significantly reduced tumor size and weight,caused tumor cell necrosis,upregulated P53 and downregulated SLC7A11 and GPX4 expression in the tumor tissue,and these effects were obviously mitigated by Fer-1 treatment.Conclusion SSD inhibits gastric cancer growth in nude mice by inducing cell ferroptosis via the P53/SLC7A11/GPX4 axis.

Objective To explore the impact of antimicrobial volume-based procurement(VBP)and classification management policy on the clinical use of carbapenem antibiotics.Methods Changing trend in defined daily doses(DDDs),procurement cost(Cost),defined daily dose cost(DDDc),and DDDs per 1 000 inhabitants daily(DID)of carbapenem antibiotics in all levels of medical institutions were analyzed by Mann-Kendall trend test.May 1,2020 was taken as the intervention cut-off point of VBP policy,September 2021 was as intervention cut-off point of cla-ssification management list.The impact of VBP and classification management policy on the clinical use of carbape-nem antibiotics were studied by interrupted time series analysis.Results After implementing VBP policy,the DDDs and DID of carbapenem antibiotics increased obviously,but the long-term trend didn't change significantly.Compared with before the implementation of the policy,the cost and DDDc of carbapenem antibiotics decreased im-mediately,the long-term trend of DDDc changed significantly,but the long-term trend of cost didn't change signifi-cantly.The DDDs and Cost of carbapenem antibiotics decreased immediately after the update of classification ma-nagement list,but the long-term downward trend was not significant,and DDDc presented a long-term upward trend.Conclusion VBP policy reduces the DDDc and short-term cost of carbapenem antibiotics,but its long-term impact on DDDs,cost and DID is limited.Classification management has limited impact on the use of carbapenem antibiotics in medical institutions.

Objective To elucidate the mechanism by which Huatan Anshen decoction inhibits neuronal apoptosis through modulation of the NOD-like receptor pyrin domain-containing protein 3(NLRP3)/interleukin-18(IL-18)/nuclear factor-activated B cell κ-light chain(NF-κB)signaling pathway.Methods The HT22 cell line derived from mouse hippocampal neurons were cultured in vitro,and serum containing Huatan Anshen Decoction was prepared from C57 mice after intragas tric administration.The optimal concentration of Huatan Anshen Decoction serum for intervention was determined with the CCK-8 method.Following treatment with different concentrations of drug-containing serum,lipopolysaccharide(LPS)was used to induce apoptosis in HT22 cells.Cell damage and apoptosis were assessed with the CCK-8 assay and Annexin V/PI staining.Western blotting and reverse transcription polymerase chain reaction was employed to measure the expression levels of NF-κB,apoptosis-associated speck-like protein containing(ASC),NLRP3,and Caspase-1,while enzyme-linked immunosorbent assay(ELISA)was used to detect IL-18 expression.The experiments was repeated after overexpression of NRLP3 to conduct single gene function verification.Results Serum containing Huatan Anshen Decoction significantly improved LPS-induced cellular damage and apoptosis in HT22 cells while reduced cellular L-lactate dehydrogenase,(L-LDH)levels(P＜0.05).Transcriptional expression of proteins related to the NLRP3/IL-18/NF-κB signaling pathway showed significant downregulation(P＜0.05).Additionally,it markedly decreased intracellular IL-18 levels.Furthermore,overexpression of NF-κB reversed the inhibitory effect of Huatan Anshen decoction-containing serum on HT22 cell apoptosis(P＜0.05).Conclusion Huatan Anshen Decoction can improve neuronal apoptosis via suppressing the NLRP3/IL-18/NF-κB signaling pathway.

OBJECTIVE To explore the indexes affecting the prognosis of the ICU patients with sepsis,establish the nomogram model for prediction of 28-day mortality rate,and validate it.METHODS On the basis of criteria for diagnosis of sepsis(3.0 version),the related data of the sepsis patients were extracted from Medical Information Mart for Intensive Care-Ⅳ(MIMIC-Ⅳ)database for retrospective study and were randomly divided into the train-ing set and the validation set in a 7∶3 ratio.Univariate analysis and multivariate Cox proportional risk regression analysis were performed for the screening of influencing factors for prediction of 28-day mortality of the sepsis pa-tients.The nomogram prediction model was established based on the screened factors and was validated by the val-idation set,and the effect was evaluated.RESULTS A total of 7 955 sepsis patients were included.Seven variables were selected to establish the nomogram model for prediction of the 28-day mortality rate.The nomogram showed favorable performance in identification between the two cohorts,the area under receiver operating characteristic curves(AUROCs)were 0.748 and 0.721,respectively.Calibration curves and Hosmer-Lemeshow test(x2=8.689,10.614;P=0.369,0.225)indicated that the model had remarkable effect on correction.With the per-formance of decision curve analysis(DCA)and clinical impact curve(CIC),the model was considered to have high clinical application value.CONCLUSIONS The nomogram model shows favorable performance in prediction of the 28-day mortality rate and calibration capability.It is worthy to be further promoted and applied.

AIM:This study aimed to investigate the protective effects of Carthamus tinctorius L.-derived nanovesicles(CDNVs)and their regulatory mechanisms in endothelial cell injury induced by oxidized low-density lipopro-tein(ox-LDL).METHODS:Human umbilical vein endothelial cells(HUVECs)were cultured in vitro and subjected to ox-LDL treatment to establish an endothelial cell injury model.The experimental groups included the normal control(NC)group,ox-LDL group(HUVECs treated with 100 mg/L ox-LDL for 24 h),and CDNVs+ox-LDL group(pre-treated with 40 mg/L CDNVs for 1 hour followed by co-culture with 100 mg/L ox-LDL for 24 hours).Cell proliferation and apoptosis were assessed by the EdU incorporation assay and flow cytometry,respectively.Changes in signal-induced proliferation-associ-ated 1-like protein 2(SIPA1L2)mRNA expression were measured by RT-qPCR,and the expression levels of autophagy-related proteins and SIPA1L2 were evaluated by Western blot.SIPA1L2 ubiquitination was evaluated by immunoprecipita-tion assay.RESULTS:(1)CDNVs were successfully isolated and purified,characterized as nanoscale vesicles with a circular shape and a double-layered membrane structure.(2)CDNVs promoted the proliferation and inhibited apoptosis of ox-LDL-treated HUVECs(P＜0.05).(3)CDNVs suppressed the prorein expression of SIPA1L2 and promoted autophagy in ox-LDL-treated HUVECs(P＜0.05).(4)CDNVs facilitated the ubiquitination of SIPA1L2 protein,and reduced its protein level through the ubiquitin-proteasome pathway(P＜0.05).CONCLUSION:CDNVs exert a protective effect against ox-LDL-induced endothelial cell injury by mediating SIPA1L2 ubiquitination and promoting endothelial cell au-tophagy.

Aim To investigate the protective and reparative effect of empagliflozin on oxidized-low density lipo-protein(ox-LDL)-induced injury in human umbilical vein endothelial cells(HUVEC)and its mechanism of action.Methods Primary HUVEC were cultured in vitro.ox-LDL was used to induce HUVEC injury model,and the cell sur-vival rate was measured by CCK-8 assay.EDU method was used to detect cell proliferation.Western blot was used to detect the protein levels of Ki-67,Bcl-2,cleaved Caspase-3,Bax,endothelial nitric oxide synthase(eNOS),intercellular adhesion molecule-1(ICAM-1),vascular cell adhesion molecule 1(VCAM-1)and epidermal growth factor receptor(EGFR)in HUVEC.RT-qPCR was used to detect the mRNA expression levels of interleukin-6(IL-6)and tumor necro-sis factor-α(TNF-α)in HUVEC.Using Swiss targets,GeneCards databases,gene ontology(GO)and Kyoto encyclope-dia of genes and genomes(KEGG),protein-protein interaction(PPI)network analysis,and ClickDocking(https://mcule.com/apps/1-click-docking/)to predict the target of empagliflozin.Results CCK-8 results showed that 0.025 μmol/L empagliflozin significantly alleviated ox-LDL-induced HUVEC injury(P＜0.01).EDU results showed that ox-LDL treatment for 24 h significantly inhibited the proliferation of HUVEC(P＜0.01),while empagliflozin treatment sig-nificantly alleviated the inhibition of cell proliferation(P＜0.01).The results of Western blot showed ox-LDL treatment significantly decreased the protein expression levels of Ki-67,Bcl-2,and eNOS,and increased the protein expression levels ofcleaved Caspase-3,Bax,ICAM-1,and VCAM-1 in HUVEC(all P＜0.05).However,empagliflozin treatment reversed these changes(all P＜0.05).RT-qPCR results showed that ox-LDL treatment increased the mRNA expression levels of IL-6 and TNF-α in HUVEC(P＜0.01),while empagliflozin treatment decreased their expression levels(P＜0.05).However,after adding EGFR agonist NSC 228155,the protective effect of empagliflozin against ox-LDL-mediated HUVEC injury was significantly reversed(P＜0.05).Conclusion Empagliflozin can significantly reduce ox-LDL-in-duced HUVEC injury,which may be related to EGFR signaling pathway.