Objective To develop a predictive model for postoperative mortality risk in patients with acute aortic dissection(AAD)using the Extreme Gradient Boosting(XGBoost)algorithm combined with Shapley Additive Explanation(SHAP),and to establish a prediction website to serve as a diagnostic and therapeutic support platform for clinicians and patients.Methods A retrospective cohort study design was adopted.Data from 782 AAD patients who underwent surgical treatment at the Fourth Hospital of Hebei Medical University from January 2013 to December 2023 were collected,including basic information and initial serum biomarker test results.Patients were randomly divided into training and test sets at a 7:3 ratio.An external validation set consisting of 313 AAD patients admitted to the Second Hospital of Hebei Medical University from January 2020 to December 2023 was also established for further model validation.Variables were screened using LASSO regression,and an XGBoost machine learning model was constructed and interpreted using SHAP.The predictive performance of the model was evaluated using receiver operating characteristic(ROC)curve analysis.Using the Shiny package,the XGBoost model was deployed to shinyapps.io to create a prediction website for postoperative mortality risk in AAD patients.One patient was selected by simple random sampling from the test set and the external validation set respectively for the prediction example on the Shiny webpage.Results The XGBoost model demonstrated high predictive performance for postoperative mortality in AAD patients,with area under the ROC curve(AUC)values of 0.928(95%CI 0.901-0.956)in the training set,0.919(95%CI 0.891-0.949)in the test set,and 0.941(95%CI 0.915-0.967)in the external validation set.SHAP values indicated the following order of variable importance in the model(from highest to lowest):"lactate dehydrogenase""blood chlorine""multiple organ injury""carbon dioxide combining power""prothrombin time""α-hydroxybutyric acid""creatine kinase isoenzyme""Stanford classification""combined use of bedside blood purification""gender""acute kidney injury""gastrointestinal bleeding""brain injury"and"shock".A risk prediction website for adverse postoperative outcomes in AAD patients was developed using XGBoost-SHAP method(https://dun-dunxiaolu.shinyapps.io/document/)and validated with examples.One randomly selected patient from each of the test and external validation sets was applied:the predicted mortality risk value for patient 1(who died postoperatively)was 0.9539,and that for patient 2(who survived postoperatively)was 0.0206.Conclusions The XGBoost-SHAP model demonstrates high accuracy in predicting postoperative mortality risk for AAD patients.The online prediction tool established based on this model enhances the identification efficiency of high-risk postoperative mortality patients.

AIM:This study aims to explore the role of asprosin(ASP)in regulating hepatic lipid anabolic metabolism,as well as the effects of ASP and its downstream pathways on hepatic lipid anabolic metabolism under obesity and exercise intervention.METHODS:To explore the effect of ASP on liver lipid synthesis under physiological condi-tion,5-week-old male C57BL/6J were randomly divided into 4 groups:wild-type(WT)group,WT+ASP group,knockout(KO)group,and KO+ASP group.The mice in KO and KO+ASP groups were ASP gene heterozygous KO mice,and the re-combinant ASP protein was intraperitoneally injected into the mice in WT+ASP and KO+ASP groups for one month before sampling.To explore the role of ASP on liver lipid synthesis under obesity and exercise intervention,5-week-old male C57BL/6J mice were randomly divided into 3 groups:normal control(NC)group,high-fat diet(HFD)group,and HFD+exercise group.After 10 weeks of HFD feeding,the mice in HFD group received no intervention,while those in HFD+ex-ercise group underwent 8 weeks of treadmill exercise intervention.The mice in both groups were fed with HFD during the intervention period.After the interventions,liver tissues were collected from the mice.Western blot and RT-qPCR meth-ods were used to detect the expression levels of ASP,fibroblast growth factor 21(FGF21),nuclear factor E2-related factor 2(NRF2),stearoyl-coenzyme A desaturase 1(SCD1)and fatty acid synthase(FASN)in the mouse liver.ELISA was used to detect the triglycerol(TG)and cyclic adenosine monophosphate(cAMP)levels in the mouse liver,and HE stain-ing and oil red O staining were performed to observe the morphological changes of mouse liver tissues.RESULTS:(1)Compared with WT mice,KO mice exhibited significantly reduced body weight and liver weight,while liver index and he-patic TG levels were significantly increased.The mRNA and protein levels of cAMP,ASP,FGF21 and NRF2 in the liver were significantly decreased,whereas the mRNA and protein levels of SCD1 and FASN were significantly increased.In the WT+ASP group,liver index and hepatic TG levels were significantly reduced,but there were no statistical differences in body weight and liver weight.The mRNA and protein levels of SCD1 and FASN in the liver were significantly de-creased,while the cAMP level and the mRNA and protein levels of NRF2 were significantly increased.The FGF21 mRNA level decreased,but the protein level increased.(2)Compared with KO mice,KO+ASP mice had significantly reduced hepatic TG level,with a certain degree of reduction in liver weight and liver index,but without statistical significance.The cAMP level and the mRNA and protein levels of ASP,FGF21 and NRF2 in the liver were significantly increased,while the mRNA and protein levels of SCD1 and FASN were significantly decreased.(3)Compared with NC mice,HFD mice showed increased body weight,liver weight,and hepatic TG level.The cAMP level and the mRNA and protein levels of NRF2 in the liver were significantly decreased,while the mRNA and protein levels of SCD1 and FASN were significant-ly increased.The FGF21 mRNA level increased,but its protein level decreased.The ASP mRNA level decreased,but its protein level increased.(4)Compared with HFD mice,HFD+exercise mice had significantly reduced body weight,liver weight,and hepatic TG level.The mRNA and protein levels of SCD1 and FASN in the liver were significantly decreased,while the cAMP level and the mRNA and protein levels of NRF2 were significantly increased.The FGF21 mRNA level de-creased,but its protein level increased.The ASP mRNA level increased,but its protein level decreased.CONCLU-SION:(1)The ASP exerts an inhibitory effect on hepatic lipogenesis through the cAMP/FGF21/NRF2 pathway.(2)Un-der HFD feeding condition,the protein expression of FGF21 decreases,leading to our speculation that ASP may develop resistance.Aerobic exercise intervention can attenuate ASP resistance under high-fat condition and alleviate hepatic lipid accumulation caused by HFD.

AIM:This study aims to explore the role of asprosin(ASP)in regulating hepatic lipid anabolic metabolism,as well as the effects of ASP and its downstream pathways on hepatic lipid anabolic metabolism under obesity and exercise intervention.METHODS:To explore the effect of ASP on liver lipid synthesis under physiological condi-tion,5-week-old male C57BL/6J were randomly divided into 4 groups:wild-type(WT)group,WT+ASP group,knockout(KO)group,and KO+ASP group.The mice in KO and KO+ASP groups were ASP gene heterozygous KO mice,and the re-combinant ASP protein was intraperitoneally injected into the mice in WT+ASP and KO+ASP groups for one month before sampling.To explore the role of ASP on liver lipid synthesis under obesity and exercise intervention,5-week-old male C57BL/6J mice were randomly divided into 3 groups:normal control(NC)group,high-fat diet(HFD)group,and HFD+exercise group.After 10 weeks of HFD feeding,the mice in HFD group received no intervention,while those in HFD+ex-ercise group underwent 8 weeks of treadmill exercise intervention.The mice in both groups were fed with HFD during the intervention period.After the interventions,liver tissues were collected from the mice.Western blot and RT-qPCR meth-ods were used to detect the expression levels of ASP,fibroblast growth factor 21(FGF21),nuclear factor E2-related factor 2(NRF2),stearoyl-coenzyme A desaturase 1(SCD1)and fatty acid synthase(FASN)in the mouse liver.ELISA was used to detect the triglycerol(TG)and cyclic adenosine monophosphate(cAMP)levels in the mouse liver,and HE stain-ing and oil red O staining were performed to observe the morphological changes of mouse liver tissues.RESULTS:(1)Compared with WT mice,KO mice exhibited significantly reduced body weight and liver weight,while liver index and he-patic TG levels were significantly increased.The mRNA and protein levels of cAMP,ASP,FGF21 and NRF2 in the liver were significantly decreased,whereas the mRNA and protein levels of SCD1 and FASN were significantly increased.In the WT+ASP group,liver index and hepatic TG levels were significantly reduced,but there were no statistical differences in body weight and liver weight.The mRNA and protein levels of SCD1 and FASN in the liver were significantly de-creased,while the cAMP level and the mRNA and protein levels of NRF2 were significantly increased.The FGF21 mRNA level decreased,but the protein level increased.(2)Compared with KO mice,KO+ASP mice had significantly reduced hepatic TG level,with a certain degree of reduction in liver weight and liver index,but without statistical significance.The cAMP level and the mRNA and protein levels of ASP,FGF21 and NRF2 in the liver were significantly increased,while the mRNA and protein levels of SCD1 and FASN were significantly decreased.(3)Compared with NC mice,HFD mice showed increased body weight,liver weight,and hepatic TG level.The cAMP level and the mRNA and protein levels of NRF2 in the liver were significantly decreased,while the mRNA and protein levels of SCD1 and FASN were significant-ly increased.The FGF21 mRNA level increased,but its protein level decreased.The ASP mRNA level decreased,but its protein level increased.(4)Compared with HFD mice,HFD+exercise mice had significantly reduced body weight,liver weight,and hepatic TG level.The mRNA and protein levels of SCD1 and FASN in the liver were significantly decreased,while the cAMP level and the mRNA and protein levels of NRF2 were significantly increased.The FGF21 mRNA level de-creased,but its protein level increased.The ASP mRNA level increased,but its protein level decreased.CONCLU-SION:(1)The ASP exerts an inhibitory effect on hepatic lipogenesis through the cAMP/FGF21/NRF2 pathway.(2)Un-der HFD feeding condition,the protein expression of FGF21 decreases,leading to our speculation that ASP may develop resistance.Aerobic exercise intervention can attenuate ASP resistance under high-fat condition and alleviate hepatic lipid accumulation caused by HFD.

Objective Recombinase-aided polymerase chain reaction(RAP)is a sensitive,single-tube,two-stage nucleic acid amplification method.This study aimed to develop an assay that can be used for the early diagnosis of three types of bacteremia caused by Staphylococcus aureus(SA),Pseudomonas aeruginosa(PA),and Acinetobacter baumannii(AB)in the bloodstream based on recombinant human mannan-binding lectin protein(M1 protein)-conjugated magnetic bead(M1 bead)enrichment of pathogens combined with RAP. Methods Recombinant plasmids were used to evaluate the assay sensitivity.Common blood influenza bacteria were used for the specific detection.Simulated and clinical plasma samples were enriched with M1 beads and then subjected to multiple recombinase-aided PCR(M-RAP)and quantitative PCR(qPCR)assays.Kappa analysis was used to evaluate the consistency between the two assays. Results The M-RAP method had sensitivity rates of 1,10,and 1 copies/μL for the detection of SA,PA,and AB plasmids,respectively,without cross-reaction to other bacterial species.The M-RAP assay obtained results for<10 CFU/mL pathogens in the blood within 4 h,with higher sensitivity than qPCR.M-RAP and qPCR for SA,PA,and AB yielded Kappa values of 0.839,0.815,and 0.856,respectively(P<0.05). Conclusion An M-RAP assay for SA,PA,and AB in blood samples utilizing M1 bead enrichment has been developed and can be potentially used for the early detection of bacteremia.

This study aims to explore the mechanism of Qingkailing(QKL) Oral Preparation's heat-clearing, detoxifying, mind-tranquilizing effects based on "component-target-efficacy" network. To be specific, the potential targets of the 23 major components in QKL Oral Preparation were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The target genes were obtained based on UniProt. OmicsBean and STRING 10 were used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the targets. Cytoscape 3.8.2 was employed for visualization and construction of "component-target-pathway-pharmacological effect-efficacy" network, followed by molecular docking between the 23 main active components and 15 key targets. Finally, the lipopolysaccharide(LPS)-induced RAW264.7 cells were adopted to verify the anti-inflammatory effect of six monomer components in QKL Oral Preparation. It was found that the 23 compounds affected 33 key signaling pathways through 236 related targets, such as arachidonic acid metabolism, tumor necrosis factor α(TNF-α) signaling pathway, inflammatory mediator regulation of TRP channels, cAMP signaling pathway, cGMP-PKG signaling pathway, Th17 cell differentiation, interleukin-17(IL-17) signaling pathway, neuroactive ligand-receptor intera-ction, calcium signaling pathway, and GABAergic synapse. They were involved in the anti-inflammation, immune regulation, antipyretic effect, and anti-convulsion of the prescription. The "component-target-pathway-pharmacological effect-efficacy" network of QKL Oral Preparation was constructed. Molecular docking showed that the main active components had high binding affinity to the key targets. In vitro cell experiment indicated that the six components in the prescription(hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide) can reduce the expression of nitric oxide(NO), TNF-α, and interleukin-6(IL-6) in cell supernatant(P<0.05). Thus, the above six components may be the key pharmacodynamic substances of QKL Oral Preparation. The major components in QKL Oral Prescription, including hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide, cholic acid, isochlorogenic acid A, and γ-aminobutyric acid, may interfere with multiple biological processes related to inflammation, immune regulation, fever, and convulsion by acting on the key protein targets such as IL-6, TNF, prostaglandin-endoperoxide synthase 2(PTGS2), arachidonate 5-lipoxygenase(ALOX5), vascular cell adhesion molecule 1(VCAM1), nitric oxide synthase 2(NOS2), prostaglandin E2 receptor EP2 subtype(PTGER2), gamma-aminobutyric acid receptor subunit alpha(GABRA), gamma-aminobutyric acid type B receptor subunit 1(GABBR1), and 4-aminobutyrate aminotransferase(ABAT). This study reveals the effective components and mechanism of QKL Oral Prescription.
Chlorogenic Acid ; Drugs, Chinese Herbal/pharmacology* ; gamma-Aminobutyric Acid ; Interleukin-6 ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Tumor Necrosis Factor-alpha/genetics* ; Animals ; Mice ; RAW 264.7 Cells

Starting with the relationship between mulberry leaves and silkworm droppings as food and metabolites, this study systematically compared the chemical components, screened out differential components, and quantitatively analyzed the main differential components based on ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) and UPLC-Q-TRAP-MS combined with principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA). Moreover, the in vitro enzymatic transformation of the representative differential components was studied. The results showed that(1) 95 components were identified from mulberry leaves and silkworm droppings, among which 27 components only exist in mulberry leaves and 8 components in silkworm droppings. The main differential components were flavonoid glycosides and chlorogenic acids.(2) Nineteen components with significant difference were quantitatively analyzed, and the components with significant differences and high content were neochlorogenic acid, chlorogenic acid, and rutin.(3) The crude protease in the mid-gut of silkworm significantly metabolized neochlorogenic acid and chlorogenic acid, which may be an important reason for the efficacy change in mulberry leaves and silkworm droppings. This study lays a scientific foundation for the development, utilization, and quality control of mulberry leaves and silkworm droppings. It provides references for clarifying the possible material basis and mechanism of the pungent-cool and dispersing nature of mulberry leaves transforming into the pungent-warm and dampness-resolving nature of silkworm droppings, and offers a new idea for the study of nature-effect transformation mechanism of traditional Chinese medicine.
Animals ; Bombyx ; Morus/chemistry* ; Chlorogenic Acid/analysis* ; Gas Chromatography-Mass Spectrometry ; Chromatography, High Pressure Liquid/methods* ; Plant Leaves/chemistry*

Qingjin Huatan Decoction is a classic prescription with the effects of clearing heat, moistening lung, resolving phlegm, and relieving cough. In order to explore the critical quality attributes of Qingjin Huatan Decoction, we identified the blood components of Qingjin Huatan Decoction by ultra-performance liquid chromatography quadrupole time of flight mass spectrometry(UPLC-Q-TOF-MS) under the following conditions, chromatographic column: Acquity UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 μm); mobile phase: 0.1% formic acid acetonitrile(A)-0.1% formic acid in water(B); gradient elution; flow rate: 0.2 mL·min~(-1); column temperature: 30 ℃; injection volume: 5 μL. The electrospray ionization(ESI) source was used to collect data in both positive and negative ion modes under the following conditions, capillary voltage: 3 kV for the positive ion mode and 2 kV for the negative ion mode; ion source temperature: 110 ℃; cone voltage: 30 V; cone gas flow rate: 50 L·h~(-1); nitrogen degassing temperature: 350 ℃; degassing volume flow rate: 800 L·h~(-1); scanning range: m/z 50-2 000. In this experiment, a total of 66 related components of Qingjin Huatan Decoction were identified, including 22 prototype components and 44 metabolites. The results of this study preliminarily revealed the pharmacodynamic material basis of Qingjin Huatan Decoction in vivo, which has provided an experimental basis for the determination of quality markers of Qingjin Huatan Decoction and the development of new drugs.
Chromatography, High Pressure Liquid/methods* ; Chromatography, Liquid ; Drugs, Chinese Herbal/chemistry* ; Tandem Mass Spectrometry/methods*

This study aims to establish a method for analyzing the chemical constituents in Cistanches Herba by high performance liquid chromatography(HPLC) and quadrupole-time-of-flight tandem mass spectrometry(HPLC-Q-TOF-MS/MS), and to reveal the pharmacological mechanism based on network pharmacology for mining the quality markers(Q-markers) of Cistanches Herba. The chemical constituents of Cistanche deserticola and C. tubulosa were analyzed via HPLC-Q-TOF-MS/MS. The potential targets and pathways of Cistanches Herba were predicted via SwissTargetPrediction and DAVID. The compound-target-pathway-pharmacological action-efficacy network was constructed via Cytoscape. A total of 47 chemical constituents were identified, involving 95 targets and 56 signaling pathways. We preliminarily elucidated the pharmacological mechanisms of echinacoside, acteoside, isoacteoside, cistanoside F, 2'-acetylacteoside, cistanoside A, campneoside Ⅱ, salidroside, tubuloside B, 6-deoxycatalpol, 8-epi-loganic acid, ajugol, bartsioside, geniposidic acid, and pinoresinol 4-O-β-D-glucopyranoside, and predicted them to be the Q-markers of Cistanches Herba. This study identified the chemical constituents of Cistanches Herba, explained the pharmacological mechanism of the traditional efficacy of Cistanches Herba based on network pharmacology, and introduced the core concept of Q-markers to improve the quality evaluation of Cistanches Herba.
Chromatography, High Pressure Liquid/methods* ; Cistanche ; Drugs, Chinese Herbal/pharmacology* ; Network Pharmacology ; Tandem Mass Spectrometry/methods*

We explored the pharmacodynamic material basis and network regulatory mechanism of Fufang Yuxingcao Mixture (FYM) for the treatment of fever and inflammation. Targets of the 25 compounds in FYM were predicted according to the reverse pharmacophore method and TCMSP, UniProt database. Gene ontology (GO) function enrichment and pathway analysis of the targets was analyzed by Omicsbean software and the Kyoto Gene and Genome Encyclopedia (KEGG) database. A "compound-target-pathway-pharmacological action-effect" network was established with Cytoscape 3.6.1 software. The lipopolysaccharide (LPS)-induced RAW264.7 cell inflammation model was used to verify the anti-inflammatory effects of FYM and its 10 important components. The network pharmacology experiment showed that 25 compounds affected 97 pathways through 211 targets, of which 15 key targets [including RAC-alpha serine/threonine-protein kinase (AKT1), insulin (INS), vascular endothelial growth factor A (VEGFA), interleukin-6 (IL-6), cellular tumor antigen p53 (TP53), tumor necrosis factor (TNF), transcription factor AP-1 (JUN), caspase-3 (CASP3), matrix metalloproteinase-9 (MMP9), interleukin-8 (IL-8), prostaglandin G/H synthase 2 (PTGS2), proto-oncogene c-Fos (FOS), tyrosine-protein kinase SRC (SRC), c-Jun N-terminal kinase 1 (MAPK8), estrogen receptor 1 (ESR1)] and 46 pathways (including NF-kappa B signaling pathway, Toll-like receptor signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, arachidonic acid metabolism, cAMP signaling pathway, T cell receptor signaling pathway, calcium signaling pathway, inflammatory mediator regulation of TRP channels, chemokine signaling pathway, Th1 and Th2 cell differentiation, natural killer cell mediated cytotoxicity, etc.) were related to anti-inflammatory, antipyretic, immune regulation, and analgesia. In vitro cell experiments showed that FYM and the 10 components (including isoquercitrin, luteoloside, baicalein, wogonin, wogonoside, phillyrin, forsythoside A, chlorogenic acid, isochlorogenic acid A, and sweroside) could significantly reduce the expression of nitric oxide (NO), TNF-α and IL-6 in cell supernatants, indicating that the above 10 components may be the key pharmacodynamic material basis of FYM.

Objective:To explore the effects of diverse exogenous substances at different concentrations on the growth of Polyporus umbellatus mycelium and polysaccharide content and screen out the optimal growth condition for P. umbellatus mycelium， so as to provide a reference for its large-scale artificial cultivation. Method:P. umbellatus mycelium was cultured in media containing different exogenous substances using the method for fungal culturing in plate. The growth rate of the mycelium was judged by the colony diameter and the polysaccharide content was determined by the phenol-sulfuric acid method. Result:The high-dose cyclic adenosine monophosphate， 6-benzyl aminopurine （6-BA）， gibberellic acid （GA）， 2，4-dichlorophenoxyacetic acid （2，4-D）， vitamin （V） B₁， VB₃， VB₆， VB₉， and VB₁₂ all promoted the growth of P. umbellatus mycelium and elevated polysaccharides content. By contrast， indole acetic acid （IAA）， VC， and VB₂ inhibited its growth， with the most obvious inhibition detected in the high-dose VC group. IAA and VB₂ both reduced the polysaccharide content， whereas the high-dose VC significantly increased the polysaccharide content. Cyclic adenosine monophosphate， 6-BA， GA， 2，4-D， VB₁， VB₃， VB₆， VB₉， and VB₁₂ at the concentrations of 2 mmol·L^-1， 6 mg·L^-1， 15 mg·L^-1， 2 mg·L^-1， 4 mg·L^-1， 2 mg·L^-1， 4 mg·L^-1， 6 mg·L^-1， and 10 mg·L^-1， respectively， contributed to the growth of P. umbellatus mycelium and polysaccharide accumulation. Conclusion:The growth of P. umbellatus mycelium and polysaccharide accumulation can be regulated by adding exogenous substances to the culture medium.