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.

Objective: To explore the clinical characteristics and prognostic factors of female patients with Stanford type B aortic dissection. Methods: This is a single-centre retrospective study. Consecutive patients diagnosed with Stanford type B aortic dissection in General Hospital of Northern Theater Command from June 2002 to August 2021 were enrolled, and grouped based on sex. According to the general clinical conditions and complications of aortic dissection tear, patients were treated with thoracic endovascular aortic repair, surgery, or optimal medication. The clinical characteristics and aortic imaging data of the patients at different stages were collected, adverse events including all-cause deaths, stroke, and occurrence of aortic-related adverse events were obtained during hospitalization and within 30 days and at 1 and 5 years after discharge. According to the time of death, death was classified as in-hospital death, out-of-hospital death, and in-hospital death was divided into preoperative death, intraoperative death and postoperative death. According to the cause of death, death was classified as aortic death, cardiac death and other causes of death. Aortic-related adverse events within 30 days after discharge included new paraplegia, post-luminal repair syndrome, and aortic death; long-term (≥1 year after discharge) aortic-related adverse events included aortic death, recurrent aortic dissection, endoleak and distal ulcer events. The clinical characteristics, short-term and long-term prognosis was compared between the groups. Logistic regression analysis was used to explore the association between different clinical factors and all-cause mortality within 30 days in female and male groups separately. Results: A total of 1 094 patients with Stanford type B aortic dissection were enrolled, mean age was (53.9±12.1) years, and 861 (78.7%) were male and 233 (21.3%) were female. (1) Clinical characteristics: compared with male patients, female patients were featured with older average age, higher proportion of aged≥60 years old, back pain, anemia, optimal medication treatment, and higher cholesterol level; while lower proportion of smoking and drinking history, body mass index, calcium antagonists use, creatine kinase level, and white blood cell count (all P<0.05). However, there was no significant difference in dissection tear and clinical stage, history of coronary heart disease, diabetes, hypertension, and cerebrovascular disease between female and male patients (all P>0.05). (2) Follow-up result: compared with male patients, female patients had a higher rate of 30-day death [6.9% (16/233) vs. 3.8% (33/861), P=0.047], in-hospital death (5.6% (13/233) vs. 2.7% (23/861), P=0.027), preoperative death (3.9% (9/233) vs. 1.5% (12/861), P=0.023) and aorta death (6.0% (14/233) vs. 3.1% (27/861), P=0.041). The 1-year and 5-year follow-up results demonstrated that there were no significant differences in death, cerebrovascular disease, and aorta-related adverse events between the two groups (all P>0.05). (3) Prognostic factors: the results of the univariate logistic regression analysis showed that body mass index>24 kg/m² (HR=1.087, 95%CI 1.029-1.149, P=0.013), history of anemia (HR=2.987, 95%CI 1.054-8.468, P=0.032), hypertension (HR=1.094, 95%CI 1.047-1.143, P=0.040) and troponin-T>0.05 μg/L (HR=5.818, 95%CI 1.611-21.018, P=0.003)were associated with an increased risk of all-cause mortality within 30 days in female patients. Conclusions: Female patients with Stanford type B aortic dissection have specific clinical characteristics, such as older age at presentation, higher rates of anemia and combined back pain, and higher total cholesterol levels. The risk of death within 1 month is higher in female patients than in male patients, which may be associated with body mass index, hypertension, anemia and troponin-T, but the long-term prognosis for both female and male patients is comparable.
Humans ; Male ; Female ; Adult ; Middle Aged ; Aged ; Prognosis ; Hospital Mortality ; Retrospective Studies ; Troponin T ; Aortic Aneurysm, Thoracic/surgery* ; Blood Vessel Prosthesis Implantation/adverse effects* ; Treatment Outcome ; Endovascular Procedures/adverse effects* ; Aortic Dissection ; Hypertension/complications* ; Cholesterol ; Risk Factors

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*

OBJECTIVE: To investigate the effect of Yinlai Decoction (YD) on the microstructure of colon, and activity of D-lactic acid (DLA) and diamine oxidase (DAO) in serum of pneumonia mice model fed with high-calorie and high-protein diet (HCD). METHODS: Sixty male Kunming mice were randomly divided into 6 groups by the random number table method: normal control, pneumonia, HCD, HCD with pneumonia (HCD-P), YD (229.2 mg/mL), and dexamethasone (15.63 mg/mL) groups, with 10 in each group. HCD mice were fed with 52% milk solution by gavage. Pneumonia mice was modeled with lipopolysaccharide inhalation and was fed by gavage with either the corresponding therapeutic drugs or saline water, twice daily, for 3 days. After hematoxylin-eosin staining, the changes in the colon structure were observed under light microscopy and transmission electron microscope, respectively. Enzyme-linked immunosorbent assay was used to detect the protein levels of DLA and DAO in the serum of mice. RESULTS: The colonic mucosal structure and ultrastructure of mice in the normal control group were clear and intact. The colonic mucosal goblet cells in the pneumonia group tended to increase, and the size of the microvilli varied. In the HCD-P group, the mucosal goblet cells showed a marked increase in size with increased secretory activity. Loose mucosal epithelial connections were also observed, as shown by widened intercellular gaps with short sparse microvilli. These pathological changes of intestinal mucosa were significantly reduced in mouse models with YD treatment, while there was no significant improvement after dexamethasone treatment. The serum DLA level was significantly higher in the pneumonia, HCD, and HCD-P groups as compared with the normal control group (P<0.05). Serum DLA was significantly lower in the YD group than HCD-P group (P<0.05). Moreover, serum DLA level significantly increased in the dexamethasone group as compared with the YD group (P<0.01). There was no statistical significance in the serum level of DAO among groups (P>0.05). CONCLUSIONS YD can protect function of intestinal mucosa by improving the tissue morphology of intestinal mucosa and maintaining integrity of cell connections and microvilli structure, thereby reducing permeability of intestinal mucosa to regulate the serum levels of DLA in mice.
Mice ; Male ; Animals ; Lactic Acid/pharmacology* ; Intestinal Mucosa ; Colon/pathology* ; Dexamethasone/pharmacology* ; Diet, High-Protein ; Pneumonia/pathology*

Abstract：Objective To improve the replication level of varicella⁃zoster virus（VZV）in human diploid cell line MRC⁃5 and increase the yield of VZV vaccine by reducing the expression of interferon（IFN）related genes via optimizing the cell line MRC⁃5. Methods Interferon receptor 1（IFNAR1）silenced MRC⁃5 cell line（MRC⁃5IFNAR1⁃）was constructed by CRISPR／Cas9 gene editing technology，which was determined for the relative expression of IFNAR1 mRNA，and for those of mRNA of IFN related genes IFNβ and OAS1 after VZV infection by qRT⁃PCR to evaluate the effect of gene silencing. Gene mutation sequences were further identified by sequencing of the silenced sites. The replication of VZV in MRC⁃5 and MRC⁃5IFNAR1⁃ cell lines was compared 168 h after VZV infection by using qRT⁃PCR and plaque formation unit（PFU）assay， to evaluate the effect of MRC⁃5IFNAR1⁃cell line on VZV replication. Results The growth status of MRC⁃5IFNAR1⁃ cell line wasconsistent with that of MRC ⁃ 5 cells，and the relative expression of IFNAR1 mRNA decreased by 73%；The relative expressions of IFNβ and OAS1 mRNA in MRC⁃5IFNAR1⁃ cell line were 61% and 90% lower than those in MRC⁃ 5 cells respectively after VZV infection；In addition，168 h after VZV infection，the level of DNA replication and the titer of VZV increased by 5. 7 folds and 4 folds respectively. Conclusion The successful establishment of MRC⁃5IFNAR1⁃ cell line may be a potential scheme to increase the yield of vaccines based on human diploid cells，and provided a reference for expanding production of VZV vaccine.

Dead heart is an important trait of pith-decayed Scutellariae Radix. The purpose of this study was to clarify the scientific connotation of the dead heart using multi-omics. Metabolomics and transcriptomics combined with multivariate statistical analysis such as principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA) were used to systematically compare the differences in chemical composition and gene expression among phloem, outer xylem and near-dead xylem of pith-decayed Scutella-riae Radix. The results revealed significant differences in the contents of flavonoid glycosides and aglycones among the three parts. Compared with phloem and outer xylem, near-dead xylem had markedly lowered content of flavonoid glycosides(including baicalin, norwogonin-7-O-β-D-glucuronide, oroxylin A-7-O-β-D-glucuronide, and wogonoside) while markedly increased content of aglycones(including 3,5,7,2',6'-pentahydroxy dihydroflavone, baicalin, wogonin, and oroxylin A). The differentially expressed genes were mainly concentrated in KEGG pathways such as phenylpropanoid metabolism, flavonoid biosynthesis, ABC transporter, and plant MAPK signal transduction pathway. This study systematically elucidated the material basis of the dead heart of pith-decayed Scutellariae Radix with multiple growing years. Specifically, the content of flavonoid aglycones was significantly increased in the near-dead xylem, and the gene expression of metabolic pathways such as flavonoid glycoside hydrolysis, interxylary cork development and programmed apoptosis was significantly up-regulated. This study provided a theoretical basis for guiding the high-quality production of pith-decayed Scutellariae Radix.
Drugs, Chinese Herbal/chemistry* ; Scutellaria baicalensis/chemistry* ; Glucuronides ; Multiomics ; Flavonoids/chemistry*

Aim To study the effect of Rubus irritans Focke extract on adipogenic differentiation of 3T3-L1 preadipocytes, and to further explore the potential mechanism of Rubus irritans Focke on adipocyte metabolism, so as to provide a new basis for the prevention and treatment of obesity. Methods Rubus irritans Focke extract was separated and prepared by MCI medium pressure chromatographic column. MTT method was used to detect cell proliferation, and oil red 0 staining and kit test was used to to detect the level of lipid accumulation. Western blot was employed to detect the expressions of peroxisome proliferator-activated receptor ¦y (PPAR7), CCAAT enhancer binding protein a (C/ EBPa), adenosine 5'-monophosphate activated protein kinase (AMPK) and phosphorylated AMPK (p-AMPK) protein. Results When the concentration of Rubus irritans Focke extract was less than 100 mg •L