Objective To investigate the mechanism of Fuzheng Yangxin Prescription in improving cardiac function in rats with heart failure with reduced ejection fraction(HFrEF)through regulation of AMPK/mTOR signaling pathway.Methods An HFrEF rat model was established via left anterior descending coronary artery ligation.Rats were randomized divided into sham-operation group,model group,Fuzheng Yangxin Prescription group and Entresto group,followed by 28 days of intervention.Echocardiography was used to measure left ventricular internal dimension at end-systole(LVIDs),left ventricular internal dimension at end-diastole(LVIDd),left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),HE staining and Masson staining were used to observe myocardial morphology and fibrosis,serum contents of NT-proBNP and inflammatory factors(TNF-α,IL-1β,IL-6)were detected by ELISA,Western blot was performed to analyze p-AMPK,p-mTOR and protein expressions of autophagy markers(Beclin1,LC3,p62).Results Compared with sham-operation group,the LVIDs and LVIDd in model group significantly increased(P<0.05),while LVEF and LVFS significantly decreased(P<0.05),the structure of myocardial cells was disordered and arranged loosely,the deposition of collagen fibers in the infarct area was increased,and the contents of NT-proBNP,TNF-α,IL-1β and IL-6 in serum significantly increased(P<0.05),the protein expressions of p-AMPK,Beclin1 and LC3Ⅱ/LC3Ⅰ in myocardial tissue significantly decreased(P<0.05),while the protein expressions of p-mTOR and p62 significantly increased(P<0.05);compared with the model group,the LVIDs and LVIDd of rats in Fuzheng Yangxin Prescription group significantly decreased(P<0.05),the LVEF and LVFS were significantly increased(P<0.05),the disorder of myocardial cell arrangement and fibrosis were alleviated,the contents of NT-proBNP,TNF-α,IL-1β and IL-6 in serum significantly decreased(P<0.05),the protein expressions of p-AMPK,Beclin1 and LC3Ⅱ/LC3Ⅰ in myocardial tissue significantly increased(P<0.05),while the protein expressions of p-mTOR and p62 significantly decreased(P<0.05).Conclusion Fuzheng Yangxin Prescription may regulate autophagy by activating AMPK/mTOR pathway and improve cardiac function in HFrEF rats.

Objective: To evaluate the effects of different surface treatment methods and simulated aging on the roughness, microhardness, and color stability of lithium disilicate glass ceramics(LDC). Methods: The LDC were grouped and performed 5 kinds of surface treatments: control group, polishing group, polishing+polishing paste group, glazing group, polishing+glazing group. The roughness and microhardness of the specimen were measured. Then the specimens were divided into two subgroupswhich were treated with water and staining solution. The specimens were measured color parameters before and after processing. The above data was analyzed. Results: The LDC had changes in surface roughness and microhardness after different surface treatments. The polishing+polishing paste group had the lowest surface roughness, and the surface microhardness of the LDC decreased after glazing. After simulating aging, the difference of color and transparency of the polishing+polishing paste group, glazing group, and polishing+glazing group were the smallest. Conclusion Different surface treatments and simulated aging have a certain impact on the roughness, microhardness, and color stability of LDC. Fine polishing with polishing paste has a comparable anti staining effect to glazing on LDC.

Objective:To explore the clinical application value of a combined model based on the radiomics features of magnetic resonance imaging(MRI)and MRI signs in predicting recurrence after radical resection for hepatocellular carcinoma(HCC).Methods:A retrospective analysis was conducted on the imaging data of 100 patients with radical resection for HCC who admitted to Zibo 148 Hospital from May 2016 to May 2020.All patients underwent abdominal enhanced MRI examination before surgery,and they were followed up for at least 2 years after the surgery.They were randomly divided into training group(70 cases)and verification group(30 cases)as a ratio of 7:3.According to the postoperative follow-up results,the training group existed 12 cases of recurrence and 58 cases without recurrence,and the verification group existed 5 cases of recurrence and 25 cases without recurrence.The 3D-slicer software was used to extract radiomics features of preoperative MRI images of each HCC patient.The intra-group correlation coefficient(ICC)of the extracted imaging features of the observers was calculated.The maximum related minimum redundancy(mRMR)algorithm and LASSO regression were selected to analyze the established radiomics labels after dimensionality reduction and screening.Univariate and multivariate logistic regression analysis were used to screen the independent risk factors of predicting recurrence in MRI signs,and they were used respectively to construct radiomics models with the radiomics labels of plain scan,arterial phase,portal phase and hepatobiliary phase.The receiver operating characteristic(ROC)curve was used to assess the diagnostic efficacy of each radiomics model in predicting recurrence.Results:The ICC range of two physicians in selecting radiomics features from the MRI images of all patients were between 0.903 and 0.957,which consistency was favorable(ICC≥0.9).Compared with other predictive models,the highest area under curve(AUC)values of ROC curve of the radiomics model of plain scan of training group[0.951(95%CI:0.901-1.000)]and verification group[0.968(95%CI:0.917-1.000)]were respectively 0.951 and 0.968 in predicting recurrence after radical resection for liver cancer.Conclusion:The combined model that is constructed on the basis of MRI radiomics features has favorable predictive value for the recurrence of patients after radical resection for HCC.Among of them,the radiomics model of plain scan has a certain guiding role in the clinical implementation of personalized treatment plans under the absence of enhancement,and in underdeveloped areas.

Objective To investigate the mechanism of Fuzheng Yangxin Prescription in improving cardiac function in rats with heart failure with reduced ejection fraction(HFrEF)through regulation of AMPK/mTOR signaling pathway.Methods An HFrEF rat model was established via left anterior descending coronary artery ligation.Rats were randomized divided into sham-operation group,model group,Fuzheng Yangxin Prescription group and Entresto group,followed by 28 days of intervention.Echocardiography was used to measure left ventricular internal dimension at end-systole(LVIDs),left ventricular internal dimension at end-diastole(LVIDd),left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),HE staining and Masson staining were used to observe myocardial morphology and fibrosis,serum contents of NT-proBNP and inflammatory factors(TNF-α,IL-1β,IL-6)were detected by ELISA,Western blot was performed to analyze p-AMPK,p-mTOR and protein expressions of autophagy markers(Beclin1,LC3,p62).Results Compared with sham-operation group,the LVIDs and LVIDd in model group significantly increased(P<0.05),while LVEF and LVFS significantly decreased(P<0.05),the structure of myocardial cells was disordered and arranged loosely,the deposition of collagen fibers in the infarct area was increased,and the contents of NT-proBNP,TNF-α,IL-1β and IL-6 in serum significantly increased(P<0.05),the protein expressions of p-AMPK,Beclin1 and LC3Ⅱ/LC3Ⅰ in myocardial tissue significantly decreased(P<0.05),while the protein expressions of p-mTOR and p62 significantly increased(P<0.05);compared with the model group,the LVIDs and LVIDd of rats in Fuzheng Yangxin Prescription group significantly decreased(P<0.05),the LVEF and LVFS were significantly increased(P<0.05),the disorder of myocardial cell arrangement and fibrosis were alleviated,the contents of NT-proBNP,TNF-α,IL-1β and IL-6 in serum significantly decreased(P<0.05),the protein expressions of p-AMPK,Beclin1 and LC3Ⅱ/LC3Ⅰ in myocardial tissue significantly increased(P<0.05),while the protein expressions of p-mTOR and p62 significantly decreased(P<0.05).Conclusion Fuzheng Yangxin Prescription may regulate autophagy by activating AMPK/mTOR pathway and improve cardiac function in HFrEF rats.

Objective:To explore the clinical application value of a combined model based on the radiomics features of magnetic resonance imaging(MRI)and MRI signs in predicting recurrence after radical resection for hepatocellular carcinoma(HCC).Methods:A retrospective analysis was conducted on the imaging data of 100 patients with radical resection for HCC who admitted to Zibo 148 Hospital from May 2016 to May 2020.All patients underwent abdominal enhanced MRI examination before surgery,and they were followed up for at least 2 years after the surgery.They were randomly divided into training group(70 cases)and verification group(30 cases)as a ratio of 7:3.According to the postoperative follow-up results,the training group existed 12 cases of recurrence and 58 cases without recurrence,and the verification group existed 5 cases of recurrence and 25 cases without recurrence.The 3D-slicer software was used to extract radiomics features of preoperative MRI images of each HCC patient.The intra-group correlation coefficient(ICC)of the extracted imaging features of the observers was calculated.The maximum related minimum redundancy(mRMR)algorithm and LASSO regression were selected to analyze the established radiomics labels after dimensionality reduction and screening.Univariate and multivariate logistic regression analysis were used to screen the independent risk factors of predicting recurrence in MRI signs,and they were used respectively to construct radiomics models with the radiomics labels of plain scan,arterial phase,portal phase and hepatobiliary phase.The receiver operating characteristic(ROC)curve was used to assess the diagnostic efficacy of each radiomics model in predicting recurrence.Results:The ICC range of two physicians in selecting radiomics features from the MRI images of all patients were between 0.903 and 0.957,which consistency was favorable(ICC≥0.9).Compared with other predictive models,the highest area under curve(AUC)values of ROC curve of the radiomics model of plain scan of training group[0.951(95%CI:0.901-1.000)]and verification group[0.968(95%CI:0.917-1.000)]were respectively 0.951 and 0.968 in predicting recurrence after radical resection for liver cancer.Conclusion:The combined model that is constructed on the basis of MRI radiomics features has favorable predictive value for the recurrence of patients after radical resection for HCC.Among of them,the radiomics model of plain scan has a certain guiding role in the clinical implementation of personalized treatment plans under the absence of enhancement,and in underdeveloped areas.

Objective To analyze the core functional component groups(CFCG)in Yinchenhao Decoction(YCHD)and their possible pathways for treating hepatic fibrosis based on network pharmacology.Methods PPI data were extracted from DisGeNET,Genecards,CMGRN and PTHGRN to construct a weighted network using Cytoscape 3.9.1.The data of the chemical components in YCHD were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the potential active components and targets were selected using PreADMET Web server and SwissTargetPrediction.A fusion model was constructed to obtain the functional effect space and evaluate the effective proteins to identify the CFCG followed by GO and KEGG pathway enrichment analyses for all the targets.In cultured human hepatic stellate cells(LX-2 cells),the cytotoxicity of different compounds in YCHD was tested using CCK-8 assay;the effects of these compounds on collagen α1(Col1a1)mRNA expression and the pathways in 20 ng/mL TGF-β1-stimulated cells were analyzed using RT-qPCR and Western blotting.Results A total of 1005 pathogenic genes,226 potential active components and 1529 potential targets in YCHD and 52 potential targets of CFCG were obtained.Benzyl acetate,vanillic acid,clorius,polydatin,lauric acid and ferulic acid were selected for CCK-8 verification,and they all showed minimal cytotoxicity below the concentration of 200 μmol/L.Clorius,polydatin,lauric acid and ferulic acid all effectively inhibited TGF-β1-induced LX-2 cell activation.At the concentration of 200 μmol/L,all these 4 components inhibited PI3K,p-PI3K,AKT,p-AKT,ERK,p-ERK,P38 MAPK and p-P38 MAPK expressions in TGF-β1-induced LX-2 cells.Conclusion The therapeutic effect of YCHD on hepatic fibrosis is probably mediated by its core functional components including benzyl acetate,vanillic acid,clorius,polydatin,lauric acid and ferulic acid,which inhibit the PI3K-AKT and MAPK pathways in hepatic stellate cells.

Objective:To discuss the effect of long-term use of chlorhexidine on the resistance of Enterococcus faecalis(E.faecalis),and to clarify its mechanism.Methods:The standard strain of E.faecalis was repeatedly exposed to chlorhexidine for 10 generations,and the minimum inhibitory concentration(MIC)was recorded at each passage.The bacteria collected from the 10th generation with increased MIC values were designated as the E.faecalis chlorhexidine-resistant strains(E.faecalis-Cs).The growth curves of two strains were drawn;the morphology of two strains were observed by transmission electron microscope;the number of biofilm formation of two strains was detected by crystal violet staining;the bacterial hydrophobicities of two strains were detected by microbial adhesion to hydrocarbons(MATH)method;the expression levels of S-ribosylhomocysteine lyase(LuxS)mRNA in the bacterial biofilms of two strains were detected by real-time fluorescence quantitative PCR(RT-qPCR)method.Results:From the 0th to the 10th generation,the MIC values of E.faecalis were gradually increased.The growth curves of E.faecalis and E.faecalis-Cs showed no significant differences.The transmission electron microscope observation results showed that both E.faecalis and E.faecalis-Cs appeared oval or diplococcal,with intact cell wall structures,smooth edges,and evenly distributed cytoplasm.There were no significant differences in the morphology,size,cell wall thickness,or integrity between two types of bacteria.The crystal violet staining results showed that compared with E.faecalis,the number of biofilm formation of E.faecalis-Cs was significantly increased(P<0.05).The MATH results showed tha the hydrophobicity of E.faecalis-Cs was significantly higher than that of E.faecalis(P<0.05).The RT-qPCR results showed that the expression level of LuxS mRNA in the biofilms of E.faecalis-Cs was significantly higher than that of E.faecalis(P<0.05).Conclusion:E.faecalis develops the resistance after repeated exposure to the chlorhexidine,and the pathogenicity of the resistant strain is enhanced.The high expressin of quorum sensing(QS)system LuxS gene and stronger biofilm forming ability of bacteria may be the potential mechanism for E.faecalis to tolerate the chlorhexidine.

Objective To analyze the core functional component groups(CFCG)in Yinchenhao Decoction(YCHD)and their possible pathways for treating hepatic fibrosis based on network pharmacology.Methods PPI data were extracted from DisGeNET,Genecards,CMGRN and PTHGRN to construct a weighted network using Cytoscape 3.9.1.The data of the chemical components in YCHD were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the potential active components and targets were selected using PreADMET Web server and SwissTargetPrediction.A fusion model was constructed to obtain the functional effect space and evaluate the effective proteins to identify the CFCG followed by GO and KEGG pathway enrichment analyses for all the targets.In cultured human hepatic stellate cells(LX-2 cells),the cytotoxicity of different compounds in YCHD was tested using CCK-8 assay;the effects of these compounds on collagen α1(Col1a1)mRNA expression and the pathways in 20 ng/mL TGF-β1-stimulated cells were analyzed using RT-qPCR and Western blotting.Results A total of 1005 pathogenic genes,226 potential active components and 1529 potential targets in YCHD and 52 potential targets of CFCG were obtained.Benzyl acetate,vanillic acid,clorius,polydatin,lauric acid and ferulic acid were selected for CCK-8 verification,and they all showed minimal cytotoxicity below the concentration of 200 μmol/L.Clorius,polydatin,lauric acid and ferulic acid all effectively inhibited TGF-β1-induced LX-2 cell activation.At the concentration of 200 μmol/L,all these 4 components inhibited PI3K,p-PI3K,AKT,p-AKT,ERK,p-ERK,P38 MAPK and p-P38 MAPK expressions in TGF-β1-induced LX-2 cells.Conclusion The therapeutic effect of YCHD on hepatic fibrosis is probably mediated by its core functional components including benzyl acetate,vanillic acid,clorius,polydatin,lauric acid and ferulic acid,which inhibit the PI3K-AKT and MAPK pathways in hepatic stellate cells.

Objective To screen ischemia and hypoxiarelated genes(IAHRGs)after spinal cord injury(SCI)and analyze their immune infiltration patterns by bioinformatics methods.Methods The expression profiles of SCI-related GSE5296,GSE47681 and GSE217797 were downloaded from the Gene Expression Omnibus(GEO)database,where GSE5296,GSE47681 samples were used as the test set and GSE217797 samples as the validation set,and the differentially expressed genes(DEGs)between SCI and healthy samples were obtained.IAHRGs were screened in GeneCards and MSigDB databases.The intersection of DEGs and IAHRGs yielded ischemic and hypoxia related differentially expressed genes(IAHRDEGs).Based on the IAHRDEGs,the key genes were jointly screened by LASSO model and SVM analysis.The key genes were subjected to logistic regression analysis and a diagnostic model was constructed.The diagnostic ability of the diagnostic model was analyzed by Nomogram and the column line graph of Logistic predictive values was plotted.The diagnostic value of the diagnostic model and key genes for SCI was evaluated using the receiver operating characteristics(ROC).Immune cell infiltration patterns of the disease were analyzed using the CIBERSORT tool.Results A total of 388 IAHRGs were screened,313 differentially expressed genes were detected between SCI and healthy samples,among which 312 were up-regulated and 1 was down-regulated.A sum of 27 up-regulated IAHRDEGs genes were obtained.Five key genes related to ischemia and hypoxia after SCI(Abca1,Caspl,Lpl,Procr,Tnfrsf1a)were screened by LASSO model and SVM analysis based on IAHRDEGs.Nomogram analysis confirms the effect of logistics diagnosis model.ROC curve analysis showed that Casp1,Lpl and Tnfrsf1a had higher diagnostic efficacy(AUC＞0.9),followed by Abca1 and Procr(AUC:0.7～0.9),and the logistics linear predictors had the best diagnostic effect(AUC=0.964).CIBERSORT analysis showed that five key genes were associated with the infiltration of eight types of immune cells(neutrophil cells,B cells naive,plasma cells,M0 macrophage,T cells CD4 naive,T cells CD4 follicular,Th17 cells,and NK resting).Conclusion The five key genes of Abcal,Caspl,Lpl,Procr,and Tnfrsfla,may be closely related to ischemic-hypoxic pathogenesis after SCI,and can be used as candidate molecular markers for the diagnosis and treatment after SCI.

Objective:To evaluate the role of histogram analysis based on amide proton transfer weighted (APTw) and apparent diffusion coefficient (ADC) imaging in predicting alpha-thalassemia/mental retardation syndrome X-linked ( ATRX) mutation in isocitrate dehydrogenase ( IDH)-mutant WHO grading 2/3 gliomas. Methods:Seventy-eight patients with IDH-mutant WHO grading 2/3 gliomas, admitted to and confirmed by surgical pathology in Department of Functional Neurosurgery, Neurosurgery Center, Zhujiang Hospital, Southern Medical University from June 2017 to October 2023, including 52 with ATRX wild and 26 with ATRX mutant-type, were selected. Preoperative 3D-APTw and ADC imaging data were collected; after post-processing, the lesions were segmented using lesion outlining method based on inclusion of peri-tumor edema and lesion outlining method based on tumor entity, respectively; after that, the histogram features (the 10 th percentile, 90 th percentile, maximum, mean, median, minimum, skewness, kurtosis, entropy, range, uniformity, and variance) were extracted from 3D-APTw and ADC imaging, respectively. Univariate Logistic regression was used to compare the differences in histogram features between patients in the ATRX mutant group and ATRX wild-type group, and multivariate Logistic regression was used to screen the independent predictors for ATRX mutation (a Logistic regression prediction model was constructed). Predictive values of independent predictors and Logistic regression prediction models in ATRX mutation were evaluated by receiver operating characteristic (ROC) curve. Results:(1) With lesion outlining method based on inclusion of peri-tumor edema, univariate analysis indicated significant difference between ATRX mutant group and ATRX wild-type group in 9 histogram features: relative 3D-APTw minimum, 3D-APTw skewness, relative ADC 90 th percentile, relative ADC mean, relative ADC median, ADC kurtosis, ADC skewness, ADC uniformity, and ADC entropy ( P<0.05). With lesion outlining method based on tumor entity, univariate analysis indicated significant difference between ATRX mutant group and ATRX wild-type group in 9 histogram features: relative 3D-APTw 90 th percentile, 3D-APTw skewness, relative ADC 90 th percentile, relative ADC mean, relative ADC median, ADC kurtosis, ADC skewness, ADC uniformity and ADC entropy ( P<0.05). (2) With lesion outlining method based on inclusion of peri-tumor edema, multivariate Logistic regression showed that 3D-APTw skewness and ADC kurtosis were the independent predictor for ATRX mutation in IDH mutant WHO grading 2/3 glioma patients ( OR=0.168, 95% CI: 0.034-0.800, P=0.025; OR=0.508, 95% CI: 0.319-0.807, P=0.004). The constructed Logistic regression prediction model was P(Y=1|X)=1/1+e -(1.827-1.785×3D-APTw skewness-0.678×ADC kurtosis). With lesion outlining method based on tumor entity, multivariate Logistic regression showed that 3D-APTw skewness and ADC kurtosis were independent predictors for ATRX mutation in IDH mutant WHO grading 2/3 glioma patients ( OR=0.164, 95% CI: 0.034-0.791, P=0.024; OR=0.496, 95% CI: 0.312-0.788, P=0.003); the constructed Logistic regression prediction model was P(Y=1|X)=1/1+e -(1.585-1.810×3D-APTw skewness-0.702×ADC kurtosis). (3) ROC curve analysis showed that, with lesion outlining method based on inclusion of peri-tumor edema, area under ROC curve (AUC) of 3D-APTw skewness and ADC kurtosis was 0.725 (95% CI: 0.608-0.842, P=0.001) and 0.794 (95% CI: 0.685-0.904), respectively ( P<0.001); AUC of Logistic regression prediction model was 0.836 (95% CI: 0.729-0.942, P<0.001), and its sensitivity and specificity were 73.10% and 90.40% when the best threshold was 0.505. ROC curve showed that, with lesion outlining method based on tumor entity, AUC of 3D-APTw skewness and ADC kurtosis was 0.705 (95% CI: 0.587-0.823, P=0.003) and 0.808 (95% CI: 0.704-0.913), respectively ( P<0.001); AUC of Logistic regression prediction model was 0.844 (95% CI: 0.739-0.949, P<0.001), and its sensitivity and specificity were 84.60% and 80.80% when the best threshold was 0.399. Conclusion:Histogram analysis based on 3D-APTw and ADC imaging can predict ATRX mutation in IDH mutant WHO grading 2/3 gliomas to a certain extent.