ObjectiveTo elucidate the chemical composition of Danshenyin and its blood components in rats after oral administration. MethodsUltra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry（UPLC-Q-TOF-MS/MS） coupled with PeakView 1.2 software was used to systematically characterize and identify the components of Danshenyin aqueous extract and its migratory components in rat blood after oral administration based on the retention time， quasi-molecular ion peaks， secondary fragmentation ions， and literature reports， and a preliminary compounds identification of Salviae Miltiorrhizae Radix et Rhizoma aqueous extract， the co-decoction of Santali Albi Lignum and Amomi Fructus was carried out to attribute the chemical constituents of the aqueous extract of Danshenyin. ResultsA total of 73 compounds， including 21 phenolic acids， 23 diterpenes， 6 flavonoids， 7 organic acids， 3 volatile oils and 13 others， were identified from the aqueous extract of Danshenyin. And 36 prototypes and 15 metabolites were identified in rat plasma， the major metabolic pathways included reduction， hydration， hydroxylation， demethylation， methylation， sulfation and others， these metabolites were mainly derived from tanshinones and salvianolic acids. ConclusionThe main blood components of the aqueous extract of Danshenyin are salvianolic acids and tanshinones， which may be the material basis of the efficacy. This study can provide reference for pharmacological research， quality control， and clinical application of Danshenyin.

Objective To investigate the clinical value of serum mast cell carboxypeptidase(MC-CP),C-C motif chemokine 26(CCL26),and decoy receptor 3(DcR3)in the diagnosis of obstructive sleep apnea syndrome(OSAS)in chronic obstructive pulmonary disease(COPD).Methods Ninety COPD patients who visited the First Affiliated Hospital of Hebei North University from January 2021 to January 2023 were collected.Among them,48 patients with simple COPD were included in the COPD group,and 42 patients with COPD combined with OSAS were included in the COPD-OSAS group.During the same period,48 healthy volunteers who underwent physical examination in that Hospital of Hebei North collected as the control group.Enzyme linked immunosorbent assay(ELISA)was applied to detect serum level of MC-CP,CCL26,and DcR3.Receiver operating characteristic(ROC)curve was applied to analyze the clinical value of serum level of MC-CP,CCL26,and DcR3 in the diag-nosis of COPD complicated with OSAS.Multivariate Logistic regression was applied to analyze the influencing fac-tors of COPD complicated with OSAS.Results Compared with the control group,the smoking index,C-reactive protein(CRP)and white blood cell count(WBC)in the COPD and COPD-OSAS groups increased obviously in sequence,the ratio of forced expiratory volume in first second to forced vital capacity(FEV1/FVC)decreased obviously in sequence(P<0.05);Compared with the control group,the level of MC-CP,CCL26,and DcR3 in patients with COPD and COPD-OSAS increased significantly in sequence(P<0.05);The combination of serum MC-CP,CCL26 and DcR3 had a higher area under the curve(AUC)for the diagnosis of COPD complicated with OSAS compared to the individual diagnosis(Z=4.066,P<0.001;Z=2.391,P<0.05;Z=2.353,P<0.05).Multivariate Logistic regression analysis showed that smoking index,serum level of MC-CP,CCL26 and DcR3 were influencing factors for COPD complicated with OSAS(P<0.05).Conclusions The simultane-ously increased expression of MC-CP,CCL26 and DcR3 in the serum of COPD may support clinical diagnostic of COPD patients with OSAS.

Objective:To develop an artificial intelligence (AI)-based automatic scoring model for magnetic resonance imaging-detected extramural vascular invasion (AI-mrEMVI) and evaluate its performance and prognostic value in patients with rectal cancer.Methods:In this multicenter retrospective cohort study, a total of 2 501 rectal cancer patients from seven centers between November 2012 and December 2020 were included and divided into completely independent training ( n=1 830) and validation ( n=671) cohorts. A nnUNet-based AI-mrEMVI scoring model was constructed. Manual mrEMVI scores assigned by two radiologists served as the reference standard for accessing the accuracy of the AI-mrEMVI scoring. Kaplan-Meier survival analysis and Cox regression were used to evaluate the prognostic stratification ability of the AI-mrEMVI scores. The concordance index (C-index) was calculated to evaluate prognostic performance. Results:In the validation cohort, the manual mrEMVI scores were 0-2 in 425 patients (63.3%), 3 in 89 (13.4%), and 4 in 157 (23.4%). The AI-mrEMVI model identified 0-2 in 375 patients (55.9%), 3 in 95 (14.2%), and 4 in 201 (30.0%), with an overall accuracy of 81.1% (544/671, 95% CI 77.9%-84.0%). The 3-year disease-free survival (DFS) rates for patients with AI-mrEMVI scores of 0-2, 3, and 4 were 85.2%, 70.0%, and 58.2%, respectively, and the 5-year overall survival (OS) rates were 87.2%, 81.6%, and 62.6%, respectively (DFS: χ2=48.74, P<0.001; OS: χ2=30.04, P<0.001). Multivariable Cox regression showed that for DFS, AI-mrEMVI scores of 3 and 4 were associated with hazard ratios ( HR) of 1.75 (95% CI 1.11-2.77, P=0.016) and 2.65 (95% CI 1.86-3.78, P<0.001), respectively. For OS, an AI-mrEMVI score of 4 was associated with an HR of 2.56 (95% CI 1.62-4.03, P<0.001). The C-index values of the AI-mrEMVI scoring model for predicting DFS and OS were 0.647 (95% CI 0.608-0.686) and 0.650 (95% CI 0.598-0.702), respectively. Conclusion:The proposed AI-mrEMVI automatic scoring model demonstrated high diagnostic accuracy and performed favorably in predicting DFS and OS prognostic risk in patients with rectal cancer.

Objective To investigate the expression levels and diagnostic value of long non coding RNA(lncRNA)DNA damage inducible transcript 4 like protein 4 antisense RNA1(lncRNA DDIT4-AS1)and long chain non coding RNA(lncRNA)radial spoke head protein 9 homolog 4(RSPH9-4)in serum of patients with bacterial meningitis.Methods A total of 94 patients with meningitis in the Fifth Hospital of Deyang City from May 2022 to May 2024 were regarded as the bacterial meningitis group.According to the severity of damage to the central nervous system caused by bacterial meningitis,they were further separated into a general group(n=63)and a severe group(n=31).94 patients with suspected meningitis upon admission but excluded meningitis after examination were selected as the non bacterial meningitis group.A total of 94 patients diagnosed with bacterial meningitis in the Fifth Hospital of Deyang City from May 2022 to May 2024 were selected as the bacterial meningitis group 94 healthy volunteers who underwent physicalexamination were as the control group.Real-time fluorescence quantitative PCR(qRT-PCR)method was applied to detect the expression levels of lncRNA DDIT4-AS1 and lncRNA RSPH9-4 in serum samples of all personnel.Spearman analysis was applied to analyze the correlation between serum levels of lncRNA DDIT4-AS1 and lncRNA RSPH9-4 with the severity of bacterial meningitis.Multivariate Logistic analysis was applied to analyze the influencing factors of bacterial meningitis.Receiver operating characteristic(ROC)curve was plotted to analyze the diagnostic value of serum lncRNA DDIT4-AS1 and lncRNA RSPH9-4 levels for bacterial meningitis.Results Compared with the control group,the expression levels of serum lncRNA DDIT4-AS1(1.35±0.27,1.67±0.35 vs 1.01±0.18)and lncRNA RSPH9-4(1.30±0.25,1.56±0.32 vs 1.00±0.19)were increased in non bacterial meningitis group and bacterial meningitis group(t=10.159,16.259;9.263,14.589),compared with the non bacterial meningitis group,the expression levels of serum lncRNA DDIT4-AS1 and lncRNA RSPH9-4 in the bacterial meningitis group were increased(t=7.019,6.208),and the differences were statistically significant(all P<0.05),respectively.Compared with the general group,the expression levels of serum lncRNA DDIT4-AS1(1.88±0.38 vs 1.56±0.31)and lncRNA RSPH9-4(1.79±0.35 vs 1.45±0.28)were increased in the severe group,and the differences were statistically significant(t=4.361,5.088,all P＜0.05).Spearman correlation analysis results showed that serum levels of lncRNA DDIT4-AS1,lncRNA RSPH9-4 were positively correlated with the severity of bacterial meningitis(r=0.524,0.548,all P<0.05).The expression levels of PCT,LDH and CRP in patients with bacterial meningitis were higher than those in patients without bacterial meningitis,and the differences were statistically significant(t=7.459,4.234,8.565,all P<0.05).Multivariate Logistic analysis showed that PCT,LDH,CRP,lncRNA DDIT4-AS1 and lncRNA RSPH9-4 were influencing factors for bacterial meningitis(Wald χ2=4.768～12.035,all P＜0.05).The receiver operating characteristic(ROC)curve results showed that the combined diagnosis of serum lncRNA DDIT4-AS1 and lncRNA RSPH9-4 levels for bacterial meningitis had a significantly larger area under the curve(AUC)than the diagnosis of lncRNA DDIT4-AS1 and lncRNA RSPH9-4 alone,and the differences were statistically significant(Z=2.426,2.545,all P<0.05).Conclusion The expression levels of serum lncRNA DDIT4-AS1 and lncRNA RSPH9-4 are elevated in patients with bacterial meningitis,and the combination of the two has high diagnostic value for the disease.

Objective:To develop an artificial intelligence (AI)-based automatic scoring model for magnetic resonance imaging-detected extramural vascular invasion (AI-mrEMVI) and evaluate its performance and prognostic value in patients with rectal cancer.Methods:In this multicenter retrospective cohort study, a total of 2 501 rectal cancer patients from seven centers between November 2012 and December 2020 were included and divided into completely independent training ( n=1 830) and validation ( n=671) cohorts. A nnUNet-based AI-mrEMVI scoring model was constructed. Manual mrEMVI scores assigned by two radiologists served as the reference standard for accessing the accuracy of the AI-mrEMVI scoring. Kaplan-Meier survival analysis and Cox regression were used to evaluate the prognostic stratification ability of the AI-mrEMVI scores. The concordance index (C-index) was calculated to evaluate prognostic performance. Results:In the validation cohort, the manual mrEMVI scores were 0-2 in 425 patients (63.3%), 3 in 89 (13.4%), and 4 in 157 (23.4%). The AI-mrEMVI model identified 0-2 in 375 patients (55.9%), 3 in 95 (14.2%), and 4 in 201 (30.0%), with an overall accuracy of 81.1% (544/671, 95% CI 77.9%-84.0%). The 3-year disease-free survival (DFS) rates for patients with AI-mrEMVI scores of 0-2, 3, and 4 were 85.2%, 70.0%, and 58.2%, respectively, and the 5-year overall survival (OS) rates were 87.2%, 81.6%, and 62.6%, respectively (DFS: χ2=48.74, P<0.001; OS: χ2=30.04, P<0.001). Multivariable Cox regression showed that for DFS, AI-mrEMVI scores of 3 and 4 were associated with hazard ratios ( HR) of 1.75 (95% CI 1.11-2.77, P=0.016) and 2.65 (95% CI 1.86-3.78, P<0.001), respectively. For OS, an AI-mrEMVI score of 4 was associated with an HR of 2.56 (95% CI 1.62-4.03, P<0.001). The C-index values of the AI-mrEMVI scoring model for predicting DFS and OS were 0.647 (95% CI 0.608-0.686) and 0.650 (95% CI 0.598-0.702), respectively. Conclusion:The proposed AI-mrEMVI automatic scoring model demonstrated high diagnostic accuracy and performed favorably in predicting DFS and OS prognostic risk in patients with rectal cancer.

Objective To investigate the expression levels and diagnostic value of long non coding RNA(lncRNA)DNA damage inducible transcript 4 like protein 4 antisense RNA1(lncRNA DDIT4-AS1)and long chain non coding RNA(lncRNA)radial spoke head protein 9 homolog 4(RSPH9-4)in serum of patients with bacterial meningitis.Methods A total of 94 patients with meningitis in the Fifth Hospital of Deyang City from May 2022 to May 2024 were regarded as the bacterial meningitis group.According to the severity of damage to the central nervous system caused by bacterial meningitis,they were further separated into a general group(n=63)and a severe group(n=31).94 patients with suspected meningitis upon admission but excluded meningitis after examination were selected as the non bacterial meningitis group.A total of 94 patients diagnosed with bacterial meningitis in the Fifth Hospital of Deyang City from May 2022 to May 2024 were selected as the bacterial meningitis group 94 healthy volunteers who underwent physicalexamination were as the control group.Real-time fluorescence quantitative PCR(qRT-PCR)method was applied to detect the expression levels of lncRNA DDIT4-AS1 and lncRNA RSPH9-4 in serum samples of all personnel.Spearman analysis was applied to analyze the correlation between serum levels of lncRNA DDIT4-AS1 and lncRNA RSPH9-4 with the severity of bacterial meningitis.Multivariate Logistic analysis was applied to analyze the influencing factors of bacterial meningitis.Receiver operating characteristic(ROC)curve was plotted to analyze the diagnostic value of serum lncRNA DDIT4-AS1 and lncRNA RSPH9-4 levels for bacterial meningitis.Results Compared with the control group,the expression levels of serum lncRNA DDIT4-AS1(1.35±0.27,1.67±0.35 vs 1.01±0.18)and lncRNA RSPH9-4(1.30±0.25,1.56±0.32 vs 1.00±0.19)were increased in non bacterial meningitis group and bacterial meningitis group(t=10.159,16.259;9.263,14.589),compared with the non bacterial meningitis group,the expression levels of serum lncRNA DDIT4-AS1 and lncRNA RSPH9-4 in the bacterial meningitis group were increased(t=7.019,6.208),and the differences were statistically significant(all P<0.05),respectively.Compared with the general group,the expression levels of serum lncRNA DDIT4-AS1(1.88±0.38 vs 1.56±0.31)and lncRNA RSPH9-4(1.79±0.35 vs 1.45±0.28)were increased in the severe group,and the differences were statistically significant(t=4.361,5.088,all P＜0.05).Spearman correlation analysis results showed that serum levels of lncRNA DDIT4-AS1,lncRNA RSPH9-4 were positively correlated with the severity of bacterial meningitis(r=0.524,0.548,all P<0.05).The expression levels of PCT,LDH and CRP in patients with bacterial meningitis were higher than those in patients without bacterial meningitis,and the differences were statistically significant(t=7.459,4.234,8.565,all P<0.05).Multivariate Logistic analysis showed that PCT,LDH,CRP,lncRNA DDIT4-AS1 and lncRNA RSPH9-4 were influencing factors for bacterial meningitis(Wald χ2=4.768～12.035,all P＜0.05).The receiver operating characteristic(ROC)curve results showed that the combined diagnosis of serum lncRNA DDIT4-AS1 and lncRNA RSPH9-4 levels for bacterial meningitis had a significantly larger area under the curve(AUC)than the diagnosis of lncRNA DDIT4-AS1 and lncRNA RSPH9-4 alone,and the differences were statistically significant(Z=2.426,2.545,all P<0.05).Conclusion The expression levels of serum lncRNA DDIT4-AS1 and lncRNA RSPH9-4 are elevated in patients with bacterial meningitis,and the combination of the two has high diagnostic value for the disease.

OBJECTIVE To explore the effects of different concentrations of aconitine on the ventricular electrophysiology of the rat heart when applied to the heart. METHODS By optical mapping technology, the effects of different concentrations of aconitine on ventricular action potential and calcium signal in rats before and 15 min after administration were observed by in vitro administration of aconitine 0.3, 1, 3 ng·mL−1. RESULTS Compared with the blank group, aconitine could be concentration-dependent to delay the conduction of action potentials under both spontaneous and 6 Hz stimulation rhythms, and there was a significant difference at a concentration of 3 ng·mL−1(P<0.05 or P<0.01). Compared with blank group, when the concentration of aconitine was 1 and 3 ng·mL−1, the action potential duration(APD) of the ventricle was significantly prolonged(P<0.01). Aconitine could also increase the dispersion of action potential conduction(P<0.05) and reduce the ratio of effective refractory period(ERP) to APD90(P<0.01). In addition, aconitine could also be concentration-dependent delay of calcium signal conduction, reduce the speed of calcium conduction(P<0.05 or P<0.01), increase the dispersion of calcium conduction and calcium transient duration(P<0.05 or P<0.01), and reduce the amplitude of calcium signal(P<0.01). CONCLUSION Using the optical labeling technique, it can be visualized that aconitine induces arrhythmia by concentration-dependent delay of ventricular action potential and calcium signaling in rats.To explore the effects of different concentrations of aconitine on the ventricular electrophysiology of the rat heart when applied to the heart. METHODS By optical mapping technology, the effects of different concentrations of aconitine on ventricular action potential and calcium signal in rats before and 15 min after administration were observed by in vitro administration of aconitine 0.3, 1, 3 ng·mL−1. RESULTS Compared with the blank group, aconitine could be concentration-dependent to delay the conduction of action potentials under both spontaneous and 6 Hz stimulation rhythms, and there was a significant difference at a concentration of 3 ng·mL−1(P<0.05 or P<0.01). Compared with blank group, when the concentration of aconitine was 1 and 3 ng·mL−1, the action potential duration(APD) of the ventricle was significantly prolonged(P<0.01). Aconitine could also increase the dispersion of action potential conduction(P<0.05) and reduce the ratio of effective refractory period(ERP) to APD90(P<0.01). In addition, aconitine could also be concentration-dependent delay of calcium signal conduction, reduce the speed of calcium conduction(P<0.05 or P<0.01), increase the dispersion of calcium conduction and calcium transient duration(P<0.05 or P<0.01), and reduce the amplitude of calcium signal(P<0.01). CONCLUSION Using the optical labeling technique, it can be visualized that aconitine induces arrhythmia by concentration-dependent delay of ventricular action potential and calcium signaling in rats.

Objective To investigate the causal relationship between gut microbiota and pigmented villonodular synovitis using Mendelian randomization analysis.Methods We conducted a two-sample Mendelian randomization analysis to investigate the causal relationship between 211 gut microbiome taxa and pigmented villonodular synovitis based on GWAS summary data,with inverse variance weighted(IVW)analysis as the primary result and the other methods as supplementary analyses.The reliability of the results was tested using Cochran's Q test,MR-Egger regression,MR-PRESSO method and conditional Mendelian randomization analysis(cML-MA).Results The increased abundance of Barnesiella(OR=3.12,95%CI:1.15-8.41,P=0.025)and Rumatococcaceae UCG010(OR=4.03,95%CI:1.19-13.68,P=0.025)may increase the risk of pigmented villous nodular synovitis,and elevated abundance of Lachnospiraceae(OR=0.33,95%CI:0.12-0.91,P=0.032),Alistipes(OR=0.16,95%CI:0.05-0.53,P=0.003),Blautia(OR=0.20,95%CI:0.06-0.61,P=0.005),and Lachnospiraceae FCS020 group(OR=0.38,95%CI:0.15-0.94,P=0.036)and Ruminococcaceae UCG014(OR=0.36,95%CI:0.14-0.94,P=0.037)were all associated with a reduced risk of pigmented villonodular synovitis,which were supported by the results of sensitivity analyses.Reverse Mendelian randomization analysis did not reveal any inverse causal association.Conclusion Increased abundance of specific intestinal microorganisms is associated with increased or decreased risks of developing hyperpigmented villonodular synovitis,and gut microbiota plays an important role in the pathogenesis of this disease.

Objective To investigate the causal relationship between gut microbiota and pigmented villonodular synovitis using Mendelian randomization analysis.Methods We conducted a two-sample Mendelian randomization analysis to investigate the causal relationship between 211 gut microbiome taxa and pigmented villonodular synovitis based on GWAS summary data,with inverse variance weighted(IVW)analysis as the primary result and the other methods as supplementary analyses.The reliability of the results was tested using Cochran's Q test,MR-Egger regression,MR-PRESSO method and conditional Mendelian randomization analysis(cML-MA).Results The increased abundance of Barnesiella(OR=3.12,95%CI:1.15-8.41,P=0.025)and Rumatococcaceae UCG010(OR=4.03,95%CI:1.19-13.68,P=0.025)may increase the risk of pigmented villous nodular synovitis,and elevated abundance of Lachnospiraceae(OR=0.33,95%CI:0.12-0.91,P=0.032),Alistipes(OR=0.16,95%CI:0.05-0.53,P=0.003),Blautia(OR=0.20,95%CI:0.06-0.61,P=0.005),and Lachnospiraceae FCS020 group(OR=0.38,95%CI:0.15-0.94,P=0.036)and Ruminococcaceae UCG014(OR=0.36,95%CI:0.14-0.94,P=0.037)were all associated with a reduced risk of pigmented villonodular synovitis,which were supported by the results of sensitivity analyses.Reverse Mendelian randomization analysis did not reveal any inverse causal association.Conclusion Increased abundance of specific intestinal microorganisms is associated with increased or decreased risks of developing hyperpigmented villonodular synovitis,and gut microbiota plays an important role in the pathogenesis of this disease.

Monoamine oxidase A(MAOA)is a membrane-bound mitochondrial enzyme that exists in almost all vertebrate tissues,where it catalyzes the degradation of biogenic and dietary-derived monoamines.MAOA has the function of regulating neurotransmitter metabolism and is associated with anti-tumor immune responses.Most previous studies have focused on the role of MAOA in tumor cells,while more recent findings suggest that MAOA plays an equally significant role in tumor-associated immune cells.In this review,we summarize the regulatory effect of MAOA on the inhibitory tumor microenvironment.The suppressing function of MAOA on various types of tumor-associated immune cells(e.g.,CD8+T cells and tumor-associated macrophages)by its direct effect on monoamines and their metabolic characteristics are discussed.We propose that developing novel MAOA-inhibitor drugs and exploring multidrug-combination strategies may enhance the efficacy of immune therapy for tumors.In conclusion,MAOA may act as a novel target in tumor immunity and influence the effect of tumor immunotherapy.