Objective:To investigate the effect of Simiao Yong'an Decoction on AMPK/ULK1 autophagy axis and inflammatory reaction in atherosclerotic(AS)mice.Methods:ApoE-/-mice were randomly divided into control group,model group,low,medium and high doses of Simiao Yong'an Decoction groups and simvastatin group,with 10 mice in each group.Mice model of AS was induced by high-fat diet.Simao Yong'an Decoction given low(10.13 g/kg),medium(20.25 g/kg),high dose(40.5 g/kg)and simvastatin tablets(3 mg/kg)by gavage for 6 weeks.After administration,serum and aortic tissue of mice were collected,and serum lipid level was detected by automatic biochemical analyzer;HE staining was used to observe the pathological changes of aorta;autophagy level of plaque tissue was observed by transmission electron microscope;levels of inflammatory factors IL-18,IFN-γ and CRP in serum were detected by ELISA;expression levels of AMPK,ULK1 and p62 mRNA were detected by qRT-PCR;expressions of LC3Ⅱ and p-ULK1 protein were detected by immunofluorescence labeling;expressions of p-AMPK and p62 were detected by immunohistochemis-try.Results:Compared with model group,aortic plaque in Simiao Yong'an Decoction and simvastatin groups were significantly reduced,and serum levels of TC,TG,LDL-C,IFN-γ,IL-18 and CRP were significantly decreased(P<0.05 or P<0.01),while the level of HDL-C was increased(P<0.05 or P<0.01);electron microscopy showed that autophagic bodies were increased;expressions of autophagy related factors LC3 Ⅱ,AMPK and ULK1 were induced,and expression of p62 was inhibited.Conclusion:Simiao Yong'an Decoction can induce AMPK/ULK1 autophagy axis and inhibit IFN-γ,IL-18 and CRP overexpressions in AS mice of may be one of the important mechanisms of Simiao Yong'an Decoction in anti-atherosclerosis.

Objective Network pharmacology and molecular docking techniques were used to predict the potential mechanisms by which the active components of Piper nigrum(PN)regulate depressive-like behaviors in chronic restraint stress(CRS)mice.Methods The major chemical components and targets of PN were screened using the Traditional Chinese Medicine Systems Pharmacology database.Targets related to ferroptosis and depression were obtained from the Online Mendelian Inheritance in Man,GeneCards,and FerrDB databases.The intersecting targets were then subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Gnomes(KEGG)pathway enrichment analyses,and molecular docking was performed to validate the binding capacities between the core targets and their corresponding active components.Finally,we established a CRS mouse model.Mice were treated with PN 75,150,and 300 mg/kg for 4 weeks,followed by behavioral assessments and reverse transcription-quantitative polymerase chain reaction(RT-qPCR)to verify the expression of core genes.Results Nine active components were screened from PN,corresponding to 27 targets,and 8377 targets related to depression and 547 targets associated with ferroptosis were screened from the databases.The intersection of these three sets resulted in 25 target genes.KEGG enrichment analysis revealed that these core targets were predominantly enriched in signaling pathways,including cholinergic synapses,serotonergic synapses,and neuroactive ligand-receptor interactions.Molecular docking result showed that the main active components of PN had strong binding affinities for the targets CHRM2,SLC6A4,PTGS2,and SLC6A2.Behavioral assessments demonstrated that PN significantly increased the sucrose preference index(P＜0.01,P＜0.001),reduced immobility time in the tail suspension and forced swimming tests(P＜0.01,P＜0.001),and enhanced exploratory behavior in the open field test(P＜0.05.P＜0.01,P＜0.001).PN significantly reduced the serum levels of inflammation markers(P＜0.05.P＜0.01,P＜0.001),as shown by enzyme-linked immunosorbent assay,and neurotransmitter analysis revealed that PN significantly increased the levels of serotonin and acetylcholine in the mouse hippocampus(P＜0.05).RT-qPCR showed that PN demonstrated the mRNA expression of SLC6A4(P＜0.05.P＜0.01,P＜0.001).Conclusions PN may improve depressive-like behavior in mice by modulating serotonin and acetylcholine levels,inhibiting inflammatory responses,participating in immune regulation,and exerting neuroprotective effects.

Viral hepatitis and related liver diseases are among the most significant global healthcare issues. Viral hepatitis not only directly affects liver function but also interacts with the gut microbiota through the gut-liver axis. Imbalance in the gut microbiota may be associated with the occurrence, development and prognosis of viral hepatitis and related liver diseases. Detection and analysis of the gut microbiota can help to comprehensively understand the health status of patients with viral hepatitis and related liver diseases, providing a basis for early diagnosis. Recovery of gut microbiota dysbiosis may help to alleviate liver inflammation and to improve liver function. Regulating the gut microbiota through gut microbiota transplantation, probiotics and prebiotics may be new strategies for treating viral hepatitis and related liver diseases. By analyzing the latest research progress of gut microbiota in viral hepatitis and related liver diseases, this article provides new methods for the diagnosis and treatment of viral hepatitis and related liver diseases.

Objective:To investigate the effect of Simiao Yong'an Decoction on AMPK/ULK1 autophagy axis and inflammatory reaction in atherosclerotic(AS)mice.Methods:ApoE-/-mice were randomly divided into control group,model group,low,medium and high doses of Simiao Yong'an Decoction groups and simvastatin group,with 10 mice in each group.Mice model of AS was induced by high-fat diet.Simao Yong'an Decoction given low(10.13 g/kg),medium(20.25 g/kg),high dose(40.5 g/kg)and simvastatin tablets(3 mg/kg)by gavage for 6 weeks.After administration,serum and aortic tissue of mice were collected,and serum lipid level was detected by automatic biochemical analyzer;HE staining was used to observe the pathological changes of aorta;autophagy level of plaque tissue was observed by transmission electron microscope;levels of inflammatory factors IL-18,IFN-γ and CRP in serum were detected by ELISA;expression levels of AMPK,ULK1 and p62 mRNA were detected by qRT-PCR;expressions of LC3Ⅱ and p-ULK1 protein were detected by immunofluorescence labeling;expressions of p-AMPK and p62 were detected by immunohistochemis-try.Results:Compared with model group,aortic plaque in Simiao Yong'an Decoction and simvastatin groups were significantly reduced,and serum levels of TC,TG,LDL-C,IFN-γ,IL-18 and CRP were significantly decreased(P<0.05 or P<0.01),while the level of HDL-C was increased(P<0.05 or P<0.01);electron microscopy showed that autophagic bodies were increased;expressions of autophagy related factors LC3 Ⅱ,AMPK and ULK1 were induced,and expression of p62 was inhibited.Conclusion:Simiao Yong'an Decoction can induce AMPK/ULK1 autophagy axis and inhibit IFN-γ,IL-18 and CRP overexpressions in AS mice of may be one of the important mechanisms of Simiao Yong'an Decoction in anti-atherosclerosis.

Objective Network pharmacology and molecular docking techniques were used to predict the potential mechanisms by which the active components of Piper nigrum(PN)regulate depressive-like behaviors in chronic restraint stress(CRS)mice.Methods The major chemical components and targets of PN were screened using the Traditional Chinese Medicine Systems Pharmacology database.Targets related to ferroptosis and depression were obtained from the Online Mendelian Inheritance in Man,GeneCards,and FerrDB databases.The intersecting targets were then subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Gnomes(KEGG)pathway enrichment analyses,and molecular docking was performed to validate the binding capacities between the core targets and their corresponding active components.Finally,we established a CRS mouse model.Mice were treated with PN 75,150,and 300 mg/kg for 4 weeks,followed by behavioral assessments and reverse transcription-quantitative polymerase chain reaction(RT-qPCR)to verify the expression of core genes.Results Nine active components were screened from PN,corresponding to 27 targets,and 8377 targets related to depression and 547 targets associated with ferroptosis were screened from the databases.The intersection of these three sets resulted in 25 target genes.KEGG enrichment analysis revealed that these core targets were predominantly enriched in signaling pathways,including cholinergic synapses,serotonergic synapses,and neuroactive ligand-receptor interactions.Molecular docking result showed that the main active components of PN had strong binding affinities for the targets CHRM2,SLC6A4,PTGS2,and SLC6A2.Behavioral assessments demonstrated that PN significantly increased the sucrose preference index(P＜0.01,P＜0.001),reduced immobility time in the tail suspension and forced swimming tests(P＜0.01,P＜0.001),and enhanced exploratory behavior in the open field test(P＜0.05.P＜0.01,P＜0.001).PN significantly reduced the serum levels of inflammation markers(P＜0.05.P＜0.01,P＜0.001),as shown by enzyme-linked immunosorbent assay,and neurotransmitter analysis revealed that PN significantly increased the levels of serotonin and acetylcholine in the mouse hippocampus(P＜0.05).RT-qPCR showed that PN demonstrated the mRNA expression of SLC6A4(P＜0.05.P＜0.01,P＜0.001).Conclusions PN may improve depressive-like behavior in mice by modulating serotonin and acetylcholine levels,inhibiting inflammatory responses,participating in immune regulation,and exerting neuroprotective effects.

Objective To investigate the value of serum thymidine kinase 1(TK1),hypoxia-inducible fac-tor-1α(HIF-1α)and squamous cell carcinoma antigen(SCC)in the diagnosis and prognosis of esophageal cancer.Methods A total of 105 patients with esophageal cancer treated in the Qinhuai Medical Zone of East-ern Theater General Hospital from February 2019 to October 2021 were selected as the study group,and 80 healthy subjects were selected as the control group during the same period.The serum levels of TK1,HIF-1αand SCC were compared between study group,control group and patients with different pathological charac-teristics.Patients with esophageal cancer were followed up for 3 years,and the overall survival(OS)and pro-gression-free survival(PFS)were recorded.Receiver operating characteristic curve was used to analyze the di-agnostic efficiency of serum TK1,HIF-1α and SCC combined detection for esophageal cancer,Pearson correla-tion analysis was used to analyze the correlation between the serum indicators,and Kaplan-Meier survival a-nalysis was used to analyze the OS and PFS of patients with different serum levels of TK1,HIF-1α and SCC.Multivariate COX regression was performed to analyze prognostic factors.Results Compared with the control group,the serum TK1,HIF-1α and SCC levels in the study group increased(P＜0.05).The area under the curve(AUC)of serum TK1,HIF-1α,SCC alone and combined for diagnosis of esophageal cancer were 0.893,0.744,0.841,0.922,respectively,and their combined diagnoses of esophageal cancer had the largest AUC.Se-rum TK1,HIF-1α and SCC in patients with different TNM stages and differentiation stages were significantly different(P＜0.05).Serum TK1,HIF-1α and SCC in patients with lymph node metastasis were higher than those without lymph node metastasis(P＜0.05).Serum TK1 was positively correlated with HIF-1α and SCC levels in patients with esophageal cancer(P＜0.05).The survival functions of OS and PFS in TK1,HIF-1αand SCC low expression group were better than those in high expression group(P＜0.05).Multivariate COX regression analysis showed that low differentiation and lymph node metastasis were independent risk factors for poor prognosis in esophageal cancer patients(P＜0.05).Conclusion Serum levels of TK1,HIF-1α and SCC are increased in patients with esophageal cancer,the combined diagnosis of the three is effective.The high expression of TK1 and HIF-1αand SCC will shorten OS and PFS.

Viral hepatitis and related liver diseases are among the most significant global healthcare issues. Viral hepatitis not only directly affects liver function but also interacts with the gut microbiota through the gut-liver axis. Imbalance in the gut microbiota may be associated with the occurrence, development and prognosis of viral hepatitis and related liver diseases. Detection and analysis of the gut microbiota can help to comprehensively understand the health status of patients with viral hepatitis and related liver diseases, providing a basis for early diagnosis. Recovery of gut microbiota dysbiosis may help to alleviate liver inflammation and to improve liver function. Regulating the gut microbiota through gut microbiota transplantation, probiotics and prebiotics may be new strategies for treating viral hepatitis and related liver diseases. By analyzing the latest research progress of gut microbiota in viral hepatitis and related liver diseases, this article provides new methods for the diagnosis and treatment of viral hepatitis and related liver diseases.

Objective:To explore the causal relationship between gut microbiota and lung function (FEV1/FVC) using two-sample Mendelian randomization method; To explore its application in the TCM field.Methods:This was a Mendelian randomization study. The GWAS data of gut microbiota from the MiBioGen consortium study and the GWAS data of lung function (FEV1/FVC) published by IEU OpenGWAS in the public database were used, and instrumental variables were extracted according to prespecified thresholds. The inverse variance weighted method (IVW) was mainly used for analysis. The results were evaluated according to the effect indicator β value and 95% CI. When the IVW method was statistically significant, further sensitivity analysis was performed. Leave-one-out test, heterogeneity test, horizontal gene pleiotropy test and MR-Egger regression intercept analysis were used to verify the stability and reliability of the results. Results:A total of 10 causal relationships between gut microbiota and lung function (FEV1/FVC) were determined using the IVW method: family. BacteroidalesS24.7group ( β=-0.029, P=0.015), family. ClostridialesvadinBB60group ( β=-0.028, P=0.040), family. Streptococcaceae ( β=-0.056, P=0.042), genus. LachnospiraceaeFCS020group ( β=0.025, P=0.029), genus. Lactococcus ( β=-0.024, P=0.038), genus. Peptococcus ( β=0.025, P=0.049), genus. RuminococcaceaeUCG011 ( β=-0.030, P=0.038), genus. Ruminococcus2 ( β=0.028, P=0.033), genus. Terrisporobacter ( β=-0.030, P=0.018), phylum. Cyanobacteria ( β=0.027, P=0.039). Leave-one-out analysis showed that the results were stable, and the effects of heterogeneity and horizontal gene pleiotropy on causal effect estimation could be removed. Conclusion:The gut microbiota may play a role in the changes of lung function, which to a certain extent confirms the TCM theory of "exterior-interior relationship between the lung and large intestine", and can provide certain reference for the research direction of TCM.

Objective To explore the difference in gut microbiota composition between patients with obstructive sleep apnea(OSA)and healthy individuals and the role of gut microbiota in the pathogenesis of OSA.Methods Thirty-nine patients with OSA admitted to our hospital between May and December,2022 and 20 healthy individuals were enrolled in this study.Stool samples were collected from all the participants for analysis of microbiome composition using 16S rRNA high-throughput sequencing analysis.The alpha diversity,beta diversity,and species difference were determined between the two groups and marker species analysis and metabolic pathway function prediction analysis were performed.Results The species diversity(Shannon and Simpson)indexes,richness(observed species)and evenness(Pielou)of gut microbiota were significantly lower in OSA patients than in the healthy individuals(P<0.05).The OSA patients had also a significantly lowered community diversity(P<0.05)with different gut microbial communities from those of the healthy individuals shown by increased relative abundance of potentially pathogenic bacteria such as Pseudomonas and Monocytogenes(P<0.05).LEfSe analysis showed that the abundance of 23 species of gut microbiota differed significantly between the two groups and the OSA patients had significant increases in the abundance of Pseudomonas,Meganomonas,and Fusobacterium(P<0.05).The differential marker flora affected host homeostasis.Random Forest and ROC curve analyses confirmed that Pseudomonas could be used as important biomarkers for a differential diagnosis.Metabolic pathway function prediction analysis showed that biosynthesis function had the greatest contribution to maintaining gut microbiota homeostasis,and Pseudomonas affected the occurrence and progression of OSA by participating in aromatic bioamine degradation and ketogluconic acid metabolic pathway.Conclusion OSA patients have obvious gut microbiota disturbances,and Pseudomonas may affect the development of OSA by participating in substance metabolism to serve as the potential target gut bacteria for OSA treatment.

Objective:To construct a new thrombus risk assessment model and evaluate its predictive ability for venous thromboembolism(VTE)in the patients with malignant tumors,and to provide the basis for the early predition of the malignant tumor patients with high risk for VTE.Methods:A total of 128 untreated malignant tumor patients were included,of which 40 were diagnosed with VTE within 2 months of malignant tumor diagnosis and categorized as VTE group.A total of 88 patients who did not develop VTE were categorized as non-VTE group.The clinical risk factors and laboratory indicators of the patients in two groups were compared and analyzed;the types of thrombotic events of the patients were analyzed;the diagnostic values of thrombin-antithrombin-complex(TAT),α2-plasmin inhibitor-plasmin complex(PIC),D-dimer(D-dimer),and fibrin degradation products(FDP)in malignant tumors complicated by VTE were assessed using receiver operating characteristic(ROC)curve analysis;Multivariate Logistic regression analysis was used to analyze the correlations of the clinical risk factors and biomarkers with the malignant tumors complicated with VTE.A new thrombus risk assessment model was constructed,consisting of TAT≥0.70 μg·L-1,poor differentiation,and cardiovascular risk factors.The predictive probability of the model for malignant tumors complicated by VTE was evaluated based on the significance,goodness of fit,calibration curve,and C value of the model.The clinical application value of the new thrombus risk assessment model,COMPASS-CAT risk score(CRS),and Khorana risk score(KRS)in assessing malignant tumor patients complicated by VTE was compared using the C value and decision curve analysis(DCA).Results:The plasma levels of TAT(P＜0.001),PIC(P＜0.001),D-dimer(P＜0.05),and FDP(P＜0.01)of the patients in VTE group were higher than those in non-VTE group.Compared with the patients without cardiovascular risk factors,poor differentiation,and lymphatic metastasis,the malignant tumor patients with cardiovascular risk factors(P＜0.001),poor differentiation(P＜0.001),and lymphatic metastasis(P＜0.05)were more likely to develop VTE.Most VTE events(65％)were isolated deep vein thromboembolism(DVT).The ROC curve analysis showed that the area under the curve(AUC),sensitivity,and specificity of TAT and PIC were higher than those of D-dimer and FDP.TAT≥0.70 μg·L-1(P＜0.05),poor differentiation(P＜0.01),and cardiovascular risk factors(P＜0.01)were the independent risk factors for VTE in the malignant tumor patients.A new thrombus risk assessment model consisting of TAT≥0.70 μg·L-1,poor differentiation,and cardiovascular risk factors was constructed.The new risk assessment model had a high goodness of fit(P=0.805)and good predictive ability during internal validation(x2=75.266,P＜0.001).The ROC curve analysis results showed that the C values for the new thrombus risk prediction model,CRS,and KRS were 0.908,0.676,and 0.541,respectively.The DCA curve analysis results showed that the new thrombus risk assessment model had a higher net benefit rate compared with CRS and KRS.Conclusion:TAT and PIC have greater diagnostic efficiency than D-dimer in the early prediction of the malignant tumor patients with high-risk VTE.For the patients included in this study,the new thrombus risk assessment model,constructed from TAT≥0.70 μg·L-1,poor differentiation,and cardiovascular risk factors,has superior diagnostic efficiency and clinical predictive value compared with CRS and KRS.