ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

OBJECTIVE: To investigate the effect of Tongmai Hypoglycemic Capsule (THC) on myocardium injury in diabetic cardiomyopathy (DCM) rats. METHODS: A total of 24 Sprague Dawley rats were fed for 4 weeks with high-fat and high-sugar food and then injected with streptozotocin intraperitoneally for the establishment of the DCM model. In addition, 6 rats with normal diets were used as the control group. After modeling, 24 DCM rats were randomly divided into the model, L-THC, M-THC, and H-THC groups by computer generated random numbers, and 0, 0.16, 0.32, 0.64 g/kg of THC were adopted respectively by gavage, with 6 rats in each group. After 12 weeks of THC administration, echocardiography, histopathological staining, biochemical analysis, and Western blot were used to detect the changes in myocardial structure, oxidative stress (OS), biochemical indexes, protein expressions of myocardial fibrosis, and nuclear factor erythroid 2-related faactor 2 (Nrf2) element, respectively. RESULTS: Treatment with THC significantly decreased cardiac markers such as creatine kinase, lactate dehydrogenase, and creatine kinase-MB, etc., (P<0.01); enhanced cardiac function indicators including heart rate, ejection fraction, cardiac output, interventricular septal thickness at diastole, and others (P<0.05 or P<0.01); decreased levels of biochemical indicators such as fasting blood glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, aspartate transaminase, (P<0.05 or P<0.01); and decreased the levels of myocardial fibrosis markers α-smooth muscle actin (α-SMA), and collagen I (Col-1) protein (P<0.01), improved myocardial morphology and the status of myocardial interstitial fibrosis. THC significantly reduced malondialdehyde levels in model rats (P<0.01), increased levels of catalase, superoxide dismutase, and glutathione (P<0.01), and significantly increased the expression of Nrf2, NAD(P)H:quinone oxidoreductase 1, heme oxygenase-1, and superoxide dismutase 2 proteins in the left ventricle of rats (P<0.01). CONCLUSION THC activates the Nrf2 signaling pathway and plays a protective role in reducing OS injury and cardiac fibrosis in DCM rats.
Animals ; Diabetic Cardiomyopathies/physiopathology* ; Oxidative Stress/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Rats, Sprague-Dawley ; Myocardium/metabolism* ; Fibrosis ; Male ; Capsules ; Hypoglycemic Agents/therapeutic use* ; NF-E2-Related Factor 2/metabolism* ; Rats ; Diabetes Mellitus, Experimental/drug therapy*

Objective To explore the predictive value of coronary artery calcium score(CACS)combined with C-X-C motif chemokine ligand 12(CXCL12)and soluble CD40 ligand(sCD40L)for major adverse cardiovascular events(MACE)within 5 years in patients with stable coronary artery disease(SCAD).Methods A total of 206 elderly SCAD patients admitted in our depart-ment from March 2015 to November 2018 were recruited,and according to whether MACE occurred within 5 years of follow-up,they were divided into MACE group(42 cases)and control group(164 cases).Multivariate logistic regression analysis was performed to identify the inde-pendent predictors of MACE.ROC curve analysis was applied to evaluate the predictive value of the combined model,and its area under curve(AUC)value was calculated.Results Compared with the control group,the MACE group had significantly older age,larger proportions of hyper-tension and diabetes mellitus,higher CACS,and elevated CXCL12 and sCD40L levels(P＜0.05,P＜0.01).Multivariate logistic regression analysis revealed that age,hypertension,diabetes melli-tus,CACS,CXCL12 and sCD40L were independent risk factors for MACE in the elderly SCAD patients within 5 years(P＜0.05,P＜0.01).ROC curve analysis indicated that the AUC value of CACS,CXCL12,sCD40L,and these three indicators combined together in predicting MACE in elderly SCAD patients within 5 years was 0.872(95％CI:0.819-0.915),0.768(95％CI:0.704-0.824),0.726(95％CI:0.660-0.786),and 0.935(95％CI:0.893-0.965),respectively,with the value of the combination obviously higher than that of each indicator alone(P＜0.01).Conclusion Increased CACS,CXCL12 and sCD40L have predictive value for MACE in elderly SCAD patients,and the combination of the three indicators has obvious advantages in the prediction.

Objective To investigate the role of cathepsin K(CTK)and secreted frizzled-related protein 2(sFRP2)in ventricular remodeling in very old patients with acute myocardial infarction(AMI)after percutaneous coronary intervention(PCI),and analyze the correlation.Methods A total of 192 very old AMI patients undergoing PCI in our department from January 2020 to December 2023 were recruited,and based on clinical outcomes at 6 months after surgery,they were assigned into a ventricular remodeling group(74 cases)and a non-ventricular remodeling group(118 cases).The clinical data and postoperative biochemical indicators were collected in the two groups.Multivariate logistic regression analysis was performed to assess the correlation between CTK and sFRP2 levels and ventricular remodeling.ROC curves were plotted to analyze the predictive value of CTK and sFRP2 in ventricular remodeling.Results The ventricular remodeling group had significantly longer length of hospital stay,larger left ventricular end-diastolic diameter,and higher levels of CTK,sFRP2,C-reactive protein(CRP)and IL-6,but lower left ventricular ejection fraction than the non-ventricular remodeling group(P＜0.05,P＜0.01).Multivariate logistic regression analysis suggested that CTK and sFRP2 were independent risk factors for postoperative ventricular remodeling in very old AMI patients(P＜0.01).ROC curve analysis manifested that the area under curve value of CTK,sFRP2,CRP and IL-6 combined together in predicting ventricular remodeling in very old AMI patients after PCI was 0.892,with a sensitivity of 79.73％and a specificity of 88.14％(P＜0.01).Conclusion CTK and sFRP2 are significantly increased in ventricular remodeling in very old AMI patients after PCI,and are closely related to the occurrence of ventricular remodeling.They can be used as potential biomark-ers in the prediction of ventricular remodeling and provide important reference for clinical diagno-sis and treatment.

Objective To explore the predictive value of coronary artery calcium score(CACS)combined with C-X-C motif chemokine ligand 12(CXCL12)and soluble CD40 ligand(sCD40L)for major adverse cardiovascular events(MACE)within 5 years in patients with stable coronary artery disease(SCAD).Methods A total of 206 elderly SCAD patients admitted in our depart-ment from March 2015 to November 2018 were recruited,and according to whether MACE occurred within 5 years of follow-up,they were divided into MACE group(42 cases)and control group(164 cases).Multivariate logistic regression analysis was performed to identify the inde-pendent predictors of MACE.ROC curve analysis was applied to evaluate the predictive value of the combined model,and its area under curve(AUC)value was calculated.Results Compared with the control group,the MACE group had significantly older age,larger proportions of hyper-tension and diabetes mellitus,higher CACS,and elevated CXCL12 and sCD40L levels(P＜0.05,P＜0.01).Multivariate logistic regression analysis revealed that age,hypertension,diabetes melli-tus,CACS,CXCL12 and sCD40L were independent risk factors for MACE in the elderly SCAD patients within 5 years(P＜0.05,P＜0.01).ROC curve analysis indicated that the AUC value of CACS,CXCL12,sCD40L,and these three indicators combined together in predicting MACE in elderly SCAD patients within 5 years was 0.872(95％CI:0.819-0.915),0.768(95％CI:0.704-0.824),0.726(95％CI:0.660-0.786),and 0.935(95％CI:0.893-0.965),respectively,with the value of the combination obviously higher than that of each indicator alone(P＜0.01).Conclusion Increased CACS,CXCL12 and sCD40L have predictive value for MACE in elderly SCAD patients,and the combination of the three indicators has obvious advantages in the prediction.

Objective To investigate the role of cathepsin K(CTK)and secreted frizzled-related protein 2(sFRP2)in ventricular remodeling in very old patients with acute myocardial infarction(AMI)after percutaneous coronary intervention(PCI),and analyze the correlation.Methods A total of 192 very old AMI patients undergoing PCI in our department from January 2020 to December 2023 were recruited,and based on clinical outcomes at 6 months after surgery,they were assigned into a ventricular remodeling group(74 cases)and a non-ventricular remodeling group(118 cases).The clinical data and postoperative biochemical indicators were collected in the two groups.Multivariate logistic regression analysis was performed to assess the correlation between CTK and sFRP2 levels and ventricular remodeling.ROC curves were plotted to analyze the predictive value of CTK and sFRP2 in ventricular remodeling.Results The ventricular remodeling group had significantly longer length of hospital stay,larger left ventricular end-diastolic diameter,and higher levels of CTK,sFRP2,C-reactive protein(CRP)and IL-6,but lower left ventricular ejection fraction than the non-ventricular remodeling group(P＜0.05,P＜0.01).Multivariate logistic regression analysis suggested that CTK and sFRP2 were independent risk factors for postoperative ventricular remodeling in very old AMI patients(P＜0.01).ROC curve analysis manifested that the area under curve value of CTK,sFRP2,CRP and IL-6 combined together in predicting ventricular remodeling in very old AMI patients after PCI was 0.892,with a sensitivity of 79.73％and a specificity of 88.14％(P＜0.01).Conclusion CTK and sFRP2 are significantly increased in ventricular remodeling in very old AMI patients after PCI,and are closely related to the occurrence of ventricular remodeling.They can be used as potential biomark-ers in the prediction of ventricular remodeling and provide important reference for clinical diagno-sis and treatment.

A 5-year-old girl was admitted due to one episode of melena and one episode of hematemesis.Upon admission,gastroscopy revealed esophageal and gastric varices.Abdominal CT scan,MRI,and color Doppler ultrasound suggested cirrhosis,intrahepatic bile duct dilation,and bilateral kidney enlargement.Genetic testing identified compound heterozygous mutations in the PKHD1 gene:c.2264C>T(p.Pro755Leu)and c.1886T>C(p.Val629Ala).The c.2264C>T(p.Pro755Leu)mutation is a known pathogenic variant with previous reports,while c.1886T>C(p.Val629Ala)is a novel mutation predicted to have pathogenic potential according to Mutation Taster and PolyPhen2.The child was diagnosed with autosomal recessive polycystic kidney disease.In children presenting with gastrointestinal bleeding without obvious causes,particularly those with liver or kidney disease,consideration should be given to the possibility of autosomal recessive polycystic kidney disease,and genetic testing should be conducted for definitive diagnosis when necessary.

Alzheimer's disease(AD)is a neurodegenerative disorder characterized by widespread dementia.Despite the extensive research conducted on the pathogenesis of AD over the past 50 years,the underlying mechanisms responsible for AD-related cellular damage and cognitive impairment remain elusive.Multiple studies have confirmed alterations in the glucose metabolism patterns occur within the nerve cells of individuals with AD.This metabolic transition plays a crucial role in cell survival and disease progression,occurring decades before pathological changes and cognitive dysfunction even manifest.This article provides an overview of the potential mechanisms through which glucose metabolism reprogramming contributes to AD development in various types of nerve cells and brain regions,as well as the implication of their interplay.We aim to establish a foundation for further investigations into AD while offering insights and ideas for the development of novel preventive and therapeutic approaches.

Objective To evaluate the immunogenicity of inactivated quadrivalent influenza vaccine (QIV) in people over 60 years old. Methods Databases including PubMed, EMBASE, Cochrane Library, China Biology Medicine disc, Wangfang Database and China National for Biotechnology Information were searched for random control studies comparing and analyzing the immunogenicity and safety between QIV and inactivated trivalent influenza vaccine (TIV) in people over 60 years old. Meta-analysis of the included literature data was performed using Stata11.0 software. Results A total of 9 articles were included in this study. There was no difference in seroconversion rates (SCR) and seroprotection rates (SPR) for the same vaccine strain after inoculation between QIV and TIV, while for the B vaccine strain (B/Victoria or B/Yamagata) not included in TIV, the SCR and SPR of QIV were significantly higher: SCR RR of 2.04 (95%CI:1.48~2.83) and SPR RR of 1.21 (95%CI:1.11~1.31) for B/Victoria; SCR RR of 2.35 (95%CI:2.04~2.69) and SPR RR of 1.12 (95%CI:1.02~1.23) for B/Yamagata. Conclusion For people over 60 years old, QIV has good immunogenicity, and produces better immunogenicity against influenza B vaccine strains not included in TIV.

Purpose: This study aimed to analyze the expression and prognosis of SRY-box transcription factor 11 (SOX11) in neuroblastoma (NB), as well as the biological function and potential regulatory mechanism of SOX11 in NB. Methods: Public RNA sequencing was used to detect the expression level of SOX11. The Kaplan-Meier curve and hazard ratios (HR) were used to determine the prognostic value of SOX11 in NB. Functional analyses were performed using CCK8, wound healing assay, and transwell invasion assay. Finally, the potential target genes of SOX11 were predicted by Harmonizonme (Ma'ayan Laboratory) and Cistrome Data Browser (Cistrome Project) database to explore the potential molecular mechanism of SOX11 in NB. Results: Compared with normal adrenal tissue, the expression of SOX11 in NB tissue was significantly upregulated. The Kaplan-Meier curve showed that high expression of SOX11 was associated with poor prognosis in children with NB (HR, 1.719; P = 0.049). SOX11 knockdown suppressed the migration capacity of SK-N-SH cells but did not affect proliferation and invasion capacity. Enhancer of zeste homolog 2 (EZH2) may be a potential downstream target gene for the transcription factor SOX11 to play a role in NB. Conclusion The transcription factor SOX11 was significantly upregulated in NB. SOX11 knockdown suppressed the migration capacity of NB cell SK-N-SH. SOX11 may promote the progression of NB by targeting EZH2.