ObjectiveTo investigate the diagnostic accuracy and grading capability of ultrasound-derived fat fraction （UDFF）， controlled attenuation parameter （CAP）， and hepatic/renal ratio （HRR） in assessing hepatic steatosis in metabolic associated fatty liver disease （MAFLD） with magnetic resonance imaging-proton density fat fraction （MRI-PDFF） as the gold standard. MethodsA total of 150 patients with MAFLD who attended The First Hospital of Hebei Medical University from January 2023 to December 2024 were enrolled， and 148 healthy volunteers were recruited. All subjects underwent MRI-PDFF， UDFF， CAP， and HRR examinations. Hepatic steatosis was graded based on MRI-PDFF （S0：148 cases； S1：92 cases； S2：21 cases； S3：37 cases）， and the MAFLD patients with different grades of hepatic steatosis were compared in terms of UDFF， CAP， HRR， and clinical features. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups and the Tukey HSD test was used for further comparision between two groups； the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups， and the Mann-Whitney U test was used for further comparison between two groups； the chi-square test was used for comparison of categorical data between groups. The Spearman correlation analysis was used to investigate the correlation between UDFF， CAP， HRR， and MRI-PDFF in different grades of MAFLD； the receiver operating characteristic （ROC） curve was used to investigate the efficacy of UDFF， CAP， and HRR in the diagnosis of different degrees of hepatic steatosis in MAFLD； the Bland-Altman difference plot was used to analyze the consistency between UDFF and MRI-PDFF in different degrees of hepatic steatosis in MAFLD. ResultsUDFF measurement gradually increased with the increase in the grade of fatty liver （H=201.52，P0.001）. The Spearman correlation analysis showed that there was a strong correlation between any two indicators of UDFF， CAP， HRR， and MRI-PDFF in S1， S2， and S3 MAFLD （all P0.001）， with the strongest correlation between UDFF and MRI-PDFF （r_s1=0.884，r_s2=0.962，r_s3=0.929， all P0.001）. The ROC curve analysis showed that UDFF had a larger area under the ROC curve （AUC） than CAP and HRR in the graded diagnosis of S1 and S3 （all P0.05）， while in the diagnosis of S2 MAFLD， UDFF had a significantly larger AUC than HRR （P0.05） and a similar AUC to CAP （P0.05）. The Bland-Altman difference plot showed good consistency between UDFF and MRI-PDFF in different degrees of hepatic steatosis in MAFLD. ConclusionCompared with CAP and HRR， UDFF can accurately measure liver fat content and has good efficacy in identifying varying degrees of hepatic steatosis in MAFLD.

Iron metabolism is a critical factor in tumorigenesis and development. Although TP53 mutations are prevalent in glioblastoma (GBM), the mechanisms by which TP53 regulates iron metabolism remain elusive. We reveal an imbalance iron homeostasis in GBM via TCGA database analysis. TP53 mutations disrupted iron homeostasis in GBM, characterized by elevated total iron levels and reduced ferritin (FTH). The gain-of-function effect triggered by TP53 mutations upregulates itchy E3 ubiquitin-protein ligase (ITCH) protein expression in astrocytes, leading to FTH degradation and an increase in free iron levels. TP53-mut astrocytes were more tolerant to the high iron environment induced by exogenous ferric ammonium citrate (FAC), but the increase in intracellular free iron made them more sensitive to Erastin-induced ferroptosis. Interestingly, we found that Erastin combined with FAC treatment significantly increased ferroptosis. These findings provide new insights for drug development and therapeutic modalities for GBM patients with TP53 mutations from iron metabolism perspectives.
Ferroptosis/drug effects* ; Humans ; Iron/metabolism* ; Glioblastoma/metabolism* ; Tumor Suppressor Protein p53/metabolism* ; Homeostasis/physiology* ; Ferritins/metabolism* ; Brain Neoplasms/genetics* ; Mutation ; Astrocytes/drug effects* ; Cell Line, Tumor ; Piperazines/pharmacology* ; Quaternary Ammonium Compounds/pharmacology* ; Ferric Compounds

Otitis media is an infection of the middle ear mainly caused by bacteria, and current treatments rely heavily on antibiotics. However, the emergence of antibiotic-resistant bacterial strains seriously affects their efficacy. In our study, we found that extracellular vesicles (EVs) derived from human natural killer cells (NKs) inhibit the proliferation of both standard and levofloxacin (LVX)-resistant strains of Staphylococcus aureus in a dose-dependent manner. Moreover, compared to LVX, EVs were more effective at reducing effusion and rescuing hearing thresholds in animal models. For LVX-sensitive strains, EVs were significantly more effective in terms of curative time but not curative rate. For LVX-resistant strains, EVs were significantly more effective in terms of both curative rate and curative time when applied alone or applied jointly with LVX. In summary, we found that NK EVs are highly effective in treating otitis media, providing an alternative approach for treating this common disease.
Killer Cells, Natural/metabolism* ; Exosomes/metabolism* ; Animals ; Humans ; Otitis Media/therapy* ; Staphylococcus aureus/drug effects* ; Disease Models, Animal ; Anti-Bacterial Agents/pharmacology* ; Levofloxacin/pharmacology*

To compare the therapeutic effects of short-term spinal cord stimulation (stSCS) and long-term spinal cord stimulation (ltSCS) on patients with prolonged disorders of consciousness(pDoC).

Objective:To investigate effect of cordycepin on lung injury in rats with acute respiratory distress syndrome(ARDS)and its mechanism.Methods:Sixty Wistar rats were randomly divided into control group,lipopolysaccharide group(LPS),cordyce-pin low-dose group(5 mg/kg),cordycepin medium-dose group(15 mg/kg),cordycepin high-dose group(30 mg/kg),Compound C group(high-dose cordycepin 30 mg/kg+AMPK inhibitor 15 mg/kg),with 10 rats in each group.ARDS model of LPS rats was estab-lished,pathological changes of lung tissues were observed by HE staining and lung tissue pathological injury score was performed;wet/dry weight ratio(W/D)of rat lungs was measured;activity of myeloperoxidase(MPO)was detected;IL-6,IL-1β and TNF-α were measured by ELISA;malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione peroxidase(GSH)were detected by kit;Western blot was used to detect expressions of AMP-activated protein kinase(AMPK),p-AMPK,mammalian target of rapamy-cin(mTOR),p-mTOR,P70 ribosomal protein S6 kinase(p70S6K)and p-p70S6K.Results:Compared with control group,rats in LPS group had obvious lung tissue damage,and a large number of inflammatory cells infiltration,lung W/D,pathological injury score of lung tissue,MPO activity,IL-6,IL-1β,TNF-α,MDA levels were increased,p-mTOR/mTOR,p-p70S6K/p70S6K protein expres-sions were increased(P<0.05),SOD,GSH levels were decreased,p-AMPK/AMPK protein expression was decreased(P<0.05);after treatment with cordycepin,lung tissue damage was reduced,a small amount of inflammatory cells were infiltrated,lung W/D,pathological injury score of lung tissue,MPO activity,IL-6,IL-1β,TNF-α,MDA levels were decreased,p-mTOR/mTOR,p-p70S6K/p70S6K protein expressions were decreased(P<0.05),SOD,GSH levels were increased,p-AMPK/AMPK protein expressions were increased(P<0.05);AMPK inhibitor Compound C reversed improvement of cordycepin on lung injury in ARDS rats.Conclusion:Cordycepin can improve LPS induced lung injury of rats,reduce inflammatory and oxidative stress,whose mechanism may be related to regulation of AMPK/mTOR/p70S6K pathway.

OBJECTIVE To explore the mechanism of action of Qihuang Zhuyu formula(QHZYF)in improving depression after myocardial infarction(MI),with a focus on revealing its regulatory effect on the inflammatory response of the heart and brain.METH-ODS The active ingredients of QHZYF and the action targets for intervening in depression after MI were analyzed by using ultra-per-formance liquid chromatography-high-resolution mass spectrometry(UPLC-Q-TOF/MS)combined with network pharmacology and molecular docking.A rat model of depression after MI was established by ligation of the left anterior descending coronary artery com-bined with chronic restraint stress.Echocardiography was used to evaluate cardiac function,hematoxylin-eosin(HE)and Masson stai-ning were used to evaluate myocardial injury,behavioral tests were used to detect melancholic behaviors,Nissl staining was used to e-valuate hippocampal neuron injury.Western blot detection of tumor necrosis factor receptor 2(TNFR2),phosphatidylinositol-3-kinase(PI3K),phosphorylated seronine protein kinase(p-AKT),seronine protein kinase(AKT),tumor necrosis factor receptor 1(TNFR1),phosphorylated nuclear factor κB(p-NF-κB),and nuclear factor κB(NF-κB)in cardiac and hippocampal tissues was conducted.The levels of serum IL-6 and IL-10 were detected by enzyme-linked immunosorbent assay(ELISA),and the expression of TNFR1 and TNFR2 was detected by immunohistochemical technique(IHC).In vitro experiments,co-culture of rat cardiomyocyte line H9C2 cells and rat adrenal pheochromocytoma cell line with high differentiation PC12 cells was conducted,TNFR1 inhibitor(H398)and TNFR2 agonist(C-6His)were administered for intervention,and the expression of TNFR2,PI3K,p-AKT,AKT,TN-FR1,NF-κB,p-NF-κB was detected by Western blot.Observe the apoptosis of cells by TUNEL staining,ELISA was used to detect the levels of IL-6 and IL-10 in the cell supernatant.RESULTS Network pharmacological analysis indicates that the TNF signaling pathway was a key target for the treatment of depression after MI with the QHZYF.In vivo experiments have confirmed that the interven-tion of QHZYF could significantly improve the cardiac function,myocardial tissue and hippocampal neuron structure damage of de-pressed rats after MI,and improve their depression-like behaviors.At the molecular level,the high-dose group of QHZYF significant-ly upregulated TNFR2,p-AKT/AKT,and IL-10 in cardiac and hippocampal tissues(P＜0.01),and downregulated TNFR1,p-NF-κB/NF-κB and IL-6(P＜0.01).In vitro experiments showed that the drug-containing serum of QHZYF significantly upregulated the expression of TNFR2,p-AKT/AKT and IL-10 in H9C2 and PC12 cells(P＜0.01),downregulated the expression of TNFR1,p-NF-κB/NF-κB and IL-6(P＜0.01),and significantly inhibited cell apoptosis(P＜0.01).Furthermore,experiments on the combined ap-plication of H398 or C-6His further confirmed that its protective and anti-inflammatory effects were mediated by regulating the TN-FR2/PI3K/AKT and TNFR1/NF-κB pathways.CONCLUSION QHZYF improves the homeostasis of heart and brain inflammation by regulating the TNF pathway,and ameliorates myocardial injury and depressive state in depressed rats after MI.

Objective To investigate the association between single nucleotide polymorphisms(SNP)rs57095329 and rs6864584 of miR-146a gene and cervical intraepithelial neoplasia(CIN).Methods A total of 96 patients diagnosed with CIN were randomly collected as the CIN group,and 225 healthy individuals examined during the same period were selected as the control group using SPSS software.Genotyping of the above SNP loci was performed using the TaqMan probe method,and their correlation with CIN was analyzed.Results The allele and genotype distribution of rs57095329 showed a statistically significant differences compared to the control group,with the frequency of the allele A in the CIN group significantly lower than that in the control group(P<0.001;OR=0.48,95%CI:0.32～0.70).In the dominant model,individuals carrying the G allele(A/G-G/G)had a significantly increased risk of CIN(P<0.001;OR=2.67,95%CI:1.64～4.37).In contrast,no correlation was found between the rs6864584 and the risk of CIN.Conclusion The A allele of the miR-146a gene at the rs57095329 locus may be a protective factor for CIN.

Objective To observe the value of machine learning(ML)models based on quantitative ultrasound(QUS)and clinical indexes for predicting metabolic associated fatty liver disease(MAFLD).Methods Totally 298 patients underwent abdominal MR and QUS examinations were retrospectively enrolled,including 150 cases with and 148 cases without MAFLD.The patients were divided into training set(including 107 cases of MAFLD and 101 cases of non-MAFLD)and test set(including 43 cases of MAFLD and 47 cases of non-MAFLD)at a ratio of 7∶3.Features were selected using least absolute shrinkage and selection operator(LASSO)regression and logistic regression(LR),based on which predictive models were constructed using 6 ML classifiers,including Gaussian naive Bayes(GNB),LR,random forest(RF),support vector machine(SVM),extreme gradient boosting(XGBoost)and K-nearest neighbor(KNN),respectively.Then the receiver operating characteristic curves were drawn,and the area under the curve(AUC)and the Brier score were calculated to evaluate the predictive efficacy of the models.Results The elevated age,glutamic-pyruvic transaminase(GPT),glutamic-oxaloacetic transaminase(GOT),uric acid(UA),low-density lipoprotein cholesterol(LDL-C),controlled attenuation parameter(CAP),ultrasound-derived fat fraction(UDFF)and shear wave velocity(SWV),as well as blurred liver contour were all independent indicators for higher likelihood of MAFLD(all P＜0.05).The AUC and Brier score of XGBoost model in training set was 0.991 and 0.006,in test set was 0.973 and 0.069,respectively,both higher than those of other models,and decision curve analysis(DCA)indicated that XGBoost model had high net benefit.Conclusion ML models based on QUS and clinical indexes,especially XGBoost model had high efficacy for predicting MAFLD.

Objective To retrieve,evaluate and summarise the best evidence on screening and management of psychological distress in patients who had ostomy for colorectal cancer.Methods Literatures on psychological distress screening and management in patients undergoing colorectal cancer ostomy were systematically searched across various websites and databases of home and abroad from inception to 20th June,2024 including Cochrane Library,PubMed,Embase,CINAHL,Web of Science,CNKI,Wangfang,VIP,UpToDate,National Guideline Clearing-house,National Comprehensive Cancer Network,the National Institute for Health and Care Excellence,Scottish Intercollegiate Guidelines Network,the International Guideline Collaboration Network,Wound,Ostomy and Continence Nurses Society,World Council of Enterostomal Therapists,Medlive,Chinese Nursing Association.The search aimed to identify evidence on psychological distress screening and management in patients with colorectal cancer and stomas,including guidelines,evidence summaries,expert consensuses,systematic reviews,and Meta-analyses.The search was limited to articles published from the inception of each database to 20th June,2024.The searched literature included guidelines,evidence summary,expert consensus,systematic review,meta-analysis,etc..Two researchers independently evaluated the quality of literature and extracted evidences,as well as checked and integrated the evidences together with a panel of evidence-based research experts.Results A total of 14 articles were included,comprising four guidelines,one expert consensus,two evidence summaries,four meta-analyses and three systematic reviews.The articles encompassed 7 dimensions with a total of 18 pieces of evidence,including one in screening timing,one in screening tools,3 in screening content,3 in drug intervention,3 in self-management,5 in psychological support and 2 in health education.Conclusion The evidence summarised in this study on the screening and management of psychological distress in patients who had ostomy for colorectal cancer is scientifically comprehensive.It provides an evidence-based basis for medical staff in prevention and management of psychological distress in patients.It is necessary to formulate a scientific management plan in clinical practice,according to the specific requirements of departments,the patients and their family members.