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*

Objective:This study investigated the expression level of phosphatidylserine-specific phospholipase A1(PLA1A)in colorectal can-cer(CRC)and analyzed its correlations with clinicopathological features,prognosis,and immune infiltration.Methods:The expression level of PLA1A in CRC was screened,and the influence of this expression level on patient prognosis was analyzed using bioinformatics methods.A cohort of 192 patients diagnosed with CRC at Shanxi Province Cancer Hospital from January to December 2020 were selected.The PLA1A ex-pression level in those with CRC was determined using immunohistochemistry(IHC)and real-time quantitative reverse transcription PCR(RT-qPCR).The relationship between PLA1A level and the clinicopathological features of the patients with CRC was analyzed using the chi-square test.The expression levels of immune cell markers CD4 and CD8 as well as immunosuppressive checkpoints PD-1,TIM-3,and CTLA-4 in CRC were detected via IHC,and their correlations with PLA1A level were analyzed using the chi-square test.Results:The results of bioinformatics analysis showed that the expression level of PLA1A in CRC tissue was higher than paracancerous tissue,which correlated with overall surviv-al(OS)(P<0.05).The IHC and RT-qPCR results showed that PLA1A expression level was significantly upregulated in CRC tissiue(P<0.05).High PLA1A level was closely associated with the TNM stage,degree of differentiation,and lymph node metastasis(P<0.05).The IHC results demonstrated that PLA1A positively correlated with the infiltrating CD8+T cell level(P<0.05).In addition,the elevated PLA1A levels upregu-lated the expressions of immunosuppressive checkpoints PD-1,TIM-3,and CTLA-4(P<0.05).Conclusions:PLA1A is highly expressed in CRC,which is closely related to immune infiltrating cells and immunosuppressive checkpoints,suggesting that PLA1A plays an important role in immune infiltration in CRC,a finding that provides guidance in the treatment of CRC.

Objective:To understand the factors influencing new infections of 9-valent vaccine-type human papillomavirus (9-valent type HPV) among men who have sex with men (MSM) in Urumqi City and to construct a prediction model of individual dynamics of new infections of 9-valent type HPV among MSM.Methods:In this study, a snowball method was adopted to recruit MSM in Urumqi City to establish a dynamic cohort, and participants were followed up every 6 months from 2016 to 2023, and perianal exfoliated cells were collected for HPV genotyping; joint models were established using the number of same-sex sexual partners in the last six months and the number of anal intercourse in the last one week as longitudinal variables, respectively, and joint models were utilized to analyze the influence factors of 9-valent HPV new infections in MSM individuals were analyzed by the joint model; the predictive efficacy of the model in the follow-up period was evaluated by using the time-dependent receiver operating characteristic area under the curve (AUC) values. Based on the prediction model, two study participants were randomly selected for individual dynamic prediction of new-onset HPV infections of 9-valent type types.Results:MSM with at least two follow-up visits 579 individuals were included in the analysis. The results of the two joint models showed that being divorced/widowed [hazard ratio ( HR)=1.544, 95% CI: 1.033-2.233], having a sexual behavior style of being the inserted party ( HR=1.366, 95% CI: 1.053-1.764), and having a history of STDs ( HR=1.659, 95% CI: 1.057-2.558) increased the 9-valent types of new HPV infections risk. The results of the shared parameter of the joint model of the number of same-sex partners in the last six months showed that each 2.72 increase in the number of same-sex partners in the last six months was associated with a 28.2% increase in the risk of new 9-valent HPV infections in MSM individuals ( HR=1.282, 95% CI: 1.065-1.540). The time-dependent AUC results showed that the joint model for the number of same-sex sexual partners in the last six months (0.808 0) predicted better performance than the joint model for the number of anal intercourse in the last one week (0.750 0). The joint model based on the number of same-sex sexual partners in the last six months for the prediction of MSM individual dynamics was consistent with the real situation. Conclusion:The joint model based on the number of same-sex sexual partners in the last six months, sexual behavior, history of STDs, and other risk factors has high accuracy in predicting the risk of new MSM 9-valent HPV infections in Urumqi City, which can provide a scientific basis for the prediction of individual dynamics of new MSM 9-valent HPV infections.

Objective:To analyze the clinical characteristics, treatment, response to treatment, prognosis, and the importance of early recognition and treatment of pediatric systemic lupus erythematosus (SLE) complicated with thrombotic microangiopathy (TMA).Methods:A retrospective summary of the clinical data of 5 children diagnosed with SLE complicated by TMA at Beijing Children′s Hospital, Capital Medical University, from November 2024 to January 2025.Results:Among the 5 children (1 boy and 4 girls, male-to-female ratio of 1∶4), the age of onset ranged from 11 years and 9 months to 14 years and 9 months. All cases had acute onset, rapid disease progression, severe illness, and involvement of multiple organs and systems. The disease activity of SLE was moderately to severely active when TMA was diagnosed. During the course of TMA, all 5 children exhibited varying degrees of hemolytic anemia, thrombocytopenia, renal dysfunction, and proteinuria. Elevated sC5b-9 levels were observed in all 5 children, with 3 showing severely reduced ADAMTS13 activity and 2 with elevated ADAMTS13 inhibitors. Two children had elevated sC5b-9, severely reduced ADAMTS13 activity, and elevated ADAMTS13 inhibitors simultaneously. Four children had newly diagnosed SLE with TMA and achieved stable condition within 2-3 weeks after aggressive treatment, including methylprednisolone pulse therapy, immunosuppressive agents, biologics, plasma infusion, plasma exchange, or dialysis. One child, who had been diagnosed with SLE for 8 years and had irregular oral medication for half a year, suddenly developed TMA with refractory hemolytic anemia and severe thrombocytopenia. This child responded poorly to methylprednisolone pulse therapy, cyclosporine, and eculizumab but showed improvement with plasma exchange. However, the condition was prone to relapse when the interval between plasma exchanges was prolonged. The child eventually responded well to low-dose rituximab and was discharged after 6 weeks of combined treatment. Four children were diagnosed with TMA within 1 week of admission and achieved stable condition after 3 months of follow-up, with no anemia or thrombocytopenia, negative proteinuria, normal complement C3 and C4 levels, and an SLE disease activity score of 0. One child, who had been treated with high-dose glucocorticoid, multiple immunosuppressive agents, and biologics at another hospital, was transferred and diagnosed with TMA 2 weeks after admission. The condition gradually stabilized after treatment with methylprednisolone pulse therapy, immunosuppressive agents, biologics, and plasma exchange. However, at 3-month follow-up, the child still had alopecia and proteinuria, with an SLE disease activity score of 6, indicating mild disease activity.Conclusion:For children with moderate to severe active SLE, especially those with acute onset, rapid disease progression, and prominent manifestations of anemia, thrombocytopenia, renal dysfunction, and poor response to high-dose methylprednisolone pulse therapy, the risk of TMA should be vigilantly monitored. Early diagnosis and aggressive treatment are crucial.

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.

This study aims to analyze the biological characteristics such as pathogenicity,serotype,virulence genes,and drug resistance of Escherichia coli(E.coli)causing diarrhea in dairy and meat calves in different farms in the Northern Hebei.From 2022 to 2023,120 diseased tissue sam-ples(feces,anal swabs,and livers)of calves(0-2 months old)suffering from diarrhea in the north-ern Hebei region were collected.The detection of viral and parasitic pathogens was negative.Bacte-rial isolation and cultivation,morphological observation,biochemical identification,and PCR meth-ods were used to identify E.coli.Biological characteristics such as pathogenicity,serum typing,vir-ulence genes,and drug resistance were detected using mouse virulence test,glass plate agglutina-tion test,PCR method,and K-B drug sensitivity paper method,and determine the median lethal dose(LD50)of representative strains of dominant serotypes in mice respectively.The results showed that 76 strains of E.coli were isolated,and 56 strains were pathogenic E.coli that could cause varying degrees of death in mice,with mortality rates all above 40％.Among 56 pathogenic E.coli strains,O6 and O152 were the dominant pathogenic serotypes,among which 48 strains(85.7％)were enterotoxic E.coli(ETEC),6 strains(10.7％)were enteropathogenic E.coli(EPEC),and 2 strains(3.6％)were enterohemorrhagic E.coli(EHEC).The detection rates of vir-ulence genes fyuA,irp2,fliC,stx1,stx2,K88,K99,eaeA and ler were over 50％,while the de-tection rates of other types of virulence genes were 3.6％to 37.0％.The resistance rates to nine drugs such as ampicillin,neomycin,and amoxicillin were over 42.9％,and the resistance rates to other drugs were 12.5％to 32.1％,showing multiple drug resistance and at least resistance to three types of antibiotics.The LD50 values of the dominant serotype of representative strains ETO 152 strain and EPO6 were 3.16×104 and 3.22×106 CFU/mL,respectively.This study can provide ref-erence for the prevention and control of E.coli disease in dairy and meat calves in the Northern Hebei region.

Objective:To understand the factors influencing new infections of 9-valent vaccine-type human papillomavirus (9-valent type HPV) among men who have sex with men (MSM) in Urumqi City and to construct a prediction model of individual dynamics of new infections of 9-valent type HPV among MSM.Methods:In this study, a snowball method was adopted to recruit MSM in Urumqi City to establish a dynamic cohort, and participants were followed up every 6 months from 2016 to 2023, and perianal exfoliated cells were collected for HPV genotyping; joint models were established using the number of same-sex sexual partners in the last six months and the number of anal intercourse in the last one week as longitudinal variables, respectively, and joint models were utilized to analyze the influence factors of 9-valent HPV new infections in MSM individuals were analyzed by the joint model; the predictive efficacy of the model in the follow-up period was evaluated by using the time-dependent receiver operating characteristic area under the curve (AUC) values. Based on the prediction model, two study participants were randomly selected for individual dynamic prediction of new-onset HPV infections of 9-valent type types.Results:MSM with at least two follow-up visits 579 individuals were included in the analysis. The results of the two joint models showed that being divorced/widowed [hazard ratio ( HR)=1.544, 95% CI: 1.033-2.233], having a sexual behavior style of being the inserted party ( HR=1.366, 95% CI: 1.053-1.764), and having a history of STDs ( HR=1.659, 95% CI: 1.057-2.558) increased the 9-valent types of new HPV infections risk. The results of the shared parameter of the joint model of the number of same-sex partners in the last six months showed that each 2.72 increase in the number of same-sex partners in the last six months was associated with a 28.2% increase in the risk of new 9-valent HPV infections in MSM individuals ( HR=1.282, 95% CI: 1.065-1.540). The time-dependent AUC results showed that the joint model for the number of same-sex sexual partners in the last six months (0.808 0) predicted better performance than the joint model for the number of anal intercourse in the last one week (0.750 0). The joint model based on the number of same-sex sexual partners in the last six months for the prediction of MSM individual dynamics was consistent with the real situation. Conclusion:The joint model based on the number of same-sex sexual partners in the last six months, sexual behavior, history of STDs, and other risk factors has high accuracy in predicting the risk of new MSM 9-valent HPV infections in Urumqi City, which can provide a scientific basis for the prediction of individual dynamics of new MSM 9-valent HPV infections.