Aim To examine the pathogenesis of disul-fide death gene in vascular dementia(VD)by bioin-formatics analysis of disulfide death differentially ex-pressed genes(DEGs)combined with experimental verification.Methods The death DEGs of disulfide were screened and their correlation was analyzed.The VD patients data in the data set were analyzed by clus-tering and typing and gene set variation.The clustering risk of DEGs was tested with a nomogram model,and the optimal learning model was predicted.After the es-tablishment of VD rat model,water maze test,HE stai-ning and RT-qPCR detection were performed to verify the results of health information.Results Four DEGs including SLC7A11 were obtained,which had antago-nistic or synergistic interaction with each other.The genetic data could be divided into two subtypes with significant differences.After typing,VD disulfide DEGs were mainly concentrated in GnRH signaling pathways.The accuracy of the nomogram prediction model was high.Generalized linear was the best ma-chine learning model.Compared with the sham opera-tion group,the escape latency of rats in the model group was prolonged,the number of crossing platforms decreased,the relative mRNA expression levels of Slc3a2 and Slc7a11 decreased,and LRPPRC in-creased.Conclusions SLC7A11 and other disulfide death DEGs and its related GnRH signaling pathway may be an important part of the pathogenesis of VD di-sulfide death.SLC3A2,LRPPRC and SLC7A11 can be used as characteristic genes in the regulation of VD by disulfide death,which may affect VD progression through the regulation of disulfide death.

Objective:To explored the application value of dynamic susceptibility contrast-perfusion weighted imaging(DSC-PWI)combined with amide proton transfer(APT)imaging in brian glioma grading.Methods:Retrospective analysis of clinical data of 100 patients with brian glioma admitted to The Second Affiliated Hospital of Xinjiang Medical University from January 2022 to September 2024.They were divided into a low-grade group(WHO grades Ⅰ-Ⅱ,n=62)and high-grade group(WHO grades Ⅲ-Ⅳ,n=38)according to the World Health Organization(WHO)grading system for tumors.All patients underwent DSC-PWI and APT imaging preoperative examinations.Apparent diffusion coefficien(ADC),cerebral blood volume(CBV),cerebral blood flow(CBF),mean transit time(MTT),time to peak(TTP),maximum APT value(APTmax),minimum APT value(APTmin),the average APT value of the whole lesion(APTwhole)were recorded.The general datas and ADC,CBV,CBF,MTT,TTP,APTmax,APTmin,APTwhole of two group were compared.The influencing factors of high-grade brian glioma were analysed by Multivariate logistic regression.The diagnostic value of high-grade brian glioma was analysed of DSC-PWI combined with APT imaging by receiver operating characteristic(ROC)curve.Results:There was no statistically significant difference in age,gender,lesion location,basilar artery occlusion,necrosis and growth pattern between the two groups(P＞0.05),there was a statistically significant difference in the maximum diameter of lesions ≥2 cm and cystic lesions(P＜0.05).The ADC of the high-gradel group was lower than that of the low-grade group,while APTmax,APTmin,APTwhole,CBF,CBV,MTT and TTP were all higher than those of the low-grade group(P＜0.05).Elevated APTmax,APTmin,CBV,MTT,and TTP were risk factors for high-grade brian glioma(P＜0.05),while elevated ADC was a protective factor(P＜0.05).The results of ROC analysis showed that,the area under the curve(AUC)values of APTmax,APTmin,ADC,CBV,MTT,and TTP for diagnostic high-grade brian glioma were 0.830,0.868,0.852,0.843,0.803 and 0.827(all P＜0.05).The results of ROC analysis showed that,the AUC values of the logistic model for diagnostic high-grade brian glioma was 0.993.Conclusion:Single detection of DSC-PWI and APT imaging parameters has high diagnostic value in brian glioma grading,and combined detection of APTmax,APTmin,ADC,CBV,MTT and TTP imaging parameters can further improve diagnostic accuracy.

Aim To explore the effects of nuciferine on cognitive behavior and the underlying mechanisms,white matter injury(WMI),neuroinflammation,and ferroptosis in mice with chronic ischemic WMI.Meth-ods Sixty C57BL/6 mice were divided into a control group,a bilateral common carotid artery stenosis(BCAS)model group,and low/high-dose nuciferine groups(20/40 mg·kg-1).A chronic ischemic WMI model was established using BCAS surgery.Following eight weeks of treatment,cognitive behavior(Y-maze,novel object recognition,Morris water maze),white matter integrity(LFB/MBP staining),microglial acti-vation(Iba-1 immunofluorescence),inflammatory cy-tokines(ELISA for TNF-α,IL-1β,IL-6),ferroptosis markers(Fe2+,ROS,MDA,GSH),mitochondrial ultrastructure(electron microscopy),and protein ex-pression of the PI3K/Akt and NRF2/xCT/GPX4 signa-ling pathways(Western blot)were evaluated.Results Compared with the control group,the BCAS group showed significant cognitive decline(P＜0.05),re-duced myelin density,elevated inflammatory cytokines and ferroptosis markers(Fe2+,ROS,MDA),shrunk-en mitochondria,and downregulated PI3K/Akt and NRF2/xCT/GPX4 pathway proteins(P＜0.05).Nu-ciferine intervention significantly ameliorated these in-juries in BCAS mice,with the high-dose group exhibi-ting superior effects(P＜0.05).Conclusions Nu-ciferine exerts protective effects against chronic ische-mic WMI and cognitive impairment by activating the PI3K/Akt and NRF2/xCT/GPX4 signaling pathways,thereby suppressing neuroinflammation and ferroptosis.

Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.

Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.

AIM To study the chemical constituents from Inula japonica Thunb.and their anti-asthmatic activity.METHODS Separation and purification were performed using silica gel and Sephadex LH-20,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The effect of compounds on the release rate of β-Hex was evaluated by substrate coloration method.RESULTS Twenty-three compounds were isolated and identified as dehydrodontic acid(1),vitexin(2),alternariol(3),globuxanthone(4),1,3,6,7-tetrahydroxyxanthone(5),hydroxyhydrolapachol(6),isoscopoletin(7),elephanmollen(8),benzoylcholine(9),hoconobiflavone(10),clovandiol(11),hydroxydihydrobovolide(12),5,7-dihydroxycoumarin(13),scopoletin(14),orlichenol glucoside(15),urolignoside(16),9-angeloyloxythymol(17),6,3′,4′-trihydroxyaurone(18),flufuran(19),sweroside(20),guajadial(21),5,7,4′-trimethoxy-4-phenylcoumarin(22),dibutylphthalate(23).After intervention with compounds 9 and 16,the release rates of β-Hex were(56.64±2.37)％and(58.07±2.29)％,respectively.CONCLUSION Compounds 1-23 are isolated from Ⅰ.japonica for the first time.Compounds 9 and 16 have anti-asthmatic activity.

Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

Objective:To explore the influence of initial high-risk cytogenetic abnormalities on the outcomes of children with acute myeloid leukemia (AML) after post-transplant Cyclophosphamide (PTCy)-based allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:A retrospective cohort study.AML children who underwent PTCy-based allo-HSCT after the first complete remission at Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science and Technology between April 2017 and April 2024 were enrolled.Patients were divided into intermediate-risk and high-risk groups based on their initial cytogenetic features.These patients were further divided into complex karyotype, 11q23 rearrangement, and other karyotype groups.Clinical characteristics and survival outcomes were compared among these groups.Measurement and count data were analyzed using Wilcoxon rank-sum/Kruskal-Wallis and χ2 tests, respectively.Survival and risk factor analyses were performed using Kaplan-Meier and Cox proportional hazards methods, respectively. Results:A total of 51 AML children who underwent allo-HSCT were included in this study.The median age at transplantation was 3.2 years and the median follow-up time was 4.6 years.There were 26 cases in the intermediate-risk group and 25 cases in the high-risk group; 8 cases in the complex karyotype group, 14 cases in the 11q23 rearrangement group, and 29 cases in the other karyotype groups.By the end of the follow-up on November 30, 2024, 11 patients relapsed, 8 patients died, and 13 patients developed grades Ⅱ-Ⅳ acute graft-versus-host disease (GVHD).The 3-year overall survival (OS), relapse-free survival (RFS), and grades Ⅱ-Ⅳ acute GVHD-free and relapse-free survival (GRFS) were 84.0% (95% CI: 74.4%-94.8%), 74.5% (95% CI: 63.4%-87.5%), and 58.8% (95% CI: 46.7%-74.0%), respectively.The 3-year OS of the high-risk group was significantly lower than that of the intermediate-risk group (71.8% vs.96.2%, P=0.022), while differences in 3-year RFS and GRFS between the 2 groups were not statistically significant (68.0% vs.80.8%, P=0.400; 52.0% vs.65.4%, P=0.420).The 3-year OS, RFS and GRFS of the complex karyotype group were significantly lower than those of 11q23 rearrangement and other karyotype groups (50.0% vs.85.7%, 93.1%, P=0.009; 37.5% vs.85.7%, 79.3%, P=0.022; 25.0% vs.64.3%, 65.5%, P=0.049).Multivariate analysis showed that a complex karyotype was an independent prognostic factor affecting 3-year OS and GRFS [OS: HR=6.79 (95% CI: 1.13-43.80), P=0.044; GRFS: HR=3.72(95% CI: 1.13-12.20), P=0.030]. Conclusions:High-risk cytogenetic features are significant predictors of survival outcomes in pediatric AML patients undergoing PTCy-based allo-HSCT.

This study was aimed at understanding the antimicrobial resistance patterns,virulence characteristics,and phyloge-netic relationships of foodborne Listeria monocytogenes in Weifang.A total of 67 strains of Listeria monocytogenes were isolated from livestock,poultry meat,and clinical samples in Weifang between 2020 and 2023.The susceptibility of these isolates was determined through broth microdilution.Whole-genome sequencing and genetic characterization of these isolates were conducted.The 67 strains were divided into 12 STs,among which ST121,ST8,ST9,and ST87 predominated(76.12%).Eight groups of closely related strains were identified through cgMLST typing.Three Listeria pathogenicity islands and two genomic islands were identified in all strains:100%of the strains carried LIPI-1,5.97%carried LIPI-3,14.93%carried LIPI-4,2.99%carried LGI-2,and 4.48%of the strains carried LGI-3.No antibiotic resistance genes were found in any strains.All isolates were susceptible to ampicillin,penicillin,merope-nem,trimethoprim-sulfamethoxazole,and vancomycin.Five isolates were resistant to tetracycline,and three strains of ST87,one strain of ST8,one strain of ST224,and two strains of ST87 were simultaneously resistant to erythromycin.The tet(M)tetracycline re-sistance genes and msr(D)and mef(A)erythromycin resistance genes from three strains of ST87 and one strain of ST8 were carried by a phage similar to phi1605 in Erysipelothrix,with>95%identity.The tet(M)gene from the ST224 isolates was carried by a transposon similar to Tn5801_B15 in Enterococcus faecalis,with>95%identity.Drug-resistant strains of Listeria monocytogenes were found in livestock and poultry meat on sale in Weifang,particularly strains of type ST87 and ST224 simultaneously carrying highly pathogenic virulence islands,thus posing a threat to food safety and public health.These findings therefore warrant attention from relevant depart-ments and strengthened monitoring efforts.

Objective:To explored the application value of dynamic susceptibility contrast-perfusion weighted imaging(DSC-PWI)combined with amide proton transfer(APT)imaging in brian glioma grading.Methods:Retrospective analysis of clinical data of 100 patients with brian glioma admitted to The Second Affiliated Hospital of Xinjiang Medical University from January 2022 to September 2024.They were divided into a low-grade group(WHO grades Ⅰ-Ⅱ,n=62)and high-grade group(WHO grades Ⅲ-Ⅳ,n=38)according to the World Health Organization(WHO)grading system for tumors.All patients underwent DSC-PWI and APT imaging preoperative examinations.Apparent diffusion coefficien(ADC),cerebral blood volume(CBV),cerebral blood flow(CBF),mean transit time(MTT),time to peak(TTP),maximum APT value(APTmax),minimum APT value(APTmin),the average APT value of the whole lesion(APTwhole)were recorded.The general datas and ADC,CBV,CBF,MTT,TTP,APTmax,APTmin,APTwhole of two group were compared.The influencing factors of high-grade brian glioma were analysed by Multivariate logistic regression.The diagnostic value of high-grade brian glioma was analysed of DSC-PWI combined with APT imaging by receiver operating characteristic(ROC)curve.Results:There was no statistically significant difference in age,gender,lesion location,basilar artery occlusion,necrosis and growth pattern between the two groups(P＞0.05),there was a statistically significant difference in the maximum diameter of lesions ≥2 cm and cystic lesions(P＜0.05).The ADC of the high-gradel group was lower than that of the low-grade group,while APTmax,APTmin,APTwhole,CBF,CBV,MTT and TTP were all higher than those of the low-grade group(P＜0.05).Elevated APTmax,APTmin,CBV,MTT,and TTP were risk factors for high-grade brian glioma(P＜0.05),while elevated ADC was a protective factor(P＜0.05).The results of ROC analysis showed that,the area under the curve(AUC)values of APTmax,APTmin,ADC,CBV,MTT,and TTP for diagnostic high-grade brian glioma were 0.830,0.868,0.852,0.843,0.803 and 0.827(all P＜0.05).The results of ROC analysis showed that,the AUC values of the logistic model for diagnostic high-grade brian glioma was 0.993.Conclusion:Single detection of DSC-PWI and APT imaging parameters has high diagnostic value in brian glioma grading,and combined detection of APTmax,APTmin,ADC,CBV,MTT and TTP imaging parameters can further improve diagnostic accuracy.