Background: and Purpose Vertebrobasilar fusiform aneurysms (VBFAs) carry substantial morbidity and mortality, but optimal management for unruptured VBFAs remains unclear. We compared the safety and efficacy of conservative management (CM), stent-assisted coiling (SAC), and flow diverters (FDs) in patients with unruptured VBFAs, focusing on long-term prognosis. Methods: This study included data from a nationwide Chinese cohort of patients with vertebrobasilar dissecting aneurysms. Inverse probability of treatment weighting (IPTW) balanced confounders across groups. The primary outcome was poor prognosis (modified Rankin Scale score >2). Secondary outcomes included aneurysm rupture, ischemic stroke, compression symptoms, and VBFA-related deaths. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed. Results: Among 1,115 patients with unruptured VBFAs, 838 (median age, 54 years; 655 men) were included. After IPTW, baseline characteristics were balanced. Median follow-up was 54 months. FD was associated with a lower risk of poor prognosis than CM (OR, 0.48 [95% CI, 0.30 to 0.77]; p=0.002), with no difference between CM and SAC. FD also reduced aneurysm rupture (OR, 0.20 [95% CI, 0.07 to 0.60]; p=0.004) and compression symptoms (OR, 0.30 [95% CI, 0.13 to 0.68]; p=0.004) versus CM. Time-to-event analyses further revealed significant differences in vertebral artery lesions and Type I–II VBFAs, whereas no significant differences were observed in basilar or vertebrobasilar junction lesions or in Type III–IV VBFAs. Conclusions Compared with CM, FD was associated with improved long-term outcomes in unruptured VBFAs, particularly in vertebral artery lesions and Type I–II VBFAs, although residual confounding cannot be excluded.

Objective:To analyze the predictive role of WT1 expression levels pre-and early post-transplantation on relapse and overall survival(OS)in patients with acute myeloid leukemia(AML)undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT)during their first complete remission(CR1).Methods:A retrospective analysis was conducted on the clinical data of 107 adult AML patients who underwent allo-HSCT during their CR1 at our center between May 2012 and December 2021.The predictive role of bone marrow WT1 expression levels before transplantation and at 3 and 6 months post-transplantation on relapse and OS was explored in combination with relevant clinical factors.Results:The median follow-up time for the 107 patients was 70(range:11-117)months.Among the patients,15 cases died.Kaplan-Meier survial analysis showed that the 3-year overall survival(OS)rate was 85.0％.20 patients experienced relapse,with a median time to relapse of 8(range:0.5-44)months and a l-year cumulative relapse rate of 13.1％.The overall median value of WT1 before transplantation,3 months after transplantation,and 6 months after transplantation was 0.26％(range:0％-23.64％),with an upper quartile value of 0.74％.No statistically significant differences in WT1 expression levels were observed among the pre-transplantation,3-month post-transplantation,and 6-month post-transplantation time points(P=0.227).Univariate analysis showed that patients with WT1 levels＞0.74％at 3 months post-transplantation had a higher 1-year relapse rate(P=0.029)and lower 3-year OS rate(P＜0.001)compared to patients with WT1 levels ≤0.74％.Other significant factors affecting 1-year relapse included stem cell source(P=0.041)and chronic graft-versus-host disease(cGVHD)(P=0.013).For 3-year OS,additional influencing factors were genetic high risk(P=0.048)and stem cell source(P=0.016).Multivariate analysis revealed that WT1 level＞0.74％at 3 months post-transplantation had a trend to affect 1-year relapse rate(HR=3.309,95％CI:0.958-11.431,P=0.058),while the absence of cGVHD was an independent risk factor for 1-year relapse(HR=3.473,95％CI:0.749-16.100,P=0.037).Only WT1 level＞0.74％at 3 months post-transplantation was an independent risk factor for 3-year OS(HR=6.886,95％CI:2.402-19.738,P＜0.001).Conclusion:High WT1 expression level at 3 months post-transplantation in AML patients undergoing allo-HSCT during CR1 affects the 1-year relapse rate and 3-year OS,and is an independent risk factor affecting 3-year OS.These findings suggest that dynamic monitoring of WT1 expression levels has certain value in prognostic assessment of AML patients who received allo-HSCT during CR1.

Objective:To investigate the molecular characteristics of low-risk acute myeloid leukemia(AML)at recurrence,and analyze the factors affecting retreatment efficacy and prognosis.Methods:A retrospective analysis was conducted on the clinical and laboratory data of 31 patients with newly diagnosed low-risk AML who relapsed during consolidation treatment or follow-up after treatment in our hospital from April 2017 to January 2023.Gene mutations before and after relapse were compared,retreatment efficacy following relapse was evaluated,and univariate and multivariate analyses were performed to identify factors influencing treatment efficacy and prognosis.Results:Gene sequencing results after relapse showed that the most common newly acquired mutation was FLT3-ITD,while RAS mutation detected at initial diagnosis were predisposed to loss of expression during relapse.The median overall survival(OS)after relapse for the entire cohort was 349(170-528)days,with non-hematopoietic stem cell transplantation(HSCT)group and HSCT group demonstrating median survival times of 210(106-314)days and not reached,respectively(P=0.001).Multivariate analysis revealed that age ≥60 years was a significant risk factor for achieving remission after retreatment in initially diagnosed low-risk AML patients who experienced relapse(OR=18.222,95％CI:1.188-279.597,P=0.037).Additionally,DNMT3A mutation was identified as an independent risk factor for OS(HR=13.165,95％CI:2.018-85.877,P=0.007),while HSCT post-relapse demonstrated significant survival benefits(HR=0.133,95％CI:0.025-0.698,P=0.017)and served as an independent protective factor for OS.Conclusion:Relapsed low-risk AML is often associated with loss of RAS and novel mutations in FLT3-ITD.Age ≥ 60 years and DNMT3A mutations were identified as independent adverse factors for achieving subsequent remission and post-relapse survival,respectively,while HSCT significantly improved patient outcomes.

Aim To investigate the effect of total fla-vones of Coreopsis tinctoria Nutt(CF)on cognitive im-pairment in vascular dementia(VD).Methods The VD rat models were established by modified bilateral common carotid arteries ligation method.SD rats were divided into the sham operation group,model group,positive control group(nicergoline),and low,medium,and high dose CF groups.After eight weeks of admin-istration,the short term memory and spatial learning and memory abilities were evaluated by the platform jumping test,dark avoidance test and Morris water maze test.The pathological changes of the hippocam-pal tissues were inspected by HE and Nissl staining.The contents of TNF-α and IL-1β in the hippocampal were examined by ELISA.The protein expression lev-els of TLR4,MyD88,NF-κB p65,and p-NF-κB p65 in the hippocampal were detected by Western blot.The mRNA expression levels of miR-93,TLR4,MyD88,and NF-κB p65 in the hippocampal were determined by qRT-PCR.Results CF obviously improved the short term memory and spatial learning and memory abilities of VD rats,and alleviated the pathological damage of the hippocampus.CF also obviously decreased the lev-els of TNF-α and IL-1β,declined the protein expres-sion levels of TLR4,MyD88,and p-NF-κB p65,and re-duced the miR-93,TLR4,and MyD88 mRNA expres-sion in the hippocampus.Conclusion CF has a nota-ble protective effect on the neuroinflammation and cog-nitive impairments in VD rats by inhibiting the miR-93-mediated TLR4 signaling pathway.

Objective:To investigate the clinical efficacy and underlying mechanisms of endoscopic sinus surgery(ESS)combined with budesonide nasal spray in the treatment of chronic rhinosinusitis with nasal polyps(CRSwNP),with a focus on its effects on symptom control,nasal mucosal function repair,immune regulation,and recurrence rate.Methods:A total of 110 patients with CRSwNP were randomly divided into a matched group(60 cases,receiving ESS alone)and an observation group(50 cases,receiving ESS followed by 6 months of postoperative budesonide nasal spray).The Lund-Kennedy score,Visual Analog Scale(VAS)score for symptoms,nasal mucociliary clearance rate(MTR),nasal mucosal T-cell subsets(CD4+/CD8+),inflammatory factors(TGF-β1,VEGF),serum marker(IL-3,IL-4,IL-5,IL-13,TSLP)and complications,recurrence rate(6 months and 12 months)were compared between the two groups before surgery and at 3 and 6 months postoperatively.Results:At 3 months postoperatively,the VAS scores for nasal obstruction,hyposmia,and facial pain in the observation group were lower than those in the matched group(0.76±0.21 vs 1.26±0.34,0.88±0.17 vs 1.48±0.33,0.37±0.07 vs 0.55±0.11,all P＜0.001).At 6 months postoperatively,the Lund-Kennedy score(1.34±0.31 vs 1.65±0.33)and MTR(7.53±1.67 vs 6.54±1.39 mm/min)in the observation group were superior to those in the matched group(both P＜0.05).The CD4+/CD8+ratio(1.03±0.17 vs 0.87±0.14)and TGF-β1 levels(568.33±75.48 vs 506.27±72.87 μg/L)were higher,while VEGF levels(145.95±27.94 vs 178.33±36.37 ng/L)were lower in the observation group(all P＜0.001).At 6 months after surgery,the levels of IL-4,IL-5,IL-13,and TSLP were lower than those in the matched group(P＜0.05).The complication rate(8.00％vs 16.67％)and recurrence rate(4.00％vs 18.33％)in the observation group were lower than those in the matched group(P＜0.05).Conclusion:ESS combined with budesonide can significantly alleviate CRSwNP symptoms and reduce the risk of recurrence by inhibiting Th2-type inflammatory responses,regulating T-cell immune balance,improving ciliary function,and suppressing angiogenesis.The synergistic mechanism involves the dynamic regulation of inflammatory microenvironment remodeling and mucosal repair,demonstrating significant clinical efficacy and safety.This study is the first to propose a postoperative management strategy that integrates mucosal repair,Th2 suppression,and inflammatory remodeling,filling a gap in research on postoperative immune microenvironment regulation.

Objective:This study aims to investigate the expression of uridine diphosphate-glucose[]pyrophos-phorylase 2(UGP2)in breast cancer(BC)tissues and its oncogenic mechanism,assessing its potential value as a diag-nostic and prognostic biomarker for breast cancer.Methods:(1)Online database analysis was conducted to assess UGP2 mRNA and protein expression levels in breast cancer and explore their correlation with clinical characteristics.Im-munohistochemistry(IHC)was used to verify UGP2 expression in human breast cancer tumor tissues and evaluate its relationship with clinicopathological features.(2)Kaplan-Meier survival analysis and COX regression models were used to analyze the impact of UGP2 expression on breast cancer patient prognosis.(3)Bioinformatics methods were em-ployed to investigate the correlation between UGP2 and tumor immune cell infiltration,and to predict the biological func-tions and associated signaling pathways of UGP2 in breast cancer.Results:(1)The mRNA and protein expression levels of UGP2 were upregulated in breast cancer tissues(both P<0.05),and were negatively correlated with ER-positive and PR-positive status(OR<1,P<0.05),while positively correlated with Ki-67 levels and the triple-negative breast cancer(TNBC)subtype(OR>1,P<0.05).(2)Elevated expression levels of UGP2 were associated with poorer survival rates in breast cancer patients(both P<0.05)and were identified as an independent adverse prognostic factor for breast cancer(HR=1.40,P<0.05).(3)Functional analysis results suggested that UGP2 may promote tumor progression by regulating metabolism,hormone signaling,and the immune microenvironment.Additionally,UGP2 expression was negatively cor-related with NK cell activation status and positively correlated with the inhibitory state.Conclusion:UGP2 expression is elevated in breast cancer tissues and is closely associated with poor patient prognosis.It may promote cancer pro-gression through mechanisms such as metabolic reprogramming and immune suppression.UGP2 shows promise as a potential biomarker and therapeutic target in breast cancer,providing a basis for personalized treatment.

AIM To study the chemical constituents from Tylophora ovata(Lindl.)Hook.ex Steud.and their antibacterial activities.METHODS Ethanol extract was isolated and purified by MCI,silica gel,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by spectral data.The inhibitory activities of each compound against Phomopsis sp.were determined by mycelial growth rate method.RESULTS Twenty-six compounds were identified as paeonol(1),stigmast-4-en-3-one(2),ergosta-4,6,8(14),22-tetraen-3-one(3),2,4-methoxyphenol(4),1,2,4-trimethoxybenzene(5),3-methoxyphenol(6),3,4-dimethoxyacetophenone(7),5α,8α-epidioxy-ergosta-6,22(E)-diene-3β-ol(8),kaempferol 3-O-β-D-galactopyranoside(9),glaucogenind C(10),glaucoge-nin A 3-O-β-D-cymaropyranoside(11),dibutyl phthalate(12),cynatratoside A(13),hirundigoside C(14),sublanceoside B2(15),cynanoside A(16),dipentyl phthalate(17),5-hydroxymethyl-2-furancarboxaldehyde(18),bis-(2-ethyl)hexylphthalate(19),p-hydroxybenzoic acid(20),syringic acid(21),β-hydroxypropiovanillone(22),3-hydroxy-l-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone(23),(+)-syringare sinol(24),(-)-syringare sinol(25),(+)-medioresinol(26).IC50 value of compound 12 was 37.27 μg/mL.CONCLUSION Compounds 1-26 are isolated from this plant for the first time.Compound 12 has inhibitory activity against Phomopsis sp.

Aim To investigate the effect of total fla-vones of Coreopsis tinctoria Nutt(CF)on cognitive im-pairment in vascular dementia(VD).Methods The VD rat models were established by modified bilateral common carotid arteries ligation method.SD rats were divided into the sham operation group,model group,positive control group(nicergoline),and low,medium,and high dose CF groups.After eight weeks of admin-istration,the short term memory and spatial learning and memory abilities were evaluated by the platform jumping test,dark avoidance test and Morris water maze test.The pathological changes of the hippocam-pal tissues were inspected by HE and Nissl staining.The contents of TNF-α and IL-1β in the hippocampal were examined by ELISA.The protein expression lev-els of TLR4,MyD88,NF-κB p65,and p-NF-κB p65 in the hippocampal were detected by Western blot.The mRNA expression levels of miR-93,TLR4,MyD88,and NF-κB p65 in the hippocampal were determined by qRT-PCR.Results CF obviously improved the short term memory and spatial learning and memory abilities of VD rats,and alleviated the pathological damage of the hippocampus.CF also obviously decreased the lev-els of TNF-α and IL-1β,declined the protein expres-sion levels of TLR4,MyD88,and p-NF-κB p65,and re-duced the miR-93,TLR4,and MyD88 mRNA expres-sion in the hippocampus.Conclusion CF has a nota-ble protective effect on the neuroinflammation and cog-nitive impairments in VD rats by inhibiting the miR-93-mediated TLR4 signaling pathway.

To investigate the antimicrobial resistance of Enterococci isolated from 596 anal swabs,feces and environmental samples were collected from pig,cattle,chicken and quail farms in Chang-sha,Hunan Province,Enterococci were isolated and identified by mass spectrometry.The minimum inhibitory concentrations(MICs)of 10 antimicrobial agents were determined by AGAR diffusion method.Whole genome sequencing(WGS)was used to detect the distribution of multilocus se-quence typing(ST),drug resistance genes and virulence genes.A total of 272 strains of Enterococ-cus were isolated(45.6％).The isolates were resistant to cefoxitin(68.9％)and cefotiofur(58.5％),followed by trimethoprim/sulfamethoxazole(52.2％),vancomycin(4.4％),and linezolid(13.6％).In this study,six linezolid highly resistant Enterococci isolates were analyzed by whole genome sequencing to explore the transmission mechanism of linezolid resistance because linezolid is forbidden to be used in aquaculture.ST403(4/6),ST16(1/6)and ST476(1/6)were the most common ST types,which all originated from the same farm.Three oxazolidinone resistance genes(cfr,poxtA and optrA)were found in all 21 strains.One strain(Ecc60)carried all three oxazo-lidinone resistance genes,but none of them were located on the plasmid.tet(M),aph(3')-Ⅲ,and lsa(A)were found in all six Enterococcus isolates.Interestingly,the present study is the first to i-dentify enterococci carrying the optrA gene in quail fecal samples.The analysis of the genetic envi-ronment of oxazolidinone resistance genes showed that the genetic environment of cfr(D),poxtA and optrA of isolates from the same farm was similar.A total of 19 virulence genes were detected in 6 isolates,of which 12 genes(ElrA,SrtA,ace,agg,cCF10,cOB1,cad,camE,ebpA,ebpC,efaAfs,tpx)were carried by all 6 isolates,and the types of virulence genes in strains from the same farm were extremely similar.The results showed that the drug resistance of Enterococci iso-lated from the fish farms in Changsha was serious,and the resistance rate to linezolid,which was prohibited in the fish farms,was high.The oxazolidinone resistance gene loci were accompanied by other resistance genes,especially the florfenicol resistance gene(FexA),which may be related to the abuse of florfenicol in the fish farms.

Parkinson's disease(PD)is one of the most common neurodegenerative disorders.Recent evidence implicates pyroptosis as one of the pathogenic mechanisms in central nervous system disorders,although its specific mechanisms remain unclear.In this study,SH-SY5Y cells were transfected with py-roptosis-related proteins GSDME full-length(GSDME-F)or GSDME-N terminal(GSDME-N)plasmids revealed that GSDME-N significantly reduced mitochondrial membrane potential(P＜0.0001).To inves-tigate the mechanism by which GSDME mediates mitochondrial dysfunction,Western blotting analysis demonstrated that transfection with GSDME-N plasmids significantly increased BAX expression and en-hanced its translocation to mitochondria in both HEK 293T and SH-SY5Y cells(P＜0.05).SH-SY5Y cells treated with varying concentrations of rotenone(ROT)exhibited GSDME cleavage,elevated BAX expression(P＜0.05),increased mitochondrial BAX aggregation(P＜0.05),and reduced mitochondrial membrane potential(P＜0.01),as confirmed by Western blotting and JC-1 staining.Concurrently,MTT assays assessing cell viability and lactate dehydrogenase(LDH)release assays indicated that ROT in-duced these processes prior to pyroptosis.Furthermore,in a ROT-induced mouse PD model,ROT trig-gered GSDME cleavage,enhanced BAX expression,caused dopaminergic neuronal damage,and induced motor deficits.In summary,this study demonstrates that GSDME-N exacerbates mitochondrial damage and increases cytotoxicity by upregulating BAX expression and facilitating its mitochondrial translocation.This study provides novel insights into the role of GSDME in PD pathogenesis and suggests potential avenues for therapeutic intervention.