Objective To investigate the potential value of exosomes derived from rat ectoderm mesenchymal stem cells(EMSCs-exo)for repairing secondary spinal cord injury.Methods EMSCs-exo were obtained using ultracentrifugation from EMSCs isolated from rat nasal mucosa,identified by transmission electron microscope,nanoparticle tracking analysis(NTA),and Western blotting,and quantified using the BCA method.Neonatal rat microglia purified by differential attachment were induced with 100 μg/L lipopolysaccharide(LPS)and treated with 37.5 or 75 mg/L EMSCs-exo.PC12 cells were exposed to 400 μmol/L H2O2 and treated with EMSCs-exo at 37.5 or 75 mg/L.The protein and mRNA expressions of Arg1 and iNOS in the treated cells were determined with Western blotting and qRT-PCR,and the concentrations of IL-6,IL-10,and IGF-1 in the supernatants were measured with ELISA.The viability and apoptosis of PC12 cells were detected using CCK-8 assay and flow cytometry.Results The isolated rat EMSCs showed high expressions of nestin,CD44,CD105,and vimentin.The obtained EMSCs-exo had a typical cup-shaped structure under transmission electron microscope with an average particle size of 142 nm and positivity for CD63,CD81,and TSG101 but not vimentin.In LPS-treated microglia,EMSCs-exo treatment at 75 mg/L significantly increased Arg1 protein level and lowered iNOS protein expression(P<0.05).EMSCs-exo treatment at 75 mg/L,as compared with the lower concentration at 37.5 mg/L,more strongly increased Arg1 mRNA expression and IGF-1 and IL-10 production and decreased iNOS mRNA expression and IL-6 production in LPS-induced microglia,and more effectively promoted cell survival and decreased apoptosis rate of H2O2-induced PC12 cells(P<0.05).Conclusion EMSCs-exo at 75 mg/L can effectively reduce the proportion of M1 microglia and alleviate neuronal apoptosis under oxidative stress to promote neuronal survival,suggesting its potential in controlling secondary spinal cord injury.

Acute myeloid leukemia (AML) is a common malignant disease of the hematological system, with high EVI1 expression accounting for 8%-10% of adult AML. Studies have shown that high EVI1 expression plays an important role in the treatment and prognosis of AML. In recent years, researchers have continuously revealed the structure and role of EVI1, but its mechanism of mediating AML has not been fully clarified. Therefore, systematically exploring the role of EVI1 in AML may provide a useful reference for the precise treatment of AML patients with high EVI1 expression.

Objective To investigate the potential value of exosomes derived from rat ectoderm mesenchymal stem cells(EMSCs-exo)for repairing secondary spinal cord injury.Methods EMSCs-exo were obtained using ultracentrifugation from EMSCs isolated from rat nasal mucosa,identified by transmission electron microscope,nanoparticle tracking analysis(NTA),and Western blotting,and quantified using the BCA method.Neonatal rat microglia purified by differential attachment were induced with 100 μg/L lipopolysaccharide(LPS)and treated with 37.5 or 75 mg/L EMSCs-exo.PC12 cells were exposed to 400 μmol/L H2O2 and treated with EMSCs-exo at 37.5 or 75 mg/L.The protein and mRNA expressions of Arg1 and iNOS in the treated cells were determined with Western blotting and qRT-PCR,and the concentrations of IL-6,IL-10,and IGF-1 in the supernatants were measured with ELISA.The viability and apoptosis of PC12 cells were detected using CCK-8 assay and flow cytometry.Results The isolated rat EMSCs showed high expressions of nestin,CD44,CD105,and vimentin.The obtained EMSCs-exo had a typical cup-shaped structure under transmission electron microscope with an average particle size of 142 nm and positivity for CD63,CD81,and TSG101 but not vimentin.In LPS-treated microglia,EMSCs-exo treatment at 75 mg/L significantly increased Arg1 protein level and lowered iNOS protein expression(P<0.05).EMSCs-exo treatment at 75 mg/L,as compared with the lower concentration at 37.5 mg/L,more strongly increased Arg1 mRNA expression and IGF-1 and IL-10 production and decreased iNOS mRNA expression and IL-6 production in LPS-induced microglia,and more effectively promoted cell survival and decreased apoptosis rate of H2O2-induced PC12 cells(P<0.05).Conclusion EMSCs-exo at 75 mg/L can effectively reduce the proportion of M1 microglia and alleviate neuronal apoptosis under oxidative stress to promote neuronal survival,suggesting its potential in controlling secondary spinal cord injury.

OBJECTIVES: Diabetes mellitus is closely associated with sudden sensorineural hearing loss (SSNHL), but no definitive evidence has established a causal relationship between type 1 diabetes mellitus (T1DM) and SSNHL. This study aims to investigate the impact of T1DM on SSNHL from a genetic perspective, providing insights for risk prediction and treatment strategies. METHODS: Genetic data related to exposure (T1DM) and outcome (SSNHL) were obtained from publicly available genome-wide association studies (GWAS). Instrumental variables were selected, and Mendelian randomization (MR) analysis was conducted to explore the causal association between T1DM and SSNHL. Inverse variance weighted (IVW) analysis was used as the primary method, with random-effects IVW serving as the main analytical approach. MR-Egger, weighted median, simple mode, and weighted mode analyses were utilized as supplementary methods. Cochran's Q test was applied to evaluate the heterogeneity of the selected instrumental variables, MR-PRESSO was applied to detect outliers, MR-Egger regression was used to assess horizontal pleiotropy and leave-one-out analysis was conducted to examine the robustness of individual single nucleotide polymorphisms (SNPs) on the overall results. RESULTS: A total of 127 SNPs were selected as instrumental variables for the MR analysis. IVW analysis demonstrated a genetically determined association between T1DM and SSNHL (OR=1.036, 95% CI 1.002 to 1.071, P=0.038). Forest plots and scatter plots indicated a causal relationship, suggesting that T1DM increases the risk of SSNHL. Cochran's Q test demonstrated no significant heterogeneity among SNPs (MR-Egger: Q=126.030, P=0.356; IVW: Q=126.450, P=0.373). The funnel plot appeared symmetrical, indicating that the selected instrumental variables were primarily related to exposure rather than potential confounding factors. The MR-Egger intercept was not significantly different from zero (P=0.527), indicating no evidence of horizontal pleiotropy among the SNPs. MR-PRESSO analysis did not identify any outlier SNPs (P=0.356). Leave-one-out analysis confirmed the robustness of the findings, as the results remained stable after removing individual SNPs. CONCLUSIONS Two-sample MR analysis supports the conclusion that T1DM patients have an increased risk of developing SSNHL.
Humans ; Mendelian Randomization Analysis ; Hearing Loss, Sensorineural/etiology* ; Diabetes Mellitus, Type 1/genetics* ; Genome-Wide Association Study ; Hearing Loss, Sudden/etiology* ; Polymorphism, Single Nucleotide ; Risk Factors ; Genetic Predisposition to Disease

Objective:To explore the effectiveness and safety of endovascular treatment (EVT) for patients with acute anterior circulation ischemic stroke with symptom onset exceeding 24 h.Methods:In this retrospective cohort study, data were extracted from patients who underwent endovascular treatment for acute anterior circulation ischemic stroke at the First Hospital of Jilin University from February 2019 to April 2022. A total of 569 patients were included, with a mean age of 63 (54-70) years. Among them, 398 (69.9%) were male. The patients were divided into two groups based on symptom onset time:>24 h group and≤24 h group. Propensity score matching (PSM) was used to match the patients in a 1︰1 ratio between the>24 h group and the≤24 h group. Logistic regression was used to evaluate the impact of symptom onset time on outcome events.Results:Before PSM, compared with≤24 h group, the>24 h group had a younger age [56 (48, 64) vs. 64 (55, 70), Z=-3. 60, P<0.001]; lower proportion of prior atrial fibrillation [1.8% (1/57) vs. 21.1% (108/512), χ2=12.39, P<0.001]; lower proportion of wake-up stroke [7.0% (4/57) vs. 27.7% (142/512), χ2=11.54, P<0.001]; lower baseline NIHSS score [11.0 (7.5, 14.0) vs. 13.0 (10.0, 16.0), Z=-3.22, P<0.001]; and a higher American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology(ASITN/SIR) grading ( P<0.001). After PSM, there were no significant differences in baseline characteristics between the two groups. There was no significant difference in the proportion of patients with a modified Rankin Scale (mRS) score≤2 at 90 days after surgery between the two groups (before matching: 42.0% vs. 40.4%, OR=0.745, 95% CI 0.407-1.362, P=0.339; after matching: 51.8% vs. 39.3%, OR=0.511, 95% CI 0.212-1.236, P=0.136). No significant differences were observed in the incidence of any safety outcomes between the>24 h group and the≤24 h group. Conclusion:For patients with acute anterior circulation ischemic stroke with symptom onset exceeding 24 h, EVT is feasible after strict radiological screening and has similar safety and effectiveness as for patients with symptom onset under 24 h.

Objective To explore the safety and efficacy of endovascular treatment(EVT)in patients with acute posterior circulation ischemic stroke over 24 hours from onset.Methods This retrospective study retrospectively analyzed patients with acute posterior circulation ischemic stroke who received EVT in the Department of Neurology,First Hospital of Jilin University from June 2018 to June 2023.The patient's gender,age and other related demographic information were collected.The related examination results of patients were collected,including admission rapid blood glucose,admission systolic blood pressure,admission diastolic blood pressure.The related risk factors of stroke of patients were collected,including previous transient ischemic attack,hypertension,diabetes,atrial fibrillation,and history of drinking,smoking history,etc.;other related indicators were collected,including intravenous thrombolysis,tandem lesions,awakening stroke,baseline National Institutes of Health stroke scale(NIHSS)score,and baseline posterior circulation Alberta stroke program early CT score(pc-ASPECTS),collateral circulation grade of American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology(ASITN/SIR),onset to EVT puncture time,the trial of org 10172 in acute stroke treatment(TOAST)classification and outcome indicators(efficacy indicators included 90 days Modified Rankin scale[mRS]score≤3 after EVT,successful recanalization[extended cerebral infarction thrombolytic recanalization class 2b-3];security indexes included symptomatic intracranial hemorrhage[sICH]within 24 h after EVT and 90 d mortality after EVT).According to the symptom onset to EVT puncture time,the patients were divided into two groups:≤24h group and＞24h group.The patients with onset time＞24 h and those with onset time≤24 h were matched at a ratio of 1:1 by propensity score matching(PSM).All patients were divided into poor prognosis group(mRS score＞3)and good prognosis group(mRS score ≤ 3)according to mRS score at 90 days after EVT.Using univariate and multivariate Logistic regression was used to analyze the effect of onset time on clinical outcomes at 90 days after EVT.Results A total of 366 patients were enrolled in this study,including 284 males and 82 females.The median age was 61(55,68)years old,ranging from 25 to 91 years old.Before PSM,the＞24h group had lower prevalence of atrial fibrillation(2.02％[2/99]vs.9.74％[26/267],P=0.025)and lower baseline NIHSS score(10.0[5.0,19.0]vs.14.0[10.0,35.0],P＜0.01)and higher ASTIN/SIR collateral grade(P=0.018).After PSM,we did not find statistical difference between the two groups in baseline characteristics except for the onset to EVT puncture time.Before and after PSM,there was no significant difference in efficacy and safety between the onset time＞24 h group and the onset time ≤24h group.Univariate binary Logistic regression analysis showed that hypertension(OR,0.613,95％CI 0.391-0.942,P=0.025),intravenous thrombolysis(OR,3.235,95％CI 1.316-9.237,P=0.010),baseline NIHSS score(OR,0.975,95％CI 0.957-0.988,P＜0.01),baseline pc-ASPECTS(OR,1.281,95％CI 1.101-1.482,P=0.001)and sICH within 24 h after EVT(OR,0.070,95％CI 0.000-0.330,P＜0.01)were significantly correlated with prognosis.Gender,age,hypertension,baseline NIHSS score,intravenous thrombolysis,baseline pc-ASPECTS,ASTIN/SIR collateral grade,onset time＞24 h and sICH within 24 h after EVT were included in the multivariate binary Logistic regression analysis.The multivariate binary Logistic regression analysis showed that the onset time＞24 h was not associated with poor prognosis 90 d after EVT(aOR,1.635,95％CI 0.936-2.893,P=0.087).Conclusion EVT for acute posterior circulation ischemic stroke more than 24 hours after onset is feasible under strict imaging screening,and its safety and efficacy are similar to those in patients with onset under 24 hours.

In this study,ecofriendly and economic carboxy-terminated plant fibers(PFs)were used as adsorbents for the effective in-syringe solid phase extraction(IS-SPE)of fluoroquinolone(FQ)residues from water.Based on the thermal esterification and etherification reaction of cellulose hydroxy with citric acid(CA)and sodium chloroacetate in aqueous solutions,carboxy groups grafted onto cotton,cattail,and corncob fibers were fabricated.Compared with carboxy-terminated corncob and cotton,CA-modified cattail with more carboxy groups showed excellent adsorption capacity for FQs.The modified cattail fibers were reproducible and reusable with relative standard deviations of 3.2％-4.2％within 10 cycles of adsorption-desorption.A good extraction efficiency of 71.3％-80.9％was achieved after optimizing the extraction condition.Based on carboxylated cattail,IS-SPE coupled with ultra-performance liquid chromatography with a photodiode array detector was conducted to analyze FQs in environmental water samples.High sensitivity with limit of detections of 0.08-0.25 μg/L and good accuracy with recoveries of 83.8％—111.7％were obtained.Overall,the simple and environment-friendly modified waste PFs have potential appli-cations in the effective extraction and detection of FQs in natural waters.