BACKGROUND:Ferroptosis is closely associated with the pathogenesis of ischemic stroke,and targeting ferroptosis is a promising regimen for the treatment of ischemic stroke,but the specific regulatory targets are unclear. OBJECTIVE:To screen ferroptosis-related characterized genes in ischemic stroke by bioinformatics and machine learning methods and validate them by cellular experiments to investigate the role of ferroptosis in ischemic stroke. METHODS:Eligible ischemic stroke-related datasets and ferroptosis expression datasets were selected based on GEO database and FerrDb database,and ferroptosis-related differential genes were screened by t-test.GO functional enrichment analysis with KEGG signaling pathway enrichment analysis was performed for ferroptosis-related differential genes.Characterized genes for ferroptosis in ischemic stroke were screened by PPI network analysis and machine learning.The reliability and biological functions of the characterized genes were explored using ROC analysis and GSEA analysis,followed by cell experiment.HT22 cells were divided into control and ischemic stroke groups.No intervention was made in the control group,and 0.1 mM H2O2 was added to the ischemic stroke group for 24 hours to simulate cellular oxidative stress injury and ferroptosis.The ferroptosis and the expression of characterized genes were verified by real-time fluorescence quantitative polymerase chain reaction(RT-PCR)and western blot assay. RESULTS AND CONCLUSION:(1)Forty-five ferroptosis-associated differential genes were obtained,and GO and KEGG enrichment analyses revealed that the differential genes were closely associated with oxidative stress,autophagy,ferroptosis,adipocytokine signaling pathway,and mitochondrial metabolism.(2)A total of one ferroptosis characterized gene,nuclear factor erythroid 2-related factor 2(NFE2L2),was identified by the MCODE plugin and cytoHubba plugin in the PPI network with the LASSO algorithm and SVM-RFE algorithm in machine learning.(3)Receiver operating characteristic curve analysis of NFE2L2 revealed that the diagnostic prediction models constructed in the training and validation sets had good accuracy and specificity.GSEA analysis of NFE2L2 revealed that the characterized gene was involved in the regulation of ischemic stroke pathogenesis through immunity,inflammatory response,amino acid metabolism,and neurofactor regulation.(4)RT-PCR and western blot analyses showed that the acyl coenzyme A synthetase long chain family,member 4(ACSL4)mRNA and protein expression levels were significantly higher in the ischemic stroke group compared with the control group(P<0.05),and the glutathione peroxidase 4(GPX4)mRNA and protein expression levels were significantly lower in the ischemic stroke group(P<0.05).Compared with the control group,the mRNA and protein expression levels of the characterized gene NFE2L2 were significantly higher in the ischemic stroke group(P<0.05).(5)It suggests that ischemic stroke is closely related to ferroptosis,and targeting the characterized gene NFE2L2 may provide certain ideas and directions for the study and treatment of ischemic stroke.

Objective To evaluate the value of an optimized three-dimensional inversion-recovery with real reconstruction (3D-real IR) sequence with a longer repetition time (TR, 16 000 ms) based on modulated flip angle technique in refocused imaging with extended echo train (MATRIX) in the endolymphatic hydrops (EH) imaging after intratympanic gadolinium (Gd) administration, and to compare it with a conventional 3D-real IR based on the turbo spin echo (TSE) sequence. Methods From July 2021 to November 2022, twenty-seven patients received both the conventional and optimized 3D-real IR sequences after bilateral intratympanic Gd administration. Images of the two sequences were qualitativly evaluated and compared. Contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), and area ratio of endolymph against the total lymphatic space from the two sequences were measured and compared. Results 14(25.9%) ears with insufficient contrast for the EH diagnosis on the conventional sequence were clearly displayed on the optimized sequence. Image score, CNR and SNR of the optimized sequence were significantly higher than those of the conventional sequence (P ＜ 0.001). The scanning time of two sequences was similar. The area ratio of endolymph against the total lymphatic space in the cochlear was significantly higher on the conventional 3D-real IR than that on the optimized 3D-real IR (P ＜ 0.001); there was no statistical difference in the vestibule between the two sequences. Conclusions Compared with conventional sequence, optimized 3D-real IR sequence with a longer TR may be better for evaluation of EH after intratympanic Gd administration.

Objective To investigate the value of artificial intelligence-assisted compressed sensing (ACS) technology for intravenous gadolinium contrast-enhanced magnetic resonance imaging of the inner ear using three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) sequence. Methods The patients received gadolinium contrast-enhanced magnetic resonance imaging using ACS and united compressed sensing (uCS) 3D-FLAIR at Zhongshan Hospital, Fudan University from January to November 2024 were prospectively enrolled. The repetition time was 16 000 ms, and acquisition time was 6 min 40 s and 10 min 24 s in ACS 3D-FLAIR and uCS 3D-FLAIR, respectively. The images on the two sequences were evaluated independently by two radiologists. The image quality of the two sequences was subjectively evaluated and compared. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were compared between the two sequences. The grading consistencies using two sequences and between the two doctors were analyzed. Results There was no statistically difference in subjective score of image quality between the two sequences. SNR and CNR of the ACS 3D-FLAIR sequence were significantly higher than those of the uCS 3D-FLAIR sequence (P＜0.001). The kappa values of grades of cochlear and vestibular endolymphatic hydrops were 0.942 and 0.888 using two sequences (P＜0.001). The kappa values of grades of cochlear and vestibular endolymphatic hydrops using the ACS 3D-FLAIR sequence between the two doctors were 0.784 and 0.831, respectively (P＜0.001); the kappa values of grades of cochlear and vestibular endolymphatic hydrops using uCS 3D-FLAIR sequence between the two doctors were 0.725 and 0.756, respectively (P＜0.001). Conclusions ACS 3D-FLAIR could provide higher SNR and CNR than uCS 3D-FLAIR, and is more suitable for intravenous gadolinium contrast-enhanced magnetic resonance imaging of the inner ear; the endolymphatic hydrops grades using ACS 3D-FLAIR is similar to use uCS 3D-FLAIR.

ObjectiveTo investigate the impact of early intervention with Yishen Huazhuo prescription （YHP） on the learning and memory of accelerated aging model mice， as well as its underlying mechanism. MethodForty-eight 3-month-old male SAMP8 mice were randomly assigned into four groups， including the model group， low-dose YHP group， high-dose YHP group， and donepezil group. Additionally， 24 SAMR1 mice of the same age were divided into a control group and a YHP treatment control group， each consisting of 12 mice. The YHP groups received YHP at doses of 6.24 g·kg^-1 and 12.48 g·kg^-1， while the donepezil group was treated with donepezil at a dose of 0.65 mg·kg^-1. The model group and control groups were given physiological saline. The mice were gavaged once daily for a duration of four weeks. Spatial learning and memory abilities of mice were assessed using the Morris water maze test. Immunofluorescence staining was employed to evaluate neuronal density as well as expression levels of M1 microglial （MG） polarization marker inducible nitric oxide synthase （iNOS） and M2 MG polarization marker arginase-1 （Arg-1） in the hippocampus region. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum levels of pro-inflammatory factor interleukin 1β （IL-1β） and anti-inflammatory factor transforming growth factor-β₁ （TGF-β₁）. Furthermore， Western blot analysis was conducted to determine expressions of amyloid β peptide1-42 （Aβ_1-42） along with triggering receptor expressed on myeloid cells 2 （TREM2）/nuclear factor kappa B （NF-κB） signaling pathway-related proteins TREM2， phospho （p）-NF-κB p65， and phospho-inhibitory kappa B kinase β （IKKβ） in the hippocampus. ResultCompared with the control group， the model group exhibited a significantly prolonged escape latency （P<0.01）， a significant reduction in neuron-specific nuclear protein （NeuN） expression in the hippocampus， a significant increase in iNOS expression in MG， and a significant decrease in Arg-1 expression. The serum IL-1β content was significantly increased， while the TGF-β₁ content was significantly decreased. Additionally， there was a significant decrease in TREM2 expression in the hippocampus and significant increases in p-NF-κB p65， p-IKKβ， and Aβ_1-42 expressions （P<0.05， P<0.01）. However， no significant changes were observed in escape latency， times of crossing the platform， and hippocampal NeuN expression in the YHP treatment control group. Conversely， iNOS expression in MG as well as the hippocampal p-NF-κB p65， p-IKKβ， and Aβ_1-42 expressions were significantly decreased. Furthermore， TREM2 expression was significantly increased （P<0.05， P<0.01）. In comparison to the model group， the low-dose YHP group showed a significantly shortened escape latency and an increased number of crossing the platform （P<0.05， P<0.01）. In the high-dose YHP group， the escape latency was significantly shortened （P<0.05）. In the low-dose YHP group， high-dose YHP group， the expression of NeuN in the hippocampus was significantly increased， the expression of iNOS in MG was significantly decreased， and the expression of Arg-l was significantly increased. The serum IL-1β content was significantly decreased， while the TGF-β₁ content was significantly increased. Furthermore， the expression of TREM2 in the hippocampus was significantly increased， and the expressions of p-NF-κB p65， p-IKKβ， and Aβ_1-42 were significantly decreased （P<0.01）. ConclusionEarly YHP intervention may promote the transformation of hippocampal MG from M1 to M2 by regulating the TREM2/NF-κB signaling pathway， reduce the release of neuroinflammatory factors， protect hippocampal neurons， and reduce the deposition of Aβ_1-42， and finally delay the occurrence of learning and memory decline in SAMP8 mice.

Objective·To evaluate the changes in cognitive function in overweight and obese adolescents,and explore the association between cognitive function and fibroblast growth factor 21(FGF21).Methods·A total of 175 adolescents from a senior high school in Shanghai were divided into normal weight group(n=50),overweight group(n=50)and obese group(n=75)based on their body mass index(BMI).General information,anthropometric data and laboratory testing indicators of the adolescents were collected and compared.The cognitive function of the three groups of adolescents was assessed by using the accuracy(ACC)and reaction time of Flanker task and n-back task.Enzyme-linked immunosorbent assay(ELISA)was used to detect the serum FGF21 level of the three groups of adolescents.Partial correlation analysis and multiple linear regression model were used to evaluate the correlation between cognitive task performance and anthropometric data and laboratory testing indicators.Results·Compared with the normal weight group,systolic blood pressure,diastolic blood pressure,and the levels of fasting plasma glucose,glycosylated hemoglobin and triacylglycerol in the obese group were higher(all P<0.05).Under congruent or incongruent stimulus conditions in the Flanker task,there was no significant difference in ACC between any two groups;compared with the normal weight and overweight groups,the reaction time of the adolescents in the obese group was prolonged(all P<0.05).In the n-back task,there were no significant differences in ACC between any two groups,while the obese group had longer reaction time in the 1-back and 2-back tasks compared to the normal weight and overweight groups(all P<0.05).Compared with the normal weight group,serum FGF21 levels of the adolescents in the obese group were higher(P=0.000).Partial correlation analysis showed that the reaction time of the adolescents in Flanker and n-back tasks was correlated with their BMI,body fat mass,waist circumference,waist-to-hip ratio and FGF21 level(all P<0.05).Multiple linear regression analysis further confirmed that BMI was associated with prolonged reaction time in cognitive-related behavioral tasks in the adolescents(all P<0.05),and FGF21 level was associated with ACC in the 2-back task(P=0.000)and reaction time in the incongruent stimulus condition(P=0.048).Conclusion·Overweight and obese adolescents have cognitive impairments,and BMI and serum FGF21 levels are associated with changes in their cognitive function.

BACKGROUND:Exercise has a regulatory effect on intestinal flora dysbiosis,which can effectively protect the beneficial flora and improve the intestinal environment.However,the effect of treadmill exercise on the structure and diversity of intestinal microbial community in Parkinson's disease and the specific mechanism are not clear. OBJECTIVE:Using 16S rDNA technique to analyze the effect of treadmill exercise on the structure and diversity of the intestinal flora of rats with Parkinson's disease,and to investigate the mechanism of non-pharmacological treadmill exercise to improve Parkinson's disease. METHODS:Twelve of the 18 Sprague-Dawley rats were randomly selected to make animal models of Parkinson's disease using unilateral 2-point nigrostriatal injection of 6-hydroxydopamine.The remaining six rats were used as sham-operation group,which were injected with the same dose of saline containing 0.2%ascorbic acid using the same positioning and injection method.After successful modeling,12 rats with Parkinson's disease were randomly divided into model group and treadmill exercise group(n=6 per group).The treadmill exercise group was subjected to a middle and low intensity tread mill exercise,10 m/min,30 minutes per day,5 days per week for 4 weeks.Fresh feces were collected and stored in liquid nitrogen 24 hour after the last exercise session,and the changes in fecal flora were analyzed by 16S rDNA sequencing technique. RESULTS AND CONCLUSION:Treadmill exercise significantly improved behavior and nigrostriatal tyrosine hydroxylase-positive cell expression in rats with Parkinson's disease model and alleviated changes in the structure and diversity of the gut microbial community caused by Parkinson's disease,increased the number of operational taxonomic units and modulated Alpha and Beta diversity in rats.At the phylum and genus levels,the abundance ratio of Firmicutes/Bacteroidetes in the model group decreased compared with the sham-operated group,while beneficial bacteria such as Prevotella,Bacteroides,and Clostridium_XlV increased significantly after treadmill exercise.To conclude,treadmill exercise has a significant modulating effect on behavioral abnormalities,toxic damage to dopaminergic neurons and gut microbial imbalance caused by Parkinson's disease,alleviates the symptoms of flora-related diseases,and has a positive effect on the improvement of Parkinson's disease.

Fatigue-related traffic accidents and fatalities have been extensively studied by scholars globally.Specialized vehicles,due to their unique mission profiles,are more likely to cause driving-related fatigue and serious consequences.This paper reviews the current research of fatigue driving by using an inductive analysis method to summarize the mechanisms,risk factors,and monitoring methods.This paper also offers a vision of priorities and methodologies for research in the future.It is recommended that the mechanisms of driving fatigue be explored at the molecular biological level and that fatigue monitoring systems be made more feasible via the combined application of non-intrusive monitoring in order to reduce the toll on life and property taken by driving fatigue.

Objective To investigate the clinical and pathological characteristics of the extrapleural solitary fibrous tumor and the relevant differential diagnosis.Methods HE and immunohistochemical staining were performed on 26 samples of isolated fibrous tumors outside the pleura,and a comprehensive analysis was conducted based on the clinical and imaging data.Results The histological morphology of isolated fibrous tumors was diverse,with typical cases showing the irregular arrangement of oval or spindle shaped cells.In the stroma,thick collagen bands,antler like blood vessels,and peritubular transparent degeneration could be seen.The immunohistochemical staining demonstrated that the positive rates of STAT-6、CD34、Bcl-2、CD99、SMA were 96.2% 、92.3% 、92.3% 、76.9% and 26.9%,respectively.Conclusion SFT commonly occurs in the pleura and can also occur in other areas.Its histological characteristics and immunohistochemical phenotype help to clarify the diagnosis.However,when it occurs in uncommon anatomical sites,it is necessary to carefully and meticulously distinguish and comprehensively judge the clinical prognosis of key diseases that need to be distinguished or excluded..

Objective To investigate the pollution of antibiotic resistance genes (ARGs) in the Lhasa River and provide a scientific basis for the safety of drinking water for the regional population and the prevention and control of water environment pollution. Methods A total of five water samples were collected in the Lhasa River in July 2022. Using quantitative real-time polymerase chain reaction (qPCR) assay, 19 types of ARGs, including eight ^“last-resort^” ARGs (LARGs) were detected and analyzed. Statistical analysis was conducted using the SPSS 22.0 software, and Student's t-test was used to compare data between two groups. Results All the 19 ARGs were detected with high frequencies, with the aminoglycoside resistance gene aadA having the highest concentration, followed by the sulfonamide resistance gene sul1 and the macrolide resistance gene ermB. Among the eight LARGs, the carbapenem resistance gene blaOXA-48 had the highest concentration. The absolute and relative concentrations of LARGs were lower than those of common ARGs. There was a statistically significant difference in the absolute concentrations between them, but no significant difference was observed in the relative concentrations. Conclusion Both ^“conventional^” ARGs and LAGRs have been detected in the Lhasa River. Although they are at a relatively low level compared to other domestic waters, in view of the serious adverse effects that ARGs, especially LARGs, may cause, the pollution of ARGs in the Lhasa River should be taken seriously.

Objective To describe the outcomes of extracorporeal membrane oxygenation (ECMO) for patients after aortic surgery and to summarize the experience. Methods The clinical data of patients who received ECMO support after aortic surgery in Fuwai Hospital from 2009 to 2020 were retrospectively analyzed. The patients who received an aortic dissection surgery were allocated into a dissection group, and the other patients were allocated into a non-dissection group. The in-hospital and follow-up survival rates were compared between the two groups, and the causes of death were analyzed. Results A total of 22 patients were enrolled, including 17 patients in the dissection group [13 males and 4 females, with a median age of 54 (46, 61) years] and 5 patients in the non-dissection group [3 males and 2 females, with a median age of 51 (41, 65) years]. There was no statistical difference in the age and gender between the two groups (P>0.05). The in-hospital survival rate (11.8% vs. 100.0%, P=0.001) and follow-up survival rate (11.8% vs. 80.0%, P=0.009) of the patients in the dissection group were significantly lower than those in the non-dissection group. The causes of death in the dissection group included massive bleeding and disseminated intravascular coagulation (3 patients), ventricular thrombosis (1 patient), irreversible brain injury (2 patients), visceral malperfusion syndrome (4 patients) and irreversible heart failure (5 patients). Conclusion ECMO after aortic dissection surgery is associated with high mortality, which is related to the pathological features of aortic dissection and severely disrupted coagulation system after the surgery. For these patients, strict indication selection and optimal management strategy are important.