Objective To explore the relationship between triglyceride-glucose index(TyG)and acute ischemic stroke with large vessel occlusion(AIS-LVO)of anterior circulation.Methods A retrospective study was conducted on patients with anterior circulation AIS-LVO who underwent emergency endovascular thrombectomy at Neurovascular Center of The First Affiliated Hospital of Naval Medical University from Jan.2018 to Dec.2019.According to modified Rankin scale(mRS)score 90 d after operation,the patients were assigned to favorable outcome group(mRS score 0-2)or unfavorable outcome group(mRS score 3-6),and the TyG was compared.According to the median of TyG,the patients were assigned to low-TyG group(TyG＜8.57)or high-TyG group(TyG ≥8.57),and the clinical data,laboratory indexes,and imaging characteristics were compared.Receiver operating characteristic curve was used to evaluate the predictive value of TyG for poor prognosis.Results A total of 135 patients were enrolled,with 72 in the favorable outcome group and 63 in the unfavorable outcome group.The TyG of the unfavorable outcome group was significantly higher than that of the favorable outcome group(8.82+0.63 vs 8.43+0.60,P＜0.001).There were 67 patients in the low-TyG group and 68 in the high-TyG group.Compared with the low-TyG group,the proportion of patients with hyperlipidemia history(P=0.003),systolic blood pressure at admission(P=0.018),fasting blood glucose level(P＜0.001),and triglyceride level(P＜0.001)were significantly higher in the high-TyG group,the infarct core volume was significantly larger(P=0.025),the high density lipoprotein-cholesterol level was significantly lower(P=0.013),and the mRS score 90 d after operation was significantly higher(3[1,5]vs 1[0,5],P=0.049).The TyG had certain predictive value for poor prognosis in anterior circulation AIS-LVO patients(area under curve value=0.662,95％confidence interval 0.571-0.753).Conclusion TyG is elevated in anterior circulation AIS-LVO patients with poor prognosis,and may be a potential prognostic indicator for anterior circulation AIS-LVO patients.

Objective To investigate the safety and effectiveness of endovascular treatment in patients with acute ischemic stroke due to large vessel occlusion(AIS-LVO)over 24 h after onset.Methods The clinical data of AIS-LVO patients who received endovascular treatment in Neurovascular Center of The First Affiliated Hospital of Naval Medical University from Jan.2018 to Dec.2022 were retrospectively analyzed,including baseline characteristics,imaging findings,treatment,degree of vascular recanalization(modified thrombolysis in cerebral infarction grade 2b and 3 for successful recanalization)and prognosis.Results A total of 57 patients were included,including 42 males and 15 females,aged from 30 to 84 years old.The most common risk factors were hypertension(39 cases,68.4%),followed by smoking history(24 cases,42.1%),diabetes mellitus(17 cases,29.8%),previous stroke history(16 cases,28.1%),and atrial fibrillation(9 cases,15.8%).Before treatment,the National Institutes of Health stroke scale score was 12.84±7.04,and the Alberta Stroke Program early computed tomography score was 9.00(7.00,10.00).Vascular occlusion sites included middle cerebral artery occlusion in 27(47.4%)cases,internal carotid artery occlusion in 24(42.1%)cases,and tandem lesions in 6(10.5%)cases.The time from onset to femoral artery puncture was 38.30(28.17,53.71)h,and the time from femoral artery puncture to vascular recanalization was 52.00(38.50,92.50)min.General anesthesia was the main anesthesia method,accounting for 64.9%(37/57).The etiological types of stroke were mainly large artery atherosclerosis(38 cases,66.7%),cardiogenic embolism(9 cases,15.8%),unknown causes(6 cases,10.5%),and other clear causes(4 cases,7.0%).Mechanical thrombectomy was the first choice in 41(71.9%)cases,balloon dilatation/stenting was used in 35(61.4%)cases,of which 15(26.3%)cases were the first choice.Finally,53(93.0%)cases were recanalized successfully.In terms of complications,1(1.8%)case had symptomatic intracranial hemorrhage.The 90-d prognosis rate was 59.6%(34/57),and 3(5.3%)cases died.Conclusion Endovascular treatment for AIS-LVO patients over 24 h after onset has high recanalization rate and good safety,but it still needs to be further verified by randomized controlled trials.

OBJECTIVE To determine the species,quantity,and dispersion patterns of airborne pollen in two districts and five counties of Handan City,Hebei Province.METHODS The gravity sedimentation method was employed from October 1,2023,to September 30,2024,for daily and consecutive pollen exposure slides in two districts(Congtai District and Yongnian District)and five counties(Qiu County,Daming County,Cheng'an County,Cixian County,and She County)of Handan City,Hebei Province.The types of pollen were counted and identified under an optical microscope,and the pollen data were statistically analyzed.RESULTS The annual pollen quantity in the two districts and five counties of Handan City ranged from 24 031 grains/1 000 mm2 to 85 131 grains/1 000 mm2.The dissemination of major allergenic pollen presented two peaks.The first peak occurred in spring(March to April),mainly composed of Platanus(25.15％),Broussonetia(13.61％),Pinus(8.48％);the second peak occurred in(August to September),mainly consisting of Humulus/Cannabis(13.71％)and Artemisia(8.44％).Pollen in spring was significantly higher than that in summer and autumn.CONCLUSION The major allergenic airborne pollen in the two districts and five counties of Handan City exhibited two peaks in spring and summer-autumn,with Platanus pollen,Broussonetia pollen,Pinus pollen,Humulus/Cannabis pollen,and Artemisia pollne being the dominant pollen types.Among them,Platanus pollen was the absolute dominant pollen in this region.

AIM:To explore the mechanism of Salvia miltiorrhiza(Danshen)-derived exosome-like nanoparti-cles(DDN)in attenuating oxidative damage in endothelial cells through the activation of the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(PKB/Akt)/endothelial nitric oxide synthase(eNOS)signaling pathway.METHODS:The DDN were characterized by transmission electron microscopy and dynamic light scattering.Fluorescence microscopy and flow cytometry were used to evaluate the uptake of DDN by human umbilical vein endothelial cells(HUVECs).The viability,migration and invasion of HUVECs were assessed using CCK8 assay,wound-healing assay and Transwell assay,respec-tively.The HUVECs were induced by angiotensin II(Ang II)for oxidative stress and intervened with DDN or LY294002(a PI3K inhibitor).The levels of reactive oxygen species were determined by flow cytometry,and intracellular nitric oxide(NO)content was measured using a biochemical assay kit.Additionally,the protein levels of NADPH oxidase 4(NOX4),NOX2,endothelial nitric oxide syntnase(eNOS),p-eNOS,Akt and p-Akt were examined by Western blot.RESULTS:(1)Transmission electron microscopy and dynamic light scattering analysis revealed that DDN had good bio-compatibility and stability.(2)According to fluorescence images and flow cytometry results,DDN were strongly taken up by HUVECs.(3)Compared with control group,DDN significantly promoted the viability,migration and invasion of HUVECs,showing a dose-dependent effect.(4)Compared with control group,DDN remarkably increased intracellular NO levels,thereby enhancing endothelial cell vasodilation via activating the PI3K/Akt/eNOS signaling pathway.(5)The PI3K/Akt/eNOS pathway played a critical role in mitigating oxidative stress and improving cellular function in response to DDN treat-ment.CONCLUSION:The DDN mediate PI3K/Akt/eNOS signaling pathway activation to significantly alleviate Ang II-induced oxidative damage in endothelial cells,suggesting a potential vascular protective effect of DDN.

Objective To explore the role of nucleolin 6(NOL6)in the occurrence and development of hypertension and its mechanism of regulating ribosome biogenesis.Methods Differentially expressed genes were screened based on the GEO database(chip GSE212338),and intersection analysis was conducted in combination with genes related to ribosome generation to obtain genes related to ribosome biogenesis in hypertension.The rats were divided into control group and model group(L-NAME group).The hypertensive rat model was induced by N-nitro-L-arginine methyl ester(L-NAME),and the thickness and pathological changes of the aortic wall in each group were observed by HE staining.The expression of ribosomal RNA(rRNA)in rat aortic tissues was detected by qPCR to reflect ribosome biogenesis,and the protein expression of NOL6 was detected by Western blotting.Human umbilical vein endothelial cells(HUVECs)were cultured and grouped for treatment(control group,L-NAME group,AngⅡ group,AngⅡ+si-NC group,AngⅡ+si-NOL6 group,and AngⅡ+CX-5461 group).The generation of neocRNA in HUVEC was detected by EU.The protein and mRNA expressions of NOL6 in HUVEC were detected by Western blotting and qPCR,respectively.Western blotting was used to detect the protein expressions of endothelial nitric oxide synthase(eNOS)and p-eNOS.Results By combining the differential expression analysis of the GEO hypertension dataset GSE212338 and the ribosome biogenesis gene set,six core genes with significantly altered expression in hypertension and related to ribosome biogenesis were identified.The difference in NOL6 was the most significant.Compared with the control group,the aortic wall thickness of rats in the L-NAME group increased significantly.Ribosomal RNA expression was significantly upregulated;the protein and mRNA expressions of NOL6 were significantly upregulated,too.Compared with the control group,the generation of neoRNA in the cells of the L-NAME group increased significantly;the levels of NOL6 protein and mRNA,ribosomal RNA and neoRNA in the Ang Ⅱ group were significantly increased compared with the control group but significantly decreased compared with the Ang Ⅱ+si-NC group.Compared with the Ang Ⅱ+si-NOL6 group,the protein and mRNA expressions of NOL6 in the AngⅡ+si-NC group and the AngⅡ+CX-5461 group cells were significantly increased.Compared with the AngⅡ+si-NC group,the levels of ribosomal RNA and neoRNA in the AngⅡ+si-NOL6 group and the AngⅡ+CX-5461 group were significantly decreased;the protein expressions of eNOS and p-eNOS were significantly increased.Conclusion NOL6 is associated with abnormal ribosome biogenesis in hypertension.NOL6 can affect the expression of eNOS by regulating ribosome biogenesis,thereby regulating the occurrence and development of hypertension.

OBJECTIVE To construct a prediction model for the efficacy of serotonin-norepinephrine reuptake inhibitor(SNRI)in inpatients with moderate and severe depression by using a machine learning method.METHODS The case records of inpatients with moderate and severe depression treated with SNRI antidepressants were collected from a third-grade class-A hospital in Xinjiang from January 2022 to October 2024;those patients were divided into effective group and ineffective group based on the Hamilton depression scale-24 score reduction rate.After screening the characteristic variables related to the therapeutic efficacy of SNRI drugs through LASSO regression,five prediction models including support vector machine,k-nearest neighbor,random forest,lightweight gradient boosting machine and extreme gradient boosting were constructed using the training set.Bayesian optimization was used to adjust the hyperparameters of these models.The performance of the models was evaluated in the validation set to select the optimal model.The Shapley additive explanations method was used to perform explainable analysis on the best model.RESULTS The medical records from 355 hospitalized patients with moderate and severe depression were collected,comprising 285 cases in the effective group and 70 cases in the ineffective group,resulting in an overall therapeutic response rate of 80.28%.After feature variable screening,five characteristic variables for therapeutic efficacy were obtained,including Hamilton anxiety scale,blood urea nitrogen,combination of anti-anxiety drugs,drinking history,and first onset of the disease.Compared with other models,the random forest model performed the best.The area under the receiver operating characteristic curve was 0.85,the area under the precision-recall curve was 0.87,the accuracy was 0.74,and the recall rate value was 0.75.CONCLUSIONS The random forest model constructed based on five characteristic variables demonstrates potential for predicting the therapeutic efficacy of SNRI antidepressants in hospitalized patients with moderate and severe depression.

Objective To investigate the effect of irisin regulating early B cytokine 3(EBF3)/arachidonic acid-15-lipoxygenase(ALOX15)pathway on the proliferation and migration of lung adenocarcinoma cells.Methods A549 cells were assigned into the irisin solvent group,the irisin group,the sh-NC group,the EBF3 inhibitor(sh-EBF3)group,the irisin+sh-NC group and the irisin+sh-EBF3 group randomly.5-bromo-2-deoxyuracil(EdU)staining and CCK-8 method were applied to detect cell proliferation.5-Scratch experiment was applied to detect the scratch healing rate.2',7'-dichlorofluorescein diacetate(DCFH-DA)staining was applied to detect the level of reactive oxygen species(ROS)in cells.The reagent kit was used to detect glutathione(GSH),malondialdehyde(MDA)and ferrous ion(Fe2+)in cells.Transmission electron microscopy was applied to observe mitochondrial morphology in A549 cells.QRT-PCR was applied to detect mRNA levels of proliferating cell nuclear antigen(PCNA),matrix metalloproteinase 2(MMP-2)and glutathione peroxidase 4(GPX4)in A549 cells.Western blot assay was applied to detect EBF3 and ALOX15 proteins in cells.Results Compared with the irisin solvent group,the mitochondria of A549 cells in the irisin group showed ferroptosis characteristics,the positive rate of EdU,OD450 value,scratch healing rate,GSH level,PCNA,MMP-2 and GPX4 mRNA levels decreased,and the ROS relative fluorescence intensity,MDA,Fe2+level,and EBF3 and ALOX15 protein levels increased(P＜0.05).Compared with the sh-NC group,the mitochondrial ferroptosis phenomenon of A549 cells was reduced in the sh-EBF3 group,the positive rate of EdU,OD450 value,scratch healing rate,GSH level,PCNA,MMP-2 and GPX4 mRNA levels increased,and the ROS relative fluorescence intensity,MDA,Fe2+levels and EBF3 and ALOX15 protein levels reduced(P＜0.05).Sh-EBF3 reversed the effect of irisin on ferroptosis,proliferation and migration of A549 cells.Conclusion Irisin may induce ferroptosis in A549 cells and inhibit cell proliferation and migration by activating the EBF3/ALOX15 pathway.

RNA-based gene therapy has been widely used for various diseases, and extensive studies have proved that suitable delivery routes greatly help the development of RNA therapeutics. Identifying a safe and effective delivery system is key to realizing RNA therapeutics' clinical translation. Inhalation is a non-invasive pulmonary delivery modality that can enhance the retention of therapeutic agents in the lungs with negligible toxicity, thereby improving patient compliance. Inhaled RNA therapeutics are increasingly becoming an area of focus for researchers; however, only several clinical trials have explored inhaled delivery of RNA for pulmonary diseases. This review presents an overview of recent advances in inhaled delivery systems for RNA therapeutics, including viral and nonviral systems, highlighting state of the art regarding inhalation in the messenger RNA (mRNA) field. We also summarize the applications of mRNA inhalants in infectious and other lung diseases. Simultaneously, the research progresses on small interfering RNAs (siRNAs), antisense oligonucleotides (ASOs), and different types of RNA are also discussed to provide new strategies for developing RNA inhalation therapy. Finally, we clarify the challenges inhaled RNA-based therapeutics face before their widespread adoption and provide insights to help advance this exciting field to the bedside.

Objective:To investigate the relationship between work fit, work stress, and occupational fatigue among medical staff, and to analyze the independent and interactive effects of work fit and work stress on occupational fatigue.Methods:A stratified random sampling method was employed to select 1162 employees from two top-tier hospitals as the research subjects. A questionnaire survey was conducted to collect information on basic demographics, work stress, work fit, and occupational fatigue. Chi-square test, analysis of variance, and logistic regression equations were used to evaluate the interactive effects of work fit and work stress on occupational fatigue.Results:This study included 1162 medical Homo sapiens personnel, among whom 884 were job-adapted and 362 were in a stressful state. Univariate logistic regression analysis showed that the risk of occupational fatigue significantly increased in the 40-49 age group ( OR=1.89) and the bachelor's degree group ( OR=2.52, P<0.01). Smoking and alcohol consumption were also associated with a significantly higher risk of occupational fatigue ( P<0.01). In terms of occupational characteristics, compared to clinical doctors, nurses and pharmaceutical/technical Homo sapiens personnel had lower risks ( OR=0.57, 0.43, P<0.05). Compared to high-ranking Homo sapiens personnel, those with no title or junior titles exhibited lower risks ( OR=0.51, 0.43, P<0.05). Working hours exceeding 55 hours per week and night shifts 3-4 times per week significantly increased fatigue risk ( OR=1.94, 1.90, P<0.05). Occupational stress and job discomfort were identified as risk factors for occupational fatigue ( OR=11.94, 3.26, P<0.05). Job adaptation and occupational stress exhibited a multiplicative interaction on physical fatigue after adjusting for confounders[ OR (95% CI) =0.43 (0.22, 0.84) ]. Additionally, job adaptation and occupational stress demonstrated an additive interaction on mental fatigue, with RERI (95% CI) =2.64 (0.11, 5.59), API (95% CI) =0.38 (0.08, 0.67), and SI (95% CI) =1.78 (1.01, 3.14). Medical Homo sapiens personnel in a stressful state had a 7.25-fold higher risk of fatigue compared to those not in a stressful state, while those with job discomfort had a 2.01-fold higher risk compared to those in an adapted state. Conclusion:Occupational stress and job fit have interactive effects on physical fatigue and mental fatigue in medical Homo sapiens personnel. A stressful state combined with job discomfort increases the risk of fatigue occurrence, providing a basis for developing intervention strategies for occupational fatigue among medical Homo sapiens personnel.

Objective:To investigate whether brown adipose tissue-derived exosomes(BAT-exos) could ameliorate endothelial cell injury by activating Pink1-Parkin pathway-mediated mitophagy.Methods:Endothelial cell injury was induced with angiotensin Ⅱ(Ang Ⅱ) to establish a cellular injury model. Exosomes were isolated from both brown adipose tissue and white adipose tissue and characterized by transmission electron microscopy(TEM), nanoparticle tracking analysis(NTA), fluorescence labeling, and Western blot. Cell viability was assessed using the CCK-8 assay, and apoptosis rates were determined by flow cytometry. Levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-6, and IL-8 were measured by ELISA. Mitochondrial autophagy was assessed by immunofluorescence colocalization, and protein expression levels of Pink1, Parkin, and LC3 Ⅱ/I were determined by Western blot.Results:Ang Ⅱ induced endothelial cell apoptosis, activated inflammatory responses, and suppressed mitophagy, as evidenced by decreased expression of mitophagy-related proteins. Following the successful characterization of BAT-exos, we found that BAT-exos activated mitophagy and alleviated endothelial cell injury, whereas white adipose tissue-derived exosomes(WAT-exos) inhibited mitophagy and exacerbated injury. Mechanistically, BAT-exos targeted the Pink1-Parkin signaling pathway to activate mitophagy.Conclusion:BAT-exos markedly improve endothelial cell injury by activating mitophagy through the Pink1-Parkin pathway, providing new insights and potential therapeutic targets for cardiovascular diseases.