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 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 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.

Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

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 explore the feasibility and safety of ultrasound-guided percutaneous microwave ablation for unresectable pancreatic cancer.Methods Totally 84 patients who underwent ultrasound-guided percutaneous microwave ablation for unresectable pancreatic cancer were enrolled,and the technical success rate,complete ablation rate,complication rate,pain relief rate and survival time,etc.were observed.Results The median age of 84 cases was 61.5 years.Totally 86 tumors,including 44.19％(38/86)at the head/neck and 55.81％(48/86)at the body/tail of pancreas were detected,and a total of 85 ablation sessions were performed with the median ablation energy applied per tumor of 9.90(1.08,21.60)kJ and the complete ablation rate of 42.86％(36/84).The technical success rate was 100％(85/85).Thirty-nine complication events occurred in 25 cases,no ablation-related death.Among 34 patients underwent ablation mainly for pain symptoms,the pain score decreased from(6.22±1.12)points before treatment to(1.94±1.64)points after treatment(P＜0.001).During 6.8(3.3,12.9)months' follow-up,the mean survival time was(8.5±6.7)months,and all 47 patients died due to tumor progression.Conclusion Ultrasound-guided percutaneous microwave ablation was safe and feasible for unresectable pancreatic cancer.

Objective This study mainly focuses on the relationship between the serum glycoprotein non-metastatic melanoma protein B(GPNMB)concentration and the degree of neurological damage and prognosis in patients with acute ischemic stroke(AIS),and screens potential biomarkers to provide a reference for clinical diagnosis and treatment.Methods A total of 105 AIS patients hospitalized in the Department of Neurology of the Hospital 2 of Nantong University from June 2023 to March 2024 were selected as the sample group.In this study,the patients were divided into mild group(n=42)and moderate to severe group(n=63)according to the National Institutes of Health Strobe Scale(NIHSS)score within 24 hours of admission.The Modified Rankin Scale(mRS)was used to evaluate the functional recovery 3 months after discharge.The samples were subdivided into good prognosis group(n=34)and poor prognosis group(n=71).The serum GPNMB protein level was detected by ELISA,and the correlation between serum GPNMB protein level and NIHSS and mRS scores was analyzed.The binary Logistic regression model was used to evaluate the predictive value and prognostic evaluation value of serum GPNMB protein level for AIS neurological function damage.Results The serum GPNMB protein concentration in patients with moderate to severe neurological impairment and poor prognosis was significantly lower than that in patients with mild and good prognosis(P<0.05).The serum GPNMB protein level was significantly negatively correlated with the NIHSS score(r=-0.196,P<0.05)and the mRS score(r=-0.334,P<0.05).Multivariate regression analysis showed that GPNMB was still a key independent risk factor for AIS(P<0.05).The evaluation results obtained based on the receiver operating characteristic curve(ROC)showed that the serum GPNMB protein level had diagnostic value in predicting neurological impairment and poor prognosis(sensitivity reached 55.6%,specificity was 81.8%,and the overall accuracy was 63.81%,P<0.05).Conclusion There is a significant positive correlation between the decrease in serum GPNMB protein concentration and the degree of neurological damage in AIS patients,and it is likely to become an important biological indicator for measuring the severity of the disease and long-term prognosis.

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.

The original version of this article (Yang et al., 2023) unfortunately contained a mistake. In Acknowledgments, the funding information for the Zhejiang Provincial Natural Science Foundation of China (No. LBY21H160001) was wrong. The correct funding should be the Zhejiang Health Science and Technology Project (No. 2022KY682), China.