ObjectiveObesity, a global chronic metabolic disease, is closely associated with disruptions in lipid metabolism and gut microbiota. Current intervention strategies still have limitations in terms of safety and microecological regulation, necessitating the exploration of novel natural regulatory approaches. Based on the early pathological characteristics of obesity, this study innovatively employs a rectal delivery method alongside a high-fat diet (HFD)-induced obesity model to systematically evaluate the inhibitory effects, safety, and gut microbiota regulation mechanisms of leek-derived and konjac-derived extracellular vesicles on obesity development. By simulating early clinical intervention scenarios, this study aims to explore the preventive potential of plant-derived extracellular vesicles during the initial stages of obesity onset. MethodsExtracellular vesicles from leek and konjac were isolated using ultracentrifugation combined with density gradient centrifugation. Their nanoscale properties were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). Male C57BL/6J mice were randomly divided into four groups: normal control (NC), high-fat diet (HFD), leek-derived extracellular vesicles (LEVs), and konjac-derived extracellular vesicles (KEVs). Beginning simultaneously with HFD feeding, mice in the intervention groups received 20 g/L vesicles rectally every 3 d for 4 weeks. Body mass and body composition were monitored throughout. At endpoint, mouse serum, adipose tissue, and colonic contents were collected. Serum biochemical indices (lipid profile, liver and kidney function, cardiac markers) were assessed to evaluate safety and metabolic efficacy, while 16S rRNA sequencing was employed to analyze gut microbial structure and diversity. ResultsDLS, NTA, and TEM confirmed that both LEVs and KEVs exhibited typical cup-shaped nanostructures with average particle sizes of approximately 284 nm and 223 nm, respectively. LEVs and KEVs treatment significantly suppressed HFD-induced weight gain and elevation of body-fat percentage (P<0.05), and reduced accumulation of abdominal white and epididymal adipose tissue. Serological analyses showed that both vesicles lowered total cholesterol, triglycerides and LDL-cholesterol, and ameliorated liver enzyme profiles (ALT, AST), demonstrating lipid-metabolic regulation and hepatoprotective effects. No hepatic, renal or cardiac dysfunction was observed, indicating favorable safety. Gut microbiota analyses revealed that vesicle intervention partially restored HFD-depleted microbial diversity and reshaped community structure. Notably, LEVs markedly increased the relative abundance of the beneficial taxon Lachnospiraceae at the family level, which is known for producing short-chain fatty acids and enhancing intestinal barrier function. Furthermore, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) functional prediction suggested that LEVs and KEVs modulated gut microbial functions through distinct mechanisms: LEVs downregulated pathways related to ribosomes and DNA replication while enhancing xenobiotic degradation, whereas KEVs tended to upregulate energy metabolism and protein synthesis toward healthy levels. ConclusionRectally administered LEVs and KEVs exhibit excellent safety and pronounced metabolic benefits during the early phase of obesity, suppressing weight gain, correcting lipid dysregulation, and exerting effects via modulation of gut microbial composition and function. This study provides systematic experimental evidence supporting plant-derived exosome-like vesicles as an early intervention strategy against obesity.

ObjectiveObesity, a global chronic metabolic disease, is closely associated with disruptions in lipid metabolism and gut microbiota. Current intervention strategies still have limitations in terms of safety and microecological regulation, necessitating the exploration of novel natural regulatory approaches. Based on the early pathological characteristics of obesity, this study innovatively employs a rectal delivery method alongside a high-fat diet (HFD)-induced obesity model to systematically evaluate the inhibitory effects, safety, and gut microbiota regulation mechanisms of leek-derived and konjac-derived extracellular vesicles on obesity development. By simulating early clinical intervention scenarios, this study aims to explore the preventive potential of plant-derived extracellular vesicles during the initial stages of obesity onset. MethodsExtracellular vesicles from leek and konjac were isolated using ultracentrifugation combined with density gradient centrifugation. Their nanoscale properties were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). Male C57BL/6J mice were randomly divided into four groups: normal control (NC), high-fat diet (HFD), leek-derived extracellular vesicles (LEVs), and konjac-derived extracellular vesicles (KEVs). Beginning simultaneously with HFD feeding, mice in the intervention groups received 20 g/L vesicles rectally every 3 d for 4 weeks. Body mass and body composition were monitored throughout. At endpoint, mouse serum, adipose tissue, and colonic contents were collected. Serum biochemical indices (lipid profile, liver and kidney function, cardiac markers) were assessed to evaluate safety and metabolic efficacy, while 16S rRNA sequencing was employed to analyze gut microbial structure and diversity. ResultsDLS, NTA, and TEM confirmed that both LEVs and KEVs exhibited typical cup-shaped nanostructures with average particle sizes of approximately 284 nm and 223 nm, respectively. LEVs and KEVs treatment significantly suppressed HFD-induced weight gain and elevation of body-fat percentage (P<0.05), and reduced accumulation of abdominal white and epididymal adipose tissue. Serological analyses showed that both vesicles lowered total cholesterol, triglycerides and LDL-cholesterol, and ameliorated liver enzyme profiles (ALT, AST), demonstrating lipid-metabolic regulation and hepatoprotective effects. No hepatic, renal or cardiac dysfunction was observed, indicating favorable safety. Gut microbiota analyses revealed that vesicle intervention partially restored HFD-depleted microbial diversity and reshaped community structure. Notably, LEVs markedly increased the relative abundance of the beneficial taxon Lachnospiraceae at the family level, which is known for producing short-chain fatty acids and enhancing intestinal barrier function. Furthermore, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) functional prediction suggested that LEVs and KEVs modulated gut microbial functions through distinct mechanisms: LEVs downregulated pathways related to ribosomes and DNA replication while enhancing xenobiotic degradation, whereas KEVs tended to upregulate energy metabolism and protein synthesis toward healthy levels. ConclusionRectally administered LEVs and KEVs exhibit excellent safety and pronounced metabolic benefits during the early phase of obesity, suppressing weight gain, correcting lipid dysregulation, and exerting effects via modulation of gut microbial composition and function. This study provides systematic experimental evidence supporting plant-derived exosome-like vesicles as an early intervention strategy against obesity.

Objective To investigate the regulation of synaptic plasticity by cannabinoid receptor 1(CB1R)and its effects on autism spectrum disorder(ASD)-like behavior.Methods CB1R-knockout(KO)mice and valproic acid(VPA)-induced ASD model mice(VPA mice)were used as study subjects.Behavioral experiments were used to assess the effects of CB1R on ASD-like behavior in mice,neuronal structural integrity and dendritic density were detected by microtubule-associated protein 2(MAP2)staining experiments,and the expression of synapse-associated proteins was detected by Western blot,to assess the effects of CB1R on synaptic plasticity.Results Behavioral result showed that VPA mice demonstrated significant ASD-like behavior,while CB1R-/-mice spent a significantly smaller proportion of residence time in the central region of the open field(P＜0.0001),showed significant increases in the number of marbles buried and self-grooming time(P＜0.01),significantly less time spent socializing with unfamiliar mice 2 and exploring unfamiliar objects(P＜0.001),and significantly more time exploring old objects(P＜0.05).The relative dwelling time was significantly reduced in CB1R+/-mice(P＜0.001),and the number of marbles buried and self-grooming time were significantly increased(P＜0.05).Synaptic plasticity assays revealed significant synaptic plasticity impairment in VPA mice.Hippocampal MAP2-positive neuron densities were significantly reduced in CB1R-/-and CB1R+/-mice,and expression levels of synapsin-1 were significantly increased(P＜0.05).Conclusions CB1R KO leads to ASD-like behavior such as anxiety and repetitive stereotyped behavior,social and cognitive impairments,as well as neuronal damage,dendritic dysplasia and disrupted synaptic protein expression in mice,suggesting that CB1R is involved in regulating synaptic plasticity as a pathological mechanism for the development of ASD-like behavior.

Objective·To investigate the causal relationship between type 2 diabetes mellitus(T2DM)and cognitive dysfunction using two-sample Mendelian randomisation(MR).Methods·Instrumental variables associated with T2DM were pooled from a large-scale genome-wide association study(GWAS)dataset.Inverse variance weighting was used as the primary analytical technique,supplemented by MR-Egger regression,weighted median and simple median analyses.Meta-analysis was jointly applied to combine different endpoints and to analyse the possibility of a causal relationship between T2DM and dementia,Alzheimer's disease,and Parkinson's dementia.Horizontal pleiotropy was examined by MR-PRESSO global test and MR-Egger analysis.Results·There was a causal relationship between genetically predicted T2DM and dementia(OR=1.11,95%CI 1.02～1.20,P=1.96×10-2)and AD(OR=1.16,95%CI 1.04～1.30,P=8.41×10-3).Meta-analysis also supported the association between T2DM and cognitive impairment(OR=1.12,95%CI 1.05～1.20,P=4.22×10-4).A series of sensitivity analyses suggested the absence of heterogeneity and horizontal pleiotropy.Reverse MR analysis showed no significant causal relationship of various types of dementia on T2DM.Conclusion·T2DM is positively associated with the risk of developing various types of dementia,suggesting that T2DM may be an important risk factor for cognitive impairment.

Objective:To quantitatively evaluate the policy texts on mutual recognition of examination and inspection results at the national and local levels in China from 2006 to 2025 based on the PMC index model,and provide reference for policy formulation and improvement.Methods:The ROSTCM6 software was used to sort out and conduct text mining on 27 policy documents issued at the national and local levels,establishing the PMC index model for the mutual recognition of examination and inspection results in China.Quantitative analysis was conducted through a PMC evaluation system consisting of 9 first-level variables and 39 second-level variables.Results:The average PMC index was 6.06(excellent level).Among the 27 policies,4 were rated as perfect,18 as excellent,and 5 as acceptable.Conclusions:Current policies need to strengthen the formulation of scientific and feasible goals,improve legal guarantees and medical insurance coordination mechanisms,and build a complete data security maintenance system to provide policy support and guarantees for the continuous advancement of the mutual recognition of examination and inspection results.

Objective To investigate the efficacy and safety of domestic RECO flow restoration device in endovascular treatment of acute ischemic stroke(AIS)patients in a real-world setting.Methods From January 2019 to June 2021,consecutive patients with acute intracranial vessel occlusion treated with RECO device from 8 stroke centers in Jiangsu Province were analyzed retrospectively.Baseline and clinical data were collected,including age,gender,baseline modified Rankin scale(mRS)scores,National Institutes of Health stroke scale(NIHSS)score on admission,trial of Org 10172 in acute stroke treatment(TOAST)classification,responsible location of occlusion,wake-up stroke,and medical history(hypertension,diabetes mellitus,hyperlipidemia,atrial fibrillation,coronary heart disease,peripheral arterial disease),smoking,and alcohol consumption.Furthermore,surgical parameters were collected,including time indicators(intervals between symptom onset,admission,puncture and recanalization),preoperative intravenous thrombolysis,general anesthesia,combination of aspiration,number of passes,first pass effect(modified thrombolysis in cerebral infarction[mTICI]grade 3 achieved with s single stent-based thrombectomy),rescue therapy(including thrombectomy with other stents,intra-arterial urokinase thrombolysis,intra-arterial application of tirofiban,emergency angioplasty[stent implantation,balloon dilatation,balloon dilatation combined with stent implantation]),balloon guided catheter and NIHSS score at discharge.The effectiveness indicators included immediate successful recanalization after the operation(mTICI grade ≥ 2b),complete recanalization(mTICI grade 3),and a good prognosis at 90 d after the operation(mRS score ≤2).The safety indicators included symptomatic intracranial hemorrhage(sICH)within 24 h after the operation,device-related intraoperative complications(such as thrombus escape,iatrogenic dissection,bleeding at the surgical site),and all-cause mortality within 90 days after the operation.All patients were divided into the anterior circulation occlusion group and the posterior circulation occlusion group according to the location of the responsible occluded vessel,and the effectiveness and safety indexes were analyzed.Results A total of 366 patients with AIS caused by intracranial vessel occlusion who underwent mechanical thrombectomy with the domestic RECO thrombectomy stent were included.The average age was(69±11)years,with 54 patients(14.8％)over 80 years old and 221 patients(60.4％)male.There were 296 patients in the anterior circulation occlusion group and 70 patients in the posterior circulation occlusion group.(1)Immediate successful recanalization(mTICI grade≥2b)was achieved in 337 patients(92.1％),and complete recanalization was achieved in 282 patients(77.0％)immediately after the operation.The average number of thrombectomies was(1.9±1.0)times,and 141 patients(38.5％)achieved recanalization on the first attempt.9 patients(2.5％)used other stents during the operation,and 65 patients(17.8％)underwent emergency angioplasty.The incidence of sICH within 24 h after the operation was 10.9％(40/366),the good prognosis rate at 90 d after the operation was 53.6％(196/366),and the all-cause mortality rate at 90 d after the operation was 23.0％(84/366).The incidence of device-related intraoperative complications was 3.6％(13/366).The median time from arterial puncture to recanalization was 75(52,110)min,and the median time from onset to recanalization was 370(280,488)min.(2)The good prognosis rates at 90 d after the operation in the anterior and posterior circulation occlusion groups were 55.1％(163/296)and 47.1％(33/70),respectively.The immediate successful recanalization rates were 93.2％(276/296)and 87.1％(61/70),respectively.The immediate complete recanalization rates were 79.1％(234/296)and 68.6％(48/70),respectively.The incidence of sICH within 24h after the operation was 12.2％(36/296)and 5.7％(4/70),respectively.The incidence of device-related intraoperative complications was 3.7％(11/296)and 2.9％(2/70),respectively.The all-cause mortality rate within 90 d after the operation was 21.6％(64/296)and 28.6％(20/70),respectively.There were no statistically significant differences between the two groups in the above aspects(all P＞0.05).Conclusions The application of the domestic RECO thrombectomy stent in the treatment of AIS caused by intracranial vessel occlusion can effectively and safely achieve vascular recanalization.The results of this study still need to be further verified by prospective controlled studies.

Objective To explore the application value of MRI diaphragmatic navigation technology combined with three dimensional liver acquisition with volume acceleration-flexible(3D LAVA-FLEX)sequence in abdominal enhanced imaging of infants and young children.Methods A retrospective analysis was conducted on imaging data of 84 infants and young children who underwent abdominal enhanced MRI examination in our hospital between January 2021 and December 2023.All 84 infants and young children initially underwent conventional dynamic contrast-enhanced 3D LAVA-FLEX sequence scanning;the delayed phase images obtained were included in the dynamic enhancement group.Subsequently,diaphragmatic navigation combined with 3D LAVA-FLEX sequence examination was implemented,and the obtained images were included in the diaphragm navigation group.Subjective scoring was performed for images in both groups,while the signal to noise ratio(SNR),contrast to noise ratio(CNR),and artifact quantification(AQ)were measured and compared between the two groups.Results The respiratory motion artifacts,the clarity of liver parenchyma enhancement,the clarity of liver vascular enhancement,the clarity of spleen parenchyma enhancement and the overall image quality score in the diaphragm navigation group were higher than those in the dynamic enhancement group,and the differences were statistically significant(P<0.05).There were statistically significant differences in SNR and AQ between the two groups of images(P<0.000 1),while there was no statistically significant difference in CNR between the two groups of images(P>0.05).Conclusion Diaphragmatic navigation technology combined with 3D LAVA-FLEX sequence imaging can improve the image quality of abdominal MRI enhanced imaging in infants and young children,and provide a reference for clinical diagnosis and treatment.

Intra-aortic balloon pump(IABP),as the most commonly used percutaneous mechanical circulatory assist device,is routinely implanted through the femoral artery pathway.However,when implantation through the femoral artery pathway is difficult or contraindicated,other pathways including the brachial artery pathway,axillary artery pathway,etc.can be considered.IABP assisted interventional treatment for complex high-risk and indicated patients(CHIP)can reduce the risk of intraoperative complications,stabilize hemodynamics,increase the complete revascularization rate of CHIP,and improve long-term prognosis.The reverse guidewire technique can improve the success rate of percutaneous coronary intervention(PCI)for chronic total occlusion(CTO)of coronary arteries.In clinical practice,the reverse pathway is often chosen in addition to the forward pathway,such as the contralateral radial and brachial artery pathway,femoral artery pathway,etc.This article reports a case of bilateral femoral artery occlusion,in which IABP was implanted through the left brachial artery pathway,and then with the assistance of IABP,the right coronary artery CTO lesion was successfully opened through the right radial artery in the forward direction and the right brachial artery in the reverse direction,with the aim of providing reference for clinical PCI treatment for such special cases.

Aim To investigate the effect of high-fat diet on the tight junction function injury of Sertoli cells through the NF-κB/NLRP3 signaling pathway in mice and to explore the underlying mechanism.Methods Male C57BL/6J mice were fed with high-fat or normal diet for five months.The body and gonadal organ weight of mice were measured,and their indices were calculated.The sperm concentration,the sperm viabili-ty,the testicular histomorphology and the expression levels of tight junction proteins ZO-1,Occludin and Claudin-11 were measured.TM4 cells were treated with palmitic acid(PA)for 24 h.Cell viability was detected by CCK-8 method.Then,TM4 cells were di-vided into different groups treated with PA(0,50,100,200 and 300 μmnol·L-1),and the expression lev-els of tight junction proteins ZO-1,Occludin and Clau-din-11 were detected by Western blot.The tight junc-tion permeability of TM4 cells were detected by transepithelial electrical resistance(TEER)and FITC-dextran.The expression levels of mRNA and proteins for the NF-κB/NLRP3 pathway-related factors were de-tected by RT-qPCR and Western blot.Results The results from animal experiments showed that high-fat diet increased body weight and seminal vesicle weight of mice,and decreased testicular index,epididymal in-dex,sperm concentration and sperm motility of mice.High-fat diet also caused testicular tissue structure damage and down-regulated the expression levels of tight junction proteins ZO-1 and Occludin,without af-fecting the expression of Claudin-11.In vitro,PA sig-nificantly down-regulated the expression levels of ZO-1,Occludin and Claudin-11 in TM4 cells,increased the cell permeability,as well as up-regulated the mRNA and protein expression levels of NLRP3/NF-κB signa-ling pathway-related factors in TM4 cells.Conclusions High-fat diet can impair the function of tight junction of testicualr Sertoli cells,and the machanism may be related to the activation of the NF-κB/NLRP3 signaling pathway,resulting in Sertoli cell inflammation in mice.

Objective To explore the application value of MRI diaphragmatic navigation technology combined with three dimensional liver acquisition with volume acceleration-flexible(3D LAVA-FLEX)sequence in abdominal enhanced imaging of infants and young children.Methods A retrospective analysis was conducted on imaging data of 84 infants and young children who underwent abdominal enhanced MRI examination in our hospital between January 2021 and December 2023.All 84 infants and young children initially underwent conventional dynamic contrast-enhanced 3D LAVA-FLEX sequence scanning;the delayed phase images obtained were included in the dynamic enhancement group.Subsequently,diaphragmatic navigation combined with 3D LAVA-FLEX sequence examination was implemented,and the obtained images were included in the diaphragm navigation group.Subjective scoring was performed for images in both groups,while the signal to noise ratio(SNR),contrast to noise ratio(CNR),and artifact quantification(AQ)were measured and compared between the two groups.Results The respiratory motion artifacts,the clarity of liver parenchyma enhancement,the clarity of liver vascular enhancement,the clarity of spleen parenchyma enhancement and the overall image quality score in the diaphragm navigation group were higher than those in the dynamic enhancement group,and the differences were statistically significant(P<0.05).There were statistically significant differences in SNR and AQ between the two groups of images(P<0.000 1),while there was no statistically significant difference in CNR between the two groups of images(P>0.05).Conclusion Diaphragmatic navigation technology combined with 3D LAVA-FLEX sequence imaging can improve the image quality of abdominal MRI enhanced imaging in infants and young children,and provide a reference for clinical diagnosis and treatment.