ObjectivePost-ischemic acute inflammation and the subsequent persistent dysregulation of the immune microenvironment represent major pathological drivers that aggravate neuronal injury and severely restrict functional recovery following ischemic stroke. Although current reperfusion therapies partially restore blood flow, they fail to effectively modulate the secondary inflammatory cascade and oxidative stress, which remain critical barriers to neurological restoration. To address this challenge, this study aimed to engineer and systematically evaluate a biomimetic nanosystem composed of transforming growth factor-β1 (TGF-β1)-loaded platelet membrane-camouflaged lipid nanoparticles (PLP). This nanosystem was designed to achieve dual lesion-targeted delivery and immune microenvironment remodeling. By verifying its spatiotemporal accumulation, anti-inflammatory activity, and neuroprotective efficacy, we sought to establish an integrated therapeutic strategy that simultaneously enables lesion targeting, immune regulation, and functional recovery after ischemic injury. MethodsThe physicochemical properties of PLP, including hydrodynamic particle size, zeta potential, structural stability, and morphology, were characterized using dynamic light scattering, zeta potential analysis, and transmission electron microscopy. The preservation of platelet membrane-derived adhesion and immunoregulatory proteins was confirmed by SDS-PAGE through comparative analysis of protein band profiles between PLP and native platelet membranes. The in vitro biological activities of PLP were evaluated using two complementary cellular models. LPS-induced M1-polarized RAW264.7 macrophages were employed to assess inflammatory modulation, while oxygen glucose deprivation/reperfusion (OGD/R)-induced BV2 microglial cells and SH-SY5Y neuronal cells were utilized to investigate neuroinflammatory regulation and neuronal protection. For in vivo validation, a transient middle cerebral artery occlusion (tMCAO) mouse model was established to mimic ischemia-reperfusion injury. The spatiotemporal biodistribution and lesion-targeting capability of the PLP were monitored through live fluorescence imaging. Therapeutic efficacy was comprehensively evaluated by triphenyltetrazolium chloride (TTC) staining, glial fibrillary acidic protein (GFAP) immunofluorescence analysis, body weight monitoring, and neurological severity score (NSS) assessment. ResultsPLP nanoparticles displayed a uniform spherical morphology, nanoscale particle size distribution, and stable negative surface charge, indicating favorable colloidal stability and circulation potential. SDS-PAGE results confirmed the effective retention of key platelet membrane proteins associated with endothelial adhesion, immune evasion, and inflammatory regulation, demonstrating the successful biomimetic construction. Optimal therapeutic concentrations were determined in OGD/R-induced BV2 cells, where PLP exhibited excellent cytocompatibility and anti-inflammatory activity.In vitro experiments demonstrated that PLP significantly inhibited the polarization of RAW264.7 macrophages toward the pro-inflammatory M1 phenotype and markedly reduced neuronal apoptosis under ischemia-reperfusion conditions. In vivo fluorescence imaging revealed that PLP rapidly accumulated in the ischemic brain hemisphere and maintained prolonged retention for up to 7 d, suggesting enhanced lesion-specific targeting and sustained drug release. Compared with control group, PLP treatment significantly reduced cerebral infarct volume, attenuated reactive astrogliosis, improved weight recovery, and accelerated neurological functional restoration, as reflected by significantly improved NSS scores. ConclusionThis study establishes a multifunctional biomimetic nanoplatform that integrates platelet membrane-mediated active targeting with the anti-inflammatory, antioxidative, and neuroprotective properties of TGF-β1. The PLP system enables rapid lesion homing and long-term retention while synergistically regulating the post-stroke inflammatory microenvironment by suppressing pro-inflammatory immune activation, reducing neuronal apoptosis, and limiting excessive astrocyte reactivity. Importantly, this study proposes a conceptually therapeutic paradigm that combines targeted delivery with immune microenvironment remodeling to achieve comprehensive neurovascular protection. These findings provide strong experimental evidence supporting the translational potential of biomimetic nanotherapeutics as next-generation precision interventions for ischemic stroke.

BACKGROUND:Neurodegenerative diseases are closely related to the imbalance of mitochondrial autophagy regulation.Previous studies by the research group have shown that lycium barbarum polysaccharide has neuroprotective effects,but whether it can improve the damage of SH-SY5Y cells induced byβ-amyloid protein 1-42 by regulating mitochondrial autophagy is still unclear.OBJECTIVE:To explore the protective effect and mechanism of Lycium barbarum polysaccharide on SH-SY5Y cells induced by β-amyloid protein 1-42.METHODS:An Alzheimer's disease cell model was established by inducing SH-SY5Y cells with β-amyloid protein 1-42,and then intervening with Lycium barbarum polysaccharide.SH-SY5Y cells were divided into three groups:control group,β-amyloid protein 1-42 group(20 μmol/L β-amyloid protein 1-42 for 24 hours),and Lycium barbarum polysaccharide group(1 g/L Lycium barbarum polysaccharide was added 1 hour in advance to form a protective effect,and then 20 μmol/L β-amyloid protein 1-42 was added to intervene with Lycium barbarum polysaccharide for 24 hours).CCK8 assay was used to detect cell viability.Mitochondrial membrane potential was detected by JC-1.TUNEL staining was used to detect cell apoptosis.Immunofluorescence and western blot assay were used to detect the expression of synaptic,apoptosis,and mitophagy-related indicators.RESULTS AND CONCLUSION:(1)Compared with the control group,the cell viability of the β-amyloid protein 1-42 group decreased(P＜0.05);cell apoptosis rate increased(P＜0.05);mitochondrial membrane potential decreased(P＜0.05);the expressions of pro-apoptotic proteins Bax and Caspase3 increased(P＜0.05);the expression of anti-apoptotic protein Bcl-2 decreased(P＜0.05);the expression levels of synaptic-related proteins Syn and PSD-95 decreased(P＜0.05);the expression levels of mitochondrial autophagy-related proteins Pink1,LC3A/B,Parkin,and Beclin-1 decreased(P＜0.05);and the expression of P62 increased(P＜0.05).(2)Compared with the β-amyloid protein 1-42 group,the cell viability in the Lycium barbarum polysaccharide group was increased(P＜0.05);the apoptosis rate was decreased(P＜0.05);the mitochondrial membrane potential was increased(P＜0.05);the expression levels of Bax and Caspase3 were decreased(P＜0.05);the expression of Bcl-2 was increased(P＜0.05);the expressions of Syn and PSD-95 were increased(P＜0.05);the expression levels of Pink1,LC3A/B,Parkin,and Beclin-1 were increased(P＜0.05),and the expression of P62 was decreased(P＜0.05).These findings indicate that Lycium barbarum polysaccharide may inhibit β-amyloid protein 1-42-induced damage to SH-SY5Y cells by regulating mitophagy,reduce cell apoptosis,and increase neuronal synaptic plasticity.

Objective:To investigate the neuroprotective effect of nicotinamide riboside(NR)on experimental autoimmune en-cephalomyelitis(EAE)mice.Methods:C57BL/6 female mice were induced by myelin oligodendrocyte glycoprotein(MOG35-55)to pro-duce EAE model and were randomly divided into EAE group and NR group.From day 3 to day 27 after immunization,each mouse in EAE group was given normal saline(200 μl/d)and each mouse in NR group was given NR(500 mg/kg,200 μl/d)by intragastric administration.Clinical score and body weight of mice in EAE group and NR group were recorded every day.On the 28th day after immunization,the spinal cord protein of mice in each group was extracted and the frozen sections of spinal cord of mice in each group were prepared.LFB staining was used to detect demyelination,immunofluorescence staining was used to detect the expression of MAP-2 and the number of positive cells of NeuN,BDNF,GDNF,NGF and NT-3,and Western blot was used to detect the expressions of BDNF,GDNF,NGF and NT-3 of spinal cord.Results:Compared with EAE group,NR significantly delayed the onset time of EAE mice(P<0.05),decreased clinical score(P<0.05),reduced weight loss,alleviated spinal cord demyelination(P<0.05),increased the expression of MAP-2(P<0.01)and the number of NeuN positive cells(P<0.01),and up-regulated the expressions of BDNF,GDNF,NGF and NT-3(P<0.05).Conclusion:NR shows a good neuroprotective effect on EAE mice.The mechanism may be related to NR significantly increasing the expression of spinal neurotrophic factors,improving the microenvironment of the central nervous sys-tem,nourishing nerves,promoting nerve repair and nerve growth,etc.

BACKGROUND:A large number of studies have shown that neurodegenerative diseases are closely related to oxidative stress injury and the imbalance of mitochondrial dynamics.Lycium barbarum polysaccharides have a neuroprotective effect.However,it is not clear whether lycium barbarum polysaccharides can ameliorate apoptosis induced by oxidative stress injury by regulating abnormal mitochondrial dynamics.OBJECTIVE:To study the effect of lycium barbarum polysaccharides on apoptosis induced by H2O2 in SH-SY5Y human neuroblastoma cells.METHODS:SH-SY5Y cells were cultured in three groups.The control group was cultured for 24 hours.The hydrogen peroxide group was treated with H2O2 for 24 hours,and the lycium barbarum polysaccharide group was treated with lycium barbarum polysaccharide for 2 hours and then treated with H2O2 for 24 hours.After treatment,the levels of malondialdehyde,glutathione,and superoxide dismutase in the precipitation of the cells were detected by kit.Mitochondrial membrane potential was detected by JC-1 kit.Cell viability was detected by MTT assay.Apoptosis was detected by TUNEL.The expression levels of mitochondrial dynamics-related proteins (phosphorylated promoter protein 1,mitochondrial fission protein 1,mitochondrial fusion protein 1,mitochondrial fusion protein 2,and optic atrophy protein 1) and apoptotic proteins (Bax,Bcl-2,and Caspase-3) were detected by immunofluorescence staining and western blot assay.RESULTS AND CONCLUSION:(1) Compared with the control group,the levels of malondialdehyde were increased (P<0.05),and the levels of superoxide dismutase and glutathione were decreased (P<0.05) in the H2O2 group.Compared with the H2O2 group,the malondialdehyde level was decreased (P<0.05),and the superoxide dismutase and glutathione levels were increased (P<0.05) in the lycium barbarum polysaccharide group.(2) The mitochondrial membrane potential in the H2O2 group was lower than that in the control group (P<0.05),and that of lycium barbarum polysaccharide group was higher than that of the H2O2 group (P<0.05).(3) Compared with the control group,the apoptosis rate and the expression of Bax and Caspase-3 protein were increased (P<0.05),while the cell viability and the expression of Bcl-2 protein were decreased (P<0.05) in the H2O2 group.Compared with the H2O2 group,the apoptosis rate and the expression of Bax and Caspase-3 protein were decreased (P<0.05),while the cell viability and the expression of Bcl-2 protein were increased (P<0.05) in the lycium barbarum polysaccharide group.(4) Compared with the control group,the protein expression levels of phosphorylated promoter protein 1 and mitochondrial fission protein 1 were increased (P<0.05),and the protein expression levels of mitochondrial fusion protein 1,mitochondrial fusion protein 2,and optic atrophy protein 1 were decreased (P<0.05) in the H2O2 group.Compared with the H2O2 group,the protein expression levels of phosphorylated promoter protein 1 and mitochondrial fission protein 1 were decreased (P<0.05),and the protein expression levels of mitochondrial fusion protein 1,mitochondrial fusion protein 2,and optic atrophy protein 1 were increased (P<0.05) in the lycium barbarum polysaccharide group.(5) These results indicate that lycium barbarum polysaccharide can improve SH-SY5Y cell apoptosis caused by oxidative stress damage by regulating mitochondrial dynamics.

Objective:To construct a competency-oriented assessment index system based on entrustable professional activities (EPAs) for 5-year undergraduate clinical medical students in oncology internship.Methods:From June to December 2023, the scoping review approach and Bicomb 2.0 were used to construct and manage an item pool. The draft of EPAs and competencies was designed based on truncated word frequency. SPSS 25.0 was used for cluster analysis and UCINET 6.0 was used for visualization. Combining the characteristics and consensus of oncology, a multi-center expert group used the KJ method to draft the framework of EPAs and competencies. Subsequently, the expert group defined milestones and mapped the milestones to the framework to establish the assessment system.Results:Based on 26 included studies, a draft was created containing 19 EPA indicators and 72 competency characteristic indicators. After cluster analysis, 13 experts from 6 medical institutions established a framework including 13 EPAs and 10 competencies as well as 50 milestones, leading to the construction of the "EPAs-competencies-milestones" assessment system.Conclusions:The "EPAs-competencies-milestones" assessment system aligns with the trend of reform, demonstrating universality, specificity, and scientificity. It provides a reference for the development and assessment of oncology internship courses in medical universities.

Objective:To evaluate the association between heatwaves and fall-related mortality.Methods:A total of 61 421 fall-related mortality from 2013 to 2022 in 7 provinces of China were included in a time-stratified case-crossover design, with daily meteorological data derived from the fifth generation European Reanalysis dataset produced by the European Centre for Medium-Range Weather Forecasts. Conditional logistic regression chimeric distributed lag nonlinear model was used to analyze the association between heatwaves and fall-related mortality and stratified analysis was conducted according to gender and age.Results:Heatwaves were associated with an increased risk of fall-related morality. The risk of fall-related mortality during heatwaves was higher than during non-heatwave periods ( OR=1.11, 95% CI: 1.05-1.18). The attributable fraction of fall-related motality due to heatwaves was 10.25% (95% CI: 4.49%-15.36%). For each 1 ℃ increase above the heatwave threshold, the risk of fall-related mortality increased by 34% ( OR=1.34, 95% CI: 1.02-1.76). The effect of heatwave duration on fall-related mortality was not statistically significant. Stratified analyses indicated that women experienced a higher risk of fall-related mortality during heatwaves ( OR=1.13, 95% CI: 1.04-1.22) compared to man ( OR=1.10, 95% CI: 1.04-1.17). Conclusions:Heatwave increases the risk of fall-related mortality, and the intensity of heatwaves modify this risk. Women are vulnerable populations.

Objective:To assess the association between temperature and risk of animal injury, and identifying vulnerable populations.Methods:Based on a time-stratified case-crossover design, the number of animal injuries monitored in hospitals of Guangdong Provincial Injury Surveillance System in 2011 and 2015-2016 was included, and the daily meteorological data were derived from the fifth generation of European ReAnalysis-Land, which was produced by the European Centre for Medium-Range Weather Forecasts. Conditional logistic regression combined with a distributed lagged nonlinear model was applied to analyze the association of temperature and animal-specific injuries. We also conducted stratified analysis by region, sex, age, occupation, and location of injury occurrence.Results:There was an almost linear relationship between temperature and the occurrence of animal injury. The excess risk ( ER) of animal injury was 2.65% (95% CI: 2.27%-3.04%) for a 1 ℃ rise in temperature with much higher risk of occurrence ( ER=9.34%, 95% CI: 7.57%-11.13%) for non-mammalian injury than that for mammalian injuries ( ER=2.30%, 95% CI: 1.90%-2.70%). Stratified analysis revealed that the occurrence of animal injury was more susceptible to temperature influences in urban ( ER=2.78%, 95% CI: 2.35%-3.21%), female ( ER=2.71%, 95% CI: 2.16%-3.27%), the elderly aged 60 years and above ( ER=3.05%, 95% CI: 1.65%- 4.47%), farmer ( ER=4.66%, 95% CI: 3.03%-6.32%) and agricultural area ( ER=10.63%, 95% CI: 7.57%-13.79%) than their correspondents. In terms of mammalian injury, dog bites showed the highest risk ( ER=2.71%, 95% CI: 2.12%-3.30%). In terms of non-mammalian,snake injuries were highly influenced by temperature ( ER=16.74%, 95% CI: 11.33%-22.40%). Conclusions:The ambient temperature rises could increase the risk of animal injury with much higher risk for non-mammalian than that for mammalian injuries. Our findings suggest that global warming may increase the risk and disease burden from animal injuries.

Objective:To investigate the effect and mechanism of lycium barbarum polysaccharide(LBP)on lipopolysaccharide(LPS)-induced inflammatory response of NLRP3 inflammasome in BV2 microglial cells.Methods:BV2 microglial cells were routinely cultured.CCK-8 assay was used to detect the effect of different concentrations(0.5,1,1.5,2 g/L)LBP on cell activity.Cells were di-vided into three groups:control group,LPS group and LBP+LPS group.Effect of LBP on LPS-induced cell activity was detected by CCK-8 method;RT-qPCR and immunofluorescence assay were used to detect NLRP3,ASC,Caspase-1,IL-18 and IL-1β expressions.Western blot was used to detect expressions of NLRP3,ASC,Caspase-1,TLR4,MyD88,NF-κB p65,IL-18,IL-1β and TNF-α pro-teins.Results:CCK-8 assay showed that 1 g/L LBP was the most applicable.Compared with control group,cell viability in LPS group was decreased;RT-qPCR,immunofluorescence and Western blot results showed that fluorescence intensity,mRNA and protein expres-sions of NLRP3,ASC,Caspase-1,IL-18 and IL-1β were increased in LPS group.Western blot results showed that TLR4,MyD88,NF-κB p65 and TNF-α protein expressions were increased in LPS group.After LBP treatment,cell viability was increased;expres-sions of NLRP3,ASC,Caspase-1,NF-κB p65,TLR4,MyD88,IL-18,IL-1β and TNF-α were decreased.Conclusion:LBP may in-hibit LPS-induced NLRP3 inflammatory vesicles in BV2 cells via TLR4/MyD88/NF-κB signaling pathway.

To effectively exploit the tumor microenvironment (TME), TME-responsive nanocarriers based on cascade reactions have received much attention. In this study, we designed a novel nanoparticle PB@SiO₂@MnO₂@P-Arg (PMP) to construct a cascade reaction nanoplatform. While using biosafety Prussian blue (PB) for photothermal therapy (PTT), this nanoplatform uses silica (SiO₂) as an intermediate layer to assemble Prussian blue and manganese dioxide (MnO₂) into a core-shell structure, which effectively enhances the response of the nanoplatform to TME and promotes the effect of chemodynamic therapy (CDT) resulting from glutathione (GSH) depletion and Fenton-like reaction. The released Mn²⁺ can also be used for magnetic resonance imaging (MRI). Through the cascade reaction, poly-l-arginine (P-Arg) coated on the surface of the nanoparticles can react with hydroxyl radical (•OH) obtained from the Fenton-like reaction to release nitric oxide (NO), which further reacts with O₂•^- to produce the more toxic peroxynitrite anion (ONOO^-). The photothermal effect of PB further enhances the effect of the cascade reaction while reducing the amount of heat required for treatment. In vitro and in vivo studies confirmed the antitumor effects of cascade reaction-based nanoplatforms in combined photothermal/chemodynamic/gas cancer therapies, providing new strategies for the design and fabrication of multifunctional nanoplatforms that integrate diagnostic and therapeutic functions, as well as the application of cascade reactions in multimodal synergistic therapy.

OBJECTIVE: To evaluate the effectiveness of functional perforator flaps utilizing the superficial circumflex iliac artery as a vascular pedicle, as well as chimeric iliac bone flaps, in the reconstruction of composite tissue defects in the hand and foot. METHODS: A retrospective review of the clinical data from 13 patients suffering from severe hand or foot injuries, treated between May 2019 and January 2025, was conducted. The cohort comprised 8 males and 5 females, with ages ranging from 31 to 67 years (mean, 48.5 years). The injuries caused by mechanical crush incidents (n=9) and traffic accidents (n=4). The distribution of injury sites included 8 cases involving the hand and 5 cases involving the foot. Preoperatively, all patients exhibited bone defects ranging from 2.0 to 6.5 cm and soft tissue defects ranging from 10 to 210 cm². Reconstruction was performed using functional perforator flaps based on the superficial circumflex iliac artery and chimeric iliac bone flaps. The size of iliac bone flaps ranged from 2.5 cm×1.0 cm×1.0 cm to 7.0 cm×2.0 cm×1.5 cm, while the size of the soft tissue flaps ranged from 4 cm×3 cm to 15 cm×8 cm. In 1 case with a significant hand defect, a posterior interosseous artery perforator flap measuring 10.0 cm×4.5 cm was utilized as an adjunct. Likewise, an anterolateral thigh perforator flap measuring 25 cm×7 cm was combined in 1 case involving a foot defect. All donor sites were primarily closed. Postoperative flap survival was monitored, and bone healing was evaluated through imaging examination. Functional outcomes were assessed based on the location of the defects: for hand injuries, grip strength, pinch strength, and flap two-point discrimination were measured; for foot injuries, the American Orthopaedic Foot & Ankle Society (AOFAS) score, visual analogue scale (VAS) score, Maryland Foot Score, plantar pressure distribution and gait symmetry index (GSI) were evaluated. RESULTS: All flaps survived completely, with primary healing observed at both donor and recipient sites. All patients were followed up 6-18 months (mean, 12.2 months). No significant flap swelling or deformity was observed. Imaging examination showed a bone callus crossing rate of 92.3% (12/13) at 3 months after operation, and bone density recovered to more than 80% of the healthy side at 6 months. The time required for bone flap integration ranged from 2 to 6 months (mean, 3.2 months). One patient with a foot injury exhibited hypertrophic scarring at the donor site; however, no major complication, such as infection or bone nonunion, was noted. At 6 months after operation, grip strength in 8 patients involving the hand recovered to 75%-90% of the healthy side (mean, 83.2%), while pinch strength recovered to 70%-85% (mean, 80%). Flap two-point discrimination ranged from 8 to 12 mm, approaching the sensory capacity of the healthy side (5-8 mm). Among the 5 patients involving the foot, the AOFAS score at 8 months was 80.5±7.3, VAS score was 5.2±1.6. According to the Maryland Foot Score, 2 cases were rated as excellent and 3 as good. Gait analysis at 6 months after operation showed GSI above 90%, with plantar pressure distribution closely resembling that of the contralateral foot. CONCLUSION The use of functional perforator flaps based on the superficial circumflex iliac artery, combined with chimeric iliac bone flaps, provides a reliable vascular supply and effective functional restoration for the simultaneous repair of composite bone and soft tissue defects in the hand or foot. This technique represents a viable and effective reconstructive option for composite tissue defects in these anatomical regions.
Humans ; Male ; Middle Aged ; Female ; Perforator Flap/transplantation* ; Adult ; Plastic Surgery Procedures/methods* ; Hand Injuries/surgery* ; Aged ; Retrospective Studies ; Foot Injuries/surgery* ; Ilium/transplantation* ; Iliac Artery/surgery* ; Soft Tissue Injuries/surgery* ; Bone Transplantation/methods* ; Treatment Outcome