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.

Abstract The prevention and control of myopia in Chinese children and adolescents has become a major public health issue. While maintaining increased outdoor activity as a cornerstone intervention, there is an urgent need to explore new complementary approaches that can be effectively implemented in both indoor and outdoor settings. In recent years, environmental spatial frequency has gained increasing attention as one of the key environmental factors influencing the development and progression of myopia. Both animal studies and human research have confirmed that indoor environments lacking mid to high spatial frequency components, often characterized as "visually impoverished", can promote axial elongation and myopia through mechanisms such as disruption of retinal neural signaling, impaired accommodative function, and altered expression of related molecules. Based on the scientific consensus, it is recommended that "enriching of environmental spatial frequency" should be integrated into the myopia prevention and control framework. Following the principles of schoolled organization, family cooperation, community involvement, and student participation, specific measures are put forward in three areas：optimizing school visual settings, improving home spatial environments, and promoting healthy visual behavior. The aim is to create "visually friendly" indoor environments as an important supplement to outdoor activity, thereby providing a novel perspective and strategy for comprehensively advancing myopia prevention and control among children and adolescents.

ObjectiveTo investigate the therapeutic effect of Astragali Radix-mediated changes in gut microbiota on treating type 2 diabetes （T2DM）. MethodsA 12-week randomized， placebo-controlled clinical trial enrolled eighty patients with newly diagnosed type 2 diabetes and poor glycemic control in the Qi deficiency type. All patients received insulin therapy. The observation group （40 cases） was administered with Astragali Radix Granules， while the control group （40 cases） received a placebo. Both treamtents were taken orally twice daily. Changes in gut microbiota were assessed by 16s rDNA sequencing. Serum glucagon-like peptide-1 （GLP-1） levels were measured using enzyme-linked immunosorbent assay （ELISA）. Glucose metabolism indicators including fasting blood glucose （FPG）， 2-hour postprandial blood glucose （2 h PG），glycated albumin（GA）， and glycated hemoglobin （HbA1c） were evaluated. Pancreatic function was evaluated using fasting C-peptide （FCP）， 2-hour postprandial C-peptide （2 h CP）， and C-peptide area under the curve （AUC_cp）. Traditional Chinese medicine （TCM） syndrome scores， clinical efficacy， and safety indicators were also observed. ResultsIn terms of glucose metabolism indicators， compared with the baseline， both groups exhibited significantly lower FPG， 2 h PG， GA and HbA1C （P<0.01），while FCP， 2 h CP and AUC_cp were significantly higher （P<0.01）. Compared with the control group after the treatment， the observation group showed significantly lower FPG， 2 h PG， GA and HbA1C（P<0.05， P<0.01），and significantly higher FCP， 2 h CP and AUC_cp （P<0.05， P<0.01）， indicating that Astragali Radix can improve glucose metabolism. In terms of the diversity of gut microbiota， no significant differences were detected in the Chao1， Shannon and Simpson indexes of the two groups compared with their respective baselines. However， compared with the post-treatment control group， the observation group demonstrated significant increases in the Chao1， Shannon and Simpson indexes （P<0.05， P<0.01）. The β-diversity analysis showed significant separation in gut microbiota composition before and after treatment in both groups， indicating that Astragali Radix can significantly alter the structure and improve the diversity of gut microbiota. At the phylum level， compared with the baseline， both groups showed a significant increase in the relative abundance of Bacteroidota（P<0.01）. The relative abundance of the potentially harmful phylum Proteobacteria was significantly lower in the observation Group after treatment （P<0.01）. Compared with the post-treatment control group， the observation group had a significantly higher relative abundance of Bacteroidota（P<0.01）. No significant difference was found in Firmicutes/Bacteroidota （F/B） ratio between the two groups after treatment， and other phyla showed no significant differences. At the genus level， compared with the baseline， the observation group exhibited a significant increase in Bacteroides （P<0.01） and a significant decrease in Escherichia-Shigella （P<0.01）， whereas no significant difference was seen in the control group . Compared with the control group after treatment， the observation group after treatment had a significantly higher relative abundance of Bacteroides （P<0.01）. No significant differences were seen in other genera. Linear discriminant analysis （LDA） identified potential characteristics taxa： in the observation group， Bacteroidota at the phylum level and Bacteroides and Dubosiella at the genus level， in the control group， Proteobacteria at the phylum level as well as Barnesiella and Staphylococcus at the genus level. Correlation analysis based on a heatmap revealed that GLP-1 levels were positively correlated with Firmicutes， F/B ratio and Fusobacterium， and negatively correlated with Bacteroidota， Proteobacteria， Bacteroides and Escherichia-Shigella. In terms of clinical efficacy， compared with the control group， the total effective rate of the observation group was significantly higher （P<0.05）. Compared with the baseline， the scores for shortness of breath， fatigue， weakness， spontaneous sweating and reluctance to speak significantly decreased in both groups （P<0.01）. Compared with the control group after treatment， the score for weakness was significantly lower in the observation group （P<0.01），indicating that Astragali Radix could improve clinical symptoms and alleviate weakness symptoms. In terms of safety， compared with the baseline， alanine aminotransferase （ALT） levels significantly decreased in both groups （P<0.05，P<0.01），indicating that Astragali Radix did not induce any significant abnormalities in liver and kidney functions. ConclusionAstragali Radix demonstrates the potential to significantly improve the gut microbiota environment in patients of newly diagnosed type 2 diabetes with Qi deficiency. The therapeutic effect may contribute to glycemic control， possibly mediated by an elevation in GLP-1 level. These findings may support its further clinical investigations and potential applications.

Objective To conduct bibliometrics and visual analysis of local benign paroxysmal positional verti-go(BPPV)research in the past 20 years for further basic and clinical research in the future.Methods We collected the journal articles on BPPV published between January 1,2004 and December 31,2023 from the databases of CNKI,Wanfang,VIP and Web of Science Core Collection.Multidimensional measurement and visual analysis were carried out using bibliometrics software to identify the research hotspots and new trends in this field,and to deter-mine the cooperation and influence among authors,institutions and journals.Results A total of 717 Chinese papers and 212 SCI papers were utilized for the analysis.The literature in this field gradually increased at an average annual growth rate of 12.8％,among which the Journal of Clinical Otolaryngology Head and Neck Surgery published the most articles(n=167),followed by the Chinese Journal of Otology(n=94)and the Journal of Audiology and Speech Pathology(n=76).The journal with the largest number of SCI publications is Frontiers in Neurology(n=44).In terms of authors and institutions,Zhuang Jianhua published the most Chinese papers,Yang Xu published the most SCI papers,and Shanghai Jiaotong University published the earliest and most SCI papers in this field(n=21).The main research keywords in this realm in recent years involve video head pulse test,vestibular migraine,re-sidual symptoms,residual dizziness and anxiety.The keywords retaining burst intensity to 2023 include video head pulse test,residual dizziness,children,anxiety,and residual symptoms.Conclusion Video head impulse test,re-sidual dizziness,children,anxiety and other aspects are critical areas of ongoing research in BPPV.

Objective:To investigate the association between hearing loss and the type of indoor fuel applications in Chinese middle-aged and elderly people through longitudinal cohort study.Methods:Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS), including adults aged 45 years and older enrolled in 2011, with follow-up for cooking and heating analyses extending to 2018 and 2015, respectively. The study calculated the incidence of hearing loss based on an indoor cooking or heating fuel type and expressed in terms of per 100 person-years. The Cox proportional hazard model was used to assess the association between solid fuel use and hearing loss, and covariates such as gender, education, and economy were controlled. We also analyzed the impact of indoor fuel type and its switching on hearing loss.Results:A total of 6, 772 participants using household fuels for cooking (2011-2018) and 4, 618 for heating (2011-2015) were included. Those using solid fuels for cooking [(58.0±8.2) years] and heating [(58.1±8.5) years] were generally slightly older than that of those who used clean fuels. In the cooking analysis, the overall incidence of hearing loss was higher among solid fuel users compared to clean fuel users (Clean fuel: 2.6 cases per 100 person-years; solid fuel: 3.6 cases per 100 person-years; the difference between the two was statistically significant, P<0.05). However, no significant difference was observed in the heating analysis ( P>0.05). Further classification of fuel-type use revealed that the incidence of hearing loss was the highest among people who had been using solid fuels consistently. Compared to the clean fuel group, the fully adjusted hazard ratio (HR) was 1.5 (95% CI: 1.3-1.7) in the cooking analysis and 1.5 (95% CI: 1.1-2.0) in the heating analysis. Compared with using clean fuels, switching from clean fuels to solid fuels increased the risk of hearing loss both during cooking and heating processes. Conclusion:In the CHARLS database, individuals who use solid fuels for indoor cooking and heating are older than those who use clean fuels. Compared with clean fuel use, the use of solid fuels increases the risk of hearing loss in middle-aged and elderly people. Reducing the use of solid fuels, choosing clean fuels as substitutes for solid fuels, and avoiding the switch from clean fuels to solid fuels will help protect the hearing health of middle-aged and elderly individuals.

The aim of this experiment was to study the effects of different feeding modes on growth performance,blood biochemical indexes and intestinal flora of lactating Holstein male calves.Twenty-four newborn Holstein male calves with body mass of(40.00±1.01)kg and similar day old were selected and randomly divided into four groups of six calves each.The subgroups were low-milk group(LM),high-milk group(HM),high-milk milk replacer feeding group(HMR),and low-milk switching to high-milk milk replacer feeding group(CMR).The results showed that:At 45 d,the body mass of calves in the HM group was significantly higher than that of calves in the other groups(P＜0.05),and at 60 d,the body mass of calves in the HM group was significantly higher than that of calves in the LM &.CMR groups(P＜0.05).At 90 d,the body mass of calves in the LM group was significantly higher than that of calves in the HM group.Throughout the ex-perimental period,the average daily weight gain and average pellet feed intake of calves in the LM group were significantly higher than that of calves in the HM group(P＜0.05).The calf globulin level in the HMR group was significantly higher than that in the LM and HM groups(P＜0.05);the plasma immunoglobulin A level of calves in the HM group was significantly lower than that of calves in the LM and HMR groups(P＜0.05);and the plasma immunoglobulin M level of calves in the HM group was significantly higher than that of calves in the LM and CMR groups(P＜0.05),and HMR group was also significantly higher than that of LM group(P＜0.05);plasma glutathione peroxidase level of calves in HMR group was significantly higher than that of LM group(P＜0.05);plasma malondialdehyde level of calves in LM group was significantly higher than that of calves in HMR and HM groups(P＜0.05),and CMR group was also significantly higher than that of HM group(P＜0.05).Relative abundance of Thermodesulfovibrio was higher in the HM group(P＜0.05),relative abundance of Bacteroidetes in the LM group was significantly higher than that in the HMR and HM groups(P＜0.05),relative abundance of Blautia in the HM group(P＜0.05),and relative abundance of Corynebacterium in the CMR group was significantly higher than that in the LM and HM groups(P＜0.05).In summary,calves in the LM group had better weaning weights and pellet feed intake;calves in the CMR group could compensate for growth by supplemental feeding of milk replacer to obtain more optimal weaning weights and pel-let feed intake;the HMR group proved that milk-free feeding could ensure stable growth of calves;and calves in the HM group had a better pre-lactation growth performance,lower levels of oxida-tive stress,and a healthier fecal flora.

Objective To observe the effects of Bushen Huoxue Prescription on the pathway related to necroptosis of nucleus pulposus cells in a model rabbit of intervertebral disc degeneration;To explore its mechanisms in delaying intervertebral disc degeneration.Methods A intervertebral disc degeneration rabbit model was established using the spinal instability method.Totally 40 model rabbits were randomly divided into model group,ibuprofen group and Bushen Huoxue Prescription low-,medium-and high-dosage groups.Additionally,a normal control group and a sham-operation group were set up,with 8 rabbits in each group.Each treatment groups received the corresponding drugs via gavage for two consecutive weeks.HE staining was used to observe morphology of nucleus pulposus tissue,transmission electron microscopy was used to observe ultrastructure in nucleus pulposus cells,immunohistochemical staining was used to assess the expressions of Aggrecan and Collagen Ⅱ in nucleus pulposus tissue,Western blot was used to detect the expressions of p-RIPK1,p-RIPK3 and p-MLKL protein in nucleus pulposus tissue.Results Compared with the sham-operation group,the model group showed a significant decrease in nucleus pulposus cells,disordered cell arrangement,reduced extracellular matrix,interrupted cell membrane continuity under transmission electron microscopy,organelle swelling,nuclear membrane disruption,partial chromatin loss,and positive expression of Aggrecan and Collagen Ⅱ in nucleus pulposus tissue decreased(P<0.01),while the expressions of p-RIPK1,p-RIPK3 and p-MLKL protein significantly increased(P<0.01).Compared with the model group,the treatment groups showed an increased number of nucleus pulposus cells with orderly arrangement and more extracellular matrix,the ultrastructural damage of the cell membrane,organelle and nucleus in nucleus pulposus cells was partially restored under transmission electron microscopy,the positive expressions of Aggrecan and Collagen Ⅱ significantly increased in Bushen Huoxue Prescription medium-and high-dosage groups and the ibuprofen group(P<0.05,P<0.01),while the expressions of p-RIPK1,p-RIPK3 and p-MLKL protein significantly decreased(P<0.05,P<0.01).Conclusion Bushen Huoxue Prescription may delay intervertebral disc degeneration of the model rabbit by inhibiting the expressions of p-RIPK1,p-RIPK3 and p-MLKL protein in nucleus pulposus cells,and promoting the generation of extracellular matrix components Aggrecan and Collagen Ⅱ.

Objective To investigate the effects of Shuwei Decoction on calcium homeostasis,oxidative stress,mitochondrial autophagy and cell apoptosis of interstitial cells of Cajal(ICC)in functional dyspepsia(FD)rat with liver depression and spleen deficiency syndrome;To discuss its mechanism in the treatment of FD.Methods Totally 50 SD rats were randomly divided into blank group,model group and Shuwei Decoction low-,medium-and high-dosage groups(3.78,7.56,15.34 g/kg),with 10 rats in each group.An improved composite etiology method was used to establish a rat model of FD with liver depression and spleen deficiency syndrome,and rats in the Shuwei Decoction low-,medium-and high-dosage groups were orally administered for 14 days.The gastric antrum was taken,the primary ICC was isolated and cultures,and Fluo-4 AM and Rhod-2 AM staining was used to detect the accumulation of calcium ions in the cytoplasm and mitochondria of ICC,DCFH-DA and MitoSox Red were used to detect the content of reactive oxygen species(ROS)in ICC cytoplasm and mitochondria respectively,immunofluorescence staining and flow cytometry were used to detect mitochondrial autophagy and apoptosis in ICC,Western blot was used to detect ICC mitochondrial LC3 and voltage dependent anion channel(VDAC)1 protein expression.Results Compared with the blank group,the model group exhibited significantly increased accumulation of cytoplasmic and mitochondrial Ca2+and ROS in ICC,the co-localization of TOM20 and LAMP2 markedly increased(P<0.01),along with a significant increase in cell apoptosis rate(P<0.01),the expressions of mitochondrial LC3 Ⅱ/Ⅰ and VDAC1 proteins significantly increased(P<0.01).Compared with the model group,the accumulation of Ca2+and ROS in ICC cytoplasm and mitochondria was significantly decreased in Shuwei Decoction medium-and high-dosage groups(P<0.05,P<0.01),the co-expression of TOMM20 and LAMP2 significantly decreased(P<0.01),the apoptosis rate decreased(P<0.01),and the expressions of mitochondrial LC3 Ⅱ/Ⅰ and VDAC1 proteins significantly decreased(P<0.01).Conclusion Shuwei Decoction may achieve the treatment of FD with liver depression and spleen deficiency syndrome in rats by inhibiting Ca2+overload,reducing the accumulation of ROS and excessive autophagy of mitochondria,inhibiting the apoptosis of ICC and restoring ICC function.

Objective To observe the effects of Bushen Huoxue Prescription on pressure-induced necroptosis in human nucleus pulposus cells and the expressions of RIPK1/RIPK3/MLKL pathway;To explore its potential mechanism in delaying intervertebral disc degeneration.Methods Human primary nucleus pulposus cells were cultured in vitro,and a model of nucleus pulposus cell degeneration was established using continuous load pressure method.After modeling,the nucleus pulposus cells were divided into model group,Bushen Huoxue Prescription group and inhibitor group,blank serum,Bushen Huoxue Prescription containing serum and necroptotic apoptosis inhibitor(Nec-1)intervention were administered,respectively.Normal group nucleus pulposus cells were cultured routinely.AO/EB fluorescence dual staining method was used for detecting cell apoptosis,flow cytometry was used to detect the necroptosis rate of nucleus pulposus cells,Western blot was used to detect the protein expressions of p-receptor interacting protein kinase(RIPK)1,p-RIPK3 and p-mixed lineage kinase domain like protein(MLKL),RT-qPCR was used to detect the mRNA expressions of RIPK1,RIPK3 and MLKL.Results Compared with the normal group,the model group showed more red fluorescence under AO/EB staining of nucleus pulposus cells,which were round and condensed,the necroptosis rate of nucleus pulposus cells increased(P<0.05),the protein expressions of p-RIPK1,p-RIPK3 and p-MLKL increased(P<0.05,P<0.01),while there was no significant difference in RIPK1 mRNA expression(P>0.05),and RIPK3 and MLKL mRNA expression increased(P<0.01).Compared with the model group,Bushen Huoxue Prescription group and the inhibitor group had less red condensed chromatin in the nucleus pulposus cells,Bushen Huoxue Prescription group had a lower rate of necroptosis(P<0.05),while the inhibitor group showed a decreasing trend in necroptosis rate(P>0.05),the protein expressions of p-RIPK1,p-RIPK3 and p-MLKL decreased in Bushen Huoxue Prescription group and the inhibitor group(P<0.05,P<0.01),while there was no significant difference in RIPK1 mRNA expression(P>0.05),and RIPK3 and MLKL mRNA expressions decreased(P<0.01).Conclusion Bushen Huoxue Prescription can alleviate pressure-induced damage to nucleus pulposus cells and inhibit necroptosis,thereby slowing the progression of intervertebral disc degeneration.Its mechanism may be related to the RIPK1/RIPK3/MLKL pathway mediated necroptosis.

Objective·To develop a graph neural network(GNN)-based auxiliary diagnostic model for gallbladder cancer on CT images,and validate its accuracy and feasibility.Methods·From January 2010 to November 2023,1 774 contrast-enhanced CT arterial-phase images were acquired from 887 patients with normal gallbladder,benign gallbladder disease,or gallbladder cancer at Xinhua Hospital and Renji Hospital,Shanghai Jiao Tong University School of Medicine.These images were randomly divided into training and testing sets at a 4∶1 ratio to develop a hybrid GNN-convolutional neural network(CNN)model,named VJK-GIN.The model constructed a pixel-level graph in which each pixel served as a node,and spatial adjacency defined the edges,enabling extraction of local texture features.In the model architecture design,VJK-GIN integrated a three-layer graph isomorphism network,augmented with virtual nodes and jump-knowledge connections;global pooling compressed node features into a graph-level representation,which was classified by a multi-layer perceptron head.Five-fold cross-validation was used to compare VJK-GIN with GNN baselines(GCN,GraphSAGE,GAT,and GIN)and CNN baselines(ViT,EfficientNetV2,and ConvNeXt)in terms of accuracy,precision,recall,F1-score,and area under the receiver operating characteristic curve(AUC).Results·The results of five-fold cross-validation showed that VJK-GIN achieved an F1-score of 0.799(95%CI 0.775?0.823),recall of 0.795(95%CI 0.773?0.817),precision of 0.799(95%CI 0.775?0.823),AUC of 0.812(95%CI 0.792?0.832),and accuracy of 0.773(95%CI 0.748?0.798),surpassing all competing models across every metric.Conclusion·The VJK-GIN model exhibits high stability and accuracy in identifying contrast-enhanced CT images of normal,benign,and malignant gallbladder conditions.