Cuproptosis, a recently discovered form of regulated cell death involving copper ion metabolism, has emerged as a promising approach for tumor therapy. This pathway not only directly eliminates tumor cells but also promotes immunogenic cell death (ICD), reshaping the tumor microenvironment (TME) and initiating robust anti-tumor immune responses. However, translating cuproptosis-based therapies into clinical applications is hindered by challenges, including complex metabolic regulation, TME heterogeneity, and the precision required for effective drug delivery. To address these limitations, nanoparticles offer transformative solutions by providing precise delivery of cuproptosis-inducing agents, controlled drug release, and enhanced therapeutic efficacy through simultaneous modulation of metabolic pathways and immune responses. This review systematically discusses recent advancements in nanoparticle-based cuproptosis delivery systems, highlighting nanoparticle design principles and their synergistic effects when integrated with other therapeutic modalities such as ICB, PTT, and CDT. Furthermore, we explore the potential of cuproptosis-based nanomedicine for personalized cancer treatment by emphasizing strategies for TME stratification and therapeutic optimization tailored to patient profiles. By integrating current insights from metabolic reprogramming, tumor immunotherapy, and nanotechnology, this review aims to facilitate the clinical translation of cuproptosis nanomedicine and significantly contribute to the advancement of precision oncology.

ObjectiveTo investigate the regulatory effect of Changju Zhidong prescription on gut microbiota structure of children with tic disorder（TD）. MethodTwenty-four children with TD who visited the pediatric outpatient clinic of Dongzhimen Hospital of Bejjing University of Chinese Medicine from November 2020 to January 2022 were selected as the observation group， and eight healthy children were selected as the normal group. The observation group was treated with Changju Zhidong prescription for 12 weeks， and the clinical efficacy was observed by Yale global tic severity scale（YGTSS）， traditional Chinese medicine（TCM） syndrome score， and score of TCM symptom evaluation scale for pediatric gastrointestinal tract. Meanwhile， The fecal samples of the observation and normal groups were collected before and after treatment， and 16S rDNA sequencing was used to explore the effects of Changju Zhidong prescription on the distribution of gut microbiota of the children. ResultCompared with the pre-treatment， the YGTSS， TCM syndrome score， and score of TCM symptom evaluation scale for pediatric gastrointestinal tract of the observation group were significantly reduced after 12 weeks of treatment（P<0.05）， Simpson and Pieloue indices in alpha diversity were significantly reduced（P<0.05）. Before treatment， the relative abundance of Streptococcus parasanguini in the observation group was significantly higher than that of the normal group， while the relative abundances of Citrobacter， Lactobacillus， Lacticaseibacillus， Muribaculaceae unclassified， Odoribacter and 7 other bacterial groups were significantly lower than that in the normal group. Compared with the pre-treatment， the observation group showed a significant decrease in Ruminococcus torques group unclassified and Ruminococcus torques group， and a significant increase in Olsenella， Acetivibrio and 4 other bacterial groups. Functional enrichment analysis showed that the main pathways of Changju Zhidong prescription regulating gut microbiota were bacterial secretion system， insect hormone biosynthesis， limonene and pinene degradation， novobiocin biosynthesis， tropane piperidine and pyridine alkaloid biosynthesis. ConclusionThe pathogenesis of children with TD is accompanied by intestinal flora disorders， and Changju Zhidong prescription can improve core and gastrointestinal symptoms， increase the abundance of beneficial and decrease the abundance of harmful gut microbiota in children with TD， and its mechanism may be through the metabolism of terpenoids and polyketides.

Microglia, originating from primitive macrophages in the yolk sac, serves as both immune system defenders and regulators of homeostasis. These cells exhibit two primary polarization states: conventionally activated(M1)and alternatively activated(M2). The polarization of microglia plays a crucial role in influencing inflammatory disorders, metabolic imbalances, and neural degeneration. This process is implicated in various aspects of ocular diseases, especially age-related macular degeneration(AMD), including inflammation, oxidative stress and pathological angiogenesis. The distinct functional phenotypes of microglia impact disease progression and prognosis. Thus, regulating the polarization or functional phenotype of microglia at different stages of AMD holds promise for personalized therapeutic approaches. This comprehensive review outlines the involvement of microglia polarization in both physiological and pathological conditions, emphasizing its relevance in AMD. The discussion underscores the potential of polarization as a foundation for personalized treatment strategies for AMD.

Objective:To construct a novel respiratory syncytial virus (RSV) vaccine based on a recombinant influenza virus vector and evaluate its immune protective effects in mice.Methods:A recombinant H1N1 influenza A virus (IAV) expressing the extracellular domain (Gecto) of RSV A2 G protein was constructed and rescued, named as PR8NAGecto/WSN. After in vitro verification of the Gecto expression and PR8NAGecto/WSN growth kinetics, a single dose of PR8NAGecto/WSN was used to immunize BALB/c mice through intranasal administration to evaluate the efficacy of PR8NAGecto/WSN by assessing humoral (IgG, neutralizing antibody), mucosal (IgA) and cellular immunity (IFN-γ ELISPOT). Four weeks after immunization, the mice were challenged with RSV A2 or RSV B9320 to evaluate the protective effects of PR8NAGecto/WSN by analyzing mouse body weight changes, lung tissue virus titers and pathological changes. Results:A single-dose intranasal immunization with PR8NAGecto/WSN induced robust humoral, mucosal and cellular immunity in mice. Moreover, the mice in the immunized group had lower lung virus loads and mild lung pathological damages following the challenge with RSV A or RSV B subtype as compared with the control group.Conclusions:A single-dose intranasal immunization with PR8NAGecto/WSN induces robust immunity and provide protection against RSV A and B challenges in mice. This study provides new ideas and reference for the development of novel mucosal vaccines against RSV.

Methods:From February 2018 to January 2022, the clinical data of 1 123 patients who underwent Starclose vascular closure device, Angio-Seal and Exoseal vascular occlusion devices and Perclose ProGlide vascular suture device at femoral artery puncture hemostasis after neuro-intervention, in the Department of Interventional Radiology (Eastern District), The First Affiliated Hospital of Zhengzhou University, were retrospectively analyzed. The patients were divided into three groups based on the intervention method: the closure group (Starclose, n=271), the occlusion group (Angio-Seal, n=327 and Exoseal, n=352) and the suture group (ProGlide, n=173). Next, the hemostatic efficacy and complications associated with the three devices were analyzed and compared. Additionally, regression analysis was conducted to identify any relevant factors that may contribute to complications. Results:Three vascular hemostatic devices demonstrated effective hemostasis and the success rate were 92.6% in the closure group (Starclose), 93.4% in the occlusion group (Angio-Seal 93.0% and Exoseal 93.8%) and 89.6% in the suture group (ProGlide). There was no statistically significant difference( χ2=3.026, P=0.388). Single or multiple complications were observed in 102 patients (9.1%), including local oozing (16 cases in the closure group, 39 cases in the occlusion group, 13 cases in the suture group), local hematoma (14 cases in the closure group, 31 cases in the occlusion group, 11 cases in the suture group), pseudoaneurysm (13 cases in the closure group, 35 cases in the occlusion group, 10 cases in the suture group), local infection (2 cases in the closure group, 3 cases in the occlusion group, 1 case in the suture group). There were no statistically significant differences ( P>0.05). Moreover, serious complications such as femoral artery occlusion, embolus shedding and permanent nerve injury weren′t observed in the three groups. Multivariate logistic regression analysis revealed that overweight ( OR=1.562,95% CI 1.023—2.385, P=0.039), femoral artery with calcified plaque ( OR=1.934,95% CI 1.172-3.189, P=0.010), combined use of multiple antiplatelet drugs ( OR=1.769,95% CI 1.103—2.839, P=0.018), use of an 8F sheath( OR=2.824,95% CI 1.406—5.671, P=0.004) and the operator′s proficiency ( OR=0.508,95% CI 0.328—0.788, P=0.002) were the independent factors influencing complications, of which the first four were identified as risk-promoting factors for complications while the operator′s rich experience and high proficiency were the protective factors. Conclusions:Three hemostatic devices demonstrate effective hemostasis and comparable rates of complications at femoral artery puncture hemostasis after neuro-intervention. Overweight, femoral artery with calcified plaque, combined use of multiple antiplatelet drugs, use of an 8 F sheath and the operator′s proficiency were independent factors influencing complications.Ojective:To investigate the efficacy and complications associated with vascular suture, closure and occlusion devices at femoral artery puncture hemostasis after neuro-intervention.

To investigate the dynamic homing process and characteristics of macrophages in different organs of immune-mediated aplastic anemia (AA) model mice. Macrophages in donor lymph nodes were sorted by magnetic beads and labeled with PKH67. After modeling according to the preparation method of the AA model, peripheral blood rountine analysis, bone marrow biopsy and HE staining results were analyzed to verify the modeling effect. On days 4, 8, and 12 of modeling, the bone marrow, spleen, and lymph node mononuclear cells were collected, and dynamic changes of PKH67-labeled macrophages in donor mice were analyzed by flow cytometry. In this study, dynamic changes in PKH67-labeled macrophages in the pathogenesis of AA model mice were explored. Macrophages in donor mice homed to the lymph nodes, expanding and differentiating in the lymph nodes, and finally transported to the bone marrow and spleen. Through proteomics mass spectrometry analysis, the related immune inflammatory response pathway of macrophages involved in the activation of the AA bone marrow microenvironment was preliminarily revealed, which provides a basis for the pathological macrophages involved in the pathogenesis of AA model mice.

Objective:To systematically evaluate the risk of bias and applicability of risk prediction models for the progression of diabetic nephropathy (DN) .Methods:A systematic search was conducted in CNKI, CBMdisc, Wanfang, VIP, PubMed, Web of Science, Embase, and CINAHL for literature related to DN progression prediction models, with a search timeline up to April 30, 2023. Two researchers independently screened the literature and extracted data according to a checklist for key assessments of prediction model studies and the PROBAST tool for assessing risk of bias in prediction models.Results:A total of nine articles encompassing 15 models were included. Of these, eight studies were retrospective study, and one was a randomized controlled trial. The area under the receiver operating characteristic curve ( AUC) for these models ranged from 0.626 to 0.986. Three studies conducted external validation, and seven studies conducted internal validation. Commonly repeated predictive factors included eGFR, cystatin C, and glycated hemoglobin (HbA1c). While the overall applicability of the models was good, methodological issues such as inappropriate data acquisition, selection of predictive factors, and neglect of model performance evaluation contributed to a certain risk of bias. Conclusions:The current DN progression risk prediction models demonstrate good discrimination and applicability. However, most models lack comprehensive calibration assessments and exhibit methodological flaws. Future research should focus on developing models with better applicability and lower bias, coupled with effective internal and external validation.

Nerve regeneration in adult mammalian spinal cord is poor because of the lack of intrinsic regeneration of neurons and extrinsic factors - the glial scar is triggered by injury and inhibits or promotes regeneration. Recent technological advances in spatial transcriptomics (ST) provide a unique opportunity to decipher most genes systematically throughout scar formation, which remains poorly understood. Here, we first constructed the tissue-wide gene expression patterns of mouse spinal cords over the course of scar formation using ST after spinal cord injury from 32 samples. Locally, we profiled gene expression gradients from the leading edge to the core of the scar areas to further understand the scar microenvironment, such as neurotransmitter disorders, activation of the pro-inflammatory response, neurotoxic saturated lipids, angiogenesis, obstructed axon extension, and extracellular structure re-organization. In addition, we described 21 cell transcriptional states during scar formation and delineated the origins, functional diversity, and possible trajectories of subpopulations of fibroblasts, glia, and immune cells. Specifically, we found some regulators in special cell types, such as Thbs1 and Col1a2 in macrophages, CD36 and Postn in fibroblasts, Plxnb2 and Nxpe3 in microglia, Clu in astrocytes, and CD74 in oligodendrocytes. Furthermore, salvianolic acid B, a blood-brain barrier permeation and CD36 inhibitor, was administered after surgery and found to remedy fibrosis. Subsequently, we described the extent of the scar boundary and profiled the bidirectional ligand-receptor interactions at the neighboring cluster boundary, contributing to maintain scar architecture during gliosis and fibrosis, and found that GPR37L1_PSAP, and GPR37_PSAP were the most significant gene-pairs among microglia, fibroblasts, and astrocytes. Last, we quantified the fraction of scar-resident cells and proposed four possible phases of scar formation: macrophage infiltration, proliferation and differentiation of scar-resident cells, scar emergence, and scar stationary. Together, these profiles delineated the spatial heterogeneity of the scar, confirmed the previous concepts about scar architecture, provided some new clues for scar formation, and served as a valuable resource for the treatment of central nervous system injury.
Mice ; Animals ; Gliosis/pathology* ; Cicatrix/pathology* ; Spinal Cord Injuries ; Astrocytes/metabolism* ; Spinal Cord/pathology* ; Fibrosis ; Mammals ; Receptors, G-Protein-Coupled

Objective:To evaluate the radiation shielding performance for a novel self-shielded ZAP-X radiotherapy system used for intra-cranial and neck treatments. The present evaluation was performed according to the relevant Chinese national standards and the clinical placement of the radiotherapy system in an unshielded treatment room.Methods:The radiation source of the ZAP-X was a 3 MV linear accelerator. A total of 33 detection sites were selected surrounding the self-shielded system at 1.3, 2.3 and 3.3 m away from the periphery of the equipment. The maximum ambient dose equivalent rate in each irradiation condition was measured accordingly. A commonly used clinical treatment plan was selected to simulate the treatment process. During the delivery of this treatment plan, the cumulative doses of these 33 sites were measured, separately. The applicable current radiation protection standard for radiotherapy in China was chosen to evaluate the radiation shielding performance of the system.Results:According to the measurement result of the ambient dose equivalent rates along the aforementioned perimeter lines, a suggestion was put forward to redefine the existing 1 m controlled area by determining the distance at which the instantaneous dose rate of 10 μSv/h will not be exceeded. This is to meet the requirements of the Chinese standard GBZ 121-2020.Conclusions:According to the existing Chinese national radiation protection standards, the self-shielded radiotherapy system in the unshielded treatment room has the clinical applicability in China. But for such a novel self-shielded system, the corresponding performance testing and radiation protection standards shall be formulated.

Objective:To explore the stent apposition and safety of Neuroform EZ and Enterprise 2 stents in treatment of symptomatic intracranial atherosclerotic stenosis (sICAS), and their influencing factors for in-stent restenosis.Methods:A total of 143 sICAS patients treated by Enterprise 2 stents (implanted 143 Enterprise 2 stents, E2 group) and 202 patients treated by Neuroform EZ stents (implanted 202 Neuroform EZ stents, EZ group) were selected from Department of Interventional Radiology, First Affiliated Hospital of Zhengzhou University from January 2017 to January 2022. Stent apposition was evaluated based on reconstructive images of high-resolution flat detector CT. The complications 30 d after surgery and during 6-24 months of follow-up were recorded. Based on DSA or CTA 6 months after surgery, the patency of the two stents was evaluated. Univariate analysis and multivariate Logistic regression analysis were used to determine the independent risk factors for in-stent restenosis.Results:(1) Forty-nine patients had incomplete stent apposition (ISA) after stent release: 24 patients with ISA in E2 group (16.8%, 24/143; 15 of type I and 9 of type II) and 25 with ISA in the EZ group (12.4%, 25/202, 11 of type I and 14 of type II) were found, without statistical difference ( χ 2=1.334, P=0.248); however, ISA incidence in the EZ group (19.0% and 10.3%) was significantly lower than that in the E2 group (41.4% and 25.6%) when the diameter ratio of anterior and posterior vessels of the stenosis lesions≥1.30 or the angle of stent≥75° ( χ 2=4.228, P=0.040; χ 2=4.531, P=0.033). (2) Within 30 d of stenting, 17 patients developed neurological dysfunction-related complications: 8 patients in EZ group and 9 in E2 group were noted, without significant difference ( P=0.324). Clinical follow-up was obtained in 317 patients, and 20 patients developed long-term stroke associated with responsible lesion vessels: 12 patients in EZ group and 8 in E2 group were noted, without significant difference ( P=0.995). (3) Totally, 298 patients received imaging follow-up 6 months after surgery, and 65 patients developed in-stent restenosis: 36 patients in EZ group and 29 in E2 group were noted, without significant difference ( χ 2=0.309, P=0.578). Multivariate Logistic regression analysis showed that diabetes ( OR=2.714, 95% CI: 1.437-5.126, P=0.002), stent apposition ( OR=3.435, 95% CI: 1.223-9.652, P=0.019), lesion stenosis length ( OR=1.176, 95% CI: 1.065-1.300, P=0.001) and immediate postoperative residual stenosis ( OR=1.038, 95% CI: 1.004-1.074, P=0.029) were independent influencing factors for in-stent restenosis. Conclusions:Enterprise 2 and Neuroform EZ stents have high stent apposition and safety in sICAS treatment, but in cases with large diameter ratio of the anterior and posterior vessels of the stenosis lesions (diameter ratio≥1.30) or large angle of the stent (≥75°), Neuroform EZ stent has better stent apposition. Patients with diabetes, ISA, long lesion stenosis or high residual stenosis may trend to have in-stent restenosis.