BACKGROUND:Hippocampal injury caused by aortic coarctation has been poorly studied,and combined detection of tumor necrosis factor α,nuclear factor κB and ionized calcium binding adaptor molecule-1 expression in aortic dissection has not been reported.OBJECTIVE:To observe histomorphologic changes in the hippocampus of a mouse model of aortic dissection and investigate the expression and significance of tumor necrosis factor alpha,nuclear factor kappaB and ionized calcium binding adaptor molecule-1 in the hippocampus of aortic dissection mice.METHODS:Sixteen healthy 3-week-old male C57BL/6 mice were randomly divided into two groups:control group and aortic dissection group,with eight mice in each group.In the aortic dissection group,mice were given β-aminopropionitrile monofumarate as drinking water for 4 weeks,and the angiotensin Ⅱ microinfiltration pump was then implanted to establish an animal model of aortic dissection.Mice in the control group were given normal diet and water.After the model was established,the maximum diameter of the ascending aorta was measured,hematoxylin-eosin staining and EVG staining were performed to evaluate the model formation rate,and the levels of inflammatory factors tumor necrosis factor α and interleukin 6 in serum were detected by enzyme-linked immunosorbent assay.The hippocampus was dissected and stained with hematoxylin-eosin to observe the pathological changes of the hippocampus in brain sections.The protein expression of tumor necrosis factor α,nuclear factor κB and ionized calcium binding adaptor molecule-1 was detected by western blot analysis.RESULTS AND CONCLUSION:(1)Compared with the control group,the maximum diameter of the ascending aorta in the aortic dissection group was significantly enlarged.(2)Hematoxylin-eosin staining of the aorta showed obvious thickening of the middle aorta and destruction and disorder of the aortic wall structure in mice.Neurons in the CA1 and CA3 regions of mice were sparsely arranged,reduced in size,and showed pyknosis with deeply stained nuclei.(3)Serum levels of inflammatory factors tumor necrosis factor α and interleukin 6 were increased in the aortic dissection group compared with the control group(P＜0.01).(4)The expression levels of tumor necrosis factor α,nuclear factor κB,phosphorylated nuclear factor κB,and ionized calcium binding adaptor molecule-1 in the hippocampus were increased in the aortic dissection group compared with the control group(P＜0.05).To conclude,microglial activation and increased expression of tumor necrosis factor α and nuclear factor κB may be involved in hippocampal neuron injury in aortic dissection mice.

Chronic obstructive pulmonary disease （COPD）， as one of the three major causes of death， is a complex systemic disease with high prevalence， high mortality， high disability， frequent acute exacerbations， and a variety of pulmonary complications. The pathogenesis is complex. Western medicine has no effective specificity scheme for a complete cure. However， multiple-component and multiple-target characteristics of traditional Chinese medicine （TCM） demonstrate significant advantages in COPD treatment through multi-link， multi-pathway， and multi-mechanism intervention. Therefore， exploring the essence of COPD pathogenesis and discovering effective TCM treatment drugs through the application of TCM principles and prescriptions is a key focus of modern research. Animal models are of paramount importance in medical research. It is the first consideration to select appropriate animals， adopt reasonable modeling methods to replicate stable animal models that closely resemble the clinical manifestations and pathophysiological characteristics of COPD， and use appropriate evaluation methods to determine the success of COPD animal models in experimental research. The core of experimental research lies in observing the intervention effect of TCM on COPD animal models， exploring the specific pathways and regulatory mechanisms of TCM on COPD disease， and finding TCM monomers， single herbs， and TCM formulas with definite curative effects. At present， animal model research on COPD mainly involves model establishment， model evaluation， efficacy observation， mechanism exploration， and other aspects. In recent years， there has been no systematic organization， update， and reflection on the relevant research on TCM intervention in COPD animal models. This study reviewed the selection of animals for the COPD model， methods for establishing COPD animal models， model evaluation methods， and the intervention effects of TCM on COPD animal models. It aims to grasp the current research status and identify existing problems for further improvement， in order to provide evidence and support for scientific research and clinical treatment of COPD.

Chronic obstructive pulmonary disease （COPD）， as one of the three major causes of death， is a complex systemic disease with high prevalence， high mortality， high disability， frequent acute exacerbations， and a variety of pulmonary complications. The pathogenesis is complex. Western medicine has no effective specificity scheme for a complete cure. However， multiple-component and multiple-target characteristics of traditional Chinese medicine （TCM） demonstrate significant advantages in COPD treatment through multi-link， multi-pathway， and multi-mechanism intervention. Therefore， exploring the essence of COPD pathogenesis and discovering effective TCM treatment drugs through the application of TCM principles and prescriptions is a key focus of modern research. Animal models are of paramount importance in medical research. It is the first consideration to select appropriate animals， adopt reasonable modeling methods to replicate stable animal models that closely resemble the clinical manifestations and pathophysiological characteristics of COPD， and use appropriate evaluation methods to determine the success of COPD animal models in experimental research. The core of experimental research lies in observing the intervention effect of TCM on COPD animal models， exploring the specific pathways and regulatory mechanisms of TCM on COPD disease， and finding TCM monomers， single herbs， and TCM formulas with definite curative effects. At present， animal model research on COPD mainly involves model establishment， model evaluation， efficacy observation， mechanism exploration， and other aspects. In recent years， there has been no systematic organization， update， and reflection on the relevant research on TCM intervention in COPD animal models. This study reviewed the selection of animals for the COPD model， methods for establishing COPD animal models， model evaluation methods， and the intervention effects of TCM on COPD animal models. It aims to grasp the current research status and identify existing problems for further improvement， in order to provide evidence and support for scientific research and clinical treatment of COPD.

ObjectiveTo observe the effects of Jiangtang No. 3 prescription on inflammatory pathways and insulin resistance-related indicators in rats with type 2 diabetes mellitus （T2DM）， and to elucidate its molecular mechanism in combating diabetes. MethodsA T2DM rat model was established using a high-fat diet combined with intraperitoneal injection of streptozotocin （STZ）. Successfully modeled rats were randomly assigned to the model group， metformin group， and low-， medium-， and high-dose Jiangtang No. 3 prescription groups， and a normal group was also set. Daily gavage was administered for 8 weeks as follows： metformin at 0.1 g·kg^-1·d^-1， Jiangtang No. 3 prescription granules at 1.62， 3.24， 6.48 g·kg^-1·d^-1 for the respective dose groups， and sterile water for the normal and model groups. Rat body weight， fasting blood glucose （FBG）， oral glucose tolerance test （OGTT）， and insulin tolerance test （ITT） were measured. After drug intervention， enzyme-linked immunosorbent assay （ELISA） was used to determine serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL）， high-density lipoprotein cholesterol （HDL）， non-esterified fatty acids （NEFA）， interleukin （IL）-1β， IL-18， and insulin （INS）. Hematoxylin-eosin （HE） staining was used to observe morphological changes in adipose tissue. Real-time quantitative PCR was used to detect the mRNA expression of Toll-like receptor 4 （TLR4）， nuclear factor-κB （NF-κB）， NOD-like receptor protein 3 （NLRP3）， Caspase-1， IL-1β， IL-18， and gasdermin D （GSDMD） in adipose tissue. Western blot was used to measure the corresponding protein expression levels. ResultsCompared with the model group， Jiangtang No. 3 prescription groups exhibited significantly increased body weight （P<0.05， P<0.01）， significantly reduced FBG （P<0.05， P<0.01）， significant reductions in TC， TG， NEFA， and LDL （P<0.05， P<0.01）， and a significant increase in HDL （P<0.01）. Serum levels of inflammatory mediators IL-1β and IL-18 were significantly decreased （P<0.01）， the homeostatic model assessment of insulin resistance （HOMA-IR） index was significantly reduced （P<0.05， P<0.01）， and adipose tissue pathology was improved. The protein expression levels of TLR4， NF-κB， NLRP3， Caspase-1， IL-1β， IL-18， and GSDMD were markedly decreased （P<0.05， P<0.01）， and the mRNA expression levels of these indicators were also significantly downregulated （P<0.05， P<0.01）. Some effects were superior to those of the positive control drug metformin， and certain indicators exhibited dose-dependent improvements. ConclusionT2DM rats display significant inflammatory responses， disordered glucose and lipid metabolism， and insulin resistance. Jiangtang No. 3 prescription effectively suppresses inflammatory mediators， improves glucose and lipid metabolism and insulin resistance， and ameliorates pathological changes in adipose tissue. Its mechanism may be related to the regulation of the TLR4/NF-κB/NLRP3 signaling pathway in visceral adipose tissue， thereby influencing downstream inflammatory mediators.

Epstein-Barr virus-positive diffuse large B-cell lymphoma, not otherwise specified(EBV+DLBCL, NOS) is a lymphoma subtype characterized by distinct biological features and a poor prognosis. This disease is frequently complicated by cytokine release syndrome(CRS), a severe condition closely linked to its intrinsic biological characteristics, which is receiving increasing clinical attention. This article systematically elaborates on the latest advances in the molecular mechanisms, diagnostic grading, and therapeutic strategies for EBV+ DLBCL, NOS complicated by CRS, aiming to provide a more comprehensive evidence-based foundation for clinical decision-making.

AIM: To investigate the diagnostic and prognostic value of differential expression of Cyclin D1 and p53 in eyelid tumors.METHODS: This retrospective study enrolled patients who underwent surgical resection for eyelid tumors at our hospital between March 2018 and March 2023. Participants were categorized into benign and malignant groups based on tumor characteristics. Clinical data were collected. Genetic data for eyelid tumors were obtained from the GEO database, and differential gene analysis, including volcano plot visualization and KEGG pathway enrichment analysis, was performed using the Sangerbox 3.0 platform. Immunohistochemistry was used to detect the expression levels of Cyclin D1, p53, and BAX in tissue samples. Correlations with clinical features were analyzed using Spearman analysis, and prognostic factors were identified via Logistic regression analysis.RESULTS: This study included 69 patients with eyelid tumors(78 eyes), categorized into a benign group(37 patients, 41 eyes)and a malignant group(32 patients, 37 eyes)based on tumor characteristics. There were significant differences between the two groups in histological subtype, TNM staging, vascular invasion, differentiation status, and local infiltration(all P<0.05). Among benign tumors: pigmented nevi in 11 eyes(27%), hemangiomas in 9 eyes(22%), squamous cell papillomas in 5 eyes(12%), epidermoid cysts in 5 eyes(12%), seborrheic keratoses in 4 eyes(10%), neurofibromas in 3 eyes(7%), and both calcifying epithelioma and xanthelasma in 2 eyes each(5%); among malignant tumors: basal cell carcinoma in 18 eyes(49%), meibomian gland carcinoma in 8 eyes(22%), squamous cell carcinoma in 5 eyes(14%), sebaceous gland carcinoma in 4 eyes(11%), lymphoma and malignant melanoma each in 1 eye(3%). At the follow-up cutoff date of March 2025, the 2-year survival rate in the benign group(95%)was significantly higher than that in the malignant group(78%; P<0.05). Bioinformatics analysis identified 4 103 differentially expressed genes, including Cyclin D1, p53, and BAX, which were predominantly involved in pathways such as the p53 signaling pathway and calcium-related signaling. Spearman analysis revealed that local invasion(rs=0.71, P<0.05)and TNM stage(rs=0.73, P<0.05)correlated with Cyclin D1 expression; local invasion(rs=0.76, P<0.05)and histological subtype(rs=0.65, P<0.05)correlated with p53 expression. Logistic regression results indicated that Cyclin D1, p53, TNM staging, and local invasion were prognostic risk factors. ROC curve analysis demonstrated that the combined detection of these four indicators had the highest predictive value for prognosis(AUC=0.83).CONCLUSION: High expression of cyclin D1 and p53 serves as molecular markers for distinguishing benign from malignant eyelid tumors and assessing prognosis. Combined detection of these markers with TNM staging and local invasion demonstrates high predictive value for prognosis.

Objective To investigate the effect of ubiquitin specific peptidase 22 (USP22) on the occurrence and development of esophageal squamous cell carcinoma (ESCC) under hypoxic conditions, and its regulatory relationship with hypoxia-inducible factor-1α (HIF-1α). Methods Western blotting and quantitative polymerase chain reaction were used to detect the differences in USP22 protein and mRNA expression between normal esophageal epithelial cells HEEC and ESCC cell lines KYSE30, KYSE150, EC9706, and TE-1 under normoxic (5% CO2, 20% O2, 75% N2) and hypoxic (5% CO2, 1% O2, 94% N2) conditions. By transfecting USP22 plasmid or siUSP22, ESCC cells were divided into a normoxia control group, a normoxia+USP22 group, a normoxia+siUSP22 group, a hypoxia control group, a hypoxia+USP22 group, and a hypoxia+siUSP22 group. The proliferation and migration abilities of cells in each group were detected. The expression of USP22 and HIF-1α under hypoxic conditions after up-regulating or down-regulating USP22 was detected, and their regulatory relationship was verified. The interaction between USP22 and HIF-1α was verified by co-immunoprecipitation (Co-IP) technique. Results Compared with HEEC cells, the expression of USP22 in ESCC cells was significantly increased (P<0.05). Up-regulation of USP22 expression promoted the proliferation and migration of ESCC cells, while silencing USP22 inhibited the proliferation and migration of ESCC cells (P<0.05). Under hypoxic conditions, the expression of USP22 and HIF-1α increased, and with the up-regulation of USP22 expression, the expression of HIF-1α also significantly increased (P<0.05). Co-IP experiment confirmed the binding between USP22 and HIF-1α. Conclusion Up-regulation of USP22 expression promotes the proliferation and migration of ESCC cells. Hypoxia microenvironment can induce the increase of USP22 expression in ESCC. USP22 may participate in the regulation of the occurrence and development of ESCC by directly binding to HIF-1α.

Pediatric acute liver failure (PALF) is a rare and critical clinical syndrome with a poor prognosis. Its etiology is complex, with a significant proportion of cases having remained classified as indeterminate or cryptogenic PALF. With the application of high-throughput sequencing technologies, a spectrum of disorders caused by specific genetic metabolic defects and characterized by stress-sensitive Recurrent acute liver failure (RALF) has been gradually unveiled, collectively termed Infantile liver failure syndrome (ILFS). Although the molecular mechanisms underlying the subtypes ILFS1, ILFS2, and ILFS3 differ by involving aminoacyl-tRNA synthetase defects, vesicular transport disorders, and autophagy abnormalities, respectively, they share a common clinical phenotype of RALF triggered by fever or infection. This article has systematically reviewed the clinical phenotypic spectrum, molecular genetic characteristics, differential diagnosis strategies, and therapeutic advances of the three ILFS subtypes, with the goal of improving early clinical recognition and precise intervention, and providing an important reference for evaluating the prognosis of different subtypes.
Humans ; Liver Failure, Acute/therapy* ; Infant ; Diagnosis, Differential

p21 (encoded by the CDKN1A gene) is a critical cell cycle regulatory protein endowed with versatile biological functions. In various sex hormone-related cancers, p21 exhibits a paradoxical dual role, capable of both inhibiting tumorigenesis and promoting cancer progression, exerting dual, often opposing, effects on cellular fate that are dictated by the specific context. The clinical targeting of p21 remains elusive, largely due to its functionally pleiotropic and context-dependent nature within intricate regulatory networks. During the initial, hormone-dependent phase of cancers like breast and prostate cancer, p21 expression and activity are largely governed by the transcriptional programs of estrogen or androgen receptor signaling. This hormonal regulation contributes to the control of tumor cell proliferation and underpins the initial efficacy of endocrine therapies. In contrast, as these diseases advance to late stages or evolve into non-hormone-dependent subtypes—exemplified by castration-resistant prostate cancer (CRPC) and specific forms of triple-negative breast cancer (TNBC)—these conventional hormonal control mechanisms often become dysfunctional or are entirely bypassed. This fundamental transition creates a critical therapeutic void, highlighting the urgent need to identify and exploit alternative molecular pathways to effectively target p21’s function. Promising strategies may include the precise modulation of its upstream transcriptional regulators, downstream effector proteins, or the intersecting parallel signaling networks that critically influence its activity. This review provides a systematic synthesis of the intricate and interconnected mechanisms that underpin the dual effects of p21 in sex hormone-related tumors. These mechanisms are categorized into three core, interrelated functional domains. (1) cell cycle regulation: p21 executes its canonical tumor-suppressive role by binding to and inhibiting cyclin-dependent kinases (CDKs) and by directly interacting with proliferating cell nuclear antigen (PCNA), thereby inducing cell cycle arrest, predominantly at the G1/S checkpoint; (2) apoptosis modulation: p21 exerts a highly context-dependent influence on programmed cell death, functioning either as a pro-apoptotic agent under severe genotoxic stress or as a pro-survival factor by inhibiting apoptosis through interactions with proteins like Bcl-2; (3) hormonal and signaling crosstalk: p21 is an integral node within broader cellular networks, engaging in direct physical interactions with hormone receptors(e.g., AR, ER) and participating in complex feedback loops with key oncogenic pathways, including PI3K/AKT, MAPK/ERK, and p53. Critically, the role of p21 is not static but highly dynamic. It can undergo a functional switch from tumor-suppressive to tumor-promoting in response to therapeutic pressures, metabolic alterations, or evolving tumor microenvironment cues. These adaptive shifts are frequently implicated in the development of therapy resistance and disease recurrence, particularly in advanced, hormone-resistant cancers. By synthesizing these insights, this review aims to establish a coherent theoretical framework to guide the future development of novel therapeutic strategies that target the p21 pathway. It underscores the necessity of moving beyond a simplistic, binary view of p21 and emphasizes the forthcoming challenges, such as the discovery of reliable biomarkers to predict its functional state and the rational design of context-specific pharmacological modulators to selectively harness its therapeutic potential.

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.