Ningxia Hui Autonomous Region Peoples Hospital

Nanozymes represent a class of functional nanomaterials that exhibit catalytic or enzyme-like activities and imaging capabilities, making them potential candidates for addressing biomedical challenges in diagnostics, therapeutics, and potential disease prevention. Moreover, their unique advantages, including stability under harsh physiological conditions, tunable catalytic behaviors, and facile surface modification, have established nanozymes as promising platforms for drug delivery, capable of precise payload loading, targeted release, and stimuli-responsive activation. Notably, their inherent enzyme-mimicking characteristics and imaging properties enable the integration of diagnostic and therapeutic functions within a single vector. This review systematically examines the catalytic mechanisms and property modulation strategies of nanozymes, while highlighting their significant advantages and recent breakthroughs in intelligent drug delivery applications. We comprehensively summarize cutting-edge advances in nanozyme-based delivery systems for managing inflammations, infections, and malignancies, and other conditions. Additionally, we also discuss nanozymes serve as contrast agents for magnetic resonance imaging (MRI), photoacoustic imaging, and computed tomography (CT) to achieve imaging-guided diagnosis. Building upon this foundation, designing smart drug carriers based on nanozymes with the potential to support future clinical translation of multifunctional drug delivery systems. This review is expected to provide insights into the advancements in nanozymes for enhanced applications in the biomedical field.

A 6-year-old male pediatric patient with Malan syndrome presented to the Ningxia Fye Hospital of Ningxia Hui Autonomous Region People's Hospital with low vision in both eyes. The patient had a history of night blindness and exhibited bilateral enophthalmos. Best-corrected visual acuity was 0.2 in both eyes, with no improvement after refractive correction. Both direct and consensual pupillary light reflexes were sluggish. Fundus examination revealed bilateral pale optic discs, with a cup-to-disc ratio of approximately 0.6. Optical coherence tomography revealed marked thinning of the peripapillary retinal nerve fiber layer and the macular ganglion cell and inner plexiform layer in both eyes. The field electroretinogram indicated moderately impaired rod and cone function bilaterally, while the flash visual evoked potential suggested bilateral optic nerve atrophy. These findings indicate that children with Malan syndrome require comprehensive ophthalmic evaluation, routine assessment of the optic nerve status across all age groups, and timely implementation of appropriate interventions to maximize residual visual function and improve quality of life and social adaptability.

AHNAK2 is acknowledged to function as an oncoprotein that enhances the invasive and metastatic potential of tumor cells in multiple types of malignancy. Nevertheless, its specific role in gastric cancer (GC) remains unclear. Immunohistochemistry (IHC) was used to examine AHNAK2 expression in matched GC tissues and paracancerous tissues, Clinical and pathological data was gathered for the purpose of investigate the association of AHNAK2 expression and prognosis in patients with GC. AHNAK2 protein expression and location was examined using Western blotting (WB) and immunofluorescence (IF). The effects of AHNAK2 knockdown on the malignant biological behavior of GC cells were evaluated. Transcriptome sequencing and WB analyses were conducted to explore the potential molecular mechanisms underlying AHNAK2-mediated regulation of GC progression. WB, IF, and IHC analyses demonstrate that AHNAK2 expression is upregulated in GC, and patients with high AHNAK2 protein expression exhibit poorer overall survival rates. Knockdown of AHNAK2 results in reduced invasive, proliferative, and migratory capacities of GC cells, along with increased apoptosis. RNA sequencing and WB analysis further confirmed that AHNAK2 exacerbates the malignant phenotypic characteristics of GC through activation of the Wnt/β-catenin pathway. AHNAK2 may serve as a new prognostic biomarker and a prospective therapeutic target in GC.

BackgroundEndometriosis (EM) is associated with immune dysregulation, while dysfunction of natural killer (NK) cells is regarded as a key mechanism underlying immune escape and the persistent growth of ectopic lesions.MethodThis study used single‐cell RNA sequencing (scRNA‐seq) on lesions from three patients with EM and on three normal endometrium samples and integrated these data with three bulk RNA‐seq datasets from GEO (GSE105765, GSE7305, and GSE6364). Seurat, Monocle, limma, least absolute shrinkage and selection operator (LASSO), and support vector machine recursive feature elimination (SVM‐RFE) were used for cell clustering, trajectory inference, differential expression analysis, and feature selection. Immune‐cell composition and pathway activity were evaluated with CIBERSORT and GSVA. Gene expression was validated by qPCR, and cell migration and invasiveness were assessed using wound healing and Transwell assays.ResultscRNA‐seq resolved 11 clusters assigned to eight major cell types. By integrating pseudotime features with bulk data, 20 differentially expressed genes (DEGs) were prioritized, and machine‐learning analyses identified three key genes: granulysin (GNLY), perforin 1 (PRF1), and ENTPD1. The three‐gene model showed good discrimination in the training set and two external validation cohorts (AUCs 0.84, 0.67, and 0.77, respectively). GNLY and PRF1 were predominantly expressed in NK cells and CD8+ T cells and correlated with activation signatures, whereas ENTPD1 was highly expressed in endometrial stromal cells and enhanced their migratory and invasive capacities. ENTPD1 may contribute to disease via adenosine signaling–mediated modulation of NK–cell function. In silico analyses also nominated candidate agents targeting this pathway, including resveratrol, ibuprofen, and danazol.ConclusionThis study highlights the central role of NK–cell dysfunction in EM pathogenesis and proposes GNLY, PRF1, and ENTPD1 as potential molecular diagnostic biomarkers. Notably, ENTPD1 appears to have dual functions, including immunomodulation and promotion of stromal cell migration, which promotes lesion formation. These findings provide a mechanistic rationale and actionable targets for earlier screening and targeted therapy in EM.

Skeletal muscle atrophy is a debilitating condition that significantly affects patients’ quality of life and prognosis, yet its underlying mechanisms remain poorly understood. Here, we identify Optineurin (OPTN) as an active regulator for maintenance of muscle homeostasis during muscle atrophy. Knockdown (KD) of Optn induces muscle atrophy, while overexpression of Optn alleviated dexamethasone-induced muscle atrophy in mice. Mechanistically, we for the first time identified Junction plakoglobin (JUP) as a novel interacting partner of OPTN. OPTN alleviates muscle atrophy in a JUP-dependent manner, corroborating JUP as the downstream effector of OPTN-mediated muscle atrophy. RNA-seq analysis revealed that PI3K-AKT pathway is markedly downregulated in Optn-KD muscle, and pharmacological activation of PI3K-AKT pathway effectively rescued muscle atrophy in Optn-KD mice. We further show that OPTN coordinates the interaction between JUP and PI3-Kinase p85 in muscle, promoting activation of the PI3K-AKT pathway. Collectively, our study proposed a conceptual novelty that OPTN-JUP axis mediated activation of the PI3K-AKT pathway during muscle atrophy. These findings offer new insights into the mechanisms of muscle atrophy and suggest potential therapeutic strategies for this condition.

ObjectiveTo investigate the potential crosstalk between TrkA, the high-affinity nerve growth factor receptor (NGFR), and cyclin-dependent kinase 5 (CDK5) in the pathogenesis of diabetic kidney disease (DKD). Furthermore, this study aims to evaluate the therapeutic potential of targeting TrkA in DKD.MethodsThe renal transcriptional profiles were evaluated in db/db mice and controls. High glucose (HG) stimulation was used to induce an in vitro model of podocyte injury. The therapeutic effects of the TrkA inhibitor GW441756 were evaluated in both DKD model mice and HG-stimulated podocytes.ResultsRNA sequencing detected NGFR upregulation in db/db mice. Phosphorylation of TrkA (Tyr490) increased in HG-stimulated podocytes, and TrkA overexpression aggravated HG-induced injury. Mechanistically, TrkA activation functionally links to CDK5 in the pathogenesis of DKD. Specifically, phosphorylation of TrkA at Tyr490 triggers the activation of the downstream ERK/EGR1 pathway. The accumulation of p35 activated CDK5, resulting in an inflammation-mediated podocyte injury. The TrkA inhibitor reduced its phosphorylation and attenuated downstream inflammation.ConclusionOur findings suggest a TrkA-p35/CDK5 axis contributes to podocyte inflammation and injury, connecting neurotrophic signalling and renal metabolic inflammation through a novel mechanism. This work indicates that TrkA represents a potential therapeutic target for DKD therapy.

PurposeInfections caused by clinical carbapenem-resistant Acinetobacter baumannii (CRAB) are associated with an increased risk of mortality and present a significant challenge for hospitals worldwide. This study aims to analyze the molecular epidemiological characteristics, drug resistance traits, and virulence features of CRAB isolated from bronchoalveolar lavage fluid (BALF) at a hospital in Ningxia, China.MethodsWe collected clinical characteristic data of patients with isolated strains and conducted statistical analysis. Antibiotic susceptibility testing was conducted using the VITEK-2 compact system. Carbapenemase and virulence genes were examined through PCR and Sanger sequencing. Multilocus Sequence Typing (MLST) was performed according to the Oxford MLST scheme by comparing the obtained sequences with known allele sequences available on the MLST website (http://pubmlst.org/abaumannii/). The virulence of CRAB was assessed using the Galleria mellonella infection assay.ResultsThe results indicated that all tested CRAB strains carried the blaOXA-23 and blaOXA-51 genes, exhibiting multidrug resistance characteristics while remaining sensitive to polymyxins. MLST typing revealed that ST195 and ST369 strains were the most prevalent, with several other types identified, including ST208, ST136, ST469, ST368, and a rare ST1779. Notably, 94.2% of CRAB belonged to Global clone 2. Significant clinical differences were observed between ST195 and non-ST195 infection cases. Virulence assessment results indicated that 71 strains (58.6%) exhibited high virulence characteristics. Additionally, virulence factors such as ompA, adeH, pgaA, abal, BasJ, and plcD were detected in all tested strains, confirming an evolutionary trend towards high virulence in CRAB, which poses a serious threat to clinical treatment and patient prognosis.ConclusionThe emergence of highly virulent multidrug-resistant CRAB strains in the Ningxia region has increased a clinical burden, highlighting the importance of clinical surveillance and diagnosis of these strains.

ObjectiveThis study sought to identify knee osteoarthritis (KOA) contributing factors and develop a preliminary forecasting model for its development.MethodsParticipants were systematically invited to complete an exhaustive medical questionnaire designed to capture relevant health and demographic information. Following data collection, univariate analyses were conducted to assess the significance of the variables obtained from the questionnaire. To delineate the association between identified risk factors and the occurrence of KOA, a binary logistic regression model was utilized. The reliability of the model was evaluated through internal validation, encompassing both calibration and discrimination analyses. Calibration was quantified using the Hosmer–Lemeshow χ² statistic to assess the model’s goodness of fit, while discrimination was gauged utilizing the receiver operating characteristic (ROC) curve, providing a comprehensive evaluation of the model’s predictive accuracy.ResultsIn the present study, a total of 445 cases were analyzed, with 266 cases employed for model development and 179 cases reserved for internal validation. Univariate analysis revealed significant statistical differences between the two groups with respect to several variables, including family history of KOA, heating methods, stair usage, anxiety and depression, toilet type, and the frequency of consumption of vegetables, fruits, red meat, and dairy products. Binary logistic regression analysis identified advanced age, lower educational level, use of a squat toilet, family history of KOA, and psychological conditions such as anxiety and depression as significant risk factors for the development of KOA. Furthermore, a moderate predictive value was observed for incident KOA based on a combination of factors, including age, gender, weight, height, family history of KOA, toilet type, mode of transportation, dairy product consumption, and emotional state.ConclusionsOur findings indicate that, in addition to established risk factors such as age, gender, height, and weight, lifestyle and dietary habits also play a pivotal role in the etiology of KOA. These factors not only serve as potential risk markers but also exhibit predictive utility for the onset of KOA, suggesting a comprehensive approach to prevention and intervention strategies.

Family factors are often related to health and mental well-being. We aimed to investigate the causal relationship between family factors and the risk of stroke using Mendelian randomization (MR). The genome-wide association study data used in this analysis was obtained from the Neale Lab, Medical Research Council Integrative Epidemiology Unit. Family factors included financial difficulties, marital separation/divorce and family relationship satisfaction, and all exposures were binary. Stroke was classified as intracerebral hemorrhage (ICH) and ischemic stroke (IS). An inverse-variance weighted method was used mainly in the MR analysis, and the weighted median and MR-Egger methods supplemented the findings. Sensitivity analyses were performed to assess the robustness and reliability of our findings. A total of 30, 11 and 28 single nucleotide polymorphisms were selected as instrumental variables to assess the causal effects of financial difficulties, marital separation/divorce, and family relationship satisfaction on the risk of ICH and IS. Our study found that financial difficulties were causally linked to an elevated risk of ICH (odds ratio [OR] = 1.014, 95% confidence interval [CI] = 1.001–1.028, P = .04), whereas no significant associations were observed with IS (OR = 1.012, 95% CI = 0.988–1.036, P = .33). Additionally, marital separation/divorce showed genetic evidence with higher ICH incidence (OR = 1.054, 95% CI = 1.009–1.101, P = .017), but no statistically significant relationships were detected with IS (OR = 1.026, 95% CI = 0.961–1.096, P = .44). There was no causal correlation of family relationship satisfaction identified with ICH (OR = 0.999, 95% CI = 0.996–1.002, P = .56) or IS (OR = 1.001, 95% CI = 0.996–1.002, P = .17). Sensitivity analyses confirmed the robustness of these findings. This study provides genetic evidence supporting a link between family factors and stroke risk. Specifically, genetic predisposition to financial difficulties and marital separation/divorce suggests a potential causal association with an increased risk of ICH.