Objective To evaluate the drug-loading performance,biocompatibility,bone tissue compati-bility,and therapeutic efficacy of vancomycin(VA)-loaded hydroxyapatite(HA)/β-tricalcium phosphate(β-TCP)scaffolds in treating infectious bone defects in mice.Methods HA/β-TCP scaffolds were fabricated by using 3D printing technology,and VA was loaded onto the scaffolds via freeze-drying to create the composite VA/HA/β-TCP scaffolds.The scaffolds were observed by using scanning electron microscopy(SEM),and their encapsulation efficiency,drug-loading capacity,and release kinetics were assessed.An in vitro co-culture system was established with mouse embryonic osteoblasts(MC3T3-E1)and the scaffolds,The cells were di-vided into the control group(HA/β-TCP scaffolds)and the VA/HA/β-TCP group.Cell viability was assessed by using the methyl thiazolyl tetrazolium(MTT)assay,and osteocalcin(OCN)expression levels were meas-ured by ELISA at 7,12,and 14 days of co-culture.Antibacterial activity was evaluated through adhesion ex-periments.A mouse cranial defect model was constructed and implanted with the scaffolds for 4 weeks.Hema-toxylin and eosin(HE)staining was performed to observe material degradation and bone formation in the sur-rounding tissues.Results The VA/HA/β TCP scaffolds exhibited uniform pore size distribution and excel-lent drug-loading performance,with an encapsulation efficiency of 70.32％and an actual drug-loading rate of 30.53％,effectively loading VA.The scaffolds sustained VA release over 36 hours.Compared to the control group,MC3T3-E1 cell viability on the VA/HA/β-TCP scaffolds was significantly inhibited at 7 and 12 days of co-culture(P＜0.01),but no significant difference in proliferation activity was observed between the two groups after 14 days(P＞0.05).No significant differences in OCN expression levels were found in MC3T3-E1 cells on the VA/HA/β-TCP scaffolds compared to the control group at any time point(P＞0.05).The VA/HA/β-TCP scaffolds demonstrated strong antibacterial properties,with significantly reduced numbers of Escherichia coli in the co-cultured bacterial solution and on the scaffold surface compared to the control group(P＜0.001).Compared with the control group,the VA/HA/β-TCP group demonstrated significantly reduced cranial hemorrhage and inflammatory infiltration,alongside a marked increase in new bone tissue.Conclusion The VA/HA/β-TCP scaffolds exhibit excellent drug-loading performance,controlled drug re-lease,biocompatibility,antibacterial activity,and bone tissue compatibility,offering a novel approach for trea-ting bone infections.

OBJECTIVE: High-altitude hypoxia exposure often damages hippocampus-dependent learning and memory. Nogo-A is an important axonal growth inhibitory factor. However, its function in high-altitude hypoxia and its mechanism of action remain unclear. METHODS: In an in vivo study, a low-pressure oxygen chamber was used to simulate high-altitude hypoxia, and genetic or pharmacological intervention was used to block the Nogo-A/NgR1 signaling pathway. Contextual fear conditioning and Morris water maze behavioral tests were used to assess learning and memory in rats, and synaptic damage in the hippocampus and changes in oxidative stress levels were observed. In vitro, SH-SY5Y cells were used to assess oxidative stress and mitochondrial function with or without Nogo-A knockdown in Oxygen Glucose-Deprivation/Reperfusion (OGD/R) models. RESULTS: Exposure to acute high-altitude hypoxia for 3 or 7 days impaired learning and memory in rats, triggered oxidative stress in the hippocampal tissue, and reduced the dendritic spine density of hippocampal neurons. Blocking the Nogo-A/NgR1 pathway ameliorated oxidative stress, synaptic damage, and the learning and memory impairment induced by high-altitude exposure. CONCLUSION: Our results demonstrate the detrimental role of Nogo-A protein in mediating learning and memory impairment under high-altitude hypoxia and suggest the potential of the Nogo-A/NgR1 signaling pathway as a crucial therapeutic target for alleviating learning and memory dysfunction induced by high-altitude exposure. GRAPHICAL ABSTRACT available in www.besjournal.com.
Animals ; Oxidative Stress ; Hippocampus/metabolism* ; Rats ; Nogo Proteins/genetics* ; Male ; Rats, Sprague-Dawley ; Hypoxia/metabolism* ; Altitude ; Synapses ; Humans ; Altitude Sickness/metabolism*

A 14-year-old boy was admitted to the hospital due to a single episode of afebrile seizure and four hours of impaired consciousness. Three months prior to admission, he had a history of bilateral uveitis. Cerebrospinal fluid analysis revealed a mild elevation in white blood cell count. Cranial magnetic resonance imaging and contrast-enhanced scans showed multiple abnormal signals in both cerebral hemispheres, with punctate and nodular enhancement. Susceptibility-weighted imaging revealed multiple punctate hemorrhages within lesions in the bilateral frontal and left parietal lobes, suggestive of vasculitis. Brain biopsy demonstrated inflammatory granulomatous lesions. No secondary causes were identified, and the final diagnosis was granulomatous primary central nervous system vasculitis. The patient's condition improved after treatment with methylprednisolone sodium succinate and mycophenolate mofetil. This report describes a rare case of granulomatous central nervous system vasculitis in a child and provides valuable insights for the diagnosis and treatment of this disease.
Humans ; Male ; Vasculitis, Central Nervous System/diagnosis* ; Adolescent ; Magnetic Resonance Imaging ; Granuloma/diagnosis*

BACKGROUND: Ferroptosis-related genes play a crucial role in regulating intracellular iron homeostasis and lipid peroxidation, and they are involved in the regulation of tumor growth and drug resistance. The expression of ferroptosis-related genes in tumor tissues can be used to predict patients' future survival times, aiding doctors and patients in anticipating disease progression. Based on the sequencing data of lung adenocarcinoma (LUAD) patients from The Cancer Genome Atlas (TCGA) database, this study identified genes involved in the regulation of ferroptosis, constructed a prognostic model, and evaluated the predictive performance of the model. METHODS: A total of 1467 ferroptosis-related genes were obtained from the GeneCards database. Gene expression profiles and clinical data from 541 LUAD patients were collected from the TCGA database. The expression data of all ferroptosis-related genes were extracted, and differentially expressed genes were identified using R software. Survival analysis was performed on these genes to screen for those with prognostic value. Subsequently, a prognostic risk scoring model for ferroptosis-related genes was constructed using LASSO regression model. Each LUAD patient sample was scored, and the patients were divided into high-risk and low-risk groups based on the median score. Receiver operating characteristic (ROC) curves were plotted, and the area under the curve (AUC) was calculated. Kaplan-Meier survival curves were generated to assess model performance, followed by validation in an external dataset. Finally, univariate and multivariate Cox regression analyses were conducted to evaluate the independent prognostic value and clinical relevance of the model. RESULTS: Through survival analysis, 121 ferroptosis-related genes associated with prognosis were initially identified. Based on this, a LUAD prognostic risk scoring model was constructed using 12 ferroptosis-related genes (ALG3, C1QTNF6, CCT6A, GLS2, KRT6A, LDHA, NUPR1, OGFRP1, PCSK9, TRIM6, IGF2BP1 and MIR31HG). The results indicated that patients in the high-risk group had significantly shorter survival time than those in the low-risk group (P<0.001), and the model demonstrated good predictive performance in both the training set (1-yr AUC=0.721) and the external validation set (1-yr AUC=0.768). Risk scores were significantly associated with the prognosis of LUAD patients in both univariate and multivariate Cox regression analyses (P<0.001), suggesting that this score is an important prognostic factor for LUAD patients. CONCLUSIONS This study successfully established a LUAD risk scoring model composed of 12 ferroptosis-related genes. In the future, this model is expected to be used in conjunction with the tumor-node-metastasis (TNM) staging system for prognostic predictions in LUAD patients.
Humans ; Ferroptosis/genetics* ; Prognosis ; Adenocarcinoma of Lung/pathology* ; Lung Neoplasms/pathology* ; Male ; Female ; Gene Expression Regulation, Neoplastic ; Middle Aged ; ROC Curve

To explore the protective effect of Angelica sinensis polysaccharide(ASP)on leptospiro-sis induced by pathogenic Leptospira infection,the golden hamster model of leptospirosis was se-lected for the experiment.The Leptospira and Leptospira+ASP groups were intraperitoneally injected with Leptospira interrogans serovar Lai strain 56601(1 × 10 6 per hamster).After infec-tion,the Leptospira+ASP group was injected intraperitoneally with ASP(50 mg/kg)for three consecutive days,while the Leptospira group was injected intraperitoneally with normal saline for three days.The experiment employed methods such as daily observation of the clinical symptoms of golden hamsters,statistics of the survival status of each group of golden hamsters,pathological damage of liver,kidney,and lung,bacterial load in organs,and the expression of inflammatory cy-tokines(IL-1β and TNF-α).The results indicated that ASP could effectively alleviate the clinical symptoms of the infected hamsters,enhance the survival rate,ameliorate the pathological damage of the body,reduce the bacterial load in various organs,and mitigate tissue inflammation.This study demonstrated for the first time that ASP has a protective effect on leptospirosis,providing medication guidance for the clinical treatment of leptospirosis.

IgA vasculitis is a common childhood vasculitis disorder.Its primary clinical manifestation is cutaneous purpura,which is often accompanied by gastrointestinal and joint symptoms.Renal involvement can present as hematuria or proteinuria.This condition is recurrent and protracted,significantly affecting the health of children.The pathogenic factors in pediatric IgA vasculitis are diverse."Wind-toxin damaging collaterals"is presented as the core pathogenesis based on clinical practice and theoretical exploration.This concept essentially entails the latent attack of wind-toxin,collateral damage leading to blood extravasation,and healthy qi deficiency and lingering toxins,with the disease primarily located in the collateral vessels.The disease course is divided into three stages:acute,lingering,and recovery.Clinical practice should adhere to the pathogenesis principles and apply stage-based pattern differentiation and treatment.The acute stage involves wind-toxin attacking collaterals with dampness-heat accumulation.Treatment focuses on dispersing wind,clearing heat,and eliminating dampness to expel wind-toxin from the muscular exterior.The self-prescribed Qufeng Xiaodian Formula is a frequently selected modified formula.The lingering stage features latent wind-toxin in the collaterals and congealed accumulations in the kidney collaterals.Treatment aims to resolve wind-toxin,disperse stasis,and eliminate accumulation to remove densely accumulated wind-toxin.A modified Taohong Siwu Decoction is selected.The recovery stage involves deficient healthy qi with persistent wind assault and lingering toxins.Emphasis should be placed on cultivating the fundamental,strengthening the root,and nourishing yin,as well as supporting the healthy qi to dispel wind and expel toxins,while conditioning the body to prevent recurrence.A modified Guomin Decoction is selected.Clinical application emphasizes the combination of characteristic medicines,such as wind medicines to expel pathogens,insect medicines to identify collaterals,and vine medicines to unblock the meridians,to enhance the effects of identifying wind,resolving toxins,unblocking collaterals,and dispersing congealed accumulations.This study aims to systematically elaborate on the stage-based treatment strategy from the perspective of"wind-toxin damaging collaterals,"providing a theoretical basis and clinical practice reference for the traditional Chinese medicine diagnosis and treatment of pediatric IgA vasculitis.

Objective To introduce how to import and analyze data using the Research Electronic Data Capture(REDCap)system,taking a multi-center randomized controlled clinical research of total knee arthroplasty as an example.Methods Various tools within the REDCap system,including data import tools,data export functions,reports and statistics,project dashboards,and coding manuals,were used to systematically process and analyze the multi-center randomized controlled clinical trial data for total knee arthroplasty.Initially,electronically collected clinical data were adjusted and standardized,then uploaded in bulk to the system using the REDCap data import tool.Subsequently,the data were organized through REDCap's data export feature,and basic descriptive statistical analysis was performed using its reporting and statistical functions to ensure data quality and completeness.Results An electronic data collection and management platform for clinical research on knee osteoarthritis wase successfully created by the REDCap system.The platform enabled real-time data collection from multiple centers,and ensured data accuracy and consistency through built-in data management and quality control mechanisms.With the statistical analysis features of REDCap,the research team could monitor the progress of data in real time,conduct effective quality assessments,and perform dynamic analysis for further in-depth statistical evaluations.Conclusion The REDCap system can be used not only to build a new clinical research project,but also to import and analyze data that has been previously digitized of ongoing clinical researches into the system,which improved the scientificity of data management and research efficiency.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

The wear debris generated during artificial joint prosthesis service can react with bone tissues to form osteolysis,seriously affecting the life-time of artificial joint prostheses.This paper reviews,summarizes,and analyzes domestic and international research literature on the extraction,characterization,and identification of wear debris from different artificial joint materials,aiming to provide references and feasible ideas for the future construction of a systematic and hierarchical research system for artificial joint wear debris.The main findings are as follows:strong alkali protein degradation test,strong acid protein degradation test,and protease protein degradation test are the commonly used method for extracting artificial joint wear debris,and researchers have clarified the protein degradation mechanisms of these three debris extraction methods.The characterization of wear debris in-vitro and in-vivo is mostly for hip and knee joints,with a small amount involving cervical spine and ankle joints.Studies have shown that the size,quantity,shape,and volume of wear particles are influenced by factors such as joint type,contact area,material selection,and implantation time.Both domestic and international studies have conducted characterization research on wear debris after in-vitro simulation testing,but there is still a lack of wear debris characterization analysis of clinical retrievals in China.Currently,most research is on the recognition of wear debris in the traditional mechanical field,but research on the intelligent recognition of artificial joint wear debris is relatively few,indicating that there is a certain lag in the application of computer technology in the field of artificial joint wear debris recognition.

Lung cancer poses a serious threat to global public health security.Chemotherapy,as the main strategy for cancer treatment,faces challenges such as high toxicity and drug resistance.Anticancer peptides have the potential of being developed into new anticancer drugs due to their advantages of broad-spectrum anticancer activity,rapid action,and difficulty in generating drug resistance,but they also face shortcomings such as weak activity and strong toxic side effects.The weakly acidic microenvironment of tumors(pH 6.5-6.8)provides a good idea for the design of anticancer peptides of high-efficiency and low-toxicity.Previously,we designed the acid-sensitive antibacterial peptide pHly-1 using the wolf spider(Lycosa singoriensis)toxin Lycosin-Ⅰ as a template.In this study,we found that pHly-1 also had acid-sensitive anticancer activity.Further alanine scanning analysis of pHly-1 was carried out,and we ob-tained a mutant pHTP-2 with better acid sensitivity,whose IC50(half maximal inhibitory concentration)against A549 cells was 15.68 μmol/L at pH 6.6 and was greater than 100 μmol/L at pH 7.4.At pH 6.6,pHTP-2 could act on various lung cancer cell lines and induce the death of A549 cells by rapid ly-sis;at pH 7.4,500 μmol/L pHTP-2 had weak toxicity to red blood cells(the hemolysis rate was ap-proximately 38％)and primary myocardial cells(the inhibition rate was 49.7％,with P＜0.05).Analy-sis of its charge,particle size,morphology,and secondary structure showed that at pH 6.6,the histidine in the sequence of pHTP-2 was protonated,increasing the positive charge(P＜0.01),decreasing the hy-drated particle size(P＜0.05)and forming an α-helical structure to induce membrane lysis of A549 cells.At pH 7.4,it was deprotonated,the positive charge decreases,a β-sheet structure was formed and self-aggregation occurred,limiting its effect on the A549 cell membrane and showing weak activity.In summary,pHTP-2 could respond to the weakly acidic microenvironment of tumors to exert selective cyto-toxic activity,effectively overcoming the shortcomings of anticancer peptides such as low efficiency and high toxicity.Our findings suggest that it is a high-quality lead molecule for anticancer drugs.