Animal experimentation constitutes a critical link between basic research and clinical application, making its research quality and translational efficiency paramount. Although considerable progress has been made in standardizing operational procedures and ethical guidelines, the standardization of outcome evaluation systems has significantly lagged, creating a key bottleneck that constrains the quality of biomedical research and evidence synthesis. This deficiency is manifested by pronounced heterogeneity in outcome selection across similar studies, incomplete methodological reporting, and disparate criteria for result interpretation, which severely impairs the comparability of findings and the evidence integration. To cope with this challenge, this paper systematically introduces a mature methodological tool from clinical research–the core outcome set (COS)–and explores its construction strategies and application potential in the field of animal experimentation. Given the extensive diversity of animal experiments, a pragmatic strategy of "focusing on key areas, implementing phased pilots, and promoting gradual expansion" should be adopted. This approach prioritizes the development of domain-specific COS for disease areas characterized by high research volume, urgent translational needs, and well-established animal models. A multi-source integration pathway for COS development is detailed, comprising systematic literature searches, methodological appraisals, and expert consensus, with the feasibility of leveraging artificial intelligence (AI) to enhance efficiency also being examined. The development and promotion of such COS are not intended to restrict scientific exploration; rather, they aim to establish a new, tiered evaluation paradigm consisting of "core outcomes" (mandatory), "recommended outcomes" (encouraged), and "exploratory outcomes" (optional). This framework is expected not only to enhance research quality through standardization and to adhere to the "3R" principles but also to accelerate the accumulation of high-quality evidence. This, in turn, provides a solid foundation for higher-level evidence synthesis, ultimately facilitating the effective translation of basic research findings into clinical practice and providing an essential methodological framework for scientific advancement in relevant disciplines.

BackgroundIn recent years， the incidence of depression among adolescents has been increasing steadily， posing a serious threat to their physical and mental health and even leading to severe consequences such as self-harm and suicide. At the same time， the detection rate of subclinical depression symptoms among adolescents is even higher. Although these symptoms do not meet the clinical diagnostic criteria， they have significantly affected their quality of life， and their persistence over time may further develop into depression. Therefore， in-depth exploration of adolescent depression symptoms and the predictive factors holds significant practical significance and research value. However， up to now， no large-scale investigation and research on depression symptoms among children and adolescents has been conducted in Inner Mongolia Autonomous Region. ObjectiveTo understand the prevalence of depressive symptoms among children and adolescents in Inner Mongolia Autonomous Region， in order to provide references for formulating scientific and effective prevention strategies and intervention measures. MethodsBy using the cluster stratified random sampling method， 6 281 students from the third grade of primary school to the second grade of high school in 12 leagues and cities of Inner Mongolia Autonomous Region were selected in March 2024. A self-designed questionnaire and the Self-rating Depression Scale （SDS） were used for on-site investigation. ResultsA total of 6 058 （96.45%） children and adolescents completed the valid questionnaire survey， and 2 728 cases （45.03%） were found to have depressive symptoms. There were statistically significant differences in the detection rates of depressive symptoms among children and adolescents of different genders， ages， whether they were only children， different family types， family monthly income， parents' educational levels， and whether the mother was employed （χ²=33.769， 40.618， 48.593， 29.972， 142.648， 195.999， 168.190， 5.445， P<0.05 or 0.01）.The results of the Logistic regression analysis showed that for children and adolescents， being female， aged between 12 and 16， over 16 years old， not being an only child， living in a reconstituted family， having a monthly family income of less than 5 000 yuan， and having parents with an education level of primary school or below were predictors of depressive symptoms （OR=1.241， 1.427， 1.273， 1.177， 1.549， 1.278， 1.462， 1.417， 1.514， 1.929， 1.660， 1.528， P<0.05 or 0.01）. ConclusionThe detection rate of depressive symptoms among children and adolescents in Inner Mongolia Autonomous Region is relatively high. Factors that may predict depressive symptoms in children and adolescents include female gender， ages between 12 and 16， ages over 16 years old， non-only children， families with a restructured structure， monthly family income of less than 5 000 yuan， and parents with an education level of primary school or below. ［Funded by Science and Technology Planning Project of the Inner Mongolia Autonomous Region （number， 2022YFSH0119）］

ObjectiveTo develop and validate a diagnostic prediction model for differentiating pulmonary tuberculosis from community-acquired pneumonia based on routine blood parameters. MethodsA total of 642 patients with pulmonary tuberculosis and 503 patients with community-acquired pneumonia were retrospectively enrolled from the Seventh Hospital of Tangshan. They were randomly divided into a training set and an internal validation set at a 7∶3 ratio. Additionally， 218 patients from the 981st Hospital were independently included as an external validation set. The Boruta algorithm and recursive feature elimination were employed to select predictors from 82 blood parameters， sex， and age. A multivariate Logistic regression model was established and evaluated using receiver operating characteristic （ROC） curves， calibration curves， and decision curve analysis. ResultsThe final model incorporated eight predictors， namely uric acid， urea nitrogen， alkaline phosphatase， monoamine oxidase， alanine aminotransferase， glutathione， neutrophil percentage， and age. The model achieved areas under the curve （AUCs） of 0.800 （95%CI： 0.769-0.830）， 0.787 （95%CI： 0.738-0.836）， and 0.736 （95%CI： 0.667-0.835） in the training， internal validation， and external validation sets， respectively. The model demonstrated good calibration， and decision curve analysis showed clinical net benefit within the threshold probability range of 10%-80%. ConclusionThe developed model exhibits good discriminative ability and clinical utility， serving as an effective early screening tool for primary healthcare institutions.

Parkinson disease(PD)is defined by two hallmark pathological features:the progressive degeneration of dopaminergic(DAergic)neurons in the substantia nigra pars compacta(SNc)and the pathological aggregation of alpha-synuclein(α-syn).Despite extensive research,the molecular mechanisms driving PD remain incompletely understood,and effective treatments are still lacking.Growing evidence implicates α-syn aggregation and impaired protein clearance—particularly through dysfunction of the autophagy-lysosomal pathway(ALP)and ubiquitin-proteasome system(UPS)—as central contributors to neurodegeneration through disrupted proteostasis.Genetically engineered rodent models,developed using advanced gene-editing tools,faithfully replicate core PD pathological features,including α-syn aggregation dynamics,selective neuronal vulnerability,and motor deficits.These models serve as indispensable platforms for dissecting α-syn-mediated toxicity mechanisms.By identifying critical regulatory nodes in α-syn homeostasis,they provide a strategic foundation for therapies targeting clearance pathway restoration or aggregation inhibition,positioning themselves as essential tools for overcoming current therapeutic limitations in PD.

A 36-year-old male developed unconsciousness and no response to voice stimuli after taking approximately 2 050 mg felodipine (the specific time was unknown). Two hours later, he was sent to the department of emergency by his family and admitted to the hospital. His vital signs showed body temperature 35.1 ℃, pulse 148 times/min, respiration 32 times/min, and blood pressure 65/34 mmHg. Acute drug poisoning, acute toxic cardiomyopathy, acute toxic shock, acute type Ⅱ respiratory failure, acute toxic encephalopathy, and acute renal failure were diagnosed based on the patient′s clinical manifestations combined with laboratory tests results, cardiac ultrasound, chest and abdominal CT scans. Endotracheal intubation connected to a ventilator for invasive assisted ventilation, pressure boosting, and fluid resuscitation were given. At the same time, repeated gastric lavage and enema were performed to remove toxins. Blood perfusion was intermittently and repeatedly administered, and continuous renal replacement therapy was used. The blood concentration of felodipine was 1 298 μg/L at 2 hours after admission, and cardiac arrest occurred at 4 hours. Venous-arterial extracorporeal membrane oxygenation (V-A ECMO) treatment was administered immediately. After 48 hours of ECMO operation, sedatives were discontinued and the patient′s consciousness was improved after 4 hours. On the 5th day of ECMO treatment, his heart rate was 72 beats per minute, and blood pressure was 127/65 mmHg. The blood concentration of felodipine decreased to 2 μg/L. The patient′s vital signs were significantly improved and ECMO supportive treatment was withdrawn. After 26 days of hospitalization, the patient recovered and was discharged.

Gastric cancer is a high-incidence malignancy that poses a serious threat to public health in China, ranking among the top three cancers in both incidence and mortality. The majority of patients are diagnosed at an advanced stage, resulting in limited treatment options and poor prognosis. To address key challenges in gastric cancer diagnosis and treatment, a research team led by Professor Jiafu Ji at Peking University Cancer Hospital has focused on the project "Development and Dissemination of Precision Medicine Approaches in Gastric Cancer Management". Through a series of high-quality multicenter clinical studies, the team established a set of new international standards in perioperative treatment, individua-lized drug selection, intelligent noninvasive diagnostics, and novel immunotherapy strategies. These advances have significantly improved treatment efficacy and reduced surgical trauma, achieving key technological breakthroughs in diagnosis, therapy, and mechanistic understanding, and systematically enhancing outcomes for gastric cancer patients. The project ' s findings had a broad international impact, including hosting China ' s first International Gastric Cancer Congress. Through nationwide dissemination, they have promoted the development of precision diagnosis and treatment of gastric cancer as a discipline, and led the formulation of the National Health Commission's guidelines for gastric cancer diagnosis and treatment. In recognition of its achievements, the project was awarded the First Prize of the 2024 Chinese Medical Science and Technology Award.
Stomach Neoplasms/genetics* ; Humans ; Precision Medicine/methods* ; China ; Immunotherapy/methods*

OBJECTIVES: Osteoarthritis (OA) and sarcopenia are significant health concerns in the elderly, substantially impacting their daily activities and quality of life. However, the relationship between them remains poorly understood. This study aims to uncover common biomarkers and pathways associated with both OA and sarcopenia. METHODS: Gene expression profiles related to OA and sarcopenia were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between disease and control groups were identified using R software. Common DEGs were extracted via Venn diagram analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to identify biological processes and pathways associated with shared DEGs. Protein-protein interaction (PPI) networks were constructed, and candidate hub genes were ranked using the maximal clique centrality (MCC) algorithm. Further validation of hub gene expression was performed using 2 independent datasets. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of key genes for OA and sarcopenia. Mouse models of OA and sarcopenia were established. Hematoxylin-eosin and Safranin O/Fast Green staining were used to validate the OA model. The sarcopenia model was validated via rotarod testing and quadriceps muscle mass measurement. Real-time reverse transcription PCR (real-time RT-PCR) was employed to assess the mRNA expression levels of candidate key genes in both models. Gene set enrichment analysis (GSEA) was conducted to identify pathways associated with the selected shared key genes in both diseases. RESULTS: A total of 89 common DEGs were identified in the gene expression profiles of OA and sarcopenia, including 76 upregulated and 13 downregulated genes. These 89 DEGs were significantly enriched in protein digestion and absorption, the PI3K-Akt signaling pathway, and extracellular matrix-receptor interaction. PPI network analysis and MCC algorithm analysis of the 89 common DEGs identified the top 17 candidate hub genes. Based on the differential expression analysis of these 17 candidate hub genes in the validation datasets, AEBP1 and COL8A2 were ultimately selected as the common key genes for both diseases, both of which showed a significant upregulation trend in the disease groups (all P<0.05). The value of area under the curve (AUC) for AEBP1 and COL8A2 in the OA and sarcopenia datasets were all greater than 0.7, indicating that both genes have potential value in predicting OA and sarcopenia. Real-time RT-PCR results showed that the mRNA expression levels of AEBP1 and COL8A2 were significantly upregulated in the disease groups (all P<0.05), consistent with the results observed in the bioinformatics analysis. GSEA revealed that AEBP1 and COL8A2 were closely related to extracellular matrix-receptor interaction, ribosome, and oxidative phosphorylation in OA and sarcopenia. CONCLUSIONS AEBP1 and COL8A2 have the potential to serve as common biomarkers for OA and sarcopenia. The extracellular matrix-receptor interaction pathway may represent a potential target for the prevention and treatment of both OA and sarcopenia.
Sarcopenia/genetics* ; Osteoarthritis/genetics* ; Computational Biology/methods* ; Humans ; Protein Interaction Maps/genetics* ; Animals ; Mice ; Gene Expression Profiling ; Gene Ontology ; Transcriptome ; Male ; Signal Transduction/genetics* ; Gene Regulatory Networks

OBJECTIVES: Osteoarthritis (OA) is one of the most common chronic degenerative diseases, with chondrocyte apoptosis and extracellular matrix (ECM) degradation as the major pathological changes. The mechanical stimulation can attenuate chondrocyte apoptosis and promote ECM synthesis, but the underlying molecular mechanisms remain unclear. This study aims to investigate the role of primary cilia (PC) in mediating the effects of mechanical stimulation on OA progression. METHODS: In vivo, conditional knockout mice lacking intraflagellar transport 88 (IFT88^flox/flox IFT88 knockout; i.e., primary cilia-deficient mice) were generated, with wild-type mice as controls. OA models were established via anterior cruciate ligament transection combined with destabilization of the medial meniscus, followed by treadmill exercise intervention. OA progression was evaluated by hematoxylin-eosin staining, safranin O-fast green staining, and immunohistochemistry; apoptosis was assessed by TUNEL staining; and limb function by rotarod testing. In vitro, primary articular chondrocytes were isolated from mice and transfected with lentiviral vectors to suppress IFT88 expression, thereby constructing a primary cilia-deficient cell model. Interleukin-1β (IL-1β) was used to induce an inflammatory environment, while cyclic tensile strain (CTS) was applied via a cell stretcher to mimic mechanical loading on chondrocytes. Immunofluorescence and Western blotting were used to detect the protein expression levels of type II collagen α1 chain (COL2A1), primary cilia, IFT88, and caspase-12; reverse transcription polymerase chain reaction was performed to assess COL2A1 mRNA levels; and flow cytometry was used to evaluate apoptosis. RESULTS: In vivo, treadmill exercise significantly reduced Osteoarthritis Research Society International (OARSI) scores and apoptotic cell rates, and improved balance ability in wild-type OA mice, whereas IFT88-deficient OA mice showed no significant improvement. In vitro, CTS inhibited IL-1β-induced ECM degradation and apoptosis in primary chondrocytes; however, this protective effect was abolished in cells with suppressed primary cilia expression. CONCLUSIONS Mechanical stimulation delays OA progression by mediating signal transduction through primary cilia, thereby inhibiting cartilage degeneration and chondrocyte apoptosis.
Animals ; Chondrocytes/cytology* ; Apoptosis/physiology* ; Mice ; Cilia/metabolism* ; Osteoarthritis/pathology* ; Extracellular Matrix/metabolism* ; Mice, Knockout ; Disease Progression ; Interleukin-1beta ; Male ; Cells, Cultured

Objective:X-linked non-syndromic hearing loss is an extremely rare type of hearing impairment. This study conducted a phenotypic and genetic analysis of a family with X-linked dominant inheritance to explore the causes of hearing loss. Methods:Clinical data were collected from a patient with non-syndromic hearing loss who visited the Otorhinolaryngology Department of the First Affiliated Hospital of Zhengzhou University in June 2023. Phenotypic and genetic analyses were performed on family members, including audiometric tests, whole-exome sequencing, and PCR-Sanger sequencing verification. Audiological assessments comprised pure-tone audiometry, impedance audiometry, auditory brainstem response, and otoacoustic emission tests. Results:The affected individuals in this pedigree have X-linked dominant non-syndromic deafness caused by mutations in the SMPX gene. The proband, along with their mother and maternal grandmother, exhibit varying degrees of sensorineural hearing loss. Whole-exome sequencing revealed a novel pathogenic variant, NM_014332.3: c. 133-2A>C, in the SMPX gene in the proband. Sanger sequencing confirmed that the proband, proband's mother, and grandmother all carried this pathogenic variant. Conclusion:This study reports a novel pathogenic variant in the SMPX gene, providing additional medical evidence for the diagnosis and treatment of X-linked dominant inherited non-syndromic hearing loss. It enriches the mutation spectrum of the SMPX gene.
Humans ; Pedigree ; Mutation ; Phenotype ; Male ; Hearing Loss, Sensorineural/genetics* ; Exome Sequencing ; Female ; Adult ; Hearing Loss/genetics* ; Evoked Potentials, Auditory, Brain Stem ; Muscle Proteins

In current clinical practice, various dermal templates and skin substitutes are used to enhance wound healing. However, the role of wound commensal microbiome in regulating scaffold performance and the healing process remains unclear. In this study, we investigated the influence of both natural and synthetic scaffolds on the wound commensal microbiome and wound repair in three distinct models including diabetic wounds, burn injuries, and germ-free (GF) wounds. Remarkably, synthetic electrospun polycaprolactone (PCL) scaffolds were observed to positively promote microbiome diversity, leading to enhanced diabetic wound healing compared to the natural scaffolds Integra® (INT) and MatriDerm® (MAD). In contrast, both natural and synthetic scaffolds exhibited comparable effects on the diversity of the microbiome and the healing of burn injuries. In GF wounds with no detectable microorganisms, a reversed healing rate was noted showing natural scaffold (MAD) accelerated wound repair compared to the open or the synthetic scaffold (PCL) treatment. Furthermore, the response of the wound commensal microbiome to PCL scaffolds appears pivotal in promoting anti-inflammatory factors during diabetic wound healing. Our results emphasize that the wound commensal microbiome, mediated by different scaffolds plays an important role in the wound healing process.