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.

Animal experiments are essential tools in biomedical research, serving as a bridge between basic research and clinical trials. Systematic reviews and meta-analyses (SRs/MAs) of animal experiments are crucial methods for integrating evidence from animal experiment, which can facilitate the translation of findings into clinical research, reduce translational risks, and promote resource integration in basic research. With the continuous development of the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology, its application in SRs/MAs of animal experiments has gained increasing attention. This article first outlines the principles and specific applications of the GRADE methodology in SRs/MAs of animal experiments, including qualitative descriptive systematic reviews, meta-analyses, and network meta-analyses. It then deeply analyzes the misuse of the GRADE methodology in practice, including incorrect evidence grading, improper classification of evidence, misapplication in qualitative systematic reviews, inconsistencies between the documentation of the upgrading and downgrading process and results, and inappropriate use for making recommendations. Furthermore, this article comprehensively discusses the factors influencing the grading of evidence certainty in SRs/MAs of animal experiments, including the impact of bias risk, indirectness, inconsistency, imprecision, and publication bias on evidence downgrading, as well as the role of large effect sizes and cross-species consistency in evidence upgrading. Finally, in response to the issues discussed, improvement strategies are proposed, including further research and optimization of the GRADE methodology for SRs/MAs of animal experiments, the development of reporting guidelines tailored to the characteristics of SRs/MAs in animal experiment research, and enhanced professional training for researchers in the GRADE methodology. This article aims to improve the quality of evidence in SRs/MAs of animal experiments, strengthen their reliability in clinical decision-making, and promote the more efficient translation of findings from animal experiment research into clinical practice.

This study aimed to investigate the anti-inflammatory and antioxidant effects of atractylon on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Changes in lung function parameters were measured in mice after intraperitoneal administration of atractylon. Pathological changes in lung tissue were observed by H&E staining, and the degree of pulmonary edema was assessed by the lung wet/dry weight ratio (W/D). Kit assays were used to detect changes in oxidative stress markers in mouse serum and the protein concentration in bronchoalveolar lavage fluid (BALF). ELISA was employed to measure the expression levels of inflammatory cytokines in BALF and serum. Western blot was used to detect the expression levels of proteins related to the cGAS-STING pathway and vascular cell adhesion molecule-1 (VCAM-1) in lung tissue. Results showed that, compared to the ALI model group, mice in the low-dose and high-dose atractylon groups exhibited significant improvement in lung function parameters, alleviated pulmonary edema, and reduced inflammatory cell infiltration in lung tissue. Protein content and inflammatory cytokine levels in serum and BALF were decreased, while serum oxidative stress indicators were improved. Western blot results further indicated that atractylon could regulate the cGAS-STING pathway, blocking the generation of inflammatory signals, and simultaneously inhibit VCAM-1 expression, thereby reducing pulmonary vascular injury. The results suggest that atractylon may alleviate LPS-induced ALI by modulating the cGAS-STING signaling pathway, reducing the expression of pro-inflammatory cytokines and the production of pro-inflammatory mediators, and improving vascular endothelial injury. This study provides a new potential target and theoretical basis for the treatment of ALI, as well as a potential drug candidate for ALI therapy.

Ameloblastoma is a benign tumor characterized by locally invasive phenotypes,leading to facial bone destruction and a high recurrence rate.However,the mechanisms governing tumor initiation and recurrence are poorly understood.Here,we uncovered cellular landscapes and mechanisms that underlie tumor recurrence in ameloblastoma at single-cell resolution.Our results revealed that ameloblastoma exhibits five tumor subpopulations varying with respect to immune response(IR),bone remodeling(BR),tooth development(TD),epithelial development(ED),and cell cycle(CC)signatures.Of note,we found that CC ameloblastoma cells were endowed with stemness and contributed to tumor recurrence,which was dominated by the EZH2-mediated program.Targeting EZH2 effectively eliminated CC ameloblastoma cells and inhibited tumor growth in ameloblastoma patient-derived organoids.These data described the tumor subpopulation and clarified the identity,function,and regulatory mechanism of CC ameloblastoma cells,providing a potential therapeutic target for ameloblastoma.

Objective To summarize the current research status and cutting-edge trends of the off-label drug use in China,with a view to providing reference for researchers in this field.Methods CNKI and SinoMed databases were searched to collect research of the off-label drug use in China,and used Microsoft Excel 2021,the R software Bibliometric,and VOSviewer 1.6.18 to visualize the time and trend of publication,province,issuing authors and units,journals,keywords,and topic evolution of the included studies.Results 1 475 papers were included in the research.A total of 2 808 authors from 31 provinces,cities and regions had conducted relevant studies on over-the-counter medication,with an overall increasing trend in the number of publications.Among them,Guangdong province published the most studies related to this field,the Straits Pharmacy Journal and China Pharmacy published the most studies in this field.Proprietary Chinese medicines,antimicrobials,antitumor drugs,and other drugs were the research hotspots.In addition,the patients in pediatrics,outpatient emergency,obstetrics and gynecology,psychiatry and other departments as a special sick population,the clinical use of medication exists in the overspecification situation was also a future research trend.Conclusion At present,research in this field focuses more on OLDU for special populations,special diseases,special drugs,etc.In the future,researchers should conduct evidence-based evaluation of drugs on the basis of more high-quality evidence in order to seek the best evidence for guiding the clinical use of medication.At the same time,drug administration and medical institutions should also develop standardized management policies and systems to promote the rational and safe use of medication in healthcare institutions.

Objective To observe the change of histone acetylation homeostasis of the central cholinergic circuits in mice with post-stroke cognitive impairment (PSCI). Methods The male ICR mice were divided into sham group (n=60) and PSCI group (n=60). The middle cerebral artery occlusion (MCAO) model was established. The Morris water maze test was used to test the cognitive function, and the changes of function and the histone acetylation homeostasis of the central cholinergic circuits of unaffected side were detected by molec-ular biology methods. Results Compared with the sham group, the scores of Morris water maze test decreased in PSCI group (t>29.412, P<0.05); while the acetylcholine (Ach) level decreased (t>26.227, P<0.05), as well as the expression of choline acetyltransferase (ChAT) mRNA and protein (t>28.593, P<0.05), acetylated histone H3 (Ac-H3) (t>24.126, P<0.05), phosphorylated cAMP response element-binding protein (p-CREB) and CREB binding protein (CBP) (t>25.634, P<0.05), and the acetylated histone level of M promoter of ChAT (t>24.704, P<0.05). Conclusion Transient MCAO could cause PSCI. The function of the central cholinergic circuits was impaired, especially the his-tone acetylation homeostasis of the central cholinergic circuits, such as the acetylated histone level of ChAT promoter decreased. All of that might be related with the decline of p-CREB and CBP level in the corresponding brain regions induced by stroke.

Objective To evaluate the applicability of Mini-Nutritional Assessment(MNA),Short-Form Mini-Nutritional Assessment(MNA-SF)in the malnutrition screening of patients with Alzheimer's disease(AD).Methods MNA and MNA-SF were performed in 267 AD patients.The correlation between the screening results were compared.Results According to MNA,the rates of malnutrition,potential malnutrition,and normal nutritional status were 59.7%,20.9%,and 19.4%,respectively.The sensitivity was 73.4%and the specificity was 60.1%.According to MNA-SF,the rates of malnutrition and normal nutritional status were 70.4%and 29.6%.The sensitivity was 50.6%and the specificity was 92.4%.The screening results of these two tools were significantly correlated(r=0.924,P<0.01).Conclusions MNA and MNA-SF are reliable tools for evaluating the nutritional status of AD patients.While MNA-SF is more convenient and feasible,the combination of these two tools may be helpful.

Objective To dynamically monitor the blood glucose in traumatic brain injury (TBI) patients within three days after admission, and to assess the impact of hyperglycemia on prognosis. Method Between 2007 and 2008, 62 TBI patients, who were admitted within 6 hours after the ineidence of injury without diahetes or severe combined injuries, were involved in this study. Blood glucose was monitored at 4 time points (instantly, 24 hours, 48 hours, and 72 hours after admission). Patients were classified into the mild, the moderate, or the se-vere TBI group according to GCS (Glasgow Coma Scale) scores, being classified into the survival or the dead group according to prognosis, or into the mile or severe hyperglycemia group depending on whether the blood glucose ex-ceeds 11.1mmol/L on admission. T tests and χ2 tests were applied to analyze the relationship among blood glucose levels, the degrees of injury, and the prognosis of studied patients. Results Patients with mild, moderate, or se-vere TBI showed hyperglycemia with different levels, and the blood glucose levels was consistent with the degree of the injury. The blood glucose of the patients in the dead group were significantly higher at all checked time points than those of the survival group, particularly instantly after admission (8.51±2.01 mmol/L vs. 11.54±2.45 mmol/L, P=0.0001, t=4.988). The mortality of patients with severe hyperglycemia was 64.71%, signifl-candy higher than that of the mild hyperglycemia group 13.95% (P=0.0002, χ2=15.46). The Intensive Care Unit Length of Stay (ICULOS) of the above two groups was 22.6 and 10.2 days,respectively (P=0.021, t= 3.216), but their hospital length of stay (HLOS) showed no statistical difference (P=0.052). Conclusions Hyperglycemia, as an early stress response to TBI, may reflect the degree of the injury. Blood glucose levels that exceed 11.1 mmol/L on admission may imply high mortality of TBI patients, so this could be used as a simple indi-cator to predict prognosis.

Objective To analyze the emergercy epidemiological characteristics of coeualties with head in-jury in Shanghai. Method By a prospective study,the data of 18 076 casualties with head injury during the whole year 2004 collected from 12 joint hospitals in Shanghai were documented well in the unified survey tables with wide-range items failed in by the attending physician, who got the firsthand information from patients and witness.The data were analyzed by using SPPS version 11.5 software. Results Of 18 076 casualties with head injury,the ratio of male to female was 2.11: 1.The mean age of female was older than that of male (t=10.575, P<0.01).The highest incidence of casualties occurred in people of twenties (24.7 % ). The local residents of Shanghai ac-counted for 34.2% of casualties. More casualties often occurred in December,January,Mareh and August than in he rest. Of 5.1% casualties with head injury were assochted with labour work.The leading cause of injury was dif-ferent in patient cohorts of different ages. Fall was the most main cause of trauma in children cohort (aged<14)and the senile patients cohort (aged > 60). The violert assault and traffic accident caused the most head injuries in the adolescent people cohort ( aged 15～34 years old) and the young people cohort ( aged 35～59 year old). The majority of casualties (85.5%) received CT scan.The scalp laceration (40.2% of patients) was seen more often than other types of injury . The mortality of easualties with traumatic brain injury was 0. 5 % . Conclusions The kmowledge of epidemiologieal aend of emergency deparhnent visitors with head injury is amportant guidance to physicians arranging emergency medical resources rationally and formulating a comprehesive prevention stategy of castahies with head injury.