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.

This study systematically examined the effects of atomization as a transdermal permeation enhancer on the transdermal delivery of active ingredients with different physicochemical properties and investigated the underlying mechanisms. Porcine ear skin served as an in vitro model, and skin permeation experiments were conducted using Franz diffusion cells. Receptor fluids were collected at specific time points, and samples of the stratum corneum and viable epidermis–dermis were separated and prepared. Quantitative and visualization methods, including high-performance liquid chromatography, fluorescence derivatization, and confocal laser scanning microscopy, were used to compare skin retention and transdermal permeation of adenosine (AD), tranexamic acid (TXA), calcein (CAL), and tocopheryl acetate (TA) under atomized and non-atomized conditions. Additionally, transepidermal water loss (TEWL) measurements and attenuated total reflectance–Fourier transform infrared spectroscopy (ATR-FTIR) were employed to analyze the mechanism behind the penetration enhancement caused by atomization. The findings showed that atomization increased skin retention within the stratum corneum and viable epidermis–dermis, as well as the transdermal permeation of all four active ingredients to varying degrees. The most significant enhancement was observed for TXA, which has a relatively low molecular weight and moderate lipophilicity, while the enhancement effects for highly hydrophilic AD and highly lipophilic TA were comparatively limited; however, atomization significantly increased the skin retention of TA. TEWL results indicated that skin permeability increased within 4 hours after atomization and largely recovered within 8 hours. ATR-FTIR analysis suggested that atomization may facilitate transdermal delivery by disrupting the lipid order and keratin conformation in the stratum corneum.This study provides theoretical support and experimental references for the advancement of atomization transdermal delivery technology, as well as the design and development of related atomization products.

ObjectiveTo investigate the therapeutic mechanism of artemether in diabetic sarcopenia（DS）using network pharmacology and animal experiments. MethodsPotential active components and therapeutic targets were screened using artemisinin as the parent compound. The predicted targets were intersected with DS-related targets， followed by construction of a protein-protein interaction （PPI） network. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses were performed to identify the key biological processes and signaling pathways. Molecular docking was further used to evaluate the binding affinity between artemether and core targets. The DS mouse model was established using db/db mice， followed by artemether intervention. Fasting blood glucose， body weight， diabetes-related symptoms， body composition， grip strength， serum and skeletal muscle triglyceride levels， and muscle fiber cross-sectional area （CSA） were assessed. The expression levels of forkhead box O1 （FoxO1）， Atrogin-1， muscle RING finger protein 1 （MuRF1）， acyl-CoA synthetase short-chain family member 2 （ACSS2）， carnitine palmitoyltransferase 2 （CPT2）， and fatty acid-binding protein 3 （FABP3） in skeletal muscle were detected by qRT-PCR， Western blot， immunofluorescence， and immunohistochemistry. In addition， metabolomics was performed to analyze changes in acylcarnitine metabolites in skeletal muscle. ResultsA total of 68 overlapping targets between artemether and diabetic sarcopenia （DS） were identified. The core targets included AKT1， FoxO1， NFKB1， FBXO32， and TRIM63， which were mainly enriched in the phosphoinositide 3-kinase/protein kinase B （PI3K-Akt） signaling pathway， forkhead box O （FoxO） signWaling pathway， tumor necrosis factor （TNF） signaling pathway， and insulin resistance-related pathways. Molecular docking analysis showed that artemether exhibited favorable binding affinity with the core targets. Animal experiments demonstrated that artemether reduced fasting blood glucose， ameliorated metabolic symptoms， increased lean mass and grip strength， decreased serum and skeletal muscle triglyceride levels， and increased muscle fiber cross-sectional area （CSA） in DS mice. In addition， artemether downregulated the mRNA and protein expression levels of FoxO1， FBXO32/Atrogin-1， TRIM63/MuRF1， ACSS2， CPT2， and FABP3， and improved the disturbance of acylcarnitine metabolism in skeletal muscle. ConclusionArtemether improves metabolic and skeletal muscle phenotypes in DS mice. Its effects may be associated with the amelioration of lipid metabolic disorders and the downregulation of FoxO1 and its downstream ubiquitin-proteasome pathway-related factors Atrogin-1 and MuRF1 in skeletal muscle.

Objective To analyze the occupational medical examination (OME) conclusions for noise-exposed workers issued by OME institutions in Shijiazhuang City. Methods A total of 1 111 noise-exposed workers, whose OME reports were issued by 32 OME institutions in Shijiazhuang City from 2022 to 2024, were selected as the study subjects using the convenience sample method. Expert review was conducted to re-evaluate the initial OME conclusions for noise-exposed workers, and reasons for inconsistencies between the initial and reviewed conclusions were analyzed. Results Initial OME conclusions included occupational contraindications, re-examination, other diseases or abnormalities, and no abnormal findings, with 109, 286, 378, and 338 cases, respectively. After expert review, the consistency rate for occupational contraindication conclusions was 91.7%, with two suspected cases of occupational noise-induced deafness (ONID) and seven cases of other diseases or abnormalities identified. For other diseases or abnormalities, the consistency rate was 95.5%, with one cases of suspected ONID and 16 occupational contraindications detected. In terms of no abnormal findings, the consistency rate was 70.4%, with 100 cases reclassified as other diseases or abnormalities. Regarding the 286 re-examination cases, experts identified 72 cases of suspected occupational diseases, 99 cases of occupational contraindications, and 115 cases of other diseases or abnormalities. Conclusion The chief physicians of OME institutions demonstrate insufficient rigor in determining noise-related target diseases, ambiguous understanding of OME conclusions, and inadequate follow-up on cases recommended for re-examination.

Tripterygium wilfordii is a traditional Chinese medicinal herb with a long history of therapeutic use but remains controversial in modern medicine because of its potent toxicity. Among its diverse chemical constituents, the diterpenoid triptolide and the triterpenoid celastrol have emerged as prominent compounds due to their remarkable pharmacological activities, including antitumor, immunosuppressive, anti-obesity, and neuroprotective effects. However, their clinical translation is limited by toxicity concerns and restricted natural availability. This review summarizes the medicinal history and chemical constituents of T. wilfordii, with particular emphasis on the pharmacological mechanisms, structural modification strategies, and recent advances in the biosynthesis of triptolide and celastrol. In addition, we discuss perspectives on toxicity mitigation and lead compound development, aiming to provide theoretical guidance and valuable references for modern drug development and the green manufacturing of T. wilfordii-derived resources.

BACKGROUND:Peripheral nerve axon rupture seriously affects patients' physical function and mental health.Microsurgery,nerve autograft,nerve allograft,fibrin glue and catheter technology are the main treatments for peripheral nerve injury,each of which has its own advantages and disadvantages,but the overall treatment effect is not satisfactory.Despite the clinical success of Schwann cells in promoting axonal regeneration,there are still many challenges in the treatment with Schwann cells,such as slow expansion of Schwann cells,immune rejection,and low survival rate of transplanted cells.OBJECTIVE:To summarize the role and mechanism of Schwann cells in promoting the regeneration of peripheral nerve axons,and the difficulties and challenges of Schwann cells in the process of nerve regeneration treatment.METHODS:PubMed,Medline,WanFang,VIP,and CNKI were searched by computer using the search terms of"Schwann cells,synaptic Schwann cell,macrophage,peripheral nerve axon rupture,Wallerian degeneration,Peripheral nerve axon regeneration,Central nervous system repair"in English and Chinese.Literature related to Schwann cell proliferation and differentiation,promotion of peripheral nerve regeneration,and clinical applications was retrieved from database inception to October 2024,and a total of 95 articles were finally included for review.RESULTS AND CONCLUSION:Schwann cells interact with macrophages,T cells and other cells,to initiate the regeneration process through signaling pathways,including Krox20/C-Jun,NRG-1/ErbB,Notch,MAPK,and PI3K/Akt/mTOR,synthesize and release nerve growth factors,and thus promote regeneration of the peripheral nervous system.Schwann cells have been experimentally demonstrated to have great potential in peripheral nerve repair and are expected to become the key target of therapeutic intervention.However,there are still problems such as difficulties in cell harvest and culture,as well as the occurrence of other diseases during the treatment process.

BACKGROUND:Peripheral nerve axon rupture seriously affects patients' physical function and mental health.Microsurgery,nerve autograft,nerve allograft,fibrin glue and catheter technology are the main treatments for peripheral nerve injury,each of which has its own advantages and disadvantages,but the overall treatment effect is not satisfactory.Despite the clinical success of Schwann cells in promoting axonal regeneration,there are still many challenges in the treatment with Schwann cells,such as slow expansion of Schwann cells,immune rejection,and low survival rate of transplanted cells.OBJECTIVE:To summarize the role and mechanism of Schwann cells in promoting the regeneration of peripheral nerve axons,and the difficulties and challenges of Schwann cells in the process of nerve regeneration treatment.METHODS:PubMed,Medline,WanFang,VIP,and CNKI were searched by computer using the search terms of"Schwann cells,synaptic Schwann cell,macrophage,peripheral nerve axon rupture,Wallerian degeneration,Peripheral nerve axon regeneration,Central nervous system repair"in English and Chinese.Literature related to Schwann cell proliferation and differentiation,promotion of peripheral nerve regeneration,and clinical applications was retrieved from database inception to October 2024,and a total of 95 articles were finally included for review.RESULTS AND CONCLUSION:Schwann cells interact with macrophages,T cells and other cells,to initiate the regeneration process through signaling pathways,including Krox20/C-Jun,NRG-1/ErbB,Notch,MAPK,and PI3K/Akt/mTOR,synthesize and release nerve growth factors,and thus promote regeneration of the peripheral nervous system.Schwann cells have been experimentally demonstrated to have great potential in peripheral nerve repair and are expected to become the key target of therapeutic intervention.However,there are still problems such as difficulties in cell harvest and culture,as well as the occurrence of other diseases during the treatment process.

Objective:To analyze the short-term hospital-based transmission characteristics and gene variation of Carbapenem-Resistant Klebsiella pneumoniae (CRKP) by genome-wide technique to provide evidence for transmission control. Methods:The experimental strain was derived from all the CRKP isolated in Affiliated Hospital of North China University of Science and Technology from October 2022 to December 2023. Strain identification and drug susceptibility were tested with VITEK 2-Compact automatic bacterial identification drug susceptibility analyzer or disk method, and the results were interpreted through whole genome sequencing. The ST type, carbapenem resistance gene, virulence factor, and O serotype of the collected strains were analyzed.Results:Among the 115 strains of CRKP, 94 strains were isolated from the intensive care unit (ICU), accounting for 81.7%, and 21 strains were isolated from the non-intensive care unit (NICU), accounting for 18.3%. The 115 strains of CRKP can be divided into 11 ST types, of which ST11 type was the most (54.8%, 63/115), followed by ST15 type (22.6%, 26/115) and ST5492 type (15.7%, 18/115). Type ST5492 was a new clonal group in the region. The 115 strains of CRKP could be divided into 7 O serotypes, most of which were O2a type(32.2%,37/115), followed by O5 type(30.4%,35/115) and O1 type(27.8%,32/115). The resistance genes of carbapenem antibiotics showed that there were 107 strains carrying the blaKPC-2 gene, one strain with the blaNDM-1 gene, and one strain with both the blaKPC-2 and blaNDM-13 genes. Virulence genes were detected in 55 CRKP strains (47.8%, 55/115), among which six strains detected peg-344, iucA, iroB, rmpA, and rmpA2 virulence genes (5.2%, 6/115). Four virulence genes ( peg-344, iucA, rmpA, and rmpA2) were detected in 34 strains (29.6%, 34/115). Three virulence genes ( iucA, iroB and rmpA) were detected in two strains (1.7%, 2/115). Three virulence genes ( peg-344, iucA and rmpA) were detected in one strain (0.8%, 1/115). IucA and rmpA virulence genes were detected in 12 strains (10.4%, 12/115). KPC-2_ST11_O2a, KPC-2_ST15_O1 and KPC-2_ST5492_O5 were dominant clones, and their distribution was mainly in the intensive care unit. The whole genome sequence analysis showed that there were three dominant clones, among which ST11 clones were subdivided into three dominant O serotypes, all of which were mainly in the intensive care unit. Conclusion:The popular strain in the hospital of CRKP is a KPC-2_ST11 clone group carrying iucA, rmpA/rmpA2, with cross-department transmission and mutation. ST5492 is a newly-launched clone type. The intensive care unit of hvKP carrying five virulence genes, including peg-344, should be alert to the epidemic risk of CR-hvKP outbreak.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Objective:To investigate the association between different types of lung nodules and the risk of lung cancer in a population at high risk of lung cancer and to provide an epidemiologic basis for the comprehensive management of lung nodules.Methods:Using the free lung cancer screening program of low-dose CT (LDCT) in Wenling, Zhejiang Province, we collected baseline and imaging information of high-risk groups for lung cancer who underwent LDCT screening from April 2019 to October 2021 and patients with previous history of lung cancer, tuberculosis, pneumoconiosis, and silicosis were excluded. A total of 28 539 study subjects were included in the analysis, and the follow-up ended on 31 December 2023. Based on the characteristics of the detected pulmonary nodules, the study subjects were classified with no nodules, with solid nodules, with pure ground glass nodules, and with part solid nodules groups. The association between different characteristics of lung nodules and the risk of lung cancer development was analyzed using the Cox proportional hazard regression model with a new diagnosis of lung cancer during the follow-up period as the outcome.Results:The overall detection rate of lung nodules with a mean diameter of ≥3 mm was 76.5%, of which 53.7%, 18.2%, and 4.6% were detected in the solid nodule, pure ground glass nodule, and partially solid nodule groups, respectively. There were statistically significant differences between the different nodule groups in terms of age, gender, BMI, history of toxic exposure education level, smoking status, history of lung disease, and family history of lung cancer (all P<0.05). The median follow-up time of the study population was 3.4 years, and 485 new lung cancer cases were diagnosed during the follow-up period. After adjusting for covariates, the results of multifactorial Cox proportional hazard regression model analysis showed that the risk of lung cancer was higher in pure ground glass nodules and part solid nodules compared with solid nodules, with HR values (95% CI) of 1.89 (1.52-2.35) and 6.49 (5.18-8.14), respectively. The results of subgroup analysis showed that patients in the group of part solid nodules had the highest risk of lung cancer in all strata of the population, followed by patients with pure ground glass nodules. Patients in the solid nodule group who were older or had previous lung disease had a higher risk of lung cancer, and the risk of lung cancer in the part solid nodule group differed between genders. Conclusions:The proportion of lung nodules detected is high in the high-risk group of lung cancer, and among them, patients with pure ground glass and part solid nodules have a higher risk of developing lung cancer. Attention should be paid to the annual follow-up management for patients with solid nodules who are older or who have had lung diseases, as well as for female patients with part solid nodules.