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.

Objective This study was performed to establish and compare guinea pig models of tuberculosis using intranasal and aerosol infection routes at different doses.The overall goal was to provide a foundation for establishing a standardized guinea pig model of tuberculosis for the study of respiratory tract infection.Methods Twenty-four female guinea pigs were randomly divided into six groups of four guinea pigs each.They were then infected with two doses of Mycobacterium tuberculosis through either the aerosol route(groups A,B,and C)or intranasal route(groups D,E,and F).Aerosol infection groups consist of 3 groups:group A(Aerosol control group,uninfected control group),group B(Aerosol low-dose group,5×102 CFU),and group C(Aerosol high-dose group,5×103 CFU)Intranasal infection groups also consist of 3 groups:group D(Intranasal control group,uninfected control group),group E(Intranasal low-dose group,1×104 CFU),and group F(Intranasal high-dose group,5×104 CFU).The clinical manifestations of the guinea pigs were observed after infection.All guinea pigs were euthanized on day 14.Lung,spleen,and liver tissues were obtained for gross examination and histopathological analysis using hematoxylin-eosin staining to identify characteristic lesions associated with tuberculosis.Acid-fast staining was performed on in situ tissues and organs followed by bacterial culture to analyze the bacterial load.Results The guinea pigs in four infection groups(B,C,E,and F)exhibited macroscopic tuberculosis lesions in the lung,spleen,and liver.Histopathological examination revealed the presence of tuberculous granuloma lesions.Acid-fast staining and bacterial load analysis demonstrated that the bacteria were primarily localized in the lung tissue of aerosol-infected groups B and C,with a few also present in the spleen and liver,and the bacterial load was 104～105 CFU/mL.In intranasal infection groups E and F,bacteria were found in the lung,spleen,and liver with a similar bacterial load of 104～105 CFU/mL.There was no significant difference in lesion severity or bacterial load among groups B,C,E,and F;however,groups B,C,and F showed low standard deviations for both pathology and etiology.Conclusions A guinea pig model of acute tuberculosis was successfully established using two doses administered through distinct routes of infection.Pathological examination and pathogenic analysis demonstrated that an aerosol dose of 5×102 CFU of Mtb effectively established a homogeneous model of acute tuberculosis with good consistency among the animals.Additionally,intranasal infection with 5×104 CFU of Mtb produced a relatively uniform model of tuberculosis.Notably,however,aerosol infection at 5×102 CFU progressed to an acute tuberculosis model more rapidly than intranasal infection at 5×104 CFU.

OBJECTIVE To explore the role of Yes-associated protein(YAP)in epidermal stem cell(EPSC)differentiation after ionizing radiation(IR).METHODS ① A punch was used to induce skin injuries on the back of mice.The IR group received localized irradiation with 60 Co γ-rays,while the normal control group did not.Samples were collected at 0,1,3,6,9,and 12 d for RNA and protein extraction.Western blotting was used to detect changes in YAP protein expressions during wound healing.Real-time quantitative polymerase chain reaction(RT-qPCR)was performed to assess the mRNA levels of Yap and its downstream target genes,connective tissue growth factor(Ctgf),and cysteine-rich protein 61(Cyr61).② EPSCs were exposed to 60 Co γ at a dose of 4 or 8 Gy,while the control group was not irradiated.Cells were collected to detect the levels of YAP protein via Western blotting.Cells were collected at 4,12,24,and 36 h post-IR to assess the levels of YAP mRNA by RT-qPCR.③ Short hairpin RNA(shRNA)was used to establish stable YAP knockdown cell lines,and the knockdown efficiency of sh YAP was verified by Western blotting.RT-qPCR was then performed to detect the impact of YAP knockdown on mRNA levels of K1 and K10 after IR.RESULTS① Compared with the control group,the YAP protein level in the IR group during wound healing was significantly reduced(P<0.05,P<0.01),so were the mRNA levels of Yap and its downstream target genes Ctgf and Cyr61(P<0.05,P<0.01).② Compared to the cell control group,the mRNA and protein levels of YAP in the IR group cells were significantly reduced(P<0.01).③ In the sh YAP cells,the YAP protein level was significantly reduced(P<0.01).Furthermore,the mRNA levels of K1 and K10 were significantly decreased after IR in sh YAP cells(P<0.01).CONCLUSION YAP can regulate EPSC differentiation in wound healing after IR.

Objective To investigate the clinical utility of iFlow color flow coding imaging technology in the diagnosis of lower extremity arteriosclerosis obliterans(LEASO).Methods A total of 106 patients diagnosed with LEASO between March 2022 and October 2023 were included as the LEASO group,while 80 volunteers without arterial disease but matched with LEASO were selected as the control group.Both groups underwent digital subtrac-tion angiography(DSA),and iFlow color flow coding imaging technology was employed to assess time to peak(TTP)in the femoral head and ankle regions.The difference value of TTP between these two regions was calculated,along with measurement of ankle-brachial index(ABI).Results There were no significant differences in age,sex,body mass index,smoking history,hypertension history,diabetes history,coronary heart disease history and TTP in the femoral head between the two groups(P＞0.05).However,the TTP in the ankle area and the difference values of TTP in the LEASO group were significantly higher than those in the control group(P＜0.05).The com-parison of TTP in the femoral head region among patients with different Rutherford classifications and between patients with left and right lesions in the LEASO group showed no statistical significance(P＞0.05).Furthermore,a negative correlation was observed between Rutherford classification and both TTP values in ankle joint region as well as TTP difference value(P＜0.05),indicating that higher Rutherford classification is associated with lower TTP values.Pearson test results revealed a significant negative correlation between TTP values and ankle joint region/TTP difference value of LEASO patients with ABI(P＜0.05).Receiver operating characteristic curve analysis demonstrated that both TTP values in ankle joint region and TTP difference value are effective diagnostic indicators for LEASO;moreover,Delong test indicated that area under ROC curve for TTP difference value was significantly higher than that for TTP value alone(P＜0.05)Conclusion iFlow color flow coding imaging technology enables quantitative assessment of both TPP values within ankle joint region as well as their differences which can be utilized for diagnosis of LEASO.

Objective:To evaluate the 10-year protective effect and immunogenicity of quadrivalent human papillomavirus (HPV) vaccine in Chinese women aged 20 to 45 years.Methods:From October 2019 to April 2020, a long-term follow-up study was conducted on the subjects of the Phase III clinical trial of the quadrivalent HPV vaccine (NCT00834106). Participants underwent a questionnaire survey, venous blood sampling, gynecological examination, cervical exfoliated cell pathology examination, and serum neutralizing antibody titers for HPV-6, 11, 16, and 18 were measured using a pseudovirus neutralization assay. The results of the cytological examination and the positive rate and titers of serum antibodies of different cervical exfoliated cells were compared.Results:A total of 889 subjects were followed up, including 240 in the control group, 453 in the vaccination group and 196 in the post-trial vaccination group. The age of the control group was (40±7) years old, which was higher than that of the supplementary vaccination group and the vaccination group [(38±4) and (38±6) years old, respectively] ( P<0.05). There were no statistically significant differences in condom use and sexual frequency among all groups (all P values>0.05). The abnormal proportion of cervical exfoliation cytopathology in the vaccination group was 3.7% (17/453), which was significantly lower than that in the control group [9.6% (23/240)] and post-trial vaccination group [5.6% (11/196)] ( P<0.05). There were two cases of cervical intraepithelial neoplasia (CIN) grade 1 in the vaccination group, two cases of CIN grade 1 and three cases of CIN grade 2 and above in the control group, and no CIN grade 1 and above cases in the post-trial vaccination group. The positive rate of HPV-18 antibody was 35.5% (161/453) in the vaccination group and 76.0% (149/196) in the post-trial vaccination group, which was significantly lower than that of other types ( P<0.05). The neutralizing antibody GMT ratio between the vaccination group and the control group ranged from 2.62 to 25.33 (9.05 to 83.08). Conclusion:Protective neutralizing antibodies are sustained in Chinese women aged 20 to 45 years after ten years of vaccination with quadrivalent HPV vaccine.

Objective:To evaluate the 10-year protective effect and immunogenicity of quadrivalent human papillomavirus (HPV) vaccine in Chinese women aged 20 to 45 years.Methods:From October 2019 to April 2020, a long-term follow-up study was conducted on the subjects of the Phase III clinical trial of the quadrivalent HPV vaccine (NCT00834106). Participants underwent a questionnaire survey, venous blood sampling, gynecological examination, cervical exfoliated cell pathology examination, and serum neutralizing antibody titers for HPV-6, 11, 16, and 18 were measured using a pseudovirus neutralization assay. The results of the cytological examination and the positive rate and titers of serum antibodies of different cervical exfoliated cells were compared.Results:A total of 889 subjects were followed up, including 240 in the control group, 453 in the vaccination group and 196 in the post-trial vaccination group. The age of the control group was (40±7) years old, which was higher than that of the supplementary vaccination group and the vaccination group [(38±4) and (38±6) years old, respectively] ( P<0.05). There were no statistically significant differences in condom use and sexual frequency among all groups (all P values>0.05). The abnormal proportion of cervical exfoliation cytopathology in the vaccination group was 3.7% (17/453), which was significantly lower than that in the control group [9.6% (23/240)] and post-trial vaccination group [5.6% (11/196)] ( P<0.05). There were two cases of cervical intraepithelial neoplasia (CIN) grade 1 in the vaccination group, two cases of CIN grade 1 and three cases of CIN grade 2 and above in the control group, and no CIN grade 1 and above cases in the post-trial vaccination group. The positive rate of HPV-18 antibody was 35.5% (161/453) in the vaccination group and 76.0% (149/196) in the post-trial vaccination group, which was significantly lower than that of other types ( P<0.05). The neutralizing antibody GMT ratio between the vaccination group and the control group ranged from 2.62 to 25.33 (9.05 to 83.08). Conclusion:Protective neutralizing antibodies are sustained in Chinese women aged 20 to 45 years after ten years of vaccination with quadrivalent HPV vaccine.