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.

Swine enteric coronaviruses(SeCoV),such as porcine epidemic diarrhea virus(PEDV),transmissible gastroenteritis virus(TGEV),and porcine delta coronavirus(PDCoV),cause severe diarrhea in piglets,resulting in substantial losses in pig farming.In this study we establish a triple fluorescence reverse transcription-quantitative PCR(RT-qPCR)method for the simultaneous de-tection of PEDV,TGEV,and PDCoV.The specific primers and probes for each target virus were designed based on conserved sequences from the PEDV M gene,the TGEV ORF 1b gene,and the PDCoV ORF 1b gene respectively.Following the optimization of parameters and conditions,a triple RT-qPCR method was successfully established to simultaneously detect PEDV,TGEV,and PD-CoV.The developed assay exhibits strong specificity for these three pathogens without any cross-reaction with other common porcine viruses like CSFV,PCV2,PoRVA,PRV,and PRRSV.The de-tection limit of linear templates for pTOPO-PEDV 128,pTOPO-TGEV 116,and pTOPO-PDCoV 125 recombinant plasmids were 16.835,17.610 and 17.020 copies/μL,respectively.The intra group and inter group coefficients of variation were less than 5％,with no significant differences observed(P＞0.05).Moreover,the detection consistency rate of the developed RT-qPCR was compared with standard method and showed 100％agreement.Out of 35 small intestine tissue samples,17 tested positive for PEDV,resulting in a positive rate of 48.57％(17/35).The tests for TGEV and PDCoV yielded negative results,and no mixed infections were detected.Based on the above results,the tri-ple RT-qPCR method established is specific,sensitive,stable,and rapid,and can be used for clinical detection and differential diagnosis of PEDV,TGEV,and PDCoV simultaneously,providing a method for the detection and epidemiological investigation of porcine diarrhea coronaviruses.

Objective:To explore the surgical methods and treatment outcomes of nasal endoscopic surgery for nasal deformity secondary to unilateral cleft lip and palate, combined with nasal septal deviation, using nasal septal cartilage and bone.Methods:Eleven patients who underwent surgical treatment for unilateral cleft lip and palate secondary to nasal deformity in the Department of Otorhinolaryngology, Head and Neck Surgery, Linyi People′s Hospital, Shandong Second Medical University, from March 2021 to March 2023, were retrospectively analyzed. The cohort included 8 males and 3 females, aged (22.0±8.4) years (range: 17 to 35 years). Preoperatively, all of them underwent CT scanning and three-dimensional reconstruction of the nasal bones and sinuses to evaluate the size of the nasal septal cartilage and the design of the material to be taken, and to assess the degree of nasal deformity. During the operation, an open “V”-shaped incision was made through the nasal columella, and part of the septal bone and cartilage were removed under direct nasal endoscopic visualization. The septal cartilage and bony structures were used to correct the nasal deformity, and a nasal brace was used as an intraoperative support for the reconstruction of the nasal cartilage, which was then worn for 1 month after the operation to maintain a stable nasal shape. A visual analog scale (VAS) was used before and after surgery to assess the patient′s satisfaction with the nasal shape and the degree of nasal ventilation. Corresponding data on both sides of the external nose were measured, including nasal tip height, nostril height, nostril width, nasal base width, and nasal columella inclination, to assess the symmetry of the external nose objectively. SPSS 22.0 software was used for statistical analysis to evaluate the surgical results.Results:The surgical incisions of all 11 patients healed at stage Ⅰ. At 6-24 months of postoperative follow-up, nasal symmetry was restored, and the nostrils were equal in size. The difference in symmetry indexes before and after the surgery was statistically significant. The t value for nasal tip height, the nostril height, the nostril width, the nasal base width, and the nasal columellar inclination were 4.21, 2.26, 3.38, 3.65, and 2.36, respectively (all P<0.05). Postoperative incision scarring was not obvious, and patients were satisfied with the nasal appearance [VAS score (9.14±0.48) points vs (3.45±1.23) points, t=14.29, P<0.001], and nasal ventilation was significantly improved [VAS score (9.32±1.24) points vs (4.61±0.85) points, t=10.39, P<0.001]. Conclusion:Nasal endoscopic surgery using septal cartilage and bone to treat nasal deformity secondary to unilateral cleft lip and palate, combined with deviated septum, can simultaneously improve the patients′ nasal shape and nasal ventilation, yielding good clinical outcomes.

Objective:To investigate and analyze the surgical method and therapeutic effect of removing benign masses between the nasal radix and eyebrow via a V-shaped cosmetic incision approach through the columella with the assistance of nasal endoscopy.Methods:The data of patients who underwent surgical treatment from May 2020 to August 2023 at the Department of Otorhinolaryngology, Head and Neck Surgery, Linyi People’s Hospital were retrospectively analyzed, because of a mass involving the radix of the nose and the interbrow area. Preoperative CT examination of the nose was performed to clarify the nature, size, and level of the mass, and a V-shaped incision was made in the middle and lower third of the nasal columella, with subcutaneous tunnels along the dorsal median line of the nose, and the mass was excised with the aid of nasal endoscopy. Postoperative follow-up was performed for recurrence of swelling, diplopia, ocular dyskinesia, frontal-facial numbness, and recovery of the operative area; patients were evaluated by visual analogue scoring (VAS) to assess satisfaction with the appearance of the incorporeal scar (0~10 points, higher scores indicate higher satisfaction).Results:A total of 4 patients were included, with an average age of 18.5 years (15-21 years). All 4 patients had complete resection of the tumor through the columellar V-shaped incision approach, and the surgical incisions were all healed by primary intention. Postoperative pathology suggested epidermoid cysts in 1 case, lipoma in 1 case, sebaceous cysts in 1 case, and osteomas in 1 case. Postoperative follow-up ranged from 6 to 24 months, with an average follow-up of 12 months, with no recurrence of the mass, no depression at the radix of the nose and between the eyebrows, and no noticeable scar at the columella. The patients were satisfied with the appearance of the incision scar with a VAS score of 10 points.Conclusion:Nasal endoscopic transnasal columella approach to excision of benign tumors at the root of the nose and between the eyebrows has the advantages of small skin incision and hidden scarring, and has good treatment effect.

The rupture of carotid vulnerable plaques is the core pathological basis for major cardiovascular and cerebrovascular events. However， the insufficient alignment between existing animal models and the clinical disease and syndrome characteristics of traditional Chinese and western medicine has limited research progress. In this study， biomedical databases in China and abroad were systematically searched， and the modeling mechanisms and evaluation systems of carotid vulnerable plaque animal models were systematically assessed based on diagnostic criteria of both traditional Chinese and western medicine. Analysis of the clinical correspondence indicated that existing animal models can be categorized into four types： simple high-fat diet， surgical induction combined with high-fat feeding， genetic engineering combined with high-fat feeding， and drug induction combined with high-fat feeding. Among these， the compound strategy of surgical induction combined with high-fat feeding has become the current mainstream approach， showing good concordance with western medicine. The study found that the double balloon injury rabbit model and the ApoE^-/- mouse carotid artery tandem constriction combined with high-fat feeding model demonstrated a high degree of clinical correspondence with both traditional Chinese and western medicine in terms of vulnerable plaque imaging and pathological features. Nevertheless， existing models still face significant technical limitations in faithfully simulating plaque pathology and in translating findings to clinical applications. To address these challenges， integrating complex comorbidity mechanism construction， multimodal dynamic mechanism monitoring， and collaborative evaluation systems of traditional Chinese and western medicine could enable the development of highly concordant carotid vulnerable plaque disease-syndrome combination animal models. Such models would provide a reproducible experimental platform for targeted drug development to regulate plaque stability and for individualized precision treatment， as well as a theoretical basis for innovation in clinical diagnostic and therapeutic strategies.

Objective To investigate the efficacy and mechanism of individualized treatment for hypertension patients with coronary heart disease under non-invasive cardiac output measurement.Methods A total of 94 hypertension patients with coronary heart disease in the hospital from January 2020 to August 2022 were selected and randomly divided into two groups,with 47 cases in each group.Control group was treated with conventional treatment,while observation group was treated with individualized treatment under non-invasive cardiac output measurement,and both group were continuously treated for 3 months.Clinical efficacy,the blood pressure control[diastolic blood pres-sure(DBP),systolic blood pressure(SBP)],cardiac ultrasound parameters[left ventricular end-systolic diameter(LVESD),left ventricular mass index(LVMI),interventricular septal thickness(IVS),left ventricular end-diastolic diameter(LVEDD)],heart rate variability[the standard devia-tion of the average RR interval(SDANN),the standard deviation of the RR interval of all sinus beats(SDNN),and the proportion of adjacent NN＞50 ms in the number of sinus beats(PNN50)],indi-cators of myocardial injury[α-hydroxybutyrate dehydrogenase(α-HBDH),lactate dehydrogenase(LDH),creatine kinase(CK)],transforming growth factor-β1(TGF-β1)/pancreatic cancer-deficiency factor(Smads)signaling pathway,and incidence of major adverse cardiovascular events(MACE)were compared between the two groups.Results The total effective rate of the observation group was 95.74％,which showed no significant difference compared with 85.11％of the control group(P＞0.05).After 1 and 3 months of treatment,the levels of DBP and SBP in both groups were de-creased significantly compared with those before treatment(P＜0.05),and the LVMI,IVS,LVEDD and LVESD in the observation group were significantly lower than those in the control group(P＜0.05).After 3 months of treatment,the SDANN,PNN50 and SDNN in observation group were significantly higher than those in control group(P＜0.05),while CK,α-HBDH and LDH as well as the expression levels of TGF-β1R Ⅰ,TGF-β1R Ⅱ,Smad1 and Smad2 were significantly lower than those in the control group(P＜0.05).After 3 months of follow-up,the incidence rate of MACE in observation group was 6.38％,which showed no significant difference compared with 14.89％in control group(P＞0.05).Conclusion Compared with conventional treatment regi-men,individualized treatment regimen with non-invasive cardiac output measurement can signifi-cantly alleviate myocardial injury,reverse ventricular hypertrophy and improve heart rate variability,and its mechanism may be related to the inhibition of the TGF-β1/Smads signaling pathway.

Objective:To explore the causal relationship between 1 400 blood metabolites and hyperthyroidism or hypothyroidism by using Mendelian randomization(MR) approach.Methods:This study employed a bi-directional Mendelian randomization analysis and sourced data of blood metabolites related to hyperthyroidism and hypothyroidism from the genome-wide association study(GWAS) database. R software and TwoSampleMR software package were used for analysis. The inverse variance weighting method(IVW) was used as the main method, and MR-Egger regression, weighted median method, simple mode and weighted mode were used as supplementary methods to analyze the causal relationship between blood metabolites and hyperthyroidism and hypothyroidism. The false-positive rate was corrected by false discovery rate(FDR, FDR<0.2) to control for false positives; Meta-analysis of different sample pools was performed for overall assessment. Results:The analysis found three blood metabolites significantly linked to hypothyroidism: pregnenediol disulfate(IVW: OR=1.068, 95% CI 1.032-1.106, P<0.001), 1-(1-enyl-palmitoyl)-2-linoleoyl-GPE(IVW: OR=0.891, 95% CI 0.840-0.944, P<0.001), and linoleic-arachidonic glycerin(IVW: OR =0.923, 95% CI 0.885-0.963, P<0.001). Glutamine was also noted(IVW: OR=0.998, 95% CI 0.997-0.999, P<0.001). Reverse MR showed no significant correlation between hyperthyroidism and the four metabolites(IVW: P>0.05). Validation from FinnGen Biospecimen Library and UKB Biospecimen Library confirmed these findings. Conclusions:Among 1 400 blood metabolites, pregnenediol disulfate showed a positive correlation with hypothyroidism. In contrast, 1-(1-enyl-palmitoyl)-2-linoleoyl-GPE and linoleic-arachidonic glycerin exhibited negative correlations with hypothyroidism, while glutamine showed a negative correlation with hyperthyroidism. This study offers insights into the pathogenesis, early screening, and treatment of hyperthyroidism and hypothyroidism.

Swine enteric coronaviruses(SeCoV),such as porcine epidemic diarrhea virus(PEDV),transmissible gastroenteritis virus(TGEV),and porcine delta coronavirus(PDCoV),cause severe diarrhea in piglets,resulting in substantial losses in pig farming.In this study we establish a triple fluorescence reverse transcription-quantitative PCR(RT-qPCR)method for the simultaneous de-tection of PEDV,TGEV,and PDCoV.The specific primers and probes for each target virus were designed based on conserved sequences from the PEDV M gene,the TGEV ORF 1b gene,and the PDCoV ORF 1b gene respectively.Following the optimization of parameters and conditions,a triple RT-qPCR method was successfully established to simultaneously detect PEDV,TGEV,and PD-CoV.The developed assay exhibits strong specificity for these three pathogens without any cross-reaction with other common porcine viruses like CSFV,PCV2,PoRVA,PRV,and PRRSV.The de-tection limit of linear templates for pTOPO-PEDV 128,pTOPO-TGEV 116,and pTOPO-PDCoV 125 recombinant plasmids were 16.835,17.610 and 17.020 copies/μL,respectively.The intra group and inter group coefficients of variation were less than 5％,with no significant differences observed(P＞0.05).Moreover,the detection consistency rate of the developed RT-qPCR was compared with standard method and showed 100％agreement.Out of 35 small intestine tissue samples,17 tested positive for PEDV,resulting in a positive rate of 48.57％(17/35).The tests for TGEV and PDCoV yielded negative results,and no mixed infections were detected.Based on the above results,the tri-ple RT-qPCR method established is specific,sensitive,stable,and rapid,and can be used for clinical detection and differential diagnosis of PEDV,TGEV,and PDCoV simultaneously,providing a method for the detection and epidemiological investigation of porcine diarrhea coronaviruses.

Objective:To explore the causal relationship between 1 400 blood metabolites and hyperthyroidism or hypothyroidism by using Mendelian randomization(MR) approach.Methods:This study employed a bi-directional Mendelian randomization analysis and sourced data of blood metabolites related to hyperthyroidism and hypothyroidism from the genome-wide association study(GWAS) database. R software and TwoSampleMR software package were used for analysis. The inverse variance weighting method(IVW) was used as the main method, and MR-Egger regression, weighted median method, simple mode and weighted mode were used as supplementary methods to analyze the causal relationship between blood metabolites and hyperthyroidism and hypothyroidism. The false-positive rate was corrected by false discovery rate(FDR, FDR<0.2) to control for false positives; Meta-analysis of different sample pools was performed for overall assessment. Results:The analysis found three blood metabolites significantly linked to hypothyroidism: pregnenediol disulfate(IVW: OR=1.068, 95% CI 1.032-1.106, P<0.001), 1-(1-enyl-palmitoyl)-2-linoleoyl-GPE(IVW: OR=0.891, 95% CI 0.840-0.944, P<0.001), and linoleic-arachidonic glycerin(IVW: OR =0.923, 95% CI 0.885-0.963, P<0.001). Glutamine was also noted(IVW: OR=0.998, 95% CI 0.997-0.999, P<0.001). Reverse MR showed no significant correlation between hyperthyroidism and the four metabolites(IVW: P>0.05). Validation from FinnGen Biospecimen Library and UKB Biospecimen Library confirmed these findings. Conclusions:Among 1 400 blood metabolites, pregnenediol disulfate showed a positive correlation with hypothyroidism. In contrast, 1-(1-enyl-palmitoyl)-2-linoleoyl-GPE and linoleic-arachidonic glycerin exhibited negative correlations with hypothyroidism, while glutamine showed a negative correlation with hyperthyroidism. This study offers insights into the pathogenesis, early screening, and treatment of hyperthyroidism and hypothyroidism.

Objective:To explore the surgical methods and treatment outcomes of nasal endoscopic surgery for nasal deformity secondary to unilateral cleft lip and palate, combined with nasal septal deviation, using nasal septal cartilage and bone.Methods:Eleven patients who underwent surgical treatment for unilateral cleft lip and palate secondary to nasal deformity in the Department of Otorhinolaryngology, Head and Neck Surgery, Linyi People′s Hospital, Shandong Second Medical University, from March 2021 to March 2023, were retrospectively analyzed. The cohort included 8 males and 3 females, aged (22.0±8.4) years (range: 17 to 35 years). Preoperatively, all of them underwent CT scanning and three-dimensional reconstruction of the nasal bones and sinuses to evaluate the size of the nasal septal cartilage and the design of the material to be taken, and to assess the degree of nasal deformity. During the operation, an open “V”-shaped incision was made through the nasal columella, and part of the septal bone and cartilage were removed under direct nasal endoscopic visualization. The septal cartilage and bony structures were used to correct the nasal deformity, and a nasal brace was used as an intraoperative support for the reconstruction of the nasal cartilage, which was then worn for 1 month after the operation to maintain a stable nasal shape. A visual analog scale (VAS) was used before and after surgery to assess the patient′s satisfaction with the nasal shape and the degree of nasal ventilation. Corresponding data on both sides of the external nose were measured, including nasal tip height, nostril height, nostril width, nasal base width, and nasal columella inclination, to assess the symmetry of the external nose objectively. SPSS 22.0 software was used for statistical analysis to evaluate the surgical results.Results:The surgical incisions of all 11 patients healed at stage Ⅰ. At 6-24 months of postoperative follow-up, nasal symmetry was restored, and the nostrils were equal in size. The difference in symmetry indexes before and after the surgery was statistically significant. The t value for nasal tip height, the nostril height, the nostril width, the nasal base width, and the nasal columellar inclination were 4.21, 2.26, 3.38, 3.65, and 2.36, respectively (all P<0.05). Postoperative incision scarring was not obvious, and patients were satisfied with the nasal appearance [VAS score (9.14±0.48) points vs (3.45±1.23) points, t=14.29, P<0.001], and nasal ventilation was significantly improved [VAS score (9.32±1.24) points vs (4.61±0.85) points, t=10.39, P<0.001]. Conclusion:Nasal endoscopic surgery using septal cartilage and bone to treat nasal deformity secondary to unilateral cleft lip and palate, combined with deviated septum, can simultaneously improve the patients′ nasal shape and nasal ventilation, yielding good clinical outcomes.