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:To summarize the clinical manifestations and diagnosis, treatment experience of vertically transmitted eschar-free scrub typhus in newborns.Methods:A case summary was made.The clinical data of 3 newborns clinically diagnosed as vertically transmitted eschar-free scrub typhus and treated at the Department of Neonatology, the Sixth Affiliated Hospital, Sun Yat-sen University Yuexi Hospital/Xinyi People′s Hospital from August 2022 to July 2024 were retrospectively analyzed.Results:The age of onset of scrub typhus in the 3 newborns was within 24 h after birth.The children presented a fever, the clinical manifestations of early onset sepsis, and also multiple organ damage.Laboratory examination showed that all the 3 children have an abnormal elevation in C-reactive protein, a decrease of blood platelet (PLT) and an increase in D-dimer within 24 h after birth.The diagnosis was confirmed in all the patients via the metagenomic sequencing technology of pathogenic microorganism of blood samples.Two of the 3 children presented hepatomegaly and were treated with Azithromycin.All the children were clinically cured finally.Conclusions:The early clinical manifestation of vertically transmitted eschar-free scrub typhus in newborns is early onset sepsis and easily combined with multi-organ dysfunction, PLT reduction, and D-dimer elevation.Pathogenic microorganism metagenomic sequencing technology is conductive to the diagnosis of the disease, and Azithromycin is effective.

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.

Objective:To summarize the clinical manifestations and diagnosis, treatment experience of vertically transmitted eschar-free scrub typhus in newborns.Methods:A case summary was made.The clinical data of 3 newborns clinically diagnosed as vertically transmitted eschar-free scrub typhus and treated at the Department of Neonatology, the Sixth Affiliated Hospital, Sun Yat-sen University Yuexi Hospital/Xinyi People′s Hospital from August 2022 to July 2024 were retrospectively analyzed.Results:The age of onset of scrub typhus in the 3 newborns was within 24 h after birth.The children presented a fever, the clinical manifestations of early onset sepsis, and also multiple organ damage.Laboratory examination showed that all the 3 children have an abnormal elevation in C-reactive protein, a decrease of blood platelet (PLT) and an increase in D-dimer within 24 h after birth.The diagnosis was confirmed in all the patients via the metagenomic sequencing technology of pathogenic microorganism of blood samples.Two of the 3 children presented hepatomegaly and were treated with Azithromycin.All the children were clinically cured finally.Conclusions:The early clinical manifestation of vertically transmitted eschar-free scrub typhus in newborns is early onset sepsis and easily combined with multi-organ dysfunction, PLT reduction, and D-dimer elevation.Pathogenic microorganism metagenomic sequencing technology is conductive to the diagnosis of the disease, and Azithromycin is effective.

Objective: To investigate the relationships among psychological resilience, parental control, and behavioral problems in middle school students, aiming to provide evidencebased recommendations for the prevention and intervention of behavioral issues in middle school students, as well as for the development of related policies. Methods: A stratified cluster sampling method was used to select 2 745 participants from three cities in Guizhou Province with different levels of economic development from August to December 2021. The Child Behavior Checklist (CBCL), Parental Control Questionnaire, and Psychological Resilience Questionnaire were administered to junior high school students and their parents. A network analysis method was employed to construct a network analysis model of factors influencing behavioral problems. Results: The detection rate of behavioral problems among junior high school students in Guizhou Province was 22.62%. The scores for psychological resilience (goal focus, emotional control, positive cognition, family support, and interpersonal assistance) and proactive inquiry in behavior control were higher in the group without behavioral problems than in the group with behavioral problems. Scores for psychological control (inducing guilt, with drawing affection, and asserting authority) were higher in the group with behavioral problems than in the group without behavioral problems, with statistically significant differences (t=9.80, 17.76, 6.21, 12.20, 13.18, 6.28, 11.58, 11.10, 10.74, P<0.05). The network model showed that among the same variable factors, the strongest connection weight was between inducing guilt and withdrawing affection, with a weight of 0.79. Between different variables, there were negative correlation between behavioral problems and psychological resilience (goal focus, emotional control, positive cognition, family support, interpersonal assistance) and behavior control (proactive inquiry, behavioral restraint) with correlation coefficients (r=-0.25, -0.42, -0.16, -0.31, -0.33, -0.17, -0.03, P<0.05), respectively. There were positive correlation between psychological control factors (inducing guilt, withdrawing affection, and asserting authority) and behavioral problems (r=0.29, 0.27, 0.27), and a negative correlation between these psychological control factors and psychological resilience factors (goal focus, emotional control, positive cognition, family support, interpersonal assistance)(r=-0.53--0.13)(P<0.05). The strongest connection weight was between withdrawing affection and family support, with a connection weight of -0.53. Family support was an important bridge symptom connecting the entire behavioral problem network model, with a high centrality. Conclusions The detection rate of behavioral problems among junior high school students in Guizhou Province is relatively high. Assisting adolescents in establishing a supportive family environment facilitates the cultivation of their psychological resilience, thereby mitigating the occurrence of behavioral problems.

Integrating evidence from animal experiments is a critical component of biomedical research, providing essential prior information for in-depth investigations of disease mechanisms and new drug development. Animal models have played an irreplaceable role in simulating human diseases. However, the integration of evidence from animal experiments has faced numerous challenges, including insufficient emphasis, significant heterogeneity in study designs, high publication bias, and discrepancies with clinical research practices. This paper first identifies existing issues in the original research evidence from animal experiments, such as the selection and applicability of animal models, considerations in the design of experimental studies, and factors influencing the translation of animal experimental evidence. It then discusses various methods for integrating this evidence, including systematic review and meta-analysis, overview of systematic review/umbrella review, scoping review, and evidence mapping, while highlighting recent advancements in their application. Finally, the paper addresses the main challenges currently encountered in the integration of evidence from animal experiments and proposes targeted improvement strategies aimed at enhancing the efficiency of translating research outcomes into clinical practice and promoting the advancement of evidence-based medicine. By continuously optimizing original experimental research protocols and evidence integration practices, this work aims to establish a more efficient and scientific environment for the synthesis of evidence from animal experiments, ultimately contributing to clinical trials and human health.

Objective To establish an ideal modeling method for diarrhea predominant irritable bowel syndrome(IBS-D)with anxiely and depression in rats,and to provide a basis for the clinical study of IBS-D.Methods 60 rats were used in this study.(1)At first,20 rats were randomly divided into blank,3%acetic acid enema,4%acetic acid enema,and 5%acetic acid enema groups.After the modeling and observation period,the diarrhea status and the degree of colon injury caused by different modeling concentrations were observed by diarrhea related index and colon histopathology.(2)After the optimal modeling concentration was assessed,40 rats were randomly divided into control(a),acetic acid enema(b),acetic acid+binding(c),and acetic acid+binding+tail clip(d)groups and correspondingly treated for 8 days.After the treatments,the general condition,diarrhea-related index,open field test(OFT)score,and colonic histopathology of rats were evaluated.Results(1)Compared with the blank group,the fecal trait score of 4%acetic acid enema group was increased on days 1 to 3 after intervention(P＜0.001),and gradually decreased on days 4 to 7 after intervention.After 1 week,there was no significant difference between the fecal trait score and that of the blank group(P＞0.05).Body weight was lower(P＜0.01),fecal water content was higher(P＜0.001).Compared with blank group,body weight of the 5%acetic acid enema group was decreased(P＜0.001),the fecal trait score and diarrhea index were increased(P＜0.01).No significant difference was found between 3%acetic acid enema and blank groups.The pathological colon tissue showed that,compared with the blank group,the mucosal structure of the 4%acetic acid enema group was complete with a small amount of inflammatory cell infiltration,and the pathological tissue score showed no significant difference(P＞0.05),whereas the 5%acetic acid enema had a medium to large amount of inflammatory cell infiltration,and the pathological tissue score was increased(P＜0.01).(2)Compared with group a,group b had lower body weight(P＜0.001),and higher fecal trait score,fecal water content and diarrhea index(P＜0.01).Compared with a and b groups,the body weight of c and d groups was lower(P＜0.001),the fecal traits score,fecal water content,and diarrhea index were increased(P＜0.01),and the colon running time was decreased(P＜0.01).Compared with group c,Fecal water content in group D was higher(P＜0.001).In the OFT score,compared with a and b groups,the OFT distance,standing times,and upright times in c and d groups were lower(P＜0.05).Compared with c,the OFT distance,standing times,and upright times in d group were lower(P＜0.05).The pathological tissue of colon showed that the mucosal structure of the four groups was complete,and there were different degrees of inflammatory cell infiltration.The pathological tissue scores of groups c and d were higher than those of groups a and b(P＜0.05).Conclusions The 4%acetic acid concentration is appropriate for IBS-D modeling.After superposition and binding,the IBS-D diarrhea and internal hypersensitivity characteristic state can be better simulated.After superposition of a tail clip,the IBS-D model of liver stagnation and spleen deficiency can be established successfully.

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 provide reference for the management of antithrombotic therapy in thrombocytopenia patients with atrial fibrillation and atherosclerosis. METHODS The clinical pharmacist participated in the treatment of a thrombocytopenia patient with atrial fibrillation and atherosclerosis， and analyzed the causes of thrombocytopenia according to the patient’s medical history and laboratory examination results. At the same time， the risk of thrombosis-bleeding was evaluated according to the relevant guidelines， and the clinicians were assisted in formulating individual antithrombotic therapy plan and pharmaceutical care plan for the patient. The literature on antithrombotic therapy related to thrombocytopenia was collected and analyzed by retrieving CNKI. RESULTS Thrombocytopenia was considered as primary thrombocytopenia in this patient， and the main risk of bleeding was age ≥65 years old， bleeding tendency， and combined use of antithrombotic drugs. After the clinical pharmacist assessed the risk of thrombosis and bleeding， the clinician was recommended to give full dose of Bemiheparin sodium injection + Dronedarone hydrochloride tablets + Metoprolol succinate sustained-release tablets. In view of thrombocytopenia， the clinician gave Compound zaofan pill， Caffeic acid tablet and Sheng xuexiaoban capsule， but the patient developed diarrhea after the medication. The clinical pharmacist suggested stopping Sheng xuexiaoban capsule， and the clinician adopted the clinical pharmacist’s suggestion. When the patient was discharged from hospital， the clinical pharmacist suggested that the antithrombotic therapy plan for discharge was anticoagulation alone or selective anticoagulation. The clinician chose selective anticoagulation treatment considering that the patient’s current thrombocytopenia， urinary occult blood （+） and fecal occult blood were weakly positive， and ordered the patient to take Metoprolol succinate sustained-release tablets + Atorvastatin calcium tablets at discharge. Literature analysis showed that the causes of thrombocytopenia of patients with thromboembolism mainly included heparin induced-thrombocytopenia， immune thrombocytopenia， etc. All patients were improved after symptomatic treatment. CONCLUSIONS By participating in the management of antithrombotic therapy for the thrombocytopenia patient with atrial fibrillation and atherosclerosis， clinical pharmacists can help effectively control the patient’s condition and ensure the safety and effectiveness of drug use.

OBJECTIVE To provide a reference for the safe use of drugs in patients with complex venous thromboembolism （VTE） and acute renal insufficiency. METHODS Clinical pharmacists participated in the management of anticoagulant therapy for a patient with complex VTE complicated with acute renal insufficiency， and evaluated the patient as high-risk thrombosis and bleeding based on their medical history， laboratory test results， etc.； combined with the complexity of thrombosis and renal insufficiency， clinical pharmacists suggested that enoxaparin sodium should be used in the acute stage of thrombosis （5 to 21 days after onset）， and then warfarin should be adopted for oral anticoagulation treatment. Because the patient’s anticoagulation was not up to the standard （the target range of the international normalized ratio was 2-3）， clinical pharmacists suggested increasing the warfarin dose， detecting the warfarin metabolism genotype， and adjusting the warfarin dose according to the genotype； at the same time， clinical pharmacists developed an anticoagulation monitoring plan to ensure the safety of anticoagulation treatment. RESULTS Doctors had adopted all the recommendations of clinical pharmacists. The patient did not experience adverse events such as bleeding or worsening of thromboembolism during anticoagulation in the hospital. When the anticoagulation met the standards， the patient was allowed to be discharged with medication. CONCLUSIONS By participating in the anticoagulation treatment management of patients with complex VTE and acute renal insufficiency， clinical pharmacists have assisted doctors in formulating personalized anticoagulation plans to promote the compliance with the anticoagulation treatment standard and ensure the safety and effectiveness of medication for patients.