Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

ObjectiveIn the context of the digital transformation of education, this study aims to construct a triadic interactive teaching model for surgical animal surgery in clinical medicine using modern information technology. It explores the effectiveness of different teaching methods in improving students' practical skills, aseptic awareness, and teamwork abilities, providing a reference for the reform of clinical practice education. MethodsA quasi-experimental research design was adopted. A total of 80 students from the eight-year clinical medicine program at Nanjing University were selected, including the Class of 2020 (control group, n=40) and the Class of 2021 (experimental group, n=40). The control group received traditional teaching methods, while the experimental group implemented the "Teacher-Student-AI" triadic interactive teaching model. This model utilized a smart teaching platform for personalized pre-class preparation , as well as data-driven post-class review and feedback throughout the entire teaching process. The "assessment indicators and scoring criteria for the surgical animal surgery course" were used to evaluate teaching effectiveness, with independent samples t-tests used for statistical analysis. ResultsPre-course assessments revealed no statistically significant differences in baseline theoretical knowledge or practical skills between the two groups (P>0.05). Upon completion of the course, the experimental group achieved higher scores than the control group across three key dimensions: practical skills (47.98±1.34 vs 46.92±2.51, P=0.022), aseptic awareness (17.84±1.16 vs 16.94±2.29, P=0.029), and teamwork (16.82±1.44 vs 15.95±1.22, P=0.004). However, no statistically significant difference was observed in the scores for humane care awareness between the two groups (8.24±0.70 vs 8.16±0.53, P=0.589). ConclusionThe AI-based triadic interactive teaching model can, to some extent, address the limitations of traditional surgical animal surgery education. It plays a positive role in enhancing medical students' surgical skills, aseptic awareness, and collaborative abilities. This model facilitates the transition from traditional to personalized teaching and offers a practical framework for the digital reform of clinical practice education.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

This study investigated the association between a proximal promoter polymorphism of IFNGR1 (interferon-γ receptor α chain, IFNGR-α) and breast cancer susceptibility, as well as the prognostic value of its expression variation in breast cancer patients. A case-control study was conducted at the Sixth Medical Center of PLA General Hospital from June 2020 to June 2022. The study included 182 pathologically confirmed breast cancer patients as the breast cancer group, 177 non-tumor patients with benign breast lesions as the benign breast lesions group, and 229 healthy individuals as the normal control group. 2-3 ml EDTA anticoagulant whole blood samples were collected from all participants, and genomic DNA was extracted and stored for further analysis. Basic patient information was retrieved from the hospital′s electronic medical records by patients′ ID number. The proximal promoter sequence of IFNGR1 was obtained from NCBI, and sequencing primers were designed using Primer Premier 6.0. Sanger sequencing was employed to analyze the IFNGR1 promoter sequence in the three groups, and the results were compared with the Eukaryotic Promoter Database (EPD) sequence using Bioedit software. Statistical analysis was performed on single nucleotide polymorphisms (SNPs) in the IFNGR1 promoter. The TCGA database was utilized to assess the relationship between IFNGR1 expression levels and breast cancer patient survival. The findings revealed that the -56 TG genotype of the IFNGR1 promoter was significantly associated with increased breast cancer risk ( Z=2.73, P<0.05). Notably, IFNGR1 expression was lower in breast cancer group compared to normal control group ( P<0.05). Analysis of the TCGA database indicated that patients with high IFNGR1 expression had longer survival times than those with low expression ( HR=0.87, 95% CI:0.77-0.98, P<0.05). In summary, the IFNGR1 -56 TG genotype is associated with an increased risk of breast cancer, and there is a positive correlation between IFNGR1 expression levels and the survival of breast cancer patients.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.

Long-term hypertension causes excessive vascular remodeling and leads to adverse cardiovascular events. Balance of ubiquitination and deubiquitination has been linked to several chronic conditions, including pathological vascular remodeling. In this study, we discovered that the expression of ubiquitin-specific protease 25 (USP25) is significantly up-regulated in angiotensin II (Ang II)-challenged mouse aorta. Knockout of Usp25 augments Ang II-induced vascular injury such as fibrosis and endothelial to mesenchymal transition (EndMT). Mechanistically, we found that USP25 interacts directly with Forkhead box O3 (FOXO3) and removes the K63-linked ubiquitin chain on the K258 site of FOXO3. We also showed that this USP25-mediated deubiquitination of FOXO3 increases its binding to light chain 3 beta isoform and autophagosomic-lysosomal degradation of FOXO3. In addition, we further validated the biological function of USP25 by overexpressing USP25 in the mouse aorta with AAV9 vectors. Our studies identified FOXO3 as a new substrate of USP25 and showed that USP25 may be a potential therapeutic target for excessive vascular remodeling-associated diseases.

This study was aimed at understanding the prevalence and influencing factors of food-borne parasitic diseases in ethnic minority areas of Guizhou Province,to provide a scientific basis for the development of appropriate intervention measures based on the human-animal-environment One Health concept.In 2023,the infection status of the human population,reservoir hosts,intermediate hosts,food-borne parasitic diseases,and related social and environmental factors were investigated in Congjiang County in Qidongnan Miao and Dong Autonomous Prefecture;Luodian County in Qiannan Buyi and Miao Autonomous Prefecture;and Ceheng County in Qianxinan Buyi and Miao Autonomous Prefecture.At least 1 000 individuals were sampled from each county,along with at least 50 insect-protected host samples from each location.Food-borne parasite infections were detected with the modified Kato thick smear method.A questionnaire survey was administered to the population.Detection of food-borne parasitic metacercariae was performed in intermediate host fish through the flaking and digestion method,and in crabs through the pounding and sedimentation method.The chi-square test was used to compare rates,and logistic regression was applied for multivariate analysis.A total of 3 023 questionnaires and fecal samples were collected.Males accounted for 47.50%,females accounted for 52.50%,and members of ethnic minorities accounted for 96.06%.A total of 186 food-borne parasitic infections were identified,and the infection rate was 6.15%.Five insect species were detected,which showed an infection rate of 5.39%.The infection rate of Clonorchis sinensis was 0.33%,that of Taenia was 0.40%,that of Heteroceles was 0.17%,that of Acanthus was 0.17%,and that of Echinostoma was 0.03%.Human infections with Echinostomus colloides and Echinostomia transferoris had not previously been reported in China.Single-factor analysis revealed statistically significant differences in food-borne parasite infections according to various factors,including the consumption of untreated water,raw fish and shrimp,raw pig blood,raw cow gastric juice,and raw pork and beef,as well as raw pig and cow viscera(P<0.05).Multivariate analysis indicated that the risk factors for food-borne parasite infections among residents in minority areas of Guizhou Province included the consumption of raw pig blood(OR=2.841,95%CI:1.809-4.463),raw cow gastric juice(OR=2.122,95%CI:1.297-3.469),and raw fish and shrimp(OR=1.779,95%CI:1.049-3.018).A total of 173 fecal samples of the reservoir host were examined,which showed a rate of food-borne parasite infection of 5.2%.A total of 510 intermediate host fish were examined,which showed a 4.51%positivity rate of encysted metacercaria of Clonorchis sinensis.The crab,pig,and beef samples were not positive.In conclusion,food-borne parasitic infections were prevalent in ethnic minority regions of Guizhou Province,and consumption of raw food were influencing factors.A focus on populations with raw food consumption habits,including raw pig blood,cow gastric juice,fish and shrimp,is essential.Concurrently,monitoring of animal hosts must be strengthened to perform key interventions according to the One Health concept.

Objective:To analyze the factors associated with long-term survival after radical resection of hepatitis B virus(HBV)-associated hepatocellular carcinoma(HCC),and to construct random forest and Cox regression models,to evaluate the two models.Methods:A total of 368 patients with HBV-infected HCC who underwent radical resection were selected retrospectively.These patients were categorized as having a good prognosis(n=266)or a poor prognosis(n=102)based on their survival and mortality status.Univariate and Cox regression analysis were used to identify fac-tors that predict poor prognosis in HCC patients after surgery,and Cox regression and random forest prediction models were constructed and evaluated.Results:There were significant differences in smoking history,Child-Pugh classifica-tion,cirrhosis,microvascular invasion,TNM staging,tumor capsule integrity,platelet-to-lymphocyte ratio(PLR),regular antiviral therapy,HBV-DNA load,alpha-fetoprotein(AFP),neutrophil-to-lymphocyte ratio(NLR),systemic immune in-flammatory index(SII),and albumin-to-globulin ratio(AGR)between the two groups(P<0.05);Cox regression showed that cirrhosis,microvascular invasion,regular antiviral treatment,HBV-DNA load,NLR,PLR,SII,and AGR were related factors that negatively affected the prognosis of patients with HBV-infected HCC after surgery(P<0.05),with an AUC of 0.870 for predicting prognosis;the importance ranking obtained by the random forest model was HBV-DNA load,cirrho-sis,regular antiviral therapy,microvascular invasion,NLR,PLR,AGR,and SII,with an AUC of 0.926 for predicting prog-nosis;the AUC predicted by the random forest model was greater than that predicted by the Cox regression model(Z=2.411,P=0.016).Conclusion:HBV-DNA load,cirrhosis,regular antiviral therapy,microvascular invasion,NLR,PLR,AGR,and SII are factors that affect the poor prognosis of patients with HBV-related HCC after surgery.The random for-est prediction model constructed based on these factors has high predictive value and is superior to the Cox regression prediction model.

Insulin is an important protein hormone that participates in multiple metabolic pathways.Biosynthetic insulin has been widely used in the treatment of type 1 and type 2 diabetes.Currently,the number of reported cases of insulin overdose both at home and abroad is gradually increasing,and insulin homicide is no longer a means of"committing murder without leaving a trace".At present,there are no systematic protocols for the identification of insulin overdose in the field of forensic medi-cine in China.This article introduces the causes,toxicological characteristics,forensic examination,labo-ratory testing methods and indicator reference of insulin overdose.Based on the identification practice and research results and referring to relevant studies on insulin overdose at home and abroad,this pa-per aims to provide recommendations and references for the formulation of forensic identification guide-lines for insulin overdose cases.