Objective:To explore drug detoxification motivation in methamphetamine-dependent female youth and its relationship with time perspective,perceived social support and emotion regulation strategies.Methods:To-tally 200 methamphetamine-dependent female youths under compulsory isolation were assessed with the Drug De-toxification Motivation Scale,Zimbardo Time Perspective Inventory-Chinese(ZTPI-C),Emotion Regulation Scale(ERS),and Perceived Social Support Scale(PSSS).Results:Multiple linear regression analysis showed that drug detoxification motivation scores were positively correlated with the scores of ERS reevaluation and expression inhi-bition,PSSS family support scores and level of education(β=0.24,0.16,0.20,0.16).Conclusion:Time perspec-tive,perceived social support and emotion regulation strategies are closely related to drug detoxification motivation in methamphetamine-dependent female youth.

Objective Human facial morphology is an appearance phenotype with high heritability,high diversity,and complexity.Traditional facial morphological genetic analysis is mostly based on facial landmark measurements,using linear regression for genome-wide association studies,but this method extracts limited facial morphological feature information.This study established an extraction method for multidimensional facial representations and validated the correlation between 473 single-nucleotide polymorphisms(SNPs)previously reported to be significantly associated with facial features and facial representations in the Han Chinese population.Methods After acquiring facial 3D images,3D morphable face models and HR-net network were used to align and quantify the 3D images,obtaining high-density 3D facial point cloud data.After unsupervised clustering of the point cloud,principal component analysis was applied to reduce dimensionality and extract multidimensional morphological phenotypes for each facial region.Based on these multidimensional phenotypes,partial least squares regression(PLSR)and canonical correlation analysis(CCA)were used for genetic association analysis.Results A total of 10 SNPs were validated to be significantly associated with facial morphology in Han Chinese,of which 7 SNPs were validated by the PLSR method,2 SNPs were validated by the CCA method,and 1 SNP was validated by both methods.Conclusion Among the 10 significantly associated SNP sites,9 related facial morphological regions were consistent with previous reports in other populations,indicating that genes affecting complex facial morphology have cross-population effects.

Liver transplantation is a crucial treatment for end-stage liver disease,yet its complexity continues to limit clinical application.With the development of the internet and big data,artificial intelligence(AI)technologies have gradually expanded their use in liver transplantation surgery,covering donor liver evaluation,organ allocation,robot-assisted surgery,and postoperative management,demonstrating significant advantages.However,the application of AI also raises a series of ethical issues,notably fairness in resource allocation,conflicts between technical limitations and the principle of non-maleficence,ambiguous responsibility attribution,patient privacy security,and informed consent.This article systematically reviews the current applications of AI in liver transplantation surgery and the related ethical challenges,aiming to provide a reference for its rational use and sustainable development.

Objective To establish an animal model of hand,foot,and mouth disease(HFMD)in Syrian hamsters coinfected with coxsackievirus A6(CVA6)and coxsackievirus B1(CVB1).Methods 42 Syrian hamsters were divided into a CVA6 infection group,CVB1 infection group,CVA6 and CVB1 coinfection group and control group.A HFMD model was established by nasal instillation of virus solution and phosphate-buffered saline.Clinical and physiological indicators and detoxification status were monitored and recorded for 15 d,and animals were selected on day 7(D7)after infection for histopathology and viral antigen and nucleic acid testing.Results Hamsters in the single-infection and coinfection groups showed clinical symptoms similar to human HFMD.White blood cell,neutrophil,and lymphocyte result were characteristic of viral infection.Both viral nucleic acids were detected in throat swabs,feces,blood,and tissues and both viruses were isolated from fecal samples.Pathological damage and positive co-localization of CVA6 and CVB1 viral antigen proteins and nucleic acids were found in brain and other tissues.Conclusions Nasal instillation of a CVA6 and CVB1 mixture can successfully coinfect Syrian hamsters,replicate herpes infection similar to human HFMD,and cause pathological viral myocarditis and encephalitis damage.The result showed that the coinfection group was more seriously affected than the single-infection group,with worse clinical symptoms,increased viral replication,and obvious tissue pathological damage.This study provides a reference for further basic and clinical research into human enterovirus coinfection.

ObjectiveTo determine the optimal combination of the effective monomer components "quercetin-kaempferol-abietic acid-boswellic acid" in Fujin Shengjisan for promoting diabetic ulcer （DU） wound healing through uniform design， thereby achieving the modern application of the ancient formula. MethodsFollowing the principle of "uniform design-pharmacodynamic experiment-mathematical modeling and model verification"， the U₁₄（14⁵） uniform design table was adopted.The four monomer components of Chinese medicine were considered as the independent variables， and the proliferation rate of human umbilical vein endothelial cells （HUVECs） induced by glucose was used as the pharmacodynamic indicator. A mathematical model was constructed using DPS software to correlate the effective monomer components with the pharmacodynamic indicator. The results of uniform design were verified through CCK-8 assay， cell scratch healing， tube formation， Western blot， and Real-time PCR. ResultsAmong the 14 compatibility groups， compared with the high-glucose model group， compound compatibility group 6 showed the strongest proliferation effect and statistical significance （P<0.05）. Four quadratic polynomial regression equations （Y₁-Y₄） were obtained through DPS modeling. Considering the model's fit， stability， and practical application， equations Y₁-Y₃ were selected for the follow-up verification. To ensure experiment reproducibility， group 6 was used for validation. Group 6 and equations Y₁-Y₃ were renamed as compound prescription ① to compound prescription④， respectively， to represent the modern application of the ancient FJSJ Powder through compatibility of monomer components. Verification experiments showed that in the CCK-8， scratch healing， and tube formation assays， the cell viability， wound healing rate， and tube formation number of HUVECs stimulated with 50 mmol·L^-1 glucose were significantly reduced compared with the blank group. Moreover， the expression levels of angiogenesis-related cytokines， vascular endothelial growth factor （VEGF） and fibroblast growth factor 2 （FGF2）， and CD31 secretion were significantly down-regulated. However， after intervention with compound prescriptions ① to ④， compound prescriptions ① and ③ significantly improved the biological functions of HUVECs induced by 50 mmol·L^-1 glucose. Further analysis of the regression coefficients of compound prescriptions ① and ③， and the relative dose ratios of each monomer component， indicated that abietic acid， quercetin， and boswellic acid promoted angiogenesis of HUVECs in the high glucose environment， with a major effect （positive partial correlation coefficients， all > 0.9）. Abietic acid and boswellic acid， as well as kaempferol and boswellic acid， promoted angiogenesis in HUVECs through interaction （positive partial correlation coefficients）. ConclusionCompound prescriptions ① and ③ are the optimal combinations. They can reverse the inhibitory effects of high glucose， stimulate the proliferation， migration， and tube formation abilities of HUVECs in a high glucose environment， and promote the expression of vascular endothelial growth factorA（VEGFA）， FGF2， and CD31， thereby promoting angiogenesis and facilitating DU wound healing. This finding not only confirms the good reproducibility and feasibility of compound prescriptions ① and ③ but also provides new insights and methods for the rational construction of mathematical models to further study the compatibility theory of Chinese medicine.

Objective To establish a pediatric rare disease catalog,analyze the current status of therapeutic drugs and their coverage of the medical insurance in China,and propose strategies to enhance drug accessibility.Methods Pediatric rare diseases were identified from China's two national rare disease catalogs combined with the EU Orphanet database,US FDA orphan drug database,and the Diagnosis and Treatment Standards for Rare Diseases in Children.We created a specialized drug catalog for pediatric rare diseases,then analyzed drug types(ATC classification),pricing,and medical insurance coverage using descriptive statistics based on Yaozhi.com drug bidding prices and the 2024 Drug of List National Basic Medical Insurance(NBMIDL).Drug affordability was assessed through annual treatment cost calculations.Results The national catalogs included 151 pediatric rare diseases(72.95%of listed conditions),spanning 13 disease systems.We identified 94 dedicated orphan drugs(by generic name)for these conditions,among which 43 were approved internationally but unavailable in China.The average unit price per package was 6 113.53 yuan.Overall NBMIDL coverage was 68.83%,but drugs priced above 7 000 yuan per unit had only 7.69%coverage.Annual treatment costs reached 4.54 million for laronidase(mucopolysaccharidosis).Conclusions Critical gaps persist in China's pediatric rare disease treatment landscape,including catalog deficiencies,inadequate coverage for high-cost drugs and insufficient domestic innovation.It is recommended to establish a list of orphan drugs for pediatric rare diseases,accelerate the import of foreign drugs and the local innovative drugs through policy incentives,optimizing medical insurance reimbursement mechanisms for pediatric rare disease drugs to comprehensively improve therapeutic accessibility.

Objective To establish an animal model of hand,foot,and mouth disease(HFMD)in Syrian hamsters coinfected with coxsackievirus A6(CVA6)and coxsackievirus B1(CVB1).Methods 42 Syrian hamsters were divided into a CVA6 infection group,CVB1 infection group,CVA6 and CVB1 coinfection group and control group.A HFMD model was established by nasal instillation of virus solution and phosphate-buffered saline.Clinical and physiological indicators and detoxification status were monitored and recorded for 15 d,and animals were selected on day 7(D7)after infection for histopathology and viral antigen and nucleic acid testing.Results Hamsters in the single-infection and coinfection groups showed clinical symptoms similar to human HFMD.White blood cell,neutrophil,and lymphocyte result were characteristic of viral infection.Both viral nucleic acids were detected in throat swabs,feces,blood,and tissues and both viruses were isolated from fecal samples.Pathological damage and positive co-localization of CVA6 and CVB1 viral antigen proteins and nucleic acids were found in brain and other tissues.Conclusions Nasal instillation of a CVA6 and CVB1 mixture can successfully coinfect Syrian hamsters,replicate herpes infection similar to human HFMD,and cause pathological viral myocarditis and encephalitis damage.The result showed that the coinfection group was more seriously affected than the single-infection group,with worse clinical symptoms,increased viral replication,and obvious tissue pathological damage.This study provides a reference for further basic and clinical research into human enterovirus coinfection.

Objective:To study the changes of immune cells in allergic airway inflammation induced by house dust mites(HDM)in the mouse model,and investigate the effect of alveolar macrophages(AM)on allergic airway inflammation.Methods:Al-lergic airway inflammation was induced by intratracheal injection of HDM,and AM were specifically depleted by intratracheal injec-tion of chlorophosphonate liposomes(CL)before HDM treatment;the immune cells of mouse lung were isolated by heart perfusion.The immune cells of mouse alveolar lavage fluid were isolated by tracheal lavage.The level of type Ⅱ cytokines in alveolar lavage fluid was determined by ELISA.The changes of immune cells in mouse lung tissue and alveolar lavage fluid were detected by flow cytome-try;HE staining and PAS staining were performed to observe the infiltration of inflammatory cell,goblet cell proliferation and mucus secretion in the lung sections after HDM treatment.Results:The effector cells of type Ⅱ immune response,such as group 2 innate lymphoid cells(ILC2)and eosinophils,were significantly increased in allergic airway inflammation induced by HDM in mice.Histo-logical analysis also revealed substantial inflammatory cell infiltration,goblet cells proliferation and mucus secretion in lung tissue.The depletion of AM alleviated HDM induced type Ⅱ immune response,but promoted the infiltration of neutrophils and aggravated the pathological injury of the lung.Conclusion:AM plays an important role in HDM induced allergic airway inflammation.

Objective To establish a pediatric rare disease catalog,analyze the current status of therapeutic drugs and their coverage of the medical insurance in China,and propose strategies to enhance drug accessibility.Methods Pediatric rare diseases were identified from China's two national rare disease catalogs combined with the EU Orphanet database,US FDA orphan drug database,and the Diagnosis and Treatment Standards for Rare Diseases in Children.We created a specialized drug catalog for pediatric rare diseases,then analyzed drug types(ATC classification),pricing,and medical insurance coverage using descriptive statistics based on Yaozhi.com drug bidding prices and the 2024 Drug of List National Basic Medical Insurance(NBMIDL).Drug affordability was assessed through annual treatment cost calculations.Results The national catalogs included 151 pediatric rare diseases(72.95%of listed conditions),spanning 13 disease systems.We identified 94 dedicated orphan drugs(by generic name)for these conditions,among which 43 were approved internationally but unavailable in China.The average unit price per package was 6 113.53 yuan.Overall NBMIDL coverage was 68.83%,but drugs priced above 7 000 yuan per unit had only 7.69%coverage.Annual treatment costs reached 4.54 million for laronidase(mucopolysaccharidosis).Conclusions Critical gaps persist in China's pediatric rare disease treatment landscape,including catalog deficiencies,inadequate coverage for high-cost drugs and insufficient domestic innovation.It is recommended to establish a list of orphan drugs for pediatric rare diseases,accelerate the import of foreign drugs and the local innovative drugs through policy incentives,optimizing medical insurance reimbursement mechanisms for pediatric rare disease drugs to comprehensively improve therapeutic accessibility.

Objective:To explore drug detoxification motivation in methamphetamine-dependent female youth and its relationship with time perspective,perceived social support and emotion regulation strategies.Methods:To-tally 200 methamphetamine-dependent female youths under compulsory isolation were assessed with the Drug De-toxification Motivation Scale,Zimbardo Time Perspective Inventory-Chinese(ZTPI-C),Emotion Regulation Scale(ERS),and Perceived Social Support Scale(PSSS).Results:Multiple linear regression analysis showed that drug detoxification motivation scores were positively correlated with the scores of ERS reevaluation and expression inhi-bition,PSSS family support scores and level of education(β=0.24,0.16,0.20,0.16).Conclusion:Time perspec-tive,perceived social support and emotion regulation strategies are closely related to drug detoxification motivation in methamphetamine-dependent female youth.