Traditional Chinese medicine(TCM)is an ancient medical system distinctive and effective in treating cancer,depression,coronavirus disease 2019(COVID-19),and other diseases.However,the relatively abstract diagnostic methods of TCM lack objective measurement,and the complex mechanisms of action are difficult to comprehend,which hinders the application and internationalization of TCM.Recently,while breakthroughs have been made in utilizing methods such as network pharmacology and virtual screening for TCM research,the rise of machine learning(ML)has significantly enhanced their inte-gration with TCM.This article introduces representative methodological cases in quality control,mechanism research,diagnosis,and treatment processes of TCM,revealing the potential applications of ML technology in TCM.Furthermore,the challenges faced by ML in TCM applications are summarized,and future directions are discussed.

Traditional Chinese medicine (TCM) is an ancient medical system distinctive and effective in treating cancer, depression, coronavirus disease 2019 (COVID-19), and other diseases. However, the relatively abstract diagnostic methods of TCM lack objective measurement, and the complex mechanisms of action are difficult to comprehend, which hinders the application and internationalization of TCM. Recently, while breakthroughs have been made in utilizing methods such as network pharmacology and virtual screening for TCM research, the rise of machine learning (ML) has significantly enhanced their integration with TCM. This article introduces representative methodological cases in quality control, mechanism research, diagnosis, and treatment processes of TCM, revealing the potential applications of ML technology in TCM. Furthermore, the challenges faced by ML in TCM applications are summarized, and future directions are discussed.

Objective To construct a theoretical framework for early home-based education and rehabilitation for infants and tod-dlers with developmental disabilities,using the bio-psycho-social model of the International Classification of Functioning,Disability and Health(ICF).Methods On the base of integrating ecosystem theory,neuroplasticity theory,family systems theory and rehabilitation concept of World Health Organization,a home-based education and rehabilitation system encompassing biologi-cal,psychological,social and policy dimensions was developed.Results Within the ICF framework,it was set the operational intervention goals for infants and toddlers in dimensions of motor,language,cognition,emotion and social interaction,while personalized goals were formulated in consider-ation of different types of developmental disabilities.Furthermore,a home-based education and rehabilitation sys-tem was designed,including early screening and assessment,development of personalized intervention plans,home-based education and rehabilitation training,continuous monitoring and adjustment,digital empowerment and remote guidance,as well as disability prevention,and early education and rehabilitation.It involved five stag-es:needs assessment,plan development,plan implementation,dynamic assessment and feedback,and summary and referral.Conclusion This study has constructed a five-stage process,providing an effective framework for the comprehensive re-habilitation of infants and toddlers.ICF framework provides both theoretical and practical guidance for early in-tervention in infants and toddlers with developmental disabilities.

Objective To analyze the core syndromes of patients with generalized anxiety disorder(GAD),explore the core pathogenesis,and offer innovative perspectives and practical strategies for the traditional Chinese medicine(TCM)diagnosis and treatment of GAD.Methods The basic information of GAD patients was collected,and depression symptoms were evaluated with Hamilton Anxiety Scale to evaluate anxiety symptoms,Hamilton Depression Scale,and the TCM psychiatric and somatic symptoms were evaluated with Traditional Chinese Medicine Symptom Observation Form.Based on the data collected from the Traditional Chinese Medicine symptom observation table,the systematic clustering method was used to cluster the symptoms with a frequency greater than 10％,determine the disease type syndrome and disease location syndrome,and form a syndrome symptom relationship table.According to this table,the traditional Chinese medicine syndrome score of each patient is calculated.The complex network analysis was carried out to evaluate core syndromes and analyze the relationships between core syndromes and psychiatric symptoms and core syndromes and other syndromes.Results A total of 517 patients with GAD were included.There were 81 symptoms with a frequency of more than 10％,including 21 psychological symptoms and 60 physical symptoms.The clustering analysis led to a total of 12 syndromes,including 6 pathological syndromes,namely yin deficiency,heat,phlegm dampness,qi stagnation,blood stasis,and qi deficiency,and 6 disease location syndromes,namely liver,spleen,kidney,gallbladder,stomach,and heart.The results of complex network analysis show that the core pathological syndrome of GAD is kidney,and the core pathological syndrome is yin deficiency.The joint analysis of pathological syndrome and pathological syndrome network suggests that yin deficiency is the core of the integrated network.The relationship between yin deficiency syndrome and various organs is in the order of kidney,spleen,gallbladder,liver,heart,and stomach.The syndrome element of yin deficiency has the highest correlation with being easily frightened,excessive thinking,indecisiveness,repetitive behavior,and groundless worry.The kidney syndrome has the highest correlation with the symptoms such as being easily scared,unfounded worry,repetitive actions,excessive rumination,and restlessness.Conclusion The core pathological pattern of GAD is kidney and the core pathological pattern is yin deficiency.Kidney yin deficiency may be the core pathogenesis of GAD.

Objective:To investigate whether kisspeptin can influence the maternal-fetal interface regulatory T cells(Treg),thereby participating in the pathogenesis of recurrent spontaneous abortion(RSA).Methods:Normal pregnancy(NP)and RSA mice models were established,where NP mice received a tail vein injection of PBS(NP-PBS group),and RSA mice received a tail vein in-jection of PBS(RSA-PBS group)and active fragment of kisspeptin KP10(RSA-KP10 group),observing embryo absorption rates.Im-munohistochemistry was employed to assess expressions of kisspeptin and Foxp3 in mice uterine tissues.Peripheral blood Treg cells were isolated and expanded through magnetic bead separation.Intervention with KP10 and KP234(kisspeptin receptor antagonist)was administered,and flow cytometry was used to detect levels of IL-10 and TGF-β1 secretion by Treg cells,as well as differences in proliferation and apoptosis.RNA-Seq transcriptomic sequencing was conducted on uterine tissues from RSA-PBS group and RSA-KP10 group of mice.Differentially expressed genes(DEGs)were subjected to GO,KEGG and GSEA enrichment analyses.Results:Embryo absorption rate in RSA mice was higher than that in NP mice,the embryo absorption rate was decreased after tail vein injec-tion of KP10.Expressions of kisspeptin and Foxp3 in uterus of RSA mice was lower than that in NP mice,while increased after injec-tion of KP10.Kisspeptin could modulate the secretion of IL-10 and TGF-β1 by Treg cells,influencing their proliferation without affect-ing apoptosis.Enrichment analysis results showed that DEGs were mainly enriched in reproductive structure development,IL-17,and TGF-β signaling pathways.Conclusion:Kisspeptin can influence both the quantity and function of Treg cells,offering a new theoreti-cal foundation for investigating the pathogenesis and treatment of RSA.

Objective To analyze the core syndromes of patients with generalized anxiety disorder(GAD),explore the core pathogenesis,and offer innovative perspectives and practical strategies for the traditional Chinese medicine(TCM)diagnosis and treatment of GAD.Methods The basic information of GAD patients was collected,and depression symptoms were evaluated with Hamilton Anxiety Scale to evaluate anxiety symptoms,Hamilton Depression Scale,and the TCM psychiatric and somatic symptoms were evaluated with Traditional Chinese Medicine Symptom Observation Form.Based on the data collected from the Traditional Chinese Medicine symptom observation table,the systematic clustering method was used to cluster the symptoms with a frequency greater than 10％,determine the disease type syndrome and disease location syndrome,and form a syndrome symptom relationship table.According to this table,the traditional Chinese medicine syndrome score of each patient is calculated.The complex network analysis was carried out to evaluate core syndromes and analyze the relationships between core syndromes and psychiatric symptoms and core syndromes and other syndromes.Results A total of 517 patients with GAD were included.There were 81 symptoms with a frequency of more than 10％,including 21 psychological symptoms and 60 physical symptoms.The clustering analysis led to a total of 12 syndromes,including 6 pathological syndromes,namely yin deficiency,heat,phlegm dampness,qi stagnation,blood stasis,and qi deficiency,and 6 disease location syndromes,namely liver,spleen,kidney,gallbladder,stomach,and heart.The results of complex network analysis show that the core pathological syndrome of GAD is kidney,and the core pathological syndrome is yin deficiency.The joint analysis of pathological syndrome and pathological syndrome network suggests that yin deficiency is the core of the integrated network.The relationship between yin deficiency syndrome and various organs is in the order of kidney,spleen,gallbladder,liver,heart,and stomach.The syndrome element of yin deficiency has the highest correlation with being easily frightened,excessive thinking,indecisiveness,repetitive behavior,and groundless worry.The kidney syndrome has the highest correlation with the symptoms such as being easily scared,unfounded worry,repetitive actions,excessive rumination,and restlessness.Conclusion The core pathological pattern of GAD is kidney and the core pathological pattern is yin deficiency.Kidney yin deficiency may be the core pathogenesis of GAD.

Objective:To investigate whether kisspeptin can influence the maternal-fetal interface regulatory T cells(Treg),thereby participating in the pathogenesis of recurrent spontaneous abortion(RSA).Methods:Normal pregnancy(NP)and RSA mice models were established,where NP mice received a tail vein injection of PBS(NP-PBS group),and RSA mice received a tail vein in-jection of PBS(RSA-PBS group)and active fragment of kisspeptin KP10(RSA-KP10 group),observing embryo absorption rates.Im-munohistochemistry was employed to assess expressions of kisspeptin and Foxp3 in mice uterine tissues.Peripheral blood Treg cells were isolated and expanded through magnetic bead separation.Intervention with KP10 and KP234(kisspeptin receptor antagonist)was administered,and flow cytometry was used to detect levels of IL-10 and TGF-β1 secretion by Treg cells,as well as differences in proliferation and apoptosis.RNA-Seq transcriptomic sequencing was conducted on uterine tissues from RSA-PBS group and RSA-KP10 group of mice.Differentially expressed genes(DEGs)were subjected to GO,KEGG and GSEA enrichment analyses.Results:Embryo absorption rate in RSA mice was higher than that in NP mice,the embryo absorption rate was decreased after tail vein injec-tion of KP10.Expressions of kisspeptin and Foxp3 in uterus of RSA mice was lower than that in NP mice,while increased after injec-tion of KP10.Kisspeptin could modulate the secretion of IL-10 and TGF-β1 by Treg cells,influencing their proliferation without affect-ing apoptosis.Enrichment analysis results showed that DEGs were mainly enriched in reproductive structure development,IL-17,and TGF-β signaling pathways.Conclusion:Kisspeptin can influence both the quantity and function of Treg cells,offering a new theoreti-cal foundation for investigating the pathogenesis and treatment of RSA.

Objective:To investigate the correlation of combined detection of p16 and Rb with high-risk human papilloma virus (HR-HPV) infection in non-oropharyngeal squamous cell carcinoma (NOPSCC) of the head and neck.Methods:A total of 68 NOPSCC cases of the head and neck (23 cases of the nasal cavity and paranasal sinuses and 45 cases of larynx) with complete clinical and pathological data, diagnosed at the Beijing Tongren Hospital, Capital Medical University, Beijing, China from November 2013 to December 2023, were collected. The expression of p16 and Rb was detected using immunohistochemistry of the EnVision two-step method, while the HR-HPV mRNA expression was detected using in situ hybridization. The concordance, sensitivity, and specificity of p16 alone and the combined detection of p16 and Rb for detecting HR-HPV infection were analyzed.Results:Among the 68 patients with NOPSCC, 53 were male and 15 were female, with a median age of 63.5 (range, 57.3 to 66.8) years. 41 patients had a smoking history and 27 did not. 33 patients had an early T stage (T1/T2) and 35 had advanced T stage (T3/T4). 14 patients had lymph node metastasis and 2 had distant metastasis. Histological types included 62 cases of keratinized squamous cell carcinoma, 5 cases of non-keratinized squamous cell carcinoma, and 1 case of basal-like squamous cell carcinoma. 25 cases were positive for p16. Among the 25 cases, 16 cases were positive for Rb, and 6 cases were positive for HR-HPV mRNA. 43 cases were negative for p16, including 38 cases positive for Rb and no cases positive for HR-HPV mRNA. The concordance between p16 and HR-HPV mRNA expression was poor ( Kappa=0.285, P=0.001), with a sensitivity of 100.0% and specificity of 69.4%. In contrast, the combined detection of p16+/Rb- showed high concordance with HR-HPV mRNA expression ( Kappa=0.719, P<0.001), with a sensitivity of 100.0% and specificity of 95.2%. Conclusions:In NOPSCC of the head and neck, the combined detection of p16 and Rb may be used as a marker for assessing HR-HPV infection. Recognizing the p16+/Rb- expression pattern in NOPSCC can improve the specificity of HR-HPV detection.

Objective To construct a theoretical framework for early home-based education and rehabilitation for infants and tod-dlers with developmental disabilities,using the bio-psycho-social model of the International Classification of Functioning,Disability and Health(ICF).Methods On the base of integrating ecosystem theory,neuroplasticity theory,family systems theory and rehabilitation concept of World Health Organization,a home-based education and rehabilitation system encompassing biologi-cal,psychological,social and policy dimensions was developed.Results Within the ICF framework,it was set the operational intervention goals for infants and toddlers in dimensions of motor,language,cognition,emotion and social interaction,while personalized goals were formulated in consider-ation of different types of developmental disabilities.Furthermore,a home-based education and rehabilitation sys-tem was designed,including early screening and assessment,development of personalized intervention plans,home-based education and rehabilitation training,continuous monitoring and adjustment,digital empowerment and remote guidance,as well as disability prevention,and early education and rehabilitation.It involved five stag-es:needs assessment,plan development,plan implementation,dynamic assessment and feedback,and summary and referral.Conclusion This study has constructed a five-stage process,providing an effective framework for the comprehensive re-habilitation of infants and toddlers.ICF framework provides both theoretical and practical guidance for early in-tervention in infants and toddlers with developmental disabilities.

Objective:To investigate the correlation of combined detection of p16 and Rb with high-risk human papilloma virus (HR-HPV) infection in non-oropharyngeal squamous cell carcinoma (NOPSCC) of the head and neck.Methods:A total of 68 NOPSCC cases of the head and neck (23 cases of the nasal cavity and paranasal sinuses and 45 cases of larynx) with complete clinical and pathological data, diagnosed at the Beijing Tongren Hospital, Capital Medical University, Beijing, China from November 2013 to December 2023, were collected. The expression of p16 and Rb was detected using immunohistochemistry of the EnVision two-step method, while the HR-HPV mRNA expression was detected using in situ hybridization. The concordance, sensitivity, and specificity of p16 alone and the combined detection of p16 and Rb for detecting HR-HPV infection were analyzed.Results:Among the 68 patients with NOPSCC, 53 were male and 15 were female, with a median age of 63.5 (range, 57.3 to 66.8) years. 41 patients had a smoking history and 27 did not. 33 patients had an early T stage (T1/T2) and 35 had advanced T stage (T3/T4). 14 patients had lymph node metastasis and 2 had distant metastasis. Histological types included 62 cases of keratinized squamous cell carcinoma, 5 cases of non-keratinized squamous cell carcinoma, and 1 case of basal-like squamous cell carcinoma. 25 cases were positive for p16. Among the 25 cases, 16 cases were positive for Rb, and 6 cases were positive for HR-HPV mRNA. 43 cases were negative for p16, including 38 cases positive for Rb and no cases positive for HR-HPV mRNA. The concordance between p16 and HR-HPV mRNA expression was poor ( Kappa=0.285, P=0.001), with a sensitivity of 100.0% and specificity of 69.4%. In contrast, the combined detection of p16+/Rb- showed high concordance with HR-HPV mRNA expression ( Kappa=0.719, P<0.001), with a sensitivity of 100.0% and specificity of 95.2%. Conclusions:In NOPSCC of the head and neck, the combined detection of p16 and Rb may be used as a marker for assessing HR-HPV infection. Recognizing the p16+/Rb- expression pattern in NOPSCC can improve the specificity of HR-HPV detection.