1.Knowledge graph-enhanced long-tail learning approach for traditional Chinese medicine syndrome differentiation
Weikang KONG ; Chuanbiao WEN ; Yue LUO
Digital Chinese Medicine 2026;9(1):57-67
Objective:
To address the dual challenges of long-tail distribution and feature sparsity in traditional Chinese medicine (TCM) syndrome differentiation within real clinical settings, we propose a data-efficient learning framework enhanced by knowledge graphs.
Methods:
We developed Agent-GNN, a three-stage decoupled learning framework, and validated it on the Traditional Chinese Medicine Syndrome Diagnosis (TCM-SD) dataset containing 54 152 clinical records across 148 syndrome categories. First, we constructed a comprehensive medical knowledge graph encoding the complete TCM reasoning system. Second, we proposed a Functional Patient Profiling (FPP) method that utilizes large language models (LLMs) combined with Graph Retrieval-Augmented Generation (RAG) to extract structured symptom-etiology-pathogenesis subgraphs from medical records. Third, we employed heterogeneous graph neural networks to learn structured combination patterns explicitly. We compared our method against multiple baselines including BERT, ZY-BERT, ZY-BERT + Know, GAT, and GPT-4 Few-shot, using macro-F1 score as the primary evaluation metric. Additionally, ablation experiments were conducted to validate the contribution of each key component to model performance.
Results:
Agent-GNN achieved an overall macro-F1 score of 72.4%, representing an 8.7 percentage points improvement over ZY-BERT + Know (63.7%), the strongest baseline among traditional methods. For long-tail syndromes with fewer than 10 samples, Agent-GNN reached a macro-F1 score of 58.6%, compared with 39.3% for ZY-BERT + Know and 41.2% for GPT-4 Few-shot, representing relative improvements of 49.2% and 42.2%, respectively. Ablation experiments confirmed that the explicit modeling of etiology-pathogenesis nodes contributed 12.4 percentage points to this enhanced long-tail syndrome performance.
Conclusion
This study proposes Agent-GNN, a knowledge graph-enhanced framework that effectively addresses the long-tail distribution challenge in TCM syndrome differentiation. By explicitly modeling manifestation-mechanism-essence patterns through structured knowledge graphs, our approach achieves superior performance in data-scarce scenarios while providing interpretable reasoning paths for TCM intelligent diagnosis.
2.Research progress on the mechanisms of traditional Chinese medicine in treating functional constipation based on the gut microbiota-bile acid axis
Xiangrui KONG ; Qimeng ZHANG ; Yue ZOU ; Yong LIANG ; Yu SHI ; Yang ZHANG ; Hongxi ZHANG
China Pharmacy 2026;37(2):244-249
Functional constipation (FC) is a common functional disorder of the intestines, mainly characterized by reduced bowel movement frequency, difficulty in defecation, a sensation of incomplete evacuation, and hard stools, which severely affect patients’ quality of life. Research indicates that the pathogenesis of FC is closely related to gut microbiota dysbiosis and abnormal bile acid secretion. Bile acids, as endogenous natural laxatives, promote bowel movements by enhancing colonic secretion and regulating intestinal motility; meanwhile, gut microbiota influence colonic transit function by regulating the enteric nervous system, immune system, and their metabolic products. Based on an overview of the relationship between gut microbiota and bile acid metabolism, this article systematically reviews the current research status on the mechanisms of traditional Chinese medicine (TCM) in treating FC by regulating the balance of the gut microbiota-bile acid axis. It is found that single Chinese medicinal herbs (such as Atractylodes macrocephala), isolated compounds (such as Platycodon grandiflorum polysaccharides), herbal formulas (such as Shanger huang pill), acupuncture, and moxibustion can up-regulate the abundance of beneficial bacteria, reshape the microbial structure, correct bile acid metabolism, and activate the Takeda G-protein receptor 5/farnesoid X receptor pathway to treat FC.
3.Research progress on traditional Chinese medicine regulation of MAPK signaling pathway in intervening slow transit constipation
Xiangrui KONG ; Qimeng ZHANG ; Yue ZOU ; Yong LIANG ; Yu SHI ; Yang ZHANG ; Ke MENG ; Hongxi ZHANG
China Pharmacy 2026;37(11):1508-1514
low transit constipation (STC) is a common functional intestinal disorder caused by impaired colonic transit function, characterized by reduced bowel movement frequency, hard stools, and difficulty in defecation. The mitogen-activated protein kinase (MAPK) signaling pathway, which mainly includes extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 subtypes, plays a critical regulatory role in the occurrence and development of STC. This paper systematically reviews the multiple pathogenic mechanisms of the MAPK signaling pathway in STC and the research progress of traditional Chinese medicine (TCM) intervention.At the mechanistic level, the MAPK signaling pathway promotes the progression of STC through the following links:(1) Activation of p38 upregulates the expression of aquaporin 3 (AQP3)/AQP4 in the colon, leading to excessive reabsorption of water in the intestinal lumen; (2) It forms a positive feedback loop with nuclear factor-κB (NF-κB) to maintain low-grade intestinal inflammation, releases inflammatory factors such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and inhibits smooth muscle contraction; (3) Overactivation of p38 downregulates the expression of occludin and mucin 2 while upregulates the expression of claudin-2, thereby disrupting the mucosal barrier; (4) The JNK/p38 signaling pathway activates the caspase cascade to induce apoptosis of intestinal epithelial cells, neurons, and interstitial cells of Cajal; (5) Abnormal ERK signaling and excessive activation of p38/JNK inhibit intestinal smooth muscle contraction and reduce 5-hydroxytryptamine secretion, ultimately resulting in impaired colonic transit function.At the intervention level, TCM compound formulas and single herbs have been proven to improve STC by regulating the MAPK signaling pathway. Their effects are syndrome type-dependent:yin-nourishing formulas (Zengye Chengqi Tang, Tongbian Tang) mainly regulate the ERK/AQP axis; yang-warming formulas (Jichuan Jian) target both ERK/JNK and anti-apoptosis; heat-clearing formulas (Sanren Tang) focus on p38/NF-κB anti-inflammation. A single drug can simultaneously cover multiple aspects including water metabolism, inflammation, barrier function, apoptosis, and intestinal motility.Current relevant studies still have limitations such as mechanisms mostly remaining at the correlational level and a lack of disease-syndrome integrated research models. Future studies should combine specific inhibitors or gene knockout to identify core targets, establish disease-syndrome integrated STC models, and use network pharmacology and molecular docking techniques to deeply analyze the fine mechanism of “component-target-phenotype”, so as to provide high-quality evidence for the precise regulation of the MAPK signaling pathway by TCM in the intervention of STC.
4.Overview of the Research on Mechanisms and Application of Essential Oil of Aromatic Chinese Medicinals in Prevention of Respiratory Infectious Disease
Wan Ling LI ; Xinxin WU ; Xiaolei LI ; Mingzhao HAO ; Fang ZHANG ; Yue ZHANG ; Haoyue LI ; Jing ZHAO
Journal of Traditional Chinese Medicine 2025;66(6):638-644
Aromatic Chinese medicinal essential oils are volatile oils extracted from aromatic Chinese herbs, which can prevent and treat respiratory infectious diseases through multiple synergistic mechanisms including pathogen inhibition, immune regulation, and inflammatory response regulation. Essential oils are primarily used externally on the body to prevent infections and alleviate symptoms through methods like inhalation, smearing, topical application, bathing, gargling or as a suppository. They can also be utilized in the environment for disinfection and air purification, through methods like diffusion, vaporization, or spraying. The external application of essential oils extracted from Chinese aromatic herbs has the advantages of convenience, quick absorption, and simultaneous influence on both the body and mind. However, there are still challenges and deficiencies in aspects such as the positioning of functions, indications, safety, and the research on the mechanism of action. It has been proposed to combine the theory of aromatic Chinese medicinals with the characteristics of essential oils, and formulate prescriptions of Chinese medicinal essential oils under the principles of traditional Chinese medicine syndrome differentiation, and prevent and treat respiratory infectious diseases efficiently, accurately, and safely, thereby expanding the clinical application of aromatic Chinese medicinals and the preventive theory of traditional Chinese medicine.
5.Role of noninvasive tests in the prognostication of metabolic dysfunction-associated steatotic liver disease
Yue WANG ; Sherlot Juan SONG ; Yichong JIANG ; Jimmy Che-To LAI ; Grace Lai-Hung WONG ; Vincent Wai-Sun WONG ; Terry Cheuk-Fung YIP
Clinical and Molecular Hepatology 2025;31(Suppl):S51-S75
In managing metabolic dysfunction-associated steatotic liver disease, which affects over 30% of the general population, effective noninvasive biomarkers for assessing disease severity, monitoring disease progression, predicting the development of liver-related complications, and assessing treatment response are crucial. The advantage of simple fibrosis scores lies in their widespread accessibility through routinely performed blood tests and extensive validation in different clinical settings. They have shown reasonable accuracy in diagnosing advanced fibrosis and good performance in excluding the majority of patients with a low risk of liver-related complications. Among patients with elevated serum fibrosis scores, a more specific fibrosis and imaging biomarker has proved useful to accurately identify patients at risk of liver-related complications. Among specific fibrosis blood biomarkers, enhanced liver fibrosis is the most widely utilized and has been approved in the United States as a prognostic biomarker. For imaging biomarkers, the availability of vibration-controlled transient elastography has been largely improved over the past years, enabling the use of liver stiffness measurement (LSM) for accurate assessment of significant and advanced fibrosis, and cirrhosis. Combining LSM with other routinely available blood tests enhances the ability to diagnose at-risk metabolic dysfunction-associated steatohepatitis and predict liver-related complications, some reaching an accuracy comparable to that of liver biopsy. Magnetic resonance imaging-based modalities provide the most accurate quantification of liver fibrosis, though the current utilization is limited to research settings. Expanding their future use in clinical practice depends on factors such as cost and facility availability.
6.Spotting undiagnosed significant liver fibrosis in the general population: impact on subsequent clinical care: Editorial on “Prevalence of clinically significant liver fibrosis in the general population: A systematic review and meta-analysis”
Nana PENG ; Mary Yue WANG ; Sherlot Juan SONG ; Terry Cheuk-Fung YIP
Clinical and Molecular Hepatology 2025;31(1):256-260
7.Study of a family with different phenotypes of Gerstmann-Str?ussler-Scheinker syndrome
Yihao WANG ; Zhongyun CHEN ; Yu KONG ; Ailing YUE ; Deming JIANG ; Min CHU ; Liyong WU ; Hong YE
Chinese Journal of Neurology 2025;58(2):161-168
Objective:To explore the differences in clinical phenotype characteristics and auxiliary test results of Gerstmann-Str?ussler-Scheinker syndrome (GSS) patients in the same family with GSS carrying a P102L mutation in the PRNP gene. Methods:A family with GSS carrying a P102L mutation in the PRNP gene, which was identified and treated at the Department of Neurology, Xuanwu Hospital, Capital Medical University in January 2024 was collected. A comprehensive evaluation was conducted on the proband, including neuropsychological examination, imaging studies, electroencephalogram, cerebrospinal fluid (CSF) analysis, real-time quaking-induced conversion (RT-QuIC) assay of skin biopsy samples, and genetic testing. At the same time, a survey and analysis were conducted on the family members. Skin RT-QuIC, genetic testing and neuropsychological evaluation were performed on some of the family members. Results:Among the 4-generation members of the GSS family, there were 5 GSS patients, including the proband′s father, younger brother, uncle and cousin. The proband, her younger brother and cousin all carried the P102L mutation in the PRNP gene, and her son was a carrier of the P102L mutation in the PRNP gene. The proband was a 53 years old female, and had a typical GSS phenotype, with the initial symptom of ataxia. The CSF 14-3-3 protein was negative and there were no abnormalities observed on her brain magnetic resonance imaging. The skin and CSF RT-QuIC test results of the proband were both negative. The cousin of the proband had a typical GSS phenotype, and his skin RT-QuIC test result was negative. The younger brother of the proband had a GSS phenotype of Creutzfeldt-Jakob disease type, with the initial symptom of rapidly progressing dementia and a positive skin RT-QuIC test result. The first symptoms of the proband′s father and uncle were both ataxia, and they had passed away without undergoing genetic testing. The son of the proband was a carrier of the P102L mutation in the PRNP gene and had no clinical symptoms. Conclusion:Different family members in the same GSS family may exhibit different clinical phenotypes, and GSS with different phenotypes have differences in RT-QuIC results.
8.Expert consensus on holistic integrative management of oral squamous cell carcinoma
Moyi SUN ; Zongxuan HE ; Haoyue XU ; Xiaoying LI ; Jie ZHANG ; Haijun LU ; Xiaohong ZHAN ; Dapeng HAO ; Shizhu BAI ; Wei GUO ; Zhangui TANG ; Guoxin REN ; Jian MENG ; Zhijun SUN ; Jichen LI ; Yue HE ; Chunjie LI ; Lizheng QIN ; Kai YANG ; Qing XI ; Lin KONG ; Bing HAN ; Lingxue BU ; Yuanyong FENG ; Kai SONG ; Hongyu HAN ; Jieying LI ; Qianwei NI ; Yun LI ; Juan CHAI ; Xiaochen YANG ; Man HU ; Mingjin XU ; Wei SHANG
Journal of Practical Stomatology 2025;41(4):437-449
Oral squamous cell carcinoma(OSCC)is a malignant lesion originating from the oral mucosal squamous epithelium,account-ing for over 80%of oral and maxillofacial malignancies.Key etiological factors include tobacco,alcohol abuse,and betel quid chewing.In China,its incidence has shown an overall upward trend,posing a significant threat to public health.OSCC exhibits high local invasive-ness,making early diagnosis critical for improving prognosis.Its clinical management requires close multidisciplinary collaboration among oral and maxillofacial surgery,head and neck surgery,radiation oncology,medical oncology,reconstructive surgery,radiology,patholo-gy,and nutritional support teams.Given the increasing disease burden of OSCC and rapid development of multidisciplinary collaborative models,an expert panel has formulated this integrated management consensus based on evidence-based medicine and extensive deliber-ation.Centered on the'Prevention-Screening-Diagnosis-Treatment-Rehabilitation'framework,the consensus provides comprehensive guidance for the entire disease course of OSCC patients,aiming to standardize clinical practice.
9.Analysis of EEG microstate characteristics and their correlation with irritability in children with autism spectrum disorder
Ran WEI ; Yonglu WANG ; Jianxing GAO ; Xinyue XU ; Jie XIA ; Lingxi XU ; Yue KONG ; Hui FANG ; Gongkai JIAO ; Xiaoyan KE
Chinese Journal of Psychiatry 2025;58(11):822-829
Objective:To investigate the differences in electroencephalographic (EEG) microstate characteristics between children with autism spectrum disorder (ASD) and typically developing (TD) children, and to explore the correlation between irritability and EEG microstate features in ASD children.Methods:A total of 104 children with ASD [ASD group, 83 boys, 21 girls; aged 4-13 years, mean age (9.47±1.74)years] from the Autism Cohort of Nanjing Medical University and 60 TD children [TD group; 50 boys, 10 girls; aged 5-13 years, mean age(9.86±1.78) years ]from the IEEE Dataport database were enrolled. Irritability severity was assessed using the Affective Reactivity Index-Parent (ARI-P). Resting-state EEG data with eyes closed were recorded using a 24-channel dry-electrode EEG cap. Group-level EEG microstate topographic maps and microstate parameters, including mean duration, frequency, and time coverage, were extracted and compared between groups using nonparametric tests. In the ASD group, Spearman correlation analysis was used to examine the associations between microstate features and ARI-P in ASD children. Multiple linear regression was used to identify predictors of irritability.Results:Four group-level microstates (A, B, C, D) were identified in both groups. Compared to TD children, ASD children exhibited significantly longer mean duration for all microstates, in microstates A[ M(Q1, Q3)]: 0.060 (0.054,0.070) vs 0.091 (0.0530, 0.155) s, microstate B: 0.059 (0.050, 0.066) vs 0.087 (0.057,0.149) s, microstate C: 0.059 (0.050, 0.066) vs 0.095 (0.056, 0.183) s and microstate D: 0.055 (0.049,0.075) vs 0.095 (0.053,0.162) s ( Z=-3.51, -4.89, -4.71, -4.21; all P<0.001); However, microstate occurrence frequencies were significantly lower in the ASD group: A: 5.423 (3.640,21.024) vs 1.834 (1.327,3.395) Hz, microstate B: 4.949 (3.439,20.038) vs 2.146 (1.314,3.834) Hz, microstate C: 5.888 (3.998,22.078) vs 2.234 (1.441,3.768) Hz and microstate D: 5.371 (3.170,15.208) vs 2.074 (1.147,3.582) Hz ( Z=-7.72, -6.41, -7.85, -6.60; all P<0.001). In the ASD group, ARI-P scores were positively correlated with the mean duration of microstates B, C, and D ( r=0.28, 0.26, 0.33; all P<0.05) and negatively correlated with the occurrence frequency of microstates A, C, and D ( r=-0.26, -0.27, -0.21; all P<0.05). Multiple linear regression analysis revealed that the mean duration of microstate B was a significant predictor of irritability severity ( β=0.436, 95% CI: 1.260-4.202, P<0.001). Conclusion:Resting-state EEG microstate characteristics in Children with ASD differ from those in TD children and are associated with the severity of irritability. Prolonged duration of microstate B may serve as a risk factor for increased irritability in children with ASD.
10.Clinical analysis of older patients with hematologic malignancies treated by allogeneic hematopoietic stem cell transplantation
Xin KONG ; Baoquan SONG ; Xiaowen TANG ; Shengli XUE ; Miao MIAO ; Yue HAN ; Ying WANG ; Jian ZHANG ; Suning CHEN ; Aining SUN ; Zhihong LIN ; Jun CHEN ; Feng CHEN ; Huiying QIU ; Depei WU
Chinese Journal of Geriatrics 2025;44(10):1376-1382
Objective:To investigates the efficacy and safety of allogeneic hematopoietic stem cell transplantation(allo-HSCT)in treating older patients(≥60 years old)with hematologic malignancies.Methods:We conducted a retrospective study involving 67 patients aged 60 years and above, diagnosed with malignant hematological diseases, who received allo-HSCT at the Clinical Research Centrer for Haematologic Diseases of the First Affiliated Hospital of Soochow University between June 2015 and March 2023.We collected pre-transplant data, including the patients' age, gender, pre-transplantation disease risk stratification, disease status, and the haematopoietic cell transplantation comorbidity index(HCT-CI). We retrospectively analyzed clinical data regarding treatment-related toxicity, infections, acute and chronic graft-versus-host disease(a/cGVHD), as well as recurrent and non-recurrent deaths, to estimate the overall survival(OS)rate and event-free survival (EFS)rate.Results:Sixty-seven patients were included in the study, comprising 55 males(82.1%)and 12 females(17.9%), with a median age of 63(61, 65) years .The cohort consisted of 42 cases of acute myeloid leukaemia, 22 cases of myelodysplastic syndromes, and 3 cases of acute lymphoblastic leukaemia.The Kaplan-Meier analysis showed that the 1-year OS and EFS rates were 62.9% and 59.2%, respectively, while the 2-year OS and EFS rates were 55.3% and 51.8%, respectively.The cumulative incidence of 1-year non-relapse mortality and relapse was 25.4% and 21.2%, respectively.A total of 13 patients developed grade Ⅱ-Ⅳ aGVHD, with a 1-year cumulative incidence of 22.0%, and 7 patients developed cGVHD requiring treatment.When stratified by age group, the OS rate was higher in patients aged 60~64 years compared to those aged ≥65 years; however, this difference was not statistically significant(Log-rank χ2=0.99, P=0.317). In contrast, when stratified by disease load, the OS rate was significantly higher in the complete remission(CR)group than in the non-CR group, with a statistically significant difference(Log-rank χ2=15.04, P<0.001). When stratified by donor type, the OS rate was higher in the human leukocyte antigens (HLA) allogeneic group compared to the haploinsufficiency group; however, the difference was not statistically significant(Log-rank χ2=2.71, P=0.100). Twenty-seven patients died at an average of 125 days (range 3-1 054 days) after HSCT.The causes of death included leukemia recurrence in 9 cases (33.3%), infection in 8 cases (29.6%), GVHD in 5 cases (18.5%), poor implantation in 3 cases (11.1%), multi-organ failure in 1 case (3.7%), and cerebrovascular accident in 1 case (3.7%). The results of multifactorial analysis indicated that a pre-transplant tumor load greater than 5% was an independent risk factor for OS after transplantation ( HR=4.59, 95% CI: 2.01-10.42, P<0.001)as well as for disease recurrence ( OR=13.11, 95% CI: 1.96-87.87, P=0.008). Additionally, the occurrence of infection was identified as an independent risk factor for non-recurrent death after transplantation( OR=3.95, 95% CI: 1.13 to 13.71, P=0.031). Conclusions:For patients aged 60 years or older with hematologic malignancies, HSCT can serve as a viable treatment option, particularly for those with refractory recurrence and high cytogenetic risk, as it has the potential to significantly enhance prognosis and increase both EFS and OS rates.

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