Objective To explore the compatibility law of amenorrhea and commonly used local herbs in southwest China using hypergraph;To provide drug choice for the clinical treatment of modern TCM amenorrhea and promote the development and utilization of local Chinese materia medica resources.Methods In this study,the data of prescriptions for the treatment of amenorrhea in Southwest China were used as the data source.By constructing formulas related to amenorrhea-hypergraph(AFR-HG),the topological structure of AFR-HG was analyzed,and the core subnet was extracted according to the node weighted hypercentrality.Based on the sub-network AFR-HG-p1 extracted from the top 20 kinds of Chinese materia medica in AFR-HG,the Kumar algorithm was used to divide the efficacy community network.Results A total of 123 amenorrhea prescriptions were included in this study.Angelicae Sinensis Radix,Carthami Flos,Cyperi Rhizoma,Chuanxiong Rhizoma and other drugs with the efficacy of promoting blood circulation and removing blood stasis,soothing liver and regulating qi,and warming and tonifying were the main drugs with high frequency.Three layers of core subnets were extracted layer by layer through weighted hyper-centrality sorting.The first layer contained Angelicae Sinensis Radix,Chuanxiong Rhizoma,Hyperici Sampsonii Herba,etc.;the second layer of drugs were mainly Lycopi Herba,Rubiae Radix et Rhizoma,Bombycis Feculae,etc.;the third layer of drugs were mainly Ginseng Radix et Rhizoma Rubra,Moutan Cortex,Sargentodoxae Caulis and other drugs;based on the top 20 node overdose drugs,community drugs were obtained through community detection:the first community subnet was Armeniacae Semen Amarum,Draconis Sanguis,Corydalis Rhizoma,etc.,the second community subnet was Rubiae Radix et Rhizoma,Rosae Chinensis Flos,Hyperici Sampsonii Herba,etc.,and the third community subnet was Akebiae Caulis,Homalomenae Rhizoma,Bombycis Feculae,etc.Conclusion In prescriptions of amenorrhea in Southwest China,the treatment principles are basically consistent with modern clinical practice.In addition to commonly used drugs,local herbal medicines and similar medicines are also common.It is of great value to explore the rules of prescriptions for the development and utilization of Chinese materia medica resources.

ObjectiveThis study aims to develop a prediction model for the compatibility of Chinese medicinal pairs based on Graph Convolutional Networks （GCN）， named HC-GCN. The model integrates the properties of herbs with modern pharmacological mechanisms to predict pairs with specific therapeutic effects. It serves as a demonstration by applying the model to predict and validate the efficacy of blood-activating herb pairs. MethodsThe training dataset for herb pair prediction was constructed by systematically collecting commonly used herb pairs along with their characteristic data， including Qi， flavor， meridian tropism， and target genes. Integrating traditional characteristics of herb with modern bioinformatics， we developed an efficacy-oriented herb pair compatibility prediction model （HC-GCN） using graph convolutional networks （GCN）. This model leverages machine learning to capture the complex relationships in herb pair compatibility， weighted by efficacy features. The performance of the HC-GCN model was evaluated using accuracy （ACC）， recall， precision， F1 score （F1）， and area under the ROC curve （AUC）. Its predictive effectiveness was then compared to five other machine learning models： eXtreme Gradient Boosting （XGBoost）， logistic regression （LR）， Naive Bayes， K-nearest neighbor （KNN）， and support vector machine （SVM）. ResultsUsing herb pairs with blood-activating effects as a demonstration， a prediction model was constructed based on a foundational dataset of 46 blood-activating herb pairs， incorporating their Qi， flavor， meridian tropism， and target gene characteristics. The HC-GCN model outperforms other commonly used machine learning models in key performance metrics， including ACC， recall， precision， F1 score， and AUC. Through the predictive analysis of the HC-GCN model， 60 herb pairs with blood-activating effects were successfully identified. Among of these potential herb pairs， 44 include at least one herb with blood-activating effects. ConclusionIn this study， we established an efficacy-oriented compatibility prediction model for herb pairs based on GCN by integrating the unique characteristics of traditional herbs with modern pharmacological mechanisms. This model demonstrated high predictive performance， offering a novel approach for the intelligent screening and optimization of traditional Chinese medicine prescriptions， as well as their clinical applications.

Objective:To investigate the relationships among coping styles,negative life events,meaning in life,and psychological resilience in adolescents.Methods:A total of 1 434 adolescents aged 13 to 17 years comple-ted online questionnaire survey.The Simplified Coping Style Questionnaire(SCSQ),Adolescent Self-Rating Life E-vents Checklist(ASLEC),Chinese Meaning in Life Questionnaire(C-MLQ),and Connor-Davidson resilience scale(CD-RISC)were used to assess coping styles,perceived impact of negative life events,experience and pursuit of meaning in life,and ability to cope with and adapt to adversity,respectively.Logistic regression was used to explore the associations among these variables.Results:A total of 723 students(50.4％)tended to adopt negative coping styles when facing adverse events.Positive coping styles were negatively associated with being in senior high school(OR=0.62,P＜0.05)and impact of life events(OR=0.97,P＜0.001),while positively associated with sense of meaning in life(OR=1.04,P＜0.001)and psychological resilience(OR=1.04,P＜0.001).Conclusion:Among adolescents,positive coping styles are inversely associated with impact of negative life events,and positively associ-ated with both the sense of life meaning and psychological resilience.

Maternal health during pregnancy has a direct impact on the risk and severity of neurodevelopmental disorders (NDDs) in the offspring, especially in the case of drug exposure. However, little progress has been made to assess the risk of drug exposure during pregnancy due to ethical constraints and drug use factors. We collected and manually curated sub-pathways and pathways (sub-/pathways) and drug information to propose an analytical framework for predicting drug candidates. This framework linked sub-/pathway activity and drug response scores derived from gene transcription data and was applied to human fetal brain development and six NDDs. Further, specific and pleiotropic sub-/pathways/drugs were identified using entropy, and sex bias was analyzed in conjunction with logistic regression and random forest models. We identified 19 disorder-associated and 256 regionally pleiotropic and specific candidate drugs that targeted risk sub-/pathways in NDDs, showing temporal or spatial changes across fetal development. Moreover, 5443 differential drug-sub-/pathways exhibited sex-biased differences after filling in the gender labels. A user-friendly NDDP visualization website ( https://ndd-lab.shinyapps.io/NDDP ) was developed to allow researchers and clinicians to access and retrieve data easily. Our framework overcame data gaps and identified numerous pleiotropic and specific candidates across six disorders and fetal developmental trajectories. This could significantly contribute to drug discovery during pregnancy and can be applied to a wide range of traits.
Humans ; Female ; Pregnancy ; Neurodevelopmental Disorders/metabolism* ; Male ; Prenatal Exposure Delayed Effects ; Fetal Development/drug effects* ; Drug Discovery/methods* ; Brain/metabolism*

Objective To explore the compatibility law of amenorrhea and commonly used local herbs in southwest China using hypergraph;To provide drug choice for the clinical treatment of modern TCM amenorrhea and promote the development and utilization of local Chinese materia medica resources.Methods In this study,the data of prescriptions for the treatment of amenorrhea in Southwest China were used as the data source.By constructing formulas related to amenorrhea-hypergraph(AFR-HG),the topological structure of AFR-HG was analyzed,and the core subnet was extracted according to the node weighted hypercentrality.Based on the sub-network AFR-HG-p1 extracted from the top 20 kinds of Chinese materia medica in AFR-HG,the Kumar algorithm was used to divide the efficacy community network.Results A total of 123 amenorrhea prescriptions were included in this study.Angelicae Sinensis Radix,Carthami Flos,Cyperi Rhizoma,Chuanxiong Rhizoma and other drugs with the efficacy of promoting blood circulation and removing blood stasis,soothing liver and regulating qi,and warming and tonifying were the main drugs with high frequency.Three layers of core subnets were extracted layer by layer through weighted hyper-centrality sorting.The first layer contained Angelicae Sinensis Radix,Chuanxiong Rhizoma,Hyperici Sampsonii Herba,etc.;the second layer of drugs were mainly Lycopi Herba,Rubiae Radix et Rhizoma,Bombycis Feculae,etc.;the third layer of drugs were mainly Ginseng Radix et Rhizoma Rubra,Moutan Cortex,Sargentodoxae Caulis and other drugs;based on the top 20 node overdose drugs,community drugs were obtained through community detection:the first community subnet was Armeniacae Semen Amarum,Draconis Sanguis,Corydalis Rhizoma,etc.,the second community subnet was Rubiae Radix et Rhizoma,Rosae Chinensis Flos,Hyperici Sampsonii Herba,etc.,and the third community subnet was Akebiae Caulis,Homalomenae Rhizoma,Bombycis Feculae,etc.Conclusion In prescriptions of amenorrhea in Southwest China,the treatment principles are basically consistent with modern clinical practice.In addition to commonly used drugs,local herbal medicines and similar medicines are also common.It is of great value to explore the rules of prescriptions for the development and utilization of Chinese materia medica resources.

Objective:To investigate the relationships among coping styles,negative life events,meaning in life,and psychological resilience in adolescents.Methods:A total of 1 434 adolescents aged 13 to 17 years comple-ted online questionnaire survey.The Simplified Coping Style Questionnaire(SCSQ),Adolescent Self-Rating Life E-vents Checklist(ASLEC),Chinese Meaning in Life Questionnaire(C-MLQ),and Connor-Davidson resilience scale(CD-RISC)were used to assess coping styles,perceived impact of negative life events,experience and pursuit of meaning in life,and ability to cope with and adapt to adversity,respectively.Logistic regression was used to explore the associations among these variables.Results:A total of 723 students(50.4％)tended to adopt negative coping styles when facing adverse events.Positive coping styles were negatively associated with being in senior high school(OR=0.62,P＜0.05)and impact of life events(OR=0.97,P＜0.001),while positively associated with sense of meaning in life(OR=1.04,P＜0.001)and psychological resilience(OR=1.04,P＜0.001).Conclusion:Among adolescents,positive coping styles are inversely associated with impact of negative life events,and positively associ-ated with both the sense of life meaning and psychological resilience.

Danggui Sinitang is first recorded in the Treatise on Cold Damage written by ZHANG Zhongjing in the Han dynasty. It is composed of Angelicae Sinensis Radix， Cinnamomi Ramulus， Paeoniae Radix Alba， Asari Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma， Tetrapanacis Medulla， and Jujubae Fructus and serves as a classic formula for treating the syndrome of blood deficiency and cold reversal. This study systematically reviews the records of Danggui Sinitang in ancient Chinese medicine books of various dynasties and the modern clinical applications to probe into the composition， plant species， processing， dosage， decocting method， and indications of Danggui Sinitang， aiming to provide a reference for the development and clinical application of this classic formula. The review of the records showed that there were a variety of records of Danggui Sinitang with different composition， and the composition of this formula listed in the Treatise on Cold Damage has a significant impact on later generations and has been used by medical practitioners throughout history. Although the dosage of some drugs decreased during the Ming and Qing dynasties， the medical practitioners continued to use the original formula. In terms of processing， although there were slight changes in the processing of Angelicae Sinensis Radix， Paeoniae Radix Alba， Glycyrrhizae Radix et Rhizoma， and Tetrapanacis Medulla， the original processing method was inherited. In terms of indications， Danggui Sinitang was designed to treat cold reversal due to blood deficiency and dysentery. Furthermore， it was used to treat headache， convulsive disease， infantile convulsion， and private part adduction in the Ming and Qing dynasties. Nowadays， this formula is mostly used to treat diabetes peripheral neuropathy， rheumatoid arthritis， dysmenorrhea， Raynaud's disease and other diseases. In terms of precautions， ancient physicians believed that Danggui Sinitang should not be taken by pregnant women and should only be used for limb chills caused by blood deficiency and cold coagulation. For limb chills caused by other reasons， this formula should not be used indiscriminately. Modern research has not reported any serious adverse reactions related to this formula. Danggui Sinitang has a definite therapeutic effect. In subsequent research and development， quality control standards of Danggui Sinitang should be established while its safety is ensured， and the related preparations should be developed and applied.

ObjectiveTo investigate the effects of thyme herbal tea （BLX） on the proliferation of human coronavirus OC43 （HCoV-OC43） in vitro and in vivo. MethodThe chemical composition of BLX was analyzed by UPLC-MS. The cytotoxicity of BLX in HRT-18 cells and the effect of BLX treatment on the proliferation of HCoV-OC43 in cells were analyzed. Copies of viral gene were detected by real-time PCR. The effect of BLX treatment on the life cycle of HCoV-OC43 was detected by time-of-addition assay. The maximum tolerated dose of BLX and the influences of BLX on the body weight and survival time of suckling mice infected with HCoV-OC43 were determined. The expression of viral protein in the brain and lung tissue was analyzed by immunohistochemistry. ResultThere were 11 chemical components identified in BLX by UPLC-MS. BLX showed the 50% cytotoxic concentration （CC₅₀） of （13 859.56±319） mg·L^-1， the median inhibitory concentration （IC₅₀） of （1 439.09±200） mg·L^-1， and the selection index of 8.26-11.44 for HCoV-OC43 in HRT-18 cells. Compared with the cells infected with HCoV-OC43， BLX at the concentrations of 1 500， 1 000， 500 mg·L^-1 inhibited the proliferation of this virus （P<0.05， P<0.01）. BLX exhibited antiviral effect in the early stage of virus infection， and the inhibition role in the attachment stage was more significant than that in the entry stage （P<0.05）. In the suckling mice infected with HCoV-OC43， BLX at 1200 and 600 mg·kg^-1·d^-1 alleviated the symptoms， prolonged the survival period， reduced the death rate， and down-regulated the mRNA level of nucleocapsid protein in the mice. Moreover， BLX at 1 200 mg·kg^-1·d^-1 down-regulated the expression of nucleocapsid protein in the brain （P<0.01） and the lung （P<0.01）. ConclusionBLX contained multiple antiviral ingredients. It inhibited the proliferation of HCoV-OC43 both in vitro and in vivo by interference with viral attachment. This study provides theoretical reference for the treatment of acute respiratory tract infection with HCoV-OC43 and for further development and application of BLX.

ObjectiveTo explore the efficacy-driving mechanism of Danhong injection （DHI） in the treatment of stable angina pectoris （SAP） based on the composition-activity relationship of target modules and clarify the pharmacological effects of DHI. MethodAccording to the angina frequency （AF） in the Seattle Angina Questionnaire （SAQ） that was obtained in the previous clinical trial， the patients before and after DHI treatment were grouped based on efficacy. The transcriptomic data of the patients before treatment and in the best efficacy group 30 days post-treatment were selected as the data source， and then weighted gene co-expression network analysis （WGCNA） was employed to construct the co-expression network. Relevant modules in the network were identified and associated with clinical features. In addition， the On-modules （Z value below 0） were identified by Zsummary. The topological indicators such as density， centrality， and clustering coefficient were adopted to explore the dynamics of DHI efficacy at the network level and module level， respectively. In addition， the driver genes were screened by the personalized network control （PNC） algorithm. Finally， rat H9C2 cells were used to establish the model of hypoxia/reoxygenation （H/R）， which was used to confirm the potential therapeutic target of DHI for SAP and provide a scientific basis for revealing the therapeutic mechanism of DHI. ResultWe identified 19 modules in the best efficacy group of DHI for SAP， and the comparison between day 0 and day 30 revealed 12 On-modules. The changes of network topological indicators at the network and module levels confirmed the correlation between the best efficacy of DHI treatment and topological dynamics. Finally， the driver genes， Klotho and fibroblast growth factor 22 （FGF22）， in DHI treatment of SAP were verified by the H9C2 cell model of H/R. ConclusionBased on clinical transcriptome data， this study determined the composition-activity relationship of target modules of DHI for SAP， which provided a scientific basis for deciphering the efficacy-driven mechanism of DHI for SAP.

ObjectiveTo support intelligent clinical decision-making in traditional Chinese medicine（TCM）， this study utilized ontology and knowledge graph construction techniques to achieve the IT application of clinical practice guidelines. MethodBased on the principles of findability， accessibility， interoperability， and reusability （FAIR principles）， this study employed ontology techniques to construct an ontology for TCM clinical practice guidelines and built a knowledge graph using coronary heart disease as an example. Based on the Checklist for Reporting Practice Guidelines in Traditional Chinese Medicine and Recommendation Grading in TCM Clinical Guidelines/Consensus （T/CAS 530—2021），the ontology of TCM clinical practice guidelines was constructed using the seven-step ontology construction method. On this basis，the TCM diagnosis and treatment data from the Guidelines for the Diagnosis and Treatment of Stable Angina Pectoris in Coronary Heart Disease were stored in Neo4j in the form of triples through knowledge extraction，integration，and storage. ResultThe information in the clinical practice guidelines was divided into three categories： onset and prevention information， diagnosis information， and treatment information， and the TCM clinical practice guideline ontology was constructed. A total of 27 concepts related to TCM clinical diagnosis and treatment and 14 data attributes were obtained， and 12 conceptual relationships including hierarchical relationships and object attributes were established. By taking coronary heart disease as an example and the TCM clinical practice guideline ontology as the model layer， the knowledge map of TCM diagnosis and treatment guidelines for stable angina pectoris in coronary heart disease with 276 nodes and 336 relationships was constructed， realizing the visual display and query of the guideline content. ConclusionThe ontology of TCM clinical practice guidelines and the knowledge graph of stable angina pectoris in coronary heart disease constructed by combining the seven-step ontology construction method and Neo4j graph database technology are efficient and flexible，providing an intelligent TCM diagnosis and treatment scheme and promoting the standardization and objectification of TCM diagnosis and treatment.