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*

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.

Objective:To explore the correlation between protein energy wasting(PEW)and frailty in elderly patients on maintenance hemodialysis(MHD)and influencing factors of frailty.Methods:Clinical data of patients over 60 who had received regular hemodialysis treatment at Beijing Huairou Hospital between September to December 2021 were collected.According to Fried's evaluation criteria, patients were divided into a frailty group and a non-frailty group, and differences between the two groups were compared.Spearman correlation analysis was conducted to assess the correlation between protein energy wasting and frailty.Logistic regression was used to analyze the influencing factors of frailty in elderly patients on MHD.Results:A total of 81 MHD patients enrolled in this study, with 36 in the frailty group.The frailty group was older, had a higher proportion of patients with PEW, and underwent more months of dialysis, with a higher proportion of patients with diabetic nephropathy as the primary disease, having high levels of C-reactive protein(CRP), and having low KT/V, hemoglobin, albumin, body mass index(BMI), mid-arm circumference(MAC)and mid-arm muscle circumference(MAMC), and the differences with the control group were statistically significant(all P<0.05). The Fried frailty phenotype was positively correlated with age( r=0.021, P=0.047), but negatively associated with HGB( r=-0.329, P=0.003), albumin( r=0.021, P=0.047), BMI( r=0.021, P=0.047), TSF( r=-0.274, P=0.013), MAC( r=-0.554, P<0.001)and MAMC( r=-0.293, P=0.008). A Logistic regression equation was constructed using frailty as the dependent variable.The results showed that age, months of dialysis, KT/V, serum albumin and CRP were independent factors influencing the development of frailty in elderly patients with MHD. Conclusions:PEW and frailty coexist and interact with each other in elderly patients with MHD.Clinicians should place emphasis on the assessment of frailty and protein energy wasting in elderly dialysis patients and achieve early detection and intervention to avoid adverse clinical outcomes.

Background: Acute lung injury (ALI) is a severe and life-threatening lung inflammation with high morbidity and mortality, underscoring the importance to develop effective drugs. Qingjin Huatan decoction (QJHTD), as a classic ancient prescription, has been widely used for treating respiratory diseases. However, the role and mechanism of QJHTD against ALI remain unclear. Objective: This study aimed to explore the therapeutic effect of QJHTD on lipopolysaccharide (LPS)-induced ALI in mice and uncover its mechanism. Methods: The therapeutic effect of QJHTD on LPS-induced ALI in mice was evaluated by the histopathological changes in the lung tissue, the lung wet/dry weight ratio, and the levels of inflammatory cytokines and thrombin-antithrombin complexes. Transcriptomics was used to predict the mechanism of QJHTD in treating ALI. The expression levels of citrullinated histone 3 in the lung tissue, the content of cell-free DNA in the bronchoalveolar lavage fluid (BALF), and the platelet-associated formation of neutrophil extracellular traps (NETs) in vitro were determined. Results: Qingjin Huatan decoction exerted protective effect against LPS-induced ALI by suppressing interstitial edema, maintaining the alveolar-capillary barrier, inhibiting the infiltration of neutrophils and platelets in the lung tissue, and lowering the levels of tumor necrosis factor α, interleukin 1β, interleukin 6, and thrombin-antithrombin complexes in BALF. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that the formation of NETs was the main regulatory pathway for QJHTD against ALI. Qingjin Huatan decoction could treat ALI by inhibiting the release of NETs via reducing the content of citrullinated histone 3 in lung tissue and cell-free DNA in BALF in vivo, and suppressing the NETs formation induced by LPS-stimulated platelets under flow and static conditions in vitro. The formation of NETs was considered to bridge the interactions between neutrophils and platelets. Conclusions: This research demonstrated the effects of QJHTD in treating ALI and provided new insights for clarifying the complex regulation of neutrophils, platelets, and NETs in ALI.

Objective:To compare the clinicopathological differences between elderly and non-elderly patients with idiopathic membranous nephropathy(IMN).Methods:Patients diagnosed with IMN via renal biopsy at Beijing Huairou Hospital, Beijing Changping Hospital of Traditional Chinese Medicine, and Beijing Hospital of Traditional Chinese Medicine from January 2017 to August 2021 were retrospectively enrolled.They were classified into the elderly group(≥65 years)and the non-elderly group(<65 years), and the clinicopathological differences between the two groups were compared.Results:A total of 207 IMN patients were included in the study, with a male to female ratio of 1.7∶1.0.There were 56 patients in the elderly group, aged(68.2±3.1)years, and 151 patients in the non-elderly group, aged(48.2±6.2)years.Compared with the non-elderly group, the elderly group had a longer time from onset to renal biopsy and a higher proportion of patients with renal insufficiency and hypertension( P<0.05). The elderly group had a lower eGFR, lower serum albumin, higher serum cholesterol, and higher low-density lipoprotein than the non-elderly group( P<0.05). The proportions of patients with glomerulosclerosis, renal tubular atrophy, and interstitial fibrosis in the elderly group were higher than in the non-elderly group( P<0.05). The positive rates of glomerular PLA2R antigen staining in the two groups were 90.6%(29/32)and 91.0%(111/122), respectively, and there was no statistically significant difference between the two groups.IgG4 deposition represented the most common IgG subtype, with 93.8%(30/32)in the elderly group and 94.3%(115/122)in the non-elderly group.There was no statistical significance between the two groups( P>0.05). Conclusions:Compared with non-elderly IMN patients, a higher proportion of elderly IMN patients has renal insufficiency, hypertension and chronic renal pathology.The glomerular deposition of pathogenic antigens in elderly IMN patients was similar to that in non-elderly IMN patients, suggesting no difference in pathogenesis between the two groups.The clinicopathological differences between the two groups may be related to age and complications.

Literature of TCM contains abundant information of Chinese medicine. Traditional Chinese medicine information is characterized by its high degree of knowledge-intensive and complex inter-knowledge, so it is difficult to integrate and share knowledge. TheShanghanlun is one of the Chinese medical classics, and it includes the rules and methods of syndrome differentiation and treatment and it showed good effects in the clinical application. However, it is difficult to master for beginners. As a kind of knowledge organization tool, topic maps can flexibly define the relationship between knowledge, which realizes the visualization of knowledge network, and integrates and shares the distributed knowledge. This paper focused on the current situation of topic maps researches. The topic maps was used to organize the original content ofShanghanlun, construct the concept model of it and explore the specific application of topic maps technology in the field of traditional Chinese medicine.