[Investigation of the mechanism of action and identification of candidate traditional Chinese medicines for the treatment of ischemic stroke in the Danshen-Jiangxiang pair based on drug-target-disease association network].

The therapeutic efficacy of Danshen and Jiangxiang in the treatment of ischemic stroke (IS) is relatively significant. Studying the mechanism of action of Danshen and Jiangxiang in the treatment of IS can effectively identify candidate traditional Chinese medicines (TCM) with efficacy. However, it is challenging to analyze the effector substances and explain the mechanism of action of Danshen-Jiangxiang from a systematic perspective using traditional pharmacological approaches. In this study, a systematic study was conducted based on the drug-target-symptom-disease association network using complex network theory. On the basis of the association information about Danshen, Jiangxiang and IS, the protein-protein interaction (PPI) network and the "drug pair-pharmacodynamic ingredient-target-IS" network were constructed. The different topological features of the networks were analyzed to identify the core pharmacodynamic ingredients including formononetin in Jiangxiang, cryptotanshinone and tanshinone IIA in Danshen as well as core target proteins such as prostaglandin G/H synthase 2, retinoic acid receptor RXR-alpha, sodium channel protein type 5 subunit alpha, prostaglandin G/H synthase 1 and beta-2 adrenergic receptor. Further, a method for screening IS candidates based on TCM symptoms was proposed to identify key TCM symptoms and syndromes using the "drug pair-TCM symptom-syndrome-IS" network. The results showed that three TCMs, namely Puhuang, Sanleng and Zelan, might be potential therapeutic candidates for IS, which provided a theoretical reference for the development of drugs for the treatment of IS.

[Biological connotation of four traditional Chinese medicine syndromes of rheumatoid arthritis based on "disease-syndrome-symptom" association network].

The present study explored the biological connotation of traditional Chinese medicine(TCM) syndromes of rheumatoid arthritis(RA) from the "disease-syndrome-symptom" association network. RA patients with four TCM syndromes(dampness-heat obstruction, phlegm-stasis obstruction, Qi-blood deficiency, and liver and kidney deficiency), three for each type, were assigned as the RA TCM syndrome group, and three healthy volunteers as the normal control group. The differential gene sets of four syndromes were screened out through transcriptome expression profiling and bioinformatics mining. The relevant gene sets of syndrome-related clinical symptoms were collected from TCMIP v2.0(http://www.tcmip.cn/). The "disease-syndrome-symptom" association networks of four RA syndromes were established by using the intersection genes of syndrome-related differential genes and symptom-related genes, and the key network target genes of each syndrome were screened out and the corresponding biological functions were mined through topological feature calculation and enrichment analysis. The genes associated with clinical symptoms such as vasculitis, joint pain, and fever in the damp-heat obstruction syndrome ranked the top, and the key network target genes of this syndrome were most significantly enriched in the pathways related to material and energy metabolism and thermal reaction biological processes. The clinical symptom-related genes of the phlegm-stasis obstruction syndrome were most significantly enriched in the pathways related to "immunity-inflammation", nervous system regulation, and sensory response. The clinical symptoms such as hypoglycemia, hypotension, weight loss, palpitation, and arrhythmia in Qi-blood deficiency syndrome were predominant, and its key network target genes were most significantly enriched in the pathways related to the nervous system and "immunity-inflammation" response. The abnormal symptoms in the liver and kidney in the liver and kidney deficiency syndrome were commonly seen, and its key network target genes were most significantly enriched in the "immunity-inflammation" regulatory pathways, and liver and kidney development and metabolic response. In conclusion, the differences and connections of the biological basis between different TCM syndromes of RA are in line with the theoretical interpretation of TCM on the etiology and pathogenesis of RA. This study summarized the objective essence of syndromes to a certain extent from the "disease-syndrome-symptom" association network and is expected to provide a theoretical basis for the discovery of serum biomarkers of RA syndromes.

[Mechanism of Tianhe Zhuifeng Ointment in treating rheumatoid arthritis with syndrome of internal obstruction and cold-dampness and compatibility principles based on "disease-syndrome-formula" association network].

This study aims to explore the mechanism of Tianhe Zhuifeng Ointment in treating rheumatoid arthritis(RA) with syndrome of internal obstruction and cold-dampness and the compatibility characteristics based on the "disease-syndrome-formula" association network. A gene set associated with the clinical symptoms of RA was collected from Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine v2.0(TCMIP v2.0). The different expression gene set of RA with syndrome of internal obstruction and cold-dampness was screened out by transcriptomic expression profile detection and bioinformatics data mining of the comparison of RA patients with syndrome of internal obstruction and cold-dampness and healthy volunteers. The chemical composition information of 35 Chinese medicines from Tianhe Zhuifeng Ointment was collected from TCMIP v2.0 and Traditional Chinese Medicine Bank(TCMBank). The candidate targets were predicted based on the similarity principle of compounds structure. The interactive network of "related gene of RA with syndrome of internal obstruction and cold-dampness-candidate target of Tianhe Zhuifeng Ointment" was constructed. The core network targets were screened out by topological characteristics of calculating network, and the functional exploration was carried out based on Kyoto Encyclopedia of Genes and Genomes(KEGG) and Reactome Pathway Database. The compatibility mechanisms of various efficacy groups of Tianhe Zhuifeng Ointment were further explored. The results showed that the candidate targets of Tianhe Zhuifeng Ointment were mainly involved into the modules of "immune-inflammation" regulation, nervous system function, cell function, and substance and energy metabolism, etc. The mechanisms of various efficacy groups emphasized on different aspects. The group of dispelling wind and removing dampness-dredging channels and activating collaterals, the group of extinguishing wind and stopping convulsions, and the group of pungent analgesia regulated "immune-inflammation" system by warming meridians and dissipating cold. The group of activating blood and resolving stasis and the group of strengthening sinews and bones regulated "immune-inflammation" system by activating blood and dredging channels. The group of dispelling wind and removing dampness-dredging channels and activating collaterals, the group of extinguishing wind and stopping convulsions, the group of activating blood and resolving stasis, the group of strengthening sinews and bones, and the group of clearing heat and draining water affected the nervous system by invigorating Qi-blood and benefiting spirit. The group of dispelling wind and removing dampness-dredging channels and activating collaterals and the group of extinguishing wind and stopping convulsions regulated cell function and substance and energy metabolism by dispelling wind and eliminating cold-dampness. The group of activating blood and resolving stasis and the group of strengthening sinews and bones regulated the cell function and substance and energy metabolism by activating blood and strengthening sinews and bones. The results showed that Tianhe Zhuifeng Ointment exerted the comprehensive efficacy of dispelling wind, removing dampness, activating blood, removing stasis, warming meridians, dredging channels, and strengthening sinews and bones through adjusting the imbalance of "immune-inflammation", regulating nervous system, cell function, and interfering with substance and energy metabolism, thus improving the syndrome of internal obstruction and cold-dampness. The findings of this study laid foundations for clarifying the therapeutic characteristics and clinical orientation of Tianhe Zhuifeng Ointment.

Identifying Symptom Clusters Among People Living With HIV on Antiretroviral Therapy in China: A Network Analysis.

CONTEXT: There exists a research interest shift from separate symptoms to symptom clusters among people living with HIV (PLWH), which may provide a better understanding of symptom management in HIV/AIDS care. However, the symptom clusters among Chinese PLWH are still unknown. OBJECTIVES: The aim of our study was to identify symptom clusters and to examine demographic and health-related factors associated with these symptom clusters among PLWH prescribing antiretroviral therapy (ART) in China. METHODS: From April to September 2017, we recruited 1116 participants through a convenience sampling in five HIV/AIDS designated facilities in the eastern, middle, and southwest regions of China. The principal component analysis was used to identify the symptom clusters. Association network was adopted to describe the relationships among symptoms and clusters. A multiple linear model was used to investigate the associated factors for the severity of overall symptoms and the prevalence of each symptom clusters. RESULTS: Five symptom clusters were identified, including cognitive dysfunction, mood disturbance, wasting syndrome, dizziness/headache, and skin-muscle-joint disorder. Cognitive dysfunction was the most central symptom cluster. Variables including primary caregiver during ART treatment, years of HIV diagnosis and ART use, having comorbidity, self-rated health, and quality of life were associated with the prevalence of these five symptom clusters. CONCLUSION: Our study suggests that there is a need to evaluate symptom clusters for the improvement of symptom management among PLWH. It is particularly important to include assessment and treatment of cognitive symptoms as an essential component of the HIV care.

A network perspective on comorbid depression in adolescents with obsessive-compulsive disorder.

People with obsessive-compulsive disorder [OCD] frequently suffer from depression, a comorbidity associated with greater symptom severity and suicide risk. We examined the associations between OCD and depression symptoms in 87 adolescents with primary OCD. We computed an association network, a graphical LASSO, and a directed acyclic graph (DAG) to model symptom interactions. Models showed OCD and depression as separate syndromes linked by bridge symptoms. Bridges between the two disorders emerged between obsessional problems in the OCD syndrome, and guilt, concentration problems, and sadness in the depression syndrome. A directed network indicated that OCD symptoms directionally precede depression symptoms. Concentration impairment emerged as a highly central node that may be distinctive to adolescents. We conclude that the network approach to mental disorders provides a new way to understand the etiology and maintenance of comorbid OCD-depression. Network analysis can improve research and treatment of mental disorder comorbidities by generating hypotheses concerning potential causal symptom structures and by identifying symptoms that may bridge disorders.

The interplay between cognitive risk and resilience factors in remitted depression: A network analysis.

BACKGROUND: Individuals in remission from depression are at increased risk for developing future depressive episodes. Several cognitive risk- and resilience factors have been suggested to account for this vulnerability. In the current study we explored how risk- and protective factors such as cognitive control, adaptive and maladaptive emotion regulation, residual symptomatology, and resilience relate to one another in a remitted depressed (RMD) sample. METHODS: We examined the relationships between these constructs in a cross-sectional dataset of 69 RMD patients using network analyses in order to obtain a comprehensive, data-driven view on the interplay between these constructs. We subsequently present an association network, a concentration network, and a relative importance network. RESULTS: In all three networks resilience formed the central hub, connecting perceived cognitive control (i.e., working memory complaints), emotion regulation, and residual symptomatology. The contribution of the behavioral measure for cognitive control in the network was negligible. Moreover, the directed relative importance network indicates bidirectional influences between these constructs, with all indicators of centrality suggesting a key role of resilience in remission from depression. LIMITATIONS: The presented findings are cross-sectional and networks are limited to a fixed set of key constructs in the literature pertaining cognitive vulnerability for depression. CONCLUSIONS: These findings indicate the importance of resilience to successfully cope with stressors following remission from depression. Further in-depth studies will be essential to identify the specific underlying resilience mechanisms that may be key to successful remission from depression.