Exploring the Active Ingredients and Mechanism of Action of Huanglian Huazhuo Capsule for the Treatment of Obese Type-2 Diabetes Mellitus Based on Using Network Pharmacology and Molecular Docking.

Background: Obese type 2 diabetes mellitus (obese T2DM) is one of the prime diseases that endangers human health. Clinical studies have confirmed the ability of the Huanglian Huazhuo capsule to treat obese T2DM; however, its mechanism of action is still unclear. In this study, effects and mechanisms of the Huanglian Huazhuo capsule in obese T2DM were systematically investigated using network pharmacology and molecular docking techniques. Methods: The active ingredients and targets of the Huanglian Huazhuo capsule were extracted from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Obese T2DM diabetes-related targets were retrieved from a geographic dataset combined with a gene card database. A protein-protein interaction (PPI) network was constructed to screen core targets. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using Database for Annotation Visualization and Integrated Discovery (DAVID). Interactions between potential targets and active compounds were assessed using molecular docking. Molecular docking was performed on the best core protein complexes obtained using molecular docking. Results: A total of 89 and 108 active ingredients and targets, respectively, were identified. Seven core targets were obtained using a topological analysis of the PPI network. The GO and KEGG pathway enrichment analyses showed that the effects of the Huanglian Huazhuo capsules were mediated by inflammation, lipid response, oxidative stress-related genes, and HIF-1 and IL-17 signaling pathways. Good binding ability was observed between the active compounds and screened targets using molecular docking. Conclusions: The active ingredients, potential targets, and pathways of the Huanglian Huazhuo capsule for the treatment of obese T2DM were successfully predicted, providing a new strategy for further investigation of its molecular mechanisms. In addition, the potential active ingredients provide a reliable source for drug screening in obese T2DM.

Long-term unmet needs after stroke: systematic review of evidence from survey studies.

OBJECTIVES: To synthesise evidence on longer term unmet needs perceived by stroke survivors, and psychometric properties of the tools used to evaluate unmet care needs after stroke. DESIGN: Systematic review. SETTING: Community or patients' home. PARTICIPANTS: Stroke survivors. METHODS: We searched PubMed, PsycINFO, CINAHL, EMBASE from inception to 31 March 2018 to identify survey studies that evaluated unmet needs perceived by stroke survivors after hospital discharge. Reported unmet needs were categorised under three domains: body functioning, activity/participation and environmental factors. Ranges of prevalence rates of unmet needs reported in studies were presented. RESULTS: We included 19 eligible studies, with considerable heterogeneity in patients, survey methods and results. Psychometric properties of two stroke-specific tools were formally evaluated, indicating their moderate reliability and content/concurrent validity. The median number of reported unmet needs per stroke survivor was from two to five, and the proportion of stroke survivors with at least one unmet needs was on average 73.8% (range 19.8%- 91.7%). Unmet needs perceived by stroke survivors included 55 records of unmet body functioning needs, 47 records of unmet activities/participatory needs and 101 records of unmet environmental needs. Common unmet service needs were unmet information needs (3.1%- 65.0%), transport (5.4%-53.0%), home help/personal care (4.7%-39.3%) and therapy (2.0%-35.7%). CONCLUSIONS: The prevalence of unmet long-term needs is high among stroke survivors, and there is considerable heterogeneity in type and frequency of specific unmet needs. More research is required to link regular assessment of long-term unmet needs of stroke survivors with the provision of cost-effective patient-centred health and social care services.

A Comparison of Midazolam, Lorazepam, and Diazepam for the Treatment of Status Epilepticus in Children: A Network Meta-analysis.

Midazolam, lorazepam, and diazepam were recommended as emergent initial therapy for status epilepticus. However, there are no current studies to confirm the best agent for pediatric status epilepticus. We compared the efficacy of midazolam, lorazepam, and diazepam in treating pediatric status epilepticus using a network meta-analysis method. In total, 16 randomized controlled trials containing 1821 patients were included. Nonintravenous midazolam, intravenous lorazepam, and intravenous diazepam were more successful in achieving seizure cessation when compared with nonintravenous diazepam (odds ratio = 2.23, 95% credibility interval: 1.62, 3.10; odds ratio = 2.71, 95% credibility interval: 1.25, 5.89; odds ratio = 2.65, 95% credibility interval: 1.12, 6.29; respectively). Among lorazepam, midazolam, and diazepam, midazolam had the highest probability (surface under the cumulative ranking area [SUCRA] = 0.792) of achieving seizure cessation, and lorazepam had the largest probability (surface under the cumulative ranking area = 0.4346) of being the best treatment in reduction of respiratory depression. In conclusion, nonintravenous midazolam and intravenous lorazepam were superior to intravenous or nonintravenous diazepam, and intravenous lorazepam was at least as effective as nonintravenous midazolam in treating pediatric status epilepticus.