Molecular mechanisms underlying the therapeutic effects of Linggui Zhugan decoction in stroke: Insights from network pharmacology and single-cell transcriptomics analysis.

Linggui Zhugan decoction (LZD), a traditional Chinese medicine formula, has demonstrated significant therapeutic effects in managing poststroke cognitive impairment and hemiplegia. However, the precise molecular mechanisms underlying its efficacy remain incompletely elucidated. The active ingredients and target proteins of LZD were retrieved from the traditional Chinese medicine systems pharmacology database and analysis platform database, which is specifically designed for traditional Chinese medicine research. The stroke-related genes were obtained from publicly available databases. Protein-protein interaction, enrichment analysis, and single-cell data analysis were conducted to identify key cells, targets, and pathways. Molecular docking was employed to assess the binding affinity between key components and targets. Network pharmacology analysis identified 190 active ingredients and 248 targets in LZD. These targets were significantly enriched in processes and pathways such as cellular response to lipid, orexin receptor pathway, and were significantly associated with Cerebral infarction and Middle Cerebral Artery Occlusion. Intersection analysis with 2035 stroke-related genes revealed 144 potential targets, which exhibited 2870 interactions and were significantly enriched in signaling pathways such as PI3K-AKT single pathway, MAPK single pathway, and tumor necrosis factor single pathway. Gene set variation analysis showed that the targets of LZD exhibited higher enrichment scores in microglia, M2 macrophages, endothelial cells, and neutrophils, while lower enrichment scores were observed in oligodendrocytes. Furthermore, molecular docking demonstrated a strong binding affinity between key active ingredients and targets. Network pharmacology and single-cell sequencing analysis elucidated the key cells, pathways, targets, and components involved in the therapeutic mechanism of LZD for the treatment of stroke.

Association between gut microbiota and post-stroke depression in Chinese population: A meta-analysis.

Background: Post-stroke depression (PSD) is a common neuropsychological complication after a stroke with a range of poor outcomes. Evidence of gut microbiota disorder for PSD has recently accumulated. This study aimed to systematically evaluate the association between PSD and gut microbiota. Methods: We searched PubMed, Web of Science, Embase, and VIP, CNKI, Wangfang without language restrictions for eligible studies and performed a meta-analysis and systematic review to assess the pooled differences in gut microbiota compositions between PSD and healthy individuals. Results: We included nine eligible studies reporting the differences in the intestinal microbiome between PSD and healthy control. The pooled results demonstrated that the sequencing depth index (Good's coverage), richness indexes (Chao1 and ACE), evenness, and alpha diversity (Shannon and Simpson) were not significantly changed in PSD patients as compared to healthy controls. The observed species (operational taxonomic unit, OUT) in PSD was significantly higher than that in healthy individuals (SMD, 1.86, 95%CI: 1.47 to 2.25). Furthermore, we observed significant differences between PSD and healthy individuals at the phylum level. The pooled estimation of relative abundance of Proteobacteria (SMD, 0.37, 95%CI: 0.19 to 0.55), Bacteroidetes (SMD, 1.87, 95%CI: 1.25 to 2.48), and Fusobacteria (SMD, 1.06, 95%CI: 0.76 to 1.37) in patients with PSD significantly was increased as compared to controls, while the pooled relative abundance of Firmicutes (SMD, -0.84, 95%CI: -1.21 to -0.47) was significantly decreased in PSD as compared to healthy controls. Moreover, significant differences in intestinal microbiota were observed between PSD patients and healthy controls at the family and genus levels. Conclusions: This meta-analysis indicates a significant alteration of observed species and microbiota composition at the phylum, family and genus levels in PSD as compared to healthy individuals.

Effectiveness of rehabilitation training combined acupuncture for the treatment of neurogenic bladder secondary to spinal cord injury.

BACKGROUND: This study will aim to assess the effectiveness of the rehabilitation training (RT) combined acupuncture for the treatment of patients with neurogenic bladder (NB) secondary to the spinal cord injury (SCI). METHODS: We will conduct a comprehensive literature search from the following databases from the inceptions to the present with no language limitation: PUBMED, EMBASE, Cochrane Library, SinoMed, Web of Science, Allied and Complementary Medicine Database, VIP, WANGFANG, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. Additionally, we will also search gray literature, including dissertations and conference proceedings. RevMan V.5.3 software will be used for the study selection, assessment of bias of bias, and data synthesis. RESULTS: This study will synthesize the available evidence of RT combined with acupuncture for NB secondary to SCI, including episodes of urinary incontinence, urinary retention, urinary tract infection, bladder overactivity, quality of life, and adverse events. CONCLUSION: This study will determine whether RT combined acupuncture is an effective and safety therapy for NB secondary to SCI. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019146127.