OBJECTIVE: To explore the research history, hotspots and development trends of acupuncture and moxibustion in the treatment of gastroesophageal reflux disease（GERD）based on knowledge graph technology, and to provide references for clinical and basic research in this field. METHODS: The literature of acupuncture and moxibustion for gastroesophageal reflux disease was searched from the CNKI, Wanfang, VIP and SinoMed, from the establishment of the databases to December 31th, 2023. CiteSpace 6.2.R6 Advance was used to draw the knowledge graph of authors, institutions, keywords and other elements, and then perform the visual analysis. RESULTS: A total of 341 articles were included, with the number of publications showing an upward trend and the research types continually diversifying. A total of 832 authors and 308 institutions were analyzed, with XIE Sheng from the First Affiliated Hospital of Guangxi University of CM and BAI Xinghua from the Beijing University of CM as representative figures, forming core research teams. However, there was a lack of close collaboration between institutions, and no significant cross-regional research networks had been formed. A total of 192 keywords were included, forming 8 cluster labels, which mainly included 4 categories：treatment methods, disease types, TCM syndrome types, and literature types. The burst analysis showed that the methods of acupuncture and moxibustion in the treatment of gastroesophageal reflux disease had gradually become more integrated, the treatment methods had transitioned from simple acupuncture therapy to combined therapies with proton pump inhibitors or TCM decoctions, the disease types had become more refined, the focus of mechanism research had shifted from lower esophageal sphincter pressure and esophageal motility to changes in gastrointestinal hormone levels, and the research hotspots had gradually shifted from improving clinical symptoms to considering both mental and psychological states. Twenty-three high-frequency acupoints were obtained, forming 8 clusters of "acupuncture techniques-acupoints" for the treatment of gastroesophageal reflux disease with acupuncture and moxibustion, indicating a gradual enrichment of acupuncture and acupoint treatment protocols. CONCLUSION The research on acupuncture and moxibustion in the treatment of gastroesophageal reflux disease has gradually deepened, in the future, the cooperation among research teams should be strengthened, the quality of clinical research should be improved, more multi-dimensional mechanism research and horizontal comparative research of different acupuncture and moxibustion methods should be made, to provide a basis for clinical promotion and deeper exploration.
Humans ; Moxibustion/trends* ; Gastroesophageal Reflux/therapy* ; Acupuncture Therapy/trends*

This study aimed to observe the protective effect of momordicine I, a triterpenoid compound extracted from momordica charantia L., on isoproterenol (ISO)-induced hypertrophy in rat H9c2 cardiomyocytes and investigate its potential mechanism. Treatment with 10 μM ISO induced cardiomyocyte hypertrophy as evidenced by increased cell surface area and protein content as well as pronounced upregulation of fetal genes including atrial natriuretic peptide, β-myosin heavy chain, and α-skeletal actin; however, those responses were markedly attenuated by treatment with 12.5 μg/ml momordicine I. Transcriptome experiment results showed that there were 381 and 447 differentially expressed genes expressed in comparisons of model/control and momordicine I intervention/model, respectively. GO enrichment analysis suggested that the anti-cardiomyocyte hypertrophic effect of momordicine I may be mainly associated with the regulation of metabolic processes. Based on our transcriptome experiment results as well as literature reports, we selected glycerophospholipid metabolizing enzymes group VI phospholipase A 2 (PLA2G6) and diacylglycerol kinase ζ (DGK-ζ) as targets to further explore the potential mechanism through which momordicine I inhibited ISO-induced cardiomyocyte hypertrophy.Our results demonstrated that momordicine I inhibited ISO-induced upregulations of mRNA levels and protein expressions of PLA2G6 and DGK-ζ. Collectively, momordicine I alleviated ISO-induced cardiomyocyte hypertrophy, which may be related to its inhibition of the expression of glycerophospholipid metabolizing enzymes PLA2G6 and DGK-ζ.

Inflammation-driven endothelial dysfunction is the major initiating factor in atherosclerosis, while the underlying mechanism remains elusive. Here, we report that the non-canonical stimulator of interferon genes (STING)-PKR-like ER kinase (PERK) pathway was significantly activated in both human and mice atherosclerotic arteries. Typically, STING activation leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor-kappa B (NF-κB)/p65, thereby facilitating IFN signals and inflammation. In contrast, our study reveals the activated non-canonical STING-PERK pathway increases scaffold protein bromodomain protein 4 (BRD4) expression, which encourages the formation of super-enhancers on the proximal promoter regions of the proinflammatory cytokines, thereby enabling the transactivation of these cytokines by integrating activated IRF3 and NF-κB via a condensation process. Endothelium-specific STING and BRD4 deficiency significantly decreased the plaque area and inflammation. Mechanistically, this pathway is triggered by leaked mitochondrial DNA (mtDNA) via mitochondrial permeability transition pore (mPTP), formed by voltage-dependent anion channel 1 (VDAC1) oligomer interaction with oxidized mtDNA upon cholesterol oxidation stimulation. Especially, compared to macrophages, endothelial STING activation plays a more pronounced role in atherosclerosis. We propose a non-canonical STING-PERK pathway-dependent epigenetic paradigm in atherosclerosis that integrates IRF3, NF-κB and BRD4 in inflammatory responses, which provides emerging therapeutic modalities for vascular endothelial dysfunction.