BackgroundThe epigenetic study of childhood trauma has become a valuable field. However, the evolution and emerging trends in epigenetics and childhood trauma have not been studied by bibliometric methods.ObjectiveThis study aims to evaluate status of epigenetic studies in childhood trauma and reveal the research trends based on bibliometrics.MethodsA total of 1,151 publications related to childhood trauma and epigenetics published between 2000 and 2021 were retrieved from the Web of Science Core Collection (WoSCC). CiteSpace (5.8. R 3) was used to implement bibliometric analysis and visualization.ResultsSince 2010, the number of related publications has expanded quickly. The United States and McGill University are the most influential countries and research institutes, respectively. Elisabeth Binder is a leading researcher in childhood trauma and epigenetic-related research. Biological Psychiatry is probably the most popular journal. In addition, comprehensive keyword analysis revealed that “glucocorticoid receptor,” “brain development,” “epigenetic regulation,” “depression,” “posttraumatic stress disorder,” “maternal care,” “histone acetylation,” “telomere length,” “microRNA,” and “anxiety” reflect the latest research trends in the field. A comprehensive reference analysis demonstrated NR3C1 gene methylation, FKBP5 DNA methylation, BDNF DNA methylation, and KITLG methylation have been hot spots in epigenetic studies in the field of childhood trauma in recent years. Notably, the relationship between childhood adversity and NR3C1 gene methylation levels remains unresolved and requires well-designed studies with control for more confounding factors.ConclusionAs the best of our knowledge, this is the first bibliometric analysis of the association between childhood trauma and epigenetics. Our analysis of the literature suggests that childhood trauma may induce depression, anxiety, and post-traumatic stress disorder through epigenetic regulation of glucocorticoid receptor expression and brain development. The hypothalamic-pituitary-adrenal axis is the key points of epigenetic research. The current researches focus on NR3C1 gene methylation, FKBP5 DNA methylation, BDNF DNA methylation, and KITLG methylation. These results provide a guiding perspective for the study of epigenetic effects of childhood trauma, and help researchers choose future research directions based on current keywords.

Aims: To evaluate the clinical efficacy of Naoxueshu oral liquid in the treatment of intracerebral hemorrhage (ICH) patients.Methods: In our study, December 2008 to August 2010, 88 patients with intracerebral hemorrhage were enrolled and 87 patients with complete information of whom 44 patients received Naoxueshu oral liquid plus regular treatment (Naoxueshu group), 43 patients received regular treatment (control group) only. Naoxueshu oral liquid 10 ml was taken in the Naoxueshu group, with 3 times a day for 21 consecutive days. The regular treatment included (1) dehydration treatment by 20% mannitol; (2) therapy to deal with complications including; (3) supportive therapy. The general clinical information, neurological assessment information, laboratory information, and the hematoma volume information were collected and analyzed pre-and post-treatment.Results: We did not find differences in the information between two groups before treatment (p > 0.05). 21-day after treatment, the white blood cell (WBC) count, hematoma volume, the National Institutes of Health Stroke Scale (NIHSS) score, modified Rankin Scale (mRS), Barthel index (BI), and traditional Chinese medicine (TCM) syndrome score in the Naoxueshu group and control group were significantly decreased than before (pnaoxueshu < 0.01, pcontrol < 0.05), and the changes of the WBC count, hematoma volume, NIHSS score, mRS score, and TCM syndrome score in Naoxueshu group were greater than that of control group (P < 0.001).Conclusion: Naoxueshu oral liquid plus regular treatment could decrease the inflammatory response and hematoma, and improve outcomes of ICH patients than regular treatment only. This suggests that Maixueshu oral liquid is a potential treatment for ICH patients.

Objectives Surgical treatment is expected to remove clot immediately in acute spontaneous intracerebral hemorrhage (SICH) patients. The aim of this study was to evaluate whether Naoxueshu could enhance the efficacy of clot removal surgery in acute SICH patients. Methods One hundred twenty patients who had been diagnosed as SICH according to neuroimaging were enrolled in this study. They received craniotomy, decompressive craniectomy, or minimally invasive surgical evacuation as appropriate and then were randomized into two groups: the Naoxueshu group (NXS group, n = 60) and the control group (n = 60). All the patients received standard medical management while patients in NXS group also took Naoxueshu oral liquid 10 ml with three times a day for seven consecutive days. The primary outcome was the 7‐day hematoma volume and secondary outcomes were 7‐day National Institutes of Health Stroke Scale (NIHSS) score and 7‐day cerebral edema score. Results After clot removal surgery, hematoma volume in NXS group (9.5 ± 8.0) was significantly decreased than that in Control group (21.3 ± 22.9, p < .0001) 7 days after surgery. Moreover, cerebral edema was also relieved after 7‐day's Naoxueshu treatment (2.5 ± 0.9 vs. 2.9 ± 0.7, p = .043). Since patients in NXS group had worse baseline NIHSS score (17.2 ± 8.1 vs. 13.7 ± 10.1, p = .039), it was reasonable to conclude that Naoxueshu treatment could improve patients’ neurological function because 7‐day NIHSS score of the two groups was similar. Conclusion Naoxueshu oral liquid could relieve hematoma volume and cerebral edema after clot removal surgery in acute SICH patients. Moreover, it had the potential to improve patients’ short‐term neurological function.

Tanhuo formula (THF), a traditional Chinese medicinal formula, has been demonstrated to be effective in the clinical treatment of acute ischemic stroke (AIS). However, its active ingredients, potential targets, and molecular mechanisms remain unknown. Based on the validation of active ingredient concentrations, our study attempted to elucidate the possible mechanisms of THF based on network pharmacological analysis and experimental validation. Components of THF were screened using network pharmacological analysis, and a compound–target network and protein–protein interaction (PPI) network were constructed. In total, 42 bioactive compounds and 159 THF targets related to AIS were identified. The PPI network identified AKT1, TNF, IL6, IL1B, and CASP3 as key targets. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis demonstrated that the inflammation and apoptotic pathways were enriched by multiple targets. The main components of THF were identified via high-performance liquid chromatography. Subsequently, a validation experiment was conducted, and the expressions of GFAP, C3, TNF-α, and IL-6 were detected via immunofluorescence staining, confirming the inflammatory response at 30 min and 3 days post injury. Immunohistochemical staining for caspase-3 and TUNEL was also performed to assess apoptosis at the same time points. These results indicate that THF can effectively decrease neural cell apoptosis through the caspase-3 pathway and restrain excessive abnormal activation of astrocytes and the release of TNF-α and IL-6, which might be accompanied by the recovery of motor function. Thus, THF may serve as a promising therapeutic strategy for AIS through multiple targets, components, and pathways.

Objective To evaluate the efficacy and safety outcome and related risk factors of Naoxueshu in the treatment of acute SICH. Methods Two hundred twenty patients were enrolled in this study. Diagnosis of SICH was based on neuroimaging. All the patients received regular treatment and Naoxueshu oral liquid 10 ml 3 times a day for 14 consecutive days. Surgical intervention was conducted as needed. Efficacy and safety outcomes were evaluated. Results Hematoma volume decreased significantly 7 days after Naoxueshu treatment (from 27.3 ± 20.0 to 15.1 ± 15.1 ml, P < 0.0001), and it decreased further in 14-day result (6.9 ± 10.4 ml, P < 0.0001). Patients’ neurological function was improved remarkably with NIHSS scores from baseline 13 points to 7-day 7 points (P < 0.0001) and 14-day 4 points (P < 0.0001). Cerebral edema was relieved only 14 days after Naoxueshu treatment (from 3 to 2 points, P < 0.0001). No clinically significant change was found in 7-day and 14-day safety results. Female sex was related independently to large 7-day hematoma volume and worse 7-day NIHSS score while it would not affect patients’ 14-day outcomes. Rare cause of SICH (B = 17.4, P = 0.009) alone was related to large 14-day hematoma volume. Worse baseline NIHSS score (B = 0.3, P = 0.003) and early use of Naoxueshu (B = 2.9, P = 0.005) were related to worse 7-day and14-day neurological function. Conclusion Naoxueshu oral liquid could relieve hematoma volume and cerebral edema safely; meanwhile, it could improve patients’ neurological function. Sex, cause of SICH, and time from onset to receive Naoxueshu should be taken into consideration in the treatment of SICH.