Yougui Pill in the treatment of lumbar disc herniation:network pharmacological analysis of active ingredients and potential targets / 中国组织工程研究

BACKGROUND:Yougui Pill is a famous formula of the Chinese traditional medicine,which has good efficacy for lumbar disc herniation due to kidney yang insufficiency. OBJECTIVE:To investigate the potential targets and mechanism of action of Yougui Pill in the treatment of lumbar disc herniation by using network pharmacology and molecular docking technology,and verified by animal experiments. METHODS:(1)Network pharmacological analysis:We obtained the active ingredients and targets of Yougui Pill from TCMSP and other databases,collected genes related to lumbar disc herniation from GeneCards database,and took the intersection of the two for the topological analysis to derive the main active ingredients and core therapeutic targets.Gene ontology function analysis and Kyoto encyclopedia of genes and genomes pathway enrichment analysis were performed using R software.(2)Molecular docking:Autodock and Pymol software were utilized for the prediction of molecular binding energy of TCM active ingredients to core therapeutic targets.(3)Animal experiments:Eighteen Sprague-Dawley rats were randomly divided into a control group,a degeneration group and a Yougui Pill group,with 6 rats in each group.A rat model of intervertebral disc degeneration was prepared by fiber puncture method in the degeneration and Yougui Pill groups.At 2 weeks after modeling,Yougui Pill was given by gavage in the Yougui Pill group,once a day for 2 consecutive weeks.The level of tumor necrosis factor-α in serum was detected by the ELISA method,and morphological changes of the annulus fibrosus and nucleus pulposus cells were observed using hematoxylin-eosin staining. RESULTS AND CONCLUSION:There were 90 active ingredients and 64 targets,and the main active ingredients were found to be quercetin,kaempferol,β-carotene,soybean flavonoid,and 4'-O-methylnyasol.The core targets of Yougui Pill for the treatment of lumbar disc herniation were interleukin 6,tumor necrosis factor-α,AKT1,interleukin 1B,and vascular endothelial growth factor A.Enrichment analysis revealed that the intersecting genes might be expressed through the interleukin-17 signaling pathway,tumor necrosis factor signaling pathway,MAPK signaling pathway,PI3K-AKT signaling pathway,and other signaling pathways to improve intervertebral disc degeneration.The molecular docking test verified that quercetin,kaempferol,and β-carotene had strong binding ability to the core targets.Animal experiments showed that the level of serum tumor necrosis factor α in the degeneration group was higher than that in the control group(P<0.05),and the level of serum tumor necrosis factor α in the Yougui Pill group was lower than that in the degeneration group(P<0.05).Hematoxylin-eosin staining showed that the fibrous annulus of the intervertebral discs and the structure of the nucleus pulposus in the degeneration group were destroyed,and the number of nucleus pulposus cells was reduced;there was a tendency to reconstructing the fibrous annulus of the intervertebral discs in the Yougui Pill group,and the number of nucleus pulposus cells increased compared with the degeneration group.To conclude,Yougui Pill may treat lumbar disc herniation by improving disc degeneration through the effects of quercetin,kaempferol,beta-carotene and other key active ingredients on core targets such as tumor necrosis factor.

Characteristics of auditory steady-state response in first-degree relatives of schizophrenic patients under eye-open/closed state / 中华行为医学与脑科学杂志

Objective:To study the effect of eye-open/closed state on 40 Hz auditory steady state response (ASSR) in first-degree relatives of schizophrenia.Methods:Thirty-eight first-degree relatives of schizophrenic patients treated in Shanghai Mental Health Center from March 2010 to October 2011 were selected, and 31 healthy controls were recruited in the same period. All subjects were assessed with schizotypal personality questionnaire (SPQ). The 40 Hz EEG ASSR signals lasting for 3 min under open and closed eyes of all subjects were sequentially collected.Event-related spectrum perturbation (ERSP) and intertribal phase coherence (ITC) were used to evaluate ASSR. SPSS 22.0 software was used for statistical analysis. Two-way analysis of variance was used to compare ITC and ERSP between the two groups under open and closed eyes. Spearman correlation analysis was used to analyze the correlation between each measurement.Results:ITC in group main effect and group×the eye open/closed interaction effect were not significant (both P>0.05), but the main effect of eye-open and eye-closed was significant ( F(1, 67)=10.61, P=0.002). In the healthy control group, the ITC in eye-open state was significantly higher than that in eye-closed state ( P=0.014), and in the first-degree relatives group, the ITC in eye-open state was higher than that in eyes closed state ( P=0.039). ERSP in the main effect of eye-open and eye-closed ( F(1, 67)=0.195, P=0.660), group main effect ( F(1, 67) =0.627, P=0.431), group × the eye-open/closed interaction effect ( F(1, 67)= 1.034, P=0.313) was not significant. Spearman correlation analysis showed that there was no correlation between ERSP (eye open: r=-0.260, P=0.210; eye closed: r=-0.318, P=0.122), ITC (eye open: r=-0.248, P=0.232; eye closed: r=-0.260, P=0.209) and SPQ score in the healthy control group. There was also no correlation between ERSP (eye open: r=-0.387, P=0.226; eye closed: r=-0.363, P=0.238) or ITC (eye open: r=0.126, P=0.485; eye closed: r=0.096, P=0.595) and SPQ score in the first-degree relatives group of schizophrenia. Conclusion:The regulation pattern of 40 Hz ASSR in schizophrenic first-degree relatives is not significantly impaired in the eye-open/closed state, suggesting that the open/closed regulation pattern of 40 Hz ASSR may not be a potential marker for predicting the genetic high-risk prognosis of schizophrenia.

Event-related potentials as predictors of clinical outcomes in patients with clinical high risk of psychosis / 中华行为医学与脑科学杂志

Most patients with schizophrenia have experienced a period called clinical high risk (CHR) preceding the first episode of psychosis.Early identification of CHR and timely medication or psychological intervention may reduce conversion to psychosis.By exploring biomarkers that predict the onset of psychosis and improving the accuracy of predicting the prognosis of CHR state, it is possible to take a more active intervention measure.As a fast and economical neurophysiological test, event-related potential (ERP) may reflect the perception process, pre-attention process, and attention distribution of the cognitive processes.And it holds promise for becoming objective indices in predicting the clinical outcomes of the CHR patients.This paper reviews the current studies on different ERP components in the CHR population and their performance as predictors of clinical outcomes.The results show that among ERP abnormalities, P300 and MMN amplitude reductions appear to be more reliable than others, which may indicate that distinct components reflect different stages of the disease.However, as a physiological index in the CHR group, aberrant ERP lacks certain specificity.The algorithm analysis combining different ERP components or combining components with symptoms may make the test more specific in the future.

Chimeric antigen receptor T-cell therapy: a promising treatment modality for relapsed/refractory mantle cell lymphoma / 医学前沿

Mantle cell lymphoma (MCL) is a distinct histological type of B-cell lymphoma with a poor prognosis. Several agents, such as proteasome inhibitors, immunomodulatory drugs, and inhibitors of B cell lymphoma-2 and Bruton's tyrosine kinase have shown efficacy for relapsed or refractory (r/r) MCL but often have short-term responses. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a novel treatment modality for r/r non-Hodgkin's lymphoma. However, long-term safety and tolerability associated with CAR T-cell therapy are not defined well, especially in MCL. In this report, we described a 70-year-old patient with r/r MCL with 48-month duration of follow-up who achieved long-term remission after CAR T-cell therapy. CAR T-cell-related toxicities were also mild and tolerated well even in this elderly patient. This report suggested that CAR T-cell therapy is a promising treatment modality for patients with MCL, who are generally elderly and have comorbid conditions.

Different sites of extranodal involvement may affect the survival of patients with relapsed or refractory non-Hodgkin lymphoma after chimeric antigen receptor T cell therapy / 医学前沿

Factors associated with complete and durable remissions after anti-CD19 chimeric antigen receptor T (CAR-T) cell immunotherapy for relapsed or refractory non-Hodgkin lymphoma (r/r NHL) have not been well characterized. In this study, we found that the different sites of extranodal involvement may affect response, overall survival (OS), and progression-free survival (PFS) in patients with r/r NHL treated with anti-CD19 CAR-T cells. In a cohort of 32 treated patients, 12 (37.5%) and 8 (25%) patients exhibited soft tissue lymphoma and bone marrow (BM) infiltrations, respectively, and 13 (41%) patients exhibited infiltration at other sites. The factors that may affect prognosis were identified through multivariable analysis. As an independent risk factor, soft tissue infiltration was the only factor significantly correlated with adverse prognosis (P < 0.05), whereas other factors did not reach statistical significance. Furthermore, the site of extranodal tumor infiltration significantly and negatively affected OS and PFS in patients with r/r NHL treated with anti-CD19 CAR-T cell therapy. PFS and OS in patients with BM involvement were not significantly different from those of patients with lymph node involvement alone. Thus, anti-CD19 CAR-T cell therapy may improve the prognosis of patients with BM infiltration.