Integrated UPLC-MS, network pharmacology, and intestinal flora analysis to determine the treatment effect of Qiangzhi decoction on comorbid Tourette syndrome and RRTI.

Background: Tourette syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics. Recurrent respiratory tract infection (RRTI), a commonly occurring disease in childhood, correlates with recurrent and severe course of tic symptoms. Qiangzhi decoction (QZD) is a traditional Chinese medicine that can alleviate TS symptoms while reducing the recurrence of RRTI. However, the mechanism of QZD on TS and RRTI remains unclear. This study aimed to determine the treatment effect of QZD on comorbid TS and RRTI by integrating ultrahigh-performance liquid chromatography mass spectrometry (UPLC-MS), network pharmacology, and intestinal flora analysis. Methods: The components of QZD were first identified by UPLC-quadrupole (Q)-orbitrap-MS/MS. The mechanism of QZD on comorbid RRTI and TS was investigated by a series of network pharmacological methods, including target prediction and bioinformatics analysis. Finally, a comorbid TS and RRTI rat model was established by intraperitoneal injection of 3,3-iminodipropionitrile (IDPN), cyclophosphamide (CTX), and lipopolysaccharide (LPS). Alteration of gut microbiota in the alleviation of TS and RRTI by QZD was investigated via intestinal flora analysis. Results: The results of UPLC-Q-orbitrap-MS/MS showed that QZD had 96 types of chemical components. The network pharmacology results demonstrated that targets of QZD involved in the treatment of TS and RRTI involved 1045 biological processes (BPs), 109 cellular components (CCs), and 133 molecular functions (MFs), including synaptic and transsynaptic signaling, chemical synaptic transmission, neurotransmitter receptor activity, G protein-coupled amine receptor activity, and serotonin receptor activity, among others. Firmicutes, Bacteroidetes, Coprococcus, and Lachnospiraceae played crucial roles in gut microbiota of a QZD-treated comorbid TS and RRTI model. Conclusions: Our results revealed QZD provided a multicomponent, multitarget, and multipathway synergistic treatment of comorbid TS and RRTI.

Quality of evidence supporting the role of non-steroidal anti-inflammatory drugs for the treatment of anxious depression: a protocol for an overview of systematic reviews and meta-analyses.

INTRODUCTION: There have been several studies showing the effectiveness of non-steroidal anti-inflammatory drugs (NSAIDs) for anxious depression. We aimed to summarise the evidence and evaluate the methodological quality regarding the effectiveness and safety of NSAIDs for anxious depression from systematic reviews/meta-analyses (SRs/MAs). METHODS AND ANALYSIS: Two researchers searched seven databases for SRs/MAs, which are randomised controlled trials on NSAIDs for anxious depression. Two investigators used the Assessment System for Evaluating Methodological Quality 2, the Risk of Bias in Systematic reviews tool, the list of preferred reporting items for SRs/MAs and the Grading of Recommendations, Assessment, Development and Evaluation system to assess the included SRs/MAs. ETHICS AND DISSEMINATION: The findings of the study will be disseminated through peer-reviewed journals, and national and international conference presentations.

The Effect and Safety of Xuefu Zhuoyue Prescription for Coronary Heart Disease: An Overview of Systematic Reviews and Meta-Analyses.

Background: In China, the traditional Chinese medicine compound Xuefu Zhuoyue prescription (XFZY) has been widely used in the therapy of coronary heart disease (CHD). Currently, several systematic reviews (SRs)/meta-analyses (MAs) of XFZY for the treatment of CHD have been published. This overview aims to evaluate the existing SRs/MAs and provide a scientific basis for evaluating the efficacy and safety of XFZY for the therapy of CHD. Methods: The SRs/MAs of XFZY for the treatment of CHD were obtained from 7 electronic databases with the search date set at March 7, 2022. Two researchers independently assessed the methodological quality, reporting quality, and evidence quality of the included SRs/MAs using the following tools: the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2), the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PRISMA 2020), and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Results: A total of 11 SRs/MAs were included in this overview. All SRs/MAs assessed by means of AMSTAR-2 had more than one critical defect, so all SRs/MAs were rated low. Regarding the assessment of reporting quality, the results of PRISMA 2020 showed that none of the SRs/MAs were fully reported. In addition, the results of the GRADE assessment of the quality of evidence indicated that only one outcome was rated as high quality across all SRs/MAs. Conclusion: Current evidence suggests that XFZY is effective and safe for the management of patients with CHD. However, the high risk of bias of the original clinical studies and the low quality of the SRs/MAs reduced the reliability of the results.

Scientific Evidence of Traditional Chinese Exercise (Qigong) for Chronic Obstructive Pulmonary Disease: An Overview of Systematic Reviews and Meta-Analyses.

Background: As a traditional Chinese exercise, Qigong has potential benefits for the management of chronic obstructive pulmonary disease (COPD). This overview is aimed at assessing the existing evidence for the intervention of Qigong in COPD so as to provide scientific guidance for clinical decision-making. Methods: The systematic reviews (SRs)/meta-analyses (MAs) of Qigong for the treatment of COPD were obtained from 7 electronic databases with the search date set at April 5, 2022. Two researchers independently assessed the methodological quality, reporting quality, and evidence quality for the included SRs/MAs using the following tools: the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2), the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PRISMA 2020), and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Results: A total of 13 SRs/MAs were included in this overview. All SRs/MAs assessed by AMSTAR-2 had more than one critical defect, so all SR/MAs were rated very low. Regarding the assessment of reporting quality, the results of PRISMA 2020 showed that none of the SRs/MAs were fully reported. In addition, the results of the GRADE assessment of the quality of evidence indicated that only 3 outcomes were rated as high quality across all SRs/MAs. Conclusion: Current evidence suggests that Qigong is effective and safe for the management of patients with COPD. However, the high risk of bias in the original clinical studies and the low quality of the SRs/MAs reduced the reliability of the results.

The Effects of Tai Chi Exercise for Patients with Type 2 Diabetes Mellitus: An Overview of Systematic Reviews and Meta-Analyses.

Objectives: Tai chi (TC) is a potential complementary treatment for type 2 diabetes mellitus (T2DM). This overview systematically summarizes and evaluates the existing evidence of TC in the treatment of T2DM. Methods: Systematic reviews (SRs)/meta-analyses (MAs) on TC interventions for T2DM were comprehensively searched in seven databases. Methodological quality, risk of bias, reporting quality, and quality of evidence were assessed using the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2), the Risk of Bias in Systematic (ROBIS) scale, the list of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Results: Eight published SRs/MAs were included in our study. Based on the methodology and quality of evidence assessment, all SRs/MAs are considered to be of very low quality, and only 1 SR/MA has been assessed as low risk of bias, and none of the SR/MA has been fully reported on the checklist. A total of 65 outcome indicators extracted from the included SRs/MAs were evaluated, and only 1 item was assessed as high quality. Conclusions: TC may be an effective and safe complementary treatment for T2DM. However, this conclusion must be treated with caution because the quality of the evidence provided by the included SRs/MAs is generally low.

Quality of Evidence Supporting the Role of Tripterygium Glycosides for the Treatment of Diabetic Kidney Disease: An Overview of Systematic Reviews and Meta-Analyses.

Background: Tripterygium glycosides (TG) is widely used in the treatment of diabetic kidney disease (DKD) in China. To systematically assess and synthesize the available evidence, we present an overview of systematic reviews (SRs) and meta-analyses (MAs) on the topic of TG interventions for DKD. Methods: SRs/MAs on TG interventions for DKD were comprehensively searched in seven databases. Methodological quality, risk of bias, reporting quality, and quality of evidence were assessed using the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2), the Risk of Bias in Systematic (ROBIS) scale, the list of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), as well as the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Results: This overview includes 13 SRs/MAs that use quantitative calculations to comprehensively assess various outcomes in TG interventions for DKD. The methodological quality, reporting quality, and risk of bias of SRs/MAs, and the quality of evidence for outcome indicators are unsatisfactory. Limitations of the included SRs/MAs consist in the lack of essential procedures such as protocol registration, screening of duplicate study, provision of the list of excluded studies, and assessment of publication bias. Besides, the reliance on small samples for quantitative synthesis of effect sizes also constitutes an important limitation. Conclusion: TG may be a potential complementary treatment modality to DKD therapy. However, this conclusion must be treated with caution as the quality of the evidence provided by SRs/MAs is generally low.

A critical overview of systematic reviews and meta-analyses of light therapy for non-seasonal depression.

Light therapy has increasingly been used in relieving non-seasonal depression. We aimed to summarize the evidence and evaluate the methodological quality regarding the effectiveness and safety of light therapy for non-seasonal depression from systematic reviews/meta-analyses (SRs/MAs). In this study, five databases were searched from their inceptions to January 24, 2022. SRs/MAs on light therapy treatment for non-seasonal depression were included. Methodological quality assessment was performed using the Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2), and evidence quality assessment was performed using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE). Six SRs/MAs on light therapy treatment for non-seasonal depression were included. The AMSTAR-2 showed that the methodological level of five included SRs/MAs were evaluated as critically low quality, and one included SRs/MAs were rated as low quality. According to the evaluation results of GRADE, the quality of evidence was mostly unsatisfactory. The results and descriptions in the included SRs/MAs suggest that light therapy is effective as a non-pharmacological intervention for the treatment of non-seasonal depression. However, the generally unsatisfied evidence quality and methodological quality of the SRs/Mas indicate that these results must be interpreted with caution.

Evidence Quality Assessment of Tai Chi Exercise Intervention in Cognitive Impairment: An Overview of Systematic Review and Meta-Analysis.

Background: Tai Chi (TC) exercise has recently received wide attention for its efficacy in the management of cognitive impairment. The purpose of this overview is to summarize the available evidence on TC treatment of cognitive impairment and assess its quality. Methods: We retrieved relevant systematic reviews/meta-analyses (SRs/MAs) from 7 databases from the time they were established to January 2, 2022. Two reviewers independently evaluated the methodological quality, risk of bias, report quality, and evidence quality of the included SRs/MAs on randomized controlled trials (RCTs). The tools used are Assessment System for Evaluating Methodological Quality 2 (AMSTAR-2), the Risk of Bias In Systematic (ROBIS) scale, the list of Preferred Reporting Items for Systematic Reviews And Meta-Analysis (PRISMA), and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Results: This overview finally included 8 SRs/MAs. According to the results of AMSTAR-2, all included SRs/MAs were rated as very low quality. Based on the ROBIS tool, none of the SR/MA had a low risk of bias. In light of PRISMA, all SRs/MAs had reporting deficiencies. According to the GRADE system, there was only 1 high-quality piece of evidence. Conclusion: TC is a promising complementary and alternative therapy for cognitive impairment with high safety profile. However, in view of the low quality of the included SRs/MAs supporting this conclusion, high-quality evidence with a more rigorous study design and a larger sample size is needed before making a recommendation for guidance.

Quality of Evidence Supporting the Effects of Tai Chi Exercise on Essential Hypertension: An Overview of Systematic Reviews and Meta-Analyses.

Objectives: Tai Chi (TC) is a potential complementary treatment for essential hypertension (EH). This overview systematically summarizes and evaluates the existing evidence of TC in the therapy of EH. Methods: Systematic reviews (SRs)/meta-analyses (MAs) on TC interventions for EH were comprehensively searched in seven databases. Methodological quality, risk of bias, reporting quality, and quality of evidence were assessed by means of the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2), the Risk of Bias in Systematic (ROBIS) scale, the list of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), as well as the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Results: Twelve published SRs/MAs were included in our study. According to the results of the AMSTAR-2, ROBIS, PRISMA, and GRADE assessment, only 1 SR/MA was assessed as high quality and only 1 SR/MA was assessed as low risk of bias. Only 2 SRs/MAs have been fully reported on the checklist. In addition to that, the quality of evidence was assessed for a total of 69 outcome indicators extracted from the SRs/MAs included in this overview, and only 3 items were assessed as high quality. Conclusions: TC may be an effective and safe complementary treatment for EH. However, this conclusion must be approached with caution, as the quality of the evidence provided by the SRs/MAs is usually low.

Efficacy and Safety of Transcutaneous Electrical Acupoint Stimulation for Postoperative Pain: A Meta-Analysis of Randomized Controlled Trials.

Objective: This meta-analysis aims to evaluate the effectiveness and safety of transcutaneous electrical acupoint stimulation (TEAS) in treating post-operative pain. Methods: This meta-analysis was registered in PROSPERO (CRD42021286753). We searched PubMed, Embase, and the Cochrane Library for relevant randomized controlled trials (RCTs) about TEAS in treating postoperative pain that were published before November 2021. The primary outcome was visual analogue scale (VAS) within 24 h after surgery. The secondary outcomes included postoperative opioid analgesic drug consumption and the occurrence of adverse reactions within the postoperative 24-72 h. Adverse reactions included dizziness, nausea, and vomiting. Continuous variables were analyzed using mean difference (MDs) or standardized mean difference (SMDs) and 95% CIs. Relative risk (RR) and 95% CI were used for dichotomous data. The data were pooled and analyzed by RevMan 5.4 and STATA15.0 software. Results: Seventeen trials with 1375 participants were included. The current results suggested that application of TEAS showed obvious superiority in reducing VAS scores (SMD = -1.51, 95% CI = -2.20∼-0.82, I2 = 96%). Subgroup analysis was performed according to open surgery and minimally invasive surgery. VAS scores were decreased after surgery at 24 h (SMD = -0.84, 95% CI = -1.07∼-0.6, I2 = 96%; SMD = -0.88, 95% CI = -1.02∼-0.75, I2 = 96%). The incidence of postoperative dizziness and nausea and vomiting was significantly lower in the TEAS group within postoperative 24-72 h (RR = 0.48, 95% CI = 0.34∼0.68, I2 = 0%; RR = 0.66, 95% CI = 0.44∼1.01, I2 = 69%; and RR = 0.49, 95% CI = 0.24∼1.00, I2 = 51%). Postoperative opioid analgesics were also reduced in the TEAS group within 72 h after surgery (SMD = -2.10, 95% CI = -3.37∼-0.82, I2 = 96%). Conclusions: TEAS can reduce postoperative pain as well as the incidence of dizziness, nausea, and vomiting and the number of analgesics used after surgery. TEAS is a reasonable modality to incorporate into a multimodal management approach for postoperative pain.

Quality of Evidence Supporting the Role of Curcuma Longa Extract/Curcumin for the Treatment of Osteoarthritis: An Overview of Systematic Reviews.

Background: Well known for its good anti-inflammatory effect, curcuma longa extract (CLE)/curcumin (C) has a potential effect on osteoarthritis (OA), and a large number of researchers have completed several systematic reviews/meta-analyses (SRs/MAs) in this research area. However, the methodological and evidentiary quality of these SRs/MAs need to be further evaluated, and whether these findings provide reliable evidence for clinicians remains controversial. Methods: Two researchers collected data from seven databases for SRs/MAs that are about randomized controlled trials (RCTs) on CLE/C for OA. Assessment was made for the SRs/MAs included in this article by means of the Assessment System for Evaluating Methodological Quality 2 (AMSTAR-2), the Risk of Bias in Systematic (ROBIS) scale, the list of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Results: Nine published SRs/MAs were included in our study. According to the results of the AMSTAR-2 assessment, only one SR/MA was assessed as high quality. According to the ROBIS evaluation results, only 2 SRs/MAs have a low risk of bias. According to the results of the PRISMA checklist assessment, only 2 SRs/MAs studies fully reported the checklist, while other studies had reporting flaws. According to GRADE, a total of 59 effect sizes extracted from the included SRs/MAs were evaluated, among which no effect size was rated as high. Conclusions: CLE/C may be an effective and safe complementary treatment for OA. However, further standard SRs/MAs and RCTs are needed to provide an evidence-based medical rationale for this.

Helicobacter pylori infection and the progression of atherosclerosis: A systematic review and meta-analysis.

OBJECTIVE: In recent years, many studies have tried to prove whether Helicobacter pylori (H. pylori) can promote the progression of atherosclerosis (AS), but the reported results are conflicting. Carotid intima-media thickness (CIMT), flow-mediated dilation (FMD), or pulse wave velocity (PWV) are the most commonly used indicators to evaluate the progress of AS. So, we collected and evaluated these three indicators to provide evidence-based medicine for the clinic. MATERIALS AND METHODS: We included and evaluated studies on H. pylori infection and CIMT, FMD, or PWV from PubMed, Cochrane trials, and Embase databases before September 1, 2021, and language restrictions: English. Research types include cross-sectional studies, cohort studies, and case-control studies. The MINORS scale was used to evaluate the quality of these studies. For all studies, we choose a random-effects model and calculate the weighted mean difference (WMD) for analysis, and all our analyses use STATA software. RESULTS: Meta-analysis shows that H. pylori infection can significantly increase CIMT (WMD = 0.059, 95% CI: 0.039, 0.079, p < 0.001). Based on subgroup analysis, we found that the relationship between the two is more significant in the young and middle-aged people younger than 60 years old and people without cardiovascular disease. In addition, we also found an association between H. pylori infection and FMD (WMD = -3.873, 95% CI: -5.684, -2.062, p < 0.001), but it is a pity that there are few literatures that meet the standards. Finally, We concluded that H. pylori infection can significantly increase PWV (WMD = 88.033, 95%CI: 67.297,108.768. I2  = 99.63%, p < 0.001). In the subgroup analysis, we also found that this correlation is similar to CIMT, and it is more significant in the young and middle-aged population under 60 and those without cardiovascular disease. We also found in the sub-analysis that there was a significant increase in CIMT in CagA-positive individuals in H. pylori-infected patients (WMD = 0.16, 95%CI: 0.02, 0.29. p = 0.03). CONCLUSION: Helicobacter pylori infection can promote the process of AS, especially in people under the age of 60 and people without cardiovascular risk factors, and we hope that our meta-analysis can provide ideas for the early prevention of AS.

Constructing and validating of m7G-related genes prognostic signature for hepatocellular carcinoma and immune infiltration: potential biomarkers for predicting the overall survival.

Background: To investigate the prognostic significance of N7-methylguanosine (m7G) regulators and immune infiltration in liver hepatocellular carcinoma (LIHC). Methods: The research measured predictive m7G genes in LIHC samples from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets. Data on the stemness index based on mRNA expression (mRNAsi), gene mutations, and corresponding clinical characteristics were obtained from TCGA and ICGC. Lasso regression was used to construct the prediction model to assess the m7G prognostic signals in LIHC. Based on these genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to identify key biological functions and pathways. The correlation between m7G RNA methylation regulators and the prognosis and immune infiltration of LIHC was evaluated. Results: There were 21 m7G-related differentially expressed genes (DEGs) in LIHC and healthy tissues, and LIHC patients could be divided into two categories by consensus clustering of these DEGs. A five-gene predictive approach was employed using least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Patients in the low-risk group showed a significantly higher survival rate compared with those in the high-risk group (P=0.001). Validations using the ICGC database. Also, univariate and multivariate Cox regression analyses suggested that the risk score produced by the predictive model is an independent predictor for LIHC [hazard ratio (HR): 1.848, 95% confidence interval (CI): 1.286-2.656; HR: 2.597, 95% CI: 1.358-4.965]. The ROC curves of the ICGC cohort revealed that the five-gene prediction model performed well [area under the curve (AUC) =0.642 at 1 year, AUC =0.686 at 2 years, and AUC =0.667 at 3 years]. Immuno-oncology scoring revealed that in the high-risk group, among 16 immune cells, the expressions of neutrophils and natural killer (NK) cells were low and that of regulatory T-cells (Tregs) was high. Conclusions: LIHC occurrence and progression are linked to m7G-related genes. Corresponding prognostic models help forecast the prognosis of LIHC patients. m7G-related genes and associated immune cell infiltration in the TME may serve as potential therapeutic targets in LIHC, which requires further trials. In addition, the m7G-related gene signature offers a viable alternative to predict LIHC, and these m7G-related genes show a prospective research area for LIHC targeted treatment in the future.

Establishment and evaluation of a compound fear behavior model of Tourette's syndrome in rats.

BACKGROUND: Tourette syndrome (TS) is a common childhood disorder characterized by unwanted movements or vocal sounds called tics. It is often accompanied by other psychobehavioral disorders, including fearful behavior. The establishment and evaluation of rat models of TS and comorbid fear can provide an experimental basis for the treatment of TS and its comorbid fear disorder. METHODS: Sixteen rats were randomly divided into a model group (n=8) and control group (n=8). In the model group, rats were injected intraperitoneally with iminodipropionitrile (IDPN) for 1 week to establish the TS model, which was followed by acoustic and electrical stimulation for 3 weeks to establish the rat models of TS and comorbid fear. The control group received intraperitoneal injection of saline for 1 week, and no further intervention was given in the last 3 weeks. The behavioral changes of the rats were observed and analyzed by the open field test (OFT). Protein kinase A (PKA), cyclic adenosine monophosphate (cAMP), and dopamine (DA) were measured by enzyme-linked immunosorbent assay (ELISA), and tyrosine hydroxylase (TH) and microRNA-134 (miRNA-134) in the brain tissue were detected by using polymerase chain reaction (PCR). RESULTS: One rat in the model group died on the 24th day. Compared with the control group, the model group had significantly higher scores of locomotor activity, stereotyped behavior, and motor behavior, along with prolonged freezing time and significantly lower expression of miRNA-134. The differences in the expressions of PKA, cAMP, DA, and TH in brain tissue were not statistically significant. CONCLUSIONS: The rat models of TS and comorbid fear have similar changes in behaviors and miRNA-134 level to those in clinical settings and therefore can be used as a reliable animal model to study the mechanism of action of TS and comorbid fear.

Network pharmacology study on the mechanism of Qiangzhifang in the treatment of panic disorder.

BACKGROUND: Panic disorder (PD) is a kind of mental illness characterized by the symptom of recurring panic attacks. Qiangzhifang (QZF) is a novel decoction developed by Professor Zhaojun Yan based on a unique system of syndrome differentiation and clinical experience. It has achieved remarkable results after long-term clinical practice, but its mechanism of action is still unclear. This study aims to use network pharmacology and molecular docking to explore the mechanism of QZF in the treatment of PD. METHODS: We used the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), a literature search, and Encyclopedia of Traditional Chinese Medicine (ETCM) to find active ingredients and targets of QZF. We searched for PD targets in GeneCards, Online Mendelian Inheritance in Man (OMIM), the Comparative Toxicogenomics Database (CTD), and DrugBank. We established a PD target database, constructed a protein-protein interaction (PPI) network, and performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis in order to screen possible pathways of action and analyze the mechanism. RESULTS: This study identified 84 effective components of QZF, 691 potential targets, 357 PD targets, and 97 intersectional targets. Enrichment analysis using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) showed that QZF was associated with 118 biological processes (BPs), 18 cellular components (CCs), 35 molecular functions (MFs) [false discovery rate (FDR) <0.01], and 62 pathways (FDR <0.01). QZF mainly acts on its targets AKT1, FOS, and APP through active ingredients such as quercetin, ß-sitosterol, 4-(4'-hydroxybenzyloxy)benzyl methyl ether, harmine, 1,7-dimethoxyxanthone, and 1-hydroxy-3,7-dimethoxyxanthone to regulate serotonin, gamma-aminobutyric acid (GABA), cyclic adenosine monophosphate (cAMP), and other signal pathways to treat PD. CONCLUSIONS: Through network pharmacology and molecular docking technology, we predicted the possible mechanism of QZF in the treatment of PD, revealed the interaction targets and potential value of QZF, and provided a basis for its clinical application.

Construction of a ceRNA immunoregulatory network related to the development of vascular dementia through a weighted gene coexpression network analysis.

BACKGROUND: To date, vascular dementia (VaD) lacks effective treatment in clinical practice. There is also growing evidence that VaD may be closely related to the immune response. The development of high-throughput technology, and the recently discovered group of new mediators called competitive endogenous RNAs (ceRNA), provides a unique opportunity to study the immunomodulation of VaD. METHODS: In this study, we used gene expression profiles in the Gene Expression Omnibus (GEO) database to obtain immune-related gene coexpression modules through a weighted gene coexpression network analysis (WGCNA) and gene enrichment analysis. We extracted and merged long non-coding RNA (lncRNA) and microRNA (miRNA) expressions from the GEO database and mapped them with related databases. Subsequently, we used Cytoscape to construct a lncRNA-miRNA-mRNA network, and then we performed an enrichment analysis on the mRNAs in the network to determine their regulatory function. Subsequently, we used an ImmuCellAI immune infiltration analysis and constructed a ceRNA sub-network of related immune cells. Finally, we conducted a gene set enrichment analysis (GSEA) to determine the potential regulatory pathways of the key factors. RESULTS: As a result, we identified the blue module as the key module of immunity and constructed the related CeRNA network. Immune infiltration analysis showed that natural killer T (NKT) cells may be the key immune cells of VaD. Using a Pearson correlation analysis, we identified that B4GALT1, PPP1R3B, MICB, HHAT, DSC2, DNA2, SCARA3, and lncRNA NEAT1 may be the key factors of VaD. Our subsequent GSEA analysis showed that lncRNA NEAT1 may be regulated by NK cells and toll-like receptors. CONCLUSIONS: Our research provides new therapeutic targets for vascular dementia from the immunological perspective for the first time, including B4GALT1, PPP1R3B, MICB, HHAT, DSC2, DNA2, SCARA3, and lncRNA NEAT1, and our research hopes to provide new treatment options for VaD.

Ping Feng Qingfei mixture treats airway hyperresponsiveness: a network pharmacology and molecular docking study.

BACKGROUND: As air pollution has increased in severity over recent years, fine particulate matter (PM) (<25 µm; PM2.5) has led to a greater incidence of disease, including airway hyperresponsiveness (AHR). Ping Feng Qingfei Mixture (PFQF) is effective in treating AHR caused by PM2.5. As there is a lack of knowledge regarding the mechanisms of PFQF in the treatment of AHR, we conducted a network pharmacology study to clarify this issue. METHODS: We obtained the composition of PFQF from the traditional Chinese medicine (TCM) systems pharmacology database and its potential targets. The potential targets of AHR were obtained from the Online Mendelian Inheritance in Man and Gene Cards databases. Then psychophysiological interaction, KEGG pathway, and Gene Ontology biological process analyses were carried out for targeting PFQF in treating AHR. We further constructed a related network diagram and verified the experimental results in molecular docking. RESULTS: We identified a total of 4 core active compounds, and through KEGG analysis obtained multiple signaling pathways, including T helper17 (Th17) cell differentiation and interleukin-17 (IL-17) signaling pathway. Our molecular docking also verified that PFQF could effectively regulate the imbalance of Th17-T regulatory (Treg) cells. CONCLUSIONS: PFQF can effectively treat the AHR caused by PM2.5 through Th17-Treg immune balance. The combination of molecular docking and network pharmacology provides a way to elucidate the complex mechanism of action of this Chinese herbal medicine.

Network pharmacology study on the mechanism of the herb pair of prepared Rehmannia root-Chinese arborvitae kernel for anxiety disorders.

BACKGROUND: Although anxiety disorders are one of the most common mental illness in population, antianxiety drugs often only have single action targets, require long-term use, and are associated with many adverse reactions and dependencies. Professor Yan Zhaojun from Shandong Provincial Hospital of Traditional Chinese Medicine (TCM) has applied the modified Renshu Powder, a TCM formula, to treat anxiety disorders, with satisfactory outcomes. Here, we investigated the mechanism of action of two core herbs (prepared Rehmannia root and Chinese arborvitae kernel) in the Renshu Powder in the treatment of anxiety disorders by using network pharmacology approaches. METHODS: Candidate compounds of the herb pair of prepared Rehmannia root-Chinese arborvitae kernel were extracted via the Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform. The targets of action of the main compounds were collected using the SwissTargetPrediction database. Targets associated with anxiety disorders were retrieved from DisGeNET, Online Mendelian Inheritance in Man (OMIM), DrugBank, GeneCards, and Comparative Toxicogenomics Database (CTD) databases. The compound-target interaction network was constructed by Cytoscape 3.7.2 software, and the protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) platform. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses the data by using Metascape. RESULTS: The main active compounds of the herb pair included arachidonic acid, stigmasterol, and beta-sitosterol. The key targets included Nitric Oxide Synthase 3 (NOS3), Epidermal growth factor (EGF), Prostaglandin-Endoperoxide Synthase 2 (PTGS2), Caspase 3 (CASP3), Mitogen-Activated Protein Kinase 1 (MAPK1), Peroxisome proliferator-activated receptor gamma (PPARG), RELA Proto-Oncogene, NF-KB Subunit (RELA), Estrogen Receptor 1 (ESR1), Solute Carrier Family 6 Member 4 (SLC6A4), and Phosphatase and Tensin homolog deleted on chromosome 10 (PTEN). Anxiety disorder-related GO analysis mainly involved synaptic signaling, neurotransmitter receptor activity, and G protein-coupled neurotransmitter receptor activity. The KEGG pathways involved neuroactive ligand-receptor interaction, serotonergic synapse, PI3K/AKT/mTOR signaling pathway, and MAPK signaling pathway. CONCLUSIONS: The mechanism of action of the prepared Rehmannia root-Chinese arborvitae kernel in treating anxiety disorders involves multiple ingredients, multiple targets, and pathways.

Exploring the mechanism of Yizhi Tongmai decoction in the treatment of vascular dementia through network pharmacology and molecular docking.

BACKGROUND: Vascular dementia (VaD) is a degenerative cerebrovascular disease that leads to progressive decline of patients' cognitive ability and memory. Yizhi Tongmai (YZTM) decoction is an empirical prescription first formulated by Professor Guomin Si. Our previous experiments proved the effectiveness of this prescription in the treatment of VaD. In this study, we aimed to use network pharmacology and molecular docking technology to systematically explain the potential anti-VaD mechanism of YZTM. METHODS: We identified the core compounds of YZTM and their potential targets through the TCMSP, BATMAN, and SwissTargetPrediction databases. Then, we identified the molecular targets of YZTM in VaD using the Online Mendelian Inheritance in Man and GeneCards databases. The common targets of YZTM and VaD were screened out, and then the pathways of these target genes were analyzed using the Database for Annotation, Visualization and Integrated Discovery v6.8. Molecular docking was used to verify the relationship between the core compounds and proteins. RESULTS: Through network pharmacology analysis, we discovered that the 5 core compounds in YZTM exert an anti-VaD effect. The potential mechanism of YZTM anti-VaD may be through inhibiting the NLRP3 inflammasome, TNF signaling pathway, and toll-like receptor signaling pathways. Subsequently, key compounds were docked with related proteins in the NLRP3 inflammasome (NLRP3, ASC, caspase-1, interleukin-18, and interleukin-1 ß) using molecular docking technology. The compounds were found to spontaneously bind to the proteins. CONCLUSIONS: YZTM may exert an anti-VaD effect through inhibition of the NLRP3 inflammasome. In addition, TNF signaling pathway and toll-like receptor signaling pathway may also be its underlying mechanism. The application of network pharmacology and molecular docking technology may provide a novel method for research of Chinese herbal medicine. YZTM may also provide a complementary treatment option for patients with VaD.

Utilizing network pharmacology to explore the underlying mechanism of Qiangzhi decoction in treating Tourette's syndrome.

BACKGROUND: Tourette's syndrome (TS) is a neurodevelopmental condition characterized by multiple motor and vocal tics. Qiangzhi decoction (QD), a well-known herbal decoction, has been used in treating TS in China for decades. We have found relevance between the indications of QD and the classic symptoms of TS. The pharmacological mechanisms of QD in treating TS are still unclear. METHODS: The active compounds of QD were extracted from multi-database, including TCMSP (the Traditional Chinese Medicine Systems Pharmacology database), and potential targets of the compounds were compiled by target fishing. The TS target database was established, and then the protein-protein interaction (PPI) network was constructed to analyze the interactions between the potential targets of compounds in QD and targets associated with TS and screened the core targets by topology. The DAVID bioinformatics database was used to conduct the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. RESULTS: 59 active molecules and 585 potential targets of QD were selected. The consequences of the DAVID enrichment analysis show that 36 cellular biological processes (FDR <0.01) and 65 pathways (FDR <0.01) of QD chiefly took part in the convoluted treating effects relevant to the dopamine system, inflammation, and infection, and miRNA pathway. Fourteen core targets of QD were found as potential targets of the treatment of TS. CONCLUSIONS: QD could relieve the symptoms of TS through the molecular mechanisms predicted by network pharmacology. This study supplies insight into how network pharmacology can predict traditional Chinese herbal medicine's possible molecular mechanisms (TCHM).