Publications by authors named "Fengbin Liu"

58 Publications

Examining the Mechanisms of Huachansu injection on Liver Cancer through Integrated Bioinformatics Analysis.

Recent Pat Anticancer Drug Discov 2022 May 11. Epub 2022 May 11.

Department of gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

Objective: To explore the potential anti-liver cancer mechanism of Huachansu injection through integrated bioinformatics analysis.

Methods: Active ingredients of Huachansu injection (extraction of toad skin) were obtained, and their potential drug targets were predicted via SwissTargetPrediction database. Liver cancer disease targets were identified from the GEO (Gene Expression Omnibus) dataset and four public databases. Then protein-protein interaction(PPI) network of toad skin was constructed. GO (Gene ontology) enrichment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis were performed subsequently. Finally, molecular docking was performed using AutoDock Vina.

Results: In the search for therapeutic targets, twenty active components of toad skin were screened for further study, five hundred and sixty-eight targets of components were identified. In the search for disease targets, three thousand two hundred and twenty-seven genes were identified after removal of duplicated genes, one hundred and fifty-nine genes were up-regulated in liver cancer samples while two hundred and seventy-eight were down-regulated in liver cancer patients. After predicting the therapeutic targets of the components, the results were cross-checked with the disease targets, thirteen up-regulated targets and ten down-regulated targets were obtained. Finally, in the results of molecular docking, seven targets (CDK1, AKR1B1, MMP12, AURKB, CHEK1, AURKA, TTK) were potential up-regulated targets, three targets (SHBG, SRD5A2, NR1I2) were potential down-regulated targets, all of which have the best binding energy and molecular interactions.

Conclusion: CDK1, AKR1B1, MMP12, AURKB, CHEK1, AURKA, TTK could be potential up-regulated target proteins of Huachansu injection for treating liver cancer. The mechanism of Huachansu injection in the treatment of liver cancer through these up-regulated targets is related to cell cycle, cellular senescence cellular senescence, viral carcinogenesis, p53 signaling pathway. SHBG, SRD5A2, and NR1I2 could be potential down-regulated target proteins of Huachansu injection in treating liver cancer.
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http://dx.doi.org/10.2174/1574892817666220511162046DOI Listing
May 2022

Effectiveness of modified Buzhong Yiqi decoction in treating myasthenia gravis: study protocol for a series of N-of-1 trials.

Trials 2022 Apr 27;23(1):365. Epub 2022 Apr 27.

Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

Background: Myasthenia gravis (MG) is an acquired autoimmune disease with high heterogeneity. The disease is chronic, relapsing repeatedly and progressive with acute exacerbation occasionally. Although the treatment of MG has developed, it is still unsatisfactory and has some unexpected side effects. Traditional Chinese medicine (TCM) has shown great potential in MG treatment, including relief of muscle weakness syndrome, improvement of patient's quality of life, and reduction of side effects of western medicine. The purpose of this study is to evaluate the effectiveness of modified Buzhong Yiqi decoction (MBYD) as an add-on therapy for MG through a small series of N-of-1 trials.

Methods: Single-centre, randomized, double-blind, 3 crossover N-of-1 trials will be conducted to enroll patients with MG diagnosed as spleen-stomach deficiency syndrome or spleen-kidney deficiency syndrome in TCM. Each N-of-1 trial has 3 cycles of two 4-week periods containing the MBYD period and placebo period. The wash-out interval of 1 week is prior to switching each period.

Primary Outcome: quantitative myasthenia gravis (QMG).

Secondary Outcomes: the following scales: myasthenia gravis composite (MGC), myasthenia gravis activities of daily living profile (MG-ADL), myasthenia gravis quality of life (MG-QOL); the level of CD4+FoxP3+Treg cells and cytokines (IL-4, IL-17A, INF-γ, TGF-β) in the peripheral blood; the alterations of the composition of gut microbiota; reduction of the side effects of western medicine.

Discussion: Used by WinBUGS software, we will conduct a hierarchical Bayesian statistical method to analyze the efficacy of MBYD in treating MG in individuals and populations. Some confounding variables such as TCM syndrome type and potential carryover effect of TCM will be introduced into the hierarchical Bayesian statistical method to improve the sensitivity and applicability of the trials, and the use of prior available information within the analysis may improve the sensitivity of the results of a series of N-of-1 trials, from both the individual and population level to study the efficacy of TCM syndrome differentiation. We assumed that this study would reveal that MBYD is effective for MG and provide robust evidence of the efficacy of TCM to treat MG.

Trial Registration: Chinese Clinical Trial Register, ID: ChiCTR2000040477 , registration on 29 November 2020.
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http://dx.doi.org/10.1186/s13063-022-06287-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9044679PMC
April 2022

Mitochondrial dynamics and biogenesis indicators may serve as potential biomarkers for diagnosis of myasthenia gravis.

Exp Ther Med 2022 Apr 24;23(4):307. Epub 2022 Feb 24.

Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China.

Due to challenges in diagnosing myasthenia gravis (MG), identifying novel diagnostic biomarkers for this disease is essential. Mitochondria are key organelles that regulate multiple physiological functions, such as energy production, cell proliferation and cell death. In the present study, Mfn1/2, Opa1, Drp1, Fis1, AMPK, PGC-1α, NRF-1 and TFAM were compared between patients with MG and healthy subjects to identify potential diagnostic biomarkers for MG. Blood samples were collected from 50 patients with MG and 50 healthy subjects. The participants' demographic information and routine blood test results were recorded. Mitochondrial dynamics were evaluated and levels of Mfn1/2, Opa1, Drp1, Fis1, AMPK, PGC-1α, NRF-1 and TFAM were determined in peripheral blood mononuclear cells using western blotting and reverse transcription-quantitative PCR, respectively. Receiver operating characteristic curve analysis was used to evaluate the diagnostic accuracy of these indicators. The areas under the curve values of Mfn1/2, Opa1, Drp1, Fis1,AMPK, PGC-1α, NRF-1 and TFAM were 0.5408-0.8696. Compared with control subjects, mRNA expression levels of Mfn1/2, Opa1, AMPK, PGC-1α, NRF-1 and TFAM were lower, while those of Drp1 and Fis1 were higher in patients with MG. The protein expression levels of all these molecules were lower in patients with MG than in control subjects. These results suggested that mitochondrial dynamics and biogenesis indicators may be diagnostic biomarkers for MG.
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http://dx.doi.org/10.3892/etm.2022.11236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8931634PMC
April 2022

Exploration of Potential Roles of m5C-Related Regulators in Colon Adenocarcinoma Prognosis.

Front Genet 2022 24;13:816173. Epub 2022 Feb 24.

Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

The purpose of this study was to investigate the role of 13 mC-related regulators in colon adenocarcinoma (COAD) and determine their prognostic value. Gene expression and clinicopathological data were obtained from The Cancer Genome Atlas (TCGA) datasets. The expression of mC-related regulators was analyzed with clinicopathological characteristics and alterations within mC-related regulators. Subsequently, different subtypes of patients with COAD were identified. Then, the prognostic value of mC-related regulators in COAD was confirmed univariate Cox regression and least absolute shrinkage and selection operator (LASSO) Cox regression analyses. The prognostic value of risk scores was evaluated using the Kaplan-Meier method, receiver operating characteristic (ROC) curve. The correlation between the two mC-related regulators, risk score, and clinicopathological characteristics were explored. Additionally, Gene Set Enrichment Analysis (GSEA), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and Gene Ontology (GO) analysis were performed for biological functional analysis. Finally, the expression level of two mC-related regulators in clinical samples and cell lines was detected by quantitative reverse transcription-polymerase chain reaction and through the Human Protein Atlas database. mC-related regulators were found to be differentially expressed in COAD with different clinicopathological features. We observed a high alteration frequency in these genes, which were significantly correlated with their mRNA expression levels. Two clusters with different prognostic features were identified. Based on two independent prognostic mC-related regulators (NSUN6 and ALYREF), a risk signature with good predictive significance was constructed. Univariate and multivariate Cox regression analyses suggested that the risk score was an independent prognostic factor. Furthermore, this risk signature could serve as a prognostic indicator for overall survival in subgroups of patients with different clinical characteristics. Biological processes and pathways associated with cancer, immune response, and RNA processing were identified. We revealed the genetic signatures and prognostic values of mC-related regulators in COAD. Together, this has improved our understanding of mC RNA modification and provided novel insights to identify predictive biomarkers and develop molecular targeted therapy for COAD.
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http://dx.doi.org/10.3389/fgene.2022.816173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8908034PMC
February 2022

Restrains Hepatic Pro-Inflammatory Macrophages to Ameliorate Non-Alcoholic Fatty Liver Disease.

Front Pharmacol 2021 18;12:816032. Epub 2022 Jan 18.

Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

Non-alcoholic fatty liver disease (NAFLD) has become a progressive metabolic disease that is emerging as a global epidemic. Considering that the complex pathogenesis has not been fully elucidated, barely specific pharmacological therapy is recommended in current guidelines. (GS) is a commonly used herb in Tibetan medicine, which has received much attention in recent years due to its diverse pharmacological properties, including anti-inflammation, anti-oxidation, and anti-fibrosis. However, the therapeutic mechanisms are still unclear. Our investigation demonstrated a regulatory effect of GS on pro-inflammatory macrophages, which was extensively investigated in NAFLD that revealed intimate participation in the disease evolution, and the non-canonical IKK family member TANK-binding kinase 1 (TBK1) was involved in this process. Plasmid vectors for shTBK1 and amlexanox (AML), an inhibitor of TBK1, were used in this study to verify the mechanisms of TBK1 both and , while a co-culture system for hepatocytes and BMDMs was constructed to confirm the critical role of macrophages for inflammatory cascade. The results revealed that metabolic burden up-regulated the phosphorylation of TBK1, resulting in activation of NF-κB signaling pathway, and consequently caused an elevated expression of MCP1 to induce the macrophage recruitment and accelerate the inflammatory cascade. In contrast, GS could inhibit the TBK1 phosphorylation and the MCP1 expression to restrain the recruitment of pro-inflammatory macrophages, so as to provide curative effects on metabolic dysfunction and inflammation. Considering that GS is non-toxic and can be used as a kind of tea for long-term drinking, we propose it may be an effective option for the prevention and treatment of NAFLD, which deserves further exploration and application, and may provide new insights to improve the current standardized intervention strategy.
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http://dx.doi.org/10.3389/fphar.2021.816032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8803634PMC
January 2022

Stigmasterol Restores the Balance of Treg/Th17 Cells by Activating the Butyrate-PPARγ Axis in Colitis.

Front Immunol 2021 6;12:741934. Epub 2021 Oct 6.

Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder with gut microbiota disequilibrium and regulatory T (Treg)/T helper 17 (Th17) immune imbalance. Stigmasterol, a plant-derived sterol, has shown anti-inflammatory effects. Our study aimed to identify the effects of stigmasterol on experimental colitis and the related mechanisms. Stigmasterol treatment restored the Treg/Th17 balance and altered the gut microbiota in a dextran sodium sulfate (DSS)-induced colitis model. Transplantation of the faecal microbiota of stigmasterol-treated mice significantly alleviated inflammation. Additionally, stigmasterol treatment enhanced the production of gut microbiota-derived short-chain fatty acids (SCFAs), particularly butyrate. Next, human naïve CD4+ T cells sorted from IBD patients were cultured under Treg- or Th17-polarizing conditions; butyrate supplementation increased the differentiation of Tregs and decreased Th17 cell differentiation. Mechanistically, butyrate activated peroxisome proliferator-activated receptor gamma (PPARγ) and reprogrammed energy metabolism, thereby promoting Treg differentiation and inhibiting Th17 differentiation. Our results demonstrate that butyrate-mediated PPARγ activation restores the balance of Treg/Th17 cells, and this may be a possible mechanism, by which stigmasterol attenuates IBD.
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http://dx.doi.org/10.3389/fimmu.2021.741934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526899PMC
December 2021

CXCR4 is a Novel Biomarker Correlated With Malignant Transformation and Immune Infiltrates in Gastric Precancerous Lesions.

Front Mol Biosci 2021 5;8:697993. Epub 2021 Oct 5.

Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

As early gastric cancer (EGC) has a far better prognosis than advanced gastric cancer (GC), early diagnosis and treatment are essential. However, understanding the mechanism of the process from gastric precancerous lesion (GPL) becoming EGC has made little advances. Besides, biomarkers that can monitor the progression of GPL-to-GC are still much insufficient. Key gene modules associated with GPL progression to EGC were identified by integrating two GPL-related data sets, GSE55696 and GSE130823, using the WGCNA method. Combining with the TCGA-STAD cohort, hub genes were identified. Immunofluorescence was conducted to validate the expression. To explore the implication of hub genes in GPL malignant transformation, a correlation test was conducted to identify their co-expression genes, co-expression cytokines, and co-expression immune cells. Least absolute shrinkage and selection operator (LASSO) Cox regression was applied to shrink CXCR4-related predictors and construct a prognostic model. Functional enrichment was applied for exploring the potential mechanism. The green module in GSE55696 and the yellow module in GSE130823 were regarded as key gene modules associated with GPL progression to EGC, and 219 intersection genes from them were mainly enriched in critical immune biological processes. Combining with the TCGA-STAD cohort, CXCR4 was identified as a novel biomarker correlated with the malignant transformation of GPL, the positive rate of which was increased with GPL progression according to immunofluorescence. CXCR4 co-expression genes were found mainly involved in regulation of actin. CXCR4 co-expression cytokines were enriched in regulation of chemotaxis, cell chemotaxis, mononuclear cell migration, leukocyte chemotaxis, etc. As for co-expression immune cells, the expression level of CXCR4 was positively correlated with the abundance of macrophages but negatively correlated with that of effector memory T cells and NKT cells during GPL malignant transformation. In addition, the CXCR4-related prognostic model was able to predict the prognosis of GC and serve as an independent predictor for overall survival (OS). CXCR4 was a novel biomarker correlated with malignant transformation of GPL and played a vital role in the control of tumor immunity. CXCR4 is possible to serve as a therapeutic target for malignant transformation of GPL.
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http://dx.doi.org/10.3389/fmolb.2021.697993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8523893PMC
October 2021

Ferroptosis Patterns Correlate with Immune Microenvironment Characterization in Gastric Cancer.

Int J Gen Med 2021 12;14:6573-6586. Epub 2021 Oct 12.

Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People's Republic of China.

Objective: We aimed to build a ferroptosis-based classifier to characterize the molecular features of gastric cancers (GC) and investigate the relationship between different ferroptosis patterns and GC tumor microenvironment (TME).

Methods: Based on the genomic and clinical information from TCGA portal and GEO database, non-negative matrix factorization (NMF) was used to identify ferroptosis subtypes in GC patients. In order to estimate the ferroptosis levels, we established ferroptosis subtype score (FSS) to quantify ferroptosis patterns and ferroptosis potential index (FPI) by principal component analysis (PCA). The correlations of different ferroptosis patterns with TME cell-infiltrating characteristics (including immune cell infiltration, immune checkpoints expression levels, tumor mutational burden (TMB) and immunotherapy response) were systematically analyzed.

Results: Two ferroptosis subtypes, C1 (with lower FSS) and C2 (with higher FSS), were determined. C2 displayed a significantly lower FPI than C1. Besides, C2 was associated with diffuse subtype while C1 with intestinal subtype. As for TME characteristics, C2 was in accordance with the immune-excluded phenotype as it showed more active immune and stromal activities but lower TMB, less probability of immunotherapy response and poorer prognosis. C1 was linked to immune-inflamed phenotype as it had lower stromal activities but increased neoantigen load, enhanced response to immunotherapy and relatively better prognosis.

Conclusion: The systematic assessment of ferroptosis patterns and ferroptosis levels presented in our study implied that ferroptosis serves as an important factor in the formation of TME, which may expand the understanding of TME and provide a novel perspective for the development of targeted immunotherapeutic strategies for GC patients.
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http://dx.doi.org/10.2147/IJGM.S331291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8520437PMC
October 2021

Identification of N6-Methylandenosine-Related lncRNAs for Subtype Identification and Risk Stratification in Gastric Adenocarcinoma.

Front Oncol 2021 27;11:725181. Epub 2021 Sep 27.

Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

Objectives: The purpose of this study was to investigate the role of mA-related lncRNAs in gastric adenocarcinoma (STAD) and to determine their prognostic value.

Methods: Gene expression and clinicopathological data were obtained from The Cancer Genome Atlas (TCGA) database. Correlation analysis and univariate Cox regression analysis were conducted to identify mA-related prognostic lncRNAs. Subsequently, different clusters of patients with STAD were identified consensus clustering analysis, and a prognostic signature was established by least absolute shrinkage and selection operator (LASSO) Cox regression analyses. The clinicopathological characteristics, tumor microenvironment (TME), immune checkpoint genes (ICGs) expression, and the response to immune checkpoint inhibitors (ICIs) in different clusters and subgroups were explored. The prognostic value of the prognostic signature was evaluated using the Kaplan-Meier method, receiver operating characteristic curves, and univariate and multivariate regression analyses. Additionally, Gene Set Enrichment Analysis (GSEA), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and Gene Ontology (GO) analysis were performed for biological functional analysis.

Results: Two clusters based on 19 mA-related lncRNAs were identified, and a prognostic signature comprising 14 mA-related lncRNAs was constructed, which had significant value in predicting the OS of patients with STAD, clinicopathological characteristics, TME, ICGs expression, and the response to ICIs. Biological processes and pathways associated with cancer and immune response were identified.

Conclusions: We revealed the role and prognostic value of mA-related lncRNAs in STAD. Together, our finding refreshed the understanding of mA-related lncRNAs and provided novel insights to identify predictive biomarkers and immunotherapy targets for STAD.
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http://dx.doi.org/10.3389/fonc.2021.725181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8504261PMC
September 2021

Serum exosomal miR-122-5p, GAS, and PGR in the non-invasive diagnosis of CAG.

Open Med (Wars) 2021 8;16(1):1350-1355. Epub 2021 Sep 8.

Department of Traditional Chinese Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University, Gonghexiheng Street 1, Guangzhou 510080, Guangdong, People's Republic of China.

Objective: The aim of this study was to integrate the serum exosomal miRNA miR-122-5p with canonical serological biomarkers for the non-invasive screening of chronic atrophic gastritis (CAG) patients.

Methods: miR-122-5p and U6 were amplified by the quantitative reverse transcription polymerase chain reaction (RT-qPCR), gastrin (GAS), pepsinogen I (PG-I), and PG-II and were measured by ELISA. The area under the receiver operating characteristic (ROC) curves and their correlation were analyzed.

Results: In the present study, GAS level and PG-I/PG-II ratio (PGR) were increased in CAG group, but there was no significant difference in PG-I or PG-II levels between CAG group and chronic non-atrophic gastritis (CNAG) group. Only GAS level and PG-I/PG-II ratio were significantly correlated with atrophy, and not any other clinicopathologic factors. Expression of hsa-miR-122-5p positively correlated with GAS level, PG-I level, and PGR, while it negatively correlated with PG-II level; however, none of them had significant difference. The combination of GAS, PGR, and hsa-miR-122-5p presented as a better model for non-invasive screening of CAG compared to others.

Conclusion: These results suggested that serum exosomal hsa-miR-122-5p combined with GAS and PGR would elevate accuracy and specificity in non-invasive screening of CAG.
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http://dx.doi.org/10.1515/med-2021-0342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428623PMC
September 2021

Regulation of decorin by ursolic acid protects against non-alcoholic steatohepatitis.

Biomed Pharmacother 2021 Nov 21;143:112166. Epub 2021 Sep 21.

Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China; Baiyun Hospital of The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. Electronic address:

Non-alcoholic steatohepatitis (NASH) has become a global health issue, which poses additional financial burden to public health care. However, no specific pharmacological therapy is recommended in current guidelines. Ursolic acid (UA) has been proven to perform multiple biological activities, thereby having a broad application prospect in healthcare field. Thus, this current research was conducted to investigate the protective mechanisms of UA on NASH. Integrative genomic analyses were performed to identify characteristic genes for NASH, and human proteomics chip was applied to seek out differentially binding proteins for UA. The combining bioinformatic analyses revealed 529 and 502 differentially expressed genes for NASH and UA, respectively. And further enrichment analyses indicated that IGF-IR signaling pathway was intimately involved in the therapeutic effects of UA on NASH. Experimental studies displayed that UA up-regulated the decorin expression to activate IGF-IR signaling as well as to inhibit HIF-1 signaling, resulting in alleviation on metabolic dysfunction, liver steatosis, inflammation and hypoxia in high-fat-fed mice. And additionally, these results were confirmed by lipotoxic and decorin-interference cell model. Taken together, we found that UA could regulate IGF-IR and HIF-1 signaling pathways via decorin to provide dual protective functions on metabolic dysfunction and liver hypoxia, and therefore turned to be an effective option for the treatment of NASH.
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http://dx.doi.org/10.1016/j.biopha.2021.112166DOI Listing
November 2021

Scientometric Analysis of Medicinal and Edible Plant .

Front Pharmacol 2021 12;12:725162. Epub 2021 Aug 12.

Postgraduate College, Guangzhou University of Chinese Medicine, Guangzhou, China.

A scientometric analysis to obtain knowledge mapping of revealed the current research situation, knowledge base and research hotspots in research. -related documents published from 1987 to 2020 were selected through the Web of Science Core Collection. CiteSpace, VOSviewer and Microsoft Excel were used to construct knowledge maps of the research field. A total of 367 documents and their references were analyzed. These papers were primarily published in mainland China (214), followed by Japan (57) and South Korea (52), and they each formed respective cooperation networks. The document co-citation analysis suggested that the identification of Salisb. species, the production of alkaloids, and the mechanisms of action of these alkaloids formed the knowledge bases in this field. A keyword analysis further revealed that the research hotspots were primarily concentrated in three fields of research involving berberine, Franch, and (Thunb) Makino. Oxidative stress, rat plasma (for the determination of plasma alkaloid contents), and Alzheimer's disease are recent research hotspots associated with . research was mainly distributed in three countries: China, Japan, and South Korea. Researchers were concerned with the identification of species, the production of alkaloids, and the efficacy and pharmacological mechanism of the constituent alkaloids. In addition, the anti-oxidative stress, pharmacokinetics, and Alzheimer's disease treatment of are new hotspots in this field. This study provides a reference for researchers.
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http://dx.doi.org/10.3389/fphar.2021.725162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387930PMC
August 2021

AURKB, CHEK1 and NEK2 as the Potential Target Proteins of on Hepatocellular Carcinoma: An Integrated Bioinformatics Analysis.

Int J Gen Med 2021 12;14:3295-3312. Epub 2021 Jul 12.

Department of gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China.

Objective: We aim to explore the potential anti-HCC mechanism of through integrated bioinformatics analysis.

Methods: We searched active ingredients and related targets of via TCMSP database, PubChem and SwissTargetPrediction database. Then, we identified HCC disease targets from GEO dataset by WGCNA. Next, the intersected targets of disease targets and drug targets were input into STRING database to construct PPI networking in order to obtain potential therapeutic targets of . Cytoscape software was used to carry out network topology analysis of potential targets. We used the R package for GO analysis and KEGG analysis. Finally, we used AutoDock vina and PyMOL software for molecular docking.

Results: Sixteen active components from were lastly selected for further investigation. A total of 442 component targets were identified from 16 active ingredients of after the removal of duplicate targets. GSE45436 was selected for construction of WGCNA and screening of differentially expressed genes. A total of 354 genes were up-regulated in HCC samples and 100 were down-regulated in HCC patients. Twenty-one common genes were obtained by intersection and 10 critical targets were filtered for further investigation. The enrichment analysis showed that cell cycle, DNA replication, p53 signaling pathway were mainly involved. The molecular docking results showed that 4 potential combinations were with the best binding energy and molecular interactions.

Conclusion: AURKB, CHEK1 and NEK2 could be the potential target proteins of in treating HCC. Cell cycle, DNA replication, p53 signaling pathway consist of the fundamental regulation cores in this mechanism.
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http://dx.doi.org/10.2147/IJGM.S318077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285231PMC
July 2021

Development of a Computerized Adaptive Test for Quantifying Chinese Medicine Syndrome of Myasthenia Gravis on Basis of Multidimensional Item Response Theory.

Evid Based Complement Alternat Med 2021 24;2021:9915503. Epub 2021 May 24.

The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510000, China.

Background: Making comprehensive management of myasthenia gravis (MG) is a challenge in clinical practice due to heterogeneity and multiple comorbidities among patients.

Aim: To develop an end-to-end instrument for individualized assessment of MG in the perspective of Chinese medicine (TCM) with the application of multidisciplinary quantification approaches.

Methods: A self-administrated questionnaire was developed integrating typical symptoms of MG and spleen-kidney deficiency syndrome on basis of the conceptual framework of TCM. With data collected in a multicenter cross-sectional study, confirmatory factor analysis together with multidimensional item response theory (MIRT) was used for evaluating the psychometric property of the questionnaire. A computerized adaptive test was developed based on the MIRT model, and scores of syndrome factors were calculated in simulation. A logistics regression model was also estimated for evaluating the consistency between the quantitative result and the clinical diagnosis of syndrome from clinical practitioners.

Result: With 337 patients enrolled and assessed, the 14-item questionnaire was evaluated to be with adequate validity and reliability (Cronbach's alpha indices = 0.87, AIC = 195.827, BIC = 348.631, CFI = 0.921, RMR = 0.006, GFI = 0.954, RMSEA = 0.048, and 2/df = 1.782). With adequate factor loadings of symptoms on related syndrome factor, the instrument was evaluated with preliminary interpretation and was suitable for evaluating patients with moderate severity of the spleen and kidney deficiency syndrome.

Conclusion: Setting typical symptoms of MG together with systemic discomforts in a computerized adaptive test on the basis of MIRT, this study proposed an innovative research paradigm for quantifying individual condition in the perspective of TCM with application of interdisciplinary approaches.
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http://dx.doi.org/10.1155/2021/9915503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166489PMC
May 2021

Identifying Dendritic Cell-Related Genes Through a Co-Expression Network to Construct a 12-Gene Risk-Scoring Model for Predicting Hepatocellular Carcinoma Prognosis.

Front Mol Biosci 2021 24;8:636991. Epub 2021 May 24.

Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

The prognostic prediction of hepatocellular carcinoma (HCC) is still challenging. Immune cells play a crucial role in tumor initiation, progression, and drug resistance. However, prognostic value of immune-related genes in HCC remains to be further clarified. In this study, the mRNA expression profiles and corresponding clinical information of HCC patients were downloaded from public databases. Then, we estimated the abundance of immune cells and identified the differentially infiltrated and prognostic immune cells. The weighted gene co-expression network analysis (WGCNA) was performed to identify immune-related genes in TCGA cohort and GEO cohort. The least absolute shrinkage and selection operator (LASSO) Cox regression model was applied to establish a risk-scoring model in the TCGA cohort. HCC patients from the GSE14520 datasets were utilized for risk model validation. Our results found that high level of dendritic cell (DC) infiltration was associated with poor prognosis. Over half of the DC-related genes (58.2%) were robustly differentially expressed between HCC and normal specimens in the TCGA cohort. 17 differentially expressed genes (DEGs) were found to be significantly associated with overall survival (OS) by univariate Cox regression analysis. A 12-gene risk-scoring model was established to evaluate the prognosis of HCC. The high-risk group exhibits significantly lower OS rate of HCC patients than the low-risk group. The risk-scoring model shows benign predictive capacity in both GEO dataset and TCGA dataset. The 12-gene risk-scoring model may independently perform prognostic value for HCC patients. Receiver operating characteristic (ROC) curve analysis of the risk-scoring model in GEO cohort and TCGA cohort performed well in predicting OS. Taken together, the 12-gene risk-scoring model could provide prognostic and potentially predictive information for HCC. SDC3, NCF2, BTN3A3, and WARS were noticed as a novel prognostic factor for HCC.
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http://dx.doi.org/10.3389/fmolb.2021.636991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181399PMC
May 2021

The Synergistic Effects of 5-Aminosalicylic Acid and Vorinostat in the Treatment of Ulcerative Colitis.

Front Pharmacol 2021 21;12:625543. Epub 2021 May 21.

Lingnan Medical Reserch Center of Guangzhou University of Chinese Medicine, Guangzhou, China.

The drug 5aminosalicylic acid (5-ASA) is the first-line therapy for the treatment of patients with mild-to-moderate ulcerative colitis (UC). However, in some cases, 5-ASA cannot achieve the desired therapeutic effects. Therefore, patients have to undergo therapies that include corticosteroids, monoclonal antibodies or immunosuppressants, which are expensive and may be accompanied by significant side effects. Synergistic drug combinations can achieve greater therapeutic effects than individual drugs while contributing to combating drug resistance and lessening toxic side effects. Thus, in this study, we sought to identify synergistic drugs that can act synergistically with 5-ASA. We started our study with protein-metabolite analysis based on peroxisome proliferator-activated receptor gamma (PPARG), the therapeutic target of 5-ASA, to identify more additional potential drug targets Then, we further evaluated the possibility of their synergy with PPARG by integrating Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analysis, pathway-pathway interaction analysis, and semantic similarity analysis. Finally, we validated the synergistic effects with and experiments. The combination of 5-ASA and vorinostat (SAHA) showed lower toxicity and mRNA expression of p65 in human colonic epithelial cell lines (Caco-2 and HCT-116), and more efficiently alleviated the symptoms of dextran sulfate sodium (DSS)-induced colitis than treatment with 5-ASA and SAHA alone. SAHA can exert effective synergistic effects with 5-ASA in the treatment of UC. One possible mechanism of synergism may be synergistic inhibition of the nuclear factor kappa B (NF-kB) signaling pathway. Moreover, the metabolite-butyric acid may be involved.
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http://dx.doi.org/10.3389/fphar.2021.625543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176098PMC
May 2021

Corrigendum: Current Evidence and Future Perspective of Accuracy of Artificial Intelligence Application for Early Gastric Cancer Diagnosis With Endoscopy: A Systematic and Meta-Analysis.

Front Med (Lausanne) 2021 14;8:698483. Epub 2021 May 14.

Department of Gastroenterology, First Affiliation Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China.

[This corrects the article DOI: 10.3389/fmed.2021.629080.].
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http://dx.doi.org/10.3389/fmed.2021.698483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161500PMC
May 2021

Network pharmacology dissection of multiscale mechanisms for jiaoqi powder in treating ulcerative colitis.

J Ethnopharmacol 2021 Jul 9;275:114109. Epub 2021 Apr 9.

Department of Gastroenterology,The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China; Baiyun Hospital of the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510000, China. Electronic address:

Ethnopharmacological Relevance: The incidence of ulcerative colitis (UC) is increasing worldwide, making it a serious public health challenge. Currently, there are no accepted curative treatments for UC. As such, the exploration of new therapeutic strategies for UC treatment is of considerable clinical importance. Jiaoqi powder (JQP) is a classic Chinese medicinal formula commonly used as a complementary and alternative medicine for treating gastrointestinal bleeding. JQP is thus a potential alternative medicine for UC treatment. However, the protective mechanism underlying the action of JQP has not been elucidated, thereby, necessitating further studies to decipher the mechanisms involved in the complex interplay among its components.

Aim Of The Study: To explore the protective effect of JQP against UC and to further investigate its mechanism in silico and in vivo using a systems pharmacology approach.

Materials And Methods: A systems pharmacology approach was used to predict the active components of JQP. Putative targets and the potential mechanism of JQP on UC were obtained through target fishing, network construction, and enrichment analyses. An animal-based model of dextran sodium sulfate (DSS)-induced colitis in C57BL/6 mice was further used to validate the treatment mechanisms of JQP. The underlying pharmacological mechanisms of JQP in UC were determined using polymerase chain reaction tests, histological staining, immunohistochemistry, enzyme-linked immunoassays, and flow cytometry analysis.

Results: In this study, 17 effective components and 941 potential targets of JQP were identified. Similarly, 2104 UC-related targets were also identified. Construction of PPI networks led to the identification of 184 putative therapeutic targets of JQP. Sixty-nine core targets among these 184 were further screened based on their DC values. Gene ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that the core targets were primarily enriched in immune response and inflammatory signalling pathways. Subsequent animal-based in vivo experiments revealed that JQP ameliorated symptoms and histological changes in DSS colitis by significantly impairing DSS's ability to induce high expression levels of NF-κB/p65, IL-1β, IL-6, and TNF-α. JQP also reduced the levels of COX-2, CCL2, CXCL2, HIF-1α, MMP3 and MMP9 and regulated the Th17/Treg cell balance in DSS-induced mice.

Conclusions: This study demonstrated that JQP could treat UC by improving the mucosal inflammatory response, repairing the intestinal barrier, and modulating the Th17/Treg immune balance. The results of this study provide new insights into UC treatment and further elucidate the theoretical and practical implications of the pharmaceutical development of TCMs.
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http://dx.doi.org/10.1016/j.jep.2021.114109DOI Listing
July 2021

Current Evidence and Future Perspective of Accuracy of Artificial Intelligence Application for Early Gastric Cancer Diagnosis With Endoscopy: A Systematic and Meta-Analysis.

Front Med (Lausanne) 2021 15;8:629080. Epub 2021 Mar 15.

Department of Gastroenterology, First Affiliation Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China.

Gastric cancer is the common malignancies from cancer worldwide. Endoscopy is currently the most effective method to detect early gastric cancer (EGC). However, endoscopy is not infallible and EGC can be missed during endoscopy. Artificial intelligence (AI)-assisted endoscopic diagnosis is a recent hot spot of research. We aimed to quantify the diagnostic value of AI-assisted endoscopy in diagnosing EGC. The PubMed, MEDLINE, Embase and the Cochrane Library Databases were searched for articles on AI-assisted endoscopy application in EGC diagnosis. The pooled sensitivity, specificity, and area under the curve (AUC) were calculated, and the endoscopists' diagnostic value was evaluated for comparison. The subgroup was set according to endoscopy modality, and number of training images. A funnel plot was delineated to estimate the publication bias. 16 studies were included in this study. We indicated that the application of AI in endoscopic detection of EGC achieved an AUC of 0.96 (95% CI, 0.94-0.97), a sensitivity of 86% (95% CI, 77-92%), and a specificity of 93% (95% CI, 89-96%). In AI-assisted EGC depth diagnosis, the AUC was 0.82(95% CI, 0.78-0.85), and the pooled sensitivity and specificity was 0.72(95% CI, 0.58-0.82) and 0.79(95% CI, 0.56-0.92). The funnel plot showed no publication bias. The AI applications for EGC diagnosis seemed to be more accurate than the endoscopists. AI assisted EGC diagnosis was more accurate than experts. More prospective studies are needed to make AI-aided EGC diagnosis universal in clinical practice.
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http://dx.doi.org/10.3389/fmed.2021.629080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005567PMC
March 2021

Construction and Validation of a Ferroptosis-Related Prognostic Model for Gastric Cancer.

J Oncol 2021 28;2021:6635526. Epub 2021 Feb 28.

Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong, China.

Background: Gastric cancer (GC), an extremely aggressive tumor with a very different prognosis, is the third leading cause of cancer-related mortality. We aimed to construct a ferroptosis-related prognostic model that can be distinguished prognostically.

Methods: The gene expression and the clinical data of GC patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database (GEO). The ferroptosis-related genes were obtained from the FerrDb. Using the "limma" R package and univariate Cox analysis, ferroptosis-related genes with differential expression and prognostic value were identified in the TCGA cohort. Last absolute shrinkage and selection operator (LASSO) Cox regression was applied to shrink ferroptosis-related predictors and construct a prognostic model. Functional enrichment, ESTIMATE algorithm, and single-sample gene set enrichment analysis (ssGSEA) were applied for exploring the potential mechanism. GC patients from the GEO cohort were used for validation.

Results: An 8-gene prognostic model was constructed and stratified GC patients from TCGA and meta-GEO cohort into high-risk groups or low-risk groups. GC patients in high-risk groups have significantly poorer OS compared with those in low-risk groups. The risk score was identified as an independent predictor for OS. Functional analysis revealed that the risk score was mainly associated with the biological function of extracellular matrix (ECM) organization and tumor immunity.

Conclusion: In conclusion, the ferroptosis-related model can be utilized for the clinical prognostic prediction in GC.
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http://dx.doi.org/10.1155/2021/6635526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937463PMC
February 2021

Identification of LINC00665-miR-let-7b-CCNA2 competing endogenous RNA network associated with prognosis of lung adenocarcinoma.

Sci Rep 2021 02 24;11(1):4434. Epub 2021 Feb 24.

Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 12 Airport Road, Baiyun District, Guangzhou, 510407, China.

Prognosis of patients with lung cancer remains extremely poor; thus, we sought to unearth novel competing endogenous RNA (ceRNA) networks associated with the prognosis of lung adenocarcinoma (LUAD). Aberrant mRNAs were identified from the intersection of three Gene Expression Omnibus (GEO) datasets. A protein-protein interaction (PPI) network was constructed, and miRNAs and long noncoding RNAs (lncRNAs) upstream of mRNAs were predicted. In the present study, 402 upregulated and 638 downregulated genes in lung cancer tissues were identified. Functional analysis showed significant enrichment of cancer pathways. In these top hub genes, 10 upregulated and 7 downregulated genes had substantial prognostic values in LUAD. Thirty-seven miRNAs were predicted to target 17 key genes, and only five miRNAs exhibited prognostic correlation. Through stepwise reverse prediction and validation from miRNA to lncRNA, four key lncRNAs were identified using expression and survival analysis. Ultimately, the co-expression analysis identified LINC00665-miR-let-7b-CCNA2 as the key ceRNA network associated with the prognosis of LUAD. We successfully constructed a novel ceRNA network wherein each component was significantly associated with the prognosis of LUAD. Hence, we propose that this network may provide key biomarkers or potential therapeutic targets for LUAD prognosis.
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http://dx.doi.org/10.1038/s41598-020-80662-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904782PMC
February 2021

Therapeutic efficacy and immunoregulatory effect of Qiangji Jianli Capsule for patients with myasthenia gravis: Study protocol for a series of randomized, controlled N-of-1 trials.

Medicine (Baltimore) 2020 Dec;99(51):e23679

Department of Spleen-Stomach, First Affiliated Hospital of Guangzhou University of Chinese Medicine.

Introduction: Myasthenia gravis (MG) is an autoimmune disease in which antibodies directly target components of the neuromuscular junction, causing neuromuscular conduction damage that leads to muscle weakness. The current pharmaceutical treatment for MG is still not ideal to address the problems of disease progression, high recurrence rate, and drug side effects. Clinical observations suggest that traditional Chinese medicine (TCM) can strengthen immunity and improve symptoms of MG patients, delay the progression of the disease, reduce or even prevent the need for immunosuppressive therapy when used in combination with acetylcholinesterase inhibitors or low-dose prednisone, as well as improve the quality of life of patients. The Qiangji Jianli Capsule (QJC) is a combination of medicinal herbs which is used in traditional Chinese medicine. Since MG is a rare disorder, randomized controlled trials comparing large cohorts are difficult to conduct. Therefore, we proposed to aggregate data from a small series of N-of-1 trials to assess the effect of the Chinese medical prescription QJC, which strengthens the spleen and nourishes Qi, as an add-on treatment for MG with spleen and stomach Qi deficiency syndrome.

Methods And Analysis: Single-center, randomized, double-blind, multiple crossover N-of-1 studies will compare QJC versus placebo in 5 adult MG patients with spleen and stomach Qi deficiency syndrome. Patients will undergo 3 cycles of two 4-week intervention periods. According to the treatment schedule, patients will continue to be treated with pyridine bromide tablets, prednisone acetate, tablets and/or tacrolimus capsules throughout the entire trial. Each period consisting of 4-week oral add-on treatment with QJC will be compared with 4-week add-on treatment with a placebo. The primary endpoints are quantitative myasthenia gravis (QMG) test; measurement of the amount of Treg cells and cytokines such as interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-17A (IL-17A), and transforming growth factor-β (TGF-β); and corticosteroid or immunosuppressive agent dosage. Secondary outcome measures: Clinical: Evaluation of the effect of TCM syndromes; MG-activities of daily living (MG-ADL) scales; adverse events.

Ethics And Dissemination: This study was approved by The First Affiliated Hospital of Guangzhou University of Chinese Medicine (GZUCM), No. ZYYECK[2019]038. The results will be published in a peer-reviewed publication. Regulatory stakeholders will comment on the suitability of the trial for market authorization and reimbursement purposes. Trial registration: Chinese Clinical Trial Register, ID: ChiCTR2000033516. Registered on 3 June 2020, http://www.chictr.org.cn/showprojen.aspx?proj=54618.
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http://dx.doi.org/10.1097/MD.0000000000023679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748195PMC
December 2020

Prognostic Model of Colorectal Cancer Constructed by Eight Immune-Related Genes.

Front Mol Biosci 2020 27;7:604252. Epub 2020 Nov 27.

Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

Background: Colorectal cancer (CRC) is a common malignant tumor of the digestive tract with a high mortality rate. Growing evidence demonstrates that immune-related genes play a prominent role in the occurrence and development of CRC. The aim of this study was to investigate the prognostic value of immune-related genes in CRC.

Methods: Gene expression profiles and clinical data of 568 CRC and 44 non-tumorous tissues were obtained from The Cancer Genome Atlas (TCGA) database. First, we performed a differentially expressed gene (DEG) analysis and univariate Cox regression analysis to determine the DEGs associated with overall survival. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were subsequently performed for prognostic immune-related genes. Then, a multivariate Cox regression analysis was performed to establish the immune prognostic model and identify the independent prognostic factors of CRC. Next, experiments were done to further validate the model. Finally, we analyzed the correlation among immune-related genes, clinical traits, and immune cell infiltration.

Results: In total, 3,702 DEGs were obtained, and 338 prognostic immune-related genes were identified. Among them, 45 genes were significantly correlated with the prognosis of CRC patients. A TF-mediated network was set up to explore its internal mechanism. GO and KEGG analyses further illustrated that these genes were enriched in immune-and inflammatory-related pathways. Then, a prognostic prediction model composed of eight immune-related genes (SLC10A2, UTS2, FGF2, UCN, IL1RL2, ESM1, ADIPOQ, and VIP) was constructed. The AUC of the ROC curve for 1, 3, 5, and 10 years overall survival (OS) was 0.751, 0.707, 0.680, and 0.729, respectively. The survival analysis suggested that the OS of the high-risk group was significantly poorer than that of the low-risk group. Meanwhile, assays revealed that ESM1 and SLC10A2 exert opposing roles in colon cancer cell proliferation, validating the accuracy of the model. The correlation analysis indicated that immune cell infiltration was positively related to the model.

Conclusion: This study screened prognosis-related immune genes and developed a prognostic prediction model of CRC. These findings may help provide potential novel prognostic biomarkers and therapeutic targets for CRC. At the same time, the understanding of the CRC immune microenvironment status was deepened.
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http://dx.doi.org/10.3389/fmolb.2020.604252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729086PMC
November 2020

Expansion of Polymorphonuclear Myeloid-Derived Suppressor Cells in Patients With Gout.

Front Immunol 2020 14;11:567783. Epub 2020 Oct 14.

The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China.

Gout is an inflammatory joint disease caused by monosodium urate (MSU) crystals; however, the mechanism underlying MSU-induced inflammation is unclear. Previous research has suggested that inflammation or cancer can drive the expansion of myeloid-derived suppressor cells (MDSCs). In this study, the role of MDSCs in MSU-induced gout inflammation was evaluated. A total of 28 patients with gout, and 20 healthy controls were recruited for the study. MDSCs, and their functions, were analyzed by flow cytometry and a T cell co-culture assay, respectively. We observed a higher frequency of PMN-MDSCs, and a stronger immunosuppressive function, in patients with gout compared to the controls. Moreover, circulating PMN-MDSCs were positively correlated with pathological indicators, including uric acid and C-reactive protein levels. We also demonstrated that MSU can induce significant PMN-MDSC expansion, using and experiments. Finally, MSU-induced PMN-MDSCs produced higher levels of IL-1β, which mediated gout inflammatory progression. Our results demonstrate that MSU modulates the expansion and suppressive function of PMN-MDSCs, providing insights into a novel mechanism underlying the pathogenesis of MSU-induced gout. Thus, MDSCs may be useful for the development of novel therapeutic strategies for the prevention and treatment of gout.
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http://dx.doi.org/10.3389/fimmu.2020.567783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591715PMC
May 2021

Quantifying Liver-Stomach Disharmony Pattern of Functional Dyspepsia Using Multidimensional Analysis Methods.

Evid Based Complement Alternat Med 2020 10;2020:2562080. Epub 2020 Oct 10.

Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China.

Purpose: This study aims to develop and validate a quantitative model for measuring severity of a typical traditional Chinese medicine (TCM) pattern for functional dyspepsia (FD) using multidimensional analysis methods including confirmatory factor analysis (CFA) and multidimensional item response theory (MIRT).

Methods: A scale and theoretical models were constructed according to the definition of pathogenesis about "liver-stomach disharmony" patterns of FD. With data collected from 502 patients in a cross-section study, the theoretical model was validated with CFA, and the related validity and reliability were evaluated in Amos 21.0. By the use of the MIRT paradigm, psychometric properties of the scale were estimated and evaluated for pattern quantification.

Results: A scale consisting of 12 items was constructed detecting three latent traits of the pattern. The theoretical model was evaluated to be with adequate consistency with clinical data as RMSEA < 0.05, CFI = 0.94, and /D = 2.29. As the correlation between symptoms and related pattern factors evaluated to be with adequate factor loading, the instrument is of preliminary interpretation. Most precision of assessment could be achieved for patients with moderate severity of the pattern as shown in test information and standard error functions.

Conclusions: An instrument with an interpretable conceptual framework was developed for pattern quantification in TCM clinical practice. By constructing and evaluating both psychological and physical effects in a multidimensional model of the TCM pattern of FD, the paradigm raised in this article provided a valuable reference for interpreting complex diseases and theories such as FD and TCM patterns.
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http://dx.doi.org/10.1155/2020/2562080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569453PMC
October 2020

A Methodological and Reporting Quality Assessment of Systematic Reviews/Meta-Analyses about Chinese Medical Treatment for Gastroesophageal Reflux Disease.

Gastroenterol Res Pract 2020 24;2020:3868057. Epub 2020 Sep 24.

Gastroenterology Department, The First Affiliated Hospital, of Guangzhou University of Chinese Medicine, Guangzhou Guangdong, China.

Objective: To access the methodological and reporting quality of systematic reviews (SRs)/meta-analyses (MAs) about Chinese medical treatment for gastroesophageal reflux disease (GERD).

Methods: The PubMed, Wanfang Data, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), Chinese Biomedical (CBM), Web of Science, and Cochrane Library databases were searched from inception to June 2020. Two researchers independently screened the literature considering the eligibility criteria. Overview Quality Assessment Questionnaire (OQAQ), Assessment of Multiple Systematic Reviews 2 (AMSTAR 2), and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to assess the methodological and reporting quality of the included reports. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to evaluate the level of evidence in each report.

Results: Thirty-three SRs/MAs met the inclusion criteria. The OQAQ results showed that defects in the methodological quality of 17/32 reports were major, with scores of 3 points. Analyzing a single item as the object, search strategies (item 2), and risk of bias in individual studies (item 4) was considered poor. The AMSTAR 2 results showed that 25.4% of the items were not reported, and 7.8% of the items were only partially reported. The overall assessment of AMSTAR 2 showed the majority of systematic reviews and meta-analyses were of low/very low (31/33, 93.9%) methodological quality, with a lack of protocol registration and excluded study list. The PRISMA results showed that 19.9% of items were not reported, and 15.2% of items were only partially reported, due to a lack of protocol registration and study selection methods. The methodological and reporting quality of the included studies was generally poor. Evidence evaluation with GRADE showed that most (31/33) of the included studies had low or very low levels of evidence.

Conclusion: The methodological and reporting quality of SRs/MAs about Chinese medical treatment for GERD is generally poor. The main problems included incomplete search strategies, risk of bias in individual studies, the lack of protocol registration and excluded study list, and incorrect study selection methods.
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http://dx.doi.org/10.1155/2020/3868057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532378PMC
September 2020

Ginger relieves intestinal hypersensitivity of diarrhea predominant irritable bowel syndrome by inhibiting proinflammatory reaction.

BMC Complement Med Ther 2020 Sep 14;20(1):279. Epub 2020 Sep 14.

Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, P.R. China.

Background: Ginger or ginger extracts have been used in traditional medicine relieve pain caused by diarrhea predominant irritable bowel syndrome (IBS-D), but few data exists about its effectiveness. This present study was to validate the effect of ginger on visceral pain, and to further explore the possible underlying mechanism by which ginger is used to relieve IBS-D intestinal hypersensitivity.

Methods: First, the IBS-D rat model was established by chemical stimulation and acute and chronic pressure stimulation. Then, different dose of ginger were administrated to IBS-D rats and evaluate the defecation frequency, fecal water content (FWC) and abdominal withdrawal reflex (AWR) scores in IBS-D rats. Further, the IBS-D rats were sacrificed to collecte the colonic tissues to evaluate the effect of ginger administration on its pathology and changes of pro-inflammatory factors, and changes of NF-κB pathway. Second, the ginger was taken to HPLC analysis and 6-gingerol was choosen to further experiment. Then, IBS-D rats were treated with different dose of 6-gingerol, and the behavioral evaluation were to evaluate the effect of 6-gingerol on IBS-D rats. Further, colonic epithelial cells (CECs) were collectted and to evaluate the effect of 6-gingerol on the expression of inflammatory factors and changes of NF-κB pathway.

Results: The IBS-D rat model was successfully established by chemical stimulation and acute and chronic pressure stimulation. And ginger treatment significantly reduced the defecation frequency, fecal water content and AWR scores in IBS-D rats. Histopathological analysis showed that ginger treatment can significantly reduce colonic edema and promote the recovery of inflammation in IBS-D rats, and the effect is equivalent to rifaximin. Elisa and RT-qPCR showed that ginger inhibited the expression of proinflammatory factors (TNF-α, IL-6, iNOS) in IBS-D rats. Western blot showed IkBα was up-regulated while p-p65 was inhibited under ginger treatment. HPLC analysis showed that 6-gingerol was the main component of ginger, which could improve clinical symptoms in IBS-D rats. Western blot and RT-qPCR showed that 6-gingerol inhibited the expression of proinflammatory factors (TNF-α, IL-6, iNOS) in CECs, and inhibition of IκBα degradation and phosphorylation of p65 involved in NF-κB pathway.

Conclusion: Ginger and ginger extract could relieve intestinal hypersensitivity of IBS-D by inhibiting proinflammatory response.
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http://dx.doi.org/10.1186/s12906-020-03059-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489045PMC
September 2020

Construction and validation of a TP53-associated immune prognostic model for gastric cancer.

Genomics 2020 11 25;112(6):4788-4795. Epub 2020 Aug 25.

The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong, China. Electronic address:

Increasing evidence indicates that TP53 mutation impacts the patients' prognosis by regulating the gastric cancer (GC) immunophenotype. An immune prognostic signature (IPS) was constructed based on TP53 status. The effects of the IPS on the immune microenvironment of GC were analyzed. We also constructed a nomogram integrating the IPS and other clinical factors. An IPS was constructed in the TCGA cohort and validated in the meta-GEO cohort. TP53 mutation resulted in the downregulation of the immune response in GC. Concretely, high-risk patients were characterized by increased monocyte, macrophage M0 and T cell follicular helper infiltration; increased stromal score, ESTIMATE score and immune score; higher TIM3 and BTLA expression; and decreased dendritic cell and T cell CD4 memory-activated infiltration and tumor purity. The nomogram also showed good predictive performance. These results suggest that the IPS is an effective prognostic indicator for GC patients, which might provide a theoretical foundation for immunotherapy.
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http://dx.doi.org/10.1016/j.ygeno.2020.08.026DOI Listing
November 2020

LC01 Regulates Intestinal Epithelial Permeability through miR-144 Targeting of OCLN and ZO1.

J Microbiol Biotechnol 2020 Oct;30(10):1480-1487

Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510176, P.R. China.

Our previous report determined that miR-144 is a key regulator of intestinal epithelial permeability in irritable bowel syndrome with diarrhea (IBS-D) rats. Recent evidence has shown that lactobacilli play an important role in the relief of IBS-D symptoms. However, few studies have addressed the mechanisms by which microRNAs and lactobacilli exert their beneficial effects on intestinal epithelial permeability. Hence, to elucidate whether miRNAs and lactobacilli play roles in intestinal epithelial barrier regulation, we compared miRNA expression levels in intestinal epithelial cells (IECs) under ( LC01) treatment. IECs and LC01 were co-cultured and then subjected to microRNA microarray assay. qRT-PCR, western blot and ELISA were used to detect the expression of occludin (OCLN) and zonula occludens 1 (ZO1/TJP1). The interaction between miRNAs and LC01 acting in IECs was investigated through transfection of RNA oligoribonucleotides and pcDNA 3.1 plasmid. The results are as follows: 1) LC01 decreased the expression of miR-144 and FD4 and promoted OCLN and ZO1 expression in IECs; 2) LC01 enhanced the barrier function of IECs via downregulation of miR-144 and upregulation of OCLN and ZO1; 3) Under LC01 treatment, OCLN and ZO1 overexpression could partially eliminate the promoting effect of miR-144 on intestinal permeability in IECs. Our results demonstrate that LC01 regulates intestinal permeability of IECs through miR-144 targeting of OCLN and ZO1. LC01 can be a possible therapeutic target for managing dysfunction of the intestinal epithelial barrier.
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http://dx.doi.org/10.4014/jmb.2002.02059DOI Listing
October 2020

Regulation of MFN2 by berberine alleviates obesity exacerbated colitis.

Biochem Biophys Res Commun 2020 10 12;531(2):250-255. Epub 2020 Aug 12.

Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, China. Electronic address:

Obesity has become a global health issue, which can cause metabolic abnormalities systemically leading to increased morbidity of series diseases. At present, researches have presented obesity is a high-risk factor for colitis, and berberine shows positive therapeutic effect on colitis. Thus, we explored the beneficial effects and potential mechanisms of berberine on obesity-exacerbated colitis in this article. High-fat diet (HFD) exacerbated dextran sulfate sodium (DSS) induced colitis mice model was applied, the results showed that HFD promoted DSS-induced weight loss and inflammatory manifestations in intestine. The results of cytokines in serum and mRNA expression of inflammatory indicators in colon showed that HFD increased all their levels evidently, and the outcomes of Western blot analyses presented that HFD downregulated the MFN2 expression, inhibited the phosphorylation of AMPK as well as upregulated the BIP/Grp78 expression, while berberine could significantly reverse all these situations. In vitro, we stimulated Caco-2 cells with palmitic acid (PA) to replicate the lipotoxicity damage in the intestine, and the results presented that intervention therapy of berberine effectively enhanced the MFN2 expression, inhibited the mRNA levels of inflammatory factors, and reversed the PA induced protein level changes of AMPK and BIP/Grp78. In general, we proposed that berberine could regulate MFN2 to alleviate obesity exacerbated colitis.
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http://dx.doi.org/10.1016/j.bbrc.2020.07.051DOI Listing
October 2020
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