1.Thesium chinense Turcz. alleviates antibiotic-associated diarrhea in mice by modulating gut microbiota structure and regulating the EGFR/PI3K/Akt signaling pathway.
Haonan XU ; Fang ZHANG ; Yuying HUANG ; Qisheng YAO ; Yueqin GUAN ; Hao CHEN
Journal of Southern Medical University 2025;45(2):285-295
OBJECTIVES:
To investigate the therapeutic mechanism of Thesium chinense Turcz. (TCT) for antibiotic-associated diarrhea (AAD).
METHODS:
Network pharmacology, KEGG pathway enrichment analysis and molecular docking were used to identify the shared targets and genes of TCT and AAD, the key signaling pathways and the binding between the active components in TCT and the core protein targets. In a Kunming mouse model of AAD established by intragastric administration of lincomycin hydrochloride, the effects of daily gavage of 1% carboxymethyl cellulose sodium or TCT gel solutions at 1.5 g/kg and 3 g/kg (n=10) on body weight and diarrhea were observed. HE staining, ELISA, 16S rRNA sequencing, and Western blotting were used to examine pathologies, expression levels of IL-6 and TNF-α, changes in gut microbiota, and protein expressions of EGFR, p-EGFR, PI3K, p-PI3K, Akt, and p-Akt in the colon tissues of the mice.
RESULTS:
We identified a total of 66 active components of TCT and 68 core targets including EGFR, STAT3 and PIK3CA. KEGG pathway enrichment analysis suggested that the therapeutic effects of TCT was mediated primarily through the PI3K/Akt signaling pathway. Molecular docking showed that EGFR had the highest binding affinity with coniferin, and the EGFR-coniferin complex maintained a stable conformation at 10 ns, whose stability was also confirmed by Gibbs free energy analysis. In the mouse models of AAD, treatment with TCT significantly improved colonic tissue morphology, decreased colonic levels of TNF-α and IL-6, increased gut microbiota diversity, and modulated the relative abundances of the key genera including Lactobacillus and Bacteroides. TCT treatment also markedly reduced protein expressions of p-EGFR, p-PI3K and p-Akt in the colon tissues of the mice.
CONCLUSIONS
TCT can alleviate AAD in mice by modulating gut microbiota composition, regulating the EGFR/PI3K/Akt signaling pathway, and reducing TNF‑α and IL-6 expressions.
Animals
;
Gastrointestinal Microbiome/drug effects*
;
Signal Transduction/drug effects*
;
Mice
;
ErbB Receptors/metabolism*
;
Proto-Oncogene Proteins c-akt/metabolism*
;
Diarrhea/drug therapy*
;
Phosphatidylinositol 3-Kinases/metabolism*
;
Anti-Bacterial Agents/adverse effects*
;
Drugs, Chinese Herbal/therapeutic use*
;
Molecular Docking Simulation
2.Thesium chinense Turcz.alleviates antibiotic-associated diarrhea in mice by modulating gut microbiota structure and regulating the EGFR/PI3K/Akt signaling pathway
Haonan XU ; Fang ZHANG ; Yuying HUANG ; Qisheng YAO ; Yueqin GUAN ; Hao CHEN
Journal of Southern Medical University 2025;45(2):285-295
Objective To investigate the therapeutic mechanism of Thesium chinense Turcz.(TCT)for antibiotic-associated diarrhea(AAD).Methods Network pharmacology,KEGG pathway enrichment analysis and molecular docking were used to identify the shared targets and genes of TCT and AAD,the key signaling pathways and the binding between the active components in TCT and the core protein targets.In a Kunming mouse model of AAD established by intragastric administration of lincomycin hydrochloride,the effects of daily gavage of 1%carboxymethyl cellulose sodium or TCT gel solutions at 1.5 g/kg and 3 g/kg(n=10)on body weight and diarrhea were observed.HE staining,ELISA,16S rRNA sequencing,and Western blotting were used to examine pathologies,expression levels of IL-6 and TNF-α,changes in gut microbiota,and protein expressions of EGFR,p-EGFR,PI3K,p-PI3K,Akt,and p-Akt in the colon tissues of the mice.Results We identified a total of 66 active components of TCT and 68 core targets including EGFR,STAT3 and PIK3CA.KEGG pathway enrichment analysis suggested that the therapeutic effects of TCT was mediated primarily through the PI3K/Akt signaling pathway.Molecular docking showed that EGFR had the highest binding affinity with coniferin,and the EGFR-coniferin complex maintained a stable conformation at 10 ns,whose stability was also confirmed by Gibbs free energy analysis.In the mouse models of AAD,treatment with TCT significantly improved colonic tissue morphology,decreased colonic levels of TNF-α and IL-6,increased gut microbiota diversity,and modulated the relative abundances of the key genera including Lactobacillus and Bacteroides.TCT treatment also markedly reduced protein expressions of p-EGFR,p-PI3K and p-Akt in the colon tissues of the mice.Conclusion TCT can alleviate AAD in mice by modulating gut microbiota composition,regulating the EGFR/PI3K/Akt signaling pathway,and reducing TNF-α and IL-6 expressions.
3.The role of pyroptosis in rat articular cartilage injury induced by T-2 toxin
Hexuan DONG ; Xin ZHANG ; Haonan LI ; Fang QI ; Qian YU ; Hong JIANG ; Buyi LIN ; Jun YU
Chinese Journal of Endemiology 2025;44(1):10-16
Objective:To investigate the role of pyroptosis in T-2 toxin induced articular cartilage injury.Methods:A total of 145 SPF grade male Wistar rats were randomly divided into blank control group ( n = 45), solvent control group ( n = 45), and T-2 toxin group ( n = 55) based on body weight (50 - 70 g). The T-2 toxin group and the solvent control group were given 100 ng·g -1·d -1 T-2 toxin and an equal amount of anhydrous ethanol by gavage, respectively; the blank control group was fed routinely. Fifteen rats from each group were euthanized at 6, 12, and 24 weeks of intervention, and bilateral knee joints of the rats were collected. Pathological changes in rat knee articular cartilage were observed using hematoxylin and eosin staining. TdT-mediated dUTP nick-end labeling (TUNEL) staining was used to detect chondrocyte injury. Western blot was used to detect the protein expression of gasdermin D (GSDMD), cleaved N-terminal of gasdermin D (GSDMD-N), NOD like receptor thermal protein domain associated protein 3 (NLRP3), cysteinyl aspartate specific proteinase 1 (Caspase-1), interleukin 1β (IL-1β), interleukin 18 (IL-18), and apoptosis-associated spike-like protein containing CARD (ASC). Results:At 6, 12, and 24 weeks of intervention, the T-2 toxin group rats showed varying degrees of damage to the knee articular cartilage tissue, including a decrease in the number of chondrocytes and death. At 24 weeks of intervention, the TUNEL staining positivity rates of chondrocytes in the blank control group, solvent control group, and T-2 toxin group were (1.28 ± 0.45)%, (0.73 ± 0.27)%, and (4.01 ± 2.37)%, respectively, with statistically significant differences between the groups ( F = 6.11, P = 0.036); and the T-2 toxin group was higher than the blank control group ( P < 0.05). At 24 weeks of intervention, there were statistically significant differences in the expression levels of NLRP3, Caspase-1, GSDMD, GSDMD-N, and IL-1β proteins among the blank control group, solvent control group, and T-2 toxin group ( F = 3.81, 11.81, 6.74, 3.71, 155.49, P = 0.044, 0.003, 0.023, 0.036, 0.001); and the T-2 toxin group was higher than the blank control group ( P < 0.05). At different intervention cycles, there was no statistically significant difference in the expression levels of ASC and IL-18 proteins among the groups ( F = 0.78, 0.93, 3.73, 2.26, 0.88, 0.11, P > 0.05). Conclusion:The NLRP3/Caspase-1/GSDMD pathway mediated pyroptosis is involved in T-2 toxin induced articular cartilage injury in rats.
4.Summary of best evidence for prevention and management of enteral nutrition intolerance in postoperative patients with gastric cancer
Qiang ZHOU ; Xiaoshuang ZHANG ; Lin SUN ; Xi WANG ; Jiacheng WANG ; Li YUAN ; Haonan FANG
Chinese Journal of Modern Nursing 2025;31(23):3117-3125
Objective:To identify and synthesize the best available evidence for the prevention and management of enteral nutrition intolerance in postoperative patients with gastric cancer.Methods:Following the hierarchical structure of the "6S Evidence Resource Pyramid" model, evidence was systematically retrieved from evidence-based databases, clinical guidelines and professional societies' websites, and comprehensive literature databases. Studies related to the prevention and management of enteral nutrition intolerance in postoperative gastric cancer patients were screened. Two researchers, both trained in evidence-based nursing, independently conducted quality appraisal, evidence extraction, and integration. The search covered literature published from database inception to February 25, 2025.Results:A total of 23 studies were included, comprising 2 clinical guidelines, 1 evidence summary, 2 systematic reviews, 4 expert consensuses, 9 randomized controlled trials, 1 quasi-experimental study, 1 cohort study, 2 analytical cross-sectional studies, and 1 case-control study. Based on 6 key aspects (including preparation by Medical staff before surgery, postoperative patient assessment, formulation of feeding, rehabilitation exercises, traditional Chinese medicine interventions, and management of enteral nutrition intolerance), a total of 26 best evidence recommendations were summarized.Conclusions:The evidence summarized in this study provides an evidence-based foundation for clinical medical staff, contributing to the reduction of enteral nutrition intolerance in postoperative patients with gastric cancer.
5.Summary of best evidence for prevention and management of enteral nutrition intolerance in postoperative patients with gastric cancer
Qiang ZHOU ; Xiaoshuang ZHANG ; Lin SUN ; Xi WANG ; Jiacheng WANG ; Li YUAN ; Haonan FANG
Chinese Journal of Modern Nursing 2025;31(23):3117-3125
Objective:To identify and synthesize the best available evidence for the prevention and management of enteral nutrition intolerance in postoperative patients with gastric cancer.Methods:Following the hierarchical structure of the "6S Evidence Resource Pyramid" model, evidence was systematically retrieved from evidence-based databases, clinical guidelines and professional societies' websites, and comprehensive literature databases. Studies related to the prevention and management of enteral nutrition intolerance in postoperative gastric cancer patients were screened. Two researchers, both trained in evidence-based nursing, independently conducted quality appraisal, evidence extraction, and integration. The search covered literature published from database inception to February 25, 2025.Results:A total of 23 studies were included, comprising 2 clinical guidelines, 1 evidence summary, 2 systematic reviews, 4 expert consensuses, 9 randomized controlled trials, 1 quasi-experimental study, 1 cohort study, 2 analytical cross-sectional studies, and 1 case-control study. Based on 6 key aspects (including preparation by Medical staff before surgery, postoperative patient assessment, formulation of feeding, rehabilitation exercises, traditional Chinese medicine interventions, and management of enteral nutrition intolerance), a total of 26 best evidence recommendations were summarized.Conclusions:The evidence summarized in this study provides an evidence-based foundation for clinical medical staff, contributing to the reduction of enteral nutrition intolerance in postoperative patients with gastric cancer.
6.The role of pyroptosis in rat articular cartilage injury induced by T-2 toxin
Hexuan DONG ; Xin ZHANG ; Haonan LI ; Fang QI ; Qian YU ; Hong JIANG ; Buyi LIN ; Jun YU
Chinese Journal of Endemiology 2025;44(1):10-16
Objective:To investigate the role of pyroptosis in T-2 toxin induced articular cartilage injury.Methods:A total of 145 SPF grade male Wistar rats were randomly divided into blank control group ( n = 45), solvent control group ( n = 45), and T-2 toxin group ( n = 55) based on body weight (50 - 70 g). The T-2 toxin group and the solvent control group were given 100 ng·g -1·d -1 T-2 toxin and an equal amount of anhydrous ethanol by gavage, respectively; the blank control group was fed routinely. Fifteen rats from each group were euthanized at 6, 12, and 24 weeks of intervention, and bilateral knee joints of the rats were collected. Pathological changes in rat knee articular cartilage were observed using hematoxylin and eosin staining. TdT-mediated dUTP nick-end labeling (TUNEL) staining was used to detect chondrocyte injury. Western blot was used to detect the protein expression of gasdermin D (GSDMD), cleaved N-terminal of gasdermin D (GSDMD-N), NOD like receptor thermal protein domain associated protein 3 (NLRP3), cysteinyl aspartate specific proteinase 1 (Caspase-1), interleukin 1β (IL-1β), interleukin 18 (IL-18), and apoptosis-associated spike-like protein containing CARD (ASC). Results:At 6, 12, and 24 weeks of intervention, the T-2 toxin group rats showed varying degrees of damage to the knee articular cartilage tissue, including a decrease in the number of chondrocytes and death. At 24 weeks of intervention, the TUNEL staining positivity rates of chondrocytes in the blank control group, solvent control group, and T-2 toxin group were (1.28 ± 0.45)%, (0.73 ± 0.27)%, and (4.01 ± 2.37)%, respectively, with statistically significant differences between the groups ( F = 6.11, P = 0.036); and the T-2 toxin group was higher than the blank control group ( P < 0.05). At 24 weeks of intervention, there were statistically significant differences in the expression levels of NLRP3, Caspase-1, GSDMD, GSDMD-N, and IL-1β proteins among the blank control group, solvent control group, and T-2 toxin group ( F = 3.81, 11.81, 6.74, 3.71, 155.49, P = 0.044, 0.003, 0.023, 0.036, 0.001); and the T-2 toxin group was higher than the blank control group ( P < 0.05). At different intervention cycles, there was no statistically significant difference in the expression levels of ASC and IL-18 proteins among the groups ( F = 0.78, 0.93, 3.73, 2.26, 0.88, 0.11, P > 0.05). Conclusion:The NLRP3/Caspase-1/GSDMD pathway mediated pyroptosis is involved in T-2 toxin induced articular cartilage injury in rats.
7.Inhibitory effect of royal jelly acid on proliferation of human colon cancer SW620 cells and its network pharmacological analysis
Yaxin LIU ; Jian LIU ; Zhen LI ; Zhanhong CAO ; Haonan BAI ; Yu AN ; Xingyu FANG ; Qing YANG ; Hui LI ; Na LI
Journal of Jilin University(Medicine Edition) 2024;50(1):150-160
Objective:To discuss the effect of royal jelly acid(10-HDA)on the proliferation and migration of the human colon cancer SW620 cells based on the network pharmacology,and to clarify its related molecular mechanism.Methods:The active ingredients such as 10-HDA and their corresponding targets were retrieved by using the keyword"royal jelly"from the Traditiomal Chinese Medicine Systems Pharmacology(TMSCP)Database and the Traditiomal Chinese Medicine Integrated Database(TCMID);the small molecule targets were predicted by the Swiss Target Prediction Database.The GeneCards Database and the Online Mendelian Inheritance in Man(OMIM)Database were used to obtain the targets with the keyword"Colon Cancer";the protein-protein interaction(PPI)network was constructed by using the String Database and Cytoscape 3.8.0 Software to screen the core targets;the Gene Ontology(GO)function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were analyzed by Metascape Database;the specific ingredient 10-HDA was screened for the in vitro activity experiments.The human colon cancer SW620 cells with good growth status were divided into control group and different doses(1,5,10,15,and 20 mmol·L-1)of 10-HDA groups.The viabilities of the cells in various groups were detected by MTT method and the survival rates of the cells were calculated.The SW620 cells were divided into control group,low dose(5 mmol·L-1)of 10-HDA group,middle dose(10 mmol·L-1)of 10-HDA group,and high dose(15 mmol·L-1)of 10-HDA group;Hoechst33342 staining method was used to observe the morphology of the cells in various groups;cell scratch test was used to detect the scratch healing rates of the cells in various groups;flow cytometry was used to detect the percentages of the cells at different cell cycles in various groups;biochemical method was used to detect the activities of total antioxidant capacity(T-AOC)and superoxide dismutase(SOD)in the cells in various groups;Western blotting method was used to detect the expression levels of B-cell lymphoma 2(Bcl-2),Bcl-2-associated X protein(Bax),cysteine-containing aspartate proteolytic enzyme-3(Caspase-3),cysteine-containing aspartate proteolytic enzyme-9(Caspase-9),glycogen synthase kinase 3β(GSK3β),β-catenin,and cyclin D1 proteins in the cells in various groups.Results:Six active ingredients of royal jelly were screened out by the TCMSP Database,and 28 core targets of 10-HDA in the treatment of colon cancer were obtained.The GO function enrichment analysis mainly included the signaling pathways such as cell proliferation and apoptosis.The KEGG signaling pathway enrichment analysis included the cell cycle,prostate cancer,cell senescence,and p53 signaling pathways;the GSK3β/β-catenin signaling pathway was closely related to the cell cycle.Compared with control group,the viabilities of the cells in 5,10,15,and 20 mmol·L-110-HDA groups were decreased in a dose-dependent manner(P<0.05 or P<0.01),the numbers of apoptotic cells in different doses of 10-HDA groups were significantly increased,and the scratch healing rates of the cells were significantly decreased(P<0.05 or P<0.01);the percentages of the cells at S phase in middle and high doses of 10-HDA groups were significantly increased(P<0.05 or P<0.01),the activities of T-AOC and SOD in the cells in different doses of 10-HDA groups were significantly decreased(P<0.05 or P<0.01).Compared with control group,the expression level of Bcl-2 protein in the cells in low dose of 10-HDA group was significantly decreased(P<0.01),and the expression level of GSK3β protein was significantly increased(P<0.05);compared with control group,the expression levels of Bax,Caspase-3,Caspase-9,and GSK3β proteins in the cells in middle and high doses of 10-HDA groups were significantly increased(P<0.05 or P<0.01),and the expression levels of Bcl-2,β-catenin,and CyclinD1 proteins were significantly decreased(P<0.01).Conclusion:10-HDA can significantly inhibit the proliferation and migration of the colon cancer cells and promote the apoptosis and oxidation levels of the colon cancer cells,and its mechanism may be related to the activation of the GSK3β/β-catenin signaling pathway.
8.Risk factors for massive blood loss in pediatric patients with congenital scoliosis undergoing posterior hemivertebra resection
Duoyi LI ; Haonan LIU ; Jianmin ZHANG ; Lijing LI ; Fang WANG ; Xuejun ZHANG
Chinese Journal of Anesthesiology 2021;41(4):427-429
Objective:To identify the risk factors for massive blood loss in pediatric patients with congenital scoliosis undergoing posterior hemivertebra resection.Methods:The clinical data of pediatric patients with congenital scoliosis who underwent posterior hemivertebra resection in our hospital from May 2017 to July 2019 were collected.The children were divided into group A (massive blood loss, blood loss/blood volume ≥30%) and group B (non-massive blood loss, blood loss/blood volume <30%) according to intraoperative blood loss.Logistic regression analysis was used to stratify the risk factors.Results:A total of 108 pediatric patients were enrolled in the study including 29 cases in group A and 79 cases in group B, respectively.There were significant differences in the preoperative Cobb angle, body mass index, the number of fused levels, the number of screws and operative time between the two groups ( P<0.05). Logistic regression analysis showed that the preoperative Cobb angle, operative time, the number of fused levels and body mass index were the risk factors for intraoperative massive blood loss ( P<0.05). Conclusion:Lower BMI, larger Cobb angle, increased operative time and more fused levels are the risk factors for massive blood loss in pediatric patients with congenital scoliosis undergoing posterior hemivertebra resection.
9.Research trends and hot spots in campus bullying using CiteSpace software
Chinese Journal of School Health 2019;40(5):716-720
Objective:
To explore the hot issues and developing trend of the research of campus bulling,and to provide a reference for the research on campus bullying.
Methods:
The power of research, high-impact authors, highly cited journals, high-frequency keywords, and burst terms related to school bullying from the Web of Science database were analyzed using CiteSpace software. The data collection time was May 9, 2018.
Results:
A total of 3 561 literature data were obtained. The results showed that the country with the highest number of publications was the United States; England had the highest centrality and was in a critical position in the research. The University of Turku in Finland was the core research institution. Salmivalli C was the author of the highest publication, Olweus D was the most frequent cited author. The high-impact journal was Aggressive Behavior. In terms of high-frequency keywords, the core vocabulary such as bully, adolescence, and victim were listed. Middle school students were the most frequently studied; in the form of bullying, the frequency of violence, aggression, and cyberbully was more common; depression, mental health and health appeared more frequently in terms of bullying outcomes. Mutant words including school children, bullying, victimization, relational aggression were more common.
Conclusion
The research hotspots on campus bullying during the past decade include violence, gender, social support, and mental health. Bullying among college students will be a hot research topic in the future. Continued efforts should be carried out in the field of campus bullying in China.
10.Roux-en-Y versus Billroth Ⅱ alimentary canal reconstruction after pancreaticoduodenectomy: a meta-analysis
Haonan GUAN ; Qiang HUANG ; Ji YANG ; Chao WANG ; Fang XIE ; Cheng WANG
Chinese Journal of Hepatobiliary Surgery 2018;24(7):470-475
Objective To study the effectiveness and safety comparing Roux-en-Y versus Billroth Ⅱ alimentary canal reconstruction after pancreaticoduodenectomy (PD).Methods A computer search was conducted on PubMed,Embase,Web of Science,Science Direct,Springer Link,Cochrane Center,CBM,CNKI,Wan Fang and VIP databases before September 2017 for all RCT and CCT articles on Roux-en-Y versus Billroth Ⅱ reconstruction after PD.The quality of the included trials was studied by assessing the inclusive and exclusive criteria (the PRISMA statement) by 2 researchers independently.The data were extracted and analyzed using the RevManS.3 software.Results 9 articles (3 RCTs,6 CCTs) which involved 1 599 patients (563 Roux-en-Y patients,1 036 Billroth Ⅱ patients) were studied.Meta analysis revealed that Billroth Ⅱ patients had a lower postoperative delayed gastric emptying (DGE,grades B,C) rate (OR =3.76,95% CI:1.32 ~ 10.68,P < 0.05) and a shorter operation time (WMD =32.75,95% CI:8.17 ~57.33,P < 0.05) than Roux-en-Y patients.There were no significant differences in the rates of postoperative delayed gastric emptying (grades A,B,C),pancreatic fistula,bile leak,postoperative hemorrhage,reoperation,postoperative complications and the duration of postoperative stay (P > 0.05).Conclusions The incidence of DGE (grades B,C) after PD was lower after Billroth Ⅱ than that of Roux-en-Y reconstruction.Large prospective randomized controlled trials are needed to confirm the findings of this meta-analysis.


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