BACKGROUND There are several surgical options for treating early gastric cancers(EGCs), such as endoscopic resection, laparoscopic or open gastrectomy with D1 or D2 lymphadenectomy. Endoscopic resection for EGC with l...BACKGROUND There are several surgical options for treating early gastric cancers(EGCs), such as endoscopic resection, laparoscopic or open gastrectomy with D1 or D2 lymphadenectomy. Endoscopic resection for EGC with low risk of lymph node metastasis has been widely accepted as a therapeutic alternative. The role of endoscopic submucosal dissection(ESD) in treating EGC is not well established,especially when compared with resection surgery cases in a long-term follow-up scope.AIM To compare the safety and efficacy of the short-and long-term outcomes between ESD and resection surgery.METHODS We searched the databases of PubMed, EMBASE, Web of Science, and the Cochrane Library from January 1990 to June 2018, enrolling studies reporting short-or long-term outcomes of ESD in comparison with resection surgery for EGC. The quality of the studies was assessed by the Newcastle-Ottawa Quality Assessment Scale. Stata software(version 12.0) was used for the analysis. Pooling analysis was conducted using either fixed-or random-effects models depending on heterogeneity across studies.RESULTS Fourteen studies comprising 5112 patients were eligible for analysis(2402 for EGC and 2710 for radical surgery). Our meta-analysis demonstrated that the ESD approach showed advantages through decreased operation time [weighted mean difference(WMD):-140.02 min, 95%CI:-254.23 to-34.82 min, P = 0.009], shorter hospital stay(WMD:-5.41 d, 95% CI:-5.93 to-4.89 d, P < 0.001), and lowerpostoperative complication rate [Odds ratio(OR) = 0.39, 95%CI: 0.28-0.55, P <0.001). Meanwhile, EGC patients who underwent ESD had higher recurrence rate(OR = 9.24, 95%CI: 5.94-14.36, P < 0.001) than resection surgery patients.However, the long-term survival including overall survival [Hazard ratio(HR) =0.51, 95%CI: 0.26-1.00, P = 0.05] and event-free survival(HR = 1.59, 95%CI: 0.66-9.81, P = 0.300) showed no significant differences between these two groups.CONCLUSION In the treatment of EGC, ESD was safe and feasible in comparison with resection surgery, with advantages in several surgical and post-operative recovery parameters. Although the recurrence rate was higher in ESD group, the longterm survival was still comparable in these two groups, suggesting ESD could be recommended as standard treatment for EGC with indications.展开更多
BACKGROUND Colon cancer is one of the most common malignancies worldwide,and chemotherapy is a widely used strategy in colon cancer clinical therapy.However,chemotherapy resistance is a major cause of disease recurren...BACKGROUND Colon cancer is one of the most common malignancies worldwide,and chemotherapy is a widely used strategy in colon cancer clinical therapy.However,chemotherapy resistance is a major cause of disease recurrence and progression in colon cancer,and thus novel drugs for treatment are urgently needed.Tetramethylpyrazine(TMP),a component of the traditional Chinese medicine Chuanxiong Hort,has been proven to exhibit a beneficial effect in tumors.AIM To investigate the potential anticancer activity of TMP in colon cancer and its underlying mechanisms.METHODS Colon cancer cells were incubated with different concentrations of TMP.Cell viability was evaluated by crystal violet staining assay and cell counting kit-8 assay,and cell apoptosis and cell cycle were assessed by flow cytometry.RESULTS TMP significantly inhibited the proliferation of colon cancer cells in a dose-and time-dependent manner.In addition,flow cytometry revealed that TMP induced cell cycle arrest at the G0/G1 phase.TMP treatment caused early stage apoptosis in SW480 cells,whereas it caused late stage apoptosis in HCT116 cells.CONCLUSION Our studies demonstrated that TMP inhibits the proliferation of colon cancer cells in a dose-and time-dependent manner by inducing apoptosis and arresting the cell cycle at the G0/G1 phase.Our findings suggest that TMP might serve as a potential novel therapeutic drug in the treatment of human colon cancer.展开更多
BACKGROUND Postoperative peritoneal adhesion(PPA),characterized by abdominal pain,female infertility,and even bowel obstruction after surgery,has always been a major concern.The occurrence and formation of adhesion ar...BACKGROUND Postoperative peritoneal adhesion(PPA),characterized by abdominal pain,female infertility,and even bowel obstruction after surgery,has always been a major concern.The occurrence and formation of adhesion are from complex biological processes.However,the molecular mechanisms underlying the basis of microarray data profile,followed by peritoneal adhesion formation,are largely unknown.AIM To reveal the underlying pathogenesis of PPA at the molecular level.METHODS The gene expression profile was retrieved from the Gene Expression Omnibus database for our analysis.We identified a panel of key genes and related pathways involved in adhesion formation using bioinformatics analysis methods.We performed quantitative PCR and western blotting in vivo to validate the results preliminarily.RESULTS In total,446 expressed genes were altered in peritoneal adhesion.We found that several hub genes(e.g.,tumor necrosis factor,interleukin 1 beta,interleukin 6,CX-C motif chemokine ligand 1,C-X-C motif chemokine ligand 2)were marked as significant biomarkers.Functional analysis suggested that these genes were enriched in the Toll-like receptor signaling pathway.According to the Kyoto Encyclopedia of Genes and Genomes pathway and published studies,TLR4,myeloid differentiation primary response protein 88(MyD88),and nuclear factor kappa B(NF-κB)played essential roles in Toll-like signaling transduction.Here,we obtained a regulatory evidence chain of TLR4/MyD88/NF-κB/inflammatory cytokines/peritoneal adhesion involved in the pathogenesis of postoperative adhesion.The results of the microarray analysis were verified by the animal experiments.These findings may extend our understanding of the molecular mechanisms of PPA.CONCLUSION The regulatory evidence chain of TLR4/MyD88/NF-κB/inflammatory cytokines/peritoneal adhesion may play key roles in the pathogenesis of PPA.Future studies are required to validate our findings.展开更多
BACKGROUND Post-traumatic stress disorder(PTSD)is a serious stress-related disorder.AIM To identify the key genes and pathways to uncover the potential mechanisms of PTSD using bioinformatics methods.METHODS Gene expr...BACKGROUND Post-traumatic stress disorder(PTSD)is a serious stress-related disorder.AIM To identify the key genes and pathways to uncover the potential mechanisms of PTSD using bioinformatics methods.METHODS Gene expression profiles were obtained from the Gene Expression Omnibus database.The differentially expressed genes(DEGs)were identified by using GEO2R.Gene functional annotation and pathway enrichment were then conducted.The gene-pathway network was constructed with Cytoscape software.Quantitative real-time polymerase chain reaction(qRT-PCR)analysis was applied for validation,and text mining by Coremine Medical was used to confirm the connections among genes and pathways.RESULTS We identified 973 DEGs including 358 upregulated genes and 615 downregulated genes in PTSD.A group of centrality hub genes and significantly enriched pathways(MAPK,Ras,and ErbB signaling pathways)were identified by using gene functional assignment and enrichment analyses.Six genes(KRAS,EGFR,NFKB1,FGF12,PRKCA,and RAF1)were selected to validate using qRT-PCR.The results of text mining further confirmed the correlation among hub genes and the enriched pathways.It indicated that these altered genes displayed functional roles in PTSD via these pathways,which might serve as key signatures in the pathogenesis of PTSD.CONCLUSION The current study identified a panel of candidate genes and important pathways,which might help us deepen our understanding of the underlying mechanism of PTSD at the molecular level.However,further studies are warranted to discover the critical regulatory mechanism of these genes via relevant pathways in PTSD.展开更多
Objective:The purpose of this study is to explore the effect of Hirudin on the farnesoid X receptor(FXR)pathway during acute intrahepatic cholestasis in vivo and in vitro.Method:In vivo,sixty male Sprague-Dawley rats ...Objective:The purpose of this study is to explore the effect of Hirudin on the farnesoid X receptor(FXR)pathway during acute intrahepatic cholestasis in vivo and in vitro.Method:In vivo,sixty male Sprague-Dawley rats were randomly divided into six groups:regular group,model group,ursodeoxycholic acid(UDCA)group(60 mg/kg),hirudin treatment group(84 u/kg),hirudin treatment group(63 u/kg)and hirudin treatment group(42 u/kg).The male Sprague-Dawley rats of UDCA group were intragastrically administered with a corresponding concentration of 0.005 mL/g body weight for seven days,once a day;and the hirudin treatment group was injected subcutaneously with different concentrations of Hirudin for seven days,once a day;Except for the normal group,other groups of rats were given 100 mg/kg ANIT by gavage on the 5th day.The model was administered by gavage once a day for three days.In vitro,(Z)-Guggulsterone was used to stimulate the L02 cells(0.05μmol/ml),with or without different concentrations of Hirudin(2,4 and 8 u/ml)for 24 h.The liver tissue was examined by HE microscope and the pathological state of the rat liver was observed;FXR,Small heterodimeric chaperone receptor(SHP),uridine diphosphate glucuronide transfer 2B4(UGT2B4),bile salt output pump(BSEP)mRNA and protein expressions were tested by real-time fluorescent quantitative PCR and Western blot test.And immunohistochemistry(IHC)was used to analyze the expression of FXR.Results:Compared with the model group,the hirudin group can improve liver tissue damage,and promote FXR,SHP,BSEP and UGT2B4 proteins and mRNA expression in vivo and in vitro.Conclusion:Hirudin can alleviate intrahepatic cholestasis,reduce liver tissue damage.Hirudin can up-regulate the expression of FXR gene,promote the up-regulation of SHP,BSEP and UGT2B4 genes,and inhibit the cholestasis pathway to protect liver cells.The study may provide an effective drug for clinical treatment of intrahepatic cholestasis.展开更多
Postoperative adhesion(PA)is currently one of the most unpleasant complications following surgical procedures.Researchers have developed several new strategies to alleviate the formation of PA to a great extent,but so...Postoperative adhesion(PA)is currently one of the most unpleasant complications following surgical procedures.Researchers have developed several new strategies to alleviate the formation of PA to a great extent,but so far,no single measure or treatment can meet the expectations and requirements of clinical patients needing complete PA prevention.Chinese medicine(CM)has been widely used for thousands of years based on its remarkable efficacy and indispensable advantages CM treatments are gradually being accepted by modern medicine.Therefore,this review summarizes the formating process of PA and the efficacy and action mechanism of CM treatments,including their pharmacological effects,therapeutic mechanisms and advantages in PA prevention.We aim to improve the understanding of clinicians and researchers on CM prevention in the development of PA and promote the in-depth development and industrialization process of related drugs.展开更多
Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3(NLRP3)is an intracellular sensor that detects endogenous danger signals and environmental irritants to assemble into the NLRP3 i...Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3(NLRP3)is an intracellular sensor that detects endogenous danger signals and environmental irritants to assemble into the NLRP3 inflammasome.Activation of the NLRP3 inflammasome leads to the secretion of the proinflammatory cytokines interleutkin(IL)-1β and IL-18 and induces pyroptosis.Recent studies have shown that the NLRP3 inflammasome participates in the initiation and progression of diabetic atherosclerosis through pathological mechanisms such as β-cell dysfunction,insulin resistance,endothelial cell dysfunction,monocyte adhesion and infiltration,and smooth muscle cell proliferation and migration.In diabetic atherosclerosis,Chinese medicine has been proven effective for the inflammatory response mediated by the NLRP3 inflammasome.This review summarizes the latest progress on the NLRP3 inflammasome in the pathogenesis and potential Chinese medicine treatment of diabetic atherosclerosis.展开更多
基金Supported by Municipal Science Funds of Xingtai,No.2015ZC202
文摘BACKGROUND There are several surgical options for treating early gastric cancers(EGCs), such as endoscopic resection, laparoscopic or open gastrectomy with D1 or D2 lymphadenectomy. Endoscopic resection for EGC with low risk of lymph node metastasis has been widely accepted as a therapeutic alternative. The role of endoscopic submucosal dissection(ESD) in treating EGC is not well established,especially when compared with resection surgery cases in a long-term follow-up scope.AIM To compare the safety and efficacy of the short-and long-term outcomes between ESD and resection surgery.METHODS We searched the databases of PubMed, EMBASE, Web of Science, and the Cochrane Library from January 1990 to June 2018, enrolling studies reporting short-or long-term outcomes of ESD in comparison with resection surgery for EGC. The quality of the studies was assessed by the Newcastle-Ottawa Quality Assessment Scale. Stata software(version 12.0) was used for the analysis. Pooling analysis was conducted using either fixed-or random-effects models depending on heterogeneity across studies.RESULTS Fourteen studies comprising 5112 patients were eligible for analysis(2402 for EGC and 2710 for radical surgery). Our meta-analysis demonstrated that the ESD approach showed advantages through decreased operation time [weighted mean difference(WMD):-140.02 min, 95%CI:-254.23 to-34.82 min, P = 0.009], shorter hospital stay(WMD:-5.41 d, 95% CI:-5.93 to-4.89 d, P < 0.001), and lowerpostoperative complication rate [Odds ratio(OR) = 0.39, 95%CI: 0.28-0.55, P <0.001). Meanwhile, EGC patients who underwent ESD had higher recurrence rate(OR = 9.24, 95%CI: 5.94-14.36, P < 0.001) than resection surgery patients.However, the long-term survival including overall survival [Hazard ratio(HR) =0.51, 95%CI: 0.26-1.00, P = 0.05] and event-free survival(HR = 1.59, 95%CI: 0.66-9.81, P = 0.300) showed no significant differences between these two groups.CONCLUSION In the treatment of EGC, ESD was safe and feasible in comparison with resection surgery, with advantages in several surgical and post-operative recovery parameters. Although the recurrence rate was higher in ESD group, the longterm survival was still comparable in these two groups, suggesting ESD could be recommended as standard treatment for EGC with indications.
文摘BACKGROUND Colon cancer is one of the most common malignancies worldwide,and chemotherapy is a widely used strategy in colon cancer clinical therapy.However,chemotherapy resistance is a major cause of disease recurrence and progression in colon cancer,and thus novel drugs for treatment are urgently needed.Tetramethylpyrazine(TMP),a component of the traditional Chinese medicine Chuanxiong Hort,has been proven to exhibit a beneficial effect in tumors.AIM To investigate the potential anticancer activity of TMP in colon cancer and its underlying mechanisms.METHODS Colon cancer cells were incubated with different concentrations of TMP.Cell viability was evaluated by crystal violet staining assay and cell counting kit-8 assay,and cell apoptosis and cell cycle were assessed by flow cytometry.RESULTS TMP significantly inhibited the proliferation of colon cancer cells in a dose-and time-dependent manner.In addition,flow cytometry revealed that TMP induced cell cycle arrest at the G0/G1 phase.TMP treatment caused early stage apoptosis in SW480 cells,whereas it caused late stage apoptosis in HCT116 cells.CONCLUSION Our studies demonstrated that TMP inhibits the proliferation of colon cancer cells in a dose-and time-dependent manner by inducing apoptosis and arresting the cell cycle at the G0/G1 phase.Our findings suggest that TMP might serve as a potential novel therapeutic drug in the treatment of human colon cancer.
基金Supported by the National Natural Science Foundation of China,No.81704084,No.81603529,and No.81673982the Science and Technology Projects of Jiangsu Provincial Bureau of Traditional Chinese Medicine,No.YB2017002 and No.YB2015002+4 种基金the Natural Science Foundation of the Jiangsu Higher Education Institutions,No.16KJB360002the Postgraduate Research and Practice Innovation Program of Jiangsu Province,No.KYCX18_1541the Qing Lan Projectthe Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),the Open Projects of the Discipline of Chinese Medicine of Nanjing University of Chinese Medicine(ZYX03KF63)Jiangsu Government Scholarship for Overseas Studies and China Scholarship Council
文摘BACKGROUND Postoperative peritoneal adhesion(PPA),characterized by abdominal pain,female infertility,and even bowel obstruction after surgery,has always been a major concern.The occurrence and formation of adhesion are from complex biological processes.However,the molecular mechanisms underlying the basis of microarray data profile,followed by peritoneal adhesion formation,are largely unknown.AIM To reveal the underlying pathogenesis of PPA at the molecular level.METHODS The gene expression profile was retrieved from the Gene Expression Omnibus database for our analysis.We identified a panel of key genes and related pathways involved in adhesion formation using bioinformatics analysis methods.We performed quantitative PCR and western blotting in vivo to validate the results preliminarily.RESULTS In total,446 expressed genes were altered in peritoneal adhesion.We found that several hub genes(e.g.,tumor necrosis factor,interleukin 1 beta,interleukin 6,CX-C motif chemokine ligand 1,C-X-C motif chemokine ligand 2)were marked as significant biomarkers.Functional analysis suggested that these genes were enriched in the Toll-like receptor signaling pathway.According to the Kyoto Encyclopedia of Genes and Genomes pathway and published studies,TLR4,myeloid differentiation primary response protein 88(MyD88),and nuclear factor kappa B(NF-κB)played essential roles in Toll-like signaling transduction.Here,we obtained a regulatory evidence chain of TLR4/MyD88/NF-κB/inflammatory cytokines/peritoneal adhesion involved in the pathogenesis of postoperative adhesion.The results of the microarray analysis were verified by the animal experiments.These findings may extend our understanding of the molecular mechanisms of PPA.CONCLUSION The regulatory evidence chain of TLR4/MyD88/NF-κB/inflammatory cytokines/peritoneal adhesion may play key roles in the pathogenesis of PPA.Future studies are required to validate our findings.
基金Supported by the National Natural Science Foundation of China,No.81603529,81673982,and 81704084the Natural Science Foundation of the Jiangsu Higher Education Institutions,No.16KJB360002+3 种基金the Advantages of the Nursing Discipline Project of Jiangsu Province,No.2019YSHL005China Scholarship Council,No.201908320373the Jiangsu Government Scholarship for Overseas Studiesand the Qing Lan Project,No.014000773/2018-00376.
文摘BACKGROUND Post-traumatic stress disorder(PTSD)is a serious stress-related disorder.AIM To identify the key genes and pathways to uncover the potential mechanisms of PTSD using bioinformatics methods.METHODS Gene expression profiles were obtained from the Gene Expression Omnibus database.The differentially expressed genes(DEGs)were identified by using GEO2R.Gene functional annotation and pathway enrichment were then conducted.The gene-pathway network was constructed with Cytoscape software.Quantitative real-time polymerase chain reaction(qRT-PCR)analysis was applied for validation,and text mining by Coremine Medical was used to confirm the connections among genes and pathways.RESULTS We identified 973 DEGs including 358 upregulated genes and 615 downregulated genes in PTSD.A group of centrality hub genes and significantly enriched pathways(MAPK,Ras,and ErbB signaling pathways)were identified by using gene functional assignment and enrichment analyses.Six genes(KRAS,EGFR,NFKB1,FGF12,PRKCA,and RAF1)were selected to validate using qRT-PCR.The results of text mining further confirmed the correlation among hub genes and the enriched pathways.It indicated that these altered genes displayed functional roles in PTSD via these pathways,which might serve as key signatures in the pathogenesis of PTSD.CONCLUSION The current study identified a panel of candidate genes and important pathways,which might help us deepen our understanding of the underlying mechanism of PTSD at the molecular level.However,further studies are warranted to discover the critical regulatory mechanism of these genes via relevant pathways in PTSD.
基金the 2017 Wuhan Science and Technology Bureau Project(2017060201010222).
文摘Objective:The purpose of this study is to explore the effect of Hirudin on the farnesoid X receptor(FXR)pathway during acute intrahepatic cholestasis in vivo and in vitro.Method:In vivo,sixty male Sprague-Dawley rats were randomly divided into six groups:regular group,model group,ursodeoxycholic acid(UDCA)group(60 mg/kg),hirudin treatment group(84 u/kg),hirudin treatment group(63 u/kg)and hirudin treatment group(42 u/kg).The male Sprague-Dawley rats of UDCA group were intragastrically administered with a corresponding concentration of 0.005 mL/g body weight for seven days,once a day;and the hirudin treatment group was injected subcutaneously with different concentrations of Hirudin for seven days,once a day;Except for the normal group,other groups of rats were given 100 mg/kg ANIT by gavage on the 5th day.The model was administered by gavage once a day for three days.In vitro,(Z)-Guggulsterone was used to stimulate the L02 cells(0.05μmol/ml),with or without different concentrations of Hirudin(2,4 and 8 u/ml)for 24 h.The liver tissue was examined by HE microscope and the pathological state of the rat liver was observed;FXR,Small heterodimeric chaperone receptor(SHP),uridine diphosphate glucuronide transfer 2B4(UGT2B4),bile salt output pump(BSEP)mRNA and protein expressions were tested by real-time fluorescent quantitative PCR and Western blot test.And immunohistochemistry(IHC)was used to analyze the expression of FXR.Results:Compared with the model group,the hirudin group can improve liver tissue damage,and promote FXR,SHP,BSEP and UGT2B4 proteins and mRNA expression in vivo and in vitro.Conclusion:Hirudin can alleviate intrahepatic cholestasis,reduce liver tissue damage.Hirudin can up-regulate the expression of FXR gene,promote the up-regulation of SHP,BSEP and UGT2B4 genes,and inhibit the cholestasis pathway to protect liver cells.The study may provide an effective drug for clinical treatment of intrahepatic cholestasis.
基金Supported by the National Natural Science Foundation of China(Nos.82174394,81673982,81704084)the Science and Technology Development Fund,Macao SAR(No.0121/2022/A3)+5 种基金the Faculty Research Grants of Macao University of Science and Technology(No.FRG-22-110-FC)the Natural Science Foundation of JiangsuProvince(No.BK20201401)the Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.KYCX21_1667)Chinese Medicine Technology Development Project of Jiangsu Province(No.QN202002)the Natural Science Foundation of Nanjing University of Chinese Medicine(No.NZY81704084)the Open Projects of the Discipline of Chinese Medicine of Nanjing University Supported by the Subject of Academic priority discipline of Jiangsu Higher Education Institutions(No.ZYX03KF63)。
文摘Postoperative adhesion(PA)is currently one of the most unpleasant complications following surgical procedures.Researchers have developed several new strategies to alleviate the formation of PA to a great extent,but so far,no single measure or treatment can meet the expectations and requirements of clinical patients needing complete PA prevention.Chinese medicine(CM)has been widely used for thousands of years based on its remarkable efficacy and indispensable advantages CM treatments are gradually being accepted by modern medicine.Therefore,this review summarizes the formating process of PA and the efficacy and action mechanism of CM treatments,including their pharmacological effects,therapeutic mechanisms and advantages in PA prevention.We aim to improve the understanding of clinicians and researchers on CM prevention in the development of PA and promote the in-depth development and industrialization process of related drugs.
基金Supported by National Natural Science Foundation of China(No.81704011)Special Scientific Research Project of National Traditional Chinese Medicine Clinical Research Base of Henan Provincial Health Commission(No.2019JDZX2026)。
文摘Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3(NLRP3)is an intracellular sensor that detects endogenous danger signals and environmental irritants to assemble into the NLRP3 inflammasome.Activation of the NLRP3 inflammasome leads to the secretion of the proinflammatory cytokines interleutkin(IL)-1β and IL-18 and induces pyroptosis.Recent studies have shown that the NLRP3 inflammasome participates in the initiation and progression of diabetic atherosclerosis through pathological mechanisms such as β-cell dysfunction,insulin resistance,endothelial cell dysfunction,monocyte adhesion and infiltration,and smooth muscle cell proliferation and migration.In diabetic atherosclerosis,Chinese medicine has been proven effective for the inflammatory response mediated by the NLRP3 inflammasome.This review summarizes the latest progress on the NLRP3 inflammasome in the pathogenesis and potential Chinese medicine treatment of diabetic atherosclerosis.