Marsdenia tenacissima extract(MTE, trade name: Xiao-Ai-Ping injection) is an extract of a single Chinese plant medicine. It has been used for the treatment of cancer in China for decades, especially for esophageal can...Marsdenia tenacissima extract(MTE, trade name: Xiao-Ai-Ping injection) is an extract of a single Chinese plant medicine. It has been used for the treatment of cancer in China for decades, especially for esophageal cancer and other cancers in the digestive tract. In the present study, the potential mechanism for MTE's activity in esophageal cancer was explored. The effects of MTE on the proliferation of human esophageal cancer cells(KYSE150 and Eca-109) were investigated by the MTT assay, the Brd U(bromodeoxyuridine) incorporation immunofluorescence assay, and flow cytometric analysis. MTE inhibited cell proliferation through inducing G0/G1 cell cycle arrest in KYSE150 and Eca-109. Western blot analysis was employed to determine protein levels in the MTE treated cells. Compared with the control cells, the expression levels of the cell cycle regulatory proteins cyclin D1/D2/D3, cyclin E1, CDK2/4/6(CDK: cyclin dependent kinase), and p-Rb were decreased significantly in the cells treated with MTE at 40 mg·m L-1. In addition, MTE had an inhibitory effect on the MAPK(mitogen-activated protein kinase) signal transduction pathway, including ERK(extracellular signal-regulated kinase), JNK(c-Jun N-terminal kinase), and p38 MAPK. Moreover, MTE showed little additional effects on the regulation of cyclin D1/D3, CDK4/6, and p-Rb when the ERK pathway was already inhibited by the specific ERK inhibitor U0126. In conclusion, these data suggest that MTE inhibits human esophageal cancer cell proliferation through regulation of cell cycle regulatory proteins and the MAPK signaling pathways, which is probably mediated by the inhibition of ERK activation.展开更多
Objective：To investigate the action of Shen-Fu Injection（参附注射液,SFI） in regulating the expression of the serum complements and inflammatory cytokines synthesized and released in response to the stress of global...Objective：To investigate the action of Shen-Fu Injection（参附注射液,SFI） in regulating the expression of the serum complements and inflammatory cytokines synthesized and released in response to the stress of global ischemia accompanying cardiac arrest（CA） and resuscitation.Methods：Thirty pigs were randomly divided into the sham（n=6） and 3 returns of spontaneous circulation（ROSC） groups（n=24）.After 8-min untreated ventricular fibrillation and 2-min basic life support,24 pigs of the ROSC groups were randomized into three groups（n=8 per group）,which received central venous injection of SFI（SFI group）,epinephrine（EP group）,or saline（SA group）.Hemodynamic status and blood samples were obtained at 0,0.5,1,2,4,6,12,and 24 h after ROSC.Results：Serum concentrations of specific activation markers of the complement system C3,C4 and C5b-9 were increased during cardiopulmonary resuscitation th rough1 24 h after ROSC.There were intense changes of various pro-inflammatory cytokines and anti-inflammatory cytokines as early as 0.5 h after CA.Compared with the EP and SA groups,SFI treatment reduced the proinflammatory cytokines levels of interleukin（IL）-6,IL-8and tumor necrosis factor α（TNF-α,P〈0.05）,and increased the anti-inflammatory cytokine levels of IL-4 and IL-10（P〈0.05）.Further,SFI treatment decreased the values of C3,C4 and C5b-9 compared with the EP and SA groups.Conclusions：SFI,derived from the ancient Chinese medicine,has significant effects in attenuating post-resuscitation immune dysfunction by modulating the expression of complements and cytokines levels.The current study provided an experimental basis for the clinical application of a potential pharmacologic target for post resuscitation immune dysfunction.展开更多
Background:The optimal time to save a person who has had a sudden cardiac arrest is within the first few minutes of the incident.Early compression and early defibrillation should be performed at this time.Timeliness i...Background:The optimal time to save a person who has had a sudden cardiac arrest is within the first few minutes of the incident.Early compression and early defibrillation should be performed at this time.Timeliness is the key to successful CPR; as such,Prof.He proposed the 'platinum 10 min' system to study early CPR issues.This paper systematically evaluates the success rates of heartbeat restoration within the 'platinum 10min' among patients suffering from sudden cardiac arrest.Methods:The clinical data of outpatients suffering from a cardiac arrest were retrieved from the China Knowledge Network(January 1975-January 2015),the Chongqing VIP database(January 1989-January 2015),and the Wanfang database(January 1990-January 2015).The success of the cardiopulmonary resuscitation(CPR) performed at different times after the patients had cardiac arrests was analyzed.Two researchers screened the literature and extracted the data independently.A meta-analysis was conducted using Stata 12.0.A total of 57 papers met the inclusion criteria,including 29,269 patients.Of these patients,1,776 had their heartbeats successfully restored.The results showed high heterogeneity(χ~2=3428.85,P<0.01,I2=98.4%).The meta-analysis was conducted using a random-effects model.The combined effect size was 0.171(0.144-0.199).Results:1) The success rate of heartbeat restoration did not differ among the four emergency treatment methods that patients received:the methods described in the 2000 Guidelines for CPR and Emergency Cardiovascular Care,that described in the 2005 version,2010 version,and another CPR method.2) The patients were divided into five groups based on the time when CPR was performed:the ?1min group,the 1-5min group,the 5-10 min group,the 10-15 min group and the >15min group.The CPR success rates of these five groups were 0.247(0.15-0.344),0.353(0.250-0.456),0.136(0.109-0.163),0.058(0.041-0.075),and 0.011(0.004-0.019),respectively.The CPR success rates did not differ between the patients in the ?1min group and the 1-5min group.Thi展开更多
BACKGROUND: This meta-analysis aimed to determine whether extracorporeal cardiopulmonary resuscitation(ECPR), compared with conventional cardiopulmonary resuscitation(CCPR), improves outcomes in adult patients with ca...BACKGROUND: This meta-analysis aimed to determine whether extracorporeal cardiopulmonary resuscitation(ECPR), compared with conventional cardiopulmonary resuscitation(CCPR), improves outcomes in adult patients with cardiac arrest(CA).DATA RESOURCES: Pub Med, EMBASE, Web of Science, and China Biological Medicine Database were searched for relevant articles. The baseline information and outcome data(survival, good neurological outcome at discharge, at 3–6 months, and at 1 year after CA) were collected and extracted by two authors. Pooled risk ratios(RRs) and 95% confidence intervals(CIs) were calculated using Review Manager 5.3.RESULTS: In six studies 2 260 patients were enrolled to study the survival rate to discharge and longterm neurological outcome published since 2000. A signi? cant effect of ECPR was observed on survival rate to discharge compared to CCPR in CA patients(RR 2.37, 95%CI 1.63–3.45, P<0.001), and patients who underwent ECPR had a better long-term neurological outcome than those who received CCPR(RR 2.79, 95%CI 1.96–3.97, P<0.001). In subgroup analysis, there was a significant difference in survival to discharge favoring ECPR over CCPR group in OHCA patients(RR 2.69, 95%CI 1.48–4.91, P=0.001). However, no signi? cant difference was found in IHCA patients(RR 1.84, 95%CI 0.91–3.73, P=0.09).CONCLUSION: ECPR showed a bene? cial effect on survival rate to discharge and long-term neurological outcome over CCPR in adult patients with CA.展开更多
Postresuscitation myocardial dysfunction is reversible heart failure and B-type natriuretic peptide （BNP） is a biochemical marker of ventricular disorders secreted from ventricle, which can be used to assess the sta...Postresuscitation myocardial dysfunction is reversible heart failure and B-type natriuretic peptide （BNP） is a biochemical marker of ventricular disorders secreted from ventricle, which can be used to assess the status of left ventricular function. This study investigated the effect of β-adrenergic blocker on concentration of BNP and cardiac function after cardiopulmonary resuscitation in rabbits.展开更多
Hypoxia plays an important role in the genesis and progression of renal fibrosis.The underlying mechanisms, however, have not been sufficiently elucidated. We examined the role of p53 in hypoxia-induced renal fibrosis...Hypoxia plays an important role in the genesis and progression of renal fibrosis.The underlying mechanisms, however, have not been sufficiently elucidated. We examined the role of p53 in hypoxia-induced renal fibrosis in cell culture (human and rat renal tubular epithelial cells) and a mouse unilateral ureteral obstruction (UUO) model. Cell cycle of tubular cells was determined by flow cytometry, and the expression of profibrogenic factors was determined by RT-PCR, immunohistochemistry, and western blotting. Chromatin immunoprecipitation and luciferase reporter experiments were performed to explore the effect of HIF-lα on p53 expression. We showed that, in hypoxic tubular cells, p53 upregulation suppressed the expression of CDK1 and cyclins Bl and DI, leading to cell cycle (G2/M) arrest (or delay) and higher expression of TGF-β, CTGF, collagens, and fibronectin. p53 suppression by siRNA or by a specific p53 inhibitor (PIF-α) triggered opposite effects preventing the G2/M arrest and profibrotic changes. In vivo experiments in the UUO model revealed similar antifibrotic results following intraperitoneal administration of PIF-α(2.2 mg/kg). Using gain-of-function, loss-of-function, and luciferase assays, we further identified an HRE3 region on the p53 promoter as the HIF-lα-binding site. The HIF-la-HRE3 binding resulted in a sharp transcriptional activation of p53. Collectively, we show the presence of a hypoxia-activated, p53-responsive profibrogenic pathway in the kidney. During hypoxia, p53 upregulation induced by HIF-la suppresses cell cycle progression, leading to the accumulation of G2/M cells, and activates profibrotic TGF-β and CTGF-mediated signaling pathways, causing extracellular matrix production and renal fibrosis.展开更多
Objective： To study the mechanisms in gambogic acid （GA） -induced JeKo-1 human Mantle Cell Lymphoma cell apoptosis in vitro. Methods： The proliferation of GA-treated JeKo-1 cells was measured by CCK-8 assay and Ki...Objective： To study the mechanisms in gambogic acid （GA） -induced JeKo-1 human Mantle Cell Lymphoma cell apoptosis in vitro. Methods： The proliferation of GA-treated JeKo-1 cells was measured by CCK-8 assay and Ki-67 immunocytochemical detection. Apopt0sis, cell cycle and mitochondrial membrane potential were measured by flow cytometric analysis. Caspase-3, -8 and -9 were detected by colorimetric assay. Bcl-2 and Bax were analyzed by Western blotting. Results： GA inhibited cell growth in a time- and dose- dependent manner. GA induces apoptosis in JeKo- 1 cells but not in normal bone marrow cells, which was involved in reducing the membrane potential of mitochondria, activating caspases-3, -8 and -9 and decreasing the ratio of Bd-2 and Bax without cell cycle arresting. Conclusions： GA induced apoptosis in human MCL JeKo-1 cells by regulating Bcl-2/Bax and activating caspase-3, -8 and -9 via mitochondrial pathway without affecting cell cycle.展开更多
基金financially supported by National Natural Science Foundation of China(Nos.81302794,81071841,81102853)the Study of Marsdenia tenacissima extract(MTE):Study on quality control of antitumor traditional Chinese medicine Xiao-Ai-Ping injection(No.2011ZX09201-201)
文摘Marsdenia tenacissima extract(MTE, trade name: Xiao-Ai-Ping injection) is an extract of a single Chinese plant medicine. It has been used for the treatment of cancer in China for decades, especially for esophageal cancer and other cancers in the digestive tract. In the present study, the potential mechanism for MTE's activity in esophageal cancer was explored. The effects of MTE on the proliferation of human esophageal cancer cells(KYSE150 and Eca-109) were investigated by the MTT assay, the Brd U(bromodeoxyuridine) incorporation immunofluorescence assay, and flow cytometric analysis. MTE inhibited cell proliferation through inducing G0/G1 cell cycle arrest in KYSE150 and Eca-109. Western blot analysis was employed to determine protein levels in the MTE treated cells. Compared with the control cells, the expression levels of the cell cycle regulatory proteins cyclin D1/D2/D3, cyclin E1, CDK2/4/6(CDK: cyclin dependent kinase), and p-Rb were decreased significantly in the cells treated with MTE at 40 mg·m L-1. In addition, MTE had an inhibitory effect on the MAPK(mitogen-activated protein kinase) signal transduction pathway, including ERK(extracellular signal-regulated kinase), JNK(c-Jun N-terminal kinase), and p38 MAPK. Moreover, MTE showed little additional effects on the regulation of cyclin D1/D3, CDK4/6, and p-Rb when the ERK pathway was already inhibited by the specific ERK inhibitor U0126. In conclusion, these data suggest that MTE inhibits human esophageal cancer cell proliferation through regulation of cell cycle regulatory proteins and the MAPK signaling pathways, which is probably mediated by the inhibition of ERK activation.
基金Supported by the National Natural Science Foundation of China(No.81372025)
文摘Objective：To investigate the action of Shen-Fu Injection（参附注射液,SFI） in regulating the expression of the serum complements and inflammatory cytokines synthesized and released in response to the stress of global ischemia accompanying cardiac arrest（CA） and resuscitation.Methods：Thirty pigs were randomly divided into the sham（n=6） and 3 returns of spontaneous circulation（ROSC） groups（n=24）.After 8-min untreated ventricular fibrillation and 2-min basic life support,24 pigs of the ROSC groups were randomized into three groups（n=8 per group）,which received central venous injection of SFI（SFI group）,epinephrine（EP group）,or saline（SA group）.Hemodynamic status and blood samples were obtained at 0,0.5,1,2,4,6,12,and 24 h after ROSC.Results：Serum concentrations of specific activation markers of the complement system C3,C4 and C5b-9 were increased during cardiopulmonary resuscitation th rough1 24 h after ROSC.There were intense changes of various pro-inflammatory cytokines and anti-inflammatory cytokines as early as 0.5 h after CA.Compared with the EP and SA groups,SFI treatment reduced the proinflammatory cytokines levels of interleukin（IL）-6,IL-8and tumor necrosis factor α（TNF-α,P〈0.05）,and increased the anti-inflammatory cytokine levels of IL-4 and IL-10（P〈0.05）.Further,SFI treatment decreased the values of C3,C4 and C5b-9 compared with the EP and SA groups.Conclusions：SFI,derived from the ancient Chinese medicine,has significant effects in attenuating post-resuscitation immune dysfunction by modulating the expression of complements and cytokines levels.The current study provided an experimental basis for the clinical application of a potential pharmacologic target for post resuscitation immune dysfunction.
文摘Background:The optimal time to save a person who has had a sudden cardiac arrest is within the first few minutes of the incident.Early compression and early defibrillation should be performed at this time.Timeliness is the key to successful CPR; as such,Prof.He proposed the 'platinum 10 min' system to study early CPR issues.This paper systematically evaluates the success rates of heartbeat restoration within the 'platinum 10min' among patients suffering from sudden cardiac arrest.Methods:The clinical data of outpatients suffering from a cardiac arrest were retrieved from the China Knowledge Network(January 1975-January 2015),the Chongqing VIP database(January 1989-January 2015),and the Wanfang database(January 1990-January 2015).The success of the cardiopulmonary resuscitation(CPR) performed at different times after the patients had cardiac arrests was analyzed.Two researchers screened the literature and extracted the data independently.A meta-analysis was conducted using Stata 12.0.A total of 57 papers met the inclusion criteria,including 29,269 patients.Of these patients,1,776 had their heartbeats successfully restored.The results showed high heterogeneity(χ~2=3428.85,P<0.01,I2=98.4%).The meta-analysis was conducted using a random-effects model.The combined effect size was 0.171(0.144-0.199).Results:1) The success rate of heartbeat restoration did not differ among the four emergency treatment methods that patients received:the methods described in the 2000 Guidelines for CPR and Emergency Cardiovascular Care,that described in the 2005 version,2010 version,and another CPR method.2) The patients were divided into five groups based on the time when CPR was performed:the ?1min group,the 1-5min group,the 5-10 min group,the 10-15 min group and the >15min group.The CPR success rates of these five groups were 0.247(0.15-0.344),0.353(0.250-0.456),0.136(0.109-0.163),0.058(0.041-0.075),and 0.011(0.004-0.019),respectively.The CPR success rates did not differ between the patients in the ?1min group and the 1-5min group.Thi
文摘BACKGROUND: This meta-analysis aimed to determine whether extracorporeal cardiopulmonary resuscitation(ECPR), compared with conventional cardiopulmonary resuscitation(CCPR), improves outcomes in adult patients with cardiac arrest(CA).DATA RESOURCES: Pub Med, EMBASE, Web of Science, and China Biological Medicine Database were searched for relevant articles. The baseline information and outcome data(survival, good neurological outcome at discharge, at 3–6 months, and at 1 year after CA) were collected and extracted by two authors. Pooled risk ratios(RRs) and 95% confidence intervals(CIs) were calculated using Review Manager 5.3.RESULTS: In six studies 2 260 patients were enrolled to study the survival rate to discharge and longterm neurological outcome published since 2000. A signi? cant effect of ECPR was observed on survival rate to discharge compared to CCPR in CA patients(RR 2.37, 95%CI 1.63–3.45, P<0.001), and patients who underwent ECPR had a better long-term neurological outcome than those who received CCPR(RR 2.79, 95%CI 1.96–3.97, P<0.001). In subgroup analysis, there was a significant difference in survival to discharge favoring ECPR over CCPR group in OHCA patients(RR 2.69, 95%CI 1.48–4.91, P=0.001). However, no signi? cant difference was found in IHCA patients(RR 1.84, 95%CI 0.91–3.73, P=0.09).CONCLUSION: ECPR showed a bene? cial effect on survival rate to discharge and long-term neurological outcome over CCPR in adult patients with CA.
基金This study was supported by a grant from the Natural Science Foundation of Gansu Province (No.YS-011-A23-19).
文摘Postresuscitation myocardial dysfunction is reversible heart failure and B-type natriuretic peptide （BNP） is a biochemical marker of ventricular disorders secreted from ventricle, which can be used to assess the status of left ventricular function. This study investigated the effect of β-adrenergic blocker on concentration of BNP and cardiac function after cardiopulmonary resuscitation in rabbits.
文摘Hypoxia plays an important role in the genesis and progression of renal fibrosis.The underlying mechanisms, however, have not been sufficiently elucidated. We examined the role of p53 in hypoxia-induced renal fibrosis in cell culture (human and rat renal tubular epithelial cells) and a mouse unilateral ureteral obstruction (UUO) model. Cell cycle of tubular cells was determined by flow cytometry, and the expression of profibrogenic factors was determined by RT-PCR, immunohistochemistry, and western blotting. Chromatin immunoprecipitation and luciferase reporter experiments were performed to explore the effect of HIF-lα on p53 expression. We showed that, in hypoxic tubular cells, p53 upregulation suppressed the expression of CDK1 and cyclins Bl and DI, leading to cell cycle (G2/M) arrest (or delay) and higher expression of TGF-β, CTGF, collagens, and fibronectin. p53 suppression by siRNA or by a specific p53 inhibitor (PIF-α) triggered opposite effects preventing the G2/M arrest and profibrotic changes. In vivo experiments in the UUO model revealed similar antifibrotic results following intraperitoneal administration of PIF-α(2.2 mg/kg). Using gain-of-function, loss-of-function, and luciferase assays, we further identified an HRE3 region on the p53 promoter as the HIF-lα-binding site. The HIF-la-HRE3 binding resulted in a sharp transcriptional activation of p53. Collectively, we show the presence of a hypoxia-activated, p53-responsive profibrogenic pathway in the kidney. During hypoxia, p53 upregulation induced by HIF-la suppresses cell cycle progression, leading to the accumulation of G2/M cells, and activates profibrotic TGF-β and CTGF-mediated signaling pathways, causing extracellular matrix production and renal fibrosis.
基金supported by a grant from the Key Project supported by medical science and technology development Foundation of Nanjing Department of Health (No. ZKX09016)
文摘Objective： To study the mechanisms in gambogic acid （GA） -induced JeKo-1 human Mantle Cell Lymphoma cell apoptosis in vitro. Methods： The proliferation of GA-treated JeKo-1 cells was measured by CCK-8 assay and Ki-67 immunocytochemical detection. Apopt0sis, cell cycle and mitochondrial membrane potential were measured by flow cytometric analysis. Caspase-3, -8 and -9 were detected by colorimetric assay. Bcl-2 and Bax were analyzed by Western blotting. Results： GA inhibited cell growth in a time- and dose- dependent manner. GA induces apoptosis in JeKo- 1 cells but not in normal bone marrow cells, which was involved in reducing the membrane potential of mitochondria, activating caspases-3, -8 and -9 and decreasing the ratio of Bd-2 and Bax without cell cycle arresting. Conclusions： GA induced apoptosis in human MCL JeKo-1 cells by regulating Bcl-2/Bax and activating caspase-3, -8 and -9 via mitochondrial pathway without affecting cell cycle.
