Background:The interrelation between intestinal polyps,metabolic syndrome(MetS),and colorectal cancer(CRC)is a critical area of study.This research focuses on pinpointing potential molecular targets to understand the ...Background:The interrelation between intestinal polyps,metabolic syndrome(MetS),and colorectal cancer(CRC)is a critical area of study.This research focuses on pinpointing potential molecular targets to understand the link between intestinal polyp formation,metabolic irregularities,and CRC progression.Methods:We examined clinical samples from patients with intestinal polyps coexisting with MetS and compared them with samples from patients with standard intestinal polyps.Transcriptome sequencing and public database analysis were employed to identify significant pathways and genes.These targets were then validated through immunohistochemistry(IHC).Following the RNA interference of key target expression,a series of experiments,including the cell counting kit-8 assay,colony formation,wound healing,and Transwell assays,were conducted.Results:Comparative analysis revealed 75 up-regulated and 61 down-regulated differentially expressed genes(DEGs)in the MetS polyp group vs.the control.Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment suggested these DEGs were primarily associated with cell cycle and mitosis.Integration with comparative toxicogenomics database(CTD)and the cancer genome atlas(TCGA)databases highlighted 44 key CRC-related genes.Protein interaction networks indicated connections of purkinje cell protein 4(PCP4),olfactomedin 1(OLFM1),fibronectin 1(FN1),and transforming growth factor beta 3(TGF-β3)with the mitogen-activated protein kinase(MAPK)pathway.Tumor correlation studies suggested higher risk associations with FN1,PCP4,and TGF-β3,while OLFM1 was identified as a lower risk gene.Immunohistochemical analysis revealed a decrease in OLFM1 in MetS-associated intestinal polyps.Upon interference with OLFM1 in polyp epithelial cells,there was a significant enhancement in cell proliferation,colony formation,and cell migration and invasion capabilities.Conclusion:Our study highlights a significant decrease in OLFM1 expression in MetS-associated intestinal polyps.And,this reduction in OLFM1 is associated with enhanced cell proliferation,colony formation,and increased cell migration and invasion capabilities.These findings underscore the reduced OLFM1 expression in MetS-associated intestinal polyps may play a crucial role in promoting tumorigenic processes in colorectal pathology.Further research on OLFM1 may provide valuable insights into understanding and targeting MetS-associated intestinal polyps.展开更多
We previously reported that postsynaptic density-93 mediates neuron-microglia crosstalk by interacting with amino acids 357–395 of C-X3-C motif chemokine ligand 1(CX3 CL1) to induce microglia polarization. More impor...We previously reported that postsynaptic density-93 mediates neuron-microglia crosstalk by interacting with amino acids 357–395 of C-X3-C motif chemokine ligand 1(CX3 CL1) to induce microglia polarization. More importantly, the peptide Tat-CX3 CL1(comprising amino acids 357–395 of CX3 CL1) disrupts the interaction between postsynaptic density-93 and CX3 CL1, reducing neurological impairment and exerting a protective effect in the context of acute ischemic stroke. However, the mechanism underlying these effects remains unclear. In the current study, we found that the pro-inflammatory M1 phenotype increased and the anti-inflammatory M2 phenotype decreased at different time points. The M1 phenotype increased at 6 hours after stroke and peaked at 24 hours after perfusion, whereas the M2 phenotype decreased at 6 and 24 hours following reperfusion. We found that the peptide Tat-CX3 CL1(357–395 aa) facilitates microglial polarization from M1 to M2 by reducing the production of soluble CX3 CL1. Furthermore, the a disintegrin and metalloprotease domain 17(ADAM17) inhibitor GW280264 x, which inhibits metalloprotease activity and prevents CX3 CL1 from being sheared into its soluble form, facilitated microglial polarization from M1 to M2 by inhibiting soluble CX3 CL1 formation. Additionally, Tat-CX3 CL1(357–395 aa) attenuated long-term cognitive deficits and improved white matter integrity as determined by the Morris water maze test at 31–34 days following surgery and immunofluorescence staining at 35 days after stroke, respectively. In conclusion, Tat-CX3 CL1(357–395 aa) facilitates functional recovery after ischemic stroke by promoting microglial polarization from M1 to M2. Therefore, the Tat-CX3 CL1(357–395 aa) is a potential therapeutic agent for ischemic stroke.展开更多
Background:Patients with colon cancer who receive chemotherapy usually experience various gastrointestinal adverse reactions,including nausea,vomiting,and diarrhea,which make it challenging for them to adhere to treat...Background:Patients with colon cancer who receive chemotherapy usually experience various gastrointestinal adverse reactions,including nausea,vomiting,and diarrhea,which make it challenging for them to adhere to treatment.As an effective traditional Chinese medicine,the Jianpi Bushen formula has been widely used to alleviate the side effects of chemotherapy.Objective:To evaluate the efficacy and safety of Jianpi Bushen formulae for patients who undergo chemotherapy.This statistical analysis plan(SAP)is intended to enhance the transparency and research quality of our randomized controlled trial.Methods:Our study is a multicenter,double-blind,randomized controlled clinical trial.This trial aimed to compare the completion rate of chemotherapy in colon cancer patients who are using and not using Jianpi Bushen formula.To attenuate possible selection bias in the final report,we declared the overall trial design,outcome measures,subgroup analyses,and safety measures.Also,we described the data management and statistical analysis methods in detail.Conclusion:The SAP provides more detailed information than the trial protocol for data management and statistical analysis methods.Further post-hoc analyses can be performed by referring to the SAP,and possible selection bias can be attenuated.展开更多
As a two-dimensional(2D)material,monolayer MoS2which limits its optical applications has a low absorption efficiency.In this paper,we propose a three-band perfect metamaterial absorber in the visible light range based...As a two-dimensional(2D)material,monolayer MoS2which limits its optical applications has a low absorption efficiency.In this paper,we propose a three-band perfect metamaterial absorber in the visible light range based on monolayer MoS_(2).The peak absorptivity of the structure at each resonance wavelength is nearly perfect,moreover,the light absorption of monolayer MoS2is obviously enhanced at the three resonant wavelengths.The dielectric–dielectric–metal structure we designed produces the coupling of Fabry–Perot resonance and high-order diffraction guided-mode resonance at different absorption peaks,which has been proved by the slab waveguide theory.In addition,the multi-modal absorption phenomenon is explained by extracting the equivalent impedance.The results show that we can adjust the absorption peak wavelength by regulating the parameters of the structure.This structure not only provides an idea for enhancing the interaction between light and two-dimensional materials but also has potential applications for optical detection devices.展开更多
AIM:To investigate the prevalence of minimal hepatic encephalopathy(MHE)and to assess corresponding health-related quality of life(HRQoL)in hospitalized cirrhotic patients in China.METHODS:This multi-center cross-sect...AIM:To investigate the prevalence of minimal hepatic encephalopathy(MHE)and to assess corresponding health-related quality of life(HRQoL)in hospitalized cirrhotic patients in China.METHODS:This multi-center cross-sectional study included 16 teaching hospitals,which were members of "Hepatobiliary Cooperation Group,Society of Gastroenterology,Chinese Medical Association",from different areas of China carried out between June and October in 2011.All the eligible hospitalized cirrhotic patients(n = 538)were required to complete triplicate number connection tests combined with one digit symbol test for diagnosing MHE.Patients' clinical examination data were complemented by a modified questionnaire assessing HRQoL.Written informed consent was obtained from each patient.RESULTS:Male was predominant(68.6%)in 519 patients who met the criteria of the study,with a mean age of 49.17 ± 11.02 years.The most common cause of liver cirrhosis was chronic hepatitis B(55.9%).The prevalence of MHE was 39.9% and varied by ChildPugh-Classification score(CPC-A:24.8%,CPC-B:39.4% and CPC-C:56.1%,P < 0.01).MHE(P < 0.01)and higher CPC scores(P < 0.01)were associated with a high HRQoL scores(reflecting poorer quality of life).The prevalence of MHE was proportionate to CPC(P = 0.01)and high quality of life scores(P = 0.01).CONCLUSION:Hospitalized cirrhotic patients have a high prevalence of MHE that is proportionate to the degree of liver function and HRQoL impairment.展开更多
AIM:To investigate the effect of the demethylating reagent 5-aza-2'-deoxycitidine(DAC) on telomerase activity in hepatocellular carcinoma(HCC) cell lines,SMMC-7721 and HepG2.METHODS:The related gene expression in ...AIM:To investigate the effect of the demethylating reagent 5-aza-2'-deoxycitidine(DAC) on telomerase activity in hepatocellular carcinoma(HCC) cell lines,SMMC-7721 and HepG2.METHODS:The related gene expression in cell lines was examined by real-time reverse transcription-polymerase chain reaction and Western blotting analysis.The telomerase activity was examined by telomeric repeat amplification protocol-enzyme-linked immunosorbent assay and DNA methylation was determined by methylation-specific polymerase chain reaction.RESULTS:The telomerase activity was significantly reduced in both cell lines treated with DAC,accompanied by downregulation of telomerase reverse transcriptase(hTERT).We also observed the effect of DAC on the methylation status of hTERT promoter and the expression of regulatory genes,such as c-myc,p15,p16,p21,E2F1,and WT1.The methylation status of hTERT promoter could be reversed in SMMC-7721 by DAC,but not in HepG2 cells.However,p16 expression could be reactivated by demethylation of its promoter,and c-Myc expression was repressed in both cell lines.Moreover,DAC could enhance the sensitivity to the chemotherapeutic agents,such as cisplatin,by induction of apoptosis of HCC cells.CONCLUSION:The DAC exerts its anti-tumor effects in HCC cells by inhibiting the telomerase activity.展开更多
Background: Percutaneous radiofrequency ablation(RFA) is a first?line treatment for very?early?stage hepatocellular carcinoma(HCC), whereas the efficacy of percutaneous microwave ablation(MWA) for very?early?stage HCC...Background: Percutaneous radiofrequency ablation(RFA) is a first?line treatment for very?early?stage hepatocellular carcinoma(HCC), whereas the efficacy of percutaneous microwave ablation(MWA) for very?early?stage HCC remains unclear. The purpose of this study was to clarify this issue by comparing the safety and efficacy of percutaneous MWA with percutaneous RFA in treating very?early?stage HCC.Methods: Clinical data of 460 patients who were diagnosed with very?early?stage HCC and treated with percutane?ous MWA or RFA between January 2007 and July 2012 at the Eastern Hepatobiliary Surgery Hospital, The Second Mili?tary Medical University, in Shanghai, China were retrospectively analyzed. Of these 460 patients, 159 received RFA, 301 received MWA. Overall survival(OS), recurrence?free survival(RFS), local tumor progression(LTP), complete ablation, and complication occurrence rates were compared between the two groups, and the prognostic factors associated with survival were analyzed.Results: No significant differences were observed between the two groups in terms of the 1?, 3?, or 5?year OS rates(99.3%, 90.4%, and 78.3% for MWA vs. 98.7%, 86.8%, and 73.3% for RFA, respectively; P = 0.331). Furthermore, no signif?icant differences were observed between the two groups in terms of the corresponding RFS rates(94.4%, 71.8%, and 46.9% for MWA vs. 89.9%, 67.3%, and 54.9% for RFA, respectively; P ete ablation rates(98.3% vs. 98.1%, P = 0.309), the LTP rates(9.6% vs. 10.1%, P = 0.883), the compl multivariate analysis, LTP, an= 0.860), or the occurrence rates of major complications(0.7% vs. 0.6%, P = 0.691). Bytiviral therapy, and treatment of recurrence were independent risk fac?tors for OS(P < 0.001), and the alpha?fetoprotein level was an independent prognostic factor for RFS(P = 0.002).Conclusions: MWA is as safe and effective as RFA in treating very?early?stage HCC, supporting MWA as a first?line treatment option for this disease.展开更多
An iterative learning control(ILC) algorithm using quantized error information is given in this paper for both linear and nonlinear discrete-time systems with stochastic noises. A logarithmic quantizer is used to guar...An iterative learning control(ILC) algorithm using quantized error information is given in this paper for both linear and nonlinear discrete-time systems with stochastic noises. A logarithmic quantizer is used to guarantee an adaptive improvement in tracking performance. A decreasing learning gain is introduced into the algorithm to suppress the effects of stochastic noises and quantization errors. The input sequence is proved to converge strictly to the optimal input under the given index. Illustrative simulations are given to verify the theoretical analysis.展开更多
Amyloid beta(Aβ)-induced neurotoxicity and oxidative stress plays an important role in the pathogenesis of Alzheimer’s disease(AD).ZL006 is shown to reduce over-produced nitric oxide and oxidative stress in ischemic...Amyloid beta(Aβ)-induced neurotoxicity and oxidative stress plays an important role in the pathogenesis of Alzheimer’s disease(AD).ZL006 is shown to reduce over-produced nitric oxide and oxidative stress in ischemic stroke by interrupting the interaction of neuronal nitric oxide synthase and postsynaptic density protein 95.However,few studies are reported on the role of ZL006 in AD.To investigate whether ZL006 exerted neuroprotective effects in AD,we used Aβ1–42 to treat primary cortical neurons and N2a neuroblastoma cells as an in vitro model of AD.Cortical neurons were incubated with ZL006 or dimethyl sulfoxide for 2 hours and treated with Aβ1–42 or NH3·H2O for another 24 hours.The results of cell counting Kit-8(CCK-8)assay and calcein-acetoxymethylester/propidium iodide staining showed that ZL006 pretreatment rescued the neuronal death induced by Aβ1–42.Fluorescence and western blot assay were used to detect oxidative stress and apoptosis-related proteins in each group of cells.Results showed that ZL006 pretreatment decreased neuronal apoptosis and oxidative stress induced by Aβ1–42.The results of CCK8 assay showed that inhibition of Akt or NF-E2-related factor 2(Nrf2)in cortical neurons abolished the protective effects of ZL006.Moreover,similar results were also observed in N2a neuroblastoma cells.ZL006 inhibited N2a cell death and oxidative stress induced by Aβ1–42,while inhibition of Akt or Nrf2 abolished the protective effect of ZL006.These results demonstrated that ZL006 reduced Aβ1–42-induced neuronal damage and oxidative stress,and the mechanisms might be associated with the activation of Akt/Nrf2/heme oxygenase-1 signaling pathways.展开更多
BACKGROUND: Tongxinluo has been clinically proven to be effective in improving memory and cognitive function in patients with post-stroke vascular dementia. Is the mechanism related to the deposition of beta-amyloid ...BACKGROUND: Tongxinluo has been clinically proven to be effective in improving memory and cognitive function in patients with post-stroke vascular dementia. Is the mechanism related to the deposition of beta-amyloid peptide (A β ) in hippocampus? OBJECTIVE: To observe the effect of Tongxinluo on cognitive impairment in a mouse model with vascular dementia and the changes of A β deposition and β -secretase 1 (BACE1) expression. DESIGN: Randomized controlled study. SETTING: State Key Laboratory of Pharmaceutical Biotechnology of Nanjing University and Affiliated Drum Tower Hospital of Nanjing University Medical School. MATERIALS: The experiment was carried out in the State Key Laboratory of Pharmaceutical Biotechnology of Nanjing University and Affiliated Drum Tower Hospital of Nanjing University Medical School from March 2006 to January 2007. A total of 36 healthy Kunming mice, 18 of each gender, were chosen. The study was conducted in accordance with the National Regulations of Experimental Animal Administration, and all animal experiments were approved by the Committee of Experimental Animal Administration of Nanjing University. Tongxinluo was provided by Shijiazhuang Yiling Pharmaceutical Co., Ltd. METHODS: All mice were randomly divided into 6 groups, including naive control (n=6), sham-operated control (n=6) and experimental groups treated with different doses of Tongxinluo (0.2, 0.4, and 0.6 g/kg/d; n=6 for each group) or vehicle (n=6). Five groups were subjected to bilateral common carotid arteries (2-VO) occlusion to produce a vascular dementia model (no occlusion was performed in sham-operated group). The mice in the Tongxinluo treatment groups were intragastricly administered daily with a Tongxinluo suspension (40 g/L in distilled water) at doses of 0.2, 0.4 or 0.6 g/kg/d from day 1 to day 30 post-surgery. The animals in vehicle, sham-operated and naive groups were administered an equal volume of distilled water. MAIN OUTCOME MEASURES: ①Escape latency time determined in all groups of mice before and after 2-VO occlusion by Morris water maze. ②Changes in BACEI mRNA expression in the hippocampi of mice among the six groups by RT-PCR assay, and BACEI and A β protein expression in the hippocampi of mice by Western blot. RESULTS: All 36 mice were involved in the final analysis.① No difference was detected in escape latency time to a hidden platform among all groups in water maze test before surgery (P 〉 0.05) At 30 days after 2-VO occlusion, the vehicle animals exhibited a significantly longer latency in finding the hidden platform compared to that of sham-operated and naive animals (P 〈 0.01). The prolonged escape latency was significantly reduced by oral administration of 0.4 g or 0.6 kg/day (P 〈 0.01, P 〈 0.05). BACEI mRNA and protein expression in vehicle animals were much higher than in sham-operated and naive animals (P 〈 0.01). The ischemia-induced increases in BACE1 mRNA and protein level were attenuated by all three doses of Tongxinluo treatment (P 〈 0.01), and the 0.4 g/kg/d treatment was the most effective. A β protein expression in vehicle animals after 2-VO occlusion were much higher than in sham-operated and naive animals (P 〈 0.01). 2-VO occlusion-induced A β generation was significantly attenuated by all doses of Tongxinluo treatment, with the most effective dose being 0.4 g/kg/d (P 〈 0.01). CONCLUSION: BACE1 mRNA levels and protein levels of BACEI and A β are reduced in the hippocampi of vascular dementia model mice by all three doses of Tongxinluo treatment, with the most effective dose being 0.4 g/kg/d. The results suggest that inhibition of post-ischemia BACEI expression and A β generation in brain might underlie Tongxinluo's effects in improving cognitive impairment.展开更多
基金This work was supported by Hospital Incubation Fund of the First Affiliated Hospital of Chongqing Medical and Pharmaceutical College(No.201704).
文摘Background:The interrelation between intestinal polyps,metabolic syndrome(MetS),and colorectal cancer(CRC)is a critical area of study.This research focuses on pinpointing potential molecular targets to understand the link between intestinal polyp formation,metabolic irregularities,and CRC progression.Methods:We examined clinical samples from patients with intestinal polyps coexisting with MetS and compared them with samples from patients with standard intestinal polyps.Transcriptome sequencing and public database analysis were employed to identify significant pathways and genes.These targets were then validated through immunohistochemistry(IHC).Following the RNA interference of key target expression,a series of experiments,including the cell counting kit-8 assay,colony formation,wound healing,and Transwell assays,were conducted.Results:Comparative analysis revealed 75 up-regulated and 61 down-regulated differentially expressed genes(DEGs)in the MetS polyp group vs.the control.Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment suggested these DEGs were primarily associated with cell cycle and mitosis.Integration with comparative toxicogenomics database(CTD)and the cancer genome atlas(TCGA)databases highlighted 44 key CRC-related genes.Protein interaction networks indicated connections of purkinje cell protein 4(PCP4),olfactomedin 1(OLFM1),fibronectin 1(FN1),and transforming growth factor beta 3(TGF-β3)with the mitogen-activated protein kinase(MAPK)pathway.Tumor correlation studies suggested higher risk associations with FN1,PCP4,and TGF-β3,while OLFM1 was identified as a lower risk gene.Immunohistochemical analysis revealed a decrease in OLFM1 in MetS-associated intestinal polyps.Upon interference with OLFM1 in polyp epithelial cells,there was a significant enhancement in cell proliferation,colony formation,and cell migration and invasion capabilities.Conclusion:Our study highlights a significant decrease in OLFM1 expression in MetS-associated intestinal polyps.And,this reduction in OLFM1 is associated with enhanced cell proliferation,colony formation,and increased cell migration and invasion capabilities.These findings underscore the reduced OLFM1 expression in MetS-associated intestinal polyps may play a crucial role in promoting tumorigenic processes in colorectal pathology.Further research on OLFM1 may provide valuable insights into understanding and targeting MetS-associated intestinal polyps.
基金supported by the National Natural Science Foundation of China,Nos. 82071304 (to QXZ), 81671149 (to QXZ),and 81971179 (to XML)the Natural Science Foundation of Jiangsu Province,Nos. BK20191463 (to XML) and BK20161167 (to QXZ)。
文摘We previously reported that postsynaptic density-93 mediates neuron-microglia crosstalk by interacting with amino acids 357–395 of C-X3-C motif chemokine ligand 1(CX3 CL1) to induce microglia polarization. More importantly, the peptide Tat-CX3 CL1(comprising amino acids 357–395 of CX3 CL1) disrupts the interaction between postsynaptic density-93 and CX3 CL1, reducing neurological impairment and exerting a protective effect in the context of acute ischemic stroke. However, the mechanism underlying these effects remains unclear. In the current study, we found that the pro-inflammatory M1 phenotype increased and the anti-inflammatory M2 phenotype decreased at different time points. The M1 phenotype increased at 6 hours after stroke and peaked at 24 hours after perfusion, whereas the M2 phenotype decreased at 6 and 24 hours following reperfusion. We found that the peptide Tat-CX3 CL1(357–395 aa) facilitates microglial polarization from M1 to M2 by reducing the production of soluble CX3 CL1. Furthermore, the a disintegrin and metalloprotease domain 17(ADAM17) inhibitor GW280264 x, which inhibits metalloprotease activity and prevents CX3 CL1 from being sheared into its soluble form, facilitated microglial polarization from M1 to M2 by inhibiting soluble CX3 CL1 formation. Additionally, Tat-CX3 CL1(357–395 aa) attenuated long-term cognitive deficits and improved white matter integrity as determined by the Morris water maze test at 31–34 days following surgery and immunofluorescence staining at 35 days after stroke, respectively. In conclusion, Tat-CX3 CL1(357–395 aa) facilitates functional recovery after ischemic stroke by promoting microglial polarization from M1 to M2. Therefore, the Tat-CX3 CL1(357–395 aa) is a potential therapeutic agent for ischemic stroke.
基金funded by the Key R&D project of the Ministry of Science and Technology,China(2017YFC1700604).
文摘Background:Patients with colon cancer who receive chemotherapy usually experience various gastrointestinal adverse reactions,including nausea,vomiting,and diarrhea,which make it challenging for them to adhere to treatment.As an effective traditional Chinese medicine,the Jianpi Bushen formula has been widely used to alleviate the side effects of chemotherapy.Objective:To evaluate the efficacy and safety of Jianpi Bushen formulae for patients who undergo chemotherapy.This statistical analysis plan(SAP)is intended to enhance the transparency and research quality of our randomized controlled trial.Methods:Our study is a multicenter,double-blind,randomized controlled clinical trial.This trial aimed to compare the completion rate of chemotherapy in colon cancer patients who are using and not using Jianpi Bushen formula.To attenuate possible selection bias in the final report,we declared the overall trial design,outcome measures,subgroup analyses,and safety measures.Also,we described the data management and statistical analysis methods in detail.Conclusion:The SAP provides more detailed information than the trial protocol for data management and statistical analysis methods.Further post-hoc analyses can be performed by referring to the SAP,and possible selection bias can be attenuated.
基金the Strategic Priority Research Program of Chinese Academy of Sciences(Grant No.XDB43010000)the National Natural Science Foundation of China(Grant Nos.61835011 and 12075244)+1 种基金Key Research Projects of the Frontier Science of the Chinese Academy of Sciences(Grant No.QYZDY-SSW-JSC004)the National Key Research and Development Program of China(Grant No.2020YFB2206103).
文摘As a two-dimensional(2D)material,monolayer MoS2which limits its optical applications has a low absorption efficiency.In this paper,we propose a three-band perfect metamaterial absorber in the visible light range based on monolayer MoS_(2).The peak absorptivity of the structure at each resonance wavelength is nearly perfect,moreover,the light absorption of monolayer MoS2is obviously enhanced at the three resonant wavelengths.The dielectric–dielectric–metal structure we designed produces the coupling of Fabry–Perot resonance and high-order diffraction guided-mode resonance at different absorption peaks,which has been proved by the slab waveguide theory.In addition,the multi-modal absorption phenomenon is explained by extracting the equivalent impedance.The results show that we can adjust the absorption peak wavelength by regulating the parameters of the structure.This structure not only provides an idea for enhancing the interaction between light and two-dimensional materials but also has potential applications for optical detection devices.
文摘AIM:To investigate the prevalence of minimal hepatic encephalopathy(MHE)and to assess corresponding health-related quality of life(HRQoL)in hospitalized cirrhotic patients in China.METHODS:This multi-center cross-sectional study included 16 teaching hospitals,which were members of "Hepatobiliary Cooperation Group,Society of Gastroenterology,Chinese Medical Association",from different areas of China carried out between June and October in 2011.All the eligible hospitalized cirrhotic patients(n = 538)were required to complete triplicate number connection tests combined with one digit symbol test for diagnosing MHE.Patients' clinical examination data were complemented by a modified questionnaire assessing HRQoL.Written informed consent was obtained from each patient.RESULTS:Male was predominant(68.6%)in 519 patients who met the criteria of the study,with a mean age of 49.17 ± 11.02 years.The most common cause of liver cirrhosis was chronic hepatitis B(55.9%).The prevalence of MHE was 39.9% and varied by ChildPugh-Classification score(CPC-A:24.8%,CPC-B:39.4% and CPC-C:56.1%,P < 0.01).MHE(P < 0.01)and higher CPC scores(P < 0.01)were associated with a high HRQoL scores(reflecting poorer quality of life).The prevalence of MHE was proportionate to CPC(P = 0.01)and high quality of life scores(P = 0.01).CONCLUSION:Hospitalized cirrhotic patients have a high prevalence of MHE that is proportionate to the degree of liver function and HRQoL impairment.
基金Supported by The National Natural Science Foundation of China,No.30901722,30973433,81000970,81030041,31171321 and 81101622
文摘AIM:To investigate the effect of the demethylating reagent 5-aza-2'-deoxycitidine(DAC) on telomerase activity in hepatocellular carcinoma(HCC) cell lines,SMMC-7721 and HepG2.METHODS:The related gene expression in cell lines was examined by real-time reverse transcription-polymerase chain reaction and Western blotting analysis.The telomerase activity was examined by telomeric repeat amplification protocol-enzyme-linked immunosorbent assay and DNA methylation was determined by methylation-specific polymerase chain reaction.RESULTS:The telomerase activity was significantly reduced in both cell lines treated with DAC,accompanied by downregulation of telomerase reverse transcriptase(hTERT).We also observed the effect of DAC on the methylation status of hTERT promoter and the expression of regulatory genes,such as c-myc,p15,p16,p21,E2F1,and WT1.The methylation status of hTERT promoter could be reversed in SMMC-7721 by DAC,but not in HepG2 cells.However,p16 expression could be reactivated by demethylation of its promoter,and c-Myc expression was repressed in both cell lines.Moreover,DAC could enhance the sensitivity to the chemotherapeutic agents,such as cisplatin,by induction of apoptosis of HCC cells.CONCLUSION:The DAC exerts its anti-tumor effects in HCC cells by inhibiting the telomerase activity.
文摘Background: Percutaneous radiofrequency ablation(RFA) is a first?line treatment for very?early?stage hepatocellular carcinoma(HCC), whereas the efficacy of percutaneous microwave ablation(MWA) for very?early?stage HCC remains unclear. The purpose of this study was to clarify this issue by comparing the safety and efficacy of percutaneous MWA with percutaneous RFA in treating very?early?stage HCC.Methods: Clinical data of 460 patients who were diagnosed with very?early?stage HCC and treated with percutane?ous MWA or RFA between January 2007 and July 2012 at the Eastern Hepatobiliary Surgery Hospital, The Second Mili?tary Medical University, in Shanghai, China were retrospectively analyzed. Of these 460 patients, 159 received RFA, 301 received MWA. Overall survival(OS), recurrence?free survival(RFS), local tumor progression(LTP), complete ablation, and complication occurrence rates were compared between the two groups, and the prognostic factors associated with survival were analyzed.Results: No significant differences were observed between the two groups in terms of the 1?, 3?, or 5?year OS rates(99.3%, 90.4%, and 78.3% for MWA vs. 98.7%, 86.8%, and 73.3% for RFA, respectively; P = 0.331). Furthermore, no signif?icant differences were observed between the two groups in terms of the corresponding RFS rates(94.4%, 71.8%, and 46.9% for MWA vs. 89.9%, 67.3%, and 54.9% for RFA, respectively; P ete ablation rates(98.3% vs. 98.1%, P = 0.309), the LTP rates(9.6% vs. 10.1%, P = 0.883), the compl multivariate analysis, LTP, an= 0.860), or the occurrence rates of major complications(0.7% vs. 0.6%, P = 0.691). Bytiviral therapy, and treatment of recurrence were independent risk fac?tors for OS(P < 0.001), and the alpha?fetoprotein level was an independent prognostic factor for RFS(P = 0.002).Conclusions: MWA is as safe and effective as RFA in treating very?early?stage HCC, supporting MWA as a first?line treatment option for this disease.
基金supported by National Natural Science Foundation of China(61304085)Beijing Natural Science Foundation(4152040)
文摘An iterative learning control(ILC) algorithm using quantized error information is given in this paper for both linear and nonlinear discrete-time systems with stochastic noises. A logarithmic quantizer is used to guarantee an adaptive improvement in tracking performance. A decreasing learning gain is introduced into the algorithm to suppress the effects of stochastic noises and quantization errors. The input sequence is proved to converge strictly to the optimal input under the given index. Illustrative simulations are given to verify the theoretical analysis.
基金supported by the National Natural Science Foundation of China,Nos.81671055,81971009(to XLZ)the Key Research and Development Program of Jiangsu Province of China,No.BE2016610(to YX)+3 种基金the National Key Research and Development Program of China,No.2016YFC1300504(to YX)and No.2018YFC1704405(to XLZ)Jiangsu Province Key Medical Discipline,No.ZDXKA2016020(to YX)Jiangsu Province Medical Youth Talent,No.QNRC2016024(to XLZ)Young Talent Support Program from Jiangsu Association for Science and Technology(to XLZ)。
文摘Amyloid beta(Aβ)-induced neurotoxicity and oxidative stress plays an important role in the pathogenesis of Alzheimer’s disease(AD).ZL006 is shown to reduce over-produced nitric oxide and oxidative stress in ischemic stroke by interrupting the interaction of neuronal nitric oxide synthase and postsynaptic density protein 95.However,few studies are reported on the role of ZL006 in AD.To investigate whether ZL006 exerted neuroprotective effects in AD,we used Aβ1–42 to treat primary cortical neurons and N2a neuroblastoma cells as an in vitro model of AD.Cortical neurons were incubated with ZL006 or dimethyl sulfoxide for 2 hours and treated with Aβ1–42 or NH3·H2O for another 24 hours.The results of cell counting Kit-8(CCK-8)assay and calcein-acetoxymethylester/propidium iodide staining showed that ZL006 pretreatment rescued the neuronal death induced by Aβ1–42.Fluorescence and western blot assay were used to detect oxidative stress and apoptosis-related proteins in each group of cells.Results showed that ZL006 pretreatment decreased neuronal apoptosis and oxidative stress induced by Aβ1–42.The results of CCK8 assay showed that inhibition of Akt or NF-E2-related factor 2(Nrf2)in cortical neurons abolished the protective effects of ZL006.Moreover,similar results were also observed in N2a neuroblastoma cells.ZL006 inhibited N2a cell death and oxidative stress induced by Aβ1–42,while inhibition of Akt or Nrf2 abolished the protective effect of ZL006.These results demonstrated that ZL006 reduced Aβ1–42-induced neuronal damage and oxidative stress,and the mechanisms might be associated with the activation of Akt/Nrf2/heme oxygenase-1 signaling pathways.
基金the NatureScience Foundation of Jiangsu Province, No.BK2005002the International Cooperation Program and talented manprogram of Jiangsu Provinceof China, No. BZ2006045,06-B-002
文摘BACKGROUND: Tongxinluo has been clinically proven to be effective in improving memory and cognitive function in patients with post-stroke vascular dementia. Is the mechanism related to the deposition of beta-amyloid peptide (A β ) in hippocampus? OBJECTIVE: To observe the effect of Tongxinluo on cognitive impairment in a mouse model with vascular dementia and the changes of A β deposition and β -secretase 1 (BACE1) expression. DESIGN: Randomized controlled study. SETTING: State Key Laboratory of Pharmaceutical Biotechnology of Nanjing University and Affiliated Drum Tower Hospital of Nanjing University Medical School. MATERIALS: The experiment was carried out in the State Key Laboratory of Pharmaceutical Biotechnology of Nanjing University and Affiliated Drum Tower Hospital of Nanjing University Medical School from March 2006 to January 2007. A total of 36 healthy Kunming mice, 18 of each gender, were chosen. The study was conducted in accordance with the National Regulations of Experimental Animal Administration, and all animal experiments were approved by the Committee of Experimental Animal Administration of Nanjing University. Tongxinluo was provided by Shijiazhuang Yiling Pharmaceutical Co., Ltd. METHODS: All mice were randomly divided into 6 groups, including naive control (n=6), sham-operated control (n=6) and experimental groups treated with different doses of Tongxinluo (0.2, 0.4, and 0.6 g/kg/d; n=6 for each group) or vehicle (n=6). Five groups were subjected to bilateral common carotid arteries (2-VO) occlusion to produce a vascular dementia model (no occlusion was performed in sham-operated group). The mice in the Tongxinluo treatment groups were intragastricly administered daily with a Tongxinluo suspension (40 g/L in distilled water) at doses of 0.2, 0.4 or 0.6 g/kg/d from day 1 to day 30 post-surgery. The animals in vehicle, sham-operated and naive groups were administered an equal volume of distilled water. MAIN OUTCOME MEASURES: ①Escape latency time determined in all groups of mice before and after 2-VO occlusion by Morris water maze. ②Changes in BACEI mRNA expression in the hippocampi of mice among the six groups by RT-PCR assay, and BACEI and A β protein expression in the hippocampi of mice by Western blot. RESULTS: All 36 mice were involved in the final analysis.① No difference was detected in escape latency time to a hidden platform among all groups in water maze test before surgery (P 〉 0.05) At 30 days after 2-VO occlusion, the vehicle animals exhibited a significantly longer latency in finding the hidden platform compared to that of sham-operated and naive animals (P 〈 0.01). The prolonged escape latency was significantly reduced by oral administration of 0.4 g or 0.6 kg/day (P 〈 0.01, P 〈 0.05). BACEI mRNA and protein expression in vehicle animals were much higher than in sham-operated and naive animals (P 〈 0.01). The ischemia-induced increases in BACE1 mRNA and protein level were attenuated by all three doses of Tongxinluo treatment (P 〈 0.01), and the 0.4 g/kg/d treatment was the most effective. A β protein expression in vehicle animals after 2-VO occlusion were much higher than in sham-operated and naive animals (P 〈 0.01). 2-VO occlusion-induced A β generation was significantly attenuated by all doses of Tongxinluo treatment, with the most effective dose being 0.4 g/kg/d (P 〈 0.01). CONCLUSION: BACE1 mRNA levels and protein levels of BACEI and A β are reduced in the hippocampi of vascular dementia model mice by all three doses of Tongxinluo treatment, with the most effective dose being 0.4 g/kg/d. The results suggest that inhibition of post-ischemia BACEI expression and A β generation in brain might underlie Tongxinluo's effects in improving cognitive impairment.