AIM： Enterovirus 71 （EV71） has been implicated as the etiological agent responsible for the recent outbreaks of hand, foot and mouth disease associated with severe neurological diseases in the Asia-Pacific region. ...AIM： Enterovirus 71 （EV71） has been implicated as the etiological agent responsible for the recent outbreaks of hand, foot and mouth disease associated with severe neurological diseases in the Asia-Pacific region. METHODS： The assembly process was hypothesized to occur via an orchestrated proteolytic processing of the P1 precursor by the viral protease 3CD. To test this hypothesis, we constructed 3 recombinant baculoviruses： Bac-P1 expressing P1; Bac-3CD expressing 3CD; and Bac-P1-3CD co-expressing P1 and 3CD. RESULTS： Both single infection by Bac-P1-3CD and coinfection by Bac-P1 and Bac-3CD resulted in correct cleavage of P1 to yield individual proteins VP0, VP1 and VP3, while the former approach yielded higher VLP production. In the cells, the structural proteins selfassembled into clusters of virus-like particles （VLP） resembling the authentic EV71 particle aggregates. After ultracentrifugation purification, the dispersed VLPs were indistinguishable from the authentic virus in size, appearance, composition and surface epitopes, as determined by SDS-PAGE, Western blot, transmission electron microscopy and immunogold labeling. CONCLUSION： Our data, for the first time, suggest that in insect cells EV71 structural proteins adopt a processing and assembly pathway similar to poliovirus assembly. The preservation of particle morphology and composition suggest that the VLP may be a valuable vaccine candidate to prevent EV71 epidemics.展开更多
We report a case of pseudocirrhosis arising in the setting of regression of liver metastases from pancreatic cancer. A 55-year-old asymptomatic woman presented to our clinic with newly diagnosed metastatic pancreatic ...We report a case of pseudocirrhosis arising in the setting of regression of liver metastases from pancreatic cancer. A 55-year-old asymptomatic woman presented to our clinic with newly diagnosed metastatic pancreatic cancer with extensive liver metastases. She underwent systemic chemotherapy with gemcitabine and oxaliplatin (GEMOX). After 8 cycles of therapy, she had a remarkable response to the therapy evidenced by decline of carcinoembryonic antigen (CEA) and CA19 by > 50% and nearly complete resolution of hepatic metastases in computed tomography (CT) scan. Shortly after, she developed increasing bilateral ankle edema and ascites, associated with dyspnea, progressive weight gain, and declining performance status. Gemcitabine and oxaliplatin were discontinued as other causes of her symptoms such as congestive heart disease or venous thrombosis were ruled out. CT scan 6 mo after the initiation of GEMOX revealed worsening ascites with a stable pancreatic mass. However, it also revealed a lobular hepatic contour, segmental atrophy, and capsular retraction mimicking the appearance of cirrhosis. She was managed with aggressive diuresis and albumin infusions which eventually resulted in a resolution of the above- mentioned symptoms as well as complete resolution of pseudocirrhotic appearance of the liver and ascites in CT scan. This case demonstrates that pancreatic cancer patients can develop pseudocirrhosis. Clinicians and radiologist should be well aware of this entity asearly recognition and management can lead to a near complete recovery of liver function and much improved quality of life as illustrated in this case.展开更多
AIM： To investigate the antiproliferative effect of paeonol （Pae） used alone or in combination with chemotherapeutic agents [cisplatin （CDDP）, doxorubicin （DOX） and 5-fluorouracil （5-FU）] on human hepatoma ce...AIM： To investigate the antiproliferative effect of paeonol （Pae） used alone or in combination with chemotherapeutic agents [cisplatin （CDDP）, doxorubicin （DOX） and 5-fluorouracil （5-FU）] on human hepatoma cell line HepG2 and the possible mechanisms. METHODS： The cytotoxic effect of drugs on HepG2 cells was measured by 3-（4, 5-dimethylthiazol-2- yl）-2, 5-diphenyltetra-zolium bromide （MTT） assay. Morphologic changes were observed by acridine orange （AO） fuorescence staining. Cell cycle and apoptosis rate were detected by flow cytometry （FCM）. Drug-drug interactions were analyzed by the coefficient of drug RESULTS： Pae （7.81-250 mg/L） had an inhibitory effect on the proliferation of HepG2 cells in a dose-dependent manner, with the IC50 value of （104.77±7.28） mg/L. AO fluorescence staining and FCM assays showed that Pae induced apoptosis and arrested cell cycle at S phase in HepG2 cells. Further, different extent synergisms were observed when Pae （15.63, 31.25, 62.5 rag/L） was combined with CDDP （0.31-2.5 mg/L）, DOX （0.16-1.25 mg/L）, or 5-FU （12.5-100 mg/L） at appropriate concentrations. The IC50 value of the three drugs decreased dramatically when combined with Pae （P 〈 0.01）. Of the three different combinations, the sensitivity of cells to drugs was considerably different.CONCLUSION： Pae had a significant growth-inhibitory effect on the human hepatoma cell line HepG2, which may be related to apoptosis induction and cell cycle arrest. It also can enhance the cytotoxicity of chemotherapeutic agents on HepG2 cells, and the S phase arrest induced by Pae may be one of the mechanisms of these interactions.展开更多
New approaches for facility distribution in chemical plants are proposed including an improved non-overlapping constraint based on projection relationships of facilities and a novel toxic gas dispersion constraint. In...New approaches for facility distribution in chemical plants are proposed including an improved non-overlapping constraint based on projection relationships of facilities and a novel toxic gas dispersion constraint. In consideration of the large number of variables in the plant layout model, our new method can significantly reduce the number of variables with their own projection relationships. Also, as toxic gas dispersion is a usual incident in a chemical plant, a simple approach to describe the gas leakage is proposed, which can clearly represent the constraints of potential emission source and sitting facilities. For solving the plant layout model, an improved genetic algorithm (GA) based on infeasible solution fix technique is proposed, which improves the globe search ability of GA. The case study and experiment show that a better layout plan can be obtained with our method, and the safety factors such as gas dispersion and minimum distances can be well handled in the solution.展开更多
AIM： TO evaluate the impact of hepatitis C virus （HCV） infection with genotype 1 or 3 and the presence or absence of liver cirrhosis （LC） in the early viral kinetics response to treatment. METHODS： Naive patien...AIM： TO evaluate the impact of hepatitis C virus （HCV） infection with genotype 1 or 3 and the presence or absence of liver cirrhosis （LC） in the early viral kinetics response to treatment. METHODS： Naive patients （n = 46） treated with interferon-α （IFN-α） and ribavirin and followed up with frequent early HCV-RNA determinations were analysed. Patients were infected with genotype 1 （n = 28, 7 with LC） or 3 （n = 18, 5 with LC）. RESULTS： The first phase decline was larger in genotype 3 patients than in genotype 1 patients （1.72 vs 0.95 log IU/mL, P 〈 0.001）. The second phase slope decline was also larger in genotype 3 patients than in genotype 1 patients （0.87 vs 0.15 log/wk, P 〈 0.001）. Differences were found in both cirrhotic and non-cirrhotic patients. Genotype 1 cirrhotic patients had a slower 2^nd phase slope than non-cirrhotic patients （0.06 vs 0.18 log/wk, P 〈 0,02）. None of genotype 1 cirrhotic patients had a 1^st phase decline larger than 1 log （non-cirrhotic patients： 55%, P 〈 0.02）. A similar trend toward a slower 2nd phase slope was observed in genotype 3 cirrhotic patients but the 1^st phase slope decline was not different. Sustained viral response was higher in genotype 3 patients than in genotype 1 patients ,（72% vs 14%, P 〈 0.001） and in genotype 1 non-cirrhotic patients than in genotype 1 cirrhotic patients （19% vs 0%）. A second phase decline slower than 0.3 log per week was predictive of non-response in all groups. CONCLUSION： Genotype 3 has faster early viral decline than genotype 1. Cirrhosis correlates with a slower 2nd phase decline and possibly with a lower 1^st phase slope decline in genotype 1 patients.展开更多
基金Supported by the National Science Council,No.93-2214-E-007-016 Ministry of Economic Affairs,No.93-EC-17A-17S1-0009
文摘AIM： Enterovirus 71 （EV71） has been implicated as the etiological agent responsible for the recent outbreaks of hand, foot and mouth disease associated with severe neurological diseases in the Asia-Pacific region. METHODS： The assembly process was hypothesized to occur via an orchestrated proteolytic processing of the P1 precursor by the viral protease 3CD. To test this hypothesis, we constructed 3 recombinant baculoviruses： Bac-P1 expressing P1; Bac-3CD expressing 3CD; and Bac-P1-3CD co-expressing P1 and 3CD. RESULTS： Both single infection by Bac-P1-3CD and coinfection by Bac-P1 and Bac-3CD resulted in correct cleavage of P1 to yield individual proteins VP0, VP1 and VP3, while the former approach yielded higher VLP production. In the cells, the structural proteins selfassembled into clusters of virus-like particles （VLP） resembling the authentic EV71 particle aggregates. After ultracentrifugation purification, the dispersed VLPs were indistinguishable from the authentic virus in size, appearance, composition and surface epitopes, as determined by SDS-PAGE, Western blot, transmission electron microscopy and immunogold labeling. CONCLUSION： Our data, for the first time, suggest that in insect cells EV71 structural proteins adopt a processing and assembly pathway similar to poliovirus assembly. The preservation of particle morphology and composition suggest that the VLP may be a valuable vaccine candidate to prevent EV71 epidemics.
文摘We report a case of pseudocirrhosis arising in the setting of regression of liver metastases from pancreatic cancer. A 55-year-old asymptomatic woman presented to our clinic with newly diagnosed metastatic pancreatic cancer with extensive liver metastases. She underwent systemic chemotherapy with gemcitabine and oxaliplatin (GEMOX). After 8 cycles of therapy, she had a remarkable response to the therapy evidenced by decline of carcinoembryonic antigen (CEA) and CA19 by > 50% and nearly complete resolution of hepatic metastases in computed tomography (CT) scan. Shortly after, she developed increasing bilateral ankle edema and ascites, associated with dyspnea, progressive weight gain, and declining performance status. Gemcitabine and oxaliplatin were discontinued as other causes of her symptoms such as congestive heart disease or venous thrombosis were ruled out. CT scan 6 mo after the initiation of GEMOX revealed worsening ascites with a stable pancreatic mass. However, it also revealed a lobular hepatic contour, segmental atrophy, and capsular retraction mimicking the appearance of cirrhosis. She was managed with aggressive diuresis and albumin infusions which eventually resulted in a resolution of the above- mentioned symptoms as well as complete resolution of pseudocirrhotic appearance of the liver and ascites in CT scan. This case demonstrates that pancreatic cancer patients can develop pseudocirrhosis. Clinicians and radiologist should be well aware of this entity asearly recognition and management can lead to a near complete recovery of liver function and much improved quality of life as illustrated in this case.
基金Supported by the Natural Science Foundation of Anhui Province, No. 00044414, No. 050430901 the Key Project of the Natural Science Foundation of the Department of Education, Anhui Province, No. 2003Kj037zd and the Natural Science Foundation of the Department of Health, Anhui Province, No. 2002A025
文摘AIM： To investigate the antiproliferative effect of paeonol （Pae） used alone or in combination with chemotherapeutic agents [cisplatin （CDDP）, doxorubicin （DOX） and 5-fluorouracil （5-FU）] on human hepatoma cell line HepG2 and the possible mechanisms. METHODS： The cytotoxic effect of drugs on HepG2 cells was measured by 3-（4, 5-dimethylthiazol-2- yl）-2, 5-diphenyltetra-zolium bromide （MTT） assay. Morphologic changes were observed by acridine orange （AO） fuorescence staining. Cell cycle and apoptosis rate were detected by flow cytometry （FCM）. Drug-drug interactions were analyzed by the coefficient of drug RESULTS： Pae （7.81-250 mg/L） had an inhibitory effect on the proliferation of HepG2 cells in a dose-dependent manner, with the IC50 value of （104.77±7.28） mg/L. AO fluorescence staining and FCM assays showed that Pae induced apoptosis and arrested cell cycle at S phase in HepG2 cells. Further, different extent synergisms were observed when Pae （15.63, 31.25, 62.5 rag/L） was combined with CDDP （0.31-2.5 mg/L）, DOX （0.16-1.25 mg/L）, or 5-FU （12.5-100 mg/L） at appropriate concentrations. The IC50 value of the three drugs decreased dramatically when combined with Pae （P 〈 0.01）. Of the three different combinations, the sensitivity of cells to drugs was considerably different.CONCLUSION： Pae had a significant growth-inhibitory effect on the human hepatoma cell line HepG2, which may be related to apoptosis induction and cell cycle arrest. It also can enhance the cytotoxicity of chemotherapeutic agents on HepG2 cells, and the S phase arrest induced by Pae may be one of the mechanisms of these interactions.
基金Supported by the National Natural Science Foundation of China （61074153, 61104131）, and the Fundamental Research Funds for Central Universities of China （ZY1111, JD1104）.
文摘New approaches for facility distribution in chemical plants are proposed including an improved non-overlapping constraint based on projection relationships of facilities and a novel toxic gas dispersion constraint. In consideration of the large number of variables in the plant layout model, our new method can significantly reduce the number of variables with their own projection relationships. Also, as toxic gas dispersion is a usual incident in a chemical plant, a simple approach to describe the gas leakage is proposed, which can clearly represent the constraints of potential emission source and sitting facilities. For solving the plant layout model, an improved genetic algorithm (GA) based on infeasible solution fix technique is proposed, which improves the globe search ability of GA. The case study and experiment show that a better layout plan can be obtained with our method, and the safety factors such as gas dispersion and minimum distances can be well handled in the solution.
基金Supported by the Alves de Queiroz Family Fund for Research
文摘AIM： TO evaluate the impact of hepatitis C virus （HCV） infection with genotype 1 or 3 and the presence or absence of liver cirrhosis （LC） in the early viral kinetics response to treatment. METHODS： Naive patients （n = 46） treated with interferon-α （IFN-α） and ribavirin and followed up with frequent early HCV-RNA determinations were analysed. Patients were infected with genotype 1 （n = 28, 7 with LC） or 3 （n = 18, 5 with LC）. RESULTS： The first phase decline was larger in genotype 3 patients than in genotype 1 patients （1.72 vs 0.95 log IU/mL, P 〈 0.001）. The second phase slope decline was also larger in genotype 3 patients than in genotype 1 patients （0.87 vs 0.15 log/wk, P 〈 0.001）. Differences were found in both cirrhotic and non-cirrhotic patients. Genotype 1 cirrhotic patients had a slower 2^nd phase slope than non-cirrhotic patients （0.06 vs 0.18 log/wk, P 〈 0,02）. None of genotype 1 cirrhotic patients had a 1^st phase decline larger than 1 log （non-cirrhotic patients： 55%, P 〈 0.02）. A similar trend toward a slower 2nd phase slope was observed in genotype 3 cirrhotic patients but the 1^st phase slope decline was not different. Sustained viral response was higher in genotype 3 patients than in genotype 1 patients ,（72% vs 14%, P 〈 0.001） and in genotype 1 non-cirrhotic patients than in genotype 1 cirrhotic patients （19% vs 0%）. A second phase decline slower than 0.3 log per week was predictive of non-response in all groups. CONCLUSION： Genotype 3 has faster early viral decline than genotype 1. Cirrhosis correlates with a slower 2nd phase decline and possibly with a lower 1^st phase slope decline in genotype 1 patients.
