AIM:To evaluate the relationship between increased intraocular pressure(IOP),is chemia-modified albumin levels in serum(IMA-s)and in humor aqueous(IMA-HA)in rabbits.METHODS:Twenty-five albino New Zealand rabbits weigh...AIM:To evaluate the relationship between increased intraocular pressure(IOP),is chemia-modified albumin levels in serum(IMA-s)and in humor aqueous(IMA-HA)in rabbits.METHODS:Twenty-five albino New Zealand rabbits weighing between 2.0 and 2.8 kg were used in this pilot study.With permission from Canakkale Onsekiz Mart University Animal Ethics Committee,the IOP of both eyes of each rabbit were recorded with a Tonopen(Tono-Pen XL,Reichart Inc.,Depew,NY,USA)after the application of topical proparacaine 0.5%HCl anesthesia.Blood(4 mL)was collected from the marginal ear vein and an intracameral injection of 2.3 mg/mL sodium hyaluronate and subconjunctival dexamethasone was given in the right eye.Anterior chamber aqueous fluid was obtained using a limbal approach with a 27 gauge needle from both eyes.The left eyes were used as controls.IOP was measured on the 1st,3rdand 10thday after the initial injection,with Tonopen,IMA-s levels and IMA-HA examined simultaneously.RESULTS:Beforetheinjections,IOPwas11.4±3.0mmHg in the right eye and 11.3±3.1 mm Hg in the left eye(P】0.05).There was a statistically significant difference between IMA-s levels before the IOP increase(IMA-s0)and IMA-s levels on the 1stand 3rddays after the increase in IOP(P=0.012 and P=0.01,respectively).No difference was observed between IMA-s0and serum IMA levels on the 10thday(IMA-s10)after IOP increase(P=0.989).IMA-HA in the right eye in the first day after the injection was positively correlated with IOP(r=0.748;P=0.02).No othercorrelation is found between any other parameter with IMA-HAlevels at any test time.A statistically significant positive correlation was observed between IMA-s values and IOP on the 1stand 3rddays(r=0.398,P=0.04 and r=0.382,P=0.04,respectively).There was no correlation between IMA-s levels and increased IOP on the 10thday after IOP increase(r=0.026,P=0.902).CONCLUSION:IMA may be an important indicator of acute damage caused by diseases involving ischemic damage to the eye,especially in case of increased intraocular pressure.展开更多
<strong>Background:</strong> <span style="font-family:""><span style="font-family:Verdana;">Beta-thalassemia is a hereditary haemoglobinopathy caused by defective hemog...<strong>Background:</strong> <span style="font-family:""><span style="font-family:Verdana;">Beta-thalassemia is a hereditary haemoglobinopathy caused by defective hemoglobin (Hb) </span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;">-globin synthesis, leading to excess </span><i><span style="font-family:Verdana;">α</span></i><span style="font-family:Verdana;">-globin chains that cause hemolysis and impair erythropoiesis. Ischemia modified albumin (IMA) is not a signal protein and not generated in pro-inflammatory state alone but rather an end product of oxidative stress.</span><b><span style="font-family:Verdana;"> Objectives: </span></b><span style="font-family:Verdana;">The aim of the study was to evaluate ischemia modified albumin (IMA) and C-reactive protein (CRP) in children with </span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;">-thalassemia major and its relation to different iron chelators. </span><b><span style="font-family:Verdana;">Patients and Methods: </span></b><span style="font-family:Verdana;">The study was carried on 40 children diagnosed as beta-thalassemia major recruited from the outpatient clinic and the pediatric department, at Al-Zahraa University Hospital, Faculty of medicine for Girls, Al-Azhar University and EL Minia Insurance Hospital. They were 20 male and 20 female, aged from 4 - 11 years. Another 40 apparently healthy children age and sex matched as control group. CRP and IMA were determined for all participants.</span><b><span style="font-family:Verdana;"> Results:</span></b><span style="font-family:Verdana;"> There were significant increases in serum CRP, IMA and ferritin levels in patients group compared to control group. There were significant decreases of IMA and CRP levels of thalassemic patients on chelation deferiprone (DFP) compared to deferasirox (DFX) P-value (<0.01) for each. There was a significant positive correlation between serum ferritin and both CRP and IMA levels in thalassemic children (r = 0.40, p < 0.01), (r = 0.44, p < 0.01) respectively. There was a significant positive correlation between IMA and CRP in beta-thalassemic patients (r = 0.31, p = 0.02). </span><b><span style="font-family:Verdana;">Conclusion: </span></b><span style="font-family:Verdana;">IMA, CRP and Serum ferritin were higher in children with </span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;">-thalassemia major than controls. Moreover, IMA and CRP levels in thalassemic children on deferiprone (DFP) were significantly lower compared with children on deferasirox (DFX). So it could be considered as useful markers in the follow up assessment of thalassemic patients for early detection of complications.</span></span>展开更多
Pulmonary embolism is a common and potentially lethal condition. Clinical signs and symptoms for pulmonary embolism are nonspecific. New and simple tests are therefore needed in order to help in early diagnosis of pul...Pulmonary embolism is a common and potentially lethal condition. Clinical signs and symptoms for pulmonary embolism are nonspecific. New and simple tests are therefore needed in order to help in early diagnosis of pulmonary embolism. The aim of this work is to elucidate the role of IMA in the diagnosis of pulmonary embolism. Subjects and Methods: 75 patients with suspected pulmonary embolism and 20 control healthy subjects were included in this study. Measurement of IMA was done in all subjects. Results: The mean values of IMA were statistically significantly higher among the PE patient group (0.43 ± 0.104 ABSU) in comparison with non PE patient group (0.27 ± 0.053 ABSU) and healthy control subjects (0.21 ± 0.080 ABSU). At cut-off value of 0.305 ABSU, IMA had 97.5% sensitivity and 71.42% specificity. The area under the curve was 0.952. The positive predictive value of this cut-off value was 79.59% while the negative predictive value was 96.15%. Conclusions: IMA is a good alternative to D-dimer in the diagnosis and exclusion of PE. Larger studies are needed to augment our results.展开更多
AIM: To investigate the uptake difference between bovine serum albumin nanoparticle (BSA-NP) and bovine serum albumin nanoparticles with their surface modified byglycyrrhizin (BSA-NP-GL) and to develop a novel hepatoc...AIM: To investigate the uptake difference between bovine serum albumin nanoparticle (BSA-NP) and bovine serum albumin nanoparticles with their surface modified byglycyrrhizin (BSA-NP-GL) and to develop a novel hepatocyte targeting BSA-NP-GL based on active targeting technology mediated by specific binding site of GL on rat cellular membrane. METHODS: Calcein loaded bovine serum albumin nanoparticles (Cal-BSA-NP) were prepared by desolvation process. Glycyrrhizin was conjugated to the surface reactive amino groups (SRAG) of Cal-BSA-NP by sodium periodate oxidization, which resulted in calcein-loaded bovine serum albumin nanoparticles with their surface modified by glycyrrhizin (Cal-BSA-NP-GL). The morphology of the two types of prepared nanoparticles (NP) was observed by transmission electron microscopy. The diameter of NP was measured with a laser particle size analyzer. The interaction between Cal-BSA-NP-GL and primary cultured hepatocytes was studied through cellular uptake experiments. The uptake amount of Cal-BSA-NPGL and Cal-BSA-NP by rat hepatocytes was determinedby fluorospectrophotometry. Uptake characteristics were investigated through experiments of competitive inhibition of specific binding site of GL. RESULTS: Both Cal-BSA-NP-GL and Cal-BSA-NP had regular spherical surfaces. The average diameter of CalBSA-NP-GL and Cal-BSA-NP was 77 and 79 nm respectively. The uptake amount of the two NP by hepatocytes reached its maximum at 2 h after incubation. The uptake amount of Cal-BSA-NP-GL by rat hepatocytes was 4.43-fold higher than that of Cal-BSA-NP. There was a significant difference in the uptake of Cal-BSA-NP-GL and Cal-BSA-NP by hepatocytes (P<0.01). The uptake of Cal-BSA-NP-GL was inhibited when GL was added previously to isolated rat hepatocytes, and the uptake of Cal-BSA-NP was not affected by GL.CONCLUSION: A binding site of GL is present on the surface of rat hepatocytes, BSA-NP-GL may be internalized via this site by hepatocytes and can be used as a drug carrier for active targeting of delivery drugs to hepatocytes.展开更多
Background: The deep understanding of pathogenesis is a key moment in the formation of the modern strategy of modern medicine. We conducted the thorough analysis of the microscopic processes occurring in the bodies of...Background: The deep understanding of pathogenesis is a key moment in the formation of the modern strategy of modern medicine. We conducted the thorough analysis of the microscopic processes occurring in the bodies of patients with purulent-septic complications. The modified pathogenetic concept of the diagnostic and treatment model of diseases with septic complications is presented. The obtained information about the mechanisms of origin and development of these diseases is fundamentally important for finding the modern effective methods of treating patients. The aim of the research is to modify treatment tactics for patients with sepsis and burn injuries based on the modified pathogenetic concept using modern diagnostics, i.e. the method of fluorescence spectroscopy (MFS) and biomarkers. Materials and Methods: The proposed modified pathogenetic concept of the diagnostic and treatment model of diseases with purulent-septic complications along with standard methods was used successfully for effective treatment of 15 patients with sepsis and 25 with burn injuries. Results: 3 main scenarios of behaviour of spectral-fluorescence characteristics of patients with sepsis are illustrated. Spectral-fluorescence markers of sepsis were studied, which are informative 24 to 48 hours before the appearance of obvious clinical and laboratory signs of significant changes in the general somatic status of patients. Conclusions: The proposed diagnostic and therapeutic approach is new and fundamentally important for diagnostics and monitoring of the process of treatment of patients with purulent-septic diseases and burn injuries. An in-depth understanding of the dynamics of septic complications and the corresponding changes of the main markers of these diseases during treatment is especially relevant. The use of infusion therapy with solutions of donor albumin as an effective pathogenetic treatment is scientifically justified.展开更多
BACKGROUND Hepatectomy is the main treatment for patients with hepatocellular carcinoma(HCC)and it has a high possibility for long-term cure potential.But the postoperative mortality and recurrence rates remain high.S...BACKGROUND Hepatectomy is the main treatment for patients with hepatocellular carcinoma(HCC)and it has a high possibility for long-term cure potential.But the postoperative mortality and recurrence rates remain high.Since the long-term prognosis of HCC patients is strongly linked to liver function,preoperative assessment of liver function is very important for HCC patients.AIM To compare the predictive power of the modified Child-Pugh(MCP)and albumin-bilirubin(ALBI)grades for the long-term outcome of HCC.METHODS From January 2010 to June 2017,a total of 204 patients with HCC who underwent surgery at the Second Affiliated Hospital of Chongqing Medical University were enrolled in this retrospective study.Multivariate Cox regression analysis was used to determine the independent predictive factors of survival and relapse.The area under the curve(AUC)was used to evaluate the discriminative performance of the MCP grade and ALBI grade to predict the postoperative overall survival(OS)time and recurrence-free survival(RFS)time.RESULTS The median OS and RFS times were 44.0 mo(range:22.0-74.0 mo)and 22.0 mo(range:5.0-45.0 mo),respectively.The median OS and RFS times of MCP grades 1,2,and 3 patients were 60.0,39.0,and 18.0 mo(P<0.001)and 36.0,15.0,and 7.0 mo(P<0.001),respectively.The median OS and RFS times of ALBI grades 1,2,and 3 patients were 56.0,26.0,and 6.0 mo(P<0.001)and 25.0,10.0,and 3.0 mo(P=0.003),respectively.Both the MCP and ALBI grades were more accurate than the Child-Pugh grade for predicting long-term prognosis.Further analysis demonstrated that for both predicting OS and RFS,the MCP grade performed better than the ALBI grade(AUC:0.642 vs 0.605 for OS;0.659 vs 0.594 for RFS).CONCLUSION The MCP grade is more accurate than the ALBI grade for predicting long-term outcome of patients with HCC.展开更多
The electrochemical behaviors of lomefloxacin at a single-wall carbon nanotube-modified glassy carbon electrode have been investigated by cyclic voltammetry.In a Britton-Robinson buffer (pH 4.5),lomefloxacin yields a ...The electrochemical behaviors of lomefloxacin at a single-wall carbon nanotube-modified glassy carbon electrode have been investigated by cyclic voltammetry.In a Britton-Robinson buffer (pH 4.5),lomefloxacin yields a sensitive and well-defined oxidation peak at ca.1.24 V (vs.SCE) on the modified electrode.Compared with the bare glassy carbon electrode,the oxidation peak current of lomefloxacin significantly increases and the oxidation peak potential positively shifts.Under the optimal conditions,the interaction of lomefloxacin with bovine serum albumin is also investigated.The results indicate that an electrochemically inactive supramolecular complex is formed and the formation of complex between lomefloxacin and bovine serum albumin is an intercalation mechanism.The proposed methods offer a reference for the studies on the biological effects and action mechanism of lomefloxacin with albumins in vivo.展开更多
OBJECTIVE The greatest challenge in chemotherapy of ischemic stroke is the construction a suitable delivery system to overcome the poor physicochemical properties of drug and its low permeability across the blood brai...OBJECTIVE The greatest challenge in chemotherapy of ischemic stroke is the construction a suitable delivery system to overcome the poor physicochemical properties of drug and its low permeability across the blood brain barrier(BBB).METHODS In the present study,dendrimer,polyamidoamine(PAMAM),was synthesized as the nano-drug carriers.Angiopep-2,which has been proved excellent ability to cross the BBB,was exploited as the targeting ligand to conjugate PAMAM via bifunctional polyethylene glycol(PEG).Then scutellarin(STA)was encapsulated into the functionalized nanoparticles(NPs)to formulate Angiopep-2 modified STA-loaded PEG-PAMAM NPs.Ischemic stroke model was established to evaluate the treatment efficacy and protective mechanism of Angiopep-2-STA-PEG-PAMAM NPs.RESULTS The pharmacokinetics and biodistribu-tion demonstrated that Angiopep-2-STA-PEG-PAMAM NPs exhibited significantly higher plasma concentration from 1 h to 10 h after intravenous administration and improve accumulation in brain(4.7-fold)compared with STA solution.Moreover,prolonged elimination half-life(4.8-fold)and lower clearance(3.4-fold)were observed.The brain uptake study of 6-coumarin confirmed that Angiopep-2-PEG-PAMAM NPs possessed better brain targeting efficacy(3.2-fold)than PEG-PAMAM NPs.Angiopep-2-STA-PEG-PAMAM NPs obviously ameliorated infarct volume,neurological deficit,histopathological severity and neuronal apoptosis.In addition,Angiopep-2-STA-PEG-PAMAM NPs markedly inhibited the calcium content and the levels of IL-12p40,IL-13,IL-17 and IL-23.Furthermore,Angiopep-2-STA-PEG-PAMAM NPs significantly decreased the m RNA and protein expressions of HMGB1,TLR2,TLR4,TLR5,My D88,TRIF,TRAM,IRAK-4,TRAF6,IкBα,IKKβand NF-кBp65.CONCLUSION The results suggested that Angiopep-2modified scutellarin-loaded PEG-PAMAM nanocarriers possessed remarkable neuroprotective effects on ischemic stroke through modulation of inflammatory cascades and HMGB1/TLRs/MyD 88-induced NF-κB activation pathways.展开更多
基金Supported by Canakkale Onsekiz MartUniversity,Scientific Research Project Center(No.2010/206)
文摘AIM:To evaluate the relationship between increased intraocular pressure(IOP),is chemia-modified albumin levels in serum(IMA-s)and in humor aqueous(IMA-HA)in rabbits.METHODS:Twenty-five albino New Zealand rabbits weighing between 2.0 and 2.8 kg were used in this pilot study.With permission from Canakkale Onsekiz Mart University Animal Ethics Committee,the IOP of both eyes of each rabbit were recorded with a Tonopen(Tono-Pen XL,Reichart Inc.,Depew,NY,USA)after the application of topical proparacaine 0.5%HCl anesthesia.Blood(4 mL)was collected from the marginal ear vein and an intracameral injection of 2.3 mg/mL sodium hyaluronate and subconjunctival dexamethasone was given in the right eye.Anterior chamber aqueous fluid was obtained using a limbal approach with a 27 gauge needle from both eyes.The left eyes were used as controls.IOP was measured on the 1st,3rdand 10thday after the initial injection,with Tonopen,IMA-s levels and IMA-HA examined simultaneously.RESULTS:Beforetheinjections,IOPwas11.4±3.0mmHg in the right eye and 11.3±3.1 mm Hg in the left eye(P】0.05).There was a statistically significant difference between IMA-s levels before the IOP increase(IMA-s0)and IMA-s levels on the 1stand 3rddays after the increase in IOP(P=0.012 and P=0.01,respectively).No difference was observed between IMA-s0and serum IMA levels on the 10thday(IMA-s10)after IOP increase(P=0.989).IMA-HA in the right eye in the first day after the injection was positively correlated with IOP(r=0.748;P=0.02).No othercorrelation is found between any other parameter with IMA-HAlevels at any test time.A statistically significant positive correlation was observed between IMA-s values and IOP on the 1stand 3rddays(r=0.398,P=0.04 and r=0.382,P=0.04,respectively).There was no correlation between IMA-s levels and increased IOP on the 10thday after IOP increase(r=0.026,P=0.902).CONCLUSION:IMA may be an important indicator of acute damage caused by diseases involving ischemic damage to the eye,especially in case of increased intraocular pressure.
文摘<strong>Background:</strong> <span style="font-family:""><span style="font-family:Verdana;">Beta-thalassemia is a hereditary haemoglobinopathy caused by defective hemoglobin (Hb) </span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;">-globin synthesis, leading to excess </span><i><span style="font-family:Verdana;">α</span></i><span style="font-family:Verdana;">-globin chains that cause hemolysis and impair erythropoiesis. Ischemia modified albumin (IMA) is not a signal protein and not generated in pro-inflammatory state alone but rather an end product of oxidative stress.</span><b><span style="font-family:Verdana;"> Objectives: </span></b><span style="font-family:Verdana;">The aim of the study was to evaluate ischemia modified albumin (IMA) and C-reactive protein (CRP) in children with </span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;">-thalassemia major and its relation to different iron chelators. </span><b><span style="font-family:Verdana;">Patients and Methods: </span></b><span style="font-family:Verdana;">The study was carried on 40 children diagnosed as beta-thalassemia major recruited from the outpatient clinic and the pediatric department, at Al-Zahraa University Hospital, Faculty of medicine for Girls, Al-Azhar University and EL Minia Insurance Hospital. They were 20 male and 20 female, aged from 4 - 11 years. Another 40 apparently healthy children age and sex matched as control group. CRP and IMA were determined for all participants.</span><b><span style="font-family:Verdana;"> Results:</span></b><span style="font-family:Verdana;"> There were significant increases in serum CRP, IMA and ferritin levels in patients group compared to control group. There were significant decreases of IMA and CRP levels of thalassemic patients on chelation deferiprone (DFP) compared to deferasirox (DFX) P-value (<0.01) for each. There was a significant positive correlation between serum ferritin and both CRP and IMA levels in thalassemic children (r = 0.40, p < 0.01), (r = 0.44, p < 0.01) respectively. There was a significant positive correlation between IMA and CRP in beta-thalassemic patients (r = 0.31, p = 0.02). </span><b><span style="font-family:Verdana;">Conclusion: </span></b><span style="font-family:Verdana;">IMA, CRP and Serum ferritin were higher in children with </span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;">-thalassemia major than controls. Moreover, IMA and CRP levels in thalassemic children on deferiprone (DFP) were significantly lower compared with children on deferasirox (DFX). So it could be considered as useful markers in the follow up assessment of thalassemic patients for early detection of complications.</span></span>
文摘Pulmonary embolism is a common and potentially lethal condition. Clinical signs and symptoms for pulmonary embolism are nonspecific. New and simple tests are therefore needed in order to help in early diagnosis of pulmonary embolism. The aim of this work is to elucidate the role of IMA in the diagnosis of pulmonary embolism. Subjects and Methods: 75 patients with suspected pulmonary embolism and 20 control healthy subjects were included in this study. Measurement of IMA was done in all subjects. Results: The mean values of IMA were statistically significantly higher among the PE patient group (0.43 ± 0.104 ABSU) in comparison with non PE patient group (0.27 ± 0.053 ABSU) and healthy control subjects (0.21 ± 0.080 ABSU). At cut-off value of 0.305 ABSU, IMA had 97.5% sensitivity and 71.42% specificity. The area under the curve was 0.952. The positive predictive value of this cut-off value was 79.59% while the negative predictive value was 96.15%. Conclusions: IMA is a good alternative to D-dimer in the diagnosis and exclusion of PE. Larger studies are needed to augment our results.
基金Supported by the National Natural Science Foundation of China,No. 30271613
文摘AIM: To investigate the uptake difference between bovine serum albumin nanoparticle (BSA-NP) and bovine serum albumin nanoparticles with their surface modified byglycyrrhizin (BSA-NP-GL) and to develop a novel hepatocyte targeting BSA-NP-GL based on active targeting technology mediated by specific binding site of GL on rat cellular membrane. METHODS: Calcein loaded bovine serum albumin nanoparticles (Cal-BSA-NP) were prepared by desolvation process. Glycyrrhizin was conjugated to the surface reactive amino groups (SRAG) of Cal-BSA-NP by sodium periodate oxidization, which resulted in calcein-loaded bovine serum albumin nanoparticles with their surface modified by glycyrrhizin (Cal-BSA-NP-GL). The morphology of the two types of prepared nanoparticles (NP) was observed by transmission electron microscopy. The diameter of NP was measured with a laser particle size analyzer. The interaction between Cal-BSA-NP-GL and primary cultured hepatocytes was studied through cellular uptake experiments. The uptake amount of Cal-BSA-NPGL and Cal-BSA-NP by rat hepatocytes was determinedby fluorospectrophotometry. Uptake characteristics were investigated through experiments of competitive inhibition of specific binding site of GL. RESULTS: Both Cal-BSA-NP-GL and Cal-BSA-NP had regular spherical surfaces. The average diameter of CalBSA-NP-GL and Cal-BSA-NP was 77 and 79 nm respectively. The uptake amount of the two NP by hepatocytes reached its maximum at 2 h after incubation. The uptake amount of Cal-BSA-NP-GL by rat hepatocytes was 4.43-fold higher than that of Cal-BSA-NP. There was a significant difference in the uptake of Cal-BSA-NP-GL and Cal-BSA-NP by hepatocytes (P<0.01). The uptake of Cal-BSA-NP-GL was inhibited when GL was added previously to isolated rat hepatocytes, and the uptake of Cal-BSA-NP was not affected by GL.CONCLUSION: A binding site of GL is present on the surface of rat hepatocytes, BSA-NP-GL may be internalized via this site by hepatocytes and can be used as a drug carrier for active targeting of delivery drugs to hepatocytes.
文摘Background: The deep understanding of pathogenesis is a key moment in the formation of the modern strategy of modern medicine. We conducted the thorough analysis of the microscopic processes occurring in the bodies of patients with purulent-septic complications. The modified pathogenetic concept of the diagnostic and treatment model of diseases with septic complications is presented. The obtained information about the mechanisms of origin and development of these diseases is fundamentally important for finding the modern effective methods of treating patients. The aim of the research is to modify treatment tactics for patients with sepsis and burn injuries based on the modified pathogenetic concept using modern diagnostics, i.e. the method of fluorescence spectroscopy (MFS) and biomarkers. Materials and Methods: The proposed modified pathogenetic concept of the diagnostic and treatment model of diseases with purulent-septic complications along with standard methods was used successfully for effective treatment of 15 patients with sepsis and 25 with burn injuries. Results: 3 main scenarios of behaviour of spectral-fluorescence characteristics of patients with sepsis are illustrated. Spectral-fluorescence markers of sepsis were studied, which are informative 24 to 48 hours before the appearance of obvious clinical and laboratory signs of significant changes in the general somatic status of patients. Conclusions: The proposed diagnostic and therapeutic approach is new and fundamentally important for diagnostics and monitoring of the process of treatment of patients with purulent-septic diseases and burn injuries. An in-depth understanding of the dynamics of septic complications and the corresponding changes of the main markers of these diseases during treatment is especially relevant. The use of infusion therapy with solutions of donor albumin as an effective pathogenetic treatment is scientifically justified.
基金Supported by National Natural Science Foundation of China,No.81572888
文摘BACKGROUND Hepatectomy is the main treatment for patients with hepatocellular carcinoma(HCC)and it has a high possibility for long-term cure potential.But the postoperative mortality and recurrence rates remain high.Since the long-term prognosis of HCC patients is strongly linked to liver function,preoperative assessment of liver function is very important for HCC patients.AIM To compare the predictive power of the modified Child-Pugh(MCP)and albumin-bilirubin(ALBI)grades for the long-term outcome of HCC.METHODS From January 2010 to June 2017,a total of 204 patients with HCC who underwent surgery at the Second Affiliated Hospital of Chongqing Medical University were enrolled in this retrospective study.Multivariate Cox regression analysis was used to determine the independent predictive factors of survival and relapse.The area under the curve(AUC)was used to evaluate the discriminative performance of the MCP grade and ALBI grade to predict the postoperative overall survival(OS)time and recurrence-free survival(RFS)time.RESULTS The median OS and RFS times were 44.0 mo(range:22.0-74.0 mo)and 22.0 mo(range:5.0-45.0 mo),respectively.The median OS and RFS times of MCP grades 1,2,and 3 patients were 60.0,39.0,and 18.0 mo(P<0.001)and 36.0,15.0,and 7.0 mo(P<0.001),respectively.The median OS and RFS times of ALBI grades 1,2,and 3 patients were 56.0,26.0,and 6.0 mo(P<0.001)and 25.0,10.0,and 3.0 mo(P=0.003),respectively.Both the MCP and ALBI grades were more accurate than the Child-Pugh grade for predicting long-term prognosis.Further analysis demonstrated that for both predicting OS and RFS,the MCP grade performed better than the ALBI grade(AUC:0.642 vs 0.605 for OS;0.659 vs 0.594 for RFS).CONCLUSION The MCP grade is more accurate than the ALBI grade for predicting long-term outcome of patients with HCC.
基金National Natural Science Foundation of China (No. 20775047)the Natural Science Foundation of Henan Province (No. 0511022300)
文摘The electrochemical behaviors of lomefloxacin at a single-wall carbon nanotube-modified glassy carbon electrode have been investigated by cyclic voltammetry.In a Britton-Robinson buffer (pH 4.5),lomefloxacin yields a sensitive and well-defined oxidation peak at ca.1.24 V (vs.SCE) on the modified electrode.Compared with the bare glassy carbon electrode,the oxidation peak current of lomefloxacin significantly increases and the oxidation peak potential positively shifts.Under the optimal conditions,the interaction of lomefloxacin with bovine serum albumin is also investigated.The results indicate that an electrochemically inactive supramolecular complex is formed and the formation of complex between lomefloxacin and bovine serum albumin is an intercalation mechanism.The proposed methods offer a reference for the studies on the biological effects and action mechanism of lomefloxacin with albumins in vivo.
基金The project supported by National Natural Science Foundation of China(NSFC 21476054)the Natural Science Foundation of Heilongjiang Province(B201407)
文摘OBJECTIVE The greatest challenge in chemotherapy of ischemic stroke is the construction a suitable delivery system to overcome the poor physicochemical properties of drug and its low permeability across the blood brain barrier(BBB).METHODS In the present study,dendrimer,polyamidoamine(PAMAM),was synthesized as the nano-drug carriers.Angiopep-2,which has been proved excellent ability to cross the BBB,was exploited as the targeting ligand to conjugate PAMAM via bifunctional polyethylene glycol(PEG).Then scutellarin(STA)was encapsulated into the functionalized nanoparticles(NPs)to formulate Angiopep-2 modified STA-loaded PEG-PAMAM NPs.Ischemic stroke model was established to evaluate the treatment efficacy and protective mechanism of Angiopep-2-STA-PEG-PAMAM NPs.RESULTS The pharmacokinetics and biodistribu-tion demonstrated that Angiopep-2-STA-PEG-PAMAM NPs exhibited significantly higher plasma concentration from 1 h to 10 h after intravenous administration and improve accumulation in brain(4.7-fold)compared with STA solution.Moreover,prolonged elimination half-life(4.8-fold)and lower clearance(3.4-fold)were observed.The brain uptake study of 6-coumarin confirmed that Angiopep-2-PEG-PAMAM NPs possessed better brain targeting efficacy(3.2-fold)than PEG-PAMAM NPs.Angiopep-2-STA-PEG-PAMAM NPs obviously ameliorated infarct volume,neurological deficit,histopathological severity and neuronal apoptosis.In addition,Angiopep-2-STA-PEG-PAMAM NPs markedly inhibited the calcium content and the levels of IL-12p40,IL-13,IL-17 and IL-23.Furthermore,Angiopep-2-STA-PEG-PAMAM NPs significantly decreased the m RNA and protein expressions of HMGB1,TLR2,TLR4,TLR5,My D88,TRIF,TRAM,IRAK-4,TRAF6,IкBα,IKKβand NF-кBp65.CONCLUSION The results suggested that Angiopep-2modified scutellarin-loaded PEG-PAMAM nanocarriers possessed remarkable neuroprotective effects on ischemic stroke through modulation of inflammatory cascades and HMGB1/TLRs/MyD 88-induced NF-κB activation pathways.