BACKGROUND： Recurrence of hepatocellular carcinoma （HCC） after curative resection remains a major cause of treatment failure and tumor-related death. Patterns of HCC recur- rence can be categorized into early recur...BACKGROUND： Recurrence of hepatocellular carcinoma （HCC） after curative resection remains a major cause of treatment failure and tumor-related death. Patterns of HCC recur- rence can be categorized into early recurrence and late recurrence which have different underlying mechanisms. In this study, we investigated if simple inflammation-based clinical markers can distinguish patterns of recurrence after curative resection of HCC.展开更多
Background: Hepatic ischemia/reperfusion(I/R) injury remains a significant problem in clinical practice. Sphingosine kinase 1(Sph K1) phosphorylates sphingosine to sphingosine-1-phosphate(S1 P) which participates in m...Background: Hepatic ischemia/reperfusion(I/R) injury remains a significant problem in clinical practice. Sphingosine kinase 1(Sph K1) phosphorylates sphingosine to sphingosine-1-phosphate(S1 P) which participates in multiple bioactive processes. However, little is known about the role of Sph K1 in hepatic I/R injury. This study aimed to investigate the effect of Sph K1 knockout on liver I/R injury and to explore underlying mechanisms. Methods: Sph K1 knockout and wild type mice were subjected to 70% partial hepatic I/R. Serum alanine aminotransferase was determined to indicate the degree of liver damage. Hematoxylin-eosin staining and TUNEL assay were used to assess histological changes and hepatocellular apoptosis, respectively. Immunohistochemistry was performed to detect the expression and translocation of phosphorylated p65 and signal transducer and activator of transcription 3(STAT3). Western blotting was used to determine the expression of S1 P receptor 1(S1 PR1), phosphorylated p65 and STAT3. Real-time PCR was used to demonstrate the changes of proinflammatory cytokines. Oxidative stress markers were also determined through biochemical assays. Results: Sph K1 knockout significantly ameliorated I/R-induced liver damage, mitigated liver tissue necrosis and apoptosis compared with wild type control. I/R associated inflammation was alleviated in Sph K1 knockout mice as demonstrated by attenuated expression of S1 PR1 and reduced phosphorylation of nuclear factor kappa B p65 and STAT3. The proinflammatory cytokines interleukin-1 β, interleukin-6 and tumor necrosis factor-α were also inhibited by Sph K1 genetic deletion. The oxidative stress markers were lower in Sph K1 knockout mice after I/R injury than wild type mice. Conclusions: Knockout of Sph K1 significantly alleviated damage after hepatic I/R injury, possibly through inhibiting inflammation and oxidative stress. Sph K1 may be a novel and potent target in clinical practice in I/R-related liver injury.展开更多
A simple, precise and accurate method was developed and validated for the determination of allicin release from alliin/alliinase double-layer tablets. According to Appendix XC Ⅱ of Chinese Pharmacopoeia 2010 edition ...A simple, precise and accurate method was developed and validated for the determination of allicin release from alliin/alliinase double-layer tablets. According to Appendix XC Ⅱ of Chinese Pharmacopoeia 2010 edition Volume II, a small glass-method was adopted at the rotational speed of 100 r/min using 100 mL phosphate buffer （pH 6.8） as release medium. The release amount was determined by HPLC with a C18 column （250 mm × 4.6 mm, 5 μm） using the mobile phase consisting of methanol -0.4% carboxylic acid （65：35） at a flow rate of 1 mL/min and UV detection at 242 nm. The current method demonstrates good linearity over the range 4.052- 405.2 μg/mL （r2=0.9999） with an average recovery of 105.5%（RSD= 1.25%）. The accumulative release of alliin/alliinase double-layer tablets had good homogeneity for withinand betweenbatches. The method established is simple, accurate and repeatable for the determination of allicin release from alliin/alliinase double-layer tablets.展开更多
BACKGROUND：Early recurrence of hepatocellular carcinoma（HCC）is associated with worse prognosis after liver resection This study aimed to investigate the prognostic value of com mon liver enzyme markers in HCC early...BACKGROUND：Early recurrence of hepatocellular carcinoma（HCC）is associated with worse prognosis after liver resection This study aimed to investigate the prognostic value of com mon liver enzyme markers in HCC early recurrence after cu rative hepatectomy and to establish a simple predictive model for HCC early recurrence.METHODS： A total of 200 patients who had undergone curative resection for HCC were retrospectively analyzed. The patients were divided into early recurrence （within 2 years） and non-early recurrence groups. Demographical characteristics, preopera- tive liver function parameters, surgical factors and tumor related factors of the patients were assessed by univariate analysis to identify potential significant predictors for early recurrence after resection of HCC. Parameters with statisti- cal significance were entered into a Cox proportional hazard model to find independent risk factors. Receiver operating characteristic analysis was done to determine optimal cut-off values and the number of combined factors in multi-factor predictive model. RESULTS： Of 13 potential risk factors for early recurrence identified by univariate analysis, high lactate dehydrogenase （LDH〉206 U/L, HR=1.711, P=0.006）, high aspartate aminotransferase （AST）/alanine aminotransferase （ALT） ratio （AST/ ALT〉0.96, HR=1.769, P=0.006）, elevated alpha-fetoprotein （AFP〉8.6 ng/mL, HR=2.079, P=0.007）, small resection margin （〈1 cm, HR=2.354, P〈0.001） and advanced TNM stage （TNM III-IV, HR=2.164, P〈0.001） were independent risk factors for early recurrence of HCC shown by multivariate analysis. Patients with three or more concurrent independent risk factors had significantly higher risk for early recurrence than those with low risk factors. The sensitivity and specificity of this predictive model are 53.6% and 80.7%, respectively （area under curve=0.741, 95% CI 0.674-0.800, P〈0.0001）. CONCLUSIONS： Preoperative common fiver enzyme markers, LDH and AST/ALT ratio, were independently associated with early recurrence of HCC. The combination of serum liver enzyme markers with AFP, resection margin and TNM stage bet- ter predicted early recurrence of HCC after curative resection in a simple multi-factor model.展开更多
Ionic gel(IG)electrolytes are emerging as promising components for the development of next-generation supercapacitors(SCs),offering benefits in terms of safety,cost-effectiveness,and flexibility.The ionic conductivity...Ionic gel(IG)electrolytes are emerging as promising components for the development of next-generation supercapacitors(SCs),offering benefits in terms of safety,cost-effectiveness,and flexibility.The ionic conductivity,stability,and mechanical properties of the gel electrolyte are relevant factors to be considered and the key to improving the performance of the SC.However,the structure–activity relationship between the internal structure of IGs and their SC properties is not fully understood.In the current study,the intuitive and regular structure–activity relationship between the structure and properties of IGs was revealed via combining computational simulation and experiment.In terms of conductivity,the ionic liquid(IL)([EMIM][TFSI])in the IG has a high self-diffusion coefficient calculated by molecular dynamics simulation(MDS),which is conductive to transfer and then improves the conductivity.The radial distribution function of the MDS shows that the larger the g(r)between the particles in the polymer network,the stronger the interaction.For stability,IGs based on[EMIM][TFSI]and[EOMIM][TFSI]ILs have higher density functional theory calculated binding energy,which is reflected in the excellent thermal stability and excellent capacitor cycle stability.Based on the internal pore size distribution and stress-strain characterization of the gel network([ME3MePy][TFSI]and[BMIM][TFSI]as additives),the highly crosslinked aggregate network significantly reduces the internal mesoporous distribution and plays a leading role in improving the mechanical properties of the network.By using this strategy,it will be possible to design the ideal structure of the IG and achieve excellent performance.展开更多
[Cp^(*)Co(CO)l_(2)]effectively catalyzes pyridyl-directed C-H allylation of arenes with allylic amines in the presence of AgOAc and CF_(3)COOAg.The reaction features ortho-position monoallylation of 2-pyridylarenes,gi...[Cp^(*)Co(CO)l_(2)]effectively catalyzes pyridyl-directed C-H allylation of arenes with allylic amines in the presence of AgOAc and CF_(3)COOAg.The reaction features ortho-position monoallylation of 2-pyridylarenes,giving the allylated arenes in moderate to high yields.A range of functional groups including OMe,Me,Ph,F,Cl,Br,CF_(3),C(0)Me,COOEt,and COOH groups are tolerated.Pyrim-idyl-directed C-H allylation of arenes were also performed under the same conditions.Reaction of 2-phenylpyrimidine,2-(4-methoxyphenyl)pyrimidine/and 2-(3-fluorophenyl)pyrimidine leads to a mixture of ortho-position mono-and bisallylation products.Reaction of other 2-(substituted aryl)pyrimidines resulted in ortho-position monoallylation products.展开更多
基金supported by grants from the National Natural Science Foundation of China(81572393)Key Project of Medical Science and Technology Development Foundation,Nanjing Department of Health(ZKX15020)+1 种基金Jiangsu Province Innovation for Ph.D.Candidate(KYLX_0058)Scientific Research Foundation of Graduate School of Nanjing University(2013CL14)
文摘BACKGROUND： Recurrence of hepatocellular carcinoma （HCC） after curative resection remains a major cause of treatment failure and tumor-related death. Patterns of HCC recur- rence can be categorized into early recurrence and late recurrence which have different underlying mechanisms. In this study, we investigated if simple inflammation-based clinical markers can distinguish patterns of recurrence after curative resection of HCC.
基金supported by grants from the National Natural Science Foundation of China(81572393 and 81602093)the Natural Science Foundation of Jiangsu Province(BK20160118)+1 种基金the Key Projects supported by Medical Science and Technology Develop-ment Foundation,Nanjing Municipality Health Bureau(ZKX15020 and ZKX17022)Fundamental Research Funds for the Central Universities(021414380215,020414380080 and 021414380329)
文摘Background: Hepatic ischemia/reperfusion(I/R) injury remains a significant problem in clinical practice. Sphingosine kinase 1(Sph K1) phosphorylates sphingosine to sphingosine-1-phosphate(S1 P) which participates in multiple bioactive processes. However, little is known about the role of Sph K1 in hepatic I/R injury. This study aimed to investigate the effect of Sph K1 knockout on liver I/R injury and to explore underlying mechanisms. Methods: Sph K1 knockout and wild type mice were subjected to 70% partial hepatic I/R. Serum alanine aminotransferase was determined to indicate the degree of liver damage. Hematoxylin-eosin staining and TUNEL assay were used to assess histological changes and hepatocellular apoptosis, respectively. Immunohistochemistry was performed to detect the expression and translocation of phosphorylated p65 and signal transducer and activator of transcription 3(STAT3). Western blotting was used to determine the expression of S1 P receptor 1(S1 PR1), phosphorylated p65 and STAT3. Real-time PCR was used to demonstrate the changes of proinflammatory cytokines. Oxidative stress markers were also determined through biochemical assays. Results: Sph K1 knockout significantly ameliorated I/R-induced liver damage, mitigated liver tissue necrosis and apoptosis compared with wild type control. I/R associated inflammation was alleviated in Sph K1 knockout mice as demonstrated by attenuated expression of S1 PR1 and reduced phosphorylation of nuclear factor kappa B p65 and STAT3. The proinflammatory cytokines interleukin-1 β, interleukin-6 and tumor necrosis factor-α were also inhibited by Sph K1 genetic deletion. The oxidative stress markers were lower in Sph K1 knockout mice after I/R injury than wild type mice. Conclusions: Knockout of Sph K1 significantly alleviated damage after hepatic I/R injury, possibly through inhibiting inflammation and oxidative stress. Sph K1 may be a novel and potent target in clinical practice in I/R-related liver injury.
文摘A simple, precise and accurate method was developed and validated for the determination of allicin release from alliin/alliinase double-layer tablets. According to Appendix XC Ⅱ of Chinese Pharmacopoeia 2010 edition Volume II, a small glass-method was adopted at the rotational speed of 100 r/min using 100 mL phosphate buffer （pH 6.8） as release medium. The release amount was determined by HPLC with a C18 column （250 mm × 4.6 mm, 5 μm） using the mobile phase consisting of methanol -0.4% carboxylic acid （65：35） at a flow rate of 1 mL/min and UV detection at 242 nm. The current method demonstrates good linearity over the range 4.052- 405.2 μg/mL （r2=0.9999） with an average recovery of 105.5%（RSD= 1.25%）. The accumulative release of alliin/alliinase double-layer tablets had good homogeneity for withinand betweenbatches. The method established is simple, accurate and repeatable for the determination of allicin release from alliin/alliinase double-layer tablets.
基金supported by grants from the Key Project of Medical Science and Technology Development FoundationNanjing Municipality Health Bureau(ZKX12011)+1 种基金Jiangsu Provincial Innovation Program for Ph D Candidates(KYLX_0058)Scientific Research Foundation of Graduate School of Nanjing University(2013CL14)
文摘BACKGROUND：Early recurrence of hepatocellular carcinoma（HCC）is associated with worse prognosis after liver resection This study aimed to investigate the prognostic value of com mon liver enzyme markers in HCC early recurrence after cu rative hepatectomy and to establish a simple predictive model for HCC early recurrence.METHODS： A total of 200 patients who had undergone curative resection for HCC were retrospectively analyzed. The patients were divided into early recurrence （within 2 years） and non-early recurrence groups. Demographical characteristics, preopera- tive liver function parameters, surgical factors and tumor related factors of the patients were assessed by univariate analysis to identify potential significant predictors for early recurrence after resection of HCC. Parameters with statisti- cal significance were entered into a Cox proportional hazard model to find independent risk factors. Receiver operating characteristic analysis was done to determine optimal cut-off values and the number of combined factors in multi-factor predictive model. RESULTS： Of 13 potential risk factors for early recurrence identified by univariate analysis, high lactate dehydrogenase （LDH〉206 U/L, HR=1.711, P=0.006）, high aspartate aminotransferase （AST）/alanine aminotransferase （ALT） ratio （AST/ ALT〉0.96, HR=1.769, P=0.006）, elevated alpha-fetoprotein （AFP〉8.6 ng/mL, HR=2.079, P=0.007）, small resection margin （〈1 cm, HR=2.354, P〈0.001） and advanced TNM stage （TNM III-IV, HR=2.164, P〈0.001） were independent risk factors for early recurrence of HCC shown by multivariate analysis. Patients with three or more concurrent independent risk factors had significantly higher risk for early recurrence than those with low risk factors. The sensitivity and specificity of this predictive model are 53.6% and 80.7%, respectively （area under curve=0.741, 95% CI 0.674-0.800, P〈0.0001）. CONCLUSIONS： Preoperative common fiver enzyme markers, LDH and AST/ALT ratio, were independently associated with early recurrence of HCC. The combination of serum liver enzyme markers with AFP, resection margin and TNM stage bet- ter predicted early recurrence of HCC after curative resection in a simple multi-factor model.
基金This study was supported by the National Natural Science Foundation of China(22222502)The authors would like to thank the Key Project of the Education Department of Liaoning Province of China(No.LJKZ1010)+1 种基金the Zhenjiang“Jinshan Talents”Project 2021,the Doctoral Foundation of Bohai University(0521bs005)the Innovation Fund Project for Graduate Students of Bohai University(YJC2023-016).
文摘Ionic gel(IG)electrolytes are emerging as promising components for the development of next-generation supercapacitors(SCs),offering benefits in terms of safety,cost-effectiveness,and flexibility.The ionic conductivity,stability,and mechanical properties of the gel electrolyte are relevant factors to be considered and the key to improving the performance of the SC.However,the structure–activity relationship between the internal structure of IGs and their SC properties is not fully understood.In the current study,the intuitive and regular structure–activity relationship between the structure and properties of IGs was revealed via combining computational simulation and experiment.In terms of conductivity,the ionic liquid(IL)([EMIM][TFSI])in the IG has a high self-diffusion coefficient calculated by molecular dynamics simulation(MDS),which is conductive to transfer and then improves the conductivity.The radial distribution function of the MDS shows that the larger the g(r)between the particles in the polymer network,the stronger the interaction.For stability,IGs based on[EMIM][TFSI]and[EOMIM][TFSI]ILs have higher density functional theory calculated binding energy,which is reflected in the excellent thermal stability and excellent capacitor cycle stability.Based on the internal pore size distribution and stress-strain characterization of the gel network([ME3MePy][TFSI]and[BMIM][TFSI]as additives),the highly crosslinked aggregate network significantly reduces the internal mesoporous distribution and plays a leading role in improving the mechanical properties of the network.By using this strategy,it will be possible to design the ideal structure of the IG and achieve excellent performance.
基金the National Natural Science Foundation of China(No.21372212)the National Basic Research Program of China(No.2015CB856600)is greatly acknowledged.
文摘[Cp^(*)Co(CO)l_(2)]effectively catalyzes pyridyl-directed C-H allylation of arenes with allylic amines in the presence of AgOAc and CF_(3)COOAg.The reaction features ortho-position monoallylation of 2-pyridylarenes,giving the allylated arenes in moderate to high yields.A range of functional groups including OMe,Me,Ph,F,Cl,Br,CF_(3),C(0)Me,COOEt,and COOH groups are tolerated.Pyrim-idyl-directed C-H allylation of arenes were also performed under the same conditions.Reaction of 2-phenylpyrimidine,2-(4-methoxyphenyl)pyrimidine/and 2-(3-fluorophenyl)pyrimidine leads to a mixture of ortho-position mono-and bisallylation products.Reaction of other 2-(substituted aryl)pyrimidines resulted in ortho-position monoallylation products.
