We describe a specific procedure for the synthesis of deuterium-labelled 2-（1-methylalkyl）succinate established via alkylation of diethyl malonate, Krapcho decarboxylation reaction with D20 and hydrolysis reaction. ...We describe a specific procedure for the synthesis of deuterium-labelled 2-（1-methylalkyl）succinate established via alkylation of diethyl malonate, Krapcho decarboxylation reaction with D20 and hydrolysis reaction. Two novel compounds, 2-[^2H]-2-ethylsuccinic acid and 2-[^2H]-2-（1-methylhep- tyl）succinic acid were prepared via this synthetic route and characterized by mass spectrometry and ^1H NMR. The results showed that the 2-（1-methylalkyl）succinic acids were deuterated at the β-position, which is considered as an important reaction centre in the anaerobic degradation of n-alkanes.展开更多
2-oxo-3-aryl-succinates are not only important intermediates of organic and medical synthesis,but also good substances of direct asymmetric aldol additions using L-proline as a chiral catalyst.Nine new 2-oxo-3-aryl-su...2-oxo-3-aryl-succinates are not only important intermediates of organic and medical synthesis,but also good substances of direct asymmetric aldol additions using L-proline as a chiral catalyst.Nine new 2-oxo-3-aryl-succinates were synthesized,their structures were confirmed by IR and 1H NMR.2-oxo-3-aryl-succinates were produced in high yields under simple and mild reaction conditions.展开更多
Gastrointestinal stromal tumors(GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and have gained considerable research and treatment interest,especially in the last two decades. GISTs are dr...Gastrointestinal stromal tumors(GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and have gained considerable research and treatment interest,especially in the last two decades. GISTs are driven by mutations commonly found in the KIT gene and less commonly in the platelet-derived growth factor receptor alpha gene,BRAF gene and succinate dehydrogenase gene. GISTs behave in a spectrum of malignant potential,and both the tumor size and mitotic index are the most commonly used prognostic criteria. Whilst surgical resection can offer the best cure,targeted therapy in the form of tyrosine kinase inhibitors(TKIs) has revolutionized the management options. As the first-line TKI,imatinib offers treatment for advanced and metastatic GISTs,adjuvant therapy in high-risk GISTs and as a neoadjuvant agent to downsize large tumors prior to resection. The emergence of drug resistance has altered some treatment options,including prolonging the first-line TKI from 1 to 3 years,increasing the dose of TKI or switching to second-line TKI. Other newer TKIs,such as sunitinib and regorafenib,may offer some treatment options for imatinib-resistant GISTs. New molecular targeted therapies are being evaluated,such as inhibitors of BRAF,heat shock protein 90,glutamine and mitogenactivated protein kinase signaling,as well as inhibitors of apoptosis proteins antagonist and even immunotherapy. This editorial review summarizes the recent research trials and potential treatment targets that may influence our future patient-specific management of GISTs. The current guidelines in GIST management from Europe,North America and Asia are highlighted.展开更多
OBJECTIVE:To evaluate systematically the clinical efficacy and safety of potassium dehydroandrographolide succinate injection(PDS) in treatment of infantile pneumonia.METHODS:Randomized controlled trials(RCTs) of infa...OBJECTIVE:To evaluate systematically the clinical efficacy and safety of potassium dehydroandrographolide succinate injection(PDS) in treatment of infantile pneumonia.METHODS:Randomized controlled trials(RCTs) of infantile pneumonia treated by PDS were searched in China National Knowledge Infrastructure Database,China Science and Technology Journal Database,Wanfang Database,Chinese Biomedical Literature Database,PubMed,and Cochrane Library,from January 1979 to July 2013.Two reviewers independently retrieved the RCTs and extracted the information.The quality of included studies was assessed by the Cochrane risk of bias,and a Meta-analysis was conducted with Review Manager 5.2 software.RESULTS:A total of 9 studies with 1056 participants were included.The quality of the studies was generally no high,only one study mentioned the random method.The Meta-analysis indicated that PDS was significantly superior to the conventional therapy in the total effective rate[relative risk(RR)=1.21,95%CI(1.14,1.27),P<0.000 01],the time of temperature recovery[mean difference(MD)=-1.43,95%CI(-1.75,-1.11),P<0.000 01],rale disappeared and cough relieving[MD=-1.44,95%CI(-1.93,-0.90),P<0.000 01].Six adverse drug reactions from five studies mainly represented rash and diarrhea,and no serious ADRs were reported.CONCLUSION:Based on this systematic review,PDS was proved effective and relatively safe in treatment of infantile pneumonia.However the articles enrolled in the study were not high in quality,studies with higher quality should be conducted for assessment of efficacy and safety of PDS in treatment of infantile pneumonia.展开更多
Vitamin E succinate was synthesized in organic solvents using a modified Novozym-435 as catalyst.In order to improve the catalytic performance of Novozym-435,the enzyme was modified using acetic anhydride, propionic a...Vitamin E succinate was synthesized in organic solvents using a modified Novozym-435 as catalyst.In order to improve the catalytic performance of Novozym-435,the enzyme was modified using acetic anhydride, propionic anhydride and succinic anhydride separately.We found that both the hydrolytic activity and the thermal stability of the modified Novozym-435 were enhanced compared with the unmodified enzyme.The modified Novozym-435 catalysts were used to synthesize the succinate derivative of vitamin E.Compared with the native Novozym-435,the catalytic activity of the modified novozym-435 in promoting the synthesis of vitamin E succinate was dramatically increased,with the novozym-435 modified with succinic anhydride（N435-S）as the most active catalyst.Conditions for the synthesis of vitamin E succinate were also optimized.A mixture of tert-butanol and DMSO（volume ratio of 2︰3）was the most suitable medium for the reaction,whereas the appropriate molar ratio of vitamin E to succinic anhydride and reaction temperature were 1︰5 and 40°C,respectively.Under these reaction conditions,the yield of vitamin E succinate reached 94.4%.N435-S could be reused for five batches.展开更多
In two experiments, the effects of succinate and NADH（reduced nicotinamide adenine dinucleotide） on metmyoglobin reductase activity and electron transport chain-linked metmyoglobin reduction were investigated and co...In two experiments, the effects of succinate and NADH（reduced nicotinamide adenine dinucleotide） on metmyoglobin reductase activity and electron transport chain-linked metmyoglobin reduction were investigated and compared. In experiment 1, metmyoglobin（MetMb）, substrate and inhibitors were incubated with mitochondria. Comparsion of the effects of succinate and NADH on MetMb reduction was investigated. The MetMb percentage in sample treated with 8 mol L-1 succinate decreased by about 69% after 3 h incubation, and the effect was inhibited by the addition of 10 mol L-1 electron transfer chain complex II inhibitor malonic acid; the MetMb percentage in samples treated with 2 mol L-1 NADH decreased by 56% and the effect was inhibited by the addition of 0.02 mol L-1 electron transport chain complex I inhibitor rotenone. These results indicated that electron transport chain played an important role in MetMb reduction. Both complex II and complex I take part in the MetMb reduction in mitochondria through different pathways. NADH-MetMb reduction system was less stable than succinateMetMb system. In experiment 2, the beef longissimus dorsi muscle was blended with different concentrations of succinate or NADH. Enhancing patties with higher concentration of succinate or NADH improved colour stability in vacuum packaged samples（P〈0.05）. These results verified that mitochondria electron transport chain is related to the MetMb reduction in meat system.展开更多
基金supported by the National Natural Science Foundation of China(No.41373070,51174092)the National Natural Science Foundation of China/Research Grants Council Joint Research Fund(No.41161160560)
文摘We describe a specific procedure for the synthesis of deuterium-labelled 2-（1-methylalkyl）succinate established via alkylation of diethyl malonate, Krapcho decarboxylation reaction with D20 and hydrolysis reaction. Two novel compounds, 2-[^2H]-2-ethylsuccinic acid and 2-[^2H]-2-（1-methylhep- tyl）succinic acid were prepared via this synthetic route and characterized by mass spectrometry and ^1H NMR. The results showed that the 2-（1-methylalkyl）succinic acids were deuterated at the β-position, which is considered as an important reaction centre in the anaerobic degradation of n-alkanes.
文摘2-oxo-3-aryl-succinates are not only important intermediates of organic and medical synthesis,but also good substances of direct asymmetric aldol additions using L-proline as a chiral catalyst.Nine new 2-oxo-3-aryl-succinates were synthesized,their structures were confirmed by IR and 1H NMR.2-oxo-3-aryl-succinates were produced in high yields under simple and mild reaction conditions.
文摘Gastrointestinal stromal tumors(GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and have gained considerable research and treatment interest,especially in the last two decades. GISTs are driven by mutations commonly found in the KIT gene and less commonly in the platelet-derived growth factor receptor alpha gene,BRAF gene and succinate dehydrogenase gene. GISTs behave in a spectrum of malignant potential,and both the tumor size and mitotic index are the most commonly used prognostic criteria. Whilst surgical resection can offer the best cure,targeted therapy in the form of tyrosine kinase inhibitors(TKIs) has revolutionized the management options. As the first-line TKI,imatinib offers treatment for advanced and metastatic GISTs,adjuvant therapy in high-risk GISTs and as a neoadjuvant agent to downsize large tumors prior to resection. The emergence of drug resistance has altered some treatment options,including prolonging the first-line TKI from 1 to 3 years,increasing the dose of TKI or switching to second-line TKI. Other newer TKIs,such as sunitinib and regorafenib,may offer some treatment options for imatinib-resistant GISTs. New molecular targeted therapies are being evaluated,such as inhibitors of BRAF,heat shock protein 90,glutamine and mitogenactivated protein kinase signaling,as well as inhibitors of apoptosis proteins antagonist and even immunotherapy. This editorial review summarizes the recent research trials and potential treatment targets that may influence our future patient-specific management of GISTs. The current guidelines in GIST management from Europe,North America and Asia are highlighted.
基金Supported by National Natural Science Foundation of China(Study on the Key Factors of Allergic Reaction That Caused by Chinese Herbal Injection Based on the Three-dimensional Database and Multi-dimensional Data Mining,No.81473547)Scientific Research Innovation Team Project of Beijing University of Chinese Medicine(Research on the Disciplinary of Clinical Pharmacology of Traditional Chinese Medicine,No.2011-CXTD-14)Ministry of Education Research Fund for Doctor Program(No.20130013120001,20120013130002)
文摘OBJECTIVE:To evaluate systematically the clinical efficacy and safety of potassium dehydroandrographolide succinate injection(PDS) in treatment of infantile pneumonia.METHODS:Randomized controlled trials(RCTs) of infantile pneumonia treated by PDS were searched in China National Knowledge Infrastructure Database,China Science and Technology Journal Database,Wanfang Database,Chinese Biomedical Literature Database,PubMed,and Cochrane Library,from January 1979 to July 2013.Two reviewers independently retrieved the RCTs and extracted the information.The quality of included studies was assessed by the Cochrane risk of bias,and a Meta-analysis was conducted with Review Manager 5.2 software.RESULTS:A total of 9 studies with 1056 participants were included.The quality of the studies was generally no high,only one study mentioned the random method.The Meta-analysis indicated that PDS was significantly superior to the conventional therapy in the total effective rate[relative risk(RR)=1.21,95%CI(1.14,1.27),P<0.000 01],the time of temperature recovery[mean difference(MD)=-1.43,95%CI(-1.75,-1.11),P<0.000 01],rale disappeared and cough relieving[MD=-1.44,95%CI(-1.93,-0.90),P<0.000 01].Six adverse drug reactions from five studies mainly represented rash and diarrhea,and no serious ADRs were reported.CONCLUSION:Based on this systematic review,PDS was proved effective and relatively safe in treatment of infantile pneumonia.However the articles enrolled in the study were not high in quality,studies with higher quality should be conducted for assessment of efficacy and safety of PDS in treatment of infantile pneumonia.
基金Supported by the Fundamental Research Funds for the Central Universities and the State Key Development Program for Basic Research of China(2007CB714304)
文摘Vitamin E succinate was synthesized in organic solvents using a modified Novozym-435 as catalyst.In order to improve the catalytic performance of Novozym-435,the enzyme was modified using acetic anhydride, propionic anhydride and succinic anhydride separately.We found that both the hydrolytic activity and the thermal stability of the modified Novozym-435 were enhanced compared with the unmodified enzyme.The modified Novozym-435 catalysts were used to synthesize the succinate derivative of vitamin E.Compared with the native Novozym-435,the catalytic activity of the modified novozym-435 in promoting the synthesis of vitamin E succinate was dramatically increased,with the novozym-435 modified with succinic anhydride（N435-S）as the most active catalyst.Conditions for the synthesis of vitamin E succinate were also optimized.A mixture of tert-butanol and DMSO（volume ratio of 2︰3）was the most suitable medium for the reaction,whereas the appropriate molar ratio of vitamin E to succinic anhydride and reaction temperature were 1︰5 and 40°C,respectively.Under these reaction conditions,the yield of vitamin E succinate reached 94.4%.N435-S could be reused for five batches.
基金the National Natural Science Foundation of China (31071624)
文摘In two experiments, the effects of succinate and NADH（reduced nicotinamide adenine dinucleotide） on metmyoglobin reductase activity and electron transport chain-linked metmyoglobin reduction were investigated and compared. In experiment 1, metmyoglobin（MetMb）, substrate and inhibitors were incubated with mitochondria. Comparsion of the effects of succinate and NADH on MetMb reduction was investigated. The MetMb percentage in sample treated with 8 mol L-1 succinate decreased by about 69% after 3 h incubation, and the effect was inhibited by the addition of 10 mol L-1 electron transfer chain complex II inhibitor malonic acid; the MetMb percentage in samples treated with 2 mol L-1 NADH decreased by 56% and the effect was inhibited by the addition of 0.02 mol L-1 electron transport chain complex I inhibitor rotenone. These results indicated that electron transport chain played an important role in MetMb reduction. Both complex II and complex I take part in the MetMb reduction in mitochondria through different pathways. NADH-MetMb reduction system was less stable than succinateMetMb system. In experiment 2, the beef longissimus dorsi muscle was blended with different concentrations of succinate or NADH. Enhancing patties with higher concentration of succinate or NADH improved colour stability in vacuum packaged samples（P〈0.05）. These results verified that mitochondria electron transport chain is related to the MetMb reduction in meat system.
