Hepatic encephalopathy(HE)is a formidable complication in patients with decompensated cirrhosis,often necessitating the administration of rifaximin(RFX)for effective management.RFX,is a gut-restricted,poorly-absorbabl...Hepatic encephalopathy(HE)is a formidable complication in patients with decompensated cirrhosis,often necessitating the administration of rifaximin(RFX)for effective management.RFX,is a gut-restricted,poorly-absorbable oral rifamycin derived antibiotic that can be used in addition to lactulose for the secondary prophylaxis of HE.It has shown notable reductions in infection,hospital readmission,duration of hospital stay,and mortality.However,limited data exist about the concurrent use of RFX with broad-spectrum antibiotics,because the patients are typically excluded from studies assessing RFX efficacy in HE.A pharmacist-driven quasi-experimental pilot study was done to address this gap.They argue against the necessity of RFX in HE during broad-spectrum antibiotic treatment,particularly in critically ill patients in intensive care unit(ICU).The potential for safe RFX discontinuation without adverse effects is clearly illuminated and valuable insight into the optimization of therapeutic strategies is offered.The findings also indicate that RFX discontinuation during broadspectrum antibiotic therapy was not associated with higher rates of delirium or coma,and this result remained robust after adjustment in multivariate analysis.Furthermore,rates of other secondary clinical and safety outcomes,including ICU mortality and 48-hour changes in vasopressor requirements,were comparable.However,since the activity of RFX is mainly confined to the modulation of gut microbiota,its potential utility in patients undergoing extensive systemic antibiotic therapy is debatable,given the overlapping antibiotic activity.Further,this suggests that the action of RFX on HE is class-specific(related to its activity on gut microbiota),rather than drug-specific.A recent double-blind randomized controlled(ARiE)trial provided further evidence-based support for RFX withdrawal in critically ill cirrhotic ICU patients receiving broad-spectrum antibiotics.Both studies prompt further discussion about optimal therapeutic strategy for patients facing the dual challenge of HE and systemic infections.Despite these compelling results,both studies have limitations.A prospective,multi-center evaluation of a larger sample,with placebo control,and comprehensive neurologic evaluation of HE is warranted.It should include an exploration of longer-term outcome and the impact of this protocol in non-critically ill liver disease patients.展开更多
We retrospectively evaluated the efficacy and safety of the combination drug piperacillin/tazobactam (PIPC/TAZ) in comparison with those of fourth-generation cephalosporins (4th Cephs) as initial empirical treatment i...We retrospectively evaluated the efficacy and safety of the combination drug piperacillin/tazobactam (PIPC/TAZ) in comparison with those of fourth-generation cephalosporins (4th Cephs) as initial empirical treatment in hematological malignancies patients with febrile neutropenia (FN). Among 200 patients assessed in this study, 49 had received PIPC/TAZ and 151 4th Cephs. Patient background characteristics were comparable between the two treatment groups. The overall efficacy rate in those receiving 4th Cephs and PIPC/TAZ was 57.0% (86/151 patients) and 59.2% (29/49 patients), respectively, with no significant difference detected between the two treatment regimens (P = 0.78). Treat-ment did not need to be discontinued or interrupted due to development of adverse drug reactions in any of the patients. Therefore in this study the efficacy and safety of PIPC/TAZ as initial antimicrobial treatment for FN in patients with hematological malignancies were not inferior to those of 4th Cephs. Based on the preliminary data obtained in this study, we propose to conduct a multicenter, prospective, controlled study to compare PIPC/TAZ versus CFPM given as empirical antimicrobial treatment against FN in patients with hematological malignancies.展开更多
A simple, accurate and precise spectrophotometric method has been proposed for the determination of eleven cephalosporins, namely;cefaclor monohydrate, cefadroxil monohydrate, cefalexin anhydrous, cefradine anhydrous,...A simple, accurate and precise spectrophotometric method has been proposed for the determination of eleven cephalosporins, namely;cefaclor monohydrate, cefadroxil monohydrate, cefalexin anhydrous, cefradine anhydrous, cefotaxime sodium, cefoperazone sodium, ceftriaxone sodium, ceftazidime penthydrate, cefazolin sodium, cefixime and cefpodoxime pro- xetil in bulk drug and in pharmaceutical formulations. The method depends on hydrolysis of the studied drugs using 0.5M NaOH at 100°C and subsequent reaction of the formed sulfide ions with NBD-Cl (4-chloro-7-nitrobenzo-2-oxa-1, 3-diazole) to form a yellow-colored chromogen measured at 390 nm. Different variables affecting the reaction (e.g. NaOH concentration, hydrolysis time, NBD-Cl concentration and diluting solvent) were studied and optimized. Under the optimum conditions, linear relationships with good correlation coefficients (0.9990- 0.9999) were found in the range of 5-160 μg mL-1 for all studied drugs. The limits of assay detection and quantitiation ranged from 0.289 to 5.867 and from 0.878 to 17.778 μg mL-1;respectively. The accuracy and precision of the proposed method were satisfactory. The method was successfully applied for analysis of the studied drugs in their pharmaceutical formulations and the recovery percentages ranged from 96.6 to 103.5%.展开更多
A simple, precise and accurate kinetic spectro-photometric method for determination of ce-fradine anhydrous, cefaclor monohydrate, ce-fadroxil monohydrate, cefalexin anhydrous and cefixime in bulk and in pharmaceutica...A simple, precise and accurate kinetic spectro-photometric method for determination of ce-fradine anhydrous, cefaclor monohydrate, ce-fadroxil monohydrate, cefalexin anhydrous and cefixime in bulk and in pharmaceutical formula-tions has been developed. The method based on a kinetic investigation of the reaction of the free carboxylic acid group of the drug with a mixture of potassium iodate and potassium iodide at room temperature to form yellow coloured triiodide ions. The reaction was followed up spectrophotometrically by measuring the increase in absorbance at 352 nm as a function of time. The initial rate, fixed time, variable time and rate-constant methods were adopted for constructing the calibration curves but fixed time method has been found to be more applicable. The analytical performance of the method, in terms of accuracy and precision, was statistically validated;the results were satisfactory. The method has been successfully applied to the determination of the studied drugs in commercial pharmaceutical formulations. Statistical comparison of the results with a well established reported method showed excellent ag- reement and proved that there is no significant difference in the accuracy and precision.展开更多
Two universal spectral ranges(4550-4100 cm^(-1) and 6190-5510 cm^(-1))for construction of quantitative models of homologous analogs of cephalosporins were proposed by evaluating theperformance of five spectral ranges ...Two universal spectral ranges(4550-4100 cm^(-1) and 6190-5510 cm^(-1))for construction of quantitative models of homologous analogs of cephalosporins were proposed by evaluating theperformance of five spectral ranges and their combinations,using three data sets of cephalos-porins for injection,ie.,cefuroxime sodium,cetriaxone sodium and cefoperazone sodium.Subsequently,the proposed ranges were validated by using eight calibration sets of otherhomologous analogs of cephalosporins for injection,namely cefmenoxime hydrochloride,ceftezole sodium,cefmetazole,cefoxitin sodium,cefotaxime sodium,cefradine,cephazolin sodium and ceftizoxime sodium.All the constructed quantitative models for the eight kinds of cephalosporinsusing these universal ranges could fulill the requirements for quick quantification.After that,competitive adaptive reweighted sampling(CARS)algorithm and infrared(IR)-near infrared(NIR)two-dimensional(2D)correlation spectral analysis were used to determine the scientific basis of these two spectral ranges as the universal regions for the construction of quantitativemodels of cephalosporins.The CAR.S algorithm demonstrated that the ranges of 4550-4100 cm^(-1) and 6190-5510 cm^(-1) included some key wavenumbers which could be attributed to content changes of cephalosporins.The IR-NIR 2D spectral analysis showed that certain wavenumbersin these two regions have strong correlations to the structures of those cephalosporins that wereeasy to degrade.展开更多
Nine new derivatives of 7 β - (5- methyl- 1- aryl- 1H-1, 2, 3- triazoly- 4- carboxamido) cephalosporins were synthesized by acylction of 7 β -amino group of 7-ACA, 7-ADCA and 7-ACT with 5 -methsyl- 1 -aryl- 1 H- 1,2...Nine new derivatives of 7 β - (5- methyl- 1- aryl- 1H-1, 2, 3- triazoly- 4- carboxamido) cephalosporins were synthesized by acylction of 7 β -amino group of 7-ACA, 7-ADCA and 7-ACT with 5 -methsyl- 1 -aryl- 1 H- 1,2,3-triazoly-4-formyl chloride. The structure of the compounds were confirmed by elementray analysis IR, HNMR and FAB-MS. Some of them showed significant antibacterial activity展开更多
The emergent two-dimensional(2D)material,tin diselenide(SnSe_(2)),has garnered significant consideration for its potential in image capturing systems,optical communication,and optoelectronic memory.Nevertheless,SnSe_(...The emergent two-dimensional(2D)material,tin diselenide(SnSe_(2)),has garnered significant consideration for its potential in image capturing systems,optical communication,and optoelectronic memory.Nevertheless,SnSe_(2)-based photodetection faces obstacles,including slow response speed and low normalized detectivity.In this work,photodetectors based on SnS/SnSe_(2)and SnSe/SnSe_(2)p−n heterostructures have been implemented through a polydimethylsiloxane(PDMS)−assisted transfer method.These photodetectors demonstrate broad-spectrum photoresponse within the 405 to 850 nm wavelength range.The photodetector based on the SnS/SnSe_(2)heterostructure exhibits a significant responsivity of 4.99×10^(3)A∙W^(−1),normalized detectivity of 5.80×10^(12)cm∙Hz^(1/2)∙W^(−1),and fast response time of 3.13 ms,respectively,owing to the built-in electric field.Meanwhile,the highest values of responsivity,normalized detectivity,and response time for the photodetector based on the SnSe/SnSe_(2)heterostructure are 5.91×10^(3)A∙W^(−1),7.03×10^(12)cm∙Hz^(1/2)∙W−1,and 4.74 ms,respectively.And their photodetection performances transcend those of photodetectors based on individual SnSe_(2),SnS,SnSe,and other commonly used 2D materials.Our work has demonstrated an effective strategy to improve the performance of SnSe_(2)-based photodetectors and paves the way for their future commercialization.展开更多
Diverse bacterial and fungal pathogens attack plants,causing biotic stress and severe yield losses globally.These losses are expected to become more serious as climate change improves conditions for many pathogens.The...Diverse bacterial and fungal pathogens attack plants,causing biotic stress and severe yield losses globally.These losses are expected to become more serious as climate change improves conditions for many pathogens.Therefore,identifying genes conferring broad-spectrum disease resistance and elucidating their underlying mechanisms provides important resources for plant breeding.WRKY transcription factors affect plant growth and stress responses.However,the functions of many WRKY proteins remain to be elucidated.Here,we demonstrated the role of rice(Oryza sativa)WRKY groupⅢtranscription factor OsWRKY65 in immunity.OsWRKY65 localized to the nucleus and acted as transcriptional repressor.Genetic and molecular functional analyses showed that OsWRKY65 increases resistance to the fungal pathogen Fusarium fujikuroi through downregulation of GA signaling and upregulation of JA signaling.Moreover,OsWRKY65 modulated the expression of the key genes that confer susceptibility or resistance to Xanthomonas oryzae pv.oryzae to enhance immunity against the pathogen.In particular,OsWRKY65directly bound to the promoter region of OsSWEET13 and repressed its expression.Taken together,our findings demonstrate that the OsWRKY65 enhances resistance to fungal and bacterial pathogens in rice.展开更多
基金Supported by the Chang Gung Medical Research Project,No.CMRPG3M1931-1932the National Science and Technology Council,No.MOST 110-2314-B-182A-093-and No.NMRPG3L0331.
文摘Hepatic encephalopathy(HE)is a formidable complication in patients with decompensated cirrhosis,often necessitating the administration of rifaximin(RFX)for effective management.RFX,is a gut-restricted,poorly-absorbable oral rifamycin derived antibiotic that can be used in addition to lactulose for the secondary prophylaxis of HE.It has shown notable reductions in infection,hospital readmission,duration of hospital stay,and mortality.However,limited data exist about the concurrent use of RFX with broad-spectrum antibiotics,because the patients are typically excluded from studies assessing RFX efficacy in HE.A pharmacist-driven quasi-experimental pilot study was done to address this gap.They argue against the necessity of RFX in HE during broad-spectrum antibiotic treatment,particularly in critically ill patients in intensive care unit(ICU).The potential for safe RFX discontinuation without adverse effects is clearly illuminated and valuable insight into the optimization of therapeutic strategies is offered.The findings also indicate that RFX discontinuation during broadspectrum antibiotic therapy was not associated with higher rates of delirium or coma,and this result remained robust after adjustment in multivariate analysis.Furthermore,rates of other secondary clinical and safety outcomes,including ICU mortality and 48-hour changes in vasopressor requirements,were comparable.However,since the activity of RFX is mainly confined to the modulation of gut microbiota,its potential utility in patients undergoing extensive systemic antibiotic therapy is debatable,given the overlapping antibiotic activity.Further,this suggests that the action of RFX on HE is class-specific(related to its activity on gut microbiota),rather than drug-specific.A recent double-blind randomized controlled(ARiE)trial provided further evidence-based support for RFX withdrawal in critically ill cirrhotic ICU patients receiving broad-spectrum antibiotics.Both studies prompt further discussion about optimal therapeutic strategy for patients facing the dual challenge of HE and systemic infections.Despite these compelling results,both studies have limitations.A prospective,multi-center evaluation of a larger sample,with placebo control,and comprehensive neurologic evaluation of HE is warranted.It should include an exploration of longer-term outcome and the impact of this protocol in non-critically ill liver disease patients.
文摘We retrospectively evaluated the efficacy and safety of the combination drug piperacillin/tazobactam (PIPC/TAZ) in comparison with those of fourth-generation cephalosporins (4th Cephs) as initial empirical treatment in hematological malignancies patients with febrile neutropenia (FN). Among 200 patients assessed in this study, 49 had received PIPC/TAZ and 151 4th Cephs. Patient background characteristics were comparable between the two treatment groups. The overall efficacy rate in those receiving 4th Cephs and PIPC/TAZ was 57.0% (86/151 patients) and 59.2% (29/49 patients), respectively, with no significant difference detected between the two treatment regimens (P = 0.78). Treat-ment did not need to be discontinued or interrupted due to development of adverse drug reactions in any of the patients. Therefore in this study the efficacy and safety of PIPC/TAZ as initial antimicrobial treatment for FN in patients with hematological malignancies were not inferior to those of 4th Cephs. Based on the preliminary data obtained in this study, we propose to conduct a multicenter, prospective, controlled study to compare PIPC/TAZ versus CFPM given as empirical antimicrobial treatment against FN in patients with hematological malignancies.
文摘A simple, accurate and precise spectrophotometric method has been proposed for the determination of eleven cephalosporins, namely;cefaclor monohydrate, cefadroxil monohydrate, cefalexin anhydrous, cefradine anhydrous, cefotaxime sodium, cefoperazone sodium, ceftriaxone sodium, ceftazidime penthydrate, cefazolin sodium, cefixime and cefpodoxime pro- xetil in bulk drug and in pharmaceutical formulations. The method depends on hydrolysis of the studied drugs using 0.5M NaOH at 100°C and subsequent reaction of the formed sulfide ions with NBD-Cl (4-chloro-7-nitrobenzo-2-oxa-1, 3-diazole) to form a yellow-colored chromogen measured at 390 nm. Different variables affecting the reaction (e.g. NaOH concentration, hydrolysis time, NBD-Cl concentration and diluting solvent) were studied and optimized. Under the optimum conditions, linear relationships with good correlation coefficients (0.9990- 0.9999) were found in the range of 5-160 μg mL-1 for all studied drugs. The limits of assay detection and quantitiation ranged from 0.289 to 5.867 and from 0.878 to 17.778 μg mL-1;respectively. The accuracy and precision of the proposed method were satisfactory. The method was successfully applied for analysis of the studied drugs in their pharmaceutical formulations and the recovery percentages ranged from 96.6 to 103.5%.
文摘A simple, precise and accurate kinetic spectro-photometric method for determination of ce-fradine anhydrous, cefaclor monohydrate, ce-fadroxil monohydrate, cefalexin anhydrous and cefixime in bulk and in pharmaceutical formula-tions has been developed. The method based on a kinetic investigation of the reaction of the free carboxylic acid group of the drug with a mixture of potassium iodate and potassium iodide at room temperature to form yellow coloured triiodide ions. The reaction was followed up spectrophotometrically by measuring the increase in absorbance at 352 nm as a function of time. The initial rate, fixed time, variable time and rate-constant methods were adopted for constructing the calibration curves but fixed time method has been found to be more applicable. The analytical performance of the method, in terms of accuracy and precision, was statistically validated;the results were satisfactory. The method has been successfully applied to the determination of the studied drugs in commercial pharmaceutical formulations. Statistical comparison of the results with a well established reported method showed excellent ag- reement and proved that there is no significant difference in the accuracy and precision.
基金supported by grant from the National Department Public Benefit Research Foundation(General Administration of Quality Supervision,inspection and Quarantine of the People's Republicof China)(Grant No.2012104008)At the sametime,the authors would like to thank Prof Yi zeng Liang(Central South University,PR China)for freely providing us with CARS program。
文摘Two universal spectral ranges(4550-4100 cm^(-1) and 6190-5510 cm^(-1))for construction of quantitative models of homologous analogs of cephalosporins were proposed by evaluating theperformance of five spectral ranges and their combinations,using three data sets of cephalos-porins for injection,ie.,cefuroxime sodium,cetriaxone sodium and cefoperazone sodium.Subsequently,the proposed ranges were validated by using eight calibration sets of otherhomologous analogs of cephalosporins for injection,namely cefmenoxime hydrochloride,ceftezole sodium,cefmetazole,cefoxitin sodium,cefotaxime sodium,cefradine,cephazolin sodium and ceftizoxime sodium.All the constructed quantitative models for the eight kinds of cephalosporinsusing these universal ranges could fulill the requirements for quick quantification.After that,competitive adaptive reweighted sampling(CARS)algorithm and infrared(IR)-near infrared(NIR)two-dimensional(2D)correlation spectral analysis were used to determine the scientific basis of these two spectral ranges as the universal regions for the construction of quantitativemodels of cephalosporins.The CAR.S algorithm demonstrated that the ranges of 4550-4100 cm^(-1) and 6190-5510 cm^(-1) included some key wavenumbers which could be attributed to content changes of cephalosporins.The IR-NIR 2D spectral analysis showed that certain wavenumbersin these two regions have strong correlations to the structures of those cephalosporins that wereeasy to degrade.
文摘Nine new derivatives of 7 β - (5- methyl- 1- aryl- 1H-1, 2, 3- triazoly- 4- carboxamido) cephalosporins were synthesized by acylction of 7 β -amino group of 7-ACA, 7-ADCA and 7-ACT with 5 -methsyl- 1 -aryl- 1 H- 1,2,3-triazoly-4-formyl chloride. The structure of the compounds were confirmed by elementray analysis IR, HNMR and FAB-MS. Some of them showed significant antibacterial activity
基金supported by the Jilin Scientific and Technological Development Program(Grant No.20230101286JC)National Natural Science Foundation of China(Grant Nos.61975051,6227503,and 52002110)Hebei Provincial Department of Education Innovation Ability Training Funding Project for graduate students.
文摘The emergent two-dimensional(2D)material,tin diselenide(SnSe_(2)),has garnered significant consideration for its potential in image capturing systems,optical communication,and optoelectronic memory.Nevertheless,SnSe_(2)-based photodetection faces obstacles,including slow response speed and low normalized detectivity.In this work,photodetectors based on SnS/SnSe_(2)and SnSe/SnSe_(2)p−n heterostructures have been implemented through a polydimethylsiloxane(PDMS)−assisted transfer method.These photodetectors demonstrate broad-spectrum photoresponse within the 405 to 850 nm wavelength range.The photodetector based on the SnS/SnSe_(2)heterostructure exhibits a significant responsivity of 4.99×10^(3)A∙W^(−1),normalized detectivity of 5.80×10^(12)cm∙Hz^(1/2)∙W^(−1),and fast response time of 3.13 ms,respectively,owing to the built-in electric field.Meanwhile,the highest values of responsivity,normalized detectivity,and response time for the photodetector based on the SnSe/SnSe_(2)heterostructure are 5.91×10^(3)A∙W^(−1),7.03×10^(12)cm∙Hz^(1/2)∙W−1,and 4.74 ms,respectively.And their photodetection performances transcend those of photodetectors based on individual SnSe_(2),SnS,SnSe,and other commonly used 2D materials.Our work has demonstrated an effective strategy to improve the performance of SnSe_(2)-based photodetectors and paves the way for their future commercialization.
基金funded by Research Program for Agricultural Science and Technology Development(PJ01570601)and the Fellowship Program(PJ01661001 and PJ01570601)of the National Institute of Agricultural Sciences,Rural Development Administration,Republic of Korea。
文摘Diverse bacterial and fungal pathogens attack plants,causing biotic stress and severe yield losses globally.These losses are expected to become more serious as climate change improves conditions for many pathogens.Therefore,identifying genes conferring broad-spectrum disease resistance and elucidating their underlying mechanisms provides important resources for plant breeding.WRKY transcription factors affect plant growth and stress responses.However,the functions of many WRKY proteins remain to be elucidated.Here,we demonstrated the role of rice(Oryza sativa)WRKY groupⅢtranscription factor OsWRKY65 in immunity.OsWRKY65 localized to the nucleus and acted as transcriptional repressor.Genetic and molecular functional analyses showed that OsWRKY65 increases resistance to the fungal pathogen Fusarium fujikuroi through downregulation of GA signaling and upregulation of JA signaling.Moreover,OsWRKY65 modulated the expression of the key genes that confer susceptibility or resistance to Xanthomonas oryzae pv.oryzae to enhance immunity against the pathogen.In particular,OsWRKY65directly bound to the promoter region of OsSWEET13 and repressed its expression.Taken together,our findings demonstrate that the OsWRKY65 enhances resistance to fungal and bacterial pathogens in rice.
