Objective:To evaluate the effects of a 48-week course of adefovir dipivoxil(ADV)plus Chinese medicine(CM)therapy,namely Tiaogan Jianpi Hexue(调肝健脾和血)and Tiaogan Jiedu Huashi(调肝解毒化湿)fomulae,in hepatitis B e ...Objective:To evaluate the effects of a 48-week course of adefovir dipivoxil(ADV)plus Chinese medicine(CM)therapy,namely Tiaogan Jianpi Hexue(调肝健脾和血)and Tiaogan Jiedu Huashi(调肝解毒化湿)fomulae,in hepatitis B e antigen(HBeAg)-positive Chinese patients.Methods:A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group(EG,received ADV plus CM)and control group(CG,received ADV plus CM-placebo)for 48 weeks.The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12,24,36,48,respectively.Secondary endpoints including liver functions(enzymes and bilirubin readings)were evaluated every 4 weeks at the beginning of week 24,36,and 48.Routine blood,urine,and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations.Adverse events(AEs)were documented.Results:The combination therapy demonstrated superior HBeAg loss at 48 weeks,without additional AEs.The full analysis population was 560 and 280 in each group.In the EG,population achieved HBeAg loss on week 12,24,36,and 48 were 25(8.90%),34(12.14%),52(18.57%),and 83(29.64%),respectively;the equivalent numbers in the CG were 20(7.14%),41(14.64%),54(19.29%),and 50(17.86%),respectively.There was a statistically significant difference between two groups on week 48(P<0.01).No additional AEs were found in EG.Subgroup analysis suggested different outcomes among treatment patterns.Conclusion:Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy.The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile(ChiCTR-TRC-11001263).展开更多
Background： The domestic prevalence of chronic hepatitis B （CHB） in China is 7.18% in 2006, imposing great societal healthcare burdens. Nucleot（s）ide analogues （NUCs） anti-hepatitis B virus （HBV） therapies ar...Background： The domestic prevalence of chronic hepatitis B （CHB） in China is 7.18% in 2006, imposing great societal healthcare burdens. Nucleot（s）ide analogues （NUCs） anti-hepatitis B virus （HBV） therapies are widely applied despite the relatively low rate of seroconversion and high risk of drug-resistant mutation. More effective treatments for CHB deserve further explorations. Combined therapy of NUCs plus Chinese herbal medicine （CHM） is widely accepted in China, which is recognized as a prospective alternative approach. The study was primarily designed to confirm the hypothesis that Tiaogan-Yipi Granule （调肝益脾颗粒, TGYP） or Tiaogan-Jianpi-Jiedu Granule （调肝健脾解毒颗粒, TGJPJD） plus entecavir tablet （ETV） was superior over ETV monotherapy in enhancing HBeAg loss rate. Methods： The study was a nationwide, large-scale, multi-center, double-blind, randomized, placebo-controlled trial with a designed duration of 108 weeks. A total of 16 hospitals and 596 eligible Chinese HBeAg positive CHB patients were enrolled from November 2012 to September 2013 and randomly allocated into 2 groups in 1：1 ratio via central randomization system： experimental group （EG） and control group （CG）. Subjects in EG received CM formulae （TGYP or TGJPJD, 50 g per dose, twice daily） plus ETV tablet （or ETV placebo） 0.5 mg per day in the first 24 weeks （stage 1）, and CHM granule plus ETV tablet （0.5 mg per day） from week 25 to 108 （stage 2）. Subjects in CG received CHM Granule placebo plus E＇IV tablet （0.5 mg per day） for 108 weeks throughout the trial. The assessments of primary outcomes （HBV serum markers and HBV-DNA） were conducted by a third-party College of American Pathologists （CAP） qualified laboratory. Adverse effects were observed in the hospitals of recruitment. Discussion： The study was designed to compare the curative effect of CM plus E＇IV and ETV monotherapy in respect of HBeAg loss, which is recognized by the European Association for the Study of the Liver as ＂a valuable endpoint＂. We believe this trial could provide a reliable status for patients＇ ＂joumey＂ towards durable responses after treatment discontinuation. The trial was registered before recruitment on Chinese Clinical trial registry （No. ChiCTR-TRC-12002784, Version 1.0, 2015/12/23）.展开更多
Lonicerae Japonicae Flos(LJF),a kind of traditional Chinese medicines(TCMs),has functions of detoxifying and evacuating heat.In the study,a method based on ultra-high performance liquid chromatography coupled with lin...Lonicerae Japonicae Flos(LJF),a kind of traditional Chinese medicines(TCMs),has functions of detoxifying and evacuating heat.In the study,a method based on ultra-high performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS)was developed for the chemical constituent analysis of organic acids,flavonoids,iridoids and new-generated compounds in sulfur-fumigated LJF(SF-LJF).Based on the accurate mass measurement(<±5 ppm),chromatographic behavior and diagnostic product ions(DPIs),113 constituents were unambiguously or tentatively characterized from SFLJF extract,including 46 chlorogenic acids,19 flavonoids,29 iridoid glycosides and 19 newly-generated compounds(including 17 sulfur-containing derivatives).In addition,5-CQA(5-caffeoylquinic acid,chlorogenic acid)was chosen to be sulfur-fumigated for the result validation.It was found that the most significant change of LJF after sulfur fumigation was the occurrence of sulfate or sulfite esterification reactions,which resulted in the emergence of many new sulfur-containing components.Our results demonstrated that the established method was a useful and efficient analytical tool to comprehensively characterize the material basis of SF-LJF,and also an excellent guidance of quality control about LJF.展开更多
基金Supported by the China National Science and Technology Major Projects,11th 5-year Project(No.2008ZX10005-006)。
文摘Objective:To evaluate the effects of a 48-week course of adefovir dipivoxil(ADV)plus Chinese medicine(CM)therapy,namely Tiaogan Jianpi Hexue(调肝健脾和血)and Tiaogan Jiedu Huashi(调肝解毒化湿)fomulae,in hepatitis B e antigen(HBeAg)-positive Chinese patients.Methods:A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group(EG,received ADV plus CM)and control group(CG,received ADV plus CM-placebo)for 48 weeks.The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12,24,36,48,respectively.Secondary endpoints including liver functions(enzymes and bilirubin readings)were evaluated every 4 weeks at the beginning of week 24,36,and 48.Routine blood,urine,and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations.Adverse events(AEs)were documented.Results:The combination therapy demonstrated superior HBeAg loss at 48 weeks,without additional AEs.The full analysis population was 560 and 280 in each group.In the EG,population achieved HBeAg loss on week 12,24,36,and 48 were 25(8.90%),34(12.14%),52(18.57%),and 83(29.64%),respectively;the equivalent numbers in the CG were 20(7.14%),41(14.64%),54(19.29%),and 50(17.86%),respectively.There was a statistically significant difference between two groups on week 48(P<0.01).No additional AEs were found in EG.Subgroup analysis suggested different outcomes among treatment patterns.Conclusion:Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy.The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile(ChiCTR-TRC-11001263).
基金Supported by China National Science and Technology Major Projects 12th 5-year Plan(No.2012ZX10005004)
文摘Background： The domestic prevalence of chronic hepatitis B （CHB） in China is 7.18% in 2006, imposing great societal healthcare burdens. Nucleot（s）ide analogues （NUCs） anti-hepatitis B virus （HBV） therapies are widely applied despite the relatively low rate of seroconversion and high risk of drug-resistant mutation. More effective treatments for CHB deserve further explorations. Combined therapy of NUCs plus Chinese herbal medicine （CHM） is widely accepted in China, which is recognized as a prospective alternative approach. The study was primarily designed to confirm the hypothesis that Tiaogan-Yipi Granule （调肝益脾颗粒, TGYP） or Tiaogan-Jianpi-Jiedu Granule （调肝健脾解毒颗粒, TGJPJD） plus entecavir tablet （ETV） was superior over ETV monotherapy in enhancing HBeAg loss rate. Methods： The study was a nationwide, large-scale, multi-center, double-blind, randomized, placebo-controlled trial with a designed duration of 108 weeks. A total of 16 hospitals and 596 eligible Chinese HBeAg positive CHB patients were enrolled from November 2012 to September 2013 and randomly allocated into 2 groups in 1：1 ratio via central randomization system： experimental group （EG） and control group （CG）. Subjects in EG received CM formulae （TGYP or TGJPJD, 50 g per dose, twice daily） plus ETV tablet （or ETV placebo） 0.5 mg per day in the first 24 weeks （stage 1）, and CHM granule plus ETV tablet （0.5 mg per day） from week 25 to 108 （stage 2）. Subjects in CG received CHM Granule placebo plus E＇IV tablet （0.5 mg per day） for 108 weeks throughout the trial. The assessments of primary outcomes （HBV serum markers and HBV-DNA） were conducted by a third-party College of American Pathologists （CAP） qualified laboratory. Adverse effects were observed in the hospitals of recruitment. Discussion： The study was designed to compare the curative effect of CM plus E＇IV and ETV monotherapy in respect of HBeAg loss, which is recognized by the European Association for the Study of the Liver as ＂a valuable endpoint＂. We believe this trial could provide a reliable status for patients＇ ＂joumey＂ towards durable responses after treatment discontinuation. The trial was registered before recruitment on Chinese Clinical trial registry （No. ChiCTR-TRC-12002784, Version 1.0, 2015/12/23）.
基金supported by Beijing Nova Program(No.Z171100001117029)Beijing University of Chinese Medicine Fund for Distinguished Young Scholars(No.2018-JYB-XJ008)+1 种基金the Independent Topic Selection of Beijing University of Chinese Medicine(Innovation and Entre-preneurship Project,No.2019-JYB-XSCXCY-06)the Second Batch of Scientific Research Projects for the Construction of National TCM Clinical Research Base(JDZX2015181)。
文摘Lonicerae Japonicae Flos(LJF),a kind of traditional Chinese medicines(TCMs),has functions of detoxifying and evacuating heat.In the study,a method based on ultra-high performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS)was developed for the chemical constituent analysis of organic acids,flavonoids,iridoids and new-generated compounds in sulfur-fumigated LJF(SF-LJF).Based on the accurate mass measurement(<±5 ppm),chromatographic behavior and diagnostic product ions(DPIs),113 constituents were unambiguously or tentatively characterized from SFLJF extract,including 46 chlorogenic acids,19 flavonoids,29 iridoid glycosides and 19 newly-generated compounds(including 17 sulfur-containing derivatives).In addition,5-CQA(5-caffeoylquinic acid,chlorogenic acid)was chosen to be sulfur-fumigated for the result validation.It was found that the most significant change of LJF after sulfur fumigation was the occurrence of sulfate or sulfite esterification reactions,which resulted in the emergence of many new sulfur-containing components.Our results demonstrated that the established method was a useful and efficient analytical tool to comprehensively characterize the material basis of SF-LJF,and also an excellent guidance of quality control about LJF.
