Objective:To provide high-quality clinical evidence of the efficacy of Tibetan medicine Honghua Ruyi(HHRY)pills for endometriosis-associated dysmenorrhea.Methods:This study constitutes a multicenter,randomized,double-...Objective:To provide high-quality clinical evidence of the efficacy of Tibetan medicine Honghua Ruyi(HHRY)pills for endometriosis-associated dysmenorrhea.Methods:This study constitutes a multicenter,randomized,double-blind,placebo-controlled trial encompassing a three-menstrual cycle intervention followed by a three-menstrual cycle follow-up period.A total of 164 eligible females with endometriosis-associated dysmenorrhea were randomly divided into HHRY pills and placebo groups in a 1:1 ratio.The primary outcome included dysmenorrhea symptoms assessed using Visual Analog Scale(VAS)scores and quality of life,whereas the secondary outcome measures included the maximum VAS for non-menstrual pelvic pain,duration of pain episodes(in days),frequency and quantity of the consumption of ibuprofen sustained-release capsules(or other non-steroidal anti-inflammatory drugs),and days off work/study for staff/student due to dysmenorrhea,ovarian cyst,and/or pelvic nodule size.The safety was monitored throughout the treatment period.All the analyses were based on the intention-to-treat principle.For continuous outcomes,simple or multiple linear regressions were used to estimate the differences between the HHRY pills and placebo groups,with categorical data expressed as the number and percentage of occurrences.Differences were compared using the chi-square test or Fisher's exact test.The predefined analysis was adjusted for concomitant treatment,a variable considered to be associated with outcomes but unaffected by treatment allocation.Estimates of treatment effects were reported with 95%confidence intervals.Two-tailed P values≤.05 were considered statistically significant.Conclusion:Positive results from this trial,upon completion would provide robust evidence for the efficacy and safety of HHRY pills in treating dysmenorrhea in patients with endometriosis.展开更多
Background:Hai Honghua medicinal liquor(HHML)formula has been used in clinical practice for a long time,mainly for the treatment of freshly closed fractures,to promote osteogenesis,to increase bone mass,and thus to pr...Background:Hai Honghua medicinal liquor(HHML)formula has been used in clinical practice for a long time,mainly for the treatment of freshly closed fractures,to promote osteogenesis,to increase bone mass,and thus to promote fracture healing.However,the underlying mechanisms of HHML in the treatment of osteoporosis(OP)are still unclear.Methods:Firstly,Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform and The Encyclopedia of Traditional Chinese Medicine were used to screen the targets of the active compounds of HHML.At the same time,OP targets were identified through GeneCards,Online Mendelian Inheritance in Man,DisGeNET,Therapeutic Target Database,Comparative Toxicogenomics Database and Human Phenotype Ontology databases.Next,protein-protein interaction and pathway networks were constructed for compound-disease common targets,and core targets and compounds were screened for molecular docking.Furthermore,rat bone marrow mesenchymal stem cells were extracted as model cells,and the osteogenic effects of HHML were verified via in vitro experiments.Results:Total of 343 common targets of HHML-OP and the top 10 target proteins in the protein-protein interaction network are TP53,AKT1,STAT3,HSP90AA1,ESR1,TNF,IL6,MAPK1,MAPK3 and MAPK8.Enrichment analysis yielded that the key molecular pathway was the PI3K/Akt signaling pathway.Molecular docking analysis showed that baicalein,erysodienone and naringenin docked with the target proteins AKT1,STAT3 and TP53,respectively,with low binding energy and high affinity.In addition,In vitro experiments demonstrated that HHML promoted the proliferation of bone marrow mesenchymal stem cells;compared with the control group,HHML-treated cells showed enhanced alkaline phosphatase staining,promoted the expression of OCN,RUNX2,BSP,and COL1 mRNAs as well as the expression of PI3K and AKT phosphorylated proteins.Secondly,the expression of target proteins revealed that HHML promoted the phosphorylation of STAT3 protein and inhibited the expression of P53.Conclusions:Our study investigated that HHML treatment with OP promotes bone formation possibly through activation of the PI3K/Akt signaling pathway and may involve STAT3 and TP53 target interactions.展开更多
Background:Hai Honghua medicinal liquor(HHML),a famous hospital formula composed of 19 traditional Chinese medicines,has been successfully applied in treating soft tissue injury,fresh closed fracture,limb dysfunction ...Background:Hai Honghua medicinal liquor(HHML),a famous hospital formula composed of 19 traditional Chinese medicines,has been successfully applied in treating soft tissue injury,fresh closed fracture,limb dysfunction after fracture healing,shoulder,neck and leg pain,knee joint pain and other clinical multiple diseases for 30 years in clinical.However,research on the material basis of HHML for the treatment of fracture healing-related disorders is still in a gap.Therefore,it is particularly important to explore the active ingredients,core targets and potential pharmacological mechanisms of HHML to promote fracture healing.Methods:We screened the core active components of each traditional Chinese medicine in formula and its action targets through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Encyclopedia of Traditional Chinese Medicine database.The fracture related targets were retrieved from several different public databases,including GeneCards,Online Mendelian Inheritance in Man,DisGeNET and Therapeutic Target Database.Bioinformatics analysis to obtain key bioactive components,underlying targets and signaling pathways,containing the Venn diagram of the intersection with components and diseases gene targets,protein–protein interaction,as well as the Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analysis,and finally molecular docking.Results:A total of 249 bioactive ingredients of HHML and 325 HHML-fracture-related targets were screened.The network analysis revealed that quercetin,luteolin,kaempferol,Licochalcone A,naringenin and 8-Isopentenyl-kaempferol may be potential candidate agents.Multiple targets are involved including TP53,MAPK3,STAT3,AKT1,MAPK1,HSP90AA1,ESR1 and PIK3CA may be closely linked targets.PI3K-AKT signaling pathway may play a significant role of HHML in treatment of fracture.What’s more,molecular docking suggested that 8-isopentenyl kaempferol,glycyrrhiza chalcone A,and naringenin bound to AKT1,PIK3CA,and ESR1,respectively,exhibiting lower energy and more stable characteristics.Conclusions:The findings indicate the potential active ingredients,target proteins and molecular mechanisms of HHML for the treatment of fractures to provide the exact idea for the next research on the mechanism of action of HHML formula for fracture treatment.展开更多
AIM:To investigate the efficacy and safety of Honghua preserved amniotic membrane(AM)for preventing scar formation of the filtering bleb in a rabbit model of glaucoma trabeculectomy surgery.METHODS:Totally 36 rabbits(...AIM:To investigate the efficacy and safety of Honghua preserved amniotic membrane(AM)for preventing scar formation of the filtering bleb in a rabbit model of glaucoma trabeculectomy surgery.METHODS:Totally 36 rabbits(36 eyes)were randomly divided into 3 groups:the experimental group(ocular trabeculectomy in combination with Honghua preserved AM transplantation),the control group(ocular trabeculectomy surgery in combination with AM implantation),and the blank group(single trabeculectomy).Clinical observations[including intraocular pressure(IOP),filtering blebs and complications],MassonTrichrome staining,real-time quantitative reverse transcription-polymerase chain reaction(real-time PCR),Western blot were performed on different time points(D1,D7,D14,D21 and D56)after the surgery.RESULTS:After operated for 14d,there were statistically significant differences in the filtering blebs compared to the situation before operation(P<0.05),whereas no statistically difference on that among three groups(P>0.05).After 21d,the IOP of experimental group was lowest(P<0.05).There was significant difference between control group and blank group(P<0.05).On postoperative D14,the mean number of fibroblasts in the experimental group was significantlylower(40.6±10.2)compared to those in the control group(54.4±10.8)and blank group(68.2±11.6)(P<0.05,respectively).The mean numbers of the macrophage in the experimental and control groups were respcitively significantly lower versus the blank group(P<0.05,P<0.05,respectively).Compared to that in blank group,the level of transforming growth factor-β(TGF-β1)expression in sclera and conjunctival areas was reduced in the experimental and control groups on protein and mRNA level(P<0.05),but not significant difference between these two groups(P>0.05).CONCLUSION:The trabeculectory surgery with Honghua preserved AM can control IOP,sustain the functional filtration bleb,inhibit the proliferation of fibroblasts and open the filtrating pathway on the rabbit glaucoma models.展开更多
OBJECTIVE Danshen injection and Honghua injection,traditional Chinese medicine(TCM)injections,made from the extracts of Salvia miltiorrhiza Bge.and Carthamus tinctorius L.,have a potential to be developed into the use...OBJECTIVE Danshen injection and Honghua injection,traditional Chinese medicine(TCM)injections,made from the extracts of Salvia miltiorrhiza Bge.and Carthamus tinctorius L.,have a potential to be developed into the useful drugs for the.As the common TCM injections,Danshen injection is often combined with Honghua injection to treat cardiovascular disease.The purpose of this study was to investigate the pharmacokinetic parameters of Honghua injection combined with Danshen injection when they were coadministered intravenously in human and rats through the tail vein.METHODS Single and multiple doses of Danshen injection to study Danshen injection on Honghua injection pharmacokinetics parameters and single and multiple doses of Honghua injection to study Honghua injection on Danshen injection pharmacokinetics parameters.The plasma concentrations of hydroxysafflor A(HSYA)and tanshinol and salvianolic acid B were determined by the reliable high-performance liquid chromatography(HPLC)method.The concentrations of HSYA in urine of rats and human were also determined by HPLC method.DAS 2.1.1software was adopted for calculating the pharmacokinetic parameters.RESULTS The simultaneous intravenous Honghua injection and salvia miltiorrhiza injiection significantly altered the pharmacokinetic parameters of both injections when compared with the individual intravenous administration of each injection.The area under the concentration-timecurve(AUC)and maximum plasma concentration(Cmax)of HSYA and tanshinol and salvianolic acid B were significantly increased.The cumulative urine excretion of HSYA in human and rats during 24 h was decreased after two drugs were administered simultaneously by the intravenous.CONCLUSION Honghua injection and Danshen injection interact with each other following simultaneous intravenous and they have a synergistic action.This experiment has identified the pharmacokinetic parameters and provided a rationale for the clinical use of the drug combination.展开更多
In Changxing(长兴) stage,Manyue(满月)-Honghua(红花) Section of Kaixian(开县),northeastern Sichuan(四川) Province was located in the platform-margin slope,which was the advantage area of reef-shoal depositional system ...In Changxing(长兴) stage,Manyue(满月)-Honghua(红花) Section of Kaixian(开县),northeastern Sichuan(四川) Province was located in the platform-margin slope,which was the advantage area of reef-shoal depositional system developing.The strata of Changxing Formation are continuously exposed on both Honghua Section and Manyue Section.Four and two depositional cycles can be identified in Honghua Section and Manyue Section,respectively.They are all platform-margin reef-shoal deposits.Their lithologic associations have obvious sequence,which is as follows:micrite bioclast limestone,bafflestone,bindstone,framestone,and bioclast limestone,in order from below.The paleontological assemblages are controlled by water depth and genetic facies.Six paleontological assemblages can be identified in Honghua Section and Manyue Section;they are coral-calcareous algaecalcareous sponge assemblage,calcareous sponge-calcareous algae assemblage,calcareous spongecalcareous algae-coral-bryozoan assemblage,calcareous sponge-calcareous algae-hydra assemblage,calcareous sponge-calcareous algae-hydra-bryozoan assemblage,and calcareous sponge-calcareous algae-hydra-bryozoan-coral assemblage.The study of lithologic associations and paleontological assemblages indicates that the water body shallowed upward in both the growth cycle of a single reef and the higher-grade depositional cycle.According to the water depth types of reef(bioherm) developing,three different reef-shoal depositional systems can be identified in study area:deep-water-type bioherm,transitional-type reef(bioherm),and more shallow-water-type reef.展开更多
基金supported by the National Natural Science Foundation of China(81830115).
文摘Objective:To provide high-quality clinical evidence of the efficacy of Tibetan medicine Honghua Ruyi(HHRY)pills for endometriosis-associated dysmenorrhea.Methods:This study constitutes a multicenter,randomized,double-blind,placebo-controlled trial encompassing a three-menstrual cycle intervention followed by a three-menstrual cycle follow-up period.A total of 164 eligible females with endometriosis-associated dysmenorrhea were randomly divided into HHRY pills and placebo groups in a 1:1 ratio.The primary outcome included dysmenorrhea symptoms assessed using Visual Analog Scale(VAS)scores and quality of life,whereas the secondary outcome measures included the maximum VAS for non-menstrual pelvic pain,duration of pain episodes(in days),frequency and quantity of the consumption of ibuprofen sustained-release capsules(or other non-steroidal anti-inflammatory drugs),and days off work/study for staff/student due to dysmenorrhea,ovarian cyst,and/or pelvic nodule size.The safety was monitored throughout the treatment period.All the analyses were based on the intention-to-treat principle.For continuous outcomes,simple or multiple linear regressions were used to estimate the differences between the HHRY pills and placebo groups,with categorical data expressed as the number and percentage of occurrences.Differences were compared using the chi-square test or Fisher's exact test.The predefined analysis was adjusted for concomitant treatment,a variable considered to be associated with outcomes but unaffected by treatment allocation.Estimates of treatment effects were reported with 95%confidence intervals.Two-tailed P values≤.05 were considered statistically significant.Conclusion:Positive results from this trial,upon completion would provide robust evidence for the efficacy and safety of HHRY pills in treating dysmenorrhea in patients with endometriosis.
基金supported by the Project of State Administration of Traditional Chinese Medicine of Sichuan Province of China (No.2021MS407).
文摘Background:Hai Honghua medicinal liquor(HHML)formula has been used in clinical practice for a long time,mainly for the treatment of freshly closed fractures,to promote osteogenesis,to increase bone mass,and thus to promote fracture healing.However,the underlying mechanisms of HHML in the treatment of osteoporosis(OP)are still unclear.Methods:Firstly,Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform and The Encyclopedia of Traditional Chinese Medicine were used to screen the targets of the active compounds of HHML.At the same time,OP targets were identified through GeneCards,Online Mendelian Inheritance in Man,DisGeNET,Therapeutic Target Database,Comparative Toxicogenomics Database and Human Phenotype Ontology databases.Next,protein-protein interaction and pathway networks were constructed for compound-disease common targets,and core targets and compounds were screened for molecular docking.Furthermore,rat bone marrow mesenchymal stem cells were extracted as model cells,and the osteogenic effects of HHML were verified via in vitro experiments.Results:Total of 343 common targets of HHML-OP and the top 10 target proteins in the protein-protein interaction network are TP53,AKT1,STAT3,HSP90AA1,ESR1,TNF,IL6,MAPK1,MAPK3 and MAPK8.Enrichment analysis yielded that the key molecular pathway was the PI3K/Akt signaling pathway.Molecular docking analysis showed that baicalein,erysodienone and naringenin docked with the target proteins AKT1,STAT3 and TP53,respectively,with low binding energy and high affinity.In addition,In vitro experiments demonstrated that HHML promoted the proliferation of bone marrow mesenchymal stem cells;compared with the control group,HHML-treated cells showed enhanced alkaline phosphatase staining,promoted the expression of OCN,RUNX2,BSP,and COL1 mRNAs as well as the expression of PI3K and AKT phosphorylated proteins.Secondly,the expression of target proteins revealed that HHML promoted the phosphorylation of STAT3 protein and inhibited the expression of P53.Conclusions:Our study investigated that HHML treatment with OP promotes bone formation possibly through activation of the PI3K/Akt signaling pathway and may involve STAT3 and TP53 target interactions.
基金This work was supported by the Project of State Administration of Traditional Chinese Medicine of Sichuan Province of China(No.2021MS407).
文摘Background:Hai Honghua medicinal liquor(HHML),a famous hospital formula composed of 19 traditional Chinese medicines,has been successfully applied in treating soft tissue injury,fresh closed fracture,limb dysfunction after fracture healing,shoulder,neck and leg pain,knee joint pain and other clinical multiple diseases for 30 years in clinical.However,research on the material basis of HHML for the treatment of fracture healing-related disorders is still in a gap.Therefore,it is particularly important to explore the active ingredients,core targets and potential pharmacological mechanisms of HHML to promote fracture healing.Methods:We screened the core active components of each traditional Chinese medicine in formula and its action targets through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Encyclopedia of Traditional Chinese Medicine database.The fracture related targets were retrieved from several different public databases,including GeneCards,Online Mendelian Inheritance in Man,DisGeNET and Therapeutic Target Database.Bioinformatics analysis to obtain key bioactive components,underlying targets and signaling pathways,containing the Venn diagram of the intersection with components and diseases gene targets,protein–protein interaction,as well as the Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analysis,and finally molecular docking.Results:A total of 249 bioactive ingredients of HHML and 325 HHML-fracture-related targets were screened.The network analysis revealed that quercetin,luteolin,kaempferol,Licochalcone A,naringenin and 8-Isopentenyl-kaempferol may be potential candidate agents.Multiple targets are involved including TP53,MAPK3,STAT3,AKT1,MAPK1,HSP90AA1,ESR1 and PIK3CA may be closely linked targets.PI3K-AKT signaling pathway may play a significant role of HHML in treatment of fracture.What’s more,molecular docking suggested that 8-isopentenyl kaempferol,glycyrrhiza chalcone A,and naringenin bound to AKT1,PIK3CA,and ESR1,respectively,exhibiting lower energy and more stable characteristics.Conclusions:The findings indicate the potential active ingredients,target proteins and molecular mechanisms of HHML for the treatment of fractures to provide the exact idea for the next research on the mechanism of action of HHML formula for fracture treatment.
基金Supported by the National Natural Science Foundation of China(No.81160118)Clinical Medicine Research Special-purpose Foundation of China(No.L2012052)+3 种基金Science and Technology Foundation of Jiangxi Province(No.20111BBG70026-2)Jiangxi Province Youth Science Foundation(No.20114BAB215036)Science and Technology Platform Construction Project of Jiangxi Province(No.2013-116)Health Department Tradition Chinese Medicine Science and Technology Foundation(No.2012A087)
文摘AIM:To investigate the efficacy and safety of Honghua preserved amniotic membrane(AM)for preventing scar formation of the filtering bleb in a rabbit model of glaucoma trabeculectomy surgery.METHODS:Totally 36 rabbits(36 eyes)were randomly divided into 3 groups:the experimental group(ocular trabeculectomy in combination with Honghua preserved AM transplantation),the control group(ocular trabeculectomy surgery in combination with AM implantation),and the blank group(single trabeculectomy).Clinical observations[including intraocular pressure(IOP),filtering blebs and complications],MassonTrichrome staining,real-time quantitative reverse transcription-polymerase chain reaction(real-time PCR),Western blot were performed on different time points(D1,D7,D14,D21 and D56)after the surgery.RESULTS:After operated for 14d,there were statistically significant differences in the filtering blebs compared to the situation before operation(P<0.05),whereas no statistically difference on that among three groups(P>0.05).After 21d,the IOP of experimental group was lowest(P<0.05).There was significant difference between control group and blank group(P<0.05).On postoperative D14,the mean number of fibroblasts in the experimental group was significantlylower(40.6±10.2)compared to those in the control group(54.4±10.8)and blank group(68.2±11.6)(P<0.05,respectively).The mean numbers of the macrophage in the experimental and control groups were respcitively significantly lower versus the blank group(P<0.05,P<0.05,respectively).Compared to that in blank group,the level of transforming growth factor-β(TGF-β1)expression in sclera and conjunctival areas was reduced in the experimental and control groups on protein and mRNA level(P<0.05),but not significant difference between these two groups(P>0.05).CONCLUSION:The trabeculectory surgery with Honghua preserved AM can control IOP,sustain the functional filtration bleb,inhibit the proliferation of fibroblasts and open the filtrating pathway on the rabbit glaucoma models.
基金The project supported by 2016-2018 Anhui University Research Platform Innovation Team
文摘OBJECTIVE Danshen injection and Honghua injection,traditional Chinese medicine(TCM)injections,made from the extracts of Salvia miltiorrhiza Bge.and Carthamus tinctorius L.,have a potential to be developed into the useful drugs for the.As the common TCM injections,Danshen injection is often combined with Honghua injection to treat cardiovascular disease.The purpose of this study was to investigate the pharmacokinetic parameters of Honghua injection combined with Danshen injection when they were coadministered intravenously in human and rats through the tail vein.METHODS Single and multiple doses of Danshen injection to study Danshen injection on Honghua injection pharmacokinetics parameters and single and multiple doses of Honghua injection to study Honghua injection on Danshen injection pharmacokinetics parameters.The plasma concentrations of hydroxysafflor A(HSYA)and tanshinol and salvianolic acid B were determined by the reliable high-performance liquid chromatography(HPLC)method.The concentrations of HSYA in urine of rats and human were also determined by HPLC method.DAS 2.1.1software was adopted for calculating the pharmacokinetic parameters.RESULTS The simultaneous intravenous Honghua injection and salvia miltiorrhiza injiection significantly altered the pharmacokinetic parameters of both injections when compared with the individual intravenous administration of each injection.The area under the concentration-timecurve(AUC)and maximum plasma concentration(Cmax)of HSYA and tanshinol and salvianolic acid B were significantly increased.The cumulative urine excretion of HSYA in human and rats during 24 h was decreased after two drugs were administered simultaneously by the intravenous.CONCLUSION Honghua injection and Danshen injection interact with each other following simultaneous intravenous and they have a synergistic action.This experiment has identified the pharmacokinetic parameters and provided a rationale for the clinical use of the drug combination.
基金supported by the SINOPEC Forward Looking Projects of China (Nos. YPH08114 and 2009026324)
文摘In Changxing(长兴) stage,Manyue(满月)-Honghua(红花) Section of Kaixian(开县),northeastern Sichuan(四川) Province was located in the platform-margin slope,which was the advantage area of reef-shoal depositional system developing.The strata of Changxing Formation are continuously exposed on both Honghua Section and Manyue Section.Four and two depositional cycles can be identified in Honghua Section and Manyue Section,respectively.They are all platform-margin reef-shoal deposits.Their lithologic associations have obvious sequence,which is as follows:micrite bioclast limestone,bafflestone,bindstone,framestone,and bioclast limestone,in order from below.The paleontological assemblages are controlled by water depth and genetic facies.Six paleontological assemblages can be identified in Honghua Section and Manyue Section;they are coral-calcareous algaecalcareous sponge assemblage,calcareous sponge-calcareous algae assemblage,calcareous spongecalcareous algae-coral-bryozoan assemblage,calcareous sponge-calcareous algae-hydra assemblage,calcareous sponge-calcareous algae-hydra-bryozoan assemblage,and calcareous sponge-calcareous algae-hydra-bryozoan-coral assemblage.The study of lithologic associations and paleontological assemblages indicates that the water body shallowed upward in both the growth cycle of a single reef and the higher-grade depositional cycle.According to the water depth types of reef(bioherm) developing,three different reef-shoal depositional systems can be identified in study area:deep-water-type bioherm,transitional-type reef(bioherm),and more shallow-water-type reef.
