Objective:To explore the kidney yang deficiency pattern(KYDP)in a chronic kidney disease(CKD)rat model and the mechanisms underlying the effects of Zhenwu decoction(ZWD)by conducting tran-scriptomic and metabolomic an...Objective:To explore the kidney yang deficiency pattern(KYDP)in a chronic kidney disease(CKD)rat model and the mechanisms underlying the effects of Zhenwu decoction(ZWD)by conducting tran-scriptomic and metabolomic analyses.Methods:Adriamycin(ADR)combined with hydrocortisone(HC)was used to induce CKD with KYDP in rats.ADR was injected into the tail vein twice.HC was injected intramuscularly for 8 weeks.ZWD was administered by gavage for 8 weeks.The general condition was observed,24-h urine protein was detected,serum corticosterone,triiodothyronine,thyroxine,TSH,testosterone,cAMP,and cGMP levels were determined,and pathological analysis was conducted.Transcriptomic and metabolomic analyses were conducted to screen differentially expressed genes(DEGs),differentially expressed metabolites(DEMs),and differentially expressed pathways(DEPs).The core DEMs and DEGs were input to Metab-oanalyst 5.0 to identify the pathways affected by ZWD.Results:In the HC group,KYDP symptoms were observed.Compared with control group,the levels of 24-h urine protein,TSH,and cGMP significantly increased(all P<0.01),and corticosterone,triiodothyronine,thyroxine,and cAMP significantly decreased(all P<0.01)in the HC group.After ZWD intervention,the levels of above-mentioned indicators could be reversed to some extent.Pathological analysis in the HC group revealed kidney lesions.DEGs in the ZWD group were mainly associated with pathways such as nucleotide synthesis and endocrine pathways.In the ZWD group,differences in biosynthesis of unsat-urated fatty acids and butanoate metabolism were observed.The following pathways were significantly affected by ZWD:arachidonic acid metabolism,valine,leucine,and isoleucine biosynthesis,linoleic acid metabolism,and alpha-linolenic acid metabolism.Conclusion:ZWD can be used to treat KYDP in CKD through regulating arachidonic acid metabolism,valine,leucine,and isoleucine biosynthesis,linoleic acid metabolism,and alpha-linolenic acid metabolism.展开更多
Objective:To explore the protective effect and potential mechanisms of danshen root(Salvia miltiorrhiza Bge.,S.miltiorrhiza) and its extracts for the treatment of diabetic nephropathy(DN).Methods:Preclinical studies o...Objective:To explore the protective effect and potential mechanisms of danshen root(Salvia miltiorrhiza Bge.,S.miltiorrhiza) and its extracts for the treatment of diabetic nephropathy(DN).Methods:Preclinical studies of S.miltiorrhiza and its extracts on DN were systematically searched in nine databases.The primary outcomes were blood glucose,kidney function,proteinuria,and renal histopathology.The secondary outcomes included the related mechanisms.The methodological quality of animal studies was assessed based on the risk of bias tool of the Systematic Review Centre for Laboratory Animal Experimentation(SYRCLE) for animal studies.Meta-analysis was performed using R software(version 4.1.2).Results:Twenty-nine animal experimental studies that met the eligibility criteria were included in this study.Compared to the control group,S.miltiorrhiza reduced the serum creatinine,blood urea nitrogen,24-h urine protein,24-h urine albumin,blood glucose,and kidney index(kidney weight/body weight),and alleviated renal pathological damage.In terms of the mechanism of action,compared to the control group,S.miltiorrhiza reduced the levels of transforming growth factor β1,collagen Ⅳ,malondialdehyde,tumor necrosis factor α,interleukin-6,and monocyte/macrophage(ED-1),and increased the levels of superoxide dismutase,glutathione peroxidase,nuclear factor E2-related factor 2,and heme oxygenase-1.Conclusion:The existing evidence shows that S.miltiorrhiza has beneficial effects on the animal model of DN,and its mechanism is mainly related to improving kidney fibrosis,oxidative stress,and inflammatory response.展开更多
Purpose To evaluate the efficacy and safety of Ginkgo biloba extract(GBE)in acute ischaemic stroke and its impact on the recurrence of vascular events.Methods We conducted a multicentre,prospective,randomised,open lab...Purpose To evaluate the efficacy and safety of Ginkgo biloba extract(GBE)in acute ischaemic stroke and its impact on the recurrence of vascular events.Methods We conducted a multicentre,prospective,randomised,open label,blinded,controlled clinical trial enrollingpatients with an onset of acute stroke within 7 days from five hospitals in China Jiangsu Province.Participants were assigned to the GBE group(450 mg GBE with 100 mg aspirin daily)or the control group(100 mg aspirin daily)for 6 months.The primary outcome was the decline in the Montreal Cognitive Assessment score at 6 months.Secondary outcomes were other neuropsychological tests of cognitive and neurological function,the the incidence of adverse events and vascular events.results 348 patients were enrolled:179 in the GBE group and 169 in the control group.With 18 patients lost to follow-up,the dropout rate was 5.17%.Admission data between two groups were similar,but in the GBE group there was a marked slow down in the decline in the Montreal Cognitive Assessment scores(−2.77±0.21 vs−1.99±0.23,P=0.0116(30 days);−3.34±0.24 vs−2.48±0.26,P=0.0165(90 days);−4.00±0.26 vs−2.71±0.26,P=0.0004(180 days))compared with controls.The National Institutes of Health Stroke Scale scores at 12 and 30 days,the modified Rankin Scale scores for independent rate at 30,90 and 180 days,and the Barthel Index scores at 30,90 and 180 days in the GBE group were significantly improved compared with controls.Improvements were also observedin GBE groups for Mini-Metal State Examination scores of 30,90 and 180 days,Webster's digit symbol test scores at 30 days and Executive Dysfunction Index scores at 30 and 180 days.No significant differences were seen in the incidence of adverse events or vascular events.conclusions We conclude that GBE in combination with aspirin treatment alleviated cognitive and neurological deficits after acute ischaemic stroke without increasing the incidence of vascular events.展开更多
基金This study was supported by the National Key Research and Development Program of the Ministry of Science and Technology of the People's Republic of China(2018YFC1704304).
文摘Objective:To explore the kidney yang deficiency pattern(KYDP)in a chronic kidney disease(CKD)rat model and the mechanisms underlying the effects of Zhenwu decoction(ZWD)by conducting tran-scriptomic and metabolomic analyses.Methods:Adriamycin(ADR)combined with hydrocortisone(HC)was used to induce CKD with KYDP in rats.ADR was injected into the tail vein twice.HC was injected intramuscularly for 8 weeks.ZWD was administered by gavage for 8 weeks.The general condition was observed,24-h urine protein was detected,serum corticosterone,triiodothyronine,thyroxine,TSH,testosterone,cAMP,and cGMP levels were determined,and pathological analysis was conducted.Transcriptomic and metabolomic analyses were conducted to screen differentially expressed genes(DEGs),differentially expressed metabolites(DEMs),and differentially expressed pathways(DEPs).The core DEMs and DEGs were input to Metab-oanalyst 5.0 to identify the pathways affected by ZWD.Results:In the HC group,KYDP symptoms were observed.Compared with control group,the levels of 24-h urine protein,TSH,and cGMP significantly increased(all P<0.01),and corticosterone,triiodothyronine,thyroxine,and cAMP significantly decreased(all P<0.01)in the HC group.After ZWD intervention,the levels of above-mentioned indicators could be reversed to some extent.Pathological analysis in the HC group revealed kidney lesions.DEGs in the ZWD group were mainly associated with pathways such as nucleotide synthesis and endocrine pathways.In the ZWD group,differences in biosynthesis of unsat-urated fatty acids and butanoate metabolism were observed.The following pathways were significantly affected by ZWD:arachidonic acid metabolism,valine,leucine,and isoleucine biosynthesis,linoleic acid metabolism,and alpha-linolenic acid metabolism.Conclusion:ZWD can be used to treat KYDP in CKD through regulating arachidonic acid metabolism,valine,leucine,and isoleucine biosynthesis,linoleic acid metabolism,and alpha-linolenic acid metabolism.
基金This study was supported by the National Natural Science Foundation of China(81373831)the National Key Research and Development Program of the Ministry of Science and Technology of China(2018YFC1704304).
文摘Objective:To explore the protective effect and potential mechanisms of danshen root(Salvia miltiorrhiza Bge.,S.miltiorrhiza) and its extracts for the treatment of diabetic nephropathy(DN).Methods:Preclinical studies of S.miltiorrhiza and its extracts on DN were systematically searched in nine databases.The primary outcomes were blood glucose,kidney function,proteinuria,and renal histopathology.The secondary outcomes included the related mechanisms.The methodological quality of animal studies was assessed based on the risk of bias tool of the Systematic Review Centre for Laboratory Animal Experimentation(SYRCLE) for animal studies.Meta-analysis was performed using R software(version 4.1.2).Results:Twenty-nine animal experimental studies that met the eligibility criteria were included in this study.Compared to the control group,S.miltiorrhiza reduced the serum creatinine,blood urea nitrogen,24-h urine protein,24-h urine albumin,blood glucose,and kidney index(kidney weight/body weight),and alleviated renal pathological damage.In terms of the mechanism of action,compared to the control group,S.miltiorrhiza reduced the levels of transforming growth factor β1,collagen Ⅳ,malondialdehyde,tumor necrosis factor α,interleukin-6,and monocyte/macrophage(ED-1),and increased the levels of superoxide dismutase,glutathione peroxidase,nuclear factor E2-related factor 2,and heme oxygenase-1.Conclusion:The existing evidence shows that S.miltiorrhiza has beneficial effects on the animal model of DN,and its mechanism is mainly related to improving kidney fibrosis,oxidative stress,and inflammatory response.
基金The work was supported by the National Natural Science Foundation of China(81230026,81630028)the Science and Technology Department of Jiangsu Province(BE2016610)Jiangsu Province Key Medical Discipline(ZDXKA2016020).
文摘Purpose To evaluate the efficacy and safety of Ginkgo biloba extract(GBE)in acute ischaemic stroke and its impact on the recurrence of vascular events.Methods We conducted a multicentre,prospective,randomised,open label,blinded,controlled clinical trial enrollingpatients with an onset of acute stroke within 7 days from five hospitals in China Jiangsu Province.Participants were assigned to the GBE group(450 mg GBE with 100 mg aspirin daily)or the control group(100 mg aspirin daily)for 6 months.The primary outcome was the decline in the Montreal Cognitive Assessment score at 6 months.Secondary outcomes were other neuropsychological tests of cognitive and neurological function,the the incidence of adverse events and vascular events.results 348 patients were enrolled:179 in the GBE group and 169 in the control group.With 18 patients lost to follow-up,the dropout rate was 5.17%.Admission data between two groups were similar,but in the GBE group there was a marked slow down in the decline in the Montreal Cognitive Assessment scores(−2.77±0.21 vs−1.99±0.23,P=0.0116(30 days);−3.34±0.24 vs−2.48±0.26,P=0.0165(90 days);−4.00±0.26 vs−2.71±0.26,P=0.0004(180 days))compared with controls.The National Institutes of Health Stroke Scale scores at 12 and 30 days,the modified Rankin Scale scores for independent rate at 30,90 and 180 days,and the Barthel Index scores at 30,90 and 180 days in the GBE group were significantly improved compared with controls.Improvements were also observedin GBE groups for Mini-Metal State Examination scores of 30,90 and 180 days,Webster's digit symbol test scores at 30 days and Executive Dysfunction Index scores at 30 and 180 days.No significant differences were seen in the incidence of adverse events or vascular events.conclusions We conclude that GBE in combination with aspirin treatment alleviated cognitive and neurological deficits after acute ischaemic stroke without increasing the incidence of vascular events.