Background:Tongyang Huoxue Decoction(TYHX)can modulate calcium homeostasis andmitochondrial quality management to safeguard sinus node function.Nonetheless,theprecise chemical process remains unclear.This study aimed ...Background:Tongyang Huoxue Decoction(TYHX)can modulate calcium homeostasis andmitochondrial quality management to safeguard sinus node function.Nonetheless,theprecise chemical process remains unclear.This study aimed to verify the upstreamregulatory influence of SERCA2a on the enhancement of calcium homeostasis andmitochondrial unfolded protein response(mtUPR)in sinus node cells(SANCs)by TYHX,while elucidating the protective mechanism of TYHX on SNC activity.Methods:In vitromodels of sh/ad-SERCA2a and si-β-tubulin were established,and TYHX was employed tointervene in each cell group.Various approaches were employed to detect functionsincluding mitochondrial membrane potential,mitochondrial respiration,oxidative stress,mitochondrial biosynthesis,and mitochondrial autophagy and UPR.In vivo confirmationthat TYHX suppresses apoptosis and inflammatory injury.Results:I/R injury led todiminished SANCs activity,compromised mitochondrial membrane potential,reducedmitochondrial respiratory function,and heightened oxidative stress.This further impededmitochondrial production,destabilized the proteome structure,triggered the mtUPR,andinhibited mitochondrial autophagy,thereby upsetting the dynamic equilibrium of themitochondrial quality control network.Furthermore,I/R injury intensified intracellularcalcium excess and worsened oxidative stress damage.Conversely,TYHX interventionmitigated intracellular calcium overload,augmented mitochondrial antioxidant capacity,stimulated mitochondrial autophagy,and decreased the mtUPR.Sh-SERCA2a counteractedthe regulatory influences of TYHX on calcium homeostasis,mitochondrial biogenesis,mtUPR,mitochondrial autophagy,and apoptosis.Conversely,ad-SERCA2a exerted minimalinfluence on the efficacy of TYHX.SERCA2a is a major target protein for TYHX todemonstrate its efficacy.When tubulin expression was minimal,there was no statisticallysignificant difference in the expression levels of mitochondrial autophagy,mitochondrialbiosynthesis,calcium homeostasis regulation,and mtUPR between the sh-SERCA2a andad-SERCA2a groups.This indicates that the normal expression of tubulin is essential forSERCA2a to enhance the efficiency of TYHX.Tubulin may serve as an upstream regulatorymolecule of SERCA2a.In vivo tests confirmed that TYHX may suppress apoptosis andmitigate cellular inflammatory damage.Conclusion:TYHX preserved intracellular calciumequilibrium,mitigated mitochondrial oxidative stress,sustained mitochondrial stability,enhanced mitochondrial biosynthesis,suppressed the mtUPR,facilitated mitochondrialautophagy,and inhibited apoptosis viaβ-tubulin-SERCA2a,thereby safeguarding sinus nodefunctionality from I/R injury.展开更多
OBJECTIVE: To evaluate the efficacy of Tongyang Fumai decoction(通阳复脉方, TYFM) on the quality of life(QOL) as a complementary therapy for sick sinus syndrome(SSS). METHODS: This randomized controlled study involved...OBJECTIVE: To evaluate the efficacy of Tongyang Fumai decoction(通阳复脉方, TYFM) on the quality of life(QOL) as a complementary therapy for sick sinus syndrome(SSS). METHODS: This randomized controlled study involved 224 patients with symptomatic SSS. Patients were randomly assigned to either the TYFM group or the control group(receiving theophylline sustained-release tablets). The primary endpoints included changes in average heart rate, the longest R to R(RR) interval, and the occurrences of long RR intervals. Secondary endpoints comprised the Short Form(SF)-36 questionnaires, the Self-Rating Anxiety Scale(SAS), and the Self-Rating Depression Scale(SDS). RESULTS: TYFM significantly improved average heart rate(TYFM: 6 bpm vs control: 3 bpm, P < 0.01), shortened longest RR interval(TYFM:-0.20 s vs control:-0.0027 s, P < 0.05), and reduced numbers of long RR(TYFM:-99 vs control:-59, P < 0.01). In SF-36, TYFM enhanced physical and mental components(P < 0.01), outperforming the control group. TYFM also improved eight SF-36 dimensions significantly(P < 0.05 or P < 0.01). Regarding SAS and SDS, TYFM reduced scores significantly(P < 0.01), while SAS improved in the control group(P < 0.01), with no change in SDS. Statistically significant differences(P < 0.01) were observed in SAS and SDS between TYFM and control groups postintervention. CONCLUSIONS: TYFM emerges as a promising alternative strategy for treating SSS, demonstrating favorable therapeutic effects and significant improvements in the quality of life for patients with SSS.展开更多
Objective： To measure the proportions of blood T cel subsets, Th1, Th2, Th17, Th22, and Treg cel s, and other parameters in patients with chronic immune thrombocytopenia（CITP） before and after treatment with Yiqi T...Objective： To measure the proportions of blood T cel subsets, Th1, Th2, Th17, Th22, and Treg cel s, and other parameters in patients with chronic immune thrombocytopenia（CITP） before and after treatment with Yiqi Tongyang Decoction（益气通阳方, YTD） to explore T cel status of patients with CITP, and to define the mechanism of action of YTD. Methods： The changes in peripheral blood T lymphocyte subsets, and those of Th1, Th2, Th17, Th22, and Treg cel s in 30 patients with CITP（22 females and 8 males） were analyzed using multiparametric flow cytometry before and after treatment with YTD for 6 months, and 26 healthy volunteers（14 males and 12 females） acted as a control. T-box expressed in T-cel s（T-bet） and GATA binding protein 3（GATA-3） m RNA levels in patients and controls were analyzed using real-time reverse transcription-polymerase chain reaction. Results： The proportions of Th1, Th17, Th22, Th1/Th2, and Th17/Treg cells increased in the peripheral blood of patients with CITP compared to those in controls before YTD therapy（P〈0.05）. Th1 cel numbers and the Th1/Th2 ratio fel in the treated patients with CITP to approximate the values of the control group（P〉0.05）. Th17 cel numbers and the Th17/Treg ratio also decreased in the treatment group（P〈0.05）, but not to the levels of the controls. The number of Treg cel s in the peripheral blood of patients with CITP before treatment was lower than that in the control group（P〈0.05）, but increased after YTD treatment（P〈0.05）, but not to the level of controls. T-bet and GATA-3 m RNA levels in peripheral blood were initially higher in patients before treatment than controls（P〈0.05）, but decreased after YTD therapy（P〈0.05）. Conclusions： Imbalances in T lymphocyte levels, particularly those of Th1/Th2 and Th17/Treg cel s, play important roles in the pathogenesis of CITP. YTD efficiently regulated the dynamics of Th1/Th2 and Th17/Treg equilibria.展开更多
基金supported by Academic inheritance and communication project of China Academyof Chinese Medical Sciences(CI2022E012XB)High Level Chinese Medical Hospital Promotion Project(HLCMHPP2023053)Beijing Traditional Chinese Medicine Inheritance“New 3+3”Project Zhi-Ming Liu’s(Ru-Xiu Liu)Inheritance Workstation(2023-SZ-G-02).
文摘Background:Tongyang Huoxue Decoction(TYHX)can modulate calcium homeostasis andmitochondrial quality management to safeguard sinus node function.Nonetheless,theprecise chemical process remains unclear.This study aimed to verify the upstreamregulatory influence of SERCA2a on the enhancement of calcium homeostasis andmitochondrial unfolded protein response(mtUPR)in sinus node cells(SANCs)by TYHX,while elucidating the protective mechanism of TYHX on SNC activity.Methods:In vitromodels of sh/ad-SERCA2a and si-β-tubulin were established,and TYHX was employed tointervene in each cell group.Various approaches were employed to detect functionsincluding mitochondrial membrane potential,mitochondrial respiration,oxidative stress,mitochondrial biosynthesis,and mitochondrial autophagy and UPR.In vivo confirmationthat TYHX suppresses apoptosis and inflammatory injury.Results:I/R injury led todiminished SANCs activity,compromised mitochondrial membrane potential,reducedmitochondrial respiratory function,and heightened oxidative stress.This further impededmitochondrial production,destabilized the proteome structure,triggered the mtUPR,andinhibited mitochondrial autophagy,thereby upsetting the dynamic equilibrium of themitochondrial quality control network.Furthermore,I/R injury intensified intracellularcalcium excess and worsened oxidative stress damage.Conversely,TYHX interventionmitigated intracellular calcium overload,augmented mitochondrial antioxidant capacity,stimulated mitochondrial autophagy,and decreased the mtUPR.Sh-SERCA2a counteractedthe regulatory influences of TYHX on calcium homeostasis,mitochondrial biogenesis,mtUPR,mitochondrial autophagy,and apoptosis.Conversely,ad-SERCA2a exerted minimalinfluence on the efficacy of TYHX.SERCA2a is a major target protein for TYHX todemonstrate its efficacy.When tubulin expression was minimal,there was no statisticallysignificant difference in the expression levels of mitochondrial autophagy,mitochondrialbiosynthesis,calcium homeostasis regulation,and mtUPR between the sh-SERCA2a andad-SERCA2a groups.This indicates that the normal expression of tubulin is essential forSERCA2a to enhance the efficiency of TYHX.Tubulin may serve as an upstream regulatorymolecule of SERCA2a.In vivo tests confirmed that TYHX may suppress apoptosis andmitigate cellular inflammatory damage.Conclusion:TYHX preserved intracellular calciumequilibrium,mitigated mitochondrial oxidative stress,sustained mitochondrial stability,enhanced mitochondrial biosynthesis,suppressed the mtUPR,facilitated mitochondrialautophagy,and inhibited apoptosis viaβ-tubulin-SERCA2a,thereby safeguarding sinus nodefunctionality from I/R injury.
基金Beijing Clinical Application Research Project:Evaluation of the Therapeutic Efficacy of Tongyang Huoxue Decoction based on the Heart-Kidney Simultaneous Treatment for Sick Sinus Syndrome (No. Z181100001718184)Academic Inheritance and Communication Project of China Academy of Chinese Medical Sciences:Academic Experience Inheritance of Liu Zhiming (No. CI2022E012XB)+1 种基金High Level Chinese Medical Hospital Promotion Project:In-Hospital Pharmaceutical Preparation based on the Experience of Renowned Traditional Chinese Medicine Physicians (No. HLCMHPP2023053)the Fundamental Research Funds for the Central Public Welfare Research Institutes:Mechanism of'Kidney Tonifying,Yang Activating,Blood Circulating'Chinese Medicine in Improving Sinoatrial Node Injury Under Hypoxic Stress (No. ZZ17-XRZ-028)。
文摘OBJECTIVE: To evaluate the efficacy of Tongyang Fumai decoction(通阳复脉方, TYFM) on the quality of life(QOL) as a complementary therapy for sick sinus syndrome(SSS). METHODS: This randomized controlled study involved 224 patients with symptomatic SSS. Patients were randomly assigned to either the TYFM group or the control group(receiving theophylline sustained-release tablets). The primary endpoints included changes in average heart rate, the longest R to R(RR) interval, and the occurrences of long RR intervals. Secondary endpoints comprised the Short Form(SF)-36 questionnaires, the Self-Rating Anxiety Scale(SAS), and the Self-Rating Depression Scale(SDS). RESULTS: TYFM significantly improved average heart rate(TYFM: 6 bpm vs control: 3 bpm, P < 0.01), shortened longest RR interval(TYFM:-0.20 s vs control:-0.0027 s, P < 0.05), and reduced numbers of long RR(TYFM:-99 vs control:-59, P < 0.01). In SF-36, TYFM enhanced physical and mental components(P < 0.01), outperforming the control group. TYFM also improved eight SF-36 dimensions significantly(P < 0.05 or P < 0.01). Regarding SAS and SDS, TYFM reduced scores significantly(P < 0.01), while SAS improved in the control group(P < 0.01), with no change in SDS. Statistically significant differences(P < 0.01) were observed in SAS and SDS between TYFM and control groups postintervention. CONCLUSIONS: TYFM emerges as a promising alternative strategy for treating SSS, demonstrating favorable therapeutic effects and significant improvements in the quality of life for patients with SSS.
基金Supported by the National Natural Science Foundation of China(No.81072928)
文摘Objective： To measure the proportions of blood T cel subsets, Th1, Th2, Th17, Th22, and Treg cel s, and other parameters in patients with chronic immune thrombocytopenia（CITP） before and after treatment with Yiqi Tongyang Decoction（益气通阳方, YTD） to explore T cel status of patients with CITP, and to define the mechanism of action of YTD. Methods： The changes in peripheral blood T lymphocyte subsets, and those of Th1, Th2, Th17, Th22, and Treg cel s in 30 patients with CITP（22 females and 8 males） were analyzed using multiparametric flow cytometry before and after treatment with YTD for 6 months, and 26 healthy volunteers（14 males and 12 females） acted as a control. T-box expressed in T-cel s（T-bet） and GATA binding protein 3（GATA-3） m RNA levels in patients and controls were analyzed using real-time reverse transcription-polymerase chain reaction. Results： The proportions of Th1, Th17, Th22, Th1/Th2, and Th17/Treg cells increased in the peripheral blood of patients with CITP compared to those in controls before YTD therapy（P〈0.05）. Th1 cel numbers and the Th1/Th2 ratio fel in the treated patients with CITP to approximate the values of the control group（P〉0.05）. Th17 cel numbers and the Th17/Treg ratio also decreased in the treatment group（P〈0.05）, but not to the levels of the controls. The number of Treg cel s in the peripheral blood of patients with CITP before treatment was lower than that in the control group（P〈0.05）, but increased after YTD treatment（P〈0.05）, but not to the level of controls. T-bet and GATA-3 m RNA levels in peripheral blood were initially higher in patients before treatment than controls（P〈0.05）, but decreased after YTD therapy（P〈0.05）. Conclusions： Imbalances in T lymphocyte levels, particularly those of Th1/Th2 and Th17/Treg cel s, play important roles in the pathogenesis of CITP. YTD efficiently regulated the dynamics of Th1/Th2 and Th17/Treg equilibria.
