1.Ershen Zhenwu Decoction Treats Chronic Heart Failure by Regulating miR-423-5p/Smad7/TGF-β1/Smads Axis and Myocardial Fibrosis Indicators
Lan GE ; Zhenpeng ZHU ; Xinyue WANG ; Dan CHENG ; Yulong LIU ; Maomao ZHANG ; Xiaoyu CHENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):157-165
ObjectiveTo investigate the clinical effect of Ershen Zhenwu Decoction on chronic heart failure (CHF) due to heart-kidney Yang deficiency and blood stasis and its regulatory effects on miR-423-5p/Smad7/transforming growth factor-β1 (TGF-β1)/Smads axis and myocardial fibrosis indicators. MethodsOne hundred and fourteen patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with mildly reduced ejection fraction (HFmrEF) were randomly allocated into a control group and an observation group. The control group was treated with dapagliflozin tablets, sacubitril-valsartan sodium tablets, metoprolol succinate, and spironolactone, and the observation group was treated with Ershen Zhenwu Decoction on the basis of the therapy in the control group. The course of treatment was 8 weeks in both groups. The 6-min walking distance, New York Heart Association (NYHA) heart function grade, Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, N-terminal pro-B-type natriuretic peptide (NT-proBNP), angiotensin Ⅱ (Ang Ⅱ), left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVIDd), left ventricular end-systolic diameter (LVIDs), interventricular septum thickness at diastole (IVSd), left ventricular end-diastolic posterior wall thickness (LVPWd), left ventricular shortening fraction (FS), miR-423-5p, Smad7, Smad2, Smad3, Smad4, TGF-β1, Ang Ⅱ, type Ⅰ collagen (Col Ⅰ), type Ⅲ collagen (Col Ⅲ), mRNA levels of fibronectin (Fn) and α-smooth muscle actin (α-SMA) in the myocardial tissue were observed before and after treatment in both groups to evaluate the efficacy of cardiac function and drug safety. ResultsAfter treatment, both groups showed declined levels of NT-proBNP, Ang Ⅱ, miR-423-5p, Smad2, Smad3, Smad4, TGF-β1, Col Ⅰ, Col Ⅲ, and mRNA levels of Fn and α-SMA (P0.05), and the levels of the indicators above were lower in the observation group than in the control group (P0.05). After treatment, the Smad7 level increased obviously in both groups (P0.05) and was higher in the observation group than in the control group (P0.05). After treatment, both groups showed decreased MLHFQ scores and increased 6-min walking distance (P0.05), and the observation group had lower MLHFQ score and longer 6-min walking distance than the control group (P0.05). After treatment, the control group showed increased LVEF and FS (P0.05) and the observation group showcased decreased LVIDd and LVIDs and increased LVEF and FS (P0.05). Moreover, the observation group had lower LVIDd and LVIDs (P0.05) and higher LVEF and FS (P0.05) than the control group. The total response rate of cardiac function in the observation group was 90.38% (47/52), which was higher than that (70.59%, 36/51) in the control group (P0.05). No adverse reactions associated with Ershen Zhenwu Decoction were observed during the study period. ConclusionErshen Zhenwu Decoction can improve the cardiac function, exercise tolerance, and quality of life, regulate neuroendocrine factors, and slow down/reverse myocardial remodeling in the patients with HFrEF and HFmrEF (syndrome of heart-kidney Yang deficiency and blood stasis by regulating the miR-423-5p/Smad7/TGF-β1/Smads axis, inhibiting α-SMA and Fn expression, and alleviating myocardial fibrosis. It is worthy of further study.
2.Ershen Zhenwu Decoction Treats Chronic Heart Failure by Regulating miR-423-5p/Smad7/TGF-β1/Smads Axis and Myocardial Fibrosis Indicators
Lan GE ; Zhenpeng ZHU ; Xinyue WANG ; Dan CHENG ; Yulong LIU ; Maomao ZHANG ; Xiaoyu CHENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):157-165
ObjectiveTo investigate the clinical effect of Ershen Zhenwu Decoction on chronic heart failure (CHF) due to heart-kidney Yang deficiency and blood stasis and its regulatory effects on miR-423-5p/Smad7/transforming growth factor-β1 (TGF-β1)/Smads axis and myocardial fibrosis indicators. MethodsOne hundred and fourteen patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with mildly reduced ejection fraction (HFmrEF) were randomly allocated into a control group and an observation group. The control group was treated with dapagliflozin tablets, sacubitril-valsartan sodium tablets, metoprolol succinate, and spironolactone, and the observation group was treated with Ershen Zhenwu Decoction on the basis of the therapy in the control group. The course of treatment was 8 weeks in both groups. The 6-min walking distance, New York Heart Association (NYHA) heart function grade, Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, N-terminal pro-B-type natriuretic peptide (NT-proBNP), angiotensin Ⅱ (Ang Ⅱ), left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVIDd), left ventricular end-systolic diameter (LVIDs), interventricular septum thickness at diastole (IVSd), left ventricular end-diastolic posterior wall thickness (LVPWd), left ventricular shortening fraction (FS), miR-423-5p, Smad7, Smad2, Smad3, Smad4, TGF-β1, Ang Ⅱ, type Ⅰ collagen (Col Ⅰ), type Ⅲ collagen (Col Ⅲ), mRNA levels of fibronectin (Fn) and α-smooth muscle actin (α-SMA) in the myocardial tissue were observed before and after treatment in both groups to evaluate the efficacy of cardiac function and drug safety. ResultsAfter treatment, both groups showed declined levels of NT-proBNP, Ang Ⅱ, miR-423-5p, Smad2, Smad3, Smad4, TGF-β1, Col Ⅰ, Col Ⅲ, and mRNA levels of Fn and α-SMA (P0.05), and the levels of the indicators above were lower in the observation group than in the control group (P0.05). After treatment, the Smad7 level increased obviously in both groups (P0.05) and was higher in the observation group than in the control group (P0.05). After treatment, both groups showed decreased MLHFQ scores and increased 6-min walking distance (P0.05), and the observation group had lower MLHFQ score and longer 6-min walking distance than the control group (P0.05). After treatment, the control group showed increased LVEF and FS (P0.05) and the observation group showcased decreased LVIDd and LVIDs and increased LVEF and FS (P0.05). Moreover, the observation group had lower LVIDd and LVIDs (P0.05) and higher LVEF and FS (P0.05) than the control group. The total response rate of cardiac function in the observation group was 90.38% (47/52), which was higher than that (70.59%, 36/51) in the control group (P0.05). No adverse reactions associated with Ershen Zhenwu Decoction were observed during the study period. ConclusionErshen Zhenwu Decoction can improve the cardiac function, exercise tolerance, and quality of life, regulate neuroendocrine factors, and slow down/reverse myocardial remodeling in the patients with HFrEF and HFmrEF (syndrome of heart-kidney Yang deficiency and blood stasis by regulating the miR-423-5p/Smad7/TGF-β1/Smads axis, inhibiting α-SMA and Fn expression, and alleviating myocardial fibrosis. It is worthy of further study.
3.Effects of combined use of active ingredients in Buyang Huanwu Decoction on oxygen-glucose deprivation/reglucose-reoxygenation-induced inflammation and oxidative stress of BV2 cells.
Tian-Qing XIA ; Ying CHEN ; Jian-Lin HUA ; Qin SU ; Cun-Yan DAN ; Meng-Wei RONG ; Shi-Ning GE ; Hong GUO ; Bao-Guo XIAO ; Jie-Zhong YU ; Cun-Gen MA ; Li-Juan SONG
China Journal of Chinese Materia Medica 2025;50(14):3835-3846
This study aims to explore the effects and action mechanisms of the active ingredients in Buyang Huanwu Decoction(BYHWD), namely tetramethylpyrazine(TMP) and hydroxy-safflor yellow A(HSYA), on oxygen-glucose deprivation/reglucose-reoxygenation(OGD/R)-induced inflammation and oxidative stress of microglia(MG). Network pharmacology was used to screen the effective monomer ingredients of BYHWD and determine the safe concentration range for each component. Inflammation and oxidative stress models were established to further screen the best ingredient combination and optimal concentration ratio with the most effective anti-inflammatory and antioxidant effects. OGD/R BV2 cell models were constructed, and BV2 cells in the logarithmic growth phase were divided into a normal group, a model group, an HSYA group, a TMP group, and an HSYA + TMP group. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of inflammatory cytokines such as interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6). Oxidative stress markers, including superoxide dismutase(SOD), nitric oxide(NO), and malondialdehyde(MDA), were also measured. Western blot was used to analyze the protein expression of both inflammation-related pathway [Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)] and oxidative stress-related pathway [nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)]. Immunofluorescence was used to assess the expression of proteins such as inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1). The most effective ingredients for anti-inflammatory and antioxidant effects in BYHWD were TMP and HSYA. Compared to the normal group, the model group showed significantly increased levels of IL-1β, TNF-α, IL-6, NO, and MDA, along with significantly higher protein expression of NF-κB, TLR4, Nrf2, and HO-1 and significantly lower SOD levels. The differences between the two groups were statistically significant. Compared to the model group, both the HSYA group and the TMP group showed significantly reduced levels of IL-1β, TNF-α, IL-6, NO, and MDA, lower expression of NF-κB and TLR4 proteins, higher levels of SOD, and significantly increased protein expression of Nrf2 and HO-1. Additionally, the expression of the M1-type MG marker iNOS was significantly reduced, while the expression of the M2-type MG marker Arg-1 was significantly increased. The results of the HSYA group and the TMP group had statistically significant differences from those of the model group. Compared to the HSYA group and the TMP group, the HSYA + TMP group showed further significant reductions in IL-1β, TNF-α, IL-6, NO, and MDA levels, along with significant reductions in NF-κB and TLR4 protein expression, an increase in SOD levels, and elevated Nrf2 and HO-1 protein expression. Additionally, the expression of the M1-type MG marker iNOS was reduced, while the M2-type MG marker Arg-1 expression increased significantly in the HSYA + TMP group compared to the TMP or HSYA group. The differences in the results were statistically significant between the HSYA + TMP group and the TMP or HSYA group. The findings indicated that the combined use of HSYA and TMP, the active ingredients of BYHWD, can effectively inhibit OGD/R-induced inflammation and oxidative stress of MG, showing superior effects compared to the individual use of either component.
Oxidative Stress/drug effects*
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Drugs, Chinese Herbal/pharmacology*
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Animals
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Mice
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Glucose/metabolism*
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Cell Line
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Inflammation/genetics*
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Oxygen/metabolism*
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Pyrazines/pharmacology*
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Microglia/metabolism*
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NF-E2-Related Factor 2/immunology*
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NF-kappa B/immunology*
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Toll-Like Receptor 4/immunology*
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Anti-Inflammatory Agents/pharmacology*
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Humans
4.Correction to: Scorpion Venom Heat-Resistant Peptide is Neuroprotective Against Cerebral Ischemia-Reperfusion Injury in Association with the NMDA-MAPK Pathway.
Xu-Gang WANG ; Dan-Dan ZHU ; Na LI ; Yue-Lin HUANG ; Ying-Zi WANG ; Ting ZHANG ; Chen-Mei WANG ; Bin WANG ; Yan PENG ; Bi-Ying GE ; Shao LI ; Jie ZHAO
Neuroscience Bulletin 2025;41(3):549-550
5.Development and application of chiral separation technology based on chiral metal-organic frameworks.
Gege ZHU ; Li GE ; Xinyu LI ; Bing NIU ; Qin CHEN ; Dan ZHONG ; Xiaodong SUN
Journal of Pharmaceutical Analysis 2025;15(7):101176-101176
Chirality is not only a natural phenomenon but also a bridge between chemistry and life sciences. An effective way to obtain a single enantiomer is through racemates resolution. Recent literature shows that chiral metal-organic frameworks (CMOFs) have many applications in various fields because of their diverse topologies and functionalities. This review outlines the design idea and summarizes the latest synthesis strategies and applications of CMOFs. It highlights key advances and issues in the separation domain. In conclusion, the review provides perspectives on the challenges and prospective advancements of CMOFs materials and CMOFs-based separation technologies.
6.Practical research of blended teaching mode based on BOPPPS in the teaching of Natural Medicinal Chemistry
Lili SUI ; Dan ZHAO ; Chiyu SUN ; Jiayin YUE ; Yating SUN ; Tian LUAN ; Ge JIN
Journal of Shenyang Medical College 2024;26(5):537-541
Objective:To investigate the teaching effect of blended teaching mode based on BOPPPS in the teaching of Natural Medicinal Chemistry.Methods:The undergraduate students of grade 2019 majoring in pharmacy of a medical college were selected as the research objects and divided into 2 groups randomly.Students in class 2 were set as the control group(n=27)and students in class 1 were set as the experimental group(n=29).The students of the two classes were taught by the same group of teachers.The control group adopted traditional teaching methods and classroom teaching as the main teaching mode combines with multimedia teaching.The experimental group received blended teaching mode based on BOPPPS.The final examination scores,teaching effects and student satisfaction of the two groups were compared and analyzed.Results:The survey results showed that the teaching effect of the blended teaching model based on BOPPPS was recognized by 96.55%of the students in the experimental group.The final examination score in the experimental group was higher than that in the control group(P<0.05).The teaching effect of the experimental group was significantly better than that of the control group(P<0.05),and the satisfaction of students in the experimental group was higher than that in the control group(P<0.05).Conclusion:The application of blended teaching mode based on BOPPPS in the teaching of Natural Medicinal Chemistry can effectively stimulate students'learning interest and improve the teaching quality.
7.Mechanism of X-ray radiation-induced rat myocardial cell apoptosis based on miRNA-134-5p/BDNF/Akt signaling pathway
Jing GU ; Liwen FU ; Xiaofei HAN ; Dan FANG ; Ge JIN ; Xiaoli DONG ; Yahui XIE ; Min HOU
Academic Journal of Naval Medical University 2024;45(11):1352-1361
Objective To investigate the effect of radiation on cardiomyocyte apoptosis and its related mechanism.Methods Rat H9C2 cardiomyocytes were divided into blank control group,X-ray irradiation group(X-ray group),X-ray irradiation+microRNA(miRNA)-134-5p inhibitor group(X-inhibitor group)and X-ray irradiation+miRNA-134-5p inhibitor negative control group(X-NC group).H9C2 cardiomyocytes were irradiated with 6 Gy X-ray,and the changes of various indexes were detected 48 h after irradiation.Cell viability was detected by cell counting kit 8 assay.The apoptosis rate was detected by flow cytometry and Hoechst 33342 staining.The level of reactive oxygen species(ROS)in cells was detected by DCFH-DA fluorescence probe.The mitochondrial membrane potential was detected by JC-1 method.The activity of superoxide dismutase(SOD)and the level of malondialdehyde(MDA)in cells were measured by kits.The expression of miRNA-134-5p was detected by quantitative polymerase chain reaction.The protein expression of brain-derived neurotrophic factor(BDNF),protein kinase B(Akt),phosphorylated Akt(p-Akt),Bcl2 and Bax was detected by Western blotting.Results Compared with the blank control group,in the X-ray group the levels of ROS and MDA were significantly increased,the activity of SOD was significantly decreased,the decreased percentage in mitochondrial membrane potential was significantly increased,the number of micronuclei of DNA damage was significantly increased,and the apoptosis rate was significantly increased(all P<0.01).Compared with the X-ray group,all the indexes of the X-inhibitor group were reversed(P<0.05 or P<0.01),while there was no significant difference in the above parameters in the X-NC group(all P>0.05).Compared with the blank control group,the X-ray group had a significant increase in the miRNA-134-5p level and significant reductions in the protein level of BDNF,Bcl2/Bax ratio,and p-Akt/Akt ratio(all P<0.01).Compared with the X-ray group,the X-inhibitor group had a significant reduction in the level of miRNA-134-5p and significant increases in the protein level of BDNF,Bcl2/Bax ratio,and p-Akt/Akt ratio(all P<0.01),and there was no significant difference in all parameters in the X-NC group(all P>0.05).Conclusion X-ray irradiation can induce oxidative stress,mitochondrial damage,and DNA damage,eventually leading to apoptosis in rat cardiomyocytes,and the mechanism may involve miRNA-134-5p/BDNF/Akt signaling pathway.
8.Clinical Study of High-Intensity Focused Ultrasound Combined with Endome-trial Thermal Balloon Ablation for the Treatment of Menorrhagia Associated with Adenomyosis
Dan WANG ; Zhuoting JIN ; Ligang WANG ; Jia GE ; Yong ZHANG
Journal of Practical Obstetrics and Gynecology 2024;40(7):560-565
Objective:To investigate the efficacy and safety of high intensity focused ultrasound(HIFU)com-bined with endometrial thermal Balloon ablation(TBEA)in the treatment of menorrhagia associated with adenomy-osis(AM).Methods:A retrospective cohort study was performed on clinical data of 77 patients with menorrhagia associated with adenomyosis(AM)in Mianyang Central Hospital from January 2021 to December 2022.According to different treatment methods,they were divided into HIFU combined with TBEA(HIFU+TBEA group,n=26)and HIFU combined with gonadotropin-releasing hormone agonist(GnRH-a)and levonorgestrel-releasing intrauterine system(LNG-IUS)(HIFU+drug group,n=51).The pictorial blood loss assessment chart(PBAC)at different fol-low-up time after HIFU ablation was used as the main outcome index,dysmenorrhea score(NRS),serum CA125 level,re intervention rate,treatment effectiveness rate and adverse reactions were used as the secondary out-come indexes.Evaluate the efficacy and safety of HIFU combined with TBEA in the treatment of menorrhagia as-sociated with AMby comparing the difference of outcome indexes between two groups before and after treatment at different times.Results:Compared with pre-treatment,the PBAC score,NRS score and CA125 level were signif-icantly decreased after treatment in both groups(P<0.05).Compared with HIFU+drug group,PBAC score of HIFU+TBEA group decreased more at 6,9 and 12 months after treatment(P<0.05),but there was no signifi-cant difference in PBAC score at 1 and 3 months after treatment(P>0.05).There was no significant difference in NRS scores between the two groups at 1,3,6,9 and 12 months after treatment(P>0.05).There was no signifi-cant difference in reintervention rate between HIFU+TBEA group(11.54% )and HIFU+drug group(21.57% )after treatment(P>0.05).There was no significant difference in treatment effectiveness between HIFU+TBEA group(80.77% )and HIFU+drug group(70.59% )(P>0.05).The adverse reactions of the two groups after treatment were graded as SIR A-B,and no serious adverse events occurred.Conclusions:The combination of HIFU and TBEA has good efficacy and safety in the treatment of AM,and can be used as a long-term manage-ment program for patients with no fertility needs,especially for AM patients with menorrhagia,which also has good clinical application value.
9.Clinical Study of High-Intensity Focused Ultrasound Combined with Endome-trial Thermal Balloon Ablation for the Treatment of Menorrhagia Associated with Adenomyosis
Dan WANG ; Zhuoting JIN ; Ligang WANG ; Jia GE ; Yong ZHANG
Journal of Practical Obstetrics and Gynecology 2024;40(7):560-565
Objective:To investigate the efficacy and safety of high intensity focused ultrasound(HIFU)com-bined with endometrial thermal Balloon ablation(TBEA)in the treatment of menorrhagia associated with adenomy-osis(AM).Methods:A retrospective cohort study was performed on clinical data of 77 patients with menorrhagia associated with adenomyosis(AM)in Mianyang Central Hospital from January 2021 to December 2022.According to different treatment methods,they were divided into HIFU combined with TBEA(HIFU+TBEA group,n=26)and HIFU combined with gonadotropin-releasing hormone agonist(GnRH-a)and levonorgestrel-releasing intrauterine system(LNG-IUS)(HIFU+drug group,n=51).The pictorial blood loss assessment chart(PBAC)at different fol-low-up time after HIFU ablation was used as the main outcome index,dysmenorrhea score(NRS),serum CA125 level,re intervention rate,treatment effectiveness rate and adverse reactions were used as the secondary out-come indexes.Evaluate the efficacy and safety of HIFU combined with TBEA in the treatment of menorrhagia as-sociated with AMby comparing the difference of outcome indexes between two groups before and after treatment at different times.Results:Compared with pre-treatment,the PBAC score,NRS score and CA125 level were signif-icantly decreased after treatment in both groups(P<0.05).Compared with HIFU+drug group,PBAC score of HIFU+TBEA group decreased more at 6,9 and 12 months after treatment(P<0.05),but there was no signifi-cant difference in PBAC score at 1 and 3 months after treatment(P>0.05).There was no significant difference in NRS scores between the two groups at 1,3,6,9 and 12 months after treatment(P>0.05).There was no signifi-cant difference in reintervention rate between HIFU+TBEA group(11.54% )and HIFU+drug group(21.57% )after treatment(P>0.05).There was no significant difference in treatment effectiveness between HIFU+TBEA group(80.77% )and HIFU+drug group(70.59% )(P>0.05).The adverse reactions of the two groups after treatment were graded as SIR A-B,and no serious adverse events occurred.Conclusions:The combination of HIFU and TBEA has good efficacy and safety in the treatment of AM,and can be used as a long-term manage-ment program for patients with no fertility needs,especially for AM patients with menorrhagia,which also has good clinical application value.
10.Clinical Study of High-Intensity Focused Ultrasound Combined with Endome-trial Thermal Balloon Ablation for the Treatment of Menorrhagia Associated with Adenomyosis
Dan WANG ; Zhuoting JIN ; Ligang WANG ; Jia GE ; Yong ZHANG
Journal of Practical Obstetrics and Gynecology 2024;40(7):560-565
Objective:To investigate the efficacy and safety of high intensity focused ultrasound(HIFU)com-bined with endometrial thermal Balloon ablation(TBEA)in the treatment of menorrhagia associated with adenomy-osis(AM).Methods:A retrospective cohort study was performed on clinical data of 77 patients with menorrhagia associated with adenomyosis(AM)in Mianyang Central Hospital from January 2021 to December 2022.According to different treatment methods,they were divided into HIFU combined with TBEA(HIFU+TBEA group,n=26)and HIFU combined with gonadotropin-releasing hormone agonist(GnRH-a)and levonorgestrel-releasing intrauterine system(LNG-IUS)(HIFU+drug group,n=51).The pictorial blood loss assessment chart(PBAC)at different fol-low-up time after HIFU ablation was used as the main outcome index,dysmenorrhea score(NRS),serum CA125 level,re intervention rate,treatment effectiveness rate and adverse reactions were used as the secondary out-come indexes.Evaluate the efficacy and safety of HIFU combined with TBEA in the treatment of menorrhagia as-sociated with AMby comparing the difference of outcome indexes between two groups before and after treatment at different times.Results:Compared with pre-treatment,the PBAC score,NRS score and CA125 level were signif-icantly decreased after treatment in both groups(P<0.05).Compared with HIFU+drug group,PBAC score of HIFU+TBEA group decreased more at 6,9 and 12 months after treatment(P<0.05),but there was no signifi-cant difference in PBAC score at 1 and 3 months after treatment(P>0.05).There was no significant difference in NRS scores between the two groups at 1,3,6,9 and 12 months after treatment(P>0.05).There was no signifi-cant difference in reintervention rate between HIFU+TBEA group(11.54% )and HIFU+drug group(21.57% )after treatment(P>0.05).There was no significant difference in treatment effectiveness between HIFU+TBEA group(80.77% )and HIFU+drug group(70.59% )(P>0.05).The adverse reactions of the two groups after treatment were graded as SIR A-B,and no serious adverse events occurred.Conclusions:The combination of HIFU and TBEA has good efficacy and safety in the treatment of AM,and can be used as a long-term manage-ment program for patients with no fertility needs,especially for AM patients with menorrhagia,which also has good clinical application value.

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