1.Clinical characteristics analysis of 6 children with anomalous origin of coronary artery supported by extracorporeal membrane oxygenation
Dongliang CHENG ; Fanfan DU ; Meng CHENG ; Changsong SHI
Chinese Journal of Pediatrics 2026;64(1):95-98
Objective:To summarize the clinical features of children with anomalous origin of coronary artery (AOCA) who received extracorporeal membrane oxygenation (ECMO) support.Methods:A case series study was conducted. Clinical data was collected from 6 children who were diagnosed with AOCA by coronary computed tomography angiography or digital subtraction angiography and received ECMO support in the Pediatric Intensive Care Unit of Henan Provincial People′s Hospital between January 2020 and August 2024. Descriptive analysis was performed on their clinical features, laboratory test results, point-of-care echocardiography results, imaging findings, surgical management, and outcomes.Results:Among the 6 children (3 males and 3 females), the age of onset was 12.5 (11.0, 13.0) years. All 6 patients were transported from other hospitals under ECMO support. Five patients were admitted with chief complaints of "cardiac arrest after strenuous activity, syncope after strenuous activity, or heart failure" and were initially diagnosed with fulminant myocarditis or cardiomyopathy. All 6 children had significantly elevated troponin and B-type natriuretic peptide levels upon admission. Point-of-care echocardiography revealed segmental left ventricular systolic dysfunction in all 6 children, and AOCA was detected in 2 cases based on bedside ultrasound. ECMO was successfully weaned in 5 children. All 6 cases were diagnosed with AOCA. Four children underwent surgical coronary artery correction, one received a heart transplantation, and one missed the optimal window for surgical correction. Heart transplantation was recommended for the latter, but the parents declined, and the patient was discharged. During the follow-up until August 2025, all 6 children survived.Conclusions:AOCA in children is prone to misdiagnosis as other diseases in the early stage. Timely ECMO support provides the possibility of surgery or heart transplantation for children experiencing acute ischemic and hypoxic episodes due to AOCA, improving survival rates.
2.Huaier Enhances Efficacy of Oxaliplatin in Treatment of Gastric Cancer by Improving Gut Microbiota
Shenglian ZHANG ; Zhimin DU ; Yi GONG ; Meiqi LAN ; Ping LIU ; Yajun XIONG ; Yanli GONG ; Xiaoyong SONG ; Junli LI ; Ruizhi WANG ; Yuting GAO ; Huanhu ZHANG ; Xinli SHI
Cancer Research on Prevention and Treatment 2026;53(3):176-186
Objective To elucidate the changes in the gut microbiota and molecular mechanism of huaier in
3.Risk Factors Analysis and Predictive Model Construction for Acute Kidney Injury Following Amphotericin B Deoxycholate Use in Hospitalized Patients
Hao XIE ; Yixun SHI ; Zhiqing XU ; Minquan LI ; Xiaoli DU ; Gang CHEN ; Bin ZHAO
Medical Journal of Peking Union Medical College Hospital 2026;17(2):429-437
To investigate the risk factors for acute kidney injury (AKI) following the use of amphotericin B deoxycholate and to develop a predictive model to guide clinical monitoring and intervention. A retrospective analysis was conducted on hospitalized patients who received amphotericin B deoxycholate between January 2014 and September 2024. Patients were divided into a training set and a validation set. Demographic data, laboratory findings, and medication orders were collected. Based on the occurrence of AKI during treatment and within 7 days after discontinuation, patients were classified into an AKI group and a non-AKI group. Univariate analysis was used to screen for potential risk factors, multivariate logistic regression was employed to construct a predictive model, and model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and the Hosmer-Lemeshow test. The training set included 473 patients, comprising 255 males (53.91%) and 218 females (46.09%), with a median age of 52(35, 62) years. The AKI group consisted of 191 cases (40.38%), and the non-AKI group consisted of 282 cases (59.62%). The validation set included 114 patients, comprising 80 males (70.18%) and 34 females (29.82%), with a median age of 43.5 (31.0, 58.5) years. The AKI group consisted of 42 cases (36.84%), and the non-AKI group consisted of 72 cases (63.16%). Univariate analysis revealed statistically significant differences between the two groups in 23 factors (all Admission to the ICU, elevated serum creatinine at admission, and comorbid cardiac insufficiency as potential risk factors for AKI, while prophylactic use of diphenhydramine/promethazine or sodium bicarbonate showed a protective association. A predictive model with good discrimina-tion and calibration was developed, which may provide a basis for early identification of high-risk patients and timely adjustment of treatment strategies in clinical practice.
4.Meta-analysis of the effects of different doses of vitamin D supplementation on maternal and infant outcomes in vitamin D-deficient pregnant women
Xiaoxia SHI ; Weina WANG ; Rui LI ; Yaheng DU ; Lu LIU
China Pharmacy 2026;37(9):1215-1221
OBJECTIVE To systematically evaluate the effects of supplementation with different doses of vitamin D on maternal and infant outcomes in vitamin D-deficient pregnant women. METHODS Related literature on the effects of supplementing different doses of vitamin D on maternal and infant outcomes was searched in databases including CNKI, Wanfang Data, VIP, PubMed, Medline, the Cochrane Library, Embase from their inception to June 30, 2025. The risk of bias assessment tool from the Cochrane Handbook 5.1 was used to evaluate the quality of included literature. Meta-analysis of outcome indicators was performed by using RevMan 5.4 software. RESULTS A total of 15 studies were included, involving 4 664 patients [2 129 in the experimental group (daily dose >2 000 IU), 2 058 in control group 1 (daily dose ≤1 000 IU) and 477 in control group 2 (daily dose >1 000-≤2 000 IU) ] . Meta-analysis results showed that the incidence of preeclampsia (PE) [OR=0.71, 95%CI (0.53, 0.96), P =0.03 ] , gestational diabetes mellitus (GDM) [OR=0.60, 95%CI (0.43, 0.84), P =0.003 ] , low birth weight of newborn [OR=0.72, 95%CI (0.53, 0.97), P =0.03 ] and macrosomia [OR=0.53, 95%CI (0.29, 0.98), P =0.04 ] in the experimental group were significant lower than control group 1; but there was no significant difference in the incidence of premature delivery [OR=0.86, 95%CI (0.65, 1.13), P =0.28 ] , cesarean delivery [OR=0.92, 95%CI (0.74, 1.15), P =0.48 ] or stillbirth rate [OR=0.77, 95%CI (0.48, 1.24), P =0.29 ] . The incidence of low birth weight of ne wborn [OR=0.64, 95%CI (0.41, 0.98), P =0.04 ] in the experimental group was significant lower than control group 2; but there was no significant difference in the incidence of PE [OR=0.61, 95%CI (0.25, 1.49), P =0.28 ] , the incidence of GDM [OR=0.73, 95%CI (0.42, 1.24), P =0.24 ] , premature delivery rate [OR=0.90, 95%CI (0.59, 1.39), P =0.63 ] , cesarean delivery rate [OR=0.92, 95%CI (0.64, 1.33), P =0.66 ] , or stillbirth rate [OR=0.68, 95%CI (0.24, 1.94), P =0.48 ] . CONCLUSIONS Different doses of vitamin D supplementation in early pregnancy have a significant impact on maternal and infant pregnancy outcomes in vitamin D-deficient pregnant women; daily doses >2 000 IU have significant advantages in reducing the incidence of PE and GDM and improving the outcome of premature delivery.
5.Correlation of mitochondrial genetic differentiation and spatial variables of Oncomelania hupensis robertsoni in Yunnan Province
Yuanyuan ZHANG ; Jing SONG ; Yuwan HAO ; Zaogai YANG ; Xinping SHI ; Siqi NING ; Hongqiong WANG ; Chunhong DU ; Jihua ZHOU ; Zongya ZHANG ; Kai LI ; Shizhu LI ; Yi DONG
Chinese Journal of Schistosomiasis Control 2026;38(1):54-59
Objective Objective To analyze the potential spatial factors affecting the genetic differentiation of Oncomelania hupensis robertsoni in Yunnan Province. Methods A total of 13 administrative villages were selected from schistosomiasis-endemic areas of Yunnan Province as O. hupensis snail sampling sites. At least 200 snails were collected in each site, and the spatial variable data of each site were recorded, including longitude, latitude and altitude. Thirty active and Schistosoma japonicum uninfected O. hupensis snails were selected from each sampling site by means of the crawling method and the cercarial shedding method. Genomic DNA was extracted from O. hupensis snails. Following PCR amplification, purification of PCR amplification products and sequencing, the gene sequences of O. hupensis snail samples were spliced and edited using the DNAstar software and the NCBI database to yield the complete mitochondrial sequences of O. hupensis snails at each sampling site, and the mitochondrial genetic distance matrix of O. hupensis robertsoni was calculated at each sampling site. The geographical coordinates of each sampling site were marked using the software ArcGIS 10.2, and the straight-line geographical distance between each sampling site was calculated. The altitude difference, longitude difference and latitude difference between each sampling site were calculated using the Excel software, and the correlation between the mitochondrial genetic distance matrix of O. hupensis robertsoni and each spatial variable matrix was examined by using the Mantel test at 13 sampling sites in Yunnan Province. Results Among the 13 O. hupensis snail sampling sites in Yunnan Province, the largest mitochondrial genetic distance of O. hupensis robertsoni snail populations was seen between Anding Village, Nanjian Yi Autonomous County and Caizhuang Village, Midu County (26.244 2), and the largest geographical distance was seen between Dongyuan Village, Gucheng District and Cangling Village, Chuxiong County (272.64 km). The highest altitude difference was seen between Anding Village, Nanjian Yi Autonomous County and Dongyuan Village, Gucheng District (1 086.10 m), and the largest longitude difference was found between Qiandian Village, Eryuan County and Cangling Village, Chuxiong County (1.86°), while the largest latitude difference was measured between Leqiu Village, Nanjian Yi Autonomous County and Dongyuan Village, Gucheng District (1.81°). In addition, the mitochondrial genetic distance of O. hupensis robertsoni snail populations was positively correlated with altitude at 13 snail sampling sites in Yunnan Province (r = 0.542 8, P < 0.001), and showed no significant correlations with geographical distance (r = 0.093 4, P > 0.05), longitude (r = −0.199 5, P > 0.05) or latitude (r = 0.205 7, P > 0.05). Conclusion Altitude may be a potential spatial factor affecting the genetic differentiation of O. hupensis robertsoni in Yunnan Province.
6.Clinical characteristics analysis of 6 children with anomalous origin of coronary artery supported by extracorporeal membrane oxygenation
Dongliang CHENG ; Fanfan DU ; Meng CHENG ; Changsong SHI
Chinese Journal of Pediatrics 2026;64(1):95-98
Objective:To summarize the clinical features of children with anomalous origin of coronary artery (AOCA) who received extracorporeal membrane oxygenation (ECMO) support.Methods:A case series study was conducted. Clinical data was collected from 6 children who were diagnosed with AOCA by coronary computed tomography angiography or digital subtraction angiography and received ECMO support in the Pediatric Intensive Care Unit of Henan Provincial People′s Hospital between January 2020 and August 2024. Descriptive analysis was performed on their clinical features, laboratory test results, point-of-care echocardiography results, imaging findings, surgical management, and outcomes.Results:Among the 6 children (3 males and 3 females), the age of onset was 12.5 (11.0, 13.0) years. All 6 patients were transported from other hospitals under ECMO support. Five patients were admitted with chief complaints of "cardiac arrest after strenuous activity, syncope after strenuous activity, or heart failure" and were initially diagnosed with fulminant myocarditis or cardiomyopathy. All 6 children had significantly elevated troponin and B-type natriuretic peptide levels upon admission. Point-of-care echocardiography revealed segmental left ventricular systolic dysfunction in all 6 children, and AOCA was detected in 2 cases based on bedside ultrasound. ECMO was successfully weaned in 5 children. All 6 cases were diagnosed with AOCA. Four children underwent surgical coronary artery correction, one received a heart transplantation, and one missed the optimal window for surgical correction. Heart transplantation was recommended for the latter, but the parents declined, and the patient was discharged. During the follow-up until August 2025, all 6 children survived.Conclusions:AOCA in children is prone to misdiagnosis as other diseases in the early stage. Timely ECMO support provides the possibility of surgery or heart transplantation for children experiencing acute ischemic and hypoxic episodes due to AOCA, improving survival rates.
7.Preoperative nebulized indocyanine green-assisted thoracoscopic anatomical lesion resection for congenital pulmonary airway malformations in children: A retrospective cohort study
Hongguang SHI ; Junpeng DU ; Jiaxi WANG ; Peiliang SUN ; Zhenqiu CHEN ; Weibo ZHANG ; Zhe FU ; Mingjun ZHENG ; Yongqian MA
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(09):1412-1418
Objective To investigate the efficacy of preoperative nebulized indocyanine green (ICG)-assisted thoracoscopic anatomical lesion resection (TALR) in treating pediatric congenital pulmonary airway malformation (CPAM). Methods A retrospective analysis was conducted on clinical data of 45 children with CPAM who underwent thoracoscopic surgery at the Third Affiliated Hospital of Zhengzhou University between June 2023 and March 2025. The patients were divided into an ICG group (preoperative nebulized ICG 0.5 mg/kg+TALR) and a non-ICG group (TALR under white light), with perioperative and postoperative recovery parameters compared between groups. Results A total of 45 children [22 males, 23 females; median age 7.4 (1.1-75.0) months] were enrolled. The ICG group (n=22) and non-ICG group (n=23) both achieved uneventful recoveries. Compared to the non-ICG group, the ICG group demonstrated significantly shorter surgical duration [91.3 (38.0-144.0) min vs. 100.0 (50.0-175.0) min, P=0.032], reduced intraoperative blood loss [3.0 (2.0-10.0) mL vs. 5.0 (1.0-10.0) mL, P=0.049], shorter postoperative drainage duration [2.7 (1.9-3.9) d vs. 3.4 (1.8-19.9) d, P=0.003], and shortened hospital stay [4.6 (2.9-9.8) d vs. 5.0 (3.9-21.5) d, P=0.013]. Residual lesions occurred in 2 patients from the non-ICG group but none in the ICG group. Intragroup comparisons revealed significant improvements in ratio of time to peak tidal expiratory flow to expiratory time, ratio of volume to peak tidal expiratory flow to expiratory volume, and tidal volume per kilogram after surgery in both groups (P<0.05), though intergroup differences showed no statistical significance (P>0.05). Conclusion Preoperative nebulized ICG administration facilitates lesion identification in CPAM, reduces technical difficulty of TALR, enhances therapeutic outcomes, and provides valuable assistance for performing TALR procedures.
8.Fangji Fulingtang Attenuates Myocardial Fibrosis by Regulating Mitochondrial Function Through AMPK/PGC-1α/MFN2-PKM2 Signaling Pathway
Xuqin DU ; Yixuan LI ; Yuxia JIN ; Hongding LI ; Ruogu YANG ; Lipeng SHI ; Yi REN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(20):1-10
ObjectiveTo investigate the effects and mechanisms of Fangji Fulingtang (FFD) on mitochondrial function in the mouse model of myocardial fibrosis (MF). MethodsSixty SPF-grade male C57BL/6J mice were randomly allocated into six groups (n=10 per group): control, model, low-dose, medium-dose, and high-dose (3.315, 6.63, and 13.26 g·kg-1, respectively) FFD, and captopril (20 mg·kg-1). MF was induced by subcutaneous injection of isoproterenol (10 mg·kg-1·d-1) in other groups except the control group for 14 consecutive days, with simultaneous gavage of corresponding drugs. Left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were measured by echocardiography. Serum levels of creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), N-terminal pro-brain natriuretic peptide (NT-pro BNP), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA). Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) levels were measured by biochemical assays. Reactive oxygen species (ROS) were detected by dihydroethidium (DHE) fluorescence staining. Hematoxylin-eosin (HE), Masson's trichrome, and wheat germ agglutinin (WGA) staining were performed to evaluate myocardial structure and fibrosis. Mitochondrial ultrastructure and function were assessed by transmission electron microscopy, adenosine triphosphate (ATP) colorimetric assay, and JC-1 fluorescence staining. The protein levels of phosphorylated adenosine monophosphate-activated protein kinase α subunit (p-AMPKα), AMPKα, peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), mitofusin 2 (MFN2), pyruvate kinase M2 isoform (PKM2), lactate dehydrogenase A (LDHA), and hypoxia-inducible factor 1 alpha (HIF-1α) were analyzed by Western blot. ResultsCompared with the control group, the model group exhibited decreased LVEF and LVFS, increased heart weight index and heart weight-to-tibia length ratio (P<0.01), elevated levels of myocardial injury markers (CK-MB, cTnI, and NT-pro BNP), inflammatory cytokines (TNF-α, IL-1β, and IL-6), and MDA, along with reduced SOD and GSH levels (P<0.01). Enhanced interstitial collagen deposition and cardiomyocyte hypertrophy were observed in the model group (P<0.01). Transmission electron microscopy and JC-1 staining revealed mitochondrial swelling, crista disruption, decreased ATP content, and reduced red/green fluorescence ratio in the model group (P<0.01). Western blot analysis demonstrated downregulation of p-AMPKα, PGC-1α, and MFN2 and upregulation of PKM2, LDHA, and HIF-1α in the model group (P<0.01). Compared with the model group, treatment with FFD or captopril improved LVEF and LVFS, reduced heart weight index and heart weight-to-tibia length ratio (P<0.05, P<0.01), lowered the serum levels of CK-MB, cTnI, NT-pro BNP, TNF-α, IL-1β, IL-6, and MDA, increased the SOD and GSH levels (P<0.05, P<0.01), attenuated the myocardial fibrosis and cardiomyocyte hypertrophy (P<0.01), and restored the mitochondrial ultrastructure. The medium and high-dose FFD groups as well as the captopril group showed increased ATP production and red/green fluorescence ratio (P<0.05, P<0.01). Furthermore, FFD upregulated the expression of p-AMPKα and PGC-1α while downregulating the expression of LDHA and HIF-1α (P<0.05, P<0.01). ConclusionFFD activates the AMPK/PGC-1α/MFN2 signaling pathway and inhibits the PKM2/LDHA/HIF-1α axis to restore mitochondrial function and energy metabolic homeostasis, thereby attenuating isoproterenol-induced myocardial fibrosis.
9.Mechanism of Huangqi Xiayuxue Decoction Against Hepatocellular Carcinoma via PI3K/Akt/FoxO Signaling Pathway
Xingru XING ; Yuanzhou SHI ; Jiawei WANG ; Di WU ; Yuyao ZHANG ; Yalin WU ; Du CHEN ; Zhen ZHANG ; Sha TIAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(20):131-141
ObjectiveTo explore the therapeutic effect and mechanism of Huangqi Xiayuxue decoction against hepatocellular carcinoma based on network pharmacology, animal experiments, and cell experiments. MethodsThe active ingredients and corresponding targets of Huangqi Xiayuxue decoction were screened via databases including the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Hepatocellular carcinoma-related targets were retrieved from the GeneCards database. The common targets shared by Huangqi Xiayuxue decoction and hepatocellular carcinoma were subjected to Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Huangqi Xiayuxue decoction-containing plasma was prepared. The cell counting kit-8 (CCK-8) assay was adopted to observe the effects of different volume fractions (5%, 10%, 15%, and 20%) of Huangqi Xiayuxue decoction-containing plasma on the proliferation of HepG2, MHCC-97H, Hepa1-6, and Huh-7 cells, and the concentration for subsequent experiments was determined. Flow cytometry was adopted to detect the effects of Huangqi Xiayuxue decoction-containing plasma (5%, 10%, 15%, and 20%) on the apoptosis of MHCC-97H cells. A mouse model of subcutaneous xenograft hepatocellular carcinoma was established. The model mice were assigned into low-, medium-, and high-dose (4.63, 9.25, 18.5 g·kg-1) Huangqi Xiayuxue decoction and sorafenib (20 mg·kg-1) groups. Body mass and tumor volume of mice were dynamically monitored during the intervention period. After 3 weeks of intervention, hematoxylin-eosin (HE) staining was performed to observe tumor morphology. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay was employed to detect cell apoptosis. Immunohistochemistry (IHC) was adopted to examine the expression of cysteinyl aspartate-specific proteinase-3 (Caspase-3), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) in the tumor tissue. Real-time PCR and Western blot were employed to verify the changes in apoptosis-related factors and the phosphatidylinositol 3-kinase/protein kinase B/forkhead box O1 (PI3K/Akt/FoxO1) signaling pathway. ResultsA total of 220 common targets shared by Huangqi Xiayuxue decoction and hepatocellular carcinoma were screened out by network pharmacology, among which tumor protein p53 (TP53), Akt1, and signal transducer and activator of transcription 3 (STAT3) were the core targets. Pathway enrichment analysis indicated that the common targets were involved in cell apoptosis and proliferation, as well as the PI3K/Akt and FoxO signaling pathways. Cell experiments showed that compared with the blank plasma group, all volume fractions of Huangqi Xiayuxue decoction-containing plasma inhibited the proliferation of HepG2, MHCC-97H, Hepa1-6, and Huh-7 cells (P<0.01). The proportion of early apoptotic cells in MHCC-97H cells was increased after treatment with different volume fractions of Huangqi Xiayuxue decoction-containing plasma (P<0.01). Animal experiments revealed that Huangqi Xiayuxue decoction inhibited the growth of tumor volume, promoted tumor cell apoptosis in the high-dose group, up-regulated the protein and mRNA levels of Bax and Caspase-3, down-regulated the protein and mRNA levels of Bcl-2, and reduced the phosphorylation level of the PI3K/Akt/FoxO1 signaling pathway (P<0.05, P<0.01). ConclusionHuangqi Xiayuxue decoction exerts anti-hepatocellular carcinoma effects by inhibiting the activation of the PI3K/Akt/FoxO1 signaling pathway and promoting hepatocellular carcinoma cell apoptosis.
10.Fangji Fulingtang Attenuates Myocardial Fibrosis by Regulating Mitochondrial Function Through AMPK/PGC-1α/MFN2-PKM2 Signaling Pathway
Xuqin DU ; Yixuan LI ; Yuxia JIN ; Hongding LI ; Ruogu YANG ; Lipeng SHI ; Yi REN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(20):1-10
ObjectiveTo investigate the effects and mechanisms of Fangji Fulingtang (FFD) on mitochondrial function in the mouse model of myocardial fibrosis (MF). MethodsSixty SPF-grade male C57BL/6J mice were randomly allocated into six groups (n=10 per group): control, model, low-dose, medium-dose, and high-dose (3.315, 6.63, and 13.26 g·kg-1, respectively) FFD, and captopril (20 mg·kg-1). MF was induced by subcutaneous injection of isoproterenol (10 mg·kg-1·d-1) in other groups except the control group for 14 consecutive days, with simultaneous gavage of corresponding drugs. Left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were measured by echocardiography. Serum levels of creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), N-terminal pro-brain natriuretic peptide (NT-pro BNP), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA). Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) levels were measured by biochemical assays. Reactive oxygen species (ROS) were detected by dihydroethidium (DHE) fluorescence staining. Hematoxylin-eosin (HE), Masson's trichrome, and wheat germ agglutinin (WGA) staining were performed to evaluate myocardial structure and fibrosis. Mitochondrial ultrastructure and function were assessed by transmission electron microscopy, adenosine triphosphate (ATP) colorimetric assay, and JC-1 fluorescence staining. The protein levels of phosphorylated adenosine monophosphate-activated protein kinase α subunit (p-AMPKα), AMPKα, peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), mitofusin 2 (MFN2), pyruvate kinase M2 isoform (PKM2), lactate dehydrogenase A (LDHA), and hypoxia-inducible factor 1 alpha (HIF-1α) were analyzed by Western blot. ResultsCompared with the control group, the model group exhibited decreased LVEF and LVFS, increased heart weight index and heart weight-to-tibia length ratio (P<0.01), elevated levels of myocardial injury markers (CK-MB, cTnI, and NT-pro BNP), inflammatory cytokines (TNF-α, IL-1β, and IL-6), and MDA, along with reduced SOD and GSH levels (P<0.01). Enhanced interstitial collagen deposition and cardiomyocyte hypertrophy were observed in the model group (P<0.01). Transmission electron microscopy and JC-1 staining revealed mitochondrial swelling, crista disruption, decreased ATP content, and reduced red/green fluorescence ratio in the model group (P<0.01). Western blot analysis demonstrated downregulation of p-AMPKα, PGC-1α, and MFN2 and upregulation of PKM2, LDHA, and HIF-1α in the model group (P<0.01). Compared with the model group, treatment with FFD or captopril improved LVEF and LVFS, reduced heart weight index and heart weight-to-tibia length ratio (P<0.05, P<0.01), lowered the serum levels of CK-MB, cTnI, NT-pro BNP, TNF-α, IL-1β, IL-6, and MDA, increased the SOD and GSH levels (P<0.05, P<0.01), attenuated the myocardial fibrosis and cardiomyocyte hypertrophy (P<0.01), and restored the mitochondrial ultrastructure. The medium and high-dose FFD groups as well as the captopril group showed increased ATP production and red/green fluorescence ratio (P<0.05, P<0.01). Furthermore, FFD upregulated the expression of p-AMPKα and PGC-1α while downregulating the expression of LDHA and HIF-1α (P<0.05, P<0.01). ConclusionFFD activates the AMPK/PGC-1α/MFN2 signaling pathway and inhibits the PKM2/LDHA/HIF-1α axis to restore mitochondrial function and energy metabolic homeostasis, thereby attenuating isoproterenol-induced myocardial fibrosis.

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