1.Depressive symptoms and associated factors among middle school and college students from 2021 to 2023 in Hunan Province
Chinese Journal of School Health 2025;46(1):96-101
		                        		
		                        			Objective:
		                        			To investigate the current status and trends of depressive symptoms among middle school and college students in Hunan Province, and to explore the primary related factors of depressive symptoms, so as to provide a scientific basis for strengthening mental health among students.
		                        		
		                        			Methods:
		                        			A total of 279 382 students in Hunan Province were selected through a stratified cluster random sampling method from 2021 to 2023. National Survey Questionnaire on Common Diseases and Health Influencing Factors among Students was adopted for the survey, and the Center for Epidemiological Studies Depression Scale was used to assess their depressive symptoms. The χ 2 test and trend χ 2 test were used to analyze depressive symptoms prevalence and trends, and multivariable Logistic regression was used to analyze the related factors of depressive symptoms.
		                        		
		                        			Results:
		                        			The prevalence of depressive symptoms among students in Hunan Province from 2021 to 2023 were 19.66%, 20.17% and 21.47%, respectively, showing an upward trend ( χ 2 trend =9.07,  P <0.01). In addition, the results of the multivariable Logistic regression analysis showed that students with healthy diet ( OR=0.43, 95%CI =0.40-0.45), adequate sleep ( OR=0.88, 95%CI =0.86-0.90), and acceptable screen time ( OR=0.61, 95%CI =0.60-0.62) had lower risks in depressive symptoms detection, while students with smoking ( OR= 1.95, 95%CI =1.88-2.02), secondhand smoke exposure ( OR=1.33, 95%CI =1.30-1.36) and Internet addiction ( OR= 4.19 , 95%CI =4.05-4.34) had higher risks in depressive symptoms detection, with differences in the degree of association among different genders, educational stages and urban rural groups ( OR=0.40-6.04, Z =-12.69-11.98) ( P <0.05).
		                        		
		                        			Conclusions
		                        			There is an increasing trend of depressive symptoms among middle school and college students in Hunan Province from 2021 to 2023.Targeted depression prevention measures should be taken for students with different demographic characteristics to promote their mental health.
		                        		
		                        		
		                        		
		                        	
2.Protective effects and mechanisms of sodium pyruvate on storage lesions in human red blood cells
Haoning CHEN ; Qi MIAO ; Qiang GAO ; Xin SUN ; Shunyu MEI ; Li WANG ; Yun LIAN ; Honglin LUO ; Chenjie ZHOU ; Hao LI
Chinese Journal of Blood Transfusion 2025;38(6):833-838
		                        		
		                        			
		                        			Objective: To investigate the protective effects and underlying mechanisms of sodium pyruvate (SP) on RBC storage lesions using an oxidative damage model. Methods: Six units of leukocyte-depleted suspended RBCs (discarded for non-infectious reasons within three days post-collection) were randomly assigned to four groups: negative control (NS), positive control (PS), experimental group 1 (SP1), and experimental group 2 (SP2). Oxidative stress was induced in the PS group by the addition of hydrogen peroxide (H
      O
      ), while SP1 and SP2 received SP supplementation at different concentrations (25 mM and 50 mM, respectively) in the presence of H
      O
      . After 1 hour of incubation, RBC morphology was assessed microscopically, and biochemical indicators including glutathione (GSH), malondialdehyde (MDA), methemoglobin (MetHb), adenosine triphosphate (ATP), and Na
      /K
      -ATPase activity were measured. Results: RBCs in the PS group exhibited pronounced morphological damage, including cell shrinkage and echinocyte formation, whereas both SP-treated groups showed significantly reduced structural injury. SP treatment led to elevated GSH levels and decreased concentrations of MDA and MetHb, suggesting attenuation of oxidative stress. Additionally, SP enhanced intracellular ATP levels and Na
      /K
      -ATPase activity, thereby contributing to membrane stability. Notably, the SP2 group (50 mM) demonstrated superior protective effects compared to SP1 (25 mM). Conclusion: Sodium pyruvate effectively attenuates oxidative storage lesions in RBCs, primarily through its antioxidant properties, energy metabolism supporting ability, and celluar membrane stabilizing function. These findings suggest SP as a promising additive for enhancing the quality and safety of stored RBCs.
    
		                        		
		                        		
		                        		
		                        	
3.Mitochondria: The Target of Ionizing Radiation Damage
Lian-Chen TIAN ; Ya-Yi YUAN ; Xu-Hong DANG
Progress in Biochemistry and Biophysics 2025;52(4):836-844
		                        		
		                        			
		                        			In recent years, due to the development of radiotherapy technology and nuclear energy, people have paid more and more attention to the various effects of ionizing radiation on organisms. Ionizing radiation can induce protein, DNA and other biological macromolecules to damage, resulting in apoptosis, senescence, cancer and a series of changes. For a long time, it has been believed that the main target of ionizing radiation damage is DNA in the nucleus. However, it has been reported in recent years that ionizing radiation has both direct and indirect effects, and the theory of ROS damage in the indirect effects believes that ionizing radiation has target uncertainty, so it is not comprehensive enough to evaluate only the DNA damage in the nucleus. It has been reported that ionizing radiation can cause damage to organelles as well as damage to cells. Mitochondria are important damaged organelles because mitochondria occupy as much as 30% of the entire cell volume in the cytoplasm, which contains DNA and related enzymes that are closely related to cellular ATP synthesis, aerobic respiration and other life activities. What is more noteworthy is that mitochondria are the only organelles in which DNA exists in the human body, which makes researchers pay attention to various damage to mitochondrial DNA caused by ionizing radiation (such as double-strand breaks, base mismatching, and fragment loss). Although these damages also occur in the nucleus, mitochondrial DNA is more severely damaged than nuclear DNA due to its lack of histone protection, so mitochondria are important targets of ionizing radiation damage in addition to the nucleus. Mitochondrial DNA is not protected by histones and has little repair ability. When exposed to ionizing radiation, common deletions occur at an increased frequency and are passed on to offspring. For large-scale mitochondrial DNA damage, mitochondria indirectly compensate for the amount of damaged DNA by increasing the number of DNA copies and maintaining the normal function of mitochondrial DNA. Mitochondria are in a state of oxidative stress after exposure to ionizing radiation, and this oxidative stress will promote the change in mitochondrial function. When mitochondria are damaged, the activity of proteins related to aerobic respiration decreases, and oxidative respiration is inhibited to a certain extent. At the same time, a large amount of active superoxide anions are continuously produced to stimulate mitochondrial oxidative stress, and the signal of such damage is transmitted to the surrounding mitochondria, resulting in a cascade of damage reaction, which further activates the signalling pathway between mitochondria and nucleus. The cell nucleus is also in a state of oxidative stress, and finally, the level of free radicals is high, causing secondary damage to the genetic material DNA of mitochondria and nucleus. In this paper, the damage effects of ionizing radiation on mitochondria are reviewed, to provide a new idea for radiation protection. 
		                        		
		                        		
		                        		
		                        	
4.Phase Change and Quantity-quality Transfer Analysis of Medicinal Materials, Decoction Pieces and Standard Decoction of Haliotidis Concha (Haliotis discus hannai)
Zhihan YANG ; Jingwei ZHOU ; Weichao WANG ; Yu HUANG ; Chuang LUO ; Lian YANG ; Chenyu ZHONG ; Hongping CHEN ; Fu WANG ; Yuan HU ; Youping LIU ; Shilin CHEN ; Lin CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):206-214
		                        		
		                        			
		                        			ObjectiveTo explore the quantity-quality transfer process of medicinal materials, decoction pieces and standard decoction of Haliotidis Concha(Haliotis discus hannai) by analyzing the physical phase and compositional changes, so as to provide references for the effective control of its quality. MethodsA total of 20 batches of Haliotidis Concha(H. discus hannai) from different habitats were collected and prepared into corresponding calcined products and standard decoction, and the content of CaCO3 of the three samples were determined and the extract yield and transfer rate of CaCO3 were calculated. The changes in elemental composition and their relative contents were investigated by X-ray fluorescence spectrometry(XRF), X-ray diffraction(XRD) was used to study the changes in the phase compositions of the three samples and to establish their respective XRD specific chromatogram. Fourier transform infrared spectrometry(FTIR) was used to study the changes in the chemical composition and content changes of the three samples and to establish their respective FTIR specific chromatogram, while combining hierarchical cluster analysis(HCA), principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) to find the common and differential characteristics, in order to explore the quantity-quality transfer relationship in the preparation process of standard decoction of Haliotidis Concha(H. discus hannai). ResultsThe CaCO3 contents of the 20 batches of medicinal materials, decoction pieces and standard decoction of Haliotidis Concha(H. discus hannai) were 93.87%-98.95%, 96.02%-99.97% and 38.29%-51.96%, respectively, and the extract yield of standard decoction was 1.71%-2.37%, and the CaCO3 transfer rate of decoction pieces-standard decoction was 0.68%-1.27%. XRF results showed that the elemental species and their relative contents contained in Haliotidis Concha and its calcined products had a high degree of similarity, and although there was no obvious difference in the elemental species contained in decoction pieces and standard decoction, the difference in the relative contents was obvious, which was mainly reflected in the decrease of the relative content of element Ca and the increase of the relative content of element Na. XRD results showed that Haliotidis Concha mainly contained CaCO3 of aragonite and calcite, while calcined Haliotidis Concha only contained CaCO3 of calcite, and standard decoction mainly contained CaCO3 of calcite and Na2CO3 of natrite. FTIR results showed that there were internal vibrations of O-H, C-H, C=O, HCO3- and CO32- groups in Haliotidis Concha, while O-H, HCO3- and CO32- groups existed in the calcined products and standard decoction. ConclusionThe changes of Haliotidis Concha and calcined Haliotidis Concha are mainly the increase of CaCO3 content, the transformation of CaCO3 aragonite crystal form to calcite crystal form and the absence of organic components after calcination, and the changes of calcined products and standard decoction are mainly the decrease of CaCO3 content and the increase of Na2CO3 relative content. The method established in the study is applicable to the quality control of the shellfish medicines-decoction pieces- standard decoction, which provides a new idea for the study of quality control of dispensing granules of shellfish medicines. 
		                        		
		                        		
		                        		
		                        	
5.Phase Change and Quantity-quality Transfer Analysis of Medicinal Materials, Decoction Pieces and Standard Decoction of Haliotidis Concha (Haliotis discus hannai)
Zhihan YANG ; Jingwei ZHOU ; Weichao WANG ; Yu HUANG ; Chuang LUO ; Lian YANG ; Chenyu ZHONG ; Hongping CHEN ; Fu WANG ; Yuan HU ; Youping LIU ; Shilin CHEN ; Lin CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):206-214
		                        		
		                        			
		                        			ObjectiveTo explore the quantity-quality transfer process of medicinal materials, decoction pieces and standard decoction of Haliotidis Concha(Haliotis discus hannai) by analyzing the physical phase and compositional changes, so as to provide references for the effective control of its quality. MethodsA total of 20 batches of Haliotidis Concha(H. discus hannai) from different habitats were collected and prepared into corresponding calcined products and standard decoction, and the content of CaCO3 of the three samples were determined and the extract yield and transfer rate of CaCO3 were calculated. The changes in elemental composition and their relative contents were investigated by X-ray fluorescence spectrometry(XRF), X-ray diffraction(XRD) was used to study the changes in the phase compositions of the three samples and to establish their respective XRD specific chromatogram. Fourier transform infrared spectrometry(FTIR) was used to study the changes in the chemical composition and content changes of the three samples and to establish their respective FTIR specific chromatogram, while combining hierarchical cluster analysis(HCA), principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) to find the common and differential characteristics, in order to explore the quantity-quality transfer relationship in the preparation process of standard decoction of Haliotidis Concha(H. discus hannai). ResultsThe CaCO3 contents of the 20 batches of medicinal materials, decoction pieces and standard decoction of Haliotidis Concha(H. discus hannai) were 93.87%-98.95%, 96.02%-99.97% and 38.29%-51.96%, respectively, and the extract yield of standard decoction was 1.71%-2.37%, and the CaCO3 transfer rate of decoction pieces-standard decoction was 0.68%-1.27%. XRF results showed that the elemental species and their relative contents contained in Haliotidis Concha and its calcined products had a high degree of similarity, and although there was no obvious difference in the elemental species contained in decoction pieces and standard decoction, the difference in the relative contents was obvious, which was mainly reflected in the decrease of the relative content of element Ca and the increase of the relative content of element Na. XRD results showed that Haliotidis Concha mainly contained CaCO3 of aragonite and calcite, while calcined Haliotidis Concha only contained CaCO3 of calcite, and standard decoction mainly contained CaCO3 of calcite and Na2CO3 of natrite. FTIR results showed that there were internal vibrations of O-H, C-H, C=O, HCO3- and CO32- groups in Haliotidis Concha, while O-H, HCO3- and CO32- groups existed in the calcined products and standard decoction. ConclusionThe changes of Haliotidis Concha and calcined Haliotidis Concha are mainly the increase of CaCO3 content, the transformation of CaCO3 aragonite crystal form to calcite crystal form and the absence of organic components after calcination, and the changes of calcined products and standard decoction are mainly the decrease of CaCO3 content and the increase of Na2CO3 relative content. The method established in the study is applicable to the quality control of the shellfish medicines-decoction pieces- standard decoction, which provides a new idea for the study of quality control of dispensing granules of shellfish medicines. 
		                        		
		                        		
		                        		
		                        	
6.Exon Sequencing of HNF1β in Chinese Patients with Early-Onset Diabetes
Siqian GONG ; Hong LIAN ; Yating LI ; Xiaoling CAI ; Wei LIU ; Yingying LUO ; Meng LI ; Si-min ZHANG ; Rui ZHANG ; Lingli ZHOU ; Yu ZHU ; Qian REN ; Xiuying ZHANG ; Jing CHEN ; Jing WU ; Xianghai ZHOU ; Xirui WANG ; Xueyao HAN ; Linong JI
Diabetes & Metabolism Journal 2025;49(2):321-330
		                        		
		                        			 Background:
		                        			Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. 
		                        		
		                        			Methods:
		                        			Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. 
		                        		
		                        			Results:
		                        			Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. 
		                        		
		                        			Conclusion
		                        			MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results. 
		                        		
		                        		
		                        		
		                        	
7.Exon Sequencing of HNF1β in Chinese Patients with Early-Onset Diabetes
Siqian GONG ; Hong LIAN ; Yating LI ; Xiaoling CAI ; Wei LIU ; Yingying LUO ; Meng LI ; Si-min ZHANG ; Rui ZHANG ; Lingli ZHOU ; Yu ZHU ; Qian REN ; Xiuying ZHANG ; Jing CHEN ; Jing WU ; Xianghai ZHOU ; Xirui WANG ; Xueyao HAN ; Linong JI
Diabetes & Metabolism Journal 2025;49(2):321-330
		                        		
		                        			 Background:
		                        			Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. 
		                        		
		                        			Methods:
		                        			Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. 
		                        		
		                        			Results:
		                        			Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. 
		                        		
		                        			Conclusion
		                        			MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results. 
		                        		
		                        		
		                        		
		                        	
8.Exon Sequencing of HNF1β in Chinese Patients with Early-Onset Diabetes
Siqian GONG ; Hong LIAN ; Yating LI ; Xiaoling CAI ; Wei LIU ; Yingying LUO ; Meng LI ; Si-min ZHANG ; Rui ZHANG ; Lingli ZHOU ; Yu ZHU ; Qian REN ; Xiuying ZHANG ; Jing CHEN ; Jing WU ; Xianghai ZHOU ; Xirui WANG ; Xueyao HAN ; Linong JI
Diabetes & Metabolism Journal 2025;49(2):321-330
		                        		
		                        			 Background:
		                        			Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. 
		                        		
		                        			Methods:
		                        			Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. 
		                        		
		                        			Results:
		                        			Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. 
		                        		
		                        			Conclusion
		                        			MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results. 
		                        		
		                        		
		                        		
		                        	
9.Exon Sequencing of HNF1β in Chinese Patients with Early-Onset Diabetes
Siqian GONG ; Hong LIAN ; Yating LI ; Xiaoling CAI ; Wei LIU ; Yingying LUO ; Meng LI ; Si-min ZHANG ; Rui ZHANG ; Lingli ZHOU ; Yu ZHU ; Qian REN ; Xiuying ZHANG ; Jing CHEN ; Jing WU ; Xianghai ZHOU ; Xirui WANG ; Xueyao HAN ; Linong JI
Diabetes & Metabolism Journal 2025;49(2):321-330
		                        		
		                        			 Background:
		                        			Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. 
		                        		
		                        			Methods:
		                        			Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. 
		                        		
		                        			Results:
		                        			Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. 
		                        		
		                        			Conclusion
		                        			MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results. 
		                        		
		                        		
		                        		
		                        	
10.The Role of AMPK in Diabetic Cardiomyopathy and Related Intervention Strategies
Fang-Lian LIAO ; Xiao-Feng CHEN ; Han-Yi XIANG ; Zhi XIA ; Hua-Yu SHANG
Progress in Biochemistry and Biophysics 2025;52(10):2550-2567
		                        		
		                        			
		                        			Diabetic cardiomyopathy is a distinct form of cardiomyopathy that can lead to heart failure, arrhythmias, cardiogenic shock, and sudden death. It has become a major cause of mortality in diabetic patients. The pathogenesis of diabetic cardiomyopathy is complex, involving increased oxidative stress, activation of inflammatory responses, disturbances in glucose and lipid metabolism, accumulation of advanced glycation end products (AGEs), abnormal autophagy and apoptosis, insulin resistance, and impaired intracellular Ca2+ homeostasis. Recent studies have shown that adenosine monophosphate-activated protein kinase (AMPK) plays a crucial protective role by lowering blood glucose levels, promoting lipolysis, inhibiting lipid synthesis, and exerting antioxidant, anti-inflammatory, anti-apoptotic, and anti-ferroptotic effects. It also enhances autophagy, thereby alleviating myocardial injury under hyperglycemic conditions. Consequently, AMPK is considered a key protective factor in diabetic cardiomyopathy. As part of diabetes prevention and treatment strategies, both pharmacological and exercise interventions have been shown to mitigate diabetic cardiomyopathy by modulating the AMPK signaling pathway. However, the precise regulatory mechanisms, optimal intervention strategies, and clinical translation require further investigation. This review summarizes the role of AMPK in the prevention and treatment of diabetic cardiomyopathy through drug and/or exercise interventions, aiming to provide a reference for the development and application of AMPK-targeted therapies. First, several classical AMPK activators (e.g., AICAR, A-769662, O-304, and metformin) have been shown to enhance autophagy and glucose uptake while inhibiting oxidative stress and inflammatory responses by increasing the phosphorylation of AMPK and its downstream target, mammalian target of rapamycin (mTOR), and/or by upregulating the gene expression of glucose transporters GLUT1 and GLUT4. Second, many antidiabetic agents (e.g., teneligliptin, liraglutide, exenatide, semaglutide, canagliflozin, dapagliflozin, and empagliflozin) can promote autophagy, reverse excessive apoptosis and autophagy, and alleviate oxidative stress and inflammation by enhancing AMPK phosphorylation and its downstream targets, such as mTOR, or by increasing the expression of silent information regulator 1 (SIRT1) and peroxisome proliferator-activated receptor‑α (PPAR‑α). Third, certain anti-anginal (e.g., trimetazidine, nicorandil), anti-asthmatic (e.g., farrerol), antibacterial (e.g., sodium houttuyfonate), and antibiotic (e.g., minocycline) agents have been shown to promote autophagy/mitophagy, mitochondrial biogenesis, and inhibit oxidative stress and lipid accumulation via AMPK phosphorylation and its downstream targets such as protein kinase B (PKB/AKT) and/or PPAR‑α. Fourth, natural compounds (e.g., dihydromyricetin, quercetin, resveratrol, berberine, platycodin D, asiaticoside, cinnamaldehyde, and icariin) can upregulate AMPK phosphorylation and downstream targets such as AKT, mTOR, and/or the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), thereby exerting anti-inflammatory, anti-apoptotic, anti-pyroptotic, antioxidant, and pro-autophagic effects. Fifth, moderate exercise (e.g., continuous or intermittent aerobic exercise, aerobic combined with resistance training, or high-intensity interval training) can activate AMPK and its downstream targets (e.g., acetyl-CoA carboxylase (ACC), GLUT4, PPARγ coactivator-1α (PGC-1α), PPAR-α, and forkhead box protein O3 (FOXO3)) to promote fatty acid oxidation and glucose uptake, and to inhibit oxidative stress and excessive mitochondrial fission. Finally, the combination of liraglutide and aerobic interval training has been shown to activate the AMPK/FOXO1 pathway, thereby reducing excessive myocardial fatty acid uptake and oxidation. This combination therapy offers superior improvement in cardiac dysfunction, myocardial hypertrophy, and fibrosis in diabetic conditions compared to liraglutide or exercise alone. 
		                        		
		                        		
		                        		
		                        	
            

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