1.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.
2.Identification, expression and protein interaction analysis of Aux/IAA and ARF gene family in Senna tora L.
Zhao FENG ; Shi-peng LIU ; Rui-hua LÜ ; Rui-hua LÜ ; Xiao-chen HU ; Ming-ying ZHANG ; Ren-jun MAO ; Gang ZHANG
Acta Pharmaceutica Sinica 2024;59(3):751-763
The early response of plant auxin gene family
3.Two new dalbergiphenols from Zhuang medicine Dalbergia rimosa Roxb
Cheng-sheng LU ; Wei-yu WANG ; Min ZHU ; Si-si QIN ; Zhao-hui LI ; Chen-yan LIANG ; Xu FENG ; Jian-hua WEI
Acta Pharmaceutica Sinica 2024;59(2):418-423
Twelve compounds were isolated from the ethyl acetate fraction of the 80% aqueous ethanol extract of the roots and stems of
4.Development and Application of a Micro-device for Rapid Detection of Ammonia Nitrogen in Environmental Water
Peng WANG ; Yong TIAN ; Chuan-Yu LIU ; Wei-Liang WANG ; Xu-Wei CHEN ; Yan-Feng ZHANG ; Ming-Li CHEN ; Jian-Hua WANG
Chinese Journal of Analytical Chemistry 2024;52(2):178-186,中插1-中插3
The analysis of ammonia nitrogen in real water samples is challenging due to matrix interferences and difficulties for rapid on-site analysis.On the basis of the standard method,i.e.water quality-determination of ammonia nitrogen-salicylic acid spectrophotometry(HJ 536-2009),a simple device for online detecting ammonia nitrogen was developed using a sequential injection analysis(SIA)system in this work.The ammonia nitrogen transformation system,color reaction system,and detection system were built in compatible with the SIA system,respectively.In particular,the detection system was assembled by employing light-emitting diode as the light source,photodiode as the detector,and polyvinylchloride tube as the cuvette,thus significantly reducing the volume,energy consumption and fabricating cost of the detection system.As a result,the accurate analysis of ammonia nitrogen in complex water samples was achieved.A quantitative detection of ammonia nitrogen in water sample was obtained in 12 min,along with linear range extending to 1000 μmol/L,precisions(Relative standard deviation,RSD)of 4.3%(C=10 μmol/L,n=7)and 4.2%(C=500 μmol/L,n=7),and limit of detection(LOD)of 0.65 μmol/L(S/N=3,n=7).The results of interfering experiments showed that the detection of ammonia nitrogen by the developed device was not interfered by the common coexisting ions and components,therefore the environmental water could be directly analyzed,such as reservoir water,domestic sewage,sea water and leachate of waste landfill.The analytical results were consistent with those obtained by the environmental protection standard method(Water quality determination of ammonia nitrogen-salicylic acid spectrophotometry,HJ 536-2009).In addition,the spiking recoveries were in the range of 92.3%-98.1%,further confirming the accuracy and practicality of the developed device.
5.Effect of Yishen Gushu Formula on bone metabolic markers and clinical efficacyn in patients with osteoporosis of kidney deficiency and blood stasis type
Xiaoyun ZHANG ; Hua LIU ; Yuan CHAI ; Feng CHEN ; Hao ZENG ; Zhengang GAO ; Yourong HUANG
Chinese Journal of Tissue Engineering Research 2024;28(8):1155-1160
BACKGROUND:With the variation of disease treatment modes and the in-depth research on senile osteoporosis in recent years,increasing studies have confirmed that traditional Chinese medicine has a significant effect on the prevention and treatment of senile osteoporosis. OBJECTIVE:To investigate the effect of Yishen Gushu Formula on bone metabolic markers in patients with osteoporosis of kidney deficiency and blood stasis type. METHODS:102 patients with senile osteoporosis of kidney deficiency and blood stasis type who were treated at Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine from July 2020 to March 2022 were enrolled,including 32 males and 70 females,aged 71-93 years.All patients were randomly divided into two groups,with 51 patients in each group.The control group was treated with calcium carbonate D3 granules and sodium alendronate tablets,while the treatment group was treated with Yishen Gushu Formula beyond the control group.Treatments in each group lasted 3 months.Bone mineral density of the L1-4 lumbar vertebrae and left femoral neck,visual analog scale score,and serum levels of osteocalcin,osteopontin,type Ⅰ collagen cross-linked C-terminal peptide and tartrate resistant acid phosphatase were measured before and 3 months after treatment.Traditional Chinese medicine syndrome score and therapeutic efficiency were also assessed. RESULTS AND CONCLUSION:After 3 months of treatment,the bone mineral density of the lumbar vertebrae(L1-4)and left femoral neck was significantly increased in both two groups(P<0.05),and the bone mineral density of the lumbar vertebrae(L1-4)and left femoral neck was significantly higher in the treatment group than the control group(P<0.05).The visual analog scale scores of both groups after 3 months of treatment were lower than those before treatment(P<0.05),and the visual analog scores of the treatment group after 3 months of treatment were lower than those of the control group(P<0.05).After 3 months of treatment,the serum levels of osteocalcin,osteopontin,type Ⅰ collagen cross-linked C-terminal peptide and tartrate resistant acid phosphatase were significantly improved in both two groups,while compared with the control group,the serum levels of osteocalcin and osteopontin were significantly higher(P<0.05)and the serum levels of type Ⅰ collagen cross-linked C-terminal peptide and tartrate resistant acid phosphatase were significantly lower in the treatment group(P<0.05).After 3 months of treatment,the Traditional Chinese medicine syndrome scores were decreased in both two groups,while the Traditional Chinese medicine syndrome scores in the treatment group were lower than those in the control group.After 3 months of treatment,no significant adverse reactions occurred in both groups.The total effective rate was 88.2%and 70.6%in the treatment and control groups respectively,and there was a significant difference between the two groups(P<0.05).To conclude,Yishen Gushu Formula combined with anti-osteoporosis drugs can significantly improve the clinical symptoms of patients with senile osteoporosis of kidney deficiency and blood stasis type and prevent disease progression by regulating bone metabolism,increasing bone mineral density,and relieving pain.
6.Salvia miltiorrhiza attenuates white matter injury induced by hypoperfusion in neonatal rats
Xuewen SU ; Haifeng YUAN ; Wanyu FENG ; Ruixia SONG ; Junlong CHEN ; Ruhan YI ; Hua ZHU ; Zhongxia DOU
Chinese Journal of Tissue Engineering Research 2024;28(20):3229-3234
BACKGROUND:Premature birth is a major global health problem associated with high mortality and morbidity.White matter injury is the most common brain injury in preterm infants.Salvia miltiorrhiza is a traditional herbal plant that is commonly used to treat cardiovascular and cerebrovascular diseases in Asian countries. OBJECTIVE:To investigate the therapeutic effect of Salvia miltiorrhiza on white matter injury in preterm infants. METHODS:Eighteen neonatal male Sprague-Dawley rats at 3-day gestational age were selected and randomized into normal group,white matter injury group,and Salvia miltiorrhiza group.Animal models of preterm white matter injury were established by permanent ligation of the right common carotid artery in the latter two groups.Rats in the Salvia miltiorrhiza group were given intraperitoneal injection of Salvia miltiorrhiza(5 mg/kg·d)for 7 consecutive days.Normal group and white matter injury group were given the same volume of PBS for intervention.On the 14th day after modeling,the rats were sacrificed.Brains were pathologically observed by hematoxylin-eosin staining under microscope,and the expression levels of myelin basic protein and CC1 in brain tissue were visualized using immunofluorescence.Furthermore,liquid chromatography-tandem mass spectrometry was used to analyze possible pathways for the action of Salvia miltiorrhiza. RESULTS AND CONCLUSION:In the white matter injury group,the structure of the corpus callosum was irregular and the cells appeared swollen and necrotic.In addition,induction of white matter injury resulted in significantly reduced myelin formation,with irregular and loosely arranged nerve fibers and significantly decreased myelin sheaths.Interestingly,white matter injury rats treated with Salvia miltiorrhiza had reduced cellular swelling,reduced lesions,and increased myelin sheaths.The expression of myelin basic protein was closely related to myelin formation,and CC1 was a marker of myelin oligodendrocytes.Salvia miltiorrhiza significantly up-regulated the expressions of myelin basic protein and CC1 in white matter injury rats(P<0.000 1),indicating that Salvia miltiorrhiza alleviated white matter injury.Liquid chromatography-tandem mass spectrometry analysis showed that the therapeutic effect of Salvia miltiorrhiza in the rat model of white matter injury was closely related to the regulation of complement and coagulation cascades.To conclude,Salvia miltiorrhiza may be a potential therapeutic agent for treating preterm white matter injury.
7.Longitudinal extrauterine growth restriction in extremely preterm infants: current status and prediction model
Xiaofang HUANG ; Qi FENG ; Shuaijun LI ; Xiuying TIAN ; Yong JI ; Ying ZHOU ; Bo TIAN ; Yuemei LI ; Wei GUO ; Shufen ZHAI ; Haiying HE ; Xia LIU ; Rongxiu ZHENG ; Shasha FAN ; Li MA ; Hongyun WANG ; Xiaoying WANG ; Shanyamei HUANG ; Jinyu LI ; Hua XIE ; Xiaoxiang LI ; Pingping ZHANG ; Hua MEI ; Yanju HU ; Ming YANG ; Lu CHEN ; Yajing LI ; Xiaohong GU ; Shengshun QUE ; Xiaoxian YAN ; Haijuan WANG ; Lixia SUN ; Liang ZHANG ; Jiuye GUO
Chinese Journal of Neonatology 2024;39(3):136-144
Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.
8.Development of a homogeneous management evaluation system for clinical observership teaching under the background of national first-class discipline construction
Weihui JIA ; Feng CHEN ; Hua ZHONG ; Chonggao YIN ; Hongli LI
Chinese Journal of Medical Education Research 2024;23(2):266-270
Objective:To develop a homogeneous management evaluation system for clinical observership teaching under the background of national first-class discipline construction.Methods:The preliminary contents of the assessment system were determined through a literature review and expert interviews, and two rounds of questionnaire-based consultation was conducted with 20 experts using the Delphi method. With the use of Excel 2016 and SPSS 26.0, we calculated the coefficient of judgement basis (Ca), the coefficient of familiarity (Cs), the coefficient of authority (Cr), and Kendall's coefficient of concordance ( W ) as well as the mean, standard deviation, and coefficient of variation of all parameters, to identify the specific items and weights for the homogeneous management evaluation system for clinical observership teaching under the background of national first-class discipline construction. Results:In the two rounds of consultation, experts were both 100.00% active in responding to the questionnaires; the coefficients of authority of experts were 0.889 and 0.935, respectively; the coefficients of familiarity were 0.856 and 0.936, respectively; the coefficients of judgment were 0.922 and 0.934, respectively; and Kendall's coefficients of concordance were 0.476 and 0.563, respectively. Finally, 7 first-level items and 21 second-level items were included in the content framework of the homogeneous management evaluation system.Conclusions:The construction process of the homogeneous management evaluation system of clinical observership teaching is complete and reliable, which can provide a reference for the homogeneous management of clinical observership teaching, but further verification and improvement are needed.
9.Application of 18F-FDG PET metabolic parameters in evaluating histopathologic grading of soft tissue sarcoma
Bo CHEN ; Tong WU ; Hua ZHANG ; Hongbo FENG ; Juan TAO ; Shaowu WANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(3):141-146
Objective:To evaluate the value of 18F-FDG PET metabolic parameters in predicting histopathological grade of soft tissue sarcoma (STS). Methods:From December 2012 to December 2021, 51 patients (26 males, 25 females, age range: 32-84 years) who underwent 18F-FDG PET/CT imaging before treatment and confirmed STS pathologically in the First Affiliated Hospital of Dalian Medical University were retrospectively collected. 18F-FDG PET metabolic parameters SUV max, metabolic tumor volume (MTV), total lesion glycolysis (TLG) and intertumoral FDG uptake heterogeneity (IFH) were measured. Kruskal-Wallis rank sum test was used to analyze the differences in metabolic parameters among different groups and Spearman rank correlation analysis was used to analyze the correlation of each metabolic parameter and histological grade. Logistic regression was used to screen and construct the prediction model for high-grade STS. ROC curve was plotted and Delong test was used to analyze the differences among AUCs. Results:The metabolic parameters SUV max, MTV, TLG and IFH were significantly different among French Federation of Cancer Centers Sarcoma Group (FNCLCC)Ⅰ( n=8), Ⅱ( n=10) and Ⅲ ( n=33) grade groups ( H values: 16.24, 10.52, 19.29 and 16.99, all P<0.05), and each metabolic parameter was positively correlated with histological grade ( rs values: 0.58, 0.45, 0.52, and 0.62, all P<0.05). Multivariate logistic regression analysis showed that SUV max(odds ratio ( OR)=1.27, 95% CI: 1.06-1.51, P=0.009) and IFH ( OR=6.83, 95% CI: 1.44-32.27, P=0.015) were independent risk indicators for high-grade STS. The prediction model constructed by combining SUV max and IFH had better diagnostic efficacy for differentiating high-grade STS with the AUC of 0.93, and the sensitivity of 93.9%(31/33) and the specificity of 16/18, respectively. The AUC of prediction model was significant different from SUV max, MTV, TLG and IFH (AUCs: 0.81, 0.78, 0.86 and 0.85; z values: 2.69, 2.53, 1.94 and 1.97, all P<0.05). Conclusions:The metabolic parameters SUV max, MTV, TLG and IFH are valuable predictors for histological grade of STS. The combination of SUV max and IFH may be a more meaningful method than using each of the above metabolic parameters alone.
10.Effect of Portable Oto-endoscopy System in Clinical Teaching of Otorhinolaryngology
Bin WANG ; Wei LYU ; Zhiqiang GAO ; Hua YANG ; Keli CAO ; Guodong FENG ; Haiyan WU ; Yingying SHANG ; Xingming CHEN ; Jian WANG ; Xu TIAN ; Weiqing WANG
Medical Journal of Peking Union Medical College Hospital 2024;15(6):1475-1479
To explore the value of portable oto-endoscopy system in clinical teaching of otolaryngology residents. The postgraduate students serving as resident doctors in the Department of Otolaryngology of Peking Union Medical College Hospital from February to March 2022 and from February to March 2023 were selected as the research objects. Random number table method was used to divide them into experimental group and control group. The control group was first taught by theoretical explanation + electrooto-endoscopy system, and the experimental group was first taught by theoretical explanation + portable oto-endoscopy system. After one month, the two groups interchanged their teaching methodologies. The results of theoretical assessment, self-evaluation at the end of the first month of clinical learning and satisfaction with teaching effectiveness at the end of two months of clinical learning were compared between the two groups. A total of 36 residents were included in this study, with 18 in each group. After one month of clinical study, the theoretical test scores of the experimental group were significantly higher than those of the control group[(93.17±4.16) points The portable oto-endoscopy system can display the anatomy and diseases of otolaryngology more vividly and intuitively in the clinical teaching of otolaryngology, facilitate the management of clinical data, increase the learning interest of residents, fully mobilize the image thinking of medical students, and improve the post competence of residents more efficiently.

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