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.Efficacy and safety of denosumab in the treatment of prostate cancer with bone metastases: A systematic review and meta-analysis.
Li YANG ; Bo FANG ; Can-Qin HE ; Xu-Xin ZHAN ; You-Ping XIAO ; Xiao-Jun QIN ; Qiang LOU ; Xue-Jun SHANG
National Journal of Andrology 2025;31(4):349-356
OBJECTIVE:
To evaluate the efficacy and safety of denosumab in the treatment of prostate cancer with bone metastases.
METHODS:
Relevant studies were retrieved from PubMed, EMBASE, Cochrane, Web of Science, Sinomed , CNKI and Wanfang databases. The Cochrane risk-of-bias assessment tool was used to evaluate the quality of included studies, and relevant data were extracted. meta-analysis was performed using RevMan 5.4 and RStudio software, and forest plots were generated.
RESULTS:
Six randomized controlled trials (RCTs) were included. Compared with the control group, denosumab significantly reduced the risk of skeletal-related events (HR=0.78, 95% CI: 0.62-0.93). In terms of safety, denosumab did not increase the risk of total adverse events, severe adverse events and the adverse events higher than CTC grade 3.
CONCLUSION
Denosumab can delay the time to first skeletal-related event with good safety. However, due to the limitations of this study, further high-quality, large-sample, multicenter RCTs are needed to confirm these findings.
Humans
;
Denosumab/therapeutic use*
;
Bone Neoplasms/drug therapy*
;
Prostatic Neoplasms/drug therapy*
;
Male
;
Randomized Controlled Trials as Topic
;
Bone Density Conservation Agents/therapeutic use*
3.Comprehensive Review on Rhodiola crenulata: Ethnopharmacology, Phytochemistry, Pharmacological Properties and Clinical Applications.
Rui ZHU ; Cui-Fen FANG ; Shu-Jing ZHANG ; Zhu HAN ; Ge-Hui ZHU ; Shang-Zuo CAI ; Cheng ZHENG ; Yu TANG ; Yi WANG
Chinese journal of integrative medicine 2025;31(8):752-759
5.Influencing factors for quality of life in patients with primary biliary cholangitis: A systematic review
Yanqiu FANG ; Gui JIA ; Lina CUI ; Yulong SHANG ; Ying HAN
Journal of Clinical Hepatology 2025;41(10):2062-2067
ObjectiveTo investigate the core influencing factors for quality of life in patients with primary biliary cholangitis through a systematic review, and to provide an evidence-based basis for understanding such factors. MethodsThe databases including CNKI, Wanfang Data, CBM, VIP, PubMed, Embase, Web of Science, Ovid, Scopus, and Medline were searched for articles assessing the influencing factors for quality of life in patients with primary biliary cholangitis using PBC-40 scale published up to January 11, 2025. Quality assessment was conducted using the scale compiled by the Agency for Healthcare Research and Quality, and then a qualitative evaluation was performed for the basic situation of the studies included in the analysis. ResultsA total of 11 articles were included, and the results showed that age, sex, albumin, alkaline phosphatase, gamma-glutamyl transferase, direct bilirubin, total bilirubin, total bile acid, alanine aminotransferase, aspartate aminotransferase, body mass index, and high-density lipoprotein cholesterol were important influencing factors for quality of life in patients with primary biliary cholangitis. ConclusionInfluencing factors include demographic features, liver function parameters, and physical and metabolic indicators; however, due to the limited number of studies, more high-quality large-sample studies are needed in the future.
6.Role of intestinal flora in hypertension complicated with osteoporosis
Mei-Long SI ; Hua JIN ; Min-Ke LIU ; Shuang-Fang LIU ; Bi-Shi LING ; Shang-Wen QI ; Xue-Li MA
The Chinese Journal of Clinical Pharmacology 2024;40(3):449-453
Hypertension and osteoporosis(OP)are common diseases in middle-aged and elderly people,and the number of patients with both diseases has gradually increased in recent years.Because the onset of the disease is hidden,it is easy to cause fractures and serious complications of heart,brain and kidney in the later stage,which not only seriously damages the quality of life of patients,but also increases the difficulty of clinical treatment.Therefore,it is particularly necessary to strengthen the research on this disease.More and more studies have found that the disorder of intestinal flora will lead to the occurrence of OP,while the intestinal flora of patients with hypertension is obviously out of balance.Therefore,this paper thinks that intestinal flora may be the key influencing factor of hypertension complicated with OP,and the imbalance of intestinal flora will lead to the imbalance of short-chain fatty acid metabolism,immune inflammatory reaction and increased sympathetic nerve activity,thus causing the imbalance of bone homeostasis and promoting the occurrence of OP.Therefore,it is suggested that regulating intestinal flora may be a new way to intervene hypertension complicated with OP.
7.Effects of Ganoderma lucidum polysaccharide peptide on proliferation,migration and apoptosis of diffuse large B-cell lymphoma cells by regulating the expression of PRMT6
Hui-Yan HUANG ; Yan-Fang WU ; Ai-Wei WANG ; Gui-Bing ZHANG ; Wen-Zhong SHANG ; Ye SUN
The Chinese Journal of Clinical Pharmacology 2024;40(15):2187-2191
Objective To investigate the effect of Ganoderma lucidum polysaccharide peptide(GLPP)on proliferation,migration and apoptosis of diffuse large B cell lymphoma(DLBCL)cells and its mechanism.Methods OCI-LY19 cells were divided into six groups:control,GLPP,si-NC,si-protein arginine methyltransferase 6(PRMT6),GLPP+pcDNA3.1-NC and GLPP+pcDNA3.1-PRMT6 groups.The si-NC,si-PRMT6,GLPP+pcDNA3.1-NC and GLPP+pcDNA3.1-PRMT6 groups were transfected with si-NC,si-PRMT6,pcDNA3.1-NC and pcDNA3.1-PRMT6,respectively.After the transfection was completed,control,si-NC and si-PRMT6 groups were treated with RPMI-1640 medium,while the GLPP,GLPP+pcDNA3.1-NC and GLPP+pcDNA3.1-PRMT6 groups were cultured with RPMI-1640 medium containing with 20 μg·mL-1 GLPP.After administration 24 h,the cell proliferation inhibition rates,mobility rates and apoptosis rates were detected.The expression levels of PRMT6 protein were measured by Western blotting.Results The cell proliferation inhibition rates of si-NC,si-PRMT6,GLPP+pcDNA3.1-NC and GLPP+pcDNA3.1-PRMT6 groups were(1.28±0.16)%,(38.61±3.29)%,(52.84±7.74)%and(22.75±3.87)%,respectively.The number of cell migrations in the control,GLPP,si-NC,si-PRMT6,GLPP+pcDNA3.1-NC and GLPP+pcDNA3.1-PRMT6 groups was(252.65±24.65),(136.54±16.46),(231.65±21.24),(142.76±15.34),(140.23±9.84)and(192.38±23.38)cells;the apoptosis rates were(4.36±0.52)%,(28.24±2.36)%,(4.23±0.45)%,(24.54±2.27)%,(28.42±3.85)%and(14.25±2.13)%);the expression levels of PRMT6 protein were 1.82±0.21,0.56±0.05,1.78±0.19,0.54±0.05,0.29±0.02 and 0.32±0.03,respectively.The differences of above indexes were statistically significant between control group and GLPP group,between si-NC group and si-PRMT6 group,between GLPP+pcDNA3.1-NC group and GLPP+pcDNA3.1-PRMT6 group(all P<0.05).Conclusion GLPP could inhibit proliferation,migration and promote apoptosis of DLBCL cells by down-regulating PRMT6 expression.
8.Effects of Zhengan Xifeng decoction on bile acid spectrum of bile and sterol 12 α hydroxylase in spontaneously hypertensive rats
Bi-Shi LING ; Hua JIN ; Shang-Wen QI ; Shuang-Fang LIU ; Zhi-Jun LIU
The Chinese Journal of Clinical Pharmacology 2024;40(15):2212-2216
Objective To observe the effects of Zhengan Xifeng decoction on bile acid spectrum of bile and sterol 12α hydroxylase(CYP8B1)in spontaneously hypertensive rats(SHR).Methods Fifty SHR were randomly divided into model group,control group(1.0 mg·kg-1·d-1 benazepril by gavage)and experimental-L,-M,-H groups(8.63,17.25 and 34.50 g·kg-1·d-1 Zhengan Xifeng decoction by gavage),another 10 homologous male Wistar-Kyoto(WKY)rats were taken as the normal group.The model group and the normal group were given the same amount of distilled water.The rats in the 6 groups were administered once a day for 8 weeks.The animal non-invasive sphygmomanometer was used to measure the blood pressure of rats in each group by tail-cuff method;the bile acid spectrum of rats in each group was detected by UPLC-MS/MS;the expression of CYP8B1 mRNA in rat liver tissue was detected by real-time fluorescence quantitative polymerase chain reaction.Results The systolic blood pressure at the 8th week of the experimental-M,-H groups,control group,model group,normal group were(169.63±12.10),(170.32±9.64),(175.95±15.47),(189.47±7.42)and(146.40±9.45)mmHg;the diastolic blood pressure at the 8th week were(135.10±11.99),(129.73±15.10),(135.18±17.62),(149.20±8.83)and(110.53±10.92)mmHg;the relative expression levels of CYP8B1 mRNA were 3.36±0.94,5.45±1.46,4.29±0.95,0.89±0.14 and 1.00±0.00,respectively.Compared with the model group,the above indexes in the experimental-M,-H groups were statistically significant(P<0.01,P<0.05).Compared with the model group,the bile acid spectrum of experimental-L,-M,-H groups bile changed significantly,and a total of 9 different bile acids were found,which were hyodeoxycholic acid,glycohyodeoxycholic acid,glycochenodeoxycholic acid,glycoursodeoxycholic acid,α-muricholic acid,ursodeoxycholic acid,cholic acid,β-muricholic acid and glycocholic acid.Conclusion Zhengan Xifeng decoction may correct bile acid spectrum disorder of bile and reduce blood pressure by up-regulating liver CYP8B1 expression.
9.Curative Effect of Jieyu Qingxin Formula Granules Combined with Remote Interactive CBT-I in Treating Chronic Insomnia of Liver-depression and Fire-turning Type
Yequn WANG ; Wujie FANG ; Shang XIANG ; Tao ZHOU ; Wenjun YIN ; Yan CAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(20):120-126
ObjectiveTo observe the clinical effect of Jieyu Qingxin formula granules combined with remote interactive cognitive behavioral therapy for insomnia (CBT-I) on chronic insomnia of liver depression and fire-turning type. MethodThis study was a prospective randomized controlled trial. 120 patients with chronic insomnia of liver depression and fire-turning type in Lu'an traditional Chinese medicine Hospital from January 2022 to June 2023 were selected as objects. They were randomly divided into two groups,with 60 cases in each group. The control group received remote interactive CBT-I. The observation group was treated with Jieyu Qingxin formula granules on the basis of the control group. Intervention treatment lasted for four weeks,and observation lasted for six weeks. Comparison of data of each group:clinical efficacy,changes in traditional Chinese medicine (TCM) syndrome score before and after treatment,changes in insomnia severity index (ISI) score,self-rating depression scale (SDS) and self-rating anxiety scale (SAS) score changes,total sleep time,wake time,sleep latency,sleep efficiency, Actigraphy sleep parameter value changes,serum neuron specific enolase (NSE) ,adenosine,dopamine (DA), 5-hydroxytryptamine (5-HT) level changes,and adverse reactions. ResultThe total effective rate in the observation group (92.45%,49/53) was higher than that in the control group(76.92%,40/52), and the difference was statistically significant(χ2=4.711 1,P<0.05). After treatment,TCM syndrome score,ISI score,SAS score, and SDS score were decreased in all groups. The total sleep time was extended,and wake time and sleep latency were shortened. The sleep efficiency was increased,but the NSE and DA levels were decreased. Adenosine and 5-HT levels were increased in all groups(P<0.05). After treatment,compared with the control group,the observation group had lower TCM syndrome score,ISI score,SAS score, and SDS score,longer total sleep time,higher sleep efficiency,shorter wake time and sleep latency,lower NSE and DA levels, and higher adenosine and 5-HT level (P<0.05). There was one case of nausea in the observation group and no adverse reaction in the control group during treatment. There was no significant difference between the two groups. ConclusionBy reducing NSE and DA and increasing the levels of 5-HT and adenosine,the anxiety (SAS score) and depression (SDS score) of patients can be improved, so as to improve their sleep and effectively treat chronic insomnia of liver depression and fire-turning type.
10.Expert Consensus on Clinical Diseases Responding Specifically to Traditional Chinese Medicine: Perimenopausal Syndrome
Shiwan HU ; Haiyan LIANG ; Kun MA ; Xiaona MA ; Zihan FANG ; Wenpei BAI ; Xinmin LIU ; Hongtian LI ; Fengmei LIAN ; Wei ZHANG ; Lihua QIN ; Min SHANG ; Ailuan LAI ; Xiuxiang TENG ; Mei MO ; Xiaoxiao ZHANG ; Linhua ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(21):234-242
Perimenopausal syndrome (MPS), a common endocrine system disease, is one of the diseases responding specifically to traditional Chinese medicine (TCM). The China Association of Chinese Medicine organized experts in endocrinology, gynecology, and interdisciplinary fields of both Western and Chinese medicine to discuss the advantages and challenges of diagnosing and treating MPS with Western medicine, TCM, and integrative medicine. Experts at the conference believe that MPS is initiated by estrogen decline and rooted in deficiency, with the pathogenesis being imbalance between Yin and Yang in the kidney. The hormone replacement therapy in Western medicine for menopause can rapidly alleviate related symptoms by quickly restoring the estrogen level and timely detect and delay complications of menopause, whereas such a therapy has certain risks, necessitating close monitoring of adverse reactions. Moreover, the various contraindications and precautions limit the clinical application of the hormone replacement therapy. TCM has advantages in synergistically alleviating symptoms such as hot flashes, sweating, sleep disorders, and emotional abnormalities of MPS without causing obvious adverse reactions. However, its efficacy is slower than the hormone replacement therapy, and the TCM evidence for preventing and treating complications of menopause remains unclear. Three suggestions were proposed for the future development of both Western and TCM for ameliorating MPS. First, an integrated diagnosis and treatment system for MPS with both Western and Chinese medicine should be established. Second, high-quality evidence-based interventions for MPS should be developed with TCM alone or in combination with Western medicine. Third, efforts should be made to promote the new TCM drug development and the interdisciplinary cooperation for treating MPS.

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