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.

Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.

BACKGROUND: China is seeing a growing demand for rehabilitation treatments for post-stroke upper limb spastic paresis (PSSP-UL). Although acupuncture is known to be effective for PSSP-UL, there is room to enhance its efficacy. OBJECTIVE: This study explored a semi-personalized acupuncture approach for PSSP-UL that used three-dimensional kinematic analysis (3DKA) results to select additional acupoints, and investigated the feasibility, efficacy and safety of this approach. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This single-blind, single-center, randomized, controlled trial involved 74 participants who experienced a first-ever ischemic or hemorrhagic stroke with spastic upper limb paresis. The participants were then randomly assigned to the intervention group or the control group in a 1:1 ratio. Both groups received conventional treatments and acupuncture treatment 5 days a week for 4 weeks. The main acupoints in both groups were the same, while participants in the intervention group received additional acupoints selected on the basis of 3DKA results. Follow-up assessments were conducted for 8 weeks after the treatment. MAIN OUTCOME MEASURES: The primary outcome was the Fugl-Meyer Assessment for Upper Extremity (FMA-UE) response rate (≥ 6-point change) at week 4. Secondary outcomes included changes in motor function (FMA-UE), Brunnstrom recovery stage (BRS), manual muscle test (MMT), spasticity (Modified Ashworth Scale, MAS), and activities of daily life (Modified Barthel Index, MBI) at week 4 and week 12. RESULTS: Sixty-four participants completed the trial and underwent analyses. Compared with control group, the intervention group exhibited a significantly higher FMA-UE response rate at week 4 (χ² = 5.479, P = 0.019) and greater improvements in FMA-UE at both week 4 and week 12 (both P < 0.001). The intervention group also showed bigger improvements from baseline in the MMT grades for shoulder adduction and elbow flexion at weeks 4 and 12 as well as thumb adduction at week 4 (P = 0.007, P = 0.049, P = 0.019, P = 0.008, P = 0.029, respectively). The intervention group showed a better change in the MBI at both week 4 and week 12 (P = 0.004 and P = 0.010, respectively). Although the intervention group had a higher BRS for the hand at week 12 (P = 0.041), no intergroup differences were observed at week 4 (all P > 0.05). The two groups showed no differences in MAS grades as well as in BRS for the arm at weeks 4 and 12 (all P > 0.05). CONCLUSION: Semi-personalized acupuncture prescription based on 3DKA results significantly improved motor function, muscle strength, and activities of daily living in patients with PSSP-UL. TRIAL REGISTRATION Chinese Clinical Trial Registry ChiCTR2200056216. Please cite this article as: Huang XY, Liao OP, Jiang SY, Tao JM, Li Y, Lu XY, Li YY, Wang C, Li J, Ma XP. Three-dimensional kinematic analysis can improve the efficacy of acupoint selection for post-stroke patients with upper limb spastic paresis: A randomized controlled trial. J Integr Med. 2025; 23(1): 15-24.
Humans ; Male ; Female ; Middle Aged ; Acupuncture Points ; Upper Extremity/physiopathology* ; Biomechanical Phenomena ; Single-Blind Method ; Aged ; Stroke/therapy* ; Acupuncture Therapy/methods* ; Stroke Rehabilitation/methods* ; Adult ; Muscle Spasticity/therapy* ; Paresis/physiopathology* ; Treatment Outcome

At present,the drug substitutes represented by new psychoactive substances are gradually be-coming popular,leading to an increasing demand for identifying novel drugs with unknown structures in drug investigation.Nuclear magnetic resonance(NMR)spectroscopy is an important tool for ana-lyzing molecular structures.In the absence of standard substances,quantitative NMR(qNMR)can un-dertake the quantitative analysis of target substances in complex mixtures and has unique advantages in the research of new drugs and their precursor drugs.Due to the limitations of the site and mainte-nance costs,as well as relatively complex operation,high-field superconducting NMR is less com-monly applied in drug research.The desktop low-field NMR developed in recent years provides a new alternative solution.Due to the use of permanent magnets,its size is reduced,and the operation and maintenance costs are lowered.It has been widely used in various research fields.This article reviews the development of low-field NMR technology,summarizes the application of desktop low-field NMR in screening and identification of suspicious substances,rapid content determination,analysis of drug manufacturing processes and synthetic routes,and correlation traceability.It also looks forward to the prospects and development directions of this technology in drug research,aiming to provide a reference for researchers who work in analytical chemistry and drug research.

Objective To investigate the effects of estrogen signaling on T-cell recruitment and polarization in acutely injured skeletal muscle.Methods One hundred C57BL/6 male mice,one hundred and eighty C57BL/6 female mice were selected.Twenty-five female mice were ovariectomized(OVX)and 10 male mice were taken as the sham-operated(sham).Then,cardiotoxin(CTX)induced tibialis anterior(TA)injury for preparing mice myoinjury model.Subcutaneous injection of 17β-estradiol(E2)or estrogen receptor antagonist 4-hydroxytamoxifen(4-OHT)was performed.A total of 140 mice(70 males and 70 females)were divided into four group including:PBS-male,CTX-male,PBS-female,and CTX-female.Serum estradiol(E2)levels were measured by ELISA,and muscle injury models were validated via HE staining.Subsequently,20 male and 20 female mice were selected for immunofluorescence(IF)and Real-time PCR to assess estrogen receptors(ER)expression in injured muscle tissue.Further,10 male and 40 female mice were allocated into five experimental groups,including CTX,CTX+E2,CTX+4-OHT,CTX+OVX,CTX+sham.HE staining and IF were performed to evaluate inflammatory infiltration in the injured muscle.Additionally,50 female mice were divided into CTX and CTX+OVX groups,and IF combined with flow cytometry were used to analyze T-cell phenotypes and muscle fiber regeneration in the injured muscle.Results In vivo,serum E2 and myofiber ERβ increased post-injury in mice of both sexes,significantly higher in females.Compared to the control group,E2 alleviated inflammation,OVX exacerbated inflammation,increased CD4+T-cell infiltration,elevated T helper 1 cell(Th1)response,decreased regulatory T cells(Tregs),impaired regeneration.In vitro,IFN-γ/LPS significantly upregulated ERβ in myotubes.Conclusion Estrogen signaling critically regulates muscle inflammation.Estrogen deficiency(OVX)delays repair of skeletal muscle by promoting Th1 response and suppressing Tregs function.

Aim To systematically investigate the ac-tive components,targets,and regulatory pathways of Po-lygonum capitatum in intervening atherosclerosis(AS)through network pharmacology,molecular docking and animal experiments.Methods Active components of Polygonum capitatum and AS-related targets were screened and identified through database searches.Protein-protein interaction(PPI)network analysis was performed using the STRING database,followed by GO and KEGG enrichment analyses via the David plat-form.Molecular docking validation was conducted with AutoDock.An AS model was established in Syrian golden hamsters fed a high-fat diet.Predicted pathways and targets were validated using qPCR,ELISA,and histopathological assessment of aortic and hepatic tis-sues via HE staining.Results Network pharmacology identified 27 potential active components of Polygonum capitatum(primarily flavonoids such as quercetin and luteolin)and 110 drug-disease intersection targets,in-cluding core targets MMP-9,ALB,and AKT1.GO and KEGG analyses enriched 593 and 125 pathways,re-spectively,with the NF-κB inflammatory pathway,TNF signaling pathway and lipid metabolism/atherosclerosis pathways highlighted as key mechanisms.Animal ex-periments demonstrated that Polygonum capitatum im-proved serum lipid profiles(reduced TC,TG,LDL-C)in AS hamsters,suppressed the MMP-9/NF-κB signa-ling pathway(downregulated MMP-9,p65 phosphoryla-tion,TNF-α,and IL-6),and inhibited VSMC synthetic phenotypic transformation(upregulated α-SMA and myocardin)by downregulating MCPIP1.Additionally,Polygonum capitatum ameliorated aortic lesions and he-patic lipid deposition in AS hamsters.Conclusions Polygonum capitatum alleviates AS by synergistically regulating the MMP-9/NF-κB/MCPIP1 axis through flavonoid components,suppressing vascular inflammato-ry cascades and maintaining VSMC contractile pheno-types.This reflects Polygonum capitatum's multi-com-ponent,multi-pathway,and multi-target characteristics in combating AS.

The integration of science and education is not only an important strategy for promoting social progress and technological development,but also a modern form of higher education aiming at cultivating innovative talents.Conducting scientific research training for undergraduate medical students is one of the important ways to cultivate their innovative abilities and comprehensive qualities.Our team proposed a"teaching,science,and ideology trinity"teaching model to comprehensively cultivate students' scientific research comprehensive abilities under the value orientation of ideological and political education by or-ganically integrating molecular biology experimental teaching with the scientific research training of under-graduate medical students.In this teaching activity,taking the experiment of gene polymorphism as an example,our team selected students with research potential from the whole grade and divided them into 4 project groups that were instructed by 4 teachers.The students were trained in the whole process of scien-tific research,including topic selection,project writing,experimental designing,application for research ethics,and project summary.Our team has always adhered to student-contentedness of educational con-cepts to stimulate students' intrinsic motivation throughout the teaching process.Students are the design-ers and implementers of the project,and teachers are only guides and promoters of learning.After this training,students not only became familiar with the writing and implementation of scientific research pro-jects,but also improved their literature reading,experimental designing,experimental skills,and prob-lem-solving abilities.More importantly,this teaching activity also cultivated students' awareness of re-search ethics and academic moral standards.

The integration of science and education is not only an important strategy for promoting social progress and technological development,but also a modern form of higher education aiming at cultivating innovative talents.Conducting scientific research training for undergraduate medical students is one of the important ways to cultivate their innovative abilities and comprehensive qualities.Our team proposed a"teaching,science,and ideology trinity"teaching model to comprehensively cultivate students' scientific research comprehensive abilities under the value orientation of ideological and political education by or-ganically integrating molecular biology experimental teaching with the scientific research training of under-graduate medical students.In this teaching activity,taking the experiment of gene polymorphism as an example,our team selected students with research potential from the whole grade and divided them into 4 project groups that were instructed by 4 teachers.The students were trained in the whole process of scien-tific research,including topic selection,project writing,experimental designing,application for research ethics,and project summary.Our team has always adhered to student-contentedness of educational con-cepts to stimulate students' intrinsic motivation throughout the teaching process.Students are the design-ers and implementers of the project,and teachers are only guides and promoters of learning.After this training,students not only became familiar with the writing and implementation of scientific research pro-jects,but also improved their literature reading,experimental designing,experimental skills,and prob-lem-solving abilities.More importantly,this teaching activity also cultivated students' awareness of re-search ethics and academic moral standards.

Aim To systematically investigate the ac-tive components,targets,and regulatory pathways of Po-lygonum capitatum in intervening atherosclerosis(AS)through network pharmacology,molecular docking and animal experiments.Methods Active components of Polygonum capitatum and AS-related targets were screened and identified through database searches.Protein-protein interaction(PPI)network analysis was performed using the STRING database,followed by GO and KEGG enrichment analyses via the David plat-form.Molecular docking validation was conducted with AutoDock.An AS model was established in Syrian golden hamsters fed a high-fat diet.Predicted pathways and targets were validated using qPCR,ELISA,and histopathological assessment of aortic and hepatic tis-sues via HE staining.Results Network pharmacology identified 27 potential active components of Polygonum capitatum(primarily flavonoids such as quercetin and luteolin)and 110 drug-disease intersection targets,in-cluding core targets MMP-9,ALB,and AKT1.GO and KEGG analyses enriched 593 and 125 pathways,re-spectively,with the NF-κB inflammatory pathway,TNF signaling pathway and lipid metabolism/atherosclerosis pathways highlighted as key mechanisms.Animal ex-periments demonstrated that Polygonum capitatum im-proved serum lipid profiles(reduced TC,TG,LDL-C)in AS hamsters,suppressed the MMP-9/NF-κB signa-ling pathway(downregulated MMP-9,p65 phosphoryla-tion,TNF-α,and IL-6),and inhibited VSMC synthetic phenotypic transformation(upregulated α-SMA and myocardin)by downregulating MCPIP1.Additionally,Polygonum capitatum ameliorated aortic lesions and he-patic lipid deposition in AS hamsters.Conclusions Polygonum capitatum alleviates AS by synergistically regulating the MMP-9/NF-κB/MCPIP1 axis through flavonoid components,suppressing vascular inflammato-ry cascades and maintaining VSMC contractile pheno-types.This reflects Polygonum capitatum's multi-com-ponent,multi-pathway,and multi-target characteristics in combating AS.