Machado-Joseph disease, or spinocerebellar ataxia type 3 (SCA3), represents the most common autosomal dominant cerebellar ataxia worldwide. Despite its progressive and debilitating nature, disease-modifying therapies remain elusive. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising non-invasive intervention; however, its clinical application has been hindered by inconsistent protocols and a lack of mechanistic understanding. A recent landmark study published in Brain Stimulation by Chen et al. addressed these challenges by combining a high-dose intermittent theta-burst stimulation (iTBS) protocol with concurrent transcranial magnetic stimulation-electroencephalography (TMS-EEG). This commentary provides an in-depth analysis of their findings, highlighting the restoration of cerebello-cortical inhibition (CBI) as a key therapeutic mechanism. Furthermore, we discuss the broader implications of this work, proposing that future translational research should integrate accelerated iTBS (aiTBS) paradigms, cortical response measurements (CRM), and individualized neuro-navigation to establish a new era of precision neuromodulation for ataxia.

Machado-Joseph disease, or spinocerebellar ataxia type 3 (SCA3), represents the most common autosomal dominant cerebellar ataxia worldwide. Despite its progressive and debilitating nature, disease-modifying therapies remain elusive. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising non-invasive intervention; however, its clinical application has been hindered by inconsistent protocols and a lack of mechanistic understanding. A recent landmark study published in Brain Stimulation by Chen et al. addressed these challenges by combining a high-dose intermittent theta-burst stimulation (iTBS) protocol with concurrent transcranial magnetic stimulation-electroencephalography (TMS-EEG). This commentary provides an in-depth analysis of their findings, highlighting the restoration of cerebello-cortical inhibition (CBI) as a key therapeutic mechanism. Furthermore, we discuss the broader implications of this work, proposing that future translational research should integrate accelerated iTBS (aiTBS) paradigms, cortical response measurements (CRM), and individualized neuro-navigation to establish a new era of precision neuromodulation for ataxia.

Childhood obesity has become a global public health issue. Current research indicates that early life obesogen exposure has emerged as a significant risk factor for childhood obesity. While obesogens have been confirmed to influence the development and progression of childhood obesity through mechanisms such as endocrine disruption and epigenetic programming, controversies remain regarding the establishment of causal relationships, assessment of combined exposures, and validation of transgenerational effects in humans. In recent years, novel approaches including multi-omics technologies, exposome-based analysis, and multigenerational cohort studies have integrated dynamic biomarker monitoring with analyses of social-environmental interactions, offering new perspectives and methodologies for constructing a systematic "exposure-mechanism-outcome" research framework. This article reviews literature from PubMed and Web of Science up to August 2025 on the association between early life obesogen exposure and childhood obesity, summarizing evidence on the health effects of early life obesogen exposure, major exposure pathways and internal exposure assessment, interactions and amplifying effects of social and environmental factors, as well as the biological mechanisms underlying obesogen action. It further examines current research frontiers and challenges, aiming to provide a theoretical foundation for early prevention and precision intervention of childhood obesity.

OBJECTIVE To investigate the mechanism of isochlorogenic acid A against hepatocellular carcinoma based on the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway and multi-omics technology. METHODS The invasion rate and migration rate of human hepatocellular carcinoma HepG2 cells after 48 h of intervention with 0 （control group）， 0.25 and 0.5 mg/mL isochlorogenic acid A were examined； mRNA expression of DEP domain-containing mTOR-interacting protein （DEPTOR）， the protein expressions of mTOR， PI3K and phosphatase and tensin homologue deleted on chromosome ten （PTEN）， as well as the phosphorylation level of Akt protein were determined in the cells. Metabolomics analysis was performed using liquid chromatography-tandem mass spectrometry， and differential metabolites were screened and subjected to Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis； transcriptomics monitoring was conducted by RNA sequencing， and differentially expressed genes were screened and subjected to gene ontology （GO） and KEGG pathway enrichment analyses. RESULTS Compared with the control group， intervention with 0.25 and 0.5 mg/mL isochlorogenic acid A for 48 h significantly inhibited the invasion rate and migration rate of HepG2 cells， significantly up-regulated the mRNA expression of DEPTOR and the protein expression of PTEN， and significantly down-regulated the protein expression of PI3K and the phosphorylation level of Akt protein （except for 0.25 mg/mL isochlorogenic acid A） （ P ＜0.05）. A total of 304 differential metabolites and 212 differentially expressed genes were screened by multi-omics analysis. KEGG pathway enrichment analysis suggested that isochlorogenic acid A regulated key signaling of HepG2 cell growth mainly by inhibiting the PI3K/Akt signaling pathway， synergizing with metabolic reprogramming such as mTOR signaling pathway， ferroptosis， pentose phosphate pathway and purine/pyrimidine metabo lism. CONCLUSIONS The anti-hepatocellular carcinoma effect of isochlorogenic acid A is associated with the blockade of abnormal activation of the PI3K/Akt/mTOR signaling pathway. In addition， it may also be related to the inhibition of the pentose phosphate pathway and purine/pyrimidine metabolism， as well as the induction of ferroptosis，etc.

ObjectiveTo investigate the inhibitory effect of gingerol， an active component of ginger， on Staphylococcus aureus （S. aureus） infection， and to preliminarily explore its mechanism related to extracellular vesicles （EVs）. MethodsS.aureus infection models were established in human umbilical vein endothelial cell （HUVECs）， Vero E6 cells， and C57BL/6 mice. Experimental groups included control， infection， and gingerol-treated groups. Bacterial load and VE-cadherin protein expression were detected using immunofluorescence and Western blot. EVs were isolated by size exclusion chromatography and characterized by transmission electron microscopy and nanoparticle tracking analysis. miRNA sequencing was performed on EVs. ResultsGingerol treatment significantly reduced the bacterial load in both in vitro and in vivo infection models and upregulated VE-cadherin expression. miRNA sequencing of EVs revealed that S. aureus infection upregulated the expression of hsa-miR-320c， while gingerol treatment reversed this abnormal expression. Bioinformatic analysis further predicted that the target genes of hsa-miR-320c were significantly enriched in cell junction-related pathways. ConclusionGingerol exhibits clear antibacterial and host-protective effects， by regulating hsa-miR-320c in EVs to maintain endothelial barrier integrity.

Tissue repair requires the reconstruction of functional vascular networks to restore oxygen and nutrient delivery, eliminate metabolic waste, and maintain tissue homeostasis. Although biochemical factors such as growth factors and cytokines have been extensively studied in vascular regeneration, increasing evidence indicates that mechanical signals from the extracellular matrix (ECM) are equally important regulators of angiogenesis. Matrix stiffness, as a major biomechanical property of the tissue microenvironment, provides critical information that influences endothelial cell (EC) behavior and vascular remodeling through mechanotransduction. However, the biological effects of matrix stiffness are not universally defined as either pro- or anti-angiogenic, but are highly dependent on tissue context, cellular composition, disease progression, and the dynamic changes occurring during tissue repair. Therefore, understanding how matrix stiffness regulates vascular regeneration is essential for developing more precise strategies for tissue engineering and regenerative medicine. In this review, we summarize recent advances in the regulation of angiogenesis by matrix stiffness during tissue repair from multiple perspectives. First, we discuss the direct effects of matrix stiffness on EC behaviors, including differentiation, morphological remodeling, migration, proliferation, barrier maintenance, and vascular network formation. ECs sense mechanical alterations in the surrounding matrix through various mechanosensitive structures, including integrins, focal adhesion complexes, and mechanosensitive ion channels such as Piezo1 and TRPV proteins. These mechanical signals are subsequently transmitted through intracellular pathways involving FAK, RhoA/ROCK, MAPK, and Hippo-YAP/TAZ signaling, leading to cytoskeletal reorganization and transcriptional regulation. Through these mechanisms, matrix stiffness regulates endothelial functional states and determines the balance between regenerative vascular formation and pathological vascular remodeling. Beyond the direct regulation of ECs, we further highlight the importance of stiffness-mediated intercellular communication within the regenerative microenvironment. Matrix stiffness can regulate the behavior and secretory profiles of vascular-associated cells, including mesenchymal stem cells and macrophages, thereby indirectly affecting endothelial function through paracrine mechanisms. Changes in matrix mechanics influence the secretion of angiogenic factors, inflammatory cytokines, and extracellular vesicles from these cells, creating a mechanical regulation network that coordinates vascular regeneration. This perspective extends the traditional concept of matrix stiffness from a physical support structure to an active regulatory signal that integrates multiple cellular responses during tissue repair. Furthermore, we discuss the tissue-specific effects of matrix stiffness in vascular regeneration across different organs, including the aorta, lung, liver, and heart. Although excessive matrix stiffening is frequently associated with fibrosis and vascular dysfunction, the consequences of mechanical changes vary considerably among tissues. Moderate stiffness alterations may support endothelial activation and vascular stabilization in certain regenerative contexts, whereas persistent pathological stiffening can promote inflammation, endothelial dysfunction, and impaired vascular repair. These findings emphasize that the biological meaning of “soft” and “stiff” microenvironments should be interpreted according to specific tissue and experimental conditions rather than as universal mechanical classifications. Finally, we summarize current challenges and future perspectives in this field. A major limitation is the lack of standardized mechanical characterization among different studies, as stiffness measurements are influenced by material properties, testing methods, and experimental conditions, limiting direct comparison across research systems. Moreover, most existing models fail to fully reproduce the dynamic and viscoelastic properties of native ECM during tissue regeneration. Future studies should combine advanced biomaterials with standardized mechanical analysis, organoid models, and multi-omics approaches to establish more accurate mechanical regulatory maps. Overall, this review proposes that matrix stiffness is not merely a structural feature of tissues, but an active biological signal that regulates vascular regeneration through coordinated mechanotransduction and multicellular interactions. A deeper understanding of stiffness-mediated vascular regulation will provide new theoretical insights and therapeutic opportunities for improving tissue repair outcomes.

Post-stroke cognitive impairment (PSCI) is a common complication of stroke, which seriously affects the quality of life of patients. Therefore, early and accurate prediction of PSCI is crucial for implementing targeted intervention measures. Quantitative electroencephalography (qEEG), as a non-invasive and objective neurophysiological technique, can provide objective basis for early prediction and targeted intervention of PSCI during the critical period of 72 hours to 1 month after stroke onset. This article reviews the current application status of qEEG in predicting PSCI, aiming to provide theoretical basis for early identification of patients with high-risk PSCI.

Objective To observe the clinical efficacy of Dan Qi Yishen Prescription in treating diabetic nephropathy(DN)and explore its renal protective mechanism.Methods A total of 150 patients with DN of qi-yin deficiency complicated with blood stasis syndrome who admitted to Sanya Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Chinese Medicine from October 2021 to April 2023 were divided into a control group and an observation group according to the random number table method,with 75 patients in each group.Both groups were given conventional therapies such as dietary treatment,blood glucose control,blood pressure control,lipid-lowering treatment and treatment of complications.Additionally,the control group was given intravenous injection of reduced glutathione,while the observation group was given oral use of the decoction of Dan Qi Yishen Prescription and ionic introduction of Dan Qi Yishen Prescription in renal region.Thirty days constituted one course of treatment,and both groups were treated for three courses.Before and after treatment,the scores of traditional Chinese medicine(TCM)syndrome,and the levels of renal function indicators,renal hemodynamic indicators,coagulation and fibrinolysis indicators,and vascular endothelial function indicators in the two groups were observed.Results(1)After treatment,the scores of TCM symptoms such as fatigue and weakness,palpitations and shortness of breath,dizziness and tinnitus,spontaneous sweating and night sweating,restlessness and insomnia,and thirst with preference for drinks in the two groups were decreased compared with those before treatment(P<0.01),and the decrease in the observation group was significantly superior to that in the control group(P<0.01).(2)After treatment,the levels of renal function indicators such as blood urea nitrogen(BUN),serum creatinine(SCr),collagen Ⅳ(CⅣ),and plasma laminin(LN)of patients in the two groups were improved compared with those before treatment(P<0.01),and the improvement in the observation group was significantly superior to that in the control group(P<0.01).(3)After treatment,the levels of renal hemodynamic indicators such as systolic maximum blood flow velocity(Vsmax)and diastolic minimum blood flow velocity(Vdmin)of the main renal artery(MRA)and interlobar artery(IRA)in the two groups were increased compared with those before treatment(P<0.05 or P<0.01),while the resistance index(RI)and pulsatility index(PI)of MRA and RI of IRA in the two group as well as PI of IRA in the observation group were decreased compared with those before treatment(P<0.05 or P<0.01).The increase of Vsmax and Vdmin of MRA and IRA as well as the decrease of RI and PI of MRA and IRA in the observation group was significantly superior to that in the control group(P<0.05 or P<0.01).(4)After treatment,the levels of coagulation and fibrinolysis indicators such as prothrombin time(PT),activated partial thromboplastin time(APTT),D-dimer(D-D),and fibrinogen(FIB)in the two groups were improved compared with those before treatment(P<0.01),and the improvement in the observation group was significantly superior to that in the control group(P<0.01).(5)The analysis of vascular endothelial function indicators showed that after treatment,the serum vasohibin 1(VASH-1)level in the two groups was increased compared with that before treatment(P<0.01),and the serum vascular endothelial growth factor(VEGF)and endothelin 1(ET-1)levels were decreased compared with those before treatment(P<0.01),and the increase of serum VASH-1 level as well as the decrease of serum VEGF and ET-1 levels in the observation group was significantly superior to that in the control group(P<0.01).Conclusion Dan Qi Yishen Prescription exerts good clinical efficacy in treating patients with DN of qi-yin deficiency complicated with blood stasis syndrome,and it has protective effect on renal function probably by improving the coagulation and fibrinolysis system and vascular endothelial function of the patients.

Objective To explore the effects of evidence-based nursing combined with multi-dimensional health education on negative emotions and postoperative rehabilitation of patients undergoing elective surgery for cholecystolithiasis.Methods A total of 100 patients with cholecystolithiasis who underwent elective surgery in Yixing Traditional Chinese Hospital Medicine from September 2023 to August 2024 were selected.The patients were assigned to control group and observation group by PEMS3.1 for Windows completely random(two groups and multiple groups)program,with 50 cases in each group.The control group received routine nursing,and the observation group received evidence-based nursing combined with multidimensional health education on the basis of routine nursing.The intervention duration of the two groups was 7 days.Visual analogue scale(VAS)scores,negative emotions(self-rating anxiety scale[SAS]and self-rating depression scale[SDS]),postoperative complications,and postoperative rehabilitation were compared between the two groups.Results The VAS scores at 24 h and 72 h after surgery were lower than those at 6 h after surgery in both groups,especially in the observation group(P<0.05).The scores of SAS and SDS in both groups after intervention were significantly decreased compared with those before intervention,and the scores of negative emotions in the observation group after intervention were significantly lower than those in the control group(P<0.05).The total incidence of gastrointestinal discomfort,biliary fistula and wound infection/bleeding in the observation group was significantly lower than that in the control group(4.00%vs.18.00%,P<0.05).The time of getting out of bed,the time of anal exhaust,the time of resuming normal diet and the time of hospitalization in the observation group were significantly lower than those in the control group(P<0.05).Conclusion The combination of evidence-based nursing and multi-dimensional health education during perioperative period of cholecystolithiasis surgery can reduce postoperative pain,improve the positive attitude of treatment,reduce complications,and promote the recovery of the disease.

Objective To study the mandibular characteristics of the modern population in Beijing region.Methods In this study,we examined 22 measurements and their sexual dimorphism index(SDI)of 193 adult mandibles(126 males,67 females)collected from the Beijing region.In addition,eight mandibular indexes were calculated.These mandibular dimensions of the Beijing population were compared with those of other modern and contemporary populations in Asia,as well as Neolithic-historical populations in Northern China.Results The predominant mandibular index in the contemporary Beijing population was dolichostenomandibular.The SDI of mandibular size exhibited a wide range of variation.It was noteworthy the minimum height of mandibular ramus,height of mandibular ramus,height of coronoid process and minimum breadth of mandibular ramus demonstrate significant sexual dimorphism(SDI≥10％).The mandibular size aligned with the variation range of modern and contemporary Asian populations,with the cluster analysis indicating an affiliation with Northern Mongoloids.But the Beijing population was far away from other Northern populations in China.The mandibular size was more gracile compared to ancient populations in Northern China,whereas the height of mandibular ramus was greater than those of the latter.Conclusion This study provides valuable insights into the physical characteristics of modern populations in Beijing region.