Objective: To develop a prediction model for mild cognitive impairment (MCI) risk among the elderly, so as to provide a tool for MCI early screening. Methods : From July 2022 to September 2024, a multi-stage stratified random cluster sampling method was used to recruit permanent residents aged ≥65 years from the Xinjiang Uygur Autonomous Region as study participants. Data on sociodemographic characteristics, nutritional status, body composition indices, bone mineral density, and handgrip strength were collected through questionnaires and physical examinations. Sarcopenia was defined based on appendicular skeletal muscle index and handgrip strength. MCI was assessed using the Mini-Mental State Examination, with adjustments for educational level. Participants were randomly divided into a training set and a validation set in a 7∶3 ratio. LASSO regression and multivariable logistic regression models were employed to screen for predictors and construct an MCI risk prediction model. The predictive performance of the model was evaluated using receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Results: A total of 1 641 participants were surveyed, including 755 males (46.01%) and 886 females (53.99%). The majority of participants were aged 65-<75 years, comprising 1 154 individuals (70.32%). MCI was detected in 517 participants, corresponding to a detection rate of 31.51%. Resultsfrom LASSO regression and multivariate logistic regression analysis showed that residence (rural, OR = 2.323, 95% CI: 1.682-3.210), age (75-<85 years, OR = 1.405, 95% CI: 1.019-1.937; ≥85 years, OR = 3.655, 95% CI: 1.696-7.875), educational level (primary school, OR = 0.341, 95% CI: 0.247-0.472; junior high school, OR = 0.255, 95% CI: 0.160-0.408; high school, OR = 0.286, 95% CI: 0.154-0.531; bachelor's degree or above, OR = 0.120, 95% CI: 0.041-0.351), history of alcohol consumption (yes, OR = 3.216, 95% CI: 2.164-4.779), risk of malnutrition (yes, OR = 1.464, 95% CI: 1.064-2.014), sarcopenia (yes, OR = 3.197, 95% CI: 2.332-4.385), and waist-to-hip ratio (abnormal, OR = 1.540, 95% CI: 1.159-2.048) were identified as predictive factors for MCI among the elderly. In the training set, the area under the ROC curve, sensitivity, and specificity were 0.788, 0.719, and 0.712, respectively. In the validation set, the corresponding values were 0.784, 0.913, and 0.542, respectively. DCA demonstrated that the model provided a higher clinical net benefit for predicting MCI risk when the risk threshold probability ranged from 0.124 to 0.764. Conclusion The prediction model developed in this study demonstrates good discriminative ability and clinical utility, indicating its substantial value for predicting the MCI risk among the elderly.

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.

ObjectiveMigraine is a leading neurological disorder and the fourth most common cause of years lived with disability worldwide, affecting nearly 116 million individuals. Although pharmacological treatments are available, their efficacy is often limited by side effects and variable response rates. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers a safe, non-invasive alternative for migraine management. However, the neurophysiological mechanisms, particularly how rTMS modulates local cortical excitability and distributed pain-related circuits, remain poorly understood. Elucidating these mechanisms is essential for optimizing treatment protocols and improving clinical outcomes. MethodsThis study employed concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to investigate neuroplastic and neurocircuitry mechanisms of DLPFC-rTMS in migraine. Study 1 compared 30 migraineurs and 28 healthy controls to identify abnormalities in TMS-evoked potentials (TEPs) and significant current density (SCD) within sensory-discriminative regions including the primary somatosensory cortex (S1) and posterior insula (pINS), cognitive-affective regions including the anterior insula (aINS) and midcingulate cortex (MCC), and a descending modulatory region, the periaqueductal gray (PAG). Study 2 used a single-blind, crossover, sham-controlled design in 34 healthy participants. Each participant received both active (10 Hz, 80% RMT, 1 500 pulses) and sham DLPFC-rTMS in counterbalanced order. TMS-EEG and cold pain tolerance were assessed before and after each session. ResultsIn Study 1, migraineurs showed a significantly less negative N120 amplitude compared to healthy controls (P=0.027, Cohen’s d=0.60), indicating local intracortical disinhibition. No group differences were observed for N40, P60, or P180 components. At the source level, migraineurs exhibited significantly higher SCD in the S1, pINS, aINS, and MCC (allQ<0.05), but not in the ventroposterior thalamus (vpTHAL), mediodorsal thalamus (mdTHAL), or PAG. In Study 2, active rTMS significantly reduced SCD from pre- to post-stimulation in the S1, aINS, and MCC (all Q<0.05). Sham stimulation also reduced SCD in the S1 (Q<0.05) but not in the aINS or MCC. Although no significant group-level analgesic effect was observed between active and sham conditions (P=0.107), correlation analyses revealed that greater SCD reductions in the S1 and MCC were significantly associated with higher post-rTMS pain tolerance (R=-0.487 and -0.495, both Q<0.01) and larger improvements in pain tolerance(R=-0.487 and -0.451, both Q<0.05). No such correlations were found following sham stimulation, suggesting that the behavioural relevance of neural changes is specific to active rTMS. ConclusionThis study provides novel evidence that migraineurs exhibit both local neuroplastic abnormalities (reduced N120 amplitude) and hyperactivity in key pain-processing regions (S1, pINS, aINS, MCC). A single session of DLPFC-rTMS reduced hyperactivity in the aINS, MCC, and S1. Notably, greater reductions in the S1 and MCC were associated with improved pain tolerance. These findings identify distinct cortical circuitries, particularly within the cognitive-affective pain network, that may serve as potential biomarkers for optimizing rTMS treatment in migraine and other chronic pain conditions. Future studies should validate these results in patient populations experiencing spontaneous migraine attacks and explore multi-session or accelerated rTMS protocols.

ObjectiveTo investigate the safety and efficacy of transparent cap-assisted peroral cholangiopancreatoscopy-guided electrohydraulic lithotripsy （EHL）. MethodsA retrospective analysis was performed for the clinical data of 60 patients with large common bile duct stones who were admitted to Department of Gastroenterology， Jilin People’s Hospital， from May 1， 2023 to January 31， 2026， and according to the treatment method， the patients were divided into transparent cap-assisted peroral cholangiopancreatoscopy-guided electrohydraulic lithotripsy group and peroral cholangiopancreatoscopy-guided electrohydraulic lithotripsy group， with 30 patients in each group. The two groups were compared in terms of the rate of successful single-session stone fragmentation and removal， procedural time， duration of electrohydraulic lithotripsy， clinical success rate， and complications. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. ResultsCompared with the peroral cholangiopancreatoscopy-guided electrohydraulic lithotripsy group， the transparent cap-assisted peroral cholangiopancreatoscopy-guided electrohydraulic lithotripsy group had a significantly higher technical success rate （83.33% vs 60.00%， χ²=4.022， P=0.045） and significantly shorter procedural time ［46.00 （42.25 — 49.00） min vs 54.50 （42.00 — 65.00） min， Z=2.012， P=0.044］ and duration of electrohydraulic lithotripsy ［8.00 （6.25 — 11.75） min vs 13.50 （9.25 — 17.75） min， Z=2.749， P=0.006］. Both groups achieved a clinical success rate of 100%， with no significant difference in the incidence rate of complications （P>0.05）. ConclusionTransparent cap-assisted peroral cholangiopancreatoscopy-guided electrohydraulic lithotripsy has a high rate of successful single-session stone fragmentation and removal and a short procedural time， with good safety and efficacy， and therefore， it holds promise for clinical application.

Introduction: The nutritional status of children with Attention-Deficit/Hyperactivity Disorder (ADHD) and Down Syndrome (DS) is influenced by multiple food environment determinants. However, the precise relationship between food environment determinants and nutritional outcomes in these children remains unclear. This study aimed to understand the food environment determinants that are associated with the intake and nutritional status of these children in Malaysia, Lao PDR, and Indonesia. Methods: This cross-sectional study involved 7- to 18-year-old students with ADHD and DS in three Southeast Asian countries. Sociodemographic characteristics, dietary habits, and repeated 24-hour food recall data were collected through a structured questionnaire. Anthropometric data were obtained through direct measurements and analysed using the WHO AnthroPlus software. Further analyses were done using descriptive statistics and chi-square tests. Results: Total participants were 284 children, comprised of 37.7% with ADHD and 62.3% with DS; 62.3% of the children were boys and 37.7% were girls. Among the food environment determinants collected during the study, monthly household income and school food assistance status had significant associations (p<0.05) with BMI-for-age z-score category and total energy, protein, zinc, and calcium intakes. While the country, type of residence, and type of school had significant associations with total energy, protein, zinc, and calcium intakes. Conclusions: Food environment determinants, particularly household income and access to school food assistance, significantly influence the nutritional status and intake of children with ADHD and Down Syndrome. Thus, strengthening inclusive nutrition programmes may improve outcomes for this vulnerable group in Southeast Asia.

Macrophages are closely related to tumor progression,and can promote tumor growth and pro-liferation by promoting inflammation,angiogenesis and immunosuppression and so on,as well as killing tumors by directly killing tumor cells and triggering specific immune responses.Iron death,as an iron-depend-ent cell death caused by lipid peroxidation,can effectively kill tumor cells when regulated from the perspective of iron homeostasis,and can also release pro-inflammatory factors,trigger inflammatory reactions,change the survival environment of tumors as well as reduce the immune susceptibility of tumor cells.In recent years,more and more studies have shown that macrophages and iron death are closely related.In this paper,the rela-tionship between macrophages and iron death in terms of their functional properties and targeting of tumors are mainly introduced,and an overview of the functional properties of the two differentiated phenotypes of macrophages for the treatment of iron death in tumors is provided.

Hepatocellular carcinoma(HCC)is the third leading cause of cancer-related deaths,and al-though considerable progress has been made in the clinical diagnosis and treatment of HCC,the prognosis for patients remains poor,with a 5-year survival rate of only about 18％.The development of HCC is driven by the occurrence of mutations in driver genes that can directly promote cell proliferation,survival and metastasis.With the development of molecular biology and genomics technologies,researchers have elucidated that driver mutations that give HCC cells a selective growth advantage,the ability of the cells to resist apoptosis,maintain proliferative signals,initiate invasion and metastasis,induce angiogenesis,enable metabolic remodeling and immune escape.Exploring the key drivers of HCC development to fur-ther elucidate the pathogenesis of HCC may provide new directions for the diagnosis and treatment of HCC as well as improving the prognosis.In this paper,we summarize the driver gene mutations in HCC from various biological pathways such as telomere maintenance,cell cycle,the Wnt signaling pathway,oxida-tive stress,and epigenetic modifications.We also summarize the application prospects of driver gene mu-tations in the diagnosis and treatment of HCC.We aim to provide a reference for the diagnosis,treatment and research of HCC.

Objective:To design two kinds of intensity modulated radiotherapy (IMRT) plans with different radiation field distributions,and to compare the dose differences of that at the dose of target region and organs at risk (OAR) for middle and lower esophageal cancer,so as to provide a reference for the design of IMRT plan. Methods:The data of 17 patients with middle and lower esophageal cancer who received IMRT at Shangluo Central Hospital from November 2022 to May 2023 were retrospectively analyzed. IMRT plans with different radiation fields for Plan 1 and Plan 2 were designed for each patient. The angles of radiation field for Plan 1 were 0°,80°,120°,160° and 200°,and those for Plan 2 were 30°,130°,180°,230° and 330°,respectively. The prescribed dose to the planning target volume (PTV) was 60 Gy/30 F. The differences in dosimetric parameters between the two plans were compared. Results:There were no statistically significant differences in the dose parameters of 2％,98％,50％ target dose (D2％,D98％,D50％),homogeneity index (HI),conformity index (CI) and monitor unit between the two groups (P>0.05). There were no significant differences in V5 of dual lungs,the mean dose (Dmean) of heart,and the maximum dose (Dmax) of spinal-cord between two groups (P>0.05). The volume percentage (V10,V20,V30) of dual lungs received radiation doses of 10,20 and 30 Gy,and the mean dose (Vmean) of lung in the Plan1 group reduced respectively 7.44％,21.16％,10.09％ and 5.31％ than those in the Plan2 group,and the differences of them were statistically significant (t=-5.845,-7.729,-2.247,-3.960,P<0.05). Heart V10 and V20 in the Plan1 group decreased respectively by 7.23％ and 5.78％,with statistical significance (t=-4.376,-3.523,P<0.01),while V30 and V40 of Plan 1 increased respectively by 2.7％ and 4.92％,without statistical significance (P>0.05). There was no significant difference in heart Dmean between the Plan1 group and the Plan2 group (P>0.05). Conclusion:Both two methods of distribution field can meet the clinical requirements,and Plan1 has more advantages in protecting organs at risk under the premise of meeting the requirements of target region.

Objective:To investigate the difference of MRI and clinicopathological characteristics between patients with breast cancer susceptibility gene (BRCA)-positive and BRCA-negative breast cancer.Methods:The study was a cross-sectional study. MRI images and clinicopathological data of breast cancer patients with postoperative pathologically confirmed and determined BRCA gene status in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from January 2012 to April 2021 were retrospectively analyzed. A total of 120 BRCA-positive patients with 122 lesions and 120 BRCA-negative patients with 126 lesions were enrolled. All patients underwent MRI examinations, including pre-contrast and post-contrast scans. The breast MRI features of the patients were analyzed, including internal necrosis, lesion depth, degree of background parenchymal enhancement (BPE), type of lesion, shape and margin of the mass lesion, internal enhancement, and edema. Clinicopathological analysis included family history, molecular subtype, nuclear grade, and the status of human epidermal growth factor 2 (HER-2), estrogen receptor (ER), and progesterone receptor (PR). The χ2 test and Fisher exact test were performed to determine the differences in MRI features and clinicopathological manifestations of BRCA-positive and BRCA-negative breast cancers. Significant features obtained by univariate analysis were included in the multivariate logistic regression analyses to select independent influencing factors for predicting BRCA mutation in breast cancer. Results:Statistically significant differences were observed between patients with BRCA-positive and BRCA-negative breast cancers in the following features: family history, molecular subtype, ER or PR-positive status, HER-2-negative status, nuclear grade, BPE, internal necrosis, edema, and the shape and margin of the mass lesion( P?0.05). The multivariate logistic regression analyses showed that HER-2 negativity ( OR=3.277, 95% CI 1.087-9.875, P=0.035), round or oval shape ( OR=2.688,95% CI 1.143-6.320, P=0.023), circumscribed margin ( OR=3.001,95% CI 1.374-6.554, P=0.006), edema ( OR=4.407,95% CI 2.100-9.244, P<0.001), and the minimal or mild degree of BPE ( OR=2.520,95% CI 1.328-4.782, P=0.005) were significant independent factors in predicting BRCA gene mutations. Conclusions:There are differences in MRI features and clinicopathological manifestations of BRCA-positive and BRCA-negative breast cancers. HER-2 status, the shape and margin of lesions, edema and the degree of BPE could independently predict the BRCA status of breast cancer.