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.

ObjectiveTo enhance teaching in postoperative cancer rehabilitation, this study developed an integrative Chinese-Western medicine postoperative oncology rehabilitation system, termed the medical oncology generative pre-trained transformer (MedOncoGPT). By introducing MedOncoGPT as an intelligent assistant, an integrated teaching model combining Chinese and Western medicine was established. The study evaluated its impact on students’ integrative clinical reasoning and practical abilities, providing support for instructional reform in related courses. MethodsUsing teaching resources as the knowledge base, MedOncoGPT was built upon the open-source ChatGLM model and incorporated Low-Rank Adaptation (LoRA) fine-tuning and retrieval-augmented generation (RAG) techniques to address postoperative integrative oncology scenarios. The system was applied in courses and clinical clerkships related to integrative oncology. In alignment with course objectives, a five-stage instructional process—pre-class preparation, in-class inquiry, simulated multidisciplinary consultation, clinical reinforcement, and teaching reflection—was designed to guide students in completing syndrome differentiation, comprehensive assessment, and follow-up planning within real or simulated case contexts. Comparative analyses of student engagement, syndrome differentiation thinking, evidence-based awareness, and interdisciplinary integration skills before and after the teaching reform were conducted using questionnaires, course assessments, classroom observations, and semi-structured interviews. ResultsFollowing the implementation of MedOncoGPT, students demonstrated improved performance in case analysis, prescription formulation, and integrative Chinese-Western medical evaluation compared with those receiving traditional instruction. Classroom participation and the relevance of student inquiries also increased. Self-assessment results indicated high levels of satisfaction with respect to clarity of integrative clinical reasoning, ability to retrieve and apply guideline-based evidence, and awareness of appropriate use of intelligent tools in clinical decision-making. More than 92% of students reported that the system facilitated understanding of abstract theoretical concepts presented in textbooks. Instructors noted that the system helped reduce lesson preparation time, enriched typical case materials and discussion scenarios, and promoted the translation of research findings into classroom teaching. Pilot data showed that, with MedOncoGPT assistance, the mean time for initial syndrome differentiation decreased from 18.4 min to 12.1 min, and the agreement rate increased from 68.3% to 82.5%. In the teaching pilot, the experimental group achieved a higher mean score on the final case analysis assessment than the control group (82.6 vs. 74.3). ConclusionThe integration of MedOncoGPT into teaching on postoperative integrative cancer rehabilitation enabled the establishment of a stable instructional process within existing curricula and enhanced students’ integrative clinical reasoning and evidence-based practice capabilities. The approach demonstrates positive potential for advancing the integration of research, clinical practice, and education and represents a valuable exploratory strategy for instructional reform in courses on integrative Chinese-Western medicine.

ObjectiveTo enhance teaching in postoperative cancer rehabilitation, this study developed an integrative Chinese-Western medicine postoperative oncology rehabilitation system, termed the medical oncology generative pre-trained transformer (MedOncoGPT). By introducing MedOncoGPT as an intelligent assistant, an integrated teaching model combining Chinese and Western medicine was established. The study evaluated its impact on students’ integrative clinical reasoning and practical abilities, providing support for instructional reform in related courses. MethodsUsing teaching resources as the knowledge base, MedOncoGPT was built upon the open-source ChatGLM model and incorporated Low-Rank Adaptation (LoRA) fine-tuning and retrieval-augmented generation (RAG) techniques to address postoperative integrative oncology scenarios. The system was applied in courses and clinical clerkships related to integrative oncology. In alignment with course objectives, a five-stage instructional process—pre-class preparation, in-class inquiry, simulated multidisciplinary consultation, clinical reinforcement, and teaching reflection—was designed to guide students in completing syndrome differentiation, comprehensive assessment, and follow-up planning within real or simulated case contexts. Comparative analyses of student engagement, syndrome differentiation thinking, evidence-based awareness, and interdisciplinary integration skills before and after the teaching reform were conducted using questionnaires, course assessments, classroom observations, and semi-structured interviews. ResultsFollowing the implementation of MedOncoGPT, students demonstrated improved performance in case analysis, prescription formulation, and integrative Chinese-Western medical evaluation compared with those receiving traditional instruction. Classroom participation and the relevance of student inquiries also increased. Self-assessment results indicated high levels of satisfaction with respect to clarity of integrative clinical reasoning, ability to retrieve and apply guideline-based evidence, and awareness of appropriate use of intelligent tools in clinical decision-making. More than 92% of students reported that the system facilitated understanding of abstract theoretical concepts presented in textbooks. Instructors noted that the system helped reduce lesson preparation time, enriched typical case materials and discussion scenarios, and promoted the translation of research findings into classroom teaching. Pilot data showed that, with MedOncoGPT assistance, the mean time for initial syndrome differentiation decreased from 18.4 min to 12.1 min, and the agreement rate increased from 68.3% to 82.5%. In the teaching pilot, the experimental group achieved a higher mean score on the final case analysis assessment than the control group (82.6 vs. 74.3). ConclusionThe integration of MedOncoGPT into teaching on postoperative integrative cancer rehabilitation enabled the establishment of a stable instructional process within existing curricula and enhanced students’ integrative clinical reasoning and evidence-based practice capabilities. The approach demonstrates positive potential for advancing the integration of research, clinical practice, and education and represents a valuable exploratory strategy for instructional reform in courses on integrative Chinese-Western medicine.

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.

Objective To analyze personal external exposure dose monitoring results of pet hospital radiation workers in Beijing from 2022 to 2024, and to provide scientific evidence for developing effective monitoring protocols, standardizing radiological practices in pet hospitals, and protecting the health of both workers and the public. Methods Personal dose equivalents, H_p(10), were measured using GR-200A thermoluminescent dosimeters. Monitoring included radiation workers at 286 pet hospitals across all 16 districts of Beijing from 2022 to 2024. Each monitoring cycle lasted no more than 90 days. Annual effective doses were calculated by summing the results of four consecutive quarterly cycles. Data were processed and analyzed using Access and TLPS 6.41 software. All evaluations complied with national laws, regulations, and technical standards. Results A total of 1,579 person-time measurements were recorded. Only 51.87% of workers completed the full four-cycle annual monitoring schedule. Over the study period, the mean annual effective dose was 0.29 mSv, and the median dose was 0.14 mSv. The collective effective dose was 238.34 man-mSv. Notably, 94.26% of workers had annual effective doses below 1.0 mSv, and only 0.12% had doses at or above 5 mSv. Dose levels showed a statistically significant downward trend (P<0.05). Both independent and chain-branded clinics had a median annual effective dose of 0.14 mSv. In independent clinics, the proportion of workers with doses below 1.0 mSv increased from 80.77% in 2022 to 98.82% in 2024. In chain-branded clinics, this proportion rose from 96.88% to 98.11% over the same period. Conclusion Radiation exposure among pet hospital workers in Beijing remains at low levels, well below regulatory limits, and shows an overall declining trend. The disparity in personal doses between independent and chain-branded pet hospitals has diminished over time. Nevertheless, the industry still faces challenges such as high staff turnover and low monitoring completion rates. Expanding monitoring coverage and harmonizing protection standards would provide a scientific basis for precise, nationwide regulation.

Objective To evaluate the influence of the wearing position of dosimeters outside lead aprons on effective dose estimation for interventional radiology workers, analyze the differences between single and double dosimeter methods in effective dose estimation, and provide a reference for the personal dose monitoring of interventional radiology workers. Methods This study employed a combined approach of on-site monitoring and Monte Carlo simulation to evaluate the impact of the wearing position of dosimeters outside lead aprons on effective dose estimation, as well as the differences between effective doses measured using single and double dosimeters. Interventional radiology workers wore dosimeters at three positions: the neck outside the lead collar, the left chest outside the lead apron, and inside the lead apron. Effective doses were estimated using the single and double dosimeter methods specified in GBZ 128-2019 Specifications for individual monitoring of occupational external exposure, and the impact of different wearing positions on the estimation results was compared. Geant4 Monte Carlo simulations were used to model dose distributions at the neck outside the lead collar and at the left chest outside the lead apron for operators performing cardiovascular interventions under tube voltages of 70, 80, 90, and 100 kVp and exposure angles of posteroanterior (PA), anteroposterior (AP), and left anterior oblique 45° (LAO45°) positions. The study assessed the impact of dosimeter wearing position on effective dose estimation. Results Monte Carlo simulations demonstrated that neck doses consistently exceeded left chest doses across different tube voltages and exposure angles, with neck-to-chest dose ratios of 0.80-0.90. Under identical tube voltage conditions, AP showed the highest doses, followed by LAO45°, and PA demonstrated the lowest doses. The single and double dosimeter methods exhibited consistent patterns in effective dose estimation. Single dosimeter method generally yielded higher effective doses with relative deviations of 9.9% to 83%, though these deviations decreased under high tube voltages. Field monitoring data indicated that most interventional radiology workers maintained relative deviations between single and double dosimeter calculations below 6%, with neck-to-chest dose ratios of 0.95-1.1. The estimation patterns remained consistent across both methods, though single dosimeter method showed slightly higher results. Conclusion Under PA, AP, or LAO45°, the doses at the neck consistently exceeded those at the left chest. Therefore, when wearing lead protective equipment, the dosimeter should be properly positioned at the neck outside the lead collar to accurately reflect the radiation doses of surgeons. Some interventional radiology workers improperly positioned the dosimeter (intended at the neck outside the lead collar) at the left chest outside the lead apron, and this may result in an underestimation of the effective dose.

ObjectiveTo evaluate the pharmacological effects of verbenalin on both in vitro and in vivo infection models of human coronavirus 229E （HCoV-229E） and to preliminarily explore the antiviral mechanism of verbenalin through proteomic analysis. MethodsIn vitro， the cell counting kit-8 （CCK-8） for cell proliferation and viability assessment was used to establish a model of HCoV-229E-induced injury in human lung adenocarcinoma cells（A549）. A549 cells were divided into five groups： normal group， model group， and three verbenalin treatment groups （125， 62.5， and 31.25 μmol·L^-1）. The cell protective activity of verbenalin was evaluated through cell viability assay and immunofluorescence staining. In vivo， 30 BALB/c mice were randomly divided into normal group， model group， chloroquine group， and high-dose， low-dose verbenalin groups （40 and 20 mg·kg^-1）， with six mice per group. An HCoV-229E-induced mouse lung injury model was established to evaluate the therapeutic effects of verbenalin. Lung injury was assessed by detecting the lung index and lung inhibition rate. The severity of pulmonary inflammation cytokines was measured by enzyme-linked immunosorbent assay （ELISA）， while the lung morphology and structure were analyzed by micro-computed tomography （Micro-CT）. Hematoxylin and eosin （HE） staining was used to assess histopathological changes in lung tissue. Additionally， four-dimensional data-independent acquisition （4D-DIA） proteomics was employed to preliminarily explore the potential mechanisms of verbenalin in treating HCoV-229E-induced lung injury in mice， through differential protein expression screening， functional annotation， enrichment analysis， and protein-protein interaction network analysis. ResultsThe A549 cells were infected with HCoV-229E at the original viral titer for 36 hours to establish an in vitro infection model. The maximum non-toxic concentration of verbenalin was 125 μmol·L^-1， and the half-maximal cytotoxic concentration （CC₅₀） was 288.8 μmol·L^-1. Compared with the normal group， the model group showed a significant decrease in cell viability （P<0.01）， a significant increase in the proportion of dead cells （P<0.01）， mitochondrial damage， and a significant reduction in mitochondrial membrane potential （P<0.01）. After treatment with different concentrations of verbenalin （125， 62.5， and 31.25 μmol·L^-1）， cell viability was significantly increased （P<0.01）， and the proportion of dead cells was reduced （P<0.01）， with mitochondrial membrane potential restored （P<0.01）. In vivo experiments further confirmed the therapeutic effect of verbenalin on HCoV-229E-infected mice. Compared to the normal group， the model group showed a significant increase in the lung index （P<0.01）， severe lung tissue injury， lung volume enlargement， and a significant increase in the expression of inflammatory cytokines， including interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） （P<0.01）. In contrast， in the verbenalin treatment groups， these pathological changes were significantly improved， with a reduction in the lung index （P<0.01）， alleviation of lung tissue injury， reduced lung volume enlargement， and a significant decrease in inflammatory cytokine expression （P<0.01）. Proteomics analysis revealed that， compared to the normal group， the model group showed enrichment in several antiviral immune-related signaling pathways， including the nuclear factor-κB （NF-κB） signaling pathway （P<0.05）. Compared to the model group， the verbenalin treatment group showed enrichment in several signaling pathways related to inflammatory response and autophagy （P<0.05）， suggesting that verbenalin may exert its antiviral and anti-inflammatory effects by regulating these pathways. ConclusionVerbenalin demonstrates significant therapeutic effects in both in vitro and in vivo HCoV-229E infection models， with its mechanism likely related to the NOD-like receptor protein 3 （NLRP3） inflammasome pathway and mitochondrial autophagy.

BACKGROUND:Post and core restoration is a common choice for tooth defects,but the repair effects of various post and core materials are different. OBJECTIVE:To evaluate the stress distribution at the post and core,tooth root,and bonding agent site of post and core models made of different elastic modulus post and core materials using finite element method. METHODS:A three-dimensional root canal treated maxillary central incisor model was built using three-dimensional modeling software,which was restored with a full ceramic crown.The post and core materials in the restoration used nanoceramic resin(elastic modulus=12.8 GPa),composite resin(elastic modulus=16 GPa),hybrid ceramic(elastic modulus=34.7 GPa),glass ceramic(elastic modulus=95 GPa),titanium alloy(elastic modulus=112 GPa),and zirconia(elastic modulus=209.3 GPa).The model was fixed in cortical bone.A 100 N concentrated force of 45° from the long axis of the tooth was applied to 1/3 of the crown and tongue side of the central incisor.The stress distribution of the post and core,dentin,and tooth-root bonding agent in the model was repaired by the maximum principal stress criterion. RESULTS AND CONCLUSION:(1)When the post and core materials with higher elastic modulus was used,the post-core stress in the repair model was more concentrated.When the elastic modulus of the post and core materials(nanoceramic resin and composite resin)was close to dentin,the stress distribution of the post and core was more uniform.The stress distribution of dentin in all restoration models was similar regardless of post and core materials.When the post and core with higher elastic modulus was used,more stress concentration was shown at the post and root bonding agent in the repair model.(2)The maximum stress values at the post and core,tooth root,and the bonding agent site of post and tooth root in the nanoceramic resin model were 31.00,33.21,and 0.51 MPa,respectively.The maximum stress values at the post and core,tooth root,and the bonding agent between the post and tooth root in the composite resin model were 36.84,33.14,and 0.59 MPa,respectively.In the mixed ceramic model,the maximum stress values at the post and core,tooth root,and the bonding agent between the post and tooth root were 64.05,32.83,and 1.00 MPa,respectively.In the glass ceramic model,the maximum stress values at the post and core,tooth root,and the bonding agent between the post and tooth root were 112.30,32.69,and 1.73 MPa,respectively.In the titanium alloy model,the maximum stress values of the post and core,tooth root,and the bonding agent between the post and tooth root were 120.00,32.17,and 1.86 MPa,respectively.In the zirconia model,the maximum stress values of the post and core,tooth root,and the bonding agent between the post and tooth root were 148.80,31.85,and 2.28 MPa,respectively.(3)The higher the elastic modulus of the post and core material,the higher the maximum stress at the post and core during restoration.The elastic modulus of the post and core material had no significant effect on the maximum stress of the dental bonding agent and dentin.

Objective To investigate the protective effect of paravertebral nerve block combined with general anesthesia on liver injury after laparoscopic hepatectomy(LH).Methods A randomized controlled trial was conducted on 51 patients undergoing LH in our hospital between April and August 2024.They were randomly divided into control group(n=25,general anesthesia)and paravertebral block group(n=26,paravertebral nerve block before general anesthesia induction).Beside anesthesia,they received same other medical treatment.The following indicators were compared between the 2 groups,that is,serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL)and albumin(ALB),and systemic-immune inflammation(SII)index within 7 d before and on the 1st and 2nd days after surgery;heart rate and mean arterial pressure(MAP)before anesthesia induction(T1),before pneumoperitoneum establishment(T2),pneumoperitoneum establishment(T3),and at the first hilar occlusion(T4);usages of intraoperative norepinephrine,sevoflurane,and analgesic drugs 24 h postoperatively;as well as operation time,extubation time,and lengths of postanesthesia care unit(PACU)stay and hospital stay.Results The paravertebral block group had significantly lower ALT on the 1st day after surgery[178.40(126.55,325.86)vs 292.20(197.20,468.95)U/L],SII on the 2nd day after surgery[704.13(486.61,1 078.59)vs 1 075.09(753.80,1 614.38)],and amount of analgesic drugs in 24 h after surgery[29.70(27.37,32.07)vs 31.99(28.92,40.81)mg],and decreased MAP level at T3 and T4,early extubation,and shorter lengths of PACU stay and hospital stay when compared with the control group(all P<0.05).Conclusion Paravertebral nerve block combined with general anesthesia can reduce inflammatory responses,relieve postoperative pain,stabilize hemodynamics for patients undergoing LH,and thereby alleviate postoperative liver injury in them.