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 explore the mechanism by which the Shenfu Xiongze prescription regulates autophagy in rats with myocardial remodeling through the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsA rat model of myocardial remodeling induced by isoprenaline （ISO） was established. Rats were divided into the blank group，the model group，the low-，medium-， and high-dose groups of Shenfu Xiongze prescription，and the captopril group， 6 rats in each group. Except for the blank group，the rat model of myocardial remodeling was established in the other groups by intraperitoneal injection of 2.5 mg·kg^-1 ISO for 3 consecutive weeks. At the same time of modeling， the low-，medium-， and high-dose groups of Shenfu Xiongze prescription were administered the corresponding doses of Shenfu Xiongze prescription solution （8.4，16.8，and 33.6 g·kg^-1），and the captopril group was administered captopril solution （25 mg·kg^-1）. As for the blank group and the model group， the same volume of normal saline was given. The treatment was continued for 3 weeks. Echocardiography was used to observe the cardiac structure and function，and the heart weight index was detected. Masson staining and hematoxylin-eosin （HE） staining were used to observe the pathological morphology changes of myocardial tissue. The levels of interleukin-6 （IL-6） and B-type natriuretic peptide （BNP） in serum were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of type Ⅰ collagen （Collagen Ⅰ），type Ⅲ collagen （Collagen Ⅲ），and microtubule-associated protein 1 light chain 3 （LC3） proteins in myocardial tissue was determined by immunohistochemistry. Autophagy was observed by transmission electron microscopy. The mRNA expression of Collagen Ⅰ，Collagen Ⅲ，α-smooth muscle actin （α-SMA），LC3，yeast Atg6 homolog protein （Beclin-1），AMPK，and mTOR in myocardial tissue was detected by quantitative real-time polymerase chain reaction （real-time PCR）. The protein expression of Collagen Ⅰ，α-SMA，transforming growth factor-β₁ （TGF-β₁），LC3，Beclin-1，p62， phosphorylation（p）-AMPK，p-mTOR，AMPK，and mTOR was detected by Western blot. ResultsCompared with the normal group，rats in the model group exhibited significantly decreased values of ejection fraction （EF） and left ventricular fractional shortening （FS） （P<0.01）， significantly increased values of left ventricular end-diastolic diameter （LVIDd） and left ventricular end-systolic diameter （LVIDs） （P<0.01）. Additionally， the model group also showed increased degrees of inflammatory infiltration and fibrosis of myocardial tissue， significantly elevated levels of serum IL-6 and BNP （P<0.01）， significantly increased mRNA and protein levels of Collagen Ⅰ，Collagen Ⅲ，α-SMA，and mTOR （P<0.01），and markedly decreased mRNA and protein levels of LC3，Beclin-1，and AMPK （P<0.05，P<0.01）. Compared with the model group， the low-，medium-， and high-dose groups of Shenfu Xiongze prescription presented significantly elevated EF and FS values （P<0.01） and lowered LVIDd and LVIDs （P<0.05）. In these groups， the inflammation and fibrosis were alleviated significantly. They also exhibited decreased serum levels of IL-6 and BNP （P<0.01）， significantly reduced protein expression of Collagen Ⅰ， α-SMA， TGF-β₁， p62， and p-mTOR （P<0.01）， significantly decreased mRNA expression of Collagen Ⅰ， Collagen Ⅲ， α-SMA， and mTOR （P<0.01）， and significantly increased mRNA and protein levels of LC3， Beclin-1， and AMPK （P<0.05，P<0.01）. ConclusionThe Shenfu Xiongze prescription can improve the myocardial remodeling induced by ISO in rats by regulating the autophagy level，enhance cardiac function，and reduce inflammatory and fibrotic levels. This effect may be achieved through the AMPK/mTOR signaling pathway.

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 investigate the efficacy and safety of transurethral water vapor thermal therapy(WVTT)using the Rezūm system for benign prostatic hyperplasia(BPH)in the real world.Methods:A total of 181 patients with BPH were recruited from the Second Affiliated Hospital of Nanjing Medical University from August 2022 to December 2023,of whom 173 patients were treated with WVTT using the Rezūm system,while 8 patients were treated with WVTT combined with TURP.They were followed up at 1,3,and 6 months postoperatively to assess changes in the IPSS,QoL,Qmax,IIEF-5,and the occurrence of any complications.Results:All 181 surgeries in this group were successfully completed.The operation time of the Rezūm system was(4.6±1.4)mi-nutes.The postoperative indwelling catheterization time was(8.0±2.1)days.With a follow-up of at least 6 months,there was a significant decrease in PV,IPSS and QoL,and a remarkable increase had been found in Qmax as well(P＜0.05).There was no sig-nificant difference in IIEF-5 before and after the operation(P＞0.05).In this groups of patients,postoperative complications mainly included 95 cases(52.5％)of gross hematuria,6 cases(3.3％)of retrograde ejaculation,5 cases(2.8％)of urethral stricture,4 cases(2.2％)of prostatitis,and 10 cases(5.5％)of urinary tract infection.Four cases(2.2％)underwent surgical retreatment for BPH after surgery.Conclusion:In the real world,the use of Rezūm thermal steam ablation system for the treatment of BPH has sat-isfactory short-term effect,short surgical time,and significant improvement in IPSS,QoL,Qmax,which does not adversely affect sexu-al function.

Objective:To analyze the therapeutic effect of a virtual reality (VR)-based accommodation training device on accommodative excess visual fatigue.Methods:A case-control study was conducted.A total of 20 normal subjects (20 eyes) and 20 patients with accommodative excess visual fatigue (20 eyes) were recruited at Zhongshan Ophthalmic Center, Sun Yat-sen University between January and December 2022.The study consisted of two phases.In the first phase, the effect of watching videos with VR glass on the subjects' subjective and objective visual function was evaluated.Normal subjects wore VR device to watch a 2D video for 30 minutes, and assessments were performed before and after viewing.These assessments included binocular accommodation/convergence function (accommodation response, accommodative convergence to accommodation ratio [AC/A]), tear film function (first tear film break-up time), subjective symptoms (visual fatigue score), and basic visual health parameters including best corrected visual acuity (BCVA) and intraocular pressure (IOP).In the second phase, the improvement in subjective and objective visual fatigue metrics with the VR-based accommodation training device was investigated.Patients with visual fatigue were divided into a traditional training group using traditional flipper lenses and a VR training group using the VR accommodation training device, with 10 eyes in each group.The effects of the VR accommodation training device on indicators such as accommodative sensitivity, accommodation response, convergence function, visual fatigue score, acceptability score, system usability score, BCVA, and IOP were evaluated and compared between the two groups.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Zhongshan Ophthalmic Center, Sun Yat-sen University (No.IIT2021007).Written informed consent was obtained from each subject.Results:In normal subjects, there was no statistically significant difference in first tear film break-up time, distance phoria, near phoria, AC/A, accommodative response, BCVA, or IOP before and after 30 minutes of continuous viewing of 2D video using VR glass ( t=1.155, 1.360, 4.479, 1.979, -1.249, -3.017, 2.211; all P>0.05).The visual fatigue score remained unchanged at (1.00±0.00) points before and after viewing.Among the subjects with visual fatigue, there were statistically significant differences in binocular accommodative sensitivity, dominant eye accommodative sensitivity, and BCVA before and after using the VR accommodation training device ( F=8.693, 4.078, 4.942; all P<0.05).Ocular accommodation sensitivity at 8 weeks after training was improved compared with 1 week after training, and BCVA at 4 weeks after training was improved compared with before training, and the differences were statistically significant (both P<0.05).In the VR training group, the average tear film break-up time, first tear film break-up time, and BCVA increased and the visual fatigue score decreased compared with before training, the differences were statistically significant (all P<0.05).In the traditional training group, the accommodation sensitivity of the dominant eye increased after training compared with before training, with a statistically significant difference ( P<0.05). Conclusions:Watching 2D videos with VR glass for 30 minutes does not induce subjective or objective symptoms of visual fatigue.The VR-based accommodation training paradigm effectively improves accommodative sensitivity and alleviates subjective symptoms of visual fatigue in individuals with accommodative excess visual fatigue.

Objective:To summarize the clinical characteristics of congenital chylothorax (CC) in neonates, and to analyze the effects of conservative treatment and the prognosis.Methods:A case control study was conducted.Clinical data of neonates with CC treated in the Department of Neonatal Surgical Intensive Care Unit, Guangzhou Women and Children′s Medical Center Guangzhou Medical University, from January 2015 to April 2023 were collected.The patients were divided into a survival group and a death group according to the outcome.SPSS 26.0 software was used for statistical analysis, and binary Logistic regression was used for the analysis of risk factors for death.Results:A total of 55 patients were included in this study, including 35 males and 20 females.The gestational age at birth and birth weight were 37.1 (34.7, 38.7) weeks and 3 250 (2 640, 3 540) g, respectively.Among the patients included, 30 cases had bilateral pleural effusion, 25 cases had unilateral pleural effusion, and 22 cases had hydrops fetalis; 50 cases were prenatally diagnosed with pleural effusion, with the mean gestational age at diagnosis being 31.0(26.0, 34.6) weeks.Additionally, 21 cases had polyhydramnios, and 18 cases had mediastinal displacement.Ten cases received intrauterine treatment and 17 cases were treated with octreotide.The maximum daily amount of pleural effusion was 31.7(12.0, 62.5) mL/kg, and pleural effusion resolved within 14 (6, 22) days.The length of hospital stay was 23 (12, 36) days.Forty-four cases survived, while 11 cases died.The differences in polyhydramnios, gestational age, bilateral pleural effusion, hydrops fetalis and Apgar score were significant between the survival and death groups (all P<0.05).Binary Logistic regression analysis revealed that bilateral pleural effusion and a low 5-minute Apgar score were independent risk factors for early death in neonates with CC (all P<0.05).A total of 38 children were followed up at the age of 2.30 (1.24, 3.46) years.There was 1 case of recurrence, and none of the patients experienced recurrent respiratory infections. Conclusions:CC is most common in full-term infants and has a predominantly bilateral effusion, its long-term prognosis with conservative treatment is promising.However, neonates with CC who present with bilateral pleural effusion or low 5-minute Apgar scores have an increased risk of early mortality.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

China has become the country with the highest global burden of heart failure(HF).Despite the widespread use of prognostic-improving medications today,the mortality rate of HF remains high,reaching 13.7％at one year-particularly among patients with heart failure with reduced ejection fraction(HFrEF).HF interventional device therapy(structural intervention)targets the structural factors underlying HF,including atrial pressure,ventricular remodeling,and valvular intervention.It leverages the heart's intrinsic physiological properties and pathological progression mechanisms to deliver treatments through interventions without external active forces,achieving anatomical or functional repair.This field has emerged as a rapidly growing area and plays an increasingly critical role in HF management.This article provides a comprehensive review and summary of the latest advancements in HF and cardiomyopathy interventional therapy over the past year.It covers various novel technologies and products currently in the research phase,aiming to provide an in-depth analysis of the current status and future directions of HF interventional therapy,and further advance the development of this discipline.

Objective To construct a medical consumables selection indicator system based on analytic hierarchy process(AHP)and fuzzy cluster method.Methods Firstly,a medical consumables selection indicator system was established preliminarily with the literature research results and actual situation of hospital consumables management;secondly,13 experts in related fields were selected to execute two rounds of online questionnaires,the expert weights were determined with AHP,the importance of each selection indicator was scored by the expert evaluation method and fuzzy cluster method,and consistency analysis was carried out on the two rounds of expert evaluation results;finally,the final medical consumables selection indicator system was built with the 100-point scale.Results The constructed medical consumables selection indicator system was composed of 5 primary indicators,12 secondary indicators and 38 tertiary indicators.The primary indicators included consumables quality,clinical demand,cost-effectiveness,supply capacity and after-sales service,with the percentage-based scores being 27,25,14,26 and 8,respectively.Conclusion The medical consumables selection indicator system based on AHP and fuzzy cluster method with high reliability provides effective and reliable references for medical institutions to select medical consumables.