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.

BACKGROUND: Chronic kidney disease (CKD) is a progressive disorder that leads to significant structural and functional changes in the kidneys, posing a major global health concern and contributing to high mortality rates. METHODS: The urgent need for innovative treatments is evident. Mesenchymal stem cells (MSCs) are well-regarded in regenerative medicine for their ability to repair tissue and modulate immune responses. Emerging research indicates that the therapeutic benefits of MSCs are largely mediated by the secretion of extracellular vesicles (EVs), particularly exosomes (MSC-Exos), which replicate the effects of MSCs by delivering genetic materials and proteins to target cells. RESULTS: MSC-Exos are novel natural carriers for targeted gene or drug delivery, offering biocompatibility, intrinsic targeting capabilities, and bioactive cargo to modulate recipient cells. They represent a groundbreaking platform for precision medicine, enhancing therapeutic efficacy with minimal immunogenicity and off-target effects. Moreover, embedding exosomes within hydrogels has emerged as a promising strategy to maintain their biological activity and enable a controlled release. CONCLUSION This review explores the roles of MSC-Exos in CKD pathophysiology, highlights the renoprotective effects of MSC-Exos for various sources, and provides a comprehensive overview of how hydrogel biomaterials present a promising approach for integrating exosomes to enhance therapeutic outcomes. The use of hydrogels to encapsulate exosomes improves their sustained release and stability in diseased kidney tissues, providing an innovative strategy to enhance precision therapies.

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.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

The implementation of the Good Pharmacovigilance Practice(GVP)in 2021 has laid a solid foundation for improving China's pharmacovigilance system,a matter of paramount importance currently emphasized by Marketing Authorization Holders(MAHs).Given the unique organizational structures of corporate groups,establishing a centralized pharmacovigilance system can optimize resource utilization.This paper analyzes the challenges faced by corporate groups in developing such central-ized systems and proposes an organizational framework with defined operational divisions.The findings aim to provide actionable insights for vaccine manufacturers in establishing and refining life cycle pharmacovigilance systems.

The implementation of the Good Pharmacovigilance Practice(GVP)in 2021 has laid a solid foundation for improving China's pharmacovigilance system,a matter of paramount importance currently emphasized by Marketing Authorization Holders(MAHs).Given the unique organizational structures of corporate groups,establishing a centralized pharmacovigilance system can optimize resource utilization.This paper analyzes the challenges faced by corporate groups in developing such central-ized systems and proposes an organizational framework with defined operational divisions.The findings aim to provide actionable insights for vaccine manufacturers in establishing and refining life cycle pharmacovigilance systems.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Chronic low back pain (CLBP) is a pervasive and debilitating condition, affecting millions of individuals globally and imposing a significant burden on healthcare systems. Traditional treatment modalities often have limited efficacy, leading to the exploration of novel therapeutic interventions. Endoscopic rhizotomy (ER) has emerged as a promising technique, particularly for managing facetogenic pain. This systematic review presents a comprehensive overview of the historical evolution, current practices, and clinical outcomes associated with ER in the treatment of CLBP. This systematic review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive literature search was conducted in Embase, PubMed, and the Cochrane Central Register of Controlled Trials, covering publications up to February 1, 2024, utilizing specific keywords related to low back pain (LBP) and full-endoscopic lumbar rhizotomy. Data extraction focused on patient demographics, clinical outcomes, and any reported complications associated with this procedure. Ten selected studies, comprising a total of 529 patients, were included. Approximately 96.7% to 97.8% of patients who underwent ER reported excellent or good results based on the MacNab score. Patients treated with ER demonstrated significantly better visual analogue scale scores (mean difference: -2.39; 95% confidence interval [C]I, -3.15 to -1.63; p<0.00001) and showed greater improvement on the Oswestry Disability Index (mean difference: -19.97; 95% CI, -37.48 to -2.46; p=0.03) than those treated with traditional percutaneous radiofrequency ablation (TPRA). No major postoperative complications were reported. Full-endoscopic lumbar rhizotomy represents a significant advancement in the treatment of CLBP, especially in cases involving facetogenic pain. The procedure offers superior outcomes compared to TPRA, with higher patient satisfaction rates and improved clinical outcomes. The absence of major complications highlights its potential as a therapeutic option for facetogenic LBP. However, the findings are limited by the small number of studies, varying follow-up durations, and potential publication bias.

Objective:Quantitative analysis of policies on equalization of basic public health services was used,to comprehensive understanding of characteristics and the use of combinations of policy tools,and to provide recommendations for promoting equalization of basic public health services in China.Methods:The research object was policies on equalization of basic public health services by the central government from 2009 to 2022,and a three-dimensional policy analysis framework of"Policy tools(dimension X)-Stakeholders(dimension Y)-Policy process(dimension Z)"was constructed to carry out the content analysis of policies.Results:The proportion of supply-oriented policy tools was reasonable,and policy focus on government departments and policy implementation stage;Public health programs have been mainly used,and capacity enhancement of primary health care institutions has been valued and given financial and human resources support.However,there were structural dysfunction,imbalance in policy patterns of interest subjects,and uneven attention at policy stages.Suggestions:Promote the optimization of internal structure of policy tools,diversify policy attention to stakeholders,and rationalize distribute policy phases.