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Insomnia has a high incidence rate among adults, severely affecting physical and mental health and increasing the risk of multiple diseases. Tuina represents an effective non-pharmacological intervention for insomnia management. Nevertheless, the majority of existing clinical evidence on Tuina for insomnia pertains to its use in conjunction with other modalities, and the relative effectiveness among different combined approaches remains unknown. Accordingly, this network meta-analysis compared the impacts of various Tuina-based combination therapies on patients with confirmed insomnia. A systematic search was performed across PubMed, Cochrane, Embase, Web of Science, CNKI, VIP, WanFang, and SinoMed electronic databases to identify randomized controlled trials (RCTs) meeting the prespecified criteria. Network meta-analysis was performed using Stata version 16.0. Thirty-four RCTs comprising 2,663 subjects were enrolled, assessing 12 distinct Tuina-based combined interventions. The network meta-analysis revealed that for the outcome of total effective rate, the following combinations were showed a statistically significant difference compared to oral medication (P < 0.05): Tuina+breath guiding+acupoint application, Tuina+music, Tuina+foot bath, Tuina+breath guiding, Tuina+foot bath+acupoint application, Tuina+acupuncture, Tuina+acupoint application, and Tuina+scraping. The top-ranked regimens were Tuina+breath guiding+acupoint application, Tuina+music, and Tuina+foot bath. For the outcome of Pittsburgh Sleep Quality Index (PSQI) score improvement, Tuina+breath guiding+acupoint application, Tuina+music, Tuina+foot bath, and Tuina+acupuncture were significantly better than oral medication (P < 0.05). The three highest-ranking interventions were again Tuina+breath guiding+acupoint application, Tuina+music, and Tuina+foot bath. Regarding safety, Tuina+acupoint application exhibited the lowest rate of adverse events; however, this finding was derived from only 5 RCTs assessing 3 interventions, and the sparse evidence network precludes definitive comparative safety conclusions. Tuina-based combination therapies showed a potential advantage over drug monotherapy in enhancing both the Total effective rate and PSQI score for insomnia. Among them, the integrated protocol of Tuina together with Breath guiding and acupoint application ranked highest in the network meta-analysis;however, given that the majority of evidence quality was assessed as low or very low, these findings are exploratory and further verification through high-quality RCTs is needed. https://www.crd.york.ac.uk/PROSPERO/view/CRD420261344347.
This study aims to systematically evaluate the efficacy and safety of different intravenous thrombolytic agents in patients with acute ischemic stroke (IS) who present between 4.5 and 24 h after symptom onset. A network meta-analysis was conducted to compare the available treatments and provide evidence to support clinical decision-making and inform updates to clinical guidelines. A systematic search was conducted in PubMed, Embase, the Cochrane Library, and Web of Science, covering the period from the inception of each database to February 1, 2026. Randomized controlled trials (RCTs) comparing different intravenous thrombolytic regimens within the extended time window were included. Primary outcomes included a modified Rankin Scale score of 0-1 at 90 days, mRS 0-2 at 90 days, improvement in the National Institutes of Health Stroke Scale at 24 h, reperfusion at 24 h, symptomatic intracranial hemorrhage at 36 h, and mortality at 90 days. A network meta-analysis using a frequentist random-effects model was conducted to report relative risks and 95% confidence intervals. Interventions were ranked using the cumulative ranked area under the curve, and the certainty of the evidence was assessed using the GRADE/CINeMA framework. A total of 10 RCTs (2,409 patients) were included, involving five interventions: alteplase (rt-PA), tenaplase (TNK), JX10, standard of care (SoC), and placebo (PBO). For the primary outcome of 90-day mRS 0-2, compared with SoC, rt-PA significantly increased the proportion of functionally independent patients (RR = 1.21, 95% CI 1.06-1.38, low certainty), JX10 (RR = 1.50, 95% CI 0.87-2.58, very low certainty) and TNK (RR = 1.07, 95% CI 0.93-1.23, low certainty) showed a trend toward improvement but did not reach statistical significance. The SUCRA ranking showed that JX10 (87.7%) and rt-PA (77.0%) ranked first and second, respectively. Regarding the early surrogate endpoint of 24-h reperfusion, rt-PA (RR = 2.65, 95% CI 1.57-4.46, low certainty) was superior to SoC and ranked first in the SUCRA ranking (99.9%). Regarding safety, rt-PA significantly increased the risk of 36-h SICH compared with SoC (RR = 5.82, 95% CI 1.47-22.95, low certainty), while JX10 had the highest risk of bleeding (SUCRA 82.1%). There were no statistically significant differences in 90-day mortality rates among the interventions. The certainty of the evidence was predominantly low to very low, primarily limited by risk of bias, imprecision, and indirectness. In patients with acute IS within 4.5-24 h of onset, rt-PA significantly improves functional independence at 90 days and 24-h reperfusion, but increases the risk of symptomatic intracranial hemorrhage. The ranking analysis suggested JX10 might have a favorable functional outcome profile, but this finding is derived from a single, small-sample, dose-exploratory study n = 90 with no direct comparative data against other thrombolytics. Consequently, the evidence for JX10 is considered hypothesis-generating only, and its clinical efficacy and safety remain unestablished. Given the high risk of hemorrhage, its clinical application is not yet supported. The therapeutic advantages of TNK have not been fully demonstrated, though its safety profile is relatively superior. Clinical decision-making requires individualized consideration based on imaging screening, bleeding risk assessment, and patient preference. There is an urgent need for larger-scale, rigorously designed head-to-head RCTs to provide higher-quality evidence for expanding the time window for thrombolytic therapy. https://www.crd.york.ac.uk/PROSPERO/view/CRD420261350208, identifier: CRD420261350208.
Hydrocephalus comprises etiologically heterogeneous disorders that converge on ventricular enlargement but may be associated with distinct protein-abundance patterns within the cerebrospinal fluid (CSF) compartment. This exploratory study compared CSF proteomic profiles in post-hemorrhagic hydrocephalus (PHH) and idiopathic normal pressure hydrocephalus (iNPH) to characterize CSF protein-abundance patterns associated with these two hydrocephalus and identify proteins for further validation. Cerebrospinal fluid samples from 11 participants, including five patients with PHH, three with iNPH, and three non-hydrocephalus controls, were analyzed using Olink proximity extension assay proteomics. Normalized protein expression values were assessed by quality-control analysis, differential expression analysis, and functional annotation using Gene Ontology, KEGG, Reactome, InterPro, Disease Ontology, and STRING-based protein interaction analyses. Differentially expressed proteins were screened using nominal p values, with false discovery rate adjustment calculated for statistical interpretation. Calcyphosine (CAPS) and follistatin-like 1 (FSTL1) were further assessed by ELISA in an expanded cohort. All samples passed quality-control criteria. Compared with the non-hydrocephalus control group, both PHH and iNPH showed predominantly downregulated CSF proteomic profiles, with different exploratory protein-abundance patterns. PHH showed relative CAPS elevation together with reduced proteins related to neuronal structural maintenance, synaptic signaling, axon guidance, immune communication, and extracellular regulation. Functional annotation analyses identified overrepresented terms related to inflammatory signaling, cytokine-receptor interaction, cell adhesion, calcium-related signaling, lysosomal clearance, glycan remodeling, and neural pathways. In iNPH, FSTL1 was relatively increased, whereas proteins involved in synaptic function, axon guidance, cell adhesion, growth-factor signaling, extracellular matrix organization, and cellular stress responses were decreased. Enrichment analyses highlighted neural connectivity, receptor-associated signaling, inflammatory pathways, proteostasis, glycosaminoglycan metabolism, and cilium- or centrosome-related processes. ELISA reproduced the direction of the proteomic findings, showing higher CSF CAPS levels in PHH and higher CSF FSTL1 levels in iNPH than in the non-hydrocephalus control group. The PHH and iNPH share a ventricular phenotype but exhibit distinct CSF proteomic signatures. CAPS and FSTL1 may represent exploratory proteins of interest within different hydrocephalus-related annotation contexts. These findings require validation in larger, independent, longitudinal cohorts before clinical biomarker inferences are made.
Spinal cord injury (SCI) can lead to substantial impairments in walking and mobility, and traditional rehabilitation methods face limitations such as high labor intensity and insufficient training intensity and precision. While robot-assisted gait training is widely used, its therapeutic advantages over conventional rehabilitation remain controversial. Through systematic reviews and meta-analysis, this study quantitatively synthesizes existing randomized controlled trial (RCT) evidence to determine the efficacy of robot-assisted gait training on walking and mobility abilities in persons with SCI. A comprehensive search was conducted across PubMed, Embase, Cochrane Library, Web of Science, and China National Knowledge Infrastructure (CNKI) databases from their inception to June 19, 2025. We included RCTs comparing robot-assisted gait training with conventional rehabilitation. Two researchers independently performed literature screening, data extraction, and risk of bias assessment. Meta-analysis was conducted using RevMan 5.4 software to calculate standardized mean differences (SMDs) and their 95% confidence intervals (CIs). A total of 8 RCTs involving 241 participants were included. Meta-analysis results showed: (1) Regarding walking ability, the robot-assisted gait training group demonstrated significant improvements in the 6-min walk test distance (SMD = 0.57, 95% CI: 0.12-1.03, p = 0.01) and Spinal Cord Injury Walking Index II score (SMD = 0.49, 95% CI: 0.13-0.84, p = 0.007); (2) Regarding functional independence, the robot-assisted gait training group demonstrated superior improvement in functional independence scores (SMD = 0.39, 95% CI: 0.05-0.72, p = 0.02); (3) Regarding lower limb muscle strength, no significant difference was observed between the two groups in the improvement of lower limb motor scores (SMD = 0.03, 95% CI: -0.27-0.34, p = 0.84). Robot-assisted gait training effectively improves functional walking endurance, gait independence, and overall function in persons with SCI. Its core mechanism lies in promoting task-specific motor learning and neuromuscular control, rather than enhancing muscle strength. It is recommended that this technology be adopted as a primary functional improvement strategy in clinical practice, combined with targeted strength training to optimize rehabilitation outcomes.
The prognostic value of vitamin-related biomarkers in acute ischemic stroke (AIS) remains incompletely defined. This study evaluated associations between serum vitamin-related markers and 3-month functional outcome and developed an internally validated nomogram for individualized risk prediction. Consecutive AIS patients admitted to Huludao Central Hospital between November 2024 and July 2025 were retrospectively included (n = 655). The analyzed sample included 342 men (52.2%) and 313 women (47.8%), with a mean age of 66.84 ± 9.85 years and a mean admission NIHSS score of 3.98 ± 4.35. Poor outcome was defined as a 3-month modified Rankin Scale (mRS) score of 3-6, and good outcome as mRS ≤ 2. Demographic and clinical characteristics, routine laboratory indices, and serum levels of vitamin D, vitamin E, vitamin A, vitamin K1, vitamin B12, folate, and homocysteine were collected. Candidate variables were screened by univariable analyses and entered into multivariable logistic regression. Multivariable analyses adjusted for age, sex, BMI, admission NIHSS score, infarct location, vascular risk factors, atrial fibrillation, coronary heart disease, moderate-to-severe arterial stenosis, serum albumin, and total protein. A nomogram was constructed using the rms package in R. Internal validation was performed with 1,000 bootstrap resamples. Discrimination, calibration, and clinical net benefit were assessed using receiver operating characteristic curves, calibration curves, and decision curve analysis. Among 655 patients, 346 (52.82%) had poor outcomes and 309 (47.18%) had good outcomes at 3 months. Multivariable analysis identified vitamin D, vitamin E, vitamin A, vitamin K1, vitamin B12, folate, and homocysteine as independent predictors of poor outcome. The nomogram showed good discrimination, with an AUC of 0.878 in the training set and 0.880 in the test set, together with favorable calibration and decision-curve performance. In the test set, both the vitamin-based model and the combined model outperformed the clinical baseline model (AUC 0.884 and 0.886 vs. 0.734; DeLong p < 0.001), whereas the combined model did not significantly improve over the vitamin-based model (ΔAUC = -0.005; p = 0.582). This serum vitamin-related biomarker nomogram may assist early risk stratification for 3-month functional outcome after AIS. However, as this was a single-center retrospective study with internal validation only, the model should be regarded as preliminary and requires external multicenter validation and prospective evaluation of clinical impact in patient management and outcomes before routine clinical use.
Dopamine D1 and D2 receptors (D1R, D2R) are widely distributed in the central nervous system and play important yet distinct roles in pain regulation. Although their involvement in reward, motivation, and emotional processing is well established, a systematic understanding of their region-specific and subtype-specific functions in pain remains incomplete. This review integrates research from the past decade on four core pain-related brain regions: the prefrontal cortex (PFC), nucleus accumbens (NAc), anterior cingulate cortex (ACC), and amygdala. Existing evidence shows that D1R and D2R exhibit significant regional heterogeneity and functional complexity. In the PFC, D1R has been implicated in pain signal integration and salience encoding in some studies, while D2R shows a context-dependent regulatory role; however, the literature remains heterogeneous, and causal evidence is limited. In the NAc, D1R may mediate the intersection of endogenous and exogenous analgesic signals and may participate in pain-reward balance; D2R has been shown to modulate inflammatory pain and neuropathic pain, opioid synergy, and stress analgesia. In the ACC, D1R appears to provide tonic suppression under physiological conditions, but its function may diminish in chronic pain, potentially contributing to hyperalgesia maintenance. Conversely, activation of D2R has been reported to suppress pain symptoms and to restore inhibitory control in some studies. In the amygdala, D1R exhibits region- and cell-type specific effects, while D2R within the central amygdala may serve as an important mediator of the VTA-CeA reward-analgesia pathway. More importantly, the interaction between D1R and D2R presents patterns of functional synergy, functional antagonism, and state-dependent reorganization, which together precisely regulate the sensory and emotional dimensions of pain. Treatment targeting the dopamine receptor system is a promising pain management strategy. However, many challenges remain in achieving precise treatment targeting specific regions and cell types. Additional clinical studies are needed in the future to evaluate the efficacy of this approach in patients with chronic pain and mood disorders.
Calcitonin gene-related peptide (CGRP) is a key mediator in migraine and a target of recent preventive therapies. Since CGRP is also expressed in bone and involved in skeletal regulation, concerns have been raised regarding potential bone effects of CGRP pathway inhibition. We report a prespecified 6-month analysis of a prospective, observational controlled, cohort study evaluating early bone outcomes during anti-CGRP monoclonal antibody (mAb) therapy. Adults with migraine initiating anti-CGRP mAb monotherapy (treated, n = 27) and age- and sex-matched migraine controls not receiving preventive therapy (controls, n = 14) underwent dual-energy X-ray absorptiometry [bone mineral density (BMD) at lumbar spine, total hip, and femoral neck], lumbar trabecular bone score (TBS), and bone turnover marker assessment (serum CTX and P1NP) at baseline and 6 months. The primary endpoint was the within-treated change from baseline to month 6 in BDM and TBS. Secondary endpoint included within-patient changes in bone turnover markers and between-group change from baseline to month 6, which were assessed using linear mixed-effects models. At baseline, BMD, TBS, CTX and P1NP were within the expected age-specific range in both groups. After 6 months of anti-CGRP mAb exposure all values remained within normal ranges and no clinically meaningful changes in BMD, TBS, CTX or P1NP were observed. In adjusted models, no significant group×time interactions were detected for BMD, CTX or P1NP (all p > 0.05). Lumbar spine TBS showed a small between-group difference in change over time (group×time interaction), with a greater decrease in treated patients than in controls (β = -0.052, 95% CI - 0.095 to -0.008; p = 0.023), with values remaining within the normal range. Anti-CGRP treatment was clinically effective, with ≥50% and ≥75% reductions in monthly migraine days achieved by 80.8 and 42.3% of patients, respectively. This prospective, observational, controlled, cohort study suggests that anti-CGRP mAb therapy is not associated with early adverse effects on bone density, structure, or turnover, while providing substantial migraine improvement. Ongoing follow-up will determine longer-term skeletal safety. ClinicalTrials.gov, NCT06035458.
This study aimed to investigate whether Sort, Set in order, Shine, Standardize, Sustain, and Safety (6S) refined individualized nursing management improves perioperative outcomes in patients with Parkinson's disease (PD) undergoing deep brain stimulation (DBS). This single-center retrospective cohort study included 96 patients with PD who underwent DBS in our hospital from January 2022 to June 2025. According to the perioperative nursing model implemented during the study period, patients were allocated to either a control group (CG) receiving routine perioperative nursing (n = 48) or a study group (SG) receiving 6S refined individualized nursing management in addition to routine care (n = 48). We compared the operation time, time to first ambulation, postoperative length of stay (LOS), anxiety and depression [self-rating Anxiety Scale / Self-rating Depression Scale (SAS/SDS)], pain [visual analog scale (VAS)], balance [Tinetti Balance and Gait Assessment (POMA)], activities of daily living (Barthel index), complication rates, and nursing satisfaction between groups. Compared to the control group, the study group had a shorter time to first ambulation (13.41 ± 1.51 vs. 14.89 ± 2.74 h) and a shorter postoperative LOS (10.34 ± 0.71 vs. 11.22 ± 0.95 days). After nursing, SAS scores were lower in the study group compared to the control group (21.52 ± 2.15 vs. 30.25 ± 3.06), as well as lower SDS scores (20.25 ± 2.04 vs. 30.26 ± 3.05). Postoperative VAS pain grades were consistently lower in the study group, for example, at 24 h after surgery (1.21 ± 0.12 vs. 2.05 ± 0.21). POMA scores and Barthel index values at discharge were higher in the study group compared to the control group (17.42 ± 1.75 vs. 15.26 ± 1.53 and 63.58 ± 6.45 vs. 60.25 ± 6.05, respectively). The incidence of nursing-recorded complications was lower in the study group than in the control group (2.1% vs. 14.6%), and overall nursing satisfaction was higher as well (97.9% vs. 83.3%). In this single-center retrospective cohort, 6S refined individualized nursing management was associated with faster postoperative recovery, reduced anxiety and depression, improved balance ability and activities of daily living, and fewer nursing-recorded perioperative complications in PD patients undergoing DBS. These findings should be regarded supportive but preliminary, and they require confirmation through larger prospective studies.
Aging is known to influence recovery following spinal cord injury (SCI) however its specific impact on locomotor outcomes remains underexplored. Understanding these age-related differences is critical for developing targeted rehabilitation strategies and improving the translational relevance of SCI research. This systematic review aimed to evaluate the effect of aging on locomotor recovery in animal models of traumatic SCI. A systematic search of MEDLINE and Embase was conducted to identify studies assessing the impact of aging on post-SCI locomotor outcomes. Inclusion criteria encompassed preclinical studies comparing locomotor recovery between young and aged animals following SCI. Extracted data included sample characteristics, SCI model, locomotor outcome measures, timing of evaluation, and key findings. Risk of bias was assessed using the SYRCLE checklist. Of 3,118 unique records screened, nine studies met inclusion criteria. Included animals were grouped into young (mean 2.5 months), intermediate (mean 11.4 months), and aged (mean 21.5 months) categories, with individual ages ranging from 4 weeks to 28 months. Six studies used rats and three studies used mice. In total, more than 340 animals were studied. SCI models included cord contusion (6/9, 66.7%), hemisection (2/9, 22.2%), and clip compression (1/9, 11.1%). Seven (7/9, 77.8%) studies employed the Basso, Beattie, Bresnahan (BBB) locomotor score as the primary outcome measure. Older animals demonstrated significantly lower BBB scores post-injury compared to younger counterparts in 100% (7/7) of studies using this outcome. Other measures of locomotor outcomes included the Basso Mouse Scale, CatWalk, and Digigait. Notably, one study reported that pre-injury and post-injury exercise improved locomotor recovery in aged rats to levels comparable with young rats. Aging is associated with poorer locomotor recovery following traumatic SCI in preclinical models. These findings underscore the importance of age as a biological variable in SCI research and suggest that rehabilitative interventions, such as exercise, may have potential to mitigate age-related deficits. Future studies should seek to define the mechanistic pathways underlying impaired recovery with age and evaluate targeted therapies that enhance neuroplasticity and functional recovery. https://www.crd.york.ac.uk/PROSPERO/view/CRD42022230021.
Safinamide is a selective, reversible monoamine oxidase type B inhibitor (MAO-B inhibitor) used as an adjunct to oral levodopa in patients with Parkinson's disease (PD) experiencing motor fluctuations. Unlike other MAO-B inhibitors, safinamide possesses a dual mechanism of action, combining dopaminergic enhancement through MAO-B inhibition with modulation of abnormal glutamatergic transmission. In clinical practice, safinamide is primarily recognized for its ability to reduce motor fluctuations. However, its pharmacological profile suggests a broader therapeutic potential beyond dopaminergic modulation alone. Randomized controlled trials have shown that safinamide increases daily ON time without worsening troublesome dyskinesia. Nevertheless, reported effects on dyskinesia have generally been modest and inconsistent across studies. Clinical observations from longer-term follow-up and real-world studies suggest that improvements in dyskinesia and certain non-motor symptoms may emerge more gradually than the early motor benefits. Based on this observed pattern, it can be hypothesized that safinamide may exhibit a dual timeline of clinical effects, with early dopaminergic improvements in motor ON time followed by later modulation of dyskinesia and selected non-motor symptoms potentially mediated through glutamatergic mechanisms. On the basis of these pharmacological characteristics and clinical observations, a phenotype-oriented approach to patient selection for safinamide therapy may be considered. In addition, recognizing the potential for a dual timeline of therapeutic effects may help clinicians guide patients' expectations of treatment and interpret treatment response, as well as optimizing follow-up strategies in routine clinical practice.
Subarachnoid hemorrhage (SAH) remains a devastating cerebrovascular disorder in which cerebral vasospasm is a key determinant of secondary injury and outcome. Sex differences are well-documented clinically, women exhibit a higher incidence of aneurysmal SAH and often worse outcomes, but whether biological sex influences vasospasm severity in controlled preclinical settings remains unclear. In a randomized, controlled rabbit model, we investigated sex-specific differences in basilar artery (BA) vasospasm after SAH. Twenty-four New Zealand White rabbits (12 male, 12 female) were allocated to Control, SHAM, or SAH groups. SAH was induced by cisterna magna injection of autologous blood; SHAM animals received saline. On Day 7, BA segments were harvested for quantitative assessment of vasospasm using the Vasospasm Index (VSI: wall area/lumen area) and blinded qualitative histopathological scoring of smooth muscle contraction, endothelial integrity, internal elastic membrane configuration, and adventitial thickness. Nonparametric statistical tests were used, with male vs. female comparison in SAH as the primary endpoint. Control and SHAM animals showed no significant sex differences in VSI (Control: p = 0.47; SHAM: p = 0.06). In contrast, SAH induced severe vasospasm in males (VSI 2.34 ± 0.63) compared with moderate vasospasm in females (1.27 ± 0.49, p < 0.001). Histopathology corroborated these findings, with severe endothelial disruption and smooth muscle hypercontraction in males versus moderate alterations in females. Male rabbits exhibited significantly more severe vasospasm than females after SAH, despite human epidemiology suggesting greater vulnerability in women. These results demonstrate sex as a fundamental biological variable in SAH pathophysiology and underscore the need for mechanistic studies exploring hormonal, autonomic, and inflammatory mediators. Incorporating sex into experimental design may ultimately inform sex-specific therapeutic strategies for SAH.
First-line serotonergic antidepressants achieve clinical response in approximately 60-65% of patients with persistent postural-perceptual dizziness (PPPD), leaving a substantial refractory population. Aripiprazole, a serotonin-dopamine modulator with partial D2 and 5-HT1A agonism and 5-HT2A antagonism, may address dopaminergic and emotional dysregulation insufficiently controlled by serotonergic agents alone. This study evaluated the preliminary efficacy and tolerability of aripiprazole as second-line pharmacotherapy in patients with refractory functional dizziness disorders, including PPPD. We retrospectively reviewed 16 patients (6 men, 10 women; mean age 50 ± 16.1 years) with refractory dizziness disorders, including PPPD (n = 9), psychogenic dizziness (n = 4), vestibular migraine (n = 2), and Ménière's disease (n = 1), who received aripiprazole (1.5-3.0 mg/day) after insufficient response to first-line antidepressants. The primary outcome was treatment response based on the Clinical Global Impression-Improvement scale (CGI-I; score 1-3 defined as improvement). Secondary outcomes included changes in Dizziness Handicap Inventory (DHI), Niigata PPPD Questionnaire (NPQ), and foam posturography in evaluable patients. CGI-I response was observed in 12 of 16 patients (75.0%). Four patients were non-responders, and one discontinued treatment because of extrapyramidal adverse effects. In patients with available questionnaire data (n=4-5), DHI and NPQ scores improved after treatment. Foam posturography showed no significant changes. In this pilot retrospective series, aripiprazole demonstrated promising preliminary efficacy as a second-line treatment for refractory functional dizziness disorders. Its multimodal serotonin-dopamine mechanism may target symptoms insufficiently controlled by serotonergic agents alone. Given the small sample size and uncontrolled design, these findings should be considered hypothesis-generating. Prospective controlled studies are warranted.
Characterizing hyperkinetic Movement Disorders (MD) in children is challenging, particularly when distinguishing tremor from myoclonus. Polymyography (EMG combined with accelerometry) and EEG jerk-locked back-averaging are well-established diagnostic tools in adults but are rarely applied in paediatric population. This study aimed to assess the feasibility and contribution of individualized neurophysiological investigations to the classification of hyperkinetic MD in children. We retrospectively reviewed clinical and neurophysiological data from consecutive patients who underwent polymyography over a two-year period being referred for unclear clinical MD phenomenology. A pediatric MD specialist and a neurophysiologist jointly performed evaluations. 56/60 patients were included (four were excluded due to absent MD during recording or lack of cooperation). Myoclonus was the most frequent polymyography diagnosis (55%), followed by tremor (36%). Initial clinical diagnoses were confirmed in 62% of cases: all suspected cases of myoclonus were validated, whereas 48% patients initially diagnosed with tremor were reclassified as having myoclonus. Polymyography revealed additional MD in 18% of patients, most often myoclonus, and supported a neurofunctional aetiology in one case. After the polymyography, symptomatic pharmacological treatment-mainly for tremor and cortical myoclonus-was proposed in 34%. Additional genetic investigations were suggested in 30% of patients. Polymyography proved feasible even in young children, including those with intellectual disability. Combined with expertise of an MD specialist, polymyography significantly improves diagnostic accuracy, particularly tremor vs. myoclonus, and guides both aetiologic and therapeutic management. These findings highlight the value of integrating polymyography into paediatric MD evaluation.
Neuropathic pain (NP) arises from injury or dysfunction within the somatosensory nervous system and represents a major clinical challenge due to its complex and multifactorial pathogenesis. Emerging evidence underscores that the onset and maintenance of NP are not solely governed by neuronal mechanisms but are critically shaped by the persistent activation and inherent heterogeneity of glial cells. Glial heterogeneity encompasses diverse molecular phenotypes, functional states, and distinct spatial distributions. Within the central nervous system (CNS), microglia and astrocytes undergo dynamic phenotypic transitions, contributing to both neurotoxic and neuroprotective effects by modulating neuroinflammatory cascades. In the peripheral nervous system, satellite glial cells actively sensitize sensory neurons through enhanced intercellular communication and the release of specific mediators, thereby facilitating the development and persistence of NP. The coordinated actions of heterogeneous glial populations drive key pathological processes-including synaptic remodeling, sustained neuroinflammation, and dysregulation of ion channels-ultimately promoting peripheral and central sensitization. Importantly, emerging therapeutic strategies targeting distinct glial subpopulations or their specific activation states, such as P2X4 receptor antagonists or NF-κB inhibitors, have shown promise beyond conventional neuron-centric approaches. This review synthesizes current insights into glial heterogeneity in NP, addressing a critical gap in the literature and providing a framework for advancing mechanism-based clinical interventions.
In Germany, approximately 23.000 individuals require home-based intensive care (HIC) provided by specialized nurses due to life-threatening conditions such as invasive ventilation, life-supporting noninvasive ventilation, or the presence of tracheal tubes requiring tracheobronchial suctioning. The current study's objective was to characterize individuals receiving home-based intensive care from a private German provider to inform healthcare structures and clinical practice guidelines. On June 12, 2024, the quality management department of a private German home-based intensive care service collected cross-sectional data on all individuals receiving home-based intensive care. Data from 851 individuals were collected, of which 511 (60%) were sixty years or older. Three hundred and thirty two individuals (39%) were female and 519 (61%) were male. Seven hundred and thirty four individuals (86%) were living in shared apartments and 117 (14%) lived at home with 24 h individual nursing care. Six hundred and eighty two individuals (80%) suffered from various neurological diseases, 116 (14%) from COPD, and 30 (4%) from oral, pharyngeal or laryngeal cancer. Twenty seven individuals (3%) had been admitted to HIC after a COVID-19 infection. Seven hundred and forty one individuals (89%) were tracheostomized, 220 (26%) needed invasive ventilation, 44 (5%) noninvasive ventilation and 14 (2%) hemodialysis. In Germany, neurological diagnoses and COPD are predominant in HIC. Most individuals are tracheostomized, and one in four requires invasive ventilation via tracheostomy. They also require multidisciplinary care by neurologists, pulmonologists, specialist nurses, respiratory therapists, speech-and-language therapists, physiotherapists, occupational therapists and other professionals. Neurological rehabilitation of individuals needing HIC should be established.
Delirium remains a prevalent and serious complication in intensive care units (ICUs), yet the translation of evidence-based monitoring and management into routine nursing practice faces persistent implementation gaps. Sustainable and scalable educational strategies are urgently needed to address this challenge. This study employed a mixed-methods approach to comprehensively evaluate the impact of a train-the-trainer (TTT) delirium education program using a multidimensional outcome framework. Quantitatively, we assessed changes in ICU nurses' competencies across the learning, behavior, and results levels of the Kirkpatrick model. Qualitatively, we explored the underlying experiential mechanisms and contextual drivers to explain the quantitative outcomes and inform program optimization. A mixed-methods quasi-experimental study with an embedded qualitative component was conducted in a tertiary ICU in China. Forty-seven nurses participated in the TTT program. Quantitative data acquisition included validated instruments for delirium knowledge assessment, standardized clinical simulation evaluations using the CAM-ICU tool, and the General Self-Efficacy Scale, collected at baseline and three months post-intervention. For qualitative data acquisition, semi-structured interviews were conducted with 12 purposively sampled nurses to explore experiential learning trajectories, behavioral drivers, and implementation barriers. Thematic analysis was guided by Social Cognitive Theory and performed using systematic coding procedures. Quantitative analysis revealed statistically significant improvements across all outcome metrics: delirium knowledge scores (p < 0.05), clinical assessment accuracy (p < 0.05), and self-efficacy (p < 0.001). Qualitative analysis identified four core thematic patterns: (1) Experiential learning trilogy-simulation, practice, and teaching; (2) From experience to evidence-the construction of clinical confidence; (3) Environmental forces-barriers and facilitators in practice implementation; and (4) Systemic spillover effects-enhanced interprofessional communication and recognition of hypoactive delirium. Nurses also provided actionable recommendations for training optimization, notably the need for standardized video resources to ensure content consistency. The TTT program significantly enhanced ICU nurses' delirium care competencies, driven by simulation-based practice, repeated application, and peer teaching. Contextual challenges and the need for standardized video resources inform future implementation and fidelity considerations. This study provides a feasible, scalable framework for evidence-based delirium care.
Immobilized neurosurgical patients are at high risk for deep vein thrombosis (DVT). While routine prophylaxis exists, a systematic, nurse-led bundle of care may offer a more comprehensive and effective approach to prevention. To evaluate the effectiveness of a nurse-led, multifaceted bundled care intervention on the incidence of DVT, patient compliance, and clinical outcomes in immobilized neurosurgical patients. This quasi-experimental study with a historical control group was conducted in the Department of Neurosurgery, Xichang People's Hospital. Adult neurosurgical patients requiring immobilization for at least 72 h were enrolled. The control group (n = 1,163, recruited January 2021-September 2022) received standard neurosurgical care. The intervention group (n = 1,625, recruited January 2023-December 2024) received a nurse-led bundled care protocol consisting of: (1) dynamic Caprini risk assessment; (2) standardized mechanical prophylaxis with graduated compression stockings (GCS) and intermittent pneumatic compression (IPC); (3) structured health education; and (4) individualized early mobilization. The primary outcome was symptomatic ultrasound-confirmed DVT incidence. Secondary outcomes included compliance, DVT-related knowledge, limb circumference difference, pain scores (Visual Analogue Scale, VAS), and patient satisfaction. Multivariable logistic regression was used to adjust for potential confounders. Baseline characteristics were comparable between groups. The incidence of DVT was significantly lower in the intervention group (1.66% vs. 2.75%, p = 0.041). Intervention group patients demonstrated significantly higher compliance with GCS/IPC use (76.5% vs. 58.1%, p < 0.001) and early mobilization (72.1% vs. 51.5%, p < 0.001), as well as significantly greater DVT-related knowledge (85.2 ± 8.5 vs. 62.1 ± 10.2, p < 0.001). The intervention group showed significantly greater reduction in limb circumference difference (1.2 ± 0.8 cm vs. 2.1 ± 1.1 cm, p < 0.001) and lower pain scores (2.3 ± 1.2 vs. 4.1 ± 1.6, p < 0.001). Patient satisfaction was significantly higher in the intervention group (94.1 ± 3.3 vs. 85.6 ± 4.8, p < 0.001). Pulmonary embolism (PE) incidence was low in both groups (0.12% vs. 0.17%, p = 0.715). After adjustment for age, sex, diagnosis, type of surgery, Caprini score, pharmacological prophylaxis, and calendar year, the intervention remained independently associated with lower DVT risk (adjusted OR = 0.54, 95% CI 0.32-0.92, p = 0.023). This nurse-led bundled care intervention was associated with a significantly lower DVT incidence and improved clinical outcomes in immobilized neurosurgical patients. The protocol's structured, evidence-based approach provides a practical model for VTE prevention in neurosurgical settings.
Gait disorder and cognitive dysfunction are the most common symptoms in patients with cerebral small vessel disease (CSVD), significantly impacting patients' quality of life. Currently, there remains a lack of effective treatment for gait disorder and cognitive dysfunction of CSVD. In this randomized, single-blind, sham-controlled study, we conducted high-dose accelerated intermittent theta burst stimulation (aiTBS) in 36 patients with CSVD to investigate the efficacy and safety of high-dose aiTBS targeting the primary motor cortex (M1 area) for treating various symptoms of CSVD, particularly gait and cognitive function. The patients were randomly assigned to two groups of real (n = 19) or sham (n = 17) aiTBS targeting the primary motor cortex. Both groups received 14 consecutive sessions of real-aiTBS or sham-aiTBS. Primary outcome was the change of 3-meter Timed Up and Go (3mTUG) duration, assessed at baseline (T0) and immediately post-intervention (T1), with follow-up evaluations at 4 weeks after intervention (T2). Secondary outcomes included changes in the Tinetti Performance-Oriented Mobility Assessment (Tinetti) score, the Chinese version of the Mini-Mental State Examination (CMMS) score, the Montreal Cognitive Assessment (MoCA) score, three-dimensional gait analysis, and multidimensional function scale scores after intervention. Compared to the sham-aiTBS group, the real-aiTBS group exhibited significantly greater improvements in multidimensional gait, cognitive, affective and autonomic nervous function assessments. At the 4-week follow-up, time effects were statistically significant for the 3mTUG duration, Tinetti, CMMS, and MoCA scores. The real-aiTBS group exhibited more pronounced group-by-time interaction effects for the 3mTUG duration, Tinetti, and CMMS scores, while no statistically significant differences from the sham-aiTBS group were observed for the MoCA score. The aiTBS intervention response is correlated to the CSVD neuroimaging features, including periventricular white matter hyperintensity, enlarged perivascular space, cortical atrophy, lacune and total CSVD burden score. The aiTBS holds promise as a valuable therapeutic approach for CSVD. High-dose aiTBS targeting the M1 area improved clinical symptoms such as gait and cognitive disorder in patients with CSVD. The therapeutic response to aiTBS in CSVD patients is related to the CSVD neuroimaging phenotypes.
Stroke is a leading cause of death and long-term disability worldwide. Most survivors develop multiple functional impairments, with lower limb dysfunction being particularly prevalent and impactful, and has emerged as a key factor undermining patients' quality of life. Electromagnetic stimulation therapy, a potential intervention for post-stroke lower limb rehabilitation, remains controversial regarding its clinical efficacy in current literature. Furthermore, no definitive conclusions exist regarding the comparative advantages of distinct electromagnetic stimulation protocols. Given these controversies and uncertainties, this study aims to perform a network meta-analysis (NMA) to systematically assess the effects of distinct electromagnetic stimulation protocols on post-stroke lower limb motor function. This analysis further aims to quantify differences in clinical benefits across these protocols and characterize their safety profiles, thereby offering evidence-based guidance for clinical decision-making. We will conduct a systematic search of the following eight databases: PubMed, Embase, the Cochrane Library, Web of Science, CNKI, the VIP Database, the Wanfang Database, and the China Biomedical Literature Database. The search will encompass randomized controlled trials published from the inception of each database until February 15, 2025. Subsequently, two independent reviewers will assess the risk of bias for all included studies using the Cochrane Risk of Bias tool (RoB 2). We will then perform an NMA using a random-effects model in Stata software to compare the efficacy and safety of various electrical stimulation therapies. The surface under the cumulative ranking curve (SUCRA) will be calculated to estimate the comparative benefits and harms of each intervention. This evaluation protocol aims to generate evidence on the efficacy of various electromagnetic stimulation regimens for improving clinical symptoms in patients with post-stroke lower limb dysfunction. This evidence will thereby provide a theoretical foundation and practical insights to aid clinicians in optimizing diagnostic and therapeutic decision-making. https://www.crd.york.ac.uk/, identifier [CRD420251247508].
Post-stroke pharyngeal dysphagia (PSD) frequently leads to aspiration, aspiration pneumonia, and malnutrition, significantly compromising patient outcomes. Although standard swallowing rehabilitation training is widely applied, many patients show slow recovery with prolonged nasogastric tube placement. Recently, neuromodulation techniques such as vagus nerve magnetic stimulation (VNMS) have shown promise; however, observational evidence supporting its real-world clinical efficacy in post-stroke dysphagia patients remains limited. This single-blind prospective observational cohort study was conducted from June 2024 to June 2025 at Guangdong Sanjiu Brain Hospital, China. A total of 78 stroke patients with dysphagia were enrolled (33 in intervention group, 45 in control group). The intervention group received left-sided VNMS combined with standard swallowing rehabilitation training, while the control group received standard training alone. Multiple confounder adjustment and causal inference approaches were applied to ensure the robustness of the results. Among 78 patients, after confounder adjustment, the intervention group demonstrated a significantly higher nasogastric tube removal rate, with an adjusted hazard ratio of 1.850 (95% CI: 1.103-3.101, p = 0.021). The intervention group removed nasogastric tubes on average 3.75 days earlier than the control group (95% CI: -5.01 to -2.50, p = 0.000), and the direction of effect was consistent across all analyses. Although swallowing safety assessment showed initial improvement, effects on overall swallowing function were inconsistent across analyses. In this prospective observational cohort, left-sided VNMS significantly accelerated nasogastric tube removal in post-stroke dysphagia patients, with an average advancement of 3.75 days. However, the improvement in swallowing physiological parameters was inconsistent, suggesting that VNMS's effects may be primarily concentrated on functional outcomes. Long-term efficacy and optimal candidate populations require further investigation. Randomized controlled trials are recommended to verify causal relationships and confirm clinical utility.