XinHua Hospital

Lower extremity nerve decompression (LEND) for painful diabetic peripheral neuropathy (PDPN) remains controversial, and evidence regarding its long-term effectiveness in real-world clinical practice is limited. This retrospective real-world cohort study included patients with PDPN treated with LEND or medical therapy alone between 2008 and 2011. Ultra-long-term outcomes were assessed after > 10 years of follow-up. Pain intensity was evaluated using the visual analogue scale (VAS). Composite pain burden and functional impact were assessed with the Brief Pain Inventory for Diabetic Peripheral Neuropathy (BPI-DPN). Psychological symptoms were measured using the Hospital Anxiety and Depression Scale (HADS), and analgesic medication burden was quantified by the Medication Quantification Scale III (MQS-III). Exploratory prognostic factor and subgroup analyses based on pain distribution were performed. Seventy-six patients in the LEND group and 31 patients in the medical group were available for ultra-long-term analysis. Compared with medical management, LEND was associated with greater long-term pain relief (mean VAS change - 5.63 ± 2.16 vs - 1.03 ± 1.92; p < 0.001) and higher responder rates (≥ 50% pain reduction: 65.8% vs 9.7%; p < 0.001). Significant long-term improvements were also observed in BPI-DPN pain severity and pain interference (both p < 0.001), anxiety and depression symptoms (both p < 0.001), and medication burden (MQS-III p < 0.001). Within the LEND cohort, younger age at surgery and lower body mass index were independently associated with greater long-term pain improvement. Both focal and diffuse pain subgroups demonstrated significant improvements in pain and functional outcomes after surgery, with no meaningful differences at ultra-long-term follow-up. Diabetic foot ulcer events occurred less frequently after LEND (0% vs 32.3%; p < 0.001). LEND demonstrated long-term efficacy in alleviating pain and concurrently improving the pain-related interference and psychological status of patients with PDPN. A Graphical Abstract is available for this article. This study was retrospectively registrated in Chinese Clinical Trial Registry chictr.org. cn (ChiCTR2500099348), https://www.chictr.org.cn/bin/project/edit?pid=266042 .

To address the current lack of standardized protocols for vestibular infant screening (VIS), this clinical consensus aims to establish a clinical consensus on VIS in infants aged 0-12 months. Given a frequent co-occurrence of vestibular dysfunction in children with sensorineural hearing loss (SNHL) and the significant impact of vestibular dysfunction on early development, early identification and management are critical. This clinical consensus was developed by a panel of 28 international experts in pediatric otolaryngology and vestibular disorders through a structured, multi-round Delphi process. Panelists were selected based on clinical and academic expertise, representing 26 institutions across Asia and Europe. A comprehensive literature review (2000-2024) informed the initial draft of consensus statements. The consensus was reached through three iterative rounds of anonymous rating and feedback, followed by virtual discussions. Statements achieving ≥ 80% agreement were retained in the final consensus, which focused on screening tools, target populations, optimal timing, and standardized cVEMP recording protocols for infants. The expert panel reached consensus on key recommendations in four domains: screening tool, target screening population, timing of vestibular function screening, and recording protocol for cervical vestibular evoked myogenic potential (cVEMP). This clinical consensus provides foundational guidance for the implementation of VIS in infants, advocating for standardized protocols to improve early diagnosis and intervention. Widespread adoption of these recommendations may enhance developmental outcomes by enabling timely detection and management of vestibular dysfunction in early childhood.

Coronary microvascular dysfunction (CMD) is a major contributor to cardiovascular complications in diabetes. Although noninvasive techniques such as arterial spin labeling cardiac MRI (ASL-MRI) and transthoracic echocardiography (TTE) are available, their comparative performance for CMD remains unclear. To compare ASL-MRI and TTE for CMD assessment in type 1 and type 2 (T1DM, T2DM) mouse models and relate functional indices to histological microvascular and myocardial remodeling, including early-stage T2DM (8w-T2DM). Prospective. Forty 8-week-old male C57BL/6J mice allocated to five groups: control, T1DM, and T2DM (n = 10 per group, imaged 16 weeks postinduction), and early-stage T2DM (8w-T2DM) and age-matched controls (n = 5 per group, imaged 8 weeks post-induction). Segmented FLASH cine, steady-pulsed labeling ASL, and inversion-recovery segmented FLASH (T1 mapping) sequences at 9.4 T. Rest/stress myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) were derived from ASL data using a model-based approach incorporating native T1 (from segmented FLASH data). Coronary flow velocity (CFV) and reserve (CFVR) were measured by TTE at rest (1.5% isoflurane) and stress (2.5% isoflurane). Histology included assessment of hematoxylin-eosin (myocyte area), Masson (collagen), and IB4 (capillary density). Group comparisons used t-tests, Mann-Whitney U tests, and one-/two-way ANOVA with Bonferroni correction; correlations were assessed with Pearson or Spearman coefficients (r). p < 0.05 was considered significant. 38 animals completed MR and TTE imaging. At 16 weeks, stress diastolic MBF was significantly lower in T1DM (14.67 ± 1.62 mL/g/min) and T2DM (13.42 ± 2.44 mL/g/min) vs. controls (22.19 ± 0.25 mL/g/min), with significantly reduced MPR in T2DM (1.53 ± 0.17 vs. 2.27 ± 0.15). TTE showed significantly reduced CFVR only in T2DM (2.16 ± 0.24 vs. 2.75 ± 0.24). In 8w-T2DM, ASL-MRI detected significantly reduced MPR (1.87 ± 0.16 vs. 2.26 ± 0.13), whereas TTE showed no significant CFVR change (p = 0.900). Capillary density significantly decreased in 16-week and 8-week T2DM. IB4-positive area correlated with CFVR (r = 0.673) and more strongly with MPR (r = 0.810). ASL-MRI detected CMD in diabetic mice, outperforming TTE in early-stage disease and showing a strong association with microvascular injury. 1. Stage 2.

Natural bone is an intrinsically piezoelectric and mechanosensitive tissue that converts mechanical stimuli into bioelectrical signals regulating bone development and regeneration. However, most existing in vitro bone models fail to recapitulate this electromechanical behavior, as current studies have largely focused on piezoelectric materials for bone repair rather than mechanical stress transmission and its piezoelectric regulation during bone development. Bone organoids have emerged as advanced three-dimensional models provides an opportunity to address this limitation, yet the electromechanical dimension of bone organoid engineering has not been systematically examined. This review advances the central argument that piezoelectric mechanosensing represents a missing but essential biophysical axis in bone organoid development. From this perspective, the piezoelectric characteristics of native bone and their roles in osteogenesis are first summarized, followed by an integrated analysis of signaling pathways activated by piezoelectric stimulation. Representative piezoelectric materials are then evaluated based on their capacity to support force-electric transduction within bone organoid systems. Finally, piezoelectric behavior-guided strategies and remaining challenges in engineering electromechanically active bone organoids are discussed. By reframing bone organoids as electromechanically regulated systems rather than purely biochemical constructs, this review provides a conceptual foundation for studying bone development under piezoelectric conditions.

Variants in OTUD5 are associated with neurodevelopmental disorders (NDDs), yet the underlying molecular mechanisms remain unclear. This study aimed to investigate the pathogenicity of a novel OTUD5 variant (c.697G > A, p.Val233Met) and elucidate its regulatory role in neural progenitor cell (NPC) proliferation and differentiation, thereby uncovering the function of OTUD5 in neurodevelopment. The OTUD5 variant was identified in two NDD patients via exome sequencing. Patient-derived induced pluripotent stem cells (iPSCs) and CRISPR/Cas9-corrected isogenic controls were generated. NPC proliferative activity was assessed by Ki67 immunofluorescence staining, cell-cycle distribution was analyzed by flow cytometry, and neuronal differentiation was evaluated by Tuj1/MAP2 immunofluorescence staining. Substrate screening was conducted in HEK293T cells using co-immunoprecipitation (Co-IP) and mass spectrometry. Deubiquitination capacity and protein stability were validated through ubiquitination assays and cycloheximide (CHX) chase experiments. The p.Val233Met variant, located within the catalytic OTU domain, induced a marked conformational alteration in the OTUD5 protein. Functionally, the variant caused aberrant NPC proliferation (1.8-fold increase in Ki67+ cells, accompanied by release of G1 arrest) and impaired neuronal differentiation (60% reduction in Tuj+ cells). Mechanistically, wild-type OTUD5 stabilized GSK3β by removing K48-linked ubiquitin chains, whereas the mutant isoform exhibited diminished deubiquitinase activity, accelerating GSK3β degradation and shortening its half-life by 40%. This study establishes a novel disease mechanism whereby OTUD5 mutations disrupt NPC homeostasis through GSK3β destabilization, highlighting the critical role of ubiquitination regulation in neurodevelopment. Our iPSC model provides a platform for testing GSK3β-targeted therapies in OTUD5-related NDDs.

This study aimed to investigate the characteristics of body composition, core symptoms, functional impairment, and comorbidities in children with attention-deficit hyperactivity disorder (ADHD) and sarcopenia. A case-control study compared children with ADHD and sarcopenia (n = 85) with matched ADHD-only controls (n = 85). Comprehensive evaluations included body composition analysis and standardized behavioral assessments (SNAP-IV, Vanderbilt, WFIRS). Compared to the control group, the ADHD with sarcopenia group exhibited significantly lower values on total body water, protein, minerals, body fat mass, fat-free mass, bone mineral content, body mass index, fat mass index, and fat-free mass index (False Discovery Rate (FDR) corrected P < 0.05), while exhibiting higher muscle-to-fat ratio. They also demonstrated lower ADHD core symptom severity, decreased comorbidity proportion (including oppositional defiant disorder [ODD]), and impaired family function (FDR corrected P < 0.05). Regression analysis identified hyperactive-impulsive symptom severity (OR 3.97, 95% CI:2.22-7.12) and increased soft lean mass (SLM) (OR 1.13, 95% CI:1.05-1.21) as predictors of comorbid ODD risk. ADHD children with sarcopenia had lower body composition values, milder core symptoms, and fewer comorbidities (including ODD). SLM and hyperactive-impulsive symptoms exhibited positive associations with comorbid ODD risk in children with ADHD. Children with ADHD and sarcopenia show skeletal muscle wasting alongside declines in fat mass, protein content, and bone mineral content compared with the control group (children with ADHD without sarcopenia). The ADHD-sarcopenia group (participants with both ADHD and sarcopenia) had significantly lower ADHD core symptom scores (inattention and hyperactivity-impulsivity) and a reduced comorbidity proportion. Hyperactivity-impulsivity symptoms and soft lean mass increased the risk of comorbid oppositional defiant disorder in children with ADHD.

Metachronous bilateral conversion in initially unilateral retinoblastoma is uncommon but clinically consequential, potentially requiring intensified treatment and carrying worse prognosis. Clarifying how age at diagnosis refines genetic-risk stratification could enable safer, more efficient surveillance protocols. To estimate the incidence and timing of metachronous bilateral conversion in unilateral retinoblastoma and assess whether age at diagnosis and RB1 testing are associated with bilateral conversion risk. This was a retrospective cohort study at a tertiary center in Shanghai, China, including 1108 consecutive children with initially unilateral retinoblastoma diagnosed from July 2010 to October 2024 (after exclusions for short follow-up [n = 139], missing data [n = 53], or synchronous bilateral disease [n = 10]). The median (IQR) follow-up was 43.4 (24.2-67.6) months. Age at diagnosis and RB1 genetic status/subtypes assessed by next-generation sequencing and multiplex ligation-dependent probe amplification, including penetrance class (high vs low) and mosaic vs germline categorization. Time to metachronous bilateral conversion; cumulative incidence functions with death as a competing risk; spatial distribution of fellow-eye tumors. Among 1108 patients (median [IQR] age at diagnosis, 22.2 [12.0-31.4] months; 591 [53.3%] male), 24 (2.2%) developed metachronous bilateral disease. At 24 months, cumulative incidence was 2.2% (95% CI, 1.3-3.1) overall. By genetic status, the 24-month cumulative incidence was 24.8% (95% CI, 13.8-35.9) in RB1 variant-positive vs 1.6% (95% CI, 0.0-3.1) in RB1 variant-negative patients. Among RB1 variant-positive patients, risk clustered among those diagnosed before 9 months, whereas no conversions were observed among those diagnosed at older than 9 months. Four RB1 variant-negative patients who were initially diagnosed at notably late ages (20.9, 42.7, 79.6, and 118 months) subsequently converted; these cases likely represent undetected low-level mosaicism, somatic variants below detection thresholds, or rare genomic events not captured by standard sequencing panels. Fellow-eye tumors did not involve macula and showed a nasal-predominant distribution. The findings in this study suggest that age at diagnosis may refine genetic risk stratification for metachronous bilateral conversion. RB1 variant-positive patients diagnosed at 9 months or later represent a very low-risk subgroup that may warrant surveillance deescalation, while rare late conversions in RB1 variant-negative patients necessitate continued long-term monitoring.