Search Results (293)

Background: 5q spinal muscular atrophy (SMA) is a hereditary neuromuscular disorder characterized by progressive muscle weakness. Nusinersen, the first disease-modifying therapy for SMA, has demonstrated efficacy in both clinical trials and real-world studies. However, the precise timing of therapeutic onset following Nusinersen administration remains unclear. Methods: This retrospective study analyzed clinical data from patients with genetically confirmed 5q SMA who received Nusinersen treatment for at least six months at Peking University First Hospital. Motor function was assessed using standardized scales prior to each dose. Results: In total, 74 patients were screened, of whom 62 were enrolled, including 14 with type 1, 29 with type 2, and 19 with type 3 SMA. Thirty-two patients completed motor function assessments. After six months of treatment, 62.5% achieved a primary clinically meaningful response (an increase of ≥4 points in CHOP-INTEND or ≥3 points in HFMSE). Seven patients (21.9%) attained or regained motor milestones. Median improvements were 6 points in CHOP-INTEND (p = 0.001), 4 points in HFMSE (p = 0.003), and 1.5 points in RULM (p = 0.045). Further analysis indicated that the available median time to treatment response was approximately 2 months. In patients with severe scoliosis or prior spinal surgery, ultrasound-guided lumbar puncture demonstrated a high success rate (94.9%). Regarding safety, intrathecal injection-related adverse events occurred in eight patients (12.9%), and no adverse events led to treatment discontinuation. Conclusions: During the loading phase, Nusinersen provides clinical benefit for the majority of patients, with a median time to therapeutic response for monitoring of approximately 2 months. Ultrasound-guided intrathecal administration is the preferred approach for individuals with complicated spinal conditions. These findings may help guide clinical expectations for physicians, patients, and caregivers. Full article

Background/Objectives: Establishing laparoscopic access remains a critical and complication-prone step in minimally invasive surgery. Previous work has shown that proximal vibroacoustic sensing can identify peritoneal puncture events in porcine cadavers. The present pilot study evaluated whether these findings translate to human anatomy under controlled, ex vivo conditions. Methods: A vibroacoustic sensing prototype was proximally attached to a standard Veress needle during 14 insertions into a fresh human body donor (within 48 h post-mortem). An endoscope was introduced laterally to provide visual ground truth of peritoneal entry. Vibroacoustic signals were recorded at the proximal end of the instrument. Time–frequency analyses, transient excitation detection, and statistical comparisons were performed to assess whether (1) peritoneal puncture can be identified in the vibroacoustic signal, (2) signal phases and dynamics correspond to those previously observed in porcine cadavers, and (3) peritoneal punctures can be statistically differentiated from non-peritoneal events. Results: All 14 peritoneal punctures were identifiable in the vibroacoustic signal under the experimental conditions. Characteristic signal phases previously described in porcine tissue, including transient excitation associated with cavity entry, were consistently reproduced with comparable temporal and spectral profiles. Statistical analyses demonstrated group-level differences between peritoneal and non-peritoneal events, and the peritoneal puncture was the highest-energy event of its insertion in 13 of 14 cases (92.9%). Conclusions: Under the controlled ex vivo conditions of this single-donor pilot study, vibroacoustic sensing was feasible for identifying peritoneal puncture in human tissue and reproduced signal dynamics observed in porcine models. To our knowledge, this is the first demonstration of the proximal vibroacoustic sensing concept on a human body donor and the first cross-species replication of the previously reported puncture phase structure, establishing an important translational stepping stone between animal cadaver studies and in vivo investigations. The study demonstrates feasibility rather than clinical reliability: the single-donor design and the retrospective annotation framework limit generalizability. Prospective validation in living patients, across multiple subjects and operators, is required before clinical deployment. Full article

Background/Objectives. Pulmonary arterial hypertension (PAH) is a rare but severe disease which leads to right ventricular (RV) maladaptation, failure and death. Currently approved drugs have limited impact on disease progression. A multitarget strategy consisting of adenosine A₂B receptor activation and phosphodiesterase-4 (PDE4) inhibition, combined with human mesenchymal stromal cells (hMSCs) therapy, was tested in experimental PAH. The main objective was to determine whether the combination improved pulmonary hemodynamics, vascular remodeling, and RV function, given the limited disease-modifying effects of currently approved vasodilators. Methods. Vascular reactivity was assessed in isolated rat pulmonary artery rings exposed to the dual-target compound (LASSBio-1860) alone or in the presence of either ZM-241385 or MRS-1706. PAH was induced in male Wistar rats with monocrotaline (MCT, 60 mg·kg⁻¹) and confirmed by a decrease in pulmonary artery acceleration time to ejection time ratio (PAAT/TET). Animals were randomized to receive vehicle, hMSC (single i.v. dose, 1 × 10⁵ cells), LASSBio-1860 (62 mg·kg⁻¹·day⁻¹, p.o., 14 days), or their combination. Outcomes included PAAT/TET and RV cardiac output (RV-CO) by echocardiography, RV systolic pressure (RVSP) by direct puncture, Fulton index and RV wall thickness, lung histology (perivascular cell counts and wall thickness), and RV protein expression (TGF-β, CaMKII) by Western blot. Results. LASSBio-1860 produced endothelium-independent vasorelaxation of rat pulmonary arteries, consistent with A₂B agonism and PDE4 inhibition. In MCT-induced PAH, combination of LASSBio-1860 and hMSCs resulted in recovery of PAAT/TET and RV-CO, decrease in RVSP, RV hypertrophy, vascular inflammation and remodeling by downregulation of ventricular TGF-β and CaMKII. Conclusions. Combination of LASSBio-1860 with hMSC improved RV function, attenuated pulmonary hypertension, RV and vascular remodeling, and reduced inflammatory/proliferative signaling in MCT induced-PAH, supporting a promising multitarget therapeutic strategy for PAH. Full article

Meningitis multiplex PCR (MMP) panels are increasingly used in acute bacterial meningitis (ABM), but their clinical integration remains incompletely characterized. We evaluated MMP panel implementation using a mixed-methods approach. We included 55 adults with ABM of confirmed etiology: Group 1 (MMP plus conventional microbiology, n = 25) and Group 2 (conventional methods only, n = 30). The qualitative component comprised semi-structured interviews with infectious disease specialists, analyzed using thematic analysis. Compared with Group 2, Group 1 had a significantly shorter time from lumbar puncture to diagnosis [1.9 (IQR 1.7–2.6) vs. 27.3 (18–47.2) h] and more frequent targeted therapy [19 (76%) vs. 13 (43.3%)]. However, MMP panel use was not associated with antibiotic de-escalation [11 (44%) vs. 12 (40%)], median length of hospitalization (22 days in both groups), median duration of therapy [14 (10–21) vs. 17 (11–22) days], ICU admission [11 (44%) vs. 13 (43.3%)], or mortality [2 (8%) vs. 6 (20%)]. Interviews (n = 20) identified four themes: rapid etiological clarification, perceived limitations, antimicrobial optimization and clinical integration. MMP may facilitate rapid diagnosis, but its impact on outcomes and clinical integration remains limited. Faster availability of etiological information does not necessarily improve antimicrobial decision-making in the absence of antimicrobial stewardship programs. Full article

Background/Objectives: Sepsis-induced systemic inflammation often leads to diaphragmatic dysfunction and muscle atrophy, contributing to impaired respiratory function. Phosphoglycerate mutase 2 (PGAM2), a key enzyme in glycolysis, plays a significant role in muscle energy metabolism but has not been previously linked to sepsis-induced diaphragmatic dysfunction. This study aims to investigate the role of PGAM2 in sepsis-induced diaphragmatic atrophy and its underlying mechanisms. Methods: A murine sepsis model was established using cecal ligation and puncture (CLP) in C57BL/6 mice. Body and diaphragm weights, along with muscle fiber cross-sectional areas, were measured. PGAM2 expression was evaluated using immunofluorescence, Western blotting, and real-time quantitative polymerase chain reaction (RT-qPCR). In vitro, C₂C₁₂ myotubes were treated with tumor necrosis factor alpha (TNF-α), and PGAM2 expression was manipulated via small interfering RNA (siRNA) knockdown and plasmid overexpression. Atrophy markers (MuRF1, MAFbx/atrogin-1) and JAK2/STAT3 pathway activation were assessed. Results: CLP induced significant diaphragmatic atrophy, as reflected by an approximately 38% reduction in diaphragm weight and an approximately 37% decrease in muscle fiber cross-sectional area compared with the sham group. In contrast, PGAM2 protein expression was increased by approximately 105% in septic diaphragms. PGAM2 expression was also significantly elevated in TNF-α-treated myotubes. PGAM2 knockdown resulted in reduced MuRF1 and MAFbx expression, attenuating myotube atrophy, while PGAM2 overexpression exacerbated atrophy. Moreover, PGAM2 knockdown suppressed activation of the JAK2/STAT3 signaling pathway. Conclusions: These findings demonstrate that PGAM2 contributes to sepsis-induced diaphragmatic atrophy through the activation of the JAK2/STAT3 signaling pathway. PGAM2 may therefore serve as a potential therapeutic target for sepsis-associated diaphragmatic dysfunction. Full article

Background/Objectives: Recently, a 6.3 Fr single-use flexible ureteroscope (f-URS) was introduced to the market. The purpose of this pilot study is to present our experience with it during Endoscopic Combined Intrarenal Surgery (ECIRS) and to compare its performance with the conventional 7.5 Fr scope. Methods: For percutaneous access, renal puncture was performed in a nonpapillary approach. Regarding retrograde access, for the first group, a 7.5 Fr single-use f-URS was used, while for the second group, a 6.3 Fr single-use f-URS was utilized. Lithotripsy was primarily performed in an antegrade manner, using the Lithoclast Trilogy^®. In cases where stones could not be reached with a nephroscope, retrograde lithotripsy was performed with either a Holmium:YAG laser or a Thulium Fiber Laser. Results: In total, 45 patients were included. Of these, 23 patients underwent ECIRS with the 6.3 Fr f-URS and 22 with the 7.5 Fr f-URS. The mean operative time, fluoroscopy time and lasing time were 59.5 ± 5.6 min, 139.7 ± 14.2 s and 18.4 ± 2.7 min in the 6.3 Fr group and 57.1 ± 3.9 min, 133.8 ± 29.7 s and 18.6 ± 1.9 min in the 7.5 Fr group, respectively. Two patients in the 6.3 Fr group and three patients in the 7.5 Fr group experienced Grade II complications. Stone-free rates were 91.3% in the 6.3 Fr group versus 86.4% in the 7.5 Fr group. Conclusions: The use of a 6.3 Fr f-URS during ECIRS is potentially a feasible, safe and efficient approach. Both the 6.3 Fr and 7.5 Fr scopes were associated with comparable outcomes during ECIRS. Additional studies are needed so as to draw safer conclusions. Full article

Background/Objectives: Mechanical thrombectomy (MT) enables direct examination of the retrieved thrombus in acute ischemic stroke. Thrombus composition may influence treatment outcomes and reflect underlying stroke mechanisms. This study aimed to analyze thrombus histological composition and CD34-positive endothelial cells and evaluate their association with clinical and radiological characteristics. Methods: Fifty-six patients with acute ischemic stroke who underwent MT were included. Thrombi were classified as fibrin-dominant or red blood cell (RBC)-dominant using hematoxylin–eosin staining (H&E). Endothelial cells were identified via CD34 immunostaining. Associations between thrombus composition, procedural variables, imaging findings, and clinical outcomes were analyzed. Results: Forty-one (73.2%) thrombi were fibrin-dominant, and 15 (26.8%) were RBC-dominant. Fibrin-dominant thrombi were significantly associated with more distal occlusions (p = 0.027) and with the use of stent-retrievers (p = 0.045). RBC-dominant thrombi were more frequently associated with the hyperdense artery sign (HAS) (p = 0.015). CD34-positive staining correlated with shorter symptom-to-door (p = 0.017) and symptom-to-puncture times (p < 0.001). Endothelial ingrowth was more common in thrombi from proximal occlusions (p = 0.017). No significant associations were observed between thrombus composition and recanalization success, number of passes, or functional outcomes. The association between RBC-dominant thrombi and HAS supports the potential role of imaging markers in predicting thrombus composition prior to intervention. In addition, the presence and distribution of CD34-positive endothelial cells in relation to time intervals and occlusion location may reflect dynamic processes such as thrombus organization and vessel wall interaction. Conclusions: These findings highlight the heterogeneous nature of thrombus in acute ischemic stroke. Further studies are needed to clarify the biological and clinical implications of these observations. Full article

Background/Objectives: Despite high recanalization rates associated with mechanical thrombectomy (MT), disability and death remain possible for many patients. Baseline stroke severity and reperfusion status predict outcomes; however, the influence of modifiable perioperative factors during general anesthesia (GA) remains unclear. We investigated actionable perioperative determinants of functional outcomes and 90-day mortality following MT under GA. Methods: We retrospectively analyzed 166 patients with acute ischemic stroke who underwent emergency MT with GA over 10 years (2014–2024). Poor functional outcomes were defined as a 90-day modified Rankin Scale score of 3–6, with all-cause 90-day mortality as the secondary endpoint. Independent predictors were identified using multivariable logistic regression, and discrimination was assessed using receiver operating characteristic analysis. Results: At 90 days, 56.6% of patients had poor functional outcomes, and mortality was 24.1%. Independent predictors of poor outcomes included preoperative hyperglycemia ≥ 140 mg/dL, vasopressor requirement, incomplete reperfusion, prolonged ventilator duration, and severe post-procedural neurological deficit. Optimal anesthetic induction dosing was strongly protective. Shorter groin puncture-to-recanalization time predicted better functional recovery. Mortality was associated with hyperglycemia, National Institutes of Health Stroke Scale ≥ 16, poor reperfusion, and prolonged ventilation. The models demonstrated excellent discrimination (area under the curve, 0.879 for poor outcomes; 0.923 for mortality). Perioperative physiological factors remained associated with outcomes independent of procedural success. Conclusions: Beyond technical success, perioperative physiological stability strongly influenced outcomes following MT under GA. Optimization of metabolic control, hemodynamic stability, procedural efficiency, and early ventilator liberation represents a clinically actionable strategy for improving neurological recovery and survival. Full article

Background: Obstructive jaundice is a common clinical condition, often caused by malignant tumors such as hepatocellular carcinoma (HCC) or cholangiocarcinoma (CCA). Percutaneous transhepatic cholangiodrainage (PTCD) is a widely used intervention method to relieve biliary obstruction in patients with obstructive jaundice; however, the impact of PTCD on hepatitis B virus (HBV) reactivation has not been thoroughly studied. Methods: A retrospective analysis was conducted from January 2016 to December 2024 on 235 patients with obstructive jaundice who underwent PTCD. Demographic, clinical, and procedural data were collected, and multivariate logistic regression was used to identify risk factors for HBV reactivation. Additionally, Cox regression was used to evaluate the time-to-reactivation variables. Results: The HBV reactivation rate in the PTCD group was 21.7%, significantly higher than the 8.9% in the non-PTCD group. Key risk factors for HBV reactivation in the PTCD group included the absence of antiviral prophylaxis, postoperative infection, elevated preoperative HBV-DNA levels, and multiple biliary punctures. Moreover, Cox regression revealed that a lack of antiviral therapy and postoperative infection were associated with earlier HBV reactivation. Conclusions: PTCD significantly increases the risk of HBV reactivation in patients with obstructive jaundice, especially in those with high preoperative HBV-DNA levels and without antiviral prophylaxis. Early detection of HBV reactivation and the initiation of antiviral therapy are critical to improving patient outcomes. These findings underscore the need for careful monitoring of HBV status in patients undergoing PTCD. Full article

Fieldwork carries a high risk of irregular, non-compressible traumatic wounds, which often initiate a vicious cycle of “traumatic bleeding-insect bite-secondary infection”. Conventional dressings cannot combine rapid hemostasis with physical protection against venomous insects, creating an urgent demand for multifunctional field trauma dressings. To solve this problem, this study developed a shape-adaptive bilayer hydrogel that concurrently provides rapid hemostasis, promotes wound repair, and acts as a robust physical barrier. The hydrogel adopts a layered design: the bottom layer (PPTY) achieves autogelation within 3 s upon blood contact, while the top armor protective layer (AP) withstands pressures up to 942 kPa. By incorporating chitosan and sodium citrate into the AP precursor solution, the hydrogel achieved in situ formation within 50 s and developed a stable self-renewing armor layer. The tightly bonded bilayer showed complementary functions. In rat models of femoral artery puncture and tail vein bleeding, PPTY-AP hydrogel significantly reduced blood loss and shortened hemostasis time. Moreover, the hydrogel demonstrated excellent tissue adhesion and moisture retention capacity, promoting full-thickness skin wound healing. This multifunctional, rapidly deployable hydrogel presents a promising solution for field trauma management and offers a new design paradigm for advanced wound dressings. Full article

Bioactive glass (BAG) S53P4 is a clinically approved bone substitute with antibacterial, osteoconductive and osteostimulatory properties. Its antibacterial effect is associated with ion release, local pH elevation and osmolality, but the precise biochemical and biophysical mode-of-action is unclear. This study investigates the antibacterial mechanism of BAG S53P4 eluates. BAG eluates, collected at 2, 4, 8, and 24 h, eradicated Staphylococcus aureus. Elemental analysis revealed an early increase in concentrations of Si and Na, a later rise in Ca, depletion of P over time and rapid loss of Mg. Membrane disturbances occurred within 5 min, evident by permeability for SYTOX, aligning with time-kill kinetics for S. aureus and Bacillus subtilis. In B. subtilis, 2h-BAG-eluate induced rapid delocalization of marker proteins for cell division and DNA repair, signaling membrane potential collapse and nucleoid condensation. Transcriptomics revealed early transcription remodeling reflecting ionic and energetic imbalance, including disruption of central metabolism, redox homeostasis, and translational stability. Scanning electron microscopy revealed severe cell surface damage and particulate deposits on S. aureus. Transmission electron microscopy showed cell envelop disruptions and cytoplasmic leakage. Energy dispersive X-ray analysis identified Si on bacterial cell surface at 4 h and intracellular accumulation in punctured, empty cells at 24 h. Overall, BAG ionic dissolution products kill bacteria through a stepwise mechanism involving membrane damage, protein delocalization and metabolic impairment, accompanied by Si deposition on bacterial surfaces and loss of Mg. This finally leads to cell wall degradation, cytoplasmic content leakage and further Si deposition on the cells and inside cell ghosts. Full article

Microinjection is one of the most established and effective techniques for introducing foreign substances into cells. However, issues such as cumbersome procedures, low success rates, and poor repeatability in manual cell microinjection have seriously restricted its practical applications in biomedical research and engineering. Responding to such problems, this paper designs an automated microinjection system that combines deep learning visual positioning and adaptive neural network sliding-mode motion control. The machine vision solution based on the deep learning YOLOv8 target detection algorithm is utilized by the system to provide positional prerequisites for automated microinjection. Then, stable and fast puncture is completed by controlling the end effector (composed of a piezoelectric actuator and a displacement amplification mechanism). Since the piezoelectric actuator has strong nonlinearity, the motion control of the end effector adopts the control strategy combining sliding mode variable structure and adaptive neural networks to meet the requirements of precise displacement output of microinjection. At the same time, a host computer control system is developed to integrate hardware equipment, visual positioning algorithms and motion control algorithms to achieve corresponding automated microinjection tasks. Finally, the effectiveness of the designed automated microinjection system is successfully verified on zebrafish embryos. Full article

Zygomatic implant perforated (ZIP) flap reconstruction offers immediate surgical rehabilitation following maxillectomy, integrating oncologic zygomatic implants with a fascio-cutaneous free flap. A critical technical challenge is safely perforating the free flap skin paddle to accommodate implants’ abutments without damaging its vasculature. Near-infrared (NIR) vein visualization technology provides real-time mapping of subcutaneous vessels and has been widely investigated in settings such as pediatric intravenous (IV) cannulation. By projecting vein pathways onto the skin, NIR visualization facilitates precise vascular identification, potentially reducing complications. We describe a case of ZIP flap reconstruction in a 25-year-old patient utilizing NIR vein visualization to preemptively locate flap vasculature and minimize the risk of vessel puncture. Our discussion places these findings within the context of the existing literature on NIR devices, underscoring their benefits of non-invasive operation, rapid imaging, and minimal need for advanced operator skills, and highlighting their utility in microvascular reconstructive surgery. Full article

Conventional separators for lithium metal batteries suffer from poor thermal stability, flammability, and limited mechanical strength. In this study, we report a self-reinforced aramid separator integrated with Li₇La₃Zr₂O₁₂ (LLZO) via a sodium–naphthalene-based selective dissolution strategy. Controlled partial disruption of hydrogen bonding in copolymerized aramid enables the formation of a hierarchical structure consisting of intact fibers and nanofibrillar networks, thereby providing intrinsic mechanical reinforcement without binders. The separator maintains structural integrity up to ~400 °C and retains over 70% weight at 600 °C, exhibiting self-extinguishing behavior (LOI > 30). Puncture strength is more than three times higher than Celgard^®, while LLZO integration doubles the ionic conductivity along with excellent electrolyte wettability. This synergistic design provides a promising route toward intrinsically safe and high-performance lithium metal battery separators. Full article

Background and Objectives: Rapid diagnosis is fundamental to acute ischemic stroke management; however, access to neuroradiological expertise remains limited. This scoping review maps the diagnostic accuracy, workflow impact, and cost-effectiveness of leading AI platforms (Brainomix, Aidoc, RapidAI, and Viz.ai), characterizing industry and peer-reviewed metrics. Materials and Methods: Following PRISMA-ScR guidelines, we searched PubMed, Cochrane Library, and HTA repositories for studies (2019–2025). Using a PICO-based framework, 29 studies were included for thematic mapping of the technological landscape. Results: Twenty-nine studies were included. Platforms show high proximal LVO sensitivity (78–97%), while performance for distal/MVO and posterior circulation occlusions was more variable. RapidAI is frequently mapped using historical perfusion trial parameters; however, volumetric discrepancies with platforms like Viz.ai indicate outputs are not interchangeable. Brainomix shows extensive validation for automated NCCT ASPECTS in triage. Aidoc demonstrates operational advantages via worklist prioritization, while. Viz.ai is associated with door-to-puncture time reductions (11–25 min). Economically, cost-effectiveness is driven by improved functional outcomes and expanded access to thrombectomy, rather than labor substitution. Conclusions: AI platforms function as diagnostic safety nets and workflow optimizers. Reported roles, such as perfusion-centric analysis (RapidAI) or workflow coordination (Viz.ai), reflect current research trends rather than definitive technological superiority. Institutional selection should consider these evidence clusters alongside local validation and specific clinical priorities. Full article