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摘要：Background:Spiral ganglion neurons (SGNs) relay auditory sensory information from the cochlea to the brain. Their loss results in permanent hearing impairment in humans due to their limited regenerative capacity. Progress in hearing restoration has been constrained by the inaccessibility of human inner ear tissue and challenges in generating functionally mature human SGN-like neurons from stem cells in vitro.Methods:To generate human SGN-like neurons from human induced pluripotent stem cells (hiPSCs), we recapitulated key signaling pathways involved in human inner ear development. On day (D) 11 of differentiation, nerve growth factor receptor-positive cells (precursors of pre-placodal ectoderm and neural crest) were isolated using magnetic sorting. From D18 to D25, cultures were treated with sonic hedgehogs to induce otic neural progenitors. Neuronal maturation was subsequently promoted by a cocktail of brain-derived neurotrophic factor, neurotrophin-3, and insulin-like growth factor-1, which supports SGN development. Cellular identity and functionality were assessed using single-cell RNA sequencing, immunocytochemistry, whole-cell patch-clamp electrophysiology, co-culture assays, and calcium ion (Ca2+) imaging.Results:hiPSC-derived SGN-like neurons exhibited morphological, molecular, electrophysiological, and functional characteristics of SGNs in vivo. Neurons acquired bipolar morphology and were wrapped by glial cells. Transcriptomic analysis revealed that SGN-like neurons were distinct from other neuronal lineages and showed similarity to type I and type Ⅱ SGNs based on expression of synaptic and intrinsic excitability-related genes. Electrophysiological recordings revealed progressive hyperpolarization of resting membrane potential and emergence of overshooting action potentials, consistent with neuronal maturation. In co-culture systems, human SGN-like neurons formed functional synaptic connections with mouse cochlear hair cells and cochlear nucleus neurons, evidenced by Ca2+ transients and induction of the immediate early gene c-Fos.Conclusions:This study reports a robust and reproducible protocol for generating human SGN-like neurons from hiPSCs, providing a versatile platform for studying human auditory development, disease modeling, drug screening, and cell-based therapies for hearing restoration.关键词：Spiral ganglion neurons (SGNs);Human induced pluripotent stem cells (hiPSCs);Auditory neurons;cochlea;Inner ear35|51|0<HTML><网络PDF> <Meta-XML>更新时间：2026-10-12
摘要：Background:Early-onset (<50 years) and never-smoker lung cancers are increasing global concerns. The emerging trends challenge current screening guidelines, which focus on adults aged >50 years with heavy smoking histories. We applied the US Preventive Services Task Force (USPSTF) 2021 screening criteria as the primary definition of high-risk individuals eligible for lung cancer screening and assessed the potential optimization of these criteria using real-world lung cancer data in China.Methods:In this nationwide, multicenter, hospital-based observational study, we enrolled asymptomatic patients with surgically resected primary lung cancer across 26 tertiary hospitals from January 1, 2014 to December 31, 2021. Screening eligibility was classified using USPSTF 2021 criteria (aged 50–80 years, ≥20 pack-year smoking history, and ≤15 quit-years for former smokers). Temporal trends in eligibility, screening utilization, and mortality risks were assessed through joinpoint regression and Cox proportional hazards models.Results:A total of 106,266 asymptomatic patients with lung cancer were enrolled. Among the 102,555 patients with complete age and smoking information, only 8.8% (8985/102,555) met the USPSTF 2021 eligibility criteria. The eligibility proportion declined sharply from 21.6% (350/1617) in 2014 to 6.1% (1737/28,582) in 2021, with the annual percentage change being –17.4% [95% confidence interval (CI) –19.1 to –15.9]. Patients with screening utilization, irrespective of eligibility status, demonstrated a higher proportion of stage Ia diagnoses compared with those who were not screened. Screening- ineligible group exhibited 40% lower mortality risk overall [adjusted hazard ratio (HR)=0.60, 95% CI 0.55–0.66], with consistent survival advantages across stage I (adjusted HR=0.63, 95% CI 0.54–0.74) and stage Ⅲ (adjusted HR=0.76, 95% CI 0.64–0.90) subgroups.Conclusions:Rigid age- and smoking-based criteria overlook substantial at-risk populations in China. Implementing individualized risk stratification is essential to advance equitable lung cancer screening.关键词：lung cancer;Screening eligibility;US Preventive Services Task Force (VSPSTF) criteria;Real-world evidence15|53|0<HTML><网络PDF> <Meta-XML>更新时间：2026-10-12
摘要：Background:Abnormal glucose metabolism often contributes to myofibroblast activation and the pathogenesis of skin fibrotic diseases. All-trans retinoic acid (ATRA), the active component of tretinoin cream, can regulate glucose metabolism and activate myofibroblasts. Importantly, investigating the potential of ATRA to inhibit myofibroblast activation by modulating glucose metabolism could reveal the translational significance of ATRA in attenuating hypertrophic scar (HS) formation.Methods:We first conducted a multicenter, double-blind, randomized controlled trial (RCT) to compare the effects of tretinoin cream with those of the first-line medication, silicone gel. In the mechanistic study, the characteristics of glucose metabolic reprogramming and the activation of hypertrophic scar fibroblasts (HSFs) after ATRA treatment were identified through multi-omics profiling, complemented by glucose metabolism assays and functional validations. Besides, genetic overexpression targeting the potential downstream molecules of ATRA, including hypermethylated in cancer 1 (HIC1), phosphoenolpyruvate carboxykinase (PCK)1, and PCK2, was conducted in vitro in HSFs and in vivo in skin fibroblasts of Col1a2-CreER mice.Results:Our RCT demonstrated that tretinoin cream is non-inferior to silicone gel in preventing HS formation, with the absdute risk difference of incidence rates [–8.65% 90% two-sided (confidence interval) CI –23.03 to 5.74] and in decreasing scar thickness [(2856.20±211.83) μm vs. (1664.57±273.50) μm], attributing to the reduction in HSF proliferation and the proportion of myofibroblasts. Moreover, tretinoin cream effectively mitigated HS formation in both mice and rabbits without impeding normal wound healing. Mechanistically, HSFs underwent glucose reprogramming, characterized by increased aerobic glycolysis, which facilitated the transition of HSFs to myofibroblasts and their proliferation. However, ATRA upregulated HIC1, PCK1, and PCK2 expression through retinoic acid receptor alpha (RARα) activation, thereby inhibiting the fibrotic phenotypes of HSFs by suppressing aerobic glycolysis and facilitating gluconeogenesis. The fibroblast-specific overexpression of HIC1, PCK1, or PCK2 in Col1a2-CreER mice significantly reduced myofibroblast activation and hypertrophic scarring.Conclusions:Our study not only substantiated that topical tretinoin cream could serve as an effective strategy to prevent HSs in clinical settings, but also established ATRA as a regulator of glucose metabolism. Importantly, ATRA/RARα-mediated glucose reprogramming was identified as a potential therapeutic target for attenuating HS formation.关键词：All-trans retinoic acid (ATRA);Randomized controlled trial (RCT);Glucose metabolic reprogramming;Myofibroblast activation;hypertrophic scar46|50|0<HTML><网络PDF> <Meta-XML>更新时间：2026-10-12
摘要：Background:Bacteria-mediated cancer therapy leverages bacteria to modulate the tumor immune microenvironment and deliver therapeutics. However, its clinical application is limited by toxicity, off-target effects, and uncontrolled drug release. Improving tumor targeting and precise payload delivery through rational bacterial engineering is essential for increasing efficacy and safety.Methods:An attenuated Salmonella ΔhtrA::luxI-VNP20009 strain expressing OmpA-SpyTag (AISI-ST) was constructed for the modular surface conjugation of SpyCatcherΔ (SC)-fused quadruple arginine-glycine-aspartic acid (RGD) peptides (named AISI-ST/SC-RGD×4) and for building biointerfaces for enhanced tumor adhesion via RGD-mediated integrin αvβ3 interactions. The tumor-bearing mice received intravenous injections of AISI-ST/SC-RGD×4, and their biodistribution was analyzed using bioluminescence imaging and colony-forming unit (CFU) counts. Quorum-sensing (QS)-regulated high-temperature requirement A (HtrA) and anti-programmed cell death protein 1 (anti-PD1) nanobody expression based on the LuxI promoter in strains was validated by Western blotting. Immune responses were assessed using flow cytometry.Results:The incubation of the fused proteins with the AISI-ST strain for 1 h was sufficient to form a stable biological interface. The quadruple RGD-modified bacteria (AISI-ST/SC-RGD×4) exhibited greater enrichment in various solid tumors and lung metastases with reduced off-target accumulation. QS induced the expression of the HtrA protein within tumors, resulting in enhanced extracellular polysaccharide-mediated immunogenicity to activate immune cells. Further expression of anti-PD1 nanobodies synergistically enhanced antitumor immunity, increasing the percentage of M1 macrophages (MACS) and CD8+ T cell proliferation while suppressing M2 MACS and regulatory T cells (Tregs). This approach achieves potent tumor suppression via targeted immune remodeling.Conclusions:This study presents octopus-inspired engineered bacteria with a “plug-and-display” system and tumor-specific drug delivery that achieves enhanced tumor targeting and potent antitumor effects. This study describes a promising strategy for the precise and safe clinical translation of bacteria-mediated cancer immunotherapy.关键词：Microbial therapeutics;Chemical biological modification;Quorum-sensing (QS);Tumor-targeted delivery;Immune activation30|37|0<HTML><网络PDF> <Meta-XML>更新时间：2026-10-12
摘要：Background:Metabolic syndrome (MetS) is characterized by chronic low-grade inflammation and immune dysregulation, which may increase susceptibility to sepsis. However, epidemiologic evidence remains limited. This study aimed to evaluate the association of MetS with the risk of sepsis and sepsis-related mortality.Methods:This study included 359,633 participants from the UK Biobank and 152,317 participants from the Kailuan Study. MetS was defined as the presence of ≥3 metabolic abnormalities. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of MetS with risk of sepsis and 28-day mortality following sepsis. Stratified analyses were conducted to assess potential effect modification. In the UK Biobank, we further evaluated the dose-response relationship between the number of MetS components and sepsis outcomes, explored potential mediation by inflammatory and immune biomarkers, and investigated the joint effect of MetS and lifestyle; in the Kailuan Study, we further investigated the impact of MetS evolution on sepsis risk. Sensitivity analyses were performed to evaluate the robustness of the results.Results:During a median follow-up of 13.7 years, 11,040 sepsis cases were identified in the UK Biobank, whereas 5672 cases were documented in the Kailuan Study during a median follow-up of 16.4 years. After multivariable adjustment, MetS was associated with higher risks of sepsis (HR=1.55, 95% CI 1.49–1.61) and 28-day mortality following sepsis (HR=1.51, 95% CI 1.37–1.65) in the UK Biobank; corresponding HRs were 1.32 (95% CI 1.25–1.40) and 1.49 (95% CI 1.32–1.69) in the Kailuan Study, respectively (all P<0.001). These associations were generally consistent across stratified analyses. Moreover, the risk of sepsis outcomes increased with the number of MetS components and was partly mediated by inflammation. Compared with individuals free of MetS, individuals with MetS and an unfavorable lifestyle had substantially higher risks of sepsis (HR=1.91, 95% CI 1.81–2.00) and 28-day mortality following sepsis (HR=1.84, 95% CI 1.64–2.07), whereas those with MetS but a favorable lifestyle showed only a modestly increased risk of sepsis and no excess risk of 28-day mortality (HR=1.18, 95% CI 1.09–1.28 and HR=1.05, 95% CI 0.88–1.27, respectively). In analyses of MetS evolution, using individuals with persistently normal metabolic status as the reference, those with a persistent MetS demonstrated the highest risks of sepsis (HR=1.46, 95% CI 1.32–1.61) and 28-day mortality following sepsis (HR=1.88, 95% CI 1.50–2.35), followed by individuals with progressive MetS (HR=1.17, 95% CI 1.05–1.31 and HR=1.36, 95% CI 1.04–1.77, respectively), whereas those who recovered from MetS did not show a significantly increased risk (HR=1.09, 95% CI 0.96–1.25 and HR=1.19, 95% CI 0.87–1.61, respectively). Sensitivity analyses confirmed the robustness of the findings.Conclusions:This study demonstrated that MetS was associated with an increased risk of sepsis and sepsis-related mortality. These associations were partially mediated through inflammatory responses. The findings highlight the importance of maintaining metabolic health as well as promoting healthy lifestyles as strategies to reduce its burden.关键词：Metabolic syndrome (MetS);sepsis;Inflammation;Mortality;UK Biobank;Kailuan Study34|41|0<HTML><网络PDF> <Meta-XML>更新时间：2026-10-12
RESEARCH
摘要：From cold-weather training to deployments in high altitude and arctic conditions, frostbite injury and its sequelae remain a serious concern in military operations. Frostbite harms tissue in two distinct ways. The first involves ice crystal formation within tissue, resulting in mechanical damage and ischemia. The second occurs secondary to the inflammatory and prothrombotic state caused by reperfusion from rewarming frozen tissue. Frostbite injuries can be classified in a number of ways, but no perfect system exists. Initial work-up and diagnosis are primarily clinical. However, in equipped treatment facilities, advanced imaging modalities such as technetium-99m (99mTc) bone scintigraphy, magnetic resonance angiography, single-photon emission computed tomography/computed tomography (SPECT/CT), and more can play a role in diagnosis and treatment. In resource-constrained environments, such as the deployed setting, management should involve an algorithmic approach. After concurrent hypothermia and/or trauma have been evaluated for and treated, active rewarming should take place so long as there is no risk of refreezing. During re-warming, surgical consultation and evacuation considerations should be considered. Once evacuated to a definitive treatment facility, thrombolytic as well as other therapies may be indicated. Unless there is evidence of severe damage or infection, surgical management is typically delayed until injury margins are fully demarcated. Longer-term prognosis is dependent on severity, with deeper injuries often resulting in longer hospital stays, more amputations, and chronic disability. Looking forward, future frostbite research should aim to bridge field and hospital care with the goal of minimizing tissue loss and accelerating functional recovery.关键词：Cold weather injury;Frostbite;Field care of frostbite;Military medicine37|36|0<HTML><网络PDF> <Meta-XML>更新时间：2026-10-12
摘要：Sepsis is a life-threatening condition characterized by an exaggerated and uncontrolled immune response, leading to widespread inflammation throughout the body. This immune response can compromise the integrity of the endothelial barrier, resulting in increased vascular permeability. The degree of vascular permeability in septic shock patients correlates with disease severity and significantly influences the outcomes of resuscitation and prognosis. This review systematically examines the structural regulation of the endothelial barrier and the dynamic mechanisms of its injury in subgroups of sepsis. In response to these mechanisms, emerging therapeutic strategies focus on glycocalyx protection, signal pathway modulation, cytoskeleton stability, and immune regulation, aiming to restore endothelial barrier function through multi-target synergism. In the future, combining analysis of endothelial barrier function and the dynamic regulation mechanism provides a new perspective for the precise treatment of sepsis.关键词：sepsis;Endothelial dysfunction;Vascular permeability;Glycocalyx injury;Therapeutic strategies44|38|0<HTML><网络PDF> <Meta-XML>更新时间：2026-10-12
摘要：Throughout pregnancy, the immune microenvironment undergoes dynamic changes in patients with concomitant autoimmune diseases (AIDs). These alterations not only affect disease activity and clinical manifestations, but also play a pivotal role in sustaining maternal-fetal immune tolerance and pregnancy outcomes. Extensive preclinical studies have elucidated the mechanisms of immune regulation in normal pregnancy, whereas the dynamic immune changes in pregnancies complicated by AIDs remain poorly understood. Recent studies have revealed significant variations in immune responses to pregnancy among individuals with AIDs, which may contribute to distinct patterns of AIDs flares during this period. Despite substantial progress in immunology and reproductive medicine, comprehensive reviews addressing the dynamic changes in the immune microenvironment during pregnancy in the context of AIDs are lacking. In this review, we summarize existing knowledge and incorporate recent multidisciplinary findings, focusing on the dynamic changes in systemic immune adaptation and maternal-fetal immune interactions in the context of AIDs during pregnancy. We emphasize the clinical significance of these immune dynamics for optimizing management and therapeutic strategies. Additionally, we propose new perspectives and provide recommendations to guide future research and the development of personalized treatment approaches.关键词：Autoimmune diseases (AIDs);pregnancy;Immune microenvironment;Maternal-fetal immune adaptation;Clinical management22|28|0<HTML><网络PDF> <Meta-XML>更新时间：2026-10-12
REVIEW
关键词：Neuropathic pain;Sleep disorders;Sleep fragmentation;Mediodorsal thalamus;Temporoparietal desynchronization37|24|0<HTML><网络PDF> <Meta-XML>更新时间：2026-10-12
LETTER TO THE EDITOR
- 关键词：Exosomes;Trace element;Diabetic foot ulcers;Stimuli-responsive hydrogel15|45|0<HTML><网络PDF> <Meta-XML>更新时间：2026-10-12
COMMENTARY
