Hepatic cold ischemia/reperfusion (I/R) injury persists during the perioperative period of liver transplantation (LT), exerting a profound impact on graft survival and being closely associated with the occurrence of early allograft dysfunction (EAD). Currently, preventive strategies against cold I/R injury remain limited. This study aimed to investigate the protective effects and underlying molecular mechanisms of caftaric acid (CA), a metabolite specifically elevated in cold-adapted hibernating animals, against hepatic cold I/R injury. The results demonstrated that CA significantly reduced the area of hepatic necrosis, attenuated liver injury, inhibited hepatocyte apoptosis, and promoted the restoration of redox homeostasis. RNA-seq analysis suggested that the MAPK pathway, particularly the activation of JNK1, plays a pivotal role in the process of cold I/R injury. Through integrated experiments including drug-target screening, molecular docking, and surface plasmon resonance (SPR), this study confirmed that CA directly binds to and interacts with JNK1, thereby regulating its phosphorylation function. Further investigations revealed that CA modulates the MAPK cascade (JNK1/FOS) to alleviate oxidative stress, mitochondrial dysfunction, and cellular apoptosis during hepatic cold I/R injury. In summary, these findings suggest that CA holds promise as a potential therapeutic strategy for ameliorating hepatic cold I/R injury, with significant clinical implications.
Pediatric acute kidney injury (AKI) often presents insidiously and progresses rapidly. Traditional diagnostic criteria based on serum creatinine and urine output are markedly delayed and insufficient to capture injury patterns across different etiologies. This paper aims to summarize recent advances in pediatric AKI biomarker research since the release of the ADQI 23 (2020) consensus. Focusing on three major clinical scenarios-cardiac surgery, sepsis, and nephrotoxic drugs-it reviews early biomarker evidence and explores their potential applications in risk stratification. At the mechanistic level, this paper outlines key pathological pathways in pediatric AKI progression: oxygenation-perfusion imbalance after cardiac surgery, endothelium-immune dysregulation driven by sepsis, and tubular-mitochondrial injury associated with nephrotoxic exposure. In CS-AKI, uNGAL shows the earliest elevation within hours after cardiopulmonary bypass, followed by sequential changes in IL-18, L-FABP, and KIM-1. [TIMP-2] × [IGFBP7] and exosomal miRNA aid in identifying high-risk or severe AKI. In SA-AKI, suPAR and glycocalyx/endothelial injury markers (e.g., syndecan-1, Angpt-2/sTM/Tie-2), combined with urinary DKK3 and complement Ba, can be used for early risk stratification and predicting poor outcomes. In NT-AKI, uNGAL has high negative predictive value for excluding severe AKI, while uKIM-1, uCysC, uOPN, and multi-biomarker combinations can indicate subclinical tubular injury earlier after drug exposure. Overall, single biomarkers struggle to cover AKI heterogeneity. Future efforts should integrate functional dynamic assessments (e.g., FST, RRI), scenario-based multi-biomarker combinations, and AI dynamic models to propose evidence-based, scenario-stratified identification pathways. These will serve as structured references for prospective studies and clinical workflow optimization.
Astragaloside IV (AS-IV), a primary bioactive component of Astragalus membranaceus (AM). It is very effective in regulating renal diseases. However, the possible underlying mechanism of AS-IV on renoprotection remains unclear. The aim of this study is to find out the regulation mechanism of AS-IV on ischemia/reperfusion injury-induced Acute kidney injury (IRI-AKI). At first, AS-IV was confirmed to significantly alleviate renal dysfunction, inflammation, and renal tubular epithelial cell apoptosis in IRI-AKI mice. Then, it was found that AS-IV alleviated mitochondrial dysfunction and renal tubular epithelial cell injury induced by IRI. Growing evidence has suggested that PINK1/Parkin-mediated mitophagy plays a critical protective role in IRI. Based on this, we hypothesized that AS-IV might exert renoprotective effects through activating the PINK1/Parkin mitophagy pathway. After 3-MA inhibition of autophagy, AS-IV no longer showed its protective effect on HK-2 cells in a hypoxic environment. Through further molecular docking, cell thermal migration, and gene targeted silencing experiments, we confirmed that AS-IV activates the PINK1/Parkin mitophagy pathway and ultimately alleviates IRI-AKI. In summary, all these comprehensive experimental findings indicated that AS-IV can be used as a functional food for the prevention of renal ischemia/reperfusion injury.
Macrophage ferroptosis contributes to sepsis-associated acute lung injury (ALI); however, its upstream regulatory mechanisms remain poorly understood. Here, using a cecal ligation and puncture (CLP) murine sepsis model, we observed that macrophages from septic mice and bone marrow-derived macrophages (BMDMs) exposed to septic bronchoalveolar lavage fluid (BALF) exhibited concurrent suppression of EPOR expression and induction of ferroptosis. EPOR deficiency selectively reduced basal GPX4 expression and amplified ferroptotic cell death upon challenge with RSL3 or septic BALF. EPORM-/- mice showed exacerbated sepsis-induced lung injury and mortality, which were rescued by the ferroptosis inhibitor ferrostatin-1 (Fer-1). Mechanistically, EPOR deficiency downregulated PPARγ, which promotes GPX4 expression. EPOR deficiency also impaired PINK1-mediated mitophagy by reducing PINK1 but not PARKIN levels, while mitophagy induction attenuated ferroptosis in EPOR-deficient cells. rhEPO stimulation enhanced the EPOR/PPARγ axis and suppressed lipid peroxidation, whereas PPARγ antagonism inhibited PINK1 expression. We further identified Rab26 as a critical stabilizer of EPOR. Specifically, Rab26 deficiency upregulated the expression of BTRC, an E3 ligase that interacts with EPOR to promote its degradation. Consequently, Rab26 deficiency decreased EPOR levels, subsequently suppressing PPARγ and PINK1, thereby reducing GPX4 expression and blunting rhEPO-induced PINK1 upregulation. Collectively, EPOR signaling protects macrophages from ferroptosis by activating PINK1-mediated mitophagy in a Rab26-dependent manner. The Rab26-EPOR-PPARγ axis represents a promising therapeutic target for sepsis-induced lung injury.
To investigate multidimensional impulsivity and its neuroelectrophysiological correlates in adolescents with depression and non-suicidal self-injury (NSSI). A case-control study was conducted including three groups: depressed adolescents with non-suicidal self-injury (NSSI group), depressed adolescents without NSSI (non-NSSI group), and healthy controls (HCs group). The Ottawa Self-Injury Questionnaire was administered to assess NSSI behaviors in depressed participants and to quantify NSSI severity within the NSSI group. Impulsivity was evaluated using a multimodal approach, including the Barratt Impulsiveness Scale-11 (BIS-11), a go/no-go task, and event-related potentials (ERPs), with particular focus on the N2 and P3 components. Both depressed groups exhibited significantly higher BIS-11 total and subscale scores than HCs, particularly in motor impulsivity (p < 0.05). A significant overall group difference was observed in go trials accuracy among the three groups (p = 0.009). Post hoc analyses with Bonferroni correction showed that the NSSI group had significantly lower go-trial accuracy than the HCs group (p_Bonf < 0.05), whereas no significant differences were observed between the NSSI and non-NSSI groups (p_Bonf > 0.05) or between the non-NSSI and HCs groups (p_Bonf > 0.05). No significant group differences were found in N2 or P3 latency or amplitude across the three groups (all p > 0.05). Correlation analyses revealed that NSSI severity over the past 1, 6, and 12 months was positively correlated with BIS-11 total and motor impulsivity scores (r = 0.198-0.417, all p < 0.001) and negatively correlated with go-task accuracy (r =  - 0.248 to - 0.193, all p < 0.001). Depressed adolescents with NSSI exhibited elevated self-reported impulsivity and impaired behavioral inhibitory control, both of which were associated with NSSI severity, whereas no significant neurophysiological differences were observed between depressed adolescents with NSSI and HCs.
Hesperetin (HSP), a natural flavonoid, demonstrates significant therapeutic effects on cardiovascular and cerebrovascular diseases and displays a strong application potential in the aspects of anti-inflammation and anti-oxidation. Cerebral ischemia-reperfusion is accompanied by the generation of inflammatory storms and the accumulation of reactive oxygen species (ROS), ultimately resulting in neuronal damage. While Hesperetin has been widely studied in the treatment of cardiovascular diseases, its potential for treating cerebral ischemia-reperfusion injury remains underexplored. This study aimed to discuss the potential protective mechanism of HSP on cerebral ischemia-reperfusion injury (CIRI). Ferroptosis, a form of cell death driven by iron-dependent phospholipid peroxidation is associated with neuronal damage during cerebral ischemia and subsequent reperfusion injury. Our findings indicate that HSP can confer neuronal protection after CIRI by inhibiting neuronal ferroptosis. Specifically, HSP could significantly up-regulate glutathione (GSH) levels, and up-regulate glutathione peroxidase 4(GPX4) after CIRI, thereby inhibiting cell ferroptosis. Furthermore, we observed a significant reduction in lipid peroxidation products and ROS levels, we have also obtained the same results in vivo animal experiments. In conclusion, HSP played a protective role in CIRI by regulating intracellular iron ions levels, as well as GSH and GPX4 contents to inhibit neuronal ferroptosis after CIRI.
Spinal cord injury (SCI) is a devastating insult to the central nervous system that causes severe motor and sensory dysfunction; however, effective therapeutic strategies remain limited because the mechanisms underlying secondary injury are not fully understood. In this study, we investigated the therapeutic effects of the bioactive compound astragaloside IV (AST-IV) in a mouse model of SCI. Through functional, histological, and molecular analyses, we demonstrated that AST-IV treatment significantly improved neurological recovery after SCI. Mechanistically, AST-IV exerted neuroprotective effects through the activation of AMPK-mediated autophagy and the enhancement of autophagic flux, thereby preserving mitochondrial homeostasis, attenuating endoplasmic reticulum stress-associated apoptosis, and suppressing pyroptosis. Importantly, pharmacological inhibition of autophagy markedly attenuated the protective effects of AST-IV, indicating that the neuroprotective effect of AST-IV is mediated by autophagy. Collectively, these findings reveal an autophagy-dependent mechanism underlying AST-IV-mediated neuroprotection and support the therapeutic potential of AST-IV for mitigating secondary injury after SCI.
Individuals with spinal cord injury (SCI) are at high risk for developing neurogenic bladder or neurogenic lower urinary tract dysfunction (NLUTD), which can lead to severe complications and negatively impact quality of life. Despite the critical need for timely urologic care, barriers to access remain poorly understood, particularly in resource-limited settings. This study aims to identify systemic and perceived barriers to urologic follow-up for individuals with SCI treated at an academic medical center. A single-center, observational study was conducted on individuals presenting with a diagnosis code indicative of complete SCI at an academic hospital between October 2015 and October 2023. Data were extracted from electronic medical records using ICD-10 codes for SCI, and phone interviews were conducted to assess symptoms, quality of life, and perceived barriers to care. Descriptive statistics summarized the findings. Univariate and multivariate Firth logistic regression analyses were performed to analyze for possible covariates impacting the odds of follow-up or having obtained a urodynamics study. Of 213 records, 136 met the inclusion criteria. Among them, only 17 (13%) received a urology consultation during their hospital stay, and 28 (21%) had been seen in a urology clinic post-injury. Phone interviews with 42 patients revealed that 93% reported NLUTD symptoms, with a mean quality of life impact score of 7.3. Barriers identified included availability (71%), accessibility (45%), accommodation (69%), affordability (43%), and acceptability (31%) barriers. Firth logistic regression demonstrated that male sex was associated with lower odds (OR = 0.205, 95% CI: 0.048, 0.772, p = 0.02) of having obtained a urodynamics study. Significant gaps in urologic care for individuals with SCI exist. Statistically significant variation in management via Firth logistic regression analyses also demonstrates potential disparities in follow-up and management. Addressing these challenges requires improved discharge planning, increased healthcare accessibility, and innovative care models such as telemedicine. Future research should explore broader geographic regions and interventions to improve outcomes.
Supraspinal somatosensory pathways neuroplasticity critically influences sensory recovery after spinal cord injury (SCI) and offers promising neuromodulation targets. However, distinctions between complete SCI (CSCI) and incomplete SCI (ISCI) patients remain unclear. We aimed to delineate injury severity-dependent neuroplasticity patterns in somatosensory pathways, and provide mechanistic insights for developing targeted rehabilitation strategies. Resting-state effective connectivity (EC) within supraspinal somatosensory pathways was analyzed using spectral dynamic causal modelling in 17 CSCI patients, 17 ISCI patients, and 37 healthy controls. The primary somatosensory cortex (S1), second somatosensory cortex (S2), thalamus (THA), insula (INS), cerebellar lobule VI (CB6) and primary motor cortex were employed as the regions of interest. A fully connected model was specified for each participant, and group-level differences in EC were assessed using parametric empirical Bayes. Connections with a posterior probability > 0.95 were considered significant. Additionally, correlation analyses were performed between significant EC and sensory scores. Both CSCI and ISCI groups exhibited impaired basic somatosensory conduction, including dysfunction from the THA to the S1 and dysregulation along the S1-S2-INS pathway. However, their specific connectivity patterns diverged. The CSCI group showed weakened self-inhibition within the THA and S1. The ISCI group exhibited stronger inhibitory EC from S2 to INS and from CB6 to S1. CSCI and ISCI patients predominantly exhibit decreased and increased EC within the supraspinal somatosensory pathways, respectively. The CSCI patients showed reduced THA/S1 self-inhibition, whereas ISCI patients exhibited strengthened S2-INS/CB6-S1 connectivity, possibly compensating for sensory deficits and suggesting neuromodulation targets for somatosensory recovery.
The biomechanical mechanism between genital hiatus (GH), intra-abdominal pressure (IAP) and pelvic organ prolapse (POP) is currently unclear. Therefore, two biomechanical models for comparative analysis are developed to discuss the biomechanical relations of IAP and GH with prolapse of anterior and posterior vaginal walls (AVW and PVW) in the injured pelvic floor system. Based on the magnetic resonance imaging (MRI) of the pelvic floor of a healthy woman, we developed two 2D finite element models by using mechanical equivalence to represent the physiological and pathological states respectively. Both models contain hollow structure rectum. We simulated biomechanical characteristics of POP progression under different IAP and GH values in the PVW injury. In the pathological state with an IAP of 83.9 cmH2O, the descending displacement of the cervix increased from 14.3 to 20.9 mm when the GH increased from 10 to 40 mm. The maximum stress of AVW and perineal body (PB) rose from 0.343 to 0.611 MPa, from 0.190 to 0.974 MPa, respectively. Compared with the physiological state, the initial GH is a significant influence on POP progression. The increase of GH leads to a reduction or loss of biomechanical support for the bladder. The influence of IAPs and GH interaction exacerbates the injury and mechanical imbalance in the pathological state, which triggers increased stress in the AVW and PB, the descending displacements of the cervix and PVM, and exacerbates POP progression.
Corneal injury is a major cause of visual impairment worldwide and involves a tightly regulated cascade of inflammation, tissue repair, and remodeling. This process typically progresses from an early inflammatory phase to proliferative repair and ultimately to stromal remodeling, with potential outcomes including corneal neovascularization and fibrosis that compromise transparency and vision. Accumulating evidence highlights macrophages as central regulators across these stages. In the early phase, pro-inflammatory (M1-like) macrophages mediate pathogen clearance and immune activation through cytokines such as IL-1β and TNF-α. During the reparative phase, a transition toward anti-inflammatory (M2-like) phenotypes facilitates epithelial regeneration, extracellular matrix remodeling, and resolution of inflammation. Dysregulation of this dynamic balance, however, contributes to chronic inflammation, pathological angiogenesis driven by hypoxia-inducible factor-VEGF signaling, and TGF-β-mediated fibrotic remodeling. This review summarizes current understanding of macrophage-associated signaling networks in corneal injury, including pathways governing inflammation, angiogenesis, and fibrosis, and highlights emerging macrophage-targeted therapeutic strategies such as cytokine modulation, nanocarrier-based delivery, and gene editing approaches. Despite promising preclinical results, challenges including macrophage heterogeneity, temporal specificity, and translational safety remain. A deeper mechanistic understanding may enable the development of more precise immunomodulatory therapies to improve corneal repair and visual outcomes.
Hepatic ischemia-reperfusion injury (HIRI) is an unavoidable complication of liver transplantation (LT) that drives allograft dysfunction and mortality. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) show therapeutic promise, yet their actions within the hepatic network remain incompletely defined. We investigated how MSC-EVs protect against LT-induced HIRI, focusing on intercellular communication and complement-mediated inflammation. Single-cell RNA sequencing, single-nucleus ATAC-seq, and spatial transcriptomics were performed in rat LT and mouse HIRI livers with or without MSC-EV treatment. Cell migration assays, AAV-mediated overexpression, and PTPN13-knockdown MSC-EVs were used to prove cellular function and mechanisms. MSC-EVs attenuated HIRI, improving liver function and reducing histologic injury and hepatocyte apoptosis. Single-cell analyses showed selective curtailment of mononuclear phagocyte and neutrophil recruitment to injured liver. Mechanistically, HIRI induced hepatocyte C5 and C5a, which engaged C5aR1 on mononuclear phagocytes and neutrophils to drive chemotaxis. Consistent with this pathway, MSC-EVs delivered PTPN13 to hepatocytes, lowering C5 and promoting ERK1/2 dephosphorylation and enhanced C/EBPα activity. Elevated C/EBPα activity directly suppressed C5 transcription, whereas PTPN13-depleted MSC-EVs showed diminished efficacy. We present a single-cell multi-omics atlas of MSC-EV therapy across rat LT and mouse HIRI, supported by clinical data. MSC-EVs mitigated HIRI by lowering hepatocyte C5 and reducing mononuclear phagocyte and neutrophil recruitment. MSC-EV delivery of PTPN13 dephosphorylated ERK1/2 and enhanced C/EBPα, repressing hepatocyte C5 and dampening C5a-C5aR1 signaling. These findings position MSC-EVs as a translational nanotherapy to improve graft outcomes after LT.
Vesicourethral foreign bodies are frequently encountered in urological emergency departments; however, cases of penetrating injury to the corpus spongiosum penis and bulbous urethra are rare. A 64-year-old man presented with difficulty removing a foreign body that he had inserted into his urethra for masturbation. Abdominal computed tomography (CT) revealed a rod-shaped foreign body lodged from the bulbous urethra to the posterior wall of the bladder. Cystoscopy confirmed penetration of the foreign body into the urethral sponge at the bulbous urethra. An attempt was made to remove the foreign body transurethrally, but it was unsuccessful, leading to the establishment of a cystostomy and subsequent hospitalization. Under general anesthesia, the foreign object was removed through a perineal incision, revealing a bamboo skewer with an attached rubber tube. No postoperative complications were noted. Urethrography performed six months postoperatively showed no urethral stricture, and the patient established spontaneous urination without erectile or ejaculatory dysfunction. In cases of penetrating urethral injury, where the wound is often sharp, perineal surgery should be considered on par with the transurethral approach, as it does not affect the patient's postoperative quality of life if infection complications are monitored carefully.
The glymphatic system facilitates cerebrospinal fluid (CSF)-interstitial fluid exchange and plays a key role in solute clearance and neurophysiological homeostasis. While dysfunction of this system has been shown in traumatic brain injury, stroke, meningitis, idiopathic normal pressure hydrocephalus and neurodegenerative diseases, direct measurement of glymphatic transport in humans remains elusive. We propose microGLYMPH as a translational, hypothesis-generating framework that combines established clinical cerebral microdialysis with controlled CSF tracer administration via existing clinical access routes, including an external ventricular drain, cisternal access during surgery, or lumbar intrathecal injection when clinically justified. The aim is to obtain time-resolved regional tracer profiles in microdialysate and to interpret these alongside arousal state, intracranial dynamics, and, where available, complementary imaging, thereby providing an indirect measure of CSF-interstitial exchange kinetics and peripheral tracer appearance. We further define the key design, analytical and practical limitations that must be resolved before the approach can extend beyond exploratory use, notably catheter-adjacent effects, blood-brain barrier disruption, drainage practices, and the intrinsically focal nature of microdialysis. microGLYMPH is therefore intended as a staged roadmap for first-in-human feasibility studies and subsequent hypothesis-driven investigations of neurofluid solute transport after acute brain injury.
Sleep disturbances are common after traumatic brain injury (TBI), yet there are no guidelines specific to non-pharmacologic management in this population. To evaluate whether adults with post-TBI sleep disturbances benefit from commonly described non-pharmacologic therapies - cognitive behavioural therapy (CBT) (including for insomnia, CBT-I), hyperbaric oxygen (HBO2), blue-wavelength light therapy (BWLT) and repetitive transcranial magnetic stimulation (rTMS) - with attention to both statistical and minimally clinically important differences (MCIDs). A systematic review (registered with the International Prospective Register of Systematic Reviews) and meta-analysis of randomised controlled trials (RCTs) were used. Databases (PubMed, APA PsycInfo and PsychArticles, Medline Complete, CINAHL Plus) were originally searched in October  2023 and updated in PubMed on 14 March 2026. The searches were conducted separately for each intervention. Outcomes included sleep quality and duration (Pittsburgh Sleep Quality Index, PSQI; Insomnia Severity Index, ISI; actigraphy), daytime sleepiness (Epworth Sleepiness Scale, ESS) and daytime dysfunction. The quality of evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation approach. Twelve RCTs met inclusion criteria. CBT significantly improved PSQI (MD: -3.44), ISI at 6-8 weeks (mean difference, MD: -2.23) and 12-16 weeks (MD: -0.91) and ESS (MD: -1.45) at 16 weeks. Only the change in PSQI reached the MCID. Evidence for HBO2, BWLT and rTMS remained very low, with small samples and heterogeneity precluding definitive conclusions regarding sleep outcomes; HBO2 showed a higher risk of mild ear barotrauma v. sham (relative risk: 2.66). CBT/CBT-I appears to improve sleep quality and daytime sleepiness in adults with TBI; online CBT-I (eCBT-I) may expand access. The paucity and heterogeneity of trials for HBO2, BWLT and rTMS precludes definitive conclusions for proposed outcomes. Larger RCTs with standardised protocols are needed.
In severe acute kidney injury (AKI), delayed renal replacement therapy (RRT) strategies allow many KDIGO stage-3 patients to avoid dialysis, but excessive postponement in those who ultimately require RRT may worsen outcomes. Early physiologically grounded markers to identify patients likely to need RRT are lacking. We evaluated whether combining early glomerular filtration kinetics and timed urinary urea excretion could improve discrimination of subsequent RRT initiation under a delayed strategy. TUBSAKI is a prospective bicentric ICU cohort including adults with KDIGO stage-3 AKI managed with a protocolized delayed RRT strategy. Blood and 24-hour urine samples were collected at diagnosis (D0) and day 1 (D1). Glomerular filtration dynamics were assessed using kinetic GFR (kGFR), and timed urinary urea excretion was assessed using UUEI. Discrimination for subsequent RRT was assessed using ROC curves and AUC. A combined logistic model (kGFR D0-D1 + UUEI D1) was internally validated by bootstrap, with sensitivity analyses adjusted for SOFA and KDIGO stage-3 oliguria. Among 110 patients, 31 (28%) required RRT. kGFR D0-D1 showed good discrimination (AUC 0.81 [0.72-0.89]), and UUEI D1 moderate discrimination (AUC 0.74 [0.63-0.82]). The combined model showed an AUC of 0.85 ([0.76-0.91]), optimism-corrected AUC 0.83, and acceptable calibration. Discrimination remained stable after adjustment for SOFA and oliguria. Incremental gain over kGFR alone was modest and not statistically significant. Early glomerular filtration kinetics and urinary urea excretion were associated with subsequent RRT initiation under a delayed strategy. The incremental clinical value of UUEI remained limited in this cohort, and external validation is required before clinical use.
Non-suicidal self-injury (NSSI) is common among adolescents and is associated with substantial psychological distress and elevated suicide risk. From an ecological-developmental perspective, adolescent NSSI may arise from interacting influences across individual vulnerabilities, developmental adversity, family relationships, and social resources. However, most previous studies have examined these factors using variable-centered approaches, which may overlook psychosocial heterogeneity within clinical populations. This study aimed to examine three-year transitions in NSSI among psychiatric adolescents and to investigate whether multidomain psychosocial profiles identified at baseline were associated with these transition outcomes. A two-wave longitudinal cohort study was conducted among 432 adolescent psychiatric inpatients (mean age = 14.6 years; 81.3% female) with a three-year follow-up interval. NSSI was assessed at baseline and follow-up, and transitions were categorized as stable no NSSI, new-onset NSSI, remission, or persistence. Latent profile analysis was used to identify psychosocial profiles based on multidomain indicators including emotional symptoms, trauma exposure, stressful life events, psychosocial resources, coping styles, and perceived parenting. Multinomial logistic regression models examined predictors of transition outcomes. NSSI prevalence declined from 22.9% at baseline to 14.1% at follow-up. Transition patterns included stable no NSSI (64.1%), remission (21.8%), new onset (13.0%), and persistence (1.2%). Latent profile analysis identified three psychosocial subgroups: a lower-risk/high-resource profile, an intermediate-risk profile, and a high-stress/low-support profile. Transition distributions differed significantly across profiles, with the lower-risk profile showing the highest remission proportion and the high-stress/low-support profile showing the lowest remission proportion. In multivariable models, low household economic status (RRR = 2.64), personal suicide history (RRR = 2.96), and lower paternal emotional warmth (RRR = 0.52) independently predicted current NSSI, whereas greater childhood trauma (RRR = 0.35) and stressful life events (RRR = 0.68) were associated with lower odds of remission. NSSI among adolescents receiving psychiatric care shows heterogeneous transition patterns and distinct psychosocial profiles. Multidomain psychosocial characteristics, including socioeconomic adversity, prior suicidality, trauma exposure, life stress, and paternal emotional warmth, appear to be important correlates of NSSI transitions. These findings highlight the value of incorporating multidomain psychosocial assessment into clinical risk evaluation and intervention planning. Not applicable.
Prestin has been identified as a potential biomarker for cochlear damage and consequent ototoxicity. Although several preclinical and clinical studies have investigated prestin, a comprehensive overview of the evidence regarding its diagnostic value across different types of auditory damage and its use for cancer treatment-related ototoxicity is currently lacking. A structured literature review, based on a systematic PubMed search, was conducted to summarize preclinical and clinical studies that evaluated serum and/or plasma prestin levels in association with cochlear damage. Studies were categorized by etiology, moment of biomarker assessment, and correlation with functional hearing outcomes. Twenty-one studies (six animal, 15 human) were included. In animal models, prestin levels increased within hours to days after cochlear injury. Clinical studies showed elevated prestin levels within 30 days after acute damage, due to cisplatin exposure, noise exposure, or surgery. Higher prestin levels correlated with elevated hearing thresholds in six studies, whereas findings were more variable in age-related or chronic hearing loss. So far, no pediatric populations have been studied, and reference values or diagnostic thresholds for prestin are lacking. Prestin shows potential for use as a biomarker for acute cochlear damage, with time-dependent patterns observed in both animal and human studies. However, heterogeneity in study design, patient populations, and measurement methods limits current general conclusions and recommendations for its use in the clinical field. Further standardized and longitudinal studies, including pediatric and cancer-survivor cohorts, are needed to determine its clinical utility.
Radiation-induced lung injury (RILI) remains a serious complication of thoracic radiotherapy, with limited treatment options. While reduced glutathione (GSH) has therapeutic potential, its efficacy is hindered by poor pulmonary bioavailability via systemic administration. This study developed a novel glutathione dry powder inhaler (GSH-DPI) through rational formulation optimization. The optimized GSH-DPI exhibited excellent aerosol performance, with a fine particle fraction of 84.48% and sustained release in simulated lung fluid. In a murine RILI model, GSH-DPI (50 mg/kg, intrapulmonary administration) demonstrated superior efficacy in alleviating histopathological damage, restoring immune homeostasis, and reducing oxidative stress and pro-inflammatory cytokine expression compared to equimolar liquid GSH or high-dose oral administration. Mechanistically, analyses of single-cell RNA sequencing data revealed that RILI involves substantial alveolar type II epithelial cell (AT2) loss, compensatory oxidative stress (Nrf2/HO-1 activation), and progressive pyroptosis. GSH-DPI improved the survival of AT2 cells, simultaneously enhancing Nrf2 response and suppressing GSDMD-N-mediated pyroptosis, thereby interrupting the "oxidative stress-pyroptosis-inflammation" vicious cycle. This study highlights GSH-DPI as a promising pulmonary-targeted strategy for RILI, leveraging dual antioxidative and antipyroptotic mechanisms.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used as part of multimodal analgesia, but their association with acute kidney injury (AKI) in patients undergoing elective surgery remains uncertain. We conducted a retrospective, propensity score-matched study at a single-center academic hospital (ChiCTR2300076725). The primary outcome was the incidence of AKI, defined by the Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria, compared between patients who did and did not receive NSAIDs during surgery. Secondary outcomes included AKI severity staging and prolonged postoperative hospitalization (≥7 days). A total of 11,139 patients were included, with 3,361 in the NSAIDs group and 7,778 in the control group. After propensity score matching (PSM), 3,361 matched pairs were obtained. The incidence of postoperative AKI was comparable between the NSAIDs and control groups after matching (4.2% vs. 4.2%, p > 0.999). The distribution of AKI stages (p = 0.830) and the median duration of postoperative hospital stay were also comparable between the two groups (both 6 days, p = 0.290). Sequentially adjusted logistic regression models consistently showed no significant association between NSAIDs and AKI, AKI staging, or prolonged hospitalization, both before and after PSM. Stratified analyses by NSAID type and dose-response analyses revealed no significant association with AKI. A sensitivity analysis using complete cases without imputation (n = 9,385) yielded consistent results. In conclusion, intraoperative NSAIDs administration was not independently associated with an increased risk of postoperative AKI in patients undergoing major noncardiac surgery.