With advances in emergency care systems, the number of patients with prolonged disorders of consciousness (pDoC) has markedly increased. To optimize the allocation of healthcare resources and mitigate risks, the early and accurate identification of recovery potential in pDoC is essential. Current machine learning models are often hindered by small sample sizes, inconsistent data standards, and limited interpretability. This study aims to overcome these issues and develop a machine learning-based prognostic model that may provide potential support for clinical decision-making in patients with pDoC. A retrospective study of pDoC patients hospitalized at Xuanwu Hospital from January 2013 to August 2024 was conducted. Data on clinical information, behavioral scales, and event-related potentials (ERPs) were collected, using 6-month consciousness recovery as the outcome. Two auditory oddball paradigms with progressively increasing difficulty were used to elicit ERPs, in which the subject’s own name (SON) was presented as the deviant stimulus, and a 1000 Hz pure tone together with the subject’s derived name (SDN) served as the standard stimuli respectively. The least absolute shrinkage and selection operator (LASSO) regression analysis selected eight variables: sex, skull state, etiology, duration, Coma Recovery Scale-Revised (CRS-R) score, diagnosis, mismatch negativity (MMN) pattern, and epilepsy status. Model performance was assessed using metrics such as macro-averaged receiver operating characteristic area under the curve (ROC-AUC), macro-averaged precision–recall area under the curve (PR-AUC) and macro-averaged F1 score. Clinical utility was evaluated via Decision Curve Analysis (DCA), and interpretability was supported by SHapley Additive exPlanations (SHAP) method. A total of 110 patients with pDoC, comprising 72 with minimally conscious state (MCS) and 38 with vegetative state/unresponsive wakefulness syndrome (VS/UWS), were enrolled in the study. Follow-up assessments identified 53 patients with improved prognosis and 57 without improvement. The efficient logistic regression model showed moderate discriminative ability with a macro-averaged ROC-AUC of 0.7504 (95
Hyperglycemia and osteoarthritis frequently coexist as comorbid conditions, and both are characterized by chronic low-grade inflammation driven by aberrant B cell differentiation. However, the interplay between hyperglycemia, osteoarthritis, and aberrant B cell function has yet to be fully elucidated. Peripheral blood samples were obtained from 100 osteoarthritis patients at various clinical stages (including 50 with normoglycemia and 50 with hyperglycemia), as well as from 20 healthy controls. Peripheral blood mononuclear cells were isolated, and B cell subset distributions were analyzed by flow cytometry. Multiplex immunofluorescence staining was performed to confirm aberrant synovial B cell populations in KOA patients with hyperglycemia. Additionally, in vitro experiments were conducted to assess the relationships among B cell activation, hyperglycemic conditions, and cartilage injury. Our study revealed that patients with hyperglycemia exhibited an overall increase in peripheral B cell counts, characterized by a significant reduction in regulatory B cells and a concomitant rise in memory B cells. Notably, the proportion of B cells in peripheral blood was positively correlated with the severity of joint degeneration. Consistently, we observed a substantial accumulation of activated B cells (CD86 +) within the synovium of patients with advanced knee osteoarthritis (KOA). In vitro, exposure to a high-glucose environment promoted chondrocyte injury, as indicated by reduced COL2A1 expression and elevated MMP13 levels; this deleterious effect was further exacerbated by the presence of B cells. These findings identify aberrant B cell responses as a key link between hyperglycemia-associated metabolic conditions and osteoarthritis progression, suggesting that targeting B cell-mediated inflammation may offer new therapeutic opportunities for patients with metabolic comorbidities.
Prognostic assessment after traumatic brain injury with intracranial hematoma relies mainly on admission variables. We evaluated whether repeat CT-derived hematoma dynamic variables add value for 6-month functional outcome prediction beyond a strong baseline model. This retrospective study included 639 adults with traumatic intracranial hematoma admitted between March 2021 and March 2023. Unfavorable outcome was defined as a Glasgow Outcome Scale score < 4 at 6 months. Sequential logistic models were developed according to information availability. The admission model included age, sex, Glasgow Coma Scale score, baseline hematoma volume, and hematoma type. Laboratory variables were then added, followed by repeat CT-derived hematoma dynamics, including volume change, CT interval, average hourly hematoma volume change, and a spline interaction between volume change and CT interval. Performance was assessed using AUC, Brier score, calibration plots, bootstrap validation, and decision curve analysis. Among 639 patients, 144 had unfavorable outcomes. The admission model showed high discrimination, with an AUC of 0.902 and a Brier score of 0.098. Adding laboratory variables improved the AUC to 0.918 and reduced the Brier score to 0.092. Incorporating Repeat CT-derived hematoma dynamics further improved performance. The spline interaction model performed best, with an AUC of 0.937, an optimism-corrected AUC of 0.911, and a Brier score of 0.080. Average hourly hematoma volume change showed a nonlinear association with unfavorable outcome, and decision curve analysis indicated greater net benefit after adding repeat CT dynamics. Repeat CT-derived hematoma dynamics improved prediction of 6-month functional outcome beyond admission variables and laboratory results. Time–volume representations of hematoma change may provide interpretable imaging markers for early risk stratification.
Hepatic steatosis commonly coexists with HBsAg positivity, but how low-cost anthropometric and lipid-metabolic indices compare in adjusted cross-sectional association and discrimination, particularly among adults with normal BMI, remains uncertain. We analyzed 7984 HBsAg-positive individuals who underwent routine health examinations between March 2014 and December 2017. Discrimination and incremental model performance were evaluated in a common complete-case sample (N = 7670; 1634 events) using areas under the receiver operating characteristic curve (AUCs) and paired DeLong tests, with pre-specified subgroup analyses by sex, age group, BMI category, and alanine aminotransferase status. Restricted cubic splines were used to assess nonlinearity for the conicity index, TyG-WC, and TyG-BMI, and 1st/99th percentile winsorization was used to assess sensitivity to extreme values. Hepatic steatosis was identified in 1681 participants (21.1
Diabetic foot ulcers (DFUs) are serious diabetes complications. Although histone lactylation has been linked to diabetic conditions, the pattern and potential diagnostic value of lactylation-related genes in DFU remain largely unexplored. Bulk RNA sequencing datasets and 376 lactylation-related genes were analyzed to identify DFU-associated lactylation-related genes (LRGs). Machine learning built a diagnostic model. Consensus clustering defined DFU subtypes. The cellular landscapes of DFUs were explored by single-cell RNA-sequencing (scRNA-seq) datasets. The gain- and loss-of-function experiments of the hub gene PFKFB2 were validated using a high-glucose-induced HUVEC model. A total of 10 differentially expressed LRGs were identified between the DFU and NC groups. Consensus clustering stratified DFU samples into two lactylation-related subtypes with distinct immune infiltration patterns and pathway enrichment. Based on machine learning methods, five LRGs (ADH1B, ARTN, KY, PFKFB2, and PFKFB4) were identified to construct the diagnostic model for DFU. A nomogram constructed from these five LRGs achieved high diagnostic accuracy in a bulk RNA set. Increased lactylation signature across all nine DFU-associated cell types, particularly in myeloid cells, fibroblasts, and epithelial cells. PFKFB2 was downregulated in vitro HUVECs model. The overexpression of PFKFB2 reduced the levels of lactate and histone lactylation and inhibited endothelial cell migration and tube formation, whereas its knockdown promoted these processes. This study established a lactylation-related diagnostic model for DFU based on five LRGs, highlighting the potential diagnostic and therapeutic target. Furthermore, PFKFB2 was identified as a key regulator, revealing a novel lactylation-associated metabolic-epigenetic mechanism in DFU.
Cardiac arrest (CA) remains a leading cause of death worldwide despite advances in cardiopulmonary resuscitation (CPR) and post-resuscitation care. Post-resuscitation myocardial dysfunction (PRMD) is a major determinant of early outcomes following return of spontaneous circulation (ROSC), with mitochondrial dysfunction serving as a core pathological driver; however, no specific pharmacological interventions targeting mitochondrial protection are currently available. Although melatonin (Mel) has demonstrated cardioprotective effects in ischemia–reperfusion injury, its role in PRMD is not fully understood. In this study, a rat model of CA/CPR was induced by ventricular fibrillation, and Mel (10 mg/kg) was administered intravenously 30 min post-ROSC. An in vitro hypoxia/reoxygenation model using H9c2 cells was employed for mechanistic validation. Mel improved post-resuscitation hemodynamics and left ventricular function, reduced arrhythmia burden and myocardial injury, and attenuated inflammation, oxidative stress, and apoptosis. It also preserved mitochondrial ultrastructure, stabilized mitochondrial membrane potential, inhibited opening of the mitochondrial permeability transition pore, and restored ATP production and the NAD+/NADH ratio. Mechanistically, Mel downregulated mitochondrial fission-related proteins, including phosphorylated DRP1, Fis1, and MFF, while upregulating fusion-related proteins (MFN1, MFN2, and OPA1). These findings indicate that melatonin treatment is associated with preserved mitochondrial homeostasis and improved mitochondrial fission–fusion balance in a rat model of PRMD, supporting further investigation of mitochondrial dynamics as a potential contributor to melatonin-related cardioprotection.
Accurate prediction of mortality remains a critical challenge in sepsis management. While various biomarkers have been studied, their comparative prognostic performance is unclear due to a lack of direct comparisons. This study aimed to systematically evaluate and rank the prognostic value of eight commonly investigated biomarkers for mortality risk in adult sepsis patients. A systematic review and network meta-analysis of observational studies was conducted. PubMed, EMBASE, Cochrane Library, and Web of Science were searched up to October 2025. Studies reporting hazard ratios (HRs) for the association between biomarkers (procalcitonin (PCT), albumin (ALB), C-reactive protein (CRP), interleukin-6 (IL-6), red cell distribution width (RDW), lactate, neutrophil-to-lymphocyte ratio (NLR), and lactate/albumin ratio (Lactate/ALB)) and mortality in adult sepsis were included. Pairwise meta-analysis and frequentist network meta-analysis were performed using random-effects models to explore the associations between these biomarkers and mortality. Biomarkers were ranked using P-scores. Heterogeneity, inconsistency, and publication bias were assessed. A total of 103 studies involving 191,561 patients were included. In the pairwise meta-analysis, the Lactate/ALB ratio demonstrated the strongest association with mortality (pooled HR = 2.94, 95
To evaluate the efficacy of the supertension-relieving suture (SRS) technique in reducing scar formation following melanocytic nevi excision. A total of 120 patients with melanocytic nevi were included and categorized into the SRS group (n = 71) and the CON group (conventional suturing, n = 49). At 12 months postoperatively, the CON group exhibited physiological changes of natural scar remodeling: PSAS, OSAS, POSAS, and VSS scores decreased from 39.41 ± 5.21, 36.51 ± 3.76, 75.92 ± 6.79, and 11.86 ± 2.06 to 8.14 ± 1.57, 5.98 ± 1.48, 14.12 ± 2.06, and 1.81 ± 0.77, respectively; scar width increased from 2.12 ± 0.62 to 2.78 ± 0.84 mm, everted wounds decreased from 8.75 ± 0.76 to 0.94 ± 0.26 mm, and 9 complications occurred. In contrast, the SRS group showed improved remodeling: PSAS, OSAS, POSAS, and VSS scores declined from 40.21 ± 4.92, 36.51 ± 4.13, 76.72 ± 6.00, and 11.43 ± 2.15 to 6.52 ± 1.28, 4.31 ± 1.21, 10.83 ± 1.83, and 1.17 ± 0.60, respectively. Meanwhile, hyperplasia was reduced, scar width only changed from 1.95 ± 0.56 to 2.36 ± 0.71 mm, everted wounds decreased from 8.92 ± 0.91 to 0.72 ± 0.16 mm, with 3 complications. Compared with the CON group, the SRS group had significantly lower PSAS, OSAS, POSAS, and VSS scores, narrower scars, less wound eversion, and fewer complications at postoperative 3, 6, and 12 months. The SRS technique improves scar healing after melanocytic nevi excision, contributing to better cosmetic outcomes and fewer complications than conventional suturing methods.
Osteoarthritis (OA) is considered the most common chronic joint disease. With the aging population and the increasing incidence of obesity, the incidence of OA has increased. This study aimed to investigate the role and mechanism of methyl isoeugenol (MIE) in OA. Differentially expressed genes and enrichment analysis of DEGs of the GEO dataset (GSE55235) showed that these genes were predominantly linked to rheumatoid arthritis, osteoclast differentiation, and the NF-κB signaling pathway. The targets of MIE were predicted on TCMS, Swiss Target Prediction, PharmMapper, and the Similarity Ensemble Approach (SEA). Molecular docking was conducted to predict the binding relationship between MIE and core OA targets. JAK2, JUN, SYK, HCK, and CXCL12 were potential targets of MIE in OA. An in vivo OA model was established through destabilization of the medial meniscus (DMM), and IL-1β-stimulated CHON-001 chondrocytes, followed by MIE administration. The results confirmed that MIE dampened matrix loss and apoptosis in the knee cartilage tissue of the OA mouse model and mitigated apoptosis and extracellular matrix degradation in CHON-001 cells. MIE suppressed the activation of “M1” macrophages and restrained the JAK2/STAT3 and NF-κB/NLRP3/ASC/Caspase−1 pathways. In conclusion, the results of this study indicate that MIE protects against OA through the inhibition of the NF-κB/NLRP3 and JAK2/STAT3 pathways.
Hepatocellular carcinoma (HCC) remains one of the most prevalent malignancies worldwide, and early detection combined with accurate therapeutic strategies is essential for improving patient prognosis. Current international guidelines on liver disease generally recommend dynamic contrast-enhanced imaging in combination with serum tumor markers as the primary non-invasive diagnostic approach. However, liver biopsy continues to hold indispensable value in specific, complex clinical circumstances. This review systematically examines the diagnostic criteria for HCC and the recommended indications for liver biopsy as outlined in the Chinese Clinical Practice Guideline for Primary Liver Cancer (CNLC), the National Comprehensive Cancer Network (NCCN), the European Association for the Study of the Liver (EASL), the Asian Pacific Association for the Study of the Liver (APASL), and the Japan Society of Hepatology (JSH). This review emphasizes that validated non-invasive criteria, including the Liver Imaging Reporting and Data System (LI-RADS) and EASL imaging hallmarks, achieve a diagnostic specificity exceeding 95
Acute myocardial infarction (AMI) is one of the severe clinical conditions where mortality and morbidity are higher in resource-limited settings, where percutaneous coronary intervention/fibrinolysis are not available or inadequate, such as in Ethiopia. However, data on the clinical spectrum and treatment outcomes of AMI in this region are scarce, and this study aimed to address these gaps. This study aims to evaluate the clinical profiles and treatment outcomes (death, improvement, or referral) of patients with AMI and to identify predictors. A retrospective observational chart review study was conducted among AMI patients from January 9, 2018, to August 31, 2023. A census of eligible records was applied to recruit participants. Logistic regression analysis was performed to identify associated factors, and variables having p-values < 0.05 were considered statistically significant. A total of 206 individuals’ charts with a diagnosis of AMI were reviewed. The hospital mortality rate was 18.4
We investigated whether admission LDL-C levels are associated with clinical profile and outcomes after acute ischaemic stroke by comparing patients stratified into five LDL-C groups. We retrospectively analyzed consecutively included patients ≥18 years admitted to the Bernese Stroke Centre (02/2015–03/2023). Patients were stratified into five LDL-C groups: >3.0 mmol/L (n=493), 2.6–3.0 mmol/L (n=225), 1.8–2.6 mmol/L (n=490), 1.4–1.8 mmol/L (n=254) and <1.4 mmol/L (n=172). LDL-C was measured within 24 h of admission. Outcomes included successful reperfusion, symptomatic intracranial haemorrhage, favourable and excellent functional outcomes at 3 months, and 3-month mortality. Separate complete-case multivariable logistic regression models evaluated LDL-C as a continuous and five-level categorical exposure, adjusting for prespecified clinical covariates. Among 1634 patients, those with LDL-C <1.4 mmol/L were older (median 78 vs. 73 years; p<0.001), more often male (59
The transepithelial potential (TEP) is a stable, long-range bioelectrical gradient maintained across epithelial barriers, generated primarily by polarized ion transport mechanisms such as the Na⁺/K⁺-ATPase and epithelial sodium channels (ENaC). Ranging from a few millivolts to over one hundred millivolts, this potential is not a passive electrical property but an active physiological signal integral to epithelial function. This review synthesizes current understanding of TEP formation, dynamic regulation, and multifaceted roles across organ systems. We emphasize its critical involvement in maintaining epithelial homeostasis, directing wound healing, and orchestrating tissue regeneration. Injury triggers localized TEP collapse, generating endogenous electric fields (EFs) of significant strength (40–200 mV/mm) that serve as potent directional cues guiding collective cell migration, proliferation, and differentiation to coordinate repair. Advances in biophysical instrumentation—including minimally invasive microneedle arrays, wearable sensors, and non-invasive field mapping devices—now enable precise, real-time spatial mapping of TEP dynamics in health and disease. Beyond physiology, TEP has emerged as a key diagnostic marker in pathologies such as cystic fibrosis (via nasal potential difference measurements) and retinal disorders like Age-related Macular Degeneration (AMD). Furthermore, TEP modulation represents a promising therapeutic target for bioelectric interventions, including ion channel pharmacology and exogenous electrical stimulation. This comprehensive overview highlights the fundamental biophysical and biological significance of TEP, bridges molecular mechanisms with tissue-level outcomes, and outlines its rapidly emerging potential in clinical diagnostics, regenerative medicine, and bioelectronic therapeutics.
Optic disc morphology and retinal nerve fiber layer (RNFL) thickness have been widely studied in populations with refractive error. This study aims to measure and analyze optic disc parameters and RNFL thickness in different regions of the optic disc in 9-year-old schoolchildren. It also seeks to investigate the influence of factors such as refractive error, axial length, gender, and body mass index (BMI) on these ocular parameters. This cross-sectional study included 1274 children aged 9 years. Participants underwent anthropometric measurements and comprehensive ophthalmic examinations, including axial length (AL), non-cycloplegic autorefraction, and optical coherence tomography (OCT). Continuous variables are presented as mean ± standard deviation or median (interquartile range). Group comparisons were performed using the Wilcoxon rank-sum test or Kruskal–Wallis test. The RNFL thickness showed the typical distribution pattern, being greatest in the inferior quadrant, followed by the superior, temporal, and nasal quadrants. No significant differences in optic disc parameters or RNFL thickness were observed across gender or BMI groups (all P > 0.05). Compared with non-myopic participants, cup-related parameters were smaller in myopic groups. Greater myopic refractive error was associated with increased global and nasal RNFL thickness. Eyes with AL ≥ 26 mm showed thicker nasal RNFL than those with AL < 26 mm (P = 0.01), with no other significant differences. In 9-year-old children from North China, optic disc morphology and RNFL thickness varied with refractive and ocular biometric characteristics. RNFL thickness was associated with refractive error and axial length.
This observational, uncontrolled study aimed to evaluate the effects of glucagon‑like peptide‑1 receptor agonist (GLP‑1RA) therapy on the morphology and microcirculation of the tibial nerve in patients with diabetic tibial neuropathy (DTN) using multimodal ultrasound. In this prospective study, 45 patients with type 2 diabetes and DTN who had not previously received GLP‑1RA therapy were treated with once‑weekly semaglutide for 6 months. A novel multimodal ultrasound protocol combining B‑mode imaging, shear‑wave elastography, and ultra‑microvascular flow imaging was used to assess the tibial nerve. Measurements included cross‑sectional area (CSA), anteroposterior diameter, stiffness values (Emin, Emean, Emax), and vascularity index (VI). Outcomes at baseline were compared with values at 1, 3, and 6 months after treatment. The anteroposterior diameter of the tibial nerve decreased from 0.46 ± 0.06 cm at baseline to 0.41 ± 0.05 cm at 6 months, but this change did not reach statistical significance (p > 0.05). CSA and Emin were 0.36 ± 0.12 cm2 and 36.63 ± 13.13 kPa, respectively, at baseline and showed statistically significant reductions beginning at month 3 (CSA: 0.31 ± 0.15 cm2; Emin: 25.70 ± 9.22 kPa; both p < 0.05). Emean and Emax decreased significantly as early as 1 month after treatment, from 61.80 ± 14.00 kPa and 102.45 ± 23.38 kPa to 49.64 ± 11.66 kPa and 88.35 ± 17.13 kPa, respectively, and remained significantly improved throughout follow‑up (p < 0.05). VI increased from 4.20 ± 2.42
Gait impairment is a major contributor to persistent disability after stroke. Several land-based and aquatic gait-training modalities are used in rehabilitation, but their comparative effects on walking capacity, balance, and functional mobility remain uncertain. To compare the efficacy of different gait-training modalities on walking and functional outcomes in adults after stroke using a Bayesian network meta-analysis. PubMed, EMBASE, Web of Science, and the Cochrane Library were searched from inception to January 22, 2026. Randomized controlled trials evaluating overground walking (OGW), land-based treadmill training (LTT), aquatic overground walking (AOW), aquatic treadmill training (ATT), or control interventions were included. The primary outcomes were walking endurance assessed using the 6-Minute Walk Test (6MWT) and walking speed assessed using the 10-Meter Walk Test. Secondary outcomes included the Berg Balance Scale (BBS), Timed Up and Go Test (TUG), cadence, and Fugl-Meyer Assessment of the Lower Extremity. Bayesian random-effects network meta-analyses were conducted for the 6MWT, walking speed, BBS, and TUG, and treatment rankings were summarized using the surface under the cumulative ranking curve. Cadence and lower-extremity motor function were summarized narratively because of sparse evidence. Twenty-six randomized controlled trials involving 1,111 participants were included. For the 6MWT, OGW had the highest ranking and was associated with a greater walking distance than control (MD 57.04 m, 95
The main cause of appendicitis is obstruction of the appendiceal lumen. Obstruction can be caused by fecaliths or by swelling of nearby lymph nodes. Appendiceal obstruction can lead to poor blood circulation, bacterial growth, and tissue hypoxia, which can then cause appendiceal necrosis, peritonitis, sepsis, and even death. Studies have also associated appendicitis with lymphoid hyperplasia, which may be caused by infections such as adenovirus; however, direct evidence of this association is lacking. We retrospectively collected pathological records from 360 patients with appendicitis (240 adults and 120 patients aged younger than 18 years) and 40 control individuals without appendicitis. Appendectomy specimens were processed into formalin-fixed paraffin-embedded (FFPE) sections. Immunohistochemistry (IHC) and quantitative polymerase chain reaction (qPCR) analyses were used to determine the presence of adenovirus in appendiceal tissue samples. In pediatric patients, the adenovirus positivity rates obtained using IHC (25.8
This study aimed to identify and evaluate the factors associated with the partial remission phase in patients with diabetes mellitus (DM). Observational studies published up to November 2025 were searched in CNKI, Wanfang, VIP, PubMed, Web of Science, Cochrane Library, and EMBASE databases. Two researchers independently performed literature screening, quality assessment, and data extraction. Study quality was evaluated using the Agency for Healthcare Research and Quality (AHRQ) checklist and the Newcastle–Ottawa Scale (NOS). A random-effects model was used to pool heterogeneous results. Effect sizes were expressed as odds ratios (ORs) with 95
Dexamethasone (DEX) is a cornerstone drug in the clinical management of rheumatoid arthritis (RA). Nonetheless, its therapeutic efficacy is hampered by systemic side effects and poor tissue specificity. In this study, a release system was developed based on poly (lactic-co-glycolic acid) (PLGA) for the delivery of DEX-loaded implants for localized and sustained drug delivery. In an adjuvant-induced arthritis rat model, peri-articular implantation of DEX-loaded implants markedly alleviated joint swelling, suppressed synovial hyperplasia, and reduced articular inflammation. The treatment also downregulated key proinflammatory cytokines, including TNF-α, IL-1β, and IL-6, demonstrating superior antirheumatic efficacy compared with oral administration. Pharmacokinetic studies confirmed that the implants exhibited sustained release profiles both in vivo and in vitro. Furthermore, Fourier transform infrared (FTIR) spectroscopy verified the favorable compatibility between the drug and excipients. These findings indicated that PLGA-based DEX implants enhance therapeutic efficacy while minimizing systemic toxicity, thereby providing an effective and safe therapeutic strategy for treating RA.
Endovascular treatment (EVT) effectively treats acute ischemic stroke (AIS) from anterior circulation large vessel occlusion (LVO), but 50
