To evaluate the diagnostic value of multislice spiral computed tomography (MSCT) in differentiating pancreatic acinar cell carcinoma (PACC) from pancreatic ductal adenocarcinoma (PDAC). The clinical, pathological, and imaging data of 17 patients with pathologically confirmed PACC and 62 patients with PDAC were retrospectively analyzed. Quantitative variables were compared between groups using the independent samples t-test or the Mann-Whitney U test, as appropriate. Qualitative variables were compared using the Pearson's chi-square test or Fisher's exact test. Variables showing statistical significance in univariate analysis were entered into multivariate logistic regression analysis to identify independent predictors for distinguishing PACC from PDAC. Diagnostic performance was assessed using receiver operating characteristic curve analysis, with calculation of the area under the curve (AUC), sensitivity, specificity, positive predictive value, negative predictive value, and accuracy. Univariate analysis demonstrated significant differences between the two groups in tumor shape, margin, pancreatic atrophy, pancreatic duct transection, maximum tumor diameter, CT attenuation values, and enhancement ratios in the pancreatic parenchymal, portal venous, and delayed phases, all of which showed statistically significant differences. Multivariate logistic regression analysis identified tumor margin, pancreatic duct transection, pancreatic parenchymal phase CT attenuation value as independent predictors for distinguishing PACC from PDAC. The combined diagnostic model incorporating these variables achieved the highest diagnostic performance, with an AUC of 0.968. The model demonstrated a sensitivity of 94.1%, specificity of 88.7%, accuracy of 89.9%, positive predictive value of 69.5%, and negative predictive value of 98.2%. Tumor margin, pancreatic duct transection, and pancreatic parenchymal phase CT attenuation value are significant imaging features for differentiating PACC from PDAC. A combined diagnostic model integrating these imaging features provides excellent diagnostic performance and may aid in improving preoperative differential diagnosis.
The optimal duration of dual antiplatelet therapy (DAPT) in patients at high bleeding risk (HBR) undergoing percutaneous coronary intervention (PCI) remains uncertain. To evaluate the safety and efficacy of abbreviated DAPT durations in patients at HBR undergoing PCI. PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched from inception to October 26, 2025. Randomized clinical trials (RCTs) comparing abbreviated (ie, 1- to 3-month) vs standard (ie, 6- to 12-month) DAPT durations in patients at HBR without an indication for oral anticoagulation. A pairwise meta-analysis was performed to compare abbreviated (ie, 1-month to 3-month) vs standard (ie, ≥6-month) DAPT durations. A frequentist network meta-analysis was performed to compare 1-month, 3-month, and standard DAPT. The coprimary safety and efficacy end points were major or clinically relevant nonmajor bleeding (MCRB) and major adverse cardiovascular events (MACE; ie, a composite of cardiovascular death, myocardial infarction, or stroke). A total of 14 RCTs encompassing 11 398 patients at HBR (mean [range] age, 74.7 [68.6-80.0] years; 39.1% female and 60.9% male) were included. Compared with standard DAPT, abbreviated DAPT was associated with lower MCRB (risk ratio [RR], 0.71; 95% CI, 0.55-0.92; P = .009) and major bleeding (RR, 0.76; 95% CI, 0.59-0.99; P = .04). The risks of MACE (RR, 0.97; 95% CI, 0.81-1.16; P = .76) and its individual components did not differ between abbreviated and standard regimens. An increased risk of MACE was observed with 1-month vs 3-month DAPT in the single trial comparing these regimens, but the network estimate was nonsignificant (RR, 1.28; 95% CI, 0.96-1.72). In this systematic review and meta-analysis, for patients at HBR undergoing PCI, abbreviated DAPT was associated with a lower risk of bleeding and, at least for 3-month regimens, was not associated with an increase in fatal or nonfatal ischemic cardiovascular or cerebrovascular events compared with standard 6- to 12-month DAPT.
The 5-HT2A receptor (5-HT2AR) is a validated target in schizophrenia (SCZ); however, the therapeutic potential of repurposed drugs targeting this pathway remains underexplored. Here, we show that the antihistamine desloratadine (DLT) robustly ameliorates a full spectrum of SCZ-like behavioral deficits in an MK-801-induced male mouse model. Single-nucleus RNA sequencing (snRNA-seq) analysis revealed 5-HT2AR expression specifically within neuronal populations of the medial prefrontal cortex (mPFC). Mechanistically, these behavioral impairments were associated with a specific upregulation of 5-HT2AR in mPFC neurons-a molecular pathology reversed by DLT. Targeted overexpression of 5-HT2AR in mPFC neurons was sufficient to recapitulate the SCZ-like phenotypes, which are rescued by DLT, establishing a causal role for this receptor in disease pathology. Through integrated transcriptomic and biochemical analyses, we identified the PI3K/AKT/mTOR pathway as a key downstream effector of 5-HT2AR. We demonstrated that 5-HT2AR-mediated activation of this pathway drives neuroinflammation, apoptosis, and long-term potentiation impairments-effects that were effectively blocked by DLT. In a definitive pharmacological reversal experiment, activation of AKT with SC79 completely abrogated DLT's therapeutic efficacy, both behaviorally and molecularly. Collectively, our findings reveal that DLT exerts its therapeutic effects by suppressing a pathogenic feed-forward loop, wherein 5-HT2AR activates the PI3K/AKT/mTOR pathway, which may, in turn, sustain its own aberrant expression. This study provides a compelling rationale for repurposing desloratadine for SCZ and validates the 5-HT2AR-PI3K/AKT/mTOR signaling axis as a pivotal, druggable target for therapeutic intervention.
Fusarium graminearum threatens grain safety through trichothecene mycotoxins, yet how it temporally orchestrates virulence during early root colonization-which compromises seedling vigor and facilitates stem invasion-remains unclear. We performed high-resolution transcriptomics of F. graminearum infecting maize roots every 6 h over 48 hpi, revealing three infection phases: Penetration Initiation (0-6 hpi), Colonization Establishment (12 hpi), and Systemic Disruption (18-48 hpi). Among 6,839 fungal genes, we delineated a three-phase virulence program: rapid activation of protein synthesis enables early secretion of effectors and hydrolases that facilitate host attachment and penetration; sustained deployment of diverse hydrolases and immunosuppressive effectors enables colonization through combined nutrient acquisition and defense suppression; and late-phase vascular degradation coupled with deoxynivalenol (DON) biosynthesis may contribute to systemic host disruption by compromising tissue integrity and disarming immunity. This program coincides with a shift from ROS scavenging to endogenous signaling that may promote toxin production and invasive growth. Notably, we identified FgCPA1, a conserved Phase II carboxypeptidase A essential for root colonization, whose protease domain triggers light-independent cell death in N. benthamiana independent of its signal peptide. This temporal framework uncovers phase-specific coordination of tissue invasion and mycotoxin production, providing actionable targets for anti-virulence strategies to safeguard grain quality.
Pilots are susceptible to neck injury during carrier-based aircraft arrested landings due to excessive head flexion. This study used a validated multibody head-neck model to examine how tether stiffness and orientation affect the performance of tether-type head-neck restraint systems. Polyester (stiff) and nylon (soft) tethers were evaluated at four sagittal-plane orientations. Results showed that the presence of a tether significantly reduced peak neck muscle force. Stiff tethers generally provided better restraint, while soft tethers showed slightly lower upper-cervical injury indices. No significant cervical injury was predicted in any condition. These findings can inform future restraint-system design.
To examine the impact of physical exercise on motor skills in children with autism spectrum disorders (ASD). This study followed PRISMA guidelines (PROSPERO: CRD42024600538). Six databases (Embase, Engineering Village, OVID, PubMed, Scopus, and Web of Science) were searched through October 30, 2025. children ≤ 12 years with ASD; randomized controlled trials (RCTs); physical exercise interventions; motor skills outcomes measured via standardized instruments (BOT-2, TGMD-2, PDMS-2, ADS-3, MABC). Two independent reviewers performed study selection and data extraction. Risk of bias was assessed using Cochrane ROB 2.0; evidence quality via GRADE. Statistical analysis used R 4.4.3, calculating standardized mean differences (SMDs) with 95% confidence intervals (CIs). Random-effects models were applied when I² ≥ 50%. Ten RCTs (256 children; mean age 6.91 ± 2.51 years) were included. Physical exercise significantly improved total motor skills (SMD = 1.58, 95%CI: 1.15-2.00, p < 0.0000), locomotion (SMD = 1.34, 95%CI: 0.98-1.70, p < 0.00001), object control (SMD = 1.37, 95%CI: 1.02-1.72, p < 0.00001), and balance (SMD = 1.73, 95%CI: 0.82-2.65, p = 0.0002). Publication bias was detected for total motor skills and balance. Meta-regression showed that intervention frequency positively correlated with balance improvement (p = 0.022), while duration negatively correlated (p = 0.002). Physical exercise significantly improves motor skills in children with ASD. Meta-regression indicates that frequency is a positive moderator for balance gains, but prolonged duration shows diminishing returns due to adaptation plateaus. Age and session length did not affect the protocol, so it remained flexible.
Scorpion venom-derived peptides, such as those from Hemiscorpius lepturus, have gained increasing attention as potent antibacterial agents. In this study, the antibacterial activity of Lep5 R8-18, a novel scorpion venom-derived peptide generated by arginine substitution, was systematically evaluated both in vitro and in vivo, and the bactericidal mechanism was subsequently explored using FITC-labeled peptides for cellular localization assessment, membrane potential assays to evaluate depolarization, reactive oxygen species (ROS) measurements to quantify oxidative stress, and membrane integrity tests to detect permeabilization. Derived peptide Lep5 R8-18 exhibited improved antibacterial activity and reduced hemolytic activity compared with the original sequence, Lep5-18. It also reduced bacterial counts, abscess area, and inflammatory cell infiltration in mouse subcutaneous abscess models established by Staphylococcus aureus ATCC25923 and Escherichia coli ATCC25922 infection. These antibacterial effects may be mediated by depolarization of bacterial membranes, elevation of intracellular ROS levels, and disruption of membrane integrity. In conclusion, the derived peptide Lep5 R8-18 exhibits significantly enhanced antibacterial activity and markedly reduced hemolytic activity. Furthermore, its favorable in vitro and in vivo performance identifies it as a promising therapeutic candidate against S. aureus and E. coli infections.
4‑Nitrophenol (4‑NP) pollution causes serious environmental risks. Traditional catalysts and surfactant‑modified metal foams suffer from insufficient active sites, poor stability and low catalytic efficiency, restricting their practical industrial applications. To solve these problems, this work develops a green, surfactant‑free one‑pot route to fabricate PdCu bimetallic foam catalysts with a unique 3D interwoven nanowire network, which effectively overcomes the above limitations. The catalyst is synthesized via room‑temperature reduction of Pd(NO3)2 and CuSO4 precursors by NaBH4, followed by water‑ethanol alternate washing and freeze‑drying. This fabrication method is simple, scalable and eco‑friendly without harsh synthetic conditions. Key structural and compositional advantages include: the 3D porous network reduces mass‑transfer resistance; surfactant‑free synthesis yields a clean catalyst surface to facilitate active site‑substrate interactions; ultrathin nanowires maximize exposed active sites; and Pd‑Cu electronic synergy decreases Pd consumption and optimizes electronic configuration for improved catalytic activity. Among as‑prepared catalysts, Pd3Cu1 exhibits the optimal performance, achieving complete 4‑NP reduction within 269 s with a high apparent rate constant (Kapp = 29.18 × 10‑3 s‑1) and TOF value of 2309 h‑1, as well as good reusability after five consecutive cycles. This green synthetic strategy and structural merits offer a facile pathway to design high‑performance bimetallic catalysts for environmental remediation.
Early childhood caries (ECC) is a prevalent dental disease with significant public health burdens. Oral microbiota plays a key role in caries development. Although several studies have compared the oral microbiota before and after caries treatment, few have investigated the dynamic changes in oral microbial communities beyond 3 months. This 6-month prospective study monitored dynamic changes in the dental plaque microbiome, salivary pH, and oral hygiene status among children with ECC undergoing caries management. The outcomes were assessed at baseline (T0), immediately post-treatment (T1), and at 1-month, 3-month, and 6-month follow-ups (T2-T4). Children's oral hygiene status improved significantly after ECC management (p < 0.001). Their salivary pH levels increased at T1 but returned to the initial level during follow-up visits. Higher Chao1 scores were observed at T2, T3, and T4 when compared to T0 and T1 (p < 0.001). The principal coordinate analysis revealed distinct clustering patterns between baseline and post-treatment visits. Significant differences were observed in the relative abundance of Corynebacterium (p < 0.01), Corynebacterium matruchotii (p < 0.01), and Selenomonas noxia (p < 0.05) during the study period. The relative abundance of Corynebacterium and Corynebacterium matruchotii was significantly higher at T3 and T4 when compared to T1 (p < 0.01). Additionally, Saccharibacteria was positively correlated with children's dmfs scores and negatively correlated with children's salivary pH values. The above findings possibly indicated that comprehensive ECC management might be associated with dynamic changes in the oral microbiome. Further well-designed randomized controlled trials are warranted to determine the impact of dental treatment on oral microbiota dynamics. KEY POINTS: • Dynamic changes observed in the oral microbiome following dental treatment • Abundance of Saccharibacteria associated with children's caries status and salivary pH values • Children's oral health-related behaviors improved after comprehensive dental management.
Gestational diabetes mellitus (GDM) causes APOs. The diagnostic OGTT has a lag, and the role of lncRNA EGFR-AS1 in GDM has potential. This study evaluated the potential of EGFR-AS1 for the GDM clinical application and explored the role of the EGFR-AS1/miR-142-5p/ROCK2 axis in placental endothelial injury. Serum EGFR-AS1, miR-142-5p and ROCK2 levels were detected via qPCR in 135 GDM patients and 110 healthy pregnant women. The clinic value of EGFR-AS1 was analyzed using ROC and logistic regression. A high glucose (HG)-induced model was established, in which EGFR-AS1 was silenced alone or co-silenced with miR-142-5p. The regulatory mechanism of EGFR-AS1/miR-142-5p/ROCK2 axis on placental endothelial injury was then analyzed via CCK-8, ELISA, qPCR, and WB. In GDM patients, serum EGFR-AS1 and ROCK2 were elevated, whereas miR-142-5p was reduced. Serum EGFR-AS1 showed high diagnostic efficiency for GDM and acted as an independent predictor of APOs occurrence. Silencing EGFR-AS1 reversed HG-induced HPVECs injury-evidenced by inhibited inflammatory factor release, balanced oxidative stress, up-regulated pro-angiogenic factors mRNA expression, and down-regulated proteins expression related to apoptosis and endothelial injury. Dual-luciferase reporter assays confirmed binding between EGFR-AS1 and miR-142-5p, as well as between miR-142-5p and ROCK2. Notably, co-inhibiting EGFR-AS1 and miR-142-5p abolished the protective effect of EGFR-AS1 silencing. EGFR-AS1 is a clinical auxiliary biomarker for GDM diagnosis and prediction. It aggravates HPVECs injury via EGFR-AS1/miR-142-5p/ROCK2 axis, which impairs placental function and triggers APOs, providing a new target for GDM intervention.
To compare axial length (AL) elongation in children with poor response to highly aspherical lenslet (HAL) wear, following different second-line myopia control interventions. This retrospective study included 4097 myopic children who completed 1 year of HAL wear. Poor responders were defined as children with axial elongation ≥0.26 mm/year despite HAL therapy. These children were followed for an additional year and categorised into four groups based on the second-year interventions: continued HAL wear (HAL-HAL), HAL combined with 0.01% atropine (HAL-HALA), switching to diffusion optics technology spectacles (HAL-DOT) and switching to orthokeratology lenses (HAL-OK). Primary outcomes included changes in spherical equivalent refraction (SER) and AL. Logistic regression and multivariable linear regression analyses were performed. After propensity score matching, 168 subjects (42 per group) were included. Significant differences in second-year SER progression and AL elongation were observed among groups (both p < 0.001). The HAL-DOT group exhibited the smallest AL elongation and less SER progression compared with the other groups. Logistic regression showed that, compared with the HAL-HAL group, the HAL-DOT (Odds Ratio (OR) = 0.11, p < 0.001) and HAL-OK groups (OR = 0.34, p = 0.04) had significantly lower odds of a poor response (axial elongation ≥0.26 mm/year). No significant association was found for the HAL-HALA group (p = 0.12). Multivariable regression showed all intervention groups reduced AL elongation, with the greatest effect in the HAL-DOT group (β = -0.227 mm, p < 0.001). Among children with a poor response to initial HAL treatment, switching to alternative interventions, especially DOT, was associated with more favourable axial elongation outcomes and less SER progression. Early treatment modification may help improve outcomes in high-risk children.
The occurrence and progression of autoimmune diseases (AIDs) result from the combined effects of genetic susceptibility, immune response defects, and environmental triggers. Among these, microorganisms, as key environmental factors, have been widely hypothesized to play a role in initiating AIDs, but the exact causal relationship remains to be demonstrated. This review aims to deeply explore the core role of specific microbial infections in triggering AIDs by integrating evidence from three dimensions: epidemiological investigations, clinical studies, and animal model research. We focused on analyzing nine AIDs, including Guillain-Barré syndrome, systemic lupus erythematosus, and rheumatoid arthritis, and confirmed that specific pathogens such as Campylobacter jejuni, Epstein-Barr virus, and Porphyromonas gingivalis can induce corresponding autoimmune pathological damage in susceptible individuals through mechanisms including molecular mimicry and bystander activation. Nevertheless, the field still faces important gaps that caused the chain from mechanism association to clinical application to break.This review integrates existing evidence and demonstrates that microbial infections are one of the important triggers for AIDS. It provides a new theoretical basis and direction for mechanistic research, risk early warning, and targeted intervention of related diseases.
In Alzheimer's disease (AD), Amyloid-β (Aβ) oligomers function as key neurotoxic agents that underpin the disease's progression. A diverse array of therapeutic entities, including peptides, single-chain variable fragments (scFvs), and small molecules, have demonstrated the ability to interact with Aβ oligomers, thereby suppressing their aggregation and associated neurotoxicity. Despite these advances, such agents frequently struggle to promote the phagocytosis and subsequent breakdown of aggregated Aβ by microglia. Moreover, the dense accumulation of Aβ oligomers may resist enzymatic hydrolysis within the acidic lysosomal lumen, contributing to lysosomal stress and dysfunction. To overcome these problems, we engineered a multifunctional fusion protein, p62-LIR-W20-Tuftsin (W20-LT), consisting of an oligomer-specific scFv, a microglia-targeting Tuftsin peptide, and a p62-LIR peptide to activate autophagy. In vitro assays demonstrated that W20-LT significantly outperformed the parental W20 by promoting the rapid microglial uptake of Aβ oligomers and enhancing their intracellular clearance through an autophagy-associated pathway. In APPswe/PS1dE9 (APP/PS1) mice, a low-dose regimen (0.5 µg, every 3 days) of W20-LT, but not W20, significantly ameliorated cognitive deficits and reduced amyloid pathology. Mechanistically, W20-LT was associated with enhanced autophagy-lysosomal pathway activity, as indicated by increased LC3B-II and reduced p62 levels, together with downregulated CatD and LAMP1 levels, thereby mitigating neuroinflammation. In summary, our findings suggest that W20-LT represents a promising proof-of-concept therapeutic strategy that combines scFv-based Aβ oligomer recognition with enhanced autophagy-associated clearance, thereby mitigating AD pathology.
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Osteoporosis (OP) is increasingly recognized as a disorder driven not only by endocrine and metabolic abnormalities but also by chronic low-grade inflammation and aging-related immune dysregulation. Neutrophil extracellular traps (NETs), web-like extracellular DNA-protein structures released by activated neutrophils, can act as structural inflammatory scaffolds that sustain sterile inflammation, oxidative injury, and microenvironmental imbalance. However, the mechanistic contribution and translational significance of NETs in osteoporosis remain incompletely integrated. This review aims to summarize the current evidence linking NET formation to bone remodeling imbalance in osteoporosis, with particular emphasis on osteoclast activation, osteoblast dysfunction, inflammaging, oxidative stress, ferroptosis, metabolic reprogramming, and potential NET-targeted therapeutic strategies. We reviewed recent studies concerning NET biology, osteoimmunology, inflammaging, and inflammation-associated osteoporosis. Based on these findings, we constructed an integrated "NETs-inflammation-bone remodeling imbalance" framework to explain how persistent NET accumulation may promote osteoclastogenesis, impair osteogenic differentiation, amplify inflammatory feedback loops, and reshape the bone microenvironment. We also discussed the potential clinical relevance of neutrophil-related inflammatory indicators and NET-specific biomarkers. Persistent NET formation and insufficient NET clearance under inflammaging conditions may contribute to a self-sustaining inflammatory-oxidative network in the bone microenvironment. NET-derived extracellular DNA, histones, neutrophil elastase, myeloperoxidase, and citrullinated proteins may activate pattern-recognition receptor pathways, including TLR4/NF-κB and potentially TLR9- and TLR2-related signaling, thereby enhancing RANKL-mediated osteoclastogenesis and suppressing osteoblast differentiation and survival. In parallel, NETs may amplify oxidative stress, disturb iron homeostasis, promote ferroptosis susceptibility, and induce metabolic reprogramming, collectively shifting bone remodeling toward bone resorption. Targeting NET formation, promoting NET degradation, or blocking NET-related inflammatory and oxidative signaling may provide new therapeutic opportunities for inflammation-driven osteoporosis. Nevertheless, the NETs-ferroptosis-metabolic reprogramming axis in osteoporosis should currently be regarded as a promising mechanistic framework that requires further experimental and clinical validation.
This study delves into the regulatory mechanism of TRERNA1 in ferroptosis of non-small cell lung cancer (NSCLC) cells. TRERNA1, KAT6A, and PIK3CA are abundantly expressed in NSCLC tissues and cells. TRERNA1 is negatively correlated with ACSL4 but positively correlated with GPX4. TRERNA1 knockdown inhibits cell proliferation and promotes ferroptosis. Mechanistically, TRERNA1 interacts with KAT6A protein to promote KAT6A expression and nuclear ectopy. KAT6A acetylates H3K23, which in turn enhances the binding of TRIM24 to H3K23ac. Therefore, TRIM24 acts as a transcriptional activator to activate the transcription of PIK3CA and inhibit ferroptosis. Overexpression of KAT6A or PIK3CA alleviateS the promoting effect of TRERNA1 knockdown on ferroptosis of NSCLC cells. In conclusion, TRERNA1 represses ferroptosis in NSCLC via the KAT6A/H3K23ac/TRIM24-PIK3CA pathway, representing a promising therapeutic strategy for NSCLC.
We regret to announce the death on May 6, in his ninety-first year, of Academician George S. Golitsyn, a member of the Editorial Board who was among the leading scientists supporting the establishment of Carbon Balance and Management in 2006.
The European Union has established a rigorous system to control food imported from third countries and ensure consumer safety. However, the illegal trade in prohibited food items remains a significant issue. Non-compliant food, often counterfeited through false labeling, can bypass checks at border inspection points, choosing the least monitored entry points. These products pose a threat to public health, as they may contain products of animal origin, undeclared allergens, or come from unauthorized facilities. A recent example is the investigation initiated by the monitoring plan, which uncovered the illicit trade of food of animal origin in some ethnic shops. The Local Health Authority Naples 1 Center carried out extensive inspections of commercial establishments, finding that some foods labeled as wheat- or soy-based snacks were, in fact, prohibited food items from China. The Italian labels reported false information, hiding the real composition of the products. The operation led to the seizure of tons of food, including fish products and difficult-to-identify foods. The analysis detected undeclared allergens and, in some cases, traces of the African swine fever virus, although inactive. Following these discoveries, the Directorate General for Food Safety launched a program of coordinated controls at national level to combat illegal trade. This episode highlights the need to use advanced technologies and strengthen national and international collaboration to protect consumers.
Adrenocortical carcinoma (ACC) is a rare tumor with highly aggressive malignancy. Its two main pathological subtypes, conventional ACC (CAC) and oncocytic ACC (OAC), are hypothesized to differ in clinical behavior, but comparative studies are limited due to the rarity of OAC. This study aimed to compare the clinical characteristics, pathological features, and prognosis between CAC and OAC. A retrospective review was conducted on 128 ACC patients (105 CAC, 23 OAC) during the period of October 2015 and October 2025. Data on clinical presentation, hormonal status, pathological findings, and survival outcomes were collected and analyzed. Statistical comparisons were performed using t-tests, Mann-Whitney U tests, chi-square tests, Cox proportional hazards regression analysis, multivariable Cox proportional hazards regression analysis, and Kaplan-Meier survival analysis with log-rank test. Compared with CAC, OAC patients had a significantly lower prevalence of Cushing's syndrome (13.0% vs. 39.0%, P < 0.05) and hypertension (17.4% vs. 48.6%, P < 0.01). In contrast, adrenal-derived sexual characteristics abnormalities were more common in OAC (65.2% vs. 26.0%, P < 0.001). Pathologically, compared with CAC, the Ki-67 index was significantly lower in OAC (median: 14% vs. 20%, P < 0.05). Also, Kaplan-Meier survival analysis revealed a more favorable overall survival(OS) for OAC, with a 5-year OS rate of 70.4% compared to 48.4% for CAC (P < 0.05). After multivariate adjustment for ENSAT stage and Ki‑67, pathological subtype lost independent prognostic significance, while ENSAT stage and Ki‑67 remained independent predictors. CAC was associated with a higher frequency of glucocorticoid excess symptom, a higher proliferative index (Ki-67). OAC was characterized by a higher prevalence of androgen excess symptoms. OAC demonstrated similar OS to CAC after adjustment for ENSAT stage and Ki‑67.
Although fibroblast growth factor 8 (FGF8) is a critical regulator of skeletal morphogenesis in vertebrates, its specific role in the formation and development of intermuscular bones (IBs) in teleost fish remains insufficiently characterized. In this study, we generated double mutants (fgf8a+/- + fgf8b+/-) in diploid Chongming crucian carp (Carassius auratus) using CRISPR/Cas9-mediated gene editing. Compared to wild-type fish, the double mutants exhibited significantly reduced IB number (p < 0.01), demonstrating a synergistic role of fgf8a and fgf8b in IB formation. Notably, reduced number of IBs did not compromise overall growth, muscle architecture, or reproductive performance. Integrated transcriptomic and metabolomic analyses revealed that the reduced IB phenotype was linked to modifications in relevant signaling pathways and a concomitant upregulation of metabolites beneficial for muscle quality and health. Our findings highlight the crucial role of fgf8 in regulating IB formation and development in crucian carp, providing insights into the genetic mechanisms underlying this process in teleosts.