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Odontoid fractures (OFs) are one of the most common fractures of the upper cervical spine, estimated to represent 9-15% of all cervical fractures. Although their relative frequency, its optimal management is still debated. When surgery is required, anterior odontoid screw fixation (AOSF) offers several advantages, such as preservation of neck rotation, reduced surgical risk, and shorter hospital stay. However, only well-selected patients are eligible for this procedure, and an accurate interpretation of imaging as well as an optimal surgical timing should be taken into account to identify who may be the "best candidates". The aim of this narrative review is to report the current advances in the treatment of OFs by AOSF. We will focus on surgical details, including minimally invasive surgery, as well as on pre- and postoperative critical aspects. With regard to preoperative imaging, type II b OFs (with fracture line oriented from anterior superior to posterior inferior) typically present favourable configuration to be treated by AOSF. Furthermore, a fracture gap >2 mm, an angulation >11° and a displacement >2 mm as well as timing duration from injury to surgery >7 days are predictors of non-union after AOSF. With regard to surgical technique, compared to traditional open technique, MIS procedures are more and more reported. This approach can be performed percutaneously under fluoroscopy or navigation guidance. Finally, the use of a single, bicortical lag screw is strongly suggested to compress the fractured bone surfaces, to reduce the fracture gap and to obtain the best mechanical stability. Our review suggests that AOSF is an effective option in the treatment of type II OFs. However, a meticulous assessment of preoperative images is mandatory, and particular attention has to be paid to fracture configuration, gap, angulation, displacement and ligament integrity. With regard to elderly population, the possibility of wearing rigid collar should be considered, and recent literature reports encouraging results even without any treatment. If a surgical intervention is required, the timing from injury to the operation represents a crucial parameter, making early decisions an important element in the management of type II OFs. Compared to the traditional open approach, minimally invasive AOSF is reliable, promotes faster recovery and in select cases can be performed even under sedation.

Dasatinib is a favorable option for patients with chronic-phase chronic myeloid leukemia (CML-CP) who have an inadequate response, treatment intolerance, or are attempting treatment-free remission (TFR). Dasatinib dose reduction is a strategy to improve tolerability while maintaining efficacy in first-line settings or patients with a stable molecular response. However, whether low-dose dasatinib is safe and effective in second-line or later setting for patients with CML-CP remains unclear. We conducted a retrospective analysis of 53 patients with CML-CP who switched to low-dose dasatinib due to inadequate molecular response (n = 37), treatment intolerance (n = 13), or to re-induce a deeper molecular response (n = 3). Among the 37 patients who had not achieved major molecular response (MMR) before switching, 10 patients (27.0%) attained MMR, 12 patients (32.4%) achieved deep molecular response (DMR/MR4), and 11 patients (29.7%) reached molecular response 4.5 (MR4.5) following low-dose dasatinib therapy. Notably, 81.8% of patients with only baseline MMR improved to MR4 or MR4.5 after switching to low-dose dasatinib. One patient lost MR4 while receiving dasatinib at 50 mg/day and subsequently switched to nilotinib. All three patients who were switched to re-induce deeper molecular responses successfully re-attained MR4.5 after switching to low-dose dasatinib. Adverse events resolved in all 13 patients who switched due to prior TKI intolerance, and no worsening grade 2 or more adverse events were observed. Our findings suggest that low-dose dasatinib for selected patients with CML-CP in second-line therapy or beyond may be safe and effective under close monitoring. Nevertheless, multicenter prospective clinical trials are needed to validate the efficacy and safety of low-dose dasatinib therapy in second-line treatment settings or beyond in CML.

Depression is a known risk factor for cardiovascular disease (CVD), but the impact of long-term depressive symptom burden remains unclear. We examined the association between cumulative depression burden and risks of CVD and all-cause death among adults aged ≥50 years in China and Mexico. Data were obtained from 2 nationally representative cohorts: CHARLS (China Health and Retirement Longitudinal Study) and MHAS (Mexican Health and Aging Study). Cumulative depression burden was quantified using 2 approaches: (1) the area under the curve of repeated depression scores and (2) the number of waves with depression. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for incident CVD and all-cause death. The analysis included 5277 CVD-free participants from CHARLS and 4779 from MHAS. Higher cumulative depression burden was significantly associated with elevated risk of CVD. Compared with the lowest-quartile group, participants in the highest-quartile group had significantly greater CVD risk (CHARLS: HR, 1.723 [95% CI, 1.420-2.090]; MHAS: HR, 1.739 [95% CI, 1.347-2.245]). Dose-response associations were observed in both cohorts. Persistent depression was also linked to higher CVD risk compared with isolated or less frequent episodes. Associations with all-cause death differed by cohort, with significant associations observed in CHARLS but not in MHAS. Long-term cumulative depression burden is strongly associated with increased CVD risk among adults aged ≥50 years. Routine screening and sustained management of depressive symptoms should be considered integral to CVD prevention strategies.

Gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDPs) are common maternal complications. We sought to evaluate the independent and joint association of GDM and HDPs with all-cause, premature, and cause-specific mortality. We used data from the UK Biobank, which included 220 953 women who reported at least one live birth. Individual and joint associations of GDM and HDPs with all-cause, premature, and cause-specific mortality were estimated using Cox regression models. During a follow-up of 12.9 years, women who experienced GDM had a higher risk of all-cause (hazard ratio (HR) = 1.57; 95% confidence interval (CI) = 1.26-1.96), premature (HR = 1.60; 95% CI = 1.24-2.06) and cardiovascular disease (CVD) mortality (HR = 2.60; 95% CI = 1.70-3.96). Women with a history of HDPs had an increased risk for CVD mortality (HR = 2.07; 95% CI = 1.51-2.83), but the association with all-cause death and premature death was not significant. Individuals who encountered both GDM and HDPs had a 3.9-fold higher relative risk of all-cause mortality (HR = 3.93; 95% CI = 1.88-8.24]) and a 4.3-fold higher risk of premature mortality (HR = 4.31; 95% CI = 1.94-9.57), compared to those without GDM or HDPs. Women with GDM have a higher risk of all-cause, premature mortality and both risks were higher than the impacts of a history of HDPs based on a large-scale population. The co-occurrence of GDM and HDPs will deteriorate the aforementioned situation compared to a single cardiometabolic pregnancy complication.

Coronary microvascular disease (CMVD) is a major cause of angina in patients with ischemia and nonobstructive coronary arteries (INOCA) syndrome. It is characterized by an imbalance between myocardial oxygen supply and demand, leading to reduced exercise tolerance and impaired quality of life. Because of heterogeneous diagnostic approaches and the lack of disease-modifying therapies, CMVD remains underdiagnosed and undertreated. Shexiang Tongxin Dropping Pill (STDP), a traditional Chinese medicine formulation, has shown protective effects on the coronary microvasculature in preclinical and preliminary clinical studies. However, high-quality randomized evidence and objective functional validation are still lacking. This study therefore aims to evaluate the efficacy and safety of STDP in patients with CMVD using cardiopulmonary exercise testing (CPET) as the primary functional outcome and to develop an artificial intelligence (AI)-assisted myocardial contrast echocardiography (MCE) tool to improve CMVD detection and subgroup classification. This is a prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial with a nested diagnostic design. CMVD will be diagnosed by stress MCE, and eligibility will require evidence of reduced myocardial perfusion or perfusion defects. Eligible patients with CMVD will be randomized at a 1:1 ratio to receive STDP or a matched placebo for 12 weeks. The primary endpoint is the change in peak oxygen uptake (peak VO₂) measured by cardiopulmonary exercise testing (CPET). The secondary outcomes include other CPET indices, angina severity, quality of life, and circulating biomarkers. The nested diagnostic study uses retrospectively and prospectively collected MCE datasets to develop AI-based models for automated myocardial segmentation, perfusion curve analysis, and CMVD classification, with performance assessed against established reference standards. By combining quantitative microvascular imaging, functional exercise assessment, and AI-assisted diagnostics in a single protocol, this study proposes a therapeutic-diagnostic framework for CMVD. This study is expected to provide high-quality randomized evidence for the use of STDP in CMVD and to offer a scalable and objective approach to improve diagnosis, risk stratification, and individualized management in patients with functional coronary ischemia. http://itmctr.ccebtcm.org.cn/, International Traditional Medicine Clinical Trial Registry (ITMCTR), TMCTR2025000414.

Panax ginseng C.A. Meyer, a renowned medicinal herb, exerts many of its systemic effects through intricate interactions with the gut microbiota, a relationship that also addresses the challenge of its own limited oral bioavailability. This review comprehensively examines the role of ginseng and its bioactive constituents in modulating gut microbiota and their subsequent influence on host health through key gut-organ axes. Based on an in-depth analysis of literature, we summarize how ginseng intervention is associated with a modulated gut microbial ecology-characterized by enriched beneficial taxa and suppressed pathogens-and is further linked to enhanced barrier integrity, regulated microbial metabolites, and reduced inflammation and oxidative stress. These mechanisms underlie its protective effects across multiple organ systems, including the gut-brain, gut-liver, gut-lung, gut-heart, and gut-kidney axes, ameliorating conditions such as cognitive decline, hepatic inflammation, pulmonary fibrosis, atherosclerosis, and renal injury. Clinical evidence further associates ginseng with improved metabolic and cognitive parameters correlated to microbial changes. We conclude that the therapeutic activity of ginseng appears to involve, and is likely modulated by, its prebiotic-like influence on the gut microbiota. However, the degree to which its efficacy is microbiota-dependent varies across different organ systems, as established by current evidence. Further mechanistic and clinical studies, particularly those employing causal models, are essential to definitively validate its potential in treating chronic diseases via microbiota-based strategies.

Increasing evidence has identified significant white matter lesions (WMLs) in Parkinson's disease (PD) patients. However, the complex relationships between WMLs and the neuropathological changes of PD remain unclear. In this study, we comprehensively elucidated the spatiotemporal dynamics of WMLs in rotenone-, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD models, and α-synuclein (α-Syn) (A53T) transgenic mice. The results showed that WMLs occurred across multiple brain regions and gradually aggravated as PD models progressed. Notably, WMLs emerged as early pathological events of PD prior to dopaminergic neuronal loss. Consistently, WMLs-related axial movement disorders, including gait and balance impairments, preceded those caused by nigrostriatal injury. Further in vitro studies revealed that oligodendrocyte precursor cells (OPCs) dysfunction caused by 1-methyl-4-phenylpyridinium (MPP⁺) or α-Syn could induce dopaminergic axonal breakage and neuronal damage, confirming myelination disorder promoted dopaminergic neuronal degeneration. This finding was certified in additional in vivo studies using lysophosphatidylcholine (LPC)-induced demyelination models. The results validated that WMLs could independently induce dopaminergic neuronal damage and nigrostriatal pathway-related movement disorders. Moreover, comorbid WMLs in PD mice further aggravated this process. In summary, our findings uncovered the spatiotemporal characteristics of WMLs and their contribution to PD pathological development, highlighting that targeting WMLs might be a potential strategy for PD intervention.

The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway is involved in the pathogenesis of a variety of inflammatory and autoimmune skin diseases, such as atopic dermatitis (AD), psoriasis, alopecia areata (AA), vitiligo, etc. Many cytokines are involved in the occurrence and development of these diseases through the JAK-STAT-mediated intracellular signaling. Small molecule JAK inhibitors (JAKi) have demonstrated substantial efficacy in the treatment of many diseases, especially in inflammatory skin diseases. For example, abrocitinib and upadacitinib have been approved for the treatment of moderate-to-severe AD, and baricitinib has been approved for the treatment of severe AA. Meanwhile, clinical and preclinical studies of various JAKis for other skin diseases are ongoing. However, the traditional classification of inflammatory skin diseases according to the T helper (Th) immune axis fails to distinguish between cytokine signals that are mechanistically dependent on the JAK-STAT pathway and those that are not, thus limiting its utility for guiding targeted therapy. Accordingly, we propose a functional refinement framework that integrates JAK-dependent cytokine modules into the established Th immune axis system. This article reviews the pathogenesis of "JAK-STAT pathway-associated skin diseases" and the available efficacy evidence of JAKi therapy, aiming to improve the mechanistic understanding and rational clinical application of JAKi and provide valuable references for clinical diagnosis and treatment.

A subset of Alzheimer's disease (AD) patients exhibits a procoagulant state that remains undiagnosed despite available treatments. We developed positron emission tomography (PET) strategies to in vivo detect cerebral microthrombi in TgCRND8 mice. PET was performed with a fibrin-binding probe (FBP) in TgCRND8 and wild-type mice using a zirconium-89-radiolabeled and a click-chemistry pre-targeted gallium-68 radiotracer. Platelet content was assessed in post mortem brain tissue from AD patients and TgCRND8 mice, and evaluated by PET using a CD41 pre-targeted gallium-68 nanoradiotracer. Cerebral FBP uptake differentiated TgCRND8 from wild-type mice, particularly ex vivo and with advancing age. Cerebral fibrin burden correlated with platelet content in AD patients, and elevated cerebral platelet burden in TgCRND8 mice was confirmed in post mortem tissue and in vivo by PET. Our findings support PET-based detection of AD-associated cerebral microthrombi and the development of imaging biomarkers to stratify AD patients by procoagulant status and inform personalized therapies.

Ovarian Mature Cystic Teratomas (MCTs), the most common type of ovarian teratoma, contain tissues from all three germ layers. The "floating ball sign," which consists of mobile spherules of sebum and keratin, is a characteristic feature seen on Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). However, the imaging features can overlap with other cystic lesions, leading to potential misdiagnosis. This case report focuses on a giant MCT initially misdiagnosed as hydatid disease on CT. Its value lies in highlighting the diagnostic pitfall of over-relying on CT and demonstrating how a systematic, multimodal approach resolves uncertainty. A 40-year-old female presented to our hospital due to a 3-month history of progressive, painless abdominal distension and recent urinary frequency/urgency. On physical examination, a soft, non-tender mass was palpated in the umbilical region. Initial abdominal-pelvic contrastenhanced CT revealed a huge cystic lesion with multiple internal cystic structures resembling "daughter cysts", a feature suggestive of hydatid disease. However, preoperative parasite tests returned negative, creating a conflict with this initial suspicion, and the mass effect caused by the lesion obscured its origin on CT. This discrepancy prompted further evaluation, which revealed mobile intracystic spherical structures via targeted ultrasound, confirming their mobility and floatability. Meanwhile, MRI identified characteristic fat content through fat-saturated sequences. These findings confirm the "floating ball sign," which collectively supported the possible diagnosis of MCT. The diagnosis was confirmed by exploratory laparotomy and subsequent histopathological analysis. This case illustrates that while CT is useful for initial evaluation of giant abdominopelvic masses, its findings can be misleading. When imaging and clinical data conflict, a deliberate diagnostic reconsideration pathway using targeted ultrasound and MRI is key to avoiding misdiagnosis.

The aim of the present study was to elucidate the regulatory effect of Morinda officinalis oligosaccharides (MOOs) on the brain‑derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB)/cAMP response element‑binding protein (CREB) signalling pathway and the gut microbiota in a corticosterone (CORT)‑induced chronic stress model. Mice received subcutaneous injections of CORT for 35 days. During this period, different concentrations of MOOs were concurrently administered by gavage. The synergistic regulatory effect of MOOs on the hippocampal BDNF/TrkB/CREB signalling pathway and gut microbiota remodelling was assessed using western blotting, ELISA, 16S ribosomal RNA sequencing, H&E/Nissl staining and reverse transcription‑quantitative PCR in the CORT‑induced chronic stress mouse model. In this model, MOOs alleviated depression‑like behaviour, promoted the expression of BDNF and neuronal nuclear antigen in the hippocampus, normalised monoamine neurotransmitter levels in the brain, activated the BDNF/TrkB/CREB signalling pathway, increased BDNF expression in the hippocampus and remodelled the intestinal microbiota, thereby exerting antidepressant effects. These results suggested that MOOs exerted antidepressant‑like effects in CORT‑exposed mice by attenuating hippocampal neuronal damage, activating the BDNF/TrkB/CREB signalling pathway and ameliorating gut microbiota dysbiosis. These findings provide novel evidence for the clinical application of MOOs in depression.

While multimodal large language models (LLMs) demonstrate significant potential in healthcare applications, their clinical utility is difficult to appraise. Current evaluations of medical-assisting LLMs are often limited by sparse human expertise, narrow specialty scope, and reliance on multiple-choice benchmarks or synthetic vignettes, which can inflate performance and obscure clinical utility. We conducted a multicenter, multidisciplinary study in which more than 400 physicians-spanning seven specialties, varied experience levels, and multiple geographic settings-evaluated LLM-generated free-text responses to real, de-identified clinical cases. In a matched-control design, we also deployed an equivalent number of AI agents configured to mirror physician characteristics to examine whether automated evaluators can supplement or replace human assessment. Our results demonstrated that physician assessments exhibited substantial heterogeneity by clinical seniority and practice environment, leading to notable shifts in relative model rankings across cohorts. While AI agents delivered highly efficient, directionally aligned assessments, they did not fully capture the nuances of human clinical judgment and could not substitute for physician-centered evaluation. Instead, they promise assistive tools that can triage or pre-screen outputs to reduce human burden.

The progression from ductal carcinoma in situ (DCIS) to invasive breast carcinoma (IBC) critically determines patient outcomes, yet its mechanisms remain incompletely understood. Integrating single-cell RNA sequencing, spatial transcriptomics, and genomics across 28 patients with synchronous DCIS and IBC, we delineate the spatial-molecular hierarchy of this transition. Invasion is primarily driven by clonal expansion of pre-existing DCIS subclones, emphasizing transcriptional reprogramming and tumor microenvironment (TME) remodeling over acquisition of additional driver alterations. IBC cells exhibit pronounced epithelial-mesenchymal transition and metabolic reprogramming. We uncover dynamic TME remodeling at the invasive front, identifying key ligand-receptor interactions (e.g., PPIA-BSG, MDK-LRP1, CXCL12-CXCR4) facilitating basement membrane disruption, angiogenesis and immunosuppression. Deconvolution of basement membrane breach reveals four molecularly defined stages (NMFT1-NMFT4) with progressively worsening patient survival. This study establishes a unified spatial-molecular atlas of DCIS-IBC progression, highlighting clonal expansion, transcriptional plasticity and TME remodeling as key drivers of invasion.

Digital medical images of pediatric orthopedic diseases are widely exchanged and transmitted on medical sharing platforms for medical usage. However, it faces serious copyright challenges due to the ease of replication and the limited effectiveness of copyright protection tools. To solve the problems, this paper pro- poses a deep learning zero-watermark scheme based on a dual-source collaborative cross-attention mechanism. First, shallow features of medical and watermark images are extracted via convolutional neural networks. Then, the proposed dual-source collaborative cross-attention fuses host and watermark features, selectively enhancing relevant information while suppressing noise, thus reducing feature homogenization and improving discriminability. Finally, the fused representation is decoded to construct the zero-watermark image. Experimental results have shown that the reconstructed watermark information remains authentic under filtering, noise, rotation, and crop attacks, achieving ideal Peak Signal-to-Noise Ratio (PSNR) and Normalized Correlation (NC) scores. It has been demonstrated that the proposed method offers technical support for the trustworthy sharing and standardized authentication of medical images related to pediatric orthopedic diseases.

Leclercia adecarboxylata is a motile, Gram-negative bacillus in the Enterobacteriaceae family and is ubiquitous in nature. In our study, we report a case of catheter-associated bloodstream infection caused by multidrug-resistant L. adecarboxylata in a colon tumor patient. The clinical symptom of the patient was high fever with chills. Initially, the patient was treated empirically with cefoperazone-sulbactam. Although cefoperazone-sulbactam was used for 4 days, the patient still had a fever. Then the bacterial cultures of the peripheral blood and catheter were positive for L. adecarboxylata. The treatment regimen was changed to meropenem. After the treatment, the patient's clinical symptoms improved and the patient was discharged. Although L. adecarboxylata is regarded as a highly sensitive pathogen, it was a multidrug-resistant bacterium in our study. We recommend that the treatment of L. adecarboxylata should be based on antimicrobial sensitivity tests.

Minimally displaced intra-articular calcaneal fractures are commonly managed with cast immobilization, but prolonged immobilization may delay recovery and contribute to hindfoot stiffness. This study compared mid-term clinical and radiographic outcomes of two institutional protocols for minimally displaced Sanders type II-III calcaneal fractures: closed reduction and percutaneous screw fixation with earlier range-of-motion exercises versus cast immobilization. This two-center retrospective cohort study included 87 patients treated between January 2018 and February 2024 with a minimum 24-month follow-up. Fifty-three patients underwent closed reduction and percutaneous fixation using two 5-mm headless cannulated screws, with range-of-motion exercises beginning at 2 weeks. Thirty-four patients were treated nonoperatively with short-leg cast immobilization for 6 weeks. The primary outcome was the Foot and Ankle Ability Measure (FAAM), including Activities of Daily Living and Sports subscales. Secondary outcomes included the AOFAS Ankle-Hindfoot score, visual analog scale pain score, and serial radiographic measurements. Pre-treatment demographic, fracture, follow-up, and radiographic characteristics were comparable between groups. At final follow-up, the fixation and earlier rehabilitation protocol was associated with higher FAAM Activities of Daily Living, FAAM Sports, and AOFAS scores. VAS pain was lower in unadjusted analysis but was not significant after adjustment. Final Böhler and Gissane angles were higher in the fixation group. The fixation group also showed greater calcaneal height increase and calcaneal length decrease from pre-treatment to final follow-up. All fractures united. No wound-healing complications or surgical-site infections occurred after fixation; posterior implant-entry-site irritation occurred in three patients and required implant removal after union. In selected minimally displaced Sanders type II-III calcaneal fractures, the institutional protocol including closed reduction, percutaneous screw fixation, and earlier rehabilitation was associated with better mid-term functional outcomes and more favorable radiographic parameters than cast immobilization. Prospective comparative studies are needed to evaluate fixation, cast immobilization, and functional nonoperative rehabilitation strategies.

Scaphoid fractures are common carpal injuries that are commonly treated operatively. Increasingly, patient-reported outcome measures (PROMs) highlight the influence of expectations on perceived success. The Trauma Expectation and Trauma Outcome Measure (TEFTOM) is a validated instrument assessing expectations (TEF) and outcomes (TOM) across domains of pain, function, disability, injury satisfaction, and overall satisfaction. While applied in other orthopaedic trauma conditions, TEFTOM has not been previously studied in scaphoid surgery. This prospective cohort study enrolled 51 adult patients with acute scaphoid fractures treated operatively and achieving union within 6 months. The TEF questionnaire was administered preoperatively, while the TOM was administered at 12 and 24 months. Expectation fulfillment was calculated as TOM/TEF (%). Clinical measures included the Mayo Wrist Score and Patient-Rated Wrist Evaluation (PRWE). Correlation analyses assessed relationships between expectations, outcomes, and satisfaction. The median patient age was 31 years; 66.7% sustained right-sided injuries, and most fractures involved the scaphoid waist (72.5%). Baseline TEF scores were uniformly high (mean 37/40). TOM scores improved from 31.3 at 12 months to 35.2 at 24 months (P&#x2009;<&#x2009;0.001). Fulfillment rose from 84.8% at 12 months to 95.4% at 24 months. Satisfaction strongly correlated with fulfillment at both 12 months (r&#x2009;=&#x2009;0.78, p&#x2009;<&#x2009;0.001) and 24 months (r&#x2009;=&#x2009;0.65, p&#x2009;<&#x2009;0.001), but not with Mayo Wrist or PRWE scores. Higher baseline expectations predicted lower fulfillment and lower satisfaction despite similar functional outcomes. Patients in the low-expectation tertile reported greater fulfillment and satisfaction compared with the high-expectation group (p&#x2009;<&#x2009;0.001). This first application of the TEFTOM instrument in scaphoid fracture surgery demonstrates its ability to differentiate objective recovery from subjective fulfillment. Despite uniformly favorable functional outcomes, higher preoperative expectations were associated with lower fulfillment and satisfaction. Continued improvement between 12 and 24 months highlights the prolonged recovery trajectory of scaphoid injuries. Integrating expectation assessment through TEFTOM may enhance patient counseling and provide a more comprehensive evaluation of surgical success beyond traditional PROMs. Prospective cohort study, Level II.

Congenital biliary dilatation (CBD) in children remains a disease of enigmatic origin. Prevailing theories focusing on anomalous pancreaticobiliary ductal union (APBDU) fail to explain the critical anatomical hallmark of Type Ia CBD: the coexistence of a distal stenotic segment (DSS) and a proximal dilated segment (PDS). We aimed to define region-specific molecular landscapes to bridge this fundamental gap. We conducted label-free proteomic and histomorphometric analyses on distinct surgical specimens-cystic duct (CD: as the least-affected internal reference), DSS, and PDS-from pediatric CBD patients (n&#x2009;=&#x2009;5 proteomics; n&#x2009;=&#x2009;12 validation). Key findings were rigorously validated using multiplex immunofluorescence, immunohistochemistry, and functional enrichment. Proteomic profiling established DSS and PDS as biologically distinct pathological entities. While both segments shared severe epithelial dysfunction and mechanosensory ciliary loss, a profound molecular dichotomy emerged in smooth muscle remodeling. The DSS was characterized by robust ferroptosis-associated fibrosis (TFR1/&#x3b1;-SMA co-localization) and &#x3b2;-amyloid-associated neural degeneration. Conversely, the PDS exhibited marked muscular atrophy and wall tension failure (CALD1 upregulation). This regional proteomic atlas reveals a pronounced spatial dichotomy, calling into question the adequacy of traditional uniform disease models. These findings suggest that ferroptosis may contribute to distal stenosis and highlight potential therapeutic targets to mitigate fibrosis and improve long-term surgical outcomes.

Salmonella enterica serovar Infantis has emerged over the past two decades as the dominant Salmonella serovar in European Union (EU) broiler production. Due to largely asymptomatic colonization in poultry, multidrug-resistant (MDR) strains can disseminate silently within flocks, leading to contamination of meat products and raising significant One Health concerns. In Italy, S. infantis represents up to 90% of Salmonella isolates from broilers chickens and approximately 40% of human cases, highlighting the need for improved monitoring tools to support risk management strategies. Quantitative microbial risk assessment (QMRA) approaches require accurate and reliable quantitative data. To this end, we developed and validated a rapid and specific method for quantifying S. infantis in poultry environmental fecal samples. The method is based on a miniaturized most-probable-number (MPN) approach adapted from ISO 6579-2, combined with confirmation by a S. infantis-specific qPCR assay. Matrix effects associated with environmental poultry feces were evaluated using the Bland-Altman approach. Method performance, including repeatability and reproducibility, was assessed using both spiked and naturally contaminated samples. Specificity was ensured by the high analytical specificity of the confirmatory qPCR. When applied to naturally contaminated samples, the method demonstrated suitability for quantifying S. infantis loads in poultry environmental feces, providing robust data to support QMRA-based interventions and surveillance strategies within broiler production systems.