Accurate etiological differentiation between hepatitis B virus (HBV)-related cirrhosis and schistosomiasis-related cirrhosis remains clinically important in endemic regions because these conditions differ substantially in their underlying pathogenesis, clinical management, and prognosis. A non-invasive imaging approach may provide complementary information for etiological assessment. To develop a CT-based clinical-radiomics model for the non-invasive differentiation of HBV-related and schistosomiasis-related cirrhosis and to evaluate its diagnostic performance in a multicenter cohort. This retrospective multicenter study included 143 patients with HBV-related or schistosomiasis-related cirrhosis from three institutions between August 2019 and December 2021. Radiomics features were extracted from non-contrast CT images, and a radiomics signature (Rad-score) was established using minimum redundancy maximum relevance (mRMR) and least absolute shrinkage and selection operator (LASSO) regression. Clinical and integrated clinical-radiomics models were subsequently developed using multivariable logistic regression. Model performance was evaluated using receiver operating characteristic analysis, calibration curves, and decision curve analysis (DCA). The Rad-score was significantly lower in patients with HBV-related cirrhosis than in those with schistosomiasis-related cirrhosis (both P < 0.001 in the training and internal validation cohorts). The integrated clinical-radiomics model demonstrated excellent diagnostic performance, with area under the receiver operating characteristic curve (AUC) values of 0.990 in the training cohort, 0.920 in the internal validation cohort, and 0.782 in the external validation cohort. Compared with the clinical model alone, both the radiomics and integrated models demonstrated more consistent performance across the internal and external validation cohorts, while the integrated model showed the greatest overall clinical utility on DCA. The proposed CT-based clinical-radiomics model provides a promising non-invasive approach for differentiating HBV-related and schistosomiasis-related cirrhosis. As a complementary imaging tool, it may assist etiological assessment in endemic regions when interpreted alongside routine clinical and laboratory evaluation. Further prospective multicenter studies are warranted to validate its clinical utility.

Neuroinflammation is a key factor contributing to cognitive decline in Alzheimer’s disease (AD). This study aims to investigate the mechanistic associations among neuroinflammation, glymphatic dysfunction, tau pathology, and cognitive decline in AD spectrum. The study included 355 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and a supportive cohort of 59 individuals from Wuhan Union Hospital (WHUH). Tau pathology was quantified using 18F-AV1451 positron emission tomography (PET). Glymphatic function was estimated through diffusion tensor image analysis along the perivascular space (DTI-ALPS). Neuroinflammation was assessed via plasma glial fibrillary acidic protein (GFAP) in two cohorts and translocator protein (TSPO) PET imaging with 18F-DPA-714 in supportive cohort. Correlation analyses and mediation models were employed to evaluate the directional relationships among tau deposition, inflammation, glymphatic function, and cognition. Higher levels of inflammation were significantly associated with lower DTI-ALPS index (β = −0.171, P = 0.046), which in turn was associated with higher tau burden (β = 0.162, P = 0.010). Path analysis revealed significant indirect associations linking neuroinflammation to cognitive performance through glymphatic dysfunction and tau pathology, with total indirect effects of − 0.165 (95

Background and objectiveObesity is a heterogeneous metabolic condition that may influence tumor biology and therapeutic outcomes. However, factors associated with the response to postoperative radioactive iodine (131I) therapy in obese patients with papillary thyroid carcinoma (PTC) remain insufficiently understood. This study aimed to identify clinical and metabolic factors associated with treatment response in this population.MethodsThis retrospective observational study included obese patients with PTC who underwent postoperative 131I therapy between January 2020 and December 2023. Clinical, biochemical, imaging, treatment, and follow-up data were collected from electronic medical records. Treatment response at the most recent follow-up was classified as excellent response (ER) or non-excellent response (NER) according to the 2025 American Thyroid Association (ATA) guidelines. Logistic regression analysis was performed to identify factors associated with treatment response, and receiver operating characteristic (ROC) analysis was used to evaluate predictive performance.ResultsA total of 219 obese patients with PTC were included, with a median follow-up of 31.00 months. At the last follow-up, 91 patients (41.6%) achieved ER. In multivariable analysis, higher high-density lipoprotein (HDL) levels were independently associated with an increased likelihood of ER (OR = 22.891, 95% CI: 2.644-198.206, P = 0.004), whereas higher pre-ablation stimulated thyroglobulin (sTg) levels were independently associated with a lower likelihood of ER (OR = 0.793, 95% CI: 0.719-0.876, P < 0.001). Triglycerides (TG) also showed a weaker association with treatment response (OR = 0.662, 95% CI: 0.442-0.991, P = 0.045). Among the individual indicators, sTg showed the best discriminatory performance (AUC = 0.767), followed by HDL (AUC = 0.672) and TG (AUC = 0.624). A combined model incorporating HDL and sTg improved predictive performance (AUC = 0.822).ConclusionIn obese patients with PTC who underwent postoperative 131I therapy, pre-ablation sTg and HDL were independently associated with treatment response, whereas TG showed a weaker association. The combination of HDL and sTg provided better discriminatory performance than either marker alone. These findings suggest that combining metabolic indicators with conventional tumor-related markers may improve individualized evaluation of treatment response in obese patients with PTC.

Fibroblast activation protein (FAP) is a serine protease overexpressed in activated fibroblasts during tissue remodeling, chronic inflammation, and fibrosis. While initially developed as a target for cancer imaging, FAP inhibitor (FAPI)-based PET imaging has shown increasing promise in a broad range of non-neoplastic inflammatory diseases. This review provides a comprehensive summary of recent advances in the application of FAPI PET/CT and PET/MR in inflammatory conditions, including immune-mediated inflammatory arthritis, thyroid-associated disorders, cardiovascular inflammatory disorders, immunoglobulin G4-related disease (IgG4-RD), infectious diseases, and others. Across these disease categories, FAPI PET demonstrates high target-to-background contrast and enables sensitive detection of fibroblast activation, which correlates with inflammatory and fibrotic burden. In conditions such as rheumatoid arthritis, Takayasu arteritis, IgG4-RD, and Crohn disease, FAPI PET has shown added diagnostic value over 18F-FDG PET, particularly in evaluating disease activity, subclinical involvement, and fibrotic changes. Furthermore, its whole-body capability facilitates accurate lesion localization, biopsy site selection, and dynamic treatment monitoring. Despite encouraging results, further research is warranted to address tracer heterogeneity, refine disease-specific imaging protocols, and validate its utility through large-scale prospective trials. Overall, FAPI PET is an emerging molecular imaging modality with significant potential for personalized diagnosis, disease stratification, and clinical decision-making in inflammation-driven conditions.

The incidence of thyroid cancer has been rising in recent years. While tumorigenesis has traditionally been attributed to the accumulation of genetic mutations in oncogenes and tumor suppressor genes, increasing attention has been directed toward the role of epigenetic regulation in cancer development. Since the 1980s, however, it has been acknowledged that the role of another key regulatory system in carcinogenesis: epigenetics, shedding light on the regulation of gene expression without altering the DNA sequence.This review synthesizes current literature on epigenetic alterations in follicular cell-derived thyroid cancers, focusing on DNA methylation, histone modifications, chromatin remodeling, and RNA regulation. Evidence indicates that dysregulation of these epigenetic processes is prevalent in thyroid cancer, influencing tumor initiation, progression, and resistance to therapy. Several epigenetic inhibitors are under development, some demonstrating synergy with existing chemotherapies and immunotherapies. Understanding these mechanisms may facilitate the development of novel, more effective strategies for early detection and treatment.

This article reviews the fundamental concepts of epigenetics and its related mechanisms, and discusses recent advances in epigenetic gene editors and their applications in disease treatment. First, the article introduces the concept of epigenetic inheritance and the four main epigenetic mechanisms. Then, after briefly outlining traditional gene editing, it presents epigenetic gene editors, their associated tools, and the historical context of their development. Subsequently, the article describes the working principles and advantages of epigenetic editing tools such as KRAB and DNMT. Addressing the current bottlenecks in the field, the article provides an in-depth analysis of editing efficiency and specificity, long-term safety, and the complexity of clinical applications. In addition, it discusses optimization strategies for delivery systems, minimization of off-target effects, and therapeutic approaches for multigene disorders. Finally, the article outlines the progress of epigenetic editors in both neoplastic and non-neoplastic disease research. In summary, this article offers a comprehensive review of the theoretical foundations of epigenetics, the evolution of gene editing tools, and the latest advances in epigenetic editors for disease treatment, providing a valuable reference for future research and clinical application.

Fibroblast activation protein (FAP) is a serine protease overexpressed in activated fibroblasts during tissue remodeling, chronic inflammation, and fibrosis. While initially developed as a target for cancer imaging, FAP inhibitor (FAPI)-based PET imaging has shown increasing promise in a broad range of non-neoplastic inflammatory diseases. This review provides a comprehensive summary of recent advances in the application of FAPI PET/CT and PET/MR in inflammatory conditions, including immune-mediated inflammatory arthritis, thyroid-associated disorders, cardiovascular inflammatory disorders, immunoglobulin G4–related disease (IgG4-RD), infectious diseases, and others. Across these disease categories, FAPI PET demonstrates high target-to-background contrast and enables sensitive detection of fibroblast activation, which correlates with inflammatory and fibrotic burden. In conditions such as rheumatoid arthritis, Takayasu arteritis, IgG4-RD, and Crohn disease, FAPI PET has shown added diagnostic value over 18 F-FDG PET, particularly in evaluating disease activity, subclinical involvement, and fibrotic changes. Furthermore, its whole-body capability facilitates accurate lesion localization, biopsy site selection, and dynamic treatment monitoring. Despite encouraging results, further research is warranted to address tracer heterogeneity, refine disease-specific imaging protocols, and validate its utility through large-scale prospective trials. Overall, FAPI PET is an emerging molecular imaging modality with significant potential for personalized diagnosis, disease stratification, and clinical decision-making in inflammation-driven conditions.

Renal dynamic scintigraphy is a crucial diagnostic tool for assessing renal function, yet unexpected findings can provide additional insights into extrarenal conditions. We report 2 rare cases of extrarenal 99m Tc-DTPA uptake associated with adrenal tumors: one adrenal cortical carcinoma and one pheochromocytoma. In both cases, significant tracer accumulation in the adrenal region was observed, highlighting an uncommon but noteworthy diagnostic consideration. These cases emphasize the importance of including adrenal tumors in the differential diagnosis when encountering abnormal 99m Tc-DTPA uptake patterns, offering valuable clinical insights for interpreting atypical imaging findings and broadening diagnostic perspectives.

Inflammatory diseases, including autoimmune, infectious, and metabolic disorders, remain major global health challenges due to their complex pathogenesis and limited therapeutic options. In recent years, bioinspired nanotechnology has emerged as a transformative approach in precision medicine. Among various strategies, macrophage membrane-coated nanoparticles (MΦ-NPs) have gained significant attention for their excellent biocompatibility, immune evasion, and lesion-targeting capabilities. This review systematically outlines the construction strategies, biological characteristics, and functional mechanisms of MΦ-NPs. It details the fabrication process, including core material design, macrophage membrane extraction and functionalization, and efficient membrane–core assembly. The current applications of MΦ-NPs in the diagnosis and treatment of non-tumor inflammatory diseases, such as bacterial and viral infections, rheumatoid arthritis, inflammatory bowel disease, atherosclerosis, and bone tissue repair are comprehensively reviewed. Special emphasis is placed on their unique behavior in inflammatory microenvironments, where they enable site-specific drug delivery, prolonged circulation, and immune modulation, offering innovative solutions to long-standing therapeutic challenges. Furthermore, we discuss the emerging hybrid membrane systems that integrate macrophage membranes with those of red blood cells, platelets, or tumor cells, enhancing both targeting and therapeutic performance. Despite promising preclinical results, challenges remain regarding large-scale production, clinical translation, and biosafety evaluation. By integrating insights from nanotechnology, immunology, and translational medicine, this review provides a comprehensive perspective on the design, functionality, and therapeutic frontiers of MΦ-NPs. Continued advances in biomimetic nanomedicine are expected to drive the development of next-generation anti-inflammatory therapies with high precision and minimal systemic toxicity.

Sphingosine-1-phosphate (S1P) and its receptors (S1PRs) are pivotal regulators of immune cell trafficking, vascular integrity, and various physiological processes, playing key roles in the pathogenesis of neuroinflammatory and immune-related disorders. Among these, multiple sclerosis (MS) is the most common chronic inflammatory condition affecting the central nervous system (CNS), marked by autoimmune-induced neurodegeneration, inflammation, and ongoing demyelination. FTY720, known as fingolimod or Gilenya, is an immunomodulatory medication that was approved in 2010 as the first oral therapy for relapsing-remitting MS. Upon phosphorylation, FTY720 mimics S1P and binds selectively to all S1PR subtypes, except S1PR2, underscoring the therapeutic possibilities of focusing on the S1P-S1PR signaling axis for neuroinflammatory conditions. This success emphasizes the relevance of S1P-mediated pathways in both disease mechanisms and treatment strategies. Emerging precision medicine approaches emphasize the importance of noninvasive imaging to elucidate molecular mechanisms in vivo. Positron emission tomography (PET) imaging-utilizing suitable radioactive tracers to probe biological targets and processes in vivo-offers a transformative approach to quantifying receptor expression, thereby delineating crucial insights into disease diagnosis, therapy monitoring, and therapeutic drug development. As such, S1PR-specific PET imaging provides a promising approach to explore the pivotal role of S1PRs in MS and other immune-mediated diseases. This review offers a comprehensive overview of the development and clinical applications of S1PR-targeted PET radiopharmaceuticals, illustrating their potential to transform therapeutic strategies. Further, recent advances in radiopharmaceutical design have yielded S1PR-targeted PET probes with high specificity, improved metabolic stability, and enhanced blood-brain barrier penetration, addressing key challenges in imaging neuroinflammation. Additionally, it critically discusses future directions for S1PR-targeted PET imaging in advancing our understanding of disease mechanisms, improving patient outcomes, and contributing to the broader vision of precision medicine.

A 30-year-old man experienced ocular motility impairment and exophthalmos immediately after a total thyroidectomy for papillary thyroid carcinoma at an external hospital. Two months later, 131 I therapy exacerbated his ocular symptoms. He presented to our ophthalmology department for evaluation, where a 68 Ga-FAPI PET/MR scan revealed active thyroid eye disease (TED) and residual tumor lesions. Based on these findings and clinical evaluation, a multidisciplinary team formulated and implemented an effective treatment plan. This case highlights the dual role of 68 Ga-FAPI PET/MR in assessing TED activity and postoperative tumor status, providing critical insights for managing TED in the context of recent thyroidectomy.

Triple-negative breast cancer (TNBC) presents considerable treatment difficulties because of its highly aggressive behavior and the absence of targeted therapeutic options. This study aimed to develop a tumor microenvironment-responsive nanoplatform combining the enhancer of zeste homologue 2 (EZH2) inhibition and targeted radionuclide therapy (TRT) to enhance antitumor efficacy and remodel immunosuppressive signaling in TNBC. A cancer cell membrane (CCm)-camouflaged nanoplatform (CCm-HSA-Taz) was engineered to encapsulate the EZH2 inhibitor Tazemetostat (Taz), enabling tumor-targeted delivery. The nanoplatform was coadministered with [177Lu]Lu-based TRT to evaluate synergistic effects. Physicochemical characterization assessed the nanoplatform stability. In vivo efficacy was tested in TNBC-bearing murine models with tumor progression monitored via imaging and histopathology. The CCm-HSA-Taz nanoplatform exhibited favorable physicochemical properties and excellent stability. In vivo radioimmunoassay studies indicated that the immune response in the CCm-HSA-Taz combined with the [177Lu]Lu radiotherapy was stronger than that observed in the CCm alone or in the [177Lu]Lu radiotherapy alone. Additionally, the combination group exhibited an observed increase in the apoptotic cell population, and antitumor immunity was enhanced at the conclusion of the 19-day observation period. Furthermore, all results were corroborated through pathological and imaging examinations. We developed a tumor microenvironment-adaptive nanoplatform delivering Taz to disrupt immunosuppression and enhance radiotherapy sensitivity in TNBC, without significant side effects in animal models. Nuclear medicine imaging revealed reduced tumor glucose metabolism and improved immune cell cytotoxicity. Utilizing components approved by the FDA suggests the potential for this strategy to be translated into clinical settings.

[This corrects the article DOI: 10.3389/fmed.2025.1613722.].

BACKGROUND:The incidence of differentiated thyroid cancer (DTC) has been increasing, highlighting the need for reliable predictors of treatment response. This study aimed to assess the prognostic value of stimulated thyroglobulin (sTg) levels before and after the first 131I treatment in DTC patients without distant metastases. METHODS:Sixty patients were classified into excellent response (ER) and non-excellent response (NER) groups based on a comprehensive evaluation of imaging findings, sTg, suppressed Tg and other parameters. Clinical and pathological variables were analyzed using univariate and multivariate logistic regression. Receiver operating characteristic (ROC) curve analysis was used to determine optimal cut-off values for pre-131I sTg levels and for the rate of sTg decline after the first 131I therapy. RESULTS:Both pre-131I sTg level (OR: 3.010, 95% CI: 1.004-9.029, p = 0.049) and the rate of sTg decline (OR: 0.756, 95% CI: 0.590-0.968, p = 0.026) were identified as independent predictors of clinical outcomes. The optimal threshold for pre-131I sTg was 14.55 μg/L (sensitivity: 95.0%, specificity: 67.5%, AUC: 0.804), and for the rate of sTg decline, 44.75% (sensitivity: 70.0%, specificity: 97.5%, AUC: 0.889). A prognostic nomogram was developed incorporating sex, age, pre- and post-131I sTg levels, T and N stages, tumor size, and thyroiditis. CONCLUSION:Lower pre-131I sTg levels and/or a greater rate of sTg decline after the first 131I treatment are associated with more favorable clinical outcomes. The proposed nomogram may assist clinicians in optimizing treatment decisions and stratifying follow-up strategies for patients with DTC.

PurposeThis mini-review delves into the realm of Langerhans cell histiocytosis (LCH) in children, focusing on its skeletal involvement. By synthesizing pertinent literature, we sought to provide a comprehensive understanding of LCH’s clinical and radiographic spectrum. Our study then demonstrates the diagnostic prowess of whole-body 99mTc-methyl diphosphonate (MDP) scintigraphy in LCH cases, underscoring its value in tandem with existing knowledge.MethodsOur approach involved an extensive literature review that contextualized LCH within the current medical landscape. Subsequently, we presented a case series featuring five pediatric instances of skeletal LCH, one accompanied by soft tissue infiltration. The principal aim was to illuminate the diagnostic and staging potential of whole-body 99mTc-MDP scintigraphy, augmenting existing insights.ResultsThrough meticulous literature synthesis, we highlighted pediatric LCH’s protean clinical manifestations and radiological variability. Aligning with this spectrum, our case series underscored the role of 99mTc-MDP scintigraphy in diagnosing and staging LCH. Among the five pediatric cases, one demonstrated concurrent soft tissue involvement. This aligns with the multifaceted nature of LCH presentations.ConclusionPediatric LCH can present with a wide range of clinical and radiologic features. By amalgamating our cases with extant literature, we stress the necessity of a multimodal strategy. 99mTc-MDP scintigraphy emerged as an indispensable tool for accurate staging and soft tissue detection. Our findings collectively advocate for a holistic approach to managing LCH, ensuring informed therapeutic decisions for optimal patient outcomes.

Abstract A 15-year-old adolescent boy was hospitalized because of abdominal pain. Blood tests indicated inflammation markers were elevated. Fecal occult blood test was weakly positive. CT revealed thickening and edema of the small bowel wall, accompanied by gas density shadows and blurring of fat interstitial spaces. Thus, intestinal perforation and gastrointestinal hemorrhage were suspected. In order to investigate the underlying cause, 99mTc-pertechnetate scintigraphy was performed. A tracer accumulated lesion was presented around the navel, suggestive of heterotopic gastric mucosa. Surprisingly, postoperative pathology confirmed coexistence of heterotopic gastric mucosa, intestinal duplication, and heterotopic pancreas, which was a rare condition.