Clodronate disodium (CD), a bisphosphonate, modulates bone metabolism. Though extra-label use in juvenile horses is anecdotally reported, impacts on skeletal development are unknown. The objective was to determine the effects of CD on systemic markers of bone turnover in yearling horses undergoing exercise, hypothesizing that biomarkers of bone resorption would decrease while biomarkers of bone formation would not change and that repeat CD treatments would have a greater effect. To test this, 32 yearling Quarter Horses were used in a 168-d trial. Horses were stratified by age (500 ± 13 d), BW (336 ± 26 kg), sex (n = 16 geldings; n = 16 fillies), and initial bone optical density and randomly allocated to one of four treatment groups receiving either 1.8 mg/kg BW CD (Osphos) or isovolumetric saline (placebo). Investigators were blinded to treatments that included control (CON; n = 8), single-dose CD (1X; n = 8; d84), two-dose CD (2X; n = 8; d0 and 84), and four-doses CD (4X; n = 8; d0, 42, 84, and 126). Horses were housed individually in stalls and fed to meet nutrient requirements. Horses exercised 5 d/wk using a free stall exerciser in a phase-based progressive workload; Phase I (d0-84) simulated sales preparation and Phase II (d85-168) mimicked an early training program. Blood was collected on d0, 42, 84, 126, and 168 before treatment injections, when applicable. Serum was analyzed for receptor activator of nuclear factor κB ligand (RANKL), tartrate resistant acid phosphatase 5 b (TRAP5b), c-terminal crosslinks of type I collagen (CTX-1), bone-specific alkaline phosphatase (BAP), and procollagen type I n-terminal propeptide (PINP) via commercial ELISA or EIA. Data were analyzed using PROC MIXED of SAS with a baseline covariate for BAP. A treatment×time interaction was noted for osteoclastic TRAP5b (P = 0.03), decreasing in 4X from d0 to 126 and returning to baseline at d168, and decreasing in 2X to d84 whereas in CON and 1X it increased or remained the same over time. Serum CTX-1, a type I collagen degradation marker, increased over time (P < 0.01) in all treatments. Osteoblastic BAP increased (P < 0.01) from d42 to 84 and remained elevated until d168. There was no change in PINP (P = 0.35) or osteoclast differentiation signal RANKL (P≥0.24). The results indicate that CD administration in horses undergoing low-intensity exercise reduces a serum biomarker of osteoclast number and activity without affecting serum biomarkers of bone formation or resorption. Clodronate disodium (CD) is a bisphosphonate, a class of bone-modulating drugs. Anecdotal reports of extra-label use in juvenile horses in efforts to mask radiographic abnormalities, promote skeletal maturation, and serve as an analgesic exist, despite being labeled for horses ≥4 yr of age. As juvenile horses subjected to exercise undergo high levels of bone turnover, there is concern regarding the effects of extra-label use of bisphosphonates, such as CD, due to lack of scientific data to inform this extra-label use. This study administered 0, 1, 2, or 4 doses of CD to yearling Quarter Horses undergoing an exercise program. Bone turnover was assessed using circulating concentrations of biomarkers that reflect bone formation and bone resorption. When undergoing low-intensity exercise, horses that received CD had lower serum concentrations of a biomarker of osteoclast number and activity, reflecting a decrease in the cells responsible for bone resorption. There were no differences in other biomarkers of bone resorption or bone formation. The CD dose approved for adult horses may not be sufficient to induce systemic changes in bone turnover in yearling, exercising horses. However, additional research is needed to determine local effects on weight-bearing bones.
Skeletal unloading during microgravity rapidly disrupts bone and metabolic homeostasis, yet sex-specific physiological responses remain poorly characterized. Dry immersion (DI), a ground-based analogue of microgravity, provides a model to investigate early determinants of unloading-induced bone deconditioning. We assessed sex differences in serum biochemical markers of bone and energy metabolism during two 5-day European Space Agency DI campaigns (VIVALDI 1 and 2) involving healthy males (n = 19) and females (n = 18). DI induced rapid alterations in bone remodeling in both sexes, characterized by increased bone resorption. Tartrate-resistant acid phosphatase isoform 5b (TRAP5b) increased more in females than in males (+22% vs. +11%; P = 0.02), whereas crosslinked C-terminal telopeptide of type I collagen (CTX) rose (+10%; P < 0.05) only in females at DI completion. Bone formation markers declined similarly in both sexes, including procollagen type I N-terminal propeptide (PINP) (-22% males, -19% females; P < 0.001), osteocalcin, and carboxylated osteocalcin, whereas bone alkaline phosphatase increased, indicating dissociation between new matrix formation and mineralization. Periostin decreased in both sexes but more markedly in females (-29%; P < 0.001) and did not recover post-DI. Calcium increased transiently at DI-48 h (P < 0.001), whereas parathyroid hormone (PTH) declined throughout immersion and recovery (P < 0.001). IGF-1 (+8%; P < 0.001) and visfatin (+63% males, +78% females; P < 0.001) increased, with visfatin normalizing post-DI only in females. Overall, although both sexes exhibited early bone deconditioning, females showed greater and more persistent resorption and periostin reduction, suggesting a faster progression toward bone loss. These early sex-specific responses identify potential biomarker that may enhance mechanistic understanding and guide the development of targeted countermeasures for spaceflight- and immobilization-related bone loss.NEW & NOTEWORTHY Dry immersion induces rapid bone deconditioning in both sexes, but females show greater skeletal sensitivity to unloading, with stronger resorptive increases [tartrate-resistant acid phosphatase isoform 5b (TRAP5b), crosslinked C-terminal telopeptide of type I collagen (CTX)] and a more pronounced periosteal decline (periostin) that does not recover after immersion. Concurrent rises in IGF-1 and visfatin are suggestive of coordinated metabolic-skeletal responses. These sex-specific biomarker patterns highlight early physiological differences and may help guide the development of targeted countermeasures for spaceflight and immobilization.
Imaging biomarkers are quantifiable features extracted from medical images that indicate health status, disease characteristics, or treatment response. Their value depends on rigorous standardization and validation-efforts advanced by QIBA and EIBALL. Variability in existing inventories highlights the need for a FAIR (Findable, Accessible, Interoperable, Reusable)-compliant catalog to enable systematic discovery, comparison, and adoption. We focused on defining the essential variables to describe imaging biomarkers across research, regulatory, and clinical settings. A three-phase approach was undertaken: (1) key resources-including FDA-NIH BEST, QIBA, EMA, ESR-EIBALL, relevant regulations, and scientific literature-were reviewed; (2) attributes were extracted and compared, with redundancies resolved by expert consensus; and (3) consolidated variables were organized into domains aligned with FAIR principles. A unified biomarker descriptor set was established across five domains: core identification (imaging biomarker name, surrogation, clinical relevance), clinical context (main target, organ(s), disease/substrate, range(s), actionability), imaging and technical information (image modality, acquisition technique, technical parameters, extraction, association type, dimensionality, units), validation (robustness and use endorsed by publications, endorsed by professional societies, regulatory qualifications), and administrative data (repository, version/author). The catalog was tested across representative imaging biomarkers in inflammatory diseases, including ADC, FDG-PET, CT-based radiomics signatures, and Doppler ultrasound indices, demonstrating coherent descriptions across diseases and organs. Diagnostic and prognostic roles were clarified, transparency and reproducibility were promoted, and the need for context-adapted entries was shown. This work proposes a harmonized, scalable approach for cataloging imaging biomarkers. Consistent descriptors across contexts facilitate integration into research, regulatory, and clinical workflows. This work proposes a unified catalog structure for imaging biomarkers that improves standardization, comparability, and reusability across clinical, research, and regulatory domains. Lack of standardization limits the integration of imaging biomarkers into research, regulatory, and clinical workflows. A harmonized catalog was developed using unified descriptors across the main identified domains. This structure enhances traceability, cross-disease comparability, and regulatory readiness of imaging biomarkers.
Previous studies on extensive-stage small cell lung cancer (ES-SCLC) have primarily focused on serum tumor markers (STM) measurements at a single time point, overlooking the prognostic value of sequential STM monitoring. We conducted a retrospective cohort study of 253 patients with ES-SCLC and applied latent class growth mixed modeling to define trajectory groups for neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), and cytokeratin 19 fragment (CYFRA21-1). Overall survival (OS) and adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) for mortality in the persistent-rising vs. low-stable groups were 1.19 (0.73 - 1.95), 1.58 (1.07 - 2.33), and 2.34 (1.11 - 4.92) for NSE, CEA, and CYFRA21-1, respectively. Persistent elevations of CEA (p = 0.021) and CYFRA21-1 (p = 0.026) were independent OS prognostic factors. For progression-free survival (PFS), adjusted HRs (95% CIs) were 2.27 (1.38 - 3.74), 1.22 (0.83 - 1.80), and 0.99 (0.48 - 2.05) for NSE, CEA, and CYFRA21-1, respectively, with NSE (p < 0.001) independently predicting PFS. Combined subgroups (three-low, one-high, and two-high) demonstrated significant OS and PFS stratification (p < 0.001). Dynamic monitoring of NSE, CEA, and CYFRA21-1 provides a valuable approach for prognostic prediction in patients with ES-SCLC. Extensive-stage small-cell lung cancer (ES-SCLC) is an aggressive form of lung cancer with a poor prognosis, and clinicians commonly monitor patients using blood tumor markers. However, most previous studies have assessed these markers at a single time point, without considering how their levels change during treatment, potentially missing important information about patient outcomes. In this study, we analyzed data from 253 patients with ES-SCLC and repeatedly measured three commonly used blood tumor markers, neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), and cytokeratin 19 fragment (CYFRA21-1), throughout treatment. Using a specialized statistical approach, patients were grouped according to marker trajectories (low-stable vs. persistent-rising) and further classified into combined subgroups based on the number of rising markers (three-low, one-high, and two-high).We found that increasing NSE levels were associated with faster disease progression, while increasing CEA and CYFRA21-1 levels were linked to shorter survival. Patients with two or more rising markers (the two-high subgroup) faced the highest risk. Monitoring dynamic changes in these markers, especially in combination, was more informative for predicting outcomes than relying on a single measurement. We therefore recommend that clinicians incorporate regular monitoring of these three markers into ES-SCLC follow-up, as early detection of rising trends may help identify high-risk patients and enable timely treatment adjustments.
Female reproductive aging is a major clinical challenge associated with declining fertility and increased pregnancy complications. The urgent clinical need for developing reliable biomarkers to evaluate ovarian aging has become increasingly evident. Cellular senescence, marked by p16, contributes to age-related tissue dysfunction. However, the relationship between p16 levels and ovarian aging remains poorly understood. Age-related changes in p16 levels across multiple tissues in ICR mice were examined in ICR mice at 4, 30, 45, and 60 weeks of age using qRT-PCR, ELISA, and immunohistochemistry. Cell-type specific p16 levels were analyzed in isolated ovarian cells. Reproductive function was assessed through superovulation, in vitro fertilization, and embryo transfer experiments. p16 mRNA levels increased progressively with age in ovarian tissue (6.8-fold increase at 60 weeks vs. 4 weeks, P < 0.05), with corresponding increases in p16 protein levels. Among tissues examined, ovaries, kidneys, liver, uterus, spleen, and pancreas showed significant age-related p16 upregulation, while brain, heart, and lung did not. Cell-type analysis revealed that somatic cells exhibited pronounced p16 upregulation with age (cumulus cells: 3.2-fold, granulosa cells: 4.6-fold, theca cells: 2.8-fold increase), whereas oocytes and blastocysts showed no significant changes. Ovulation numbers decreased significantly with age (42.3 ± 3.1 vs. 15.6 ± 1.9 oocytes in young vs. aging mice), but fertilization rates and early embryo development remained unaffected. However, post-implantation outcomes deteriorated substantially, with implantation rates declining from 78.4% to 38.1% and live birth rates from 82.3% to 43.2% in aging mice at 60 weeks of age. Age-related upregulation of p16 in ovarian somatic cells, but not in oocytes, correlated with declining reproductive function, particularly affecting post-implantation development. These findings suggest that somatic cell senescence may contribute to age-related declines in oocyte competence, leading to fertility decline with aging.
Neonatal interventions influence long-term developmental outcomes, with excessive alcohol consumption impairing metabolism and bone health. Zingerone, a natural antioxidant, may possess health benefits against alcohol-induced oxidative damage and inflammation, promoting bone health. This study investigates the effects of zingerone on markers of bone turnover and morphometry in neonatal rats subjected to alcohol exposure during critical developmental stages. Ten-day-old male Sprague-Dawley rats (N = 35) were randomized and treated with water (C), zingerone (Z) (40 mg/kg), alcohol (A) (1 g/kg) or zingerone-alcohol combination (ZA) for 9 days. During adolescence, rats received either water or a secondary A insult (20% v/v) for 54 days. At termination, ELISA kits were used to measure biomarkers of bone formation (bone-specific alkaline phosphatase, osteocalcin, and procollagen Type I N-terminal propeptide). Bone morphology and morphometry was assessed using microcomputed tomography. Neonatal zingerone (Z + A; ZA + A) and double alcohol exposure (A + A) significantly increased plasma BALP and P1NP levels (p < 0.05). Tibial length remained unchanged across groups (p > 0.05). Neonatal zingerone with adolescent alcohol (Z + A) significantly reduced tibial mass, bone mass-to-length ratios, and trabecular architecture near the growth plate (p < 0.05). Neonatal and adolescent administration of alcohol (A + A) significantly increased midshaft cortical thickness (p < 0.05). Adolescent alcohol treatment impaired bone function and morphology, neonatal zingerone alone offering limited protection. Coadministration of zingerone with alcohol neonatally produced variable and context-dependent changes with no clear evidence of sustained protection against the effects of alcohol exposure. These findings underscore the importance of optimizing timing, dosage, and combination therapies for bone health. Further studies are warranted to clarify whether zingerone has clinically meaningful bone-protective effects.
Autophagy plays a crucial role in maintaining cellular homeostasis and has been implicated in the pathogenesis of knee osteoarthritis (OA). However, data on radiographic stage-dependent transcriptional variation of autophagy-related genes in patients with knee OA, particularly using peripheral blood samples, remain limited. The aim of this study was to evaluate whether disease severity was associated with stage-dependent changes in the expression of selected autophagy-related genes within a patient cohort. A total of 200 patients diagnosed with knee OA were included in the study. Disease severity was classified according to the Kellgren-Lawrence radiographic grading system. Peripheral blood samples were collected, and the expression levels of selected autophagy-related genes were analyzed using quantitative real-time polymerase chain reaction [autophagy-related 5 (ATG5), ATG7, unc-51-like kinase 1 (ULK1), microtubule-associated protein 1 light chain 3 beta (LC3B), WD repeat domain phosphoinositide-interacting protein 1 (WIPI1), neighbor of BRCA1 gene 1 (NBR1), forkhead box O3 (FOXO3), transcription factor EB (TFEB)]. Relative gene expression was calculated using the ΔCt method, and comparisons were performed across radiographic stages. Associations between gene expression levels and systemic inflammatory markers were also assessed. Significant stage-dependent differences were observed in the expression of ULK1, TFEB, WIPI1, and NBR1 (p<0.05), with higher ΔCt values (reduced relative expression) in advanced radiographic stages compared with early-stage disease. In contrast, ATG5, ATG7, LC3B, and FOXO3 expression remained stable across radiographic stages. Furthermore, no significant associations were observed between expression of autophagy-related genes and systemic inflammatory status, as assessed by C-reactive protein levels. In patients with knee OA, regulatory and early autophagy-related genes exhibit radiographic stage-associated transcriptional alterations in peripheral blood, while expression of core autophagy machinery genes remain relatively stable. These findings suggest that disease severity is associated with selective transcriptional changes in autophagy-related pathways within the OA patient population and support further investigation of stage-dependent molecular patterns in knee OA.
Repeated implantation failure (RIF) in in vitro fertilization-embryo transfer (IVF-ET) remains a challenging clinical issue. Although acupuncture is increasingly used as an adjunctive therapy for RIF patients, robust evidence supporting its efficacy in improving pregnancy outcomes is still lacking. This pilot study therefore aims to estimate effect sizes to inform sample size calculations for future definitive trials and to assess key feasibility parameters. This single-center, two-arm, single-blind, randomized sham-controlled trial will enroll 100 women (50 per group) with RIF aged 25~40 years. Using a parallel-group design, participants will be randomized to receive either conventional Western medicine treatment combined with acupuncture (experimental group) or the same conventional Western medicine treatment combined with sham acupuncture (control group). Acupuncture or sham acupuncture will be administered twice weekly from day 5 of the menstrual cycle until the day before embryo transfer, with a minimum of three completed sessions, targeting acupoints with standardized techniques. The primary outcome will be embryo implantation rate, and secondary outcomes will include clinical pregnancy rate and serum biomarkers (β-human chorionic gonadotropin, luteinizing hormone, progesterone, and estradiol). Safety will be monitored through adverse event reporting. The findings of this study will provide preliminary data to guide the design of future large-scale, multicenter randomized controlled trials. Such trials would in turn generate more definitive evidence on the efficacy of acupuncture for improving pregnancy outcomes in RIF patients undergoing IVF-ET. https://itmctr.ccebtcm.org.cn/, identifier ITMCTR2025000838.
Neuroendocrine tumors (NETs) represent a complex, heterogeneous group of cancers with unique characteristics. Early detection and multiple modalities therapies such as surgical intervention or symptom control (e.g., somatostatin analogs). Treatment for late-stage disease including combining local treatment (surgery, radiofrequency ablation, selective internal radiation therapy, trans-hepatic arterial chemo-embolization/trans-hepatic arterial embolization) with that for systemic disease, such as peptide receptor radionuclide therapy, chemotherapy and targeted therapy, are essential for managing symptoms and improving outcomes. Current biomarkers for neuroendocrine tumors including chromogranin A, synaptophysin, Ki-67, somatostatin receptors, mammalian target of rapamycin, vascular endothelial growth factor and its receptor, and O 6-methylguanine-DNA methyl transferase are important in diagnosis and treatment of NETs. We report a rare case of multifocal primary hepatic neuroendocrine tumor (WHO grade 2) in a 79-year-old male. Due to tumor progression under octreotide therapy and the risk of rupture, a multimodal therapeutic approach was implemented. This included initial transcatheter arterial chemoembolization, followed by left lateral hepatectomy and wedge resection combined with intraoperative radiofrequency ablation. Surgical specimens were analyzed for CDK5 and p35 expression. The patient recovered well without complications and was discharged on postoperative day 9. In this case, cyclin-dependent kinase 5 (CDK5) and its activator, p35, were identified as potential novel biomarkers in NET. The differential expression of CDK5 and p35 observed in tumors of varying sizes suggests a correlation with tumor progression. These findings highlight the potential of the CDK5/p35 pathway as a therapeutic target for the management of advanced or metastatic NET.
HER2 immunohistochemistry (IHC) plays a central role in therapeutic decision-making for breast cancer. However, interpretation of equivocal (2+) IHC results remains challenging and is subject to interobserver variability, necessitating reflex in situ hybridization testing. This study evaluated the diagnostic performance and reproducibility of ChatGPT-4o, a general-purpose large language model, in scoring HER2 IHC in breast cancer cases initially classified as IHC 2+. We retrospectively analyzed 81 formalin-fixed, paraffin-embedded invasive carcinoma of no special type (NST) cases with prior HER2 IHC 2+ scores and corresponding dual in situ hybridization (DISH) results. Five high-power field images per case were independently analyzed by ChatGPT-4o across three sessions, using a standardized prompt aligned with the ASCO/CAP 2023 guidelines. Cases remaining equivocal after AI-assisted interpretation were excluded from diagnostic performance calculations. HER2 DISH served as the reference standard. Fourteen cases (17.3%) remained equivocal following AI interpretation. Among the 67 reclassified cases, ChatGPT-4o demonstrated an overall diagnostic accuracy of 79% (95% CI: 67-88%), a sensitivity of 30%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 77%. Intra-model reproducibility was good (intraclass correlation coefficient = 0.78), whereas agreement with HER2 DISH was fair (Cohen's κ = 0.375). Misclassification predominantly involved false-negative interpretations among HER2-positive cases. ChatGPT-4o demonstrated high specificity and reproducibility for identifying HER2 IHC 3+ cases but showed limited sensitivity and only fair concordance with HER2 DISH. These findings indicate that, in its current general-purpose form, ChatGPT-4o is not suitable for independent HER2 assessment and may serve, at best, as an exploratory adjunct to pathologist interpretation.
Albumin is abundant in human plasma and has been widely studied in cancer mainly in the context of systemic nutrition or the tumor microenvironment; however, the clinicopathologic significance and intracellular role of tumor-cell albumin in gastric adenocarcinoma remain unclear. We analyzed 187 patients who underwent gastrectomy for gastric adenocarcinoma between 2000 and 2010. Albumin expression was evaluated by immunohistochemistry on tissue microarrays and classified as high versus low based on intensity relative to intra-tumoral stromal cells. Associations with clinicopathologic variables were examined, and disease-free survival (DFS) and disease-specific survival (DSS) were assessed using Kaplan-Meier and Cox regression. Albumin mRNA/protein expression was examined in three metastatic gastric cancer cell lines, and functional assays (wound healing and proliferation) were performed after siRNA-mediated albumin knockdown in Hs746T cells. High albumin expression was significantly associated with larger tumor size and advanced T and N stages. Albumin expression was not significantly associated with DFS or DSS in univariate or multivariate analyses, whereas T stage and N stage remained independent prognostic factors. In vitro, albumin knockdown significantly impaired migration and reduced proliferative capacity, despite limited detectable reduction in protein levels. Tumor-cell albumin correlates with gastric cancer progression and functionally contributes to motility and growth at the intracellular level, supporting its role as a marker of aggressive tumor biology rather than an independent prognostic biomarker.
The aim of this study was to develop and validate an MRI radiomics-based predictive model to discriminate significant prostate cancer (sPCa), compare it with PI-RADS, and determine whether incorporating PI-RADS and other clinical variables improves clinical performance. A retrospective observational study was conducted using a cohort of 1497 MRI cases from 1395 men to develop the models. For each case, the index-lesion PI-RADS score, systematic ± targeted biopsy results, and six additional clinical variables were collected. Prostate biopsy samples served as the reference standard, defining sPCa as Gleason Grade ≥ 7. Handcrafted radiomic features were extracted from automatically segmented prostate glands. Four machine learning models were developed: (1) Radiomics, (2) PI-RADS, (3) PI-RADS + Radiomics, and (4) PI-RADS + Radiomics + Clinical Variables. Model performance and comparisons were evaluated using the area under the curve (AUC), while clinical utility was assessed through the decision curve analysis plot, Clinical Utility plot, and the number of avoided biopsies. The radiomics model did not perform significantly better than PI-RADS in the validation cohort (AUC 0.838 vs. 0.833, p = 0.874). The combination of radiomics, PI-RADS, and clinical variables achieved the highest performance, with an AUC of 0.891 (95% CI: 0.853-0.930), significantly outperforming the other models (p < 0.05). It also showed the highest specificity (29.41%) and biopsy avoidance rate (18.15%), although the differences were not statistically significant (p = 0.313). Incorporating radiomics and clinical variables into PI-RADS enhances its ability to discriminate sPCa, potentially decreasing false positives and unnecessary biopsies. The incorporation of clinical variables and radiomics into PI-RADS enhances its ability to predict significant prostate cancer, helping mitigate some of PI-RADS's current limitations, such as a significant false-positive rate, and might help reduce unnecessary biopsies. PI-RADS limitations result in overdiagnosis of indolent prostatic lesions and unnecessary biopsies. Radiomics and clinical variables enhance PI-RADS ability to detect significant prostate cancer. Combined clinical-radiological models reduce false positives and help avoid unnecessary biopsies.
The aim of this in vitro study was to evaluate the cytotoxicity of two direct-printed photopolymers, LuxCreo and Nylon, intended for orthodontic applications. LuxCreo (LuxCreo Inc., Chicago, IL) and Nylon (EOS, Munich, Germany) direct-printed materials were compared to conventionally used orthodontic materials including polyethylene terephthalate glycol (PETG) and polymethyl methacrylate (PMMA). Human gingival fibroblasts (hGFB) were cultured in 12-well plates on sterilized material discs for 24-h, 72-h or 7-day intervals (n = 3). Following co-incubation of hGFB with the materials, an MTT assay was conducted to evaluate cell viability, an LDH assay was used to evaluate cell death, and ELISA was used to measure IL-6, IL-8, and IL-1β production. Nylon significantly reduced cell metabolic activity at 24 h, 72 h, and 7 days, while LuxCreo showed a reduction only at 72 h and 7 days, compared to conventional materials. None of the materials induced a significant increase in cell death in hGFB. Elevated levels of IL-6 and IL-8 were observed only in the Nylon group. IL-1β levels were not significantly different between groups. Direct-printed materials reduced cell viability. While none of the materials induced cell death, Nylon did increase the pro-inflammatory cytokine response. Future studies should investigate the underlying mechanisms of cytotoxicity and pro-inflammatory responses to improve the safety and biocompatibility of orthodontic materials. The elevated pro-inflammatory cytokine response observed with direct-printed photopolymers highlight the need for clinical studies to investigate the mechanisms underlying cytotoxic and inflammatory responses. Future research should also evaluate the effects of long-term intraoral exposure and monitor relevant biomarkers during orthodontic treatment to better assess the safety and biocompatibility of these materials.
To examine the clinical characteristics of sintilimab-induced myocarditis and to provide evidence for its diagnosis and management. Retrospective analysis was conducted on clinical case reports of sintilimab-induced myocarditis documented before July 31, 2025. A total of 34 patients were included, with a median age of 64 years (range: 33-85), including 23 (67.6%) male cases. The onset of myocarditis ranged from 1 to 120 days post-treatment, with a median onset of 21 days. The primary clinical presentations included dyspnea (41.2%), chest tightness (35.3%), palpitations (17.6%), and shortness of breath (14.7%), with some cases remaining asymptomatic (8.8%). Comorbid immune-related adverse events included myasthenia gravis (44.1%), myositis (17.6%), and hepatitis (17.6%). Laboratory findings often revealed elevated cardiac troponin I, N-terminal probrain natriuretic peptide, creatine kinase MB, and lactate dehydrogenase. The electrocardiogram mainly showed atrioventricular block (41.2%), ST-T segment changes (44.1%), and atrial or ventricular arrhythmias (50.0%). Echocardiography examination can show normal (34.5%), left ventricular diastolic dysfunction (31.0%), left atrial enlargement (13.8%), and pericardial effusion (13.8%). Cardiac magnetic resonance imaging may show normal (42.9%), myocardial edema (28.6%), and delayed myocardial enhancement (28.6%). Coronary angiography showed normal (73.3%) and coronary artery stenosis of the lumen (26.7%). All patients discontinued sintilimab and received steroid and intravenous immunoglobulin treatment. Outcomes indicated that 79.4% recovered from myocarditis, while 20.6% succumbed. Sintilimab-induced myocarditis has nonspecific manifestations and a high mortality rate. Myasthenia gravis and myositis can occur simultaneously with myocarditis. During simtimab treatment, it is necessary to closely monitor cardiac parameters and symptoms.
The Scottish Inflammatory Prognostic Score (SIPS), has emerged as a simple inflammation-based biomarker; however, its prognostic value in ST-segment elevation myocardial infarction (STEMI) has not been well established. This study aimed to evaluate the prognostic utility of SIPS for predicting long-term major adverse cardiac events (MACE) in STEMI patients. We included 829 STEMI patients between 2018 and 2024. SIPS was categorized as low (0 points), moderate (1 point), or high risk (2 points). The primary endpoint was time-to-first MACE, defined as a composite of all-cause mortality, non-fatal myocardial infarction, stroke, or cardiovascular hospitalization, using Cox proportional hazards models, competing risk analysis, and measures of incremental discrimination. During follow-up, MACE occurred in 293 patients (35.3%), with a stepwise increase across SIPS categories (23%, 40%, and 63%; p < 0.001). SIPS independently predicted MACE in multivariable analysis (HR per point: 1.62, 95% CI 1.35-1.94; p < 0.001). Discriminative performance was moderate (AUC = 0.655). SIPS remained independently associated with MACE in hierarchical multivariable and competing risk analyses and provided incremental prognostic value beyond clinical predictors. SIPS is an independent predictor of long-term MACE in STEMI patients after PPCI and may serve as a simple and cost-effective tool for early risk stratification.
Although polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder among reproductive-aged women, the integrated role of adipokines in linking metabolic and hormonal dysfunction remains incompletely understood. The study aims to evaluate the associations between lipid profile alterations, selected adipokines (resistin, galectin-3, and apelin), oxidative stress markers, and the insulin resistance index (HOMA-IR) in women with PCOS compared to controls. This case-control study included 85 women with PCOS and 55 age-matched controls. Anthropometric and clinical data were collected. Levels of lipid profiles, adipokines, oxidative stress markers, and HOMA-IR were measured. Group comparisons and correlation analyses were performed. Women with PCOS demonstrated elevated levels of resistin, galectin-3, and apelin compared to the controls, with respective measurements of 3.55 ± 0.52 vs 1.07 ± 0.34, 10.01 ± 1.76 vs 3.49 ± 1.03, and 289.23 ± 20.08 vs 191.31 ± 31.30), respectively. MDA exhibited a significant increase, whereas TAC was significantly reduced in the PCOS group. HOMA-IR showed significant positive associations with lipid profiles, adipokines, and levels of MDA, and an inverse correlation with HDL and TAC. The findings support the concept that altered adipokine levels and oxidative stress indices may reflect underlying metabolic dysfunction in women with PCOS.
Cancer patients frequently present to emergency departments (EDs) with complex medical needs, requiring urgent clinical decisions. Identifying prognostic factors can help stratify patients into outcome groups and guide optimal care.Our aim was to analyze the clinical and laboratory characteristics of cancer patients in the ED and determine their relevance to prognosis across three outcome groups: Stable Discharge, Hospitalized Care, and Critical Care. This retrospective cohort study included 1,248 cancer patients admitted to a tertiary care ED between 2020 and 2022. Patients were divided into outcome groups based on their prognosis. Associations between clinical variables and outcomes were analyzed using ANOVA and Pearson Chi-Square tests. Significant laboratory markers included elevated CRP and LDH levels, lower hemoglobin, and reduced oxygen saturation in Critical Care patients. Patients who underwent invasive procedures were more likely to belong to the Hospitalized Care Group or the Critical Care Group. Patients who required intravenous antibiotic therapy were more likely to fall into the Hospitalized Care Group. This study identifies key clinical and laboratory markers associated with cancer patient outcomes in the ED. These findings can assist clinicians in prioritizing care and improving patient management strategies.
Late-life depression (LLD) is a heterogeneous psychiatric condition characterized by a wide range of psychopathological symptoms and associated with functional and structural abnormalities in brain networks implicated in mood and cognitive regulation. This cross-sectional study investigated the relationship between specific depressive symptom dimensions and cortical brain measures, as assessed by magnetic resonance imaging, in a sample of 87 community-dwelling older adults with depression. Significant associations were identified between the severity of sad mood and reduced cortical volume in the right medial orbitofrontal cortex (OFC) (p [FDR] = 0.047), as well as reduced cortical thickness in the left OFC (p [FDR] = 0.008), left ventrolateral prefrontal cortex (VLPFC) (p [FDR] = 0.02), and right dorsolateral prefrontal cortex (DLPFC) (p [FDR] = 0.054). Apathy/lassitude was also significantly associated with reduced thickness in the left OFC (p [FDR] = 0.016) and left VLPFC (p [FDR] = 0.046). Moreover, overall depression severity correlated with reduced thickness in the right middle temporal cortex (MTC) (p [FDR] = 0.035). Our results suggest that feelings of low mood and lassitude in LLD are linked to structural changes in brain regions involved in emotion regulation, motivational drive, self-referential thinking, executive control, and decision-making. The findings contribute to the understanding of the neurobiological underpinnings of LLD and support the hypothesis that symptom-specific disruptions within mood and cognitive processing circuits are integral to its pathophysiology.
To investigate the clinical efficacy of telitacicept combined with methotrexate in treating rheumatoid arthritis (RA) and its effects on related indicators including inflammatory response, oxidative stress, and bone metabolism. Clinical data of 109 RA patients were retrospectively analyzed and divided into an observation group (n=59) and a control group (n=50). Disease activity scores, inflammatory response indicators, oxidative stress indicators, bone metabolism biomarkers, and imaging scores were compared before and after treatment. After treatment, the observation group showed significantly lower disease activity scores and response indicators than the control group (all P<0.05), decreased malondialdehyde levels, increased superoxide dismutase and glutathione peroxidase levels (all P<0.05), and improved bone metabolism indicators such as procollagen type I N-terminal propeptide and matrix metalloproteinase-3. Some imaging scores indicated a short-term improvement trend. Telitacicept combined with methotrexate can effectively improve disease activity, inflammation, and oxidative stress in RA patients in the short term and exert positive effects on bone metabolism- indicators, but its long-term structural protective effect and underlying mechanism need further investigation.
Over recent decades, the prevalence of obesity has markedly surged. While excess maternal weight is a well-established risk factor for adverse pregnancy outcomes, growing evidence suggests that maternal obesity may also increase the long-term risk of cancer in offspring. This comprehensive review synthesizes epidemiological and experimental data linking maternal obesity to heightened cancer susceptibility in the next generation. Observational studies demonstrate increased risks of childhood leukemia and colorectal cancer in offspring of obese mothers, whereas preclinical models support associations with breast, liver, colon, and pancreatic cancers. Mechanistically, maternal obesity induces epigenetic reprogramming, immune dysregulation, and vertical transmission of a dysbiotic gut microbiota, which may lead to persistent alterations in metabolic and inflammatory signaling pathways in offspring, thereby promoting a pro-tumorigenic environment and potentially increasing cancer susceptibility. Given the global burden of obesity, this intergenerational risk has critical public health implications. Lifestyle modifications, weight-loss interventions, and targeted approaches such as probiotic supplementation may offer promising strategies to mitigate cancer risk in offspring, but require scientific confirmation in further studies. Future research should prioritize mechanistic dissection of exposure windows, identification of predictive biomarkers, and the development of effective, scalable preventive therapies.