Science Progress最新文献

Background and ObjectivesTumor Endothelial Marker 8 (TEM8) is integral to angiogenesis, tumor microenvironment remodeling, and cancer cell proliferation, and its expression is upregulated in a variety of malignancies. Despite its potential as both a prognostic biomarker and a therapeutic target in triple-negative breast cancer (TNBC), the exact role of TEM8 in TNBC remains poorly understood. This study seeks to examine the expression of TEM8 protein in TNBC and explore its associations with clinicopathological characteristics and patient survival outcomes.MethodsClinical and pathological data from 118 patients diagnosed with TNBC via surgical pathology between January 2015 and December 2017 were retrospectively analyzed at Harbin Medical University Cancer Hospital. A total of 35 adjacent non-cancerous tissue samples were randomly selected from the tumor tissue samples of the 118 TNBC patients. Immunohistochemistry (IHC) was employed to assess the expression levels of TEM8 and CD31 proteins. The correlations between TEM8 expression and various clinicopathological features, as well as survival status, were analyzed.ResultThe positive expression rate of TEM8 in TNBC tumor tissues was 89.8% (106/118), significantly higher than 60% (21/35) observed in adjacent non-tumorous tissues (χ² = 17.029, P < .01). TEM8 expression was significantly correlated with microvessel density (MVD), axillary lymph node status, and TNM staging. Moreover, patients with high TEM8 expression levels exhibited significantly lower overall survival (OS) rates compared to those with low TEM8 expression. Multivariate analysis revealed that TEM8 expression and tumor size were independent prognostic factors for OS.ConclusionsTEM8 is highly expressed in TNBC tissues and is closely associated with angiogenesis, tumor proliferation, lymph node metastasis, and poor prognosis. TEM8 may serve as a potential prognostic marker, offering new insights for the diagnosis and therapeutic strategies in TNBC.

Transjugular intrahepatic portosystemic shunt (TIPS) stands as a pivotal interventional therapy for managing portal hypertension (PH) and its associated complications. Distinguished from pharmacological treatments, endoscopic interventions, or surgical portocaval shunts, TIPS has achieved extensive clinical application attributed to its minimally invasive nature and efficacy. Notwithstanding, complications ensuing from TIPS, such as hepatic encephalopathy (HE) and shunt dysfunction, etc, significantly impact patient prognosis. Over the course of several decades, a diverse array of stent types and diameters have become available for TIPS procedures. Moreover, the stent puncture position and the initial stent position also exhibit variability. Our review aims to address this gap in knowledge by reviewing the research progress on stent types, diameters, puncture positions, and initial stent positions in the context of TIPS. It presents a comprehensive overview of the various stent options available for TIPS procedures and highlights the importance of individualized treatment approaches in reducing surgical complications and improving patient prognosis. The findings outlined in our review provide valuable insights for clinicians and researchers in the field.

ObjectivesDiabetes mellitus (DM) is a common comorbidity in intensive care unit (ICU) patients. The Braden skin score (BSS) has increasingly been recognized as an indicator of patient frailty. However, the association between the BSS and clinical outcomes in critically ill diabetic patients remains unclear. This study aimed to investigate the relationship between the BSS and clinical outcomes in diabetic patients in ICU settings.MethodsA retrospective cohort of diabetic patients with measured BSS was identified from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The primary outcomes included mortality at 30, 60, and 90 days. The association between BSS and survival outcomes was evaluated using time-dependent Cox proportional hazards model. Further validation was conducted through Kaplan-Meier survival analysis, restricted cubic spline fitting, and subgroup analyses.ResultsA total of 20,590 patients were included in this study, those with higher BSS had a 14% decreased risk of 30-day mortality (HR: 0.86, 95% CI: 0.84-0.87, p < .01). Based on cutoff values of 13, patients were categorized into two risk groups. After adjusting for covariates, time-dependent Cox proportional hazards model indicated that the high-risk group exhibited a significantly increased 30-day all-cause mortality compared with the low-risk groups (HR: 1.76, 95% CI: 1.62-1.91, p < .01). Kaplan-Meier curves consistently demonstrated poorer survival across all time points in the high-risk group. Subgroup analysis further indicated that the association between BSS and mortality was particularly pronounced in patients with cerebrovascular disease.ConclusionsA low BSS was independently linked to higher mortality among critically ill patients with diabetes, especially in those with concomitant cerebrovascular diseases. These results support the potential utility of BSS as a prognostic indicator in this population. Further validation through larger prospective studies remains necessary.

ObjectiveRecent advances in generative artificial intelligence (AI) and dimensional approaches in psychiatry offer scalable scoring of psychopathology, yet biological validation remains challenging. This study aimed to compare AI and human performances in scoring dimensional psychopathology and its relationship with inflammatory brain markers in psychotic disorders.MethodsIn a cross-sectional, real-world, prospective study, we generated research domain criteria (RDoC) profiles using a large-language model and human ratings from admission notes of 127 consecutively selected patients with psychotic disorders. Magnetic resonance imaging (MRI) diffusion-based restricted fraction (RF) values were extracted from the amygdala, hippocampus, and neocortex as a proxy of inflammation. We assessed the agreement between AI- and human-derived scores and their predictive value for regional RF.ResultsAI and human RDoC ratings showed moderate-to-high agreement (intraclass correlation coefficients: 0.65-0.81). AI-derived, but not human-derived, negative and positive valence RDoC scores predicted amygdala and neocortical inflammation, while social and regulatory/arousal scores predicted hippocampal RF. A significant association was found between neocortical RF and regulatory/arousal scores in the AI assessment. Both AI- and human-derived cognitive scores predicted cortical RF. When the regression analyses were corrected for multiple comparisons, only the AI-derived associations remained significant: the amygdala for negative valence and the cortex for regulatory/arousal scores.ConclusionsThese results suggest a significant correspondence between AI and human RDoC ratings. AI-based dimensional phenotyping may reflect underlying neuroinflammatory processes, offering a biologically anchored tool for precision psychiatry.

ObjectiveOrthodontic tooth movement (OTM) relies on mechanotransduction and inflammatory responses within the periodontal ligament (PDL). This study aimed to elucidate the role of transient receptor potential vanilloid 4 (TRPV4) in mediating mechanical force-induced pyroptosis in human PDL (hPDL) cells and its functional impact on osteoclast activation during OTM.MethodshPDL cells were isolated from premolars extracted for orthodontic reasons and characterized for stem cell properties (CD73+/CD90+/CD105+; CD34-/CD45-). An in vitro OTM model was established by applying compressive force (0-2.0 g/cm²). Pyroptosis was assessed via qRT-PCR, Western blot, and immunofluorescence for NLRP3, caspase-1, GSDMD, and IL-1β. Osteoclast differentiation was evaluated in hPDL-PBMC co-cultures using TRAP staining, ELISA (RANKL/OPG), and gene expression analysis (CTSK/TRAP). TRPV4 activation was modulated using agonist GSK1016790A.ResultsCompressive force (1.5 g/cm², 24 h) significantly upregulated pyroptosis markers (NLRP3, cleaved caspase-1, N-GSDMD, IL-1β) and inflammatory mediators (COX2, TNF-α, IL-6, and IL-8). TRPV4 activation was mechanosensitive and enhanced by GSK1016790A, which amplified pyroptosis and subsequent RANKL secretion. In co-cultures, hPDL pyroptosis promoted osteoclast differentiation, evidenced by increased TRAP + multinucleated cells and elevated CTSK/TRAP expression.ConclusionMechanical force activates TRPV4 to drive NLRP3/caspase-1-dependent pyroptosis in hPDL cells, which accelerates osteoclastogenesis via RANKL signaling. Targeting TRPV4-pyroptosis axis may represent a novel strategy to optimize orthodontic treatment efficiency.

ObjectiveAdolescence is a critical window for optimizing peak bone mass. This study evaluated the independent association between dietary fiber intake and total body bone mineral density (BMD) in a representative sample of U.S. adolescents.MethodsThis cross-sectional study analyzed 2476 participants (aged 12-19 years) from the National Health and Nutrition Examination Survey 2011-2018. Dietary fiber intake was calculated as the average of two 24-h recalls. Total BMD was measured using dual-energy X-ray absorptiometry. Multivariable linear regression, generalized additive models, and stratified analyses were utilized, adjusting for sociodemographics, body mass index (BMI), physical activity, renal function markers (creatinine, blood urea nitrogen), and dietary variables (calcium, vitamin C, and energy intake).ResultsDietary fiber intake was positively associated with total BMD in the fully adjusted model (β = 0.001 g/cm², 95% CI: 0.001-0.002; p = 0.029). Compared to the lowest tertile (T1), the highest tertile (T3) exhibited significantly higher BMD (β = 0.016 g/cm², 95% CI: 0.001-0.031; p = 0.038; p for trend = 0.039). Generalized additive models confirmed a stable linear relationship (effective degrees of freedom = 1.0, p for nonlinearity = 0.158). Significant interactions were identified for gender, age, race, and BMI (p for interaction < 0.05), with the association being most pronounced among Non-Hispanic White participants and those in the medium-BMI tertile. Conversely, no significant interactions were observed for poverty-income ratio and physical activity (p for interaction > 0.05).ConclusionsHigher dietary fiber intake is independently associated with increased total body BMD in U.S. adolescents. Optimizing fiber consumption may be a strategic approach for enhancing bone mass accrual, particularly among those with a healthy body weight.

ObjectiveSimultaneous bilateral cochlear implantation has been shown to provide long-term benefits in children suffering from severe-to-profound hearing loss. However, very little research has been conducted on long-term benefits in Mandarin-speaking children. We aimed to (1) evaluate tone perception with simultaneous bilateral cochlear implants (CIs) compared to unilateral CIs; and (2) evaluate early auditory and speech skills.MethodsThe longitudinal study was comprised of 20 participants, 10 with unilateral and 10 with simultaneous bilateral CIs. Participants received a CI at a mean age of 1.3 (SD ± 0.2) years. The Mandarin Early Speech Perception test, auditory thresholds, and influence of environmental factors were measured pre-operatively and after 24 months. Categories of Auditory Performance (CAP), Speech Intelligibility Rating (SIR), and LittlEARS Auditory Questionnaire (LEAQ) were measured pre-operatively and after 6, 12, and 24 months.ResultsAfter 24 months of device use, tone perception scores tended to be higher in the bilateral CI group than in the unilateral group, although the difference did not reach statistical significance (p = 0.058). Over the 24-month follow-up period, CAP, SIR, and LEAQ scores showed significant improvements in both groups (all p < 0.05).ConclusionsTone perception and early auditory and speech skills in Mandarin-speaking children were better with simultaneous bilateral CI implantation compared to unilateral after 24 months of use.

ObjectivesFluid management in critically ill obese patients is challenging due to the risk of fluid overload when using standard weight-based formulas. This study aims to evaluate the association between hydration status and mortality in elderly obese critically ill patients with acute kidney injury (AKI).MethodsThis retrospective cohort study included elderly obese critically ill patients with AKI admitted to a tertiary care ICU between January 2020 and December 2022. AKI was diagnosed according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Fluid overload was defined as body weight-adjusted fluid balance >10%. The primary outcome was 90-day all-cause mortality. Statistical analyses included Kaplan-Meier survival curves and multivariate Cox regression.ResultsA total of 539 elderly obese critically ill patients with AKI were included, of whom 244 (45.3%) developed fluid overload. During the 90-day follow-up, 209 patients (38.8%) died. Patients with fluid overload had significantly higher 90-day mortality compared to those without fluid overload (50.4% vs. 29.2%, P < 0.01). Kaplan-Meier analysis showed a higher mortality risk for fluid-overloaded patients (P < 0.01). Multivariate Cox regression indicated that fluid overload (HR = 2.04, 95% CI: 1.24-3.36, P < 0.01) and SOFA score (HR = 1.13, 95% CI: 1.04-1.22, P < 0.01) were independent predictors of increased mortality.ConclusionsFluid overload is significantly associated with increased 90-day mortality in elderly obese critically ill patients with AKI.

ObjectiveHepatocellular carcinoma (HCC) has a poor prognosis, necessitating novel biomarkers. The role of LSM7 (Like-Sm protein 7), an RNA-binding protein, in HCC remains unclear.MethodsWe employed a multiomics strategy using transcriptomic data from TCGA, GTEx, GEO, and ICGC to evaluate LSM7's expression and prognostic value. A protein-protein interaction (PPI) network was constructed via STRING, followed by Gene Ontology/KEGG/Gene Set Enrichment Analysis (GSEA) functional enrichment analysis. The relationship between LSM7 and the immune infiltration landscape was assessed using single-sample GSEA (ssGSEA) and the TISCH single-cell database. Drug sensitivity was analyzed using Genomics of Drug Sensitivity in Cancer, and structure-based virtual screening was performed on the ZINC library to identify potential LSM7 inhibitors. Key findings were validated in clinical samples and MHCC97H cells and Huh-7 cells using Western blot, IHC, and MTT assays.ResultsLSM7 was significantly overexpressed in HCC, correlating with adverse clinicopathological features (higher histological grade, elevated AFP levels, vascular invasion) and shorter overall survival, identifying it as an independent risk factor. Functionally, LSM7 was implicated in processes such as hormone regulation. Immune analysis revealed that high LSM7 expression was associated with altered immune cell abundance, upregulation of immune checkpoints, and a higher Tumor Immune Dysfunction and Exclusion score, suggesting a role in immune evasion. The high-LSM7 group showed increased sensitivity to drugs like sorafenib. Virtual screening identified Velpatasvir as a top LSM7-targeting candidate, with in vitro validation confirming that it inhibits MHCC97H cells and Huh-7 cells proliferation and downregulates LSM7 protein in a concentration- and time-dependent manner.ConclusionsBy integrating multiomics strategy and experimental validation, this study suggests that LSM7 may play a role in HCC progression and influence the tumor immune microenvironment. LSM7 may serve as a potential biomarker and therapeutic target, and Velpatasvir appears to be a candidate agent worthy of further investigation.

This study investigates optical solitons in magneto-optic waveguides while preserving the generalized anti-cubic structure of nonlinear self-phase modulation. A novel ${\varphi }^6$-model expansion technique is proposed, and its application in magneto-optic waveguides is explored. The ${\varphi }^6$ approach provides an accurate and efficient method to solve wave propagation problems in magneto-optic media, enabling improved modeling of light behavior by incorporating the combined effects of electric and magnetic fields within a unified framework. To address the challenges arising from the nonlinear magneto-optic effects on waveguide characteristics, the method yields precise dispersion relations, field distributions, and transmission properties. This technique facilitates the design of magneto-optic waveguides with tailored characteristics for next-generation photonic systems. By offering a reliable and accurate modeling framework, the ${\varphi }^6$ approach contributes to the development of more precise and efficient magneto-optic devices, advancing photonic integration, communication, and sensing technologies.