Chitosan (CS), a naturally derived biopolymer, was cross-linked with poly (vinyl alcohol) (PVA) to enhance its mechanical properties, thereby rendering it suitable for tissue regeneration. The resulting sponge-like PVA–CS hydrogel maintained its structural integrity even after five repeated compressions and five freeze–thaw cycles despite forming a network with interconnected macropores, exhibiting excellent resistance to structural degradation. Swelling measurements revealed rapid swelling, with the hydrogel reaching equilibrium in one minute, due to its interconnected porous structure. The wide-angle X-ray scattering measurements confirmed the amorphous nature of the hydrogel, which yields the excellent recovery ability of the hybrid gel. To investigate their biological performance, umbilical cord mesenchymal stem cells (UC-MSCs) were seeded into the PVA-CS hydrogel. Fluorescent and histological analyses, including DAPI staining, hematoxylin and eosin staining, calcein-AM staining, and type II collagen immunofluorescence, confirmed efficient UC-MSC adhesion and chondrogenic differentiation. The relatively low expression of type I collagen indicated that the PVA-CS hydrogel preserved the chondrocyte phenotype and delayed cellular senescence. Moreover, antibacterial assays demonstrated the intrinsic antibacterial activity of the PVA-CS hydrogel. In summary, the PVA-CS hydrogel exhibits favorable physicochemical stability, biocompatibility, and antibacterial properties. These results highlight its potential as a promising scaffold material for cartilage tissue engineering applications.
Population aging is accompanied by a progressive decline in intrinsic capacity, yet objective measures reflecting underlying physiological changes remain limited. Yin-deficiency constitution in traditional Chinese medicine has been associated with intrinsic capacity impairment, but its structural correlates remain unclear. This exploratory study investigated associations among tongue ultrasonographic characteristics, Yin-deficiency constitution, and intrinsic capacity impairment in older adults. In this exploratory cross-sectional study, community-dwelling older adults attending a traditional Chinese medicine outpatient clinic (n = 123; mean age 71.6 ± 4.6 years) completed the Constitution in Chinese Medicine Questionnaire-Elderly Edition. Tongue thickness and echo intensity were measured using standardized ultrasonographic protocols, and intrinsic capacity was assessed using the Integrated Care for Older People (ICOPE) framework. Higher tongue echo intensity was associated with lower tongue thickness and higher Yin-deficiency scores. In multivariable linear regression analyses, tongue thickness remained strongly associated with tongue echo intensity (β = -0.548, P < .001), whereas the association between Yin-deficiency scores and tongue echo intensity became attenuated and was no longer statistically significant after adjustment for tongue thickness (β = -0.135, P = .079). Yin-deficiency constitution was associated with cognitive impairment (odds ratio = 2.79, 95% confidence interval = 1.13-6.89, P = .026) and visual impairment (odds ratio = 3.74, 95% confidence interval = 1.57-8.96, P = .003), whereas tongue echo intensity alone was not independently associated with ICOPE-defined intrinsic capacity impairments. Thickness-adjusted sensitivity analyses showed attenuated but directionally consistent findings. Tongue echo intensity appears to reflect structural variation in tongue musculature rather than an independent constitution-specific characteristic. Yin-deficiency constitution was associated with cognitive and visual impairment, whereas tongue echo intensity was not independently associated with ICOPE-defined intrinsic capacity impairments. These findings are exploratory and require validation in larger multicenter cohorts.
Diisononyl cyclohexane-1,2-dicarboxylate (DINCH), a non-phthalate plasticizer adopted as a safer alternative for food-contact and medical-grade materials, is ubiquitously detected in human biomonitoring studies. Despite widespread exposure, its transcriptional effects in prostate cells and the potential prostate cancer relevance of DINCH-responsive genes remain unclear. We integrated transcriptomic profiling of DINCH-exposed human prostate epithelial cells with exploratory genetic association analyses in 630 patients with prostate cancer receiving androgen deprivation therapy (ADT). Haplotype-tagged single-nucleotide polymorphisms (SNPs) in candidate DINCH-responsive genes were evaluated for their association with overall survival (OS) and cancer-specific survival (CSS). The prostate cancer relevance of the prioritized genes was further validated using pooled multi-cohort bioinformatic analyses. DINCH exposure produced an exploratory molecular signature comprising 83 genes across all tested doses, broadly suppressing cell–matrix adhesion pathways and activating chromatin remodeling. Exploratory genetic screening identified nominal associations of LPP rs1040033 with OS (p = 0.0002, q = 0.131) and FAM111B rs7110278 with CSS (p = 0.0010, q = 0.575); neither association remained significant after multiple-testing correction. DINCH exposure significantly downregulated LPP and upregulated FAM111B expression in prostate epithelial cells. Independently, pooled analyses demonstrated reduced LPP and elevated FAM111B expression in prostate cancer tissues compared with normal prostate tissues. Higher LPP expression predicted a favorable prognosis, whereas elevated FAM111B predicted worse survival. Pathway analyses linked low LPP expression to impaired adhesion signaling and metabolic reprogramming, whereas high FAM111B expression was associated with mitotic and cell-cycle activation. DINCH exposure induced exploratory transcriptional alterations involving LPP-related adhesion pathways and FAM111B-related proliferative signaling. The genetic findings are exploratory and require independent validation. Although public datasets support the prognostic relevance of LPP and FAM111B in prostate cancer, they do not link these genes to DINCH exposure.
BACKGROUND:Transcatheter closure of ventricular septal defect (VSD) is a promising alternative to surgery; however, outcomes in patients with coexisting aortic valve prolapse (AVP) remain limited. OBJECTIVES:The authors aimed to evaluate outcomes and risk factors after VSD closure using the KONAR-MF Occluder (MFO) in a large Asian cohort with a high prevalence of AVP. METHODS:Between 2021 and 2024, consecutive patients undergoing transcatheter VSD closure at our institution using only the MFO were enrolled. Right coronary cusp (RCC) prolapse was quantified using the RCC prolapse index on transesophageal echocardiography. Device position relative to the aortic cusp was classified as nontouching, clamping, or holding. Risk factors for procedural failure and progression of aortic regurgitation (AR) were analyzed. RESULTS:Among 109 cases (13.8%, 15 of 109 doubly committed [Dc] type), 61.5% (67 of 109) had AVP. The procedural success rate was 94.5% (103 of 109; 95% CI: 88.4%-98.0%). Younger age, Dc VSD, aortic rim deficiency, and larger defect size were univariate correlates of failure, whereas RCC prolapse index was the only independent predictor in multivariate analysis (OR: 2.48; 95% CI: 1.06-5.83 per 10% increase; P = 0.037). During a median (IQR) follow-up of 14.3 (8.4-22.8) months, AR progression occurred in 7 (6.8%) patients. Device clamping of the aortic cusp was associated with AR progression (OR: 6.67; 95% CI: 1.10-58.1; P = 0.048). CONCLUSIONS:VSD closure using the MFO is safe and effective, including in patients with outlet-type VSD and AVP. Significant RCC prolapse predicts procedural failure, and clamping of the aortic cusp may compromise long-term valve function.
BACKGROUND AND STUDY AIM:Individuals classified as "high-risk" at initial colonoscopy face an elevated risk of metachronous advanced colorectal neoplasms (meta-ACRN), but risk heterogeneity within this group remains unclear. We aimed to stratify meta-ACRN risk among high-risk individuals based on their synchronous neoplastic burden. PATIENTS AND METHODS:This prospective cohort study utilized data from a Taiwanese multicenter trial (NCT03373136). We included participants with conventional high-risk findings (3-10 low-risk adenomas [LRAs] or any high-risk adenoma [HRA]). The primary outcome was meta-ACRN incidence. Adjusted incidence rate ratios (aIRRs) were calculated using multivariable Poisson regression, stratifying patients by baseline synchronous burden, with the 3-4 LRAs group as reference. RESULTS:Among 730 participants undergoing surveillance (mean follow-up 2.4 years), 81 (11.1%) developed meta-ACRN. A single HRA did not significantly increase meta-ACRN risk compared to 3-4 LRAs (aIRR 2.02; 95% confidence interval(CI) 0.83-4.90). However, risk escalated significantly when the index HRA was accompanied by synchronous LRA(s) (aIRR 2.56; 95% CI 1.24-5.39) or synchronous HRA(s) (aIRR 3.93; 95% CI 1.77-8.73) (P for trend = .001). Furthermore, applying a more severe modified advanced adenoma criteria, an identical dose-response pattern emerged, culminating in a >5-fold increased risk for severe metachronous outcomes (aIRR 5.23; 95% CI 1.50-18.22) when accompanied by synchronous HRA(s) . CONCLUSIONS:Meta-ACRN risk within the conventional high-risk population is highly heterogeneous and driven primarily by baseline synchronous neoplastic burden. Surveillance intervals should be personalized, reserving shorter intervals for patients with advanced lesions accompanied by synchronous adenomas.
