First Affiliated Hospital of Wannan Medical College

To address the inherent brittleness ofβ-tricalcium phosphate (β-TCP) bioceramics, we incorporated ZnO, SrO, or bioactive glass (AK) into aβ-TCP matrix. Porous scaffolds were fabricated via digital light processing and sintering. X-ray diffraction confirmed the preservation of theβ-TCP phase, and SEM revealed a multiscale porous architecture with uniform macropores (∼400 μm) and submicron surface micropores specifically in theβ-TCP/AK composite. This scaffold exhibited the most balanced performance: its compressive strength increased by ∼38% to 9.65 MPa compared to pureβ-TCP. During immersion in simulated body fluid, theβ-TCP/AK scaffold induced a favorable alkaline pH, exhibited the highest degradation rate (mass loss), and enabled sustained release of bioactive Si4+and Mg2+ions, which enhanced apatite mineralization.In vitro, all modified scaffolds promoted osteoblast proliferation. Notably, theβ-TCP/AK scaffold most significantly stimulated osteogenic differentiation, elevating ALP activity to 2.48 ± 0.184 (vs. 1.87 ± 0.126 for pureβ-TCP) and upregulating key osteogenic genes (ALP, OCN, RUNX2). These results demonstrate that AK doping optimally enhances the mechanical strength, biodegradation, ion release, and osteogenic capacity ofβ-TCP, presenting a highly promising composite for bone tissue engineering.

BACKGROUNDAcute intestinal obstruction is a common surgical emergency with high mortality, requiring efficient multidisciplinary collaboration to improve outcomes.AIMTo explore the optimization of nursing pathways for patients with acute intestinal obstruction using the multidisciplinary team (MDT) model.METHODSA total of 176 patients with acute intestinal obstruction admitted to the Emergency Department of our hospital between December 2023 and February 2025 were randomly divided into a control group (n = 88) and an intervention group (n = 88) using a random number table. The control group received routine emergency nursing interventions, whereas the intervention group received emergency nursing pathway interventions under the MDT model. The groups were compared in terms of emergency treatment efficiency, improvement of clinical symptoms, 36-Item Short Form Health Survey (SF-36) scores, nursing satisfaction, and early (within 72 hours) intestinal obstruction–related complications-specifically, electrolyte disturbance, strangulated obstruction, and intestinal necrosis/perforation.RESULTSThe intervention group had significantly shorter triage, condition assessment, and emergency treatment times (all P < 0.001), faster relief of abdominal pain and vomiting, and earlier return of bowel function (all P < 0.001). The rate of early complications was lower in the intervention group (2.27% vs 10.23%, P = 0.029). Nursing satisfaction was higher (96.59% vs 81.82%, P = 0.002), and post-intervention SF-36 scores were significantly higher (P < 0.05).CONCLUSIONThe MDT-based emergency nursing pathway improves emergency efficiency, relieves clinical symptoms, enhances quality of life and satisfaction, and reduces early intestinal obstruction–related complications in patients with acute intestinal obstruction.

Chronic hepatitis B (CHB) is the leading cause of acute-on-chronic liver failure (ACLF) in China and other Asian countries. A defining immunopathological feature of hepatitis B virus-related ACLF (HBV-ACLF) is immune paralysis, which significantly increases susceptibility to secondary bacterial infections and contributes to poor clinical outcomes. A critical determinant of this immunosuppressed state is impaired antigen presentation due to reduced human leukocyte antigen DR (HLA-DR) expression on monocytes; however, the epigenetic mechanism underlying HLA-DR downregulation in HBV-ACLF remains unclear. Methyl-CpG-binding domain protein 2 (MBD2), an epigenetic reader of DNA methylation, has been implicated in the regulation of monocyte-macrophage function in inflammatory diseases, but its role in HBV-ACLF pathophysiology remains to be fully elucidated. In this study, bulk RNA sequencing (RNA-seq) of circulating monocytes from patients with HBV-ACLF showed a transcriptional profile consistent with immune paralysis, characterized by suppressed antigen presentation and inflammatory pathways, alongside pronounced activation of epigenetic regulatory programs. MBD2 expression was subsequently assessed using immunohistochemistry (IHC), reverse transcription quantitative PCR (RT-qPCR), and flow cytometry. Monocyte MBD2 expression was significantly upregulated in HBV-ACLF and was positively correlated with disease severity (r = 0.2797, P =0.0182), systemic inflammation indices, and clinical prognosis. To delineate the mechanistic role of MBD2, an MBD2-knockout THP-1 cell model was established and subjected to integrated RNA-seq and assay for transposase-accessible chromatin sequencing (ATAC-seq) following differentiation and lipopolysaccharide (LPS) stimulation. The results showed that MBD2 deficiency significantly increased chromatin accessibility and transcriptional activation of genes involved in antigen presentation and pro-inflammatory responses, including pathways related to major histocompatibility complex (MHC) class II synthesis. Concurrently, enhanced promoter accessibility and activation of transcription factors associated with HLA-II class expression were observed, and increased surface HLA-DR expression was confirmed by flow cytometry. Collectively, these findings suggest that MBD2 epigenetically represses HLA-DR expression in monocytes, leading to impaired antigen presentation and immune paralysis, thereby predisposing patients with HBV-ACLF to secondary bacterial infections. Therefore, MBD2 may serve as a novel biomarker for disease progression and a potential therapeutic target for restoring immunological competence in patients with ACLF.

While androgen receptor (AR) pathway inhibitors such as enzalutamide have demonstrated significant therapeutic efficacy in prostate cancer (PCa) treatment, the inevitable development of acquired resistance continues to pose a major clinical challenge in managing advanced PCa. We characterized Neurexophilin 4 (NXPH4) as a contributor to enzalutamide resistance (EnzR). Gain- and loss-of-function studies were conducted in PCa cell lines and mouse subcutaneous xenograft models to elucidate the role of NXPH4 in castration-resistant prostate cancer (CRPC). Additionally, the regulatory mechanisms of gene expression were assessed using a series of molecular and biochemical experiments. Our study demonstrates that AR as a transcriptional activator of NXPH4. Elevated NXPH4 expression facilitated PCa proliferation under enzalutamide treatment through mitochondrial metabolic reprogramming. We identified that NXPH4 partially localizes to mitochondria and physically interacts with aldehyde dehydrogenase 1 family member L2 (ALDH1L2), a critical enzyme in one-carbon metabolism. Androgen deprivation stimulated NXPH4 mitochondrial translocation and enhanced its binding to ALDH1L2. NXPH4-mediated metabolic reprogramming promotes PCa progression. Notably, the combination of NXPH4 knockdown and enzalutamide treatment showed potent synergistic effects, significantly suppressing cell proliferation in vitro and substantially inhibiting tumor growth in vivo. These findings reveal a previously unrecognized mechanism of EnzR and identify the NXPH4-ALDH1L2 complex as a promising therapeutic target for CRPC treatment.

The prevalence of postmenopausal osteoporosis (PMOP) has been steadily increasing. Ferroptosis has been recognized as a critical factor influencing the bone-forming ability of bone marrow mesenchymal stem cells (BMSCs). Valproic acid (VPA), an HDAC inhibitor, has been suggested to play a role in regulating osteoporosis development; however, its underlying mechanism remains unclear. This study aims to explore the impact of VPA on ferroptosis, a process that is triggered by Erastin, and to assess its implications for postmenopausal osteoporosis (PMOP). We evaluated the effects of valproate sodium on Erastin-induced ferroptosis in BMSCs through invitro experiments, including CCK-8 assays, Western blot analysis, mitochondrial function assessments (MDA, GSH, ROS, and MMP), and osteogenic evaluations (ALP and ARS staining). The impact of VPA on bone integration in ovariectomized (OVX) rats was assessed using micro-CT, hematoxylin-eosin (HE) staining, Masson's trichrome staining, and RT-PCR analysis. RNA sequencing was employed to investigate the underlying mechanisms of VPA action. Our findings demonstrate that VPA treatment prevents the Erastin-induced decline in the osteogenic capacity of BMSCs. In addition, VPA treatment suppresses ferroptosis, as indicated by decreased malondialdehyde levels, reduced mitochondrial ROS, and increased glutathione concentrations. Moreover, VPA treatment promotes trabecular bone growth and enhances bone integration. Mechanistic studies reveal that SIRT1-siRNA counteracts the beneficial effects of VPA in Erastin-treated BMSCs. VPA improves bone integration in OVX rats by activating the AMPK/SIRT1 pathway and inhibiting ferroptosis.