Objective To explore the spatial heterogeneity of tumor boundary tissue metabolism in hepatocellular carcinoma (HCC) patients using time-of-flight secondary ion mass spectrometry (TOF-SIMS), and to analyze the characteristics of key metabolites in spatial distribution. Methods After obtaining adjacent non-tumor tissue samples from HCC patients, the samples were snap-frozen and embedded. Serial tissue sections were prepared using frozen section technology, and spatial metabolomic analysis was performed on the tissue sections using TOF-SIMS. The mass spectrometry data were clustered and spatially mapped at the single-cell level using the SEAM algorithm. Results TOF-SIMS combined with the SEAM algorithm successfully achieved high-resolution spatial metabolomic analysis of HCC boundary tissue. The results showed significant metabolic heterogeneity between the intra-and extra-tumoral regions, as well as within the tumor parenchyma, which could be subdivided into two cell subpopulations with different metabolic characteristics. Differential metabolite analysis identified two key phosphate-related ions (m/z=62.97 and m/z=78.96). Quantitative spatial distribution studies revealed that cell populations with high phosphate metabolism (PM+) were significantly enriched in areas close to the tumor boundary. Conclusions There is significant spatial metabolic remodeling at the HCC tumor boundary, and the boundary enrichment characteristics of PM+ cells suggest that the mechanical force environment at the tumor boundary may regulate the metabolic state of cancer cells.
Objective To investigate the changes in peripheral blood and monocyte-derived high mobility group protein B1 (HMGB1) levels in patients with non-puerperal mastitis (NPM) and their correlation with the disease. Methods A total of 83 patients with NPM were divided into the acute group (42 cases) and the chronic group (41 cases) according to their conditions Additionally, 40 healthy subjects were taken as the control group. The levels of HMGB1, C-reactive protein (CRP), and interleukin-6 (IL-6) in the peripheral blood of each group were detected by ELISA. The number of monocytes and the level of HMGB1 were detected by flow cytometry; the expression of HMGB1 in monocytes was detected by qPCR and Western blot; the correlation between the expression of HMGB1 in monocytes and the levels of CRP and IL-6 in peripheral blood was analyzed by the Pearson method. ROC curves were constructed to evaluate the diagnostic value of HMGB1 expression level in monocytes for the condition of NPM. Results The levels of HMGB1, CRP, IL-6 in the peripheral blood of patients with NPM, the number of M1-type monocytes and the HMGB1 mRNA expression in monocytes were all higher than those in the control group. Meanwhile, these levels in the acute group were higher than those in the chronic group (P＜0.05). The level of HMGB1 mRNA in monocytes was positively correlated with CRP (r=0.426) and IL-6 (r=0.569) in peripheral blood (all P＜0.05). The AUC of HMGB1 protein level in M1 monocytes for diagnosing NPM was 0.739 (95% CI: 0.67-0.82), the sensitivity and specificity were 69.8% and 77.2%. The AUC for evaluating the disease condition was 0.828 (95% CI: 0.73-0.91), the sensitivity and specificity were 83.3% and 71.4%. Conclusions The expression of HMGB1 in monocytes of patients with NPM increases and is positively correlated with the levels of peripheral blood CRP and IL-6, which is helpful for the diagnosis and condition assessment of NPM.
Cell membrane engineering is a key technology for endowing cells with novel recognition, response, and regulatory functions, which holds significant value for the advancement of cell therapy and precision medicine. DNA nanotechnology exhibits unique advantages in the precise functionalization of cell membranes owing to its excellent programmability, addressability, and biocompatibility. This article reviews the latest advances in cell membrane engineering based on oligonucleotides, focusing on two major strategies: chemical covalent modification and noncovalent binding. The modification mechanisms, technical characteristics, and application status of these methods in cell therapy are systematically elaborated. Finally, representative strategies for DNA-mediated cell membrane modification are summarized, and the development prospects in the fields of cell engineering and precision medicine are discussed.
Objective To investigate the implementation status of the 2022 edition of the Standardized Residency Training Content and Standards in emergency medicine residency training bases and to identify existing challenges, in order to provide evidence for future optimization of the standards. Methods A cross-sectional questionnaire survey was conducted among teaching administrators and residents from emergency medicine residency training bases nationwide. The questionnaire covered perceptions of standard implementation and practical challenges, implementation and effectiveness of teaching measures, as well as evaluation and reform suggestions regarding the assessment system. Results A total of 156 valid responses were collected. Most respondents (97.44%) agreed that clinical competency should serve as the core training objective. Approximately 38.46% supported allowing moderate regional flexibility within a unified national framework. During implementation, insufficient teaching incentives and heavy clinical and research workload was identified as major challenges (62.18%). Most teaching activities were routinely implemented, and practice-oriented activities were more frequently rated as effective compared with some theory-based activities. Regarding assessment, 83.33% recommended that process evaluations be tailored by individual training bases, and 78.21% supported increasing the proportion and difficulty of case-based analysis. Conclusions The overall philosophy of the emergency medicine residency training standards has been widely recognized. However, further improvements are needed in institutional support, teaching optimization, and competency-oriented assessment reform. The findings of this study provide practical evidence for future revision of the standards and continuous quality improvement in residency training.
Objective To investigate the expression pattern of platelet-derived growth factor receptor alpha (PDGFRA) in bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) from patients with adolescent idiopathic scoliosis (AIS), and to evaluate its effects on osteogenic differentiation and proliferation of BM-MSCs. Methods Previously generated BM-MSC transcriptomic sequencing data from an established cohort were analyzed to identify differentially expressed genes (AIS, n=12; controls, n=5), and the findings were validated by qRT-PCR(AIS, n=12; controls, n=9). PDGFRA was knocked down by siRNA in normal BM-MSCs. After osteogenic induction, osteogenesis-related parameters were assessed by ALP staining/activity assay, Alizarin Red S staining, qRT-PCR, and Western blot. Cell proliferation was evaluated using CCK-8 assays. Results Compared with healthy controls, PDGFRA was significantly downregulated in BM-MSCs from patients with AIS. During the early stage of osteogenic induction, PDGFRA expression increased significantly on day 6 in healthy BM-MSCs. PDGFRA knockdown suppressed both early osteogenic activity and late mineralization in BM-MSCs, and reduced the expression of osteogenesis-related markers, including RUNX2, ALP, OPN, COL1A1, OSX, and IBSP. In addition, PDGFRA knockdown impaired the proliferation capacity of BM-MSCs. Conclusions PDGFRA is involved in the proliferation and osteogenic differentiation of BM-MSCs from healthy participants. Reduced PDGFRA expression in AIS BM-MSCs may contribute to impaired osteogenesis and low bone mass in AIS.
