DHTPY-Cu@ZOL-Enhanced Photodynamic Therapy: A Strategic Platform for Advanced Treatment of Drug-Resistant Bacterial Wound Infections.

Purpose: This research was to innovate a nanozyme-based therapeutic strategy that combines aggregation-induced emission (AIE) photosensitizers with copper nanozymes. This approach is designed to address the hypoxic conditions often found in bacterial infections and aims to boost the effectiveness of photodynamic therapy (PDT) by ensuring sufficient oxygen supply for reactive oxygen species (ROS) generation. Methods: Our approach involved the synthesis of dihydroxyl triphenyl vinyl pyridine (DHTPY)-Cu@zoledronic acid (ZOL) nanozyme particles. We initially synthesized DHTPY and then combined it with copper nanozymes to form the DHTPY-Cu@ZOL composite. The nanozyme's size, morphology, and chemical properties were characterized using various techniques, including dynamic light scattering, transmission electron microscopy, and X-ray photoelectron spectroscopy. We conducted a series of in vitro and in vivo tests to evaluate the photodynamic, antibacterial, and wound-healing properties of the DHTPY-Cu@ZOL nanozymes, including their oxygen-generation capacity, ROS production, and antibacterial efficacy against methicillin-resistant Staphylococcus aureus (MRSA). Results: The DHTPY-Cu@ZOL exhibited proficient H2O2 scavenging and oxygen generation, crucial for enhancing PDT in oxygen-deprived infection environments. Our in vitro analysis revealed a notable antibacterial effect against MRSA, suggesting the nanozymes' potential to disrupt bacterial cell membranes. Further, in vivo studies using a diabetic rat model with MRSA-infected wounds showed that DHTPY-Cu@ZOL markedly improved wound healing and reduced bacterial presence, underscoring its efficacy as a non-antibiotic approach for chronic infections. Conclusion: Our study suggests that DHTPY-Cu@ZOL is a highly promising approach for combating antibiotic-resistant microbial pathogens and biofilms. The biocompatibility and stability of these nanozyme particles, coupled with their improved PDT efficacy position them as a promising candidate for clinical applications.

Hetrombopag plus recombinant human thrombopoietin for chemotherapy-induced thrombocytopenia in patients with solid tumors.

Background: Chemotherapy-induced thrombocytopenia (CIT) is a common hematological complication in patients with cancer. Hetrombopag is a novel thrombopoietin receptor agonist that has shown an additive effect in stimulating platelet production when combined with recombinant human thrombopoietin (rhTPO). Objectives: This multicenter retrospective cohort study aimed to evaluate the efficacy and safety of hetrombopag plus rhTPO compared with rhTPO alone for CIT. Methods: A total of 294 patients with solid tumors and CIT (platelet count, <50 × 109/L) who received either rhTPO plus hetrombopag (146 patients) or rhTPO alone (148 patients) at 3 centers from January to December 2022 were included in the study. The primary outcome was a platelet count at least 50 × 109/L higher than the baseline value within 14 days. Chemotherapy dose reductions/delays, bleeding, and adverse events were reported. Results: One hundred twenty patients (82.2%) in the rhTPO-hetrombopag group vs 100 patients (67.6%) in the rhTPO group achieved the primary outcome (P = .005). This significant difference persisted in adjusted analysis (odds ratio, 2.01; 95% CI, 1.12-3.60). A total of 115 patients (78.8%) in the rhTPO-hetrombopag group and 101 patients (68.2%) in the rhTPO group avoided chemotherapy dose reductions/delays (P = .041). There was no significant difference in bleeding rates, and adverse events were mild and similar between the 2 groups. No deaths occurred. Conclusion: Compared to rhTPO alone, our findings suggest that the combination of hetrombopag and rhTPO is safe and more effective in patients with CIT.

The landscape of chimeric antigen receptor T cell therapy in breast cancer: Perspectives and outlook.

Chimeric antigen receptor-T (CAR-T) cell therapy is a revolutionary adoptive cell therapy, which could modify and redirect T cells to specific tumor cells. Since CAR-T cell therapy was first approved for B cell-derived malignancies in 2017, it has yielded unprecedented progress in hematological tumors and has dramatically reshaped the landscape of cancer therapy in recent years. Currently, cumulative evidence has demonstrated that CAR-T cell therapy could be a viable therapeutic strategy for solid cancers. However, owing to the immunosuppressive tumor microenvironment (TME) and heterogenous tumor antigens, the application of CAR-T cell therapy against solid cancers requires circumventing more challenging obstacles. Breast cancer is characterized by a high degree of invasiveness, malignancy, and poor prognosis. The review highlights the underlying targets of CAR-T cell therapy in breast cancer, summarizes the challenges associated with CAR-T cell therapy, and proposes the strategies to overcome these challenges, which provides a novel approach to breast cancer treatment.

CPNE1 is a potential prognostic biomarker, associated with immune infiltrates and promotes progression of hepatocellular carcinoma.

BACKGROUND: Copine1 (CPNE1), the first discovered CPNE1 family member, participates in the process of carcinogenesis and development of diverse tumors. Our study aimed to investigate the expression and prognostic value of CPNE1 gene in hepatocellular carcinoma (HCC), to explore its functional network in HCC and its effects on biological behaviors. METHODS: HCCDB, CCLE, HPA and LinkedOmics online databases were used to explore the expression of CPNE1 gene and analyze the co-expression network of CPNE1 in hepatocellular carcinoma. Gene set enrichment analysis (GSEA) was used for GO functional annotation, KEGG pathway enrichment analysis and regulators of CPNE1 networks in LIHC. HepG2 and MHCC-97H cells were selected to construct CPNE1 knockdown cell lines by transfection with siRNA, and Hep3B cell was selected to construct CPNE1 overexpression cell line by transfection with plasmid. The effect of CPNE1 on the proliferation of hepatocellular carcinoma cells was examined by CCK8 assay and clone formation assay; the effect of CPNE1 on the migration ability of hepatocellular carcinoma cells was assessed by cell scratch assay and Transwell cell migration assay; finally, the expression of related signaling pathway proteins was examined by Western Blot. The correlation of CPNE1 expression with immune infiltration and immune checkpoint molecules in HCC tissues was analyzed using TIMER online database and GSEA. RESULTS: CPNE1 was highly expressed in HCC tissues and significantly correlated with sex, age, cancer stage and tumor grade. Overall survival (OS) was significantly lower in patients with high CPNE1 expression than in patients with low CPNE1 expression, and CPNE1 could be used as an independent prognostic indicator for HCC. Knockdown of CPNE1 gene inhibited the AKT/P53 pathway, resulting in decreased proliferation, migration and invasion of HCC cells. Overexpression of CPNE1 gene showed the opposite results. The level of CPNE1 expression in HCC was significantly and positively correlated with the level of infiltration of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells (P < 0.001). GSEA results also showed that CPNE1 of LIHC was involved in some immune response regulating signaling pathways. CONCLUSIONS: Our study firstly found the expression of CPNE1 was significantly higher in LIHC tissues than in normal liver tissues, and high CPNE1 expression was associated with poor prognosis. In addition, we identified the possible mechanism by which CPNE1 functioned in LIHC. CPNE1 influenced AKT/P53 pathway activation and LIHC cell proliferation and migration. There was a significant correlation between CPNE1 expression and tumor immune infiltration in LIHC.

Occupational identity, job satisfaction and their effects on turnover intention among Chinese Paediatricians: a cross-sectional study.

BACKGROUND: This study contributes to research on the paediatrician shortage by examining occupational identity, job satisfaction and their effects on turnover intention among paediatricians in China. METHODS: A multi-stage stratified random sampling method was employed to conduct a questionnaire survey. Of the 4906 survey recipients, valid data were collected from 4198 of the respondents (85.6%). The participants were from seven geographic regions of China (south, central, north, east, northwest, southwest, and northeast). Paediatricians who volunteered and provided written informed consent participated. All variables including basic socio-demographics and work-related characteristics, occupational identity, job satisfaction and turnover intention were based on available literature, and measured on a 5- point Likert scale. Statistical methods such as exploratory factor analysis (EFA), descriptive analysis, common method bias, one-way ANOVA test, Pearson correlation analysis and mediation analysis were used. RESULTS: Significant differences were observed among the respondents in terms of turnover intention based on age, education level, marital status, region, the type and grade of practice setting, professional title, years in practise, workload, rest days, and monthly income. Occupational identity and job satisfaction were both negatively related to turnover intention, and occupational identity was positively correlated with job satisfaction (r1 = - 0.601, p < 0.01; r2 = - 0.605, p < 0.01). The results also showed that job satisfaction played a mediating role in the association between occupational identity and turnover intention among Chinese paediatricians. CONCLUSIONS: Work conditions, workload and salary are crucial factors of turnover intention among paediatricians in China. Therefore, we suggest that healthcare managers should increase investment in paediatrics, implement salary reforms and dedicate more attention to female and young paediatricians, thus reducing turnover intention among Chinese paediatricians.