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Abstract Purpose Dexmedetomidine (Dexmed) is a highly selective alpha 2 adrenoceptor (α2-AR) agonist with excellent sedation and analgesic effects and is frequently used in breast cancer surgery. However, the exact impact of Dexmed on breast cancer prognosis is still unclear. The primary objective of this pilot study was to explore study feasibility (recruitment and dropout rates) for future large-scale randomized controlled trial (RCT) to test the hypothesis that intraoperative Dexmed reduced recurrence-free survival (RFS) and overall survival (OS) in patients after breast cancer surgery. Methods Interviews with patients were performed during the anesthetic preoperative visit for informed consent. Adult females scheduled for a mastectomy due to primary breast cancer were 1:1 randomised to saline (Group Control) or Dexmed (Group Dexmed) treatment groups. The primary outcomes were descriptions of study feasibility (recruitment and dropout rates). We also performed a preliminary analysis of RFS (time from surgery to the earliest date of recurrence/metastasis) and OS (time from surgery to the date of all-cause death) and collected data on percentages/numbers of circulating immune cells at pre- and 24 h post-operation. Results A total of 964 patients were screened; 40% (385/964) met the inclusion criteria, among which 39% (150/385) were enrolled and randomly assigned to either Group Control (n = 75) or Group Dexmed (n = 75). The median follow-up duration was 49 months (interquartile range (IQR): 34–58 months) for Group Control and 48 months (IQR: 33–60 months) for Group Dexmed. Five percent (5%, 8/150) patients were lost to follow-up and 1% (2/150) died. There was no significant difference in RFS and OS. The percentage/number of natural killer (NK), B and T-cell subsets and the CD4+/CD8+ ratio were similar between groups at 24 h post-operation. Conclusion The pilot study was feasible to deliver. In a future definitive trial, the lower recruitment rate may be improved by increasing the number of anesthesiologists involved in the study. The study about the effects of Dexmed on long-term prognoses of breast cancer patients that is planned to follow this pilot study is a large-scaled randomized control study with the aim of providing evidence-based guidelines for rational use of Dexmed in patients undergoing breast cancer surgery. Trial registration Registered at ClinicalTrials.gov on October 20, 2016 (ID: NCT03109990). Graphical Abstract

Abstract Background Parental liver transplantation (PLT) improves long-term survival rates in paediatric hepatic failure patients; however, the mechanism of PLT-induced postoperative pulmonary complications (PPCs) is unclear. Methods A total of 133 paediatric patients undergoing PLT were included. Serum levels of NET components, including circulating free DNA (cfDNA), DNA-histone complex, and myeloperoxidase (MPO)-DNA complex, were detected. The occurrence of PPCs post-PLT, prolonged intensive care unit (ICU) stay and death within one year were recorded as the primary and secondary outcomes. Results The overall rate of PPCs in the hospital was 47.4%. High levels of serum cfDNA, DNA-histone complexes and MPO-DNA complexes were associated with an increased risk of PPCs (for cfDNA, OR 2.24; for DNA-histone complex, OR 1.64; and for MPO-DNA, OR 1.94), prolonged ICU stay (OR 1.98, 4.26 and 3.69, respectively), and death within one year (OR 1.53, 2.65 and 1.85, respectively). The area under the curve of NET components for the prediction of PPCs was 0.843 for cfDNA, 0.813 for DNA-histone complexes, and 0.906 for MPO-DNA complexes. During the one-year follow-up, the death rate was higher in patients with PPCs than in patients without PPCs (14.3% vs. 2.9%, P = 0.001). Conclusions High serum levels of NET components are associated with an increased incidence of PPCs and death within one year in paediatric patients undergoing PLT. Serum levels of NET components serve as a biomarker for post-PLT PPCs and a prognostic indicator.

IntroductionBlood–brain barrier (BBB) breakdown is closely associated with cognitive dysfunction. This study aimed to categorize and summarize research topics on the correlation between BBB breakdown and its effects on cognitive function.MethodsBibliometric analysis methods were used to quantitatively and qualitatively assess research progress and predict future research hotspots. Relevant publications from the Web of the Science Core Collection were extracted on November 5, 2022 and analyzed to predict trends and hotspots in the field.ResultsWe identified 5518 articles published from 2000 to 2021 about the BBB and cognition. The number of manuscripts on this topic increased steadily during this time period, especially after 2013. We found that the number of articles published in China increased gradually and is in second place behind the United States of America (USA). In the research field of BBB breakdown and cognitive function, the USA is still far ahead. Keyword burst detection suggested that cognitive impairment, neurodegeneration disease and neuroinflammation are emerging research hotspots.DiscussionThe mechanisms of BBB integrity breakdown and its effects on the deterioration of cognitive function are complex, and clinical treatment of the affected diseases has been a hot topic in the field over the past 22 years. Looking forward, this body of research is aimed at improving or maintaining patients’ cognitive abilities, by finding preventive measures and to provide a basis for finding new treatments of cognitive disorders.

BackgroundHepatocellular carcinoma (HCC), one of the most common cancers worldwide, exhibits high immune heterogeneity and mortality. Emerging studies suggest that copper (Cu) plays a key role in cell survival. However, the relationship between Cu and tumor development remains unclear.MethodsWe investigated the effects of Cu and cuproptosis-related genes (CRGs) in patients with HCC in the TCGA-LIHC (The Cancer Genome Atlas-Liver cancer, n = 347) and ICGC-LIRI-JP (International Cancer Genome Consortium-Liver Cancer-Riken-Japan, n = 203) datasets. Prognostic genes were identified by survival analysis, and a least absolute shrinkage and selection operator (Lasso) regression model was constructed using the prognostic genes in the two datasets. Additionally, we analyzed differentially expressed genes and signal pathway enrichment. We also evaluated the effects of CRGs on tumor immune cell infiltration and their co-expression with immune checkpoint genes (ICGs) and performed validation in different tumor immune microenvironments (TIMs). Finally, we performed validation using clinical samples and predicted the prognosis of patients with HCC using a nomogram.ResultsA total of 59 CRGs were included for analysis, and 15 genes that significantly influenced the survival of patients in the two datasets were identified. Patients were grouped by risk scores, and pathway enrichment analysis suggested that immune-related pathways were substantially enriched in both datasets. Tumor immune cell infiltration analysis and clinical validation revealed that PRNP (Prion protein), SNCA (Synuclein alpha), and COX17 (Cytochrome c oxidase copper chaperone COX17) may be closely correlated with immune cell infiltration and ICG expression. A nomogram was constructed to predict the prognosis of patients with HCC using patients’ characteristics and risk scores.ConclusionCRGs may regulate the development of HCC by targeting the TIM and ICGs. CRGs such as PRNP, SNCA, and COX17 could be promising targets for HCC immune therapy in the future.