Anoikis-related genes in breast cancer patients: reliable biomarker of prognosis.

BACKGROUND: Breast cancer (BC) is the most common cancer in women, and its progression is closely related to the phenomenon of anoikis. Anoikis, the specific programmed death resulting from a lack of contact between cells and the extracellular matrix, has recently been recognized as playing a critical role in tumor initiation, maintenance, and treatment. The ability of cancer cells to resist anoikis leads to cancer progression and metastatic colonization. However, the impact of anoikis on the prognosis of BC patients remains unclear. METHOD: This study utilized data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to collect transcriptome and clinical data of BC patients. Anoikis-related genes (ARGs) were classified into subtypes A and B through consensus clustering. Subsequently, survival prognosis analysis, immune cell infiltration analysis, and functional enrichment analysis were performed for both subtypes. Using the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, a set of 10 ARGs related to prognosis was identified. Immune cell infiltration and tumor microenvironment analyses were conducted on these 10 ARGs to develop a prognostic model. Furthermore, single-cell data analysis and real-time polymerase chain reaction (RT-PCR) analysis were employed to study the expression of the 10 identified prognostic ARGs in BC cells. RESULTS: One hundred thirty-five ARGs were identified as differentially expressed genes in the TCGA and GEO databases, with 42 of them associated with the survival prognosis of BC patients. Analyses involving Principal Component Analysis (PCA), t-Distributed Stochastic Neighbor Embedding (t-SNE), and Uniform Manifold Approximation and Projection (UMAP) revealed distinct expression patterns of ARGs between types A and B. Patients in type A exhibited worse survival prognosis and lower immune cell infiltration compared to type B. Subsequent analyses identified 10 key ARGs (YAP1, PIK3R1, BAK1, PHLDA2, EDA2R, LAMB3, CD24, SLC2A1, CDC25C, and SLC39A6) relevant to BC prognosis. Kaplan-Meier analysis indicated that high-risk patients based on these ARGs had a poorer BC prognosis. Additionally, Cox regression analysis established gender, age, T (tumor), N (nodes), and risk score as predictive factors in a nomogram model for BC. The model demonstrated diagnostic value for BC patients at 1, 3, and 5 years. Decision curve analysis (DCA) verified the risk score as a reliable predictor of BC patient survival rates. Moreover, RT-PCR results confirmed differential expressions of YAP1, PIK3R1, BAK1, PHLDA2, CD24, SLC2A1, and CDC25C in BC cells, with SLC39A6, EDA2R, and LAMB3 showing low expression levels. CONCLUSION: ARGs markers can be used as BC biomarkers for risk stratification and survival prediction in BC patients. Besides, ARGs can be used as stratification factors for individualized and precise treatment of BC patients.

Effect evaluation of different preventive measures for ileus after abdominal operation: A systematic review and network meta-analysis.

Background: Different approaches to the prevention of postoperative ileus have been evaluated in numerous randomized controlled trials. This network meta-analysis aimed to investigate the relative effectiveness of different interventions in preventing postoperative ileus. Methods: Randomized controlled trials (RCTS) on the prevention of postoperative ileus were screened from Chinese and foreign medical databases and compared. STATA software was used for network meta-analysis using the frequency method. Random-effects network meta-analysis was also used to compare all schemes directly and indirectly. Results: A total of 105 randomized controlled trials with 18,840 participants were included in this report. The results of the network meta-analysis showed that intravenous analgesia was most effective in preventing the incidence of postoperative ileus, the surface under the cumulative ranking curve (SUCRA) is 90.5. The most effective intervention for reducing the first postoperative exhaust time was postoperative abdominal mechanical massage (SUCRA: 97.3), and the most effective intervention for reducing the first postoperative defecation time was high-dose opioid antagonists (SUCRA: 84.3). Additionally, the most effective intervention for reducing the time to initiate a normal diet after surgery was accelerated rehabilitation (SUCRA: 85.4). A comprehensive analysis demonstrated the effectiveness and prominence of oral opioid antagonists and electroacupuncture (EA) combined with gum. Conclusion: This network meta-analysis determined that oral opioid antagonists and EA combined with chewing gum are the most effective treatments and optimal interventions for reducing the incidence of postoperative ileus. However, methods such as abdominal mechanical massage and coffee require further high-quality research.

Evaluation of the Effect and Mechanism of Sanhuang Ointment on MRSA Infection in the Skin and Soft Tissue via Network Pharmacology.

Introduction: Skin and soft tissue infection (SSTI) is a frequently encountered clinical disease, and Sanhuang ointment, a traditional Chinese medicine, is used to treat it. However, the pharmacological effect of Sanhuang ointment on SSTI and its underlying mechanism remains unclear. Here, we investigate the protective effect of Sanhuang ointment on Methicillin-resistant Staphylococcus aureus (MRSA) infection in the skin and soft tissues and the underlying mechanism by network pharmacological analysis, followed by in vivo experimental validation. Methods: Via network pharmacology, the active components and disease targets of Sanhuang ointment were screened and intersected for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. A rat model of skin and soft tissue infection was established, and pathological features were observed. Large, medium, and small-dose groups (1 g, 0.5 g, and 0.25 g/animal, with the total amount of Vaseline, dispensed 1 g/animal) of Sanhuang ointment were prepared and Mupirocin ointment was used as a positive control (0.5 g/animal, with the total amount of Vaseline, dispensed 1 g/animal). The expressions of key proteins of the IL-17/NF-κB signaling pathway and downstream inflammatory factors were analyzed by histomorphological analysis, enzyme-linked immunosorbent assay, polymerase chain reaction, and Western blotting. Results: In all, 119 active components and 275 target genes of Sanhuang ointment were identified and intersected with MRSA infection-related genes via network pharmacology analysis, and 34 target genes of Sanhuang ointment were found to be involved in skin and soft tissue infections with MRSA. Sanhuang ointment (1 g/mouse) could effectively ameliorate histopathological changes and significantly inhibit the expression of key proteins involved in the IL-17/NF-κB signaling pathway and downstream inflammatory factors (p < 0.05). Conclusion: Sanhuang ointment has a protective effect on MRSA infection and inhibits inflammation by inhibiting the IL-17/NF-κB signaling pathway. Our findings are important for the secondary development and new drug development of Sanhuang ointment.

A Meta-analysis of the Clinical Efficacy of the Head-of-Bed Elevation for Patients With Acquired Brain Injury.

ABSTRACT: BACKGROUND: Acquired brain injury is caused by traumatic or nontraumatic factors and causes changes in cognition. Several reviews have described the influence of the head-of-bed (HOB) elevation on clinical indexes such as intracranial pressure (ICP) and cerebral perfusion pressure (CPP). However, the conclusions were inconsistent. Therefore, we aimed to evaluate the effects of HOB elevation in the care of the patients with ABI. METHODS: Two researchers independently screened the literature and extracted data. We searched PubMed, EMBASE, the Cochrane Library, Web of Science, and the Chinese Biological Literature Database to collect eligible randomized controlled trials published after September 2021. Reporting quality and methodological quality of the included studies were assessed by using the Preferred Reporting Items for Systematic Reviews and Meta-analysis and the Cochrane risk-of-bias tool. RESULTS : Eight studies were included in the meta-analysis. The results showed that, compared with the flat position, HOB elevation of 30° or 45° can significantly reduce ICP (mean difference [MD], -2.40 mm Hg; 95% confidence interval [CI], -3.19 to -1.61; P < .00001). However, there were no statistical differences in CPP (MD, -1.09; 95% CI, -3.93 to 1.75; P = .45), degree of disability at 90 days (relative risk, 1.01; 95% CI, 0.94-1.08; P = .83), and mean arterial pressure (MD, -0.44; 95% CI, -10.27 to 9.93; P = .93). CONCLUSION: Head-of-bed elevation of 30° can reduce ICP and maintain CPP, and may be an effective noninvasive nursing practice for the prognosis and rehabilitation of ABI patients. Owing to the lack of high-quality, large-sample randomized controlled trials, more rigorous trials are needed to support this conclusion.