Background: Dexmedetomidine (DEX) is commonly employed as a sedative agent to attenuate sympathetic tone and reduce norepinephrine (NE) levels. In the context of stroke-associated pneumonia (SAP), which is believed to arise from heightened sympathetic nervous system activity and elevated NE release, the precise influence of DEX remains uncertain.Methods: In this study, we generated an SAP model using middle cerebral artery occlusion (MCAO) and examined NE levels, immunological statuses in the brain and periphery, pneumonia symptoms, and extent of infarction. We aimed to determine the effects of DEX on SAP and explore the underlying. Despite its potential to reduce NE levels, DEX did not alleviate SAP symptoms or decrease the infarct area. Interestingly, DEX led to an increase in spleen size and spleen index. Furthermore, we observed a decrease in the CD3+ T cell population in both the blood and brain, but an increase in the spleen following DEX administration. The precise mechanism linking decreased CD3⁺ T cells and DEX’s role in SAP requires further investigation.Conclusion: The clinical use of DEX in stroke patients should be approached with caution, considering its inability to alleviate SAP symptoms and reduce the infarct area. Further research is necessary to fully understand the relationship between decreased CD3⁺ T cells and DEX’s influence on SAP.

Introduction: Sepsis associated acute respiratory distress syndrome (ARDS), is a life-threatening condition characterized by severe pulmonary inflammation. Previous research has suggested that allergic immune diseases are associated with a lower risk of sepsis. Therefore, we hypothesized that certain molecules involved in type 2 inflammation are beneficial for the outcome of sepsis associated ARDS. Thymic stromal lymphopoietin (TSLP) is known to promote Th2 responses in allergic disease, however, its role in sepsis associated ARDS remains limited.Methods: To investigate the role of TSLP in sepsis associated lung injury, we administered exogenous recombinant TSLP to wild-type mice, followed by lipopolysaccharide (LPS) challenge. At 24 hours post-treatment, bronchoalveolar lavage fluid (BALF) and lung tissues were collected for analysis. The ratio, number, phenotype, and function of immune cells and cytokine levels were measured. Additionally, murine bone marrow-derived macrophages (BMDMs) were prepared and stimulated with LPS and TSLP to further verify our findings experimentally. To explore the molecular mechanisms of TSLP’s effect, analysis of transcriptome sequencing and single-cell transcriptome sequencing and subsequent experiments were performed.Results: In LPS-induced acute lung injury models, pretreatment with TSLP significantly alleviated lung injury, suppressed inflammatory cytokines secretion, and reduced macrophages and neutrophils infiltration. In addition, TSLP treatment significantly inhibited M1 macrophage polarization and promoted M2 macrophage differentiation. Transcriptome sequencing suggested IFN-γ as a potential target of TSLP, and single-cell transcriptome sequencing showed that innate like T cells are important source of IFN-γ. Consistently, flow cytometry showed that proportion of IFN-γ-producing iNKT cells was decreased by TSLP administration in the acute lung injury model. Intriguingly, Jα18^−/− mice, which are completely deficient in invariant natural killer T (iNKT) cells, exhibited not only significantly less severe lung inflammation but also a notably higher degree of anti-inflammatory Arg1⁺ M2 macrophages infiltration when compared with their LPS-sensitized wild-type counterparts.Conclusions: These findings not only underscore the crucial role of TSLP in the regulation of sepsis-associated ARDS but also demonstrate its potential clinical value as both a predictive biomarker for early detection and a molecular target for therapeutic intervention.

In this study, we have investigated feasibility of remifentanil and sufentanil anesthesia in children with congenital heart disease surgery and its effects on cardiac function and serological parameters. For this purpose, a retrospective study was conducted on 120 children with congenital heart disease who underwent repair of ventricular septum or atrial septum in our hospital, specifically from January 2016 to January 2018, and 60 patients in each group were randomly divided into the control and treatment groups, respectively. The control group was anesthetized with sufentanil, and the treatment group was anesthetized with remifentanil. The heart function, serological indexes, and adverse reactions were observed and compared. We have observed that there was no significant difference in HR levels between these groups ( ), but SDP and DBP values of the two groups were decreased after anesthetic induction ( ). ACH, cortisol, and lactic acid in the treatment group were significantly lower than those in the control group, and the difference was statistically significant ( ). The incidence of bradycardia, nausea and vomiting, hypotension, muscle rigidity, and respiratory depression in the treatment group was 16.67% lower than that in the control group ( ). Remifentanil has less influence on hemodynamics and a better analgesic effect than fentanyl in inhibiting stress response in congenital heart surgery, which provides reference and basis for children congenital heart surgery.

Purpose: Oncology studies employing digital dissection methodologies have provided some insight on the biological features of tumor microenvironment of Triple-negative breast cancer (TNBC), but molecular diagnostics rarely have therapeutic impact. We aimed to identify a novel prognostic biomarker to investigate immune characteristics of TNBC using transcriptomic features. Patients and Methods: We extracted whole transcriptome from breast cancer tissue of 30 TNBC patients and then used bioinformatics approaches to characterize the different immune cell contents in tumor tissue and para-cancerous tissue. We extract 2 indicators to describe the major differences in immune infiltration in the microenvironment between tumor tissue and para-cancerous tissue. We then combined the 2 indicators that represent the levels of increased and decreased infiltration in each sample to obtain the Immune Infiltration Score (IIS). Then we compared the tumor-infiltrating immune cell contents and immune infiltrating status in TNBC samples with CIBERSORT and ESTIMATE score to validate the IIS. Finally, 132 TNBC patients from the Cancer Genome Atlas program (TCGA) dataset was used to validate the predictive power of IIS. Results: 4 types of upregulated and 4 types of downregulated immune cells were identified in the tumor tissue samples of the TNBC patients. Then we developed a novel biomarker, IIS. Results showed that IIS score can clearly separate cancer and para-cancerous tissue. Using the same cutoff value of 0 in the TNBC-TCGA cohort, we show that those patients with a higher IIS had significantly higher PD-L1 expression and shorter progression-free survival time than those with a lower IIS value, indicating IIS score can be generalized to other TNBC datasets. Conclusion: we explored the immune infiltration landscape in 30 TNBC patients and provided IIS as a novel and reliable biomarker to evaluate the progression-free survival and prognosis of the TNBC patients.

ARGLU1 (Arginine and Glutamate Rich1) is a newly identified nuclear protein with suggested multifunctional roles that may be implicated in the pathogenesis and therapeutic resistance of glioma, the most common primary malignant brain tumor. The high heterogeneity and treatment resistance of gliomas pose central challenges in clinical management. ARGLU1 has been implicated in maintaining genomic stability and may contribute to tumor progression by regulating RNA splicing and DNA damage repair pathways. This review systematically summarizes the structural and functional features of ARGLU1 and discusses its potential molecular mechanisms in glioma. These include its influence on the spliceosome assembly, alternative splicing events, and key DNA repair pathways such as homologous recombination (HR) and Fanconi anemia (FA). Furthermore, it discusses the hypothesis that ARGLU1 may enhance DNA repair capacity and thereby influence glioma resistance to temozolomide (TMZ) and radiotherapy. Targeting ARGLU1 may offer a strategy to overcome this resistance. Finally, the review outlines current research limitations and future directions, aiming to provide a new theoretical foundation for the precision treatment of glioma.