Brain‐derived neurotrophic factor precursor (proBDNF) has been reported to strengthen the dysfunction of monocytes/macrophages in animal studies. However, it is still unknown the roles of proBDNF in the dysfunction of monocytes in the inflammatory diseases in humans. In the present study, we showed that proBDNF and pan neurotrophic receptor p75 were significantly upregulated in monocytes from healthy donors (HD) after lipopolysaccharide treatment. Exogenous proBDNF treatment upregulated CD40 and proinflammatory cytokines expression in monocytes including interleukin (IL)‐1β, IL‐6, and tumor necrosis factor (TNF)‐α. In Stanford type‐A acute aortic dissection (AAD) patients, proBDNF was upregulated in CD14 ⁺ CD163 ⁺ CX3CR1 ⁺ M2‐ but not CD14 ⁺ CD68 ⁺ CCR2 ⁺ M1‐like monocytes. In addition, sera from AAD patients activated gene expression of proinflammatory cytokines in cultured PBMCs from HD, which was attenuated by proBDNF monoclonal antibody (Ab‐proB) treatment. These findings suggested that upregulation of proBDNF in M2‐like monocytes may contribute to the proinflammatory response in the AAD.

Background: The imbalance of monocyte/macrophage polarization toward the preferential proinflammatory phenotype and a lack of normal inflammation resolution are present in acute myocardial infarction (AMI). Our previous study showed that upregulation of brain‐derived neurotrophic factor precursor (proBDNF) in M2‐like monocytes may contribute to the proinflammatory response in the Stanford type‐A acute aortic dissection. The present study aimed to investigate the role of proBDNF signaling in monocytes/macrophages in the progress of AMI. Methods and Results: We observed the upregulation of proBDNF in the proinflammatory monocytes of patients with AMI. The upregulation of proBDNF was also observed in the circulating proinflammatory Ly6C ^high monocytes and cardiac F4/80 ⁺ CD86 ⁺ macrophages 3 days after AMI in a mice model. To neutralize proBDNF, the mice subjected to AMI were injected intraperitoneally with a monoclonal anti‐proBDNF antibody. Echocardiography, 2,3,5‐triphenyltetrazolium chloride staining, and positron emission tomography/computed tomography results demonstrate that monoclonal anti‐proBDNF antibody treatment further impaired cardiac functions, increased infarct size, and exacerbated the proinflammatory state. Moreover, the level of proinflammatory Ly6C ^high in the blood and F4/80 ⁺ CD86 ⁺ in the heart was further increased in monoclonal anti‐proBDNF antibody mice. RNA sequencing revealed that matrix metalloprotease‐9 protein level was dramatically increased, along with the activated proinflammatory‐related cytokines. Matrix metalloprotease‐9 inhibitor treatment attenuated the deteriorated effect of monoclonal anti‐proBDNF antibody on cardiac function and infarct areas. Conclusions: Our study shows that endogenous proBDNF in monocytes/macrophages may exert protective roles in cardiac remodeling after AMI by regulating matrix metalloprotease‐9 activity.

Patients suffering from sepsis-induced acute lung injury (ALI) exhibit a high mortality rate, and their prognosis is closely associated with infiltration of neutrophils into the lungs. In this study, we found a significant elevation of CD64⁺ neutrophils, which highly expressed p75 neurotrophin receptor (p75^NTR) in peripheral blood of mice and patients with sepsis-induced ALI. p75^NTR+CD64⁺ neutrophils were also abundantly expressed in the lung of ALI mice induced by lipopolysaccharide. Conditional knock-out of the myeloid lineage's p75^NTR gene improved the survival rates, attenuated lung tissue inflammation, reduced neutrophil infiltration and enhanced the phagocytic functions of CD64⁺ neutrophils. In vitro, p75^NTR+CD64⁺ neutrophils exhibited an upregulation and compromised phagocytic activity in blood samples of ALI patients. Blocking p75^NTR activity by soluble p75^NTR extracellular domain peptide (p75^ECD-Fc) boosted CD64⁺ neutrophils phagocytic activity and reduced inflammatory cytokine production via regulation of the NF-κB activity. The findings strongly indicate that p75^NTR+CD64⁺ neutrophils are a novel pathogenic neutrophil subpopulation promoting sepsis-induced ALI.

This study compared the efficacy of oropharyngeal airways (OA) and nasopharyngeal airways (NA) in maintaining oxygenation during painless fiberoptic bronchoscopy (PFB) in patients sedated with remimazolam besylate. Two hundred and fifty-two patients were randomized to the OA or NA group. Remimazolam besylate was used for anesthesia induction and maintenance in both groups. We measured and recorded several physiological parameters, including mean arterial pressure, heart rate and oxygen saturation (SpO2), at various time points: before anesthesia (T1), after anesthesia induction (T2), immediately after the bronchoscope reached the trachea (T3), during the procedure (T4), and 5 min after transfer to the post-anesthesia care unit (T5). The incidence and frequency of hypoxemia, minimum SpO2 during the procedure and patient awakening time after flumazenil administration were also recorded. Additionally, the relationship between minimum SpO2 and body mass index (BMI) was investigated. Patients in the NA group experienced a higher incidence of hypoxemia compared to the OA group. Patients in the OA group maintained higher SpO2 levels at T3 and had a higher minimum SpO2 during the procedure than the NA group. Furthermore, a significant negative correlation was observed between minimum SpO2 and BMI. Following flumazenil anesthesia reversal, nearly 97 % of patients awakened within 1 min. This study suggests that OA may provide a better safety profile than NA by preserving respiratory function during PFB.

Background: Hypoxemia is the most common adverse event during painless gastrointestinal endoscopy (PGIE). This study aimed to evaluate whether the combined use of remimazolam besylate and ciprofol (group RC) reduces the incidence of hypoxemia compared to ciprofol alone (group C) in patients undergoing PGIE under deep sedation. Methods: A total of 246 patients scheduled for PGIE were recruited from the Second Xiangya Hospital of Central South University and randomly assigned to group C or RC. The primary outcome measured was the incidence of intraoperative hypoxemia. Secondary outcomes included physiological parameters such as blood pressure, heart rate, and oxygen saturation (SpO2) during the procedure, along with time to loss of consciousness (LoC), time to awakening, and major adverse effects (MAEs). Additionally, correlations between minimum SpO2 and factors like body mass index (BMI), age, and preoperative SpO2 were examined. Results: Group C exhibited a significantly higher incidence and frequency of hypoxemia compared to group RC. Correlation analysis revealed that minimum SpO2 was inversely related to age and BMI, while showing a positive correlation with preoperative SpO2. Additionally, the RC group demonstrated significantly decreased induction and shorter times to LoC and awakening than group C. Conclusion: The combined administration of ciprofol and remimazolam besylate may enhance the safety profile of deep sedation for PGIE compared to ciprofol alone, offering reduced hypoxemia incidence and improved procedural efficiency. Trial Registration: www.chictr.org.cn (Registration number: ChiCTR2400092506, Registration date: November 18, 2024).