Osteocalcin (OCN), a bone-derived hormone, considered as an indicator of bone turnover. Beyond its canonical role in bone metabolism, OCN may have many other functions as well. Studies have shown that it may also regulate glucose and lipid metabolism, cognitive function, sexual function, and more. Recently, OCN has become one interesting hormone with potential effects on acute stress response (ASR), which is essential for vertebrates’ survival. This review aims to comprehensively summarize the progress on the role of OCN in the pathophysiology of ASR and to thoroughly analyze the molecular mechanisms and significance of OCN in modulating ASR. In summary, a deeper understanding of OCN’s role in the ASR will help reveal how bone-derived signals integrate into stress regulatory networks and may guide the development of novel strategies to prevent or treat stress-related disorders (e.g., anxiety, depression, or stress-aggravated cardiac events). By focusing on the emerging OCN–stress axis, our review highlights an expanding perspective on bone as an endocrine organ influencing stress physiology.

Background: Postoperative delirium (POD) is a common central nervous system complication in older adult surgical patients. At present, the mechanism for POD is still unclear. Lipocalin-2 (LCN2) may have an impact on cognitive function, but the relationship between LCN2 and POD has remained unclear. Therefore, we sought to investigate the relationship between the levels of LCN2 in plasma and cerebrospinal fluid (CSF) and the occurrence of POD in older adults undergoing hip fracture surgery.Methods: We conducted a prospective observational cohort study involving 186 older adults (≥65 years old) who underwent hip fracture surgery under spinal anesthesia. CSF and blood samples were collected. The levels of LCN2, interleukin-6 (IL-6), and interleukin-1 (IL-1) were measured using an enzyme-linked immunosorbent assay (ELISA). We used the 3-min diagnostic interview to evaluate delirium defined by the Confusion Assessment Method (3D-CAM), to screen for POD, and the Memorial Delirium Assessment Scale (MDAS) to evaluate the severity of delirium. Multivariable logistic regression was applied to identify independent predictive factors for POD. The relationship between CSF LCN2 levels and POD risk was assessed through receiver operating characteristic (ROC) curve analysis. Correlation analysis was used to investigate the association between CSF LCN2 and MDAS scores as well as IL-6.Results: Among the 186 patients ultimately included, 29 (15.6%) developed POD. Their preoperative CSF LCN2 level was significantly higher than that of those without POD (p = 0.001). The multivariable logistic regression analysis revealed that an elevated preoperative CSF LCN2 level [odds ratio (OR) 2.546, 95% confidence interval (CI) 1.345–4.822; p = 0.004] was an independent predictor of POD. Moreover, among POD group patients, preoperative CSF LCN2 levels were positively correlated with the MDAS scores (r = 0.688, p < 0.001) and CSF IL-6 levels (r = 0.379, p = 0.043). ROC analysis of preoperative CSF LCN2 showed an area under the curve of 0.713 (95% CI 0.615–0.810) with a specificity of 75.0%, and sensitivity of 58.6%.Conclusion: Elevated preoperative CSF LCN2 levels are associated with an increased risk and severity of POD in older adults undergoing hip fracture surgery.Clinical trial registration: https://www.chictr.org.cn/, ChiCTR2200061407.

Delayed neurocognitive recovery (dNCR) is a common complication that occurs post-surgery, especially in elderly individuals. The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex plays an essential role in various membrane fusion events, such as synaptic vesicle exocytosis and autophagosome–lysosome fusion. Although SNARE complex dysfunction has been observed in several neurodegenerative disorders, the causal link between SNARE-mediated membrane fusion and dNCR remains unclear. We previously demonstrated that surgical stimuli caused cognitive impairment in aged rats by inducing α-synuclein accumulation, inhibiting autophagy, and disrupting neurotransmitter release in hippocampal synaptosomes. Here, we evaluated the effects of propofol anesthesia plus surgery on learning and memory and investigated levels of SNARE proteins and chaperones in hippocampal synaptosomes. Aged rats that received propofol anesthesia and surgery exhibited learning and memory impairments in a Morris water maze test and decreased levels of synaptosome-associated protein 25, synaptobrevin/vesicle-associated membrane protein 2, and syntaxin 1. Levels of SNARE chaperones, including mammalian uncoordinated-18, complexins 1 and 2, cysteine string protein-α, and N-ethylmaleimide-sensitive factor, were all significantly decreased following anesthesia with surgical stress. However, the synaptic vesicle marker synaptophysin was unaffected. The autophagy-enhancer rapamycin attenuated structural and functional disturbances of the SNARE complex and ameliorated disrupted neurotransmitter release. Our results indicate that perturbations of SNARE proteins in hippocampal synaptosomes may underlie the occurrence of dNCR. Moreover, the protective effect of rapamycin may partially occur through recovery of SNARE structural and functional abnormalities. Our findings provide insight into the molecular mechanisms underlying dNCR.

Background: Postoperative nausea and vomiting (PONV) is a common complication after general anesthesia, contributing to patient discomfort, adverse clinical outcomes, and increased healthcare costs. While video-assisted thoracoscopic surgery (VATS) offers substantial benefits over open procedures, data on the incidence and predictors of PONV specifically following VATS are scarce and predominantly derived from retrospective studies. This study aimed to prospectively determine the incidence and identify independent risk factors for PONV within the first 72 h after VATS. Methods: In this single-center, prospective observational study, we enrolled 355 adult patients (aged ≥ 18 years) who underwent VATS under general anesthesia at Peking University Third Hospital between September 2022 and September 2023. PONV was assessed in the post-anesthesia care unit (PACU) within 2 h postoperatively and then daily on the ward for three consecutive days. The primary outcome was the incidence of PONV within 72 h. Multivariate logistic regression was employed to identify independent risk factors, with a P -value < 0.05 deemed statistically significant. Results: The overall incidence of PONV within 72 h was 19.44% (69/355). PONV was significantly more frequent in female patients (84.06% of PONV cases) than in males (15.94%, P < 0.001). The highest incidence occurred in the PACU (17.96%), followed by the day of surgery (7.89%) and postoperative day 1 (POD1, 7.61%) on the ward. The incidence decreased to 0.85% on POD2 and 1.41% on POD3. The most severe PONV episodes were reported on the day of surgery (17.86% of PONV cases) and on POD1 (22.22%). Multivariate analysis identified four independent risk factors: female gender, preoperative erector spinae plane block (ESPB), non-administration of preoperative steroids, and low intraoperative minimum mean arterial pressure (MAP). Conclusion: Approximately one in five patients experienced PONV within 72 h after VATS. Independent risk factors included female gender, preoperative ESPB, omission of preoperative steroid prophylaxis, and low intraoperative minimum MAP. These findings highlight potential targets for risk stratification and optimized PONV prophylaxis in this surgical population.