Background: Perioperative neurocognitive disorders (PND) are the most common postoperative complications with few therapeutic options. Gut microbial dysbiosis is associated with neurological diseases; however, the mechanisms by which the microbiota regulates postoperative gastrointestinal and cognitive function are incompletely understood. Methods: Behavioral testing, MiSeq 16S rRNA gene sequencing, non-target metabolism, intestinal permeability detection, protein assays, and immunofluorescence staining were employed to discern the impacts of surgery on microbial profiles, intestinal barriers, serum metabolism, and the brain. Interventions in mice included fecal microbiota transplantation, the anti-inflammatory agent dexamethasone, Lactobacillus supplementation, indole propionic acid supplementation, and palmitic amide administration. Results: Surgery-induced cognitive impairment occurs predominantly in aged mice, and surgery-induced alterations in the microbiota composition profile exacerbate intestinal barrier disruption in aged mice. These adverse effects can be mitigated by transferring microbiota from young donors or by bolstering the intestinal barrier function using dexamethasone, Lactobacillus, or indole propionic acid. Moreover, microbiota composition profiles can be restored by transplanting feces from young mice to aged surgical mice, improving neuropathology and cognitive function, and these effects coincide with increased intestinal permeability. Metabolomic screening identified alterations in metabolites in mouse serum after surgery, especially the increase in palmitic amide. Palmitic amide levels in serum and brain can be decreased by transplanting feces from young mice to aged surgical mice. Oral palmitic amide exacerbates cognitive impairment and neuropathological changes in mice. Conclusions: Gut microbial dysbiosis in mice after surgery is a key mechanism leading to cognition dysfunction, which disrupts the intestinal barrier and metabolic abnormalities, resulting in neuroinflammation and dendritic spine loss. Intestinal barrier damage and high level of palmitic amide in old mice may be the cause of high incidence of PND in the elderly. Preoperative microbiota regulation and intestinal barrier restoration may be of therapeutic benefit in preventing PND.

Background: Despite evidence that high-flow nasal cannula oxygen therapy (HFNC) promotes oxygenation, its application in sedated gastroscopy in elderly patients has received little attention. This study investigated the effect of different inhaled oxygen concentrations (FiO₂) of HFNC during sedated gastroscopy in elderly patients. Methods: In a prospective randomized single-blinded study, 369 outpatients undergoing regular gastroscopy with propofol sedation delivered by an anesthesiologist were randomly divided into three groups (n = 123): nasal cannula oxygen group (Group C), 100% FiO₂ of HFNC group (Group H100), and 50% FiO₂ of HFNC (Group H50). The primary endpoint in this study was the incidence of hypoxia events with pulse oxygen saturation (SpO₂) ≤ 92%. The secondary endpoints included the incidence of other varying degrees of hypoxia and adverse events associated with ventilation and hypoxia. Results: The incidence of hypoxia, paradoxical response, choking, jaw lift, and mask ventilation was lower in both Group H100 and Group H50 than in Group C (P < 0.05). Compared with Group H100, Group H50 showed no significant differences in the incidence of hypoxia, jaw lift and mask ventilation, paradoxical response, or choking (P > 0.05). No patients were mechanically ventilated with endotracheal intubation or found to have complications from HFNC. Conclusion: HFNC prevented hypoxia during gastroscopy with propofol in elderly patients, and there was no significant difference in the incidence of hypoxia when FiO₂ was 50% or 100%. Trial registration: This single-blind, prospective, randomized controlled trial was approved by the Ethics Committee of Nanjing First Hospital (KY20201102-04) and registered in the China Clinical Trial Center (20/10/2021, ChiCTR2100052144) before patients enrollment. All patients signed an informed consent form.

Increasing evidence indicates that high-fat diets (HFDs) are strongly associated with cognitive deficits. Tryptophan (Trp), an essential amino acid, has been implicated in regulating metabolic and neurological pathways, but its role in mitigating HFD-induced cognitive dysfunction remains insufficiently explored. We hypothesized that enhancing Trp availability (0.1 or 0.5%) could protect the brain from HFD-induced impairments by preserving blood–brain barrier (BBB) integrity and neuronal function. HFD-fed mice exhibited deficits in Morris water maze, fear conditioning, and novel object recognition tests, accompanied by decreased tight junction proteins claudin-1 and occludin. Trp supplementation restored these indices to levels comparable to normal diet mice. Indole-3-propionic acid (IPA), a Trp metabolite, was identified as a mediator underlying these protective effects. IPA administration replicated cognitive improvements and BBB preservation. Transcriptomic analyses revealed both IPA and Trp converge on pathways regulating neuronal health and BBB function, including PPAR signaling, extracellular matrix organization, and adherens junction regulation. Mechanistically, IPA activated free fatty acid receptor 3 (FFAR3) in brain endothelial cells, reducing paracellular permeability and restoring tight junction protein expression. These results highlight a Trp-rich diet as a therapeutic strategy to mitigate HFD-induced cognitive decline through IPA-mediated FFAR3 activation.

In this study, we aimed to compare the effectiveness of transnasal humidified rapid insufflation ventilator exchange (THRIVE) with facemask pre-oxygenation in 40 patients ≥65 years of age undergoing general anesthesia during gastrointestinal surgery for intestinal obstruction. Patients with gastrointestinal obstruction were randomized to either a facemask group (group M, n=20) or THRIVE group (group T, n=20). During pre-oxygenation, the 2 groups used a facemask (100% oxygen, 6 L/min) and THRIVE (100% oxygen, 40 L/min) to supply oxygen, respectively. Induction of anesthesia was performed in both groups using facemasks and without mechanical or assisted ventilation. The intubation occurred after myorelaxant action began. When the peripheral oxygen saturation (SpO₂) dropped below 95%, or 480 s after administration of muscle relaxants, mechanical ventilation was initiated immediately. The primary outcome was arterial partial pressure of oxygen (PaO₂) at 5 min after pre-oxygenation. A secondary outcome was time to SpO₂ of 95% during apnea, with a cut-off time of 480 s. PaO₂ at 5 min after pre-oxygenation was (261.5±30.9) mmHg for group M and (446.1±84.4) mmHg for group T (P<0.001). Based on survival analysis, the median time-to-event in group T was 480 s (95% CI 415.7 s – upper limit unknown) and 240 s (95% CI 225.9–254.1 s) in group M (P<0.001). In elderly patients undergoing rapid sequence induction, pre-oxygenation with THRIVE could improve oxygenation and extend safe apnea time, compared with facemask pre-oxygenation.