Jianjun Li

Emerging evidence indicates that early-life lung injuries-including bronchopulmonary dysplasia, childhood asthma, recurrent respiratory infections, and environmental tobacco smoke exposure-are significantly associated with an increased risk of neurodevelopmental disorders such as cognitive impairment, autism spectrum disorder, attention-deficit/hyperactivity disorder, and emotional or behavioral affections. The developing brain is particularly vulnerable during infancy and childhood, and pulmonary insults during this critical window may disrupt normal neurodevelopment through multiple interconnected mechanisms along the lung-brain axis. These mechanisms include the hypoxia-oxidative stress axis, which impairs oligodendrocyte maturation and myelination; pulmonary microvascular injury leading to neuronal energy metabolism dysregulation; systemic inflammation-mediated disruption of the blood-brain barrier; and a cascade from pulmonary inflammation to neuroinflammation, characterized by microglial activation, synaptic dysfunction, and impaired myelination. Together, these pathways converge to produce long-lasting neurodevelopmental consequences. Understanding the lung-brain axis provides a novel theoretical framework for explaining this comorbidity and highlights the need to integrate neurodevelopmental risk assessment and early intervention into the clinical management of early-life lung diseases. Future research should focus on longitudinal cohorts, identification of critical developmental windows, and targeted therapeutic strategies that address both pulmonary and neurological health.

Background: Flexible bronchoscopy is an essential, invasive procedure used in clinical practice for diagnosing and treating bronchial, pulmonary, thoracic and other diseases. Due to concerns about the potential for intense stimulation during flexible bronchoscopy operations, sedation is recommended by most countries and regions for all patients without contraindications. However, the use of sedative and analgesic substances for sedation during flexible bronchoscopy may result in respiratory depression, potentially leading to hypoxaemia and/or hypercapnia. Considering these side-effects and associated risks, some countries and regions do not recommend this approach. Objective: This review aims to compare and analyse differences between currently published guidelines on sedation during flexible bronchoscopy and expert consensus in five key aspects: the necessity of sedation, qualifications of the person in charge of sedation, selection of sedative or anaesthetic drugs, sedation depth and perioperative monitoring, and oxygen supplementation and remedies. Conclusions: Undeniably, more attention and clinical evidence are needed to address the controversies and disputes existing among currently published guidelines on sedation during flexible bronchoscopy or expert consensus. Furthermore, international cooperation is necessary to establish standard international training and practice guidelines for sedation during flexible bronchoscopy.

Background: Patients with breast cancer experience varying degrees of pain, depression, and anxiety after surgery, which affect their postoperative recovery. Although ketamine/esketamine exhibit potential for opioid-sparing and controlling postoperative pain and depression, their effects on postoperative pain and depression remain unclear. This meta-analysis aimed to evaluate whether perioperative administration of ketamine/esketamine could reduce postoperative pain and depression, improve postoperative recovery, and reduce the incidence of adverse events in patients after breast cancer surgery.Material and methods: PubMed, Embase, Web of Science, Cochrane Library, and Clinical Trials were searched from inception until June 2, 2024 for randomized controlled trials in English language on the effect of perioperative ketamine/esketamine on postoperative pain in patients undergoing breast cancer surgery. The primary outcome was the postoperative pain score, and the secondary outcomes were the postoperative depression score, quality of postoperative recovery, incidence of adverse events, and extubation time. The standardized mean difference and 95% confidence interval (CI) were calculated for continuous outcomes, and the risk ratio and 95% CI were calculated for binary variables.Results: Seven studies involving 748 patients were included in this meta-analysis. No significant differences were found in postoperative pain scores at 2 h, 4 h, 1 day, 3 days, 7 days, and 3 months after surgery. Postoperative depression scores at 3 and 7 days after surgery were lower in the ketamine/esketamine group. The incidence of dizziness was lower in ketamine/esketamine group. No statistically significant differences were observed in postoperative depression scores at 30 days after surgery, quality of postoperative recovery at 1 and 3 days after surgery, extubation time, or the incidence of nausea, vomiting, and nightmares.Conclusion: Perioperative ketamine/esketamine administration did not significantly reduce postoperative pain in patients undergoing breast cancer surgery; however, it may reduce depression within a short period after the surgery.Clinical Trial Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42024572414, identifier CRD42024572414.

Postoperative cognitive dysfunction (POCD) is a prevalent complication affecting the central nervous system after surgery, manifesting as a decline in cognitive abilities, particularly common among elderly patients. Surgical stress and anesthesia can activate systemic inflammation, prompting immune cells, including neutrophils, to infiltrate the brain, thereby triggering neuroinflammation and resulting in cognitive impairment. Neutrophils, as crucial effector cells in innate immunity, have been increasingly recognized in recent years for their significant role in the pathogenesis of POCD due to their vital function in inflammatory responses. They are not only rapidly activated in peripheral blood, secreting a range of cytokines, chemokines, and neutrophil extracellular traps (NETs), but also possess the capacity to alter the permeability of the blood-brain barrier (BBB), further facilitating the development of neuroinflammation. This paper systematically reviews the recent findings on the diverse functions of neutrophils and their role in POCD, aiming to provide novel theoretical foundations and cutting-edge perspectives for advancing foundational research and optimizing clinical intervention strategies for POCD.

Aims: Ischemic stroke is a major cause of disability and mortality worldwide. Transcranial direct current stimulation (tDCS) and isoflurane (ISO) preconditioning exhibit neuroprotective properties. However, it remains unclear whether tDCS enhances the protective effect of ISO preconditioning on ischemic stroke, and the underlying mechanisms are yet to be clarified.Method: A model of middle cerebral artery occlusion (MCAO), a rat ischemia–reperfusion (I/R) injury model, and an in vitro oxygen–glucose deprivation/re‐oxygenation (O/R) model of ischemic injury were developed. ISO preconditioning and tDCS were administered daily for 7 days before MCAO modeling. Triphenyltetrazolium chloride staining, modified neurological severity score, and hanging‐wire test were conducted to assess infarct volume and neurological outcomes. Untargeted metabolomic experiments, adeno‐associated virus, lentiviral vectors, and small interfering RNA techniques were used to explore the underlying mechanisms.Results: tDCS/DCS enhanced the protective effects of ISO pretreatment on I/R injury‐induced brain damage. This was evidenced by reduced infarct volume and improved neurological outcomes in rats with MCAO, as well as decreased cortical neuronal death after O/R injury. Untargeted metabolomic experiments identified oxidative phosphorylation (OXPHOS) as a critical pathological process for ISO‐mediated neuroprotection from I/R injury. The combination of tDCS/DCS with ISO preconditioning significantly inhibited I/R injury‐induced OXPHOS. Mechanistically, Akirin2, a small nuclear protein that regulates cell proliferation and differentiation, was found to decrease in the cortex of rats with MCAO and in cortical primary neurons subjected to O/R injury. Akirin2 functions upstream of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). tDCS/DCS was able to further upregulate Akirin2 levels and activate the Akirin2/PTEN signaling pathway in vivo and in vitro, compared with ISO pretreatment alone, thereby contributing to the improvement of cerebral I/R injury.Conclusion: tDCS treatment enhances the neuroprotective effects of ISO preconditioning on ischemic stroke by inhibiting oxidative stress and activating Akirin2‐PTEN signaling pathway, highlighting potential of combination therapy in ischemic stroke.

Background: Postoperative cognitive dysfunction (POCD) is a common neurological complication of anesthesia and surgery in aging individuals. Neuroinflammation has been identified as a hallmark of POCD. However, safe and effective treatments of POCD are still lacking. Itaconate is an immunoregulatory metabolite derived from the tricarboxylic acid cycle that exerts anti-inflammatory effects by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. In this study, we investigated the effects and underlying mechanism of 4-octyl itaconate (OI), a cell-permeable itaconate derivative, on POCD in aged mice. Methods: A POCD animal model was established by performing aseptic laparotomy in 18-month-old male C57BL/6 mice under isoflurane anesthesia while maintaining spontaneous ventilation. OI was intraperitoneally injected into the mice after surgery. Primary microglia and neurons were isolated and treated to lipopolysaccharide (LPS), isoflurane, and OI. Cognitive function, neuroinflammatory responses, as well as levels of gut microbiota and their metabolites were evaluated. To determine the mechanisms underlying the therapeutic effects of OI in POCD, ML385, an antagonist of Nrf2, was administered intraperitoneally. Cognitive function, neuroinflammatory responses, endogenous neurogenesis, neuronal apoptosis, and Nrf2/extracellular signal-related kinases (ERK) signaling pathway were evaluated. Results: Our findings revealed that OI treatment significantly alleviated anesthesia/surgery-induced cognitive impairment, concomitant with reduced levels of the neuroinflammatory cytokines IL-1β and IL-6, as well as suppressed activation of microglia and astrocytes in the hippocampus. Similarly, OI treatment inhibited the expression of IL-1β and IL-6 in LPS and isoflurane-induced primary microglia in vitro. Intraperitoneal administration of OI led to alterations in the gut microbiota and promoted the production of microbiota-derived metabolites associated with neurogenesis. We further confirmed that OI promoted endogenous neurogenesis and inhibited neuronal apoptosis in the hippocampal dentate gyrus of aged mice. Mechanistically, we observed a decrease in Nrf2 expression in hippocampal neurons both in vitro and in vivo, which was reversed by OI treatment. We found that Nrf2 was required for OI treatment to inhibit neuroinflammation in POCD. The enhanced POCD recovery and promotion of neurogenesis triggered by OI exposure were, at least partially, mediated by the activation of the Nrf2/ERK signaling pathway. Conclusions: Our findings demonstrate that OI can attenuate anesthesia/surgery-induced cognitive impairment by stabilizing the gut microbiota and activating Nrf2 signaling to restrict neuroinflammation and promote neurogenesis. Boosting endogenous itaconate or supplementation with exogenous itaconate derivatives may represent novel strategies for the treatment of POCD.

BACKGROUND: Spinal anaesthesia is now the most common technique for caesarean delivery. However, because of the intermittent nature of noninvasive blood pressure (NIBP) measurements, maternal blood pressure may become hypotensive between the measurements. There is thus an inbuilt delay before the anaesthesiologist can intervene to counteract the hypotension. Based on the principle that changes in blood pressure can induce compensatory changes in the heart rate (HR), combining the NIBP with real-time HR, we designed two warning windows to predict hypotension and hypertension. OBJECTIVE: To evaluate whether phenylephrine administration guided by these warning windows would help maintain haemodynamic stability. SETTING: A teaching hospital. DESIGN: A randomised controlled trial. PATIENTS: One hundred and ten pregnant women scheduled for elective caesarean delivery were enrolled, from which, after exclusions, 86 were eligible for the study. INTERVENTIONS: All eligible patients received a continuous intravenous infusion of phenylephrine as soon as spinal anaesthesia was initiated. Thereafter, patients were randomly assigned to two groups. In the test group (Win-Group): rescue phenylephrine administration was triggered by an early warning window of HR above 100 beats per minute (bpm) and SBP 90 to 110 mmHg; pausing the infusion phenylephrine was triggered by a HR lower than 60 bpm and SBP greater than 90 mmHg. In the control group, phenylephrine was guided by BP only when it appeared on the monitor: SBP less than 90 mmHg was the trigger for administering rescue phenylephrine; SBP greater than 110 mmHg was the trigger for pausing the phenylephrine infusion. MAIN OUTCOME MEASURES: The primary outcome was incidence of hypotension. Secondary outcomes were the incidence of hypertension and other adverse haemodynamic events. RESULTS: The incidence of hypotension was significantly lower in the Win-Group than in the BP-Group (27.8 vs. 66.7%, P = 0.001). The minimum SBP was significantly higher in Win-Group than in BP-Group (93.9 ± 9.49 vs. 86.7 ± 11.16 mmHg, P = 0.004). There was no significant difference in the incidence of hypertension between groups. CONCLUSION: After spinal anaesthesia for caesarean delivery, when phenylephrine infusion is guided by HR along with BP from a warning window it effectively reduces the incidence of hypotension without any significant effect on incidence of hypertension. TRIAL REGISTRATION: Chictr.org.cn; Identifier: ChiCTR 2100041812.