Background:Postoperative delirium (POD) is a common complication after cardiac surgery, but the role of preoperative gut microbiota, especially the mycobiome, in POD susceptibility remains unclear. This study investigated the association between preoperative gut bacterome and mycobiome profiles and POD in elderly patients undergoing minimally invasive direct coronary artery bypass grafting (MIDCABG). Methods:Preoperative fecal samples from 31 elderly patients scheduled for MIDCABG were analyzed via 16S rRNA and ITS high-throughput sequencing. POD was assessed twice daily using the 3D-CAM scale. Patients were divided into delirium (M, n = 7) and control (C, n = 24) groups. Microbial diversity, composition, and bacteria-fungi correlations were systematically evaluated. Results:POD incidence was 22.58%. No baseline differences were observed between groups. Group M exhibited significantly lower gut microbiome health index and higher microbial dysbiosis index at both bacterome and mycobiome levels. Alpha/beta diversity did not differ significantly. LEfSe revealed bacterial enrichment of Clostridium and Intestinibacter in Group M, and Bifidobacterium in Group C. Fungally, Aspergillus and Basidiomycota predominated in Group M, while Saccharomyces and Ascomycota were enriched in Group C. candida showed the highest abundance in Group M and was a key node in the fungal co-occurrence network. Correlation analysis revealed positive associations between bacterial genera (Klebsiella, Enterococcus, Roseburia) and fungal taxa (Wickerhamomyces, Pichia, Geotrichum), suggesting ecological interactions potentially linked to POD. Conclusion:Preoperative dysbiosis of gut bacterome and mycobiome is associated with POD in elderly MIDCABG patients. Several bacterial and fungal taxa, including Clostridium, Intestinibacter, Aspergillus, Saccharomyces, and Candida, were identified as candidate microbial biomarkers associated with POD and may contribute to future microbiota-based risk stratification strategies.

This study aimed to explore the efficacy and safety of remimazolam vs. propofol for sedation during video laryngoscopy in cervical spondylosis patients with suspected difficult laryngoscopy. In this single-center, prospective, randomized controlled study, 85 patients with Modified Mallampati class III or IV and limited cervical spine mobility were recruited and randomly assigned (1:1 ratio) to receive either remimazolam or propofol sedation. The primary outcome was the incidence of hypoxemia (SpO₂< 90

Spinal anesthesia-induced hypotension (SAIH) is a common complication during cesarean delivery and is closely associated with maternal intravascular volume status. However, reliable real-time assessment of volume changes remains challenging. This study aimed to evaluate whether transthoracic echocardiography (TTE)-derived ventricular volume parameters could dynamically reflect peri-anesthetic volume changes and predict SAIH. A total of 100 healthy singleton parturients scheduled for elective cesarean delivery under spinal anesthesia were prospectively enrolled. Left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) were measured by transthoracic echocardiography using the biplane Simpson method at three predefined time points: after admission (T1), after crystalloid fluid preloading (T2), and after stabilization of the sensory block (T3). Systolic blood pressure (SBP), mean arterial pressure (MAP), and heart rate (HR) were recorded simultaneously. SAIH was defined as an SBP < 90 mmHg or a decrease of > 30

Objective The aim of this study was to investigate the incidence, risk factors and airway management of postoperative haematoma following anterior cervical spine surgery (ACSS).Design A retrospective nested case-control study.Setting A tertiary hospital in China.Participants A total of 13 523 patients within a single-centre longitudinal ACSS cohort were identified from March 2013 to February 2022. Patients with postoperative haematoma after ACSS were enrolled as the haematoma group, and others in the cohort without haematoma were randomly selected as the non-haematoma group by individually matching with the same operator, same gender, same surgery year and similar age (±5 years) at a ratio of 4:1. Subsequently, patients with haematoma were included in a subgroup for analysis.Primary outcome measures Postoperative haematoma and difficult intubation prior to haematoma evacuation.Results The incidence of postoperative haematoma out of all ACSS was 0.4% (55/13 523). A total of 275 patients were enrolled in the study, including 55 patients in the haematoma group and 220 patients in the non-haematoma group. Anterior cervical corpectomy and fusion (ACCF) (OR 2.459; 95% CI 1.302 to 4.642; p =0.006) and the maximum mean arterial pressure (MAP) during recovery (OR 1.030; 95% CI 1.003 to 1.058; p =0.028) were identified as independent risk factors for haematoma. In the subgroup analysis, 29% of patients with haematoma experienced difficult intubation, and retropharyngeal haematoma (OR 10.435; 95% CI 1.249 to 87.144; p =0.030) was identified as an independent risk factor for difficult intubation. Patients with haematoma had longer hospitalisation duration (p <0.001) and greater costs associated with their stay (p <0.001).Conclusion ACCF and elevated maximum MAP during the recovery period were independent risk factors for postoperative haematoma following ACSS. Patients with post-ACSS haematoma are at high risk of a difficult airway, with retropharyngeal haematoma being strongly associated with challenging airway management. Postoperative haematoma was associated with longer hospitalisation duration and greater costs.Trial registration number China Clinical Trial Registry: ChiCTR2400086263.

This study aimed to compare the efficacy and safety of different active agent treatments for depression associated with sleep disorders in the elderly population. The major international databases, including Medline (via PubMed), Cochrane Library, Scopus and Embase, WHO International Clinical Trials Registry Platform, ClinicalTrials, were searched using a predesigned search strategy. Randomised controlled trials (RCTs) that had compared the pharmacological treatments or placebo therapy interventions were included. The mean difference with a 95% confidence interval was used to summarise the effect size in the network meta-analysis. The frequentist approach was used for data analysis. In total, 12 RCTs out of 8673 retrieved references met the inclusion criteria in this review (3070 participants). All types of intervention were effective in decreased Insomnia Severity Index (ISI) and depression score, and sertraline had the highest probability of being the most effective intervention in decreasing the ISI (standard mean difference (SMD) = -2.17, 95% confidence interval (95% CI): -2.60, -1.75), Hamilton Depression Scale (HAM-D: SMD = -3.10, 95% CI: -3.60, -2.61) in elderly patients with depression and insomnia. Safety assessments included treatment-emergent adverse events and serious adverse events. In terms of the number of patients reporting escitalopram and zuranolone, zolpidem, seltorexant and eszopiclone had higher risks of serious adverse events than placebo or other treatments. In conclusion, sertraline had the highest probability of being the optimal intervention for decreased ISI and HAM-D in elderly patients with depressive and insomnia. Escitalopram, zuranolone, and seltorexant did not show overall material benefits in reducing ISI. These results should serve evidence-based clinical practice.

Purpose Anesthesia nurses play an important postsurgical role during the anesthesia recovery period, which is characterized by a high incidence of complications related to anesthesia and surgery. Strengthening staff allocation and skill management in the postanesthesia care unit (PACU) is therefore particularly important in managing length of stay. We aimed to investigate the effect of two schedule modes for anesthesia nurses on PACU efficiency. Design A retrospective observational cohort study. Methods We conducted a retrospective study in a large tertiary academic medical center. In 2018, the PACU operated with traditional scheduling and the nurse-to-patient ratio was 1.2:1. The PACU implemented intensive scheduling and this ratio was adjusted to 1:1 in 2019 by adjusting the anesthesia nurse allocation scheme. We compared the number of admitted patients, length of PACU stay, the incidence of anesthesia-related complications, and nurse satisfaction with the two modes. Findings The total number of admitted patients was 10,531 in 2018 and 10,914 in 2019. PACU admitted 401 more patients in 2019 than in 2018, even with two fewer nurses per day. Nevertheless, the median length of PACU stay in 2019 was statistically significantly shorter than in 2018 (29 [22-40] vs 28 [21-39], P < .001], while the incidence of anesthesia-related complications including postoperative pain, nausea and vomiting, hypertension, and shivering were comparable in the 2 years (P > .091). The intensive scheduling implemented in 2019 received more satisfaction from nurses than the traditional scheduling applied in 2018 (P < .01). Conclusions The scheduling of anesthesia nurses affects PACU efficiency. The intensive scheduling mode implemented in 2019 resulted in a comparable number of admitted patients, a better quality of care, and higher nurse satisfaction than those under the traditional scheduling mode.

Anticipating difficult laryngoscopy is crucial for preoperative assessment, especially for patients with cervical spondylosis. Radiological assessment has become essential for improving airway management safety. This research introduces novel radiological indicators from lateral cervical X-ray in the extended head position proposed to enhance the accuracy of predicting difficult laryngoscopy. A prospective cohort study included 422 patients scheduled for elective cervical spine surgery. The Cormack-Lehane grades I and II were categorized as “easy laryngoscopy group”, while grades III and IV were labeled “difficult laryngoscopy group”. Demographic data, conventional bedside indicators including inter-incisor gap (IIG), neck circumference (NC), thyromental distance, the upper lip bite test (ULBT), and 4 radiological indicators including Mandibular Length, Laryngeal Height, the Larynx-Mandibular Angle Test (LMAT) and Larynx-Mandibular Height Test (LMHT) were analyzed comparatively. A binary logistic regression model was developed to identify independent predictive factors. The predictive value of the indicators was evaluated with the area under the curve (AUC). A total of 402 patients were analyzed in the present study. A binary logistic regression model identified IIG, NC, ULBT, and LMAT as the independent indicators associated with difficult laryngoscopy. A novel combined predictive model equation was derived: Ɩ=−0.969 − 1.33×IIG + 0.408×ULBT + 0.201×NC − 0.042×LMAT. The AUC for this composite model was 0.776, exceeding the individual AUC of 0.677 for LMHT. LMHT and the novel combined predictive model incorporating LMAT are potentially valuable predictors for difficult laryngoscopy in patients with cervical spondylosis. The study was registered at the Chinese Clinical Trial Registry (ChiCTR2200058361) on April 7, 2022.

Introduction: To analyze the blood transfusion factors of minimally invasive direct coronary artery bypass (MIDCAB) surgery using artificial intelligence. Methods: A retrospective analysis was performed for patients undergoing MIDCAB operations that no heart-lung machine was used from January 2017 to September 2022 in our hospital. The influencing factors of blood transfusion were used to build the artificial intelligence model. Eighty percent of the database was used as the training set, and twenty percent database was used as the testing set. To predict whether to use red blood cells during operation, we compared 104 artificial intelligence models. We aimed to assess whether which factors influence allogeneic transfusion in MIDCAB operations. Results: Of the 104 machine learning algorithms, the XGBoost model delivered the best performance, with an AUC of 0.726 in the testing set and an accuracy is 0.854 in the testing set. The artificial intelligence model showed preoperative hemoglobin (Hb) less than 120 g/L, prothrombin time (PT) greater than 13.75, body mass index (BMI) less than 22.7 kg/m2, coronary heart disease with additional comorbidities, a history of percutaneous coronary intervention (PCI), weight lower than 67 kg were the six major risk factors of allogeneic transfusion. Conclusion: The XGBoost model can predict transfusion or not transfusion in MIDCBA surgery with high accuracy.

Abstract Background Postoperative retropharyngeal hematoma (RH) following anterior cervical spine surgery (ACSS) can cause acute airway obstruction (AAO). In severe cases, difficult intubation (DI) may occur, posing serious challenges to airway management. The purpose of this retrospective study was to investigate the incidence and risk factors for DI and to explore airway management in RH evacuation following ACSS. Methods A series of 40 consecutive patients who underwent RH evacuation following ACSS were retrospectively identified at Peking University Third Hospital from March 2010 to March 2023. Patients were categorized into the DI group or no-DI group. Demographic, clinical symptom, and airway assessment data were recorded to identify risk factors for DI. Results The incidence of postoperative RH out of all ACSS surgery was 0.2% (40/16,127). General anesthesia was applied for RH evacuation in all 40 patients. The incidence of DI during RH evacuation was 35% (14/40). Thirty-nine patients were successfully treated and discharged, and one patient died of hypoxic-ischemic encephalopathy 24 days after RH evacuation. Class III & IV acute airway obstruction (AAO) (odds ratio [OR], 5.384; 95% confidence interval [CI], 1.098–26.398; P = 0.038) and time interval between symptom onset and airway intervention (TI) (OR, 2.073; CI [1.072–4.010]; P = 0.030) were found to be independent risk factors for DI. Patients with DI had longer tracheal catheter retention times and longer durations of stay in the intensive care unit (ICU) (P < 0.001). Conclusions Class III & IV AAO and TI are independent risk factors for DI during RH evacuation following ACSS. DI is associated with longer retention of the tracheal catheter and longer duration of stay in the ICU. Appropriate airway intervention should be performed for high-risk patients. Trial registration: ChiCTR2200061982

OBJECTIVE:To investigate the incidence and potential risk factors associated with postoperative spinal epidural hematoma (SEH) following anterior cervical spine surgery (ACSS). METHODS:A retrospective analysis was conducted on the clinical data of patients who underwent ACSS for cervical spondylosis at Peking University Third Hospital between March 2013 and February 2022. Patients who developed postoperative SEH were categorized as the SEH group, while those in the cohort without SEH were randomly selected as the non-SEH group by individually matching with the same operator, same gender, same surgery year, and similar age (±5 years) at a ratio of 4 ∶ 1. The general condition, preoperative comorbidities, anticoagulant or antiplatelet therapy, preoperative coagulation and platelet counts, American society of Anesthesiologists physical status classification, cervical spondylosis classification, preoperative modified Japanese Orthopaedic Society score and cervical disability index score, surgical modality, surgical segment levels, ossification of the posterior longitudinal ligament among the surgical level, surgery duration, estimated blood loss, postoperative drainage volume, preoperative mean arterial pressure, mean arterial pressure during postoperative awakening periods, hospital stay and hospitalization cost were compared between the two groups. A bivariate Logistic regression model was applied to screen out the independent risk factors and calculate the odds ratios of indicators associated with SEH. Receiver operating characteristic curve and area under the curve (AUC) were used to describe the discrimination ability of the indicators. RESULTS:A total of 85 patients were enrolled in the study, including 17 patients in the SEH group and 68 patients in the non-SEH group. Seventeen patients with SEH underwent hematoma evacuation, and all of them were successfully treated and discharged from the hospital. Corpectomy (OR=7.247; 95%CI: 1.962-26.766; P=0.003) and the highest mean arterial pressure during awakening (OR=1.056; 95%CI: 1.002-1.113; P=0.043) were independent risk factors for SEH. The AUC values were 0.713 (95%CI: 0.578-0.848) and 0.665 (95%CI: 0.51-0.82) respectively. The patients with SEH had longer hospital stays (P < 0.001) and greater hospitalization costs (P=0.035). CONCLUSION:Corpectomy and elevated maximum mean arterial pressure during awakening are independent risk factors for the development of postoperative SEH following ACSS. High-risk patients should be closely monitored during the perioperative period.

Difficult laryngoscopy is associated with airway injury, and asphyxia. There are no guidelines or gold standards for detecting difficult laryngoscopy. There are many opinions on which predictors to use to detect difficult laryngoscopy exposure, and no comprehensively unified comparative analysis has been conducted. The efficacy and accuracy of deep learning (DL)-based models and machine learning (ML)-based models for predicting difficult laryngoscopy need to be evaluated and compared, under the circumstance that the flourishing of deep neural networks (DNN) has increasingly left ML less concentrated and uncreative. For the first time, the performance of difficult laryngoscopy prediction for a dataset of 671 patients, under single index and integrated multiple indicators was consistently verified under seven ML-based models and four DL-based approaches. The top dog was a simple traditional machine learning model, Naïve Bayes, outperforming DL-based models, the best test accuracy is 86.6%, the F1 score is 0.908, and the average precision score is 0.837. Three radiological variables of difficult laryngoscopy were all valuable separately and combinedly and the ranking was presented. There is no significant difference in performance among the three radiological indicators individually (83.06% vs. 83.20% vs. 83.33%) and comprehensively (83.74%), suggesting that anesthesiologists can flexibly choose appropriate measurement indicators according to the actual situation to predict difficult laryngoscopy. Adaptive spatial interaction was imposed to the model to boost the performance of difficult laryngoscopy prediction with preoperative cervical spine X-ray.

Abnormal redox regulation is thought to contribute to schizophrenia (SCZ). Accumulating studies have shown that the plasma antioxidant enzyme activity is closely associated with the course and outcome in antipsychotics-naïve first-episode (ANFE) patients with SCZ. The main purpose of this study was to investigate the effect of risperidone on oxidative stress markers in ANFE patients and the relationship between risperidone response and changes in oxidative stress markers. Plasma activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) enzyme, total antioxidant status (TAS), and malondialdehyde (MDA) levels were measured in 354 ANFE patients and 152 healthy controls. The clinical symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS). Patients received risperidone monotherapy for 12 weeks and oxidative stress markers and PANSS were measured at baseline and at follow-up. Compared with healthy controls, the patients exhibited higher activities of SOD, CAT, and TAS levels, but lower MDA levels and GPx activity. A comparison between 168 responders and 50 non-responders at baseline and 12-week follow-up showed that GPx activity decreased in both groups after treatment. Moreover, GPx activity decreased less in responders and was higher in responders than in non-responders at follow-up. These results demonstrate that the redox regulatory system and antioxidant defense enzymes may have predictive value for the response of ANFE patients to risperidone treatment.

Depressive symptoms are frequent clinical manifestations in patients with schizophrenia. Decreased brain-derived neurotrophic factor (BDNF) has been shown to be involved in the development of depressive symptoms. However, the detailed molecular mechanism of BDNF in the depressive symptoms of schizophrenia patients remains to be fully elucidated. This study aimed to investigate the role of BDNF in the depressive symptoms in drug-naïve first-episode (DNFE) patients with schizophrenia and whether BDNF levels were associated with the improvement of depressive symptoms after olanzapine treatment. 50 DNFE schizophrenia patients and 55 healthy controls were recruited, and their serum BDNF levels were compared. All patients were treated with olanzapine monotherapy for 12 weeks, and 45 patients completed the trial. The serum BDNF levels and depressive symptoms were measured again at follow-up. We found that DNFE patients had lower BDNF levels, compared to controls. Last observation carried forward (LOCF) analysis was used for patients who dropped out after the second month, and 50 patients were included in the statistical analysis with LOCF. After 12 weeks of treatment with olanzapine, BDNF levels were significantly increased and depressive symptoms were significantly decreased. Correlation analysis showed that the change of BDNF levels after treatment was correlated with the change of HAMD total score from baseline. Further regression analysis showed that the change in BDNF levels was an independent predictor for the improvement in depressive symptoms, after controlling age, BMI change and the decrease of PANSS total score. However, the baseline BDNF levels were not associated with an improvement in depressive symptoms in patients. Our findings reveal that olanzapine treatment can increase BDNF levels and improve depressive symptoms in schizophrenia patients. Moreover, the changes in serum BDNF levels were related to the improvement in depressive symptoms.

AbstractBackground Patients with antipsychotic-naïve first-episode (ANFE) schizophrenia (SZ) can help clarify many confounding factors in determining sex differences in antipsychotic drug induced weight gain and its association with symptom improvement.Methods This 8-week longitudinal trial of ANFE patients with SZ enrolled 526 patients and 313 healthy controls. We evaluated bodyweight and the efficacy of antipsychotics on the Positive and Negative Syndrome Scale (PANSS) at baseline and at the end of week 8.Results Males and females after treatment showed no sex difference in weight gain, BMI increase, and percentage of weight gain. However, at baseline, male patients had more positive symptoms than female patients, and decreases in positive symptoms, general psychopathology, and total PANSS scores were less in male than female patients. Adjusting for confounding factors using multiple linear regression confirmed that weight gain was significantly associated with these decreases in PANSS symptoms only in men not women.Conclusions The relationship between weight gain and symptom reduction after 8 weeks of antipsychotic treatment exists only in male patients with ANFE SZ and not in female patients.

Background Airway management is one of the most important techniques in anesthesia practice and inappropriate airway management is related with airway injury, brain hypoxia, and even death. The patients with cervical spondylosis are often confronted with difficult laryngoscopy who are more prone to appear difficult airway, so it is important to figure out valuable predictors of difficult laryngoscopy in these patients. Methods We randomly enrolled 270 patients undergoing elective cervical spine surgery and analyzed the cervical mobility data in predicting difficult laryngoscopy. The preoperative X-ray radiological indicators were measured by an attending radiologist. Cormack-Lehane scales were assessed during intubation, and patients with a class III or IV view were assigned to the difficult laryngoscopy group. Results Univariate analysis showed that the hyomental distance (HMD, the distance between the hyoid bone and the tip of the chin) and the hyomental distance ratio (HMDR, the ratio between HMD in the extension position and the one in the neutral position) might not be suitable indicators in patients with cervical spondylosis. Binary multivariate logistic regression (backward-Wald) analyses identified two independent correlative factors from the cervical mobility indicators that correlated best as a predictor of difficult laryngoscopy: modified Mallampati test (MMT) and C 2 C 6 AR (the ratio of the angle between a line passing through the bottom of the second cervical vertebra and a line passing through the bottom of the sixth cervical vertebra in the extension position and the one in the neutral position). The odds ratio (OR) and 95 % CI were 2.292(1.093–4.803) and 0.493 (0.306–0.793), respectively. C 2 C 6 AR exhibited the largest area under the curve (0.714; 95 % CI 0.633–0.794). Conclusions C 2 C 6 AR based on preoperative X-ray images may be the most accurate predictor of cervical mobility indicators for difficult laryngoscopy in patients with cervical spondylosis. Trial registration The study was registered at the Chinese Clinical Trial Registry ( http://www.chictr.org.cn ; identifier: ChiCTR-ROC-16,008,598) on June 6, 2016.

Previous studies have demonstrated that patients with schizophrenia (SZ) have greater rate of metabolic disorder as compared with the control population, which likely be the consequence of use of atypical antipsychotics. Olanzapine is a widely used antipsychotic, which increases the weight of SZ patients. However, the underlying mechanism remains poorly understood. Here we report the metabolomics-based understanding of the weight gain induced by olanzapine. 57 first-episode drug-naïve patients (FEDN) were recruited, of whom 27 patients completed a 4-week clinical trial. We then profiled the metabolomes of their plasma with the LC-MS-based nontargeted metabolomics approach at the baseline and after olanzapine monotherapy for 4 weeks. We observed that the plasma of the olanzapine-treated patient had significantly higher lysophosphatidylcholine (LysoPC), lysophosphatidylethanolamine (LysoPE) and lower carnitine as compared with that of the baseline plasma samples. Moreover, regression analyses indicated that the change of LysoPC(14:0) level was an independent contributor to the olanzapine-induced weight gain. Our study suggests that the metabolomics-based approach may facilitate the identification of biomarkers associated with the metabolic disorder causing by antipsychotic in schizophrenia patients.

Background: Accumulating studies have shown that the pathophysiology of schizophrenia may be associated with aberrant lysophospolipid metabolism in the early stage of brain development. Recent evidence demonstrates that antipsychotic medication can regulate the phospholipase activity. However, it remains unclear whether lysophospolipid is associated with the therapeutic response to antipsychotic medication in schizophrenia. This study aimed to investigate the influence of olanzapine monotherapy on lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE) and the association between symptom improvement and changes of LPC and LPE levels during treatment in antipsychotic-naïve first-episode (ANFE) patients. Materials and Methods: The psychotic symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS). 25 ANFE patients were treated with olanzapine for 1 mo. The levels of LPC and LPE were determined and psychotic symptoms were assessed at baseline and at 1-mo follow-up. Results: Relative to baseline, the psychotic symptoms were significantly reduced after olanzapine treatment, except for negative symptoms. Moreover, the levels of most LPC and LPE increased after treatment. Interestingly, increased LPC(18:3) and LPC(20:2) levels were positively associated with the reduction rates of PANSS positive subscore. In addition, baseline levels of LPE(20:5), LPE(18:3) and LPE(22:5) were predictors for the reduction of positive symptoms. Conclusion: Our study reveals that the levels of lysophospolipid are associated with the improvement of positive symptoms, indicating that LPC may be a potential therapeutic target for olanzapine in schizophrenia. Moreover, baseline LPE levels were predictive biomarkers for the therapeutic response to olanzapine in the early stage of treatment in ANFE patients.

Preoperative airway assessment help anticipate a difficult airway. We hypothesized that a close association existed between difficult laryngoscopy and the neck circumference/inter-incisor gap ratio (RNIIG). Our aim was to determine its utility in predicting difficult laryngoscopy in cervical spondylosis patients.

Calcineurin (CaN) over-activation constrains synaptic plasticity and memory formation. Upon CaN activation, NFAT imports into the nucleus and guides its downstream genes, which also affect neuronal and synaptic function. Aberrant CaN/NFAT signaling involves in neurotoxicity and cognitive impairment in neurological disorders such as Alzheimer's disease, but its role in postoperative cognitive dysfunction (POCD) remains uninvestigated. Inhaled anesthetic isoflurane facilitates the development of POCD, and the present study investigated the role of CaN/NFAT signaling in isoflurane induced cognitive impairment of aged rats, and the therapeutic effects of CaN inhibitor cyclosporine A (CsA). The results indicated that hippocampal CaN activity increased and peaked at 6 h after isoflurane exposure, and NFAT, especially NFATc4, imported into the nucleus following CaN activation. Furthermore, phamacological inhibition of CaN by CsA markedly attenuated isoflurane induced aberrant CaN/NFATc4 signaling in the hippocampus, and rescued relevant spatial learning and memory impairment of aged rats. Overall, the study suggests hippocampal CaN/NFAT signaling as the upstream mechanism of isoflurane induced cognitive impairment, and provides potential therapeutic target and possible treatment methods for POCD.

Renal ischemia-reperfusion (I/R) injury is a major cause of acute kidney injury via inflammation and cell apoptosis. Volatile anesthetics have been shown to exert organ-protective effects against kidney damage in vivo and in vitro. In the present study, we investigated the effects of isoflurane, a commonly used volatile anesthetic, on renal I/R injury and the underlying mechanisms. Rats subjected to renal I/R displayed higher serum creatinine and blood urea nitrogen levels than sham rats as well as severe histopathological damage. Renal I/R also resulted in a nuclear factor-κB (NF-κB)-mediated inflammatory response and dysfunction of the p53-Bax-caspase-3 apoptotic pathway. Rats preconditioned with 1.5% isoflurane for 2 h had better renal function and less tubular apoptosis 24 h after I/R injury than control rats. Pretreatment with isoflurane suppressed renal NF-κB activation, leading to a reduction in proinflammatory molecules (high-mobility group box 1, interleukin-1β, and tumor necrosis factor-α) both in the kidneys and circulation. In addition, rats subjected to isoflurane preconditioning had a higher Bcl-2/Bax ratio and less cleaved caspase-3. Our findings suggest that preconditioning with a clinically relevant concentration of isoflurane attenuates renal I/R injury, based at least in part on its ability to modulate renal inflammation and apoptosis.