Tryptophan-rich diet and its effects on Htr7+ Tregs in alleviating neuroinflammation and cognitive impairment induced by lipopolysaccharide.

BACKGROUND: Neuroinflammation is a vital pathogenic mechanism for neurodegenerative diseases such as Alzheimer's, schizophrenia, and age-related cognitive decline. Regulatory T cells (Tregs) exhibit potent anti-inflammatory properties and can modulate neurodegenerative diseases arising from central nervous system inflammatory responses. However, the role of Tregs in neuroinflammation-related cognitive dysfunction remains unclear. It is highly plausible that Htr7+ Tregs expressing unique genes associated with the nervous system, including the Htr7 gene encoding the serotonin receptor 5-HT7, play a pivotal role. METHODS: Mice were given a tryptophan-rich diet (with a tryptophan content of 0.6%) or a normal diet (with a tryptophan content of 0.16%). The neuroinflammation-mediated cognitive dysfunction model was established by intracerebroventricular injection of lipopolysaccharide (LPS) in 8-week-old C57BL/6J mice. The activation and infiltration of Tregs were measured using flow cytometry. Primary Tregs were cocultured separately with primary CD8+ T cells and primary microglia for in vitro validation of the impact of 5-HT and 5-HT7 receptor on Tregs. Prior to their transfer into recombination activating gene 1 (Rag1-/-) mice, Tregs were ex vivo transfected with lentivirus to knock down the expression of Htr7. RESULTS: In this study, the tryptophan-rich diet was found to reverse LPS-induced cognitive impairment and reduce the levels of 5-HT in peripheral blood. The tryptophan-rich diet led to increased levels of 5-HT in peripheral blood, which in turn promoted the proliferation and activation of Htr7+ Tregs. Additionally, the tryptophan-rich diet was also shown to attenuate LPS-mediated neuroinflammation by activating Htr7+ Tregs. Furthermore, 5-HT and 5-HT7 receptor were found to enhance the immunosuppressive effect of Tregs on CD8+ T cells and microglia. In Rag1-/- mice, Htr7+ Tregs were shown to alleviate LPS-induced neuroinflammation and cognitive impairment. CONCLUSIONS: Our research revealed the ability of Htr7+ Tregs to mitigate neuroinflammation and prevent neuronal damage by suppressing the infiltration of CD8+ T cells into the brain and excessive activation of microglia, thereby ameliorating LPS-induced cognitive impairment. These insights may offer novel therapeutic targets involving Tregs for neuroinflammation and cognitive impairment.

Effect of intranasal insulin on perioperative cognitive function in older adults: a randomized, placebo-controlled, double-blind clinical trial.

BACKGROUND: Postoperative cognitive impairment are common neural complications in older surgical patients and exacerbate the burden of medical care on families and society. METHODS: A total of 140 older patients who were scheduled for elective orthopaedic surgery or pancreatic surgery with general anaesthesia were randomly assigned to Group S or Group I with a 1:1 allocation. Patients in Group S and Group I received intranasal administration of 400 µL of normal saline or 40 IU/400 µL of insulin, respectively, once daily from 5 minutes before anaesthesia induction until 3 days postoperatively. Perioperative cognitive function was assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment-Basic (MoCA-B) at 1 day before and 3 days after surgery and postoperative delirium (POD) incidence was assessed using the 3-minute Diagnostic Interview for CAM (3D-CAM) on postoperative days 1-3. Serum levels of interleukin-6 (IL-6), tumour necrosis factor α (TNF-α), S100-ß and C-reactive protein (CRP) were measured on the first day after surgery. RESULTS: Insulin treatment significantly increased postoperative MMSE and MoCA-B scores in group I than in group S (P < 0.001, P = 0.001, respectively), decreased the incidence of POD within the 3-day postoperative period in Group I than in Group S (10.9% vs 26.6%, P = 0.024), and inhibited postoperative IL-6 and S100-ß levels in Group I compared to Group S (P = 0.034, P = 0.044, respectively). CONCLUSIONS: Intranasal insulin administration is thus suggested as a potential therapy to improve postoperative cognition in older patients undergoing surgery. However, a more standardized multi-centre, large-sample study is needed to further validate these results.

Public Knowledge and Awareness of Anesthesiology and Anesthesiologists in China: A Cross-Sectional National Survey of 1 Million Participants.

BACKGROUND: In the past 20 years, anesthesiology has become one of the most advanced specialties and has undergone rapid development. However, public awareness regarding anesthesiology and anesthesiologists is limited, especially in developing countries. It is important for anesthesiologists to make the public aware of their role during surgery. Therefore, a nationwide survey was set up to investigate public awareness of anesthesiology and anesthesiologists in China. METHOD: A cross-sectional nationwide survey was performed from June 2018 to June 2019 in 34 provinces, municipalities, and autonomous regions across China and an overseas region. The questionnaires of the survey were divided into 2 main parts: general items and research items. General items included the demographic characteristics of the participants; research items consisted of 10 questions about the public's awareness of anesthesiologists and anesthesiology. Data quality control was undertaken by the investigation committee throughout the survey process. RESULTS: The nationwide survey enrolled 1,001,279 participants (male, 40.7%). We found that most of the participants regarded anesthesiologists as doctors. However, public knowledge of anesthesiologists' work and duties during surgery was quite low, with correct response rate ranging from 16.5% to 52.9%, and anesthesiologist responsibilities were often mistakenly attributed to surgeons or nurses. It is disappointing that more than half of participants still thought that, once the patient fell asleep after receiving anesthetics, the anesthesiologist could leave the operating room. Finally, the correct response rate was positively correlated with the economic levels of the regions. CONCLUSIONS: Public awareness regarding anesthesiology and anesthesiologists in China remains inadequate. Due to the biases and characteristics of the participants, the actual situation of the general Chinese public is likely even worse than reflected here. Therefore, extensive measures should be undertaken to improve public knowledge of anesthesiology and anesthesiologists.

Triglyceride-glucose index predicts postoperative delirium in elderly patients with type 2 diabetes mellitus: a retrospective cohort study.

BACKGROUND: Postoperative delirium (POD) is more prevalent among elderly patients with type 2 diabetes mellitus (T2DM). Insulin resistance (IR) can be assessed using the triglyceride-glucose (TyG) index, a novel biomarker. This study aims to investigate the predictive potential of the TyG index for POD in elderly patients with T2DM. MATERIALS AND METHODS: Elderly patients (≥ 65) with T2DM who underwent non-neurosurgery and non-cardiac surgery were enrolled. Univariate and multivariate logistic regression analyses were conducted to assess the association between the TyG index and POD. Additionally, subgroup analyses were performed to compare the sex-specific differences in the predictive ability of the TyG index for POD. RESULTS: A total of 4566 patients were included in this retrospective cohort. The receiver operating characteristic (ROC) curve analysis determined the optimal cut-off value for the TyG index to be 8.678. In the univariate model, a TyG index > 8.678 exhibited an odds ratio (OR) of 1.668 (95% CI: 1.210-2.324, P = 0.002) for predicting POD. In the multivariate regression models, the ORs were 1.590 (95% CI: 1.133-2.252, P < 0.008), 1.661 (95% CI: 1.199-2.325, P < 0.003), and 1.603 (95% CI: 1.137-2.283, P = 0.008) for different models. Subgroup analyses demonstrated that the predictive ability of the TyG index was more pronounced in females compared to males. CONCLUSION: The TyG index shows promise as a novel biomarker for predicting the occurrence of POD in elderly surgical patients with T2DM.

The relationship between trajectories of renal oxygen saturation and acute kidney injury: a prospective cohort study with a secondary analysis.

BACKGROUND: Acute kidney injury (AKI) is a major postoperative consequence, affecting prognosis of older patients. Effective prediction or intervention to predict or prevent the incidence of AKI is currently unavailable. AIMS: Dynamic changes of renal tissue oxygen saturation (RSO2) during surgery process are understudied and we intended to explore the distinct trajectories and associations with postoperative AKI. METHODS: This was a secondary analysis including data for older patients who underwent open hepatectomy surgery with informed consent. Latent class mixed models (LCMM) method was conducted to generate trajectories of intraoperative renal tissue RSO2 through different time points. The primary outcome was postoperative 7-day AKI. The univariate and multivariate regression analysis were performed to identify the relationship between distinct trajectories of renal tissue RSO2 and the risk of AKI. Meanwhile, the prediction efficacy of renal tissue RSO2 at different time points was compared to find potential intervention timing. RESULTS: Postoperative AKI occurred in 14 (15.2%) of 92 patients. There are two distinct renal tissue RSO2 trajectories, with 44.6% generating "high-downwards" trajectory and 55.4% generating "consistently-high" trajectory. Patients with "high-downwards" trajectory had significantly higher risk of postoperative AKI than another group (Unadjusted OR [Odds Ratio] = 3.790, 95% CI [Confidence Interval]: 1.091-13.164, p = 0.036; Adjusted OR = 3.973, 95% CI 1.020-15.478, p = 0.047, respectively). Predictive performance was 71.4% sensitivity and 60.3% specificity for "high-downwards" trajectory of renal tissue RSO2 to identify AKI. Furthermore, the renal tissue RSO2 exhibited the lowest level and the best results in terms of the sensitivity during the hepatic occlusion period, may be considered as a "time of concern". CONCLUSIONS: Older patients undergoing hepatectomy may show high-downwards trajectory of renal tissue RSO2, indicating a higher risk of AKI, and the lowest level was identified during the hepatic occlusion period. These findings may help to provide potential candidates for future early recognition of deterioration of kidney function and guide interventions.

Development and validation of a nomogram for predicting pulmonary complications in elderly patients undergoing thoracic surgery.

BACKGROUND: Postoperative pulmonary complications (PPCs) remain a prevalent concern among elderly patients undergoing surgery, with a notably higher incidence observed in elderly patients undergoing thoracic surgery. This study aimed to develop a nomogram to predict the risk of PPCs in this population. METHODS: A total of 2963 elderly patients who underwent thoracic surgery were enrolled and randomly divided into a training cohort (80%, n = 2369) or a validation cohort (20%, n = 593). Univariate and multivariate logistic regression analyses were conducted to identify risk factors for PPCs, and a nomogram was developed based on the findings from the training cohort. The validation cohort was used to validate the model. The predictive accuracy of the model was evaluated by receiver operating characteristic (ROC) curve, area under ROC (AUC), calibration curve, and decision curve analysis (DCA). RESULTS: A total of 918 (31.0%) patients reported PPCs. Nine independent risk factors for PPCs were identified: preoperative presence of chronic obstructive pulmonary disease (COPD), elevated leukocyte count, higher partial pressure of arterial carbon dioxide (PaCO2) level, surgical site, thoracotomy, intraoperative hypotension, blood loss > 100 mL, surgery duration > 180 min, and malignant tumor. The AUC value for the training cohort was 0.739 (95% CI: 0.719-0.762), and it was 0.703 for the validation cohort (95% CI: 0.657-0.749). The P-values for the Hosmer-Lemeshow test were 0.633 and 0.144 for the training and validation cohorts, respectively, indicating a notable calibration curve fit. The DCA curve indicated that the nomogram could be applied clinically if the risk threshold was between 12% and 84%, which was found to be between 8% and 82% in the validation cohort. CONCLUSION: This study highlighted the pressing need for early detection of PPCs in elderly patients undergoing thoracic surgery. The nomogram exhibited promising predictive efficacy for PPCs in elderly patients undergoing thoracic surgery, enabling the identification of high-risk patients and consequently aiding in the implementation of preventive interventions.

Association of sleep quality on the night of operative day with postoperative delirium in elderly patients: A prospective cohort study.

BACKGROUND: Sleep disturbances in the peri-operative period have been associated with adverse outcomes, including postoperative delirium (POD). However, research on sleep quality during the immediate postoperative period is limited. OBJECTIVES: This study aimed to investigate the association between sleep quality on the night of the operative day assessed using the Sleep Quality Numeric Rating Scale (SQ-NRS), and the incidence of POD in a large cohort of surgical patients. DESIGN: A prospective cohort study. SETTING: A tertiary hospital in China. PATIENTS: This study enrolled patients aged 65 years or older undergoing elective surgery under general anaesthesia. The participants were categorised into the sleep disturbance and no sleep disturbance groups according to their operative night SQ-NRS. MAIN OUTCOME MEASURES: The primary outcome was delirium incidence, whereas the secondary outcomes included acute kidney injury, stroke, pulmonary infection, cardiovascular complications and all-cause mortality within 1 year postoperatively. RESULTS: In total, 3072 patients were included in the analysis of this study. Among them, 791 (25.72%) experienced sleep disturbances on the night of operative day. Patients in the sleep disturbance group had a significantly higher risk of developing POD (adjusted OR 1.43, 95% CI 1.11 to 1.82, P  = 0.005). Subgroup analysis revealed that age 65-75 years; male sex; ASA III and IV; haemoglobin more than 12 g l -1 ; intra-operative hypotension; surgical duration more than 120 min; and education 9 years or less were significantly associated with POD. No interaction was observed between the subgroups. No significant differences were observed in the secondary outcomes, such as acute kidney injury, stroke, pulmonary infection, cardiovascular complications and all-cause mortality within 1 year postoperatively. CONCLUSIONS: The poor subjective sleep quality on the night of operative day was independently associated with increased POD risk, especially in certain subpopulations. Optimising peri-operative sleep may reduce POD. Further research should investigate potential mechanisms and causal relationships. TRIAL REGISTRY: chictr.org.cn: ChiCTR1900028545.

The modified lymphocyte C-reactive protein score is a promising indicator for predicting 3-year mortality in elderly patients with intertrochanteric fractures.

BACKGROUND: Hip fractures are common in elderly patients, and almost all the patients undergo surgery. This study aimed to develop a novel modified lymphocyte C-reactive protein (CRP) score (mLCS) to simply and conveniently predict 3-year mortality in elderly patients undergoing intertrochanteric fracture surgery. METHODS: A retrospective study was conducted on elderly patients who underwent intertrochanteric fracture surgery between January 2014 and December 2017. The mLCS was developed according to the value of CRP and lymphocyte counts. Univariate and multivariate Cox regression analyses were used to identify independent risk factors for 3-year mortality after surgery. The performances of the lymphocyte CRP score (LCS) and mLCS to predict 3-year mortality were then compared using C-statistics, decision curve analysis (DCA), net reclassification index (NRI) and integrated discrimination improvement (IDI). RESULTS: A total of 291 patients were enrolled, of whom 52 (17.9%) died within 3 years after surgery. In the multivariate Cox regression analysis, mLCS (hazard ratio (HR), 5.415; 95% confidence interval (CI), 1.743-16.822; P = 0.003) was significantly associated with postoperative 3-year mortality. The C-statistics of LCS and mLCS for predicting 3-year mortality were 0.644 and 0.686, respectively. The NRI (mLCS vs. LCS, 0.018) and IDI (mLCS vs. LCS, 0.017) indicated that the mLCS performed better than the LCS. DCA also showed that mLCS had a higher clinical net benefit. CONCLUSIONS: mLCS is a promising predictor that can simply and conveniently predict 3-year mortality in elderly patients undergoing intertrochanteric fracture surgery.

Association between intraoperative mean arterial pressure variability and postoperative delirium after hip fracture surgery: a retrospective cohort study.

BACKGROUND: Postoperative delirium (POD) is a common complication in elderly patients after hip fracture surgery. Our study was to investigate whether intraoperative mean arterial pressure variability (MAPV) was associated with POD in elderly patients after hip fracture surgery. METHODS: In this retrospective cohort study, patients aged 65 years and older undergoing hip fracture surgery were included. The correlation between MAPV and POD was investigated using univariate and multivariate logistic regression. Covariate-related confounding effects were eliminated with propensity score matching (PSM) analysis. Then, a subgroup analysis was conducted to further examine the associations between MAPV and POD. RESULTS: Nine hundred sixty-three patients with a median age of 80 years (IQR: 73-84) were enrolled. POD occurred in 115/963 (11.9%) patients within 7 days after surgery. According to multivariate regression analysis, MAPV > 2.17 was associated with an increased risk of POD (OR: 2.379, 95% CI: 1.496-3.771, P < 0.001). All covariates between the two groups were well balanced after PSM adjustment. A significant correlation between MAPV and POD was found in the PSM analysis (OR: 2.851, 95% CI: 1.710-4.746, P < 0.001). CONCLUSIONS: An increased intraoperative MAPV may be a predictor for POD.

Systemic immune-inflammation index predicts postoperative delirium in elderly patients after surgery: a retrospective cohort study.

BACKGROUND: Postoperative delirium (POD) is a common complication among elderly patients after surgery. It is unclear whether the systemic immune-inflammation index (SII) can be a predictor of POD. We explored the prognostic value of the SII in predicting POD in elderly patients undergoing non-neurosurgery and non-cardiac surgery in a large retrospective cohort. METHODS: We enrolled elderly patients undergoing non-neurosurgery and non-cardiac surgery between January 2014 and August 2019. Univariate and multivariate logistic regression analyses were performed to explore the correlation between POD and the SII value as both a continuous and categorical variable. Then, propensity score matching (PSM) analysis was applied to eliminate the confounding effect of covariates and prove our results. Subgroup analyses were then performed to discover the association between the SII and POD in different subgroups. RESULTS: A total of 29,608 patients with a median age of 70 years (IQR: 67-74) were enrolled in the retrospective cohort. The cut-off value of the SII was 650, which was determined by the receiver operating characteristic (ROC) curve. The ORs of an SII value > 650 was 2.709 (95% CI:2.373-3.092, P < 0.001), 1.615 (95% CI:1.384-1.882, P < 0.001), 1.855 (95% CI:1.602-2.146, P < 0.001), and 1.302 (95% CI:1.106-1.531, P = 0.001) for prediction of POD in univariate model and three multivariate regression models. After PSM, the OR of an SII value > 650 was 1.301 (95% CI: 1.062-1.598, P = 0.011). The subgroup analysis indicated that the SII indicates a significantly increased risk of POD in patients with Hb < 130 g/L, 4*109/L < WBC ≤ 10*109/L, albumin < 39 g/L, or duration of MAP < 60 mmHg ≥ 5 min. The SII was found to be a useful prognostic predictor of POD for patients of different ages, sexes, and ASA classifications. CONCLUSIONS: The SII had a predictive value for POD in patients undergoing non-neurosurgery and non-cardiac surgery. As an index generated from routine blood tests, the SII has advantages regarding cost and time. After further validation, the SII may provide a new option for POD prediction.

Comparison of propofol-nalbuphine and propofol-fentanyl sedation for patients undergoing endoscopic retrograde cholangiopancreatography: a double-blind, randomized controlled trial.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) has been increasingly used to treat patients with biliary/pancreatic duct obstruction or stricture outside the operating room. Effective and safe sedation techniques are needed because of painful stimuli and the long duration of the ERCP procedure.Nalbuphine has been shown to cause less respiratory depression during sedation than similar cases without nalbuphine. This study compared the effects of propofol-nalbuphine (PN) and propofol-fentanyl (PF) sedation in patients undergoing ERCP. METHODS: Four hundred patients scheduled for ERCP procedures were divided into two groups: the PF group (receiving PF sedation,n = 199) and the PN group (receiving PN sedation,n = 201). Vital signs, adverse events during surgery, patient movement scores, pain scores, and adverse events one day post-ERCP were recorded. RESULTS: Stable haemodynamics were observed in both groups.Compared to the PF group, the PN group showed significantly decreased respiratory depression (P < 0.0001) and surgical interruptions (P = 0.048).Nalbuphine decreased patient movement by reducing pain from ERCP. CONCLUSION: Nalbuphine, instead of fentanyl, precipitated less respiratory depression while permitting adequate/equivalent sedation for ERCP and therefore provides more efficient and safer sedation. Trial registration ChiCTR, ChiCTR1800016018, Registered 7 May 2018, http://www.chictr.org.cn/showproj.aspx?proj=27085.

Development and validation of a risk nomogram for postoperative acute kidney injury in older patients undergoing liver resection: a pilot study.

BACKGROUND: Postoperative acute kidney injury (AKI) is associated with poor clinical outcomes. Early identification of high-risk patients of developing postoperative AKI can optimize perioperative renal management and facilitate patient survival. The present study aims to develop and validate a nomogram to predict postoperative AKI after liver resection in older patients. METHODS: A retrospective observational study was conducted involving data from 843 older patients scheduled for liver resection at a single tertiary high caseload general hospital between 2012 and 2019. The data were randomly divided into training (70%, n = 599) and validation (30%, n = 244) datasets. The training cohort was used to construct a predictive nomogram for postoperative AKI with the logistic regression model which was confirmed by a validation cohort. The model was evaluated by receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis in the validation cohort. A summary risk score was also constructed for identifying postoperative AKI patients. RESULTS: Postoperative AKI occurred in 155 (18.4%) patients and was highly associated with in-hospital mortality (5.2% vs. 0.7%, P <  0.001). The six predictors selected and assembled into the nomogram included age, preexisting chronic kidney disease (CKD), non-steroidal anti-inflammatory drugs (NSAIDs) usage, intraoperative hepatic inflow occlusion, blood loss, and transfusion. The predictive nomogram performed well in terms of discrimination with area under ROC curve (AUC) in training (0.73, 95% confidence interval (CI): 0.68-0.78) and validation (0.71, 95% CI: 0.63-0.80) datasets. The nomogram was well-calibrated with the Hosmer-Lemeshow chi-square value of 9.68 (P = 0.47). Decision curve analysis demonstrated a significant clinical benefit. The summary risk score calculated as the sum of points from the six variables (one point for each variable) performed as well as the nomogram in identifying the risk of AKI (AUC 0.71, 95% CI: 0.66-0.76). CONCLUSION: This nomogram and summary risk score accurately predicted postoperative AKI using six clinically accessible variables, with potential application in facilitating the optimized perioperative renal management in older patients undergoing liver resection. TRIAL REGISTRATION: NCT04922866 , retrospectively registered on clinicaltrials.gov on June 11, 2021.

TMEM59 protects against cerebral ischemic stroke by suppressing pyroptosis and microglial activation.

Ischemic stroke is a common disease worldwide with high mortality and disability rates. Nevertheless, pathogenesis of ischemic stroke is still vague, and finding novel therapeutic target is urgently necessary. TMEM59 (also known as dendritic cell-derived factor 1, DCF1), a type I transmembrane protein, contains a minimal 19-amino-acid peptide in its intracellular domain, and has been involved in neurological pathology. However, its biological impacts on ischemic stroke are still unknown. In this study, we provided new evidence that TMEM59 expression was significantly down-regulated upon ischemia/reperfusion (I/R). The effect of stroke insult on TMEM59 expression change was only detected in microglial cells by in vitro studies. We observed that TMEM59 knockout markedly accelerated cerebral I/R in mice induced by middle cerebral artery occlusion (MCAO), as evidenced by the elevated infarction volume, neurological deficit scores, brain water contents and neuronal death, further contributing to the abnormal behaviors for mice. We then found that microglial activation reflected by the enhanced expression of Iba-1 was dramatically potentiated by TMEM59 knockout in MCAO-treated mice. Pyroptosis was highly triggered in mice with cerebral I/R, while being further aggravated in mice with TMEM59 deletion, as proved by the considerably increased expression of NLRP3, ASC, cleaved Caspase-1, GSDMD-N, mature-IL-1ß and mature-IL-18. Additionally, TMEM59 knockout mice exhibited accelerated activation of NF-κB signaling pathway compared with the wild type group of mice after MCAO operation, indicating the anabatic neuroinflammation. The effects of TMEM59 suppression on ischemic stroke were confirmed in microglial cells with exposure to oxygen-glucose deprivation/reoxygenation (OGD/R). In contrast, the in vitro studies verified that improving TMEM59 expression effectively hindered pyroptosis and inflammation in microglial cells upon OGD/R treatment. Taken together, these findings illustrated protective effects of TMEM59 against ischemic stroke through restraining pyroptosis and inflammatory response.

LMA® protector™ in patients undergoing laparoscopic surgeries: a multicenter prospective observational study.

BACKGROUND: Laryngeal masks airway (LMA) has been increasingly used in surgical patients. However, the use of LMA in laparoscopic surgeries remains controversial. The major concerns include the potential risk of esophageal regurgitation, aspiration, and difficulties to achieve effective ventilation. The aim of this study was to evaluate the safety and effectiveness of the LMA® Protector™ in patients undergoing laparoscopic surgery. METHODS: Patients aged 18 to 70 years, scheduled for laparoscopic surgeries were included. The insertion time, successful insertion rate, and oropharyngeal leak pressure were measured. Airway complications and airway manipulations during the procedure were documented. Effective ventilation rate was calculated. Visible bloodstains and reflux content in the drainage channel were documented after the removal of LMA® Protector™. RESULTS: Three hundred patients were enrolled. The insertion of LMA® Protector™ failed in seven patients resulting with a successful insertion rate of 97.7%. During the maintenance of anesthesia, airway manipulation was required in 19 patients (19/293, 6.48%), in three of whom the LMA was replaced with endotracheal intubation resulting with an effective ventilation rate of 96.7% (290/300). The oropharyngeal leak pressure was 30.18 ± 5.88 cmH2O. Seventy-five patients (25.86%) reported mild sore throat on the first day after surgery. Bloodstains on study devices were noticed in 58 patients (20%). Seventy-five patients (25.86%) reported mild sore throat on the first day after surgery. Gastric reflux was noticed in the drainage tube in 5 patients (1.72%) with no signs of aspiration in any of those patients. CONCLUSIONS: The LMA® Protector™ was shown to be safe and effective in patients undergoing laparoscopic surgeries. Although minor complications that require no further treatment, no clinically diagnosed aspiration was noticed in our study. Gastric reflux was noticed in the drainage tube in five patients undergoing laparoscopic gynecology surgery. Further research is needed to verify whether LMA® Protector™ is suitable for procedures in Trendelenburg position or other situations that a high risk of gastroesophageal reflux exists. TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trial Registry ( ChiCTR1800018300 , date of registration: September 2018).

[Design and Application of Perioperative Multi-center Data Center].

Based on 18 hospitals including the Chinese People's Liberation Army General Hospital and Peking University People's Hospital, and based on the "Specifications for Perioperative Data", explore the construction and application of perioperative multi-center data centers in the era of medical big data. The use of data ferry technology avoids hidden safety hazards in hospitals, realizes the integration and sharing of perioperative medical data of various medical institutions, and forms a complete data chain combining patient medical data and follow-up data.

Cottonseed oil alleviates ischemic stroke injury by inhibiting the inflammatory activation of microglia and astrocyte.

BACKGROUND: Ischemic stroke is the second leading cause of death globally. The narrow time window for administering effective thrombolytic therapy motivates the search for alternative prevention strategies. Microglia and astrocyte activation-mediated inflammation play a pivotal role in ischemic stroke injury. Cottonseed oil (CSO) has been shown to exert anti-inflammatory effects against peripheral tissue injury, although CSO is mostly used as a solvent for lipid-soluble drugs. However, the role of CSO in neuroprotection against stroke has not been previously reported. METHODS: We treated adult male rats with CSO (1.3 ml/kg, subcutaneous injection, once every other day for 3 weeks) and then constructed a middle cerebral artery occlusion (MCAO) model followed by 24 h of reperfusion. Then, we measured the neurological scores, infarction volume, neuronal injury, and brain edema; we also measured the levels of pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α), degree of microglial and astrocytic activation, protein expression levels of Toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), C3d and S100A10, and the presence of A1 type astrocytes and A2 type astrocytes. RESULTS: We found that CSO treatment significantly improved the neurological deficit, reduced infarction volume, and alleviated neuronal injuries, blood-brain barrier (BBB) disruption, and brain edema. Additionally, CSO treatment significantly reduced microglial and astrocytic activation, inhibited TLR4 and NF-κB protein expression, and reduced the release of IL-1ß, IL-6, and TNF-α. Finally, CSO treatment significantly decreased the number of C3d/glial fibrillary acidic protein (GFAP)-positive cells and C3d protein expression, and increased the number of S100A10/GFAP-positive cells and S100A10 protein expression. CONCLUSION: Our results first found that CSO treatment alleviated ischemic stroke injury by reducing microglial and astrocytic activation and inflammation, which was related to the inhibition of TLR4/NF-κB pathway and the reduction of A1 phenotype neurotoxic astrocyte activation, suggesting that CSO could be a new strategy in the prevention of ischemic stroke.

MiR-190a potentially ameliorates postoperative cognitive dysfunction by regulating Tiam1.

BACKGROUND: Postoperative cognitive dysfunction (POCD) affects a large number of post-surgery patients, especially for the elderly. However, the etiology of this neurocognitive disorder is largely unknown. Even if several studies have reported a small number of miRNAs as the essential modulatory factors in POCD, these findings are still rather limited. The aim of current study was to screen the POCD-related miRNAs in the hippocampus tissues and investigate the target genes of differentially expressed miRNAs and their biological functions underlying POCD pathophysiology. METHODS: The miRNA microarray was used to find the abnormal expression of miRNAs in the hippocampus tissues from the POCD model mice to normal mice (Discovery cohort, 3 vs 3). The nominal significant results were validated in an independent sample of hippocampus tissues of 10 mice based on same miRNA microarray (Replication cohort, 5 vs 5). Expression level of the most significantly abnormal miRNA was further validated by real-time quantitative polymerase chain reaction (PCR). To determine the expression pattern among miRNAs and genes and detect the interactions, we conducted a weighted gene co-expression network analysis (WGCNA) in the miRNAs and genes expression data from hippocampus tissue of wild type mice (n = 24). The target genes of miRNAs were predicted using the miRWalk3.0 software. Furthermore, we used the ClueGO software to decipher the pathways network and reveal the biological functions of target genes of miRNAs. RESULTS: We found that nine miRNAs showed significant associations with POCD in both datasets. Among these miRNAs, mmu-miR-190a-3p was the most significant one. By performing WGCNA analysis, we found 25 co-expression modules, of which mmu-miR-190a-3p was significantly anti-correlated with red module. Moreover, in the red module, 314 genes were significantly enriched in four pathways such as axon guidance and calcium signaling pathway, which are well-documented to be associated with psychiatric disorders and brain development. Also, 169 of the 314 genes were highly correlated with mmu-miR-190a-3p, and four genes (Sphkap, Arhgef25, Tiam1, and Ntrk3) had putative binding sites at 3'-UTR of mmu-miR-190a-3p. Based on protein-protein network analysis, we detected that Tiam1 was a central gene regulated by the mmu-miR-190a-3p. CONCLUSIONS: Taken together, we conclude that mmu-miR-190a-3p is involved in the etiology of POCD and may serve as a novel predictive indicator for POCD.

Elamipretide (SS-31) improves mitochondrial dysfunction, synaptic and memory impairment induced by lipopolysaccharide in mice.

BACKGROUND: It is widely accepted that mitochondria have a direct impact on neuronal function and survival. Oxidative stress caused by mitochondrial abnormalities play an important role in the pathophysiology of lipopolysaccharide (LPS)-induced memory impairment. Elamipretide (SS-31) is a novel mitochondrion-targeted antioxidant. However, the impact of elamipretide on the cognitive sequelae of inflammatory and oxidative stress is unknown. METHODS: We utilized MWM and contextual fear conditioning test to assess hippocampus-related learning and memory performance. Molecular biology techniques and ELISA were used to examine mitochondrial function, oxidative stress, and the inflammatory response. TUNEL and Golgi-staining was used to detect neural cell apoptosis and the density of dendritic spines in the mouse hippocampus. RESULTS: Mice treated with LPS exhibited mitochondrial dysfunction, oxidative stress, an inflammatory response, neural cell apoptosis, and loss of dendritic spines in the hippocampus, leading to impaired hippocampus-related learning and memory performance in the MWM and contextual fear conditioning test. Treatment with elamipretide significantly ameliorated LPS-induced learning and memory impairment during behavioral tests. Notably, elamipretide not only provided protective effects against mitochondrial dysfunction and oxidative stress but also facilitated the regulation of brain-derived neurotrophic factor (BDNF) signaling, including the reversal of important synaptic-signaling proteins and increased synaptic structural complexity. CONCLUSION: These findings indicate that LPS-induced memory impairment can be attenuated by the mitochondrion-targeted antioxidant elamipretide. Consequently, elamipretide may have a therapeutic potential in preventing damage from the oxidative stress and neuroinflammation that contribute to perioperative neurocognitive disorders (PND), which makes mitochondria a potential target for treatment strategies for PND.

Early administration of pyrrolidine dithiocarbamate extends the therapeutic time window of tissue plasminogen activator in a male rat model of embolic stroke.

Tissue plasminogen activator (tPA) is used in fewer than 4% of patients after ischemic stroke because of its narrow therapeutic time window. We tested whether pyrrolidine dithiocarbamate (PDTC), a drug with multiple mechanisms to provide neuroprotection, can be used to extend the therapeutic time window of tPA. Three-month-old male Sprague-Dawley rats were subjected to embolic stroke in the area supplied by the right middle cerebral artery. tPA at 10 mg/kg was given intravenously 4 h after the onset of stroke. PDTC at 50 mg/kg was given via gastric gavage at 30 min or 4 h after the onset of stroke. Two days after the stroke, neurological outcome was evaluated and the right frontal cortex area 1 (Fr1), an ischemic penumbral region, was harvested for analysis. PDTC given at 30 min after the stroke reduced infarct volumes and improved neurological functions no matter whether the rats received tPA. PDTC also reduced tPA-increased hemorrhagic volumes. Consistent with these results, PDTC in the presence or absence of tPA treatment attenuated the increase of proinflammatory cytokines, oxidative stress and matrix metalloprotease 2 activity in the right Fr1. However, PDTC given at 4 h after the onset of stroke did not improve the neurological outcome of rats treated with or without tPA. Our results suggest that PDTC given at an early time point but not in a delayed phase provides neuroprotection against embolic stroke and may be used to extend the therapeutic time window of tPA.