The triglyceride-glucose index: a novel predictor of stroke and all-cause mortality in liver transplantation recipients.

BACKGROUND: The triglyceride-glucose (TyG) index, identified as a reliable indicator of insulin resistance (IR), was reported to be associated with stroke recurrence and morbidity in the general population and critically ill patients. However, the relationship in liver transplantation (LT) recipients remains unknown. This study aimed to investigate the correlation between the TyG index and post-LT stroke along with all-cause mortality and further assess the influence of IR on the LT recipients' prognosis. METHODS: The retrospective cohort study enrolled 959 patients who underwent LT at a university-based medical centre between January 2015 and January 2021. The participants were divided into three groups according to their TyG index tertiles. The primary outcome was post-LT stroke. Multivariate logistic regression, COX proportional hazards regression, and restricted cubic spline RCS were used to examine the association between the TyG index and outcomes in LT recipients. RESULTS: With a median TyG index of 8.23 (7.78-8.72), 780 (87.18% males) patients were eventually included. The incidence of post-LT stroke was 5.38%, and the in-hospital, 1-year, and 3-year mortality rates were 5.54%, 13.21%, and 15.77%, respectively. Multivariate regression analysis showed an independent association between the TyG index and an increased risk of post-LT stroke [adjusted odds ratio (aOR), 3.398 (95% confidence interval [CI]: 1.371-8.426) P = 0. 008], in-hospital mortality [adjusted hazard ratio (aHR), 2.326 (95% CI: 1.089-4.931) P = 0.025], 1-year mortality [aHR, 1.668 (95% CI: 1.024-2.717) P = 0.039], and 3-year mortality [aHR, 1.837 (95% CI: 1.445-2.950) P = 0.012]. Additional RCS analysis also suggested a linear increase in the risk of postoperative stroke with elevated TyG index (P for nonlinearity = 0.480). CONCLUSIONS: The TyG index may be a valuable and reliable indicator for assessing stroke risk and all-cause mortality in patients undergoing LT, suggesting its potential relevance in improving risk stratification during the peri-LT period.

Connexin32 gap junction channels deliver miR155-3p to mediate pyroptosis in renal ischemia-reperfusion injury.

OBJECTIVES: To explore whether the gap junction (GJ) composed by connexin32(Cx32) mediated pyroptosis in renal ischemia-reperfusion(I/R) injury via transmitting miR155-3p, with aim to provide new strategies for the prevention and treatment of acute kidney injury (AKI) after renal I/R. METHODS: 8-10 weeks of male C57BL/ 6 wild-type mice and Cx32 knockdown mice were divided into two groups respectively: control group and renal I/R group. MCC950 (50 mg/kg. ip.) was used to inhibit NLRP3 in vivo. Human kidney tubular epithelial cells (HK - 2) and rat kidney tubular epithelial cells (NRK-52E) were divided into high-density group and low-density group, and treated with hypoxia reoxygenation (H/R) to mimic I/R. The siRNA and plasmid of Cx32, mimic and inhibitor of miR155-3p were transfected into HK - 2 cells respectively. Kidney pathological and functional injuries were measured. Western Blot and immunofluorescent staining were used to observe the expression of NLRP3, GSDMD, GSDMD-N, IL - 18, and mature IL-18. The secretion of IL-18 and IL-1ß in serum, kidney tissue and cells supernatant were detected by enzyme-linked immuno sorbent assay (ELISA) kit, and the expression of NLPR3 and miR155-3p were detected by RT-qPCR and fluorescence in situ hybridization (FISH). RESULTS: Tubular pyroptosis were found to promote AKI after I/R in vivo and Cx32-GJ regulated pyroptosis by affecting the expression of miR155-3p after renal I/R injury. In vitro, H/R could lead to pyroptosis in HK-2 and NRK-52E cells. When the GJ channels were not formed, and Cx32 was inhibited or knockdown, the expression of miR155-3p was significantly reduced and the pyroptosis was obviously inhibited, leading to the reduction of injury and the increase of survival rate. Moreover, regulating the level of miR155-3p could affect survival rate and pyroptosis in vitro after H/R. CONCLUSIONS: The GJ channels composed of Cx32 regulated tubular pyroptosis in renal I/R injury by transmitting miR155-3p. Inhibition of Cx32 could reduce the level of miR155-3p further to inhibit pyroptosis, leading to alleviation of renal I/R injury which provided a new strategy for preventing the occurrence of AKI. Video Abstract.

Functional analysis of hepatic long non-coding ribonucleic acids during liver transplantation in humans.

BACKGROUND: The potential function of long non-coding RNAs (lncRNAs) in human hepatic ischemia-reperfusion injury (HIRI) remains to be clarified. METHODS: Clinical samples of transplanted liver tissues from 26 patients undergoing liver transplantation (LT) and normal liver tissues from seven patients undergoing hepatic hemangiomactomy (Con) were collected. Typical samples were subjected to whole transcriptome sequencing (RNA-seq). Differentially expressed genes between groups were identified by DEGseq and were analyzed by enrichment analysis including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis. Transcription of five lncRNAs including NONHSAG039942, NONHSAG071405, NONHSAG027516, LXLOC_058190, and LXLOC_024376 that presented significant difference in RNA-sequencing were validated by a quantitative real-time PCR (qRT-PCR), for which the subcellular localization and the binding ability to known human RNA-binding proteins (RBPs) were respectively predicted by LncLocator and catRAPID genomics v2.1. RESULTS: We identified 2917 lncRNAs and 2811 mRNAs that were differentially expressed (p < 0.05 and log2 fold change > 1 or < -1) between groups (LT vs. Con). NONHSAG039942, NONHSAG071405, LXLOC_058190, and LXLOC_024376 were validated by qRT-PCR to be significantly increased in the LT group, and were all predicted to be localized in cytoplasm or cytosol. NONHSAG039942, NONHSAG071405, and LXLOC_058190 held an RBP interaction propensity score of 98.07%, 76.95%, and 152.99%, respectively, with heterogeneous-nuclear ribonucleoprotein U (HNRNPU). Pathways significantly activated in transplant livers that involved HNRNPU as a core enrichment gene included hypoxia, ACE2 expression, apoptosis, spliceosome formation, etc. CONCLUSIONS: NONHSAG039942, NONHSAG071405, and LXLOC_058190 were significantly increased in transplant livers after reperfusion and their role in HIRI may be associated with HNRNPU, a core protein that participates in hypoxia and chromatin accessibility.

Modified Manual Chest Compression for Prevention and Treatment of Respiratory Depression in Patients Under Deep Sedation During Upper Gastrointestinal Endoscopy: Two Randomized Controlled Trials.

BACKGROUND: We aimed to determine the preventive and therapeutic efficacy of modified manual chest compression (MMCC), a novel noninvasive and device-independent method, in reducing oxygen desaturation events in patients undergoing upper gastrointestinal endoscopy under deep sedation. METHODS: A total of 584 outpatients who underwent deep sedation during upper gastrointestinal endoscopy were enrolled. In the preventive cohort, 440 patients were randomized to the MMCC group (patients received MMCC when their eyelash reflex disappeared, M1 group) or control group (C1 group). In the therapeutic cohort, 144 patients with oxygen desaturation of a Sp o2 < 95% were randomized to MMCC group (patients who subsequently received MMCC, M2 group) or the conventional treatment group (C2 group). The primary outcomes were the incidence of desaturation episodes with an Sp o2 < 95% for the preventive cohort and the time spent below 95% Sp o2 for the therapeutic cohort. Secondary outcomes included the incidence of gastroscopy withdrawal and diaphragmatic pause. RESULTS: In the preventive cohort, MMCC reduced the incidence of desaturation episodes <95% (14.4% vs 26.1%; RR, 0.549; 95% confidence interval [CI], 0.37-0.815; P = .002), gastroscopy withdrawal (0% vs 2.29%; P = .008), and diaphragmatic pause at 30 seconds after propofol injection (74.5% vs 88.1%; RR, 0.846; 95% CI, 0.772-0.928; P < .001). In the therapeutic cohort, patients who received MMCC had a significantly shorter time spent below 95% Sp o2 (40 [20-69] seconds vs 91 [33-152] seconds, median difference [95% CI], -39 [-57 to -16] seconds, P < .001), a lower incidence of gastroscopy withdrawal (0% vs 10.4%, P = .018), and more enhanced diaphragmatic movement at 30 seconds after Sp o2 <95% (1.11 [0.93-1.4] cm vs 1.03 [0.7-1.24] cm; median difference [95% confidence interval], 0.16 [0.02-0.32] cm; P = .015). CONCLUSIONS: MMCC may exert preventive and therapeutic effects against oxygen desaturation events during upper gastrointestinal endoscopy.

Astrocyte senescence-like response related to peripheral nerve injury-induced neuropathic pain.

BACKGROUND: Peripheral nerve damage causes neuroinflammation, which plays a critical role in establishing and maintaining neuropathic pain (NeP). The mechanisms contributing to neuroinflammation remain poorly elucidated, and pharmacological strategies for NeP are limited. Thus, in this study, we planned to explore the possible link between astrocyte senescence and NeP disorders following chronic sciatic nerve injury. METHODS: An NeP animal model was established by inducing chronic constrictive injury (CCI) to the sciatic nerve in adult rats. A senolytic drug combination of dasatinib and quercetin was gavaged daily from the first postoperative day until the end of the study. Paw mechanical withdrawal threshold (PMWT) and paw thermal withdrawal latency (PTWL) were evaluated to assess behaviors in response to pain in the experimental rats. Senescence-associated ß-galactosidase staining, western blot analysis, and immunofluorescence were applied to examine the levels of proinflammatory factors and severity of the senescence-like response in the spinal cord. Lipopolysaccharide (LPS) was administered to induce senescence of spinal astrocytes in primary cultures in vitro, to explore the potential impacts of senescence on the secretion of proinflammatory factors. Furthermore, single-cell RNA sequencing (scRNA-seq) was conducted to identify senescence-related molecular responses in spinal astrocytes under neuropathic pain. RESULTS: Following sciatic nerve CCI, rats exhibited reduced PMWT and PTWL, increased levels of spinal proinflammatory factors, and an enhanced degree of senescence in spinal astrocytes. Treatment with dasatinib and quercetin effectively attenuated spinal neuroinflammation and mitigated the hypersensitivities of the rats subjected to sciatic nerve CCI. Mechanistically, the dasatinib-quercetin combination reversed senescence in LPS-stimulated primary cultured astrocytes and decreased the levels of proinflammatory factors. The scRNA-seq data revealed four potential senescence-related genes in the spinal astrocyte population, and the expression of clusterin (CLU) protein was validated via in vitro experiments. CONCLUSION: The findings indicate the potential role of astrocyte senescence in neuroinflammation following peripheral nerve injury, and suggest that targeting CLU activation in astrocytes might provide a novel therapeutic strategy to treat NeP.

Preoperative hs-CRP/HDL ratio is associated with increased risk for postoperative SIRS in elderly patients: a retrospective cohort study.

BACKGROUND: Systemic inflammatory response syndrome (SIRS) greatly affects postoperative lives of afflicted aged patients. This study aimed to determine whether preoperative high hs-CRP/HDL ratio (CHR) was associated with an increased risk of postoperative SIRS in the elderly population. METHODS: This retrospective cohort study included data on patients aged ≥ 65 years who underwent general anesthesia surgery at two clinical centers between January 2015 and September 2020. The primary exposure was preoperative CHR which was divided into two groups (≤ 12.82 and > 12.82) based on its normal range in our hospital, and the primary outcome was the incidence of postoperative SIRS. Targeted maximum likelihood estimation analyses were used to model the exposure-outcome relationship. RESULTS: The analysis included 5595 elderly patients, of whom 1410 (25.20%) developed SIRS within three postoperative days. Targeted maximum likelihood estimation analysis revealed that elderly patients with CHR > 12.82 vs. CHR ≤ 12.82 was associated with increased risk of postoperative SIRS (aOR = 1.40, 95% CI [1.33, 1.48], P < 0.001). Those results were consistent both in subgroup analyses and sensitivity analyses. Compared with patients with CHR ≤ 12.82, patients with CHR > 12.82 had a higher prevalence of postoperative SIRS (49.06% vs. 22.70%), postoperative in-hospital mortality (3.40% vs. 0.65%), a longer hospital stay after surgery [10 (IQR, 6-16) vs. 8 (IQR, 5-11) days] and higher direct medical cost [10070 (IQR, 6878-15577) vs. 7117 (IQR, 4079-10314) euros, all P < 0.001]. CONCLUSIONS: In elderly patients, preoperative CHR > 12.82 was significantly associated with a higher risk of postoperative SIRS.

Right displacement of trachea to reduce right bronchial misplacement of left double lumen tube: a prospective, double-blind, randomized study.

BACKGROUND: Misplacement of double-lumen endobronchial tubes (DLTs) during bronchial intubation, especially when bronchoscopy guidance is not applicable, threatens effective lung isolation and brings about airway injury during reposition. We aimed to examine whether a novel maneuver called right tracheal displacement (RTD) can reduce left-sided DLT misplacement during first-attempt intubation without bronchoscopy guidance. METHODS: Patients that underwent thoracic surgeries requiring one-lung ventilation during November 2020 to January 2021 were recruited and randomized into control and RTD group, with 54 cases in each group. The primary outcomes included the incidence of DLT misplacement and the time to complete desired bronchial intubation. The secondary outcomes included mucosal injury, sore throat and hoarseness upon emergence and at 24 h post-operatively. RESULT: The incidence of DLT misplacement in RTD group was significantly lower compared to control group (0% vs. 16.7%) The time to complete bronchial intubation was also significantly shortened in RTD group compared to control (52.88 ± 9.36 s vs. 63.04 ± 20.02 s). The incidence of mucosal injury, sore throat and hoarseness were comparable between two groups. CONCLUSION: RTD maneuver can effectively improve the success rate of first-attempt proper DLT positioning and shorten the time required by bronchial intubation. TRIAL REGISTRATION: This prospective, double-blind, randomized study has completed the registration of the Chinese Clinical Trial Center at 2/11/2020 with the registration number ChiCTR2000040212. It was conducted from 26/11/2020 to 31/7/2021 in third affiliated hospital of Sun Yat-sen university.

Perioperative administration of methylprednisolone was associated with postoperative pulmonary complications in elderly patients undergoing hip fracture surgery.

BACKGROUND: Postoperative pulmonary complications (PPCs) seriously affect the postoperative prognosis of elderly patients underwent hip fracture surgery. Although methylprednisolone is increasingly used, the association between perioperative methylprednisolone and PPCs is still controversial. The study aims to determine whether perioperative administration of methylprednisolone is associated with PPCs in elderly patients during hip fracture surgery. PATIENTS AND METHODS: In this retrospective cohort study, records of 584 patients (≥ 65 years) who underwent hip fracture surgery between January 2013 and October 2020 were extracted. Univariate and multivariate regression analysis were performed to identify the risk factors for PPCs. To further explore the association between administration of methylprednisolone and PPCs, 53 patients received methylprednisolone and 53 patients without methylprednisolone were matched for the confounding factors using propensity score matching (PSM) analysis. The odds ratios (OR) and 95% confidence intervals (CI) for the above variables were analyzed. RESULTS: The incidence of PPCs during postoperative hospitalization was 6.83% (38/556) among the elderly patients following hip fracture surgery. Patients with PPCs had higher postoperative mortality rate, longer hospital stay, more hospitalization cost, and higher incidence of cardiac arrest (all P < 0.05). Multivariate logistic regression analysis showed that age, hypertension, hypoglycemia, hypoproteinemia and perioperative methylprednisolone were independent risk factors for PPCs. Moreover, administration of methylprednisolone was significantly correlated with PPCs both before PSM adjustment (OR = 3.25; 95% CI, 1.67 to 6.33; P = 0.001) and after PSM adjustment (OR = 6.68; 95% CI, 1.40 to 31.82; P = 0.017). CONCLUSION: Perioperative administration of methylprednisolone is a risk factor for PPCs in elderly patients undergoing hip fracture surgery.

Nanotheranostics for the Management of Hepatic Ischemia-Reperfusion Injury.

Hepatic ischemia-reperfusion injury (IRI), in which an insufficient oxygen supply followed by reperfusion leads to an inflammatory network and oxidative stress in disease tissue to cause cell death, always occurs after liver transplantations and sections. Although pharmacological treatments favorably prevent or protect the liver against experimental IRI, there have been few successes in clinical applications for patient benefits because of the incomprehension of complicated IRI-induced signaling events as well as short blood circulation time, poor solubility, and severe side reactions of most antioxidants and anti-inflammatory drugs. Nanomaterials can achieve targeted delivery and controllable release of contrast agents and therapeutic drugs in desired hepatic IRI regions for enhanced imaging sensitivity and improved therapeutic effects, emerging as novel alternative approaches for hepatic IRI diagnosis and therapy. In this review, the application of nanotechnology is summarized in the management of hepatic IRI, including nanomaterial-assisted hepatic IRI diagnosis, nanoparticulate systems-mediated remission of reactive oxygen species-induced tissue injury, and nanoparticle-based targeted drug delivery systems for the alleviation of IRI-related inflammation. The current challenges and future perspectives of these nanoenabled strategies for hepatic IRI treatment are also discussed.

An explainable supervised machine learning predictor of acute kidney injury after adult deceased donor liver transplantation.

BACKGROUND: Early prediction of acute kidney injury (AKI) after liver transplantation (LT) facilitates timely recognition and intervention. We aimed to build a risk predictor of post-LT AKI via supervised machine learning and visualize the mechanism driving within to assist clinical decision-making. METHODS: Data of 894 cases that underwent liver transplantation from January 2015 to September 2019 were collected, covering demographics, donor characteristics, etiology, peri-operative laboratory results, co-morbidities and medications. The primary outcome was new-onset AKI after LT according to Kidney Disease Improving Global Outcomes guidelines. Predicting performance of five classifiers including logistic regression, support vector machine, random forest, gradient boosting machine (GBM) and adaptive boosting were respectively evaluated by the area under the receiver-operating characteristic curve (AUC), accuracy, F1-score, sensitivity and specificity. Model with the best performance was validated in an independent dataset involving 195 adult LT cases from October 2019 to March 2021. SHapley Additive exPlanations (SHAP) method was applied to evaluate feature importance and explain the predictions made by ML algorithms. RESULTS: 430 AKI cases (55.1%) were diagnosed out of 780 included cases. The GBM model achieved the highest AUC (0.76, CI 0.70 to 0.82), F1-score (0.73, CI 0.66 to 0.79) and sensitivity (0.74, CI 0.66 to 0.8) in the internal validation set, and a comparable AUC (0.75, CI 0.67 to 0.81) in the external validation set. High preoperative indirect bilirubin, low intraoperative urine output, long anesthesia time, low preoperative platelets, and graft steatosis graded NASH CRN 1 and above were revealed by SHAP method the top 5 important variables contributing to the diagnosis of post-LT AKI made by GBM model. CONCLUSIONS: Our GBM-based predictor of post-LT AKI provides a highly interoperable tool across institutions to assist decision-making after LT.

Prolonged symptom onset to admission time is associated with severe Coronavirus disease: A meta combined propensity-adjusted analysis.

BACKGROUND: Patients with severe COVID-19 are more likely to develop adverse outcomes with a huge medical burden. We aimed to investigate whether a shorter symptom onset to admission time (SOAT) could improve outcomes of COVID-19 patients. METHODS: A single-center retrospective study combined with a meta-analysis was performed. The meta-analysis identified studies published between 1 December 2019 and 15 April 2020. Additionally, clinical data of COVID-19 patients diagnosed between January 20 and February 20, 2020, at the First Affiliated Hospital of the University of Science and Technology of China were retrospectively analyzed. SOAT and severity of illness in patients with COVID-19 were used as effect measures. The random-effects model was used to analyze the heterogeneity across studies. Propensity score matching was applied to adjust for confounding factors in the retrospective study. Categorical data were compared using Fisher's exact test. We compared the differences in laboratory characteristic varied times using a two-way nonparametric, Scheirer-Ray-Hare test. RESULTS: In a meta-analysis, we found that patients with adverse outcomes had a longer SOAT (I2 = 39%, mean difference 0.88, 95% confidence interval = 0.47-1.30). After adjusting for confounding factors, such as age, complications, and treatment options, the retrospective analysis results also showed that severe patients had longer SOAT (mean difference 1.13 [1.00, 1.27], p = 0.046). Besides, most biochemical marker levels improved as the hospitalization time lengthened without the effect of disease severity or associated treatment (p < 0.001). CONCLUSION: Shortening the SOAT may help reduce the possibility of mild patients with COVID-19 progressing to severe illness.

Development and performance assessment of novel machine learning models to predict pneumonia after liver transplantation.

BACKGROUND: Pneumonia is the most frequently encountered postoperative pulmonary complications (PPC) after orthotopic liver transplantation (OLT), which cause high morbidity and mortality rates. We aimed to develop a model to predict postoperative pneumonia in OLT patients using machine learning (ML) methods. METHODS: Data of 786 adult patients underwent OLT at the Third Affiliated Hospital of Sun Yat-sen University from January 2015 to September 2019 was retrospectively extracted from electronic medical records and randomly subdivided into a training set and a testing set. With the training set, six ML models including logistic regression (LR), support vector machine (SVM), random forest (RF), adaptive boosting (AdaBoost), extreme gradient boosting (XGBoost) and gradient boosting machine (GBM) were developed. These models were assessed by the area under curve (AUC) of receiver operating characteristic on the testing set. The related risk factors and outcomes of pneumonia were also probed based on the chosen model. RESULTS: 591 OLT patients were eventually included and 253 (42.81%) were diagnosed with postoperative pneumonia, which was associated with increased postoperative hospitalization and mortality (P < 0.05). Among the six ML models, XGBoost model performed best. The AUC of XGBoost model on the testing set was 0.734 (sensitivity: 52.6%; specificity: 77.5%). Pneumonia was notably associated with 14 items features: INR, HCT, PLT, ALB, ALT, FIB, WBC, PT, serum Na+, TBIL, anesthesia time, preoperative length of stay, total fluid transfusion and operation time. CONCLUSION: Our study firstly demonstrated that the XGBoost model with 14 common variables might predict postoperative pneumonia in OLT patients.

Application of a protective sleeve is associated with decreased occupational anxiety during endotracheal intubation: a randomized controlled trial.

BACKGROUND: The high risk of cross-infection during tracheal intubation has caused excessive occupational anxiety for anaesthesiologists amid the novel coronavirus disease 2019 (COVID-19) pandemic. Currently, there is no effective way to attenuate their anxiety in clinical practice. We found that anaesthesiologist with better protective equipment might experience decreased levels of anxiety during intubation. METHODS: In this study, 60 patients who underwent intubation and extubation in the operating room were enrolled, and then randomized 1:1 to either wear protective sleeves (protective sleeve group) or not (control group). Visual analogue scale (VAS) was used to measure the anxiety level of anaesthesiologists during intubation. The respiratory droplets of patients on the sleeve, and the anaesthesiologists' perception including the patient's oral malodour, exertion, satisfaction degree, waist discomfort and shoulder discomfort were recorded. The patients' anxiety, oppressed feelings and hypoxia and postoperative complications were all measured and recorded. RESULTS: Compared with the control group, the anaesthesiologists in protective sleeve group achieved lower anxiety scores and better satisfaction degrees during the process of intubation and extubation (all P < 0.05). Respiratory droplets were observed only on the inner side, but not the external side, of the protective sleeves (P < 0.001). The incidence of the anaesthesiologists' perception of patients' oral malodour was significantly lower in the protective sleeve group (P = 0.02) and no patients developed hypoxemia or intubation-related complications in the protective sleeve group. CONCLUSION: Using protective devices for intubation might eliminate droplet transmission from patients to anaesthesiologists, while also decreasing their anxiety in a controlled operating room environment. TRIAL REGISTRATION: Chinese Clinical Trial. no. ChiCTR2000030705 . Registry at www.chictr.org.cn on 10/03/2020.

Correction to: Connexin32 plays a crucial role in ROS-mediated endoplasmic reticulum stress apoptosis signaling pathway in ischemia reperfusion-induced acute kidney injury.

An amendment to this paper has been published and can be accessed via the original article.

Effects of Connexin 32-Mediated Lung Inflammation Resolution During Liver Ischemia Reperfusion.

BACKGROUND: Hepatic ischemia reperfusion (HIR) leads to a lung inflammatory response and subsequent pulmonary barrier dysfunction. The gap junction communication protein connexin 32 (Cx32), which is widely expressed in the lungs, participates in intercellular signaling. This study determined whether the communication protein Cx32 could affect pulmonary inflammation caused by HIR. METHODS: Mice were randomly allocated into four groups (n = 8/group): (i) Cx32+/+ sham group; (ii) Cx32+/+ HIR model group; (iii) Cx32-/- sham group; and (iv) Cx32-/- HIR model group. Twenty-four hours after surgery, lung tissues were collected for bright field microscopy, western blot (Cx32, JAK2, p-JAK2, STAT3, p-STAT3), and immunofluorescence (ZO-1, 8-OHDG) analyses. The collected bronchoalveolar fluid was tested for levels of interleukin-6 (IL-6), matrix metalloproteinase 12 (MMP-12), and antitrypsin (α1-AT). Lung mmu-miR-26a/b expression was detected using a PCR assay. RESULTS: Increased expression of Cx32 mRNA and protein was noted in the lungs after HIR. Cx32 deletion significantly aggravated pulmonary function from acute lung injury induced by HIR. In addition, Cx32 deletion decreased the protein level of ZO-1 (pulmonary function) and increased the level of the oxidative stress marker 8-OHDG in the lungs. Moreover, in the Cx32-/- HIR model group, the levels of IL-6 and MMP-12 in bronchoalveolar lavage fluid were significantly increased leading to activation of the JAK2/STAT3 pathway, and decreased α1-AT levels. Furthermore, we found mmu-miR-26a/b was significantly downregulated in the Cx32-/- HIR model group. CONCLUSION: HIR leads to acute lung inflammatory injury. Cx32 deletion aggravates hepatic-derived lung inflammation, partly through blocking the transferring of mmu-miR-26a/b and leading to IL-6-related JAK2/STAT3 pathway activation.

Preventive effect of dexmedetomidine on postictal delirium after electroconvulsive therapy: A randomised controlled study.

BACKGROUND: Postictal delirium (PID) is a relatively common complication following electroconvulsive therapy (ECT). OBJECTIVE: We investigated whether prophylactic dexmedetomidine administration would safely decrease the incidence of PID in psychiatric patients after ECT. DESIGN: A randomised, double-blind, placebo-controlled trial. PATIENTS: A total of 223 patients undergoing ECT were randomly allocated to two groups. INTERVENTIONS: Patients received 0.5 µg kg dexmedetomidine (Dex group, n=111) or 0.9% sodium chloride (Con group, n=112) before ECT. Propofol was used for anaesthesia and succinylcholine for muscle relaxation. The incidence of PID was measured using the Confusion Assessment Method for the Intensive Care Unit. MAIN OUTCOME MEASURES: The percentage of patients who were diagnosed with PID at any ECT session during the whole treatment. RESULTS: PID occurred in 76 (67.9%) of 112 patients given saline (0.9% sodium chloride), and in 49 (44.1%) of 111 patients given dexmedetomidine during the whole treatment. There was a significant difference in the incidence of PID between two groups (P < 0.001). Post hoc analyses showed that the incidence of PID was significantly lower in the Dex group than in the Con group from the first to the seventh ECT session (P < 0.005). There were no significant differences in seizure duration or recovery time between the two groups. Heart rate and mean arterial pressure in the Dex group were significantly lower than in the Con group at 0, 5 and 15 min after electrical stimulation. No patients developed bradycardia, hypotension or respiratory depression during recovery. CONCLUSION: Pretreatment with dexmedetomidine leads to a significant reduction in the incidence of PID with no respiratory depressant effect. Dexmedetomidine might be considered an effective method for the prevention of PID post-ECT. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IOR-17012306.

Identification of potential mechanism and hub genes for neuropathic pain by expression-based genome-wide association study.

Neuropathic pain (NP) is a common pathological pain state with limited effective treatments. This study was designed to identify potential mechanisms and candidate genes using gene expression-based genome-wide association study (eGWAS). All NP-related microarray experiments were obtained from Gene Expression Omnibus and ArrayExpress. Significantly dysregulated genes were identified between experimental and untreated groups, and the number of microarray experiments in which each gene was dysregulated was calculated. Significantly dysregulated genes were ranked according to P values of the chi-square test. Using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes database, we performed functional and pathway enrichment analysis. Protein-protein interaction (PPI) network and module analysis was performed using Cytoscape software. A total of 115 candidate genes were identified from 19 independent microarray experiments by eGWAS based on the Bonferroni threshold ( P < 2.97 × 10 -6 ). Immune and inflammatory responses, and complement and coagulation cascades, were respectively the most enriched biological process and pathways for candidate genes. The hub genes with highest connectivity in PPI network and two modules Ccl2 and Jun, and Ctss application of the eGWAS methodology can identify mechanisms and candidate genes associated with NP. Our results support the validity and prevalence of inflammatory and immune mechanisms across different NP models, and Ccl2, Jun, and Ctss may be the hub genes for NP.

Laryngoscopic techniques modulate anaesthesiologists' perception of halitosis in patients: A randomised controlled trial.

BACKGROUND: Perception of halitosis in patients during intubation is a common and additional stressor for anaesthesiologists and may lead to potential health risks. OBJECTIVES: We hypothesised that intubation with videolaryngoscopy could help reduce the anaesthesiologists' perception of patients' oral malodor during intubation. DESIGN: A single-blinded, randomised controlled trial. SETTING: Single centre general hospital, Guangdong Province, China. PARTICIPANTS: A total of 440 patients who underwent intubation under general anaesthesia for elective surgery, aged 18 to 60 years old, American Society of Anaesthesiologists class I to III, without upper airway abnormality or airway infection were enrolled. INTERVENTION: Patients were randomly assigned to receive either UE videolaryngoscopy (UE) or Macintosh's direct laryngoscopy (Macintosh) group. All intubations were performed by one of six very experienced anaesthesiologists. MAIN OUTCOME MEASURES: The patient's oral odour score was measured prior to induction of anaesthesia. The anaesthesiologists' perception of the patient's oral malodor during intubation was recorded. The shortest distance from patient's mouth to the anaesthesiologist's nose (MN distance), the exertion rating and discomfort were also measured. RESULTS: The oral malodor score did not differ in the UE and Macintosh groups prior to the induction of anaesthesia. However, the incidence of the anaesthesiologists' perception of halitosis during intubation was significantly lower in the UE group compared with the Macintosh group (P < 0.001). Similarly, the MN distance was significantly greater in the UE group compared with the Macintosh group (P < 0.001). The first-attempt success rate was higher in the UE group compared to the Macintosh group (P < 0.001). However, the exertion scores were considerably higher in the Macintosh group. After intubation, anaesthesiologists experienced more waist and shoulder discomfort with the Macintosh than the UE technique of intubation. CONCLUSION: Compared with direct laryngoscopy, videolaryngoscopy might reduce the anaesthesiologists' perception of the patients' oral malodor, help improve first-attempt success rate, as well as alleviate the anaesthesiologists' waist and shoulder discomfort. TRIAL REGISTRATION: Clinicaltrials.gov (ChiCTR-IOR-15007038).

Intravenous Anesthetics Enhance the Ability of Human Bone Marrow-Derived Mesenchymal Stem Cells to Alleviate Hepatic Ischemia-Reperfusion Injury in a Receptor-Dependent Manner.

BACKGROUND/AIMS: The degree of hepatic ischemia-reperfusion injury (HIRI) is highly relevant to the incidence of postoperative liver failure and mortality. Bone marrow-derived mesenchymal stem cells (BM-MSCs) have been shown to migrate to the liver and restore the damaged liver. Intravenous anesthetics are commonly used in the perioperative period; however, it is not yet known whether they have an influence on the functions of BM-MSCs and eventually affect the recovery of HIRI. METHODS: A rat model of HIRI and a hypoxia-reoxygenation (H/R) model using L02 cells were generated, and human BM-MSCs (hBM-MSCs) were injected through the portal vein or co-cultured with L02 cells in a Transwell system, respectively. Three intravenous anesthetics, namely, dexmedetomidine, midazolam, and propofol, were given as pretreatments to hBM-MSCs. Quantitative real-time PCR for growth factors (HGF, FGF, VEGF, and IGF) and a migration assay were used to detect the paracrine and migration abilities of hBM-MSCs. NF-κB expression was detected using an immunofluorescence method. Furthermore, three receptor inhibitors, namely, yohimbine, PK11195, and bicuculline, were given to explore whether the three anesthetics worked in a receptor-dependent manner. RESULTS: Preconditioning with dexmedetomidine and midazolam, but not propofol, enhanced the efficacy of hBM-MSCs in HIRI. Dexmedetomidine and midazolam, but not propofol, changed the paracrine spectrum and NF-κB p65 nuclear translocation of hBM-MSCs co-cultured with L02 cells after H/R injury. All three anesthetics enhanced the migration ability of hBM-MSCs when cultured in L02 H/R conditioned medium. However, the addition of receptor antagonists resulted in an opposite tendency. CONCLUSIONS: The intravenous anesthetics dexmedetomidine and midazolam enhanced the liver protective effects of hBM-MSCs during HIRI more effectively than propofol, by binding with their receptors and regulating the paracrine effect, migration ability, and NF-κB p65 nuclear translocation of hBM-MSCs.

Connexin32 plays a crucial role in ROS-mediated endoplasmic reticulum stress apoptosis signaling pathway in ischemia reperfusion-induced acute kidney injury.

BACKGROUND: Ischemia-reperfusion (I/R)-induced acute kidney injury (AKI) not only prolongs the length of hospital stay, but also seriously affects the patient's survival rate. Although our previous investigation has verified that reactive oxygen species (ROS) transferred through gap junction composed of connexin32 (Cx32) contributed to AKI, its underlying mechanisms were not fully understood and viable preventive or therapeutic regimens were still lacking. Among various mechanisms involved in organs I/R-induced injuries, endoplasmic reticulum stress (ERS)-related apoptosis is currently considered to be an important participant. Thus, in present study, we focused on the underlying mechanisms of I/R-induced AKI, and postulated that Cx32 mediated ROS/ERS/apoptosis signal pathway activation played an important part in I/R-induced AKI. METHODS: We established renal I/R models with Cx32+/+ and Cx32-/- mice, which underwent double kidneys clamping and recanalization. ROS scavenger (N-acetylcysteine, NAC) and ERS inhibitors (4-phenyl butyric acid, 4-PBA, and tauroursodeoxycholic acid, TUDCA) were used to decrease the content of ROS and attenuate ERS activation, respectively. RESULTS: Renal damage was progressively exacerbated in a time-dependent manner at the reperfusion stage, that was consistent with the alternation of ERS activation, including glucose regulated protein 78 (BiP/GRP78), X box-binding protein1, and C/EBP homologous protein expression. TUDCA or 4-PBA application attenuated I/R-induced ERS activation and protected against renal tubular epithelial cells apoptosis and renal damage. Cx32 deficiency decreased ROS generation and distribution between the neighboring cells, which attenuated I/R-induced ERS activation, and improved cell apoptosis and renal damage. CONCLUSION: Cx32 mediated ROS/ERS/apoptosis signal pathway activation played an important part in I/R-induced AKI. Cx32 deficiency, ROS elimination, and ERS inhibition all could protect against I/R-induced AKI.