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.

MRI-based radiomics features for the non-invasive prediction of FIGO stage in cervical carcinoma: A multi-center study.

PURPOSE: To develop and validate a model based on MRI radiomics modals for predicting surgical high FIGO(IB3 and ≥ IIA2) and low FIGO(IB1, IB2, and IIA1) stages in patients with cervical carcinoma (CC) . METHODS: A total of 296 early-stage patients with CC (preoperative FIGO stages IB-IIA) confirmed by surgery and pathology were included in this retrospective study from two institutions For each patient,we extracted radiomics features from spectral attenuated inversion-recovery T2-weighted (SPAIR-T2W) and contrast-enhanced T1-weighted (CE-T1W) images.Manual segmentation was performed using the 3D Slicer software, while radiomics features were extracted, screened using the R software. A 2-stage feature extraction strategy involving univariate analysis and the Least Absolute Shrinkage Selection Operator technique was performed. A support vector machine-based model was eventually constructed. Predictive accuracy of the training and validation datasets was assessed in terms of area under the ROC curve (AUC). RESULTS: A total of 1130 features were extracted from SPAIR-T2WI and CET1WI images respectively, in which 8 and 7 features significantly were associated with FIGO staging. AUCs of the SPAIR-T2W and CE-T1W models were were 0.803 and 0.790, respectively, in the internal validation group. In the external validation group, the AUCs were 0.767 and 0.749, respectively, which increased to 0.771 in the combined model. CONCLUSION: Our study demonstrated the feasibility of radiomics features from SPAIR-T2W and CE-T1W images for the prediction of surgical FIGO stage in CC. Our proposed model thereby carries the potential as a non-invasive tool for the staging and treatment planning of this disease. ADVANCES IN KNOWLEDGE: A radiomics model provide a non-invasive and objective method for the detection of FIGO staging in patients with cervical cancer before surgery, thus providing a reference for the selection of treatment options for patients.

Association between intraoperative dexmedetomidine and all-cause mortality and recurrence after laparoscopic resection of colorectal cancer: Follow-up analysis of a previous randomized controlled trial.

Background: Dexmedetomidine (DEX) has been widely applied in the anesthesia and sedation of patients with oncological diseases. However, the potential effect of DEX on tumor metastasis remains contradictory. This study follows up on patients who received intraoperative DEX during laparoscopic resection of colorectal cancer as part of a previous clinical trial, examining their outcomes 5 years later. Methods: Between June 2015 and December 2015, 60 patients undergoing laparoscopic colorectal resection were randomly assigned to the DEX and control groups. The DEX group received an initial loading dose of 1µ/kg before surgery, followed by a continuous infusion of 0.3µg/kg/h during the operation and the Control group received an equivalent volume of saline. A 5-year follow-up analysis was conducted to evaluate the overall survival, disease-free survival, and tumor recurrence. Results: The follow-up analysis included 55 of the 60 patients. The DEX group included 28 patients, while the control group included 27 patients. Baseline characteristics were comparable between the two groups, except for vascular and/or neural invasion of the tumor in the DEX group (9/28 vs. 0/27, p = 0.002). We did not observe a statistically significant benefit but rather a trend toward an increase in overall survival and disease-free survival in the DEX group, 1-year overall survival (96.4% vs. 88.9%, p = 0.282), 2-year overall survival (89.3% vs. 74.1%, p = 0.144), 3-year overall survival (89.3% vs. 70.4%, p = 0.08), and 5-year overall survival (78.6% vs. 59.3%, p = 0.121). The total rates of mortality and recurrence between the two groups were comparable (8/28 vs. 11/27, p = 0.343). Conclusion: Administration of DEX during laparoscopic resection of colorectal cancer had a nonsignificant trend toward improved overall survival and disease-free survival. Clinical Trial Registration: http://www.chictr.org.cn/, identifier ChiCTRIOR-15006518.

Cellular senescence in ischemia/reperfusion injury.

Ischemia/reperfusion (IR) injury, a main reason of mortality and morbidity worldwide, occurs in many organs and tissues. As a result of IR injury, senescent cells can accumulate in multiple organs. Increasing evidence shows that cellular senescence is the underlying mechanism that transforms an acute organ injury into a chronic one. Several recent studies suggest senescent cells can be targeted for the prevention or elimination of acute and chronic organ injury induced by IR. In this review, we concisely introduce the underlying mechanism and the pivotal role of premature senescence in the transition from acute to chronic IR injuries. Special focus is laid on recent advances in the mechanisms as well as on the basic and clinical research, targeting cellular senescence in multi-organ IR injuries. Besides, the potential directions in this field are discussed in the end. Together, the recent advances reviewed here will act as a comprehensive overview of the roles of cellular senescence in IR injury, which could be of great significance for the design of related studies, or as a guide for potential therapeutic target.

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.

Comparison of the Analgesic Effects of Intravenous Infusion of Dexmedetomidine Versus Bilateral Superficial Cervical Plexus Block After Thyroidectomy: A Randomized Controlled Trial.

OBJECTIVES: Dexmedetomidine (DEX) is widely used in clinical practice because of its safety and effectiveness. Superficial cervical plexus block (SCPB) can reduce pain in thyroid surgery. The objective of this study was to investigated whether intravenous DEX has an equivalent analgesic effect and patients' satisfaction to SCPB for thyroid surgery. MATERIALS AND METHODS: Ninety patients who had been scheduled for thyroidectomy under general anesthesia with endotracheal intubation were randomly divided into 3 groups. Group D: DEX was administered intravenously at an initial dose of 1 µg/kg over 10 minutes; then induction and endotracheal intubation performed, and then a continuous intravenous infusion of DEX was administered at a rate of 0.4 µg/kg/h until 30 minutes before the end of surgery. Group B: ultrasound-guided bilateral SCPB was performed, with 10 mL of 0.375% ropivacaine injected on each side. Group C: intravenous saline was administered at the same rate and dose as in group D. Patients' perioperative status, visual analog scale scores, complications and patients' satisfaction were recorded. RESULTS: The pain at rest at 1 hour after extubation and the movement-evoked pain within 24 hours after extubation were significantly lower in groups D and B than in group C. Patients' satisfaction was significantly higher in groups D and B than in group C. There was no difference in pain at rest, movement-evoked pain and patients' satisfaction between group D and B. CONCLUSIONS: Perioperative intravenous infusion of DEX can effectively reduce wound pain after thyroidectomy, and the analgesic effect is equivalent to that of bilateral SCPB.

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.

The use of virtual reality to reduce stress among night-shift anesthesiologists: study protocol for a crossover trial.

BACKGROUND: Because of the lack of anesthesia workforce, anesthesiologists are forced to work overtime and more night shifts, which can disturb their biological rhythm and cause severe stress and depression, potentially leading to negative and even devastating outcomes for both themselves and patients. Virtual reality (VR), a new method to reduce stress and pain for patients, has been widely used in biomedical fields. The purpose of this study is to evaluate the potential effectiveness of VR technology in reducing stress among night-shift anesthesiologists. METHODS: In this randomized controlled, crossover, single-center clinical trial, a total of 30 anesthesiologists will be enrolled and randomized in a 1:1 allocation to either the VR immersion group (intervention group) or the routine night-shift group (control group) with a washout of 1 week. Anesthesiologists in the intervention group will undergo VR immersion twice, while anesthesiologists in the control group will not watch VR videos during the night shift. The primary outcome will be the difference in the NASA Task Load Index (NASA-TLX) score between the two groups. Secondary outcomes will include the Chinese Perceived Stress Scale (CPSS), perceived stress scores (visual analogue scale (VAS)), and Multidimensional Fatigue Inventory (MFI-20) scores; levels of satisfaction among the participants; incidence of arrhythmia; and incidence of chest tightness, headache, and palpitations. DISCUSSION: It is unknown whether the use of VR technology during the night shift can reduce stress among anesthesiologists. With the widespread use of VR technology, a positive result in this trial could spur hospitals to apply VR technology to reduce stress among night-shift doctors in every department and provide a relatively relaxed working environment. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000031025 . Registered on 21 March 2020.