Isoflurane post-conditioning contributes to anti-apoptotic effect after cerebral ischaemia in rats through the ERK5/MEF2D signaling pathway.

The mechanisms of brain protection during ischaemic reperfusion injury induced by isoflurane (ISO) post-conditioning are unclear. Myocyte enhancement factor 2 (MEF2D) has been shown to promote neural survival in a variety of models, in which multiple survival and death signals converge on MEF2D and modulate its activity. Here, we investigated the effect of MEF2D on the neuroprotective effects of ISO post-conditioning on rats after cerebral ischaemia/reperfusion (I/R) injury. Rats underwent middle cerebral artery occlusion (MCAO) surgery with ischaemia for 90 minutes and reperfusion for 24-48 hours. After MCAO, neurological status was assessed at 12, 24 and 48 hours by the Modified Neurological Severity Score (mNSS) test. The passive avoidance test (PAT) was used to assess cognition function. Histological and neuropathological evaluations were performed with HE staining and Nissl's staining, respectively. We measured the expression of MEF2D, ERK5, GFAP and caspase-3 by immunofluorescent staining and Western blotting, and TUNEL staining to assess the severity of apoptosis in hippocampal CA1 area. We found that MEF2D was involved in nerve protection after I/R injury, and post-treatment of ISO significantly promoted the phosphorylation of ERK5, increased MEF2D transcriptional activity, inhibited the expression of caspase-3 and played a role of brain protection.

Isoflurane Enhances Autophagy by Activating AMPK/ULK1, Inhibits NLRP3, and Reduces Cognitive Impairment After Cerebral Ischemia-Reperfusion Injury in Rats.

Cerebral ischemic stroke (CIS) has become the second leading cause of death worldwide, which is largely related to cerebral ischemia reperfusion injury (CIRI). Surgical intervention is a reliable treatment for CIS, which predictably causes cerebral reperfusion. Therefore, the choice of anesthetic drugs has important clinical significance. Isoflurane (ISO), one of the most used anesthetics, attenuates cognitive impairment and has brain protective effects. However, the role of isoflurane in regulating autophagy and its regulatory mechanism on inflammation in CIRI are still unclear. The middle cerebral artery occlusion (MCAO) method was used to establish a rat model of CIRI. After 24 h of reperfusion, all rats were evaluated by mNSS scoring and dark avoidance experiment. Western blotting and immunofluorescence were used to examine the expression of key proteins. Compared with the sham group, the MCAO group showed increased neurobehavioral scores and decreased cognitive memory function (P < 0.05). As for the ISO-treated MCAO rats, the neurobehavioral score was significantly decreased, the expression of AMPK, ULK1, Beclin1, and LC3B was significantly increased, and the cognitive and memory functions were also significantly improved (P < 0.05). After inhibition of autophagy pathway or key protein AMPK in autophagy, neurobehavioral scores and protein expression of NLRP3, IL-1ß, and IL-18 were significantly increased (P < 0.05). Isoflurane post-treatment may enhance autophagy by activating the AMPK/ULK1 signaling pathway and further inhibit the release of inflammatory factors from NLRP3 inflammasomes, thereby ameliorating neurological function and cognitive impairment and exerting a protective effect on the brain in CIRI rats.

The Relationship between Cuff Pressure and Air Injection Volume of Endotracheal Tube: A Study with Sheep Trachea Ex Vivo.

Background: Endotracheal intubation is a widely used treatment. Excessive pressure of the endotracheal tube cuff leads to a series of complications. Here, we used tracheae of sheep to analyze the relationship between the air injection volume and endotracheal tube cuff pressure so as to guide the doctors and nurses in controlling the pressure of the endotracheal tube cuff during clinical work and minimise the risk of complications. Materials and Methods: Forty sheep tracheae were utilised and were divided into five groups according to their diameters. Different sizes of endotracheal tubes were inserted into each trachea, and the cuff pressure with the increase of air injection volume was recorded. The formulas that reflect the relationship between air injection volume and cuff pressure were obtained. Then, sheep tracheae were randomly selected; different types of tubes were inserted, and the stipulated volume of air was injected. The actual pressure was measured and compared with the pressure predicted from the formulas. Statistical analysis was conducted to verify whether the formulas obtained from the first part of the experiment were in accordance with the expert evaluation table, which consists of opinions of several experts. Results: After obtaining 15 formulas, we collected the differences between the theoretical cuff pressure and the actual cuff pressure that satisfied the expert evaluation. Relying on the formulas, the medical turntable was obtained, which is a tool that consists of two round cards with data on them. The top card has a notch. The two cards are stacked together, and as the top card rotates, the data on the bottom card can be easily seen in a one-to-one relationship. Conclusion: The formulas are capable of showing the relationship between the cuff air injection volume and pressure of endotracheal tube cuff. The medical turntable can estimate the air injection volume to ensure that the pressure stays in an acceptable range.

Effects of dopamine transporter in the ventral tegmental area on sleep recovery after propofol anesthesia in sleep-deprived rats.

OBJECTIVE: Previous studies indicate that propofol can help with recovery from sleep deprivation and has anti-anxiety effects. However, the underlying neurochemical mechanism remains unclear. This study aimed to investigate the effects of dopamine transporter (DAT) in the ventral tegmental area (VTA) on sleep and anxiety recovery after propofol anesthesia in rats with 24 h total sleep deprivation (TSD). METHODS: Adult male Sprague-Dawley rats were in natural sleep or sleep deprived for 24 h in a sleep deprivation rat system. The rats received propofol anesthesia (75 mg/kg, i.p.) or natural sleep. Dopamine transporter knockdown was performed by microinjection of AAV-DAT-RNAi vector. EEG was measured in each group to evaluate the subsequent sleep. The elevated plus maze test (EPMT) and open field test (OFT) were used to evaluate locomotion and anxiety level in rats. Immunofluorescence was used to verify virus location and transfection efficiency. RESULTS: Compared with NC group, the anxiety level of Propofol group showed no significant difference, but REM sleep decreased. Compared with the TSD group, the anxiety level of the TSD + Propofol group was reduced and the sleep recovery was closer to baseline. Compared with TSD + AAV-NC group, anxiety level and sleep time increased in TSD + AAVi group, REM increased within 24 h after sleep deprivation. The sleep time of TSD + AAVi + Propofol group was between those of TSD + AAV-NC group and TSD + AAVi group. TSD + AAV-NC + Propofol group had the least sleep time and the lowest anxiety level. CONCLUSION: 1. Propofol did not change anxiety level in normal rats, but reduced REM sleep, while it could accelerate sleep recovery and reduce anxiety level in sleep-deprived rats. 2. In sleep deprived rats with DAT knockdown, propofol improved sleep and anxiety levels more slowly, especially producing more REM rebound, suggesting that the improvement of sleep and anxiety levels in sleep-deprived rats with propofol may be related to DAT in VTA region.

Isoflurane and Netrin-1 combination therapy enhances angiogenesis and neurological recovery by improving the expression of HIF-1α-Netrin-1-UNC5B/VEGF cascade to attenuate cerebral ischemia injury.

Ischemic stroke (IS) causes many morbidities and deaths worldwide. However, the current monotherapy strategy is not satisfactory. Therefore, it is urgent to explore possible combined treatment methods. Although both isoflurane (ISO) and Netrin-1 (NT-1) have angiogenesis and neuroprotective effects, it is still unclear whether combining ISO with NT-1 will provide a positive effect and the possible mechanism of action. In this study, we used a photochemical (PTI) method to establish a mouse ischemic stroke model. ISO and NT-1 were used to treat the mice for 1 week. The adhesive removal test, Morris water maze test, modified neurological severity scores and triphenyl tetrazolium chloride staining were performed to test the treatment effect. Western blotting was performed to assess protein expression, immunofluorescence staining (IF) and immunohistochemical staining (IHC) was used to evaluate angiogenesis. The results suggested that combining ISO with NT-1 resulted in a better therapeutic effect than ISO or NT-1 treatment after PTI injury (all P < 0.01). The protein expression of VEGFA and CD34 in the ISO + NT-1 group was significantly increased compared with that in the other groups (all P < 0.05). IF and IHC also showed that the ISO + NT-1 group significantly improved angiogenesis (all P < 0.01). YC-1 (an HIF-1α inhibitor) and Unc5B siRNA were used to inhibit the expression of HIF-1α and UNC5B before and after combination ISO and NT-1 treatment. The combined inhibition group not only expressed the least VEGFA and CD34 but also expressed the least HIF-1α, UNC5B, FAK, and ß-catenin in all groups (all P < 0.05). Most importantly, angiogenesis and neurological recovery were also significantly decreased by inhibiting HIF-1α and UNC5B (all P < 0.05). In conclusion, our results suggested that ISO combined with NT-1 could promote angiogenesis, recover long-term neurobehavioral function, and attenuate cerebral ischemia injury by activating the HIF-1α-Netrin-1-UNC5B/VEGF cascade.

Prediction of Left Double-Lumen Tube Size by Measurement of Cricoid Cartilage Transverse Diameter by Ultrasound and CT Multi-Planar Reconstruction.

Background: Currently, there is no uniform standard for selecting the left double lumen tubes (LDLT). Advantages, such as safety and convenience of the ultrasonic technology, and measurement accuracy, make it more widely applied in the clinical anesthesia, and computed tomography (CT) multi-planar reconstruction (MPR) technology will certainly provide a more accurate measurement. For better application for thoracic surgery choice LDLT, relieving the injury to patients, and reducing the complications, this study will compare the two approaches. Methods: The first part, 120 cases of patients were selected according to the height and gender; recording the patient's optimum LDLT and measurement the transverse diameter of the cricoid cartilage (TD-C) by ultrasound and CT MPR, and then obtained the TD-C range measurement by ultrasound and CT MPR corresponding to different types of LDLT. The second part, total of 102 patients were divided into the ultrasound group and the CT MPR group. In the ultrasound group, TD-C was measured by ultrasound, the corresponding size for intubation was selected based on the conclusions derived from the first part. In the CT MPR group, TD-C was measured by CT MPR, the corresponding size of LDLT based on the conclusions derived from the first part. Results: In the first part, 120 patients were no significant difference in the basic characteristics (P > 0.05). The accuracy of selecting the LDLT by conventional experience, namely height and gender was 58.3%. Ultrasonic measurement TD-C range was as follows: 32 Fr <15.88, 35 Fr: 15.88-16.80, 37 Fr: 16.75-17.81, and 39 Fr > 17.80. CT MPR measurement TD-C range was as follows: 32 Fr <15.74, 35 Fr: 15.74-16.65, 37 Fr: 16.56-17.68, and 39 Fr > 17.65. In the second part, there was no significant difference in the basic characteristics between the two groups (P > 0.05). The accuracy of intubation in the ultrasound group was 90.2% and the corresponding in the CT MPR group was 94.1% (P > 0.05). Conclusions: The accuracy of selecting the LDLT based on TD-C is significantly higher than conventional experience; it can significantly reduce the post-operative complications and there was no statistical significance in the accuracy of LDLT selected for TD-C measurement by ultrasound vs. CT, and both of them could be safely used for the evaluation before intubation under anesthesia in thoracic surgery.

Isoflurane post-conditioning attenuates cerebral ischemia/reperfusion injury by reducing apoptotic through activating the BMP7/SMAD signaling pathway in rats.

The expressions of different temporal patterns of bone morphogenetic proteins (BMPs) have changed after ischemic strokes, and ischemic preconditioning-induced neuroprotection was attenuated when BMP7 was inhibited. In the previous study, the neuroprotection of isoflurane postconditioning (ISPOC) against cerebral ischemia-reperfusion (I/R) injury has been addressed, with particular relevance to the role of BMP7. Consequently, in the present study, we continued to explore the mechanisms involved in the BMP7 signal mediated the neuroprotection of ISPOC. A rat model of the middle cerebral artery occlusion was used in this study. Rats were administered 1.5 % isoflurane, 60 min after 90 min of ischemia, followed by a 24 h reperfusion period. The 1.5 % ISPOC significantly ameliorated the cerebral infarct volumes, neurologic deficit scores, damaged neurons, and apoptotic neurons. Moreover, ISPOC unregulated the expressions of BMP7, p-Smad1/5/9, and p-p38. Whereas, the neuroprotective effect was weakened by LDN-193189 and SB203580, respectively, a BMP7/Smad1/5/9 and p38MAPK signaling pathway inhibitor. Furthermore, LDN-193189 downregulated the expression of p-p38. The present results of this study indicated that the neuroprotection of 1.5 % isoflurane postconditioning to cerebral ischemia-reperfusion injury is related to the activating of BMP7/Smad1/5/9 and p38MAPK signal pathway.

Identification of AK4 as a novel therapeutic target for serous ovarian cancer.

The present study aimed to assess the expression level of adenylate kinase 4 (AK4) in human serous ovarian cancer (SOC) tissues and investigate the possible involvement of AK4 in SOC progression. Bioinformatics analysis based on The Cancer Genome Atlas (TCGA) database and immunohistochemical (IHC) assays were performed to assess the expression level of AK4 in human SOC tissues. Clinical pathological features of patients with SOC were also evaluated. Colony formation, MTT, wound healing and Transwell assays were conducted to investigate the effects of AK4 on the proliferation, migration, and invasion of SOC cells in vitro. Mouse xenograft and lung metastasis models were developed to evaluate the effects of AK4 on tumor growth and metastasis in vivo. High expression levels of AK4 were identified in human SOC tissues compared with in normal tissues according to TCGA database and the results of IHC assays. A contribution of AK4 to tumor growth and metastasis of SOC cells in vivo was also shown. The present study confirmed the involvement of AK4 in the progression of SOC, and the results indicated that AK4 could serve as a novel therapeutic target for SOC treatment.

Correlation between Preoperative Anxiety and ABO Blood Types: Evidence from a Clinical Cross-Sectional Study.

Gene-environment interaction is identified as the determinant in anxiety. ABO blood types represent a part of the genetic phenotype. Therefore, we assume ABO blood types correlate with preoperative anxiety. This cross-sectional study enrolled 352 patients with different ABO blood types, scheduled for elective surgery between 2018 and 2019 in the First Affiliated Hospital of Shihezi University. HADS (hospital anxiety and depression scale) scores and VA (visual analogue scales for anxiety) scores were all used to assess the preoperative anxiety in the A, B, AB, and O groups. Bivariate correlation and logistic regression were performed to identify relationships between preoperative anxiety and related variables. A significant difference in VA and HADS-A (anxiety) scores was found between the AB and other groups. The ratio of preoperative anxiety was 3.73 (95% CI [confidence interval]: 2.32-6.00, P < 0.001) times in female than in male; 0.36 (95% CI: 0.21-0.63, P < 0.001) times in ASA (American Society of Anesthesiologists) grade II than in grade I; 0.41 (95% CI: 0.20-0.86, P < 0.05) times in ASA grade III than in grade I; 1.25 (95% CI: 1.1-1.41, P < 0.001) times in higher VAS (visual analogue scales for pain) scores than in lower VAS scores; and 0.28 (95% CI: 0.16-0.49, P < 0.01) times in non-AB blood type than in AB blood type. Differences in ABO blood types were found in preoperative anxiety, and the AB group displayed a high preoperative anxiety level. ABO blood types, sex, ASA grade, and VAS were associated with preoperative anxiety. This trial is registered with ChiCTR1800019390.