TXNIP knockdown ameliorates hepatic ischemia/reperfusion injury by inhibiting apoptosis and improving mitochondrial dysfunction via HIF-1α.

This study aims to investigate whether thioredoxin-interacting protein (TXNIP) regulates cell viability, cell apoptosis and mitochondrial damage in OGD/R-induced hepatocytes and to explore its underlying mechanism. AML12 cells were cultured under oxygen-glucose deprivation/reperfusion (OGD/R) conditions. TXNIP mRNA was detected using qRT-PCR, and the TXNIP protein was analyzed using western blotting. TXNIP-targeted short hairpin RNA (sh-TXNIP) lentivirus was used to infect the AML12 cells. CCK8 and TUNEL assays were applied to detect cell viability and apoptosis, respectively. DCFH-DA probe was used to determine reactive oxygen species (ROS) release level, and JC-1 probe was used to evaluate mitochondrial membrane potential (MMP). The localization of TXNIP and HIF-1α was observed using immunofluorescence. Our results showed that TXNIP markedly increased in AML12 cells treated with OGD/R. TXNIP knockdown increased cell viability and reduced cell apoptosis under OGD/R treatment. Moreover, MMP significantly increased and ROS release decreased in cells after TXNIP knockdown under OGD/R treatment. Additionally, TXNIP knockdown markedly increased the expression of HIF-1α. HIF-1α exhibited nuclear translocation following OGD/R induction, and TXNIP knockdown further promoted it. Compared with the OGD/R + sh-TXNIP group, HIF-1α agonist ML228 inhibited cell apoptosis and ROS release, and increased MMP. However, HIF-1α inhibitor PX478 had the opposite effect. In summary, TXNIP deletion ameliorated AML12 cell injury caused by OGD/R via promoting HIF-1α expression and nuclear translocation, manifested by inhibiting cell apoptosis and alleviating mitochondrial dysfunction.

Glyceryl triacetate promotes blood-brain barrier recovery after ischemic stroke through lipogenesis-mediated IL-33 in mice.

BACKGROUND: Lipid metabolism has a crucial role in neural repair in neurodegenerative diseases. We recently revealed that lipogenesis-mediated interleukin-33 (IL-33) upregulation lead to blood-brain barrier (BBB) repair after ischemic stroke. However, manipulating the key enzyme fatty acid synthase (FASN) to enhance lipogenesis was very challenging. Glyceryl triacetate (GTA) was used as a donor of acetate and precursor of acetyl coenzyme A, the key substrate for de novo lipogenesis catalyzed by FASN. Therefore, we hypothesized that GTA would promote lipogenesis the peri-infarct after ischemic stroke and contribute to the BBB repair through IL-33. METHODS: Middle cerebral artery occlusion (MCAO) was performed on C57BL mice and GTA was gavage administrated (4 g/kg) on day 2 and 4 after MCAO. Lipogenesis was evaluated by assessment of the protein level of FASN, lipid droplets, and fatty acid products through liquid chromatography-mass spectrometry in the peri-infarct area on day 3 after MCAO, respectively. BBB permeability was determined by extravasation of Evans blue, IgG and dextran, and levels of tight junction proteins in the peri-infarct area on day 7 after MCAO, respectively. Infarct size and neurological defects were assessed on day 7 after MCAO. Brain atrophy on day 30 and long-term sensorimotor abilities after MCAO were analyzed as well. The inhibitor of FASN, C75 and the virus-delivered FASN shRNA were used to evaluate the role of FASN-driven lipogenesis in GTA-improved BBB repair. Finally, the therapeutic potential of recombinant IL-33 on BBB repair and neurological recovery was evaluated. RESULTS: We found that treatment with GTA increased the lipogenesis as evidenced by lipid droplets level and lauric acid content, but not the FASN protein level. Treatment with GTA increased the IL-33 level in the peri-infarct area and decreased the BBB permeability after MCAO. However, infarct size and neurological defect score were unchanged on day 7 after MCAO, while the long-term recovery of sensorimotor function and brain atrophy were improved by GTA. Inhibition of lipogenesis using C75 or FASN shRNA reversed the beneficial effect of GTA. Finally, exogenous IL-33 improved BBB repair and long-term functional recovery after stroke. CONCLUSION: Collectively, we concluded that treatment with GTA improved the BBB repair and functional recovery after ischemic stroke, probably by the enhancement of lipogenesis and IL-33 expression.

Clinical Features and Blood Indicators for Severity and Prognosis in COVID-19 Patients.

BACKGROUND: This study aimed to analyze the clinical manifestations and blood indicators to deepen the understanding of Coronavirus disease 2019 (COVID-19). METHODS: COVID-19 patients admitted to C10 West Ward, Tongji Hospital in Wuhan City ("West Ward") between January 31 and March 28, 2020, were retrospectively analyzed. RESULTS: A total of 61 COVID-19 patients were hospitalized, wherein the non-critical Group had 30 cases, while the critical group had 31 (including 14 survivors and 17 deaths). Age, the proportion of fever cases, white blood cell (WBC), basophils, red blood cell (RBC), hemoglobin, lactate dehydrogenase (LDH), C-reactive protein (CRP), high-sensitivity troponin, pro-BNP (brain natriuretic peptide), prothrombin time (PT), and D-dimer were higher in the critical group while lymphocytes, eosinophils, albumin were lower compared with those of the non-critical group (all p < 0.05). WBC (p = 0.008), basophils (p = 0.034), and LDH (p = 0.005) of the death subgroup climbed remarkably in comparison with those of the survival subgroup. CONCLUSIONS: Advanced age, high fever, increases in indicators such as WBC, basophils, CRP, LDH, high-sensitivity troponin, pro-BNP, and D-dimer, and decreases in indicators, including lymphocytes, eosinophils, and albumin, might forebode a critical condition.

Effect of goal-directed fluid therapy based on plasma colloid osmotic pressure on the postoperative pulmonary complications of older patients undergoing major abdominal surgery.

BACKGROUND: As an important component of accelerated rehabilitation surgery, goal-directed fluid therapy (GDT) is one of the optimized fluid therapy strategies and is closely related to perioperative complications and mortality. This article aimed to study the effect of combining plasma colloid osmotic pressure (COP) with stroke volume variation (SVV) as a target for intraoperative GDT for postoperative pulmonary complications in older patients undergoing major abdominal surgery. METHODS: In this study, older patients (n = 100) undergoing radical resection of gastroenteric tumors were randomized to three groups: Group C (n1 = 31) received a conventional infusion regimen, Group S1 (n2 = 34) received GDT based on SVV, and Group S2 (n3 = 35) received GDT based on SVV and COP. The results were recorded, including the lung injury score (LIS); PaO2/FiO2 ratio; lactic acid value at the times of beginning (T0) and 1 h (T1), 2 h (T2), and 3 h (T3) after liquid infusion in the operation room; the total liquid infusion volume; infusion volumes of crystalline and colloidal liquids; urine production rate; pulmonary complications 7 days after surgery; and the severity grading of postoperative pulmonary complications. RESULTS: The patients in the S2 group had fewer postoperative pulmonary complications than those in the C group (P < 0.05) and the proportion of pulmonary complications of grade 1 and higher than grade 2 in S2 group was significantly lower than that in C group (P <0.05); the patients in the S2 group had a higher PaO2/FiO2 ratio than those in the C group (P < 0.05), lower LIS than those in the S1 and C groups (P < 0.05), less total liquid infusion than those in the C group (P < 0.05), and more colloidal fluid infusion than those in the S1 and C groups (P < 0.05). CONCLUSION: The findings of our study show that intraoperative GDT based on COP and SVV can reduce the incidence of pulmonary complications and conducive to shortening the hospital stay in older patients after gastrointestinal surgery. TRIAL REGISTRATION: Chinese Clinical Trial. no. ChiCTR2100045671. Registry at www.chictr.org.cn on April 20, 2021.

MicroRNA-137-mediated lysine demethylase 4A regulates the recovery of spinal cord injury via the SFRP4-Wnt/ß-Catenin axis.

OBJECTIVE: Spinal cord injury (SCI) causes great harm to the normal life of patients. Histone demethylase is involved in many biological processes, including SCI. Hence, this study explored the role and mechanism of histone lysine demethylase 4A (KDM4A) in SCI. METHODS: The acute SCI (ASCI) rat model was established after spinal compression and the SCI neuronal model was induced via treating PC12 cells with lipopolysaccharide (LPS). KDM4A expression during SCI was detected. The microRNA (miRNA) targeting KDM4A was predicted and verified. The miRNA and KDM4A expression patterns were intervened in LPS-stimulated PC12 cells to evaluate their combined effects on neuronal cells in SCI. The downstream pathways of KDM4A were predicted, and SFRP4 and H3K9me3 expressions were determined. After the intervention of SFRP4 in LPS-treated cells, ß-Catenin expression and the effect of SFRP4 on neuronal cells in SCI were detected. Finally, the effectiveness of the miR-137/KDM4A/SFRP4/Wnt/ß-Catenin axis was verified in vivo. RESULTS: KDM4A was abnormally elevated in SCI. miR-137 targeted KDM4A. miR-137 effectively inhibited the apoptosis of LPS-challenged PC12 cells, which could be reversed after overexpressing KDM4A. KDM4A promoted SFRP4 expression through demethylation of H3K9me3. Overexpression of SFRP4 blocked the Wnt/ß-Catenin pathway and promoted apoptosis of LPS-stimulated cells. In vivo, miR-137 overexpression remarkably improved SCI symptoms, accompanied by obviously increased ß-Catenin expression and notably decreased KDM4A and SFRP4 expressions, while overexpressed KDM4A treatment showed the opposite trend in the presence of miR-137. CONCLUSION: We demonstrated that miR-137 targeted KDM4A and then downregulated SFRP4 to ameliorate SCI in a Wnt/ß-Catenin-dependent manner.

Remimazolam tosilate in upper gastrointestinal endoscopy: A multicenter, randomized, non-inferiority, phase III trial.

BACKGROUND AND AIM: Remimazolam tosilate (RT) is a new short-acting GABA(A) receptor agonist, having potential to be an effective option for procedural sedation. Here, we aimed to compare the efficacy and safety of RT with propofol in patients undergoing upper gastrointestinal endoscopy. METHODS: This positive-controlled, non-inferiority, phase III trial recruited patients at 17 centers, between September 2017 and November 2017. A total of 384 patients scheduled to undergo upper gastrointestinal endoscopy were randomly assigned to receive RT or propofol. Primary endpoint was the success rate of sedation. Adverse events (AEs) were recorded to evaluate safety. RESULTS: The success rate of sedation in the RT group was non-inferior to that in the propofol group (97.34% vs 100.00%; difference in rate -2.66%, 95% CI -4.96 to -0.36, meeting criteria for non-inferiority). Patients in the RT group had longer time to adequate sedation (P < 0.0001) but shorter time to fully alert (P < 0.0001) than that in the propofol group. The incidences of hypotension (13.04% vs 42.86%, P < 0.0001), treatment-related hypotension (0.54% vs 5.82%, P < 0.0001), and respiratory depression (1.09% vs 6.88%, P = 0.0064) were significantly lower in the RT group. AEs were reported in 74 (39.15%) patients in the RT group and 114 (60.32%) patients in the propofol group, with significant difference (P < 0.0001). CONCLUSION: This trial established non-inferior sedation success rate of RT compared with propofol. RT allows faster recovery from sedation compared with propofol. The safety profile is favorable and appears to be superior to propofol, indicating that it was feasible and well tolerated for patients.

Inhibition of microRNA-148b-3p alleviates oxygen-glucose deprivation/reoxygenation-induced apoptosis and oxidative stress in HT22 hippocampal neuron via reinforcing Sestrin2/Nrf2 signalling.

MicroRNAs (miRNAs) have emerged as crucial regulators of neuronal injury during cerebral ischaemia/reperfusion injury. Various miRNAs are dysregulated during this pathological process; however, the precise role of these miRNAs in regulating neuronal injury remains largely unknown. In the current study, we explored the potential function of microRNA-148b-3p (miR-148b-3p) in regulating neuronal injury induced by oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro, a cellular model for mimicking cerebral ischaemia/reperfusion injury. We found that miR-148b-3p expression was significantly decreased in neurons in response to OGD/R exposure. Importantly, miR-148b-3p overexpression decreased cell viability and exacerbated apoptosis and reactive oxygen species (ROS) production in OGD/R-exposed neurons. By contrast, miR-148b-3p inhibition improved cell viability and decreased apoptosis and ROS production in OGD/R-exposed neurons. Notably, Sestrin2, a cytoprotective gene, was identified as a miR-148b-3p target gene. miR-148b-3p inhibition markedly increased Sestrin2 expression as well as the activation of nuclear factor erythroid-2-related factor 2 (Nrf2) antioxidant signalling. Moreover, silencing of Sestrin2 or Nrf2 significantly reversed the miR-148-3p-inhibition-mediated protective effect in OGD/R-injured neurons. Overall, these results demonstrate that miR-148b-3p inhibition protects neurons from OGD/R-induced apoptosis and ROS production through reinforcing Nrf2 antioxidant signalling via upregulation of Sestrin2. Our study indicates that the miR-148b-3p/Sestrin2/Nrf2 axis plays an important role in regulating neuronal injury and may serve as a potential therapeutic target for providing neuroprotection during cerebral ischaemia/reperfusion injury.

Anesthesia and protection in an emergency cesarean section for pregnant woman infected with a novel coronavirus: case report and literature review.

An outbreak of novel coronavirus pneumonia occurred worldwide since December 2019, which had been named COVID-19 subsequently. It is extremely transmissive that infection in pregnant women were unavoidable. The delivery process will produce large amount of contaminated media, leaving a challenge for medical personnel to ensure both the safety of the mother and infant and good self-protection. Only rare cases of pregnant women with COVID-19 are available for reference. Here, we report a 30-year-old woman had reverse transcription polymerase chain reaction-confirmed COVID-19 at 36 weeks 2 days of gestation. Significant low and high variability of fetal heart rate baseline and severe variable decelerations were repeated after admission. An emergency cesarean section at 37 weeks 1 day of gestation under combined spinal and epidural anesthesia was performed with strict protection for all personnel. Anesthesia and operation went uneventfully. None of the participants were infected. We can conclude that when confronted with cesarean section in parturient with COVID-19, careful planning and detailed preparation can improve the safety of the mother and infant and reduce the risk of infection for medical staff to help preventing and controlling the epidemic.

MicroRNA-449b-5p targets HMGB1 to attenuate hepatocyte injury in liver ischemia and reperfusion.

MicroRNAs (miRNAs) participate in the pathological process of liver ischemia/reperfusion (I/R) injury. MiR-449b-5p is the target miRNA of high mobility group box 1 (HMGB1). Its role and molecular mechanism in liver I/R injury remain unidentified. In this study, we found a protective effect of miR-449b-5p against hepatic I/R injury. HMGB1 expression significantly increased, whereas miR-449b-5p dramatically decreased in patients after liver transplant and in L02 cells exposed to hypoxia/reoxygenation (H/R). A dual-luciferase reporter assay confirmed the direct interaction between miR-449b-5p and the 3' untranslated region of HMGB1 messenger RNA. We also found that overexpression of miR-449b-5p significantly promoted cell viability and inhibited cell apoptosis of L02 cells exposed to H/R. Moreover, miR-449b-5p repressed HMGB1 protein expression and nuclear factor-κB (NF-κB) pathway activation in these L02 cells. In an in vivo rat model of hepatic I/R injury, overexpression of miR-449b-5p significantly decreased alanine aminotransferase and aspartate aminotransferase and inhibited the HMGB1/NF-κB pathway. Our study thus suggests that miR-449b-5p alleviated hepatic I/R injury by targeting HMGB1 and deactivating the NF-κB pathway, which may provide a novel and promising therapeutic target for hepatic I/R injury.

PGC-1α-Mediated Mitochondrial Biogenesis is Involved in Cannabinoid Receptor 2 Agonist AM1241-Induced Microglial Phenotype Amelioration.

Cannabinoid type 2 receptor (CB2R) agonist AM1241 induces anti-inflammation by ameliorating microglial phenotypes, the mechanism, however, is still unknown. Peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) is a transcription protein which can regulate mitochondrial biogenesis, and the aim of this study is to investigate whether PGC-1α is involved in AM1241-induced anti-inflammation in N9 microglial cells. We used 10 ng/ml lipopolysaccharide (LPS) plus 10 U/ml interferon γ (IFNγ) to activate microglia into classic activated phenotype (M1 phenotype), and found that co-administration of 10 µM AM1241 increased the expressions of mitochondria biogenesis-associated proteins, including nuclear respiratory factor 1 (NRF-1), mitochondrial transcription factor A (TFAM) and COX IV, and up-regulated the biomarker levels of microglial M2 phenotype, including arginase 1 (Arg-1) and brain-derived neurotrophic factor (BDNF), and down-regulated biomarker levels of M1 phenotype, including inducible nitric oxide synthase (iNOS) and tumor necrosis factor α (TNF-α), compared to the cells treated with LPS plus IFNγ only (P < 0.05). By using PGC-1α-siRNA, however, we found that down-regulation of PGC-1α significantly reversed the AM1241-induced effects above (P < 0.05). According to the results in this study, we found that PGC-1α may mediate CB2R agonist AM1241-induced anti-inflammation in N9 microglial cells, and the mechanism might be associated with the enhancement of mitochondria biogenesis.

Chlorogenic acid against palmitic acid in endoplasmic reticulum stress-mediated apoptosis resulting in protective effect of primary rat hepatocytes.

BACKGROUND: We demonstrated growing evidence supports a protective role of chlorogenic acid of rat hepatocytes elicited by two compounds, i.e. thapsigargin and palmitic acid. Nevertheless, little is known about the mechanisms of palmitic acid induced endoplasmic reticulum (ER) stress and cell death. METHODS: The proliferation of primary rat hepatocytes was detected by MTT assay. The expression of GRP78, CHOP and GRP94 was detected by Western blot analyses. Caspase-3 activity was detected by a Caspase-3 substrate kit. Cell apoptosis was detected by Hoechst 33342 staining. RESULTS: We demonstrated that incubation of hepatocytes for 16 h with palmitic acid elevated cell death. Moreover, Western blot analyses demonstrated increased levels of the endoplasmic reticulum stress markers - glucose regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), and glucose regulated protein 94 (GRP94). Chlorogenic acid could inhibit ER stress induced cell death and levels of indicators of ER stress caused by palmitic acid. The effect of thapsigargin, which evokes ER stress were reversed by chlorogenic acid. CONCLUSIONS: Altogether, our data indicate that in primary rat hepatocytes, chlorogenic acid prevents ER stress-mediated apoptosis of palmitic acid.

Sirtuin7 is involved in protecting neurons against oxygen-glucose deprivation and reoxygenation-induced injury through regulation of the p53 signaling pathway.

Sirtuin7 (SIRT7) is known to regulate apoptosis and stress responses. So far, very little is known about the role of SIRT7 in cerebral ischemia/reperfusion injury. In this study, we aimed to investigate the potential role of SIRT7 in regulating oxygen-glucose deprivation and reoxygenation (OGD/R)-induced injury in neurons. We found a significant increase of SIRT7 expression in neurons in response to OGD/R treatment. Knockdown of SIRT7 aggravated OGD/R-induced injury. Knockdown of SIRT7 augmented the levels of total and acetylated p53 protein. Moreover, knockdown of SIRT7 markedly increased the transcriptional activity of p53 toward apoptosis and activated the p53-mediated proapoptotic signaling pathway. By contrast, overexpression of SIRT7 showed the opposite effects. Taken together, the results of our study suggest that SIRT7 is involved in protecting neurons against OGD/R-induced injury, possibly through regulation of the p53-mediated proapoptotic signaling pathway, indicating a potential therapeutic target for cerebral ischemia/reperfusion injury.

Tea polyphenols may attenuate the neurocognitive impairment caused by global cerebral ischemia/reperfusion injury via anti-apoptosis.

BACKGROUND/AIMS: Global cerebral ischemia/reperfusion (GCIR) may incur neurocognitive impairment. Tea polyphenols (TP) have strong anti-oxidant capacity. This study planned to investigate the protective effect of TP against the neurocognitive impairment caused by GCIR and its mechanism. METHODS: One-stage anterior approach for cerebral four-vessel occlusion (4VO) was used to construct the GCIR model. Sprague Dawley rats were randomly classified into Sham group, GCIR group, and TP group (n = 50 per group). Besides receiving the same 4VO, the rats in TP group were treated with TP (6.4%) injection from the tail vein 30 minutes before cerebral ischemia. Morris water-maze test was used to evaluate the changes in space recognition and memory and open field activity test to assess the activity and motor function of rats. The cell apoptotic study in hippocampal CA1 region at specified time points (12, 24, 48, and 72 hours after surgery) was carried out by the flow cytometry, histology (hematoxylin and eosin staining), and immunohistochemical (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining) examinations. One-way analysis of variance and least significant difference t-test were used and statistical significance considered at P < 0.05. RESULTS: Compared with the GCIR group, the TP group was significantly attenuated in the impairment of space recognition and memory caused by GCIR and so was the neuronal apoptosis in the hippocampal CA1 region (P < 0.05). CONCLUSION: TP may attenuate the impairment of space recognition and memory caused by GCIR via anti-apoptosis.

Effect of Desflurane versus Sevoflurane in Pediatric Anesthesia: A Meta-Analysis.

PURPOSE: To compare the effect of desflurane versus sevoflurane in pediatric anesthesia by conducting meta-analysis. METHODS: Studies were searched from PubMed, Medline, Springer, Elsevier Science Direct, Cochrane Library and Google Scholar up to July 2014. Weighted mean difference (WMD) or risk ratio (RR) and 95% confidence intervals (CIs) were considered as effect sizes. Heterogeneity across studies was assessed by Cochran Q test and I2 statistic. The random effects model was performed in the meta-analysis when heterogeneity was observed, or the fixed effect model was used. Review Manager 5.1 software was applied for the meta-analysis. RESULTS: A total of 11 studies (13 comparisons) involving 1,273 objects were included in this meta-analysis. No heterogeneity was observed between studies for any comparison but for postoperative extubation time. The results showed significant differences between desflurane and sevoflurane groups for postoperative extubation time (WMD = -3.87, 95%CI = -6.14 to -1.60, P < 0.01), eye opening time (WMD = -1.11, 95%CI = -1.49 to -0.72, P < 0.01), awakening time (WMD = -4.27, 95%CI = -5.28 to -3.26, P < 0.01) and agitation (RR = 1.44, 95%CI = 1.05 to 1.96, P = 0.02). No significant differences (P > 0.05) were detected for discharge from the recovery room, oculocardiac reflex, nausea and vomiting and severe pain. CONCLUSIONS: Desflurane may have less adverse effects than sevoflurane when used in pediatric anesthesia with significantly shorter postoperative extubation time, eye opening time and awakening time as well as slighter agitation.

METTL3 Modulates TXNIP Expression to Affect the Activation of NLRP3 Inflammasome in Hepatic Cells Under Oxygen-Glucose Deprivation/Reperfusion Injury.

Hepatic ischemia-reperfusion (I/R) injury is still a major risk factor and unsolved problem in hepatic surgery. Methyltransferase-like 3 (METTL3), an important m6A-modified methylase, regulates inflammation and cellular stress response. In this study, we demonstrated the special role of METTL3 and its underlying mechanism in hepatic I/R injury. In the mouse model of hepatic I/R and in the oxygen-glucose deprivation and reoxygenation (OGD/R)-induced AML12 and NCTC 1469 cells, the expression of METTL3 was significantly upregulated. Inhibition of METTL3 in OGD/R-induced AML12 and NCTC 1469 cells both increased the cell viability, declined the cell apoptosis, and decreased the reactive oxygen species (ROS) and the release levels of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18), diminishing NLRP3 and Caspase1-p20 expressions. Moreover, METTL3 positively modulated TXNIP expression in an m6A manner. TXNIP overexpression reversed the effects of METTL3 knockdown on OGD/R-induced injury in AML12 cells. Furthermore, inhibition of NLRP3 inflammasome activity contributed to the protective effects of TXNIP knockdown in OGD/R-induced AML12 cells. In conclusion, METTL3 knockdown alleviated OGD/R-induced hepatocyte injury, and the specific mechanism was associated with the inhibition of NLRP3 inflammasome activation, which was attributed to the reduction of TXNIP in an m6A-dependent manner.

STING Agonist cGAMP Attenuates Sleep Deprivation-Induced Neuroinflammation and Cognitive Deficits via TREM2 Up-Regulation.

Sleep deprivation (SD) has been associated with several adverse effects, including cognitive deficit. Emerging evidence suggests microglia-associated neuroinflammation is a potential trigger of cognitive deficit after SD. Stimulator of interferon genes (STING) constitutes an important factor in host immune response to pathogenic organisms and is found in multiple cells, including microglia. STING is involved in neuroinflammation during neuronal degeneration, although how STING signaling affects SD-induced neuroinflammation remains unexplored. In the present study, the chronic sleep restriction (CSR) model was applied to examine the effects of STING signaling on cognition. The results revealed that cGAMP, a high-affinity and selective STING agonist, significantly improved cognitive deficit, alleviated neural injury, and relieved neuroinflammation in CSR mice by activating the STING-TBK1-IRF3 pathway. Moreover, triggering receptor expressed on myeloid cells 2 (TREM2) was upregulated in CSR mice treated with cGAMP, and this effect was abolished by STING knockout. TREM2 upregulation induced by cGAMP regulated the microglia from pro-inflammatory state to anti-inflammatory state, thereby relieving neuroinflammation in CSR mice. These findings indicate cGAMP-induced STING signaling activation alleviates SD-associated neuroinflammation and cognitive deficit by upregulating TREM2, providing a novel approach for the treatment of SD-related nerve injury.

Dual-specificity phosphatase 26-dificient neurons are susceptible to oxygen-glucose deprivation/reoxygenation-evoked apoptosis and proinflammatory response by affecting the TAK1-medaited JNK/P38 MAPK pathway.

Dual-specificity phosphatase 26 (DUSP26) is linked to a broad range of human disorders as it affects numerous signaling cascades. However, the involvement of DUSP26 in ischemic stroke has not been explored. Here, we investigated DUSP26 as a key mediator of oxygen-glucose deprivation/reoxygenation (OGD/R)-associated neuronal injury, an in vitro model for investigating ischemic stroke. A decline in DUSP26 occurred in neurons suffering from OGD/R. A deficiency in DUSP26 rendered neurons more susceptible to OGD/R by aggravating neuronal apoptosis and inflammation, while the overexpression of DUSP26 blocked OGD/R-evoked neuronal apoptosis and inflammation. Mechanistically, enhanced phosphorylation of transforming growth factor-ß-activated kinase 1 (TAK1), c-Jun N-terminal kinase (JNK) and P38 mitogen-activated protein kinase (MAPK) was evidenced in DUSP26-deficient neurons suffering from OGD/R, whereas the opposite effects were observed in DUSP26-overexpressed neurons. Moreover, the inhibition of TAK1 abolished the DUSP26-deficiency-elicited activation of JNK and P38 MAPK and exhibited anti-OGD/R injury effects in DUSP26-deficiency neurons. Results from these experiments show that DUSP26 is essential for neurons in defending against OGD/R insult, while neuroprotection is achieved by restraining the TAK1-mediated JNK/P38 MAPK pathway. Therefore, DUSP26 may serve as a therapeutic target for the management of ischemic stroke.

A combination of supraglottic airway and bronchial blocker for one-lung ventilation in infants undergoing thoracoscopic surgery.

Objectives: One-lung ventilation (OLV) for children under the age of two years is difficult. The authors hypothesize that a combination of a supraglottic airway (SGA) device and intraluminal placement of a bronchial blocker (BB) may provide an appropriate choice. Design: A prospective method-comparison study. Setting: Second Affiliated Hospital of Xi'an Jiaotong University, China. Participants: 120 patients under the age of two years undergoing thoracoscopic surgery with OLV. Interventions: Participants were randomly assigned to receive intraluminal placement of BB with SGA (n = 60) or extraluminal placement of BB with endotracheal tube (ETT) (n = 60) for OLV. Measurements and main results: The primary outcome was the length of postoperative hospitalization stay. The secondary outcomes were the basic parameters of OLV and investigator-defined severe adverse events. The postoperative hospitalization stay was 6 days (interquartile range, IQR 4-9) in SGA plus BB group compared with 9 days (IQR 6-13) in ETT plus BB group (P = 0.034). The placement and positioning duration of SGA plus BB was 64 s (IQR 51-75) compared with 132 s (IQR 117-152) of ETT plus BB (P = 0.001). The values of leukocyte (WBC) and C-reactive protein (CRP) of SGA plus BB group on the first day of post-operation were 9.8 × 109/L (IQR 7.4-14.5) and 15.1 mg/L (IQR 12.5-17.3) compared with 13.6 × 109/L (IQR 10.8-17.1) and 19.6 mg/L (IQR 15.0-23.5) of ETT plus BB group (P = 0.022 and P = 0.014). Conclusion: There were few if any significant adverse events in the intervention group (SGA plus BB) for OLV in children under the age of two years, and this method seems worthy of clinical application. Meanwhile, the mechanism for this novel technique to shorten the length of postoperative hospitalization stay needs to be further explored.

Influence of Sevoflurane Inhalation Anesthesia on Clinical Outcomes of Morbidly Obese Patients Undergoing Laparoscopic Bariatric Surgery.

Background: Morbid obesity is one of the fastest-growing subgroups of obesity and is associated with high mortality, with an estimated 2.8 million people dying from obesity each year. Objective: This research sets out to elucidate the impact of sevoflurane (Sevo) inhalation anesthesia on the clinical outcome of morbidly obese (MO) patients undergoing laparoscopic bariatric surgery (LBS). Methods: A retrospective study was conducted on 150 MO patients undergoing LBS in the Second Affiliated Hospital of Xi'an Jiaotong University from November 2019 to November 2021. According to the difference of anesthesia methods, 100 patients with Sevo anesthesia were set as group A, and 50 patients with propofol (P) anesthesia were set as group B. Intergroup comparisons were performed in terms of eye-opening time, tracheal intubation removal time, directional force recovery, heart rate (HR), mean arterial pressure (MAP), peak airway pressure (Ppeak), plateau pressure (Pplat), standard time out of PACU, postoperative food intake (FI), length of stay (LOS), and complication rate. Results: Group A had a shorter time to open eyes, remove tracheal intubation, and restore directional force than Group B, with better recovery of HR, MAP, Ppeak, and Pplat. Group A was also superior to Group B in the standard time out of PACU, postoperative FI, and LOS, with a lower complication rate. Conclusions: Sevo inhalation anesthesia is more effective and safer for MO patients undergoing LBS.

De novo Lipogenesis in Astrocytes Promotes the Repair of Blood-Brain Barrier after Transient Cerebral Ischemia Through Interleukin-33.

Astrocytes experience significant metabolic shifts in the "sensitive period" of neurological function recovery following cerebral ischemia. However, the changes in astrocyte lipid metabolism and their implications for neurological recovery remain unknown. In the present study, we employed a mouse middle cerebral artery occlusion model to investigate the changes in de novo lipogenesis and interleukin-33 (IL-33) production in astrocytes and elucidate their role in blood-brain barrier (BBB) repair in the subacute phase of cerebral ischemia. Neurological behavior evaluation was used to assess functional changes in mice. Pharmacological inhibition and astrocyte-specific downregulation of fatty acid synthase (FASN) were used to evaluate the role of de novo lipogenesis in brain injury. Intracerebroventricular administration of recombinant IL-33 was performed to study the contribution of IL-33 to BBB disruption. Extravasation of Evans blue dye, dextran and IgG were used to assess BBB integrity. Western blotting of tight junction proteins ZO-1, Occludin, and Claudin-5 were performed at defined time points to evaluate changes in BBB. It was found that de novo lipogenesis was activated, and IL-33 production increased in astrocytes at the subacute stage of cerebral ischemia injury. Inhibition of lipogenesis in astrocytes decreased IL-33 production in the peri-infarct area, deteriorated BBB damage and interfered with neurological recovery. In addition, supplementation of IL-33 alleviated BBB destruction and improved neurological recovery worsened by lipogenesis inhibition. These findings indicate that astrocyte lipogenesis increases the production of IL-33 in the peri-infarct area, which promotes BBB repair in the subacute phase of cerebral ischemia injury and improves long-term functional recovery.