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Propofol is widely used as an intravenous anesthetic in clinical practice. Previous studies have indicated that propofol induces apoptosis in neurons. Brain-derived neurotrophic factor (BDNF), a neurotrophic factor, is associated with neuronal apoptosis. BDNF-AS, a relatively conserved long non-coding RNA, can reverse the transcription of BDNF. This study aimed to investigate the involvement of BDNF-AS in propofol-induced apoptosis in HT22 cells. HT22 cells were treated with various concentrations of propofol at different time points. BDNF-AS was silenced using BDNF-AS-targeting siRNA. TrkB was antagonized by the TrkB inhibitor, ANA-12. Flow cytometry, quantitative reverse-transcription PCR, and western blotting were performed to analyze apoptosis and the expression of genes and proteins, respectively. In propofol-treated HT22 cells, BDNF-AS was upregulated, and BDNF was downregulated in a time- and dose-dependent manner. BDNF-AS downregulation mediated by siRNA mitigated apoptosis, upregulated the expression of Bcl-2, and downregulated the expression of Bax and caspase-3, 7, and 9. ANA-12 downregulated the expression of Bcl-2, upregulated the expression of Bax and caspase-3, 7, and 9, and increased apoptosis. Our study implied that inhibition of BDNF-AS can decrease propofol-induced apoptosis by activating the BDNF/TrkB pathway. Thus, the BDNF-AS-BDNF/TrkB signaling pathway may be a valuable target for treating propofol-induced neurotoxicity.

BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is often viewed as an indicator for heart failure. However, the prognostic association and the predictive utility of NT-proBNP for postoperative major adverse cardiovascular events (MACEs) and myocardial injury after noncardiac surgery (MINS) among older patients are unclear. METHODS: In this study, we included 5033 patients aged 65 years or older who underwent noncardiac surgery with preoperative NT-proBNP recorded. Logistic regression was adopted to model the associations between preoperative NT-proBNP and the risk of MACEs and MINS. The receiver operating characteristic curve was used to determine the predictive value of NT-proBNP. RESULTS: A total of 5033 patients were enrolled, 63 patients (1.25%) and 525 patients (10.43%) had incident postoperative MACEs and MINS, respectively. Analysis of the receiver operating characteristic curve indicated that the cutoff values of ln (NT-proBNP) for MACEs and MINS were 5.16 (174 pg/mL) and 5.30 (200 pg/mL), respectively. Adding preoperative ln (NT-proBNP) to the Revised Cardiac Risk Index score and the Cardiac and Stroke Risk Model boosted the area under the receiver operating characteristic curves from 0.682 to 0.726 and 0.787 to 0.804, respectively. The inclusion of preoperative NT-proBNP in the prediction models significantly increased the reclassification and discrimination. CONCLUSIONS: Increased preoperative NT-proBNP was associated with a higher risk of postoperative MACEs and MINS. The inclusion of NT-proBNP enhances the predictive ability of the preexisting models.

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

Objective To compare the usage of two kinds of laryngeal mask LMA SupremeTM and SLIPATM in airway management of general anesthesia in adult female patients and the related postoperative complications, so as to provide the basis evidence for guiding the usage of the laryngeal mask airway. Methods The DoCare anesthesia information management system was used to retrieve the cases of female patients treated with LMA SupremeTM (group L) or SLIPATM (group S) to manage airway during general anesthesia during Oct. 2017 to Mar. 2018. The possibly associated complications occurred during or after operation were recorded after checking the anesthesia information management system. Results A total of 924 adult female patients were undergone the LMA SupremeTM (379 cases, 41%) or SLIPATM (545 cases, 59%) during operation. The patients came from the department of breast specialist, gynecology, plastic surgery, tumor surgery and other departments. In group L, the size 3# and 4# laryngeal mask were used in proportions of 28.5% and 71.5%, respectively. And in group S, size 49# and 51# laryngeal airway were used in proportions of 86.4% and 13.6%, respectively. There were no details about the possible complications such as pharynx pain associated with the laryngeal mask application in the doctor's record 24 hours after the operation. However, there were 5 cases of hoarseness occurred 24h after operation in group L (1.3%) and 9 cases in group S (1.65%), and 12 cases of risen temperature over 38℃ occurred within 3 days after operation in group L (3.1%), and 19 cases in group S (3.5%). Conclusion Adult female patients undergone general anesthesia using SLIPATM and LMA SupremeTM laryngeal mask airway can meet clinical needs wonderful without significant difference in postoperative complications between the two kinds of laryngeal mask airway. DOI: 10.11855/j.issn.0577-7402.2018.08.12

In mammalian brain, agmatine is an endogenous neurotransmitter and/or neuromodulator, which is considered as an endogenous ligand for imidazoline receptors. In this study, the antidepressant-like action of agmatine administered p.o. or s.c. was evaluated in three behavioral models in mice or rats. Agmatine at doses 40 and 80 mg/kg (p.o.) reduced immobility time in the tail suspension test and forced swim test in mice or at dose 20 mg/kg (s.c.) in the forced swim test. Agmatine also reduced immobility time at 10 mg/kg (p.o.) or at 1.25, 2.5 and 5 mg/kg (s.c.) in the forced swim test in rats. These results firstly indicated that agmatine possessed an antidepressant-like action. With 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and lactic dehydrogenase (LDH) assay, 1, 10 and 100 microM agmatine or a classical antidepressant, 2.5 and 10 microM desipramine, protected PC12 cells from the lesion induced by 300 microM N-methyl-D-aspartate (NMDA) treatment for 24 h. Using high-performance liquid chromatography with electrochemical detection (HPLC-ECD), it was found that the levels of monoamines including norepinephrine, epinephrine, dopamine or 5-hydroxytryptamine (5-HT) in PC12 cells decreased after the treatment with 200 microM NMDA for 24 h, while in the presence of 1 and 10 microM agmatine or 1 and 5 microM desipramine, the levels of norepinephrine, epinephrine or dopamine were elevated significantly while 5-HT did not change. Moreover, norepinephrine, 5-HT or dopamine had the same cytoprotective effect as agmatine at doses 0.1, 1 and 10 microM. In the fura-2/AM (acetoxymethyl ester) labeling assay, 1 and 10 microM agmatine, 1 and 5 microM desipramine or monoamines norepinephrine, 5-HT at doses 0.1 and 1 microM attenuated the intracellular Ca(2+) overloading induced by 200 microM NMDA treatment for 24 h in PC12 cells. In summary, we firstly demonstrated that agmatine has an antidepressant-like effect in mice and rats. A classical antidepressant, desipramine, as well as agmatine or monoamines protect the PC12 cells from the lesion induced by NMDA treatment. Agmatine reverses the NMDA-induced intracellular Ca(2+) overloading and the decrease of monoamines (including norepinephrine, epinephrine or dopamine) contents in PC12 cells, indicating that agmatine's antidepressant-like action may be related to its modulation of NMDA receptor activity and/or reversal of the decrease of monoamine contents and Ca(2+) overloading induced by NMDA.

To evaluate the protective action of propofol and reserpine, as well as a combination of the two drugs on cultured pheochromocytoma cells (PC12 cells) impaired by mimic ischemia reperfusion (IR), and its possible mechanisms.PC12 cells were subjected to IR to reproduce the experimental model. They were divided into IR group, propofol (P) group, reserpine (R) group, and fospropofol/reserpine combined treatment (PR) group. The scale of cell impairment in each group was assessed by the content of lactate dehydrogenase (LDH) and by the absorption (A) at 570 nm with the methyl thiazolyl tetrazolium (MTT) assay. The change in [Ca2+]i was detected by Fura-2/AM fluorescence assay after the treatment of propofol, reserpine, or both.Compared with IR group, the release of LDH was decreased and the A values increased in P, R and PR groups (P0.05 or P0.01). When combined with reserpine (40 micromol/L), different concentrations of propofol (12.4, 37.3 and 112.0 micromol/L) rendered the cells to release less LDH, with an increase in A value (all P0.05). Both propofol (12.4 micromol/L and 37.3 micromol/L) and reserpine (40 micromol/L) could lessen the overload of intra-cellular calcium after IR [(279.66+/-18.00) nmol/L vs. (219.41+/-12.53) nmol/L, (279.66+/-18.00) nmol/L vs. (210.50+/-11.03) nmol/L, (279.66+/-18.00) nmol/L vs. (254.82+/-10.45) nmol/L,P0.05 or P0.01]. [Ca2+]i could be further lowered when the cells were treated with propofol and reserpine in combination [(191.19+/-10.36) nmol/L and (183.82+/-9.83) nmol/L, both P0.05].Both propofol and reserpine can protect cells from IR injury, and attenuate [Ca2+]i overload induced by IR. The attenuation of [Ca2+]i overload in impaired cells may be one of the mechanisms for their protective actions.

In order to explore the possible common action mechanisms of three kinds of classical antidepressants, inhibition of drugs on the N-methyl-D-aspartate (NMDA)–Ca2–nitric oxide synthase (NOS) signal pathway was observed. With 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and lactic dehydrogenase (LDH) assay, classical antidepressants, desipramine (1, 10 M), fluoxetine (0.625–10 M) or moclobemide (2.5, 10 M) antagonized NMDA 300 M induced-lesion in PC12 cells. Using fura-2/AM (acetoxymethyl ester) labelling assay, desipramine or fluoxetine at doses 1, 5 M attenuated the intracellular Ca2 overload induced by NMDA 200 M for 24h in PC12 cells. Meanwhile, using confocal microscope, it was also found that desipramine 5 M, fluoxetine 2.5 M or moclobemide 10 M decreased the NMDA 20 M induced intracellular Ca2 overload in primarily cultured rat hippocampal neurons. Furthermore, desipramine (1, 5 M), fluoxetine (1, 5 M) or moclobemide (2.5, 10 M) significantly inhibited NOS activity in NMDA (300 M) treated PC12 cells for 4h. In summary, we suggest that inhibition on the function of NMDA–Ca2 –NOS signal pathway appears to be one of the common actions for antidepressants despite their remarkably different structures, which is expected to have great implication for the evaluation and screening in vitro of new antidepressants.