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Ischemia-reperfusion injury (IRI) has indeed been shown as a main complication of hepatectomy, liver transplantation, trauma, and hypovolemic shock. A large number of studies have confirmed that microvascular and parenchymal damage is mainly caused by reactive oxygen species (ROS), which is considered to be a major risk factor for IRI. Under normal conditions, ROS as a kind of by-product of cellular metabolism can be controlled at normal levels. However, when IRI occurs, mitochondrial oxidative phosphorylation is inhibited. In addition, oxidative respiratory chain damage leads to massive consumption of adenosine triphosphate (ATP) and large amounts of ROS. Additionally, mitochondrial dysfunction is involved in various organs and tissues in IRI. On the one hand, excessive free radicals induce mitochondrial damage, for instance, mitochondrial structure, number, function, and energy metabolism. On the other hand, the disorder of mitochondrial fusion and fission results in further reduction of the number of mitochondria so that it is not enough to clear excessive ROS, and mitochondrial structure changes to form mitochondrial membrane permeable transport pores (mPTPs), which leads to cell necrosis and apoptosis, organ failure, and metabolic dysfunction, increasing morbidity and mortality. According to the formation mechanism of IRI, various substances have been discovered or synthesized for specific targets and cell signaling pathways to inhibit or slow the damage of liver IRI to the body. Here, based on the development of this field, this review describes the role of mitochondria in liver IRI, from aspects of mitochondrial oxidative stress, mitochondrial fusion and fission, mPTP formation, and corresponding protective measures. Therefore, it may provide references for future clinical treatment and research.

Objectives. Dexmedetomidine is widely used as an adjunct to general anesthesia. In this study, we evaluated the effects of perioperative dexmedetomidine infusion on postoperative analgesia in patients undergoing lateral thoracotomy for thoracic esophageal cancer. Methods. A total of 62 patients undergoing lateral thoracotomy for thoracic esophageal cancer were randomized to receive adjuvant therapy with either dexmedetomidine (0.5 μg/kg intravenous bolus injection for 10 min before induction of anesthesia, followed by continuous infusion of 0.2–0.4 μg/kg/h until the end of surgery, and 0.06 μg/kg/h for 5 days after surgery) or equal volumes of saline. Acute postoperative pain was treated with patient-controlled intravenous sufentanil and flurbiprofen axetil. The primary outcomes of this study were the numbers of analgesic requirements in the first postoperative 72 h. Results. Perioperative dexmedetomidine did not decrease the numbers of analgesic requirements in the first postoperative 72 h (dexmedetomidine group: 12.14 ± 4.76, saline group: 10.89 ± 5.66; p=0.367). Likewise, the groups did not differ with respect to total postoperative analgesic requirements, postoperative pain, perioperative inflammation, blood cell count, incidence of adverse events, surgical recovery (assessed at postoperative days 2 and 5 using the surgical recovery scale), length of hospital stay, hospital cost, incidence of chronic pain, or quality of life. Notably, dexmedetomidine had beneficial effects on decreasing intraoperative opioid consumption and improving postoperative sleep quality. Discussion. Perioperative dexmedetomidine has limited analgesic benefits in lateral thoracotomy for esophageal cancer when added to an opioid-based multimodal anesthetic regimen but can reduce opioid consumption.

Objective: MiR-203 has been shown to participate in multiple malignancies, but the role of miR-203 in hepatoblastoma (HB) remains unclear. The aim of our study was to investigate the effects of miR-203 in HB. Methods: A total of 15 pairs of HB tissues and para-tumour normal tissues were collected for the experiments. RT-qPCR and Western blotting were performed to detect the expression of CRNDE, miR-203, and VEGFA at the mRNA and/or protein levels, respectively. A dual luciferase assay verified the target relationship between miR-203 and the 3′UTR of VEGFA as well as miR-203 and CRNDE. In addition, MTT, wound healing, and tube formation assays were performed to assess the effects of miR-203, VEGFA, and CRNDE on cell proliferation, migration, and angiogenesis, respectively. Results: Our data revealed that miR-203 expression was decreased in HB tissues, while long non-coding RNA (lncRNA) CRNDE expression was increased. The dysregulation of miR-203 and CRNDE was closely related to tumour size and stage. Moreover, overexpression of miR-203 inhibited angiogenesis. A dual luciferase assay verified that VEGFA is a direct target of miR-203 and that CRNDE binds to miR-203. Furthermore, our results showed that miR-203 suppressed cell viability, migration, and angiogenesis by regulating VEGFA expression. Additionally, it was confirmed that CRNDE promoted angiogenesis by negatively regulating miR-203 expression. Conclusion: lncRNA CRNDE targets the miR-203/VEGFA axis and promotes angiogenesis in HB. These results provide insight into the underlying mechanisms of HB and indicate that CRNDE and miR-203 might be potential targets for HB therapy.

Objective This study is performed to explore the role of transcription factor FOXM1 in promoting the self-renewal and proliferation of liver cancer stem cells (LCSCs) by regulating the expression of acetaldehyde dehydrogenase-2 (ALDH2). Methods CD133+ CD24+ LCSCs were sorted and identified. A series of experiments were carried out to determine the proliferation, colony formation rate, migration, invasion, and apoptosis of LCSCs after interfering with FOXM1. Proliferation-, epithelial-mesenchymal transition (EMT)-, apoptosis-, and stemness-related factors were then detected by western blot analysis. Tumor xenograft in nude mice was used to figure out the role of FOXM1 in tumorigenesis in vivo by regulating ALDH2 expression. Luciferase activity assay was conducted to determine whether FOXM1 could target ALDH2 promoter region and thereby affecting ALDH2 expression. Results The sorted CD133+ CD24+ Huh-7 cells had the characteristic of stem cells. FOXM1 was highly expressed in CD133+ CD24+ Huh-7 cells. Silencing FOXM1 inhibited the proliferation and colony formation of LCSCs and decreased the expression of proliferating cell nuclear antigen and Ki-67 protein; inhibited the migration, invasion, and EMT of LCSCs while promoting the apoptosis of LCSCs, as well as promoted the expression of Bax and cleaved-caspase-3, and inhibited the expression of Bcl-2. Silencing FOXM1 inhibited the expression of Nanog, Oct4, and Sox2 in LCSCs by decreasing the expression of ALDH2. in vivo experiment, silencing FOXM1 suppressed tumorigenesis of LCSCs by decreasing the expression of ALDH2. Conclusion Our study provides evidence that silencing FOXM1 inhibits stemness of LCSCs by decreasing the expression of ALDH2, and represses the proliferation, migration, invasion, and tumorigenesis while inducing the apoptosis of LCSCs.

Background Patients suffering from diabetes mellitus experience poor outcomes after ischemic stroke. RTN1-C, ER-associated proteins localized in endoplasmic reticulum (ER) membrane, plays an important role in ER stress-induced apoptosis and regulates cellular susceptibility to different apoptosis pathways. Overexpression of RTN1-C can aggravate cerebral ischemia/reperfusion injury (IRI). ER stress plays a crucial role in hyperglycemia-aggravated cerebral IRI. In this study, we aimed to investigate the role of RTN1-C in high glucose-aggravated OGD/R-induced cell damage. Materials and methods N2a cells and primary neuronal cells were cultured in normal glucose or high glucose conditions. We used a model of oxygen-glucose deprivation followed by reoxygenation (OGD/R). RTN1-C shRNA was used to knock down RTN1-C. The chemical chaperone 4-phenylbutyric acid (4-PBA) is a low molecular weight fatty acid that has the ability to stabilize mutant proteins and facilitate their folding, was used to inhibited ER stress. Cell viability and apoptosis were measured by CCK-8 and flow cytometry assays. The contents of ER stress-associated proteins, such as GRP78, cleaved caspase-12, CHOP and cleaved caspase-3, were detected by western blot. Results High glucose significantly decreased cell viability and increased cell apoptosis in OGD/R-treated neuronal cells. The contents of GRP78, cleaved caspase-12, CHOP and cleaved caspase-3 under high glucose conditions were higher than those under normal glucose conditions after OGD/R. Importantly, inhibition of ER stress by 4-PBA alleviated the high glucose-aggravated OGD/R-induced cell damage. Here, we demonstrated that high glucose increases RTN1-C expression in OGD/R-treated cells. More importantly, knockdown of RTN1-C expression dramatically reversed the high glucose-aggravated change in cell viability and apoptosis and relieved ER stress in OGD/R-treated cells. Conclusions High glucose significantly increases RTN1-C expression in OGD/R-treated cells. RTN1-C affects high glucose-treated OGD/R cells by exacerbating ER stress.

Objective Cognitive impairment is common among patients with major depressive disorder (MDD), but its pathological mechanism is complex and not fully understood. Evidence suggests that the kynurenine (KYN) pathway may be implicated in the pathophysiology of depression, but few studies have explored the association between the KYN pathway and cognitive impairment in MDD. Our aim was to examine the relationship between cognitive impairment and KYN pathway metabolites in patients with MDD. Methods A total of 146 patients with MDD according to DSM-V and 72 healthy controls (HCs) were enrolled, and the severity of depressive symptoms using the 17-item Hamilton Depression Rating Scale (HAMD-17) and cognitive performance including speed of processing, working memory, visual learning and verbal learning were assessed. Blood samples were collected, and serum concentrations of tryptophan (TRP), kynurenine (KYN) and kynurenic acid (KYNA) were measured by liquid chromatography-tandem mass spectrometry. Results In females with MDD, there was a significant negative association between the KYN level and verbal learning (B=-0.039, adjusted p = 0.018), and the KYN/TRP ratio was negatively correlated with speed of processing (B=-470.086, adjusted p = 0.029), verbal learning (B=-544.251, adjusted p = 0.002) and visual learning (B=-513.777, adjusted p = 0.004). Those associations were not present in male individuals with MDD or in HCs, except for a significant negative correlation between the KYNA/KYN ratio and category fluency (B=−0.373, adjusted p = 0.039) in female HCs. Conclusion Our results suggest that learning function and speed of processing in female MDD were associated with KYN serum level and the KYN/TRP ratio, potentially implicating the KYN pathway in the pathological mechanism of cognitive function in female MDD.

BackgroundHighly structured electroencephalography (EEG) oscillations can occur in adults during etomidate-induced general anesthesia, but the link between these two phenomena is poorly understood. Therefore, in the present study, we investigated the electroencephalogram dynamics of etomidate-induced loss of consciousness (LOC) in order to understand the neurological mechanism of etomidate-induced LOC.MethodsThis study is a prospective observational study. Etomidate-induced anesthesia was performed on eligible patients undergoing elective surgery. We analyzed EEG data from 20 patients who received etomidate for the induction of general anesthesia. We used power spectra and coherence methods to process and analyze the EEG data. Our study was based on 4-channel EEG recordings.ResultsCompared with the baseline (awake period), etomidate induced an increase in power in delta, theta, alpha and beta waves during LOC. Compared with the awake period, the delta-wave (1–4 Hz), alpha-wave(8–13 Hz), and theta-wave(4–8 Hz) coherence increased significantly during LOC, while the slow-wave (p < 0.001).ConclusionsThe neural circuit mechanism of etomidate-induced LOC is closely related to the induction of oscillation in delta, theta, alpha and beta waves and the enhancement of delta-wave coherence.Trial registrationChiCTR1800017110

Hepatic ischemia/reperfusion (I/R) injury represents a major risk factor for liver transplantation and is related to graft dysfunction and acute/chronic rejection. However, a significant part of these processes remain poorly characterized. To reveal differences in the proteome during liver I/R injury, we collected human liver biopsy samples during hepatectomy before and after the Pringle maneuver and conducted a TMT-based proteomic analysis through quantitative high-throughput mass spectrometry. We used a fold-change threshold of 1.3 and a t-test p-value

RNF2 (also known as ding, Ring1B or Ring2) is a member of the Ring finger protein family, which functions as E3 ubiquitin ligase for monoubiquitination of histone H2A at lysine 119 (H2AK119ub). RNF2 gene is located at the 1q25.3 site of human chromosome and the coding region is composed of 9 exons, encoding 336 amino acids in total. Many studies have demonstrated that overexpressed RNF2 was involved in the pathological progression of multiple cancers and has an impact on their clinical features. For instance, the upregulated expression level of RNF2 is positively correlated with the occurrence and progression of hepatocellular carcinoma, melanoma, prostate cancer, breast cancer, pancreatic cancer, gastric cancer, and bladder urothelial carcinoma, as well as with the radioresistance of lung cancer and chemoresistance of ovarian cancer. This review provides an up-to-date perspective on the relationship between RNF2 and several cancers and highlights recent studies on RNF2 regulation. In particular, the relevant cellular signaling pathways and potential clinical value of RNF2 in cancers are also discussed, suggesting its potential as an epigenetic biomarker and therapeutic target for these cancers.

Background Lung cancer has high morbidity and mortality worldwide with non-small cell lung cancer (NSCLC) accounting for 85% of the cases. Therapies for lung cancer have relatively poor outcomes and further improvements are required. Circular RNAs have been reported to participate in the occurrence and progression of cancer. Information on the functions and mechanism of circRNAs in lung cancer is limited and needs more exploration. Methods We detected expression of genes and proteins by qPCR and western blot. Function of circSATB2 was investigated using RNA interference and overexpression assays. Location of circSATB2 was assessed by fluorescence in situ hybridization (FISH). Interaction of circSATB2, miR-326 and FSCN1 was confirmed by dual-luciferase reporter assay. Results Data from the investigation showed that circSATB2 was highly expressed in NSCLC cells and tissues. circSATB2 positively regulated fascin homolog 1, actin-bundling protein 1 (FSCN1) expression via miR-326 in lung cancer cells. Furthermore, circSATB2 can be transferred by exosomes and promote the proliferation, migration and invasion of NSCLC cells, as well as induce abnormal proliferation in normal human bronchial epithelial cells. Also, circSATB2 was highly expressed in serumal exosomes from lung cancer patients with high sensitivity and specificity for clinical detection and was related to lung cancer metastasis. Conclusions circSATB2 participated in the progression of NSCLC and was differentially expressed in lung cancer tissue and serumal exosomes. circSATB2 may be potential biomarker for the diagnosis of NSCLC.

It has been widely accepted that autophagic cell death exacerbates the progression of cerebral ischemia/reperfusion (I/R). Our previous study revealed that overexpression of reticulon protein 1-C (RTN1-C) is involved in cerebral I/R injury. However, the underlying mechanisms have not been studied intensively. This study was designed to evaluate the effect of RTN1-C on autophagy under cerebral I/R. Using an in vitro oxygen-glucose deprivation followed by reoxygenation and a transient middle cerebral artery occlusion model in rats, we found that the expression of RTN1-C protein was significantly upregulated. We also revealed that RTN1-C knockdown suppressed overactivated autophagy both in vivo and in vitro, as indicated by decreased expressions of autophagic proteins. The number of Beclin-1/propidium iodide-positive cells was significantly less in the LV-shRTN1-C group than in the LV-shNC group. In addition, rapamycin, an activator of autophagy, aggravated cerebral I/R injury. RTN1-C knockdown reduced brain infarct volume, improved neurological deficits, and attenuated cell vulnerability to cerebral I/R injury after rapamycin treatment. Taken together, our findings demonstrated that the modulation of autophagy from RTN1-C may play vital roles in cerebral I/R injury, providing a potential therapeutic treatment for ischemic brain injury.

Ketamine has rapid antidepressant effects on treatment-resistant depression, but the biological mechanism underpinning this effect is less clear. Our aims were to examine whether kynurenine pathway metabolites were altered by six infusions of ketamine and whether these biological factors could act as potential biomarkers to predict ketamine's antidepressant effects. Six intravenous infusions of ketamine (0.5 mg/kg) were administered to 84 patients with unipolar and bipolar depression over a 12-d period. Symptom severity and response were assessed using the Montgomery-Asberg Scale (MADRS), and blood samples were collected at baseline and 24 h following the first infusion and at 24 h and 14 d after the sixth infusion (24 h, 13 d and 26 d). Blood samples from sixty healthy controls were collected for comparison with samples from the patients. Serum concentrations of tryptophan (TRP), kynurenine (KYN) and kynurenic acid (KYNA) were measured by the liquid chromatography-tandem mass spectrometry method. At baseline, serum levels of TRP and KYNA and the KYNA/KYN ratio were lower and the KYN/TRP ratio was greater in depressed patients than in healthy controls. Overall, fifty (59.5%) patients responded to ketamine at 13 d. Ketamine responders had a greater KYNA level and KYNA/KYN ratio than nonresponders at 24 h and 13 d (all P 0.05). Elevations in the KYNA levels and KYNA/KYN ratio at 24 h were significantly associated with reductions in MADRS scores at 24 h, 13 d and 26 d in the linear regression analysis (all P 0.05). Our results showed a possible involvement of the kynurenine pathway in the rapid antidepressant effect of ketamine. Early changes in serum KYNA levels and the KYNA/KYN ratio could be potential predictors of antidepressanteffects of repeated ketamine administration.

Objective Single-dose intravenous (IV) injection of ketamine has shown rapid but transient antidepressant effects. The strategy of repeated-dose ketamine infusions to maintain antidepressant effects has received little systematic study. This study was conducted to examine the efficacy and tolerability of six ketamine infusions in Chinese patients with unipolar and bipolar depression. Methods Ninety seven patients with unipolar (n = 77) and bipolar (n = 20) depression received repeated ketamine infusions (0.5 mg/kg over 40 min) with continuous vital sign monitoring. Depressive symptoms were measured by the Montgomery-Asberg Depression Rating Scale (MADRS). Suicidal ideation was assessed using the Scale for Suicidal Ideations (SSI)-part 1. Anxiety symptoms were evaluated with the 14-item Hamilton Anxiety Scale (HAMA). Adverse psychopathological and dissociative effects were assessed using the Brief Psychiatric Rating Scale (BPRS)-positive symptoms and Clinician Administered Dissociative States Scale (CADSS), respectively. Patients were assessed at baseline, 4 and 24 h, and 3, 4, 5, 6, 8, 9, 10, 11, 12, 13 and 26 days. Results After six ketamine infusions, the response and remission rates were 68.0% and 50.5%, respectively. There were significant decreases in MADRS, SSI-part 1, and HAMA scores within four hours following the first ketamine infusion, and the decreases were sustained over the subsequent infusion period. The nonresponder subgroup manifested rapid significant improvement in suicidal ideations throughout the course of treatment. After the six ketamine infusions, the response was positively associated with the response at 24 h after the first infusion (OR = 8.94), personal income ≥4000 yuan/month (OR = 3.04), and no history of psychiatric hospitalization (OR = 3.41). Only CADSS scores had a mild but marginally significant increase after the first infusion but with a significant BPRS score decrease. Conclusion Six ketamine infusions were safe and effective in patients with unipolar and bipolar depression. The rapid and robust antidepressant and antisuicidal effects of ketamine infusion within four hours were sustained following the subsequent infusions.

Smoking is one of the major environmental risk factors for lung cancer. In recent years, the role of long-chain noncoding RNAs (lncRNAs) in chemical carcinogenesis has attracted extensive research attention. In this study, we treated human bronchial epithelial cells with cigarette smoke extract (CSE) at a dose of 2 μg/ml to establish a malignantly transformed cellular model (16HBE-M). Screening of lncRNAs highly expressed in transformed cells via differential analysis revealed a crucial role of linc00152 in CSE-induced malignant transformation. The linc00152 serum level in CSE-exposed individuals was increased in a dose-dependent manner and its high expression associated with metastasis and proliferation of lung cancer tissue. In malignantly transformed 16HBE-M cells, linc00152 was involved in regulation of cell adhesion, epithelial transition and other malignant phenotypes, which in turn, affected in vivo metastasis. Interference with linc00152 expression led to G1/S arrest and inhibition of proliferation of 16HBE-M and H1299 cells. Furthermore, linc00152 promoted cyclin D1 expression and G1/S transition by functioning as an endogenous competitive RNA targeting miR-193b. Our collective findings supported a critical regulatory role of linc00152 in cell cycle alterations and abnormal proliferation in CSE-induced malignant transformation of human bronchial epithelial cells.

Yu Mao,1,2,* Youmei Zuo,2,* Bin Mei,2 Lijian Chen,2 Xuesheng Liu,2 Zhi Zhang,1 Erwei Gu2 1Key Laboratory of Brain Function and Disease of Chinese Academy of Science, Department of Biophysics and Neurobiology, University of Science and Technology of China, Hefei City, Anhui 230027, People’s Republic of China; 2Department of Anaesthesiology, First Affiliated Hospital of Anhui Medical University, Hefei City, Anhui 230031, People’s Republic of China *These authors equally contributed to this work Purpose: The purpose of this study was to assess the efficacy of perineural dexamethasone with ropivacaine in multimodal analgesia for thoracic paravertebral block (TPVB) in patients undergoing elective thoracotomy. Patients and methods: Ninety-six patients undergoing thoracotomy were enrolled in this trial and randomized to adjuvant therapy for TPVB: group S (saline), group R (0.5% ropivacaine), or group RD (5mg dexamethasone and 0.5% ropivacaine). Postoperative analgesia, recovery duration, and chronic pain were recorded. Results: Groups R and RD spent less time in the postanaesthesia care unit, had earlier out-of-bed activity, and had shorter postoperative hospital stays compared with group S. The RD group regained consciousness faster and had lower acute pain scores and used less patient-controlled analgesia during the first 72h after surgery compared with group S. Postthoracotomy pain was decreased in group RD (19.0%) compared with group S (47.6%) 3months postoperatively, p= 0.050. Conclusion: Perineural dexamethasone with ropivacaine for TPVB improves postoperative analgesia quality, reduces recovery time, and may decrease the incidence of chronic pain after thoracotomy with an opioid-based anesthetic regimen. Keywords: chronic pain, dexamethasone, nerve block, thoracotomy

Background Late-life depression patients are at a high risk of developing Alzheimer’s disease, and diminished olfactory identification is an indicator in early screening for Alzheimer’s disease in the elderly. However, whether diminished olfactory identification is associated with risk of developing Alzheimer’s disease in late-life depression patients remains unclear. Methods One hundred and twenty-five late-life depression patients, 50 Alzheimer’s disease patients, and 60 normal controls were continuously recruited. The participants underwent a clinical evaluation, olfactory test, neuropsychological assessment, and neuroimaging assessment. Results The olfactory identification impairment in late-life depression patients was milder than that in Alzheimer’s disease patients. Diminished olfactory identification was significantly correlated with worse cognitive performance (global function, memory language, executive function, and attention) and reduced grey matter volume (olfactory bulb and hippocampus) in the late-life depression patients. According to a multiple linear regression analysis, olfactory identification was significantly associated with the memory scores in late-life depression group (B=1.623, P

Segmenting reference bones from radiographs of the hand is important for bone age assessment. Due to the influence of the irregular shapes and the adjacent positions of the wrist reference bones, it is difficult for the expert to accurately estimate the mature indication of the wrist reference bones in the figures. How to precisely segment the reference bones automatically from the radiographs is a challenge. For this is problem, an improved U-Net, Attention Residual U-Net (ARU-Net) proposed in this paper. Firstly, we extract the reference bone region of interest (ROI) by faster region-based convolutional neural networks(R-CNN). Then, the pre-processed ROI is fed into ARU-Net for segmentation. On the basis of traditional U-Net, ARU-Net adds residual mapping and attention mechanism, which improves the utilization rate of features and the accuracy of reference bone segmentation. Finally, a post-processing method including the flood fill algorithm and the morphological operation is used to eliminate jagged edges and holes in the segmented result. The hamate is one of the most difficult reference bones to segment in the wrist. This paper takes it as an example to assess the performance of ARU-Net. Experiments show that compared with Fully Convolutional Neural Network (FCN), U-Net and ResUnet, the accuracy and F1 scores of ARU-Net are higher. Its accuracy rate is 96.41%, and F1 score is 0.9529. The post-processing method can further improve the result. Finally, the accuracy rate reaches 96.51%, and the F1 score reaches 0.9544. ARU-Net can precisely segment the reference bone, which facilitates the expert to assess its mature indication, so as to accurately evaluate the bone age.

Objective Ketamine has been demonstrated to have robust and rapid antidepressant effects, and few studies have focused on the relationship between insomnia and the efficacy of ketamine. The objective of this study was to examine whether baseline insomnia predicted the antidepressant efficacy of repeated intravenous ketamine infusions for unipolar and bipolar depression. Method Patients with high insomnia (n = 64) or low insomnia (n = 68) received six intravenous infusions of ketamine (0.5 mg/kg over 40 min) over 12 days (Monday-Wednesday-Friday). The Montgomery-Asberg Depression Rating Scale (MADRS) without sleep item was used to assess depressive symptoms. Response was defined as a MADRS total score ≥ 50%, and remission was defined as a MADRS total score ≤ 10. Result There were no differences in response or remission rates between patients with high and low insomnia. However, the logistic regression model showed that high insomnia predicted an increased likelihood of response and remission. Cox proportional hazards models showed a reduced latency to respond and remit in patients with high insomnia. A linear mixed model showed that the high insomnia subgroup had greater improvement than the low insomnia subgroup (all p Limitation The major limitation of this study is the open-label design. Conclusion When given six ketamine infusions, patients with high insomnia were more likely to respond and remit than those with low insomnia. Patients with high insomnia showed not only a shorter latency to respond and remit, but also greater improvement than those with low insomnia.

Recent studies have suggested that neurocognition is changed after repeated infusions of ketamine in patients with treatment-resistant depression (TRD). The objective of this study was to investigate whether differences existed in the neurocognitive effect of six ketamine infusions in patients with anxious and nonanxious TRD and to determine the association between baseline neurocognition and changes in symptoms after the infusions.Patients with anxious (n = 30) and nonanxious TRD (n = 20) received six intravenous infusions of ketamine (0.5 mg/kg over 40 min) over 12 days. Speed of processing (SOP), working memory (WM), verbal learning and memory (VBM), visual learning and memory (VSM) and the severity of depressive and anxious symptoms were assessed at baseline, one day after the last infusion (day 13) and two weeks after the completion of the serial infusions (day 26). A linear mixed model was used to determine whether the neurocognitive changes differed between the two groups. Pearson correlation analysis was used to determine the relationship between baseline neurocognition and the changes in the symptomatic scores.Patients with anxious TRD had significant increases in SOP on day 13 and day 26 (both p 0.001), and in VBM on day 13 (p = 0.028). However, no significant increase in any neurocognitive domain was found in patients with nonanxious TRD. Faster SOP at baseline was associated with greater improvement of anxious symptoms in patients with anxious TRD, and better VSM at baseline was associated with greater improvement of depressive symptoms in patients with nonanxious TRD.The major limitation of this study is the open-label design.After six ketamine infusions, neurocognitive improvement was observed in patients with anxious TRD but not in patients with nonanxious TRD.

Background Suicide is a tremendous public health crisis and is demanded urgent intervention. Previous studies found that ketamine intervention could rapidly reduce suicidal ideation in depression. However, the comparatively study in Chinese population remains absence. The current study aims to assess the anti-suicidal efficacy of repeated ketamine infusions for Chinese depressed suicidal patients, especially distinguish between low suicidal ideation (SI) group and high SI group. Methods Eighty-six unipolar and bipolar depressive patients with current suicidal ideation received six ketamine infusions during a 12-day period. Hamilton Depression Rating Scale (HAMD) and Beck Scale for Suicide Ideation (SSI) was measured at baseline, 4 h and 24 h after each infusion, and two-week naturalistically follow-up. Results Forty-nine (57.0%) patients relief of suicidal ideation after first infusion and 56 (65.1%) after six infusions. Anti-suicidal response rate in low SI group were higher than high SI group, and anti-suicidal response at 4 h after first infusion was significant predictor of response at 24 h after sixth infusion. Furthermore, at 24 h after the sixth infusion, correlation between changes in suicidal ideation and depression was 0.23, accounting for 7.4% in the variance of suicidal ideation change. Limitation The major limitation of this study was that lack of a placebo or other control group limits the interpretation of efficacy. Conclusions We confirmed that six repeated ketamine infusions for Chinese suicidal depressed patients were effective in generating a rapid response of suicidal ideation, especially low SI achieved more benefits from ketamine infusions.

Objective: Single-dose intravenous ketamine has rapid but time-limited antidepressant effects. We aimed to examine the sustained effects of six consecutive ketamine infusions in Chinese patients with major depressive disorder. Methods: Seventy-seven patients with major depressive disorder were eligible to receive augmentation with six ketamine infusions (0.5 mg/kg over 40 min) administered over the course of 12 days (Monday–Wednesday–Friday). The coprimary outcome measures were the rates of response and remission as measured on the 10-item Montgomery-Asberg Depression Rating Scale. Psychotomimetic and dissociative symptoms were measured with the Brief Psychiatric Rating Scale-positive symptoms and the Clinician Administered Dissociative States Scale, respectively. Results: After the first ketamine infusion, only 10 (13.0%) and 6 (7.8%) patients responded and remitted, respectively; after six ketamine infusions, 52 (67.5%) patients responded and 37 (48.1%) remitted. There was a significant mean decrease in Montgomery-Asberg Depression Rating Scale score at four hours after the first ketamine infusion (7.0±7.5, pConclusion: Six ketamine infusions increased rates of response and remission when compared to a single-dose ketamine infusion in patients with major depressive disorder. Future controlled studies are warranted to confirm and expand these findings.

Background: Ketamine has proven to have rapid, robust antidepressant effects on treatment-resistant depression. However, whether repeated ketamine infusions would cause short-and long-term neurocognitive impairments was not clear. Our aims were to investigate the neurocognitive effects of six ketamine infusions and to examine the association between these infusions and the antidepressant response in patients with unipolar and bipolar depression. Methods: Six intravenous infusions of ketamine (0.5 mg/kg) over a 12-day period were administered to 84 patients with unipolar and bipolar depression. Severity of depressive symptoms and four domains of neurocognition, including speed of processing, working memory, visual learning and verbal learning, were assessed at baseline, one day following the last infusion and again two weeks post-infusion. Results: Significant improvements were found on speed of processing ( F=9.344, pConclusions: Our findings suggest that neurocognitive function would not deteriorate after six ketamine infusions, while verbal learning and speed of processing improved over 13 days and 26 days of observation, respectively. However, this change was mainly accounted for by improvements in severity of depressive symptoms over time. Greater baseline visual learning predicted an antidepressant response over six ketamine infusions.

Ketamine has demonstrated a rapid antidepressant and antisuicidal effect in patients with major depressive disorder (MDD), but the neurocognitive effects of ketamine are relatively unknown. This study aims to examine the neurocognitive effects of six ketamine infusions and the association of baseline neurocognitive function and the change in severity of depressive symptoms after the last infusions.Sixty-four patients with MDD completed six intravenous infusions of ketamine (0.5 mg/kg over 40 min) administered over a 12-day period (Monday-Wednesday-Friday), and were followed by a 2-week observational period. Four domains of neurocognitive function (including speed of processing, working memory, visual learning and verbal learning) were assessed using the MATRICS Consensus Cognitive Battery (MCCB) at 0, 13 and 26 days.In linear mixed model, significant improvements were found in terms of speed of processing (F = 20.7, p 0.001) and verbal learning (F = 11.1, p 0.001). The Sobel test showed the improvement of speed of processing (Sobel test = 2.8, p 0.001) and verbal learning (Sobel test = 3.6, p 0.001) were significantly mediated by change in depressive symptoms. Other two neurocognitive domains showed no significant changes over time. Correlation analysis showed no significant association of change in depressive symptoms with neurocognitive function at baseline.Our findings suggest that six ketamine infusions were associated with the improvement of speed of processing and verbal learning, which were partly accounted for by improvement in the severity of depression symptoms over time.

Background Major depressive disorder (MDD) is associated with neurocognitive impairment and reduced social-occupational function. However, neurocognition and social-occupational function in patients with anxious depression have been under-investigated. An increasing number of studies have demonstrated that neurocognition plays an important role in social-occupational function. The objective of this study was to investigate the association of severity of symptoms, neurocognition and social-occupational function in patients with anxious depression. Method Using a cross-sectional design, 214 patients with MDD were recruited consecutively and evaluated using the 17-item Hamilton Depression Rating scale (HAMD-17), the MATRICS Consensus Cognitive Battery (MCCB) and the Global Assessment of Functioning (GAF). Result The prevalence of anxious depression in MDD patients was 64.5%. Compared to non-anxious subjects, the anxious group had more severe symptoms. Moreover, in the anxious group, social-occupational function was associated with several domains of symptoms and neurocognition, while social-occupational function was associated with only one aspect of depressive symptoms (cognitive disturbance) in the non-anxious group. In addition, there was a mediating effect of neurocognition on the association between the severity of symptoms and social-occupational function in the anxious group. Limitations The major limitation of the present study is the use of a cross-sectional design that is unable to illuminate causal relationships. Conclusion Our results suggest that the severity of symptoms is negatively associated with neurocognition and social-occupational function and that neurocognition is positively associated with social-occupational function in patients with anxious depression.

Circular RNAs are widely expressed in eukaryotic cells and associated with cancer. However, limited studies to date have focused on the potential role of circRNAs in progression of lung cancer. Data from the current investigation showed that circRNA 100146 is highly expressed in non-small cell lung cancer (NSCLC) cell lines and the chemically induced malignant transformed bronchial cell line, 16HBE-T, as well as 40 paired tissue samples of NSCLC. Suppression of circRNA 100146 inhibited the proliferation and invasion of cells and promoted apoptosis. Furthermore, circRNA 100146 could interact with splicing factors and bind miR-361-3p and miR-615-5p to regulate multiple downstream mRNAs. Our collective findings support a role of circRNA 100146 in the development of NSCLC and further demonstrate endogenous competition among circRNA 100146, SF3B3 and miRNAs, providing novel insights into the mechanisms underlying non-small cell lung cancer. Electronic supplementary material The online version of this article (10.1186/s12943-019-0943-0) contains supplementary material, which is available to authorized users.

Background Previous studies have shown that prolonged time spent on screen-based sedentary behavior was significantly associated with lower health status in children, independent of physical activity levels. The study aimed to explore the individual and environmental correlates of screen time (ST) among 8–19-year-old students in China. Methods The study surveyed ST using a self-administered questionnaire in Chinese students aged 8–19 years; 1063 participants were included in the final analysis. Individual and environmental correlates of ST were assessed using a mixed-effects model (for continuous outcome variables) and multiple logistic regression model (for binary outcome variables). Results Prolonged ST was observed in 14.7% of boys and 8.9% of girls. Of the ST, weekend and mobile phone/tablet use represented 80% and 40%, respectively. A positive relationship was observed between media accessibility and ST in both boys and girls (p < 0.05), whereas the presence of parents/others while using screens was a negative factor for longer ST (p < 0.05). Among the assessed correlates, access to a television (TV) in students’ bedrooms was associated with prolonged total and weekend ST (p < 0.05 and p < 0.001, respectively). However, spending time on a mobile phone/tablet or a computer rather than viewing a TV, along with increased media accessibility, increased ST. Conclusions These results indicate that greater media accessibility was positively associated and the presence of parents/others was negatively associated with prolonged ST in both Chinese boys and girls. Development of new and effective strategies against prolonged ST are required, especially for small screen device-based ST on weekends.

Ring finger protein 2 (RNF2), also known as RING2 or RING1B, displays oncogenic functions in different types of cancers, yet, the function of RNF2 during mitosis has not been evaluated. A yeast two‑hybrid screen was undertaken using a human HeLa cDNA library to explore and identify proteins that interact with RNF2. Several positive clones, including Polo‑like kinase 1 (Plk1), a critical regulator of mitosis, were identified. The interaction between RNF2 and Plk1 was confirmed using a β‑galactosidase and growth test in selective media, in vitro glutathione S‑transferase pull‑down, and in vivo immunoprecipitation assays. Moreover, we confirmed that RNF2 co‑localized with Plk1 at mitotic chromosomes in the prometaphase and metaphase using an immunofluorescence assay. In addition, our results revealed that Plk1 kinase activity was required for ubiquitin‑dependent degradation of RNF2. These findings provide a new clue for understanding the function of RNF2 during mitotic regulation and tumorigenesis.

Objective. To assess different doses of nalbuphine with flurbiprofen compared to sufentanil with flurbiprofen in multimodal analgesia efficacy for elderly patients undergoing gastrointestinal surgery with a transverse abdominis plane block (TAPB). Methods. 158 elderly patients scheduling for elective open gastrointestinal surgery under general anesthesia and TAPB were randomly assigned to four groups according to different doses of nalbuphine with flurbiprofen in postoperative intravenous analgesia (PCIA). Postoperative pain intensity, effective pressing numbers of PCIA, and adverse effects were recorded at 6, 12, 24, and 48 hours after surgery. Results. Postoperative pain intensity, effective pressing numbers, and the incidence of postoperative nausea and vomiting (PONV) were similar among the four groups after surgery, while the severity of PONV was decreased in Group L compared with Group S at 6, 12, and 48 h after surgery. No individual experienced pruritus, respiratory depression, or hypotension. Conclusions. Low dose of nalbuphine (15 μg·kg−1·ml−1) combined with flurbiprofen is superior for elderly patients undergoing elective open gastrointestinal surgery with TAPB in terms of the efficient postoperative analgesia and decreased severity of PONV. This trial is registered with NCT02984865.

BACKGROUND Remifentanil postconditioning (RPC) confers robust cardioprotection against ischemia/reperfusion (I/R) injury. We recently determined that HDAC3 was involved in RPC-induced cardioprotection. However, the role of HDAC3 and its possible mechanisms in RPC-induced cardioprotection are unknown, which we aimed to evaluate in an in vitro hypoxia/reoxygenation (HR) model. METHODS Myocardium I/R injury was established after HR with H9c2 cardiomyoblasts. Cell viability and apoptosis were evaluated usingCCK-8 and flow cytometry of HR-injured cardiomyoblasts treated with or without RPC. Furthermore, effects of RPC on HDAC3 protein and mRNA expression were evaluated with Western blot and quantitative real-time PCR analyses, whereas GSK-3β expression was measured with Western blot. RESULTS RPC increased cell viability and reduced cell apoptosis (P

T. gondii is an obligate intracellular parasite, belonging to the Phylum Apicomplexa, infecting all warm-blooded animals including humans. During host cell invasion, specialized cytoskeletal and secretory organelles play a pivotal role. ROP18, as a member of the ROP2 family, has been identified as a key virulence factor mediating pathogenesis in T. gondii. Here, we identify an ER-resident protein, Derlin2, a factor implicated in the removal of misfolded proteins from the ER for cytosolic degradation, as a component of the machinery required for ER-associated protein degradation (ERAD). We identified Derlin2 interacting with ROP18 by yeast two-hybrid screening system. The interaction between ROP18 and Derlin2 was further confirmed through in vitro GST pull-down and in vivo immunoprecipitation assays. By immunofluorescence assay, we found that ROP18 co-localized with Derlin2 in the endoplasmic reticulum. Using overexpression and knockdown approaches, we demonstrated that Derlin2 was required for T. gondii ROP18 degradation. Consistently, cycloheximide chase experiments showed that the degradation of ROP18 relied on the Derlin2, but not Derlin1. These results indicate that interaction between Derlin2 and ROP18 is functionally relevant and leads ultimately to degradation of ROP18. The finding provides the basis for future studies on Derlin2-dependent ERAD of T. gondii ROP18 and subsequent antigen generation.

Novel stimuli elicit behaviors that are collectively known as specific exploration. These behaviors allow the animal to become more familiar with the novel objects within its environment. Specific exploration is frequently suppressed by defensive reactions to predator cues. Herein, we examine if this suppression occurs in Drosophila melanogaster by measuring the response of these flies to wild harvested predators. The flies used in our experiments have been cultured and had not lived under predator threat for multiple decades. In a circular arena with centrally-caged predators, wild type Drosophila actively avoided the pantropical jumping spider, Plexippus paykulli, and the Texas unicorn mantis, Phyllovates chlorophaena, indicating an innate defensive reaction to these predators. Interestingly, wild type Drosophila males also avoided a centrally-caged mock spider, and the avoidance of the mock spider became exaggerated when it was made to move within the cage. Visually impaired Drosophila failed to detect and avoid the Plexippus paykulli and the moving mock spider, while the broadly anosmic orco2 mutants were fully capable of detecting and avoiding Plexippus paykulli, indicating that these flies principally relied upon vison to perceive the predator stimuli. During early exploration of the arena, exploratory activity increased in the presence of Plexippus paykulli and the moving mock spider. The elevated activity induced by Plexippus paykulli disappeared after the fly had finished exploring, suggesting the flies were capable of habituating the predator cues. Taken together, these results indicate that despite being isolated from predators for decades Drosophila will visually detect these predators, retain innate defensive behaviors, respond by increasing exploratory activity in the arena rather than suppressing activity, and may habituate to normal predator cues.

Toxoplasma gondii, a ubiquitous and obligate intracellular pathogen, belonging to the phylum Apicomplexa, is capable of infecting a broad range of warm-blooded hosts including birds and mammals that is nearly worldwide. Preventive measures for toxoplasmosis are currently lacking and as such, development of novel vaccines is of urgent need. The plant-like calcium-dependent protein kinases (CDPKs) expressed by T. gondii, play important roles in cell invasion, gliding motility, egress and some other developmental processes, in which T. gondii CDPK3 (TgCDPK3) has been implicated as an important virulence factor. In this study, the immune protective function of recombinant TgCDPK3 (rTgCDPK3) against experimental toxoplasmosis in BALB/c were evaluated. We divided the mice into different dose groups of vaccines and all immunizations with purified rTgCDPK3 protein were injected by intramuscular at weeks 0, 2, and 4 in BALB/c mice. The rTgCDPK3 vaccine provided protection was correlated with the development of humoral and cellular immune responses demonstrated through the antigen-specific spleen cell proliferation, release of Th1 cytokines IFN-γ, and the production of the high titers of IgG antibody with a predominance of IgG2a over IgG1. Vaccination with rTgCDPK3 conferred partial protection against acute toxoplasmosis, as demonstrated by prolonged survival rate after lethal challenge. Additionally, the amount of brain tissues cysts in vaccinated mice led to 46.5% reduction compared with non-vaccinated ones. These data demonstrated that rTgCDPK3 inoculation prevents or attenuates the harmful influence of T. gondii infection, and it is a potential vaccine candidate against toxoplasmosis.

The reticulon family has been found to induce apoptosis, inhibit axon regeneration and regulate protein trafficking. However, little is known about the mechanisms of how reticulon proteins are involved in neuronal death-promoting processes during ischemia. Here, we report that the expression of Reticulon Protein 1-C (RTN1-C) was associated with the progression of cerebral ischemia/reperfusion (I/R) injury. Using a combination of rat middle cerebral artery occlusion (MCAO) stroke and oxygen-glucose deprivation followed by reoxygenation (OGD/R) models, we determined that the expression of RTN1-C was significantly increased during cerebral ischemic/reperfusion. RTN1-C overexpression induced apoptosis and increased the cell vulnerability to ischemic injury, whereas RTN1-C knockdown reversed ischemia-induced apoptosis and attenuated the vulnerability of OGD/R-treated neural cells. Mechanistically, we demonstrated that RTN1-C mediated OGD/R-induced apoptosis through ER stress and mitochondria-associated pathways. RTN1-C interacted with Bcl-xL and increased its localization in the ER, thus reducing the anti-apoptotic activity of Bcl-xL. Most importantly, knockdown of Rtn1-c expression in vivo attenuated apoptosis in MCAO rats and reduced the extent of I/R-induced brain injury, as assessed by infarct volume and neurological score. Collectively, these data support for the first time that RTN1-C may represent a novel candidate for therapies against cerebral ischemia/reperfusion injury.